I read with great interest the recent study by Alsaied et al. on diastolic dysfunction in Fontan patients. This important investigation highlights that even young Fontan survivors exhibit a striking prevalence of diastolic dysfunction; 11.3% of patients (mean age ∼ 16 years) had an elevated ventricular end-diastolic pressure >13 mmHg. Such a disproportionately high prevalence in adolescence underscores that ventricular stiffening can manifest early in the Fontan population. Moreover, diastolic dysfunction was associated with a composite adverse outcome (death, arrhythmia, plastic bronchitis/protein-losing enteropathy, transplant listing) with a hazard ratio of ∼ 3.37, emphasizing its prognostic significance. We applaud Alsaied et al. for bringing needed attention to this underappreciated facet of Fontan physiology.
Defining “diastolic dysfunction” in Fontan patients remains challenging due to heterogeneous criteria across studies. Alsaied et al. used an invasive end-diastolic pressure threshold >13 mmHg, whereas others have used cutoffs ranging from 12 to 15 mmHg or employed composite indices (e.g. Doppler E/e’ normalized to ventricular volume) in an effort to account for the Fontan’s unique loading conditions. Notably, the chronically reduced preload in Fontan circulation can mask diastolic abnormalities on routine assessment, potentially rendering them occult unless a volume-loading challenge is performed. We also note that Alsaied et al. identified several risk factors associated with diastolic dysfunction, including older patient age (longer time since Fontan completion), larger ventricular end-diastolic volume, and excessive myocardial fibrosis. These findings point toward progressive adverse ventricular remodeling over time. Fontan-associated liver disease (FALD) was also significantly more common in patients with diastolic dysfunction (40% vs 29%), echoing prior observations that myocardial fibrosis (late gadolinium enhancement/high extracellular volume on cardiac MRI) correlates with elevated filling pressures and with hepatic fibrosis in Fontan survivors. This constellation of ventricular stiffening, chamber dilation and concurrent myocardial/hepatic fibrosis suggests an interrelated heart–liver profibrotic milieu. It remains unresolved to what extent FALD exacerbates diastolic dysfunction versus being a consequence of it, likely both, in a deleterious feedback loop. Indeed, Fontan physiology appears to share parallels with cirrhotic cardiomyopathy, which is characterized by an impaired cardiac stress response and combined diastolic and systolic dysfunction despite normal baseline systolic function.
Emerging evidence further suggests that Fontan patients may not suffer from “classic preload failure” alone, but rather a distinctive form of metabolic ventricular dysfunction. In particular, chronically elevated bile acids have been implicated in mediating myocardial diastolic impairment. Our recent work has shown that Fontan patients have markedly elevated circulating bile acids, which are associated with worse exercise capacity, greater frailty, and hemodynamic abnormalities. Mechanistically, excess bile acids can induce mitochondrial dysfunction in cardiomyocytes with impaired ATP production, promoting diastolic dysfunction. This provocative hepatic–cardiac axis is the subject of new therapeutic exploration. Our pilot trial of bile acid sequestration is underway to test whether reducing bile acids can improve Fontan hemodynamics. I fully endorse Alsaied et al.’s call to recognize diastolic dysfunction as a prevalent and clinically important component of Fontan failure, and I concur that a multipronged approach, addressing hemodynamic, structural, and biochemical factors, will be essential to understand and improving the long-term health of Fontan patients.
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