Natural Course and Clinical Outcomes of Small Perimembranous Ventricular Septal Defects in Children at a Tertiary Cardiac Center: A Prospective Cohort Study

Abstract

Objectives: This study aimed to evaluate the natural course, spontaneous closure rate, and occurrence of structural complications among children with isolated small perimembranous ventricular septal defects (PM-VSDs managed at a tertiary cardiac center in Karachi. Methodology: This prospective observational cohort study was conducted at the Department of Pediatric Cardiology, National Institute of Cardiovascular Diseases (NICVD), Karachi, Pakistan, between November 2025 and May 2026. A small PM-VSD was defined echocardiographically as a ventricular septal defect measuring less than 50% of the aortic annulus diameter, demonstrating a peak Doppler pressure gradient ≥50 mmHg, with no evidence of pulmonary hypertension or left heart chamber enlargement. A total of 550 consecutive pediatric patients aged 2–15 years with isolated small PM-VSDs were enrolled and followed prospectively through serial clinical assessments and transthoracic echocardiography. The mean follow-up duration was 3.33 months (IQR: 1.8–5.2 months). Primary outcomes included spontaneous defect closure, persistence of the defect, development of structural complications, and requirement for intervention. Results: A total of 550 patients were included in the final analysis. Male patients constituted 64% of the study population, and the mean age at diagnosis was 5.69 ± 4.4 years. Incidental cardiac murmur was the most frequent presenting finding. Spontaneous closure occurred in 12.54% (n=69) of patients, whereas persistent PM-VSD was observed in 57.2% (n=315). Progressive complications requiring intervention developed in 22.54% (n=124), while 7.63% (n=42) were lost to follow-up. Structural complications included aortic valve prolapse with aortic regurgitation (48.72%), right ventricular outflow tract obstruction (13.63%), infective endocarditis (6.0%), and rhythm disturbances (1.63%). Although spontaneous closure was numerically more frequent among children diagnosed before five years of age than in older children (14.0% vs. 10.7%), the difference was not statistically significant (χ²=1.43, p=0.49). Conclusion: Small PM-VSDs demonstrated a heterogeneous clinical course characterized by relatively low spontaneous closure rates and a substantial burden of structural complications in this cohort. These findings emphasize the importance of regular long-term clinical and echocardiographic surveillance for early recognition of disease progression and timely intervention to prevent irreversible cardiac complications.