Long-Term Electrocardiographic and Echocardiographic Progression of Arrhythmogenic Right Ventricular Cardiomyopathy and Their Correlation With Ventricular Tachyarrhythmias

Abstract

Background: Prior studies of structural and electrocardiographic changes in arrhythmogenic right ventricular (RV) cardiomyopathy and their role in predicting ventricular arrhythmias (ventricular tachycardia) have shown conflicting results. Methods: We reviewed 405 ECGs, 315 transthoracic echocardiographies, and 441 implantable cardioverter defibrillator interrogations in 64 arrhythmogenic RV cardiomyopathy patients (56% men, mean age [SD], 44.2 [14.6] years) over a mean follow-up of 10 (range, 2.3–19) years. Generalized estimating equations were used to identify the association between ECG abnormalities, clinical variables, and transthoracic echocardiographic measurements (>mild degree of tricuspid regurgitation, RV outflow tract diameter in parasternal long axis and short axis, RV end-diastolic area, fractional area change). Results: There was a 4.65 (95% CI, 0.51%–8.8%) increase in RV end-diastolic area, a 3.75 (95% CI, 1.17%–6.34%) decrease in fractional area change, and 1.9 (95% CI, 1.3–2.8) higher odds (odds ratio) of RV wall motion abnormality with every 5-year increase in age after patients’ first transthoracic echocardiography. >Mild tricuspid regurgitation was an independent predictor of RV enlargement and dysfunction (hazard ratio of >10% drop in fractional area change from baseline [95% CI], 3.51 [1.77–6.95] and hazard ratio of >10% increase in RV end-diastolic area from baseline [95% CI], 4.90 [2.52–9.52]). Patients with implantable cardioverter defibrillator were more likely to develop >mild tricuspid regurgitation and larger structural and functional disease progression. More pronounced increase in RV end-diastolic area was translated into higher rates of any ventricular tachycardia. Inferior T-wave inversions and sum of R waves (mm) in V1 to V3 were predictors of RV enlargement and dysfunction with the former also predicting risk of any ventricular tachycardia. Conclusions: Arrhythmogenic RV cardiomyopathy is a progressive disease. Tricuspid regurgitation is an independent predictor of structural disease progression, which may be exacerbated by use of a transvenous implantable cardioverter defibrillator lead.

Structural Progression in Patients with Definite and Non-Definite Arrhythmogenic Right Ventricular Cardiomyopathy and Risk of Major Adverse Cardiac Events

“…The smaller rate of change in our study in definite ARVC could be due to the shorter follow-up period and the lower number of definite patients. The absence of any significant progression in LV structure or function in our cohort is in line with findings from a multinational retrospective study [17] in which 315 echocardiographic examinations were analysed over a 10-year follow-up period. Overall, our findings suggest that a follow-up should ideally be longer than 4 years if including early ARVC patients when designing intervention or therapeutic studies in ARVC based on structural changes in echocardiography.…”

Longitudinal Prediction of Ventricular Arrhythmic Risk in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

“…21,22 In contrast, studies examining longer-term followup with serial ECGs out to 10 years have demonstrated increased numbers of ECG leads with TWI. 11,23,24 As with cardiac functional changes, these findings suggest that the progression of ECG changes, and thus the electrophysiologic and structural changes they reflect, likely change over longer time spans (>5 years) than the present study was able to examine.…”

“…18 Contrasting this, Taha et al 19 found that RV fractional area change decreased by 5% over 7-year follow-up of patients with ARVC with serial imaging. Kalantarian et al 11 found that about a quarter of patients with ARVC had a drop of at least 10% in RV fractional area change over 10-year follow-up. Thus, significant functional cardiac changes in ARVC seem to occur over longer time scales (>5 years) than our present study was able to examine.…”

“…8 However, ARVC is a progressive condition, and clinical predictors included in the ARVC risk calculator may be dynamic. [9][10][11] How reliably this tool performs at subsequent evaluations after initial diagnosis is, therefore, unknown, limiting longitudinal risk assessment in these patients.…”

Arrhythmogenic cardiomyopathy as a myogenic disease: highlights from cardiomyocytes derived from human induced pluripotent stem cells

“…The various forms of arrhythmias include palpitations, premature ventricular beat, bundle branch block, ventricular tachycardia, and ventricular fibrillation ( Austin et al, 2019 ). On the ECG, ACM can manifest with a large QRS duration (>110 m), T-wave inversion, or also with the presence of an epsilon wave ( Delmar and McKenna, 2010 ; Kalantarian et al, 2021 ). Structural heart remodeling manifests as fibrosis, fatty infiltration, and aneurysm, leading to ventricular dilation and decreased heart contraction ( Kohela and van Rooij, 2022 ).…”