Jan Benes1, Martin Kotrc1, Barry A Borlaug2, Katerina Lefflerova1, Petr Jarolim3, Bela Bendlova4, Antonin Jabor1, Josef Kautzner1, Vojtech Melenovsky5. 1. Department of Cardiology, Institute of Clinical and Experimental Medicine-IKEM, Prague, Czech Republic. 2. Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota. 3. Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 4. Institute of Endocrinology, Prague, Czech Republic. 5. Department of Cardiology, Institute of Clinical and Experimental Medicine-IKEM, Prague, Czech Republic; Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota. Electronic address: vojtech.melenovsky@ikem.cz.
Abstract
OBJECTIVES: The purpose of this study was to compare the prognostic impact of clinical and biomarker correlates of resting heart rate (HR) and chronotropic incompetence in heart failure (HF) patients. BACKGROUND: The mechanisms and underlying pathophysiological influences of HR abnormalities in HF are incompletely understood. METHODS: In a prospective pilot study, 81 patients with advanced systolic HF (97% were receiving beta-blockers) and 25 age-, sex-, and body-size matched healthy controls underwent maximal cardiopulmonary exercise testing with sampling of neurohormones and biomarkers. RESULTS: Two-thirds of HF patients met criteria for chronotropic incompetence. Resting HR and HR reserve (HRR, a measure of chronotropic response) were not correlated with each other and were associated with distinct biomarker profiles. Resting HR correlated with increased myocardial stress (B-type natriuretic peptide [BNP]: r = 0.26; pro-A-type natriuretic peptide: r = 0.24; N-terminal-proBNP: r = 0.32) and inflammation (leukocyte count: r = 0.28; high-sensitivity C-reactive protein assay: r = 0.25). In contrast, HRR correlated with the neurohumoral response to HF (copeptin: r = -0.33; norepinephrine: r = -0.29) but not with myocyte stress or injury reflected by natriuretic peptides or hs-troponin I. Patients in the lowest chronotropic incompetence quartile (HRR ≤0.38) displayed more advanced HF, reduced exercise capacity, ventilatory inefficiency, and poorer quality of life. Over a median follow-up of 17 months, the combined endpoint of death or urgent transplant/assist device implantation occurred more frequently in patients with higher resting HR (>67 beats/min) or lower HRR, with both markers providing additive prognostic information. CONCLUSIONS: Increased resting HR and chronotropic incompetence may reflect different pathophysiological processes, provide incremental prognostic information, and represent distinct therapeutic targets.
OBJECTIVES: The purpose of this study was to compare the prognostic impact of clinical and biomarker correlates of resting heart rate (HR) and chronotropic incompetence in heart failure (HF) patients. BACKGROUND: The mechanisms and underlying pathophysiological influences of HR abnormalities in HF are incompletely understood. METHODS: In a prospective pilot study, 81 patients with advanced systolic HF (97% were receiving beta-blockers) and 25 age-, sex-, and body-size matched healthy controls underwent maximal cardiopulmonary exercise testing with sampling of neurohormones and biomarkers. RESULTS: Two-thirds of HF patients met criteria for chronotropic incompetence. Resting HR and HR reserve (HRR, a measure of chronotropic response) were not correlated with each other and were associated with distinct biomarker profiles. Resting HR correlated with increased myocardial stress (B-type natriuretic peptide [BNP]: r = 0.26; pro-A-type natriuretic peptide: r = 0.24; N-terminal-proBNP: r = 0.32) and inflammation (leukocyte count: r = 0.28; high-sensitivity C-reactive protein assay: r = 0.25). In contrast, HRR correlated with the neurohumoral response to HF (copeptin: r = -0.33; norepinephrine: r = -0.29) but not with myocyte stress or injury reflected by natriuretic peptides or hs-troponin I. Patients in the lowest chronotropic incompetence quartile (HRR ≤0.38) displayed more advanced HF, reduced exercise capacity, ventilatory inefficiency, and poorer quality of life. Over a median follow-up of 17 months, the combined endpoint of death or urgent transplant/assist device implantation occurred more frequently in patients with higher resting HR (>67 beats/min) or lower HRR, with both markers providing additive prognostic information. CONCLUSIONS: Increased resting HR and chronotropic incompetence may reflect different pathophysiological processes, provide incremental prognostic information, and represent distinct therapeutic targets.
Authors: Renata R T Castro; Luka Lechnewski; Alan Homero; Denilson Campos de Albuquerque; Luis Eduardo Rohde; Dirceu Almeida; João David; Salvador Rassi; Fernando Bacal; Edimar Bocchi; Lidia Moura Journal: Arq Bras Cardiol Date: 2021-01 Impact factor: 2.000