Lifetime Burden of Morbidity in Patients with Isolated Congenital Ventricular Septal Defect.
Eckerström F, Nyboe C, Redington A, Hjortdal VE. J Am Heart Assoc. 2023 Jan 3;12(1):e027477. doi: 10.1161/JAHA.122.027477. Epub 2022 Dec 24.PMID: 36565179
Commentary from Dr. Kenichiro Yamamura (Tokyo, Japan), section editor of ACHD Journal Watch
Introduction:
The assumption that an isolated ventricular septal defect (VSD) is a simple lesion without significant long-term risks is flawed. Recent evidence is suggestive of increased heart failure, arrhythmia, and infective endocarditis in this patient group.
Methods:
Data were collected from the nationwide medical registry and the Danish Civil Registry System. Patients diagnosed with a VSD were identified based on diagnostic coding until the end of 2018. Patients with other congenital cardiac malformations or chromosomal abnormalities were excluded. All patients who had a diagnosis of myocardial infarction prior to the diagnosis of the VSD were excluded to avoid including post-infarct VSDs.
Patients with a diagnosis of VSD were divided according to closure (surgical or transcatheter) and unrepaired groups. The Danish Civil Registry System was used to identify 10 controls per patient, matched by age and sex.
The endpoint of the study was classified as development of any of the following, defined according to diagnostic coding:
- Arrhythmia
- Arterial hypertension
- Diabetes mellitus
- Ischaemic cerebrovascular disease
- Chronic pulmonary disease
- Infective endocarditis
- Heart failure
- Ischaemic heart disease
- Pulmonary arterial hypertension
The first date of diagnosis was collected for each comorbidity.
Event free survival was defined as survival free from: arrhythmia, infective endocarditis, heart failure, pulmonary arterial hypertension, or death. The follow up period was taken from birth and censored at death, one of the above events or 31/12/2018. The statistics were analysed by expressing the continuous variable as median with inter quartile range and Cox hazard regression was used to generate hazard ratios, considering whether the defect was closed. The risk period was defined as 1 year post diagnosis or defect closure. Kaplan Meier’s were used to assess death rates. The Fine and Gray competing risk regression analysis was used to estimate cumulative incidence of morbidity among patients.
There were 8006 suitable patients included. The majority (58%) were diagnosed within the first year of life, inter quartile range 117 days-6 years. Closure of the VSD was performed in 682 (8.5%) of patients, of which 8 patients underwent transcatheter closure. Five hundred and eighteen patients died during follow up (6.4%: 465 unrepaired, 53 surgically closed) compared to 3.1% of controls.
The hazard ratios are best displayed in the table below, which was taken directly from the text reviewed.
The table shows the biggest risks are associated with arrhythmia, heart failure, infective endocarditis, and pulmonary arterial hypertension. Patients were not and increased risk of cerebral vascular disease following VSD closure.
The Kaplan Meier analysis showed reduced event free survival in patients with VSDs compared to controls for both the unrepaired group and closed group. This reduction in event free survival was accelerated after the fourth decade of life.
Discussion:
The findings are consistent with previous studies showing increased incidence of heart failure with VSDs. Possible causes suggested by the authors include:
- Abnormal volume and pressure loading
- Acquired left sided valve pathology.
- Left ventricular disease unrelated to the defect as part of diffuse cardiovascular disease, which may explain the association with arterial hypertension and ischaemic heart disease.
The authors acknowledge causation cannot be concluded from the study. Interestingly, the development of heart failure was not related to the development of arrhythmia.
The increased risk of pulmonary arterial hypertension may relate to the increased shunt causing long term changes in pulmonary vascular resistance, presumably in a more subtle way to that seem in overt Eisenmenger’s syndrome. Cumulative incidence of infective endocarditis was 19% in the unrepaired group compared to 50% in the closed group, but this does not mean closure increased the risk of infective endocarditis. The risk was diminished after closure, but it is likely many patients with have undergone closure because of endocarditis. The link between flow turbulence and endocarditis was proposed long ago.
Several study limitations were highlighted by the authors:
- There is the possibility of mis coding of the diagnosis.
- The analysis did not consider clinical test findings such as ECGs or echocardiograms.
The authors did not feel ascertainment bias was a factor as patients with VSDs are not routinely followed up in Denmark.
Conclusion:
The data support increased risk of arrhythmia, heart failure, infective endocarditis, and pulmonary arterial hypertension in patients with isolated congenital ventricular septal defect. This risk is amplified after the fourth decade of life. This supports long term follow up for these patients.
Positive points of the study:
- Large sample size
- Long follow up.
- Recognition of limitations regarding causation
- Appropriate division into unrepaired and closed helpful.
- Clinical relevance pointed out in conclusion.
Negative points of the study:
- Did not consider features of the VSD itself, such a position or size. For example, logically a VSD repaired using a very large patch would be more likely to predispose to heart failure due to reduced contractile myocardium.
- The majority of these VSDs were diagnosed in infancy, could this mean they are more significant defects?
- The number of patients who underwent VSD closure is relatively small.
