Body composition in heart failure and the impact of cardiac resynchronisation therapy: a proof-of-concept study.

Aims: Body composition (BC) is known to alter in heart failure. Cardiac resynchronisation therapy (CRT) improves left ventricular geometry but the impact on BC is unknown. Our aim was to evaluate BC in these patients before and after CRT implantation. Methods: Prospective proof-of-concept pilot study of heart failure patients undergoing CRT between September 2014 and December 2015. Assessments performed pre-CRT and post-CRT (6 weeks and 6 months) were: BC parameters (using air-displacement plethysmography), New York Heart Failure classification for assessing symptom severity, echocardiography to assess left ventricular geometry, electrocardiography, Minnesota Heart Failure Questionnaire and N-terminal probrain natriuretic peptide (NT-pro-BNP). Repeated measures analysis of variance was performed to assess relative change over time and potential correlations. Results: Twenty-five patients were recruited; mean-age (±SD) was 73.4±10.0 years, 23 males, 18 CRT defibrillators (remainder CRT pacemakers), 16 had ischaemic aetiology, 6 diabetics, 17 with left bundle-branch morphology on ECG and 10 had atrial fibrillation. Significant inverse correlations were observed in the first 6 weeks following CRT between fat mass and left ventricular end-diastolic volume (r=-0.69, p<0.01) and NT-pro-BNP and fat mass (r=0.41, p=0.05). No significant differences were noted over 6 months. There was an observed trend towards reduced fat mass in the first 6 weeks post-CRT implant driven by non-responders. There was no significant difference between responders and non-responders in BC over 6 months. Conclusion: This is the first study to observe interplay between BC and cardiac geometry/function following CRT; a trend in overall fat mass reduction was noted following CRT and merits further study.

Characterisation of circulating biomarkers before and after cardiac resynchronisation therapy and their role in predicting CRT response: the COVERT-HF study.

Aims: Cardiac resynchronisation therapy (CRT) is effective treatment for selected patients with heart failure (HF) but has ~30% non-response rate. We evaluated whether specific biomarkers can predict outcome. Methods: A prospective single-centre pilot study of consecutive unselected patients undergoing CRT for HF between November 2013 and December 2015 evaluating cardiac extracellular matrix biomarkers and micro-ribonucleic acid (miRNA) expression before and after CRT assessing ability to predict functional response and survival. Each underwent three assessments (pre-implant, 6 weeks and 6 months postimplant) including: New York Heart Association (NYHA) class, echocardiography, electrocardiography, 6 min walk test (6MWT), Minnesota Living with Heart Failure Questionnaire (MLHFQ) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP). Plasma markers of cardiac fibrosis assessed were: N-terminal pro-peptides of collagen I and III, collagen I C-terminal telopeptides (CTx) and matrix metalloproteinases (MMP-2 and MMP-9) as well as a panel of miRNAs (miRNA-21, miRNA-30d, miRNA-122, miRNA-133a, miRNA-210 and miRNA-486). Results: A total of 52 patients were recruited; mean age (±SD) was 72.4±9.4 years; male=43 (82.7%), ischaemic aetiology=30 (57.7%), mean QRS duration=166.4±23.5 ms, left bundle branch block (LBBB) morphology = 39 (75.0%), mean NYHA=2.7±0.6, 6MWT=238.8±130.6 m, MLHFQ=46.4±21.3 and left ventricular ejection fraction (LVEF)=24.3%±8.0%. Mean follow-up=1.7±0.3 and 5.8±0.7 months. There were 27 (55.1%) functional responders (3 no definable 6-month response; 2 missed assessments and 1 long-term lead displacement). No marker predicted response, however, CTx and LBBB trended most towards predicting functional response. Conclusion: No specific biomarkers reached significance for predicting functional response to CRT. CTx showed a trend towards predicting response and warrants further study. Trial registration number: NCT02541773.