Distinct Comorbidity Clusters in Patients With Acute Heart Failure: Data From RELAX-AHF-2

Karla Arevalo Gomez; Jasper Tromp; Sylwia M. Figarska; Iris E. Beldhuis; Gad Cotter; Beth A. Davison; G. Michael Felker; Claudio Gimpelewicz; Barry H. Greenberg; Carolyn S.P. Lam; Adriaan A. Voors; Marco Metra; John R. Teerlink; Peter van der Meer

doi:10.1016/j.jchf.2024.04.028

Distinct Comorbidity Clusters in Patients With Acute Heart Failure: Data From RELAX-AHF-2

Karla Arevalo Gomez, Jasper Tromp, Sylwia M. Figarska, Iris E. Beldhuis, Gad Cotter, Beth A. Davison, G. Michael Felker, Claudio Gimpelewicz, Barry H. Greenberg, Carolyn S.P. Lam, Adriaan A. Voors, Marco Metra, John R. Teerlink, Peter van der Meer^*

^*Corresponding author for this work

Cardiovascular Centre (CVC)

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background: Multimorbidity frequently occurs in patients with acute heart failure (AHF). The co-occurrence of comorbidities often follows specific patterns.

Objectives: This study investigated multimorbidity subtypes and their associations with clinical outcomes.

Methods: From the prospective RELAX-AHF-2 (Relaxin for the Treatment of Acute Heart Failure-2) trial, 6,545 patients (26% with HF with preserved ejection fraction, defined as LVEF ≥50%) were classified into multimorbidity groups using latent class analysis. The association between subgroups and clinical outcomes was examined. Validation of these findings was conducted in the RELAX-AHF trial, which comprised 1,161 patients.

Results: Five distinct multimorbidity groups emerged: 1) diabetes and chronic kidney disease (CKD) (often male, high prevalence of CKD and diabetes mellitus); 2) ischemic (ischemic HF); 3) elderly/atrial fibrillation (AF) (oldest, high prevalence of AF); 4) metabolic (obese, hypertensive, more often HF with preserved ejection fraction); and 5) young (fewest comorbidities). After adjusting for confounders, patients in the diabetes and CKD (HR: 1.80; 95% CI: 1.50-2.20), elderly/AF (HR: 1.42; 95% CI: 1.20-1.70), and metabolic (HR: 1.40; 95% CI: 1.20-1.80) groups had higher rates of the composite outcome than patients in the young group, primarily driven by differences in rehospitalization. Treatment allocation (placebo or serelaxin) modified these associations (P_interaction <0.001). Serelaxin-treated patients in the young group were associated with a lower risk for all-cause mortality (HR: 0.59; 95% CI: 0.40-0.90). Similarly, patients from the RELAX-AHF trial clustered in 5 multimorbidity groups. The clinical characteristics and associations with outcomes could also be validated.

Conclusions: Comorbidities naturally clustered into 5 mutually exclusive groups in RELAX-AHF-2, showing variations in clinical outcomes. These data emphasize that the specific combination of comorbidities can influence adverse outcomes and treatment responses in patients with AHF.

Original language	English
Pages (from-to)	1762-1774
Number of pages	13
Journal	JACC: Heart Failure
Volume	12
Issue number	10
DOIs	https://doi.org/10.1016/j.jchf.2024.04.028
Publication status	Published - Oct-2024

Keywords

acute heart failure
cluster
multimorbidity
poLCA
RELAX-AHF-2

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Gomez, K. A., Tromp, J., Figarska, S. M., Beldhuis, I. E., Cotter, G., Davison, B. A., Felker, G. M., Gimpelewicz, C., Greenberg, B. H., Lam, C. S. P., Voors, A. A., Metra, M., Teerlink, J. R., & van der Meer, P. (2024). Distinct Comorbidity Clusters in Patients With Acute Heart Failure: Data From RELAX-AHF-2. JACC: Heart Failure, 12(10), 1762-1774. https://doi.org/10.1016/j.jchf.2024.04.028

@article{b48966e18d094f039adf925eca9d9d3d,

title = "Distinct Comorbidity Clusters in Patients With Acute Heart Failure: Data From RELAX-AHF-2",

abstract = "Background: Multimorbidity frequently occurs in patients with acute heart failure (AHF). The co-occurrence of comorbidities often follows specific patterns. Objectives: This study investigated multimorbidity subtypes and their associations with clinical outcomes. Methods: From the prospective RELAX-AHF-2 (Relaxin for the Treatment of Acute Heart Failure-2) trial, 6,545 patients (26% with HF with preserved ejection fraction, defined as LVEF ≥50%) were classified into multimorbidity groups using latent class analysis. The association between subgroups and clinical outcomes was examined. Validation of these findings was conducted in the RELAX-AHF trial, which comprised 1,161 patients. Results: Five distinct multimorbidity groups emerged: 1) diabetes and chronic kidney disease (CKD) (often male, high prevalence of CKD and diabetes mellitus); 2) ischemic (ischemic HF); 3) elderly/atrial fibrillation (AF) (oldest, high prevalence of AF); 4) metabolic (obese, hypertensive, more often HF with preserved ejection fraction); and 5) young (fewest comorbidities). After adjusting for confounders, patients in the diabetes and CKD (HR: 1.80; 95% CI: 1.50-2.20), elderly/AF (HR: 1.42; 95% CI: 1.20-1.70), and metabolic (HR: 1.40; 95% CI: 1.20-1.80) groups had higher rates of the composite outcome than patients in the young group, primarily driven by differences in rehospitalization. Treatment allocation (placebo or serelaxin) modified these associations (Pinteraction <0.001). Serelaxin-treated patients in the young group were associated with a lower risk for all-cause mortality (HR: 0.59; 95% CI: 0.40-0.90). Similarly, patients from the RELAX-AHF trial clustered in 5 multimorbidity groups. The clinical characteristics and associations with outcomes could also be validated. Conclusions: Comorbidities naturally clustered into 5 mutually exclusive groups in RELAX-AHF-2, showing variations in clinical outcomes. These data emphasize that the specific combination of comorbidities can influence adverse outcomes and treatment responses in patients with AHF.",

keywords = "acute heart failure, cluster, multimorbidity, poLCA, RELAX-AHF-2",

author = "Gomez, {Karla Arevalo} and Jasper Tromp and Figarska, {Sylwia M.} and Beldhuis, {Iris E.} and Gad Cotter and Davison, {Beth A.} and Felker, {G. Michael} and Claudio Gimpelewicz and Greenberg, {Barry H.} and Lam, {Carolyn S.P.} and Voors, {Adriaan A.} and Marco Metra and Teerlink, {John R.} and {van der Meer}, Peter",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = oct,

doi = "10.1016/j.jchf.2024.04.028",

language = "English",

volume = "12",

pages = "1762--1774",

journal = "JACC: Heart Failure",

issn = "2213-1779",

publisher = "ELSEVIER SCI LTD",

number = "10",

}

Gomez, KA , Tromp, J, Figarska, SM, Beldhuis, IE, Cotter, G, Davison, BA, Felker, GM, Gimpelewicz, C, Greenberg, BH, Lam, CSP , Voors, AA, Metra, M, Teerlink, JR & van der Meer, P 2024, 'Distinct Comorbidity Clusters in Patients With Acute Heart Failure: Data From RELAX-AHF-2', JACC: Heart Failure, vol. 12, no. 10, pp. 1762-1774. https://doi.org/10.1016/j.jchf.2024.04.028

TY - JOUR

T1 - Distinct Comorbidity Clusters in Patients With Acute Heart Failure

T2 - Data From RELAX-AHF-2

AU - Gomez, Karla Arevalo

AU - Tromp, Jasper

AU - Figarska, Sylwia M.

AU - Beldhuis, Iris E.

AU - Cotter, Gad

AU - Davison, Beth A.

AU - Felker, G. Michael

AU - Gimpelewicz, Claudio

AU - Greenberg, Barry H.

AU - Lam, Carolyn S.P.

AU - Voors, Adriaan A.

AU - Metra, Marco

AU - Teerlink, John R.

AU - van der Meer, Peter

PY - 2024/10

Y1 - 2024/10

N2 - Background: Multimorbidity frequently occurs in patients with acute heart failure (AHF). The co-occurrence of comorbidities often follows specific patterns. Objectives: This study investigated multimorbidity subtypes and their associations with clinical outcomes. Methods: From the prospective RELAX-AHF-2 (Relaxin for the Treatment of Acute Heart Failure-2) trial, 6,545 patients (26% with HF with preserved ejection fraction, defined as LVEF ≥50%) were classified into multimorbidity groups using latent class analysis. The association between subgroups and clinical outcomes was examined. Validation of these findings was conducted in the RELAX-AHF trial, which comprised 1,161 patients. Results: Five distinct multimorbidity groups emerged: 1) diabetes and chronic kidney disease (CKD) (often male, high prevalence of CKD and diabetes mellitus); 2) ischemic (ischemic HF); 3) elderly/atrial fibrillation (AF) (oldest, high prevalence of AF); 4) metabolic (obese, hypertensive, more often HF with preserved ejection fraction); and 5) young (fewest comorbidities). After adjusting for confounders, patients in the diabetes and CKD (HR: 1.80; 95% CI: 1.50-2.20), elderly/AF (HR: 1.42; 95% CI: 1.20-1.70), and metabolic (HR: 1.40; 95% CI: 1.20-1.80) groups had higher rates of the composite outcome than patients in the young group, primarily driven by differences in rehospitalization. Treatment allocation (placebo or serelaxin) modified these associations (Pinteraction <0.001). Serelaxin-treated patients in the young group were associated with a lower risk for all-cause mortality (HR: 0.59; 95% CI: 0.40-0.90). Similarly, patients from the RELAX-AHF trial clustered in 5 multimorbidity groups. The clinical characteristics and associations with outcomes could also be validated. Conclusions: Comorbidities naturally clustered into 5 mutually exclusive groups in RELAX-AHF-2, showing variations in clinical outcomes. These data emphasize that the specific combination of comorbidities can influence adverse outcomes and treatment responses in patients with AHF.

AB - Background: Multimorbidity frequently occurs in patients with acute heart failure (AHF). The co-occurrence of comorbidities often follows specific patterns. Objectives: This study investigated multimorbidity subtypes and their associations with clinical outcomes. Methods: From the prospective RELAX-AHF-2 (Relaxin for the Treatment of Acute Heart Failure-2) trial, 6,545 patients (26% with HF with preserved ejection fraction, defined as LVEF ≥50%) were classified into multimorbidity groups using latent class analysis. The association between subgroups and clinical outcomes was examined. Validation of these findings was conducted in the RELAX-AHF trial, which comprised 1,161 patients. Results: Five distinct multimorbidity groups emerged: 1) diabetes and chronic kidney disease (CKD) (often male, high prevalence of CKD and diabetes mellitus); 2) ischemic (ischemic HF); 3) elderly/atrial fibrillation (AF) (oldest, high prevalence of AF); 4) metabolic (obese, hypertensive, more often HF with preserved ejection fraction); and 5) young (fewest comorbidities). After adjusting for confounders, patients in the diabetes and CKD (HR: 1.80; 95% CI: 1.50-2.20), elderly/AF (HR: 1.42; 95% CI: 1.20-1.70), and metabolic (HR: 1.40; 95% CI: 1.20-1.80) groups had higher rates of the composite outcome than patients in the young group, primarily driven by differences in rehospitalization. Treatment allocation (placebo or serelaxin) modified these associations (Pinteraction <0.001). Serelaxin-treated patients in the young group were associated with a lower risk for all-cause mortality (HR: 0.59; 95% CI: 0.40-0.90). Similarly, patients from the RELAX-AHF trial clustered in 5 multimorbidity groups. The clinical characteristics and associations with outcomes could also be validated. Conclusions: Comorbidities naturally clustered into 5 mutually exclusive groups in RELAX-AHF-2, showing variations in clinical outcomes. These data emphasize that the specific combination of comorbidities can influence adverse outcomes and treatment responses in patients with AHF.

KW - acute heart failure

KW - cluster

KW - multimorbidity

KW - poLCA

KW - RELAX-AHF-2

UR - http://www.scopus.com/inward/record.url?scp=85199183470&partnerID=8YFLogxK

U2 - 10.1016/j.jchf.2024.04.028

DO - 10.1016/j.jchf.2024.04.028

M3 - Article

C2 - 38970586

AN - SCOPUS:85199183470

SN - 2213-1779

VL - 12

SP - 1762

EP - 1774

JO - JACC: Heart Failure

JF - JACC: Heart Failure

IS - 10

ER -

Distinct Comorbidity Clusters in Patients With Acute Heart Failure: Data From RELAX-AHF-2

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