The effect of parity on exercise physiology in women with heart failure with preserved ejection fraction.

AIMS: Women are overrepresented amongst patients with heart failure with preserved ejection fraction (HFpEF); however, the underpinning mechanism for this asymmetric distribution is unclear. Pregnancy represents a potential gender-specific risk factor for HFpEF. It leads to significant physiological adaption, and increasing parity has been associated with some cardiovascular risk. We sought to examine the relationship between prior parity with the rest and exercise haemodynamic and echocardiographic profile of women with HFpEF. METHODS AND RESULTS: Patients referred for assessment of exertional dyspnoea and confirmed to have a haemodynamic and clinical profile consistent with HFpEF were included. Detailed evaluation consisted of rest and exercise right heart catheterization and echocardiography. A socio-economic and obstetric history was also documented. Fifty-eight women were assessed and categorized as having either 0-2 births or ≥3 births, dividing the cohort equally. Women with ≥3 births achieved a lower symptom-limited workload than those with 0-2 births [38 (24-51) vs. 46 (31-68) W, P = 0.04]. Women with ≥3 births had a greater rise in pulmonary capillary wedge pressure indexed to workload with exercise [0.5 (0.3-0.8) vs. 0.3 (0.2-0.5) mmHg/W, P = 0.03], paralleled by a greater rise in right atrial pressure [10 (8-12) vs. 7 (3-11), P = 0.01]. Pulmonary vascular resistance was also higher in women with ≥3 births [1.9 (1.6-2.4) vs. 1.6 (1.4-1.9) mmHg/L/min rest, P = 0.046, and 1.9 (2.4-2.4) vs. 1.4 (1-1.8) mmHg/L/min exercise, P = 0.024]. Left ventricular ejection fraction was lower at rest [60 (57-61) vs. 63 (60-66), P = 0.008] and during exercise [65 (62-67) vs. 68 (66-70), P = 0.038] in women with higher parity. CONCLUSIONS: Higher parity is associated with greater impairments in multiple physiologic parameters of HFpEF severity in women, including diastolic reserve, pulmonary vascular resistance, and systolic dysfunction.

Sex Differences in Heart Failure With Preserved Ejection Fraction Pathophysiology: A Detailed Invasive Hemodynamic and Echocardiographic Analysis.

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.

Impaired left atrial strain predicts abnormal exercise haemodynamics in heart failure with preserved ejection fraction.

BACKGROUND: Elevated left atrial (LA) pressure, particularly during exercise, is associated with symptomatic status and survival in patients with heart failure with preserved ejection fraction (HFpEF). We aimed to characterize the contribution of abnormal LA mechanical properties to exercise haemodynamics in HFpEF. METHODS AND RESULTS: Simultaneous echocardiography and right heart catheterization were performed in 71 subjects with left ventricular ejection fraction ≥ 50% referred for assessment of exertional dyspnoea. According to haemodynamic evaluation, 49 patients were diagnosed with HFpEF [pulmonary capillary wedge pressure (PCWP) ≥ 15 mmHg at rest and/or ≥ 25 mmHg at maximal exertion] and 22 as non-cardiac dyspnoea. Apical two- and four-chamber views were used for blinded two-dimensional LA speckle tracking analysis. HFpEF was characterized by impaired LA reservoir (24.3 ± 9.6 vs. 36.7 ± 8.4%, P < 0.001) and pump strain (-11.5 ± 3.2 vs. -17.0 ± 3.4%, P < 0.001); and increased stiffness (0.8 ± 0.7 vs. 0.2 ± 0.1 mmHg/%, P < 0.001). Reservoir and pump strain correlated with exercise PCWP (r = -0.64 and r = 0.72, P < 0.001), and remained independent predictors after adjusting for left ventricular mass index, LA volume index, mean E/e' and systolic blood pressure (B = -0.66 and B = 1.41, respectively, P < 0.001). LA stiffness was strongly related to B-type natriuretic peptide levels (r = 0.73, P < 0.001; B = 173.0, P < 0.001). Reservoir strain at cut-off of ≤ 33% predicted invasively verified HFpEF diagnosis with 88% sensitivity and 77% specificity, providing a net reclassification improvement of 12% in comparison to the 2016 European Society of Cardiology criteria for non-invasive diagnosis of HFpEF. CONCLUSIONS: Impaired LA reservoir and pump function and increased stiffness are associated with abnormal exercise haemodynamics in HFpEF. These markers provide significant HFpEF diagnostic utility in elderly ambulatory patients with dyspnoea.