T h e Ep i d e m i o l o g y of H e a r t Failure in Adults with Congenital Heart Disease Fred H. Rodriguez III, MDa,*, Ariane J. Marelli, MD, MPHb KEYWORDS Congenital heart disease Myocardial dysfunction Heart failure Epidemiology
KEY POINTS There are more adults than children with congenital heart disease and this population is rapidly growing. Lifelong exposure to myocardial dysfunction results from repeated surgical interventions and chronically abnormal biventricular loading conditions. Heart failure in adults with congenital heart disease can result from systolic and diastolic dysfunction and is most common in patients with tetralogy of Fallot, transposition of the great arteries, and single ventricle physiology. The presence of heart failure in this population adversely affects mortality and morbidity and data are needed to quantify and prevent this complication. Hospitalizations because of heart failure in adults with congenital heart disease in the United States increased substantially from 1998 to 2005, making this problem an important public health issue.
The impact of lifelong exposure to myocardial dysfunction in populations with congenital heart disease (CHD) is becoming increasingly recognized. Most children born with CHD now reach adulthood and the long-term sequelae of treatment are contributing to substantial comorbidity.1,2 Improved survival is achieved at a cost of repeated interventions. The combination of structural changes present at birth with changes resulting from cardiac surgery can result in heart failure.3,4 Thus, the effect of chronic myocardial dysfunction is amplified and increasing survivorship is resulting in longer time windows to express heart failure. Heart failure has been cited as the leading cause of cardiovascular death in adults with CHD.5 Although guidelines for the management of chronic
heart failure in acquired cardiovascular conditions exist,6 there are no directives on preventing complications or improving outcomes from chronic heart failure in the CHD population. To date, there are few data to substantiate the incidence and prevalence of heart failure in adults with CHD. This article reports on the current state of knowledge on the epidemiology of heart failure in this patient population and the current data sources that may enable better characterization of this complex condition in adults with CHD.
ADULTS WITH CONGENITAL HEART DISEASE: HOW FAST ARE THE NUMBERS GROWING? The reported prevalence of CHD at birth is approximately 8/1000 live births, although reports vary between 4/1000 and 50/1000.7,8 In the United
a Section of Cardiology, Sibley Heart Center Cardiology, Emory University, 2835 Brandywine Road, Suite 300, Atlanta, GA 30341, USA; b McGill Adult Unit for Congenital Heart Disease (MAUDE Unit), McGill University Health Center, McGill University, 687 Pine Avenue West, Montreal, QC H3A 1A1, Canada * Corresponding author. E-mail address: [email protected]
Heart Failure Clin 10 (2014) 1–7 http://dx.doi.org/10.1016/j.hfc.2013.09.008 1551-7136/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
heartfailure.theclinics.com
INTRODUCTION
2
Rodriguez III & Marelli States, the Centers for Disease Control (CDC) has reported birth prevalence rates between 8 and 10/1000 live births.9 Continental variations in birth prevalence have been reported, from 6.9/1000 births in Europe to 9.3/1000 in Asia.10 In 26,598 live births between 2000 and 2005 in Europe, the prevalence at birth of CHD was reported to be up to 13/1000 live births.11 Advances in medical and surgical therapy have led to an increase in the survival of patients with CHD and therefore an increased prevalence in the general population. There has been an increase in the median age at death in those with severe CHD by more than 20 years since 1987.12 The prevalence of CHD increased by 22% in children and 85% in adults with severe CHD from 1985 to 2000 such that in 2000, the prevalence of CHD in Quebec was 4/1000 adults and 12/1000 children.2 The median age of those alive with severe CHD has also increased from 11 to 17 years as observed from 1985 to 2000 and is expected to further increase between 2000 and 2020.2 The mortality rates of patients born with CHD have declined in recent decades.13 From 1979 to 1997, age-adjusted population death rates from all defects declined 39% in the United States from 2.5 to 1.5/100,000 or 1.9% per year.14 During the same observation period, mortality declined for both simple and complex lesions such as transposition of the great arteries (TGA), tetralogy of Fallot (TOF), atrioventricular septal defect, and aortic coarctation (COA).14 Despite such progress, CHD remains the most common cause of infant death associated with birth defects.13 As more children with moderate to severe defects are reaching adult age, there has been a shift in mortality.12 In a population-based cohort in Quebec, a total of 8561 deaths occurred in 71,686 patients with CHD (11.9%) followed for 982,363 patientyears from 1987 to 2005.12 However, long-term survival after surgical repair of complex defects remains compromised, with survival rates decreasing from the third and fourth decade onward.15 Anatomic severity of CHD is 1 of several important contributors to disease burden. The proportion of patients with adult CHD (ACHD) with complex or severe lesions has been estimated and measured, and varies from 10% to 15% on a population level1,2,7,16 but is as high as 30% in select tertiary care centers.1,2,8,16 Using estimates of survival by cohort and the Bethesda disease severity classification, approximately 15% of adults are expected to have lesions of great complexity; those with moderate lesions were estimated to account for approximately one-third of patients.
HEART FAILURE DEFINITIONS AND POPULATIONS: WHO IS AT RISK? Scope of the Problem Heart failure has been defined as a “complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood.”6 Heart failure is 1 of the most common causes for hospitalization in acquired heart disease and is associated with significant morbidity and mortality. Mortality during heart failure–related hospitalization has been reported to be between 3% and 13%.17,18 Heart failure in patients with ACHD can be complex, with symptoms of right heart failure, left heart failure, or even inadequate end-organ perfusion, which is seen in patients with portal hypertension and end-stage liver failure who have decreased systemic vascular resistance in the setting of a normal ejection fraction. Systolic dysfunction occurs in patients but is often not caused by the ischemic changes seen in the general adult population. Coronary arteries may be compromised during cardiac surgery during operations such as an arterial switch, Ross procedure, Nikaidoh procedure, or Bentall procedure when coronary arteries are translocated and resewn into an aortic or neoaortic root. Left-sided obstructive lesions such as aortic valve stenosis, subaortic stenosis, and coarctation of the aorta may lead to left ventricular hypertrophy in patients, resulting in impaired ventricular relaxation. Left ventricular noncompaction may result in a steady and progressive decline in function either early or late in life. Patients who develop bundle branch blocks may have dyssynchrony and an eventual decline in systolic function. Patients who require a pacemaker may have a pacer-dependent decrease in cardiac function over time. The prevalence of heart failure is highest in patients with single ventricle physiology, TOF, and TGA (Fig. 1).19 Diastolic dysfunction is being increasingly recognized in both left-sided and right-sided CHD. Impaired relaxation and diastolic dysfunction in the left ventricle may occur many years after an initial operation and can cause left atrial hypertension and symptoms of dyspnea and exercise intolerance.20 Measuring function of the right ventricle (RV) remains a challenge compounded by the fact that the RV in CHD can be in the subaortic or subpulmonary position. The geometrically challenging crescent-shaped RV exhibits a wide range of physiologic responses to pressure and volume overload resulting in systolic and diastolic dysfunction.21 Impaired relaxation of the RV may precede systolic dysfunction and be a sensitive marker of myocardial dysfunction.22
The Epidemiology of Heart Failure in ACHD Fig. 1. The probability of heart failure versus age and type of heart defect. (From Norozi K, Wessel A, Alpers V, et al. Incidence and risk distribution of heart failure in adolescents and adults with congenital heart disease after cardiac surgery. Am J Cardiol 2006;97(8):1241; with permission.)
Patients with TOF now have more than a 90% chance of survival to adulthood, although many of these patients have evidence of pulmonary insufficiency, right ventricular enlargement, and impaired exercise capacity. Many others experience arrhythmias, either atrial or ventricular, caused by hemodynamic stressors as well as surgical changes. Many patients with repaired TOF experience right heart failure signs and symptoms such as hepatic congestion, peripheral edema, increased filling pressures, and peripheral edema. There is also a subset of patients with repaired tetralogy who have reduced left ventricular systolic function and experience symptoms of left ventricular failure such as pulmonary edema and orthopnea. These patients with left ventricular dysfunction are at increased risk for sudden cardiac death.23 They may also have diastolic dysfunction of the left ventricle, particularly those who were repaired late.24,25 The prevalence of TGA in the United States is 4.73/10,000 live births, and more than 90% are now surviving to adulthood. From the late 1960s to the late 1980s/early 1990s, many of these patients underwent the Mustard or Senning operations. As surgical trends changed, patients usually undergo the Jatene arterial switch operation in the contemporary period, and many centers demonstrate low surgical mortality. However, the numerous atrial suture lines and burden of arrhythmias in Mustard/Senning patients, as well as the long-standing effects of a systemic RV lead to symptoms of heart failure in many patients. Many patients require a pacemaker and numerous others have depressed right ventricular systolic function and tricuspid regurgitation. Patients born with single ventricle physiology often are palliated with the Fontan procedure, separating deoxygenated blood, which directly
enters the lungs and systemic oxygenated blood flow. Compared with those with a repaired simple left to right shunt, those adolescents and adults who underwent Fontan palliation for single ventricle physiology have an odds ratio of more than 7 for developing heart failure.19 Symptoms of heart failure develop because of systolic dysfunction, diastolic dysfunction, or sometimes because of decreased systemic vascular resistance seen in portal hypertension and cirrhosis. Hepatic congestion and portal hypertension occur in patients after the Fontan operation, and cardiac cirrhosis can develop. Patients with a failing Fontan have been described as those with a deterioration in exercise tolerance, persistent arrhythmias, worsening peripheral edema, and protein-losing enteropathy, all of which may be classified as evidence of heart failure. There is a decrease in survival of more than 15 years after the Fontan operation. Actuarial freedom from death or transplantation has been reported as 87%, 83%, and 70% at 15, 20, and 25 years after surgery, respectively.26 Death in this group is related to heart failure in 7%.26 Pulmonary hypertension may develop in patients with CHD, regardless of whether they have been palliated/repaired or not.27 Long-standing left to right shunting in patients with CHD may lead to irreversible pulmonary hypertension. Muscularization of the pulmonary vascular bed is demonstrated by increased pulmonary arterial pressures and right ventricular strain, which may result in symptoms of dyspnea and heart failure.
THE NUMBERS: WHAT DO WE KNOW? Obtaining Data In the United States there are an increasing number of data sources available to identify patients with ACHD and their cross-sectional outcomes.
3
4
Rodriguez III & Marelli The Nationwide Inpatient Sample (NIS) is the largest all-payer inpatient care database in the United States, containing data from approximately 8 million hospital stays each year. This estimates data for more than 39 million hospitalizations. It is the only US national hospital database containing charge information on all patients, regardless of payer, including persons covered by Medicare, Medicaid, private insurance, and the uninsured. Studies using this database have assessed trends in hospitalizations for patients with ACHD in the United States.28 The inpatient National Claims History files from the Centers for Medicare & Medicaid Services (CMS) identifies information on patient demographics (age, sex, race), admission and discharge dates, and principal and secondary diagnosis codes (as coded by the International Classification of Diseases, Ninth Revision, Clinical Modification). The Healthcare Cost & Utilization Project (HCUP) Kids’ Inpatient Database (KID) is drawn from the State Inpatient Discharge (SID) database, which captures 90% of all US discharges each year. The KID subset captures a random sample of 2 to 3 million discharges per year in more than 3700 hospitals in 38 states, making it the largest database on hospital care of newborns, infants, children, and adolescents (age
KEY POINTS There are more adults than children with congenital heart disease and this population is rapidly growing. Lifelong exposure to myocardial dysfunction results from repeated surgical interventions and chronically abnormal biventricular loading conditions. Heart failure in adults with congenital heart disease can result from systolic and diastolic dysfunction and is most common in patients with tetralogy of Fallot, transposition of the great arteries, and single ventricle physiology. The presence of heart failure in this population adversely affects mortality and morbidity and data are needed to quantify and prevent this complication. Hospitalizations because of heart failure in adults with congenital heart disease in the United States increased substantially from 1998 to 2005, making this problem an important public health issue.
The impact of lifelong exposure to myocardial dysfunction in populations with congenital heart disease (CHD) is becoming increasingly recognized. Most children born with CHD now reach adulthood and the long-term sequelae of treatment are contributing to substantial comorbidity.1,2 Improved survival is achieved at a cost of repeated interventions. The combination of structural changes present at birth with changes resulting from cardiac surgery can result in heart failure.3,4 Thus, the effect of chronic myocardial dysfunction is amplified and increasing survivorship is resulting in longer time windows to express heart failure. Heart failure has been cited as the leading cause of cardiovascular death in adults with CHD.5 Although guidelines for the management of chronic
heart failure in acquired cardiovascular conditions exist,6 there are no directives on preventing complications or improving outcomes from chronic heart failure in the CHD population. To date, there are few data to substantiate the incidence and prevalence of heart failure in adults with CHD. This article reports on the current state of knowledge on the epidemiology of heart failure in this patient population and the current data sources that may enable better characterization of this complex condition in adults with CHD.
ADULTS WITH CONGENITAL HEART DISEASE: HOW FAST ARE THE NUMBERS GROWING? The reported prevalence of CHD at birth is approximately 8/1000 live births, although reports vary between 4/1000 and 50/1000.7,8 In the United
a Section of Cardiology, Sibley Heart Center Cardiology, Emory University, 2835 Brandywine Road, Suite 300, Atlanta, GA 30341, USA; b McGill Adult Unit for Congenital Heart Disease (MAUDE Unit), McGill University Health Center, McGill University, 687 Pine Avenue West, Montreal, QC H3A 1A1, Canada * Corresponding author. E-mail address: [email protected]
Heart Failure Clin 10 (2014) 1–7 http://dx.doi.org/10.1016/j.hfc.2013.09.008 1551-7136/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
heartfailure.theclinics.com
INTRODUCTION
2
Rodriguez III & Marelli States, the Centers for Disease Control (CDC) has reported birth prevalence rates between 8 and 10/1000 live births.9 Continental variations in birth prevalence have been reported, from 6.9/1000 births in Europe to 9.3/1000 in Asia.10 In 26,598 live births between 2000 and 2005 in Europe, the prevalence at birth of CHD was reported to be up to 13/1000 live births.11 Advances in medical and surgical therapy have led to an increase in the survival of patients with CHD and therefore an increased prevalence in the general population. There has been an increase in the median age at death in those with severe CHD by more than 20 years since 1987.12 The prevalence of CHD increased by 22% in children and 85% in adults with severe CHD from 1985 to 2000 such that in 2000, the prevalence of CHD in Quebec was 4/1000 adults and 12/1000 children.2 The median age of those alive with severe CHD has also increased from 11 to 17 years as observed from 1985 to 2000 and is expected to further increase between 2000 and 2020.2 The mortality rates of patients born with CHD have declined in recent decades.13 From 1979 to 1997, age-adjusted population death rates from all defects declined 39% in the United States from 2.5 to 1.5/100,000 or 1.9% per year.14 During the same observation period, mortality declined for both simple and complex lesions such as transposition of the great arteries (TGA), tetralogy of Fallot (TOF), atrioventricular septal defect, and aortic coarctation (COA).14 Despite such progress, CHD remains the most common cause of infant death associated with birth defects.13 As more children with moderate to severe defects are reaching adult age, there has been a shift in mortality.12 In a population-based cohort in Quebec, a total of 8561 deaths occurred in 71,686 patients with CHD (11.9%) followed for 982,363 patientyears from 1987 to 2005.12 However, long-term survival after surgical repair of complex defects remains compromised, with survival rates decreasing from the third and fourth decade onward.15 Anatomic severity of CHD is 1 of several important contributors to disease burden. The proportion of patients with adult CHD (ACHD) with complex or severe lesions has been estimated and measured, and varies from 10% to 15% on a population level1,2,7,16 but is as high as 30% in select tertiary care centers.1,2,8,16 Using estimates of survival by cohort and the Bethesda disease severity classification, approximately 15% of adults are expected to have lesions of great complexity; those with moderate lesions were estimated to account for approximately one-third of patients.
HEART FAILURE DEFINITIONS AND POPULATIONS: WHO IS AT RISK? Scope of the Problem Heart failure has been defined as a “complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood.”6 Heart failure is 1 of the most common causes for hospitalization in acquired heart disease and is associated with significant morbidity and mortality. Mortality during heart failure–related hospitalization has been reported to be between 3% and 13%.17,18 Heart failure in patients with ACHD can be complex, with symptoms of right heart failure, left heart failure, or even inadequate end-organ perfusion, which is seen in patients with portal hypertension and end-stage liver failure who have decreased systemic vascular resistance in the setting of a normal ejection fraction. Systolic dysfunction occurs in patients but is often not caused by the ischemic changes seen in the general adult population. Coronary arteries may be compromised during cardiac surgery during operations such as an arterial switch, Ross procedure, Nikaidoh procedure, or Bentall procedure when coronary arteries are translocated and resewn into an aortic or neoaortic root. Left-sided obstructive lesions such as aortic valve stenosis, subaortic stenosis, and coarctation of the aorta may lead to left ventricular hypertrophy in patients, resulting in impaired ventricular relaxation. Left ventricular noncompaction may result in a steady and progressive decline in function either early or late in life. Patients who develop bundle branch blocks may have dyssynchrony and an eventual decline in systolic function. Patients who require a pacemaker may have a pacer-dependent decrease in cardiac function over time. The prevalence of heart failure is highest in patients with single ventricle physiology, TOF, and TGA (Fig. 1).19 Diastolic dysfunction is being increasingly recognized in both left-sided and right-sided CHD. Impaired relaxation and diastolic dysfunction in the left ventricle may occur many years after an initial operation and can cause left atrial hypertension and symptoms of dyspnea and exercise intolerance.20 Measuring function of the right ventricle (RV) remains a challenge compounded by the fact that the RV in CHD can be in the subaortic or subpulmonary position. The geometrically challenging crescent-shaped RV exhibits a wide range of physiologic responses to pressure and volume overload resulting in systolic and diastolic dysfunction.21 Impaired relaxation of the RV may precede systolic dysfunction and be a sensitive marker of myocardial dysfunction.22
The Epidemiology of Heart Failure in ACHD Fig. 1. The probability of heart failure versus age and type of heart defect. (From Norozi K, Wessel A, Alpers V, et al. Incidence and risk distribution of heart failure in adolescents and adults with congenital heart disease after cardiac surgery. Am J Cardiol 2006;97(8):1241; with permission.)
Patients with TOF now have more than a 90% chance of survival to adulthood, although many of these patients have evidence of pulmonary insufficiency, right ventricular enlargement, and impaired exercise capacity. Many others experience arrhythmias, either atrial or ventricular, caused by hemodynamic stressors as well as surgical changes. Many patients with repaired TOF experience right heart failure signs and symptoms such as hepatic congestion, peripheral edema, increased filling pressures, and peripheral edema. There is also a subset of patients with repaired tetralogy who have reduced left ventricular systolic function and experience symptoms of left ventricular failure such as pulmonary edema and orthopnea. These patients with left ventricular dysfunction are at increased risk for sudden cardiac death.23 They may also have diastolic dysfunction of the left ventricle, particularly those who were repaired late.24,25 The prevalence of TGA in the United States is 4.73/10,000 live births, and more than 90% are now surviving to adulthood. From the late 1960s to the late 1980s/early 1990s, many of these patients underwent the Mustard or Senning operations. As surgical trends changed, patients usually undergo the Jatene arterial switch operation in the contemporary period, and many centers demonstrate low surgical mortality. However, the numerous atrial suture lines and burden of arrhythmias in Mustard/Senning patients, as well as the long-standing effects of a systemic RV lead to symptoms of heart failure in many patients. Many patients require a pacemaker and numerous others have depressed right ventricular systolic function and tricuspid regurgitation. Patients born with single ventricle physiology often are palliated with the Fontan procedure, separating deoxygenated blood, which directly
enters the lungs and systemic oxygenated blood flow. Compared with those with a repaired simple left to right shunt, those adolescents and adults who underwent Fontan palliation for single ventricle physiology have an odds ratio of more than 7 for developing heart failure.19 Symptoms of heart failure develop because of systolic dysfunction, diastolic dysfunction, or sometimes because of decreased systemic vascular resistance seen in portal hypertension and cirrhosis. Hepatic congestion and portal hypertension occur in patients after the Fontan operation, and cardiac cirrhosis can develop. Patients with a failing Fontan have been described as those with a deterioration in exercise tolerance, persistent arrhythmias, worsening peripheral edema, and protein-losing enteropathy, all of which may be classified as evidence of heart failure. There is a decrease in survival of more than 15 years after the Fontan operation. Actuarial freedom from death or transplantation has been reported as 87%, 83%, and 70% at 15, 20, and 25 years after surgery, respectively.26 Death in this group is related to heart failure in 7%.26 Pulmonary hypertension may develop in patients with CHD, regardless of whether they have been palliated/repaired or not.27 Long-standing left to right shunting in patients with CHD may lead to irreversible pulmonary hypertension. Muscularization of the pulmonary vascular bed is demonstrated by increased pulmonary arterial pressures and right ventricular strain, which may result in symptoms of dyspnea and heart failure.
THE NUMBERS: WHAT DO WE KNOW? Obtaining Data In the United States there are an increasing number of data sources available to identify patients with ACHD and their cross-sectional outcomes.
3
4
Rodriguez III & Marelli The Nationwide Inpatient Sample (NIS) is the largest all-payer inpatient care database in the United States, containing data from approximately 8 million hospital stays each year. This estimates data for more than 39 million hospitalizations. It is the only US national hospital database containing charge information on all patients, regardless of payer, including persons covered by Medicare, Medicaid, private insurance, and the uninsured. Studies using this database have assessed trends in hospitalizations for patients with ACHD in the United States.28 The inpatient National Claims History files from the Centers for Medicare & Medicaid Services (CMS) identifies information on patient demographics (age, sex, race), admission and discharge dates, and principal and secondary diagnosis codes (as coded by the International Classification of Diseases, Ninth Revision, Clinical Modification). The Healthcare Cost & Utilization Project (HCUP) Kids’ Inpatient Database (KID) is drawn from the State Inpatient Discharge (SID) database, which captures 90% of all US discharges each year. The KID subset captures a random sample of 2 to 3 million discharges per year in more than 3700 hospitals in 38 states, making it the largest database on hospital care of newborns, infants, children, and adolescents (age
