Outcome of congenital heart disease with modern cardiac care

For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts. Adults with congenital heart disease are a growing minority due to the impressive progress in the management of these complex conditions. Thanks to advances in surgical techniques and catheter-based interventions, many children with congenital heart disease live into adulthood and indeed enjoy an increasing life span, but remain at risk for different complications.1–4 The current increased life span as such is proof that many therapeutic interventions are effective, although evidence from randomized trials is largely lacking. Only a few therapeutic measures have actually been tested in randomized controlled trials. Rachael Cordina and colleagues from the Royal Prince Alfred Hospital in Camperdown, NSW Australia base their analysis on the available evidence to discuss ‘Management errors in adults with congenital heart disease: prevalence, sources, and consequences’. 5 The authors stress the fact that international guidelines recommend specialized care in such patients.6 Of 309 patients, 43% were referred by general cardiologists, among them 19% with highly complex lesions, and 37% from paediatric or adult specialists in congenital heart disease of which 33% had highly complex lesions, while 20% were from other medical teams. Guideline deviations were more common in referrals from general compared with specialized cardiologists. Of general cardiology referrals, 37% were non-adherent, of which a third had catastrophic or major complications. In contrast, only 10% of the referrals from paediatric or adult congenital heart specialists were non-adherent. Patients were at increased risk of adverse outcome when not under specialized care. Thus, non-adherence with guidelines is common in the care of adults with congenital heart disease, and this frequently results in adverse clinical consequences. The practical implications of these results are further discussed in an Editorial by Helmut Baumgartner from the University Hosptial Muenster in Germany.7 Atrial septal defects are among the most common congenital heart defects. Although the lesion can be closed nowadays with interventional or surgical techniques, timing and indication for such procedures to prevent pulmonary hypertension,8 right heart failure,3 and premature death is still debated. Camilla Nyboe and colleagues from the Aarhus University Hospital in Denmark address this issue in their paper entitled ‘Long-term mortality in patients with atrial septal defect: a nationwide cohort-study’.9 They included Danish individuals born before 1994 with an atrial septal defect followed up for a median of 18 years. Such patients had a higher mortality with a hazard ratio of 1.7 compared with the general population. The hazard ratio 30 days after closure was 1.4, but was 2.4 for patients without closure (Figure 1). Thus, overall, atrial septal defect patients have a higher long-term mortality than the general population, with a lower relative mortality of those undergoing closure of the defect. These important findings are put into clinical context in an Editorial by David S. Celermajer from the University of Sydney in Camperdown, Australia.10 Survival in years for atrial septal defect (ASD) patients without closure compared with the comparison cohort with age as an underlying time scale (from Nyboe C, Karunanithi Z, Nielsen-Kudsk JE, Hjortdal VE. Long-term mortality in patients with atrial septal defect: a nationwide cohort-study. See pages 993–998). Scimitar syndrome is a rare congenital lesion characterized by anomalous venous drainage of part or the entire right lung to the inferior vena cava, variable right lung hypoplasia, and variable systemic blood supply to part of the right lung. Treatment decisions in such patients are challenging, especially in those with an isolated form who are often asymptomatic. Thus, in their paper entitled ‘The natural history and surgical outcome of patients with scimitar syndrome: a multicentre European study’, Vladimiro Vida and colleagues from the Universita degli Studi di Padova in Italy queried a large multi-institutional registry of 485 Scimitar patients to evaluate the natural history and efficacy of surgical treatment.11 Of those, 57% were treated surgically and 43% were clinically monitored. Overall survival probability at 30 years of age was 88% and was lower in those with associated congenital heart disease or pulmonary hypertension (Figure 2). Two-thirds were asymptomatic at last follow-up, particularly those treated surgically compared with monitored patients (73% vs. 47%), with fewer cardiac and respiratory symptoms. However, 25% of the patients treated surgically had stenosis or occlusion of the drainage, particularly those of younger age at surgery. Thus, patients with scimitar syndrome have a high overall survival, particularly those without associated congenital heart diseases or pulmonary hypertension. Surgical treatment of scimitar syndrome is beneficial in reducing symptoms; however, given the significant risk of post-operative scimitar drainage stenosis or occlusion, it should be tailored to a comprehensive haemodynamic evaluation and to the patient’s age. These findings are complemented by an Editorial by Gary D. Webb and Alexander Opotowsky from Boston Children’s and Brigham and Women’s Hospitals in Massachusetts (USA).12 Survival probability according to Kaplan–Meier (age of patients at last follow-up examination with 95% confidence bands) of patients with pulmonary hypertension: (A) overall population and stratified by (B) patients with isolated SS (without congenital heart diseases, CHDs) and (C) patients with associated CHDs. SS, scimitar syndrome (from Vida VL, Guariento A, Milanesi O, Gregori D, Stellin G, on the Scimitar Syndrome Study Group. The natural history and surgical outcome of patients with scimitar syndrome: a multi-centre European study. See pages 1002–1011). Congenital heart defects affect almost 1% of all live born children, and the number of adults with congenital heart defects is increasing. In families with congenital heart defects, estimates of recurrence risk and the type of recurring malformation are important, but the recurrence patterns are poorly understood. In their manuscript, ‘Familial co-occurrence of congenital heart defects follows distinct patterns’, Lars Allan Larsen and colleagues from the University of Copenhagen in Denmark investigated the co-occurrences of congenital heart defects in 1163 families with known malformations, comprising 3080 individuals with confirmed diagnosis.13 By calculating odds ratios for each of the 1640 pairs of discordant lesions observed between affected family members, they were able to identify 178 pairs of malformations that co-occurred more or less often than expected in families. The data show that distinct groups of cardiac malformations co-occur in families, suggesting an influence from underlying developmental mechanisms. Analysis of human and mouse susceptibility genes showed that they were shared in 19% and 20% of pairs of co-occurring discordant malformations, respectively, but in none of the malformations that rarely co-occur, suggesting that a significant proportion of co-occurring lesions in families is caused by overlapping susceptibility genes. Thus, familial congenital heart defects follow specific patterns of recurrence, suggesting a strong influence of genetically regulated developmental mechanisms due to shared susceptibility genes. These results are critically discussed in an Editorial by Heribert Schunkert from the Deutsche Herzzentrum München in Germany.14 Remote ischaemic pre-conditioning by inducing brief ischaemia in distant tissues may protect the heart against myocardial ischaemia–reperfusion injury during infarction15 and open-heart surgery.16 The effectiveness of this procedure in children with tetralogy of Fallot is unclear. In a final research article entitled ‘Cardiac protective effects of remote ischaemic pre-conditioning in children undergoing tetralogy of Fallot repair surgery: a randomized controlled trial’, Zhengyuan Xia and colleagues from the University of Hong Kong tested the effectiveness of three cycles of 5-min lower limb occlusion and 5-min reperfusion using a cuff inflator in 112 tetralogy of Fallot children undergoing corrective surgery.17 Fifty-five children were randomized to pre-conditioning and 57 to the control group. Post-operative ventilation time and length of stay in the intensive care unit were longer in controls than in the pre-conditioning group. The levels of troponin-T at 12 and 18 h post-operatively, creatine kinase-MB (CK-MB) at 24 h, as well as the serum heart-type fatty acid binding protein (h-FABP) levels at 6 h after surgery were lower, while protein expression of cardiac Hif-1α, p-Akt, p-STAT3, p-STAT5, and p-eNOS in myocardial tissue was higher and vacuolization of mitochondria lower in the pre-conditioning group. Thus, in tetralogy of Fallot children undergoing open heart surgery, remote ischaemic pre-conditioning attenuates myocardial ischaemia–reperfusion injury and improves the short-term prognosis. The editors hope that this issue of the European Heart Journal will be of interest to its readers.