Inflammation and echocardiographic ventricular function in patients with a systemic right ventricle and heart failure

Abstract

Abstract Background Clinical deterioration is fast once heart failure (HF) develops in patients with a systemic right ventricle (sRV) [1]. Despite its established role in HF patients with a normal heart anatomy [2,3], little is known about the contribution of inflammation in sRV-HF patients. Aims To assess inflammation and echocardiography in sRV patients with or without HF and to relate inflammation to echocardiographic ventricular function. Methods In this cross-sectional prospective study, patients with a sRV due to Senning/Mustard repair or due to congenitally corrected transposition of the great arteries (ccTGA) were consecutively enrolled at the outpatient clinic of a single, tertiary care center. Echocardiography and venipuncture were performed on the same day. C-reactive protein (CRP), red cell distribution width (RDW), neutrophil-lymphocyte ratio (NLR), myeloperoxidase (MPO), myeloperoxidase and citrullinated histone H3-DNA complexes (MPO-DNA and H3Cit-DNA) and interleukin 10 were measured. Patients were stratified based on the presence or absence of HF, with HF defined as having signs and/or symptoms of HF requiring medical therapy plus one of the following: impaired ventricular function with elevated intracardiac pressures, elevated N-terminal pro-brain natriuretic peptide, and/or peak oxygen consumption in lowest quartile (according to published norms for TGA patients). Comparative statistics and univariate correlations were performed. Results Eighty-seven patients were included (mean age 39 years; 69% male; 25% ccTGA, 68% NYHA class I) from which one third (29/87) had HF. Most inflammatory markers were significantly higher in the HF group compared to non-HF: CRP (4.3 vs 2.21 mg/dL; P=0.016), RDW (13.6 vs 12.7 fL; P<0.001), NLR (3.6 vs 2.9; P=0.01), MPO (171 vs 139 ng/mL; P=0.03) and MPO-DNA (1.4 vs 1.2; P=0.04). When assessing systolic function, HF patients had: i) lower strain of the sRV free wall (10.9 vs 13.1%; P=0.008), ii) lower mitral annular plane systolic excursion (MAPSE) (1.7 vs 2.1 cm; P<0.001) and iii) lower strain rate (SR) of the subpulmonary LV (spLV) (1.0 vs 1.3 S-1; P=0.03). The spLV was also more hypertrophied (end-diastolic LV posterior wall 0.99 vs 0.79 cm; P=0.007) and more dilated (end-diastolic LV internal diameter 4.1 vs 3.3 cm; P=0.006) in HF. CRP and RDW showed the strongest correlations (Spearman correlation coefficient r>0.29) with LV and RV ventricular function. CRP correlated with lateral tricuspid annular systolic velocity (r=−0.313**), strain of the free wall (r=−0.317**) and global longitudinal strain (r=−0.292**) of the sRV. RDW correlated with MAPSE (r=−0.313**). **P<0.01. Conclusions sRV patients in HF have more systemic inflammation and lower RV free wall strain. With more remodeling and a lower MAPSE and SR of the spLV, the LV cannot be ignored when evaluating HF in sRV patients. Correlation between inflammation and ventricular systolic function, however, is limited. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): ERA-CVD JTC2019 (Fonds Wetenschappelijk Onderzoek G0G1719N to K.M. and A.V.D.B); German Bundesministerium für Bildung und Forschung 01KL2001 to T.W.)