Search Results (204)

Background and Clinical Significance: Pulmonary hypertension (PH) is a recognized complication of chronic liver disease, most commonly manifesting as portopulmonary hypertension (POHP) prior to liver transplantation. While the natural history and management of pre-transplant PH are well described, the development of de novo pulmonary arterial hypertension (PAH) following liver transplantation remains exceedingly rare and poorly understood. In such cases, establishing true causality is challenging, and alternative explanations—including previously unrecognized or masked disease—must be carefully considered. This entity poses significant diagnostic and therapeutic challenges and may adversely affect post-transplant outcomes if not promptly recognized and treated. Case Presentation: We report the case of a 46-year-old man with end-stage liver disease secondary to alcohol use who underwent deceased donor liver transplantation without preoperative evidence of PH. His pre-transplant evaluation revealed preserved biventricular function and no measurable PH. Eight days postoperatively, he was readmitted with acute dyspnea, hypoxemia, and signs of right ventricular failure. Transthoracic echocardiography demonstrated severe right ventricular dilation and dysfunction with markedly elevated pulmonary artery systolic pressure. Right heart catheterization confirmed severe PAH. Secondary causes of PH were excluded. The patient was initiated on sildenafil and continuous intravenous epoprostenol, resulting in clinical, echocardiographic, and hemodynamic improvement. Subsequent follow-up demonstrated sustained response to therapy despite concurrent progression of coronary artery disease requiring complex percutaneous intervention. Conclusions: This case highlights a rare presentation of severe PAH occurring shortly after liver transplantation, in the absence of documented pre-transplant PH. While a causal relationship cannot be definitively established, the temporal association raises important clinical considerations. It underscores the need for heightened clinical vigilance for pulmonary vascular disease in post-transplant patients presenting with cardiopulmonary symptoms. Further research is warranted to elucidate the underlying mechanisms, risk factors, and optimal management strategies for PAH diagnosed after liver transplantation. Full article

Background/Objectives: Pulmonary arterial hypertension (PAH) impacts various aspects of patients’ lives. Some questionnaires assessing health-related quality of life are specific to PAH patients. The aims of the study were to translate and investigate the factor structure and psychometric properties of the Polish version of the EmPHasis-10 health-related quality of life questionnaire in a group of adults with PAH. Construct validity was explored by the relationship with results of the 36-Item Short Form Survey (SF-36) and non-invasive prognostic factors: WHO functional class, 6 min walk distance (6MWD) and NTproBNP level were measured. Methods: In a single-center study, PAH patients were included. The diagnosis of PAH was confirmed by right heart catheterization. The demographic and clinical data were obtained. The EmPHasis-10 and the SF-36 questionnaires were administered to all patients. Results: Data from 120 PAH patients, median age 57 (IQR 45–68.7) years, 88 (73%) women, were obtained. Most of the patients suffered from IPAH (73, 61%). Results revealed a unidimensional structure of the EmPHasis-10 questionnaire and demonstrated satisfactory reliability (Cronbach α = 0.94). The EmPHasis-10 showed an adequate relationship with both SF-36 dimensions and three non-invasive prognostic parameters, i.e., WHO functional class, 6MWD and NTproBNP level. Regression analysis indicated that the 6MWD was the only predictor of the EmPHasis-10. Conclusions: The obtained results showed very good psychometric properties and adequate internal consistency of the Polish version of EmPHasis-10 in PAH patients. The results showed a unidimensional structure and very good psychometric properties, including satisfactory internal consistency and external validity of the Polish version of the EmPHasis-10 scale in patients with PAH. Full article

Background: Peripheral muscle dysfunction in chronic heart failure (CHF) potentiates hemodynamic insufficiency through neuroendocrine activation and deterioration of myocardial perfusion. Objectives: The aim of this study was to compare skeletal muscle strength in patients on the heart transplant (HT) waiting list and in patients undergoing cardiac surgery and to identify associations between muscle status and clinical and instrumental parameters. Methods: This study included 152 patients divided into two groups: Group I (n = 30)—candidates for HT; Group II (n = 122)—patients undergoing cardiac surgery. A comprehensive clinical and anamnestic assessment and instrumental diagnostics were performed. Muscle status was assessed using a Lafayette MMT01165 isokinetic dynamometer (knee and foot extensor/flexor strength) and a DK 100 dynamometer (handgrip strength). Echocardiographic parameters were assessed in the study groups; in the HT group, cardiac catheterization and volumetric sphygmography data were used. Results: Group HT had a higher proportion of men (p = 0.042) and a higher revascularization rate (p ≤ 0.027) compared with Group II. Patients in Group I had enlarged left and right heart diameters and critically low left ventricular ejection fraction (LVEF) (22%; p < 0.001). Group HT showed a significant decrease in lower extremity muscle strength compared with Group II (p < 0.001). The only independent predictors of knee extensor muscle strength were echocardiographic parameters (right atrial volume index, TAPSE, and LVEF/end diastolic volume). No association was found between knee extensor strength and the strength of other muscle groups studied. Conclusions: Patients on the HT waiting list had significant lower extremity muscle weakness compared with preoperative patients. The only independent predictors of knee extensor muscle strength were echocardiographic parameters. Knee extensor muscle strength was associated only with contralateral muscle strength, but not with other muscle groups. These results will facilitate the development and evaluation of personalized rehabilitation programs for patients on the heart transplant waiting list. Full article

Pulmonary hypertension associated with interstitial lung disease (PH-ILD) is a progressive condition with limited treatment options and associated with high mortality rates. Inhaled treprostinil (iTre) is the only approved therapy for PH-ILD and has been shown to improve exercise capacity and delay disease progression. However, the conventional outpatient titration schedule requires 8–16 weeks to achieve therapeutic dosing, which may delay clinical benefit in those with advanced disease. We conducted a retrospective study of six patients with severe PH-ILD admitted to a tertiary academic center for initiation of iTre using a rapid inpatient uptitration protocol. iTre was started at 3 breaths four times daily (QID) and increased by 2 additional breaths every 12–24 h as tolerated, aiming for ≥9–12 breaths QID within one week under close monitoring. All six patients achieved target dosing without dose reduction or interruption. At three-month follow-up, mean pulmonary artery pressure decreased from 42 ± 5.5 to 35.2 ± 4.5 mmHg, pulmonary vascular resistance from 8.0 ± 1.2 to 6.0 ± 0.9 WU, and cardiac index increased from 2.05 ± 0.13 to 2.15 ± 0.12 L/min/m². No readmissions occurred within 90 days. This study demonstrates that rapid inpatient uptitration of iTre in severe PH-ILD is feasible and well-tolerated, with preliminary evidence of short-term hemodynamic improvement. Full article

Portopulmonary hypertension (PoPH) and hepatopulmonary syndrome (HPS) present two vascular complications of portal hypertension, which make opposite extremes occur against the same pathophysiological background. In PoPH, vasoconstriction predominates, along with gradual remodeling of pulmonary arteries, while HPS develops due to pathological vasodilation and creation of intrapulmonary shunts. Even though they come about by different mechanisms, both disorders significantly affect quality of life, survival, and the possibility of liver transplant. In the early phases, in clinical practice, symptoms are mainly mild and nonspecific, and overlapping with symptoms of advanced liver disease often delays forming a diagnosis. In PoPH, elevated pressures in pulmonary arteries and increased vascular resistance are observed, while HPS exhibits arterial hypoxemia with normal or lowered pulmonary pressure. Standard diagnostic workup includes echocardiography, right-heart catheterization, and analysis of the arterial gases. In patients with severe PoPH, pronounced pulmonary hypertension can represent absolute contraindication for liver transplantation due to risk of acute right heart failure during operation. Conversely, HPS usually resolves itself after a successful transplant, which confirms that the transplant is an indication of being potentially curative. Therapeutic possibilities for both states are still limited. In PoPH, specific vasodilators and supportive measures are applied, while HPS treatment is mostly supportive, directed at maintaining oxygenation until the transplant. Future research should be focused on the development of targeted therapies that address vascular remodeling, angiogenesis, and oxidative stress, as well as on the standardization of diagnostic criteria and multicentric cooperation. This approach would facilitate earlier recognition, a precise assessment of transplantability, and a better long-term outcome for patients with portal hypertension and lung vascular complications. Key Points: Portopulmonary hypertension (PoPH) and hepatopulmonary syndrome (HPS) represent two opposite vascular complications of portal hypertension, posing distinct challenges for liver transplantation. This review summarizes their pathophysiology, diagnostic pathways, and therapeutic strategies, emphasizing the importance of hemodynamic profiling and multidisciplinary management to optimize transplant outcomes. Full article

Background/Objectives: Measuring cardiac output (CO) is essential for diagnosis and therapeutic monitoring in pulmonary hypertension (PH). CO assessment based on thermodilution (TD) or Direct Fick (DF) during standard right heart catheterization (RHC) is impractical for regular follow-up. We evaluated the accuracy and agreement of non-invasive Modelflow (MF)-based CO assessment compared with TD and DF during rest and exercise RHC in PH. Methods: This post hoc analysis from a crossover RCT included 24 PH patients (7 females, 59 ± 14 years; mean pulmonary artery pressure 37 ± 11 mmHg) who underwent RHC with repetitive CO assessments at rest and during exercise. CO was measured by TD, DF, and non-invasive MF by fingertip pulse contour analysis at rest and during stepwise cycling to maximal exertion. Results: At rest, mean CO was comparable between methods: TD = 6.05 ± 1.80 L/min, DF = 5.68 ± 1.88 L/min, MF = 6.09 ± 1.84 L/min. At end-exercise, CO increased to TD = 11.18 ± 4.38 L/min, DF = 11.84 ± 4.74 L/min, MF = 8.38 ± 2.93 L/min. Bland–Altman showed minimal bias at rest (MF vs. TD: 0.04 L/min; MF vs. DF: −0.07 L/min) but substantial variability during exercise, with underestimation of CO by MF with increasing workloads (MF vs. TD bias = −2.80 L/min; MF vs. DF bias = −4.38 L/min). Limits of agreement were wide across all workloads. Linear regression confirmed an increasing CO with workload, but MF slope was shallower than TD/DF, suggesting proportional bias. Taffé analysis identified a significant differential (5.847) and proportional bias (0.195) indicative of CO overestimation by MF at low CO and underestimation at high CO. Conclusions: MF group-level agreement is acceptable, but individual-level accuracy is limited, indicating that MF may be suitable for trend monitoring but its applicability for clinical decision-making is restricted, especially during exercise. Full article

Background: Pulmonary arterial hypertension (PAH) leads to right ventricular failure and death. Inhaled treprostinil, a tricyclic benzindene prostacyclin analog, has become available, but evidence regarding its clinical efficacy and quality-of-life (QoL) benefits—particularly in patients already receiving optimized combination vasodilator therapy—remains limited. Methods: Inhaled treprostinil was introduced to nine patients with PAH already receiving combination therapy with pulmonary vasodilators. Acute hemodynamic effects were assessed during initial right heart catheterization, and long-term effects were evaluated at baseline and 3 months after treatment. Exercise tolerance was assessed by the 6-minute walking distance (6MWD) test and cardiopulmonary exercise testing, while QoL was evaluated using the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12). Results: Mean pulmonary arterial pressure significantly improved both acutely (48.9 ± 17.8 to 43.7 ± 14.5 mmHg, p = 0.036) and at 3 months (46.4 ± 16.1 to 39.8 ± 14.1 mmHg, p = 0.014). Pulmonary vascular resistance tended to decrease, while 6MWD outcomes remained unchanged. QoL improved, with KCCQ-12 overall and clinical summary scores increasing from 59.1 ± 27.4 to 67.1 ± 26.5 and 78.1 ± 26.3 to 87.5 ± 21.2, respectively. Conclusions: Treprostinil inhalation improved hemodynamics and patient-reported outcomes despite prior combination improved hemodynamics and tended to enhance QoL in patients with PAH receiving combination vasodilator therapy. Full article

Background: In patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension (summarized as pulmonary vascular disease; PVD), it is unclear whether the brain is protected against acute hypoxia and whether acute pulmonary vascular dilatation by sildenafil would influence cerebral and muscle tissue oxygenation whilst breathing normoxia or hypoxia. Methods: Adult patients with PVD underwent right heart catheterization, while cerebral and muscular tissue oxygenation and tissue hemoglobin index were measured using near-infrared spectroscopy along with arterial and mixed-venous blood gases. Participants underwent a four-stage protocol in which they were blinded to breathing either normoxia (FiO₂ 0.21) or normobaric hypoxia (FiO₂ 0.15), both before and after a single oral dose of sildenafil (50 mg) according to a randomized, cross-over design. Results: In 22 PVD patients (9 women, age 54 ± 14 y) under hypoxia, mean cerebral tissue oxygenation decreased by −2% (95% CI −4 to 0%, p = 0.046), muscular tissue oxygenation by −1% (95% CI −3 to 0%, p = 0.011) and mean arterial partial pressure of oxygen by −2.3 kPa (95% CI −2.7 to −1.8 kPa, p < 0.0001). Sildenafil improved the cerebral tissue hemoglobin index under hypoxia compared to hypoxia without sildenafil by 0.12 (95% CI 0.00 to 0.23, p = 0.049), but not the muscular tissue hemoglobin index. Conclusions: In PVD patients, acute exposure to normobaric hypoxia leads to a reduction in arterial oxygenation as well as cerebral and muscular tissue oxygenation. Sildenafil improves cerebral blood flow but has no effect on arterial, cerebral or muscular oxygenation. Full article

The prevalence of advanced heart failure (AdHF) is increasing globally, driven by population aging and improved survival rates in chronic heart failure (CHF). Durable Mechanical Circulatory Support (DMCS), particularly Left Ventricular Assist Devices (LVADs), has become a cornerstone in AdHF management. However, its successful implantation requires a comprehensive preoperative evaluation integrating cardiac, hemodynamic, and systemic assessments. Echocardiography and cardiac magnetic resonance (CMR) provide critical data for risk stratification—e.g., LV ejection fraction < 25%, LV end-diastolic diameter < 60 mm, or free wall RV longitudinal strain (fwRVLS) > −14% predict poorer outcomes. Right heart catheterization (RHC) identifies hemodynamic contraindications (PVR > 6 WU, PAPi < 1.5, cardiac index < 2 L/min/m²), while cardiopulmonary exercise testing (CPET) remains pivotal for assessing functional reserve (peak VO₂ < 12 mL/kg/min or <50% predicted). Systemic assessment must address renal, hepatic, oncologic, and psychiatric comorbidities that influence surgical risk. Integrating these multimodal data within a multidisciplinary framework—spanning cardiologists, cardiac surgeons, anesthesiologists, and psychologists—optimizes selection and outcomes for DMCS candidates. Full article

Distributive shock and acute respiratory distress syndrome (ARDS) are syndromes of profound pathophysiological complexity, each independently associated with high morbidity and mortality. When coexistent, they create a state of synergistic cardiopulmonary failure where conventional, protocolized management approaches are often insufficient. This review synthesizes current mechanistic insights into heart–lung interactions in distributive shock with ARDS, highlighting the central role of right ventricular–pulmonary arterial coupling and the dual impact of altered lung mechanics and vascular dysregulation. We examine the distinct hemodynamic implications of pulmonary versus extrapulmonary ARDS phenotypes, including their divergent effects on transpulmonary pressure, venous return, and right ventricular afterload, and emphasize the clinical relevance of mixed phenotypes. Advanced monitoring modalities—esophageal manometry, echocardiography, and, in select cases, pulmonary artery catheterization—are presented as essential tools for dynamic phenotyping and individualized titration of ventilatory and hemodynamic strategies. Building on these principles, we outline phenotype-directed approaches to ventilation, fluid and vasoactive therapy, and adjunctive interventions such as proning and extracorporeal support. Finally, we discuss knowledge gaps and future directions, underscoring the need for integrative technologies and phenotype-stratified trials to refine precision management. The nuanced integration of cardiopulmonary physiology into bedside decision-making represents a paradigm shift toward individualized, physiology-guided care for this high-risk population. Full article

Background: Arteriovenous fistula (AVF) in patients with end-stage renal disease (ESRD) can lead to high-output heart failure (HOHF). There is limited data on the incidence and outcomes of HOHF in patients with AVF. Objective: The main goal of our study was to determine the incidence and prevalence of HOHF [diagnosed via right heart catheterization (RHC)] in chronic kidney disease (CKD)/ESRD patients with AVF. We also aimed to evaluate the clinical determinants of the development of HOHF in this group. Methods: We conducted a retrospective cohort study at the University of Kansas Medical Center from January 2011 to December 2023. Patients with CKD/ESRD with AVF who underwent RHC after AVF creation were included in the study. HOHF was defined as a cardiac index (CI) ≥ 4.0 L/min/m², measured either with the Fick or the Thermodilution method. Bivariate and multivariable regression analyses were performed to identify independent predictors of HOHF in this population. Results: Out of 84 patients with AVF, 34 patients met established inclusion and exclusion criteria. Ten out of thirty-four patients (29.4%) developed HOHF. Hemoglobin (Hb) was significantly lower in the HOHF group than the non-HOHF group (10.16 vs. 11.52 g/dL; p = 0.02). Patients with HOHF had significantly elevated CI when compared with the non-HOHF group (CI Fick: 4.54 vs. 2.91 L/min/m², p < 0.001). Similar mortality was observed in the HOHF and non-HOHF groups. After multivariant regression analysis, Hb was an independent predictor of HOHF (HR 0.86, 95% CI: 0.76–0.98, p =< 0.01). Conclusions: HOHF is common in patients with AVF; nearly 1/3 (29.4%) of the patients developed HOHF, confirmed with RHC. Low Hb was found to be an independent predictor of HOHF. Further larger studies are needed to confirm these findings and establish an early detection protocol to detect and treat this condition. Full article

Background and Clinical Significance: Idiopathic pulmonary arterial hypertension is a rare disorder, often linked to genetic predisposition. Canonical pulmonary arterial hypertension genes such as BMPR2, KCNK3, and TBX4 are well described, but novel associations continue to emerge. Glomulin (GLMN) encodes a protein essential for vascular smooth-muscle biology, classically implicated in glomuvenous malformations, yet not previously associated with pulmonary arterial hypertension. Case Presentation: We present a 49-year-old woman with progressive dyspnea, edema, and persistent hypercapnic respiratory failure. Right-heart catheterization confirmed precapillary pulmonary hypertension. Comprehensive evaluation, including ventilation/perfusion scanning, autoimmune panel, polysomnography, and high-resolution computed tomography, excluded secondary causes. Respiratory assessment revealed diaphragmatic weakness and reduced respiratory muscle pressures, consistent with primary myopathy and explaining the unusual hypercapnic profile. Whole-genome sequencing identified a heterozygous pathogenic GLMN nonsense variant, while canonical pulmonary arterial hypertension genes were negative. No cutaneous or mucosal glomuvenous malformations were found. The patient was treated with oxygen therapy, diuretics, non-invasive ventilation, and dual oral pulmonary arterial hypertension therapy (ambrisentan and tadalafil), with stabilization but persistent hypercapnia. Conclusions: To our knowledge, this is the first reported co-occurrence of idiopathic pulmonary arterial hypertension and a pathogenic GLMN variant. While causality cannot be inferred, glomulin’s role in vascular smooth-muscle maturation provides a plausible link to pulmonary vascular remodeling. This case underscores the importance of assessing respiratory muscle function in idiopathic pulmonary arterial hypertension patients with hypercapnia and highlights the potential relevance of extended genetic testing in rare pulmonary vascular disease. Full article

Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is a life-threatening vascular complication of SSc, marked by high morbidity and mortality. Early diagnosis remains a major challenge due to nonspecific symptoms and the limitations of conventional tools such as echocardiography (ECHO), pulmonary function tests (PFTs), and serum biomarkers. This review evaluates the emerging role of artificial intelligence (AI), particularly machine learning (ML) and deep learning (DL), in improving the diagnostic landscape of SSc-PAH. A comprehensive literature search was conducted across PubMed, Scopus, IEEE Xplore, Embase and Google Scholar to identify studies involving AI applications in SSc, pulmonary arterial hypertension (PAH), and their intersection. Evidence indicates that AI models can assist interpretation across modalities, including heart sounds, ECGs, chest X-rays (CXRs), ECHOs, CT pulmonary angiography (CTPA), and omics-based biomarkers. While several models show encouraging diagnostic performance, their accuracy varies by dataset and modality, and most require external validation against right heart catheterization (RHC)-confirmed cohorts. Integrating multimodal data through AI frameworks may enhance early recognition and individualized risk stratification; however, these tools remain exploratory. Future work should emphasize harmonized hemodynamic definitions, transparent validation protocols, and SSc-specific datasets to ensure clinical applicability and reproducibility. Full article

Background: Pulmonary hypertension (PH) in newborns is a rare but serious condition and potentially life-threatening disorder, often initially confused with congenital heart disease due to overlapping echocardiographic findings in the late third trimester. Evidence on prenatal predictors of postnatal PH is limited. We aimed to describe detailed third-trimester echocardiographic findings associated with postnatal PH in infants with prenatally suspected CoA based on a retrospective case series. Methods: We reviewed 18 years of fetal echocardiography (2004–2022) in a tertiary maternal–fetal–neonatal center. We identified fetuses with suspected coarctation of the aorta (CoA) in late gestation who were delivered at term (≥37 weeks) and had prolonged neonatal hospitalization (>10 days) without cardiac surgery or catheterization. Z-scores for cardiac dimensions were calculated. All examinations were performed by experienced fetal cardiologists. Postnatal evaluations confirmed PH based on echocardiographic and clinical findings. Results: Among 19,836 fetuses examined, 138 were prenatally suspected of CoA. In 70 cases, this diagnosis was not confirmed postnatally (false positives). Of these, eight infants (0.04% of the total cohort) developed postnatal PH. Postnatally, all eight neonates required intensive care. Prenatal features included ventricular/atrial disproportion (7/8), cardiomegaly (8/8), main pulmonary artery dilatation (10.2 ± 2.2 mm; Z-score +2.7 ± 1.3), tricuspid regurgitation (8/8), pulmonary regurgitation (4/8), and interventricular septal hypertrophy (>4.5 mm in 5/8). Postnatal evaluations confirmed PH based on echocardiographic criteria (elevated right ventricular pressure, septal flattening/bowing, right ventricular dilation or dysfunction, and abnormal shunt direction) combined with clinical compromise. All infants received prostaglandin E1 (PGE1) initially; none required extracorporeal membrane oxygenation-ECMO. Three died, while five survived with medical management (oxygen, inhaled nitric oxide, sildenafil). Conclusions: Specific functional abnormalities on late third-trimester echocardiography may indicate impaired pulmonary vascular adaptation and predict postnatal PH, particularly in cases initially suspected of CoA. Recognition and awareness of these findings can guide delivery planning, neonatal surveillance, and timely intervention. Prospective multicenter studies are needed to validate these associations and refine prenatal screening protocols. Full article

Background: Schistosomiasis, HIV, and tuberculosis frequently lead to pulmonary hypertension in low- and middle-income countries. Lack of specific testing and limited access to right heart catheterization hamper confirmation of the etiology of pulmonary hypertension due to schistosomiasis. In addition, low health literacy and poor socioeconomic status further compromise prevention, early diagnosis, and treatment. Clinical algorithms for early screening, including hand-held echocardiography and point-of-care testing performed by non-specialists, are needed in rural Sub-Saharan Africa to decentralize care and improve outcomes. Methods: We describe a case of pulmonary hypertension diagnosed in a child living in Mozambique, to discuss the challenges for the diagnosis of infectious pulmonary arterial hypertension in rural settings in Africa, based on a short literature review. Full article