Author + information
- Annelieke C.M.J. van Riel, MD,
- Ilja M. Blok, MD,
- Aeilko H. Zwinderman, MD, PhD,
- Elly M.C.J. Wajon, MD,
- Arthur S.J.M. Sadee, MD, PhD,
- Mirjam Bakker-de Boo, MD, PhD,
- Arie P.J. van Dijk, MD, PhD,
- Elke S. Hoendermis, MD, PhD,
- Robert K. Riezebos, MD, PhD,
- Barbara J.M. Mulder, MD, PhD and
- Berto J. Bouma, MD, PhD∗ ()
- ↵∗Department of Cardiology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
Successful repair of shunts in patients with congenital heart disease (CHD) is often erroneously considered a cure, leading to a large number of patients lost to follow-up after discharge (1). The prevalence of pulmonary hypertension (PH) appears to be high after shunt closure (2) and is associated with increased morbidity and mortality (3). Until now, only limited data on the risk of PH after shunt closure were available, and these data were hampered by the use of database encoded analyses, single-center studies, or small cohort studies in specific cardiac defects. We aimed to identify the time course of the development of PH after shunt closure in adults with CHD to optimize monitoring intervals of these patients and to identify PH in an early stage.
We used the Dutch CONgenital CORvitia registry, containing 15,800 adult CHD patients, to identify all patients with a closed systemic-to-pulmonary shunt (n = 3,340), of which a randomized sample, stratified according to secondary or tertiary center, underwent thorough review of all medical records. In this nationwide cohort sample of 1,103 patients, we determined the cumulative incidence of PH after shunt closure. Subsequently, a nested case-control study was performed to analyze predictors associated with PH after shunt closure. All cases of PH were matched with up to 2 controls on age (±5 years), sex, and presence of Down syndrome. Presence of PH was defined as documented systolic pulmonary artery pressure >40 mm Hg on echocardiography. Patients with signs of left-sided valvular disease (moderate or severe mitral stenosis or regurgitation, moderate or severe aortic stenosis or regurgitation) or elevated diastolic filling pressures (early diastolic velocity ratio >15, left ventricular ejection fraction <40%, moderate or severe left atrial dilation) were excluded.
In the cohort of 1,103 shunt patients, closure was performed in year 1987 (median, interquartile range: 1977 to 1990) at a median age of 8.5 years (interquartile range: 2.9 to 27.6). The most common diagnoses were secundum atrial septal defect (ASD) (n = 382), ventricular septal defect (n = 283), and primum ASD (n = 92). In total, 72 cases with PH were identified during a mean period of 25 ± 14 years. The cumulative incidence of PH immediately after closure was 2.1% (95% confidence interval [CI]: 0.3 to 7.7) and >15% (95% CI: 2.6 to 23.8) 50 years after closure (Figure 1A). Remarkably, even patients with mild defects such as secundum ASD closed <25 years of age, were at risk of developing PH several decades after repair (6 of 141 patients, 4.3%). The incidence of PH, specified according to age at closure, is visualized in Figure 1B. In multivariate conditional logistic regression analysis of the case-control cohort, presence of PH pre-closure (rate ratio 5.7; 95% CI: 2.4 to 13.6; p <0.001) and New York Heart Association functional class >I pre-closure (rate ratio: 2.9; 95% CI: 1.3 to 6.8; p = 0.009) were the strongest predictors for PH development after closure, corrected for age at closure, sex, underlying CHD defect, presence of right bundle branch block, right atrial or ventricular dilation, right ventricular dysfunction, and history of supraventricular tachycardia. Furthermore, patients diagnosed with PH had a significantly lower 10-year survival after diagnosis compared to their controls (odds ratio: 3.5; 95% CI: 1.2 to 10.0; p = 0.02).
These findings elucidate the time course and significance of PH after shunt closure. The hypothesis for PH development after closure might be that even short periods of volume or pressure overload to the pulmonary circulation result in changes of the pulmonary vasculature, which in time lead to PH (4). These alarming results call for monitoring of all CHD patients after shunt closure, even when closure took place during childhood. Our findings do not support the current European and Northern American guidelines, which state that patients with simple defects such as secundum ASD, repaired when the patient is <25 years of age, do not require regular follow-up (5). The presented risk factors can further aid in determining the required intensity of monitoring in specific patients.
All patients after shunt closure need follow-up, because even when repaired at early age, late risk of PH development, in absence of left-sided heart disease, is >15% and has significant impact on survival.
Please note: This study was supported by an unrestricted research grant from Actelion Pharmaceuticals Ltd. The work described in this study was carried out in the context of the Parelsnoer Institute (PSI). PSI is part of and funded by the Dutch Federation of University Medical Centers and has received initial funding from the Dutch Government (from 2007-2011). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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