Background: Genetic analysis is a first-tier test in dilated cardiomyopathy (DCM). Electrical phenotypes are common in genetic DCM, but their exact contribution to the clinical course and outcome is unknown. We determined the prevalence of pathogenic gene variants in a large unselected DCM population and determined the role of electrical phenotypes in association with outcome. Methods: This study included 689 patients with DCM from the Maastricht Cardiomyopathy Registry, undergoing genetic evaluation using a 48 cardiomyopathy-associated gene-panel, echocardiography, endomyocardial biopsies, and Holter monitoring. Upon detection of a pathogenic variant in a patient with DCM, familial segregation was performed. Outcome was defined as cardiovascular death, heart transplantation, heart failure hospitalization, and/or occurrence of life-threatening arrhythmias. Results: A (likely) pathogenic gene variant was found in 19% of patients, varying from 36% in familial to 13% in nonfamilial DCM. Family segregation analysis showed familial disease in 46% of patients with DCM who were initially deemed nonfamilial by history. Overall, 18% of patients with a nongenetic risk factor had a pathogenic gene variant. Almost all pathogenic gene variants occurred in just 12 genes previously shown to have robust disease association with DCM. Genetic DCM was independently associated with electrical phenotypes such as atrial fibrillation, nonsustained ventricular tachycardia, and atrioventricular block and inversely correlated with the presence of a left bundle branch block ( P <0.01). After a median follow-up of 4 years, event-free survival was reduced in genetic versus patients with nongenetic DCM ( P =0.01). This effect on outcome was mediated by the associated electrical phenotypes of genetic DCM ( P <0.001). Conclusions: One in 5 patients with an established nongenetic risk factor or a nonfamilial disease still carries a pathogenic gene variant. Genetic DCM is characterized by a profile of electrical phenotypes (atrial fibrillation, nonsustained ventricular tachycardia, and atrioventricular block), which carries increased risk for adverse outcomes. Based on these findings, we envisage a broader role for genetic testing in DCM.

Background: Speckle tracking echocardiographic global longitudinal strain (GLS) predicts outcome in patients with new onset heart failure. Still, its incremental value on top of left ventricular ejection fraction (LVEF) in patients with nonischemic, nonvalvular dilated cardiomyopathy (DCM) after optimal heart failure treatment remains unknown. Methods and Results: Patients with DCM were included at the outpatient clinics of 2 centers in the Netherlands and Italy. The prognostic value of 2‐dimensional speckle tracking echocardiographic global longitudinal strain was evaluated when being on optimal heart failure medication for at least 6 months. Outcome was defined as the combination of sudden or cardiac death, life‐threatening arrhythmias, and heart failure hospitalization. A total of 323 patients with DCM (66% men, age 55±14 years) were included. The mean LVEF was 42%±11% and mean GLS after optimal heart failure treatment was −15%±4%. Twenty percent (64/323) of all patients reached the primary outcome after optimal heart failure treatment (median follow‐up of 6[4–9] years). New York Heart Association class ≥3, LVEF, and GLS remained associated with the outcome in the multivariable‐adjusted model (New York Heart Association class: hazard ratio [HR], 3.43; 95% CI, 1.49–7.90, P =0.004; LVEF: HR, 2.13; 95% CI, 1.11–4.10, P =0.024; GLS: HR, 2.24; 95% CI, 1.18–4.29, P =0.015), whereas left ventricular end‐diastolic diameter index, left atrial volume index, and delta GLS were not. The addition of GLS to New York Heart Association class and LVEF improved the goodness of fit (log likelihood ratio test P <0.001) and discrimination (Harrell’s C 0.703). Conclusions: Within this bicenter study, GLS emerged as an independent and incremental predictor of adverse outcome, which exceeded LVEF in patients with optimally treated DCM. This presses the need to routinely include GLS in the echocardiographic follow‐up of DCM.

This study assessed the prognostic implications of mechanical atrial dysfunction in heart failure with preserved ejection fraction (HFpEF) patients with different stages of atrial fibrillation (AF) in detail. HFpEF patients (n = 258) systemically underwent an extensive clinical characterization, including 24-h Holter monitoring and speckle-tracking echocardiography. Patients were categorized according to rhythm and stages of AF: 112 with no history of AF (no AF), 56 with paroxysmal AF (PAF), and 90 with sustained (persistent/permanent) AF (SAF). A progressive decrease in mechanical atrial function was seen: left atrial reservoir strain (LASr) 30.5 ± 10.5% (no AF), 22.3 ± 10.5% (PAF), and 13.9 ± 7.8% (SAF), P < 0.001. Independent predictors for lower LASr values were AF, absence of chronic obstructive pulmonary disease, higher N-terminal-pro hormone B-type natriuretic peptide, left atrial volume index, and relative wall thickness, lower left ventricular global longitudinal strain, and echocardiographic signs of elevated left ventricular filling pressure. LASr was an independent predictor of adverse outcome (hazard ratio per 1% decrease =1.049, 95% confidence interval 1.014–1.085, P = 0.006), whereas AF was not when the multivariable model included LASr. Moreover, LASr mediated the adverse outcome associated with AF in HFpEF (P = 0.008). Mechanical atrial dysfunction has a possible greater prognostic role in HFpEF compared to AF status alone. Mechanical atrial dysfunction is a predictor of adverse outcome independently of AF presence or stage, and may be an underlying mechanism (mediator) for the worse outcome associated with AF in HFpEF. This may suggest mechanical atrial dysfunction plays a crucial role in disease progression in HFpEF patients with AF, and possibly also in HFpEF patients without AF.

Background: Late gadolinium enhancement and left ventricular (LV) ejection fraction on cardiovascular magnetic resonance (CMR) are prognostic markers, but their predictive value for incident heart failure or life‐threatening arrhythmias in acute myocarditis patients is limited. CMR‐derived feature tracking provides a more sensitive analysis of myocardial function and may improve risk stratification in myocarditis. In this study, the prognostic value of LV, right ventricular, and left atrial strain in acute myocarditis patients is evaluated. Methods and Results: In this multicenter retrospective study, patients with CMR‐proven acute myocarditis were included. The primary end point was occurrence of major adverse cardiovascular events: all‐cause mortality, heart transplantation, heart failure hospitalizations, and life threatening arrhythmias. LV global longitudinal strain, global circumferential strain and global radial strain, right ventricular‐global longitudinal strain and left atrial strain were measured. Unadjusted and adjusted cox proportional hazard regression analysis were performed. In total, 162 CMR‐proven myocarditis patients were included (41 ± 17 years, 75% men). Mean LV ejection fraction was 51 ± 12%, and 144 (89%) patients had presence of late gadolinium enhancement. Major adverse cardiovascular events occurred in 29 (18%) patients during a follow‐up of 5.5 (2.2–8.3) years. All LV strain parameters were independent predictors of outcome beyond clinical features, LV ejection fraction and late gadolinium enhancement (LV‐global longitudinal strain: hazard ratio [HR] 1.07, P =0.02; LV‐global circumferential strain: HR 1.15, P =0.02; LV‐global radial strain: HR 0.98, P =0.03), but right ventricular or left atrial strain did not predict outcome. Conclusions: CMR‐derived LV strain analysis provides independent prognostic value on top of clinical parameters, LV ejection fraction and late gadolinium enhancement in acute myocarditis patients, while left atrial and right ventricular strain seem to be of less importance.