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Introduction: Sleep disordered breathing (SDB) is common among patients with cardiovascular disease, but its impact on physiologic responses to exercise remains unclear. Hypothesis: We sought to determine the functional significance of... more
Introduction: Sleep disordered breathing (SDB) is common among patients with cardiovascular disease, but its impact on physiologic responses to exercise remains unclear. Hypothesis: We sought to determine the functional significance of SDB and low nocturnal oxygen saturation (SaO2) on hemodynamic responses to exercise. Methods: We investigated subjects who underwent invasive cardiopulmonary exercise tests (iCPET) to evaluate dyspnea of unclear etiology who had evidence of SDB defined as an apnea hypopnea index (AHI) > 5 events/hour during a formal sleep study done within 3 years of the iCPET. Mean pulmonary artery pressure (mPAP) and mean wedge pressure (mPW) were indexed to cardiac output (CO) during exercise, with a mPAP-CO slope > 3 mmHg·min·L(-1) and a mPW-CO slope > 2 mmHg·min·L(-1) indicating an abnormal pulmonary vascular (PV) response to exercise. Results: A total of 120 patients (mean±SD age 58.2 ± 12.6 years, body mass index 31.6 ± 7.5) with SDB (mean AHI 18.9 ± 2...
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Introduction: Hepcidin is a master regulator of iron homeostasis that reduces iron absorption when circulating levels are elevated. In preclinical models, iron deficiency and inappropriately elevat...
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Introduction: Exercise intolerance, as quantified by degree of impairment in peak oxygen uptake (VO 2 ), is a cardinal manifestation of heart failure (HF). HF patients are known to have delayed VO 2 kinetics during recovery. However, it... more
Introduction: Exercise intolerance, as quantified by degree of impairment in peak oxygen uptake (VO 2 ), is a cardinal manifestation of heart failure (HF). HF patients are known to have delayed VO 2 kinetics during recovery. However, it is unknown to what extent easily-discernible patterns of VO 2 recovery kinetics reflect circulatory response during exercise. Hypothesis: Delayed VO 2 kinetics, as indicated by the duration of recovery VO 2 plateau (RecVO 2 P), will indicate severity of impairment in cardiac output (CO) augmentation during exercise. Methods: Recovery O 2 kinetics were measured in 52 patients referred for cardiopulmonary exercise testing (CPET) with invasive hemodynamic monitoring (n=16 normal controls, n=18 HFpEF with resting pulmonary arterial wedge pressure, PAWP≥15, and n=18 HFrEF with LVEF 2 recovery kinetics was calculated as time until O 2 uptake fell permanently below peak VO 2 (highest 30s median within final min of exercise, see Figure) as well as the time t...
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Background: Heart failure with preserved ejection fraction (HFpEF) is common, yet there is currently no consensus on how to define HFpEF according to various society and clinical trial criteria. How clinical and hemodynamic profiles of... more
Background: Heart failure with preserved ejection fraction (HFpEF) is common, yet there is currently no consensus on how to define HFpEF according to various society and clinical trial criteria. How clinical and hemodynamic profiles of patients vary across definitions is unclear. We sought to determine clinical characteristics, as well as physiologic and prognostic implications of applying various criteria to define HFpEF. Methods: We examined consecutive patients with chronic exertional dyspnea (New York Heart Association class II to IV) and ejection fraction ≥50% referred for comprehensive cardiopulmonary exercise testing with invasive hemodynamic monitoring. We applied societal and clinical trial HFpEF definitions and compared clinical profiles, exercise responses, and cardiovascular outcomes. Results: Of 461 patients (age 58±15 years, 62% women), 416 met American College of Cardiology/American Heart Association (ACC/AHA), 205 met European Society of Cardiology (ESC), and 55 met ...
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Exercise improves cardiometabolic and vascular function, although the mechanisms remain unclear. Our objective was to demonstrate the diversity of circulating extracellular RNA (ex-RNA) release during acute exercise in humans and its... more
Exercise improves cardiometabolic and vascular function, although the mechanisms remain unclear. Our objective was to demonstrate the diversity of circulating extracellular RNA (ex-RNA) release during acute exercise in humans and its relevance to exercise-mediated benefits on vascular inflammation. We performed plasma small RNA sequencing in 26 individuals undergoing symptom-limited maximal treadmill exercise, with replication of our top candidate miRNA in a separate cohort of 59 individuals undergoing bicycle ergometry. We found changes in miRNAs and other ex-RNAs with exercise (e.g., Y RNAs and tRNAs) implicated in cardiovascular disease. In two independent cohorts of acute maximal exercise, we identified miR-181b-5p as a key ex-RNA increased in plasma after exercise, with validation in a separate cohort. In a mouse model of acute exercise, we found significant increases in miR-181b-5p expression in skeletal muscle after acute exercise in young (but not older) mice. Previous work ...