Over prior decades, the focus of heart failure research has been on left heart failure, whereas right ventricular (RV) dysfunction may prove to be an Achilles heel, especially in advanced heart failure management. Essentially, in all myocardial diseases including myocardial ischemia/infarction, myocarditis, takotsubo cardiomyopathy, dilated cardiomyopathy, hypertrophic cardiomyopathy, cardiac amyloidosis, and Chagas disease, the left heart may also affect the right ventricle. The treatment of RV failure remains challenging, and there is an immense need to identify molecular targets to improve prognosis for patients with RV failure. This is especially true given the anatomical and physiological particularities of the RV.1
The EARLY-MYO-CTD study (NCT04197050) is looking into the effects of sacubitril/valsartan in RV failure especially secondary to connective tissue disorders (CTDs), with primary endpoint being the 6-minute walking distance and myocardial fibrosis in patients with CTD with RV ejection fraction reduction (RV-HFrEF).2 Another study by Zandrastra et al evaluated sacubitril/valsartan for patients with a failing systemic right ventricle in the context of transposition of the great arteries after arterial switch or congenitally corrected transposition of the great arteries. This study highlighted statistically significant improvement in N-terminal pro-B-type natriuretic peptide, echocardiographic systemic RV fractional area change, global longitudinal strain, 6-minute walking distance, and the QOL domains of cognitive function, sleep, and vitality.3 A multicenter randomized, double-blind, placebo-controlled, crossover clinical trial was performed to assess the effects of losartan on exercise capacity and neurohormonal levels in patients with systemic right ventricles, but it failed to improve exercise capacity or reduce NT-proBNP levels, and lack of success was attributed to minimal baseline activation of the renin–angiotensin system.4
While the jury is still out on the effects of sacubitril/valsartan in RV failure, it has been strongly recommended as a class I drug in treating the patient with chronic heart failure with reduced ejection fraction (HFrEF) from 2017 ACC/AHA/HFSA heart failure guideline for the ability to dramatically reduce cardiovascular mortality.5 There has been increasing interest to evaluate this mechanism as a treatment modality for RV failure/dysfunction. In the present issue, Yang et al present new data looking into the effect of sacubitril/valsartan for treating RV dysfunction. Their study involving 93 subjects aimed to explore the effects of sacubitril/valsartan on RV dysfunction among patients with HFrEF. This study is first of its kind with a majority of patients being of Chinese descent. The authors found sacubitril/valsartan treatment to be associated with significant improvements in RV function indicators, including tricuspid annular plane systolic excursion, tricuspid annulars' peak velocity (S′), RV fractional area change, and pulmonary artery systolic pressure. Crude linear regression analysis revealed that tricuspid annular plane systolic excursion improvement was positively correlated with change in left ventricular ejection fraction and negatively correlated with change in left ventricular end-systolic volume. Although the study has several limitations such as the lack of control group and being underpowered, it indeed opens up an important topic for further evaluation.
Furthering this research with artificial intelligence analysis to evaluate yet-to-be discovered associations and correlations and use of a large patient database may be the way going forward to further expand our understanding of pathophysiology, management, and possibly identifying novel molecular target to improve core cardiovascular outcomes in patients with RV failure/dysfunction.6
1. Arrigo M, Huber L, Winnik S, et al. Right ventricular failure: pathophysiology, diagnosis and treatment. Card Fail Rev. 2019;5:140–146.
2. Clinical Trials. Available at: https://clinicaltrials.gov/ct2/show/NCT04197050
. Accessed October 2, 2021.
3. Zandstra TE, Nederend M, Jongbloed MRM, et al. Sacubitril/valsartan in the treatment of systemic right ventricular failure. Heart. 2021;107:1725–1730.
4. Dore A, Houde C, Chan KL, et al. Angiotensin receptor blockade and exercise capacity in adults with systemic right ventricles: a multicenter, randomized, placebo-controlled clinical trial. Circulation. 2005;112:2411–2416.
5. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American college of cardiology/American heart association task force on clinical practice guidelines and the heart failure society of America. Circulation. 2017;136:e137–e161.
6. Amritphale A, Chatterjee R, Chatterjee S, et al. Predictors of 30-day unplanned readmission after carotid artery stenting using artificial intelligence. Adv Ther. 2021;38:2954–2972.