Association of Coronary Microvascular Dysfunction With Heart Failure Hospitalizations and Mortality in Heart Failure With Preserved Ejection Fraction: A Follow-up in the PROMIS-HFpEF Study

Camilla Hage; Sara Svedlund; Antti Saraste; Ulrika Ljung Faxén; Lina Benson; Maria Lagerstrom Fermer; Li Ming Gan; Sanjiv J. Shah; Carolyn S.P. Lam; Lars H. Lund

doi:10.1016/j.cardfail.2020.08.010

Association of Coronary Microvascular Dysfunction With Heart Failure Hospitalizations and Mortality in Heart Failure With Preserved Ejection Fraction: A Follow-up in the PROMIS-HFpEF Study

Camilla Hage^*, Sara Svedlund, Antti Saraste, Ulrika Ljung Faxén, Lina Benson, Maria Lagerstrom Fermer, Li Ming Gan, Sanjiv J. Shah, Carolyn S.P. Lam, Lars H. Lund

^*Corresponding author for this work

Medicine, Cardiology Division

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

30 Scopus citations

Abstract

Background: Coronary microvascular dysfunction (CMD) is common in heart failure with preserved ejection fraction (HFpEF). We assessed the association of CMD with hospitalization and mortality in HFpEF. Methods and Results: We assessed the 1-year outcomes in patients from the PROMIS-HFpEF study, a prospective observational study of patients with chronic stable HFpEF undergoing coronary flow reserve measurements. Outcomes were (1) time to cardiovascular (CV) death/first HF hospitalization, (2) CV death/recurrent HF hospitalizations, (3) all-cause death/first HF hospitalization, and (4) first and (5) recurrent all-cause hospitalizations. CMD was defined as coronary flow reserve of <2.5. Time to CV death/first hospitalization was compared by log-rank test and recurrent HF and all-cause hospitalizations by Poisson test. Of 263 patients enrolled, 257 were evaluable at 1 year. Where the coronary flow reserve was interpretable (n = 201), CMD was present in 150 (75%). The median follow-up was 388 days (Q1, Q3 365, 418). The outcome of CV death/first HF hospitalization occurred in 15 patients (4 CV deaths). The incidence rate was in CMD 96 per 1000 person-years, 95% confidence interval 54–159, vs non-CMD 0 per1000 person-years, 95% confidence interval 0–68, P =.023, and remained significant after accounting for selected clinical variables. In patients with CMD, the incidence rates were significantly higher also for CV death/recurrent HF hospitalizations, all-cause death/first HF, and recurrent but not first all-cause hospitalization. Conclusions: In this exploratory assessment of the prognostic role of CMD in HFpEF, CMD was independently associated with primarily CV- and HF-specific events. The high prevalence of CMD and its CV and HF specific prognostic role suggest CMD may be a potential treatment target in HFpEF.

Original language	English (US)
Pages (from-to)	1016-1021
Number of pages	6
Journal	Journal of Cardiac Failure
Volume	26
Issue number	11
DOIs	https://doi.org/10.1016/j.cardfail.2020.08.010
State	Published - Nov 2020

Funding

Supported by AstraZeneca. C.H. is supported by Stockholm Country Council (grant 20180899). S.J.S. is supported by the U.S. National Institutes of Health grants [R01 HL105755 and R01 HL127028] and American Heart Association grants [#16SFRN28780016 and #15CVGPSD27260148]. C.S.L. is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore. L.H.L. is supported by grants from the Swedish Research Council [grants 2013-23897-104604-23 and 523-2014-2336], the Swedish Heart Lung Foundation [grants 20120321 and 20150557], and the Stockholm County Council [grant 20190525]. C.H. has received consulting fees from Novartis, MSD and Roche Diagnostics. S.J.S. has received research grants from Actelion, AstraZeneca, Corvia, and Novartis; and consulting fees from Actelion, Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Cardiora, Eisai, Ironwood, Merck, Novartis, Sanofi, Tenax, and United Therapeutics. C.S.L. has received research support from Boston Scientific, Bayer, Roche Diagnostics, Medtronic, and Vifor Pharma; and has consulted for Astra Zeneca, Bayer, Novartis, Amgen, Merck, Janssen Research & Development LLC, Menarini, Boehringer Ingelheim, Abbott Diagnostics, Corvia, Stealth BioTherapeutics, and Takeda. A.S. received research grants from Academy of Finland and Finnish Foundation for Cardiovascular Research during the conduct of the study; and consulting fees from GE healthcare, Novartis, Abbot, Astra Zeneca. L.H.L. has received research grants from Novartis, Boehringer-Ingelheim, Vifor Pharma, and AstraZeneca, and consulting fees from Novartis, Merck, Boehringer-Ingelheim, Sanofi, Vifor Pharma, and AstraZeneca. M.L.F., M.A.B., and L.M.G. are all employees of AstraZeneca R&D. All other authors have no disclosures.

Keywords

CV death
HF hospitalization
HFpEF
coronary flow reserve
coronary microvascular dysfunction
inflammation
outcome

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

Access to Document

10.1016/j.cardfail.2020.08.010

Cite this

Hage, C., Svedlund, S., Saraste, A., Faxén, U. L., Benson, L., Fermer, M. L., Gan, L. M., Shah, S. J., Lam, C. S. P., & Lund, L. H. (2020). Association of Coronary Microvascular Dysfunction With Heart Failure Hospitalizations and Mortality in Heart Failure With Preserved Ejection Fraction: A Follow-up in the PROMIS-HFpEF Study. Journal of Cardiac Failure, 26(11), 1016-1021. https://doi.org/10.1016/j.cardfail.2020.08.010

@article{48f2262fabf54b288a95615b1856fa79,

title = "Association of Coronary Microvascular Dysfunction With Heart Failure Hospitalizations and Mortality in Heart Failure With Preserved Ejection Fraction: A Follow-up in the PROMIS-HFpEF Study",

abstract = "Background: Coronary microvascular dysfunction (CMD) is common in heart failure with preserved ejection fraction (HFpEF). We assessed the association of CMD with hospitalization and mortality in HFpEF. Methods and Results: We assessed the 1-year outcomes in patients from the PROMIS-HFpEF study, a prospective observational study of patients with chronic stable HFpEF undergoing coronary flow reserve measurements. Outcomes were (1) time to cardiovascular (CV) death/first HF hospitalization, (2) CV death/recurrent HF hospitalizations, (3) all-cause death/first HF hospitalization, and (4) first and (5) recurrent all-cause hospitalizations. CMD was defined as coronary flow reserve of <2.5. Time to CV death/first hospitalization was compared by log-rank test and recurrent HF and all-cause hospitalizations by Poisson test. Of 263 patients enrolled, 257 were evaluable at 1 year. Where the coronary flow reserve was interpretable (n = 201), CMD was present in 150 (75%). The median follow-up was 388 days (Q1, Q3 365, 418). The outcome of CV death/first HF hospitalization occurred in 15 patients (4 CV deaths). The incidence rate was in CMD 96 per 1000 person-years, 95% confidence interval 54–159, vs non-CMD 0 per1000 person-years, 95% confidence interval 0–68, P =.023, and remained significant after accounting for selected clinical variables. In patients with CMD, the incidence rates were significantly higher also for CV death/recurrent HF hospitalizations, all-cause death/first HF, and recurrent but not first all-cause hospitalization. Conclusions: In this exploratory assessment of the prognostic role of CMD in HFpEF, CMD was independently associated with primarily CV- and HF-specific events. The high prevalence of CMD and its CV and HF specific prognostic role suggest CMD may be a potential treatment target in HFpEF.",

keywords = "CV death, HF hospitalization, HFpEF, coronary flow reserve, coronary microvascular dysfunction, inflammation, outcome",

author = "Camilla Hage and Sara Svedlund and Antti Saraste and Fax{\'e}n, {Ulrika Ljung} and Lina Benson and Fermer, {Maria Lagerstrom} and Gan, {Li Ming} and Shah, {Sanjiv J.} and Lam, {Carolyn S.P.} and Lund, {Lars H.}",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = nov,

doi = "10.1016/j.cardfail.2020.08.010",

language = "English (US)",

volume = "26",

pages = "1016--1021",

journal = "Journal of Cardiac Failure",

issn = "1071-9164",

publisher = "Churchill Livingstone",

number = "11",

}

Hage, C, Svedlund, S, Saraste, A, Faxén, UL, Benson, L, Fermer, ML, Gan, LM, Shah, SJ, Lam, CSP & Lund, LH 2020, 'Association of Coronary Microvascular Dysfunction With Heart Failure Hospitalizations and Mortality in Heart Failure With Preserved Ejection Fraction: A Follow-up in the PROMIS-HFpEF Study', Journal of Cardiac Failure, vol. 26, no. 11, pp. 1016-1021. https://doi.org/10.1016/j.cardfail.2020.08.010

Association of Coronary Microvascular Dysfunction With Heart Failure Hospitalizations and Mortality in Heart Failure With Preserved Ejection Fraction: A Follow-up in the PROMIS-HFpEF Study. / Hage, Camilla; Svedlund, Sara; Saraste, Antti et al.
In: Journal of Cardiac Failure, Vol. 26, No. 11, 11.2020, p. 1016-1021.

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

TY - JOUR

T1 - Association of Coronary Microvascular Dysfunction With Heart Failure Hospitalizations and Mortality in Heart Failure With Preserved Ejection Fraction

T2 - A Follow-up in the PROMIS-HFpEF Study

AU - Hage, Camilla

AU - Svedlund, Sara

AU - Saraste, Antti

AU - Faxén, Ulrika Ljung

AU - Benson, Lina

AU - Fermer, Maria Lagerstrom

AU - Gan, Li Ming

AU - Shah, Sanjiv J.

AU - Lam, Carolyn S.P.

AU - Lund, Lars H.

PY - 2020/11

Y1 - 2020/11

N2 - Background: Coronary microvascular dysfunction (CMD) is common in heart failure with preserved ejection fraction (HFpEF). We assessed the association of CMD with hospitalization and mortality in HFpEF. Methods and Results: We assessed the 1-year outcomes in patients from the PROMIS-HFpEF study, a prospective observational study of patients with chronic stable HFpEF undergoing coronary flow reserve measurements. Outcomes were (1) time to cardiovascular (CV) death/first HF hospitalization, (2) CV death/recurrent HF hospitalizations, (3) all-cause death/first HF hospitalization, and (4) first and (5) recurrent all-cause hospitalizations. CMD was defined as coronary flow reserve of <2.5. Time to CV death/first hospitalization was compared by log-rank test and recurrent HF and all-cause hospitalizations by Poisson test. Of 263 patients enrolled, 257 were evaluable at 1 year. Where the coronary flow reserve was interpretable (n = 201), CMD was present in 150 (75%). The median follow-up was 388 days (Q1, Q3 365, 418). The outcome of CV death/first HF hospitalization occurred in 15 patients (4 CV deaths). The incidence rate was in CMD 96 per 1000 person-years, 95% confidence interval 54–159, vs non-CMD 0 per1000 person-years, 95% confidence interval 0–68, P =.023, and remained significant after accounting for selected clinical variables. In patients with CMD, the incidence rates were significantly higher also for CV death/recurrent HF hospitalizations, all-cause death/first HF, and recurrent but not first all-cause hospitalization. Conclusions: In this exploratory assessment of the prognostic role of CMD in HFpEF, CMD was independently associated with primarily CV- and HF-specific events. The high prevalence of CMD and its CV and HF specific prognostic role suggest CMD may be a potential treatment target in HFpEF.

AB - Background: Coronary microvascular dysfunction (CMD) is common in heart failure with preserved ejection fraction (HFpEF). We assessed the association of CMD with hospitalization and mortality in HFpEF. Methods and Results: We assessed the 1-year outcomes in patients from the PROMIS-HFpEF study, a prospective observational study of patients with chronic stable HFpEF undergoing coronary flow reserve measurements. Outcomes were (1) time to cardiovascular (CV) death/first HF hospitalization, (2) CV death/recurrent HF hospitalizations, (3) all-cause death/first HF hospitalization, and (4) first and (5) recurrent all-cause hospitalizations. CMD was defined as coronary flow reserve of <2.5. Time to CV death/first hospitalization was compared by log-rank test and recurrent HF and all-cause hospitalizations by Poisson test. Of 263 patients enrolled, 257 were evaluable at 1 year. Where the coronary flow reserve was interpretable (n = 201), CMD was present in 150 (75%). The median follow-up was 388 days (Q1, Q3 365, 418). The outcome of CV death/first HF hospitalization occurred in 15 patients (4 CV deaths). The incidence rate was in CMD 96 per 1000 person-years, 95% confidence interval 54–159, vs non-CMD 0 per1000 person-years, 95% confidence interval 0–68, P =.023, and remained significant after accounting for selected clinical variables. In patients with CMD, the incidence rates were significantly higher also for CV death/recurrent HF hospitalizations, all-cause death/first HF, and recurrent but not first all-cause hospitalization. Conclusions: In this exploratory assessment of the prognostic role of CMD in HFpEF, CMD was independently associated with primarily CV- and HF-specific events. The high prevalence of CMD and its CV and HF specific prognostic role suggest CMD may be a potential treatment target in HFpEF.

KW - CV death

KW - HF hospitalization

KW - HFpEF

KW - coronary flow reserve

KW - coronary microvascular dysfunction

KW - inflammation

KW - outcome

UR - http://www.scopus.com/inward/record.url?scp=85090860149&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85090860149&partnerID=8YFLogxK

U2 - 10.1016/j.cardfail.2020.08.010

DO - 10.1016/j.cardfail.2020.08.010

M3 - Article

C2 - 32846205

AN - SCOPUS:85090860149

SN - 1071-9164

VL - 26

SP - 1016

EP - 1021

JO - Journal of Cardiac Failure

JF - Journal of Cardiac Failure

IS - 11

ER -

Association of Coronary Microvascular Dysfunction With Heart Failure Hospitalizations and Mortality in Heart Failure With Preserved Ejection Fraction: A Follow-up in the PROMIS-HFpEF Study

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this