Late outcome, therapy and systemic ventricular function in patients with a systemic right ventricle: data of the German National Register for Congenital Heart Defects

Background: Adults with systemic right ventricle have a significant risk for long-term complications such as arrhythmias or heart failure. Methods: A nationwide retrospective study based on the German National Register for Congenital Heart Disease was performed. Patients with transposition of the great arteries after atrial switch operation or congenitally corrected TGA were included. Results: Two hundred and eight-five patients with transposition of the great arteries after atrial switch operation and 95 patients with congenitally corrected transposition of the great arteries were included (mean age 33 years). Systolic function of the systemic ventricle was moderately or severely reduced in 25.5 % after atrial switch operation and in 35.1% in patients with congenitally corrected transposition. Regurgitation of the systemic atrioventricular valve was present in 39.5% and 43.2% of the cases, respectively. A significant percentage of patients also had a history for supraventricular or ventricular arrhythmias. However, polypharmacy of cardiovascular drugs was rare (4.5%) and 38.5 % of the patients did not take any cardiovascular medication. The amount of cardiovascular drugs taken was associated with NYHA class as well as systemic right ventricular dysfunction. Patients with congenitally corrected transposition were more likely to receive pharmacological treatment than patients after atrial switch operation. Conclusion: A significant portion of patients with systemic right ventricle suffer from a relevant systemic ventricular dysfunction, systemic atrioventricular valve regurgitation, and arrhythmias. Despite this, medication for heart failure treatment is not universally used in this cohort. This emphasises the need for randomised trials in patient with systemic right ventricle.

Effects of sacubitril/valsartan in patients with a systemic right ventricle: early evidence of exercise tolerance and systolic function improvement

Background Sacubitril/valsartan has been shown to reduce mortality and morbidity inpatients with heart failure and reduced systolic function. However, the effects of this novel association in patients with congenital heart disease and a systemic right ventricle (sRV) have not been investigated yet. Purpose We aimed to assess tolerability and efficacy of sacubitril/valsartan in patients with a sRV Methods From September 2020 to March 2021, 38 patients with congenitally corrected transposition of the great arteries or transposition of the great arteries after Senning or Mustard repair were prospectively enrolled. Inclusion criteria were: age ≥18 years, optimal medical therapy including ACEi/ARB for at least 6 months and EF of the sRV ≤40%. Patients with univentricular physiology, systolic blood pressure (SBP) <90mmHg, glomerular filtration rate (GFR) <30ml/min or K >5.5mEq/L were excluded. RV systolic function was assessed on echocardiography using a multiparametric evaluation. The study protocol contemplates serial assessments at 1, 3, 6 and 12 months after treatment initiation. Results Up to March 31th, 23 patients completed 1-month and 15 completed 3-month assessment after treatment initiation. Baseline patients' characteristics are summarized in table 1. The medication dose was up-titrated to the highest tolerated dose during follow-up. During early follow-up, no major adverse events were reported. Treatment did not impact significantly on the values of serum potassium (basal K+ 4.4 [4.2–4.6] mEq/L, K+ at 3 months 4.4 [4.3–4.6] mEq/L, p=0.7) and GFR (basal GFR 113.9±35ml/min, GFR at 3 months 107.8±21 ml/min, p=0.7). Although SBP did not change significantly (114±12 vs 113.9±19 mmHg at 1-month and 117.3±12 mmHg at 3 months; p=0.9 for both), 2 (5%) patients ceased the treatment due to symptomatic hypotension during the first month of treatment. There was no significant change in the NYHA class. However, the 6-minute walking distance increased significantly after 3 months (365±120 vs 498.3±71 min; p=0.01). Furthermore, while traditional echocardiographic parameters of RV systolic function (TAPSE, s wave and FAC) did not change significantly, RV global longitudinal strain (GLS) and RV free wall GLS demonstrated subclinical improvement in right ventricular systolic function (table 2). Conclusions Our short-term results from an ongoing prospective study showed that sacubitril/valsartan is well tolerated in patients with a sRV with early evidence of improvement in exercise tolerance and sRV systolic function. Longer follow-up is warranted to confirm these data. FUNDunding Acknowledgement Type of funding sources: None. Table 1 Table 2

MicroRNA-183-3p Is a Predictor of Worsening Heart Failure in Adult Patients With Transposition of the Great Arteries and a Systemic Right Ventricle

Aim: MicroRNAs (miRNAs) have been shown to play an important role in the progression of heart failure (HF). The aim of our study was to analyze miRNAs in the blood of patients with transposition of the great arteries and a systemic right ventricle (TGA-RV) in order to identify those that predict worsening HF.Materials and Methods: In 36 patients with TGA-RV, SurePrint™ 8 × 60K Human v21 miRNA microarrays were used to determine the miRNA abundance profiles and compared to 35 age- and gender-matched healthy volunteers (HVs). MiRNAs that were most significantly abundant or best related to worsening HF were further validated by RT-qPCR.Results: Using miRNA array analysis, a total of 50 down-regulated and 56 up-regulated miRNAs were found to be differentially abundant in TGA-RV patients compared to HVs. Six of these 106 miRNAs were significantly related to worsening HF. After validation by RT-qPCR, four miRNAs turned out to be significantly associated with worsening HF, namely miR-150-5p, miR-1255b-5p, miR-423-3p, and miR-183-3p. In the stepwise multivariable Cox regression analysis, ejection fraction of the systemic RV, high sensitive TNT and miR-183-3p were found to be independent predictors of worsening HF (P = 0.001, P = 0.002, and P = 0.001, respectively).Conclusions: In patients with TGA-RV, miR-183-3p is an independent predictor of worsening HF and thus may be used as additional biomarker in the risk assessment of these patients.