Transplant and Mechanical Circulatory Support in Congenital Heart Disease

It has been well documented that the prevalence of congenital heart disease (CHD) is on the rise in the United States, with estimates that 1 in 150 young adults will have some form of CHD.¹ The American Heart Association (AHA) published guidelines on the management of the coming tide of adults with CHD (ACHD) in 2008, and, more recently, issued a scientific statement on the older ACHD population, above 40 years.^1,2 This article is a focused review on the status of advanced heart failure (HF) therapies like mechanical circulatory support (MCS) and heart transplant being offered to the CHD population. As a true reflection of the current state-of-affairs, the report generates more questions than answers but is an essential first step in our understanding of the problem. It is imperative that we evolve guidelines to define and manage advanced HF in the CHD population. As acknowledged by the Heart Failure Society of America, advanced or Stage D HF is generally accompanied by frequent hospitalizations, severely limited exertional tolerance and poor quality of life despite optimal medical management, and is associated with high morbidity and mortality.³ In the context of ACHD patients, HF remains an elusive diagnosis; unlike acquired HF, these patients may have preserved systolic function until late in their course of disease.⁴

As mentioned by the authors of this review, the decision to offer advanced therapies is often arrived at after medical management has failed. A surgically correctable etiology like severe atrioventricular valve regurgitation brings with it a “Catch 22” situation where repairing the valve may increase acutely the afterload on the ventricle, unmasking ventricular dysfunction. This is especially relevant in patients with corrected transposition of the great arteries (CCTGA) where the right ventricle (RV) is the systemic pumping chamber and often harbors an abnormal tricuspid valve.

The systemic RV, in CCTGA and in patients after the atrial switch for dextro-transposition of the great arteries (d-TGA), is less conducive to the standard inflow cannula placement for MCS. This is among the many anatomic reasons why ACHD patients are less likely to receive MCS as a bridge to transplant. As reported by the authors, MCS carries a higher mortality in the CHD population, irrespective of the age group. In a comprehensive review of MCS in the pediatric CHD population, Kirklin and colleagues report on the paucity of data in this subset of patients with less than 15% of children on MCS having CHD.⁵ With the advent of the Berlin Heart EXCOR device, the fraction of this subset undergoing transplant has increased, although while supported mortality and neurologic complications remain significant. Among single ventricle patients, data on MCS are sparse and its adoption among the failing Fontan circulation patients has not been widespread.

The authors also highlight the challenges to a successful heart transplant at various levels faced by the CHD population.1 ACHD patients tend to be listed at a lower urgency status, spend more time on the waiting list, and suffer a higher mortality rate while on the list. Human leukocyte antigen sensitization and the technical difficulties stemming from potential vascular reconstructions caused by situs abnormalities and anomalies of systemic venous drainage requiring additional tissue during organ procurement contribute to the wait list delay. The authors suggest as a possible solution, a modified listing process used in some countries prioritizing patients with cyanosis and elevated panel reactive antibodies (PRAs). In a forum for transplant experts held in collaboration with various organizations involved in heart transplantation in the United States, extensive discussions were held on the current organ allocation policies and on future directions.⁶ Sensitized patients and CHD patients were considered a “disadvantaged” subgroup when it came to organ allocation, and a survey undertaken among these experts revealed “support or high support” for prioritizing these patient groups. Thus, CHD patients suffer a dual disadvantage from facing difficulty in qualifying for Status 1A and having a shrunken donor pool due to sensitization. Aggressive desensitization protocols initiated in children with a high level of PRAs have been reported to improve transplant outcomes, although such efforts need clinical validation by larger multi-institutional trials.⁷

Elevated pulmonary vascular resistance (PVR) has been associated with a greater risk of perioperative transplant mortality.³ PVR calculations in the CHD population tend to be inaccurate in the presence of shunts, cavopulmonary connections, and collateral blood vessels. Surgical challenges arising from multiple sternotomies, calcified intracardiac patches, and the need for venous and pulmonary artery reconstruction add to the ischemic times and may contribute to the higher incidence of postoperative re-explorations, strokes, infections, multi-organ failure, and need for dialysis observed in these patients. Although a higher incidence of primary graft failure has been noted in ACHD patients, the authors mention a “survival paradox” seen in this population with better long-term survival and a higher incidence of re-transplantation compared with non-CHD patients.

The authors note a decreasing proportion of CHD patients among infants undergoing transplant because of the success of palliative procedures in the current era. Consideration for primary transplantation may be given to certain high-risk situations like the single ventricle lesions with heterotaxy or a RV-dependent coronary circulation.

Considerable focus has been given in the review toward Fontan patients. Although current 10-year survival in this population exceeds 85%, the mechanisms underlying the failure of the cavopulmonary circuit are multifactorial, leading to unclear recommendations on the timing of transplant. Individualized decision-making, integrating the anatomic type of Fontan connection, the function of the single ventricle, and an appraisal of any potentially surgically reversible causes of circuit failure, is essential prior to listing for transplantation. The authors point out an 8.6-fold higher relative risk for death after transplant among Fontan patients compared with other CHD patients. The mortality risk is high for failing Fontan patients with a preserved ventricular function. This may be a result of the multi-organ dysfunction arising from chronic venous hypertension manifesting as plastic bronchitis, liver disease, renal dysfunction, and protein-losing enteropathy (PLE). Although hepatic fibrosis is almost universal among Fontan patients, there seems to be an unclear correlation with clinical outcomes.⁸ While transplantation seems to correct PLE and plastic bronchitis, data for its effect on liver disease are inadequate.

The authors should be congratulated for putting together an exhaustive review of the literature to help manage this complex patient population that will benefit from clinical guidelines starting from the definition of HF, to therapy, to prognostication, and to the timing of referral for advanced therapeutic modalities such as MCS and transplant. It is imperative that a multi-disciplinary approach involving HF expertise, vigilant medical follow-up, real-time communication amongst all caregivers, continued education, and research be employed in the care of these patients in the future.