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Clinical Trial
. 2024 Aug;26(8):1762-1774.
doi: 10.1002/ejhf.3304. Epub 2024 Jun 26.

Cardiovascular-kidney-metabolic overlap in heart failure with preserved ejection fraction: Cardiac structure and function, clinical outcomes, and response to sacubitril/valsartan in PARAGON-HF

Mats C H Lassen #  1   2   3 , John W Ostrominski #  1   4 , Brian L Claggett  1 , Milton Packer  5 , Michael Zile  6 , Akshay S Desai  1 , Amil M Shah  7 , Maja Cikes  8 , Bela Merkely  9 , Mauro Gori  10 , Xiaowen Wang  1 , Sheila M Hegde  1 , Marc A Pfeffer  1 , Martin Lefkowitz  11 , John J V McMurray  12 , Scott D Solomon  1 , Muthiah Vaduganathan  1
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Free article
Clinical Trial

Cardiovascular-kidney-metabolic overlap in heart failure with preserved ejection fraction: Cardiac structure and function, clinical outcomes, and response to sacubitril/valsartan in PARAGON-HF

Mats C H Lassen et al. Eur J Heart Fail. 2024 Aug.
Free article

Abstract

Aims: Cardiovascular-kidney-metabolic (CKM) multimorbidity is prevalent among individuals with heart failure (HF), but whether cardiac structure and function, clinical outcomes, and treatment response to sacubitril/valsartan vary in relation to CKM status is unknown.

Methods and results: In this PARAGON-HF post-hoc analysis, we evaluated the impact of CKM multimorbidity (atherosclerotic cardiovascular [CV] disease, chronic kidney disease, and type 2 diabetes) on cardiac structure and function, clinical outcomes, and treatment effects of sacubitril/valsartan versus valsartan. The primary outcome was a composite of total HF hospitalizations and CV death. Secondary outcomes included the individual components of the primary outcome and a composite kidney outcome (sustained estimated glomerular filtration rate reduction of ≥50%, end-stage kidney disease, or kidney-related death). At baseline, 35.2% had one CKM condition, 33.3% had two, 15.9% had three, and only 15.6% had HF alone. CKM multimorbidity was associated with higher septal and posterior wall thickness, lower global longitudinal strain, higher E/e', and worse right ventricular function. Total HF hospitalizations or CV death increased with greater CKM multimorbidity, with the highest relative risk observed with three CKM conditions (rate ratio 3.06, 95% confidence interval 2.33-4.03), compared with HF alone. Treatment effects of sacubitril/valsartan were consistent irrespective of the number of CKM conditions for the primary endpoint (pinteraction = 0.75), CV death (pinteraction = 0.82), total HF hospitalizations (pinteraction = 0.67), and the composite kidney endpoint (pinteraction = 0.99).

Conclusions: Cardiovascular-kidney-metabolic multimorbidity was common in PARAGON-HF and associated with adverse changes in cardiac structure and function and with a stepwise increase in risk of clinical outcomes. Treatment effects of sacubitril/valsartan were consistent irrespective of CKM burden.

Clinical trial registration: ClinicalTrials.gov NCT01920711.

Keywords: Cardiovascular‐kidney‐metabolic; Heart failure; Multimorbidity; Sacubitril/valsartan.

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References

    1. Ostrominski JW, Arnold SV, Butler J, Fonarow GC, Hirsch JS, Palli SR, et al. Prevalence and overlap of cardiac, renal, and metabolic conditions in US adults, 1999‐2020. JAMA Cardiol 2023;8:1050–1060. https://doi.org/10.1001/jamacardio.2023.3241
    1. Yki‐Järvinen H. Non‐alcoholic fatty liver disease as a cause and a consequence of metabolic syndrome. Lancet Diabetes Endocrinol 2014;2:901–910. https://doi.org/10.1016/S2213‐8587(14)70032‐4
    1. Thomas G, Sehgal AR, Kashyap SR, Srinivas TR, Kirwan JP, Navaneethan SD. Metabolic syndrome and kidney disease: A systematic review and meta‐analysis. Clin J Am Soc Nephrol 2011;6:2364–2373. https://doi.org/10.2215/CJN.02180311
    1. Malik S, Wong ND, Franklin SS, Kamath TV, L'Italien GJ, Pio JR, et al. Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation 2004;110:1245–1250. https://doi.org/10.1161/01.CIR.0000140677.20606.0E
    1. Garg PK, Biggs ML, Carnethon M, Ix JH, Criqui MH, Britton KA, et al. Metabolic syndrome and risk of incident peripheral artery disease: The Cardiovascular Health Study. Hypertension 2014;63:413–419. https://doi.org/10.1161/HYPERTENSIONAHA.113.01925

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