Elsevier

International Journal of Cardiology

Volume 344, 1 December 2021, Pages 87-94
International Journal of Cardiology

Late Fontan failure in adult patients is predominantly associated with deteriorating ventricular function

https://doi.org/10.1016/j.ijcard.2021.09.042Get rights and content

Highlights

  • Late failure of the Fontan circulation leads to heart failure and premature death.

  • Progressive ventricular dysfunction is frequently observed in adult Fontan patients.

  • Ventricular systolic and diastolic dysfunction is associated with Fontan failure.

  • Increased pulmonary vascular resistance is rather infrequent in late Fontan failure.

Abstract

Background

The Fontan operation is a palliative procedure and a substantial number of patients eventually experiences late Fontan circulation failure. Previous concepts of Fontan failure implicate increasing pulmonary vascular resistance (PVR) as a key contributor to late circulatory failure. However, data to support this assumption are sparse. We sought to characterize longitudinal hemodynamic and echocardiographic findings in adult failing Fontan patients.

Methods

We performed a retrospective cohort study in adult Fontan patients, identifying patients with Fontan failure. Hemodynamic, echocardiographic and clinical data were recorded.

Results

Of 173 adult patients (median follow-up after Fontan 20.2 years [IQR 15.7-24.3]), 48 (28%) showed signs of clinical Fontan failure. Thirty-seven patients (77.1%) exhibited ventricular dysfunction (systolic dysfunction defined by ejection fraction ≤45%, n = 22, or diastolic dysfunction defined by systemic ventricular end-diastolic pressure (SVEDP) ≥12 mmHg, n = 15). Elevated indexed PVR (≥2.5 WU*m2) was only observed in 9 (18.8%) patients. Ejection fraction declined from 60% [IQR 55-65] to 47% [IQR 35-55] during follow-up (p < 0.001). Mean pulmonary artery pressure and SVEDP increased from 11 mmHg [IQR 9-15] to 15 mmHg [IQR 12-18] and from 7 mmHg [IQR 4-10] to 11 mmHg [IQR 8-15] (both p < 0.001), respectively, while indexed PVR did not change significantly (2.1 [IQR 1.1-2.4] vs. 1.7 [IQR 1.1-2.5] WU*m2, p = 0.949). Fontan failure-associated mortality during follow-up was substantial (23/48; 48%).

Conclusions

Systolic and diastolic ventricular dysfunction are frequent features in late Fontan failure in adults, while increases in PVR were rarely observed. The intricate interplay between hemodynamic compromises in Fontan failure deserves further research to optimize treatment strategies and outcome.

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)

  • R. Margossian et al.

    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.

    (2009 Aug 1)
  • W.A. Zoghbi et al.

    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.

    (2017 Apr)
  • N. Ota et al.

    Impact of postoperative hemodynamics in patients with functional single ventricle undergoing Fontan completion before weighing 10 kg

    Ann. Thorac. Surg.

    (2012 Nov)
  • M.B. Mitchell et al.

    Evidence of pulmonary vascular disease after heart transplantation for Fontan circulation failure

    J. Thorac. Cardiovasc. Surg.

    (2004 Nov)
  • H. Mori et al.

    Sildenafil reduces pulmonary vascular resistance in single ventricular physiology

    Int. J. Cardiol.

    (2016 Oct 15)
  • G. Agnoletti et al.

    Endothelin inhibitors lower pulmonary vascular resistance and improve functional capacity in patients with Fontan circulation

    J. Thorac. Cardiovasc. Surg.

    (2017 Jun)
  • F. Fontan et al.

    Surgical repair of tricuspid atresia

    Thorax.

    (1971 May)
  • L.S. Kverneland et al.

    Five decades of the Fontan operation: a systematic review of international reports on outcomes after univentricular palliation

    Congenit. Heart Dis.

    (2018 Mar)
  • Y. d’Udekem et al.

    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.

    (2014 Sep 9)
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    Both authors contributed equally.

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