Clinical Features and Natural History of PRKAG2 Variant Cardiac Glycogenosis

Abstract

twitter: @dr_pavia // @fernidom Tweet: "Natural history study of PRKAG2 syndrome reveals high rates of AF, conduction disease, advanced HF and life-threatening arrhythmias." ABSTRACT Background: PRKAG2 gene variants cause a syndrome characterised by cardiomyopathy, conduction disease and ventricular preexcitation. Only a small number of cases have been reported to date, and the natural history of the disease is poorly understood. Objectives: To describe phenotype and natural history of PRKAG2 variants in a large multicenter European cohort. Methods: We retrospectively studied clinical, electrocardiographic and echocardiographic data from 90 individuals with PRKAG2 variants (53% males, median 33 years (IQR: 15-50) recruited from 27 centers. Results: At first evaluation, 93% of patients were in NYHA functional class I or II. Maximum left ventricular (LV) wall thickness was 18±8 mm and LV ejection fraction was 61±12%. LV hypertrophy (LVH) was present in 60 (67%) subjects at baseline. Thirty patients (33%) had ventricular preexcitation or had undergone an accessory pathway ablation; 17 (19%) had a pacemaker (median age at implantation 36 years (IQR: 27-46)) and 16 (18%) had atrial fibrillation (AF) (median age 43 years (IQR: 31-54)). After a median follow-up of 6 years (IQR:2.3-13.9), 71% of individuals had LVH, 29% had AF, 21% a de novo pacemaker (median age at implantation 37 years (IQR: 29-48)), 14% required admission for heart failure (HF), 8% experienced sudden cardiac death or equivalent, 4% required a heart transplant and 13% died. Conclusions: PRKAG2 syndrome is a progressive cardiomyopathy characterized by high rates of AF, conduction disease, advanced HF and life-threatening arrhythmias. Classical features of preexcitation and severe LVH are not uniformly present and diagnosis should be considered in patients with LVH who develop AF or require a PPM at a young age.

Phenotypic expression and clinical outcomes in a South Asian PRKAG2 cardiomyopathy cohort

“…The selection of those patients who would benefit from AICD therapy for primary prevention is not clear, although a strategy based on evaluation of individual risk factors should probably be considered, as is the established practice for HCM of the sarcomeric type 29 . Similar to this study, there was a high incidence of sudden cardiac death in the recent French (32%) and European (13%) cohorts 16,31 which clearly exceed the event rates noted in high risk sarcomeric HCM cohorts. Because of the paucity of follow up data published regarding this rare disease, risk stratification for ventricular arrythmias and sudden cardiac death remains challenging.…”

“…A recent multicenter, retrospective, longitudinal cohort study of 90 PRKAG2 syndrome patients from 27 European centers was described by Lopez-Sainz et al 31 . Notably, 88 patients were Caucasians of European ancestry.…”

Targeted Therapy in Cardiovascular Disease: A Precision Therapy Era

“…Moreover, no off-target events were detected in the selected 10 loci. Mice carrying H530 R mutation in PRKAG2 could develop cardiac hypertrophy (Lopez-Sainz et al, 2020). After being corrected by CRISPR/ cas9, the heart morphology and the cardiac function of the mutant mice were restored (Xie et al, 2016).…”

Prevalence and clinical outcomes of dystrophin‐associated dilated cardiomyopathy without severe skeletal myopathy

“…This study sought to describe the clinical profile and long‐term cardiac outcomes of DCM patients and asymptomatic relatives with DMD mutations without severe skeletal myopathy by analysing a large cohort of patients recruited from an established international multicentre collaboration 13–15 …”