Evolving concepts in dilated cardiomyopathy Merlo, Marco; Cannatà, Antonio; Gobbo, Marco ...
European journal of heart failure,
February 2018, Volume:
20, Issue:
2
Journal Article
Peer reviewed
Open access
Dilated cardiomyopathy (DCM) represents a particular aetiology of systolic heart failure that frequently has a genetic background and usually affects young patients with few co‐morbidities. The ...prognosis of DCM has improved substantially during the last decades due to more accurate aetiological characterization, the red‐flag integrated approach to the disease, early diagnosis through systematic familial screening, and the concept of DCM as a dynamic disease requiring constant optimization of medical and non‐pharmacological evidence‐based treatments. However, some important issues in clinical management remain unresolved, including the role of cardiac magnetic resonance for diagnosis and risk categorization and the interaction between genotype and clinical phenotype, and arrhythmic risk stratification. This review offers a comprehensive survey of these and other emerging issues in the clinical management of DCM, providing where possible practical recommendations.
Despite enzyme replacement therapy, disease progression is observed in patients with Fabry disease. Identification of factors that predict disease progression is needed to refine guidelines on ...initiation and cessation of enzyme replacement therapy. To study the association of potential biochemical and clinical prognostic factors with the disease course (clinical events, progression of cardiac and renal disease) we retrospectively evaluated 293 treated patients from three international centers of excellence. As expected, age, sex and phenotype were important predictors of event rate. Clinical events before enzyme replacement therapy, cardiac mass and eGFR at baseline predicted an increased event rate. eGFR was the most important predictor: hazard ratios increased from 2 at eGFR <90 ml/min/1.73m2 to 4 at eGFR <30, compared to patients with an eGFR >90. In addition, men with classical disease and a baseline eGFR <60 ml/min/1.73m2 had a faster yearly decline (-2.0 ml/min/1.73m2) than those with a baseline eGFR of >60. Proteinuria was a further independent risk factor for decline in eGFR. Increased cardiac mass at baseline was associated with the most robust decrease in cardiac mass during treatment, while presence of cardiac fibrosis predicted a stronger increase in cardiac mass (3.36 gram/m2/year). Of other cardiovascular risk factors, hypertension significantly predicted the risk for clinical events. In conclusion, besides increasing age, male sex and classical phenotype, faster disease progression while on enzyme replacement therapy is predicted by renal function, proteinuria and to a lesser extent cardiac fibrosis and hypertension.
HCM is commonly associated with AF. Current guidelines for AF management omit detailed advice for HCM because of a lack of clinical prediction tools that estimate the risk of developing AF and an ...absence of adequately powered treatment studies.
To critically review current literature on atrial fibrillation (AF) and thromboembolism in hypertrophic cardiomyopathy (HCM) and meta-analyse prevalence and incidence.
PubMed and Web of Science.
Studies investigating AF and stroke in HCM as primary or secondary endpoint.
Two investigators independently reviewed and extracted data from the identified articles. A random effect meta-regression model and I(2) statistics were used for analysis.
A population of 7381 patients (33 studies) revealed overall AF prevalence of 22.45% (95% CI 20.13% to 24.77%), I(2)=78.9% (p<0.001). Overall prevalence of thromboembolism in HCM patients with AF was 27.09% (95% CI 20.94% to 33.25%), I(2)=61.4% ( p<0.01). Overall AF incidence was 3.08% per 100 patients per year (95% CI 2.63% to 3.54%, I(2)=86.5%, p<0.001) and incidence of thromboembolism in HCM patients with AF was 3.75% per 100 patients per year (95% CI 2.88% to 4.61%), I(2)=37.9% (p=0.1). Left atrial (LA) dimension and age were common predictors for AF and thromboembolism. Meta-analysis revealed an LA diameter of 38.03 mm (95% CI 34.62% to 41.44%) in sinus rhythm and 45.37 mm (95% CI 41.64% to 49.04%) in AF. There were no randomised controlled trials of therapy; anticoagulation was associated with lower stroke incidence but data on other interventions were limited and contradictory.
AF is common in HCM and associated with high thromboembolic risk. LA dimension and age are independently associated with AF but the literature is insufficient to create robust clinical tools to predict AF or thromboembolism. Most data suggest that AF patients should be anticoagulated.
Predictive genetic screening of relatives of patients with hypertrophic cardiomyopathy (HCM) caused by sarcomere protein (SP) gene mutations is current standard of care, but there are few data on ...long-term outcomes in mutation carriers without HCM.
The aim of this study was to determine the incidence of new HCM diagnosis in SP mutation carriers.
This was a retrospective analysis of adult and pediatric SP mutation carriers identified during family screening who did not fulfill diagnostic criteria for HCM at first evaluation.
The authors evaluated 285 individuals from 156 families (median age 14.2 years interquartile range: 6.8 to 31.6 years, 141 49.5% male individuals); 145 (50.9%) underwent cardiac magnetic resonance (CMR). Frequency of causal genes was as follows: MYBPC3 n = 123 (43.2%), MYH7 n = 69 (24.2%), TNNI3 n = 39 (13.7%), TNNT2 n = 34 (11.9%), TPM1 n = 9 (3.2%), MYL2 n = 6 (2.1%), ACTC1 n = 1 (0.4%), multiple mutations n = 4 (1.4%). Median follow-up was 8.0 years (interquartile range: 4.0 to 13.3 years) and 86 (30.2%) patients developed HCM; 16 of 50 (32.0%) fulfilled diagnostic criteria on CMR but not echocardiography. Estimated HCM penetrance at 15 years of follow-up was 46% (95% confidence interval CI: 38% to 54%). In a multivariable model adjusted for age and stratified for CMR, independent predictors of HCM development were male sex (hazard ratio HR: 2.91; 95% CI: 1.82 to 4.65) and abnormal electrocardiogram (ECG) (HR: 4.02; 95% CI: 2.51 to 6.44); TNNI3 variants had the lowest risk (HR: 0.19; 95% CI: 0.07 to 0.55, compared to MYBPC3).
Following a first negative screening, approximately 50% of SP mutation carriers develop HCM over 15 years of follow-up. Male sex and an abnormal ECG are associated with a higher risk of developing HCM. Regular CMR should be considered in long-term screening.
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In this paper the Working Group on Myocardial and Pericardial Disease proposes a revised definition of dilated cardiomyopathy (DCM) in an attempt to bridge the gap between our recent understanding of ...the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis and the institution of potential preventative measures. We also provide practical hints to identify subsets of the DCM syndrome where aetiology directed management has great clinical relevance.
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a life-threatening, progressive, infiltrative disease caused by the deposition of transthyretin amyloid fibrils in the heart, and can often be ...overlooked as a common cause of heart failure. Delayed diagnosis due to lack of disease awareness and misdiagnosis results in a poorer prognosis. Early accurate diagnosis is therefore key to improving patient outcomes, particularly in the context of both the recent approval of tafamidis in some countries (including the United States) for the treatment of ATTR-CM, and of other promising therapies under development. With the availability of scintigraphy as an inexpensive, noninvasive diagnostic tool, the rationale to screen for ATTR-CM in high-risk populations of patients is increasingly warranted. Here the authors propose a framework of clinical scenarios in which screening for ATTR-CM is recommended, as well as diagnostic “red flags” that can assist in its diagnosis among the wider population of patients with heart failure.
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•ATTR-CM is a life-threatening, progressive disease that is often underdiagnosed and misdiagnosed.•Certain clinical scenarios have been identified that now warrant screening for ATTR-CM.•Once ATTR-CM is suspected, a definitive diagnosis can usually be achieved noninvasively.•Accurate, early diagnosis of ATTR-CM is key to enabling appropriate patient care.
Fabry disease leads to renal, cardiac, and cerebrovascular manifestations. Phenotypic differences between classically and nonclassically affected patients are evident, but there are few data on the ...natural course of classical and nonclassical disease in men and women. To describe the natural course of Fabry disease stratified by sex and phenotype, we retrospectively assessed event-free survival from birth to the first clinical visit (before enzyme replacement therapy) in 499 adult patients (mean age 43 years old; 41% men; 57% with the classical phenotype) from three international centers of excellence. We classified patients by phenotype on the basis of characteristic symptoms and enzyme activity. Men and women with classical Fabry disease had higher event rate than did those with nonclassical disease (hazard ratio for men, 5.63, 95% confidence interval, 3.17 to 10.00;
<0.001; hazard ratio for women, 2.88, 95% confidence interval, 1.54 to 5.40;
<0.001). Furthermore, men with classical Fabry disease had lower eGFR, higher left ventricular mass, and higher plasma globotriaosylsphingosine concentrations than men with nonclassical Fabry disease or women with either phenotype (
<0.001). In conclusion, before treatment with enzyme replacement therapy, men with classical Fabry disease had a history of more events than men with nonclassical disease or women with either phenotype; women with classical Fabry disease were more likely to develop complications than women with nonclassical disease. These data may support the development of new guidelines for the monitoring and treatment of Fabry disease and studies on the effects of intervention in subgroups of patients.
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