Skip to Main content Skip to Navigation
New interface
Journal articles

Biomarker‐based assessment of collagen cross‐linking identifies patients at risk of heart failure more likely to benefit from spironolactone effects on left atrial remodelling. Insights from the HOMAGE clinical trial

Susana Ravassa 1, 2 Begoña López 1, 2 João Pedro Ferreira 3 Nicolas Girerd 3 Erwan Bozec 3 Pierpaolo Pellicori 4 Beatrice Mariottoni 5 Franco Cosmi 5 Mark Hazebroek 6 Job a J Verdonschot 6 Joe Cuthbert 7 Johannes Petutschnigg 8 María U Moreno 1, 2 Stephane Heymans 6 Jan A Staessen 9, 10 Burkert Pieske 8, 11 Frank Edelmann 8 Andrew L Clark 7 John G F Cleland 4 Faiez Zannad 3 Javier Díez 1, 2, 12 Arantxa González 1, 2 
Abstract : Aims: The HOMAGE randomized trial found that spironolactone reduced left atrial volume index (LAVI), E:A ratio, and a marker of collagen type I synthesis (procollagen type I C-terminal propeptide) in patients at risk of heart failure (HF). Previous trials showed that patients with HF, preserved ejection fraction and low serum collagen type I C-terminal telopeptide to matrix metalloproteinase-1 ratio (CITP:MMP-1), associated with high collagen cross-linking, had less improvement in diastolic function with spironolactone. We evaluated the interaction between serum CITP:MMP-1 and spironolactone on cardiac function in the HOMAGE trial. Methods and results: Patients at risk of HF were randomized to spironolactone (n = 260) or not (n = 255). Blood sampling and echocardiography were done at baseline, one and nine months. CITP:MMP-1 was used as an indirect measure of collagen cross-linking. Higher baseline CITP:MMP-1 (i.e. lower collagen cross-linking) was associated with greater reductions in LAVI with spironolactone at both one (p = 0.003) and nine (p = 0.01) months, but no interaction was observed for E:A ratio. Spironolactone reduced LAVI after one and nine months only for those patients in the third tertile of CITP:MMP-1 (estimated lowest collagen cross-linking) [mean differencesspiro/control : -1.77 (95% confidence interval, CI -2.94 to -0.59) and -2.52 (95% CI -4.46 to -0.58) mL/m2 ; interaction pacross-tertiles = 0.005; interaction pthird tertile = 0.008] with a similar trend for N-terminal pro-B-type natriuretic peptide which was consistently reduced by spironolactone only in the lowest collagen cross-linking tertile [mean differencesspiro/control : -0.47 (95% CI -0.66 to -0.28) and -0.31 (95% CI -0.59 to -0.04) ng/L; interaction pacross-tertiles = 0.09; interaction pthird tertile < 0.001]. Conclusions: These findings suggest that, for patients at risk of HF, the effects of spironolactone on left atrial remodelling may be more prominent in patients with less collagen cross-linking (indirectly assessed by serum CITP:MMP-1).
Complete list of metadata

https://hal.univ-lorraine.fr/hal-03474611
Contributor : Erwan BOZEC Connect in order to contact the contributor
Submitted on : Friday, December 10, 2021 - 11:55:23 AM
Last modification on : Thursday, July 14, 2022 - 5:16:29 PM
Long-term archiving on: : Friday, March 11, 2022 - 7:01:00 PM

Licence


Distributed under a Creative Commons Attribution - NonCommercial - NoDerivatives 4.0 International License

Identifiers

Collections

Citation

Susana Ravassa, Begoña López, João Pedro Ferreira, Nicolas Girerd, Erwan Bozec, et al.. Biomarker‐based assessment of collagen cross‐linking identifies patients at risk of heart failure more likely to benefit from spironolactone effects on left atrial remodelling. Insights from the HOMAGE clinical trial. European Journal of Heart Failure, 2021, ⟨10.1002/ejhf.2394⟩. ⟨hal-03474611⟩

Share

Metrics

Record views

12

Files downloads

51