P6455Differences in cardiac phenotype and natural history of laminopathies with and without neuromuscular presentation
Authors: Ditaranto R , Rapezzi C , Boriani G , Pasquale F , Graziosi M , Vitale G , Berardini A , Lanati G , Corsini A , Caponetti G , Lattanzi G , Potena L , Ziacchi M , Leone O , Biagini E 
Published: October 2019

Abstract

Aim
To look for differences in cardiac phenotype and natural history of patients affected by laminopathy, according to the presence or less of neuromuscular involvement at clinical presentation.

Methods
We prospectively analyzed 47 consecutive pts with a genetic diagnosis of laminopathy followed at a single centre between 1994 and 2017. Additionally, reports of clinical and instrumental evaluations before referral at our centre were retrospectively evaluated.

Results
Neuromuscular presentation, mainly as Emery-Dreifuss muscular dystrophy (EDMD), was present in 21 (46%) cases (14 LMNA and 7 EMD gene mutations). These pts had symptoms earlier (9 vs 39 years, p<0.001) in life compared to pts without neuromuscular onset (26 LMNA gene mutations), and clinical manifestations anticipated the first evidence of cardiac disease by a mean time of 15±8 years (maximum time gap of 38 years). Despite a similar prevalence of atrial fibrillation/flutter (AF) (71% vs 65%, p=0.758) and atrio-ventricular blocks (48% vs 65%, p=0.250), pts with neuromuscular onset experienced AF and pace-maker implantation at a significantly younger age (27 vs 41 yrs, p=0.015 and 23 vs 44 yrs, p=0.027 respectively). Differently a higher prevalence of sinus node dysfunction (33% vs 4%; p=0.015) and atrial paralysis (14% vs 4%; p=0.311) was reported in pts with neuromuscular onset. Prevalence of cardiomyopathy (CMP) (73% vs 33%, p=0.008) and sustained ventricular tachyarrhythmias were higher among pts with cardiac onset (23% vs 4%, p=0.111) whereas the prevalence of heart transplantations and median age of recipients were similar in the two groups (24% vs 20%, p=1.000 and 46 vs 43, p=0.592 years respectively). All pts with neuromuscular onset who received a diagnosis of CMP had a previous history of rhythm disturbance except 2 cases, where a concomitant diagnosis of the 2 disorders was formulated. On the contrary a strict temporal progression from rhythm disturbances to CMP (or viceversa) was not appreciable in the other group: AF and AVBs could precede the diagnosis of CMP be diagnosed at the same time or later.

Conclusions
In pts affected by laminopathy neuromuscular involvement, when present, was most often the first clinical manifestation and preceded cardiological involvement, with a long time frame in some cases. Except for sinus node dysfunction, much more frequent in patients with EDMD, a similar prevalence of rhythm disturbances was reported, although pts with neuromuscular clinical onset were younger at diagnosis of AF and at PM implantation. Pts without neuromuscular presentation had a higher prevalence of CMP and ventricular arrhythmias, albeit a similar rate of heart transplantation. In pts with neuromuscular onset, cardiac involvement was characterized by a stepwise progression from rhythm disturbances to CMP, where a strict temporal progression from rhythm disturbances to CMP was not observed in the group of pts without neuromuscular clinical onset.