Clinical presentations leading to arrhythmogenic left ventricular cardiomyopathy

Abstract

ObjectivesTo describe a cohort of patients with arrhythmogenic left ventricular cardiomyopathy (ALVC), focusing on the spectrum of the clinical presentations.MethodsPatients were retrospectively evaluated between January 2012 and June 2020. Diagnosis was based on (1) ≥3 contiguous segments with subepicardial/midwall late gadolinium enhancement in the left ventricle (LV) at cardiac magnetic resonance plus a likely pathogenic/pathogenic arrhythmogenic cardiomyopathy (AC) associated genetic mutation and/or familial history of AC and/or red flags for ALVC (ie, negative T waves in V4-6/aVL, low voltages in limb leads, right bundle branch block like ventricular tachycardia) or (2) pathology examination of explanted hearts or autoptic cases suffering sudden cardiac death (SCD). Significant right ventricular involvement was an exclusion criterion.ResultsFifty-two patients (63% males, age 45 years (31–53)) composed the study cohort. Twenty-one (41%) had normal echocardiogram, 13 (25%) a hypokinetic non-dilated cardiomyopathy (HNDC) and 17 (33%) a dilated cardiomyopathy (DCM). Of 47 tested patients, 29 (62%) were carriers of a pathogenic/likely pathogenic DNA variant. Clinical contexts leading to diagnosis were SCD in 3 (6%), ventricular arrhythmias in 15 (29%), chest pain in 8 (15%), heart failure in 6 (12%) and familial screening in 20 (38%). Thirty patients (57%) had previously received a diagnosis other than ALVC with a diagnostic delay of 6 years (IQR 1–7).ConclusionsALVC is hidden in different clinical scenarios with a phenotypic spectrum ranging from normal LV to HNDC and DCM. Ventricular arrhythmias, chest pain, heart failure and SCD are the main clinical presentations, being familial screening essential for the affected relatives’ identification.

Myocarditis-like Episodes in Patients with Arrhythmogenic Cardiomyopathy: A Systematic Review on the So-Called Hot-Phase of the Disease

“…Of the remaining 35 articles, 23 were excluded as consisting of case reports, and 3 due to the presence of duplicate data in other selected papers of the same research group [ 6 , 7 , 17 ]. Overall, 9 papers were finally considered for this review ( Table 1 ) [ 5 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. A PRISMA flow diagram depicts the flow of information through the different literature review phases ( Figure 1 ).…”

“…While in the last few years the possible role of inflammation in ACM onset and progression led to a significant number of publications, few detailed clinical studies on a large cohort of patients with “hot-phases” can be found [ 23 , 24 , 25 , 26 ]. We were able to select only 9 studies describing cohorts of patients affected with ACM who showed myocarditis-like episodes [ 5 , 8 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. This is probably due to the low prevalence of these episodes in the overall ACM population, and on the other hand, to the problem of differential diagnosis with acute myocarditis.…”

“…It should be emphasized that in two of our selected studies, one of the inclusion criteria was the presence of pathogenic variant of the DSP gene, and this may have resulted in an overestimation of the incidence of hot-phase episodes in this genotype [ 14 , 15 ]. Despite this, even excluding these two studies, DSP remains the gene most frequently found associated with hot-phase [ 8 , 10 , 11 , 12 , 13 , 14 , 16 ]. On the other hand, genetic variants of PKP2 and DSG2 were detected in 17% of cases.…”

Genetic Background and Clinical Features in Arrhythmogenic Left Ventricular Cardiomyopathy: A Systematic Review

“…In addition, Casella et al (2020) evaluated a series of ALVC patients and among 12 with a positive genetic result found three DSG2 and 9 DSP genetic variant carriers [ 75 ]. Recently, Graziosi et al (2022) described a large series of ALVC patients and reported the presence of genetic variants of SCN5A and TMEM43 genes [ 76 ].…”

Desmoplakin Cardiomyopathy: Comprehensive Review of an Increasingly Recognized Entity

“…The phenotypic spectrum of DSP cardiomyopathy is wide ( Table 1 ) [ 20 ]. The main clinical presentations include extensive subepicardial late gadolinium enhancement (LGE) on CMR, which is often disproportionate to the degree of LV dysfunction, in association with frequent premature ventricular contractions (PVC) and a propensity to life-threatening ventricular arrhythmias [ 9 , 17 , 18 , 19 ].…”