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The considerable progress made in recent years in the diagnosis, risk stratification, and treatment of pulmonary hypertension was highlighted during the most recent edition of the Pulmonary Hypertension Association Scientific Sessions, which was held in Atlanta, Georgia from June 9 to 11, 2022, with the theme: Vision for the PHuture: The Evolving Science and Management of PH. Content presented over the 3‐day conference focused on scientific and management updates since the last sessions were held in 2018 and included didactic talks, debates, and roundtable discussions across a broad spectrum of topics related to pulmonary hypertension. This article aims to summarize the key messages from each of the session talks. [ABSTRACT FROM AUTHOR]

The article focuses on the potential therapeutic effects of prostaglandin I2 (PGI2) in patients with pulmonary arterial hypertension (PAH). Topics include the role of inflammation and immune responses in PAH, the vasoprotective effects of PGI2, and the hypothesis that PGI2 therapy can increase regulatory T cell (Treg) percentages and decrease the T effector cell (Teff) to Treg ratio in PAH patients.

Pulmonary arterial hypertension (PAH) is a fatal vasculopathy that ultimately leads to elevated pulmonary pressure and death by right ventricular (RV) failure, which occurs in part due to decreased fatty acid oxidation and cytotoxic lipid accumulation. In this study, we tested the hypothesis that decreased fatty acid oxidation and increased lipid accumulation in the failing RV is driven, in part, by a relative carnitine deficiency. We then tested whether supplementation of l‐carnitine can reverse lipotoxic RV failure through augmentation of fatty acid oxidation. In vivo in transgenic mice harboring a human BMPR2 mutation, l‐carnitine supplementation reversed RV failure by increasing RV cardiac output, improving RV ejection fraction, and decreasing RV lipid accumulation through increased PPARγ expression and augmented fatty acid oxidation of long chain fatty acids. These findings were confirmed in a second model of pulmonary artery banding‐induced RV dysfunction. In vitro, l‐carnitine supplementation selectively increased fatty acid oxidation in mitochondria and decreased lipid accumulation through a Cpt1‐dependent pathway. l‐Carnitine supplementation improves right ventricular contractility in the stressed RV through augmentation of fatty acid oxidation and decreases lipid accumulation. Correction of carnitine deficiency through l‐carnitine supplementation in PAH may reverse RV failure. [ABSTRACT FROM AUTHOR]

The article focuses on addressing concerns raised by Yasuma et al. about potential differential effects of prostaglandin I2 (PGI2) analogs, specifically epoprostenol and treprostinil, on T regulatory cell (Treg) generation in patients with pulmonary arterial hypertension. Topics include separating the data for each analog, revealing significant increases in Treg percentage and Foxp3 mean fluorescence intensity in patients treated with epoprostenol but not treprostinil.

Introduction: Selexipag, an oral selective prostacyclin receptor agonist, delays disease progression versus placebo in pulmonary arterial hypertension (PAH). In appropriate patients, transitioning from parenteral prostacyclin analogs to selexipag may alleviate the risks associated with long-term parenteral therapy. We report our experience with the feasibility, safety and challenges associated with systematic transition from parenteral prostacyclin therapy to selexipag in compensated PAH. Methods: From Jan. 2016 to July 2017, patients with PAH at Duke University Medical Center who were stable on parenteral prostacyclin therapy were offered the opportunity to transition to selexipag via standardized protocol. Patients underwent pre- and post-transition assessments of hemodynamics, echocardiography, biomarkers, and functional status. Patient demographics, clinical characteristics and any adverse effects were recorded in a database. Data are presented as median (Q1, Q3) unless specified. Results: Overall, 14 patients (11 women; age 53 years (48, 59); BMI 30.1 kg/m2 (26.9, 33.2)) were included with median follow-up of 5.5 months (4.1, 6.4). Of these, 13 patients tolerated the transition to selexipag and remained on drug (total daily dose 3200 mcg (3200, 4800)) at study completion. Two patients required an additional PAH medication during and after the transition period. Overall, pre- and post-transition NT-proBNP, 6MWD, TAPSE, RV function, and hemodynamics were stable (Table 1). The patient who failed the switch as assessed by worsening symptoms and surrogate markers had portopulmonary hypertension with intravenous therapy complicated by catheter-associated infection prior to the switch. Conclusions: The transition from parenteral prostacyclin therapy to selexipag was generally well tolerated in patients with compensated PAH. Our results support further study of the long-term implications of this transition in appropriate patients. [ABSTRACT FROM AUTHOR]

Introduction: Echocardiography is a key tool in the management of patients with pulmonary arterial hypertension (PAH), but many potential parameters could be used to assess response to therapy. We examined echocardiographic variables before and after initiation of PAH-specific therapy to evaluate which measures of RV function were best correlated with clinical outcomes. Methods: This retrospective study included all patients with PAH seen at Duke University Medical Center from 2010 to 2013 who had TTEs with RV-focused views and RV strain assessment performed within 6 months pre- and post-initiation of a PAH-specific therapy and had no significant intercurrent illness. In a series of exploratory analyses, pre- and post-therapy TTE parameters were compared using the Wilcoxon signed rank test, changes in TTE parameters were compared to changes in 6MWD using Spearman rank-order correlations, and Cox regression was used to assess the relationship of pre-treatment values and changes in these parameters with all-cause mortality over the 3-year period following post-treatment TTE. All data reported as median (Q1, Q3) unless specified. Results: Our cohort included 48 patients (35 women, age 49 yrs (35, 56)) with severe PAH at baseline (mPAP 50 mmHg (41, 60); PVR 8.8 Wood units (5.6, 13.9)). TAPSE, 6MWD, mid-RV and basal-RV diameters, RVSP, and RV global longitudinal strain (GLS) were all found to significantly improve after initiation of PAH therapy. Decreases in RA area (r = -0.50, p = 0.002) and mid-RV diameter (r = -0.36, p = 0.033) were most strongly correlated with improvement in 6MWD. Overall, 14 patients (32%) died within 3-years. Pre-treatment values of RA area (HR per 1 unit: 1.15; 95% CI 1.06, 1.24), mid-RV diameter (HR: 2.85; 1.30, 6.23), basal-RV diameter (HR: 3.5; 1.66, 7.35) and RV GLS (HR: 1.20; 1.04, 1.37) were all associated with increased mortality risk. TAPSE was unique in that pre-treatment TAPSE (HR: 0.17; 0.04, 0.67) and interval increase in TAPSE (HR: 0.18; 0.06, 0.62) were both significantly associated with decreased mortality risk. Conclusions: Given the strong association of both baseline TAPSE and change in TAPSE with mortality, our study supports the ongoing use of TAPSE as an important assessment of disease severity and treatment response in PAH. [ABSTRACT FROM AUTHOR]

Increased pulse pressure reflects pathologic arterial stiffening and predicts cardiovascular events and mortality. The effect of pulse pressure on outcomes in lower extremity bypass patients remains unknown. We thus investigated whether preoperative pulse pressure could predict amputation-free survival in patients undergoing lower extremity bypass for atherosclerotic occlusive disease. An institutional database identified 240 included patients undergoing lower extremity bypass from 2005 to 2014. Preoperative demographics, cardiovascular risk factors, operative factors, and systolic and diastolic blood pressures were recorded, and compared between patients with pulse pressures above and below 80 mm Hg. Factors were analyzed in bi- and multivariable models to assess independent predictors of amputation-free survival. Kaplan-Meier analysis was performed to evaluate the temporal effect of pulse pressure ⩾80 mm Hg on amputation-free survival. Patientswith a pulse pressure ⩾80mm Hg were older, male, and had higher systolic and lower diastolic pressures. Patients with pulse pressure <80 mm Hg demonstrated a survival advantage on Kaplan-Meier analysis at six months (log-rank P = 0.003) and one year (P = 0.005) postoperatively. In multivariable analysis, independent risk factors for decreased amputation-free survival at six months included nonwhite race, tissue loss, infrapopliteal target, and preoperative pulse pressure ⩾80 mm Hg (hazard ratio 2.60; P = 0.02), while only tissue loss and pulse pressure ⩾80 mm Hg (hazard ratio 2.30, P = 0.02) remained predictive at one year. Increased pulse pressure is independently associated with decreased amputation-free survival in patients undergoing lower extremity bypass. Further efforts to understand the relationship between increased arterial stiffness and poor outcomes in these patients are needed. [ABSTRACT FROM AUTHOR]