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Dilated cardiomyopathy: causes, mechanisms, and current and future treatment approaches
Stephane Heymans1, Neal K Lakdawala2, Carsten Tschöpe3
1Department of Cardiology, Cardiovascular Research Institute Maastricht, University of Maastricht & Maastricht University Medical Centre, Maastricht, Netherlands; Department of Cardiovascular Sciences, Centre for Vascular and Molecular Biology, KU Leuven, Leuven, Belgium.
Insights
Dilated cardiomyopathy, a heart muscle disease, has causes including genetics and acquired factors like infections or toxins. Diagnosis and treatment must consider both genetic mutations and acquired triggers for better patient outcomes.
Area of Science:
- Cardiology
- Genetics
- Pathophysiology
Background:
- Dilated cardiomyopathy (DCM) involves heart muscle enlargement and impaired function.
- The conventional definition of DCM is considered too restrictive.
- DCM can stem from genetic (primary) or acquired (secondary) factors.
Purpose of the Study:
- To review the current multidimensional diagnostic and therapeutic strategies for DCM.
- To explore the pathophysiology underlying DCM to inform future treatments.
- To highlight the importance of considering both genetic and acquired factors in DCM management.
Main Methods:
- Review of current literature on dilated cardiomyopathy diagnosis and treatment.
- Discussion of genetic and acquired etiologies of DCM.
- Exploration of pathophysiological mechanisms driving DCM progression.
Main Results:
- A significant percentage (5-15%) of patients with acquired DCM have underlying genetic variants.
- Current diagnostic and therapeutic approaches must integrate genetic and acquired etiological considerations.
- Future treatments may target specific genetic mutations or acquired drivers like inflammation and fibrosis.
Conclusions:
- Dilated cardiomyopathy diagnosis and management require a comprehensive approach addressing both genetic predispositions and acquired insults.
- Understanding the diverse pathophysiology of DCM is crucial for developing targeted and effective therapies.
- Personalized treatment strategies for DCM will likely evolve by targeting specific molecular and cellular pathways.
Abstract:
Dilated cardiomyopathy is conventionally defined as the presence of left ventricular or biventricular dilatation or systolic dysfunction in the absence of abnormal loading conditions (eg, primary valve disease) or significant coronary artery disease sufficient to cause ventricular remodelling. This definition has been recognised as overly restrictive, as left ventricular hypokinesis without dilation could be the initial presentation of dilated cardiomyopathy. The causes of dilated cardiomyopathy comprise genetic (primary dilated cardiomyopathy) or acquired factors (secondary dilated cardiomyopathy). Acquired factors include infections, toxins, cancer treatment, endocrinopathies, pregnancy, tachyarrhythmias, and immune-mediated diseases. 5-15% of patients with acquired dilated cardiomyopathy harbour a likely pathogenic or pathogenic gene variant (ie, gene mutation). Therefore, the diagnostic tests and therapeutic approach should always consider both genetic and acquired factors. This Seminar will focus on the current multidimensional diagnostic and therapeutic approach and discuss the underlying pathophysiology that could drive future treatments aiming to repair or replace the existing gene mutation, or target the specific inflammatory, metabolic, or pro-fibrotic drivers of genetic or acquired dilated cardiomyopathy.
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