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Adult Congenital Heart Disease: A Growing Epidemic
Canadian Journal of Cardiology 30 (2014) S410eS419
Review
Adult Congenital Heart Disease: A Growing Epidemic Pablo Ávila, MD, Lise-Andree Mercier, MD, Annie Dore, MD, François Marcotte, MD, François-Pierre Mongeon, MD, MS, Reda Ibrahim, MD, Anita Asgar, MD, Joaquim Miro, MD, Gregor Andelfinger, MD, Blandine Mondesert, MD, Pierre de Guise, MD, Nancy Poirier, MD, and Paul Khairy, MD, PhD Montreal Heart Institute Adult Congenital Center, Universite de Montre al, Montreal, Quebec, Canada
ABSTRACT
RESUM E
Medical and surgical breakthroughs in the care of children born with heart defects have generated a growing population of adult survivors and spawned a new subspecialty of cardiology: adult congenital heart disease. The prevalence of adult congenital heart disease is escalating at a rampant rate, outpacing the relatively static prevalence of pediatric congenital heart disease, because adults now surpass children in numbers by a ratio of 2:1. As such, congenital heart disease can no longer be considered primarily a pediatric specialty. Most congenital heart defects are not curable and require lifelong specialized care. Health care systems worldwide are challenged to meet the unique needs of this increasingly complex patient population, including the development of supraregional centres of excellence to provide comprehensive and multidisciplinary specialized care. In this review, we explore the incidence and prevalence of congenital heart disease and their changing patterns, address organization and delivery of care, highlight the importance of appropriate training and dedicated research, summarize the high burden of health care resource utilization, and provide an overview of common issues encountered in adults with congenital heart disease.
es me dicales et chirurgicales dans la prise en charge des Les avance s avec des malformations cardiaques ont ge ne re un nombre enfants ne naissance à une nouvelle croissant de survivants adultes et ont donne cialite de la cardiologie : la cardiopathie conge nitale chez sous-spe valence des adultes atteints de cardiopathie conl’adulte. La pre nitale s’amplifie à un rythme effre ne , de passant la pre valence relge nitales pe diatriques, puisque ativement stable des cardiopathies conge passent maintenant en nombre les enfants avec un ratio les adultes de nitale ne peut plus être de 2 : 1. En tant que telle, la cardiopathie conge re e comme e tant essentiellement une spe cialite pe diatrique. conside nitales ne sont pas curLa plupart des anomalies cardiaques conge cessitent des soins spe cialise s à vie. Les systèmes de sante ables et ne s à re pondre aux besoins particuliers de du monde entier sont amene cette population de patients de plus en plus complexe, y compris par le veloppement de centres d’excellence suprare gionaux afin de fournir de cialise s d’ensemble et multidisciplinaires. Dans cette des soins spe valence des cardiopathies revue, nous examinons l’incidence et la pre nitales et leurs particularite s changeantes, nous abordons l’orconge vidence l’imporganisation et la prestation des soins, mettons en e e et d’une recherche de die e, tance d’une formation approprie sumons la charge conside rable de l’utilisation des ressources des re , et nous fournissons un aperçu des problèmes habituels soins de sante s chez les adultes atteints de cardiopathie conge nitale. rencontre
Congenital heart malformations are the most common birth defects and the leading cause of infant mortality.1 Although several studies have attempted to quantify the incidence of congenital heart disease, generating accurate estimates is complicated by nonstandardized definitions of qualifying pathologies, nonuniform screening methods, and geographic variability. Notwithstanding these limitations, recent
estimates suggest that the incidence of congenital heart disease (excluding patent foramen ovale and bicuspid aortic valve) is in the order of 7 to 10 per 1000 live births, with moderate and severe forms afflicting 3 per 1000 newborns.2-4 Considering that there are approximately 138 million live births per year worldwide yields an estimated 1 million newborns with congenital heart disease every year. These rates have remained relatively constant since 2011.5 In developed countries, a shift toward a greater proportion of simpler defects has been reported, which might reflect enhanced sensitivity in detecting milder forms of congenital heart disease combined with a reduction in the incidence of newborns with the most severe defects because of pregnancy termination on prenatal detection.2
Received for publication June 7, 2014. Accepted July 23, 2014. Corresponding author: Dr Paul Khairy, Montreal Heart Institute Adult Congenital Center, Montreal Heart Institute, 5000 Belanger St E, Montreal, Quebec H1T 1C8, Canada. Tel.: þ1-514-376-3330 3800; fax: þ1-514593-2581. E-mail: [email protected] See page S417 for disclosure information.
http://dx.doi.org/10.1016/j.cjca.2014.07.749 0828-282X/Ó 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
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Figure 1. Distribution of age at death in patients with congenital heart disease in 1987-1988 and 2004-2005. Histogram bars depict the proportion of all deaths (x-axis) according to age at death (y-axis) in our cohort of patients with congenital heart disease in the first (19871988; left graph) and final (2004-2005; right graph) years of observation. Bold black curves with diamonds represent the corresponding age at death distribution in the general Quebec population during the same periods of observation. Reproduced from Khairy et al.7
Prevalence of Congenital Heart Disease Most patients born with moderate or severe forms of congenital heart disease in the 1950s and earlier died before reaching adulthood, with the highest mortality during the first week of life.6 Remarkable advances in diagnostic methods, medical management, interventional techniques, congenital heart disease surgery, and perioperative care have led to historical shifts in population demographic characteristics, and adults now outnumber children with congenital heart defects by a ratio of 2:1.7-9 Improved survival has been driven by a reduction in mortality in the youngest age strata, particularly in those with severe forms of congenital heart disease (Fig. 1).7 From 1987 to 2005, a > 30% reduction in mortality was reported among patients with congenital heart disease at large, with a 67% mortality reduction in children with complex disease.7 More than 85% of children born with heart defects are now expected to survive to adulthood and continue to thrive.10-12 Consequently, the population with congenital heart disease is aging. For example, the median age of patients with severe defects was 11 years in 1985 compared with 17 years in 2000.13 In 2000, the median age of adults with congenital heart disease was 40 years, with a median age of 29 in those with severe defects.13 From 1987 to 2005, the median age at death increased by 15 years, from 60 to 75 years, and the median age at death in those with severe defects increased from 2 to 23 years.7 In a manner similar to incidence, estimating the prevalence of congenital heart disease is fraught with assumptions and subject to limitations. Prevalence is defined as the number of living subjects with a particular disease during a specific time frame. Birth prevalence underestimates the true burden of congenital heart disease by not capturing those in whom the diagnosis is established afterward. Prevalence estimated at a later time excludes those who died before the assessment, thereby differentially underrepresenting higher-fatality lesions, and potentially omitting defects that resolve spontaneously. For example, up to two-thirds of ventricular septal defects diagnosed at birth
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spontaneously close within the first years of life and will not be present in adulthood, whereas other forms of congenital heart disease, such as atrial septal defects, Ebstein anomaly, and congenitally corrected transposition of the great arteries might go unrecognized until adulthood. Furthermore, prevalence estimates might not consider other factors that affect global disease epidemiology, such as migration and population mobility. A Quebec population-based study estimated that, in the year 2010, the prevalence of congenital heart disease in adults (18 years of age and older) was 6.1 per 1000.9 Similar rates were projected in a recent systematic review.14 Extrapolating this statistic to the general population, it might be estimated that there are > 100,000 adults with congenital heart disease in Canada, 1 million in the United States,15 and 1.8 million in Europe.16 It is also noteworthy that the prevalence of complex congenital heart disease in adults has been steadily increasing (eg, by 85% from 1985 to 2000), unlike the relatively stable prevalence of complex congenital heart disease in children (Fig. 2).13 By 2010, adults accounted for 60% of patients with complex congenital heart disease.9 Organization and Delivery of Care Although the provision of care for children with congenital heart disease is well established in developed countries, clinical services for adults are comparatively scarce.17-19 To attend to the progressive increase in the number of adults with congenital heart disease and the increasing complexity of their pathologies, specialized adult congenital heart centres have emerged in several countries, with increasing volume of activities (Fig. 3). Canada assumed a leadership role in establishing recommendations for optimal organization and delivery of care. In 1991, the Canadian Adult Congenital Heart (CACH) network was established as the first national society dedicated to the care of adults with congenital heart disease (www. cachnet.ca). The Canadian Cardiovascular Society, in collaboration with the CACH network, formed a panel of experts in 1996 to discuss the needs of adults with congenital heart disease and provide recommendations for referral to specialized centres. The first management guidelines were presented at the Canadian Cardiovascular Congress in Montreal in 1996, published in the Canadian Journal of Cardiology in 1998,20 and subsequently updated in 200121 and 2009.22 Similar proposals emerged from the 32nd Bethesda Conference in 2000, which focused on the need for health care professionals, patients, and governing agencies to develop strategic plans to improve access to and delivery of care for the adult with congenital heart disease.23 This call to action was followed by more specific recommendations from the American College of Cardiology/American Heart Association and the European Society of Cardiology (ESC).24,25 Current management guidelines suggest that approximately half of the adult population with congenital heart disease stand to benefit from specialized care within adult congenital heart centres. Such care is generally recommended for the initial assessment of adults with known or suspected congenital heart disease, follow-up of patients with moderate and severe lesions, cardiac surgical and nonsurgical interventions, and risk assessment and support for pregnancy and noncardiac surgery.17,20,22,25-27
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Figure 2. Number and proportion of adults and children with (A) all forms of congenital heart disease (CHD), and (B) severe CHD in 1985, 1990, 1995, and 2000. Reproduced from Marelli et al.13
Recommended personnel and services for regional adult congenital centres are summarized in Table 1.25 In short, centralized care within regional centres should be provided by a multidisciplinary team comprised of cardiologists with expertise in adult congenital heart disease, including imaging, arrhythmia management,28 interventional cardiology, and high-risk obstetrics, congenital heart surgeons, perioperative care, and psychosocial support.17,25,26 Estimates regarding the ideal number of regional adult congenital centres have varied between 1 per
2-10 million inhabitants,17,21 which translates to up to 17 specialized centres in Canada, 150 in the United States, and 365 in Europe.29 This figure balances factors such as ease of access and centralization of resources, considering that improved outcomes are proportional to volume of activity and experience.30 Although the recommended number of specialized centres has been achieved in Canada (ie, 17 centres are registered within the CACH network), most countries in the developed world fall short of this target. For example, in the United States, 108
Figure 3. Number of patients followed at the Montreal Heart Institute Adult Congenital Centre over time. A > 7-fold increase in the number of adults with congenital heart disease was observed over a 15-year period.
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Table 1. Personnel and services recommended for regional ACHD centres Type of Service Cardiologist specializing in ACHD Congenital cardiac surgeon Nurse/physician assistant/nurse practitioner Cardiac anaesthesiologist Echocardiography* Includes TEE, intraoperative TEE Diagnostic catheterization* Noncoronary interventional catheterization* Electrophysiology/pacing/ICD implantation* Exercise testing
Cardiac imaging/radiology* Multidisciplinary teams
Information technology
concluded that referral to such a centre is associated with a significant reduction in all-cause mortality (Fig. 4).36
Personnel/Resources One or several 24/7 Two or several 24/7 One or several Several 24/7 Two or several 24/7 Yes, 24/7 Yes, 24/7 One or several Echocardiography Radionuclide Cardiopulmonary Metabolic Cardiac MRI CT scanning Nuclear medicine High-risk obstetrics Pulmonary hypertension Heart failure/transplant Genetics Neurology Nephrology Cardiac pathology Rehabilitation services Social services Vocational services Financial counsellors Database collection Database support Quality assessment review/protocols
24/7, availability 24 hours per day, 7 days per week; ACHD, adult congenital heart disease; CT, computed tomography; ICD, implantable cardioverter defibrillator; MRI, magnetic resonance imaging; TEE, transesophageal echocardiography. * These modalities must be supervised/performed and interpreted by physicians with expertise and training in congenital heart disease. Reproduced from Warnes et al.25
self-declared adult congenital heart centres with variable volumes of activity and availability of resources are listed on the American Congenital Heart Association Web site (www.achaheart.org). An adequate ratio of specialized adult congenital centres is no guarantee for optimal care. A larger issue that plagues the field of congenital heart disease is the relatively small proportion of qualifying patients who actually receive specialized adult-oriented care. For example, a Canadian study found that < 25% of adults with congenital heart disease are followed by specialized centres and that waiting times to access services exceed published recommendations.31 These sobering statistics have prompted numerous educational initiatives to raise awareness about the need for lifelong care and have incited research studies into factors associated with gaps in care and impediments to long-term follow-up.32,33 Common barriers to transfer from pediatric-to adult-oriented health care include inadequate knowledge regarding the need for such care, a dearth of accessible competent adult care providers, and emotional attachment of patients and families to their pediatric caregivers and vice-versa.34,35 Lending further credence to the notion that specialized adult congenital centres with multidisciplinary expertise offer the best prospects for improving outcomes, a recent population-based study
Training and Research An important element in optimizing outcomes is the development of training programs to meet workforce requirements and provide qualified, consistent, and comprehensive care.37 Exposure of adult cardiology trainees to adult congenital heart disease didactic and clinical experience varies widely, reflecting the fact that few programs offer advanced training in this sector of cardiology.38 Surveys suggest that only approximately 25% of cardiologists who care for adults with congenital heart disease have received formal training in this discipline.31,37 The United States is the first country to officially recognize the legitimacy of adult congenital heart disease as a separate subspecialty of cardiology.39 In September 2012, the American Board of Medical Subspecialties approved a specialized certification examination via the American Board of Internal Medicine. The first examination is planned for 2015. Pediatric or adult cardiologists require a minimum 2-year fellowship within recognized adult congenital training centres to qualify. The ESC, with its working group on grown-up congenital heart disease, is poised to follow suit.40 Canada is currently contemplating recognizing adult congenital heart disease as an area of focused competence via a Diploma of the Royal College of Physicians and Surgeons of Canada (DRCPSC). While details remain to be determined, a Diploma of the Royal College of Physicians and Surgeons of Canada typically requires 1-2 years of additional training by Royal College-accredited programs and is competency-based, with assessment through a summative portfolio. Another critically important element required to advance the care of adults with congenital heart disease is well-designed research. Over the past decade, significant strides have been achieved in coordinating research efforts and creating dedicated infrastructures.41 A critical mass of patients and investigators has enabled a new era of multicentre research with more exacting standards. Several networks and organizations have emerged, some focused on multicentre research as their main objective, with others providing a supportive environment to facilitate research. These include, but are not limited to, the International Society for Adult Congenital Heart Disease (www.isachd.org), CACH network, ESC (www.escardio. org), Japanese Circulation Society (www.j-circ.or.jp/english), Society of Thoracic Surgeons (www.sts.org), Congenital Heart Surgeons’ Society (www.chss.org), and the Adult Congenital Heart Association. In the Netherlands, the Interuniversity Cardiology Institute and Heart Foundation developed a highly productive national registry and DNA bank of patients with congenital heart disease, named CONgenital CORvitia (CONCOR; www.concor.net/en).42 In North America, an Alliance for Adult Research in Congenital Cardiology was founded in 2006 to foster collaborative research, advance knowledge, and improve outcomes (www.aarcc.net). Health Care Resource Utilization Despite surgical repair, most forms of congenital heart disease are associated with sequelae and long-term complications, which engender a high level of health care resource utilization.19,43 Rates of emergency room visits, hospital
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Figure 4. Time-series analysis: referral to specialized adult congenital heart disease (ACHD) centres and ACHD patient mortality. Observed specialized ACHD centre referral (black line) and ACHD mortality (grey line) per 1000 ACHD population per year, between 1990 and 2005. The dashed lines indicate expected trends after the change points identified by Poisson regression, and the black or grey lines represent the observed trends. Reproduced with permission from Mylotte et al.36
admissions, and cardiac interventions are several-fold greater than in the general population.44-47 Figure 5 depicts common causes of hospitalizations.46 Models of health-related costs and outcomes in adults with congenital heart disease provide economic justification for expensive interventions on the basis of striking benefits on quality-adjusted life years.48 Overview of Common Issues Common complications that contribute to the growing epidemic of adults with congenital heart disease include arrhythmias, heart failure, pulmonary hypertension, endocarditis, pregnancy-related issues, and cardiac interventions. Arrhythmias Arrhythmias are the most common long-term complication in adults with congenital heart disease, the leading source of morbidity and hospital admissions, and a major cause of mortality.46,49-52 All forms of tachy- and bradyarrhythmias might be encountered.53 Figure 6 schematically summarizes factors predisposing to arrhythmias.54 The prevalence of tachyarrhythmias generally correlates with increasing age and complexity of the congenital heart lesion (Fig. 7).28,55,56 Sinus node dysfunction is highly prevalent in patients with surgery at or near the superior vena cava to the right atrial junction; atrioventricular block is common in those with displaced conduction systems and in the acute postoperative setting.57-60 In 2014, the Pediatric and Congenital Electrophysiology Society together with the Heart Rhythm Society proposed recommendations on the recognition and management of arrhythmias in adults with congenital heart disease, which were endorsed by the American College of Cardiology, American Heart Association, European Heart Rhythm Association, Canadian Heart Rhythm Society, and the International Society for Adult Congenital Heart Disease.28
volume and/or pressure overload, inability of a systemic morphologic right ventricle or single ventricle circulation to adequately meet metabolic needs, unequal flow distributions to lung fields, variable pulmonary vascular integrity, and abnormalities of myocardial tissue architecture, electrical conduction, and blood supply.61 As such, management guidelines for acquired heart disease cannot be extrapolated to the complex forms of heart failure encountered in adults with congenital heart disease. Despite the heterogeneity and imprecisions, on the whole, heart failure appears to be increasing in prevalence as the population ages. It is among the most common causes of hospitalization (see Fig. 5),45,46,52 with some studies suggesting that it has surpassed sudden cardiac death as the leading cause of mortality.8,51,62 The incidence of systolic systemic ventricular dysfunction is highest in those with cyanotic lesions, systemic right ventricles, and univentricular hearts.63 In some forms of congenital heart disease, diastolic systemic ventricular dysfunction has been correlated with arrhythmias and mortality.64 Even in the absence of overt heart failure as classically defined, some degree of exercise intolerance is documented in up to onethird.65 When contrasted against quantified exercise capacity, functional symptoms are notoriously underreported as a result of lifelong adaptation to a chronic disorder.66 Exercise intolerance consistently portends poorer midterm outcomes, such as hospitalizations and mortality.66 Moreover, in an increasing number of adults with congenital heart disease and end-stage circulatory failure in whom cardiac transplantation is not a viable option, endof-life issues and palliative care assume a prominent role.67,68 Pulmonary hypertension
Heart failure Mechanisms for heart failure in adults with congenital heart disease might involve circulatory overload, ventricular
Any nonrestrictive communication causing left-to-right shunting with increased pulmonary blood flow might produce pathological changes to the pulmonary vascular bed,
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Figure 5. Most frequent cardiovascular admission diagnoses/symptoms in the CONgenital CORvitia (CONCOR) Dutch national registry population from 2001 to 2005 (n ¼ 5798). All cardiovascular admissions with n ¼ 100 are displayed. Nos, not otherwise specified. Reproduced from Verheugt et al.46
including vasoconstriction, inflammation, cell proliferation, and vascular remodelling, resulting in increased pulmonary vascular resistance.69,70 Pulmonary arterial hypertension is prevalent in 4%-10% of adults with congenital heart disease and is associated with exercise intolerance and heart failure.69,71 At the extreme end of the spectrum, Eisenmenger syndrome is a multisystemic disorder associated with a 10- to 12-fold increase in mortality in those with complex congenital heart disease.69,72-77 If managed appropriately, many such patients survive past the third or fourth decade of life.72 In developed countries, earlier recognition and closure of
intracardiac shunts has resulted in a reduction in the prevalence of Eisenmenger syndrome.78 Nevertheless, pulmonary hypertension persists in 3%-13% of patients after septal defect closure71,79 and implies a worse prognosis.80 Endocarditis The incidence of endocarditis (approximately 1.1 per 1000 patient-years) in adults with congenital heart disease is 20-fold greater than in the general population,81,82 with a 12% recurrence rate.81,83 Factors associated with endocarditis include the type of congenital heart defect, presence of
Figure 6. Factors leading to arrhythmias in (A) before, and (B) after surgery for congenital heart disease. AV, atrioventricular; VT, ventricular tachycardia. Adapted from Escudero et al.54
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Figure 7. Risk estimates for arrhythmias according to type of congenital heart disease. Approximate risk estimates for atrial tachycardia (AT), atrial fibrillation (AF), other supraventricular arrhythmias, ventricular arrhythmia, sinus node dysfunction (SND), atrioventricular (AV) block, and ventricular dyssynchrony are shown across various congenital heart defects (CHDs) of simple, moderate, and severe complexity. D- and L-transposition denote complete and congenitally corrected transposition of the great arteries, respectively. The colour-coded pattern ranges from minimal (no shading) to mild (light blue), moderate (medium blue), and high (dark blue) risk. Reproduced Khairy et al.28
multiple defects, and male sex.81 Systemic embolization, heart failure, and valvular regurgitation are common complications.84 Surgery is required in up to one-third of patients.84,85 Improvements in antibiotic therapy and earlier surgical management have resulted in lower rates of complications and mortality over the past decades, with current in-hospital mortality ranging from 4% to 9%.81,83,84 Educational counselling, including hygienic measures and antibiotic prophylaxis when indicated, should be incorporated in the care of adults with congenital heart disease. Pregnancy When considered collectively, congenital malformations are the most prevalent form of heart disease in pregnant women86,87 and the leading cardiac cause of maternal morbidity and mortality in developed countries.25 Pregnancy is the most common noncardiac cause of hospitalization in women with congenital heart disease.45,46 Congenital heart disease carries increased maternal and fetal risks, particularly in the setting of pulmonary arterial hypertension, subaortic or subpulmonary ventricular dysfunction, left-sided valvular obstruction, unrepaired aortic coarctation, or aortic root dilatation in association with other anomalies such as a bicuspid aortic valve, Marfan, or Turner syndrome.86-89 Heart failure and arrhythmias are the most common maternal complications, whereas frequent neonatal adverse outcomes include small for gestational age birth weight, respiratory distress, and intraventricular cerebral hemorrhage.90 Women with moderate and complex forms of congenital heart disease
should be managed by a multidisciplinary team with appropriate expertise and delivery should take place in specialized centres.25-27,91 Congenital cardiac surgeries and interventions Surgical and catheter procedures are on the increase in adults with congenital heart disease.92 Percutaneous devices are increasingly used to close septal defects, abnormal vascular connections, leaks across conduits and baffles, and pseudoaneurysms; covered stents have enhanced the safety with which aortic coarctation, conduit stenosis, and branch pulmonary stenosis can be treated; and percutaneous valves have broadened the range of therapeutic options in selected patients.93 Cardiovascular surgery is also increasingly performed in adults with congenital heart disease to rectify residual or progressive lesions in the setting of previous reparative surgery, address previously unoperated disease, palliate nonreparable defects, and transplant failing hearts.94 Complications after surgery occur in 15%-25% of patients and include arrhythmias, low cardiac output, stroke, bleeds, and renal failure. Perioperative mortality risk depends on numerous factors but is generally within the 3%-8% range.95-98 Conclusion Adult congenital heart disease is the most rapidly growing sector of cardiology today, with a patient population that is swiftly increasing in size and complexity. Unique issues, challenges, and considerations are involved in managing adults
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with congenital heart disease, including arrhythmias, heart failure, pulmonary hypertension, endocarditis, pregnancy, interventions, and surgery. An increasing body of evidence suggests that outcomes can be improved by referral to specialized centres with multidisciplinary teams dedicated to clinical care, training, and research in adult congenital heart disease.
14. van der Bom T, Bouma BJ, Meijboom FJ, Zwinderman AH, Mulder BJ. The prevalence of adult congenital heart disease, results from a systematic review and evidence based calculation. Am Heart J 2012;164:568-75.
Funding Sources Dr Ávila received a research grant from the Fundación Alfonso Martín Escudero (Spain). Dr Khairy is supported by a Canada Research Chair in Adult Congenital Heart Disease and Electrophysiology.
17. Landzberg MJ, Murphy DJ Jr, Davidson WR Jr, et al. Task force 4: organization of delivery systems for adults with congenital heart disease. J Am Coll Cardiol 2001;37:1187-93.
Disclosures The authors have no conflicts of interest to disclose.
19. Report of the British Cardiac Society Working Party. Grown-up congenital heart (GUCH) disease: current needs and provision of service for adolescents and adults with congenital heart disease in the UK. Heart 2002;88(suppl 1):i1-14.
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32. Gurvitz M, Valente AM, Broberg C, et al. Prevalence and predictors of gaps in care among adult congenital heart disease patients: HEARTACHD (The Health, Education, and Access Research Trial). J Am Coll Cardiol 2013;61:2180-4.
51. Nieminen HP, Jokinen EV, Sairanen HI. Causes of late deaths after pediatric cardiac surgery: a population-based study. J Am Coll Cardiol 2007;50:1263-71.
33. Engelfriet P, Tijssen J, Kaemmerer H, et al. Adherence to guidelines in the clinical care for adults with congenital heart disease: the Euro Heart Survey on adult congenital heart disease. Eur Heart J 2006;27:737-45. 34. Fernandes SM, Verstappen A, Ackerman K, et al. Parental knowledge regarding lifelong congenital cardiac care. Pediatrics 2011;128:e1489-95. 35. Fernandes SM, Khairy P, Fishman L, et al. Referral patterns and perceived barriers to adult congenital heart disease care: results of a survey of U.S. pediatric cardiologists. J Am Coll Cardiol 2012;60:2411-8. 36. Mylotte D, Pilote L, Ionescu-Ittu R, et al. Specialized adult congenital heart disease care: the impact of policy on mortality. Circulation 2014;129:1804-12. 37. Child JS, Collins-Nakai RL, Alpert JS, et al. Task force 3: workforce description and educational requirements for the care of adults with congenital heart disease. J Am Coll Cardiol 2001;37:1183-7. 38. Gurvitz MZ, Chang RK, Ramos FJ, et al. Variations in adult congenital heart disease training in adult and pediatric cardiology fellowship programs. J Am Coll Cardiol 2005;46:893-8. 39. Mondesert B, Abadir S, Khairy P. Arrhythmias in adult congenital heart disease: the year in review. Curr Opin Cardiol 2013;28:354-9. 40. Baumgartner H, Budts W, Chessa M, et al. Recommendations for organization of care for adults with congenital heart disease and for training in the subspecialty of “Grown-up Congenital Heart Disease” in Europe. Eur Heart J 2014;35:686-90. 41. Khairy P, Hosn JA, Broberg C, et al. Multicenter research in adult congenital heart disease. Int J Cardiol 2008;129:155-9. 42. van der Velde ET, Vriend JW, Mannens MM, et al. CONCOR, an initiative towards a national registry and DNA-bank of patients with congenital heart disease in the Netherlands: rationale, design, and first results. Eur J Epidemiol 2005;20:549-57. 43. Wren C, O’Sullivan JJ. Survival with congenital heart disease and need for follow up in adult life. Heart 2001;85:438-43. 44. Mackie AS, Pilote L, Ionescu-Ittu R, Rahme E, Marelli AJ. Health care resource utilization in adults with congenital heart disease. Am J Cardiol 2007;99:839-43. 45. Opotowsky AR, Siddiqi OK, Webb GD. Trends in hospitalizations for adults with congenital heart disease in the U.S. J Am Coll Cardiol 2009;54:460-7. 46. Verheugt CL, Uiterwaal CS, van der Velde ET, et al. The emerging burden of hospital admissions of adults with congenital heart disease. Heart 2010;96:872-8. 47. Tutarel O, Kempny A, Alonso-Gonzalez R, et al. Congenital heart disease beyond the age of 60: emergence of a new population with high resource utilization, high morbidity, and high mortality. Eur Heart J 2014;35: 725-32. 48. Hunter RM, Isaac M, Frigiola A, et al. Lifetime costs and outcomes of repair of tetralogy of Fallot compared to natural progression of the disease: Great Ormond Street Hospital cohort. PLoS One 2013;8:e59734. 49. Walsh EP, Cecchin F. Arrhythmias in adult patients with congenital heart disease. Circulation 2007;115:534-45.
52. Kaemmerer H, Bauer U, Pensl U, et al. Management of emergencies in adults with congenital cardiac disease. Am J Cardiol 2008;101:521-5. 53. Khairy P, Dore A, Talajic M, et al. Arrhythmias in adult congenital heart disease. Expert Rev Cardiovasc Ther 2006;4:83-95. 54. Escudero C, Khairy P, Sanatani S. Electrophysiologic considerations in congenital heart disease and their relationship to heart failure. Can J Cardiol 2013;29:821-9. 55. Khairy P, Aboulhosn J, Gurvitz MZ, et al. Arrhythmia burden in adults with surgically repaired tetralogy of Fallot: a multi-institutional study. Circulation 2010;122:868-75. 56. Durongpisitkul K, Porter CJ, Cetta F, et al. Predictors of early- and lateonset supraventricular tachyarrhythmias after Fontan operation. Circulation 1998;98:1099-107. 57. Dos L, Teruel L, Ferreira IJ, et al. Late outcome of Senning and Mustard procedures for correction of transposition of the great arteries. Heart 2005;91:652-6. 58. Gelatt M, Hamilton RM, McCrindle BW, et al. Risk factors for atrial tachyarrhythmias after the Fontan operation. J Am Coll Cardiol 1994;24: 1735-41. 59. Cohen MI, Wernovsky G, Vetter VL, et al. Sinus node function after a systematically staged Fontan procedure. Circulation 1998;98:II352-8. 60. Connelly MS, Liu PP, Williams WG, et al. Congenitally corrected transposition of the great arteries in the adult: functional status and complications. J Am Coll Cardiol 1996;27:1238-43. 61. Kantor PF, Andelfinger G, Dancea A, Khairy P. Heart failure in congenital heart disease. Can J Cardiol 2013;29:753-4. 62. Verheugt CL, Uiterwaal CS, van der Velde ET, et al. Mortality in adult congenital heart disease. Eur Heart J 2010;31:1220-9. 63. Piran S, Veldtman G, Siu S, Webb GD, Liu PP. Heart failure and ventricular dysfunction in patients with single or systemic right ventricles. Circulation 2002;105:1189-94. 64. Cullen S, Shore D, Redington A. Characterization of right ventricular diastolic performance after complete repair of tetralogy of Fallot. Restrictive physiology predicts slow postoperative recovery. Circulation 1995;91:1782-9. 65. Engelfriet P, Boersma E, Oechslin E, et al. The spectrum of adult congenital heart disease in Europe: morbidity and mortality in a 5 year follow-up period. The Euro Heart Survey on adult congenital heart disease. Eur Heart J 2005;26:2325-33. 66. Diller GP, Dimopoulos K, Okonko D, et al. Exercise intolerance in adult congenital heart disease: comparative severity, correlates, and prognostic implication. Circulation 2005;112:828-35. 67. Tobler D, de Stoutz N, Greutmann M. Supportive and palliative care for adults dying from congenital heart defect. Curr Opin Support Palliat Care 2011;5:291-6. 68. Mondesert B, Marcotte F, Mongeon FP, et al. Fontan circulation: success or failure? Can J Cardiol 2013;29:811-20. 69. Vongpatanasin W, Brickner ME, Hillis LD, Lange RA. The Eisenmenger syndrome in adults. Ann Intern Med 1998;128:745-55.
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70. Humbert M, Morrell NW, Archer SL, et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol 2004;43:13S-24S.
84. Niwa K, Nakazawa M, Tateno S, Yoshinaga M, Terai M. Infective endocarditis in congenital heart disease: Japanese national collaboration study. Heart 2005;91:795-800.
71. Duffels MG, Engelfriet PM, Berger RM, et al. Pulmonary arterial hypertension in congenital heart disease: an epidemiologic perspective from a Dutch registry. Int J Cardiol 2007;120:198-204.
85. Takeda S, Nakanishi T, Nakazawa MA. 28-year trend of infective endocarditis associated with congenital heart diseases: a single institute experience. Pediatr Int 2005;47:392-6.
72. Daliento L, Somerville J, Presbitero P, et al. Eisenmenger syndrome. Factors relating to deterioration and death. Eur Heart J 1998;19: 1845-55.
86. Siu SC, Sermer M, Colman JM, et al. Prospective multicenter study of pregnancy outcomes in women with heart disease. Circulation 2001;104: 515-21.
73. Kidd L, Driscoll DJ, Gersony WM, et al. Second natural history study of congenital heart defects. Results of treatment of patients with ventricular septal defects. Circulation 1993;87:I38-51. 74. Diller GP, Dimopoulos K, Broberg CS, et al. Presentation, survival prospects, and predictors of death in Eisenmenger syndrome: a combined retrospective and case-control study. Eur Heart J 2006;27:1737-42. 75. D’Alto M, Diller GP. Pulmonary hypertension in adults with congenital heart disease and Eisenmenger syndrome: current advanced management strategies. Heart 2014;100:1322-8.
87. Stangl V, Schad J, Gossing G, et al. Maternal heart disease and pregnancy outcome: a single-centre experience. Eur J Heart Fail 2008;10:855-60. 88. Khairy P, Ouyang DW, Fernandes SM, et al. Pregnancy outcomes in women with congenital heart disease. Circulation 2006;113:517-24. 89. Drenthen W, Pieper PG, Roos-Hesselink JW, et al. Outcome of pregnancy in women with congenital heart disease: a literature review. J Am Coll Cardiol 2007;49:2303-11. 90. Fernandes SM, Arendt KW, Landzberg MJ, Economy KE, Khairy P. Pregnant women with congenital heart disease: cardiac, anesthetic and obstetrical implications. Expert Rev Cardiovasc Ther 2010;8:439-48.
76. Cantor WJ, Harrison DA, Moussadji JS, et al. Determinants of survival and length of survival in adults with Eisenmenger syndrome. Am J Cardiol 1999;84:677-81.
91. Harris RC, Fries MH, Boyle A, et al. Multidisciplinary management of pregnancy in complex congenital heart disease: a model for coordination of care. Congenit Heart Dis 2014; doi:10.1111/chd.12163.
77. Oechslin E, Mebus S, Schulze-Neick I, et al. The adult patient with Eisenmenger syndrome: a medical update after Dana Point part III: specific management and surgical aspects. Curr Cardiol Rev 2010;6: 363-72.
92. Uemura H. Surgical and catheter procedures in adult congenital heart disease: simple national statistics of the UK tell us something. Gen Thorac Cardiovasc Surg 2013;61:376-89.
78. Diller GP, Gatzoulis MA. Pulmonary vascular disease in adults with congenital heart disease. Circulation 2007;115:1039-50.
93. Meadows J, Landzberg MJ. Advances in transcatheter interventions in adults with congenital heart disease. Prog Cardiovasc Dis 2011;53: 265-73.
79. Engelfriet PM, Duffels MG, Moller T, et al. Pulmonary arterial hypertension in adults born with a heart septal defect: the Euro Heart Survey on adult congenital heart disease. Heart 2007;93:682-7.
94. Srinathan SK, Bonser RS, Sethia B, et al. Changing practice of cardiac surgery in adult patients with congenital heart disease. Heart 2005;91: 207-12.
80. Manes A, Palazzini M, Leci E, et al. Current era survival of patients with pulmonary arterial hypertension associated with congenital heart disease: a comparison between clinical subgroups. Eur Heart J 2014;35:716-24.
95. Giamberti A, Chessa M, Abella R, et al. Morbidity and mortality risk factors in adults with congenital heart disease undergoing cardiac reoperations. Ann Thorac Surg 2009;88:1284-9.
81. Verheugt CL, Uiterwaal CS, van der Velde ET, et al. Turning 18 with congenital heart disease: prediction of infective endocarditis based on a large population. Eur Heart J 2011;32:1926-34. 82. Tleyjeh IM, Steckelberg JM, Murad HS, et al. Temporal trends in infective endocarditis: a population-based study in Olmsted County, Minnesota. JAMA 2005;293:3022-8. 83. Li W, Somerville J. Infective endocarditis in the grown-up congenital heart (GUCH) population. Eur Heart J 1998;19:166-73.
96. Vida VL, Berggren H, Brawn WJ, et al. Risk of surgery for congenital heart disease in the adult: a multicentered European study. Ann Thorac Surg 2007;83:161-8. 97. Berdat PA, Immer F, Pfammatter JP, Carrel T. Reoperations in adults with congenital heart disease: analysis of early outcome. Int J Cardiol 2004;93:239-45. 98. Holst KA, Dearani JA, Burkhart HM, et al. Risk factors and early outcomes of multiple reoperations in adults with congenital heart disease. Ann Thorac Surg 2011;92:122-8.
Review
Adult Congenital Heart Disease: A Growing Epidemic Pablo Ávila, MD, Lise-Andree Mercier, MD, Annie Dore, MD, François Marcotte, MD, François-Pierre Mongeon, MD, MS, Reda Ibrahim, MD, Anita Asgar, MD, Joaquim Miro, MD, Gregor Andelfinger, MD, Blandine Mondesert, MD, Pierre de Guise, MD, Nancy Poirier, MD, and Paul Khairy, MD, PhD Montreal Heart Institute Adult Congenital Center, Universite de Montre al, Montreal, Quebec, Canada
ABSTRACT
RESUM E
Medical and surgical breakthroughs in the care of children born with heart defects have generated a growing population of adult survivors and spawned a new subspecialty of cardiology: adult congenital heart disease. The prevalence of adult congenital heart disease is escalating at a rampant rate, outpacing the relatively static prevalence of pediatric congenital heart disease, because adults now surpass children in numbers by a ratio of 2:1. As such, congenital heart disease can no longer be considered primarily a pediatric specialty. Most congenital heart defects are not curable and require lifelong specialized care. Health care systems worldwide are challenged to meet the unique needs of this increasingly complex patient population, including the development of supraregional centres of excellence to provide comprehensive and multidisciplinary specialized care. In this review, we explore the incidence and prevalence of congenital heart disease and their changing patterns, address organization and delivery of care, highlight the importance of appropriate training and dedicated research, summarize the high burden of health care resource utilization, and provide an overview of common issues encountered in adults with congenital heart disease.
es me dicales et chirurgicales dans la prise en charge des Les avance s avec des malformations cardiaques ont ge ne re un nombre enfants ne naissance à une nouvelle croissant de survivants adultes et ont donne cialite de la cardiologie : la cardiopathie conge nitale chez sous-spe valence des adultes atteints de cardiopathie conl’adulte. La pre nitale s’amplifie à un rythme effre ne , de passant la pre valence relge nitales pe diatriques, puisque ativement stable des cardiopathies conge passent maintenant en nombre les enfants avec un ratio les adultes de nitale ne peut plus être de 2 : 1. En tant que telle, la cardiopathie conge re e comme e tant essentiellement une spe cialite pe diatrique. conside nitales ne sont pas curLa plupart des anomalies cardiaques conge cessitent des soins spe cialise s à vie. Les systèmes de sante ables et ne s à re pondre aux besoins particuliers de du monde entier sont amene cette population de patients de plus en plus complexe, y compris par le veloppement de centres d’excellence suprare gionaux afin de fournir de cialise s d’ensemble et multidisciplinaires. Dans cette des soins spe valence des cardiopathies revue, nous examinons l’incidence et la pre nitales et leurs particularite s changeantes, nous abordons l’orconge vidence l’imporganisation et la prestation des soins, mettons en e e et d’une recherche de die e, tance d’une formation approprie sumons la charge conside rable de l’utilisation des ressources des re , et nous fournissons un aperçu des problèmes habituels soins de sante s chez les adultes atteints de cardiopathie conge nitale. rencontre
Congenital heart malformations are the most common birth defects and the leading cause of infant mortality.1 Although several studies have attempted to quantify the incidence of congenital heart disease, generating accurate estimates is complicated by nonstandardized definitions of qualifying pathologies, nonuniform screening methods, and geographic variability. Notwithstanding these limitations, recent
estimates suggest that the incidence of congenital heart disease (excluding patent foramen ovale and bicuspid aortic valve) is in the order of 7 to 10 per 1000 live births, with moderate and severe forms afflicting 3 per 1000 newborns.2-4 Considering that there are approximately 138 million live births per year worldwide yields an estimated 1 million newborns with congenital heart disease every year. These rates have remained relatively constant since 2011.5 In developed countries, a shift toward a greater proportion of simpler defects has been reported, which might reflect enhanced sensitivity in detecting milder forms of congenital heart disease combined with a reduction in the incidence of newborns with the most severe defects because of pregnancy termination on prenatal detection.2
Received for publication June 7, 2014. Accepted July 23, 2014. Corresponding author: Dr Paul Khairy, Montreal Heart Institute Adult Congenital Center, Montreal Heart Institute, 5000 Belanger St E, Montreal, Quebec H1T 1C8, Canada. Tel.: þ1-514-376-3330 3800; fax: þ1-514593-2581. E-mail: [email protected] See page S417 for disclosure information.
http://dx.doi.org/10.1016/j.cjca.2014.07.749 0828-282X/Ó 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
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Figure 1. Distribution of age at death in patients with congenital heart disease in 1987-1988 and 2004-2005. Histogram bars depict the proportion of all deaths (x-axis) according to age at death (y-axis) in our cohort of patients with congenital heart disease in the first (19871988; left graph) and final (2004-2005; right graph) years of observation. Bold black curves with diamonds represent the corresponding age at death distribution in the general Quebec population during the same periods of observation. Reproduced from Khairy et al.7
Prevalence of Congenital Heart Disease Most patients born with moderate or severe forms of congenital heart disease in the 1950s and earlier died before reaching adulthood, with the highest mortality during the first week of life.6 Remarkable advances in diagnostic methods, medical management, interventional techniques, congenital heart disease surgery, and perioperative care have led to historical shifts in population demographic characteristics, and adults now outnumber children with congenital heart defects by a ratio of 2:1.7-9 Improved survival has been driven by a reduction in mortality in the youngest age strata, particularly in those with severe forms of congenital heart disease (Fig. 1).7 From 1987 to 2005, a > 30% reduction in mortality was reported among patients with congenital heart disease at large, with a 67% mortality reduction in children with complex disease.7 More than 85% of children born with heart defects are now expected to survive to adulthood and continue to thrive.10-12 Consequently, the population with congenital heart disease is aging. For example, the median age of patients with severe defects was 11 years in 1985 compared with 17 years in 2000.13 In 2000, the median age of adults with congenital heart disease was 40 years, with a median age of 29 in those with severe defects.13 From 1987 to 2005, the median age at death increased by 15 years, from 60 to 75 years, and the median age at death in those with severe defects increased from 2 to 23 years.7 In a manner similar to incidence, estimating the prevalence of congenital heart disease is fraught with assumptions and subject to limitations. Prevalence is defined as the number of living subjects with a particular disease during a specific time frame. Birth prevalence underestimates the true burden of congenital heart disease by not capturing those in whom the diagnosis is established afterward. Prevalence estimated at a later time excludes those who died before the assessment, thereby differentially underrepresenting higher-fatality lesions, and potentially omitting defects that resolve spontaneously. For example, up to two-thirds of ventricular septal defects diagnosed at birth
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spontaneously close within the first years of life and will not be present in adulthood, whereas other forms of congenital heart disease, such as atrial septal defects, Ebstein anomaly, and congenitally corrected transposition of the great arteries might go unrecognized until adulthood. Furthermore, prevalence estimates might not consider other factors that affect global disease epidemiology, such as migration and population mobility. A Quebec population-based study estimated that, in the year 2010, the prevalence of congenital heart disease in adults (18 years of age and older) was 6.1 per 1000.9 Similar rates were projected in a recent systematic review.14 Extrapolating this statistic to the general population, it might be estimated that there are > 100,000 adults with congenital heart disease in Canada, 1 million in the United States,15 and 1.8 million in Europe.16 It is also noteworthy that the prevalence of complex congenital heart disease in adults has been steadily increasing (eg, by 85% from 1985 to 2000), unlike the relatively stable prevalence of complex congenital heart disease in children (Fig. 2).13 By 2010, adults accounted for 60% of patients with complex congenital heart disease.9 Organization and Delivery of Care Although the provision of care for children with congenital heart disease is well established in developed countries, clinical services for adults are comparatively scarce.17-19 To attend to the progressive increase in the number of adults with congenital heart disease and the increasing complexity of their pathologies, specialized adult congenital heart centres have emerged in several countries, with increasing volume of activities (Fig. 3). Canada assumed a leadership role in establishing recommendations for optimal organization and delivery of care. In 1991, the Canadian Adult Congenital Heart (CACH) network was established as the first national society dedicated to the care of adults with congenital heart disease (www. cachnet.ca). The Canadian Cardiovascular Society, in collaboration with the CACH network, formed a panel of experts in 1996 to discuss the needs of adults with congenital heart disease and provide recommendations for referral to specialized centres. The first management guidelines were presented at the Canadian Cardiovascular Congress in Montreal in 1996, published in the Canadian Journal of Cardiology in 1998,20 and subsequently updated in 200121 and 2009.22 Similar proposals emerged from the 32nd Bethesda Conference in 2000, which focused on the need for health care professionals, patients, and governing agencies to develop strategic plans to improve access to and delivery of care for the adult with congenital heart disease.23 This call to action was followed by more specific recommendations from the American College of Cardiology/American Heart Association and the European Society of Cardiology (ESC).24,25 Current management guidelines suggest that approximately half of the adult population with congenital heart disease stand to benefit from specialized care within adult congenital heart centres. Such care is generally recommended for the initial assessment of adults with known or suspected congenital heart disease, follow-up of patients with moderate and severe lesions, cardiac surgical and nonsurgical interventions, and risk assessment and support for pregnancy and noncardiac surgery.17,20,22,25-27
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Figure 2. Number and proportion of adults and children with (A) all forms of congenital heart disease (CHD), and (B) severe CHD in 1985, 1990, 1995, and 2000. Reproduced from Marelli et al.13
Recommended personnel and services for regional adult congenital centres are summarized in Table 1.25 In short, centralized care within regional centres should be provided by a multidisciplinary team comprised of cardiologists with expertise in adult congenital heart disease, including imaging, arrhythmia management,28 interventional cardiology, and high-risk obstetrics, congenital heart surgeons, perioperative care, and psychosocial support.17,25,26 Estimates regarding the ideal number of regional adult congenital centres have varied between 1 per
2-10 million inhabitants,17,21 which translates to up to 17 specialized centres in Canada, 150 in the United States, and 365 in Europe.29 This figure balances factors such as ease of access and centralization of resources, considering that improved outcomes are proportional to volume of activity and experience.30 Although the recommended number of specialized centres has been achieved in Canada (ie, 17 centres are registered within the CACH network), most countries in the developed world fall short of this target. For example, in the United States, 108
Figure 3. Number of patients followed at the Montreal Heart Institute Adult Congenital Centre over time. A > 7-fold increase in the number of adults with congenital heart disease was observed over a 15-year period.
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Table 1. Personnel and services recommended for regional ACHD centres Type of Service Cardiologist specializing in ACHD Congenital cardiac surgeon Nurse/physician assistant/nurse practitioner Cardiac anaesthesiologist Echocardiography* Includes TEE, intraoperative TEE Diagnostic catheterization* Noncoronary interventional catheterization* Electrophysiology/pacing/ICD implantation* Exercise testing
Cardiac imaging/radiology* Multidisciplinary teams
Information technology
concluded that referral to such a centre is associated with a significant reduction in all-cause mortality (Fig. 4).36
Personnel/Resources One or several 24/7 Two or several 24/7 One or several Several 24/7 Two or several 24/7 Yes, 24/7 Yes, 24/7 One or several Echocardiography Radionuclide Cardiopulmonary Metabolic Cardiac MRI CT scanning Nuclear medicine High-risk obstetrics Pulmonary hypertension Heart failure/transplant Genetics Neurology Nephrology Cardiac pathology Rehabilitation services Social services Vocational services Financial counsellors Database collection Database support Quality assessment review/protocols
24/7, availability 24 hours per day, 7 days per week; ACHD, adult congenital heart disease; CT, computed tomography; ICD, implantable cardioverter defibrillator; MRI, magnetic resonance imaging; TEE, transesophageal echocardiography. * These modalities must be supervised/performed and interpreted by physicians with expertise and training in congenital heart disease. Reproduced from Warnes et al.25
self-declared adult congenital heart centres with variable volumes of activity and availability of resources are listed on the American Congenital Heart Association Web site (www.achaheart.org). An adequate ratio of specialized adult congenital centres is no guarantee for optimal care. A larger issue that plagues the field of congenital heart disease is the relatively small proportion of qualifying patients who actually receive specialized adult-oriented care. For example, a Canadian study found that < 25% of adults with congenital heart disease are followed by specialized centres and that waiting times to access services exceed published recommendations.31 These sobering statistics have prompted numerous educational initiatives to raise awareness about the need for lifelong care and have incited research studies into factors associated with gaps in care and impediments to long-term follow-up.32,33 Common barriers to transfer from pediatric-to adult-oriented health care include inadequate knowledge regarding the need for such care, a dearth of accessible competent adult care providers, and emotional attachment of patients and families to their pediatric caregivers and vice-versa.34,35 Lending further credence to the notion that specialized adult congenital centres with multidisciplinary expertise offer the best prospects for improving outcomes, a recent population-based study
Training and Research An important element in optimizing outcomes is the development of training programs to meet workforce requirements and provide qualified, consistent, and comprehensive care.37 Exposure of adult cardiology trainees to adult congenital heart disease didactic and clinical experience varies widely, reflecting the fact that few programs offer advanced training in this sector of cardiology.38 Surveys suggest that only approximately 25% of cardiologists who care for adults with congenital heart disease have received formal training in this discipline.31,37 The United States is the first country to officially recognize the legitimacy of adult congenital heart disease as a separate subspecialty of cardiology.39 In September 2012, the American Board of Medical Subspecialties approved a specialized certification examination via the American Board of Internal Medicine. The first examination is planned for 2015. Pediatric or adult cardiologists require a minimum 2-year fellowship within recognized adult congenital training centres to qualify. The ESC, with its working group on grown-up congenital heart disease, is poised to follow suit.40 Canada is currently contemplating recognizing adult congenital heart disease as an area of focused competence via a Diploma of the Royal College of Physicians and Surgeons of Canada (DRCPSC). While details remain to be determined, a Diploma of the Royal College of Physicians and Surgeons of Canada typically requires 1-2 years of additional training by Royal College-accredited programs and is competency-based, with assessment through a summative portfolio. Another critically important element required to advance the care of adults with congenital heart disease is well-designed research. Over the past decade, significant strides have been achieved in coordinating research efforts and creating dedicated infrastructures.41 A critical mass of patients and investigators has enabled a new era of multicentre research with more exacting standards. Several networks and organizations have emerged, some focused on multicentre research as their main objective, with others providing a supportive environment to facilitate research. These include, but are not limited to, the International Society for Adult Congenital Heart Disease (www.isachd.org), CACH network, ESC (www.escardio. org), Japanese Circulation Society (www.j-circ.or.jp/english), Society of Thoracic Surgeons (www.sts.org), Congenital Heart Surgeons’ Society (www.chss.org), and the Adult Congenital Heart Association. In the Netherlands, the Interuniversity Cardiology Institute and Heart Foundation developed a highly productive national registry and DNA bank of patients with congenital heart disease, named CONgenital CORvitia (CONCOR; www.concor.net/en).42 In North America, an Alliance for Adult Research in Congenital Cardiology was founded in 2006 to foster collaborative research, advance knowledge, and improve outcomes (www.aarcc.net). Health Care Resource Utilization Despite surgical repair, most forms of congenital heart disease are associated with sequelae and long-term complications, which engender a high level of health care resource utilization.19,43 Rates of emergency room visits, hospital
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Figure 4. Time-series analysis: referral to specialized adult congenital heart disease (ACHD) centres and ACHD patient mortality. Observed specialized ACHD centre referral (black line) and ACHD mortality (grey line) per 1000 ACHD population per year, between 1990 and 2005. The dashed lines indicate expected trends after the change points identified by Poisson regression, and the black or grey lines represent the observed trends. Reproduced with permission from Mylotte et al.36
admissions, and cardiac interventions are several-fold greater than in the general population.44-47 Figure 5 depicts common causes of hospitalizations.46 Models of health-related costs and outcomes in adults with congenital heart disease provide economic justification for expensive interventions on the basis of striking benefits on quality-adjusted life years.48 Overview of Common Issues Common complications that contribute to the growing epidemic of adults with congenital heart disease include arrhythmias, heart failure, pulmonary hypertension, endocarditis, pregnancy-related issues, and cardiac interventions. Arrhythmias Arrhythmias are the most common long-term complication in adults with congenital heart disease, the leading source of morbidity and hospital admissions, and a major cause of mortality.46,49-52 All forms of tachy- and bradyarrhythmias might be encountered.53 Figure 6 schematically summarizes factors predisposing to arrhythmias.54 The prevalence of tachyarrhythmias generally correlates with increasing age and complexity of the congenital heart lesion (Fig. 7).28,55,56 Sinus node dysfunction is highly prevalent in patients with surgery at or near the superior vena cava to the right atrial junction; atrioventricular block is common in those with displaced conduction systems and in the acute postoperative setting.57-60 In 2014, the Pediatric and Congenital Electrophysiology Society together with the Heart Rhythm Society proposed recommendations on the recognition and management of arrhythmias in adults with congenital heart disease, which were endorsed by the American College of Cardiology, American Heart Association, European Heart Rhythm Association, Canadian Heart Rhythm Society, and the International Society for Adult Congenital Heart Disease.28
volume and/or pressure overload, inability of a systemic morphologic right ventricle or single ventricle circulation to adequately meet metabolic needs, unequal flow distributions to lung fields, variable pulmonary vascular integrity, and abnormalities of myocardial tissue architecture, electrical conduction, and blood supply.61 As such, management guidelines for acquired heart disease cannot be extrapolated to the complex forms of heart failure encountered in adults with congenital heart disease. Despite the heterogeneity and imprecisions, on the whole, heart failure appears to be increasing in prevalence as the population ages. It is among the most common causes of hospitalization (see Fig. 5),45,46,52 with some studies suggesting that it has surpassed sudden cardiac death as the leading cause of mortality.8,51,62 The incidence of systolic systemic ventricular dysfunction is highest in those with cyanotic lesions, systemic right ventricles, and univentricular hearts.63 In some forms of congenital heart disease, diastolic systemic ventricular dysfunction has been correlated with arrhythmias and mortality.64 Even in the absence of overt heart failure as classically defined, some degree of exercise intolerance is documented in up to onethird.65 When contrasted against quantified exercise capacity, functional symptoms are notoriously underreported as a result of lifelong adaptation to a chronic disorder.66 Exercise intolerance consistently portends poorer midterm outcomes, such as hospitalizations and mortality.66 Moreover, in an increasing number of adults with congenital heart disease and end-stage circulatory failure in whom cardiac transplantation is not a viable option, endof-life issues and palliative care assume a prominent role.67,68 Pulmonary hypertension
Heart failure Mechanisms for heart failure in adults with congenital heart disease might involve circulatory overload, ventricular
Any nonrestrictive communication causing left-to-right shunting with increased pulmonary blood flow might produce pathological changes to the pulmonary vascular bed,
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Figure 5. Most frequent cardiovascular admission diagnoses/symptoms in the CONgenital CORvitia (CONCOR) Dutch national registry population from 2001 to 2005 (n ¼ 5798). All cardiovascular admissions with n ¼ 100 are displayed. Nos, not otherwise specified. Reproduced from Verheugt et al.46
including vasoconstriction, inflammation, cell proliferation, and vascular remodelling, resulting in increased pulmonary vascular resistance.69,70 Pulmonary arterial hypertension is prevalent in 4%-10% of adults with congenital heart disease and is associated with exercise intolerance and heart failure.69,71 At the extreme end of the spectrum, Eisenmenger syndrome is a multisystemic disorder associated with a 10- to 12-fold increase in mortality in those with complex congenital heart disease.69,72-77 If managed appropriately, many such patients survive past the third or fourth decade of life.72 In developed countries, earlier recognition and closure of
intracardiac shunts has resulted in a reduction in the prevalence of Eisenmenger syndrome.78 Nevertheless, pulmonary hypertension persists in 3%-13% of patients after septal defect closure71,79 and implies a worse prognosis.80 Endocarditis The incidence of endocarditis (approximately 1.1 per 1000 patient-years) in adults with congenital heart disease is 20-fold greater than in the general population,81,82 with a 12% recurrence rate.81,83 Factors associated with endocarditis include the type of congenital heart defect, presence of
Figure 6. Factors leading to arrhythmias in (A) before, and (B) after surgery for congenital heart disease. AV, atrioventricular; VT, ventricular tachycardia. Adapted from Escudero et al.54
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Figure 7. Risk estimates for arrhythmias according to type of congenital heart disease. Approximate risk estimates for atrial tachycardia (AT), atrial fibrillation (AF), other supraventricular arrhythmias, ventricular arrhythmia, sinus node dysfunction (SND), atrioventricular (AV) block, and ventricular dyssynchrony are shown across various congenital heart defects (CHDs) of simple, moderate, and severe complexity. D- and L-transposition denote complete and congenitally corrected transposition of the great arteries, respectively. The colour-coded pattern ranges from minimal (no shading) to mild (light blue), moderate (medium blue), and high (dark blue) risk. Reproduced Khairy et al.28
multiple defects, and male sex.81 Systemic embolization, heart failure, and valvular regurgitation are common complications.84 Surgery is required in up to one-third of patients.84,85 Improvements in antibiotic therapy and earlier surgical management have resulted in lower rates of complications and mortality over the past decades, with current in-hospital mortality ranging from 4% to 9%.81,83,84 Educational counselling, including hygienic measures and antibiotic prophylaxis when indicated, should be incorporated in the care of adults with congenital heart disease. Pregnancy When considered collectively, congenital malformations are the most prevalent form of heart disease in pregnant women86,87 and the leading cardiac cause of maternal morbidity and mortality in developed countries.25 Pregnancy is the most common noncardiac cause of hospitalization in women with congenital heart disease.45,46 Congenital heart disease carries increased maternal and fetal risks, particularly in the setting of pulmonary arterial hypertension, subaortic or subpulmonary ventricular dysfunction, left-sided valvular obstruction, unrepaired aortic coarctation, or aortic root dilatation in association with other anomalies such as a bicuspid aortic valve, Marfan, or Turner syndrome.86-89 Heart failure and arrhythmias are the most common maternal complications, whereas frequent neonatal adverse outcomes include small for gestational age birth weight, respiratory distress, and intraventricular cerebral hemorrhage.90 Women with moderate and complex forms of congenital heart disease
should be managed by a multidisciplinary team with appropriate expertise and delivery should take place in specialized centres.25-27,91 Congenital cardiac surgeries and interventions Surgical and catheter procedures are on the increase in adults with congenital heart disease.92 Percutaneous devices are increasingly used to close septal defects, abnormal vascular connections, leaks across conduits and baffles, and pseudoaneurysms; covered stents have enhanced the safety with which aortic coarctation, conduit stenosis, and branch pulmonary stenosis can be treated; and percutaneous valves have broadened the range of therapeutic options in selected patients.93 Cardiovascular surgery is also increasingly performed in adults with congenital heart disease to rectify residual or progressive lesions in the setting of previous reparative surgery, address previously unoperated disease, palliate nonreparable defects, and transplant failing hearts.94 Complications after surgery occur in 15%-25% of patients and include arrhythmias, low cardiac output, stroke, bleeds, and renal failure. Perioperative mortality risk depends on numerous factors but is generally within the 3%-8% range.95-98 Conclusion Adult congenital heart disease is the most rapidly growing sector of cardiology today, with a patient population that is swiftly increasing in size and complexity. Unique issues, challenges, and considerations are involved in managing adults
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with congenital heart disease, including arrhythmias, heart failure, pulmonary hypertension, endocarditis, pregnancy, interventions, and surgery. An increasing body of evidence suggests that outcomes can be improved by referral to specialized centres with multidisciplinary teams dedicated to clinical care, training, and research in adult congenital heart disease.
14. van der Bom T, Bouma BJ, Meijboom FJ, Zwinderman AH, Mulder BJ. The prevalence of adult congenital heart disease, results from a systematic review and evidence based calculation. Am Heart J 2012;164:568-75.
Funding Sources Dr Ávila received a research grant from the Fundación Alfonso Martín Escudero (Spain). Dr Khairy is supported by a Canada Research Chair in Adult Congenital Heart Disease and Electrophysiology.
17. Landzberg MJ, Murphy DJ Jr, Davidson WR Jr, et al. Task force 4: organization of delivery systems for adults with congenital heart disease. J Am Coll Cardiol 2001;37:1187-93.
Disclosures The authors have no conflicts of interest to disclose.
19. Report of the British Cardiac Society Working Party. Grown-up congenital heart (GUCH) disease: current needs and provision of service for adolescents and adults with congenital heart disease in the UK. Heart 2002;88(suppl 1):i1-14.
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