Long-term clinical outcomes in a large-scale ventricular septal defect cohort: impact of anatomical subtype and intervention timing

Background/Introduction

Ventricular septal defect (VSD) is the most common congenital heart disease. While traditionally classified as a ‘simple’ lesion with a favourable prognosis, the long-term clinical trajectory varies significantly depending on anatomical location, defect size, accompanying intracardiac abnormalities, and timing of closure.

Purpose

This study aimed to evaluate long-term clinical outcomes in a large, comprehensive, all-comer VSD cohort, focusing on the impact of anatomical subtype, size, and intervention timing on major cardiovascular complications.

Methods

A large-scale cohort of patients with VSD was assembled using a Common Data Model, with each case validated by echocardiographic findings and medical records. To assess long-term risks, patients were stratified into five groups: three surgery-based categories defined by age at repair (infant repair <1 year, childhood repair 1–19 years, and adult repair >19 years) and two non-surgical groups with unrepaired VSD persisting beyond age 1 year (small vs non-small VSD). Small VSD was defined as a defect size ≤4 mm or qualitative assessment as small. Major cardiovascular events (MCEs) included pulmonary hypertension (PHT), heart failure (HF), infective endocarditis (IE), sustained arrhythmias, pacemaker implantation, sinus of Valsalva rupture, at least moderate aortic regurgitation (AR), and death.

Results

A total of 4,316 patients (male 53.2%) were analysed. At baseline, the mean age at initial visit was 4.3 ± 8.4 years and the mean follow-up duration was 8.4 ± 6.0 years. VSD anatomical subtype was confirmed in 1,979 patients: perimembranous (70.0%), muscular (including muscular outlet, 22.1%), and subarterial (7.8%). The incidence of MCE differed significantly among subtypes: 10.5% in perimembranous, 7.5% in muscular, and 16.8% in subarterial types (p=0.005).

Among patients with surgical repair, the risk of MCE was significantly higher in the adult repair group (>19 years) at 38.2%, compared to 10.2% in the infant group and 8.3% in the childhood group (p<0.001). Specifically, adult repair was associated with significantly increased risks of HF (7.3% vs 0.9%), IE (8.9% vs 0.4%), arrhythmias (20.3% vs 5.7%), sinus of Valsalva rupture (4.9% vs 0.1%), and at least moderate AR (7.3% vs 0.5%) compared to younger surgical groups (all p<0.001). Among unrepaired patients, non-small VSDs carried a significantly higher burden of PHT (15.5% vs 0.0%, p<0.001) than small VSDs. Notably, Eisenmenger syndrome was identified in 25 patients, associated with a mortality rate of 24.0% and a mean age of death of 25.8 years.

Conclusion(s)

In this large-scale cohort, surgical repair in adulthood and unrepaired non-small VSDs—characterised by defect size or haemodynamic load—were critical predictors of major cardiovascular events. These results highlight the clinical necessity of timely VSD closure and the importance of structured lifelong surveillance for potential complications.flowchartfigure1