心肌淀粉样变预测价值

目的 研究血清游离轻链（sFLC）检测在原发性轻链型淀粉样变（pAL）中的诊断和预后价值。 方法 回顾性分析2009年1月至2015年6月确诊且有完整sFLC数据的126例pAL患者的临床资料，探讨sFLC的诊断价值，并采用Cox回归法分析sFLC差值（dFLC）的预后价值。 结果 126例患者中男女比例为1.57∶1，中位年龄为57 (37~81）岁，λ轻链型者80例（63.5%），肾脏受累者87例（69.0%），心脏受累者79例（62.7%）。126例患者的中位dFLC为99 (1~4 263）mg/L。血清蛋白电泳、血清免疫固定电泳、尿免疫固定电泳和sFLC比值异常法检测单克隆免疫球蛋白（M蛋白）的阳性检出率分别为34.9%（44/126）、63.5%（80/126）、77.0%（97/126）和81.0%（102/126）。联合上述四种方法可将M蛋白的检出率提高至98.4%（124/126）。中位随诊16个月后，37例患者死亡，所有患者的中位生存时间尚未达到。多因素分析发现dFLC ≥130 mg/L是影响pAL患者预后的独立危险因素（HR=3.272, 95% CI 1.384~7.739，P=0.007）。 结论 sFLC检测可显著提高pAL患者M蛋白的检出率；高水平dFLC是影响患者预后的独立危险因素。

目的 探讨伴超高水平血清游离轻链（FLC）的轻链型（AL型）淀粉样变患者的临床特征及预后。 方法 回顾性分析2009年1月至2020年1月北京协和医院确诊的595例AL型淀粉样变患者的临床资料，按FLC水平将其分为两组：超高FLC组［FLC差值（dFLC）>500 mg/L，124例］与非超高FLC组（dFLC≤500 mg/L，471例），比较两组患者的临床特征和预后。 结果 超高FLC组患者与非超高FLC组相比，心脏受累比例更高（82.3％对70.1％，P＝0.007），2004梅奥分期Ⅲ期比例更高（41.8％对33.8％，P＝0.029），肾脏受累比例更低（59.7％对71.8％，P＝0.009）。超高FLC组患者与非超高FLC组相比，血液学缓解率降低（72.4％对82.3％，P＝0.048），心脏缓解率降低（37.3％对54.7％，P＝0.016），中位总生存期缩短（13.0个月对未达到，P<0.001），3个月内早期死亡率升高（28.2％对11.3％，P<0.001）。dFLC>500 mg/L是影响AL型淀粉样变患者预后的独立危险因素（HR＝2.279，95％ CI 1.685～3.083，P<0.001）。 结论 初诊时FLC超高AL型淀粉样变患者的心脏受累更多见，临床分期更晚，预后极差。

目的 回顾性分析晚期轻链（AL）型淀粉样变患者接受达雷妥尤单抗治疗的疗效和安全性。 方法 纳入20例于2017年1月至2021年3月在北京协和医院接受达雷妥尤单抗治疗的初治或复发难治晚期AL型淀粉样变患者。收集患者治疗前基线临床资料及治疗随访资料，分析患者的血液学、器官缓解情况，预后及不良反应。 结果 20例患者的中位年龄为62（45～73）岁，男女比例2.3∶1，9例为初治，11例为复发难治，梅奥2004分期为Ⅱ/Ⅲ期。4例患者于第1个疗程死亡，其余16例患者中位接受3（1～10）个疗程化疗。治疗后1个月、3个月及6个月血液学总缓解率均为80％，≥非常好的部分缓解率分别为45％、60％及60％，中位血液学起效时间为13（6～28）d，3个月、6个月及12个月心脏缓解率分别为20％、30％及40％，中位起效时间为91（30～216）d，1年总生存率为48.4％。至末次随访，9例（45％）患者死亡，1个月内死亡率为25％，Ⅲb期患者1个月内死亡率为40％。3级以上血液学不良反应以淋巴细胞减少最为常见，非血液学不良反应主要为输注反应及感染。 结论 达雷妥尤单抗治疗初治及复发难治晚期AL型淀粉样变可快速诱导高水平的血液学缓解，但Ⅲb期患者仍有较高的早期死亡率。

目的 探讨梅奥分期系统在中国原发性轻链型淀粉样变患者中的临床应用价值。 方法 回顾性分析2009年1月至2015年6月期间在北京协和医院确诊的具有梅奥分期数据的162例原发性轻链型淀粉样变患者的临床资料。 结果 具有完整梅奥2004分期数据的162例患者中，男101例（62.3%），女61例（37.7%），中位年龄57（20~81）岁；Ⅰ、Ⅱ、Ⅲ期患者分别为44例（27.2%）、69例（42.6%）和49例（30.2%），其中位总生存（OS）时间分别为未达到、23个月和12个月，预计2年OS率分别为87.3%、47.4%和29.2%（P<0.001）。具有完整梅奥2012分期数据的128例患者中，1~4期患者分别为48例（37.5%）、32例（25.0%）、32例（25.0%）和16例（12.5%），其中位OS时间分别为未达到、未达到、13个月和3个月，预计2年OS率分别为94.5%、78.6%、25.9%和24.5%（P<0.001）。 结论 梅奥分期系统对于中国原发性轻链型淀粉样变患者具有重要的预后价值。

目的 探讨极高危原发性轻链型淀粉样变（pAL）患者的临床特征及其预后。 方法 回顾性分析2009年1月至2016年2月在北京协和医院确诊的205例pAL患者的临床资料，将梅奥2004分期Ⅲb期或梅奥2012分期4期的患者定义为极高危患者。 结果 34例（16.6%）为极高危pAL患者，中位年龄57（20~84）岁，男性22例（64.7%）。所有患者均有心脏受累，15例（44.1%）患者的受累脏器≥ 3个。27例（81.8%）患者的心功能分级为3~4级，中位血清肌钙蛋白I为0.25（0.08~1.23）µg/L，中位血清N末端B型利钠肽前体为11 733（1 892~103 277）ng/L，中位血清游离轻链差值为403.0（18.1~1 911.6）mg/L，8例（24.2%）患者的骨髓浆细胞比例≥0.100。16例（47.1%）患者采用硼替佐米为主的化疗方案，总体血液学缓解率为58.3%。中位随诊27（1~40）个月，14例（41.2%）患者在诊断后3个月内死亡，中位生存时间仅为4个月。3、6、12和24个月的预期生存率分别为51.3%、44.0%、35.2%和29.6%。一线化疗后获得血液学缓解、未获得血液学缓解以及姑息治疗的患者1年预计存活率分别为90.9%、11.1%及0（P<0.001）。 结论 极高危pAL患者的预后极差，早期病死率高，获得血液学缓解的pAL患者有着明显更好的预后。

目的 分析合并轻链型淀粉样变性（AL）的初诊多发性骨髓瘤（MM）患者的临床特征、疗效及预后。 方法 回顾性分析苏州大学附属第一医院自2017年1月1日至2018年10月31日收治的160例初诊MM患者的临床资料。根据患者骨髓、皮肤和其他部位组织病理活检结果是否合并淀粉样变性分为两组，即合并淀粉样变性的MM（MM+AL）组和MM组，比较两组患者的临床特征及疗效。 结果 160例初诊MM患者中，MM+AL组42例，MM组118例。在临床特征方面，MM+AL组的受累轻链与非受累轻链差值（dFLC）明显高于MM组（P＝0.039）。诱导治疗后MM+AL组较MM组有更高的总缓解率（85.7％对79.7％，P<0.05）和非常好的部分缓解率（76.2％对55.1％，P<0.05）。中位随访26（0.25～41）个月，MM+AL组与MM组患者总生存（OS）和无进展生存的差异无统计学意义（P值均>0.05），自体造血干细胞移植组患者的OS优于未移植组患者（P值均<0.05）。MM+AL组心脏受累患者的预后较MM组和MM+AL组非心脏受累患者差（P<0.001），中位OS时间仅为13个月。 结论 MM+AL患者和MM患者的鉴别诊断需行组织病理活检，尤其是dFLC明显增高患者。MM+AL组患者4个疗程诱导化疗后总体缓解率较MM组更高。MM+AL组累及心脏患者预后较差。

目的 分析11C标记的匹兹堡化合物B（11C-PiB）PET/MRI在原发性系统性轻链型淀粉样变（pAL）中评估器官受累的价值。 方法 回顾性分析2019年1月至2021年10月在华中科技大学同济医学院附属协和医院就诊的20例pAL患者及3名健康志愿者的临床资料，比较临床标准评估器官受累和PET/MRI评估的相关性，分析心脏相关生物学指标、疾病分期与心脏最大标准摄取值（SUVmax）之间的关系及24 h尿蛋白定量与肾脏SUVmax之间的关系。 结果 ①纳入20例患者，初诊患者18例，非初诊患者2例。观察到11C-PiB摄取阳性的脏器分别为：心脏15例（75％），肺部8例（40％），骨髓10例（50％），肌肉10例（50％），舌肌7例（35％），甲状腺6例（30％），唾液腺4例（20％），脾脏2例（10％），胃壁1例（5％）。②11C-PiB在心脏及骨髓摄取的阳性率与临床评估标准具有很好的相关性。在肺组织、脾脏、腺体、肌肉和舌肌中，11C-PiB PET/MRI评估的阳性率明显高于临床标准。但对于神经系统受累和脂肪组织的评估11C-PiB PET/MRI具有局限性。③分析18例初诊患者心脏相关生物学指标与心脏SUVmax之间的关系。左心室射血分数（LVEF）<50％且室间隔厚度（ISV）≥1.2 cm的患者相较LVEF≥50％且ISV<1.2 cm的患者其心脏SUVmax更高（P<0.05）。心脏SUVmax值在Mayo2004分期、Mayo2012分期各期之间差异有统计学意义，分期越晚，SUVmax值越高（P<0.05）。心脏SUVmax与心肌肌钙蛋白酶Ⅰ、N 末端前体脑钠肽水平呈明显正相关（P<0.01），肾脏SUVmax与24 h尿蛋白定量无明显相关性（P>0.05）。 结论 全身11C-PiB PET/MRI作为一种淀粉样蛋白的可视化系统，若用于器官水平的定性评估，具有提高早期无创性诊断pAL水平的潜力；用于器官水平（尤其是心脏）的定量评估，有望更精准评估器官功能和预测疾病预后。

Abstract Aims Light-chain cardiac amyloidosis (AL-CA) is a progressive heart disease with high mortality rate and variable prognosis. The presently used Mayo staging method can only stratify patients into four stages, highlighting the necessity for a more individualized prognosis prediction method. We aim to develop a novel deep learning (DL) model for the whole-heart analysis of cardiovascular magnetic resonance-derived late gadolinium enhancement (LGE) images to predict individualized prognosis in AL-CA. Methods and results This study included 394 patients with AL-CA who underwent standardized chemotherapy and had at least 1 year of follow-up. The approach involved automated segmentation of the heart in LGE images and feature extraction using a Transformer-based DL model. To enhance feature differentiation and mitigate overfitting, a contrastive pretraining strategy was employed to accentuate distinct features between patients with different prognoses while clustering similar cases. Finally, an ensemble learning strategy was used to integrate predictions from 15 models at 15 survival time points into a comprehensive prognostic model. In the testing set of 79 patients, the DL model achieved a concordance index (C-index) of 0.91 and an area under the curve (AUC) of 0.95 in predicting 2.6-year survival (HR: 2.67), outperforming the Mayo model (C-index = 0.65; AUC = 0.71). The DL model effectively distinguished patients with the same Mayo stage but different prognoses. Visualization techniques revealed that the model captures complex, high-dimensional prognostic features across multiple cardiac regions, extending beyond the amyloid-affected areas. Conclusion This fully automated DL model can predict individualized prognosis of AL-CA through LGE images, which complements the presently used Mayo staging method.

Light‐chain cardiac amyloidosis (AL‐CA) causes structural and functional cardiac impairment. Myocardial work (MW), integrating left ventricular strain with afterload, may improve risk stratification. This study assesses the prognostic value of MW in AL‐CA patients and its potential to enhance traditional staging models. We prospectively enrolled biopsy‐confirmed AL‐CA patients between 2022 and 2024. MW indices, including global work index (GWI) and global constructive work (GCW), were derived using EchoPAC 206. The primary outcome was all‐cause mortality. Among 96 AL‐CA patients (mean age: 62.8 ± 10.2 years; 70% male), 28 died during a median follow‐up of 190 days. Multivariate Cox analysis identified GWI and GCW as independent predictors of mortality after adjusting for creatinine, heart rate, New York Heart Association class, Mayo 2012 class and pleural effusion. Kaplan–Meier analysis showed worse survival for GWI ≤840 mmHg% or GCW ≤1031 mmHg%. The likelihood ratio χ2 test demonstrated that GWI and GCW significantly improved the predictive power of the Mayo 2012 and Euro 2015 models (p < 0.001). MW indices, particularly GWI and GCW, are independent predictors of short‐term mortality in AL‐CA patients, thereby improving existing risk models and providing valuable prognostic insights.

BACKGROUND The diagnosis of cardiac amyloidosis can be established non-invasively by scintigraphy using bone-avid tracers, but visual assessment is subjective and can lead to misdiagnosis. We aimed to develop and validate an artificial intelligence (AI) system for standardised and reliable screening of cardiac amyloidosis-suggestive uptake and assess its prognostic value, using a multinational database of 99mTc-scintigraphy data across multiple tracers and scanners. METHODS In this retrospective, international, multicentre, cross-tracer development and validation study, 16 241 patients with 19 401 scans were included from nine centres: one hospital in Austria (consecutive recruitment Jan 4, 2010, to Aug 19, 2020), five hospital sites in London, UK (consecutive recruitment Oct 1, 2014, to Sept 29, 2022), two centres in China (selected scans from Jan 1, 2021, to Oct 31, 2022), and one centre in Italy (selected scans from Jan 1, 2011, to May 23, 2023). The dataset included all patients referred to whole-body 99mTc-scintigraphy with an anterior view and all 99mTc-labelled tracers currently used to identify cardiac amyloidosis-suggestive uptake. Exclusion criteria were image acquisition at less than 2 h (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, 99mTc-hydroxymethylene diphosphonate, and 99mTc-methylene diphosphonate) or less than 1 h (99mTc-pyrophosphate) after tracer injection and if patients' imaging and clinical data could not be linked. Ground truth annotation was derived from centralised core-lab consensus reading of at least three independent experts (CN, TT-W, and JN). An AI system for detection of cardiac amyloidosis-associated high-grade cardiac tracer uptake was developed using data from one centre (Austria) and independently validated in the remaining centres. A multicase, multireader study and a medical algorithmic audit were conducted to assess clinician performance compared with AI and to evaluate and correct failure modes. The system's prognostic value in predicting mortality was tested in the consecutively recruited cohorts using cox proportional hazards models for each cohort individually and for the combined cohorts. FINDINGS The prevalence of cases positive for cardiac amyloidosis-suggestive uptake was 142 (2%) of 9176 patients in the Austrian, 125 (2%) of 6763 patients in the UK, 63 (62%) of 102 patients in the Chinese, and 103 (52%) of 200 patients in the Italian cohorts. In the Austrian cohort, cross-validation performance showed an area under the curve (AUC) of 1·000 (95% CI 1·000-1·000). Independent validation yielded AUCs of 0·997 (0·993-0·999) for the UK, 0·925 (0·871-0·971) for the Chinese, and 1·000 (0·999-1·000) for the Italian cohorts. In the multicase multireader study, five physicians disagreed in 22 (11%) of 200 cases (Fleiss' kappa 0·89), with a mean AUC of 0·946 (95% CI 0·924-0·967), which was inferior to AI (AUC 0·997 [0·991-1·000], p=0·0040). The medical algorithmic audit demonstrated the system's robustness across demographic factors, tracers, scanners, and centres. The AI's predictions were independently prognostic for overall mortality (adjusted hazard ratio 1·44 [95% CI 1·19-1·74], p<0·0001). INTERPRETATION AI-based screening of cardiac amyloidosis-suggestive uptake in patients undergoing scintigraphy was reliable, eliminated inter-rater variability, and portended prognostic value, with potential implications for identification, referral, and management pathways. FUNDING Pfizer.

Background Transthyretin cardiac amyloidosis (ATTR‐CA) is a progressive and ultimately fatal cardiomyopathy. Biomarkers reflecting multiorgan dysfunction are of increasing importance in patients with heart failure; however, their significance in ATTR‐CA remains largely unknown. The aims of this study were to characterize the multifaceted nature of ATTR‐CA using blood biomarkers and assess the association between blood biomarkers and prognosis. Methods and Results This is a retrospective cohort study of 2566 consecutive patients diagnosed with ATTR‐CA between 2007 and 2023. Anemia (39%), high urea (52%), hyperbilirubinemia (18%), increased alkaline phosphatase (16%), increased CRP (C‐reactive protein; 27%), and increased troponin (98.2%) were common findings in the overall population, whereas hyponatremia (6%) and hypoalbuminemia (2%) were less common. These abnormalities were most common in patients with p.(V142I) hereditary ATTR‐CA, and became more prevalent as the severity of cardiac disease increased. Multivariable Cox regression analysis demonstrated that anemia (hazard ratio [HR], 1.19 [95% CI, 1.04–1.37]; P=0.01), high urea (HR, 1.23 [95% CI, 1.04–1.45]; P=0.01), hyperbilirubinemia (HR, 1.32 [95% CI, 1.13–1.57; P=0.001), increased alkaline phosphatase (HR, 1.20 [95% CI, 1.01–1.42; P=0.04), hyponatremia (HR, 1.65 [95% CI, 1.28–2.11]; P<0.001), and troponin‐T >56 ng/L (HR, 1.72 [95% CI, 1.46–2.03]; P<0.001) were all independently associated with mortality in the overall population. The association between biomarkers and mortality varied across the spectrum of genotypes and left ventricular ejection fraction, with anemia remining independently associated with mortality in p.(V142I) hereditary ATTR‐CA (HR, 1.58 [95% CI, 1.17–2.12]; P=0.003) and in a subgroup of the overall population with a left ventricular ejection fraction ≤40% (HR, 1.39 [95% CI, 1.08–1.81]; P=0.01). Conclusions Cardiac and noncardiac biomarker abnormalities were common and reflect the complex and multifaceted nature of ATTR‐CA, with a wide range of biomarkers remaining independently associated with mortality. Clinical trials are needed to investigate whether biomarker abnormalities represent modifiable risk factors that if specifically targeted could improve outcomes.

Background The introduction of a noninvasive diagnostic algorithm in 2016 led to increased awareness and recognition of cardiac amyloidosis (CA). Objectives The purpose of this study was to analyze the impact of the introduction of the noninvasive diagnostic algorithm on diagnosis and prognosis in a multicenter Italian CA cohort. Methods This was a retrospective analysis of 887 CA patients from 5 Italian Cardiomyopathies Referral Centers: 311 light-chain CA, 87 variant transthyretin (TTR)-related CA, 489 wild-type TTR-related CA. Clinical characteristics and outcomes (all-cause mortality and heart failure [HF] hospitalizations) were compared overall and for each CA subtype between patients diagnosed before versus after 2016. Outcomes were further compared by propensity score weighted Kaplan-Meier analysis and Cox regression analysis. Results CA diagnoses increased after 2016, in particular for wild-type TTR-related CA. Patients diagnosed after versus before 2016 were older, had less frequently a history of HF prior to diagnosis, and NYHA functional class III-IV at diagnosis. Over a median follow-up of 18 months, 172 (86%) patients diagnosed before 2016 died or had an HF hospitalization, versus 300 (44%) diagnosed after 2016. Propensity score weighted Kaplan-Meier analysis showed worse outcomes (P < 0.001) for patients diagnosed before 2016. At Cox regression analysis, CA diagnosis after 2016 was an independent protective factor for the composite outcome (HR: 0.69; P = 0.001), with interaction by CA subtype (significant in TTR-related CA and null in light-chain). Conclusions CA patients diagnosed after 2016 showed a less severe phenotype and a better prognosis. The impact of the noninvasive diagnostic algorithm on outcomes was particularly relevant in TTR-related CA.

Previous studies suggest worse outcomes in patients with variant transthyretin cardiac amyloidosis due to V122I (ATTRv-CA) compared to patients with wild-type disease (ATTRwt-CA). Given V122I is almost exclusively found in Black patients, it is unclear if this is attributable to the biology of genotype or racial differences. Patients with transthyretin cardiac amyloidosis (ATTR-CA) diagnosed between January 2001 and August 2021 were characterized into 3 categories: (1) White with ATTRwt-CA (White- WT); (2) Black with V122I ATTRv-CA (Black-V122I), and (3) Black with ATTRwt-CA (Black-WT). Event-free survival (composite of death, left ventricular assist device (LVAD), or cardiac transplant) was evaluated using univariable and multivariable analyses over a median follow-up of 1.6 (0.7-2.90) years. Of 694 ATTR-CA patients, 502 (72%) were White-WT, 139 (20%) Black-V122I, and 53 (8%) Black- WT. Notably, 28% of Black patients with ATTR-CA had wild-type disease and not the V122I variant. Using multivariable modeling to adjust for several prognostic features, Black-V122I had higher risk of the composite adverse outcome compared with a grouped cohort of patients with WT disease (White-WT and Black-WT) [hazard ratio (HR) 1.82, CI 1.30-2.56, p<0.001). Furthermore, the Black cohort as a whole (Black- V122I and Black-WT) demonstrated greater risk of adverse outcomes compared to White-WT (HR 1.63, CI 1.19-2.24, p=0.002). Black-V122I had greater risk of the primary endpoint compared to White-WT (HR 1.80, CI 1.27-2.56, p=0.001). Black patients with ATTR-CA have worse event-free survival than White-WT despite risk adjustment. However, it remains unclear whether this is driven by differences in race or genotype given the smaller number of Black-WT patients. Approximately one-quarter of Black patients had WT, of which a greater proportion were female compared to White-WT.

Background Cardiac amyloidosis (CA) is frequently found in older patients with aortic stenosis (AS). However, the prevalence of AS among patients with CA is unknown. The objective was to study the prevalence and prognostic impact of AS among patients with CA. Methods and Results We conducted a retrospective analysis of a prospective registry comprising 976 patients with native aortic valves who were confirmed with wild type transthyretin amyloid (ATTRwt), hereditary variant transthyretin amyloid (ATTRv), or immunoglobulin light‐chain (AL) CA. CA patients' echocardiograms were re‐analyzed focusing on the aortic valve. Multivariable Cox regression analysis was performed to assess the mortality risk associated with moderate or greater AS in ATTRwt CA. The crude prevalence of AS among patients with CA was 26% in ATTRwt, 8% in ATTRv, and 5% in AL. Compared with population‐based controls, all types of CA had higher age‐ and sex‐standardized rate ratios (SRRs) of having any degree of AS (AL: SRR, 2.62; 95% Confidence Interval (CI) [1.09–3.64]; ATTRv: SRR, 3.41; 95%CI [1.64–4.60]; ATTRwt: SRR, 10.8; 95%CI [5.25–14.53]). Compared with hospital controls, only ATTRwt had a higher SRR of having any degree of AS (AL: SRR, 0.97, 95%CI [0.56–1.14]; ATTRv: SRR, 1.27; 95%CI [0.85–1.44]; ATTRwt: SRR, 4.01; 95%CI [2.71–4.54]). Among patients with ATTRwt, moderate or greater AS was not associated with increased all‐cause death after multivariable adjustment (hazard ratio, 0.71; 95%CI [0.42–1.19]; P=0.19). Conclusions Among patients with CA, ATTRwt but not ATTRv or AL is associated with a higher prevalence of patients with AS compared with hospital controls without CA, even after adjusting for age and sex. In our population, having moderate or greater AS was not associated with a worse outcome in patients with ATTRwt.

Background Cardiac involvement in light chain amyloidosis (AL) is the main determinant of prognosis. Amyloid can be deposited in the extracellular space and cause an increase in extracellular volume fraction (ECV). At the same time, amyloid can also be deposited in the wall of small vessels and cause microvascular dysfunction. This study sought to investigate the extent of microvascular dysfunction and its incremental prognostic value in cardiac light-chain amyloidosis (AL-CA) by quantitative stress perfusion. Methods A total of 126 AL amyloidosis patients (61.13 ± 8.46 years, 81 male) confirmed by pathology were prospectively recruited. All subjects underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE), T1 mapping, and stress perfusion on a 3T scanner. ECV and myocardial perfusion reserve (MPR) were measured semi-automatically using a dedicated CMR software. Clinical, laboratory, and CMR parameters were analyzed for their prognostic value in the assessment of AL-CA patients. Mortality-associated markers were analyzed by univariate and multivariable Cox regression. Results The median follow-up time was 37 (33.6–40.4) months, and 62 patients died. The ECV of survivors was significantly reduced, but the stress myocardial blood flow and MPR were higher (P < 0.001). The MPR of the transmural LGE group was significantly lower than that of the no LGE and subendocardial LGE groups (P < 0.001). In multivariable analysis, ECV, MPR, and LGE were independently predictive. MPR of >1.5 and ECV of ≤53.6% were associated with improved overall survival, both of which provided predictive incremental value in patients with advanced disease. With equal Mayo staging and degree of ECV, MPR improves assessment of patient survival. Conclusion ECV and MPR showed additive incremental values and further discriminated prognosis of patients in advanced stages. CMR phenotypes with higher ECV and lower MPR had a worse prognosis.

Background - Laboratory liver anomalies are common in cardiac amyloidosis; however, their significance regarding liver stiffness is unknow. The aim of this study was to investigate the prevalence, clinical significance, and prognostic value of liver stiffness measurement (LSM) anomalies in transthyretin cardiac amyloidosis (ATTR-CA). Methods - Consecutive patients diagnosed with ATTR-CA who underwent liver stiffness assessment were included in the study. Demographic, clinical, laboratory, transthoracic echocardiography and liver stiffness data were retrospectively collected. LSM was obtained through either transient elastography or supersonic shear imaging. Patient cohort was divided in two groups according to a 10 kPa threshold. Follow up data were collected for the occurrence of hospitalization for heart failure and all-cause death. Results - Two hundred and eighty-four patients with ATTR-CA - 26 (9 %) hereditary variant ATTR, 258 (91 %) wild-type ATTR - were included. A LSM over 10 kPa was found in 4 (15 %) and 98 (38 %) patients with ATTRv and ATTRwt respectively (p = 0.02). Among patients with ATTRwt, high LSM was more frequent in advanced stages of ATTR-CA and was associated with increased risk of hospitalization for heart failure after multivariate analysis with a hazard ratio of 2.41 [1.05-5.55] (p = 0.04). Among patients with NYHA stage 1, 28 % presented high LSM associated with high NT-proBNP levels. Integration of high LSM with NT-proBNP and estimated glomerular filtration rate provided a better estimate of patient survival. Conclusion - LSM over 10 kPa is found in up to 36 % of patients with ATTR-CA and is associated with advanced stages of CM and increased risk for hospitalization for heart failure in ATTRwt patients.

Little is known regarding the prevalence and prognostic implications of non‐sustained ventricular tachycardia (NSVT) in patients with wild‐type transthyretin cardiac amyloidosis (ATTRwt‐CA). We aimed to investigate the prevalence of NSVT in patients with ATTRwr‐CA, and the association of NSVT with sustained ventricular arrhythmias (VA) and all‐cause mortality.

No abstract available

Background: Little information is available on the prognostic relevance of cardiac hemodynamic cutoffs in cardiac amyloidosis (CA) and its subtypes. Methods: Consecutive patients diagnose with light chain-CA or transthyretin CA undergoing right heart catheterization were analyzed. Prognostic relevance of classic hemodynamic cutoffs of cardiac index (CI <2.2 L/min per m2), pulmonary capillary wedge pressure (>18 mm Hg), right atrial pressure (>8 mm Hg), and mean pulmonary artery pressure (≥25 mm Hg or pulmonary hypertension) with the combined end point of cardiac transplant/left ventricular assist device and death and heart failure admissions separately was assessed. Results: A total of 469 CA patients underwent right heart catheterization (light chain CA=42% and transthyretin CA=52%) of whom 69%, 64%, and 79% had elevated right atrial pressure, pulmonary capillary wedge pressure, and pulmonary hypertension, respectively. The classic hemodynamic cutoffs for right atrial pressure (hazard ratio, 1.26 [0.98–1.62]) and mean pulmonary artery pressure (hazard ratio, 1.28 [0.96–1.71]) did not identify patients at higher risk for adverse outcome; however, cutoffs of 14 mm Hg for right atrial pressure (hazard ratio, 1.59 [1.26–2.00]) and 35 mm Hg for mean pulmonary artery pressure (hazard ratio, 1.30 [1.01–1.66]) performed better to detect worse outcome (P<0.05 for both). Reduced CI occurred in 55% of patients and was the strongest variable associated with the risk for cardiac transplant/left ventricular assist device and death, heart failure admissions, and reduced functional capacity. Reduced CI independently predicted risk on top of the Mayo-score in light chain CA and National Amyloid Center score in transthyretin CA (P<0.05 for both). Patients with light chain CA had higher pulmonary capillary wedge pressure and lower stroke volume index but maintained CI through a higher heart rate. Conclusions: Hemodynamic variables are grossly abnormal in CA, but elevated filling pressures are prognostic at significantly higher threshold values than classic cutoff values. CI is the hemodynamic variable most strongly associated with outcome and functionality in CA.

No abstract available

Cardiac involvement from amyloidosis is of growing interest in the overall literature. Despite cardiac amyloidosis (CA) has been considered for a long time a rare disease, the diagnostic awareness is increasing mainly thanks to the improvement of diagnostic softwares and of imaging techniques such as cardiac magnetic resonance (CMR). Some authors have observed an increase of prevalence rate of CA; moreover it’s often underestimated because clinical manifestations are aspecific. The interstitial infiltration of the left ventricle has been extensively studied, while the involvement of the right ventricle (RV) has been less investigated. Involvement of the RV, even in the absence of pulmonary hypertension or clearly left ventricle infiltration, plays an important role as prognostic factor and is useful to achieve an early diagnosis. Therefore, the use of fast and low-cost diagnostic methods such as ultrasound strain of the right ventricle could be used to recognize cardiac amyloidosis early. Herein the importance of evaluating the right ventricular involvement, which can predict the most severe course of the disease also without overt clinical manifestations. The role of imaging, in particular of echocardiography, CMR, and scintigraphy is here reported.

BACKGROUND Cardiac involvement in amyloid light chain (AL) amyloidosis significantly influences prognosis, necessitating timely diagnosis and meticulous risk stratification. OBJECTIVES This prospective study aimed to delineate the molecular phenotypes of AL cardiac amyloidosis (AL-CA) by characterizing fibro-amyloid deposition using 18F-florbetapir and gallium-68-labeled fibroblast activation protein inhibitor-04 (68Ga-FAPI-04) positron emission tomography (PET)/computed tomography (CT) imaging. The authors also proposed a novel molecular stratification methodology for prognosis. METHODS Patients with confirmed AL-CA underwent echocardiography and 18F-florbetapir and 68Ga-FAPI-04 PET/CT imaging. Cardiac amyloid burden was quantified as 18F-florbetapir cardiac amyloid volume and total cardiac amyloid. Meanwhile, cardiac fibroblast activation protein (FAP) was quantified as 68Ga-FAPI-04 cardiac FAP volume (CFV) and total cardiac FAP (TCF). PET/CT metrics were calculated in correlation to clinical and echocardiographic markers and their association with overall survival (OS) evaluated. RESULTS Among the 38 patients enrolled (median age: 58 years; 76.3% male), all patients exhibited amyloid deposition, and 86.8% (33 of 38) patients exhibited cardiac fibroblast activation. Cardiac amyloid burden was correlated with Mayo stage and several echocardiography metrics (P < 0.05). In addition, there was a correlation between CFV and N-terminal pro-B-type natriuretic peptide level (P < 0.05). Thirteen deaths occurred over a median follow-up of 24.8 months. Higher CFV and TCF were associated with shortened OS, particularly in Mayo stage III. In multivariable analysis, higher TCF was a primary determinant for shortened OS. CONCLUSIONS The study underscores that higher TCF on 68Ga-FAPI-04 PET/CT imaging might be a correlated factor of worse clinical outcome in newly diagnosed AL-CA, and this metric seems to be a molecular imaging tool complementary to 18F-florbetapir imaging. The combination might offer a holistic understanding of molecular attributes, assisting in clinical decision-making.

Several echocardiographic parameters have been suggested to differentiate wild‐type transthyretin cardiac amyloidosis (ATTRwt) from other causes of hypertrophy. These studies have all been performed in small samples of mixed cardiac amyloidosis. The purpose of this study was to investigate the role of echocardiographic parameters in patients with ATTRwt and aortic stenosis (AS) versus patients with AS. The secondary aim was to investigate the role of myocardial work in the prognosis of patients with ATTRwt.

Background Cardiac amyloidosis was thought to be a rare disease, but the data shows that its prevalence rate is increasing, and the light chain (AL) cardiac amyloidosis are the most common and worst [1]. Because of the lack of symptoms specificity in the preliminary stages of AL cardiac amyloidosis, resulting in underdiagnosis or severe delays in diagnosis, patients are often delayed in the optimal timing of treatment. A considerable proportion of patients are diagnosed after the onset of symptoms of heart failure which progresses rapidly and results in poor prognosis and high mortality. Patients have a mortality rate of up to 50% within 4-6 months after diagnosis of congestive heart failure and the median survival of these patients were less than 12 months [2]. Therefore, early diagnosis and treatment are particularly important for them. Speckle tracking echocardiography has a good imaging analysis of cardiac amyloidosis, which remains the most often used imaging tool. This study aimed to explore the use of speckle tracking echocardiographic parameters to build models which improve the diagnostic rate of patients with suspected AL cardiac amyloidosis and assess the prognosis of patients with AL cardiac amyloidosis. Methods We studied twenty-four patients of pathologically confirmed amyloidosis from March 2017 to February 2023 at the First Affiliated Hospital of Soochow University. According to the criteria for organ involvement, patients were divided into two groups based on whether the heart was involved or not and SPSS 26.0 was used to analyze data. The differences of characteristics and various parameters of Speckle tracking echocardiography between two groups were compared and the indicators with statistical difference were selected for single factor analysis and multivariate analysis. Statistically significant factors were used to establish diagnosis and prognosis assessment models as below. Result In this study, the rate of cardiac involvement was 62.5%. Until June 30 th, 2023, median follow-up time of twenty-four patients was 31 months, and the 5-year survival rate was 74% in CA group and 85.7% in non-CA group. Characteristics The results showed that CA group has lower baseline blood pressure, and the levels of NT-pro BNP and dFLC were significantly higher in the CA group compared to the non-CA group. In speckle tracking echocardiography parameters, CA group has significantly increased IVSd, LVPWd, RWT, E/e and decreased EF, interventricular septum e', lateral wall e' and left ventricular global strain. Diagnosis The results showed that CA group is more likely to be involved in the heart when monoclonal proteins are formed in the peripheral blood （OR=0.031, 95%CI 0.003-0.365, P=0.002）. In univariate analysis, E/e>10.85, interventricular septum e‘<5.25 cm/s, lateral wall e‘<6.05 cm/s, |left ventricular global strain|<16.3% and left ventricular diastolic function ≥Class II have the effect on CA group with statistically significant. Incorporating them into variables to construct a multivariate logistic regression model showed that: the model was built successfully (Omnibus test: P<0.001) and the goodness of fit model is well (Hosmer-Leme show test: P=1). 88.9% of the study subjects who were CA patients were predicted by the model to be CA patients, while 92.9% of the study subjects who were not CA patients were predicted by the model to be not CA patients, but the 5 factors had no significant effect on cardiac amyloidosis (P > 0.05). Prognosis assessment The result of the study shows that IVPWd>13.5mm, RWT> 0.51, NT pro-BNP>6614pg/mL and dFLC>142.35mg/L are elevated risk factors for prognosis with statistically significant. (Figure1). They were included in the variables to construct a multi-factor Cox proportional hazards model and it turns out: the model was built successfully (Omnibus test: P<0.05), but these 4 factors had no significant effect on cardiac amyloidosis (P > 0.05). Conclusion Speckle tracking echocardiography is of great value in the diagnosis and prognosis of patients with cardiac amyloidosis. The combined analysis of echocardiography parameters and serological abnormalities can help in the diagnosis and prognostic assessment of the disease, it also helps to identify patients with poor prognosis early and increasing the possibility of future treatment strategies based on risk stratification.

Cardiac amyloidosis are caused most frequently by transthyretin (ATTR) and light chain (AL) immunoglobulin amyloidosis. Echocardiographic diagnosis of cardiac amyloidosis is challenging because of diverse forms of clinical presentation and imaging. Besides some dimensional and functional left ventricular (LV) echocardiographic parameters like LV posterior wall thickness >13.6 mm, LV septal wall thickness >16 mm, E/E0 ratio (or diastolic index) >14 and at least grade 2 diastolic dysfunction, there are a few speckle tracking echocardiographic (STE) parameters that could raise the suspicion and refine cardiac amyloidosis diagnosis: apex-to-base LV strain ratio >2.5; right ventricle apical sparing with right ventricle apical free wall strain >27%; right atrial reservoir strain by 3D STE strain >24%; left atrial reservoir strain <29%. Due to the multiple echo parameters identified in this complex disease, it was imagine multiparametric echocardiographic scores to facilitate the diagnosis of these patients. Echocardiographic diagnosis criteria of cardiac amyloidosis includes, besides LV thickness, in multiparametric echocardiographic score, two parameters of strain: LV global longitudinal strain (GLS) absolute value ≤ 13% and systolic longitudinal strain apex to base ratio >2.9. The last one has three points and is stronger than the first one, which has one point. A GLS value <12% by STE allows to differentiate cardiac amyloidosis from others hypertrophic cardiomyopathy. It is very important because cardiac amyloidosis may coexist with aortic stenosis and atrial fibrillation and might be differentiated by other causes of LV hypertrophy and heart failure with preserved LV ejection fraction. STE has brought a new index in the evaluation of cardiac amyloidosis namely relative apical sparing longitudinal index or the classic Bull's eye pattern of strain distribution or “cherry-shaped” apical strain pattern or “cherry-like” strain preservation pattern in the apex segment, comparing with other LV segments. Relative apical sparing of myocardial longitudinal strain seems to be due to the regional differences in total amyloid mass instead of the proportion of amyloid deposits. However, this parameter has a high degree of spatial resolution. A value more than 1.3 of apical longitudinal strain versus basal and mid-longitudinal strain ratio could predicts cardiac amyloidosis. After this first step, staging and prognosis of this complex disease is more challenging (Figure 1). Non-invasive imaging method like STE by bi or tri-dimensional transthoracic echocardiography plays an important role not only in diagnosis of cardiac amyloidosis but also in prognosis. 3D STE seems superior to 2D STE because combines advantages of both methods: volumetric and strain analysis could be performed on the same cardiac cycle, at the same time and on the same virtual LV model. According with the statement of the ESC Working Group on Myocardial and Pericardial Diseases a few multiparametric biomarkerbased prognostic scores and biomarker-based staging systems were developed in AL and ATTR cardiac amyloidosis. There are based on the following parameters: troponin T, natriuretic peptides (NT-proBNP or BNP), estimated glomerular filtration rate, difference between involved and uninvolved free AL, heart failure NYHA class, Mayo or NAC (UK National Amyloidosis Centre) score, daily dose of furosemide or equivalent. Even these scoring systems provide an initial prognostic stratification based on parameters obtained at presentation there is a scarce of published data about of cardiac amyloidosis progression. In addition, the prognostic stratification and impact of the scores are to be validated in clinical practice by clinical trials. From this point of view, the recently published article by Földeák et al. is very important. The authors studied the prognostic role of 3DSTE-derived LV-GLS in patients with cardiac amyloidosis. This group, who studied and published recently the function of right atrial in cardiac amyloidosis by 3DSTE, shown that LV-GLS and LV end-diastolic diameter were independent predictors of cardiovascular survival in this disease. The authors used 3D echocardiography to show the existence of regional LV dyssynchrony with a characteristic temporal pattern of dispersion of regional volume systolic change. Received: 17 April 2023 Accepted: 18 April 2023

Transthyretin amyloid cardiomyopathy (ATTR‐CM) is an increasingly diagnosed disease. Echocardiography is widely utilized, but studies to confirm the value of echocardiography for tracking changes over time are not available. We sought to describe (i) changes in multiple echocardiographic parameters; (ii) differences in rate of progression of three predominant genotypes; and (iii) the ability of changes in echocardiographic parameters to predict prognosis.

No abstract available

Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognized as a treatable cause of heart failure (HF). Advances in diagnosis and therapy have increased the number of patients diagnosed at early stages, but prognostic data on patients without HF symptoms are lacking. Moreover, it is unknown whether asymptomatic patients benefit from early initiation of transthyretin (TTR) stabilizers. Objectives The aim of this study was to describe the natural history and prognosis of ATTR-CM in patients without HF symptoms. Methods Clinical characteristics and outcomes of patients with ATTR-CM without HF symptoms were retrospectively collected at 6 international amyloidosis centers. Results A total of 118 patients (78.8% men, median age 66 years [IQR: 53.8-75 years], 68 [57.6%] with variant transthyretin amyloidosis, mean left ventricular ejection fraction 60.5% ± 9.9%, mean left ventricular wall thickness 15.4 ± 3.1 mm, and 53 [45%] treated with TTR stabilizers at baseline or during follow-up) were included. During a median follow-up period of 3.7 years (IQR: 1-6 years), 38 patients developed HF symptoms (23 New York Heart Association functional class II and 14 functional class III or IV), 32 died, and 2 required cardiac transplantation. Additionally, 20 patients received pacemakers, 13 developed AF, and 1 had a stroke. Overall survival was 96.5% (95% CI: 91%-99%), 90.4% (95% CI: 82%-95%), and 82% (95% CI: 71%-89%) at 1, 3, and 5 years, respectively. Treatment with TTR stabilizers was associated with improved survival (HR: 0.31; 95% CI: 0.12-0.82; P = 0.019) and remained significant after adjusting for sex, age, ATTR-CM type, and estimated glomerular filtration rate (HR: 0.18; 95% CI: 0.06-0.55; P = 0.002). Conclusions After a median follow-up period of 3.7 years, 1 in 3 patients with asymptomatic ATTR-CM developed HF symptoms, and nearly as many died or required cardiac transplantation. Treatment with TTR stabilizers was associated with improved prognosis.

BACKGROUND Light chain (AL) and transthyretin (ATTR) amyloid fibrils are deposited in the extracellular space of the myocardium, resulting in heart failure and premature mortality. Extracellular expansion can be quantified by computed tomography, offering a rapid, cheaper, and more practical alternative to cardiac magnetic resonance, especially among patients with cardiac devices or on renal dialysis. OBJECTIVES This study sought to investigate the association of extracellular volume fraction by computed tomography (ECVCT), myocardial remodeling, and mortality in patients with systemic amyloidosis. METHODS Patients with confirmed systemic amyloidosis and varying degrees of cardiac involvement underwent electrocardiography-gated cardiac computed tomography. Whole heart and septal ECVCT was analyzed. All patients also underwent clinical assessment, electrocardiography, echocardiography, serum amyloid protein component, and/or technetium-99m (99mTc) 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. ECVCT was compared across different extents of cardiac infiltration (ATTR Perugini grade/AL Mayo stage) and evaluated for its association with myocardial remodeling and all-cause mortality. RESULTS A total of 72 patients were studied (AL: n = 35, ATTR: n = 37; median age 67 [IQR: 59-76] years, 70.8% male). Mean septal ECVCT was 42.7% ± 13.1% and 55.8% ± 10.9% in AL and ATTR amyloidosis, respectively, and correlated with indexed left ventricular mass (r = 0.426; P < 0.001), left ventricular ejection fraction (r = 0.460; P < 0.001), N-terminal pro-B-type natriuretic peptide (r = 0.563; P < 0.001), and high-sensitivity troponin T (r = 0.546; P < 0.001). ECVCT increased with cardiac amyloid involvement in both AL and ATTR amyloid. Over a mean follow-up of 5.3 ± 2.4 years, 40 deaths occurred (AL: n = 14 [35.0%]; ATTR: n = 26 [65.0%]). Septal ECVCT was independently associated with all-cause mortality in ATTR (not AL) amyloid after adjustment for age and septal wall thickness (HR: 1.046; 95% CI:1.003-1.090; P = 0.037). CONCLUSIONS Cardiac amyloid burden quantified by ECVCT is associated with adverse cardiac remodeling as well as all-cause mortality among ATTR amyloid patients. ECVCT may address the need for better identification and risk stratification of amyloid patients, using a widely accessible imaging modality.

Background Cardiac involvement is a main determinant of mortality in light chain (AL) amyloidosis but data on survival of patients with cardiac AL amyloidosis proven by endomyocardial biopsy (EMB) are sparse. Methods This study analysed clinical, laboratory, electrocardiography and echocardiographic parameters for their prognostic value in the assessment of patients with AL amyloidosis and cardiac involvement. Patients with AL amyloidosis who had their first visit to the amyloidosis centre at the University Hospital Heidelberg between 2006 and 2017 (n=1628) were filtered for cardiac involvement proven by EMB. In the final cohort, mortality-associated markers were analysed by univariate and multivariable Cox regression. Cut-off values for each parameter were calculated using the survival time. Results One-hundred and seventy-four patients could be identified. Median overall survival time was 1.5 years and median follow-up time was 5.2 years. At the end of the investigation period, 115 patients had died. In multivariable analysis, New York Heart Association-functional class >II (HR 1.65; 95% CI 1.09 to 2.50; p=0.019), left ventricular global longitudinal strain (HR 1.12; 95% CI 1.03 to 1.22; p=0.007), left ventricular end-systolic volume (HR 1.02; 95% CI 1.01 to 1.03; p=0.001), systolic pulmonary artery pressure (HR 0.98; 95% CI 0.96 to 0.99; p=0.027), N-terminal pro-B-type natriuretic peptide (HR 1.57; 95% CI 1.17 to 2.11; p=0.003) and difference in free light chains (HR 1.30; 95% CI 1.05 to 1.62; p=0.017) were independently predictive. Conclusion Among all patients with AL amyloidosis those with cardiac involvement represent a high-risk population with limited therapy options. Therefore, accurate risk stratification is necessary to identify cardiac amyloidosis patients with favourable prognosis. Incorporation of modern imaging techniques into existing or newly developed scoring systems is a promising option that might enable the implementation of risk-adapted therapeutic strategies.

Cardiac amyloidosis (CA) is a severe condition characterized by amyloid fibril deposition in the myocardium, leading to restrictive cardiomyopathy and heart failure. Differentiating between amyloidosis subtypes is crucial due to distinct treatment strategies. The individual conventional diagnostic methods lack the accuracy needed for effective subtype identification. This study aimed to evaluate the efficacy of combining 11C-PiB PET/CT and 99mTc-DPD scintigraphy in detecting CA and distinguishing between its main subtypes, light chain (AL) and transthyretin (ATTR) amyloidosis while assessing the association of imaging findings with patient prognosis. We retrospectively evaluated the diagnostic efficacy of combining 11C-PiB PET/CT and 99mTc-DPD scintigraphy in a cohort of 50 patients with clinical suspicion of CA. Semi-quantitative imaging markers were extracted from the images. Diagnostic performance was calculated against biopsy results or genetic testing. Both machine learning models and a rationale-based model were developed to detect CA and classify subtypes. Survival prediction over five years was assessed using a random survival forest model. Prognostic value was assessed using Kaplan-Meier estimators and Cox proportional hazards models. The combined imaging approach significantly improved diagnostic accuracy, with 11C-PiB PET and 99mTc-DPD scintigraphy showing complementary strengths in detecting AL and ATTR, respectively. The machine learning model achieved an AUC of 0.94 (95% CI 0.93–0.95) for CA subtype differentiation, while the rationale-based model demonstrated strong diagnostic ability with AUCs of 0.95 (95% CI 0.88-1.00) for ATTR and 0.88 (95% CI 0.770–0.961) for AL. Survival prediction models identified key prognostic markers, with significant stratification of overall mortality based on predicted survival (p value = 0.006; adj HR 2.43 [95% CI 1.03–5.71]). The integration of 11C-PiB PET/CT and 99mTc-DPD scintigraphy, supported by both machine learning and rationale-based models, enhances the diagnostic accuracy and prognostic assessment of cardiac amyloidosis, with significant implications for clinical practice.

AIMS Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure. We sought to characterize the structural and functional echocardiographic phenotype across the spectrum of wild-type (wtATTR-CM) and hereditary (hATTR-CM) transthyretin cardiomyopathy and the echocardiographic features predicting prognosis. METHODS AND RESULTS We studied 1240 patients with ATTR-CM who underwent prospective protocolized evaluations comprising full echocardiographic assessment and survival between 2000 and 2019, comprising 766 with wtATTR-CM and 474 with hATTR-CM, of whom 314 had the V122I variant and 127 the T60A variant. At diagnosis, patients with V122I-hATTR-CM had the most severe degree of systolic and diastolic dysfunction across all echocardiographic parameters and patients with T60AhATTR-CM the least; patients with wtATTR-CM had intermediate features. Stroke volume index, right atrial area index, longitudinal strain, and E/e' were all independently associated with mortality (P < 0.05 for all). Severe aortic stenosis (AS) was also independently associated with prognosis, conferring a significantly shorter survival (median survival 22 vs. 53 months, P = 0.001). CONCLUSION The three distinct genotypes present with varying degrees of severity. Echocardiography indicates a complex pathophysiology in which both systolic and diastolic function are independently associated with mortality. The presence of severe AS was independently associated with significantly reduced patient survival.

There is no unified prognostic scoring system for light chain cardiac amyloidosis (AL-CA), particularly stage IIIb AL-CA. This study aimed to use invasive haemodynamic information to investigate markers that can more accurately evaluate the prognosis of patients with stage IIIb AL-CA. In this retrospective cohort study, we conducted invasive haemodynamic measurements concurrently with myocardial biopsies to diagnose AL-CA. We used Cox regression analysis and time-dependent receiver operating characteristic curve analysis to study the associations between these measurements and overall mortality. Echocardiographic parameters were also recorded and analysed via logistic regression to explore their relationships with haemodynamic changes. Although traditional haemodynamic parameters, such as the cardiac index (CI), pulmonary artery wedge pressure (PAWP), pulmonary artery pressure, and vascular resistance, did not correlate with mortality, the PAWP/CI ratio emerged as a vital prognostic marker. Patients with a PAWP/CI ratio above 11 mmHg/L/min/m2 had markedly poorer survival. Kaplan‒Meier analysis highlighted the prognostic significance of the ratio, revealing distinct survival differences. Furthermore, logistic regression confirmed that echocardiographically measured pulmonary artery systolic pressure independently correlated with increases in the PAWP/CI ratio. In stage IIIb AL-CA patients, the PAWP/CI ratio, which surpasses traditional haemodynamic indicators, significantly predicts all-cause mortality, emphasizing its prognostic value. Our findings suggest that echocardiography-derived PASP could alternatively reflect the PAWP/CI ratio.

Anti-cancer drugs used to treat multiple myeloma (MM) can cause several cardiovascular toxic effects. HFA/ICOS risk score stratification is used to assess the baseline cardiovascular risk of cancer patients and its effectiveness has been demonstrated in breast cancer patients and some hematological malignancies but not in MM. In addition, patients with MM can have AL cardiac amyloidosis that can worsen the prognosis. to assess the effectiveness of HFA-ICOS risk score in predicting cardiovascular events in MM patients and the influence of cardiac amyloidosis and AL score on prognosis. A prospective study was carried out enrolling 71 patients with MM (35 women and 36 men; mean age 68±10 years) treated with proteasome inhibitors with or without immunomodulators and daratumumab. Cardiological evaluation was performed before starting anti-cancer drugs and after a median period of 1 years. HFA/ICOS risk score and AL score were assessed in all patients at baseline. Cardiovascular events were assessed: cardiovascular death, heart failure hospitalization, arrhythmias, myocardial ischaemia, venous thromboembolism, new onset of arterial hypertension, cancer therapy-related cardiac dysfunction. Patients were divided into 2 groups: patients with HFA/ICOS risk core high and very high (A), patients with low and medium HFA/ICOS risk score (B). Group A included 26 patients, group B included 45 patients; 19 patients had AL cardiac amyloidosis and were included in group A. Cardiovascular adverse events were significantly higher in group A (65,38%) than group B (24,4%). In particular, cardiovascular death, hospitalization for heart failure and atrial fibrillation were significantly higher in group A, especially in patients with cardiac amyloidosis. Using logistic regression analysis, cardiovascular events were significantly associated with HFA/ICOS risk score high and very high, AL score ≥ 5, cardiac amyloidosis, heart failure, global longitudinal strain (GLS) and NT-pro BNP value at baseline, left ventricular mass at echocardiogram and left atrial volume indexed (p value < 0,05). At multiple regression analysis, only HFA/ICOS risk score, GLS and NT-pro BNP were independent predictors of cardiovascular events. A GLS value -10.5% and a NT-pro BNP value >164.50 mg/dl have been identified as the parameters capable of predicting events with the greatest sensitivity and specificity (AUC 1, p value < 0,0001). All patients with cardiac amyloidosis had CV events. Our study confirms the effectiveness of HFA/ICOS risk score in patients with MM and the need to identify the presence of cardiac amyloidosis in these patients using AL score. Also AL score is associated with CV events and it is able to identify cardiac amyloidosis. NT-proBNP and GLS (included respectively in HFA/ICOS score and AL score) are independent predictors of CV events in MM patients and it should be assessed before starting treatment.

No abstract available

Relative apical longitudinal sparing (RALS) on echocardiography has become an increasingly used tool to evaluate for cardiac amyloidosis (CA), but the predictive value of this finding remains unclear. This is a retrospective analysis at a single tertiary care center across 3 years. Patients were included if they had RALS, defined by strain ratio ≥2.0 on echocardiography, and sufficient laboratory, imaging, or histopathologic workup to indicate their likelihood of CA. Patients were stratified by their likelihood of CA, and contributions of other co-morbidities previously shown to be associated with RALS. Of the 220 patients who had adequate workup to determine their likelihood of having CA, 50 (22.7%) had confirmed CA, 35 (15.9%) had suspicious CA, 83 (37.7%) had unlikely CA, and 52 (23.7%) had ruled-out CA. The positive predictive value of RALS for CA was 38.6% for confirmed or suspicious CA. The remaining 61.4% of patients who were unlikely or ruled out for CA had other co-morbidities such as hypertension, chronic kidney disease, malignancy, or aortic stenosis, 17.0% of this group had none of these co-morbidities. In our tertiary care cohort of patients with RALS pattern on echocardiography, we found that fewer than half of patients with RALS were likely to have CA. Given the increasing use of strain technology, further studies are warranted to determine the optimal strategy for assessing CA in a patient with RALS.

Introduction: In prior studies of patients with left ventricular thickness, the 2D speckle tracking strain echocardiography (STE) finding of relative apical sparing of longitudinal strain (RALS) was associated with a high sensitivity and specificity for diagnosing cardiac amyloidosis (CA). Use of STE is increasing, but the positive predictive value (PPV) of RALS for identifying CA among other etiologies in a large, contemporary patient population is unknown. Hypothesis: While RALS will still carry high predictive value for diagnosing CA, a significant proportion of patients will have other identifiable etiologies. Methods: We retrospectively reviewed 97 patients with RALS (defined as strain ratio ≥ 2.0) on echocardiography between June 2017 and June 2020 who had workup for CA, with cardiac MRI, 99m Technetium-pyrophosphate scan, serum/urine protein electrophoresis, and/or biopsies. These patients were then categorized into 4 groups relative to suspicion for CA (confirmed, suspicious, unlikely, ruled out). Patients without CA (unlikely/ruled out) were screened for comorbidities, including potential etiologies of RALS. Results: Of the 97 patients included, 40 (41%) were women and 39 (40%) were black. 17 (18%) had confirmed and 8 (8%) had suspicious CA while 72 (74%) had unlikely or ruled out CA. Of the confirmed cases, 10 (10%) were diagnosed with TTR amyloidosis and 7 (7%) were diagnosed with AL amyloidosis. The PPV of RALS for CA was 26% (25/97). Among the 72 patients with RALS without CA, 17 (24%) had no comorbidity, 4 (6%) had chronic kidney disease (CKD), 17 (24%) had hypertension (HTN), 16 (22%) had CKD and HTN, 2 (3%) had a malignancy treated with chemotherapy, 1 (1%) had aortic stenosis (AS), and 15 (24%) had multiple comorbidities (Figure 1). Conclusions: In a patient population with non-selective use of STE, the PPV of RALS for CA was 26%. Given the increasing use of STE, recognition of other etiologies of RALS should be noted.

Abstract Aims Cardiac amyloidosis (CA) is common in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Cardiac amyloidosis has poor outcomes, and its assessment in all TAVR patients is costly and challenging. Electrocardiogram (ECG) artificial intelligence (AI) algorithms that screen for CA may be useful to identify at-risk patients. Methods and results In this retrospective analysis of our institutional National Cardiovascular Disease Registry (NCDR)-TAVR database, patients undergoing TAVR between January 2012 and December 2018 were included. Pre-TAVR CA probability was analysed by an ECG AI predictive model, with >50% risk defined as high probability for CA. Univariable and propensity score covariate adjustment analyses using Cox regression were performed to compare clinical outcomes between patients with high CA probability vs. those with low probability at 1-year follow-up after TAVR. Of 1426 patients who underwent TAVR (mean age 81.0 ± 8.5 years, 57.6% male), 349 (24.4%) had high CA probability on pre-procedure ECG. Only 17 (1.2%) had a clinical diagnosis of CA. After multivariable adjustment, high probability of CA by ECG AI algorithm was significantly associated with increased all-cause mortality [hazard ratio (HR) 1.40, 95% confidence interval (CI) 1.01–1.96, P = 0.046] and higher rates of major adverse cardiovascular events (transient ischaemic attack (TIA)/stroke, myocardial infarction, and heart failure hospitalizations] (HR 1.36, 95% CI 1.01–1.82, P = 0.041), driven primarily by heart failure hospitalizations (HR 1.58, 95% CI 1.13–2.20, P = 0.008) at 1-year follow-up. There were no significant differences in TIA/stroke or myocardial infarction. Conclusion Artificial intelligence applied to pre-TAVR ECGs identifies a subgroup at higher risk of clinical events. These targeted patients may benefit from further diagnostic evaluation for CA.

RATIONALE AND OBJECTIVES This study aimed to assess the incremental diagnostic value of non-contrast T1 mapping-derived radiomics in patients with amyloid light-chain cardiac amyloidosis (AL-CA). METHODS We retrospectively collected 86 patients with suspected AL-CA and 28 control patients who underwent cardiac MRI at 3.0 T in our institution, and the MRI data were divided into a training set and a test set. Radiomic features were extracted based on native T1 maps using a freely available software package. We applied LASSO logistic regression method to select radiomic features with high diagnostic value of AL-CA and develop a predictive model. The diagnostic performance of the radiomics model was evaluated using receiver operating characteristic curve analysis and compared to T1 values. RESULTS A total of 70 people were diagnosed with AL-CA, and cardiac involvement was observed in 202 myocardial slicers. The accuracy of T1 values for the diagnosis of myocardial involvement was 0.886, with a threshold value of 1375 ms. The radiomics score comprised a total of three features. The radiomics score demonstrated significantly higher sensitivity in detecting myocardial involvement compared to T1 values in both the training set (AUC 0.886 vs. 0.924, P = 0.025) and the test set (0.862 vs 0.915, P = 0.026). The combined model comprising T1 values and a radiomic feature named S(4,-4) Correlat showed higher diagnostic performance in comparison to T1 values alone both in the training and test sets, with AUC values of 0.929 and 0.909, respectively. CONCLUSION The radiomic features derived from native T1 mapping demonstrated incremental value for the diagnosis of AL-CA, which may be an alternative to T1-derived ECV to avoid the use of contrast in patients with suspected myocardial involvement in systemic amyloidosis.

BACKGROUND Early diagnosis of cardiac amyloidosis (CA) is crucial due to the promising effect of disease-modifying treatment. This calls for screening strategies to identify CA patients with so-called "red flags", such as carpal tunnel syndrome (CTS). OBJECTIVES This study aims to assess Troponin-T (TnT) and N-terminal pro-B-type natriuretic peptide (NT-ProBNP) as predictors for CA in patients with a history of surgery for bilateral carpal tunnel syndrome, a population suitable for systematic screening. METHODS Subjects with a history of surgery for bilateral CTS 5-15 years prior, identified using national registries were investigated for CA as per international recommendations. Sensitivity, specificity, positive and negative predictive values were assessed, and receiver operating curves were generated using logistic regression. RESULTS Among the 250 participants, 12 were diagnosed with CA, all with wild-type transthyretin amyloidosis. Elevated TnT levels (≥13 ng/L) were found in all CA patients and 25.6% (±2.8) of non-CA patients. The negative predictive value (NPV) of TnT <13 ng/L was 100%. For NT-ProBNP the NPV was 99.1% when age dependent cutoff levels were used. A combination of both biomarkers yielded an NPV of 99.1% and sensitivity of 99.7%. Early disease (Mayo or NAC stage 1) was found in 83% of identified patients with CA. CONCLUSION This study demonstrates the utility of TnT and NT-ProBNP as negative predictors to exclude CA in a screening population with a history of surgery for CTS.

Background: The predictive value of soluble suppression of tumorigenicity-2 (sST2) has been demonstrated in heart failure patients. However, studies on the association between baseline sST2 levels, dynamic changes in sST2, and prognosis in patients with light chain cardiac amyloidosis (AL-CA) are limited. Aim: The study sought to assess the predictive value of baseline circulating sST2 and added prognostic value of change in sST2 levels in patients with AL-CA. Methods: Patients diagnosed with AL-CA patients in Heart Failure Center, Fuwai Hospital between October 2015 to August 2023 were enrolled. The serum sST2 levels were measured at baseline and at 30 days. The change of sST2 (ΔsST2) was defined as the sST2 level at 30 days minus baseline sST2. The primary outcome was all-cause mortality. Kaplan–Meier analysis and Cox hazard models were performed to explore the predictive value of both sST2 at baseline and ΔsST2. Results: Overall, 132 patients were included. The median follow-up was 235 days. The mean age was 58.92 years (standard deviation [SD]: 10.74 years), and 62.1% of the participants were male. The median sST2 level was 30.42 ng/mL (IQR: 18.41–51.98 ng/mL), with the cutoff value set at 35 ng/mL. Higher sST2 levels at baseline (>35ng/ml) were associated with increased risk of all-cause mortality after adjusting for N-terminal pro–B-type natriuretic peptide (NT-proBNP), cardiac troponin I (cTNI), and difference between involved and uninvolved free light chain (dFLC) levels (adjusted hazard ratio [HR] 1.86, 95% confidence interval [CI]: 1.03-3.38; P<0.05). Among 40 patients with available ΔsST2, a total of 11 primary outcome events occurred. Patients who experienced these events exhibited higher levels of ΔsST2 (median: 193.55 ng/mL, IQR: 100.86-284.86 ng/mL) compared to those who did not (median: 8.04 ng/mL, IQR: -4.69-62.44 ng/mL). Moreover, higher ΔsST2 is also an independent indicator of worse prognosis, even after adjustment for baseline sST2, NT-proBNP, cTNI, and dFLC levels (adjusted HR 12.46, 95% CI: 1.26-123; P<0.05). Conclusions: Elevated baseline sST2 blood level (>35 ng/L) is a robust and independent indicator of prognosis in AL-CA patients. A dynamic increase in sST2 levels over the short term suggests a dismal prognosis.

The aim of this study is to assess the effectiveness of conventional and two additional functional markers derived from standard cardiac magnetic resonance (CMR) images in detecting the occurrence of late gadolinium enhancement (LGE) in patients with secondary cardiac amyloidosis (CA) related to multiple myeloma (MM). This study retrospectively included 32 patients with preserved ejection fraction (EF) who had MM-CA diagnosed consecutively. Conventional left ventricular (LV) function markers and two additional functional markers, namely myocardial contraction fraction (MCF) and LV long-axis strain (LAS), were obtained using commercial cardiac post-processing software. Logistic regression analyses and receiver operating characteristic (ROC) analysis were performed to evaluate the predictive performances. (1) There were no notable distinctions in clinical features between the LGE+ and LGE− groups, with the exception of a reduced systolic blood pressure in the former (105.60 ± 18.85 mmHg vs. 124.50 ± 20.95 mmHg, P = 0.022). (2) Patients with MM-CA presented with intractable heart failure with preserved ejection fraction (HFpEF). The LVEF in the LGE+ group exhibited a greater reduction (54.27%, IQR 51.59–58.39%) in comparison to the LGE− group (P < 0.05). And MM-CA patients with LGE+ had significantly higher LVMI (90.15 ± 23.69 g/m2), lower MCF (47.39%, IQR 34.28–54.90%), and the LV LAS were more severely damaged (− 9.94 ± 3.42%) than patients with LGE− (all P values < 0.05). (3) The study found that MCF exhibited a significant independent association with LGE, as indicated by an odds ratio of 0.89 (P < 0.05). The cut-off value for MCF was determined to be 64.25% with a 95% confidence interval ranging from 0.758 to 0.983. The sensitivity and specificity of this association were calculated to be 95% and 83%, respectively. MCF is a simple reproducible predict marker of LGE in MM-CA patients. It is a potentially CMR-based method that promise to reduce scan times and costs, and boost the accessibility of CMR.

Quantitative 99mTc-3,3-diphosphono-1,2 propanodicarboxylicacid (99mTc-DPD) Single Photon Emission Computed Tomography (SPECT) may be used for risk stratifying patients with transthyretin-related amyloidosis-cardiomyopathy (ATTR-CM). We aimed to analyse the predictive value of quantitative 99mTc-DPD SPECT/CT in suspected and confirmed ATTR-CM according to different disease stages. Consecutive patients with suspected ATTR-CM referred to a single tertiary center who underwent quantitative 99mTc-DPD SPECT/CT allowing standardized uptake values (SUVmax, SUVpeak) analysis were enrolled. Patients were divided into two groups according to left ventricular ejection fraction (LVEF) at baseline (i.e. LVEF≥50% and <50%). Correlations between clinical, laboratory, and echocardiographic parameters and major adverse cardiac events (i.e. all-cause death, sustained ventricular tachyarrhythmia, hospitalization for heart failure, implantation of a cardioverter defibrillator) to quantitative uptake values were investigated. A total of 144 patients with suspected ATTR-CM were included in the study (98 with LVEF≥50% and 46 with LVEF<50%), of whom 99 were diagnosed with ATTR-CM (68,75%; 69 with LVEF≥50% and 30 with LFEV<50%). Myocardial SUVmax≥7 was predictive of MACE at 21.9±13.0 months follow-up (HR 2.875, 95%CI 1.23 – 6.71, p=0.015) in suspected ATTR-CM and in patients with confirmed ATTR-CM (global X²= 6.892, p=0.02) and LVEF≥50%. There was no predictive value for patients with LVEF<50% in suspected or confirmed ATTR-CM. In patients with suspected or confirmed ATTR-CM and preserved LVEF, representing early disease stage, a myocardial SUV≥7 is a predictive marker for MACEs. Quantitative 99mTc-DPD SPECT should be considered for improved early stage risk stratification of patients with ATTR-CM.  

Background Both light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis are types of cardiac amyloidosis (CA) that require accurate prognostic stratification to plan therapeutic strategies and follow-ups. Cardiac biomarkers, e.g., N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (Hs-cTnT), remain the cornerstone of the prognostic assessment. An increased level of soluble suppression of tumorigenesis-2 (sST2) is predictive of adverse events [all-cause death and heart failure (HF) hospitalizations] in patients with HF. This study aimed to evaluate the prognostic value of circulating sST2 levels in AL-CA and ATTR-CA. Methods We carried out a multicenter study including 133 patients with AL-CA and 152 patients with ATTR-CA. During an elective outpatient visit for the diagnosis of CA, Mayo Clinic staging [NT-proBNP, Hs-cTnT, differential of free light chains (DFLCs)] and sST2 were assessed for all AL patients. Gillmore staging [including estimated glomerular filtration rate (eGFR), NT-proBNP] and Grogan staging (including NT-proBNP and Hs-cTnT) were assessed for TTR-CA patients. Results The median age was 73 years [interquartile range (IQR) 61–81], and 53% were men. The endpoint was the composite of all-cause death or first HF-related hospitalization. The median follow-up was 20 months (IQR 3–34) in AL amyloidosis and 33 months (6–45) in TTR amyloidosis. The primary outcome occurred in 70 (53%) and 99 (65%) of AL and TTR patients, respectively. sST2 levels were higher in patients with AL-CA than in patients with ATTR-CA: 39 ng/L (26–80) vs. 32 ng/L (21–46), p < 0.001. In AL-CA, sST2 levels predicted the outcome regardless of the Mayo Clinic score (HR: 2.16, 95% CI: 1.17–3.99, p < 0.001). In TTR-CA, sST2 was not predictive of the outcome in multivariate models, including Gillmore staging and Grogan staging (HR: 1.17, CI: 95% 0.77–1.89, p = 0.55). Conclusion sST2 level is a relevant predictor of death and HF hospitalization in AL cardiac amyloidosis and adds prognostic stratification on top of NT-proBNP, Hs cTnT, and DFLC.

Background: Amyloid light-chain (AL) amyloidosis is a multisystem disorder, with cardiac amyloid infiltration being a prevalent manifestation. This study aimed to explore the prognostic value of galectin-3 (Gal-3), a soluble marker associated with fibrosis, inflammation, heart failure, and kidney injury, in patients with cardiac AL amyloidosis. Methods: A total of 60 patients who were diagnosed with cardiac AL amyloidosis from January 2015 to May 2018 were enrolled. The prognostic value of Gal-3 was assessed. Receiver operating characteristic (ROC) curves were used to evaluate the predictive accuracy of Gal-3. A Gal-3 cut-off value was identified to predict survival rates. Results: The ROC curves demonstrated a moderate predictive accuracy of Gal-3 for 0.5- and 5-year survival, with area under the curve (AUC) values of 0.722 and 0.788, respectively. A Gal-3 cut-off value of 15.154 ng/mL was found to predict survival. Kaplan–Meier survival analysis revealed a significant difference in mean overall survival between patients with Gal-3 levels below and above the established cut-off (69.2 months versus 42.1 months, respectively; p = 0.036). Multivariate analysis confirmed that Gal-3 > 15.154 ng/mL remained an independent predictor of survival (HR 2.451, 95% CI 1.017–5.910, p = 0.046). Conclusions: This study suggests that Gal-3 holds independent prognostic value for survival in patients with cardiac AL amyloidosis. Gal-3 could potentially enhance the prognostic capabilities of the current soluble markers, thereby improving the management of cardiac AL amyloidosis. However, further validation in larger prospective studies is warranted.

Objectives Since diastolic abnormalities are typical findings of cardiac amyloidosis (CA), we hypothesized that speckle-tracking-imaging (STI) derived longitudinal early diastolic strain rate (LSRdias) could predict outcome in CA patients with preserved left ventricular ejection fraction (LVEF >50%). Background Diastolic abnormalities including altered early filling are typical findings and are related to outcome in CA patients. Reduced longitudinal systolic strain (LSsys) assessed by STI predicts increased mortality in CA patients. It remains unknown if LSRdias also related to outcome in these patients. Methods Conventional echocardiography and STI were performed in 41 CA patients with preserved LVEF (25 male; mean age 65±9 years). Global and segmental LSsys and LSRdias were obtained in six LV segments from apical 4-chamber views. Results Nineteen (46%) out of 41 CA patients died during a median of 16 months (quartiles 5–35 months) follow-up. Baseline mitral annular plane systolic excursion (MAPSE, 6±2 vs. 8±3 mm), global LSRdias and basal-septal LSRdias were significantly lower in non-survivors than in survivors (all p<0.05). NYHA class, number of non-cardiac organs involved, MAPSE, mid-septal LSsys, global LSRdias, basal-septal LSRdias and E/LSRdias were the univariable predictors of all-cause death. Multivariable analysis showed that number of non-cardiac organs involved (hazard ratio [HR]  = 1.96, 95% confidence interval [CI] 1.17–3.26, P = 0.010), global LSRdias (HR = 7.30, 95% CI 2.08–25.65, P = 0.002), and E/LSRdias (HR = 2.98, 95% CI 1.54–5.79, P = 0.001) remained independently predictive of increased mortality risk. The prognostic performance of global LSRdias was optimal at a cutoff value of 0.85 S−1 (sensitivity 68%, specificity 67%). Global LSRdias <0.85 S−1 predicted a 4-fold increased mortality in CA patients with preserved LVEF. Conclusions STI-derived early diastolic strain rate is a powerful independent predictor of survival in CA patients with preserved LVEF.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure (1,2). 99mTc- pyrophosphate cardiac scintigraphy (PYP) enables accurate, noninvasive diagnosis of ATTR-CM when coupled with appropriate clinical and laboratory evaluations to rule out light chain amyloidosis (3,4). High sensitivity cardiac troponin T (hs-cTnT) is routinely assessed for diagnostic purposes when ATTR-CM is suspected in clinical practice. To investigate the diagnostic performance of hs-cTnT in patients undergoing PYP for suspected ATTR-CM. Observational study of patients undergoing PYP at a United States (US) cardiac amyloidosis referral center from 2013 to September 2022 and with at least one hs-cTnT value available within 1 year. 3-hour planar imaging followed by single photon-emission computed tomography with computed tomography was performed. Final diagnoses of ATTR-CM were validated using all clinical information. The lowest reportable clinical value for hs-cTnT in the US is <6 ng/L (limit of quantitation). A total of 1572 patients underwent PYP and had a hs-cTnT value available within the study period. Of these, ATTR-CM was diagnosed in 475 patients (30%). Median (IQR) hs-cTnT was 48 (31-67) ng/L in patients with ATTR-CM and 26 (13-48) ng/L in those without. The area under the curve of hs-cTnT for the diagnosis of ATTR-CM was 0.69 (0.67-0.72). Among patients with a very low hs-cTnT value, i.e. <6 ng/L (n=100, 6.4% of the overall cohort), 7 (7%) patients had a final ATTR-CM diagnosis while 93 (93%) did not. Therefore, a threshold of <6 ng/L demonstrated a negative predictive value (NPV) of 93% (IQR 88, 98) and a sensitivity of 99% (97, 100) for ruling out ATTR-CM. The highest NPV was achieved with a threshold of 12 ng/L; 269 (17%) patients had hs-cTnT below this value and, of those, only 16 (6%) had a final diagnosis of ATTR-CM. This resulted in a NPV of 94% (91, 97) and a sensitivity of 97% (95, 98) for ruling out ATTR-CM. When considering progressively increasing hs-cTnT values as potential thresholds to aid in the prediction of ATTR-CM (Figure), we observed a progressive increase in specificity (above 90% for hs-cTnT values > 95 ng/L), but the positive predictive value (PPV) remained low (below 50%). Among patients undergoing PYP for suspected ATTR-CM at a US referral center, a very low hs-cTnT value was present in a minority of patients but demonstrated good performance in ruling out ATTR-CM. The highest NPV (94%) was achieved with a threshold of < 12 ng/L. Higher hs-cTnT values showed a good specificity, but PPV remained low. Therefore, while a very low hs-cTnT might be of help in identifying those at low risk of ATTR-CM, the ubiquitous presence of increased hs-cTnT in many of these patients suggests the need for a multiparametric diagnostic approach to make the diagnosis.hs-cTnT in patients undergoing PYP scan

Left ventricular (LV) long-axis shortening at the cardiac base is a determinant of left atrial (LA) reservoir function. Cardiac amyloidosis (CA) is characteristic of amyloid deposition predominantly in the LV basal wall. We investigated the relationship between LV basal strain and LA reservoir strain among patients with pathological LV hypertrophy and subsequently evaluated the diagnostic ability of LA reservoir strain to identify CA etiology and its predictive value for heart failure hospitalization. We retrospectively analyzed 341 patients with LV hypertrophy. Cardiac etiologies were diagnosed by tissue biopsy, cardiac magnetic resonance imaging or 99mTc-PYP scintigraphy. LV basal strain and LA reservoir strain were analyzed. Patients were diagnosed with CA (n = 75) and other etiologies (n = 266). LV basal strain was correlated with LA reservoir strain in the CA group (r = 0.58, p < 0.01) and the non-CA group (r = 0.44, p < 0.01). A binary logistic regression analysis showed that relative apical sparing of longitudinal strain, septal E/e’ and LA reservoir strain had the ability to discriminate between the CA and non-CA groups (p < 0.01 for all). The area under the curve for relative apical sparing of longitudinal strain had a stronger ability than LA reservoir strain to discriminate CA from non-CA etiologies (0.90 versus 0.81, respectively; p < 0.01). During the follow-up period (median 2.7 years), the incidence of heart failure hospitalization was higher in the CA group than the non-CA group (35% versus 14%, respectively; p < 0.01). According to univariate Cox regression analysis, three LA factors (LA reservoir strain, E/e’ and LA volume index) were associated with heart failure hospitalization in the non-CA group (p < 0.05 for all). LA reservoir strain was associated with LV basal strain among patients with pathological LV hypertrophy. Echocardiographic assessment of LA reservoir strain might add diagnostic value to identify CA etiology in these patients.

Light chain cardiac amyloidosis (AL‐CA) is an infiltrative cardiomyopathy characterized by the deposition of abnormally folded proteins in the myocardium and atrial walls. This study aims to evaluate right atrial (RA) stiffness—defined as the ratio of tricuspid E/e’ (reflecting right ventricular diastolic function) to RA reservoir strain (right atrial reservoir strain (RASr), reflecting RA mechanical properties)—using speckle‐tracking echocardiography, predicting the primary outcome in AL‐CA, and assessing its incremental predictive value.

Cardiac amyloidosis is a rare but increasingly recognized condition characterized by the deposition of amyloid fibrils in cardiac tissue. Two major forms, transthyretin (ATTR) and immunoglobulin light chain (AL) amyloidosis, differ in pathophysiology, clinical manifestations, and management strategies. This study focuses on the comprehensive characterization of patients with these forms of amyloidosis, highlighting clinical, laboratory, imaging, and functional findings to better understand the disease and its outcomes. The study aimed to: Characterize the clinical and imaging features of patients with ATTR and AL amyloidosis. Investigate the predictive value of advanced echocardiographic methods, such as global longitudinal strain (GLS), atrial strain, and mechanical dispersion, in relation to arrhythmias and functional complications. Differentiate between wild-type (ATTRwt) and variant (ATTRv) forms and evaluate the impact of specific treatments on clinical outcomes. This retrospective observational study reviewed clinical, laboratory, and imaging data from 58 patients diagnosed with cardiac amyloidosis at a single center between August 2019 and May 2024. Advanced echocardiographic techniques and other modalities, including cardiac magnetic resonance (CMR) and bone scintigraphy, were employed for detailed evaluation. Logistic regression analysis was used to identify associations between echocardiographic parameters and clinical outcomes. Out of 58 patients (36 ATTR and 22 AL), significant differences emerged between the groups in terms of disease severity, echocardiographic findings, and treatment outcomes. ATTR patients were predominantly male, with higher body surface area (BSA) and body mass index (BMI). Advanced echocardiographic parameters such as GLS and atrial strain demonstrated predictive value for atrial fibrillation (AF) and functional complications. Logistic regression revealed associations between AF and variables such as age, left atrial volume index (LAVi), and E/e′ ratio. Troponin levels and imaging markers like extracellular volume (ECV) were significantly elevated in AL patients. Specific therapies, including tafamidis for ATTR, showed efficacy in improving clinical outcomes. This study underscores the importance of advanced imaging techniques and biomarkers in differentiating ATTR and AL amyloidosis and predicting clinical outcomes. Echocardiographic parameters provide valuable insights into the pathophysiological differences and can guide treatment decisions. Further studies are warranted to explore longitudinal outcomes and optimize management strategies for this complex condition.Echo picture of Cardiac Amyloidosis  Echo and EKG/Arrhythmias in ATTR and AL

Background: Cardiac amyloidosis (CA) is an increasingly recognized disease. Several recent advanced imaging techniques and parameters have been introduced into the diagnosis of CA. However, the first step in using those techniques is clinical suspicion. Left ventricular hypertrophy (LVH) is the main entity in rising the suspicion of CA in routine echocardiography, although it is not a diagnosis for CA. The aim of this study is to investigate the prevalence of CA and its subtypes and predictive value of clinical and echocardiographic red flags of CA among consecutive adult patients with LVH identified during routine echocardiographic examination in 25 tertiary institutions in Türkiye. Methods: This was a prospective observational multicenter, national registration study. Patients with LVH (interventricular septum thickness ≥13 mm or >15 mm in those with hypertension) were screened for CA stepwise. The first step was a clinical questionnaire for the red flags of CA. Those having ≥2 red flags were further analyzed by detailed echocardiography, blood tests, Tc-pyrophosphate (PYP) bone scintigraphy, and histopathological examination if needed. Parameters associated with CA were evaluated via univariate and multivariate analyses. Wild-type transthyretin (wTTR) vs. mutant-type TTR (mTTR), CA discriminators were also evaluated in the same manner. Results: A total of 420 patients meeting these criteria were included in the study. With a standardized algorithmic approach, 27.1% (114) of patients received a CA diagnosis. Among these patients with CA, 50.8% (58) were diagnosed with immunoglobulin free chain (AL) CA, 38.6% (44) with wTTR CA, and 7% (8) with mTTR CA. Left ventricular apical sparing pattern and restrictive type LV filling on echocardiography, low QRS voltage on ECG, bilateral carpal tunnel syndrome, low blood pressure, right ventricular diameter, and an increased basal heart rate (HR) were independent predictors for CA diagnosis. When it comes to diagnosis of wTTR CA; advanced age (age >75), lower troponin values, absence of pericardial effusion and absence of proteinuria were the independent predictors. Conclusion: Cardiac amyloidosis is highly prevalent in a patient population with LVH and >2 red flags who underwent a standardized algorithmic approach, in which apical sparing, restrictive filling pattern, low QRS voltage, carpal tunnel syndrome, low blood pressure, and increased HR are the highly suggestive signs of CA. Among this pool of newly diagnosed CA patients in Türkiye, AL-CA constituted 50.8%, wTTR CA 38.6%, and mTTR CA 7%, emphasizing that approximately 1 in 2 patients diagnosed with CA may have TTR CA.

Objectives Conventional transthoracic echocardiographic measurements like global longitudinal strain (GLS) have shown promise in distinguishing cardiac amyloidosis (CA), but with limited specificity. We investigated the performance of common echo measurements, GLS, and their combinations in discriminating CA from an undifferentiated cohort with increased left ventricular wall thickness. Methods We conducted a retrospective single-centre case–control study of 876 echos from 232 patients with CA and 1325 echos from 279 patients who underwent pyrophosphate scintigraphy but had CA definitively ruled out. Common echo measurements were collected and additional GLS measurements were performed post hoc. We reported discrimination performance with the area under the receiver operating characteristic curve (AUC) and associated sensitivity, specificity and positive predictive value at the optimal threshold. Results We found that the ratio of end-diastolic interventricular septal thickness (IVSd) to GLS had the highest performance in differentiating CA with an AUC of 0.812. At the optimal threshold of >0.15, IVSd/GLS had a sensitivity of 0.70 and specificity of 0.80 for CA. Other measurements and ratios, including the ratio of left ventricular ejection fraction to GLS (AUC 0.682), had lower performance when evaluated against a suspicious control cohort with increased left ventricular wall thickness. Conclusion If validated in prospective multi-centre studies, the routine measurement of IVSd/GLS can assist with earlier diagnosis of CA, resulting in earlier initiation of treatment in this underserved population.

Introduction: AL cardiac amyloidosis (AL-CA) is associated with poor prognosis, largely driven by cardiac involvement. The revised Mayo staging system utilizes cardiac biomarkers to risk-stratify and predict outcomes for these patients. However, its long-term predictive value remains uncertain, particularly in the era of novel therapies. This study evaluated the prognostic impact of the revised Mayo staging system, especially on five- and ten-year survival outcomes in AL-CA patients. Methods: We conducted a retrospective cohort study of patients diagnosed with AL-CA at our quaternary center between January 2012 and December 2022. Non-AL amyloidosis patients and those lacking complete data were excluded. Overall survival (OS) was defined from the date of diagnosis until death. Cox regression evaluated associations between Mayo staging and survival. Results: Of 411 patients included, 63.7% were male, 78.6% white, with a median age at AL-CA diagnosis of 68 years (IQR: 31–92). Mayo staging distribution was: stage I (3.6%), stage II (12%), stage III (27.7%), and stage IV (55.5%). During a median follow-up of 25.7 months (IQR: 4.7,56.2), 60.8% (n=250) of patients died. Survival differed significantly by Mayo stage, with a median OS of 80.2 months in stage II, 47.2 months in stage III, and 12.8 months in stage IV (log-rank p < 0.0001) (Figure 1). On multivariable Cox regression, increasing age was independently associated with worse survival (HR = 1.02, 95% CI: 1.01–1.04, p<0.001). Compared to Mayo stage I/II, stage III (HR = 2.02, p=0.005) and stage IV (HR = 2.98, p<0.001) were associated with significantly higher mortality. NYHA class IV was also independently associated with increased risk of death (HR = 1.77, p=0.035) (Figure 2) (Table 1) Long-term follow-up indicated that the 5-year OS was 53.6% (stage I), 73.3% (stage II), 45.5% (stage III), and 32.8% (stage IV). Ten-year OS was 53.6% (stage I), 47.1% (stage II), 23.9% (stage III), and 22.1% (stage IV). Notably, 67% of stage IV survivors at five years remained alive at ten years, comparable to stage II (64%). Conclusion: The revised Mayo staging remains prognostic for AL-CA, demonstrating significant stage-based survival differences. Despite improved outcomes with contemporary treatments, advanced-stage disease remains associated with poorer survival. Importantly, patients in higher-risk stages who reach the five-year mark maintain a substantial likelihood of long-term survival similar to those with less severe stages

No abstract available

Abstract Aims To evaluate the predictive value of the Columbia score in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Methods Observational study based in a prospective, multi-centre registry of patients with ATTR-CM recruited between January–2018 and December–2023 in 7 Spanish hospitals. The Baseline Columbia score was correlated by means of multivariable Cox’s regression with study endpoints all-cause death and all-cause death or heart failure (HF) hospitalisation. Discriminative capacity was evaluated by means of Harrell’s C statistics and area under 2-year time-dependent receiver-operator curves. Results We studied 374 patients with ATTR-CM. Columbia score was independently associated with increased risk of all-cause death (adjusted HR per 1 point = 1.30, 95% CI 1.17–1.45) and all-cause death or HF hospitalisation (adjusted HR per 1 point = 1.38, 95% 1.26–1.50). The score showed moderate discriminative capacity for all-cause death (Harrell’s C = 0.653) and all-cause death or HF hospitalisation (Harrell’s C = 0.697). The area under the 2-year time-dependent receiver-operator curve was 0.594 for all-cause death and 0.669 for all-cause death or HF hospitalisation. Columbia’s score was adequately calibrated for both outcomes. Conclusions We studied the prognostic performance of the Columbia score in a Spanish prospective cohort of patients with ATTR-CM. The score showed adequate calibration and moderate discriminative capacity for predicting death and HF hospitalisations.

Background Cardiac amyloidosis (CA) is an underdiagnosed, progressive and lethal disease. Machine learning applied to common measurements derived from routine echocardiogram studies can inform suspicion of CA. Objectives Our objectives were to test a random forest (RF) model in detecting CA. Methods We used 3603 echocardiogram studies from 636 patients at Cedars-Sinai Medical Center to train an RF model to predict CA from echocardiographic parameters. 231 patients with CA were compared with 405 control patients with negative pyrophosphate scans or clinical diagnosis of hypertrophic cardiomyopathy. 19 common echocardiographic measurements from echocardiogram reports were used as input into the RF model. Data was split by patient into a training data set of 2882 studies from 486 patients and a test data set of 721 studies from 150 patients. The performance of the model was evaluated by area under the receiver operative curve (AUC), sensitivity, specificity and positive predictive value (PPV) on the test data set. Results The RF model identified CA with an AUC of 0.84, sensitivity of 0.82, specificity of 0.73 and PPV of 0.76. Some echocardiographic measurements had high missingness, suggesting gaps in measurement in routine clinical practice. Features that were large contributors to the model included mitral A-wave velocity, global longitudinal strain (GLS), left ventricle posterior wall diameter end diastolic (LVPWd) and left atrial area. Conclusion Machine learning on echocardiographic parameters can detect patients with CA with accuracy. Our model identified several features that were major contributors towards identifying CA including GLS, mitral A peak velocity and LVPWd. Further study is needed to evaluate its external validity and application in clinical settings.

A longitudinal strain pattern characterized by apical sparing (RELAPS>1) has been identified as indicative of cardiac amyloidosis (CA). We conducted an analysis to assess its diagnostic accuracy in individuals with severe aortic stenosis (AS) and explored novel echocardiographic variables for predictive value. All patients diagnosed with AS who underwent transcatheter aortic valve implantation (TAVI) were prospectively enrolled. 2D-Speckle-tracking echocardiography was utilized to assess myocardial deformation parameters. Subsequent to TAVI, screening for CA was conducted through 99mTc-DPD scintigraphy and protein electrophoresis. A total of 324 patients were included (mean age 81.5 ± 5.8 years, 51% women). Among them, 38 individuals (11.7%) exhibited cardiac uptake in scintigraphy: 14 patients (4.3%) with grade 1, 13(4%) grade 2, and 11(3.4%) grade 3. RELAPS>1 was more prevalent in patients with AS-CA (74%vs.44%,p=0.006). We propose an echocardiographic prediction model (GRAM score) for CA in the context of AS that is more sensitive and specific than RELAPS >1 alone. This model incorporates the left ventricular mass index, maximum transvalvular aortic pressure gradient, RELAPS>1, and age (AUC: 0.85, 95% CI: 0.77–0.93). While RELAPS >1 is more commonly observed in individuals with AS-CA, it is noteworthy that this pattern can also manifest in nearly half of AS patients without CA, diminishing its utility as a standalone screening tool. In light of this, our study puts forth a more sensitive and specific prediction score for identifying CA in patients with severe AS.GRAM score for predicting AS-CA

Background/Objectives: Several predictive models have been proposed to estimate the probability of cardiac transthyretin amyloidosis (ATTR-CA). The aim of our study was to evaluate the usefulness of electrocardiographic parameters, as well as parameters consisting of a combination of myocardial thickness and QRS voltage, as potential predictors of ATTR-CA. Methods: In 2018–2025, 285 consecutive patients with suspected cardiac amyloidosis were evaluated, including blood tests, standard 12-lead electrocardiography, transthoracic echocardiography, and [99mTc]Tc-DPD scintigraphy. Results: The ratio of posterior wall thickness to minimum QRS voltage in limb leads (PWT/minQRS ratio) as well as several ECG-derived parameters were independent predictors of ATTR-CA. In a comparison of ROC curves, PWT/minQRS ratio exceeded both the minimum and maximum voltage of QRS complexes in limb leads, demonstrated similar predictive value to TCAS and T-amylo scores, and had similar or superior predictive characteristics to posterior wall thickness. A cut-off of >3.3 for PWT/minQRS ratio was as accurate as the published cut-offs for TCAS score ≥6, T-amylo score ≥7, and posterior wall thickness ≥14 mm. In the subgroup of patients with myocardial thickness of at least 15 mm, PWT/minQRS ratio >3.3 was superior to posterior wall thickness ≥14 mm and T-amylo score ≥7 and had similar predictive value for ATTR-CA as TCAS score ≥6. Conclusions: In a cohort of undifferentiated patients referred for [99mTc]Tc-DPD scintigraphy due to suspected cardiac amyloidosis, PWT/minQRS ratio showed strong predictive value for ATTR-CA, which was even more pronounced in the subgroup of patients with increased myocardial thickness.

Background: Systemic AL amyloidosis is a clonal plasma cell disorder characterized by the deposition of misfolded immunoglobulin light chains in vital organs, leading to progressive organ dysfunction. Accurate risk stratification at diagnosis is critical for guiding therapeutic decisions. The Mayo 2012 staging system incorporates cardiac biomarkers (troponin T, NT-proBNP) and the difference in serum free light chains (dFLC), whereas the European-modified Mayo 2004 system relies solely on cardiac biomarkers. Although both are widely used, direct head-to-head comparisons of their prognostic value are limited. We aimed to compare their prognostic performance in a real-world cohort of AL amyloidosis patients treated with bortezomib-based therapy, with a particular focus on those whose staging results were discordant between the two systems. Objectives: The objective of this study was to compare the prognostic predictive ability of the Mayo 2012 staging system and the European-modified Mayo 2004 system in patients with discordant staging results. Methods: We retrospectively analyzed 177 patients with systemic AL amyloidosis who were treated with bortezomib-based regimens between January 2020 and March 2025, all of whom were staged using both the Mayo 2012 and European-modified Mayo 2004 systems. Concordance was defined as identical risk categories after mapping stage 3 to 3A and stage 4 to 3B. Patients with discordant staging were identified for comparative analysis. Kaplan–Meier curves with log-rank tests were used to assess prognostic discrimination, and receiver operating characteristic (ROC) curves with corresponding area under the curve (AUC) values were generated to compare the ability of each staging system to predict organ responses. Results: In our cohort, 54% of patients were classified as concordant and 46% as discordant between the Mayo stage and the European modification. Among the 83 patients in the discordant group, 53 were male (64%) and 30 were female (36%), with a mean age of 65 years. For Mayo staging, heart involvement was observed in 85.7% of patients with stage 3 and 98.4% with stage 4, and kidney involvement in 55.4% and 36.5%, respectively. For the European modification, heart involvement was reported in 92.5% of patients with stage 3A and 96.4% with stage 3B, and kidney involvement in 47.3% and 42.9%, respectively, highlighting differences in organ involvement patterns between stages. To further assess the prognostic value of each staging system, overall survival curves were analyzed within the discordant group. Kaplan–Meier analysis showed that curves stratified by the Mayo stage exhibited significant overlap between stage 3 and stage 4 despite a significant log-rank p-value (p = 0.0066), indicating limited prognostic discrimination among higher-risk stages. In contrast, curves stratified by the European-modified Mayo 2004 system demonstrated clearer stepwise separation from stage 1 through stage 3B, with minimal overlap (log-rank p-value = 0.0011). Survival probabilities declined progressively across stages, with stage 3B showing markedly inferior outcomes compared with the others. Beyond survival, the European-modified system also showed superior performance in predicting organ responses within the discordant subgroup. It demonstrated significantly better discrimination for hematologic response compared with the Mayo stage (AUC 0.66 vs. 0.33, p = 0.0188) and notably stronger predictive ability for cardiac response (AUC 0.90 vs. 0.50, p = 0.0101). In contrast, no meaningful difference was observed between the two systems in predicting renal response (AUC 0.66 vs. 0.52, p = 0.3282). Conclusions: Although both the Mayo 2012 and European-modified Mayo 2004 staging systems were designed to predict prognosis based on organ involvement, previous studies had not clearly demonstrated which provided superior prognostic discrimination. In our analysis of AL amyloidosis patients with discordant staging, the European modification demonstrated superior prognostic discrimination compared with the Mayo 2012 system, with clearer separation of risk categories. These findings support the European modification as a more refined tool for prognostic assessment, particularly in challenging cases of AL amyloidosis.

Echocardiographic diagnosis of cardiac amyloidosis (CA) is frequently suggested by the presence of a left ventricular (LV) apical sparing pattern (ASP) on longitudinal strain (LS) assessment, the so-called "cherry on top" pattern, defined by strain magnitude preserved exclusively at the apex. However, it is unclear how frequently this strain pattern truly represents CA. This study aimed to evaluate the predictive value of ASP in the diagnosis of CA. We retrospectively identified consecutive adult patients who had the following studies performed within an 18-month period: (1) transthoracic echocardiogram and (2) either (a) cardiac magnetic resonance imaging, (b) Technetium-Pyrophosphate (PYP) imaging, or (c) endomyocardial biopsy. LS was retrospectively measured in the apical 4-, 3-, and 2-chamber views in patients who had adequate noncontrast images (n = 466). An apical sparing ratio (ASR) was calculated as (average apical strain)/[(average basal strain) + (average midventricular strain)]. Patients with ASR ≥1 were evaluated for the presence/absence of CA, using established criteria. Basic LV parameters were also measured. A total of 33 patients (7.1%) had ASP. Nine of these patients (27%) had "confirmed" CA, 2 (6.1%) "highly probable" CA, 1 (3.0%) "possible" CA, and 21 (64%) no evidence of CA. When comparing patients with and without confirmed CA, there were no significant differences in ASR, average global LS, ejection fraction, or LV mass. Patients with confirmed CA were older (76 ± 9 vs 59 ± 18 years, p = 0.01) and had thicker posterior wall (15 ± 3 vs 11 ± 3 mm, p = 0.004) with a trend toward thicker septal wall (15 ± 2 vs 12 ± 4 mm, p = 0.05). In conclusion, the presence of ASP on LS represents confirmed or highly probable CA in only 1/3 of patients and is more likely to indicate true CA in older patients with increased LV wall thickness. Although a larger, prospective study is needed to confirm these findings, 1/3 should be considered as a large diagnostic yield that justifies further testing, given the poor outcomes associated with CA diagnosis.

No abstract available

Aims: Systemic light-chain (AL) amyloidosis is a multisystemic disorder leading to multiple organ dysfunction and mortality that is often caused by cardiac involvement. Soluble suppression of tumorigenicity 2 (sST2) is a novel biomarker identified for risk stratification of heart disease. The aim of this study was to investigate the value of circulating sST2 levels in prognosis and mortality risk assessments for the AL amyloidosis population. Methods and Results: A total of 56 patients diagnosed with AL amyloidosis were enrolled in Peking Union Medical College Hospital (PUMCH) from January 2015 to May 2018. The relationships between the clinical parameters and overall survival (OS) and risk factors for disease progression were assessed. Additionally, receiver operating characteristic (ROC) curves, Kaplan–Meier analysis, and Cox hazard models were performed to explore the predictive value of sST2 in mortality rates. We found that the median OS of all patients was 7.3 [interquartile range (IQR) 4.4, 15.9] months. The median baseline sST2 level was 12.2 (IQR 5.1, 31.1) ng/ml, and the sST2 high group had more severe patients with a higher Mayo stage. In the ROC analysis, the area under the curve (AUC) was 0.728 [95% confidence interval (CI) 0.603–0.853] for sST2 to predict the outcomes of AL amyloidosis patients, and the optimal cutoff value was 12.34 ng/ml (sensitivity 80.2%, specificity 61.1%). Moreover, in multivariate Cox proportional hazards regression analysis, sST2 acted as an independent predictor of poor functional outcome in patients with AL amyloidosis. Conclusion: In AL amyloidosis patients, sST2 was a strong and independent prognostic biomarker for all-cause mortality, providing complementary prognostic information of a novel scoring system for risk stratification.

No abstract available

BACKGROUND Atrial fibrillation (AF) is common and poorly tolerated in cardiac amyloidosis (CA) patients. No current tool assesses AF risk in this population. METHODS We enrolled patients with light chain (AL) or transthyretin (ATTR) CA, with no prior history of AF at diagnosis between January 2015 and September 2023 across three university hospitals. Clinical, biochemical and electrocardiographic parameters were retrospectively collected and their predictive value for AF was assessed. RESULTS A total of 169 patients were included (56.2% wild-type (wt) ATTR, 35.5% AL and 8.3% variant (v) ATTR). Over a median follow-up of 21 months, 55 patients (33%) presented a first episode of AF. Five independent predictors for AF were identified using multivariate logistic regression model: obstructive sleep apnea, hypertension, CA subtype, P wave duration ≥120 ms, 1st degree atrioventricular (AV) block. Based on these variables, the Amy-Lyon AF score (range 0-46) was developed to estimate AF risk (area under the receiver operating characteristic (ROC) curve (AUC) 0.768 [0.685-0.852], p < .001). At two years of follow-up, the incidence of AF reached 82.7% in patients with a score >28. In 80 patients, the AUC of the Amy-Lyon AF score was higher than that of left atrial strain. CONCLUSIONS Five simple and readily available predictors may stratify the risk of AF in CA.

Transthyretin cardiac amyloidosis (ATTR-CM) is increasingly recognized in patients with severe aortic stenosis (AS), particularly elderly individuals undergoing transcatheter aortic valve implantation (TAVI). It may affect up to 1 in 8 patients over 65 years with severe AS. The 2021 ESC position statement by Garcia-Pavia et al. recommends screening patients aged ≥65 years with severe AS and left ventricular hypertrophy, though uptake remains low—partly due to uncertainty in selecting appropriate candidates. Extracellular volume (ECV) quantification by cardiac CT has emerged as a reproducible, objective tool to support screening. Incorporated into standard pre-TAVI protocols via delayed acquisitions, it enables myocardial tissue characterization without workflow disruption. Scully et al. validated CT-derived ECV thresholds with high sensitivity and negative predictive value (NPV) for excluding cardiac uptake on scintigraphy: ECV <29.2%: NPV 100% for Perugini ≥1 ECV <31.4%: NPV 98% for Perugini ≥1 ECV <33.4%: NPV 100% for Perugini 2–3 These thresholds support ECV’s potential role as a gatekeeper for more targeted screening. To assess the implementation of guideline-based ATTR-CM screening in severe AS and evaluate whether CT-derived ECV can optimize patient selection for diagnostic work-up. We included 207 patients with severe AS who underwent pre-procedural CT between March 2024 and March 2025. A 5-minute delayed dual-energy acquisition enabled ECV quantification via iodine density mapping. ECV was measured in basal, mid, and apical short-axis slices; the mean of basal and mid segments was used, in line with prior validation studies. Among 207 patients, 175 (84.5%) met clinical criteria for ATTR-CM screening, but only 8 (3.9%) were effectively screened. Of these, three were awaiting DPD scintigraphy and five had negative diagnostic work-ups. Notably, over half of the screened patients had ECV <29.2%, despite fulfilling clinical criteria. The median ECV was 30.25% (IQR 27.6–33.4). Applying established thresholds: 58.9% had ECV >29.2% 38.6% had ECV >31.4% 25.1% had ECV >33.4% Thus, ECV-based triage could reduce screening rates from 84.5% to a range between 58.9% and 25.1%, depending on the selected threshold—without compromising sensitivity, and improving precision in patient selection. No significant differences in age, sex, or BMI were observed across ECV strata, reinforcing its added value over conventional clinical parameters. Despite increasing awareness, real-world screening for ATTR-CM in severe AS remains rare. CT-derived ECV serves as a valuable gatekeeper, offering an objective and practical approach to streamline patient selection, reduce unnecessary testing, and enhance adherence to structured screening pathways. External validation is warranted.

OBJECTIVE To develop an artificial intelligence (AI)-based tool to detect cardiac amyloidosis (CA) from a standard 12-lead electrocardiogram (ECG). METHODS We collected 12-lead ECG data from 2541 patients with light chain or transthyretin CA seen at Mayo Clinic between 2000 and 2019. Cases were nearest neighbor matched for age and sex, with 2454 controls. A subset of 2997 (60%) cases and controls were used to train a deep neural network to predict the presence of CA with an internal validation set (n=999; 20%) and a randomly selected holdout testing set (n=999; 20%). We performed experiments using single-lead and 6-lead ECG subsets. RESULTS The area under the receiver operating characteristic curve (AUC) was 0.91 (CI, 0.90 to 0.93), with a positive predictive value for detecting either type of CA of 0.86. By use of a cutoff probability of 0.485 determined by the Youden index, 426 (84%) of the holdout patients with CA were detected by the model. Of the patients with CA and prediagnosis electrocardiographic studies, the AI model successfully predicted the presence of CA more than 6 months before the clinical diagnosis in 59%. The best single-lead model was V5 with an AUC of 0.86 and a precision of 0.78, with other single leads performing similarly. The 6-lead (bipolar leads) model had an AUC of 0.90 and a precision of 0.85. CONCLUSION An AI-driven ECG model effectively detects CA and may promote early diagnosis of this life-threatening disease.

Speckle-tracking echocardiography–derived left atrial (LA) strain parameters have emerged as reliable predictors of atrial fibrillation (AF) in the general population. Given the high prevalence of AF in patients with wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM), early identification of individuals at elevated risk is essential. LA strain analysis may serve as a valuable noninvasive tool for this purpose. To evaluate the predictive value of baseline LA strain parameters for the development of AF in patients with wtATTR-CM. This retrospective, single-center study included patients diagnosed with wtATTR-CM between 2014 and 2024 who were in sinus rhythm at the time of diagnosis. Baseline echocardiographic assessment included Peak Atrial Longitudinal Strain (PALS), Peak Atrial Contraction Strain (PACS), and Peak Atrial Conduit Strain (PCS). The primary outcome was the incidence of AF during follow-up. Receiver operating characteristic (ROC) curves and Youden index were used to identify optimal cutoff values, and logistic regression was performed to evaluate predictive strength. Of 111 patients, 59 met inclusion criteria (73% male, mean age 80 ± 6 years). Over a median follow-up of 30 months [IQR 16–36], 30 patients (51%) developed AF. Patients who developed AF had significantly lower PALS (12.13 ± 4.76% vs. 15.22 ± 6.13%, p=0.034) and PACS (–6.29 ± 3.84% vs. –9.05 ± 5.54%, p=0.030). No significant difference was observed in PCS between groups (p=0.688). The optimal cutoff for PACS was –11.4%, which was significantly associated with AF occurrence (OR 7.368; 95% CI 1.449–37.462; p=0.016). PALS showed a trend toward significance at a cutoff of 14.6% (OR 0.339; 95% CI 0.114–1.008; p=0.052). Among patients with wtATTR-CM, impaired LA strain—particularly reduced PACS—is significantly associated with the development of AF. While PALS also showed a predictive trend, PACS demonstrated stronger discriminative power. These findings support the incorporation of LA strain analysis into routine risk stratification protocols for AF in this population, warranting further validation in larger cohorts.

OBJECTIVES The prognostic value of echocardiographic atrial and ventricular strain imaging in patients with biopsy-proven cardiac amyloidosis was assessed. BACKGROUND Although left ventricular global longitudinal strain (GLS) is known to be predictive of outcome, the additive prognostic value of left (LA), right atrial (RA), and right ventricular (RV) strain is unclear. METHODS One hundred thirty-six patients with cardiac amyloidosis and available follow-up data were studied by endomyocardial biopsy, noncardiac biopsy with supportive cardiac imaging, or autopsy confirmation. One hundred nine patients (80%) had light-chain, 23 (17%) had transthyretin, and 4 (3%) had amyloid A type cardiac amyloidosis. GLS, RV free wall strain, peak longitudinal LA strain, and peak longitudinal RA strain were measured from apical views. Clinical and routine echocardiographic data were compared. All-cause mortality was followed (median 5 years). RESULTS Strain data were feasible for GLS in 127 (93%), LA strain in 119 (88%), RA strain in 117 (86%), and RV strain in 102 (75%). Strain values from all 4 chambers were significantly associated with survival. Hazard ratio (HR) and 95% confidence interval (CI) for low median strain values were as follows: GLS, HR: 2.3; 95% CI: 1.3 to 3.8 (p < 0.01); LA strain, HR: 7.5; 95% CI: 3.8 to 14.7 (p < 0.001); RA strain, HR: 3.5; 95% CI: 2.0 to 6.2 (p < 0.001); and RV free wall strain, HR: 2.8; 95% CI: 1.5 to 5.1 (p < 0.001). Peak longitudinal LA strain and RV strain remained independently associated with survival in multivariable analysis. Peak LA strain had the strongest association with survival (p < 0.001), and LA strain combined with GLS and RV free wall strain had the highest prognostic value (p < 0.001). CONCLUSIONS Strain data from all 4 chambers had important prognostic associations with survival in patients with biopsy-confirmed cardiac amyloidosis. Peak longitudinal LA strain was particularly associated with prognosis. Atrial and ventricular strain have promise for clinical utility.

Patients with rare conditions such as cardiac amyloidosis (CA) are difficult to identify, given the similarity of disease manifestations to more prevalent disorders. The deployment of approved therapies for CA has been limited by delayed diagnosis of this disease. Artificial intelligence (AI) could enable detection of rare diseases. Here we present a pipeline for CA detection using AI models with electrocardiograms (ECG) or echocardiograms as inputs. These models, trained and validated on 3 and 5 academic medical centers (AMC) respectively, detect CA with C-statistics of 0.85–0.91 for ECG and 0.89–1.00 for echocardiography. Simulating deployment on 2 AMCs indicated a positive predictive value (PPV) for the ECG model of 3–4% at 52–71% recall. Pre-screening with ECG enhance the echocardiography model performance at 67% recall from PPV of 33% to PPV of 74–77%. In conclusion, we developed an automated strategy to augment CA detection, which should be generalizable to other rare cardiac diseases. Cardiac amyloidosis is difficult to identify, given low prevalence and similarity of the symptoms to more prevalent disorders. Here the authors present a multi-modality, artificial intelligence-enabled pipeline, that enables automated detection of cardiac amyloidosis from inexpensive and accessible measures.

OBJECTIVES This study aimed to assess the diagnostic use of native T1 to detect cardiac amyloidosis (CA) in a large prospective cohort of patients referred for suspected systemic amyloidosis. BACKGROUND CA is a progressive and fatal underdiagnosed cause of heart failure. Cardiovascular magnetic resonance (CMR) has emerged as an extremely useful test for the non-invasive diagnosis of CA, but administration of contrast is still required to make a diagnosis. METHODS In this study, 868 patients with suspected CA referred between 2015 and 2017 underwent CMR with late gadolinium enhancement (LGE), T1 mapping, and an array of clinical investigations. RESULTS The final diagnosis was cardiac light-chain (AL) amyloidosis in 222, cardiac transthyretin (ATTR) amyloidosis in 214, and no cardiac involvement in 427 cases. T1 was significantly elevated in both types of CA and this was associated with high diagnostic accuracy in the overall population (area under the curve, 0.93). A native T1 <1,036 ms was associated with 98% negative predictive value for CA whereas a native T1 >1,164 ms was associated with 98% positive predictive value for CA. We propose the use of these cut-offs to exclude or confirm CA and to restrict the administration of contrast only to patients with intermediate probability (native T1 between 1,036 and 1,164 ms), 58% of patients in this population. CONCLUSIONS Native myocardial T1 enables diagnosis of CA to be made without need for gadolinium contrast in a large proportion of patients with suspected systemic amyloidosis. We propose a diagnostic algorithm for non-contrast CMR applicable to patients with suspected amyloidosis.

No abstract available

Multiple myeloma (MM) is a hematological malignancy of plasma cell origin. Cardiac amyloidosis (CA) is a common form of heart damage caused by MM and is associated with a poor prognosis. This study was a prospective cohort study and was aimed at evaluating the clinical predictive value of extracellular volume fraction (ECV) based on cardiovascular magnetic resonance (CMR) T1 mapping for cardiac amyloidosis and cardiac dysfunction in MM patients. Fifty‐one newly diagnosed MM patients in Zhongnan Hospital of Wuhan University were enrolled in the study. A total of 19 patients (19/51; 37.25%) developed CA. The basal ECV of CA group was significantly higher than that of the non‐CA group (p < 0.01). Multivariate logistic regression analysis showed that basal ECV (OR = 1.551, 95% CI 1.084‐2.219, p < 0.05) and LDH1 level (OR = 1.150, 95% CI 1.010‐1.310, p < 0.05) were two independent risk factors for CA. Further study demonstrated that basal ECV in the heart failure group was significantly higher than that of the nonheart failure group (p < 0.01). Notably, ROC curve showed that basal ECV had a good predictive value for CA and heart failure, with AUC of 0.911 and 0.893 (all p < 0.01), and the best cutoff values of 38.35 and 37.45, respectively. Taken together, basal ECV is a good predictor of CA and heart failure for MM patients.

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BACKGROUND Although impaired left ventricular (LV) global longitudinal strain (GLS) with apical sparing is a feature of cardiac amyloidosis (CA), its diagnostic accuracy has varied across studies. We aimed to determine the ability of apical sparing ratio (ASR) and most common echocardiographic parameters to differentiate patients with confirmed CA from those with clinical and/or echocardiographic suspicion of CA, but with this diagnosis ruled out. METHODS We identified 544 patients with confirmed CA and 200 controls as defined above (CTRL Patients). Measurements from transthoracic echocardiograms (TTE) were performed using artificial intelligence software (Us2.AI, Singapore) and audited by an experienced echocardiographer. Receiver-operating characteristic curve analysis was used to evaluate the diagnostic performance and optimal cutoffs for the differentiation of CA patients from CTRL Patients. Additionally, a group of 174 healthy subjects (Healthy CTRL) was included to provide insight on how Patients and Healthy controls differed echocardiographically. RESULTS LV GLS was more impaired (-13.9 ± 4.6% vs -15.9 ± 2.7%, p < 0.0005) and ASR was higher (2.4 ± 1.2 vs 1.7 ± 0.9, p < 0.0005) in the CA group vs. CTRL Patients. Relative wall thickness and ASR were the most accurate parameters for differentiating CA from CTRL Patients (AUC: 0.77 and 0.74, respectively). However, even with the optimal cutoff of 1.67, ASR was only 72% sensitive and 66% specific for CA, indicating presence of apical sparing in 32% of CTRL Patients and even in 6% Healthy CTRLs. CONCLUSIONS Apical sparing did not prove to be a CA-specific biomarker for accurate identification of CA, when compared to clinically similar controls with no CA.

Abstract Background Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) may accompany aortic stenosis (AS) in older adults. The coexistence of ATTRwt-CA and AS is associated with increased mortality and a higher incidence of heart failure hospitalization compared to AS alone. Apical sparing, manifested with a preserved apical longitudinal strain by echocardiography, is a cornerstone of diagnosing ATTRwt-CA; however, the role of this parameter in the diagnosis and follow-up of patients with AS complicated with ATTRwt-CA remain. Case summary We report a case of ATTRwt-CA complicated by AS that was successfully treated with transcatheter aortic valve implantation (TAVI) and tafamidis, a tetramer stabilizer for transthyretin. The patient exhibited a favourable clinical course, highlighting the potential benefit of this combined therapeutic approach. Notably, characteristic features suggestive of apical sparing, which were completely absent before TAVI, emerged 10 months after the interventional afterloading. Discussion This case indicates the potential benefit of combining tafamidis therapy with TAVI in patients with ATTRwt-CA and AS. Serial assessment of global longitudinal strain (GLS) provides valuable insights into myocardial function beyond the ejection fraction. The absence of the apical sparing sign prior to TAVI and the improvement of apical LS following the interventional afterloading suggest the risk of overlooking the characteristic GLS features of ATTRwt-CA when complicated with AS.

Introduction: Cardiac computed tomography (CT) not only allows for coronary artery evaluation but also enables myocardial assessment, including left ventricular (LV) ejection fraction (LVEF) and extracellular volume fraction. Advanced software makes it possible to analyze LV longitudinal strain (LS) on CT (Figures A and B). Hypothesis: LS analysis using four-dimensional cardiac CT is helpful for the differential diagnosis of LV hypertrophied myocardial diseases and detect cardiac amyloidosis (CA). Methods: We analyzed 45 patients with LV hypertrophied myocardial diseases who underwent cardiac CT using 256-detector row or 320-detector row CT in our institutions since 2009. Fifteen patients of them were diagnosed with CA (69 ± 9 years, 12 males), the other 15 patients were diagnosed with hypertrophic cardiomyopathy (HCM) (63 ± 16 years, nine males), and the rest of the 15 patients were diagnosed with aortic valve stenosis (AS) (83 ± 8 years, seven males). We analyzed LV global LS (GLS) and segmental LS using specific software and four-dimensional CT data. We evaluated relative apical LS as the value dividing the average LS of apical segments by the sum of the average LS of basal segments and mid-ventricular segments (Figure C). If the value was ≥ 1, apical sparing was defined as present. We compared the LS data and the percentage of apical sparing among those three myocardial diseases. Results: There was no significant difference in LVEF among the three groups (54 ± 12%, 58 ± 13%, and 50 ± 18%, respectively; P = 0.39). There was no significant difference in LV global LS among the three groups (-12.2 ± 3.2%, -11.2 ± 5.0%, and -11.0 ± 5.4%, respectively; P = 0.75). Apical sparing was observed in 6 cases (40%) of CA, which was significantly higher than in one case (7%) of HCM or AS (P = 0.02). Conclusions: Advanced image analysis software has made LVLS analysis by cardiac CT possible. It is considered helpful in detecting apical sparing, specifically in CA.

Wild-type transthyretin amyloidosis (wtATTR) is a multisystemic disease characterized by deposition of amyloid fibrils in the interstitium. Cardiac involvement is usually associated with an unfavorable prognosis. The echocardiographic phenomenon of "apical sparing" shows a high sensitivity and specificity for the diagnosis of cardiac amyloidosis. It is assumed that less amyloid is deposited in the apical region of the heart than in the basal region, but this has not yet been clearly demonstrated. The clinical, histological and prognostic difference between patient groups with and without apical sparing is currently the subject of scientific debate. To investigate the differences between patients with and without apical sparing, 55 patients with ATTR amyloidosis were analyzed (apical sparing n=39; no apical sparing n=16). Inclusion criteria included histologically confirmed TTR amyloidosis based on left ventricular myocardial biopsy. Patients with apical sparing showed a significantly higher amyloid content in the myocardial biopsies (p=0.0123) compared to the group without apical sparing, matching higher Perugini scores (p=0.0001), greater septal thickness (p=0.0224), increased NT-proBNP (p=0.0001) and troponin values (p<0.0001) as well as a reduced global longitudinal strain (GLS, p=0.0084). There were no significant differences between the two groups with regard to age (p=0.6750), ejection fraction (EF, p=0.6640), posterior wall thickness (p=0.2371), LVEDD (p=0.7369) and serum free kappa and lambda light chain concentrations (p=0.1877, p=0.0639, respectively). The presence of apical sparing on echocardiography is associated with a significantly higher amyloid load in the left ventricular myocardium, which is associated with an increased Perugini score and increased cardiac markers as extent of amyloidosis progression. The occurrence of apical sparing therefore seems to indicate an advanced ATTR stage and could be used for risk stratification and therapy modification in the future. Further studies are required to investigate in detail the prognostic relevance of the apical sparing phenomenon in cardiac amyloidosis.  

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Introduction: Cardiac involvement occurs in ~50% of patients with light-chain (AL) amyloidosis and conveys a poor prognosis. This study examined the role of histopathologic and echocardiographic parameters in predicting mortality. Methods: Patients with endomyocardial biopsy-proven cardiac AL amyloidosis treated at MD Anderson Cancer Center between 6/2011 and 6/2020 were identified. Stored echocardiographic images were processed for longitudinal strain (global [GLS], apical, mid, basal) as well as radial and circumferential strain of the left ventricle (LV), right ventricle (RV) free wall, left atrium (LA), and right atrium, using the Epsilon EchoInsight Software. A detailed histomorphologic characterization of stored endomyocardial biopsy samples was performed by a cardiac pathologist and scored as < or > 5% AL deposits. Results: We identified 43 patients; 44% were women and 63% white. Median age was 65 years (IQR 59-70). Twenty-two (51%) underwent stem cell transplantation (SCT). A total of 29 patients (67%) died during follow up period (median follow up: 4.2 years (95% CI, 2.8-8.6)). Median overall survival (OS) was 18 months (95% CI, 8.1-37). Lower LA GLS and absence of SCT as a time-varying covariate were significantly and independently associated with increased risk of death in the multivariable cox regression analysis (HR 3.8, 95% CI 1.4-10.2 for LA GLS < 13.5 vs >13.5, p=0.008 and 0.20, 0.06-0.65 for SCT vs no SCT, p<0.001, respectively). Higher LV mass and lower RV TAPSE were associated with increased odds of having >5% of interstitial amyloid deposition on biopsy in the multivariable logistic regression analysis (OR 5.5, 95% CI 1.1-26.8 for >195.6g vs ≤195.6g, p=0.036 and 8.1, 1.2-54.3 for RV TAPSE<1.6cm vs ≥1.6cm, p=0.032, respectively). Conclusions: LA GLS < 13.5 was an independent predictor of mortality in our cohort, and its performance in the routine assessment of AL amyloidosis may be justified. Furthermore, SCT for cardiac AL amyloidosis was associated with improved OS. This finding needs to be confirmed by larger studies in the era of contemporary systemic therapies. Although LV mass and RV TAPSE were associated with higher interstitial amyloid deposition, histopathologic parameters did not predict mortality in this cohort.

Transthyretin cardiomyopathy (ATTR-CM) is a progressive, life-threatening infiltrative disorder with reportedly lower prevalence in women. While echocardiographic red flags for identifying ATTR-CM have been established in populations overrepresented by men, their diagnostic utility is inadequately studied in women. We assessed the diagnostic accuracy of echocardiographic red flags and electrocardiography in a well-characterized, female population with hypertrophied left ventricles to differentiate ATTR-CM from left ventricular hypertrophy (LVH). We compared echocardiographic red flags and electrocardiography in 62 female patients with interventricular septal thickness of >12 mm, divided equally into well-defined ATTR-CM (n=31) and age-matched LVH. ATTR-CM displayed higher relative wall thickness (RWT), higher values for relative apical sparing (RELAPS) and lower S-wave in lead aVR (SaVR) than LVH. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) did not differ between groups. RWT/SaVR ratio displayed stronger diagnostic performance to identify ATTR-CM (AUC=0.97) when compared with RELAPS (AUC=0.83) and RWT (AUC=0.82). Further, RELAPS demonstrated lower, and SaVR higher optimal diagnostic cut-offs than those previously published in predominant male cohorts. In a well-characterized, single-center, female population with hypertrophied left ventricles, RWT/SaVR outperformed conventional echocardiographic red-flags and shows promise for diagnosing ATTR-CM. Our findings also highlight the need for sex-specific cut-offs, but generalizability is limited by single-center design and predominance of the Val30Met genotype. Validation in larger prospective cohorts is warranted.

Background Daratumumab has transformed the management of AL amyloidosis by significantly improving hematologic response rates [1]. However, its real-world impact on cardiac recovery remains uncertain, particularly in advanced disease [2]. Methods We conducted a retrospective, single-center study including 9 patients diagnosed with AL amyloidosis between 2021 and 2023 at Bourges Hospital, France. Baseline evaluation included cardiac biomarkers, echocardiography (global longitudinal strain [GLS], LVEF), cardiac MRI, and Mayo Clinic staging. Induction therapy consisted of daratumumab-CyBorD in 6 patients. Hematologic and organ responses were assessed according to ISA and consensus criteria, respectively. Results Among the 9 patients (mean age 70.4 years; 7 men), 8 presented with severe cardiac involvement (median NT-proBNP: 8,154 ng/L; median troponin T: 82.7 ng/L). GLS was markedly impaired (–14% to +6%), with an apical sparing pattern in 4/5 patients. Five of the 6 patients treated with daratumumab achieved ≥PR, including 4 VGPRs. No cardiac responses were observed: biomarkers remained elevated, GLS was unchanged, and symptoms persisted. Two patients achieved renal responses. Conclusions In real-world practice, even deep hematologic responses to daratumumab do not translate into early cardiac improvement in patients with advanced cardiac AL amyloidosis. These findings highlight the critical importance of earlier diagnosis and the urgent need for therapies targeting cardiac amyloid deposits directly [3]. References Kastritis E, et al. Daratumumab-based treatment for AL amyloidosis. N Engl J Med. 2021;385(1):46-58. Muchtar E, et al. Delayed cardiac response despite hematologic response in AL amyloidosis. 2018;131(5):525-531. Merlini G, et al. Cardiac amyloidosis: the need for early diagnosis and novel treatments. Eur Heart J. 2022;43(33):3161-3173.

Carpal tunnel syndrome (CTS) identified with ATTR cause may precede the cardiac involvement. We previously reported that basal inferosptum preferentially deformed in the clinical spectrum of transthyretin-derived cardiac amyloidosis. This study aimed to characterize the morphological and functional features of left ventricle using 2D speckle-tracking echocardiography in patients with ATTR deposition confined to carpal synovium. This study included 81 biopsy-proven wild-type ATTR amyloidosis patients (mean age 77±6 years, 88% male), categorized into three clinical groups: carpal ATTR without cardiac involvement (Group 1, n=13), asymptomatic cardiac involvement (Group 2, n=10), and overt heart failure (Group 3, n=58). Group 1 exhibited low BNP [14 pg/mL (range: 6–49)] and troponin-T [0.012 ng/mL (range: 0.006–0.022)] levels with preserved eGFR (64±9 mL/min/1.73 m²). While global longitudinal strain (GLS) and apical sparing ratios identified myocardial involvement, segmental strain analysis of the basal inferoseptum revealed significant differences: Group 1 [10.7% (range: 4.9–21.5)] vs. Group 2 [3.6% (range: 0–9.6), p<0.001] and Group 3 [2.9% (range: 0–11.4), p<0.001] (Please see the Figure below). Moreover, a cutoff value of 9.5% for basal inferoseptal longitudinal strain effectively distinguished between low and high troponin-T levels (p=0.009), while a cutoff value of 20.8 for GLS did not significantly differentiate troponin-T levels (p=0.9416). Segmental strain analysis, particularly a basal inferoseptal longitudinal strain, may provide a more sensitive measure of early myocardial amyloid deposition compared to GLS, aiding in risk stratification for CTS patients with ATTR deposits.

Additional cardiac amyloidosis (CA) in severe aortic stenosis (AS) is prevalent in around 8% of AS patients and leads to increased morbidity and mortality. Since both conditions cause comparable symptoms and echocardiographic characteristics of the left ventricle, such as apical sparing and left ventricular wall thickening, diagnosis of CA is challenging in clinical practice. The present substudy of the SAVER trial aims to compare right heart morphology and function in AS patients with and without additional CA. From 2020 to 2023, AS patients planned for surgical (SAVR) or transcatheter aortic valve replacement (TAVR) with complete echocardiography of the right heart were enrolled in the SAVER study. Transthoracic echocardiography was performed during AS evaluation prior to SAVR or TAVR and, in case of suspected CA, patients underwent further diagnostics including bone scan or MRI. In the present subanalysis, we compared right heart morphology and function of AS patients with and without additional CA as confirmed by bone scan or MRI. A total of 28 AS patients were analyzed, including 13 patients with additional CA. The median age was 81±6 years, 75% of patients were male, and 96% were treated with TAVR. Left ventricular wall thickness was comparable between AS patients with and without CA. Regarding right heart morphology and function, AS patients with CA presented a tendency to larger right atrial and ventricular dimension (right atrial area: AS with CA 22 [12-32] mm² vs. AS 17 [8-26] mm²; right ventricular diameter basal: AS with CA 42 [32-52] mm vs. AS 38 [29-47] mm) and a reduced right ventricular function measured by right ventricular fractional area change (AS with CA 37±10% vs. AS 46±11%), right ventricular global (AS with CA -15±6% vs. AS -22±6%) and free wall strain (AS with CA -18±7% vs. AS -19±5%). Right ventricular wall thickness was comparable between both groups and reached 5±1mm. Further echocardiographic parameters are listed in Table 1. AS patients with additional CA presented a tendency towards reduced right ventricular function and a more dilated right heart compared to AS patients without CA. These parameters may help to differentiate between both conditions in clinical practice.

Background: Longitudinal strain is central to the echocardiographic diagnosis of cardiac amyloidosis, typically showing reduced global values with relative apical sparing. Longitudinal displacement-an absolute measure of myocardial motion-may provide complementary diagnostic and physiological information. Methods: We retrospectively studied 24 patients with cardiac amyloidosis and 24 age-, sex-, rhythm-, and ejection fraction-matched controls. Global and regional longitudinal strain and displacement were calculated. Diagnostic performance was evaluated using receiver-operating characteristic (ROC) analysis, and reproducibility was assessed using intraclass correlation coefficients (ICC), coefficient of variation (CV), and Bland-Altman analysis. Results: In amyloidosis, both global longitudinal strain (GLS) and global longitudinal displacement (GLD) were significantly reduced compared with controls (GLS: -10.2 ± 2.6% vs. -20.1 ± 2.4%, p < 0.0001; GLD: 6.6 ± 1.9 mm vs. 11.9 ± 1.4 mm, p < 0.0001). Amyloidosis was characterized by pronounced impairment of basal displacement (9.0 ± 4.4 vs. 17.0 ± 3.9 mm, p < 0.0001) and only modest reduction in absolute apical motion (3.0 ± 2.4 vs. 5.0 ± 2.3 mm, p < 0.0001), supporting the concept that apical sparing observed on strain reflects relative rather than absolute preservation of function. ROC analysis demonstrated strong discriminatory performance within this cohort for GLD (cutoff 8.8 mm), basal displacement (~13 mm), and GLS (absolute 15.8%), with areas under the curve approaching 1.0. GLD and GLS correlated with indices of diastolic burden and functional status (E/E' and NYHA; |r| ≈ 0.32-0.41, all p ≤ 0.03). Reproducibility was good to excellent (ICC ≈ 0.84-0.89; CV 6-8%). Conclusions: Longitudinal displacement provides complementary and reproducible information alongside strain in cardiac amyloidosis. Combined assessment-reduced global or basal displacement together with reduced GLS and/or relative apical sparing-may refine the echocardiographic characterization of amyloid cardiomyopathy and link longitudinal mechanics to diastolic dysfunction and heart-failure burden.

AIMS Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) is now increasingly identified as a cause of heart failure in older adults. This study aimed to clarify the morphological and functional alterations of the left ventricle (LV) that define the early stage of this condition. METHODS We prospectively evaluated 81 patients diagnosed with wild-type ATTR (ATTRwt) amyloidosis (mean age 77 ± 6 years; 88% male), categorized into three groups based on myocardial uptake on radioactive pyrophosphate scintigraphy and histological confirmation: (i) carpal ATTR without cardiac involvement (Group 1, n = 13), (ii) asymptomatic cardiac involvement (Group 2, n = 10) and (iii) overt heart failure (Group 3, n = 58). Results Compared with Group 3, Group 1 showed higher absolute global longitudinal strain (GLS) (median 19.0 [13.2-23.8]%, P < 0.001), a lower apical-sparing ratio (median 0.66 [0.55-1.04], P < 0.001) and lower brain natriuretic peptide (BNP) (median 13.5 [6-49] pg/mL, P < 0.001) and troponin-T concentrations (0.012 [0.006-0.022] ng/mL, P < 0.001), while the estimated glomerular filtration rate remained preserved (64 ± 9 mL/mL/1.73 m², P = 0.022). Segmental longitudinal strain (LS) differentiated Group 1 from Group 2, with basal inferoseptal LS significantly lower in patients with elevated troponin-T (> 0.014 ng/mL) than in those with lower values (13.9 ± 5.6 % vs. 7.4 ± 1.8 %, P = 0.046) in Group 1. A basal inferoseptal LS cutoff of 9.1% identified high troponin-T with an area under the curve (AUC) of 0.833 (P = 0.005), outperforming GLS (AUC 0.306, P = 0.217), BNP (AUC 0.667, P = 0.292) and LV ejection fraction (AUC 0.556, P = 0.743). CONCLUSIONS Basal inferoseptal LS impairment may indicate early cardiac involvement in individuals with carpal tunnel syndrome carrying ATTRwt deposits.

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Background Late gadolinium enhancement (LGE) is a classic imaging modality derived from cardiac magnetic resonance (CMR), which is commonly used to describe cardiac tissue characterization. T1 mapping with extracellular volume (ECV) and native T1 are novel quantitative parameters. The prognostic value of multiparametric CMR in patients with light chain (AL) amyloidosis remains to be thoroughly investigated. Methods A total of 89 subjects with AL amyloidosis were enrolled from April 2016 to January 2021, and all of them underwent CMR on a 3.0 T scanner. The clinical outcome and therapeutic effect were observed. Cox regression was used to investigate the effect of multiple CMR parameters on outcomes in this population. Results LGE extent, native T1 and ECV correlated well with cardiac biomarkers. During a median follow-up of 40 months, 21 patients died. ECV (hazard ratio [HR]: 2.087 for per 10% increase, 95% confidence interval [CI]: 1.379-3.157, P < 0.001) and native T1 (HR: 2.443 for per 100 ms increase, 95% CI: 1.381-4.321, P=0.002) were independently predictive of mortality. A novel prognostic staging system based on median native T1 (1344 ms) and ECV (40%) was similar to Mayo 2004 Stage, and the 5-year estimated overall survival rates in Stage I, II, and III were 95%, 80%, and 53%, respectively. In patients with ECV > 40%, receiving autologous stem cell transplantation had higher cardiac and renal response rates than conventional chemotherapy. Conclusion Both native T1 and ECV independently predict mortality in patients with AL amyloidosis. Receiving autologous stem cell transplantation is effective and significantly improves the clinical outcomes in patients with ECV > 40%.

Aims To assess the prognostic value of myocardial pre-contrast T1 and extracellular volume (ECV) in systemic amyloid light-chain (AL) amyloidosis using cardiovascular magnetic resonance (CMR) T1 mapping. Methods and results One hundred patients underwent CMR and T1 mapping pre- and post-contrast. Myocardial ECV was calculated at contrast equilibrium (ECVi) and 15 min post-bolus (ECVb). Fifty-four healthy volunteers served as controls. Patients were followed up for a median duration of 23 months and survival analyses were performed. Mean ECVi was raised in amyloid (0.44 ± 0.12) as was ECVb (mean 0.44 ± 0.12) compared with healthy volunteers (0.25 ± 0.02), P < 0.001. Native pre-contrast T1 was raised in amyloid (mean 1080 ± 87 ms vs. 954 ± 34 ms, P < 0.001). All three correlated with pre-test probability of cardiac involvement, cardiac biomarkers, and systolic and diastolic dysfunction. During follow-up, 25 deaths occurred. An ECVi of >0.45 carried a hazard ratio (HR) for death of 3.84 [95% confidence interval (CI): 1.53–9.61], P = 0.004 and pre-contrast T1 of >1044 ms = HR 5.39 (95% CI: 1.24–23.4), P = 0.02. Extracellular volume after primed infusion and ECVb performed similarly. Isolated post-contrast T1 was non-predictive. In Cox regression models, ECVi was independently predictive of mortality (HR = 4.41, 95% CI: 1.35–14.4) after adjusting for E:E′, ejection fraction, diastolic dysfunction grade, and NT-proBNP. Conclusion Myocardial ECV (bolus or infusion technique) and pre-contrast T1 are biomarkers for cardiac AL amyloid and they predict mortality in systemic amyloidosis.

Red blood cell distribution width (RDW) and the RDW-to-albumin ratio (RAR) have emerged as significant prognostic markers for mortality in a wide range of diseases. However, whether RDW and RAR are associated with higher risk of mortality in patients with light chain cardiac amyloidosis (AL-CA) remains unclear. Consecutive patients diagnosed with AL-CA between September 2014 and November 2023, with available data were enrolled. Kaplan-Meier analysis and Cox proportional hazards models were used to evaluate the association between RDW, RAR and the risk of all-cause mortality. Restricted cubic spline regressions were applied to estimate possible nonlinear associations. A total of 182 patients were included, with a mean age of 60.54 years (standard deviation [SD]: 10.23 years); 68 patients (37.4%) were female, 149 patients (81.9%) were in European modified Mayo 2004 stage III. The cutoff value of RDW and RAR were set at 14.47% and 0.34, respectively. Over an average follow-up period of 367 days, 98 patients (53.8%) died. Kaplan-Meier survival analysis revealed that patients with higher baseline RDW and RAR levels had significantly worse survival (log-rank test, P<0.01 and P<0.001, respectively). In multivariable Cox regression analysis, both log-transformed RDW and RAR remained independently associated with the primary outcome, even after full adjustment for age, gender, European modified Mayo 2004 stages, and treatment strategies (adjusted HR: 5.08, 95% CI: 1.33–19.35, P<0.05; adjusted HR: 2.43, 95% CI: 1.10–5.38, P<0.05).RCS analysis revealed a non-linear relationship between RDW and RAR and the increased risk of mortality in these patients. Elevated baseline RDW and RAR are robust and independent indicator of worse prognosis in AL-CA patients and can be used to identify high-risk patients.Kaplan-Meier curves of overall survival.  Restricted cubic splines.

Background This study assessed the prognostic value of submaximal cardiopulmonary exercise testing (CPET) in cardiac amyloidosis and explored CPET as an alternative to the 6-min walk test (6MWT). Methods and Results In this single-center prospective observational study, 160 patients with cardiac amyloidosis (87% male; mean age 78±7 years) were evaluated. A total of 145 performed maximum symptom limited CPET. The V̇E/V̇CO2 slope was 39±8, submaximal power output (SPO) was 24.75±11.50 W, and V̇O2 at anaerobic threshold (AT) was 8.13±2.29 mL/min/kg. During follow up, 34 (21.25%) patients died, and another 34 (21.25%) experienced heart failure (HF)-related hospitalization, with 15 (9.38%) patients experiencing both events. Univariate analysis showed that V̇E/V̇CO2 slope (hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.86–0.93; P<0.001) and SPO (HR 0.91; 95% CI 0.87–0.96; P<0.001) were predictors of mortality. In multivariate analysis, V̇E/V̇CO2 slope remained a significant predictor (HR 0.92; 95% CI 0.88–0.97; P<0.001) for both all-cause mortality and HF-related hospitalization independently. A SPO cut-off of <28 W predicted a worse outcome for both measures independently. Moderate correlations for V̇E/V̇CO2 slope (−0.56 [CI −0.67, −0.42]) and SPO (0.55 [CI 0.42, 0.67]) with 6MWT distance have been found. Conclusions These findings highlight CPET parameters, particularly V̇E/V̇CO2 slope and SPO with a cut-off <28 W, as predictors of survival and HF-related hospitalization in cardiac amyloidosis.

Introduction: Patients with cardiac amyloidosis (CA) may have concomitant hypertension (HTN) that has an impact on their long-term mortality and morbidity. However, there is seldom evidence of HTN cardiovascular outcomes on CA. Hypothesis: We compared cardiovascular outcomes of HTN in patients with CA. Methodology: This retrospective cohort study using TriNetX Global Collaborative Network analyzed patients aged ≥18 years from 1/1/2007 to 5/25/2025. After 1:1 propensity score matching, cohort 1 CA + HTN (n=4,197), while cohort 2 CA-only (n=4,197) were formed. Study population mean age was 71 years (70% male, 28% female, 2% unknown sex). Primary and secondary outcomes evaluated were all-cause mortality, heart failure (HF), atrial fibrillation (AF), ventricular tachycardia (VT), and ventricular fibrillation (VF). We calculated odds ratio (OR), hazard ratio (HR), 95% confidence interval (CI) and p-value using TrinetX platform. Results: All-cause mortality was significantly lower in the CA+HTN group (26.8%) compared to the CA-only group (31.1%) with an OR of 0.811 (95% CI: 0.738–0.891), HR 0.671 (95% CI: 0.619–0.727), and p<0.0001. However, the CA+HTN group showed a higher incidence of HF (69.4% vs 57.4%; OR: 1.682, 95% CI: 1.538–1.840, HR: 1.163, 95% CI: 1.102–1.227, p<0.0001), AF (49.6% vs 38.9%; OR: 1.546, 95% CI: 1.417–1.686, HR: 1.180, 95% CI: 1.106–1.259, p<0.0001), and VT (13.8% vs 9.8%; OR: 1.484, 95% CI: 1.297–1.698, HR: 1.189, 95% CI: 1.047–1.349, p=0.0074). No significant difference was observed in VF (1.10% vs 1.12%; OR: 0.978, 95% CI: 0.650–1.473, HR: 0.800, 95% CI: 0.532–1.202, p=0.2814). Conclusion: Among patients with CA, coexisting HTN is associated with lower all-cause mortality and longer survival, possibly due to earlier detection and milder disease at diagnosis. However, these patients face a higher risk of HF and arrhythmias, such as AF and VT. HTN seems to have some degree of survival benefit when present with CA, though cardiovascular morbidity increases.

Background: ATTR-CA is associated with heart failure (HF) and premature death. It is diagnosed non-invasively with radionuclide imaging, most commonly using 99mTc-pyrophosphate (PYP). Recent advances in SPECT/CT offer potential for more precise quantification than planar imaging utilizing heart-to-contralateral (H/CL) ratio. We compare SPECT/CT-based metrics to H/CL in terms of prediction of HF hospitalization and correlation with echocardiographic (TTE) and laboratory abnormalities. Methods: All patients from 10/2023-10/2024 referred for PYP scans at Columbia University underwent SPECT/CT and planar imaging using an NM/CT 870 DR camera 3h after PYP injection. Positive scans were quantified by 2 board-certified nuclear cardiologists using Xeleris software (GE HealthCare, Milwaukee, WI). Readers selected the voxel with greatest PYP uptake. Regions of interest (ROIs) encompassing tracer uptake in the heart were generated. The reader selected a threshold to maximize heart activity and minimize bone activity. Standardized uptake values (SUV; LV radiotracer concentration normalized to body weight and injected dose), percent injected dose (%ID; proportion of injected radiotracer retained in the heart) and cardiac amyloid activity (CAA; total myocardial radiotracer burden appearing in the ROI) were determined. Mean and max SUV in the ROI (SUVmean, SUVmax) were determined. Clinical and TTE variables, from the most proximate TTE to PYP scanning, were acquired through chart review. Imaging variables were analyzed with respect to the clinical variables, and Cox hazards analysis of each quantitative variable, controlling for age and sex, predicted risk of hospitalization. Results: Of 333 patients, 43 with positive scans were included. When adjusted for age and sex, SUVmean, SUVmax, %ID, and CAA were significantly associated with hospitalization risk while H/CL was not. All quantitated variables were strongly correlated with TTE variables LVPW, IVS, and diastolic dysfunction, as well as with troponin T. Only %ID was significantly correlated with LVEF on TTE. Conclusion: Emerging quantitative SPECT/CT PYP variables were associated with significantly increased hospitalization risk in ATTR-CA patients, while H/CL was not. SPECT/CT variables were also associated with clinical variables such as LVEF, LV wall thickness and troponin T. These findings suggest that SPECT/CT quantification of PYP scans may better identify individuals at risk for hospitalization than planar imaging.

Abstract Aims Premature ventricular contractions (PVC) and non-sustained ventricular tachycardia (NSVT) are commonly observed in light chain cardiac amyloidosis (AL-CA), but their association with prognosis is still unclear. We aimed to evaluate the prognostic value of PVCs and NSVT in patients with moderate-to-advanced AL-CA. Methods and results We retrospectively included patients with AL-CA at modified 2004 Mayo stages II-IIIb between February 2014 and December 2020. Twenty-four-hour Holter recordings were assessed on admission. The outcomes included (i) new onset of adverse ventricular arrhythmia (VA) or sudden cardiac death (SCD) and (ii) cardiac death during follow-up. Of the 143 patients studied (60.41 ± 11.06 years, male 64.34%), 132 (92.31%) had presence of PVC, and 50 (34.97%) had NSVT on Holter. Twelve (8.4%) patients died in hospital and 131 patients were followed up (median 24.4 months), among whom 71 patients had cardiac death, and 15 underwent adverse VA/SCD. NSVT [hazard ratio (HR): 13.57, 95% confidence interval (CI): 3.06–60.18, P < 0.001], log-transformed PVC counts (HR: 1.46, 95%CI: 1.15–1.86, P = 0.002) and PVC burden (HR: 1.43 95%CI:1.14–1.80, P = 0.002) were predictive of new onset of adverse VA/SCD. The highest tertile of PVC counts (HR: 2.33, 95%CI: 1.27–4.28, P = 0.006) and PVC burden (HR: 2.58, 95%CI: 1.42–4.69, P = 0.002), rather than NSVT (HR: 1.16, 95%CI: 0.67–1.98, P = 0.603), was associated with cardiac death. Higher PVC counts/burden provided incremental value on modified 2004 Mayo stage in predicting cardiac death, with C index increasing from 0.681 to 0.712 and 0.717, respectively (P values <0.05). Conclusion PVC count, burden, and NSVT significantly correlated with adverse VA/SCD during follow-up in patients with AL-CA. Higher PVC counts/burdens added incremental value for predicting cardiac death.

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) affects all cardiac chambers to cause left ventricular (LV) deformation as well as left atrial (LA) remodeling and functional impairment. We investigated the associations of the LA volume index (LAVI):LV ejection fraction (LVEF) ratio with the increased risk of death, heart transplant, or LV assist device implantation (LVAD) in patients with ATTR-CM. Methods: This was a retrospective cohort study involving 69 heart failure (HF) patients with ATTR-CM at an academic medical center between 1 November 2008 and 31 March 2024. ATTR-CM was diagnosed using a technetium–diphosphonate/pyrophosphate scan or an endomyocardial biopsy. The LAVI and LVEF were measured by echocardiography. Cox proportional hazards models were used for the analysis. Results: The mean (SD) age of the participants was 77.5 (9.3) years. Over a median (IQR) follow-up period of 1.96 (0.67–2.82) years, we observed 24 composite events that included twenty-two deaths, two heart transplants, and two LVAD implantations (who subsequently died). In multivariable-adjusted analyses that accounted for age and the glomerular filtration rate, a one-unit increase in the LAVI:LVEF ratio was associated with a doubling of the risk (HR, 95% CI: 2.06, 1.11–3.82) of experiencing the composite outcome. Conclusions: A one-unit increase in the LAVI:LVEF ratio was associated with an increased risk of death, heart transplant, or LVAD implantation in patients with ATTR-CM.

AIMS To investigate the prognostic value of the right ventricle-to-pulmonary artery (RV-PA) coupling in patients with either transthyretin (ATTR) or immunoglobulin light-chain (AL) cardiac amyloidosis (CA). METHODS AND RESULTS Overall, 283 patients with CA from 3 Italian high-volume centres were included (median age 76 years; 63% males; 53% with ATTR-CA, 47% with AL-CA). The RV-PA coupling was evaluated through tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio. The median value of TAPSE/PASP was 0.45 (0.33-0.63) mm/mmHg. Patients with a TAPSE/PASP ratio <0.45 were older, had lower systolic blood pressure, more severe symptoms, higher cardiac troponin and NT-proBNP levels, greater left ventricular (LV) thickness, and worse LV systolic and diastolic function. A TAPSE/PASP ratio <0.45 was independently associated with a higher risk of all-cause death or HF hospitalization (hazard ratio [HR], 1.98; 95% confidence interval [CI], 1.32-2.96; p = 0.001) and all-cause death (HR 2.18; 95% CI, 1.31-3.62; p = 0.003). The TAPSE/PASP ratio reclassified the risk of both endpoints (net reclassification index 0.46 [95%CI 0.18-0.74], p = 0.001, and 0.49 [0.22-0.77] p < 0.001, respectively), while TAPSE or PASP alone did not (all p > 0.05). The prognostic impact of TAPSE/PASP ratio was significant both in AL-CA patients (HR for the composite endpoint 2.47, 95% CI 1.58-3.85; p < 0.001) and in ATTR-CA (HR 1.81, 95% CI 1.11-2.95; p = 0.017). Receiver operating characteristic curve showed that the optimal cut-off for predicting prognosis was 0.47 mm/mmHg. CONCLUSION In patients with CA, RV-PA coupling predicted the risk of mortality or HF hospitalization. TAPSE/PASP ratio had a better performance than TAPSE or PASP in predicting prognosis.

Transthyretin cardiac amyloidosis (ATTR-CA) is increasingly recognized as a major cause of heart failure, particularly in elderly patients. 99mTc-pyrophosphate (PYP) imaging is widely used as a noninvasive diagnostic tool; however, its prognostic significance remains unclear. Furthermore, myocardial PYP uptake has been documented in other cardiomyopathies, including Amyloid light-chain amyloidosis, hypertrophic cardiomyopathy, and high-risk coronary artery disease. The present study aimed to evaluate the prognostic value of myocardial PYP uptake in patients with suspected ATTR-CA. A retrospective cohort study was conducted on 301 consecutive patients who underwent PYP imaging for suspected ATTR-CA from July 2015 to February 2023. Myocardial PYP uptake was assessed using the Perugini classification (grades 0–3) and the heart-to-contralateral lung (H/CL) ratio. The primary outcome was a composite of cardiac death or fatal ventricular arrhythmias, including ventricular fibrillation (VF) and sustained ventricular tachycardia (VT). Prognostic significance was evaluated using Kaplan-Meier analysis and Cox proportional hazards regression. The median H/CL ratio at 3 hours was 1.25 (interquartile range, 1.16–1.40), and 90 patients (30%) exhibited positive PYP uptake. During a median follow-up of 660 days (interquartile range, 183–863 days), 36 patients (12.0%) died, including 13 cardiac deaths (4.3%). Furthermore, fatal ventricular arrhythmias were documented in six patients, including two cases of aborted VF and four instances of sustained VT. Kaplan-Meier analysis revealed that patients with an H/CL ratio ≥1.25 exhibited a significantly higher incidence of the primary outcome compared to those with a lower ratio (P=0.003). Similarly, patients with positive PYP SPECT at 3 hours also demonstrated a significantly higher incidence of the primary outcome (P=0.017). Conversely, all-cause mortality did not exhibit a significant difference between the various H/CL ratio groups (P=0.065) or the PYP SPECT positivity groups (P=0.36). Multivariable Cox proportional hazards regression analysis demonstrated that both a higher H/CL ratio (P=0.018) and PYP SPECT positivity (P=0.007) were independent predictors of the primary outcome and cardiac death in patients with suspected ATTR-CA. Significant myocardial PYP uptake was associated with an increased risk of adverse cardiovascular events in patients with suspected ATTR-CA. The findings of this study suggest that PYP imaging may be useful not only for diagnosing ATTR-CA but also for risk stratification in patients with suspected ATTR-CA, including those with other cardiomyopathies.primary endpoint(cardiac death or VT/VF)  All-cause death

AIMS In cardiac amyloidosis (CA), transthyretin-related (ATTR) CA is reported to have more microcalcifications in the interventricular septum (IVS) than other subtypes. This study investigates whether IVS microcalcifications can differentiate CA subtypes. METHODS AND RESULTS A total of 442 patients with CA were enrolled at 18 collaborating institutions of the Japan Cardiac Amyloidosis Survey of typical Echocardiographic findings (J-CASE) Study: 139 light chain/amyloid A (AL/AA) type, 255 wild type ATTR (ATTRwt), 48 variant ATTR (ATTRv), and 19 patients with hypertensive heart disease (HHD). Echocardiographic pixel brightness quantification of the IVS was performed using public domain software. The IVS brightness index (IVSBI) was defined as the ratio of the average pixel brightness in the IVS to the opposite left ventricular (LV) wall. The IVSBI from the apical 4-chamber view was higher in both the ATTRwt group (median 1.40, IQR 1.22 to 1.67) and the ATTRv group (1.59, 1.32 to 2.00) compared to the HHD group (1.20, 1.02 to 1.37) and the AL/AA group (1.25, 1.11 to 1.46), respectively (P < 0.05). In the Cox proportional hazards analysis, a 0.5 increase in IVSBI from the apical 4-chamber view was associated with a hazard ratio of 2.54 (95 % CI: 1.42-4.56, P = 0.002) for all-cause mortality in ATTRwt-CA (n = 157), adjusted for age, gender, LVEF, and National Amyloidosis Centre staging. CONCLUSION An IVSBI obtained from the apical 4-chamber view may be useful in distinguishing ATTR-CA from other forms of CA, potentially identifying subtle septal calcifications. Elevated IVSBI in ATTRwt-CA may have prognostic value.

BACKGROUND Although the relative apical sparing (RAPS) pattern of left ventricular (LV) longitudinal strain is a hallmark of cardiac amyloidosis, recent studies have raised concerns about its accuracy. The aim of this systematic review was to investigate diagnostic test accuracy (DTA) and prognostic impact of RAPS in cardiac amyloidosis. METHODS AND RESULTS We searched PubMed, Embase, and Scopus for manuscripts that could potentially be used in the DTA arm and prognosis arm. Thirty-seven studies were used for DTA analysis. The pooled sensitivity, specificity, and diagnostic odds ratio were 61% (95% confidence interval [CI] 54-68%), 83% (95% CI 80-86%), and 8.9 (95% CI 6.1-13.1), respectively. These values did not differ regardless of the presence of aortic stenosis, but the diagnostic odds ratio differed significantly among analytical software packages. For the prognosis arm, 6 studies were dichotomously assessed for RAPS, and 5 were assessed quantitatively. The pooled proportion of RAPS was 49% and the pooled estimate of the RAPS ratio was 1.40. Although RAPS was associated with outcome (hazard ratio [HR] 1.87; 95% CI 1.15-3.04; P=0.011), its significance disappeared after trim and fill analysis (HR 1.42; 95% CI 0.85-2.38; P=0.184). CONCLUSIONS RAPS has a modest DTA with a significant vendor dependency and does not provide robust prognostic information.

BACKGROUND Current echocardiographic risk factors for prognosis in cardiac amyloidosis (CA) do not distinguish between the two main subtypes: transthyretin cardiomyopathy (TTR) and immunoglobulin light chain cardiomyopathy (AL), each of which require distinct diagnostic and therapeutic approaches. Additionally, only traditional parameters have been studied with little data on advanced techniques. Accordingly, we sought to determine whether differences exist in 2D transthoracic echocardiography (2DE) predictors of survival between the CA subtypes using a comprehensive approach. METHODS 220 patients (72±12 years) with confirmed CA (AL=89, TTR=131) who underwent 2DE at the time of CA diagnosis were enrolled. Left ventricular (LV) dimensions, indexed mass (LVMi), global longitudinal strain (LVGLS), apical-sparing ratio (LVASR), diastology, right ventricular (RV) size and function indices including tricuspid annular systolic excursion (TAPSE), RV free-wall (RVFWS) and global (RVGLS) strain, indexed left (LA) and right atrial volumes (LAVi and RAVi), LA strain (reservoir and booster) and RV systolic pressure (RVSP) were measured. A propensity-score weighted stepwise variable selection Cox proportional hazards model derived from NYHA class and renal impairment status at diagnosis was used to determine the associations between 2DE parameters and mortality specific to CA subtype over a median follow-up of 36-months. RESULTS After adjusting for age, atrial fibrillation and treatment, parameters associated with survival were RVFWS (p=0.003, HR 1.15, 95% CI[1.053,1.245]) and RVSP (p=0.03, HR 1.03, 95% CI[1.004,1.063]) in AL and LVASR (p=0.007, HR 6.68, 95% CI[1.75,25.492]) and RAVi (p=0.049, HR 1.03, 95% CI[1.000,1.052]) in TTR. CONCLUSIONS Echocardiographic prognosticators for survival are specific to cardiac amyloid subtype. These results potentially provide information critical for clinical decision-making and follow-up in these patients.

Aims T1 mapping on cardiac magnetic resonance (CMR) imaging is useful for diagnosis and prognostication in patients with light-chain cardiac amyloidosis (AL-CA). We conducted this study to evaluate the performance of T1 mapping parameters, derived from artificial intelligence (AI)-automated segmentation, for detection of cardiac amyloidosis (CA) in patients with left ventricular hypertrophy (LVH) and their prognostic values in patients with AL-CA. Methods and results A total of 300 consecutive patients who underwent CMR for differential diagnosis of LVH were analyzed. CA was confirmed in 50 patients (39 with AL-CA and 11 with transthyretin amyloidosis), hypertrophic cardiomyopathy in 198, hypertensive heart disease in 47, and Fabry disease in 5. A semi-automated deep learning algorithm (Myomics-Q) was used for the analysis of the CMR images. The optimal cutoff extracellular volume fraction (ECV) for the differentiation of CA from other etiologies was 33.6% (diagnostic accuracy 85.6%). The automated ECV measurement showed a significant prognostic value for a composite of cardiovascular death and heart failure hospitalization in patients with AL-CA (revised Mayo stage III or IV) (adjusted hazard ratio 4.247 for ECV ≥40%, 95% confidence interval 1.215–14.851, p-value = 0.024). Incorporation of automated ECV measurement into the revised Mayo staging system resulted in better risk stratification (integrated discrimination index 27.9%, p = 0.013; categorical net reclassification index 13.8%, p = 0.007). Conclusions T1 mapping on CMR imaging, derived from AI-automated segmentation, not only allows for improved diagnosis of CA from other etiologies of LVH, but also provides significant prognostic value in patients with AL-CA.

In the subtypes of cardiac amyloidosis (CA), transthyretin-related (ATTR) CA has been reported to exhibit a higher prevalence of microcalcifications in the interventricular septum (IVS) compared to other subtypes. Whether microcalcifications in the IVS can stratify CA subtypes remains unclear. A total of 442 patients with CA: 76 light chain/ amyloid A (AL/AA) type; 255 wild type ATTR (ATTRwt) and 48 variant ATTR (ATTRv) and 19 patients with endomyocardial biopsy-confirmed hypertensive heart disease (HHD) were subjected to echocardiographic pixel brightness quantification of the IVS using open-access image analysis software. The IVS Brightness Index (IVSBI) was defined as the ratio of the average pixel brightness in the IVS to that in the left ventricular (LV) wall opposite the IVS (see figure 1). The IVSBI from apical 4-chamber view was higher in both the ATTRwt group (median 1.40, IQR 1.22 to 1.67) and the ATTRv group (1.59, 1.32 to 2.00) compared to the HHD group (1.20, 1.02 to 1.37) and the AL/AA group (1.25, 1.11 to 1.46), respectively (P <0.001, see figure 2). In the 273 CA patients undergoing myocardial technetium-99m-pyrophosphate scintigraphy, patients with positive results (1.41, 1.24 to 1.70) exhibited a higher IVSBI compared to those with negative (1.19, 1.09 to 1.46) (P = 0.006). In Cox proportional hazards analysis, age, gender and LV ejection fraction adjusted hazard ratio for the all-cause death of IVSBI (0.5 increase) was 2.0 (95% CI 1.2 to 3.5, P = 0.012) among ATTRwt patients (n=157). An IVSBI obtained from the apical 4-chamber view could prove valuable in differentiating ATTR subtypes in CA, potentially revealing subtle septal calcifications. A prognostic value may be derived from the elevation of IVSBI in ATTRwt patients.figure 1figure 2

No abstract available

AIMS To investigate whether left arterial reservoir strain (LASr) could predict new-onset atrial fibrillation (NOAF) in patients with light-chain-type cardiac amyloidosis (ALCA). METHODS AND RESULTS This study enrolled 427 patients with CA from two tertiary centres between 2005 and 2019. LASr was measured using a vendor-independent analysis programme. The primary outcome was NOAF. A total of 287 patients with ALCA were included [median age 63.0 (56.0-70.0) years, 53.3% male]. The median LASr was 13.9% (10.5-20.8%). During the median follow-up of 0.85 years, AF occurred in 34 patients (11.8%). In the receiver operating characteristics curve analysis, the optimal cut-off of LASr for predicting NOAF was 14.4%. Patients with LASr ≤14.4% had a higher risk of NOAF than those with LASr >14.4% (18.1% vs. 5.1%, P < 0.010). In the multivariate analysis adjusting for confounding factors, including left arterial volume index and left ventricular global longitudinal strain (LV-GLS), higher LASr (%) was independently associated with lower risk for NOAF [adjusted hazard ratio (aHR): 0.936, 95% confidence interval (95% CI): 0.879-0.997, P = 0.039]. Furthermore, LASr ≤14.4% was an independent predictor for NOAF (aHR: 3.370, 95% CI: 1.337-8.492, P = 0.010). This remained true after accounting for all-cause death as a competing risk. Compared with Model 1 (LV-GLS) and Model 2 (LV-GLS plus LAVI), Model 3, including LASr showed a better reclassification ability for predicting NOAF (net reclassification index = 0.735, P < 0.001 compared with Model 1; net reclassification index = 0.514, P = 0.003 compared with Model 2). CONCLUSION LASr was an independent predictor of NOAF in patients with ALCA.

BACKGROUND Patients with left ventricular hypertrophy (LVH) often maintain preserved left ventricular ejection fraction in the early stages of the disease. There is a need to identify simple and reliable variables beyond left ventricular ejection fraction to recognize those at risk of developing adverse clinical outcomes. AIMS To examine left atrial (LA) strain in patients with hypertrophic cardiomyopathy (HCM), cardiac amyloidosis (CA) and Fabry disease (FD), pathologies known to cause LVH, and the relationship between LA strain and adverse clinical outcomes. METHODS In this retrospective cohort study, LA strain was measured and compared among patients with HCM, CA and FD. Relationships between LA and left ventricular strain, and LA strain and adverse cardiovascular events were evaluated. The primary outcome was first occurrence of cardiovascular mortality, device implantation, heart failure hospitalization, new-onset atrial fibrillation or stroke. RESULTS A total of 191 patients were included (24 with FD, 87 with HCM, 80 with CA). LA reservoir strain was highest in patients with HCM (26%, interquartile range [IQR] 20%, 32%), followed by those with FD (20.5%, IQR: 14%, 27.8%) and CA (11%, IQR: 7%, 18.8%) (P<0.001). LA strain correlated well with left ventricular strain in patients with LVH, with CA showing the best correlation (r=-0.70, 95% confidence interval [95% CI]: -0.80 to -0.56; P<0.001). Multivariable Cox regression analysis showed that LA reservoir strain was significantly associated with the primary outcome in all patients (hazard ratio: 0.91, 95% CI: 0.84 to 0.99; P=0.03) and in those with CA (hazard ratio: 0.90, 95% CI: 0.82 to 0.99; P=0.023). CONCLUSIONS LA strain was more reduced in CA than in FD and HCM, probably as a result of atrial wall infiltration, and was associated with adverse clinical outcomes in our heterogenous LVH population and patients with CA.

Background Diagnostic rates of transthyretin cardiac amyloidosis have increased due to growing awareness, noninvasive diagnoses, and treatments that improve morbidity and mortality. We sought to investigate real‐world trends in baseline characteristics and survival in the United States. Methods Patient‐level data at 5 cardiac amyloid referral centers were used, and mortality (defined as death or surgical heart failure therapies) was compared by eras (pre‐2010, 2010–2013, 2014–2017, and 2018–2021) and National Amyloidosis Center (NAC) stage. Results Among 1165 subjects, diagnosis of transthyretin cardiac amyloidosis in a more recent era was associated with older age, white race, wild‐type disease, and tafamidis treatment (P<0.001). NAC stage was similar (P=0.866) while Columbia stage was lower (P=0.006) in recent eras, driven by lower New York Heart Association class and loop diuretic dose. Over a median follow‐up of 44.5 (interquartile range, 21–60) months, 630 subjects died, and diagnosis in a more recent era was associated with a lower mortality. Tafamidis was protective (hazard ratio [HR], 0.71; P=0.002), and NAC stage >1 portended an increased risk of death (stage 2: HR, 2.00; P<0.001; stage 3: HR, 4.02; P<0.001). There were interactions between tafamidis and both NAC stage and age, suggesting that the beneficial effects of tafamidis were attenuated at higher NAC stages (stage 2: P=0.041; stage 3: P=0.012) and older age (P=0.001). Conclusions In this multicenter study of patients seen at referral centers for transthyretin cardiac amyloidosis, diagnosis in a more recent era was associated with improved survival, while tafamidis benefits were attenuated by disease severity and older age. Significant residual mortality risk remains in treated patients at higher disease stages.

AIMS To evaluate the prognostic effect of a novel index by two-dimensional speckle-tracking echocardiography (STREI index) integrating right atrial (RA) and right ventricular (RV) strain in patients with immunoglobulin light chain (AL) cardiac amyloidosis. METHODS Ninety patients were diagnosed with AL amyloidosis at Kumamoto University Hospital from 2007 to 2022. Among these patients, 70 with evidence of cardiac amyloidosis and sufficient echocardiographic data at diagnosis, including RA and RV strain analysis, were retrospectively analysed. The STREI index was developed with the following formula: [2 × RV - free wall longitudinal strain (RV - FWLS) + RA strain during the reservoir phase]. RESULTS During a median follow-up of 854 days (interquartile range, 151-1787 days), 33 deaths occurred. The STREI index was significantly lower in the all-cause death group than in the survival group (40.5 ± 19.9 vs. 57.7 ± 18.9, p < 0.01). The STREI index was significantly and independently associated with all-cause death after adjusting for left ventricular global longitudinal strain and left atrial strain during the reservoir phase (hazard ratio: 0.96, 95 % confidence interval: 0.93-0.98, p < 0.01). The optimal cut-off value was an STREI index of 50 % (sensitivity: 78 %, specificity: 72 %, area under curve: 0.80) to predict all-cause mortality using receiver operating characteristic analysis. A Kaplan-Meier analysis showed a significantly higher risk of all-cause death and cardiovascular death in patients with a low STREI index (<50 %, n = 32) than in those with a high STREI index (≥50 %, n = 38) (both p < 0.01). CONCLUSIONS The STREI index, which is a new index of total right heart function, might be useful for predicting the prognosis in patients with AL cardiac amyloidosis.

Cardiac amyloidosis (CA) is associated with several distinct electrocardiographic (ECG) changes. However, the impact of amyloid depositions on ECG parameters is not well investigated. We therefore aimed to assess the correlation of amyloid burden with ECG and test the prognostic power of ECG findings on outcomes in patients with CA. Consecutive CA patients underwent ECG assessment and cardiac magnetic resonance imaging (CMR), including the quantification of extracellular volume (ECV) with T1 mapping. Moreover, seven patients underwent additional amyloid quantification using immunohistochemistry staining of endomyocardial biopsies. A total of 105 CA patients (wild-type transthyretin: 74.3%, variant transthyretin: 8.6%, light chain: 17.1%) were analyzed for this study. We detected correlations of total QRS voltage with histologically quantified amyloid burden (r = −0.780, p = 0.039) and ECV (r = −0.266, p = 0.006). In patients above the ECV median (43.9%), PR intervals were significantly longer (p = 0.016) and left anterior fascicular blocks were more prevalent (p = 0.025). In our survival analysis, neither Kaplan–Meier curves (p = 0.996) nor Cox regression analysis detected associations of QRS voltage with adverse patient outcomes (hazard ratio: 0.995, p = 0.265). The present study demonstrated that an increased amyloid burden is associated with lower voltages in CA patients. However, baseline ECG findings, including QRS voltage, were not associated with adverse outcomes.

Background: Cardiac amyloidosis (CA) is a progressive infiltrative cardiomyopathy associated with poor prognosis. CA is commonly due to transthyretin (ATTR) or light chain (AL) amyloid deposition. Tricuspid regurgitation (TR) is a common echocardiographic finding in CA; however, its prognostic relevance remains unclear. We aimed to evaluate the association between TR severity and clinical outcomes in patients with CA. Methods: We conducted a retrospective cohort study of adults with CA referred to a specialized Cardiac Amyloidosis Clinic between January 2014-April 2024. TR severity was assessed by transthoracic echocardiography completed within 6 months of CA diagnosis and categorized as less-than-moderate versus moderate or greater. Multivariable Cox proportional hazards models were used to evaluate the association between TR severity and survival, adjusting for baseline characteristics including age, New York Heart Association (NYHA) class, estimated glomerular filtration rate (eGFR), natriuretic peptide levels (BNP or NT-proBNP), and disease stage. Results: Among 416 patients (mean age 64.8 years, 27% AL subtype), ≥moderateTR was present in 69 (16.6%). Compared to those <moderate TR, patients with ≥moderate TR were significantly older (76.8 vs 62.4 years, P = 0.016), had lower LVEF (46.7% vs 54.4%, P < 0.0001), higher pulmonary artery systolic pressure (PASP 45.3 mmHg vs 35.7 mmHg, P < 0.0001), and worse renal function (eGFR 55.4 vs 61.5 mL/min/m2, P = 0.027). ≥moderate TR was also associated with qualitatively more severe right ventricular dysfunction (P < 0.0001), RV dilation (incidence 49.3% vs 19.3%, P < 0.0001), and worse NYHA class (P = 0.0017). No significant associations were observed with sex, natriuretic peptide levels, troponin, amyloid subtype, or National Amyloidosis Centre stage (ATTR only). Patients with ≥moderate TR had significantly reduced survival following diagnosis (median 3.2 vs 5.4 years; log-rank P < 0.0001) (Figure 1). In adjusted Cox models, TR remained independently associated with mortality in the overall cohort (hazard ratio (HR) 1.84, P<0.0001), ATTR subgroup (HR 1.77, P = 0.0023), and AL subgroup (HR 2.18, P <0.0001). Conclusion: ≥moderateTR is independently associated with worse survival in patients with CA, regardless of amyloid subtype. These findings support routine TR severity assessment for risk stratification and to identify individuals who may benefit from closer follow-up or tailored interventions.

Background The prognostic significance of dynamic changes in soluble suppression of tumorigenicity‐2 (sST2) in patients with light chain cardiac amyloidosis (AL‐CA) remains unclear. We aimed to evaluate the prognostic significance of both baseline sST2 and 30‐day changes (ΔsST2) in patients with light chain cardiac amyloidosis. Methods Patients diagnosed with light chain cardiac amyloidosis in Heart Failure Center, Fuwai Hospital (October 2015–May 2024) were enrolled in the entire cohort, with baseline sST2 measured. A prospective subcohort (October 2023–May 2024) also underwent 30‐day repeat sST2 measurement. ΔsST2 was defined as the sST2 level at 30 days minus baseline sST2. The primary outcome was all‐cause mortality. Prognostic value of both baseline and ΔsST2 was assessed using Kaplan–Meier and Cox models. The relationships between variables and primary outcome were examined with restricted cubic splines. Results In the entire cohort with 172 patients included (mean age 60.35±10.21 years; 40.1% women; median follow‐up 310 days), higher baseline sST2 levels (>35 ng/mL) were independently associated with increased all‐cause mortality risk (adjusted hazard ratio [HR], 1.82 [95% CI, 1.13–2.91], P<0.05). A non‐linear association was observed, with risk increasing initially and flattening at higher levels. Among 70 patients in the prospective cohort, 17 primary outcome events occurred. Patients experiencing these events exhibited higher ΔsST2 levels (166.06 [64.37 to 277.03] ng/mL versus 8.37 [−3.08 to 55.83] ng/mL). High ΔsST2 level (>18 ng/mL) was also an independent indicator of worse prognosis (adjusted HR, 9.87 [95% CI, 1.90–51.11], P<0.01). Conclusions Elevated baseline sST2 (>35 ng/mL) and short‐term increases in sST2 predict poor prognosis in patients with light chain cardiac amyloidosis.

Cardiac amyloidosis (CA) is associated with a high mortality rate due to sudden or progressive heart failure. The two most common amyloid subtypes are light-chain (AL) and transthyretin (ATTR) amyloidosis both of which are often misdiagnosed. Early detection and risk stratification remain crucial for optimising patient outcomes, yet comprehensive data on clinical predictors of disease progression and adverse outcomes remain limited. To describe incidence rates and risk factors for all-cause mortality in patients coded to have CA in the UK clinical setting using electronic health records. In this retrospective observational study, anonymised, linked primary and secondary care data (Clinical Practice Research Datalink, Hospital Episode Statistics, and death registrations) were used to describe individuals newly diagnosed with CA. Patients aged 18 years and older with primary care diagnosis records (SNOMED-CT/Read codes) combined with secondary care diagnosis (ICD-10: E85.x coinciding with cardiology codes) in the period between January 2004 to March 2021 were included. The primary outcome was all-cause mortality (ACM), described using crude event rates (per 1,000 person-years, PY) and analysed using Cox proportional hazards models. Demographic and clinical data were summarised using descriptive statistics. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated to account for risks of ACM. A total of 3,215 patients with CA were identified, with an average age of 71 years; 62% were male. AL amyloidosis was the predominant subtype (66%), while 34% had ATTR amyloidosis. Over a median follow-up of 9,475 PY, 1,622 (50%) patients died of any cause (crude event rate: 171 per 1000 PY). ACM incidence rates varied by ethnicity, with highest rates observed in the Black (232 per 1000 PY), followed by White (181 per 1000 PY) ethnic group. (Figure) Among the independent risk factors identified, the strongest predictors of ACM (HR >1.5) included age 85+ years (1.7), SBP <90 mmHg (1.9), eGFR 15-30 mL/min/1.73m2 (1.5), haematocrit 10-20% (25), serum monoclonal protein >10 g/L (from 2.1), severe thrombocytopenia (5), alkaline phosphatase >600 IU/L (2.4) and the presence of heart failure (2.1) and nephrotic syndrome (1.6). (Table) Mortality among patients coded to have CA is high. A key limitation of existing coding practices is that AL and ATTR amyloidosis, which are distinct conditions, cannot be distinguished. The incidence rate of all-cause mortality was highest in Black patients with CA. This study confirmed known risk factors for all-cause mortality in CA, aligning with previous reports and underscores the need for better coding practice to inform risk stratification and clinical decisions.Table  Figure

Cardiac amyloidosis (CA), including light chain (AL), hereditary transthyretin (ATTRv), and wild-type transthyretin (ATTRwt), leads to heart failure (HF). Cardiologists use the ESC guidelines to classify patients with HF based on left ventricular ejection fraction (LVEF): reduced (≤40%; HFREF), moderately reduced (41–49%; HFmrEF), and preserved (≥50%; HFPEF), tailoring HF treatment accordingly. CA is commonly associated with HFpEF, with a smaller proportion presenting with HFmrEF and HFrEF. This study aimed to assess the distribution of HF types in CA and their relationship with other left ventricular (LV) systolic function parameters such as global longitudinal strain (GLS) and cardiac index (CI) across amyloidosis subtypes. We retrospectively included symptomatic AL, ATTRv, and ATTRwt CA patients from our French referral center. LVEF was classified per ESC guidelines and compared to GLS and CI. Survival was assessed using Kaplan-Meier analyses and Cox regression. A decision tree incorporating LVEF, GLS, and CI was used to stratify patients into prognostic groups. Among 2244 patients, 557 had AL, 392 had ATTRv, 1137 had ATTRwt, and 158 were ATTR being genotyped. Of these, 61.4% presented with HFpEF, 19.0% with HFmrEF, and 19.6% with HFrEF. In AL, 13.6%, 18%, and 68.4% were classified as HFrEF, HFmrEF, and HFpEF, respectively. In ATTRv, 28.3%, 15.3%, and 56.4% were HFrEF, HFmrEF, and HFpEF, respectively. In ATTRwt, 20.2%, 21.2%, and 58.6% were HFrEF, HFmrEF, and HFpEF, respectively. LVEF correlated moderately with GLS (r = 0.673), with stronger correlations in ATTRv (r = 0.776) compared to AL (r = 0.650) and ATTRwt (r = 0.644). LVEF correlated weakly with CI (r = 0.392). Median survival was 7 months [3–31] for AL, 28 months [12–54] for ATTRv, and 23 months [10–38] for ATTRwt. Survival differed by HF type: 30 months [18–41] for HFrEF, 40 months [20–42] for HFmrEF, and 51% survival at 48 months for HFpEF. Among patients with GLS ≤8.2%, median survival was 34 months [25–39], while those with GLS >14% had 71% survival at 48 months. A CI ≤1.96 L/min/m² was associated with a median survival of 29 months [17–37], with better outcomes in higher CI quartiles. A decision tree identified four prognostic groups, with hazard ratios for 4-year mortality ranging from 1.63 (LVEF ≥50%, GLS ≤11%) to 3.68 (LVEF ≤49%, CI ≤1.96 L/min/m²), reaching 12.34 in AL amyloidosis for the most severe group. In CA, about 40% of patients present with reduced LVEF. Cardiologists should be aware that CA is not exclusively associated with HFpEF and that patients with reduced LVEF have worse prognosis. LV systolic function, assessed via LVEF, GLS, and CI, is a critical predictor of survival in CA, with distinct patterns across AL, ATTRv, and ATTRwt subtypes. Combining these parameters provides a robust prognostic tool for personalized management and treatment of CA.