Pulmonary hypertension (PH) includes multiple diseases that share as common characteristic an elevated pulmonary artery pressure and right ventricular involvement. Sex differences are observed in practically all causes of PH. The most studied type is pulmonary arterial hypertension (PAH) which presents a gender bias regarding its prevalence, prognosis, and response to treatment. Although this disease is more frequent in women, once affected they present a better prognosis compared to men. Even if estrogens seem to be the key to understand these differences, animal models have shown contradictory results leading to the birth of the estrogen paradox. In this review we will summarize the evidence regarding sex differences in experimental animal models and, very specially, in patients suffering from PAH or PH from other etiologies.

Aims: Pulmonary hypertension (PH) associated with left heart disease is an increasingly prevalent problem, orphan of targeted therapies, and related to a poor prognosis, particularly when pre- and post-capillary PH combine. The current study aimed to determine whether treatment with the selective β3 adrenoreceptor agonist mirabegron improves outcomes in patients with combined pre- and post-capillary PH (CpcPH). Methods and results: The β3 Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure (SPHERE-HF) trial is a multicentre, randomized, parallel, placebo-controlled clinical trial that enrolled stable patients with CpcPH associated with symptomatic heart failure. A total of 80 patients were assigned to receive mirabegron (50 mg daily, titrated till 200 mg daily, n = 39) or placebo (n = 41) for 16 weeks. Of them, 66 patients successfully completed the study protocol and were valid for the main analysis. The primary endpoint was the change in pulmonary vascular resistance (PVR) on right heart catheterization. Secondary outcomes included the change in right ventricular (RV) ejection fraction by cardiac magnetic resonance or computed tomography, other haemodynamic variables, functional class, and quality of life. The trial was negative for the primary outcome (placebo-corrected mean difference of 0.62 Wood units, 95% confidence interval [CI] −0.38, 1.61, p = 0.218). Patients receiving mirabegron presented a significant improvement in RV ejection fraction as compared to placebo (placebo-corrected mean difference of 3.0%, 95% CI 0.4, 5.7%, p = 0.026), without significant differences in other pre-specified secondary outcomes. Conclusions: SPHERE-HF is the first clinical trial to assess the potential benefit of β3 adrenergic agonists in PH. The trial was negative since mirabegron did not reduce PVR, the primary endpoint, in patients with CpcPH. On pre-specified secondary outcomes, a significant improvement in RV ejection fraction assessed by advanced cardiac imaging was found, without differences in functional class or quality of life.

(1) Background and aim: This study aimed to investigate the impact of prehabilitation on the postoperative outcomes of heart transplantation and its cost-effectiveness. (2) Methods: This single-center, ambispective cohort study included forty-six candidates for elective heart transplantation from 2017 to 2021 attending a multimodal prehabilitation program consisting of supervised exercise training, physical activity promotion, nutritional optimization, and psychological support. The postoperative course was compared to a control cohort consisting of patients transplanted from 2014 to 2017 and those contemporaneously not involved in prehabilitation. (3) Results: A significant improvement was observed in preoperative functional capacity (endurance time 281 vs. 728 s, p < 0.001) and quality-of-life (Minnesota score 58 vs. 47, p = 0.046) after the program. No exercise-related events were registered. The prehabilitation cohort showed a lower rate and severity of postoperative complications (comprehensive complication index 37 vs. 31, p = 0.033), lower mechanical ventilation time (37 vs. 20 h, p = 0.032), ICU stay (7 vs. 5 days, p = 0.01), total hospitalization stay (23 vs. 18 days, p = 0.008) and less need for transfer to nursing/rehabilitation facilities after hospital discharge (31% vs. 3%, p = 0.009). A cost-consequence analysis showed that prehabilitation did not increase the total surgical process costs. (4) Conclusions: Multimodal prehabilitation before heart transplantation has benefits on short-term postoperative outcomes potentially attributable to enhancement of physical status, without cost-increasing.

Objective: To evaluate segmental right ventricular (RV) dysfunction in pulmonary hypertension (PH) using cardiac magnetic resonance (CMR). Design: Cross-sectional analysis in a retrospective cohort of consecutive adult patients. Setting: Mount Sinai Hospital in New York. Patients: 192 patients with known or suspected PH undergoing right heart catheterisation and CMR. PH was defined as mean pulmonary artery pressure ≥25 mm Hg. Abnormal RV ejection fraction (RVEF) was defined as <50%. Patients were classified into: group 1 (no PH, normal RVEF; n=40), group 2 (PH, normal RVEF; n=41) or group 3 (PH, abnormal RVEF; n=111). Interventions: CMR and right heart catheterisation within a 2-week interval. Main outcome measures: On cine CMR images, the stack of RV short-axis views was divided into two equal halves. Basal and apical RVEF were calculated using Simpson's method, and a ratio of basal-to-apical RVEF (RVEF_ratio) was derived. Results: Basal RVEF did not differ between groups 1 and 2 (63±8% vs 64±8%; p=1); however, patients in group 2 had significantly lower apical RVEF (46±13% vs 58±10%; p<0.01) and higher RVEF_ratio (median 1.4 vs 1.1; p<0.01). Both apical and basal RVEF were reduced in group 3 compared with groups 1 and 2 (p<0.01), and the RVEF_ratio increased with increasing PH severity (p<0.01 for trend). An apical RVEF <50% was more sensitive than global RV dysfunction for the detection of PH. Conclusions: Apical dysfunction appears to occur before global RVEF decreases in chronic PH, potentially constituting an early and sensitive marker of RV dysfunction in this setting.