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Primary pulmonary hypertension (PPH) is a rare disorder characterised by raised pulmonary-artery pressure in the absence of secondary causes. Precapillary pulmonary arteries are affected by medial hypertrophy, intimal fibrosis, microthrombosis, and plexiform lesions. Most individuals present with dyspnoea or evidence of right heart failure. Echocardiography is the best non-invasive test to screen for suspected pulmonary hypertension. The discovery of mutations in the coding region of the gene for bone morphogenetic protein receptor 2 in patients with familial and sporadic PPH may help not only to elucidate pathogenesis but also to direct future treatment options. The pathogenesis is not completely understood, but recent investigations have revealed many possible candidate modifier genes. Without treatment, the disorder progresses in most cases to right heart failure and death. With current therapies such as epoprostenol, progression of disease is slowed, but not halted. Many promising new therapeutic options, including prostacyclin analogues, endothelin-1-receptor antagonists, and phosphodiesterase inhibitors, improve clinical function and haemodynamic measures and may prolong survival.

ObjectiveInadequate right ventricular (RV) and pulmonary arterial (PA) functional responses to exercise are important yet poorly understood features of pulmonary arterial hypertension (PAH). This study combined invasive catheterisation with echocardiography to assess RV afterload, RV function and ventricular–vascular coupling in subjects with PAH.MethodsTwenty-six subjects with PAH were prospectively recruited to undergo right heart catheterisation and Doppler echocardiography at rest and during incremental exercise, and cardiac MRI at rest. Measurements at rest included basic haemodynamics, RV function and coupling efficiency (η). Measurements during incremental exercise included pulmonary vascular resistance (Z0), characteristic impedance (ZC, a measure of proximal PA stiffness) and proximal and distal PA compliance (CPA).ResultsIn patients with PAH, the proximal PAs were significantly stiffer at maximum exercise (ZC =2.31±0.38 vs 1.33±0.15 WU×m2 at rest; p=0.003) and PA compliance was decreased (CPA=0.88±0.10 vs 1.32±0.17 mL/mm Hg/m2 at rest; p=0.0002). Z0 did not change with exercise. As a result, the resistance–compliance (RC) time decreased with exercise (0.67±0.05 vs 1.00±0.07 s at rest; p<10−6). When patients were grouped according to resting coupling efficiency, those with poorer η exhibited stiffer proximal PAs at rest, a lower maximum exercise level, and more limited CPA reduction at maximum exercise.ConclusionsIn PAH, exercise causes proximal and distal PA stiffening, which combined with preserved Z0 results in decreased RC time with exercise. Stiff PAs at rest may also contribute to poor haemodynamic coupling, reflecting reduced pulmonary vascular reserve that contributes to limit the maximum exercise level tolerated.

There is little known about performing transcatheter aortic valve replacement (TAVR) in patients with group 1 pulmonary arterial hypertension (PAH) on advanced pulmonary vasodilator therapy. Retrospective cohort study among 90 patients with systemic sclerosis‐associated pulmonary arterial hypertension and systemic sclerosis‐associated pulmonary hypertension (SSc‐PAH/PH) evaluated at a tertiary PH center. The SSc‐PAH/PH cohort was stratified by the presence or absence of aortic stenosis (AS) to identify differences in baseline characteristics, hemodynamics, and long‐term outcomes. Of the 90 SSc‐PAH/PH patients, 13 patients were diagnosed with AS at PH diagnosis and another 6 patients developed AS during the study period. The period prevalence of AS was 21.1% (19/90, 95% confidence interval: 13.2%–30.1%) of which 94.7% was mild (18/19) at diagnosis with mean age at AS diagnosis of 66.3 + 2.2 years. Among AS patients, 31.6% (6/19) progressed to severe AS, five of which underwent TAVR (median age: 70 years) while on advanced PAH therapy. One of the five TAVR patients developed worsening pulmonary hypertension post‐TAVR. The 5‐year survival rate for all AS patients from diagnosis date was 37.2%. There was a high prevalence of AS in this cohort of SSc‐PAH/PH patients, with mean age of onset younger than patients with nonbicuspid aortic valve stenosis. This is the largest series of SSc‐PAH/PH patients on advanced pulmonary vasodilator therapy who underwent TAVR with acceptable early outcomes.

Poor recovery pattern of oxygen consumption (V̇O2) post‐exercise is associated with adverse clinical outcomes. However, it remains unknown which component of the O2 pathway (Fick principle) defines this prognostic risk, for example, peripheral extraction, stroke volume, heart rate. Retrospective cohort study included 120 participants (heart failure with preserved ejection fraction: HFpEF = 68, pre‐capillary pulmonary hypertensio n = 31, non‐cardiac dyspnea = 21). Percent recovery metrics were calculated as the percent reduction of each hemodynamic variable from peak exercise to recovery, for example, (exercise‐recovery)/exercise ×100%. Overall, the mean age (standard deviation) was 62.6 (14.4) years and 54% were females. Among the three groups (HFpEF, pre‐capillary pulmonary hypertension, non‐cardiac dyspnea), recovery patterns of O2 pathway components were statistically non‐significant. Peripheral extraction recovery (r2 = 0.43, p < 0.001) and heart rate recovery (r2 = 0.25, p < 0.001) correlated with peak V̇O2, but only peripheral extraction recovery remained significant in multivariate analysis (p = 0.01). Peripheral extraction recovery (<41%; median) demonstrated poor one‐year survival from mortality and heart failure hospitalizations (HR 2.82; CI 95% 1.38–5.74, p = 0.003). Peripheral extraction recovery pattern is the most significant component of the O2 pathway and defines adverse outcomes. Physiologically, it elucidates the importance of skeletal muscle and peripheral vascular function.

Compared to idiopathic pulmonary arterial hypertension (IPAH), patients with portopulmonary hypertension (POPH) have worse survival. Health disparities may contribute to these differences but have not been studied. We sought to compare socioeconomic factors in patients with POPH and IPAH and to determine whether socioeconomic status and/or POPH diagnosis were associated with treatment and health-care utilization. We performed a cross-sectional study of adults enrolled in the Pulmonary Hypertension Association Registry. Patients with IPAH (n = 344) and POPH (n = 57) were compared. Compared with IPAH, patients with POPH were less likely to be college graduates (19.6% vs. 34.9%, p = 0.02) and more likely to be unemployed (54.7% vs. 30.5%, p < 0.001) and have an annual household income below poverty level (45.7% vs. 19.0%, p < 0.001). Patients with POPH had similar functional class, quality of life, 6-min walk distance, and mean pulmonary arterial pressure with a higher cardiac index. Compared with IPAH, patients with POPH were less likely to receive combination therapy (46.4% vs. 62.2%, p = 0.03) and endothelin receptor antagonists (28.6% vs. 55.1%, p < 0.001) at enrollment with similar treatment at follow-up. Patients with POPH had more emergency department visits (1.7 ± 2.1 vs. 0.9 ± 1.2, p = 0.009) and hospitalizations in the six months preceding enrollment (1.5 ± 2.1 vs. 0.8 ± 1.1, p = 0.02). Both POPH diagnosis and lower education level were independently associated with a higher number of emergency department visits. Compared to IPAH, patients with POPH have lower socioeconomic status, are less likely to receive initial combination therapy and endothelin receptor antagonists but have similar treatment at follow-up, and have increased health-care utilization.

Among 45 CpcPH/heart failure with preserved ejection fraction participants, 11 with normal left atrium (compared to 34 with abnormal left atrium, p  < 0.05 for all) had low left ventricle (LV) transmural pressure (2.9 ± 2.4 vs. 6.2 ± 2.9 mmHg), and increased right ventricle (RV):LV ratio (2.41 ± 1.09 vs. 1.46 ± 0.66) and interventricular septal angle (149 ± 8 vs. 136 ± 10), indicating exaggerated ventricular interdependence from a dilated RV.

Serotonin is a pulmonary vasoconstrictor and smooth muscle cell mitogen. The serotonin transporter (SERT) is abundant in pulmonary vascular smooth muscle. Compared with the short (S) allele, the long (L) SERT promoter allele is associated with increased SERT transcription and more severe pulmonary hypertension in a cohort of patients with chronic obstructive pulmonary disease, and was more prevalent in a cohort with idiopathic pulmonary arterial hypertension (IPAH), compared with control subjects. We hypothesized that the SERT L allele would associate with an earlier age at diagnosis and/or shorter survival interval in pulmonary arterial hypertension (PAH) than the S allele. SERT promoters from 166 familial PAH (FPAH), 83 IPAH, and 125 control subjects were sequenced. One hundred twenty-seven of the patients with FPAH had a known mutation in bone morphogenetic protein receptor 2 (BMPR2). The mean age at diagnosis was 35.8 yr in patients with FPAH and 41.1 yr in patients with IPAH (p = 0.02). There were no significant differences in distribution of the LL, LS, or SS genotypes in IPAH, FPAH, or unaffected BMPR2 mutation carriers. In FPAH, the LL genotype was associated with an earlier age at diagnosis (p < 0.02). In patients with IPAH, these SERT genotypes do not correlate with age at diagnosis or survival interval. In patients with FPAH, the LL genotype correlates with an earlier age at diagnosis than SL or SS, although survival among the groups was similar. The correlation of the SERT promoter polymorphism with age at diagnosis in FPAH suggests a possible relationship between the SERT and BMPR2.

To better understand the impact of the COVID‐19 pandemic on the care of patients with pulmonary hypertension, we conducted a retrospective cohort study evaluating health insurance status, healthcare access, disease severity, and patient reported outcomes in this population. Using the Pulmonary Hypertension Association Registry (PHAR), we defined and extracted a longitudinal cohort of pulmonary arterial hypertension (PAH) patients from the PHAR's inception in 2015 until March 2022. We used generalized estimating equations to model the impact of the COVID‐19 pandemic on patient outcomes, adjusting for demographic confounders. We assessed whether insurance status modified these effects via covariate interactions. PAH patients were more likely to be on publicly‐sponsored insurance during the COVID‐19 pandemic compared with prior, and did not experience statistically significant delays in access to medications, increased emergency room visits or nights in the hospital, or worsening of mental health metrics. Patients on publicly‐sponsored insurance had higher healthcare utilization and worse objective measures of disease severity compared with privately insured individuals irrespective of the COVID‐19 pandemic. The relatively small impact of the COVID‐19 pandemic on pulmonary hypertension‐related outcomes was unexpected but may be due to pre‐established access to high quality care at pulmonary hypertension comprehensive care centers. Irrespective of the COVID‐19 pandemic, patients who were on publicly‐sponsored insurance seemed to do worse, consistent with prior studies highlighting outcomes in this population. We speculate that previously established care relationships may lessen the impact of an acute event, such as a pandemic, on patients with chronic illness.

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension in which the vascular changes originate in the small pulmonary veins and venules. The pathogenesis is unknown and any link with primary pulmonary hypertension (PPH) has been speculative. Mutations in the bone morphogenetic protein receptor II (BMPR2) gene have been identified in at least 50% of familial cases and in 25% of sporadic cases of PPH. We report a patient with documented PVOD whose mother had severe pulmonary hypertension. Sequencing of the patient's BMPR2 coding region revealed a del44C mutation in Exon 1 that is predicted to encode for a truncated protein. Analysis of DNA from family members suggests that this mutation was transmitted by the proband's mother to two of her four children. The finding of PVOD associated with a BMPR2 mutation reveals a possible pathogenetic connection with PPH.