Disease progression rate is a strong predictor of ventricular arrhythmias in patients with cardiac laminopathy in a prospective cohort study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research Area Network on Cardiovascular Diseases (ERA-CVD) Background/Introduction: Cardiac laminopathy is a highly malignant and pro-arrhythmic familial dilated cardiomyopathy, caused by LMNA gene mutations. The optimal timing of primary preventive implantable cardioverter defibrillator (ICD) is a challenge in this patient population. Purpose We aimed to explore whether disease progression rate assessed by echocardiography can predict ventricular arrhythmias in LMNA genotype positive patients, and to describe the cardiac phenotype at time of first ventricular arrhythmia. Methods We prospectively included consecutively recruited LMNA genotype positive patients in a primary prevention cohort study. Patients underwent repeated clinical and echocardiographic examinations during long-term follow-up. Ventricular arrhythmia was defined as sustained ventricular tachycardia, appropriate therapy by ICD or aborted cardiac arrest. We used generalized estimating equation analyses to assess whether individual patient disease progression could predict first-time ventricular arrhythmia. Graphical illustration of disease progression rate was presented as linear prediction by patient age. Cardiac function and volumes at time of ventricular arrhythmia was assessed from echocardiograms acquired ±12 months of the arrhythmic event. Results We included 94 patients with no ventricular arrhythmia at baseline (age 38 ± 15 years, 32% probands, 53% female). Nineteen (20%) patients experienced ventricular arrhythmia during 4.6 (inter quartile range 2.1-7.3) years follow-up, at mean age 50 ± 11 years. We analysed 536 echocardiographic examinations. Individual patient disease progression were strong predictors of subsequent ventricular arrhythmia with OR 1.3 (95% CI 1.2-1.5) per 5% reduction in left ventricular ejection fraction (LVEF), OR 1.3 (95% CI 1.2-1.5) per 1% worsened left ventricular global longitudinal strain (LVGLS), and OR 1.2 (95% CI 1.1-1.3) per 5 ml/m2 increase in left ventricular end diastolic volume index (LVEDVi). Comparison of disease progression by LVEF between patients with and without ventricular arrhythmias is illustrated in Figure. At arrhythmic event, there was left ventricular structural- and functional pathology (LVEF 40 ± 12%, LVGLS -11.7 ± 4.3%, LVEDVi 83 ± 22 ml/m2), while right ventricular function was preserved in most patients (tricuspid annular plane systolic excursion 20 ± 7 mm). Conclusions First time ventricular arrhythmic event occurred in 20% of LMNA genotype positive patients during 4.6 years of follow up. Individual patient disease progression by structural and functional parameters were strong predictors of ventricular arrhythmias, indicating that the disease progression rate may have additional value to absolute measurements when considering primary preventive ICD implantation. Abstract Figure