Right ventricular remodelling in hypoplastic left heart syndrome following Fontan completion

This important study by Sobh et al. assesses the serial changes in right ventricular (RV) volume and function using MRI in 95 patients with hypoplastic left heart syndrome (HLHS) following Fontan completion [1]. Over the study interval of 4–14 years post-Fontan, RV function, assessed by ejection fraction and long axis strain, remained stable. However, a progressive increase in RV volumes was identified in those patients older than 10 years. The study provides valuable longitudinal data on RV remodelling in HLHS post-Fontan. Although the stage-1 outcomes for HLHS have improved, medium to longer term survival remains disappointing low, with a 6-year transplant free survival of 61–63% [2]. The causes relate to the physiological derangement of the Fontan circulation in general and HLHS as the single ventricle lesion in particular [3]. Even within a biventricular circulation, the morphological RV is maladapted to act as the systemic ventricle as is apparent with the reduced survival and exercise capacity in patients with d-transposition of the great arteries (d-TGA) corrected by atrial redirection compared to arterial switch [4]. The causes of RV dysfunction in the context of HLHS are multifactorial, and commence at the stage 1 palliation (S1P). With the Norwood operation pulmonary blood flow is supplied by either a BT or Sano shunt. The BT shunt risks myocardial ischaemia due to reduced perfusion in diastole, while the Sano modification requires the insult of a ventriculotomy. Although early outcomes favour the Sano shunt, beyond 2 years following S1P, survival becomes equivalent [2]. Regardless of the shunt type employed, each have their inherent mechanisms of ventricular injury that may manifest over time. At S1P a complex Damus-Kaye-Stansel with an extended patch augmentation is constructed to create an unobstructed pathway to the systemic circulation. Any geometric distortion, recurrent scar-related stenosis or patch degeneration will detriment arterial compliance, increase RV afterload and impact on function [5]. Finally, the RV can be subjected to chronic volume loading related to tricuspid valve regurgitation, semilunar valve incompetence and acquired aorto-pulmonary collaterals. The cumulative burden of the legacy of S1P and ongoing RV vulnerability to systemic afterload will contribute to the adverse outcome in this population. In the current study the increase in RV indexed volumes, apparent in patients older than 10 years, implies that the ventricle is being exposed to an increasing volume load or is beginning to decompensate. Of note the proportion of patients with moderate tricuspid regurgitation increased from 9.5% to 25.7% over the MRI scan interval, and this will promote volume loading and ventricular inefficiency. Importantly, neither aorto-pulmonary collateral flow nor neoaortic valve incompetence were quantified in the study and consequently this may be an unrecognised contributor to RV loading and dilation. The progressive increase in RV volume is a concern; Rathod et al. [6] identified that CMR-derived ventricular indexed end-diastolic volume exceeding 125 ml/m2 was a predictor of death or transplant in patients post-Fontan. In response to systemic pressure and RV dilation, myocardial hypertrophy will develop with increasing ventricular wall thickness which normalises circumferential wall stress given Laplace’s law. This could have implication for outcome following Fontan by reducing ventricular compliance and impairing diastolic function. In the current study RV myocardial mass index was similar to that reported in young adults with d-TGA following atrial redirection [7] however both RV mass and RV mass/end-diastolic volume ratio were significantly increased compared to a control population: 90 versus 21 g/m2 and 0.86 versus 0.40 g/ml respectively [8]. Babu-Narayan et al. [7] suggested that myocardial hypertrophy in the systemic RV may result in a coronary artery supply that is insufficient for the myocardial mass, promoting ventricular fibrosis and contributing to RV dysfunction. In the current study 11 patients had evidence of RV fibrosis on MRI imaging. An increased RV mass-to-volume ratio exceeding 45 g/ml has also predicted death or sustained ventricular tachycardia in patients with repaired tetralogy of Fallot [9]. Although these are very different populations and physiology, nevertheless the presence of increasing hypertrophy may herald the development of a vulnerable RV. Importantly in the current study, neither RV myocardial mass index nor mass-to-volume ratio increased over the duration of the study [1]. RV function in this study was assessed using ejection fraction and % change in long axis dimension and demonstrated a small, non-significant decline across the scan intervals. However, both parameters are load-dependent and will be altered by variation in preload and afterload irrespective of the contractile state. The intrinsic contractility of the RV can be determined using pressure-volume loop analysis with derivation of load-independent indices of maximum elastance and preload recruitable stroke work [10]. These parameters could potentially identify early reversible decline in RV contraction prior to a reduction in ejection fraction, as occurs in the presence of tricuspid regurgitation with reduced RV afterload. Analysis of the RV pressure-volume loop can be also used to determine inotropic responsiveness, ventricular-arterial coupling and RV mechanical efficiency [10]. These indices of ventricular performance may provide valuable insights into the mechanisms of RV functional decline post-Fontan and inform potential reinterventions including indication and timing of tricuspid valve repair and pharmaceutical options of afterload reduction. Finally, the haemodynamic and ventricular parameters contained within the current study dataset display a wide range of values, for example cardiac index 3.4–5.2 l/min/m2, RV end-diastolic volume 86.6–119.1 ml/m2 and RV myocardial mass index 66.7–122.5 g/m2. It would be informative to correlate these data to clinical functional outcomes including cardiopulmonary exercise testing and B-type natriuretic peptide in order to determine their clinical relevance.