Heart Failure and Transplant in Adult Congenital Heart Disease

Epidemiology of heart failure (HF) in adults with congenital heart disease (ACHD): HF is one of the leading causes of morbidity and mortality in ACHD [1]. Hospitalizations for HF in the ACHD population have nearly doubled between 1998 and 2005 [2]. Prevalence of HF increases with age, and most patients with CHD will present with heart failure for the first time in adulthood [3, 4]. Prevalence of HF is highest in [3, 4]: Transposition of the great arteries (TGA) with systemic right ventricles (i.e., D-TGA status post-atrial switch procedure or congenitally corrected TGA). Tetralogy of Fallot. Single ventricle physiology. Development of HF portends a poor prognosis for ACHD patients, with a 1-year mortality of 24% and a 3-year mortality of 35% for ACHD patients after a HF admission [5] (Fig. 38.1). Challenges inmanagement of HF in ACHD [6, 7]: Consistent definition and identification of ACHD patients in HF is difficult as the presentation and etiologies are diverse. It can be difficult to recognize HF in ACHD as many patients feel asymptomatic and may not be aware of slowly progressive exercise limitations. The major trials in HF excluded ACHD patients, so applicability of typical first-line interventions is uncertain. Various etiologies of HF in ACHD [3]: Mechanisms of cardiomyopathy: Pressure-loading lesions (such as coarctation of the aorta) leading to hypertrophy and diastolic abnormalities Volume-loading lesions causing ventricular remodeling (i.e., severe pulmonic regurgitation leading to RV dilation and dysfunction) Intrinsic congenital myopathy such as in Ebstein’s anomaly or left ventricular non-compaction Right ventricle acting as systemic ventricle (D-TGA with atrial switch procedure or congenitally corrected TGA) Tachyarrhythmia-mediated myopathy Pacemaker-mediated myopathies Dyssynchrony from abnormal development of bundle branch blocks Myocardial injury from chronic hypoxia Ischemia due to anomalous coronary origin or ostial restenosis among patients who have undergone coronary artery reimplantation Pulmonary hypertension (may be shunt-related or secondary to left-sided obstructive disease). Volume expansion during pregnancy [8]. Neurohormonal activation due to persistent abnormal cardiac pressure, compliance, volume, and flow. Always consider superimposed acquired cardiac disease as ACHD patients are living longer (atherosclerotic coronary artery disease, atrial fibrillation, diabetes-mediated cardiomyopathy). Recognizing HF in ACHD: Because of lifelong adaptation to an abnormal cardiovascular system, many patients feel asymptomatic despite progressive functional decline [9]. HF may often first manifest as arrhythmia [9]; therefore, any new onset arrhythmia in ACHD necessitates echocardiography to assess for new structural disease or ventricular dysfunction. Right heart failure is common and may be indolent and unrecognized [9]. Fontan patients may first manifest Fontan failure with evidence of lymphatic dysfunction: chronic diarrhea due to protein-losing enteropathy or coughing of bronchial casts due to plastic bronchitis [9]. Be vigilant for other common signs of progressing HF: hyponatremia, worsening renal function, and intolerance to medications (causing hypotension) [9]. Interpretation of NT-proBNP in ACHD patients is difficult [8]. Complex ACHD lesions have higher baseline levels, and hypoxia is known to increase BNP which can therefore confound interpretation in cyanotic ACHD. However, NT-proBNP has been shown to correlate with increasing ventricular size and decreasing ejection fraction, and trending NT-proBNP may offer insight into the presence of subclinical HF. Stratification of ACHD patients by the Seattle Heart Failure Model score identifies patients at high risk of HF admission and mortality [10]. Cardiopulmonary exercise testing (CPET) is a quantitative and informative tool to guide prognosis and advance of therapies [8]. Management of HF in ACHD (Fig. 38.2): Optimization of HF with typical pharmacological management is standard, though research demonstrating benefits in ACHD is limited. Decongestions with diuretics is the mainstay for management of volume expansion. Beta-blockers are often prescribed to ACHD patients regardless of arrhythmia prevention, but the benefit of beta-blockers in HF has not yet been demonstrated in ACHD and is inferred from ischemic cardiomyopathy [8]. Similarly, no studies have addressed the benefit of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in ACHD patients. It is thought that these patients often have decreased renin-angiotensin-aldosterone system activation and therefore receive less benefit from these medications [8]. Valsartan was studied in patients with systemic RVs (D-TGA with atrial switch or congenitally corrected TFA) in a randomized placebo-controlled trial (n = 88) which demonstrated some improvement in RV end diastolic volume and RV mass by MRI at 3 years but no improvement in RV ejection fraction, exercise capacity, or quality of life [11]. Pulmonary vasodilators in patients with pulmonary hypertension have shown to be beneficial in ACHD. A significant improvement in survival was noted among Eisenmenger patients who received advanced pulmonary vasodilator therapy compared to those who did not [12]. Of note, the concern for reversal of shunt in patients with right-to-left shunt has not been demonstrated in these studies [13, 14]. Early consideration of invasive procedures, in the of setting shunts or obstruction, to reduce and limit HF is key and unique to ACHD patients (i.e., is there a shunt that can be closed, a stenotic baffle that can be stented, etc.) [15] Indications for cardiac resynchronization therapy are currently extrapolated from acquired HF [8]. Potential indications for heart transplantation in ACHD: NYHA Class III, IV Cardiogenic shock (requiring inotropes or mechanical circulatory support) Decreased pVO2 (will vary), <12–14 mL/kg/min or <50% predicted (recall that mean pVO2 for the general population and for specific CHD lesions are not always similar) Intractable malignant arrhythmias Heart transplantation in ACHD: The prevalence of heart transplant among ACHD has increased by 41% from 1999 to 2008 [16]. ACHD patients who receive heart transplants have higher mortality rates immediately postoperatively than non-ACHD patients who receive transplants; however they benefit from better long-term survival [17]. ACHD patients are more frequently listed at lowest priority [6]. Wait-list mortality is similar for ACHD and non-ACHD patients on the transplant list, despite non-ACHD population receiving more transplants [6]. Death or de-listing due to worsening clinical status from the heart transplant list is more likely for ACHD patients than non-ACHD patients [6]. Transplant considerations: The criteria to determine priority status for heart transplant may misclassify prognosis in the ACHD population [6]. ACHD patients are generally not candidates for mechanical circulatory support (MCS) due to anatomic difficulties, shunts, multiple prior operations, or other hemodynamic challenges. However, the presence of an LVAD or other MCS increases priority status listing for transplantation. Only 3% of ACHD patients who receive transplant had mechanical circulatory support versus 17% of non-ACHD patients [18]. Patients may not benefit from inotropic support or may not be candidates for hemodynamic monitoring with a PA line, which also leads to a higher priority status listing. Some patients may be exempted by regional committees and assigned status 1Ae if needed. ACHD patients are often referred to transplant late, perhaps due to delayed recognition of symptoms, barriers in health-care delivery, or gaps in care 6. ACHD patients often have more comorbidities, such as renal failure, liver failure, prior strokes, protein-losing enteropathy, compromised lung function, or hematological disorders 6. These complications may preclude single-organ transplantation; some patients may be considered for dual-organ transplantation (heart/lung, heart/liver, or heart/kidney). How these comorbidities affect prognosis posttransplant as compared to non-ACHD has yet to be studied. Pretransplant considerations in ACHD [15]: Psychosocial: increased rates of depression, anxiety, post-traumatic stress disorder, obsessive-compulsive disorder in patients with ACHD. Surgical risk given multiple past cardiac surgeries. Assessment of collateral vessels within the chest wall, increase perioperative bleeding risks. Cardiac and great vessel anatomy: may require extensive reconstruction; dextrocardia and complex anatomy may be particularly challenging. HLA sensitization. Thorough evaluation of pulmonary vascular resistance. Assessment for other organ dysfunction, especially the liver and kidney. Important contraindications to heart transplant in ACHD: Multi-organ failure Active malignancy Active hepatitis C Other severe multiple congenital anomalies Relative contraindications to heart transplantation in ACHD may include: Increased pulmonary vascular resistance (though may recover or may be a candidate for heart-lung evaluation) Morbid obesity (weight loss surgery is increasingly being considered in the ACHD population) Extensive collateral vessels increasing bleeding risk Heterotaxy syndromes (may affect anatomic connections)