Camilla Hage1, Sara Svedlund2, Antti Saraste3, Ulrika Ljung Faxén4, Lina Benson4, Maria Lagerstrom Fermer5, Li-Ming Gan6, Sanjiv J Shah7, Carolyn S P Lam8, Lars H Lund9. 1. Department of Medicine, Cardiology Unit, Karolinska Institutet, Stockholm, Sweden; Karolinska University hospital, Heart, Vascular and Neuro Theme, Karolinska University hospital, Stockholm, Sweden. Electronic address: camilla.hage@sll.se. 2. Department of Clinical Physiology, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden. 3. Heart Center, Turku University Hospital, University of Turku, Turku, Finland. 4. Department of Medicine, Cardiology Unit, Karolinska Institutet, Stockholm, Sweden. 5. Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. 6. Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden; Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. 7. Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 8. National Heart Centre Singapore, Duke-National University of Singapore, Singapore; University Medical Centre Groningen, Groningen, the Netherlands. 9. Department of Medicine, Cardiology Unit, Karolinska Institutet, Stockholm, Sweden; Karolinska University hospital, Heart, Vascular and Neuro Theme, Karolinska University hospital, Stockholm, Sweden.
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.
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.