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Randomized Controlled Trial
. 2024 May;26(5):1231-1241.
doi: 10.1002/ejhf.3202. Epub 2024 Mar 25.

Proteomic profiles of left atrial volume and its influence on response to spironolactone: Findings from the HOMAGE trial and STANISLAS cohort

Masatake Kobayashi  1   2 , João Pedro Ferreira  1   3 , Kevin Duarte  1 , Emmanuel Bresso  1 , Olivier Huttin  1 , Erwan Bozec  1 , Hans-Peter Brunner La Rocca  4 , Christian Delles  5 , Andrew L Clark  6 , Frank Edelmann  7 , Arantxa González  8   9 , Stephane Heymans  4 , Pierpaolo Pellicori  5 , Johannes Petutschnigg  10 , Job A J Verdonschot  4 , Patrick Rossignol  1   11 , John G F Cleland  5 , Faiez Zannad  1 , Nicolas Girerd  1 ; HOMAGE Trial Committees and Investigators
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Free article
Randomized Controlled Trial

Proteomic profiles of left atrial volume and its influence on response to spironolactone: Findings from the HOMAGE trial and STANISLAS cohort

Masatake Kobayashi et al. Eur J Heart Fail. 2024 May.
Free article

Abstract

Aims: High left ventricular filling pressure increases left atrial volume and causes myocardial fibrosis, which may decrease with spironolactone. We studied clinical and proteomic characteristics associated with left atrial volume indexed by body surface area (LAVi), and whether LAVi influences the response to spironolactone on biomarker expression and clinical variables.

Methods and results: In the HOMAGE trial, where people at risk of heart failure were randomized to spironolactone or control, we analysed 421 participants with available LAVi and 276 proteomic measurements (Olink) at baseline, month 1 and 9 (mean age 73 ± 6 years; women 26%; LAVi 32 ± 9 ml/m2). Circulating proteins associated with LAVi were also assessed in asymptomatic individuals from a population-based cohort (STANISLAS; n = 1640; mean age 49 ± 14 years; women 51%; LAVi 23 ± 7 ml/m2). In both studies, greater LAVi was significantly associated with greater left ventricular masses and volumes. In HOMAGE, after adjustment and correction for multiple testing, greater LAVi was associated with higher concentrations of matrix metallopeptidase-2 (MMP-2), insulin-like growth factor binding protein-2 (IGFBP-2) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (false discovery rates [FDR] <0.05). These associations were externally replicated in STANISLAS (all FDR <0.05). Among these biomarkers, spironolactone decreased concentrations of MMP-2 and NT-proBNP, regardless of baseline LAVi (pinteraction > 0.10). Spironolactone also significantly reduced LAVi, improved left ventricular ejection fraction, lowered E/e', blood pressure and serum procollagen type I C-terminal propeptide (PICP) concentration, a collagen synthesis marker, regardless of baseline LAVi (pinteraction > 0.10).

Conclusion: In individuals without heart failure, LAVi was associated with MMP-2, IGFBP-2 and NT-proBNP. Spironolactone reduced these biomarker concentrations as well as LAVi and PICP, irrespective of left atrial size.

Keywords: Biomarkers; Echocardiogram; Heart failure; Left atrial volume; Spironolactone.

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References

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