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Aims Cardiomyopathies comprise a heterogeneous group of diseases, often of genetic origin. We assessed the current practice of genetic counselling and testing in the prospective European Society of Cardiology EURObservational Research Programme Cardiomyopathy Registry. Methods and results A total of 3208 adult patients from 69 centres in 18 countries were enrolled. Genetic counselling was performed in 60.8% of all patients [75.4% in hypertrophic cardiomyopathy (HCM), 39.2% in dilated cardiomyopathy (DCM), 70.8% in arrhythmogenic right ventricular cardiomyopathy (ARVC), and 49.2% in restrictive cardiomyopathy (RCM),P < 0.001]. Comparing European geographical areas, genetic counselling was performed from 42.4% to 83.3% (P < 0.001). It was provided by a cardiologist (85.3%), geneticist (15.1%), genetic counsellor (11.3%), or a nurse (7.5%) (P < 0.001). Genetic testing was performed in 37.3% of all patients (48.8% in HCM, 18.6% in DCM, 55.6% in ARVC, and 43.6% in RCM,P < 0.001). Index patients with genetic testing were younger at diagnosis and had more familial disease, family history of sudden cardiac death, or implanted cardioverter defibrillators but less co-morbidities than those not tested (P < 0.001 for each comparison). At least one disease-causing variant was found in 41.7% of index patients with genetic testing (43.3% in HCM, 33.3% in DCM, 51.4% in ARVC, and 42.9% in RCM,P = 0.13). Conclusions This is the first detailed report on the real-life practice of genetic counselling and testing in cardiomyopathies in Europe. Genetic counselling and testing were performed in a substantial proportion of patients but less often than recommended by European guidelines and much less in DCM than in HCM and ARVC, despite evidence for genetic background., This work was supported by Abbott Vascular International (2011-2021), Amgen Cardiovascular (2009-2018), AstraZeneca (2014-2021), Bayer AG (2009-2018), Boehringer Ingelheim (2009-2019), Boston Scientific (2009-2012), The Bristol Myers Squibb and Pfizer Alliance (2011-2019), Daiichi Sankyo Europe GmbH (2011-2020), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2014-2017), Edwards (2016-2019), Gedeon Richter Plc. (2014-2016), Menarini Int. Op. (2009-2012), MSD-Merck & Co. (2011-2014), Novartis Pharma AG (2014-2020), ResMed (2014-2016), Sanofi (2009-2011), Servier (2009-2021), and Vifor (2019-2022). Funders had no role in the study design, data analyses, and manuscript drafting.

Aims: Cardiac amyloidosis remains a great challenge for the cardiologist. One of the three main aetiological forms, transthyretin-related hereditary amyloidosis (ATTRm), can present with several phenotypes, depending mainly on the specific mutation. We aimed to characterize the phenotype of patients with ATTRm due to Ile68Leu mutation, comparing them to patients with wild-type transthyretin amyloidosis (ATTRwt). Methods and results: Data of 67 Ile68Leu ATTRm patients from two Italian referral centres (Bologna and Florence) were retrospectively analysed and compared to those of 82 ATTRwt patients. Fifty-five unaffected mutation carriers were also analysed. Cumulative disease onset was 50% at age 71. A total of 56/67 (84%) patients had a predominantly cardiac phenotype at presentation with concentric increase in left ventricular wall thickness [median 17 mm], and normal or near normal left ventricular ejection fraction (79% of patients). Low QRS voltages were present only in 29% of patients but voltage/mass ratio was low (0.5). Carpal tunnel syndrome was noted in 43%. The overall phenotypic profile was similar to ATTRwt but Ile68Leu ATTRm patients typically presented younger (median 71 vs. 78 years) and were more likely to have (mild) symptomatic neurological involvement (19% vs. 2%). Male prevalence was 44% in unaffected mutation carriers and 78% in affected patients. Age-adjusted survival was comparable between groups. Conclusions: Ile68Leu ATTRm is a cause of familial amyloidotic cardiomyopathy endemic in central-northern Italy and presents as hypertrophic/restrictive cardiomyopathy quite similar to ATTRwt. Male preponderance is present in affected patients but not in unaffected mutation carriers. Age-adjusted survival is similar to ATTRwt.

Objective To investigate differences in cardiac manifestations of patients affected by laminopathy, according to the presence or absence of neuromuscular involvement at presentation. Methods We prospectively analyzed 40 consecutive patients with a diagnosis of laminopathy followed at a single centre between 1998 and 2017. Additionally, reports of clinical evaluations and tests prior to referral at our centre were retrospectively evaluated. Results Clinical onset was cardiac in 26 cases and neuromuscular in 14. Patients with neuromuscular presentation experienced first symptoms earlier in life (11 vs 39 years; p p = 0.013] and 30 vs 44 years [p = 0.086] respectively), despite a similar overall prevalence of AF (57% vs 65%; p = 0.735) and atrio-ventricular (A-V) block (50% vs 65%; p = 0.500). Those with a neuromuscular presentation developed a cardiomyopathy less frequently (43% vs 73%; p = 0.089) and had a lower rate of sustained ventricular tachyarrhythmias (7% vs 23%; p = 0.387). In patients with neuromuscular onset rhythm disturbances occurred usually before evidence of cardiomyopathy. Despite these differences, the need for heart transplantation and median age at intervention were similar in the two groups (29% vs 23% [p = 0.717] and 43 vs 46 years [p = 0.593] respectively). Conclusions In patients with laminopathy, the type of disease onset was a marker for a different natural history. Specifically, patients with neuromuscular presentation had an earlier cardiac involvement, characterized by a linear and progressive evolution from rhythm disorders (AF and/or A-V block) to cardiomyopathy.

The objective of this study was to investigate the prognostic significance of 12-lead electrocardiogram (ECG) patterns in a large multicenter cohort of patients with hypertrophic cardiomyopathy; 1,004 consecutive patients with hypertrophic cardiomyopathy and a recorded standard ECG (64% men, mean age 50 +/- 16 years) were evaluated at 4 Italian centers. The study end points were sudden cardiac death (SCD) or surrogates, including appropriate implanted cardiac defibrillator discharge and resuscitated cardiac arrest and major cardiovascular events (including. SCD or surrogates and death due to heart failure, cardioembolic stroke, or heart transplantation). Prevalence of baseline electrocardiographic characteristics was: normal ECG 4%, ST-segment depression 56%, pseudonecrosis waves 33%, "pseudo ST-segment elevation myocardial infarction (STEMI)" pattern 17%, QRS duration >= 120 ms 17%, giant inverted T waves 6%, and low QRS voltages 3%. During a mean follow-up of 7.4 +/- 6.8 years, 77 patients experienced SCD or surrogates and 154 patients experienced major cardiovascular events. Independent predictors of SCD or surrogates were unexplained syncope (hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.4 to 4.5, p = 0.003), left ventricular ejection fraction = 120 ms (HR 1.69, 95% CI 1.16 to 2.47, p = 0.007), and prolonged QTc interval (HR 1.68, 95% CI 1.21 to 2.34, p = 0.002). In conclusion, a detailed qualitative and quantitative electrocardiographic analyses provide independent predictors of prognosis that could be integrated with the available score systems to improve the power of the current model. (C) 2016 Elsevier Inc. All rights reserved.

Background: Although atrial fibrillation (AF) is a known complication of amyloidotic cardiomyopathy (AC), a precise pathophysiological and prognostic characterization is not available. We therefore aimed to assess prevalence, incidence, risk factors and prognostic significance of AF in light-chain (AL), hereditary transthyretin-related (m-ATTR) and non-mutant transthyretin-related (wt-ATTR) AC. Methods: Retrospective study of 262 patients with AC (123 AL, 94 m-ATTR, 45 wt-ATTR) from a single center. Results: AF prevalence was 15% (AL 9%, m-ATTR 11%, wt-ATTR 40%). During a median follow-up of 1.2 years 11 patients developed AF (2.1% person-years). Age, heart failure (HF), left ventricular (LV) ejection fraction, renal involvement, left atrial size and right atrial pressure were independently associated with AF. AF was associated with incident HF but not with increased mortality. All AF patients were prescribed warfarin and none suffered thromboembolic events. Conclusions: In AC the prevalence of AF varies widely according to etiology with a mean value of 15% that reaches 40% in wt-ATTR amyloidosis. Age, HF, LV ejection fraction, left atrial size and right atrial pressure were the main independent risk factors, while wall thickness and etiology were not the main independent risk factors. AF does not seem to impact all-cause mortality but was strongly associated with prevalent and incident HF.

Tc-DPD (Tc-3,3-diphosphono-1,2-propanodicarboxylic acid) has a high affinity for transthyretin (TTR)-infiltrated myocardium, allowing a differential diagnosis with light chain cardiac amyloidosis and other nonamyloidotic cardiomyopathies with a hypertrophic phenotype, in which myocardial tracer uptake is low or absent. Myocardial bone tracer uptake in the rarer forms of amyloidosis (eg, apolipoprotein-related) has been rarely studied. We present 4 cases of cardiac amyloidosis that underwent Tc-DPD scintigraphy; myocardial DPD uptake was present in patients with ATTR, wtTTR and apolipoprotein AI and negative in cases with AL and apolipoprotein AII-related disease.

Cardiac amyloidosis (CA) is often misdiagnosed because of both physician-related and disease-related reasons including: fragmented knowledge among different specialties and subspecialties, shortage of centres and specialists dedicated to disease management, erroneous belief it is an incurable disease, rarity of the condition, intrinsic phenotypic heterogeneity, genotypic heterogeneity in transthyretin-related forms and the necessity of target organ tissue histological diagnosis in the vast majority of cases. Pitfalls, incorrect beliefs and deceits challenge not only the path to the diagnosis of CA but also the precise identification of aetiological subtype. The awareness of this condition is the most important prerequisite for the management of the risk of underdiagnoses and misdiagnosis. Almost all clinical, imaging and laboratory tests can be misinterpreted, but fortunately each of these diagnostic steps can also offer diagnostic “red flags” (i.e. highly suggestive findings that can foster the correct diagnostic suspicion and facilitate early, timely diagnosis). This is especially important because outcomes in CA are largely driven by the severity of cardiac dysfunction and emerging therapies are aimed at preventing further amyloid deposition.