Disease progression rate is a strong predictor of ventricular arrhythmias in patients with cardiac laminopathies: a primary prevention cohort study. Issue 2 (10th November 2022)

• Record Type: Journal Article
• Authors: Rootwelt-Norberg, Christine; Skjølsvik, Eystein T; Chivulescu, Monica; Bogsrud, Martin P; Ribe, Margareth P; Aabel, Eivind W; Beitnes, Jan Otto; Brekke, Pål H; Håland, Trine F; Hasselberg, Nina E; Lie, Øyvind H; Haugaa, Kristina H
• Is Part Of: Europace. Volume 25:Issue 2(2023)
• Page Start: 634
• Page End: 642
• Publication Date: 2022-11-10
• Subjects: LMNA cardiomyopathy -- Lamin A/C -- Laminopathy -- Ventricular arrhythmia -- Primary preventive implantable cardioverter defibrillator; Arrhythmia -- Treatment -- Periodicals; Cardiac pacing -- Periodicals; Catheter ablation -- Periodicals; Heart -- Physiology -- Periodicals; Electrophysiology -- Periodicals; 617.4120645
• DOI: 10.1093/europace/euac192
• Languages: English
• ISSNs: 1099-5129

Abstract

Abstract: Aims: Cardiac disease progression prior to first ventricular arrhythmia (VA) in LMNA genotype–positive patients is not described. Methods and results: We performed a primary prevention cohort study, including consecutive LMNA genotype–positive patients from our centre. Patients underwent repeated clinical, electrocardiographic, and echocardiographic examinations. Electrocardiographic and echocardiographic disease progression as a predictor of first-time VA was evaluated by generalized estimation equation analyses. Threshold values at transition to an arrhythmic phenotype were assessed by threshold regression analyses. We included 94 LMNA genotype–positive patients without previous VA (age 38 ± 15 years, 32% probands, 53% females). Nineteen (20%) patients experienced VA during 4.6 (interquartile range 2.1–7.3) years follow up, at mean age 50 ± 11 years. We analysed 536 echocardiographic and 261 electrocardiogram examinations. Individual patient disease progression was associated with VA [left ventricular ejection fraction (LVEF) odds ratio (OR) 1.4, 95% confidence interval (CI) 1.2–1.6 per 5% reduction, left ventricular end-diastolic volume index (LVEDVi) OR 1.2 (95% CI 1.1–1.3) per 5 mL/m 2 increase, PR interval OR 1.2 (95% CI 1.1–1.4) per 10 ms increase]. Threshold values for transition to an arrhythmic phenotype were LVEF 44%, LVEDVi 77 mL/m 2, and PR interval 280 ms. Conclusions: Incidence of first-time VA was 20% during 4.6 years follow up in LMNA genotype–positive patients. Individual patient disease progression by ECG and echocardiography were strong predictors of VA, indicating that disease progression rate may have additional value to absolute measurements when considering primary preventive ICD. Threshold values of LVEF <44%, LVEDVi >77 mL/m 2, and PR interval >280 ms indicated transition to a more arrhythmogenic phenotype. Graphical Abstract: Graphical Abstract In a primary prevention cohort of 94 LMNA genotype–positive patients without VA at baseline, VA incidence was as high as 20% after 4.6 years follow up. Individual patient disease progression by ECG and echocardiography was a strong predictor of subsequent VA, suggesting additional value to the previously described risk factors in current guidelines for primary preventive ICD implantation. Threshold values of LVEF <44% and PR interval >280 ms indicated transition to a more arrhythmogenic phenotype. ECG, electrocardiogram; ICD, implantable cardioverter defibrillator; LVEF, left ventricular ejection fraction; VA, ventricular arrhythmia.