Kidney Function and Outcomes in Patients Hospitalized With Heart Failure

Ravi B. Patel; Gregg C. Fonarow; Stephen J. Greene; Shuaiqi Zhang; Brooke Alhanti; Adam D. DeVore; Javed Butler; Paul A. Heidenreich; Joanna C. Huang; Michelle M. Kittleson; Karen E. Joynt Maddox; James J. McDermott; Anjali Tiku Owens; Pamela N. Peterson; Scott D. Solomon; Orly Vardeny; Clyde W. Yancy; Muthiah Vaduganathan

doi:10.1016/j.jacc.2021.05.002

Kidney Function and Outcomes in Patients Hospitalized With Heart Failure

Ravi B. Patel, Gregg C. Fonarow^*, Stephen J. Greene, Shuaiqi Zhang, Brooke Alhanti, Adam D. DeVore, Javed Butler, Paul A. Heidenreich, Joanna C. Huang, Michelle M. Kittleson, Karen E. Joynt Maddox, James J. McDermott, Anjali Tiku Owens, Pamela N. Peterson, Scott D. Solomon, Orly Vardeny, Clyde W. Yancy, Muthiah Vaduganathan

^*Corresponding author for this work

Medicine, Cardiology Division

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

132 Scopus citations

Abstract

Background: Few contemporary data exist evaluating care patterns and outcomes in heart failure (HF) across the spectrum of kidney function. Objectives: This study sought to characterize differences in quality of care and outcomes in patients hospitalized for HF by degree of kidney dysfunction. Methods: Guideline-directed medical therapies were evaluated among patients hospitalized with HF at 418 sites in the GWTG-HF (Get With The Guidelines–Heart Failure) registry from 2014 to 2019 by discharge CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)-derived estimated glomerular filtration rate (eGFR). We additionally evaluated the risk-adjusted association of admission eGFR with in-hospital mortality. Results: Among 365,494 hospitalizations (age 72 ± 15 years, left ventricular ejection fraction [EF]: 43 ± 17%), median discharge eGFR was 51 ml/min/1.73 m² (interquartile range: 34 to 72 ml/min/1.73 m²), 234,332 (64%) had eGFR <60 ml/min/1.73 m², and 18,869 (5%) were on dialysis. eGFR distribution remained stable from 2014 to 2019. Among 157,439 patients with HF with reduced EF (≤40%), discharge guideline-directed medical therapies, including beta-blockers, were lowest in discharge eGFR <30 mL/min/1.73 m² or dialysis (p < 0.001). “Triple therapy” with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor–neprilysin inhibitor + beta-blocker + mineralocorticoid receptor antagonist was used in 38%, 33%, 25%, 15%, 5%, and 3% for eGFR ≥90, 60 to 89, 45 to 59, 30 to 44, <30 ml/min/1.73 m², and dialysis, respectively; p < 0.001. Mortality was higher in a graded fashion at lower admission eGFR groups (1.1%, 1.5%, 2.0%, 3.0%, 5.0%, and 4.2%, respectively; p < 0.001). Steep covariate-adjusted associations between admission eGFR and mortality were observed across EF subgroups, but was slightly stronger for HF with reduced EF compared with HF with mid-range or preserved EF (p_interaction = 0.045). Conclusions: Despite facing elevated risks of mortality, patients with comorbid HF with reduced EF and kidney disease are not optimally treated with evidence-based medical therapies, even at levels of eGFR where such therapies would not be contraindicated by kidney dysfunction. Further efforts are required to mitigate risk in comorbid HF and kidney disease.

Original language	English (US)
Pages (from-to)	330-343
Number of pages	14
Journal	Journal of the American College of Cardiology
Volume	78
Issue number	4
DOIs	https://doi.org/10.1016/j.jacc.2021.05.002
State	Published - Jul 27 2021

Funding

The GWTG-HF (Get With The Guidelines–Heart Failure) program is provided by the American Heart Association and sponsored, in part, by Novartis, Boehringer Ingelheim and Eli Lilly Diabetes Alliance, Novo Nordisk, Sanofi, AstraZeneca, and Bayer. This analysis, as a part of the TRANSLATE-HF research series, was supported by AstraZeneca. Dr Patel has received support from the National Institutes of Health (NIH) National Center for Advancing Translational Sciences (grant KL2TR001424). Dr Fonarow has received research funding from the NIH; and has served as a consultant for Abbott, Amgen, AstraZeneca, Bayer, CHF Solutions, Edwards, Medtronic, Merck, and Novartis. Dr Greene has received research support from Amgen, AstraZeneca, Bristol Myers Squibb, Merck, Novartis, and Pfizer; has served on advisory boards for Amgen, AstraZeneca, and Cytokinetics; and has served as a consultant for Amgen and Merck. Dr DeVore has received research funding through the Duke Clinical Research Institute from the American Heart Association, Amgen, AstraZeneca, Bayer, Intra-Cellular Therapies, American Regent Inc., the National Heart, Lung, and Blood Institute (NHLBI), Novartis, and Patient-Centered Outcomes Research Institute; has served as a consultant for AstraZeneca; has received nonfinancial support from Amgen, Bayer, CareDx, InnaMed, LivaNova, Mardil Medical, Novartis, Procyrion, scPharmaceuticals, Story Health, and Zoll; and has received nonfinancial support from Abbott for educational activities outside the submitted work. Dr Butler has served as a consultant for Abbott, Adrenomed, Amgen, Array, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squib, CVRx, G3 Pharmaceutical, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Roche, V-Wave Limited, and Vifor. Dr Joynt Maddox has received grants from NIH/NHLBI, NIH/National Institute on Aging, and Commonwealth Fund; has previously done U.S. Department of Health and Human Services contract work outside the submitted work; and has served on the Health Policy Advisory Committee for the Centene Corp. Dr Owens has served as a consultant for MyoKardia and Cytokinetics outside the submitted work. Dr Peterson has received grant funding from the NHLBI (grant R33HL143324-02); and has received personal fees from the American Heart Association outside the submitted work. Dr Solomon has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, NIH/NHLBI, NeuroTronik, Novartis, Respicardia, Sanofi Pasteur, and Theracos; and has served as a consultant for Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, Gilead, GlaxoSmithKline, Ironwood, Merck, MyoKardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AOBiome, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, DiNAQOR, Tremeau, CellProthera, and Moderna. Dr Vardeny has received funding from the NIH and the U.S. Food and Drug Administration; and has received personal fees from the American Heart Association. Dr Yancy’s spouse is employed by Abbott Labs Inc. Dr Vaduganathan has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Relypsa, and Roche Diagnostics; has had speaker engagements with Novartis and Roche Diagnostics; and has participated on clinical endpoint committees for studies sponsored by Galmed and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Keywords

glomerular filtration rate
heart failure
kidney disease
outcomes
therapy

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jacc.2021.05.002

Cite this

Patel, R. B., Fonarow, G. C., Greene, S. J., Zhang, S., Alhanti, B., DeVore, A. D., Butler, J., Heidenreich, P. A., Huang, J. C., Kittleson, M. M., Joynt Maddox, K. E., McDermott, J. J., Owens, A. T., Peterson, P. N., Solomon, S. D., Vardeny, O., Yancy, C. W., & Vaduganathan, M. (2021). Kidney Function and Outcomes in Patients Hospitalized With Heart Failure. Journal of the American College of Cardiology, 78(4), 330-343. https://doi.org/10.1016/j.jacc.2021.05.002

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title = "Kidney Function and Outcomes in Patients Hospitalized With Heart Failure",

abstract = "Background: Few contemporary data exist evaluating care patterns and outcomes in heart failure (HF) across the spectrum of kidney function. Objectives: This study sought to characterize differences in quality of care and outcomes in patients hospitalized for HF by degree of kidney dysfunction. Methods: Guideline-directed medical therapies were evaluated among patients hospitalized with HF at 418 sites in the GWTG-HF (Get With The Guidelines–Heart Failure) registry from 2014 to 2019 by discharge CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)-derived estimated glomerular filtration rate (eGFR). We additionally evaluated the risk-adjusted association of admission eGFR with in-hospital mortality. Results: Among 365,494 hospitalizations (age 72 ± 15 years, left ventricular ejection fraction [EF]: 43 ± 17%), median discharge eGFR was 51 ml/min/1.73 m2 (interquartile range: 34 to 72 ml/min/1.73 m2), 234,332 (64%) had eGFR <60 ml/min/1.73 m2, and 18,869 (5%) were on dialysis. eGFR distribution remained stable from 2014 to 2019. Among 157,439 patients with HF with reduced EF (≤40%), discharge guideline-directed medical therapies, including beta-blockers, were lowest in discharge eGFR <30 mL/min/1.73 m2 or dialysis (p < 0.001). “Triple therapy” with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor–neprilysin inhibitor + beta-blocker + mineralocorticoid receptor antagonist was used in 38%, 33%, 25%, 15%, 5%, and 3% for eGFR ≥90, 60 to 89, 45 to 59, 30 to 44, <30 ml/min/1.73 m2, and dialysis, respectively; p < 0.001. Mortality was higher in a graded fashion at lower admission eGFR groups (1.1%, 1.5%, 2.0%, 3.0%, 5.0%, and 4.2%, respectively; p < 0.001). Steep covariate-adjusted associations between admission eGFR and mortality were observed across EF subgroups, but was slightly stronger for HF with reduced EF compared with HF with mid-range or preserved EF (pinteraction = 0.045). Conclusions: Despite facing elevated risks of mortality, patients with comorbid HF with reduced EF and kidney disease are not optimally treated with evidence-based medical therapies, even at levels of eGFR where such therapies would not be contraindicated by kidney dysfunction. Further efforts are required to mitigate risk in comorbid HF and kidney disease.",

keywords = "glomerular filtration rate, heart failure, kidney disease, outcomes, therapy",

author = "Patel, {Ravi B.} and Fonarow, {Gregg C.} and Greene, {Stephen J.} and Shuaiqi Zhang and Brooke Alhanti and DeVore, {Adam D.} and Javed Butler and Heidenreich, {Paul A.} and Huang, {Joanna C.} and Kittleson, {Michelle M.} and {Joynt Maddox}, {Karen E.} and McDermott, {James J.} and Owens, {Anjali Tiku} and Peterson, {Pamela N.} and Solomon, {Scott D.} and Orly Vardeny and Yancy, {Clyde W.} and Muthiah Vaduganathan",

note = "Publisher Copyright: {\textcopyright} 2021 American College of Cardiology Foundation",

year = "2021",

month = jul,

day = "27",

doi = "10.1016/j.jacc.2021.05.002",

language = "English (US)",

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pages = "330--343",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

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Patel, RB, Fonarow, GC, Greene, SJ, Zhang, S, Alhanti, B, DeVore, AD, Butler, J, Heidenreich, PA, Huang, JC, Kittleson, MM, Joynt Maddox, KE, McDermott, JJ, Owens, AT, Peterson, PN, Solomon, SD, Vardeny, O, Yancy, CW & Vaduganathan, M 2021, 'Kidney Function and Outcomes in Patients Hospitalized With Heart Failure', Journal of the American College of Cardiology, vol. 78, no. 4, pp. 330-343. https://doi.org/10.1016/j.jacc.2021.05.002

TY - JOUR

T1 - Kidney Function and Outcomes in Patients Hospitalized With Heart Failure

AU - Patel, Ravi B.

AU - Fonarow, Gregg C.

AU - Greene, Stephen J.

AU - Zhang, Shuaiqi

AU - Alhanti, Brooke

AU - DeVore, Adam D.

AU - Butler, Javed

AU - Heidenreich, Paul A.

AU - Huang, Joanna C.

AU - Kittleson, Michelle M.

AU - Joynt Maddox, Karen E.

AU - McDermott, James J.

AU - Owens, Anjali Tiku

AU - Peterson, Pamela N.

AU - Solomon, Scott D.

AU - Vardeny, Orly

AU - Yancy, Clyde W.

AU - Vaduganathan, Muthiah

PY - 2021/7/27

Y1 - 2021/7/27

N2 - Background: Few contemporary data exist evaluating care patterns and outcomes in heart failure (HF) across the spectrum of kidney function. Objectives: This study sought to characterize differences in quality of care and outcomes in patients hospitalized for HF by degree of kidney dysfunction. Methods: Guideline-directed medical therapies were evaluated among patients hospitalized with HF at 418 sites in the GWTG-HF (Get With The Guidelines–Heart Failure) registry from 2014 to 2019 by discharge CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)-derived estimated glomerular filtration rate (eGFR). We additionally evaluated the risk-adjusted association of admission eGFR with in-hospital mortality. Results: Among 365,494 hospitalizations (age 72 ± 15 years, left ventricular ejection fraction [EF]: 43 ± 17%), median discharge eGFR was 51 ml/min/1.73 m2 (interquartile range: 34 to 72 ml/min/1.73 m2), 234,332 (64%) had eGFR <60 ml/min/1.73 m2, and 18,869 (5%) were on dialysis. eGFR distribution remained stable from 2014 to 2019. Among 157,439 patients with HF with reduced EF (≤40%), discharge guideline-directed medical therapies, including beta-blockers, were lowest in discharge eGFR <30 mL/min/1.73 m2 or dialysis (p < 0.001). “Triple therapy” with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor–neprilysin inhibitor + beta-blocker + mineralocorticoid receptor antagonist was used in 38%, 33%, 25%, 15%, 5%, and 3% for eGFR ≥90, 60 to 89, 45 to 59, 30 to 44, <30 ml/min/1.73 m2, and dialysis, respectively; p < 0.001. Mortality was higher in a graded fashion at lower admission eGFR groups (1.1%, 1.5%, 2.0%, 3.0%, 5.0%, and 4.2%, respectively; p < 0.001). Steep covariate-adjusted associations between admission eGFR and mortality were observed across EF subgroups, but was slightly stronger for HF with reduced EF compared with HF with mid-range or preserved EF (pinteraction = 0.045). Conclusions: Despite facing elevated risks of mortality, patients with comorbid HF with reduced EF and kidney disease are not optimally treated with evidence-based medical therapies, even at levels of eGFR where such therapies would not be contraindicated by kidney dysfunction. Further efforts are required to mitigate risk in comorbid HF and kidney disease.

AB - Background: Few contemporary data exist evaluating care patterns and outcomes in heart failure (HF) across the spectrum of kidney function. Objectives: This study sought to characterize differences in quality of care and outcomes in patients hospitalized for HF by degree of kidney dysfunction. Methods: Guideline-directed medical therapies were evaluated among patients hospitalized with HF at 418 sites in the GWTG-HF (Get With The Guidelines–Heart Failure) registry from 2014 to 2019 by discharge CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)-derived estimated glomerular filtration rate (eGFR). We additionally evaluated the risk-adjusted association of admission eGFR with in-hospital mortality. Results: Among 365,494 hospitalizations (age 72 ± 15 years, left ventricular ejection fraction [EF]: 43 ± 17%), median discharge eGFR was 51 ml/min/1.73 m2 (interquartile range: 34 to 72 ml/min/1.73 m2), 234,332 (64%) had eGFR <60 ml/min/1.73 m2, and 18,869 (5%) were on dialysis. eGFR distribution remained stable from 2014 to 2019. Among 157,439 patients with HF with reduced EF (≤40%), discharge guideline-directed medical therapies, including beta-blockers, were lowest in discharge eGFR <30 mL/min/1.73 m2 or dialysis (p < 0.001). “Triple therapy” with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor–neprilysin inhibitor + beta-blocker + mineralocorticoid receptor antagonist was used in 38%, 33%, 25%, 15%, 5%, and 3% for eGFR ≥90, 60 to 89, 45 to 59, 30 to 44, <30 ml/min/1.73 m2, and dialysis, respectively; p < 0.001. Mortality was higher in a graded fashion at lower admission eGFR groups (1.1%, 1.5%, 2.0%, 3.0%, 5.0%, and 4.2%, respectively; p < 0.001). Steep covariate-adjusted associations between admission eGFR and mortality were observed across EF subgroups, but was slightly stronger for HF with reduced EF compared with HF with mid-range or preserved EF (pinteraction = 0.045). Conclusions: Despite facing elevated risks of mortality, patients with comorbid HF with reduced EF and kidney disease are not optimally treated with evidence-based medical therapies, even at levels of eGFR where such therapies would not be contraindicated by kidney dysfunction. Further efforts are required to mitigate risk in comorbid HF and kidney disease.

KW - glomerular filtration rate

KW - heart failure

KW - kidney disease

KW - outcomes

KW - therapy

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Kidney Function and Outcomes in Patients Hospitalized With Heart Failure

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UN SDGs

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