Search Results (78)

Obstructive sleep apnea (OSA) could increase pulmonary artery pressure. However, the clinical consequences vary, mainly depending on comorbidities. Patients with pulmonary hypertension associated with lung diseases (World Health Organization (WHO) Group 3 pulmonary hypertension) are particularly vulnerable increases in pulmonary artery pressure. Managing pulmonary hypertension in this specific patient population presents a considerable challenge. While positive airway pressure therapy for OSA has shown promise in improving pulmonary hemodynamics in patients with obesity hypoventilation syndrome and chronic obstructive pulmonary disease, evidence is lacking for similar improvements in those with other pulmonary diseases and hypoventilation disorders. Furthermore, pulmonary-artery-specific therapies may carry a risk of clinical worsening in this group. Weight management and new pharmacotherapy have together emerged as a crucial intervention, demonstrating benefits for both OSA and pulmonary hemodynamics. We reviewed key studies that provide insights into the influence of OSA on WHO Group 3 pulmonary hypertension and the clinical management of both conditions. Full article

Background/Objectives: Interstitial lung disease (ILD) is frequently complicated by pulmonary hypertension (PH), which is associated with reduced exercise capacity and poor prognosis. Early and accurate non-invasive detection of PH remains a clinical challenge. This study evaluated whether combining quantitative CT analysis of lung fibrosis with cardiac MRI-derived measures of right ventricular (RV) function improves the diagnostic accuracy of PH in patients with ILD. Methods: We retrospectively analyzed 72 ILD patients who underwent chest CT, cardiac MRI, and right heart catheterization (RHC). Lung fibrosis was quantified using a Gaussian Histogram Normalized Correlation (GHNC) software that computed the proportions of diseased lung, ground-glass opacity (GGO), honeycombing, reticulation, consolidation, and emphysema. MRI was used to assess RV end-systolic volume (RVESV), ejection fraction, and RV longitudinal strain. PH was defined as a mean pulmonary arterial pressure (mPAP) ≥ 20 mmHg and pulmonary vascular resistance ≥ 3 Wood units on RHC. Results: Compared to patients without PH, those with PH (n = 21) showed significantly reduced RV strain (−13.4 ± 5.1% vs. −16.4 ± 5.2%, p = 0.026) and elevated RVESV (74.2 ± 18.3 mL vs. 59.5 ± 14.2 mL, p = 0.003). CT-derived indices also differed significantly: diseased lung area (56.4 ± 17.2% vs. 38.4 ± 12.5%, p < 0.001), GGO (11.8 ± 3.6% vs. 8.65 ± 4.3%, p = 0.005), and honeycombing (17.7 ± 4.9% vs. 12.8 ± 6.4%, p = 0.0027) were all more prominent in the PH group. In receiver operating characteristic curve analysis, diseased lung area demonstrated an area under the curve of 0.778 for detecting PH. This increased to 0.847 with the addition of RVESV, and further to 0.854 when RV strain was included. Combined models showed significant improvement in risk reclassification: net reclassification improvement was 0.700 (p = 0.002) with RVESV and 0.684 (p = 0.004) with RV strain; corresponding IDI values were 0.0887 (p = 0.03) and 0.1222 (p = 0.01), respectively. Conclusions: Combining CT-based fibrosis quantification with cardiac MRI-derived RV functional assessment enhances the non-invasive diagnosis of PH in ILD patients. This integrated imaging approach significantly improves diagnostic precision and may facilitate earlier, more targeted interventions in the management of ILD-associated PH. Full article

Background/Objectives: Sotatercept has demonstrated efficacy in pulmonary arterial hypertension (PAH), but its use has not been studied in patients with Group 3 pulmonary hypertension (PH). Additionally, patients with connective tissue disease-associated PAH (CTD-PAH) were underrepresented in the STELLAR trial. Given the limited treatment options for pulmonary hypertension in patients with interstitial lung disease (PH-ILD), this study aimed to evaluate the use of sotatercept in CTD-PAH patients with concomitant ILD. Methods: Eligible patients (n = 7) had a confirmed diagnosis of CTD-PAH with concomitant ILD. The patients were already receiving background PAH therapy. Baseline hemodynamic and clinical measurements were reassessed after 24 weeks of sotatercept therapy. The variables assessed included six-minute walk distance (6MWD), pulmonary vascular resistance (PVR), echocardiographic right ventricular systolic pressure (eRVSP), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, World Health Organization (WHO) functional class, and supplemental oxygen requirements. Results: The study included seven patients with a mean age of 57 years (range: 39–73 years). After 24 weeks, the mean 6MWT distance increased from 211 m to 348 m (p < 0.01). Mean PVR decreased from 7.77 WU at baseline to 4.53 WU (p < 0.01). Mean eRVSP decreased from 79.43 mmHg to 54.14 mmHg (p < 0.01). NT-proBNP decreased from 3056.86 pg/mL to 1404.29 pg/mL (p < 0.01). The WHO functional class and supplemental oxygen requirements improved in all patients. Conclusions: Sotatercept was tolerated in patients with CTD-PAH and ILD, with no evidence of adverse respiratory effects. When added to foundational PAH therapy, sotatercept resulted in significant improvements across multiple parameters. These findings suggest that sotatercept may be a promising therapeutic option as an adjunctive treatment in this patient population. Full article

Inhaled treprostinil is approved for the treatment of pulmonary hypertension-associated interstitial lung disease (PH-ILD); however, it has not shown significant benefit in patients with a pulmonary vascular resistance (PVR) < 4 WU. As such, treatment for non-severe PH-ILD remains controversial. A total of 16 patients with non-severe PH-ILD were divided into two groups based on changes in PVR during exercise: a dynamic PVR group (n = 10), characterized by an increase in PVR with exertion, and a static PVR group (n = 6), with no increase in PVR with exercise. The dynamic PVR group received inhaled treprostinil, while the static PVR group was monitored off therapy. Baseline and 16-week follow-up values were compared within each group. At 16 weeks, the dynamic PVR group demonstrated significant improvements in mean 6 min walk distance (6MWD) (+32.5 m, p < 0.05), resting PVR (−1.04 WU, p < 0.05), resting mean pulmonary arterial pressure (mPAP) (−5.8 mmHg, p < 0.05), exercise PVR (−1.7 WU, p < 0.05), exercise mPAP (−13 mmHg, p < 0.05), and estimated right ventricular systolic pressure (−9.2 mmHg, p < 0.05). In contrast, the static PVR group remained clinically stable. These observations suggest that an exercise-induced increase in PVR, identified through Level 3 CPET, may help select patients with non-severe PH-ILD who are more likely to benefit from early initiation of inhaled treprostinil. Full article

Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) and concomitant interstitial lung disease (ILD) are particularly challenging to manage due to concerns about ventilation–perfusion mismatch with systemic vasodilators. In this case series, we evaluated the effects of selexipag in eight prostacyclin-naïve CTD-PAH patients with concomitant ILD. Clinical, functional, and laboratory data were collected at baseline and after 16 weeks of treatment. After 16 weeks of treatment, the mean six-minute walk distance increased by 101.75 m (p < 0.05), and the mean estimated right ventricular systolic pressure decreased significantly (p < 0.05). Mean N-terminal pro b-type natriuretic peptide levels declined by 63%, though this reduction did not reach statistical significance. Importantly, supplemental oxygen requirements trended downward (p < 0.05) and pulmonary function tests remained stable. Pulmonary vasodilators have long been unsuccessfully studied in PH-ILD patients until the INCREASE trial. While other systemic agents used in PAH have not shown as much success as inhaled treprostinil in treating PH-ILD, our case series highlights the potential role of selexipag in patients with concomitant CTD-PAH and ILD. Further investigation of selexipag in pure Group 3 PH-ILD patients is warranted. Full article

Background/Objectives: Hypoxic–ischemic encephalopathy (HIE), affecting 1.3–1.7/1000 live births, is treated with conventional therapeutic hypothermia (TH) but carries significant mortality and neurological impairment. Here, we compared intravascular cooling with extracorporeal membrane oxygenation (ECMO) and conventional TH in neonates with moderate to severe HIE. Methods: We retrospectively analyzed single-center neonates born in 2000–2022. Neonates with a 10 min Apgar score ≤ 3 or umbilical artery pH ≤ 6.7, along with persistent pulmonary hypertension of the newborn and an oxygenation index of ≥25 to <40, were divided into ECMO (n = 17) and conventional TH (n = 18) groups and administered the Kyoto Scale of Psychological Development at 18 months. Results: Neonatal and maternal characteristics were similar between the groups. A significantly higher proportion of the ECMO group (70.6% vs. 33.3%) achieved a developmental quotient ≥ 70. Conclusions: Intravascular cooling with ECMO may improve the neurodevelopmental outcomes of neonates with HIE, severe acidosis, and low Apgar scores. Full article

Background: Pulmonary hypertension (PH) is a condition characterized by increased pressure in the pulmonary arteries with poor prognosis and, therefore, an optimal management is necessary. The study’s aim was to search for PH phenotypes and develop a predictive model of five-year mortality using machine learning (ML) algorithms. Methods: This multicenter study was conducted on 122 PH patients. Clinical and demographic data were collected and then used to identify phenotypes through clustering. Subsequently, a predictive model was performed by different ML algorithms. Results: Three PH clusters were identified: Cluster 1 (mean age 68.57 ± 10.54) includes 57% females, 69% from non-respiratory PH groups, and better cardiac (NYHA class 2.61 ± 0.84) and respiratory function (FEV1% 78.78 ± 21.54); Cluster 2 includes 50% females, mean age of 71.36 ± 8.32 years, 44% from PH group 3, worse respiratory function (FEV 1% 68.12 ± 10.20); intermediate cardiac function (NYHA class 3.18 ± 0.49) and significantly higher mortality (75%); Cluster 3 represents the youngest cluster (mean age 61.11 ± 13.50) with 65% males, 81% from non-respiratory PH groups, intermediate respiratory function (FEV1% 70.51 ± 17.91) and worse cardiac performance (NYHA class 3.22 ± 0.58). After testing ML models, logistic regression showed the best predictive performance (AUC = 0.835 and accuracy = 0.744) and identified three mortality-risk factors: age, NYHA class, and number of medications taken. Conclusions: The results suggest that the integration of ML into clinical practice can improve risk stratification to optimize treatment strategies and improve outcomes for PH patients. Full article

Introduction: Arrhythmias are a frequent complication of pulmonary hypertension (PH). Supraventricular tachycardias (SVT) are predominantly reported and are associated with clinical deterioration and an increased mortality. In contrast, the prevalence and clinical relevance of bradycardias is largely unclear. Therefore, the aim of the present study was to determine a prevalence of bradycardias in PH patients and to outline their clinical relevance. Material and methods: Between January 2000 and June 2013, consecutive PH patients were pro- and retrospectively enrolled in two cohorts. Patients received either a 24 h or 72 h Holter ECG. Results: A total of 314 patients (58% female, mean age: 63 years) from PH groups 1–5 (39%, 11%, 19%, 28%, 3%) were included. Basic heart rhythm was sinus rhythm in 87% of patients (9% atrial fibrillation, 2% atrial flutter and 2% paced rhythm). Further arrhythmias were detected in 34% of patients (SVT: 12%, non-sustained ventricular tachycardia: 16%) with a 6% prevalence of relevant bradycardias. Atrioventricular block was revealed in 5% of patients (seven first-degree, one and three second-degree Wenckebach and Mobitz type, respectively, four third-degree), and 1% revealed sinoatrial block (one second-degree, third-degree and unspecified each). Conclusions: The prevalence of bradycardias appears to be about 5–10% in PH patients. Most of them are short and self-limiting. However, some patients experience syncope or clinical deterioration and, therefore, need specific treatment. To find these patients, long-term ECG monitoring combined with ECG-symptom correlation may be useful. Bradycardic medication should be excluded as a cause. Full article

Great progress has been made in the treatment of pulmonary arterial hypertension (WHO group 1 PAH) over the past two decades, which has significantly improved the morbidity and mortality in this patient population. Likewise, the more recent availability of antifibrotic medications for interstitial lung disease (ILD) have also been effective in slowing down the progression of disease. There is no known cure for either of these disease states. When this combination coexists, treatment can be challenging. Interstitial lung disease is a heterogenous group of chronic inflammatory and/or fibrotic parenchymal lung disorders. A subset of patients with ILD, not related to connective tissue disease, can initially present with inflammatory-predominant disease which progresses to irreversible fibrosis. This population of patients is also at risk for developing pulmonary hypertension (PH) or World Health Organization (WHO) group 3 PH. This coexistence of ILD and PH is associated with early morbidity and mortality. The early identification, diagnosis, and treatment of this combination of ILD and PH is vital. Medications available for both ILD and PH require an individualized approach with the intention of slowing down disease progression. Referral to expert centers for clinical trials and transplant evaluation is recommended. The combination of PH-ILD can be challenging to diagnose and treat effectively. Patients require a thorough clinical evaluation to enable the most accurate diagnosis. A vital part of that evaluation is the early recognition of PH. Medications can help improve disease progression along with clinical trials that will further improve our gaps in knowledge. Full article

Pulmonary hypertension associated with lung diseases and/or hypoxia is classified as group 3 in the clinical classification of pulmonary hypertension. The efficacy of existing selective pulmonary vasodilators for group 3 pulmonary hypertension is still unknown, and it is currently associated with a poor prognosis. The mechanisms by which pulmonary hypertension occurs include hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, a decrease in pulmonary vascular beds, endothelial dysfunction, endothelial-to-mesenchymal transition, mitochondrial dysfunction, oxidative stress, hypoxia-inducible factors (HIFs), inflammation, microRNA, and genetic predisposition. Among these, hypoxic pulmonary vasoconstriction and subsequent pulmonary vascular remodeling are characteristic factors involving the pulmonary vasculature and are the focus of this review. Several factors have been reported to mediate vascular remodeling induced by hypoxic pulmonary vasoconstriction, such as HIF-1α and mechanosensors, including TRP channels. New therapies that target novel molecules, such as mechanoreceptors, to inhibit vascular remodeling are awaited. Full article

Background: Treprostinil, which is administered via continuous subcutaneous or intravenous infusion, is a medication applied in the treatment of pulmonary arterial hypertension (PAH). The dose of treprostinil is adjusted on an individual basis for each patient. A number of factors determine how well patients respond to treatment. Objectives: The aim of this study was to identify factors that may influence the clinical response to the dose of treprostinil at 3 months after the start of therapy. Methods: The factors influencing treatment response were analyzed in consecutive PAH patients who started receiving treprostinil treatment. The treatment efficacy was assessed as improvement in 6 min walk distance (6MWD) and WHO functional class (WHO FC), a reduction in N-terminal prohormone of brain natriuretic peptide (NTproBNP), and the percentage of patients achieving low-risk status after 12 months of treatment. Results: A total of 83 patients were included in this analysis. Classification of patients according to the tertiles of treprostinil dose achieved at 3 months after drug inclusion shows that after 12 months of follow-up, the median WHO FC in the highest dose group was lower than that in the intermediate dose group (WHO FC II vs. WHO FC III, p = 0.005), the median NTproBNP was lower (922 pg/mL, vs. 1686 pg/mL, p = 0.036) and 6MWD was longer (300 m vs. 510 m, p = 0.015). The French Noninvasive Criteria (NIFC) scale score was higher (2 vs. 0, p = 0.008), and the Reveal scale score was lower (5.0 vs. 8.5, p = 0.034). In the group of patients who exceeded a dose of 19.8 ng/kg/min within 3 months, an improvement in 6MWD was observed significantly more often after one year of therapy, and they were more likely to show an increase in NIFC scale scores after one year of therapy than the group of patients who received the lower dose (65% vs. 30%, p = 0.02). In the group of patients younger than 50 years of age, a statistically significant correlation was observed between the dose of treprostinil achieved after three months of treatment and the parameters assessed after 12 months of treatment, including WHO FC, 6MWD, and NIFC prognostic scale scores (all p < 0.05). Conclusions: The clinical effect of treatment is critically dependent on the rapid escalation of the treprostinil dose during the first three months of treatment. Full article

Background/Objectives: Patients on chronic anticoagulation undergoing metabolic surgery represent an increased risk of complications, including both bleeding and thrombotic events, such as deep vein thrombosis (DVT) and pulmonary embolism (PE). The optimal perioperative management of patients who are receiving chronic anticoagulation therapy (CAT) is complex. In the colorectal surgery literature, patients on CAT have a 10% rate of peri-procedural bleeding and a 3% rate of thromboembolism. The aim of this study was to evaluate and compare the safety and postoperative outcomes between patients with and without CAT undergoing Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at a tertiary referral center in the United Arab Emirates (UAE). Methods: All patients who underwent primary bariatric surgery between September 2015 and July 2019 were retrospectively reviewed. The first group included patients with CAT, and the second group included patients without CAT. Demographics, perioperative outcomes, and postoperative results were examined. Results: Our study included 542 patients, 22 (4%) with CAT and 520 (96%) without CAT. Mean age was 46.3 ± 10.5 years in the CAT group and 36.0 ± 11.7 years in the non-CAT group (p < 0.001); median BMI was 41.8 (range 33.1–61.3) and 42.7 (range 30.1–78.4) kg/m², respectively (p = 0.52). The CAT group had significantly higher rates of hypertension (77.2% vs. 32.5%, p < 0.001), obstructive sleep apnea (81.8% vs. 31.5%, p < 0.001), and coronary artery disease (31.8% vs. 2.8%, p < 0.001). In the CAT group, 8/22 (36.4%) patients underwent Roux-en-Y gastric bypass and 14/22 (63.6%) sleeve gastrectomy, compared to 228/520 (43.8%) and 292/520 (56.2%), respectively, in the non-CAT group (p = 0.51). There were no statistically significant differences in postoperative emergency department (ED) visits (18.1% vs. 24.2%, p = 0.51), early major complications (4.5% vs. 3.4%, p = 0.54), readmission rates within 30 days (4.5% vs. 3.6%, p = 0.56), or late complications (4.5% vs. 4.2%, p = 0.60). Mean length of stay was significantly longer in the CAT group (4.6 vs. 2.6 days, p < 0.001). The mean follow-up was 10 ± 7.3 months for the CAT cohort and 11 ± 9.7 months for the non-CAT cohort (p = 0.22). Weight loss outcomes at 12 months were comparable, with a percent total body weight loss (TBWL) of 27.0 ± 7.3% in the CAT group and 28.9 ± 8.3% in the non-CAT group (p = 0.29). There were no deaths in either group. Conclusions: In this series, at a tertiary referral center in the UAE, metabolic surgery is safe for CAT patients. Multidisciplinary preoperative preparation might be warranted to avert potential complications. Full article

The pathophysiology of pulmonary hypertension is complex and multifactorial. It is a disease characterized by increased pulmonary vascular resistance at the level due to sustained vasoconstriction and remodeling of the pulmonary arteries, which triggers an increase in the mean pulmonary artery pressure and subsequent right ventricular hypertrophy, which in some cases can cause right heart failure. Hypoxic pulmonary hypertension (HPH) is currently classified into Group 3 of the five different groups of pulmonary hypertensions, which are determined according to the cause of the disease. HPH mainly develops as a product of lung diseases, among the most prevalent causes of obstructive sleep apnea (OSA), chronic obstructive pulmonary disease (COPD), or hypobaric hypoxia due to exposure to high altitudes. Additionally, cardiometabolic risk factors converge on molecular mechanisms involving overactivation of the mammalian target of rapamycin (mTOR), which correspond to a central axis in the development of HPH. The aim of this review is to summarize the role of mTOR in the development of HPH associated with metabolic risk factors and its therapeutic alternatives, which will be discussed in this review. Full article

(1) Background: Pulmonary hypertension (PH) increases pulmonary vascular resistance and right ventricular (RV) afterload. Assessment of RV systolic function in PH using RV fractional area change (RV FAC) as a marker directly correlates with mortality and the need for extracorporeal membrane oxygenation (ECMO). However, few studies have assessed neurodevelopmental outcomes. We hypothesize that cardiac RV systolic dysfunction with lower RV FAC is associated with worse neurodevelopmental impairment (NI). (2) Methods: Retrospective study of 42 subjects with PH to evaluate neurodevelopmental outcomes in the first two years of life based on (i) subjective assessment of RV systolic function and (ii) RV FAC, a specific echocardiographic marker for RV function. (3) Results: Subjects from the initial study cohort (n = 135) with PH who had long-term follow-up were divided into RV dysfunction (study, n = 20) and non-RV dysfunction (control, n = 22) groups. RV FAC in the study vs. control group (0.18 vs. 0.25) was lower (p = 0.00017). There was no statistically significant difference in NI either with RV dysfunction or lower RV FAC. Although not significant, RV dysfunction was associated with longer mean duration of mechanical ventilation, time on ECMO, and length of stay. In the initial cohort (135), mortality was 16.3% and the percentage of NI was 62%. (4) Conclusions: Neonatal pulmonary hypertension is associated with a high degree of neurodevelopment impairment. Early RV systolic dysfunction, as identified by RV FAC, was not an optimal predictive biomarker for infants with PH and neurodevelopmental impairment. Full article

Group-based trajectory modeling (GBTM) allows the trajectory analyses of repeated N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements during follow-up visits of pulmonary artery hypertension associated with connective tissue disease (CTD-PAH) patients. This study aimed to (1) identify trajectories of NT-proBNP changing over time, (2) explore the association between NT-proBNP trajectories and prognosis, and (3) explore the effects of baseline clinical characteristics on NT-proBNP trajectories. A retrospective, single-centred, observational study was performed on 52 CTD-PAH patients who had undergone at least three follow-up visits within 1 year from baseline. Four NT-proBNP trajectories were identified using GBTM: low stability (n = 15, 28.85%), early remission (remission within 3 months) (n = 20, 38.46%), delayed remission (remission after 6 or 9 months) (n = 11, 21.15%), and high stability (n = 6, 11.54%). The low-stability and early-remission trajectories were related to a similar positive prognosis, while the delayed-remission and high-stability trajectories were associated with a gradually worsening prognosis (p = 0.000). Intensive CTD immunotherapy (corticosteroids plus immunosuppressants) was the only factor that remained significant after least absolute shrinkage and selection operator regression and multivariate logistic regression, and was independently associated with a lower risk NT-proBNP trajectory (p = 0.048, odds ratio = 0.027, 95% confidence interval: 0.001–0.963), which preliminarily indicated a benefit of CTD-PAH patients undergoing intensive CTD immunotherapy. Full article