Chapter 15: Dilated Cardiomyopathy at the Crossroad: Multidisciplinary Approach

Patients with dilated cardiomyopathy (DCM) can present for the first time with typical cardiac symptoms, as heart failure, arrhythmias, and syncope, with cardiomyopathy as the main presenting feature. However, DCM may be a common feature of systemic diseases or presenting in the contest of different clinical settings. Symptoms of multisystem disease may be described by patients themselves or be determined on routine examination. A cardiomyopathy-specific mindset, which combines conventional cardiologic assessment with non-cardiac clinical acumen and a systematic approach, is important, because it can be used to identify specific disorders, guide rational selection of diagnostic tests, and increase the chance that disorders with tailored management strategies can be identified. Moreover, in different clinical settings, phenotypic expression in other organs may precede cardiac manifestations, and the cardiologist\u2019s role is to search for cardiac involvement in a patient who already has a non-cardiac diagnosis. In the present chapter, we consider DCM and ventricular dysfunction in the contest of peculiar clinical settings ranging from inflammatory or autoimmune disorders to specific forms of systemic disease, infectious disease, as well as toxin-induced DCM

A genetic etiology for alcohol-induced cardiac toxicity

Background: Alcoholic cardiomyopathy (ACM) is defined by a dilated and impaired left ventricle due to chronic excess alcohol consumption. It is largely unknown what factors determine cardiac toxicity on exposure to alcohol. Objectives: We sought to evaluate the role of variation in cardiomyopathy-associated genes in the pathophysiology of ACM, and to examine the effects of alcohol intake and genotype on DCM severity. Methods: We characterized 141 ACM cases, 716 dilated cardiomyopathy (DCM) cases and 445 healthy volunteers. We compared the prevalence of rare, protein-altering variants in 9 genes associated with inherited DCM. We evaluated the effect of genotype and alcohol-consumption on phenotype in DCM. Results: Variants in well-characterized DCM-causing genes were more prevalent in patients with ACM than controls (13.5% vs 2.9%; P=1.2e-05), but similar between patients with ACM and DCM (19.4%; P=0.12) and with a predominant burden of Titin-truncating variants (TTNtv, 9.9%). Separately, we identified an interaction between TTN genotype and excess alcohol consumption in a cohort of DCM patients not meeting ACM criteria. On multivariate analysis, DCM patients with a TTNtv who consumed excess alcohol had an 8.7% absolute reduction in ejection fraction (95% CI -2.3 to -15.1, P<0.007) compared with those without TTNtv and excess alcohol consumption. The presence of TTNtv did not predict phenotype, outcome or functional recovery on treatment in ACM patients. Conclusions: TTNtv represent a prevalent genetic predisposition for ACM, and are also associated with a worse LVEF in DCM patients who consume alcohol above recommended levels. Familial evaluation and genetic testing should be considered in patients presenting with ACM

Genetic Etiology for Alcohol-Induced Cardiac Toxicity

10.1016/j.jacc.2018.03.462Journal of the American College of Cardiology71202293-2302JACC

Chapter 14: Unresolved Issues and Future Perspectives

The last years witnessed an important progress in the diagnosis and treatment of dilated cardiomyopathy (DCM), improving prognosis and life expectancy. However, some important issues in clinical management remain unresolved. The role of genetic testing, the arrhythmic stratification, and the therapeutic approach still represent areas of uncertainty. The way for improving care of DCM should go through better understanding of the etiological basis of the disease, appropriate risk stratification, and development of new therapies. The abovementioned issues represent the most important and demanding challenges for the next future research on DCM

Chapter 5: Genetics of Dilated Cardiomyopathy: Current Knowledge and Future Perspectives

Nowadays, a huge claim for personalized medicine is progressively growing, and, along this way, genetic studies represent one of the most representative steps. Dilated cardiomyopathy (DCM) can be the consequence of clearly defined external etiologic factors, such as viral infections, toxins, drugs, metabolic disorders, etc., but at least 30\u201340% of cases (and maybe more) have a prevalent genetic origin, and in the remaining part, genetics may still play an important role. With the expansion of clinical genetic testing, using high-quality next-generation sequencing (NGS) extended panels, these genetic causes of DCM have been increasingly identified. More than 50 genes, mapping to multiple biological pathways, are currently considered disease related, and causative variants can be identified in up to 35% of cases. This growing amount of genetic informations, however, is still not followed by a parallel advance toward tailored clinical management. The reasons behind this gap are currently under investigation in the scientific community: the aim of this chapter is to provide a guide through the complexity of the genotype-phenotype interaction, analyzing (1) the most frequently encountered genes in DCM, (2) technical issues in NGS, (3) controversies beyond sequencing data interpretation, (4) the contribution of environmental modifiers, and (5) evidence-based genotype-phenotype correlations in DCM

European cardiomyopathy pilot registry: EURObservational research programme of the European society of cardiology

Aims: Cardiomyopathies are a heterogeneous group of disorders associated with premature death due to ventricular arrhythmia or heart failure. The purpose of this study was to examine the characteristics of patients enrolled in the pilot phase of the EURObservational Research Programme (EORP) cardiomyopathy registry. Methods and results: Between 1 December 2012 and 30 November 2013, four cardiomyopathy phenotypes were studied: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and restrictive cardiomyopathy (RCM). Twenty-seven centres in 12 countries participated; 1115 patients were enrolled. The commonest cardiomyopathy was HCM (n = 681), followed by DCM (n = 346), ARVC (n = 59), and RCM (n = 29); 423 patients (46.4% of those reported) had familial disease; and 56 (5.0%) had rare disease phenocopies. Median age at enrolment and diagnosis was 54 [interquartile range (IQR), 42-64] and 46 years (IQR, 32-58), respectively; fewer patients with ARVC and more with RCM were diagnosed in the upper age quartile (P, 0.0001). There was a male predominance for all cardiomyopathies except RCM (P = 0.0023). Most patients were in New York Heart Association functional class I (n = 813) at enrolment; 139 (12.5%) reported syncope, most frequently in ARVC (P = 0.0009). Five hundred and seven (45.5%) patients underwent cardiac magnetic resonance imaging, 117 (10.6%) endomyocardial biopsy, and 462 (41.4%) genetic testing with a causative mutation reported in 236 individuals (51.1%). 1026 patients (92.0%) were receiving drug therapy; 316 (28.3%) had received an implantable cardioverter defibrillator (highest proportion in ARVC, P, 0.0001). Conclusion: This pilot study shows that services for patients with cardiomyopathy are complex, requiring access to a large range of invasive and non-invasive investigations and involvement of multidisciplinary teams. Treatment regimens are equally multifaceted and show that patients are likely to need long-term follow-up in close liaison with expert centres