Background: Pulmonary hypertension (PH) is highly prevalent in patients with heart failure with preserved ejection fraction (HFpEF), and it is a strong predictor of adverse outcomes. We aimed to determine possible echocardiographic parameters to predict the presence of PH in patients with HFpEF Methods and Results: A total of 113 patients with HFpEF were prospectively enrolled from November 2017 to July 2022. The patients underwent invasive cardiac catheterization and simultaneous echocardiography at rest and during exercise. The parameters indicating right ventricle‐pulmonary artery uncoupling, including tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) and tricuspid annular systolic velocity (TAS’)/PASP were calculated. Receiver operating characteristic curve analysis was used to determine the optimal cut‐off points of TAPSE/PASP and TAS’/PASP to differentiate patients with HFpEF with PH from those without PH. Sixty‐eight patients with HFpEF with PH and 45 without PH were included. Those with PH had lower TAPSE/PASP and TAS’/PASP at rest and during exercise compared with those without PH. Both resting/stress TAPSE/PASP and TAS’/PASP were correlated with rest/exercise pulmonary capillary wedge pressure and mean pulmonary artery pressure. In multivariable regression analysis, TAPSE/PASP remained a significant predictor of exercise pulmonary capillary wedge pressure and mean pulmonary artery pressure. In receiver operating characteristic curve analysis, the optimal cut‐off points of TAPSE/PASP and TAS’/PASP to differentiate patients with HFpEF with PH from those without PH were ≤0.62 and ≤0.47, respectively. Conclusions: Right ventricle‐pulmonary artery uncoupling is closely correlated with abnormal rest/exercise hemodynamics (pulmonary capillary wedge pressure and mean pulmonary artery pressure) in patients with HFpEF. TAPSE/PASP and TAS’/PASP can be useful parameters to detect PH in patients with HFpEF.

Background: Contemporary evidence supports the cardiovascular and renal benefits of sodium-glucose co-transporter-2 inhibitors (SGLT2is) in patients with diabetes. While metformin has traditionally been recommended as a first-line treatment, its exact role in improving cardiovascular outcomes remains uncertain. This study aims to evaluate the impact of combination therapy with metformin on the cardiovascular and renal outcomes in high-risk, treatment-naïve diabetic patients who have undergone SGLT2i therapy. Methods: Using the National Health Insurance Research Database in Taiwan, a retrospective cohort study was conducted. Treatment-naïve patients with diabetes and established atherosclerotic cardiovascular disease (ASCVD) undertaking SGLT2i therapy from 1 January 2016 to 31 December 2021 were included. Patients were categorized based on the concomitant use of metformin. Propensity score matching was employed to minimize confounding factors. The primary outcome was major adverse cardiovascular events (MACEs), with secondary outcomes including cardiovascular death, hospitalization for heart failure, and renal outcomes. Results: In total, 10,151 treatment-naïve diabetic patients with ASCVD were identified, with 2570 in the only SGLT2i therapy group and 7581 in the SGLT2i plus metformin group. In total, 2262 pairs were analyzed after propensity score adjustment. The risk of MACEs (36.6 vs. 42.1 events per 1000 person-years; hazard ratio 0.87, 95% confidence interval 0.70–1.09) and other outcomes did not significantly differ between the two treatment groups. Conclusions: In high-risk, treatment-naïve diabetic patients, initiating SGLT2i therapy alone or in combination with metformin resulted in comparable cardiovascular and renal outcomes. These findings suggest that metformin might not be mandatory as a first-line treatment for achieving cardiovascular benefits in such patients.

Aims: A dramatic increase in pulmonary capillary wedge pressure (PCWP) during exercise is observed in patients with heart failure with preserved ejection fraction (HFpEF). This study was designed to determine whether iloprost inhalation could improve exercise haemodynamics and cardiac reserve in patients with HFpEF.Methods: Thirty‐four HFpEF patients were enrolled in this double‐blind, randomized, placebo‐controlled, parallel‐group trial. Patients received both cardiac catheterization and underwent expired gas analysis at rest, during exercise, and before and 10 minutes after treatment with either inhaled iloprost or placebo. The primary endpoint was decrease in exercise PCWP.Results: At baseline, enrolled patients showed an increase in PCWP during exercise (from 16 [range, 14–23] mmHg to 27 [21–36] mmHg; P < .0001). After iloprost inhalation, exercise PCWP was significantly reduced compared to placebo (adjusted mean: 20 [16–29] mmHg vs 23 [17–32] mmHg; P = .002). There was no difference for cardiac output reserve with exercise in the 2 groups (0.2 [−1.3–1.2] L/min vs –0.7 [−1.9–0.1] L/min; P = .099). Iloprost improved the pulmonary artery pressure flow relationships in HFpEF with exercise compared to placebo.Conclusion: Iloprost inhalation improved haemodynamic deficits during exercise in patients with HFpEF. Prospective trials testing long‐term iloprost therapy in this population are warranted.

The Authors’ reply We thank Dr Ramchand and his colleagues for valuable comments1 on our paper from the retrospective data from National Health Insurance Research Database in Taiwan.2 Several key points should be emphasised in interpretation of the observational study. First, although we did not know how many patients received cardiac MRI to establish or confirm the diagnosis of hypertrophic cardiomyopathy (HCM), it is uncommon to mistake hypertensive cardiac disease for HCM. Second, among patients with HCM without hypertension in our study, use of ACE inhibitors/angiotensin …