Risk Assessment and Personalized Treatment Options in Inherited Dilated Cardiomyopathies: A Narrative Review

Abstract

Considering the worldwide impact of heart failure, it is crucial to develop approaches that can help us comprehend its root cause and make accurate predictions about its outcome. This is essential for lowering the suffering and death rates connected with this widespread illness. Cardiomyopathies frequently result from genetic factors, and the study of heart failure genetics is advancing quickly. Dilated cardiomyopathy (DCM) is the most prevalent kind of cardiomyopathy, encompassing both genetic and nongenetic abnormalities. It is distinguished by the enlargement of the left ventricle or both ventricles, accompanied by reduced contractility. The discovery of the molecular origins and subsequent awareness of the molecular mechanism is broadening our knowledge of DCM development. Additionally, it emphasizes the complicated nature of DCM and the necessity to formulate several different strategies to address the diverse underlying factors contributing to this disease. Genetic variants that can be transmitted from one generation to another can be a significant contributor to causing family or sporadic hereditary DCM. Genetic variants also play a significant role in determining susceptibility for acquired triggers for DCM. The genetic causes of DCM can have a large range of phenotypic expressions. It is crucial to select patients who are most probable to gain advantages from genetic testing. The purpose of this research is to emphasize the significance of identifying genetic DCM, the relationships between genotype and phenotype, risk assessment, and personalized therapy for both those affected and their relatives. This approach is expected to gain importance once treatment is guided by genotype-specific advice and disease-modifying medications.

Keywords: genotype-specific therapy; inherited dilated cardiomyopathy; risk assessment.

Figure 1

Twelve-lead electrocardiogram in a patient with familial dilated cardiomyopathy. (A) Sinus rhythm with recurring premature ventricular beats (arrow). Negative T waves from V1 to V6. (B) Ventricular late potentials (arrow).

Figure 2

Twelve-lead electrocardiogram. Sustained ventricular tachycardia.

Figure 3

Familial dilated cardiomyopathy. Two-dimensional trans-thoracic conventional echography in apical longitudinal and parasternal short axis vi ews. Bull’s eye myocardial deformation with diffuse reduced left ventricular longitudinal peak strain patterns.

Figure 4

Cardiac magnetic resonance images, 4-chamber (horizontal long axis) and 2-chamber (vertical long axis). Dilated left ventricle with hyper-trabeculations of the antero-lateral wall; late gadolinium enhancement shows septal mid-wall fibrosis, suggestive of idiopathic dilative cardiomyopathy with left ventricular non-compaction.

Figure 5

Cardiac magnetic resonance image, short axis. Dilated left ventricle with thin walls; late gadolinium enhancement highlights circumferential “ring-shape” mid wall fibrosis suggestive of desmoplakin cardiomyopathy (arrows).

Figure 6

Flow-chart for assessing the risk of genetic dilated cardiomyopathy in family members. Red flags include a strong family history with 2 first-degree relatives having idiopathic dilated cardiomyopathy or sudden cardiac death at age < 35 years.

Figure 7

A practical approach for genetic testing in hereditary dilated cardiomyopathies.

Figure 8

Cellular proteins linked to DCM. Abbreviations: DSP, desmoplakin; LMNA, lamin A/C; MYHN, myosin heavy chain; MYPN, myopalladin; RBM20, RNA binding protein 20; TNNT, cardiac muscle troponin T2; TPM1, α-tropomyosin 1; SCN5A, sodium channel protein type 5.