Abstract
The deletion of the arginine 14 codon (R14del) in the phospholamban (PLN) gene is a rare cause of arrhythmogenic cardiomyopathy (ACM) and is associated with prevalent ventricular arrhythmias, heart failure, and sudden cardiac death. The pathophysiological mechanism which culminates in the ACM phenotype is multifactorial and mainly based on the alteration of the endoplasmic reticulum proteostasis, mitochondrial dysfunction and compromised Ca2+ cytosolic homeostasis. The symptoms of this condition are usually non-specific and consist of arrhythmia-related or heart failure-related manifestation; however, some peculiar diagnostic clues were detected, such as the T-wave inversion in the lateral leads, low QRS complexes voltages, mid-wall or epicardial fibrosis of the inferolateral wall of the left ventricle, and their presence should raise the suspicion of this condition. The risk stratification for sudden cardiac death is mandatory and several predictors were identified in recent years. However, the management of affected patients is often challenging due to the absence of specific prediction tools and therapies. This review aims to provide the current state of the art of PLN R14del cardiomyopathy, focusing on its pathophysiology, clinical manifestation, risk stratification for sudden cardiac death, and management.
Highlights
Arrhythmogenic cardiomyopathy (ACM) is a myocardial disease that affects the left ventricle (LV), right ventricle (RV), or both, whose most typical characteristics are the progressive fibrotic or fibrofatty myocardial replacement that predisposes to ventricular arrhythmias and can be responsible for global or regional ventricular dysfunction [1]
The treatment of HF in these patients is based on disease-modifying drugs, such as angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs), beta-blockers, mineralocorticoids antagonists (MRAs), angiotensin receptor
PLN R14del cardiomyopathy is a rare cause of ACM and is associated with prevalent
Summary
Arrhythmogenic cardiomyopathy (ACM) is a myocardial disease that affects the left ventricle (LV), right ventricle (RV), or both, whose most typical characteristics are the progressive fibrotic or fibrofatty myocardial replacement that predisposes to ventricular arrhythmias and can be responsible for global or regional ventricular dysfunction [1]. In the pre-genetic era, ACM was considered a myocardial disease that exclusively or predominantly involved the RV, the so-called arrhythmogenic RV dysplasia (ARVD) or cardiomyopathy (ARVC), whose clinical features were RV dysfunction and arrhythmias [2,3]. Cardiogenetics 2022, 12 left ventricular cardiomyopathy (ALVC), is characterized by predominant LV involvement, and the biventricular phenotype is defined as a disease involving both the ventricles [7]. With the increased knowledge of the ALVC phenotype, specific diagnostic criteria for the left-side disease variants were proposed (the “Padua Criteria”) [14], based on the following phenotypic features: electrocardiographic (ECG) abnormalities, such as low QRS voltages and T-wave inversion in the lateral or inferolateral leads; ventricular arrhythmias with a QRS morphology which denotes its origin from the LV; normal or mild hypokinetic LV with no or mild dilation; extensive myocardial fibrosis evidenced by CMR as late gadolinium enhancement (LGE) with a non-ischemic pattern of distribution. This review aims to provide the current state of the art of PLN (phospholamban) R14del cardiomyopathy, focusing on its pathophysiology, clinical manifestation, risk stratification for SCD, and management
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