The Fontan operation involves routing of systemic venous return directly into pulmonary circulation bypassing the subpulmonary ventricle. This is an effective palliation in patients with complex congenital heart disease involving single ventricle physiology.
The unoperated single ventricle physiology is characterized by intracardiac mixing of oxygenated and deoxygenated blood, creating two primary hemodynamic problems: cyanosis and ventricular volume overload. The Fontan operation separates systemic venous return (deoxygenated blood) from pulmonary venous return (oxygenated blood).
The Fontan operation has undergone several modifications since its original description in 1971. The most recent modification is the extracardiac Fontan, which involves routing of systemic venous blood to the pulmonary circulation using an extracardiac conduit.
The 20-year survival of the initial cohort of patients who underwent Fontan operation in the 1970s and 1980s was less than 50 percent. Survivors commonly have Fontan-related morbidities such as arrhythmias, chronic liver disease, protein-losing enteropathy, thromboembolic complications, heart failure, ventricular and valvular dysfunction, renal failure, and plastic bronchitis.
"Although the later modifications of the Fontan operation have resulted in improved survival and reduced morbidity, the adult congenital cardiologist still provides care for the older and sicker Fontan cohort with their myriad comorbidities," according to Alexander C. Egbe, M.B.B.S., cardiologist at Mayo Clinic's campus in Rochester, Minnesota. "There are limited data to guide management of these patients, making patient care very challenging."
As the adult Fontan population and the complexity of their comorbidities continue to increase, there is an enormous demand on the health care providers caring for these patients. Mayo Clinic has developed a dedicated, multidisciplinary group staffed by a team of congenital cardiologists, cardiovascular surgeons, electrophysiologists, cardiac radiologists and hepatologists. The purpose is to:
- Provide streamlined, individualized and comprehensive care for patients with the different Fontan-associated complications
- Develop best practice protocols for the different morbidities
- Update treatment protocols as new evidence-based data emerges
- Integrate laboratory-based and clinical research
- Become a model for other congenital heart disease centers
The Adult Congenital Heart Disease group at Mayo Clinic recently embarked on a focused Fontan research program in an effort to narrow the knowledge gaps and improve patient care in this population. This research focuses on management of atrial arrhythmias, thromboembolic complications and the role of cardiopulmonary exercise testing.
Atrial arrhythmia management
About two-thirds of adult patients who undergo Fontan procedures have a history of atrial arrhythmias. Atrial arrhythmias are poorly tolerated in these patients because of reduced preload and a dependence on atrial systole to achieve adequate ventricular filling. The use of direct current cardioversion for treatment of hemodynamically stable atrial arrhythmias in patients who undergo Fontan palliation is often viewed with skepticism because of concerns about thromboembolic complications, and the risk of provoking ventricular arrhythmia and hemodynamic instability.
A review of 86 patients who underwent Fontan procedures at Mayo Clinic and who received 152 direct current cardioversions for treatment of atrial arrhythmias, published in International Journal of Cardiology in April 2016, showed that cardioversion was successful in 73 percent of the patients, and the success rate was higher in the patients who received class I or III anti-arrhythmic drugs prior to cardioversion.
More importantly, there were no cases of thromboembolic complications related to cardioversion, likely due to meticulous anticoagulation and the liberal use of transesophageal echocardiography to screen for intracardiac thrombus even in the patients with documented therapeutic anticoagulation.
Based on this study, the Mayo Clinic practice is shifting toward a more aggressive approach to restore sinus rhythm in all patients who have undergone Fontan procedures, including anticoagulation for all patients and anti-arrhythmic drug therapy prior to direct current cardioversion when clinically feasible.
In spite of the success with direct current cardioversion as described above, arrhythmia recurrence rate was 53 percent within 36 months. Anti-arrhythmic drug therapy has been the first line treatment for chronic arrhythmia management in this population, and a common practice is to keep switching to a different class of anti-arrhythmic drug whenever patients experience arrhythmia recurrence. Invasive arrhythmia therapies such as catheter ablation and Fontan conversion surgery have been reserved for those patients who have failed multiple anti-arrhythmic drug treatment.
Dr. Egbe and his colleagues reviewed 264 patients who underwent Fontan procedures seen at Mayo Clinic, comparing recurrence rates of atrial arrhythmias in individuals who received medical therapy, catheter ablation or Fontan conversion surgery.
"Data from the study, which was published in American Heart Journal in 2017, showed that medical therapy alone was associated with unacceptably high arrhythmia recurrence rate of 93 percent within five years, in contrast to 59 percent and 41 percent for catheter ablation and Fontan conversion surgery respectively," says Dr. Egbe. "Furthermore, catheter ablation had an acute procedural success rate of 94 percent with minimal complication rate in our practice. Based on the data, our practice is shifting toward early referral for catheter ablation, as this is associated with better outcomes."
Thromboembolic prophylaxis and treatment
There is an increased risk of thromboembolic complications in patients who've had Fontan procedures, especially in those with concomitant atrial arrhythmias. Anticoagulation in this population is very challenging because of an increased risk of bleeding due to hepatic dysfunction and because procoagulant and anticoagulant factor abnormalities are prevalent in these patients.
In research published in Journal of the American College of Cardiology in 2016, Dr. Egbe and colleagues studied 278 adult patients with atrial arrhythmias who underwent Fontan procedures and estimated a thromboembolic complication rate of 6.5 per 100 patient-years. Anticoagulation with warfarin resulted in a risk reduction by 2.5 events per 100 patient-years compared with aspirin, without an increase in bleeding risk.
The clinical presentation and management of confirmed thromboembolism in patients who underwent Fontan procedures is quite different from that of patients with biventricular circulation. Even a small pulmonary embolus can cause important hemodynamic derangement because of the absence of a subpulmonary ventricle.
As a result, several published case series have shown a bias for surgical intervention such as thrombectomy or Fontan conversion in these patients. Research published in American Heart Journal in 2017 confirms that out of 98 patients who received a trial of anticoagulation for confirmed thrombotic and embolic complications in our series, none of the patients required acute surgical intervention, and 20 percent of them (mostly with right atrial thrombus and pulmonary embolus) had complete thrombus resolution.
The reduced survival of the initial cohort of patients who underwent Fontan operation is, to a large extent, due to the hemodynamic pitfalls of the old style (atriopulmonary) Fontan. In a bid to improve survival and quality of life, Fontan conversion operation (conversion of atriopulmonary Fontan to extracardiac Fontan) has emerged as a rescue strategy for patients with failing Fontan physiology.
Unfortunately this operation is associated with perioperative mortality of up to 10 percent in some series. Appropriate selection of patients who are likely to benefit from this operation is critical because of the associated perioperative mortality risk.
Cardiopulmonary exercise test (CPET) results in a study of 75 patients who underwent Fontan conversion in the Mayo Clinic practice, published in International Journal of Cardiology in 2016, showed that preoperative peak oxygen consumption was a robust prognostic tool both for predicting perioperative mortality and for identifying patients most likely to experience improved quality of life (exercise capacity and New York Heart Association functional class) after Fontan conversion.
The average age of the adult Fontan cohort at Mayo Clinic is 30 to 35 years. These patients are in their prime and want to know their expected longevity and risk of cardiovascular adverse events.
Unfortunately, no clinical, echocardiographic or demographic parameters have been shown to be prognostic in the Fontan population; however, a review of 145 patients who received Fontan procedures and who underwent serial CPET at Mayo Clinic over 10 years showed that serial peak oxygen consumption was a good predictor of future cardiovascular adverse event (deaths, cardiac surgery and transcatheter interventions). A decline in peak oxygen consumption by 3 or more percentage points per year was associated with a 2.8-fold risk of cardiovascular adverse events within five years. Study results were published in International Journal of Cardiology in 2017.
The future of Fontan research
Chronic liver disease is the second most common comorbidity in the Fontan population, affecting one-third of all adult patients who underwent Fontan procedures. A combined heart and liver transplant is currently the only treatment option for this disease.
Mayo Clinic is currently enrolling patients who underwent Fontan procedures in a pilot study to assess the efficacy of phosphodiesterase-5 inhibitor for the treatment of Fontan-associated liver disease, the Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study. This is the first study exploring alternative therapy for liver disease in this patient population, and it is hoped that the data will illuminate the clinical landscape of liver disease in this population.
Important Fontan studies have emerged from Mayo Clinic in the past two decades, mostly focused on outcomes after Fontan operation. However, the heterogeneity of the Fontan population makes it difficult to study certain rare Fontan complications even in a tertiary center such as Mayo Clinic. Doctors are pursuing multicenter collaborations with other congenital heart disease centers of excellence, providing a more in-depth understanding of this disease.
Finally, a laboratory- and animal-based Fontan research program has been initiated, with the primary goals including creating a chronic animal model of Fontan physiology and investigating the role of mechanical assistance for patients with failing Fontan physiology.
"Fontan research at Mayo Clinic has evolved over time: The past was good, the present is better and the future is bright," says Dr. Egbe. For additional information, contact Dr. Egbe at 507-284-2520 or firstname.lastname@example.org.
For more information
Egbe AC, et al. Outcome of direct current cardioversion for atrial arrhythmia in adult Fontan patients. International Journal of Cardiology. 2016;208:115.
Egbe AC, et al. Outcomes in adult Fontan patients with atrial tachyarrhythmias. American Heart Journal. 2017;186:12.
Egbe AC, et al. Thrombotic and embolic complications associated with atrial arrhythmia after Fontan operation. Journal of the American College of Cardiology. 2016;68:1312.
Egbe AC, et al. Prevalence and outcome of thrombotic and embolic complications in adults after Fontan operation. American Heart Journal. 2017;183:10.
Egbe AC, et al. When is the right time for Fontan conversion? The role of cardiopulmonary exercise test. International Journal of Cardiology. 2016;220:564.
Egbe AC, et al. Cardiopulmonary exercise test in adults with prior Fontan operation: The prognostic value of serial testing. International Journal of Cardiology. 2017;235:6.
Clinical trials: Role of sildenafil for Fontan associated liver disease (SiFALD) study. Mayo Clinic.