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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. [ABSTRACT FROM AUTHOR]

Aims: Differential microRNA expression in peripheral blood has been observed in patients with heart failure, suggesting their value as potential biomarkers and likely contributors to disease mechanisms. In the present study, we aimed to evaluate the transcardiac gradient of 84 cardio-microRNAs in healthy and failing hearts to determine which microRNAs are released or absorbed by the myocardium in heart failure.Methods and Results: Eight healthy volunteers and nine patients with congestive heart failure were included. Arterial and coronary sinus blood samples were collected, and microRNAs were extracted. The expression of microRNAs was analysed using real-time PCR by the miScript miRNA PCR Array Human Cardiovascular Disease. In coronary sinus samples, the microRNAs miR-16-5p, miR-27a-3p, miR-27b-3p, miR-29b-3p, miR-29c-3p, miR-30e-5p, miR-92a-3p, miR-125b-5p, miR-140-5p, miR-195-5p, miR-424-5p, and miR-451a were significantly down-regulated, and let-7a-5p, let-7c-5p, let-7e-5p, miR-23b-3p, miR-107, miR-155-5p, miR-181a-5p, miR-181b-5p and miR-320a were up-regulated in heart failure. Left ventricular filling pressure was negatively correlated with miR-195, miR-16, miR-29b-3p, miR-29c-3p, miR-451a, and miR-92a-3p. The failing heart released let-7b-5p, let-7c-5p, let-7e-5p, miR-122-5p, and miR-21-5p, and absorbed miR-16-5p, miR-17-5p, miR-27a-3p, miR-30a-5p, miR-30d-5p, miR-30e-5p, miR-130a-3p, miR-140-5p, miR-199a-5p, and miR-451a. In silico analyses suggest that the transcardiac gradient of microRNAs in heart failure may target pathways related to heart disease.Conclusion: We determined the transcardiac gradient of cardio-microRNAs in failing hearts, which supports the use of these microRNAs as potential biomarkers. The microRNAs described here may have a role in the pathophysiology of heart failure as they might be involved in pathways related to disease progression, including fibrosis. [ABSTRACT FROM AUTHOR]

Background: A potential role for subclinical systolic impairment as a contributor to the pathophysiology and outcomes of heart failure with preserved ejection fraction (HFpEF) has been proposed recently. However, the precise relationship of indices of systolic dysfunction with exercise hemodynamics in HFpEF is not known. Objectives: To characterize the relationship between left ventricular mechanical function assessed by strain imaging with the key hemodynamic features of HFpEF at rest and during exercise. Methods: Simultaneous echocardiography and exercise right heart catheterization was performed in 48 subjects referred for assessment of dyspnea. HFpEF was defined as left ventricular ejection fraction (LVEF) ≥50% with a pulmonary capillary wedge pressure (PCWP) ≥15mmHg at rest and/or ≥25mmHg at maximal exertion; 34 participants were diagnosed with HFpEF (LVEF 64±6%) and 16 as Non-Cardiac Dyspnea (NCD; LVEF 62±8%). Left ventricular global longitudinal strain (GLS) and systolic strain-rate (GLSRs) and brain natriuretic peptide (BNP) levels were measured at rest and peak exercise. Results: At rest, HFpEF patients had impaired GLS compared to NCD subjects (-19.2±2.5 vs -21.7±3.4%, P=0.017). GLSRs was impaired at maximal exertion (-0.89±0.15 vs -1.01±0.2 s-1, p=0.052). At rest GLS correlated significantly with pulmonary capillary wedge pressure (PCWP, r=0.38, p=0.01) and cardiac index (CI, r=-0.43, p=0.002). During exercise peak GLS correlated with exercise PCWP (r=0.47, p=0.002) and CI (r=-0.50, p=0.001). Receiver operator characteristic curve analysis showed that exercise GLS was a sensitive and specific feature of HFpEF in patients with normal LVEF and dyspnea (c statistic 0.71). GLSRs was also positively correlated with peak PCWP. Conclusions: Reduced GLS is associated with more marked hemodynamic impairment in HFpEF both a rest and during exercise. Assessment of LV strain during exercise may be particularly useful in aiding the diagnosis of HFpEF in dyspneic patients with normal LVEF. [ABSTRACT FROM AUTHOR]