Anna L Beale1, Shane Nanayakkara1, Louise Segan2, Justin A Mariani1, Micha T Maeder3, Vanessa van Empel4, Donna Vizi5, Shona Evans5, Carolyn S P Lam6, David M Kaye7. 1. Department of Cardiology, Alfred Hospital, Melbourne, Victoria, Australia; Heart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Department of Medicine, Monash University, Clayton, Victoria, Australia. 2. Department of Cardiology, Alfred Hospital, Melbourne, Victoria, Australia; Heart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia. 3. Cardiology Department, Kantonsspital St. Gallen, St. Gallen, Switzerland. 4. Department of Cardiology, Maastricht University Medical Centre, Maastricht, the Netherlands. 5. Department of Cardiology, Alfred Hospital, Melbourne, Victoria, Australia. 6. Department of Cardiology, National Heart Centre, Duke University, National University of Singapore Medical School, Singapore. 7. Department of Cardiology, Alfred Hospital, Melbourne, Victoria, Australia; Heart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Department of Medicine, Monash University, Clayton, Victoria, Australia. Electronic address: david.kaye@baker.edu.au.
Abstract
OBJECTIVES: This study sought to identify sex differences in central and peripheral factors that contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF) by using complementary invasive hemodynamic and echocardiographic approaches. BACKGROUND: Women are overrepresented among patients with HFpEF, and there are established sex differences in myocardial structure and function. Exercise intolerance is a fundamental feature of HFpEF; however, sex differences in the physiological determinants of exercise capacity in HFpEF are yet to be established. METHODS: Patients with exertional intolerance with confirmed HFpEF were included in this study. Evaluation of the subjects included resting and exercise hemodynamics, echocardiography, and mixed venous blood gas sampling. RESULTS: A total of 161 subjects included 114 females (71%). Compared to males, females had a higher pulmonary capillary wedge pressure (PCWP) indexed to peak exercise workload (0.8 [0.5 to 1.2] mm Hg/W vs. 0.6 [0.4 to 1] mm Hg/W, respectively; p = 0.001) and lower systemic (1.1 [0.9 to 1.5] ml/mm Hg vs. 1 [0.7 to 1.2] ml/mm Hg, respectively; p = 0.019) and pulmonary (2.9 [2.2 to 4.2] ml/mm Hg vs. 2.4 [1.9 to 3] ml/mm Hg, respectively; p = 0.032) arterial compliance at exercise. Mixed venous blood gas analysis demonstrated a greater rise in lactate indexed to peak workload (0.05 [0.04 to 0.09] mmol/l/W vs. 0.04 [0.03 to 0.06] mmol/l/W, respectively; p = 0.007) in women compared to men. Women had higher mitral inflow velocity to diastolic mitral annular velocity at early filling (E/e') ratios at rest and peak exercise, along with a higher ejection fraction and smaller ventricular dimensions. CONCLUSIONS: Women with HFpEF demonstrate poorer diastolic reserve with higher echocardiographic and invasive measurements of left ventricular filling pressures at exercise, accompanied by lower systemic and pulmonary arterial compliance and poorer peripheral oxygen kinetics.
OBJECTIVES: This study sought to identify sex differences in central and peripheral factors that contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF) by using complementary invasive hemodynamic and echocardiographic approaches. BACKGROUND:Women are overrepresented among patients with HFpEF, and there are established sex differences in myocardial structure and function. Exercise intolerance is a fundamental feature of HFpEF; however, sex differences in the physiological determinants of exercise capacity in HFpEF are yet to be established. METHODS:Patients with exertional intolerance with confirmed HFpEF were included in this study. Evaluation of the subjects included resting and exercise hemodynamics, echocardiography, and mixed venous blood gas sampling. RESULTS: A total of 161 subjects included 114 females (71%). Compared to males, females had a higher pulmonary capillary wedge pressure (PCWP) indexed to peak exercise workload (0.8 [0.5 to 1.2] mm Hg/W vs. 0.6 [0.4 to 1] mm Hg/W, respectively; p = 0.001) and lower systemic (1.1 [0.9 to 1.5] ml/mm Hg vs. 1 [0.7 to 1.2] ml/mm Hg, respectively; p = 0.019) and pulmonary (2.9 [2.2 to 4.2] ml/mm Hg vs. 2.4 [1.9 to 3] ml/mm Hg, respectively; p = 0.032) arterial compliance at exercise. Mixed venous blood gas analysis demonstrated a greater rise in lactate indexed to peak workload (0.05 [0.04 to 0.09] mmol/l/W vs. 0.04 [0.03 to 0.06] mmol/l/W, respectively; p = 0.007) in women compared to men. Women had higher mitral inflow velocity to diastolic mitral annular velocity at early filling (E/e') ratios at rest and peak exercise, along with a higher ejection fraction and smaller ventricular dimensions. CONCLUSIONS:Women with HFpEF demonstrate poorer diastolic reserve with higher echocardiographic and invasive measurements of left ventricular filling pressures at exercise, accompanied by lower systemic and pulmonary arterial compliance and poorer peripheral oxygen kinetics.
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