The number of adults with congenital heart disease is increasing due to the great achievements in the field of paediatric cardiology, congenital heart surgery and intensive care medicine over the last decades. Mortality has shifted away from the infant and childhood period towards adulthood. As congenital heart disease patients get older, a high prevalence of cardiovascular risk factors is encountered similar to the general population. Consequently, the contribution of acquired morbidities, especially acquired heart conditions to patient outcome, is becoming increasingly important. Therefore, to continue the success story of the last decades in the treatment of congenital heart disease and to further improve the outcome of these patients, more attention has to be given to the prevention, detection and adequate therapy of acquired heart conditions. The aim of this review is to give an overview about acquired heart conditions that may be encountered in adults with congenital heart disease.
- CORONARY ARTERY DISEASE
- HEART FAILURE
- CONGENITAL HEART DISEASE
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The number of adults with congenital heart disease (ACHD) is increasing due to the great achievements in the treatment of congenital heart defects over the last decades. Mortality has shifted away from the infant and childhood period towards adulthood, with a steady increase of age at death. Even the population of ACHD patients above the age of 60 is increasing dramatically.1 As ACHD patients are getting older, acquired morbidities, for example, heart conditions like coronary artery disease (CAD) or non-cardiac conditions like chronic renal failure, are becoming more and more important for the outcome of this population in conjunction with the underlying congenital heart defect.1 ,2 Accordingly, the percentage of patients without any comorbidity is decreasing while the number of patients with multiple comorbidities is increasing.3 Especially, acquired heart diseases are frequently encountered.4 Therefore, early prevention, detection and therapy of acquired comorbidities are of utmost importance and should be in our focus as much as the treatment of the congenital heart defect and its sequelae itself. This review aims to give an overview about acquired heart conditions that may be encountered in ACHD patients.
Coronary artery disease
A number of factors can foster the development of CAD in ACHD patients. First, congenital coronary artery abnormalities (anomalous origin and/or course) have been described in a variety of congenital heart defects, for example, congenitally corrected transposition of the great arteries.5 Another rare cause of angina and myocardial ischaemia in patients with Eisenmenger syndrome is an extrinsic compression of the left coronary ostium by a dilated pulmonary artery.6 Furthermore, manipulation of the coronary arteries can be an unavoidable part of the surgical repair of the congenital heart defect, for example, reimplantation of the coronary arteries during the arterial switch procedure in transposition of the great arteries or during aortic root replacement in Marfan patients. And finally, atherosclerotic disease similar to that found in patients without congenital heart disease can develop in ACHD patients.7 While a great deal of effort was put into improving surgical techniques to limit the effect of surgical manipulation on the coronary arteries, prevention and treatment of atherosclerotic disease is often not a priority during the care of ACHD patients since the focus is on the treatment of the congenital heart defect and its sequelae itself.
Cardiovascular risk factors
The important contribution of traditional cardiovascular risk factors (CVRF) like arterial hypertension and hyperlipidaemia to the development of atherosclerotic disease is well established in patients without congenital heart defects.8 The prevalence of these CVRF was studied in 141 ACHD patients with concomitant CAD.7 The majority of patients (82%) had one or more CVRF with systemic arterial hypertension and hyperlipidaemia being the most prevalent (53% and 25%, respectively).7 A study from Belgium that included 1976 patients with ACHD reported that only around 20% of the patients had a fully heart-healthy lifestyle without any CVRF.4 Considering that the median age of these patients was only 26 years, these findings are especially alarming. Worryingly, data on cholesterol levels were not available in this study.4 Therefore, the full picture may be even worse with a much smaller number of patients presenting without any CVRF.
Arterial hypertension is associated with stroke, myocardial infarction, sudden death, heart failure, peripheral artery disease and end-stage renal disease in the general population.9 Its prevalence in ACHD patients was found to be somewhere between 30% and 50%.4 ,10 This is in a similar range as reported for the general population.9 Furthermore, some ACHD patients with selected congenital heart defects are even more prone to have a high blood pressure than the general population or patients with other congenital heart defects. This holds especially true for patients with coarctation of the aorta, in whom the prevalence of arterial hypertension was reported to be much higher than in patients with a ventricular septal defect in a recent study (45% vs 16%).11 In contrast, some patients with complex lesions, for example, with a Fontan circulation, have low blood pressure values due to a chronic impairment in cardiac output.
Data regarding the occurrence of obesity in ACHD patients are inconclusive. While in the already mentioned Belgian study patients with ACHD were more often obese than the general population,4 a study from the Netherlands reported that the proportion of ACHD patients that were overweight or obese was smaller than in the general population.12 Nonetheless, 40% of ACHD patients were overweight or obese in the later study.12 One reason for a higher prevalence of obesity in ACHD patients could be that the issue of exercise is often not raised with ACHD patients.13 And if it is finally discussed, it is more common that patients receive prohibitive advice,13 leading to a more sedentary way of living. But in most ACHD patients exercise is safe, provided that individual exercise prescriptions are based on a comprehensive assessment of the underlying cardiac condition, possible sequelae, cardiac function, arrhythmias, pulmonary hypertension and aortic dimensions as well as individual exercise capacity.14 Recently published recommendations will hopefully lead to an improvement regarding this matter.15 A further cause for obesity discussed in ACHD patients is the encouragement of adequate nutrition as an early focus in the care of infants with CHD to catch up with their peers.16
Smoking is associated with an increased risk for all types of cardiovascular disease—CAD and stroke to name a few—as well as a plethora of non-cardiovascular diseases like cancer.8 Fortunately, the proportion of ACHD patients that smoke has been reported to be smaller than in the general population.4 ,12 But if we consider the hazardous effects of smoking, it is worrisome that still between 13 and 23% of ACHD patients smoke.4 ,12
Information regarding dyslipidemia in ACHD patients is scarce. Two large studies that assessed CVRF in ACHD patients did both not include data regarding lipid levels.4 ,12 One smaller study reported lower levels of total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in ACHD patients in comparison to a general population sample group, while triglyceride levels were not different.17 In elderly patients with ACHD, the prevalence of dyslipidemia was reported to be 27%.10 In ACHD patients with established CAD, the prevalence of hyperlipidaemia is between 10 and 75% depending on the type of congenital heart defect.7 ,11 ,18
Cardiovascular disease is the leading cause of morbidity and mortality in patients with diabetes mellitus.8 Two recent studies concordantly reported that approximately 3% of ACHD patients had diabetes.12 ,17 The prevalence was the same for ACHD patients and a control group without congenital heart disease.17
In conclusion, all traditional CVRF associated with atherosclerotic disease are present in a substantial number of ACHD patients (table 1).
The clinical picture of CAD in ACHD can be similar to that seen in the population without a congenital heart defect.7 In a study of 250 patients with ACHD that underwent coronary angiography for reasons other than suspected CAD, significant CAD was present in around 10% of these patients.18 The prevalence was similar to that in the general population. By means of CVRF, systemic arterial hypertension and hyperlipidaemia were strongly associated with CAD in this ACHD cohort.18 Interestingly, no patient with an age below 40 years had significant CAD.18 In contrast, Yalonetsky et al7 reported that in their study, 14% of ACHD patients with CAD had premature CAD (age <40 years). Therefore, even in ACHD patients below the age of 40 years, CAD cannot be ruled out. Systemic screening for ischaemic heart disease would probably reveal an even higher prevalence of CAD in ACHD.7 Therefore, as patients grew older, we have to expect a higher number of ACHD patients that are affected by CAD. This is not only of academic interest but comes along with a significant burden of morbidity and mortality. A recent study reported an almost threefold increase of percutaneous coronary interventions in a large sample of ACHD patients between 1998 and 2005.3 Furthermore, in a large registry study from the US myocardial infarction was the leading contributing cause of death in non-cyanotic ACHD patients.19 Additionally, in a study of ACHD patients beyond the age of 60, CAD was a strong prognostic factor on multivariate analysis and a key determinant of outcome in this elderly population in conjunction with the underlying congenital heart defect.1
Risk of CAD in selected congenital heart defects
Cyanotic congenital heart disease
It is often discussed that adults with cyanotic congenital heart disease may be protected from CAD because of protective antiatherosclerotic factors like hypocholesterolaemia, upregulation of nitric oxide, hyperbilirubinemia and others that are frequently encountered with cyanosis.20 And indeed, in the study by Giannakoulas et al18 none of the patients with cyanosis had significant CAD. In accordance, Fyfe and colleagues could not find obstructive CAD in any of their patients with cyanotic congenital heart disease.20 But we still have to be cautious since Yalonetsky et al7 reported in their study CAD in seven patients with Eisenmenger syndrome. Therefore, even adults with cyanotic congenital heart disease require surveillance for CAD.
Coarctation of the aorta
Multiple studies have shown that the main cause of late death in patients with corrected coarctation of the aorta (CoA) is CAD.11 ,21 Furthermore, the life expectancy of patients with CoA—even after repair—is significantly reduced compared with the general population with premature cardiovascular death as the primary contributing factor to this worse outcome.16 ,21 Additionally, peripheral vascular disease and stroke have been reported to occur with a higher prevalence in patients with CoA compared with other ACHD patients in a study encompassing a large number of participants using administrative databases from Quebec.11 Interestingly, CoA alone did not predict CAD in the same study after adjusting for CVRF like arterial hypertension or hyperlipidaemia.11 It was concluded that CAD in CoA was mainly caused by the same traditional CVRF that predispose the general population to atherosclerotic disease.11 These CVRF had a much higher prevalence in CoA than in a control group of patients with ventricular septal defects.11 The important conclusion of this study is that it stresses the fact that the diagnosis of CoA itself is not a self-fulfilling prophecy of early cardiovascular death due to CAD. Careful targeting of traditional CVRF could possibly decrease the morbidity and mortality of this patient group.11
Other acquired heart conditions
Arrhythmias are a major cause of morbidity, hospitalisations and mortality in ACHD patients.22 ,23 Bradyarrhythmias caused by sinus node dysfunction or atrioventricular conduction abnormalities are frequently encountered as well as atrial or ventricular tachyarrhythmias.24 The causative factors are multifactorial and include scar tissue due to previous cardiac surgeries, inherent structural abnormalities and acquired comorbidities.23 Accordingly, arrhythmias are often precipitated by haemodynamic deterioration and systolic dysfunction.24 It has recently been recognised that diastolic dysfunction in patients without congenital heart disease is associated with atrial arrhythmias, especially atrial fibrillation.25 Risk factors for diastolic dysfunction include age, arterial hypertension, obesity and diabetes.25 Diastolic dysfunction is also often found in ACHD patients.26 Similar to diastolic dysfunction in patients without congenital heart disease, it has been reported to be associated in ACHD patients with arterial hypertension, dyslipidemia, diabetes mellitus and the number of previous cardiac operations.26 Furthermore, it seems also to be linked to the occurrence of atrial and ventricular arrhythmias.26 ,27 Therefore, the consequent treatment of comorbidities like arterial hypertension could possibly lead to a reduction of diastolic dysfunction in ACHD patients and subsequently even to a reduction of the arrhythmia burden.
Some forms of congenital heart defects like tetralogy of Fallot are especially prone to ventricular arrhythmias and sudden cardiac death.23 ,28 This is mainly caused by inherent structural abnormalities, ventricular dysfunction and scar forming after cardiac surgery. In patients without congenital heart disease, ischaemic heart disease plays an important role in the pathogenesis of ventricular arrhythmias.29 Interestingly, a recent multicentre study assessing implantable cardioverter defibrillator (ICD) therapy in ACHD patients reported CAD as an independent predictor of appropriate ICD shocks.30 Therefore, ischaemic heart disease should also be considered as one possible cause of ventricular arrhythmias in ACHD patients and may represent an important target for risk stratification and treatment.
Chronic heart failure is an important cause for morbidity and mortality in ACHD.31 Its prevalence is highest in patients with complex anatomy, for example, single ventricle physiology or transposition of the great arteries.24 It is mainly caused by the pathophysiology of the congenital heart defect, for example, a systemic RV in congenitally corrected transposition of the great arteries, and accompanying factors like prolonged cyanosis and previous cardiac surgeries. Heart failure in ACHD is less likely to be caused by left ventricular systolic dysfunction as in the general population but is more often a consequence of right ventricular dysfunction, valve dysfunction or shunting.24 Diastolic dysfunction is also found in ACHD patients and often leads to heart failure.26 Nonetheless, considering that risk factors for the development of heart failure in the general population like arterial hypertension, diabetes and CAD to name a few are also present in ACHD patients, it seems reasonable to assume that these risk factors could also play a role in the development of heart failure in this patient group. And indeed, Giannakoulas et al18 reported that the association between CAD and systemic ventricular size and functional impairment in their patients suggested that CAD may contribute to ventricular dilatation and functional limitation. This is of importance since there are established treatment options for CVRF like arterial hypertension and diabetes mellitus, and also for CAD. In contrast, there is no good evidence-based treatment for heart failure in ACHD since the studies conducted so far were small, often not blinded and showed contradicting results. The few randomised controlled trials did not fulfil the expectations.32 Even so treatments that are established in heart failure of non-congenital origin are still used in ACHD patients despite lacking evidence.
The way forward
Because significant effort is made to address the anatomical and haemodynamic aspects of congenital heart disease, the prevention and treatment of acquired morbidities may not receive enough attention.18 Primary prevention of CAD is often not discussed in the paediatric cardiology setting.33 And even in adult life an adequate discussion of risk factors, for example, stressing the importance of fitness and a patient-centred exercise prescription, is often rare.13 Since studies assessing the application of primary prevention of CAD in ACHD are not available, we can only speculate, but it seems reasonable to assume that the recognition and treatment of traditional CVRF in ACHD patients is not well established in the daily practice of ACHD care. There are currently no studies proving that prevention and treatment of traditional CVRF for CAD in ACHD patients leads to a decrease of morbidity and mortality, but data from studies in the general population are encouraging.8 Therefore, the importance of a healthy lifestyle and the need for primary prevention should be emphasised during each follow-up visit (figure 1). The avoidance or cessation of smoking is absolutely critical, and the need of regular blood pressure control should be addressed.4 Every physician caring for ACHD patients should be alert to the fact that CAD can occur in this population. If CAD is suspected, diagnosis can be difficult since the interpretation of exercise testing can be hampered by ECG with abnormal findings like bundle branch blocks that are attributable to the underlying anatomy and previous surgeries.18 These make the assessment of ECG changes during exercise difficult. An alternative in selected patients could be stress perfusion cardiovascular MRI. It was recently shown to be a useful and accurate tool for investigation of myocardial ischaemia in ACHD patients.34
In summary, to continue the success story of the last decades in the treatment of congenital heart disease and to further improve the outcome of our patients, we should not only address the anatomical and haemodynamic aspects of congenital heart disease, but also should pay attention to the prevention, detection and adequate therapy of CVRF and acquired heart disease in our daily ACHD practice. To achieve this goal, every physician taking care of this challenging patient population should be adequately trained in the evaluation and treatment of acquired heart conditions like CAD.1
Contributors OT prepared the draft of the manuscript, revised the manuscript critically for important intellectual content and provided final approval of the manuscript.
Competing interests None.
Provenance and peer review Commissioned; externally peer reviewed.