Prevalence and Prognostic Implications of Left Ventricular Systolic Dysfunction in Adults With Congenital Heart Disease

Surgical and medical advances have allowed to a greater proportion of patients with congenital heart disease to grow into adulthood, despite significant residual lesions and sequalae. The growing population of adults with congenital heart disease (ACHD) represents a group of patients at risk of developing heart failure (HF) and cardiac death at younger age compared to their non-congenital counterparts. Due to the highly heterogeneity of this population, most studies have focused on the role of systolic dysfunction in specific lesions and therefore the real prevalence of impaired systolic function and its implications on the outcome in ACHD are still to be determined. Furthermore, most clinical trials on medical treatment or interventional procedures aimed at reducing the burden the HF have usually excluded ACHD patients, and international guidelines do not provide specific recommendations on the optimal medical management in this complex population[i], leaving to the clinicians the challenging task of determining when to start medications and which approach is the best fit for each patient, relying mainly on personal experience or data from observational studies in small groups.

The recent paper from Egbe et al [ii] aimed to describe the prevalence of left ventricular (LV) systolic dysfunction among ACHD patients with systemic LV and biventricular physiology and to establish its relation with the outcome. Moreover, the authors aimed to shed light on the effects of medical therapy, resynchronization therapy and right-sided valvular intervention on the LV mechanics.

The study population comprised a group of 4405 ACHD patients (median age 36 [25-48], 51% male) followed at the Mayo Clinic between 2003 and 2019. One third of the patients had a complex anatomy, however the whole spectrum of congenital heart disease was represented in the study population. Data were retrospectively collected in all patients and LV function was assessed on echocardiography using Simpson’s biplane method in most of the cases (97%).

Egbe at al. divided the study population in two groups: those with right-sided disease (tetralogy of Fallot, Ebstein’s anomaly, pulmonary atresia with intact ventricular septum, valvular pulmonic stenosis, double-chambered RV, and atrial septal defect/partial anomalous pulmonary venous return), those with predominant left-sided disease (coarctation of aorta, aortic stenosis, and subaortic stenosis). The main findings are:

1. LV dysfunction was present in 12% of cases (9% had only mild dysfunction) and was more frequent in patients with right-sided lesion (15% Vs 10%, p<0.001) and in those patients there was a strong correlation between LVEF and right ventricular fractional area change(RV FAC). Accordingly, RV FAC was a strong predictor of LV dysfunction in patients with right-sided lesions, while coronary artery disease(CAD) and arterial hypertension were among the determinants of LV dysfunction in those with left-sided lesions, supporting a different pathophysiological mechanism in those groups.
2. At a median follow-up of 7.6 (2.4-11.5) years, LVEF was significantly associated with the risk of events (including cardiac death, heart transplant and hospitalization for HF) independently from age, RV pacing, hypertension, renal failure, RV FAC and RV systolic pressure in patients with both left and right-sided lesions. The addition of LV global longitudinal strain increased the predictive power of the model in patients with both preserved or impaired LVEF, indicating that even subclinical changes in LV function might influence the outcome.
3. Medical therapy initiation or uptitration including at least a beta-blocker and a renin-angiotensin aldosterone system (RASS) inhibitor, resulted in increased LVEF at 2-years follow-up in both groups and was associated with decreased nt-proBNP values and improved NYHA class in 311 patients with LV dysfunction at baseline. Biventricular pacing yielded similar results, whereas no effect on LV systolic function was observed in patients who underwent right-sided valvular interventions, despite improved NYHA class and nt-proBNP and RV systolic function.

The findings of the present study are in line with previous reports of LVEF as a predictive factor of events in specific subsets of different lesions, such as tetralogy of Fallot [iii] or Ebstein’s anomaly [iv]. Nevertheless, by considering the ACHD population with systemic LV and biventricular physiology as a whole, Egbe et al. highlighted the role of LV dysfunction a “universal” marker of increased risk of adverse outcome across the whole spectrum of ACHD. The unexpected finding of higher prevalence of LV dysfunction in patients with right-sided lesion, which could be attributed to the interventricular interaction or other unknown mechanisms, outlines the potential danger of underestimating the role of the LV which may be easily overlooked in those patients, paradoxically becoming the “forgotten” chamber during follow-up. As for the effects of medical and resynchronization therapy, the retrospective design of the present study does not allow for a thorough control for multiple confounding factors potentially influencing LV function during follow-up. Despite those limitations, the paper from Egbe et al points out the urgent need of addressing the current lack of knowledge in the management of HF in this population and represents a call for international multicentric studies preferably with a control group to assess the real efficacy of traditional medical treatment, novel medications approved for HF treatment including sacubitril/valsartan and SGLT2 inhibitors and cardiac resynchronization to improve patients’ outcome across the whole ACHD spectrum.