Late Fontan failure in adult patients is predominantly associated with deteriorating ventricular function
Introduction
The introduction of the Fontan operation represented a milestone in the treatment of children with complex univentricular heart malformations. [1] Today, a large number of affected children, previously burdened with a poor life expectancy, enter adolescence and adulthood. Continuous improvements in surgical techniques and perioperative care, refinements of preoperative selection criteria and advancements in medical and interventional treatment strategies during the past decades have resulted in substantial improvements in early and late mortality. [[2], [3], [4]] However, the basic hemodynamic pathophysiological principles of the Fontan circulation and the major sequelae have remained vastly unchanged. [[4], [5], [6]] Frequent long-term comorbidities in Fontan patients include arrhythmias, exercise intolerance, cyanosis, protein-losing enteropathy, plastic bronchitis, Fontan-associated liver disease, chronic kidney disease and coagulation disorders. [[7], [8], [9], [10], [11], [12]] In addition, chronic Fontan circulation failure is associated with progressive clinical heart failure and ultimately premature death. [3,13,14] Importantly, with a continuously growing number of Fontan patients entering into adulthood, a substantial increase in the incidence of Fontan failure can be expected within the foreseeable future. [15] Since systemic ventricular preload and consequently cardiac output is critically dependent on passive pulmonary blood flow in the absence of a sub-pulmonary ventricle, PVR has been conceptualized as critical bottleneck of the Fontan circulation. [[16], [17], [18]] However, to date, there is only limited data supporting the view of PVR as the main contributor to late Fontan failure. Moreover, it has become increasingly evident that there may be profoundly differing hemodynamic phenotypes of Fontan failure. [5,19,20] With limited therapeutic options to offer patients with failing Fontan, identifying the most prevalent hemodynamic restriction might allow a more timely and targeted initiation of therapies in order to delay the most likely inevitable hemodynamic demise of the Fontan circulation. We, herein, investigate a large cohort of adult patients with Fontan failure and describe their invasive hemodynamic, echocardiographic and clinical findings associated with circulatory failure. We hypothesized that Fontan failure in adult patients may be associated with distinct predominant hemodynamic features including increased pulmonary vascular resistance, diastolic and systolic ventricular dysfunction.
Section snippets
Methods
We performed a retrospective cohort study reviewing records of Fontan patients followed in our institution during the study period from 1999 to 2020. Patients were included in the study if they were ≥ 18 years of age at their last follow-up visit during the study period and showed Fontan failure. Clinical Fontan failure was a priori defined by meeting at least one of the following criteria: (1) NYHA functional class IV, (2) NYHA functional class III for ≥12 months without sustained improvement,
Patient cohort
From a total of 544 Fontan patients followed in our institution during the study period, 173 were adult at their last follow-up (median age 26.3 [interquartile range, IQR 21.6-34.3] years) and eligible for inclusion. Out of these, 48 (28%) showed clinical signs of Fontan failure; 26 (54%) of them were originally operated in our institution. The most frequent criteria for Fontan failure as a priori defined were NYHA functional class III for ≥12 months without sustained improvement (n = 24, 50%),
Discussion
We investigated a large cohort of 48 adult Fontan patients with late failure of the Fontan circulation to determine the most prevalent hemodynamic findings associated with the development of Fontan failure which, to the best of our knowledge, has not previously been systematically studied. Interestingly, developing Fontan failure was predominantly associated with progressing systolic and diastolic ventricular dysfunction in our cohort, whereas increases in PVR were only observed in a minority
Conclusions
Our data do not support the hypotheses that PVR generally increases during long-term follow-up of Fontan patients and that increasing PVR represents the major cause of late Fontan failure. Our results rather implicate a progressive decline in systolic and/or diastolic ventricular function with subsequent increases in atrial filling pressures and pulmonary artery pressures as the predominant hemodynamic compromises observed in late Fontan failure. In regard to Fontan failure treatment, therapies
Funding sources
The German Heart Center Berlin received a contribution from the charitable foundation Stiftung KinderHerz for research dedicated to Fontan patients.
Declaration of Competing Interest
The authors report no relationships that could be construed as a conflict of interest.
Acknowledgements
This study was supported by the Stiftung KinderHerz.
References (39)
- et al.
40-year follow-up after the fontan operation: long-term outcomes of 1,052 patients
J. Am. Coll. Cardiol.
(2015 Oct 13) The relentless effects of the Fontan paradox
Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu.
(2016)- et al.
Failure of the fontan circulation
Heart Fail. Clin.
(2014 Jan) - et al.
Hepatic and renal end-organ damage in the Fontan circulation: a report from the Australian and New Zealand Fontan Registry
Int. J. Cardiol.
(2018 Dec 15) - et al.
Life after surviving Fontan surgery: A meta-analysis of the incidence and predictors of late death
Heart Lung Circ.
(2018 May) - et al.
The Fontan epidemic: population projections from the Australia and New Zealand Fontan Registry
Int. J. Cardiol.
(2016 Sep 15) - et al.
Hemodynamic and clinical implications of impaired pulmonary vascular reserve in the Fontan circulation
J. Am. Coll. Cardiol.
(2020 Dec 8) - et al.
Fontan circulation: success or failure?
Can J Cardiol.
(2013 Jul) - et al.
Venous congestion and pulmonary vascular function in Fontan circulation: Implications for prognosis and treatment
Int. J. Cardiol.
(2018 Nov 15) - et al.
Definitions and diagnosis of pulmonary hypertension
J. Am. Coll. Cardiol.
(2013 Dec 24)
Comparison of echocardiographic and cardiac magnetic resonance imaging measurements of functional single ventricular volumes, mass, and ejection fraction (from the Pediatric Heart Network Fontan Cross-Sectional Study)
Am. J. Cardiol.
Recommendations for noninvasive evaluation of native valvular regurgitation: a report from the american society of echocardiography developed in collaboration with the society for cardiovascular magnetic resonance
J. Am. Soc. Echocardiogr.
Impact of postoperative hemodynamics in patients with functional single ventricle undergoing Fontan completion before weighing 10 kg
Ann. Thorac. Surg.
Evidence of pulmonary vascular disease after heart transplantation for Fontan circulation failure
J. Thorac. Cardiovasc. Surg.
Sildenafil reduces pulmonary vascular resistance in single ventricular physiology
Int. J. Cardiol.
Endothelin inhibitors lower pulmonary vascular resistance and improve functional capacity in patients with Fontan circulation
J. Thorac. Cardiovasc. Surg.
Surgical repair of tricuspid atresia
Thorax.
Five decades of the Fontan operation: a systematic review of international reports on outcomes after univentricular palliation
Congenit. Heart Dis.
Redefining expectations of long-term survival after the Fontan procedure: twenty-five years of follow-up from the entire population of Australia and New Zealand
Circulation.
Cited by (7)
EASL-ERN position paper on liver involvement in patients with Fontan-type circulation
2023, Journal of HepatologyClinical and invasively-measured predictors of high exercise capacity in Fontan patients
2023, International Journal of CardiologyImpact of Ventricular Dominance on Long-Term Fontan Outcomes: A 25-year Single-institution Study
2023, Annals of Thoracic SurgeryCardiac Drugs in ACHD Cardiovascular Medicine
2023, Journal of Cardiovascular Development and DiseaseManagement of circulatory failure after Fontan surgery
2022, Frontiers in PediatricsOptimal Fenestration of the Fontan Circulation
2022, Frontiers in Physiology
- 1
Both authors contributed equally.
- 2
This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.