Progression of Cardiovascular Manifestations in Adults and Children With Mucopolysaccharidoses With and Without Enzyme Replacement Therapy

Front Cardiovasc Med. 2022 Jan 12;8:801147. doi: 10.3389/fcvm.2021.801147.

PMID: 35097020

Fabiano de Oliveira Poswar, Hallana Souza Santos, Angela Barreto Santiago Santos

Highlights: Adult patients with MPS may develop severe cardiovascular involvement, and clinicians should be aware of the need for careful monitoring and timely management of those potentially life-threatening complications.

Abstract

Background: One of the key characteristics of MPS diseases is cardiovascular involvement, which is also a substantial cause of morbidity and mortality. Heart valve disease, abnormal conduction, left ventricular hypertrophy, and coronary artery disease are among the variety of presentations. This study evaluated the cardiovascular symptoms and the effect of enzyme replacement therapy (ERT) in a cohort of children and adults with MPS I, II, IV, and VI.

Methods: 53 children and 23 adults with various kinds of MPS who had echocardiograms conducted between January 2000 and October 2018 were the subjects of a chart review. According to body surface area, standardized Z ratings for heart chamber sizes were determined. The evaluation of pre- and post-treatment parameters used echocardiographic measures taken before ERT and at least 18 months after that date, when available.

Results: In all four MPS types, left side valvular disease was a common observation, with the majority of patients reporting mitral and aortic thickness. 26% of the patients showed left atrial dilatation, 25% had increased relative wall thickness, and 28% had pulmonary hypertension. Conduction abnormalities (40 vs. 16%), mitral stenosis (26 vs. 6%), aortic stenosis (13 vs. 4%), and systolic dysfunction (observed in only one adult patient) were all more common and severe in adults than in children. The left ventricular hypertrophy parameters were significantly reduced by ERT, however the valve anomalies, pulmonary hypertension, and left atrial dilation did not improve.

Conclusions: Clinicians should be aware of the necessity for close monitoring and prompt therapy of those potentially fatal consequences in adult patients with MPS who develop significant cardiovascular involvement, which is uncommonly seen in children. The findings further support the limitations of long-term ERT in treating other common cardiovascular symptoms as well as its effect on left ventricular hypertrophy.

Keywords: enzyme replacement therapy, heart valve disease, left atrium, left ventricular hypertrophy, mucopolysaccharidoses, pulmonary hypertension