Author + information
- aThe Single Ventricle Survivorship Program, The Cardiac Center, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
- bDepartment of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
- cThe Philadelphia Adult Congenital Heart Disease Program, The Cardiac Center, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
- dDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
- ↵∗Address for correspondence:
Dr. Jack Rychik, The Cardiac Center, The Children’s Hospital of Philadelphia, 3401 Civic Center Boulevard, Philadelphia, Pennsylvania 19104.
Our effort to treat the most severe form of congenital cardiovascular malformations—single-ventricle—type congenital heart disease—is a continuous struggle against nature. If left untreated, these conditions are lethal. Over the past 40 years, surgical strategies have evolved that allow for survival. The principle underlying this success is the remarkable notion that sufficient pulmonary blood flow and systemic circulation with reasonable oxygen delivery can be achieved by channeling systemic venous return directly into the lungs absent a ventricle, the Fontan operation. This strategy has allowed for the survival of a generation that has never before walked the face of the Earth. However, despite this wondrous capacity to achieve survival, have we created a sustainable state that will result in a normal quality and duration of life for patients with single ventricle?
Numerous challenges stand in the way. Ironically, the condition created by the treatment strategy is part of the problem. Systemic venous hypertension with relatively low cardiac output is the foundation of a unique pathophysiology leading to a state of what can be called a Fontan circulatory syndrome with a multitude of unique end-organ consequences and clinical manifestations. Chronic venous congestion is the basis for liver fibrosis and is present in varying degrees in all patients (1). The risk for thromboembolic disease is substantially increased. Lymphatic congestion is a troubling phenomenon, and in a select few, it leads to spillage into low-pressure passages of the airway or gut with development of potentially lethal clinical conditions such as plastic bronchitis and protein-losing enteropathy (2,3). Renal impairment is present early and becomes clinically more evident as the years progress. Lymphopenia, secondary hyperparathyroidism, and altered bone health with poor somatic growth are emerging as important manifestations of the Fontan circulatory syndrome in childhood. The normal expected increase in exercise capacity with onset of adolescence is blunted. Parallel to the complications related specifically to the Fontan circulation are the phenomena of ventricular dysfunction and atrioventricular valve regurgitation, perhaps inherently “programmed” into the anatomy of the single-ventricle malformation itself, further contributing to the potential for decline. Layered on top of these physical aspects is the increasing recognition of psychological and mental health concerns, in particular clinically significant traumatic stress and anxiety, as patients enter adolescence and young adulthood.
In this issue of the Journal, Dennis et al. (4) report on the long-term outcomes of a large cohort of Fontan patients who have survived to 16 years of age. The data derive from the Australia and New Zealand Fontan Registry, a groundbreaking endeavor that has provided an important fund of knowledge concerning patients who have undergone Fontan procedures. The authors report an overall 90% survival at 30 years and 80% survival at 40 years of age. However, at 40 years of age, only 41% of all adult patients were free from a serious adverse event, and 22% of patients required reoperation or reintervention. Male sex and the presence of atrioventricular valve replacement or at least moderate regurgitation at time of the Fontan operation were predictive of death or heart transplantation.
The interpretation of these findings is a matter of perspective. It is remarkable to appreciate that reasonable survival can be achieved for some patients with a single ventricle. Hopeful is the finding that in fact better outcomes (but with shorter follow-up) are seen in the patients with a more contemporaneous style of lateral tunnel or extracardiac conduit-type Fontan surgery versus the now obsolete atriopulmonary-style operation. Conversely, the majority of survivors regardless of surgery type had serious adverse events reported. Important factors such as assessment of end-organ function or other morbidities are not included in this analysis, a limitation of a self-report registry format, as Dennis et al. (4) admit. Furthermore, the group of patients studied does not include strong representation from the growing number of single-ventricle patients with a systemic right ventricle such as hypoplastic left heart syndrome. The capacity to generalize these findings to all current single-ventricle patients is therefore somewhat limited. Most important is the need to recognize that this report describes the outcome going forward of a very select group, those patients who are alive at the age of 16 years. These are individuals who have survived multiple palliative surgical procedures and have existed with the rigors of a Fontan circulation for at least a decade. Indeed, this report truly describes the survival of only the fittest of those born with a single-ventricle anomaly. These are the outcomes for the select group of the very best.
What we learn from Dennis et al. (4) is that these patients will require substantial health care resources to deal with the challenges ahead. As early surgical outcomes steadily improve, the overall number of survivors entering adolescence and young adulthood will increase, as will their health-related complexity. Is the medical community ready, and how can we best prepare? Although technical modifications to the Fontan operation may take place in the coming years, the basic construct is here to stay for the foreseeable future. Mechanical or biological mechanisms for generating supplementary circulatory support are lofty goals and should be fully supported with efforts accelerated; however, in parallel, we need to move forward with initiatives that can improve the Fontan circulatory state for our patients who cannot wait. We will need to lay the groundwork before the age of 16 to improve outcome for after age 16.
How to proceed? Better clinical characterization and physiological understanding of the Fontan circulatory syndrome—its manifestations and mechanistic origins—through multicenter collaboration are essential (5). Development of multidisciplinary clinics with specialty expertise targeted toward Fontan-specific ailments for both young patients and those in adult congenital heart centers will allow for cohorting of patients and will concentrate clinical experiences and learning. Collaborative efforts to reduce practice variability, create models for best practices, and standardize surveillance strategies would be tremendously beneficial. Clinical trials focused on effective therapeutic strategies to mitigate the pathophysiology and end-organ consequences are necessary. Pharmacological trials using pulmonary vasodilators such as phosphodiesterase-5 inhibitors are currently under way in young patients (6); however, good rationale also exists for studying aldosterone inhibitors such as spironolactone (Aldactone) as a mild anticongestant or diuretic, antifibrotic, and heart failure agent. Other potential candidate agents with similar effects should be considered for trial. Newly emerging data suggest that specific exercise regimens that strengthen lower extremity muscle mass as well as training to improve efficiency of the thoracic cage inspiratory musculature can improve the driving force and impetus for systemic venous return (7,8). Exploring the possibility of physically training young patients in a prospective manner to adapt to the unique circulation more effectively is an exciting prospect. Finally, promoting wellness by encouraging exercise, optimizing nutrition, and providing psychological support and mental health resources will tremendously improve quality of life and is an action that can be implemented immediately.
A shift in approach is needed. We must think about how we can best prepare our young kids with single ventricle to be healthy adolescents, with foundations laid as early as possible in childhood for healthy adulthood. How these individuals will fare when exposed to the later onset aspects of cardiovascular disease such as obesity, atherosclerosis, and hypertension is unclear, but this concern looms ominously. The evidence base for best early strategies to create resilience—physiological, psychological, and otherwise—needs to be explored and tested quickly if we are going to make an impact on this “unnatural” selection and increase the number of humans with single-ventricle hearts who are “fittest” to survive.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the author and do not necessarily represent the views of JACC or the American College of Cardiology.
Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2018 American College of Cardiology Foundation
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