BACKGROUND Differential diagnosis of genetic causes of left ventricular hypertrophy (LVH) is crucial for disease-specific therapy. We aim to describe the prevalence of Cardiac Amyloidosis (CA) among patients ≥40 years with an initial diagnosis of HCM referred for second opinion to national cardiomyopathy centres. METHODS Consecutive patients aged ≥40 years referred with a tentative HCM diagnosis in the period 2014-2017 underwent clinical evaluation and genetic testing for HCM (including trans-thyretin-TTR). Patients with at least one red flag for CA underwent blood/urine tests, abdominal fat biopsy and/or bone-scintigraphy tracing and eventually ApoAI sequencing. RESULTS Out of 343 patients (age 60 ± 13 years), 251 (73%) carried a likely/pathogenic gene variant, including 12 (3.5%) in the CA-associated genes TTR (n = 11) and ApoAI (n = 1). Furthermore, 6 (2%) patients had a mutation in GLA. Among the remaining, mutation-negative patients, 26 with ≥1 CA red-flag were investigated further: 3 AL-CA and 17 wild-type-TTR-CA were identified. Ultimately, 32(9%) patients were diagnosed with CA. Prevalence of CA increased with age: 1/75 (1%) at age 40-49, 2/86 (2%) at age 50-59, 8/84 (9%) at age 60-69, 13/61 (21%) at age 70-79, 8/31 (26%) at age ≥80 (p for trend <0.01). CONCLUSIONS Among patients referred with and initial diagnosis of HCM, CA was the most common unrecognized mimic (9% prevalence) and increased with age (from 1% at ages 40-49 years to 26% >80 years). Age at diagnosis should be considered one of the most relevant red flags for CA in patients with HCM phenotypes; however, there is no clear age cut-off mandating scintigraphy and other second level investigations in the absence of other features suggestive of CA.

中文翻译：

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转诊至三级中心且初步诊断为肥厚型心肌病的成年患者中，心脏淀粉样变性的患病率。

背景技术左心室肥大（LVH）遗传原因的鉴别诊断对于疾病特异性治疗至关重要。我们的目的是描述≥40岁，最初诊断为HCM并已转介给国家心肌病中心的HCM患者中的心脏淀粉样变性（CA）患病率。方法在2014-2017年间连续进行HCM诊断的≥40岁连续患者接受了HCM的临床评估和基因检测（包括甲状腺素TTR）。至少有一个红色CA标志的患者接受了血液/尿液检查，腹部脂肪活检和/或骨闪烁描记术，并最终进行了ApoAI测序。结果在343名患者（年龄60±13岁）中，有251名（73％）携带了可能/致病基因变异，包括12种（3.5％）与CA相关的基因TTR（n = 11）和ApoAI（n = 1） ）。此外，有6名（2％）患者的GLA有突变。在其余的突变阴性患者中，进一步调查了26例≥1 CA红旗的患者：3例AL-CA和17例野生型TTR-CA。最终，有32名（9％）患者被诊断出患有CA。CA的患病率随年龄增长而增加：40-49岁时为1/75（1％），50-59岁时为2/86（2％），60-69岁时为8/84（9％），13/61（ 70-79岁时为21％），≥80岁时为8/31（26％）（趋势<0.01）。结论在接受HCM诊治和初次诊断的患者中，CA是最常见的无法识别的模仿对象（患病率为9％），并且随着年龄的增长而增加（从40-49岁时的1％增至> 80岁时的26％）。在HCM表型患者中，诊断时的年龄应被视为与CA最相关的危险信号之一。然而，