Search Results (260)

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

The right heart–pulmonary circulation unit (RH-PCU) constitutes an integrated anatomo-functional system characterized by high-volume blood flow, low intravascular pressure, and minimal pulmonary vascular resistance. The RH-PCU dysfunction is a challenge for clinicians, as it can result from numerous pathological conditions, each with different clinical presentations. The pathophysiological changes underlying the hemodynamic alterations in the pressure and volume affecting the right ventricle can lead the patient to present with the primary symptom: dyspnea. We review the clinical presentation, the laboratory test, and the role of multimodality imaging in the evaluation of the disfunction of the RHPCU, including echocardiography, stress echocardiography, computed tomography, magnetic resonance imaging, nuclear imaging, and invasive pressure measurement through catheterization. We therefore aimed to describe the various diagnostic options available to clinicians, evaluating their effectiveness and limitations of use. Full article

Pulmonary arterial hypertension (PAH) is a rare, progressive, and incurable disease characterized by an elevated pulmonary blood pressure, extensive remodeling of the pulmonary vasculature, increased pulmonary vascular resistance, and culminating in right ventricular failure. Mitochondrial dysfunction has a major role in the pathogenesis of PAH and secondary right ventricular failure, and its targeting may offer therapeutic benefit. In this study, we provide proof-of-concept for the use of the mitochondrially active drug SUL-150 to treat PAH. PAH was induced in rats by monocrotaline, followed by the placement of an aortocaval shunt one week later. The mitoprotective compound SUL-150 (~6 mg·kg⁻¹·day⁻¹) or vehicle was administered intraperitoneally via osmotic minipump for 28 days, implanted at the time of aortocaval shunt placement. Vehicle-treated PAH rats had dyspnea and showed pulmonary artery remodeling with increased responsiveness to phenylephrine, in addition to remodeling of the intrapulmonary arterioles. SUL-150 administration mitigated the dyspnea and the remodeling responses. Vehicle-treated PAH rats developed right ventricular hypertrophy, fibrosis, and failure. SUL-150 administration precluded cardiomyocyte hypertrophy and inhibited ventricular fibrogenesis. Right ventricular failure in vehicle-treated PAH rats induced mitochondrial loss and dysfunction associated with a decrease in mitophagy. SUL-150 was unable to prevent the mitochondrial loss but improved mitochondrial health in the right ventricle, which culminated in the preservation of right ventricular function. We conclude that SUL-150 improves PAH-associated morbidity by the amelioration of pulmonary vascular remodeling and right ventricular failure and may be considered a promising therapeutic candidate to slow disease progression in pulmonary arterial hypertension and secondary right ventricular failure. Full article

Protein S-nitrosylation is a selective post-translational modification in which a nitrosyl group is covalently attached to the reactive thiol group of cysteine, forming S-nitrosothiol. This modification plays a pivotal role in modulating physiological and pathological cardiovascular processes by altering protein conformation, activity, stability, and other post-translational modifications. It is instrumental in regulating vascular and myocardial systolic and diastolic functions, vascular endothelial cell and cardiomyocyte apoptosis, and cardiac action potential and repolarization. Aberrant S-nitrosylation levels are implicated in the pathogenesis of various cardiovascular diseases, including systemic hypertension, pulmonary arterial hypertension, atherosclerosis, heart failure, myocardial infarction, arrhythmia, and diabetic cardiomyopathy. Insufficient S-nitrosylation leads to impaired vasodilation and increased vascular resistance, while excessive S-nitrosylation contributes to cardiac hypertrophy and myocardial fibrosis, thereby accelerating ventricular remodeling. This paper reviews the S-nitrosylated proteins in the above-mentioned diseases and their impact on these conditions through various signaling pathways, with the aim of providing a theoretical foundation for the development of novel therapeutic strategies or drugs targeting S-nitrosylated proteins. 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

Pulmonary hypertension (PH) is broadly defined as a mean pulmonary arterial pressure (mPAP) exceeding 20 mm Hg at rest. Pulmonary arterial hypertension (PAH) is a specific subset of PH characterized by a normal pulmonary arterial wedge pressure (PAWP), combined with elevated mPAP and increased pulmonary vascular resistance (PVR), without other causes of pre-capillary hypertension such as lung diseases or chronic thromboembolic pulmonary hypertension. The majority of PAH cases are idiopathic; other common etiologies include connective tissue disease-associated PAH, congenital heart disease, and portopulmonary hypertension. To a lesser extent, genetic and familial forms of PAH can also occur. The pathophysiology of PAH involves the following four primary pathways: nitric oxide, endothelin-1, prostacyclin, and activin/bone morphogenetic protein (BMP). Dysregulation of these pathways leads to a progressive vasculopathy marked by vasoconstriction, vascular proliferation, elevated right heart afterload, and ultimately right-sided heart failure. Diagnosing PAH is challenging and often occurs at advanced stages. The gold standard for diagnosis remains invasive right heart catheterization. Along with invasive hemodynamic measurements, several noninvasive imaging modalities such as echocardiography and ventilation-perfusion scanning are key adjunct techniques. Also, recent advancements in cardiac magnetic resonance (CMR) have opened a new era for PAH management. Additionally, CMR and echocardiography not only enable diagnosis but also aid in evaluating disease severity and monitoring treatment responses. Current PAH treatments focus on targeting molecular pathways, reducing inflammation, and inhibiting right-sided heart failure. Integrating imaging with basic science techniques is crucial for enhanced patient diagnosis, and precision medicine is emerging as a key strategy in PAH management. Additionally, the incorporation of artificial intelligence into both molecular and imaging approaches holds significant potential. There is a growing need to integrate new imaging modalities with high resolution and reduced radiation exposure into clinical practice. In this review, we discuss the molecular pathways involved in PAH, the imaging modalities utilized for diagnosis and monitoring, and current targeted therapies. Advances in molecular understanding and imaging technologies, coupled with precision medicine, could hold promise in improving patient outcomes and revolutionizing the management of PAH patients. 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

Background: Pulmonary arterial hypertension (PAH) is a rare and severe condition characterized by increased pulmonary arterial pressure and vascular resistance. Women are more susceptible to PAH yet have higher survival rates than men, a phenomenon called the “estrogen paradox”. This study aims to investigate the sex-based differences in PAH using plasma untargeted metabolomics. Methods: Plasma samples were collected from 43 PAH patients and 37 healthy controls. The samples were analyzed using two complementary analytical techniques: gas chromatography–mass spectrometry (GC-QqQ/MS) and liquid chromatography–mass spectrometry (LC-Q-ToF/MS). The metabolic differences between male and female PAH patients and controls were identified using multivariate statistical analyses. Results: Our results show changes in the lipid, fatty acid, and amino acid metabolism in both sexes. Women presented additional changes in the carbohydrate, bile acid, and nucleotide metabolism. The metabolites affected by PAH in women included decreased threonine, tryptophan, and lipid intermediates and elevated bile acids. Men were found to have additional changes in the heme catabolism, cholesterol synthesis, and lipoxygenase pathways. The metabolites affected by PAH in men included decreased branched-chain amino acids and increased bilirubin, phospholipids, and oxidized fatty acids. Conclusions: The gender differences observed in the development of PAH are likely multifactorial. While estrogens and potentially other sex hormones have been implicated in modulating relevant biological pathways, their exact role in disease progression and pathogenesis remains to be fully elucidated. The specific metabolic changes in women and men point to distinct disease mechanisms, potentially explaining the differences in prevalence, prognosis, and treatment response of patients with PAH. The obtained results should be validated with the use of targeted quantitative analyses and larger numbers of patients. Full article

Background: Pulmonary hypertension (PHT) is a rare but serious condition in children, requiring early diagnosis to prevent right ventricular failure. Non-invasive imaging modalities such as computed tomography angiography (CTA) have gained importance in assessing vascular changes, including main pulmonary artery (MPA) dilatation, increased vessel stiffness, and elevated pulmonary vascular resistance, which are characteristic of pulmonary hypertension (PHT). Objective: This study aimed to evaluate the diagnostic value of the main pulmonary artery-to-ascending aorta (MPA/AA) and main pulmonary artery-to-descending aorta (MPA/DA) ratios on CTA in pediatric patients with confirmed PHT. Methods: In this retrospective cohort study, 76 pediatric patients who underwent both cardiac catheterization and thoracic CTA were included. Patients were divided into PHT (mean pulmonary artery pressure ≥ 25 mmHg) and non-PHT groups. Vascular measurements were obtained from CTA, and MPA/AA and MPA/DA ratios were calculated. Statistical analyses included Mann–Whitney U tests and ROC curve analysis. Results: The MPA diameter and MPA/AA and MPA/DA ratios were significantly higher in the PHT group compared to controls (p < 0.05). ROC analysis showed strong diagnostic performance for both ratios. The MPA/DA ratio had an AUC of 0.927 with 78.5% sensitivity and 94% specificity at a cut-off value of 1.85. The MPA/AA ratio had an AUC of 0.896 with 76.5% sensitivity and 95% specificity at a cut-off value of 1.25. Conclusions: Both MPA/AA and MPA/DA ratios are reliable non-invasive indicators of pediatric PHT, with the MPA/DA ratio demonstrating slightly higher diagnostic accuracy. These findings support the use of CTA-derived vascular ratios, especially MPA/DA, as effective screening tools in clinical practice. Full article

Background/Objectives: Persistent pulmonary hypertension of the newborn (PPHN) is characterized by increased pulmonary vascular resistance, resulting in severe hypoxemia. This study determined the factors associated with increased risk of mortality and survival rate in infants with PPHN. Methods: This retrospective study was conducted between 2010 and 2023. The risk factors for mortality were assessed by Cox’s proportional hazard models, and the Kaplan–Meier survival curve was used to analyze the survival rates. Results: This study included 233 neonates with PPHN. Gestational age (GA) less than 28 weeks (adjusted hazard ratio [AHR] = 5.46, 95% confidence interval [CI]: 2.25–13.24, p < 0.001), Small for gestational age (SGA) (AHR = 2.93, 95% confidence interval [CI]: 1.24–6.92, p = 0.026), acute kidney injury (AKI) (AHR = 2.48, 95% CI: 1.27–4.84, p = 0.01), pneumothorax (AHR = 3.03, 95% confidence interval [CI]: 1.48–6.21, p = 0.003), vasoactive-inotropic score (VIS) at 24 h of age (AHR = 1.0026, 95% confidence interval [CI]: 1.0004–1.005, p = 0.026), and score for neonatal acute physiology II (SNAP-II) ≥ 43 (AHR = 4.03, 95% CI: 1.66–9.77, p = 0.005) were associated with an increased risk of mortality. The overall survival rate was 82.4%; it rose from 63.8% to 87.1% after inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO) were introduced (p < 0.001). The cumulative survival rates at the end of the 30 days were 62.1% (95% CI: 49.0–78.7) in the Pre-iNO era and 87.5% (95% CI: 82.7–92.6) in the Post-iNO/ECMO era, respectively (p < 0.001). Conclusions: GA less than 28 weeks, SGA, AKI, pneumothorax, high VIS and SNAP-II scores were associated with mortality in infants with PPHN. The improvement in the survival rate was related to the provision of advanced care, including iNO and ECMO therapy. Full article

Pulmonary hypertension (PH) can develop from multiple etiologic mechanisms and disease states. Of all such conditions, left-sided heart disease (LHD) is commonly understood to be the most common etiology or mechanism. Given the widespread prevalence of left heart disease and the prognostic implications of PH, early diagnosis is imperative. More recently, the diagnostic cut-offs for mean pulmonary arterial pressure as well as peripheral vascular resistance have been lowered to achieve this objective. Despite these revised standards, the current indications for right heart catheterization are mostly aimed at identifying advanced disease. Proven vasodilator therapies for pulmonary arterial hypertension have so far not shown a meaningful role in the management of PH in LHD. This is largely related to the fact that multiple mechanisms and co-morbidities can independently lead to the development of PH in an individual patient. Understanding and identifying those phenotypes remain important in devising future treatment strategies. Molecular pathways that eventually lead to irreversibility of PH can provide another frontier in the pharmacologic management of PH in LHD. Full article

Background: The HeartMate 3 (HM3) left ventricular assist device (LVAD) has demonstrated improved clinical outcomes in patients with advanced heart failure (HF). However, the influence of underlying HF etiology—ischemic cardiomyopathy (ICM) versus dilated cardiomyopathy (DCM)—on post-implantation outcomes remains insufficiently characterized. Objectives: This paper aims to evaluate early postoperative outcomes following HM3 LVAD implantation in patients with ICM versus DCM and to identify the preoperative hemodynamic and clinical predictors of early mortality and hemodynamic instability. Methods: We conducted a retrospective single-center cohort study of 30 patients who underwent HM3 LVAD implantation between 2017 and 2024. Patients were stratified by HF etiology (ICM, n = 17; DCM, n = 13), and preoperative clinical, echocardiographic, and right heart catheterization data were analyzed. The primary endpoint was 30-day postoperative survival. Secondary endpoints included postoperative hemodynamic stability and the need for vasopressor support. Results: Non-survivors (n = 13) demonstrated elevated central venous pressure (>16.5 mmHg), mean right ventricular pressure (>31.5 mmHg), and pulmonary vascular resistance (>7.5 Wood units), in addition to higher preoperative creatinine levels and longer cardiopulmonary bypass times. Vasopressor requirement postoperatively was associated with elevated pre-implant systolic pulmonary artery pressure. Conclusions: Preoperative right-sided pressures and renal dysfunction are strong predictors of early mortality following HM3 LVAD implantation. Patients with ICM exhibit greater early left ventricular recovery compared to those with DCM. These findings underscore the importance of comprehensive and personalized preoperative risk stratification—particularly in patients with DCM and pulmonary hypertension—to optimize postoperative outcomes and guide patient selection for durable LVAD support. Full article

Introduction: Among aortic diseases in children, congenital defects such as coarctation of the aorta (CoA), interrupted aortic arch (IAA), hypoplastic aortic arch (HAA), and hypoplastic left heart syndrome (HLHS) predominate. Tissue patches are applied in pediatric cardiovascular surgery for the repair of congenital aortic defects as a filling material to replenish missing tissue or as a substitute material for the complete reconstruction of the vascular wall along the course of the vessel. This retrospective single-center study aimed to present the safety and feasibility of extracellular matrix (ECM) biological scaffolds in pediatric aortic surgery. Patients and methods: There were 26 patients (17 newborns and nine children), who underwent surgical procedures in the Department of Pediatric Cardiac Surgery (Poznań, Poland) between 2023 and 2024. The patients’ population was divided into two subgroups according to the hemodynamic nature of the primary diagnosis of the congenital heart defect and the performed pediatric cardiovascular surgery. The first group included 18 (72%) patients after aortic arch repair for interrupted aortic arch and/or hypoplastic aortic arch, while the second group included seven (28%) patients after aortopulmonary anastomosis. In the first group, patches were used to reconstruct the aortic arch by forming an artificial arch with three separate patches sewn together, primarily addressing the hypoplastic or interrupted segments. In the second group, patches were applied to augment the anastomosis site between the pulmonary trunk and the aortic arch, specifically at the connection points in procedures, such as the Damus–Kaye–Stansel or Norwood procedures. The analysis was based on data acquired from the national cardiac surgery registry. Results: The overall mortality in the presented group was 15%. All procedures were performed using median sternotomy with a cardiopulmonary bypass. The cardiopulmonary bypass (CPB) and aortic cross-clamp (AoX) median times were 144 (107–176) and 53 (33–79) min, respectively. There were two (8%) cases performed in deep hypothermic circulatory arrest (DHCA). The median postoperative stay in the intensive care unit (ICU) was 284 (208–542) h. The median mechanical ventilation time was 226 (103–344) h, including 31% requiring prolonged mechanical ventilation support. Postoperative acute kidney failure requiring hemodiafiltration (HDF) was noticed in 12% of cases. Follow-up data, collected via routine transthoracic echocardiography (TTE) and clinical assessments over a median of 418 (242.3–596.3) days, showed no evidence of patch-related complications such as restenosis, aneurysmal dilation, or calcification in surviving patients. One patient required reintervention on the same day due to a significantly narrow ascending aorta, unrelated to patch failure. No histological data from explanted patches were available, as no patches were removed during the study period. The median (Q1–Q3) hospitalization time was 21 (16–43) days. Conclusions: ProxiCor^® biological patches derived from the extracellular matrix can be safely used in pediatric patients with congenital aortic arch disease. Long-term follow-up is necessary to confirm the durability and growth potential of these patches, particularly regarding their resistance to calcification and dilation. Full article

Nitric oxide (NO), an endogenous vasodilator, has been proposed as a biomarker for pulmonary hypertension (PH) in humans. NO is synthesized by endothelial nitric oxide synthase (eNOS). Alterations in NO/eNOS have not been studied in dogs with PH. We assessed alterations in NO and eNOS in the blood of dogs with PH (n = 17) and healthy dogs (n = 10) and analyzed their correlations with echocardiographic parameters. The results showed significantly higher plasma NO and serum eNOS levels in dogs with PH compared with healthy dogs. Dogs with PH and ascites (n = 11) had significantly lower plasma NO levels than those without ascites (n = 6) and presented a decreasing eNOS trend. In dogs with PH, plasma NO was positively correlated with left ventricular hemodynamics, right ventricular compliance, and pulmonary distensibility, but was negatively correlated with pulmonary vascular resistance and right cardiac remodeling. Serum eNOS was positively correlated with the main pulmonary artery diameter. Increments in NO/eNOS reflected compensatory responses to cardiovascular changes in PH. These compensations were downward in the advanced stages. Other factors may also impact NO/eNOS compensation. Although the role of NO/eNOS as biomarkers for PH in dogs remains equivocal, they may indicate compensatory consequences of cardiovascular alterations. Full article

Introduction: Placebo-controlled studies are crucial in clinical trials, but the placebo effect can vary across conditions. We aimed to assess the placebo effect in chronic thromboembolic pulmonary hypertension (CTEPH) trials. Methods: We conducted a systematic review and included randomized placebo-controlled trials investigating CTEPH interventions. Primary outcomes were the pre–post changes in the 6 min walk test (6MWT) and quality of life in the placebo arms. Secondary outcomes included mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index, and NT-proBNP levels. Meta-analyses were performed using random-effects models. Results: Seven trials with 270 CTEPH patients in placebo arms were analyzed. The average 6MWT change was not significant (−1.31 m; 95%CI −12.49 to +9.79). Quality of life with EQ-5D was not significantly improved (−0.04; 95%CI −0.10 to +0.02). mPAP, PVR, cardiac index, and NT-proBNP also demonstrated non-significant changes with small magnitudes. Conclusions: The placebo effect in CTEPH trials was not statistically significant and had small magnitude but should not discourage the use of placebo-controlled trials where applicable and ethical. Full article