Search Results (1,969)

Chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) increasingly co-occur in low- and middle-income countries and aging populations. Prior pulmonary TB is a robust, smoking-independent determinant of COPD and is linked to persistent systemic inflammation, endothelial dysfunction, dyslipidemia, and hypercoagulability axes that also amplify cardiovascular disease (CVD) risk. We conducted a targeted narrative non-systematic review (2005–2025) of PubMed/MEDLINE, Embase, Scopus, and Web of Science, selecting studies for clinical relevance across epidemiology, clinical phenotypes, pathobiology, biomarkers, risk scores, sleep-disordered breathing, and management. No quantitative synthesis or formal risk-of-bias assessment was performed. Accordingly, findings should be interpreted as a qualitative synthesis rather than pooled estimates. Prior TB is associated with a distinctive COPD phenotype characterized by mixed obstructive–restrictive defects, reduced diffusing capacity (DLCO), radiographic sequelae, and higher exacerbation/hospitalization burden. Mechanistic insights: Convergent mechanisms chronic immune activation, endothelial injury, prothrombotic remodeling, molecular mimicry, and epigenetic reprogramming provide biologic plausibility for excess CVD, venous thromboembolism, and pulmonary hypertension. Multimarker panels spanning inflammation, endothelial injury, myocardial strain/fibrosis, and coagulation offer incremental prognostic value beyond clinical variables. While QRISK4 now includes COPD, it does not explicitly model prior TB or COPD-TB outcomes, but data specific to post-TB cohorts remain limited. Clinical implications: In resource-constrained settings, pragmatic screening, prioritized PAP access, guideline-concordant pharmacotherapy, and task-shifting are feasible adaptations. A history of TB is a clinically meaningful modifier of cardiopulmonary risk in COPD. An integrated, multimodal assessment history, targeted biomarkers, spirometry/lung volumes, DLCO, 6 min walk test, and focused imaging should guide individualized care while TB-aware prediction models and implementation studies are developed and validated in high-burden settings. Full article

Particulate matter (PM) is a significant contributor to air pollution-associated negative health effects, and cardiovascular disease patients are more susceptible to air pollution-mediated damage of the heart and vessels. The present study investigated the protective effects against PM-induced cardiovascular damage by classic cardiovascular drugs, as used for the standard therapy of cardiovascular disease patients. Male C57BL/6J mice were exposed to ambient PM_2.5 (<2.5 µm) for 3 days with or without treatment with the cholesterol-lowering drug atorvastatin (20 mg/kg/d) or the angiotensin-converting enzyme (ACE) inhibitor captopril (50 mg/kg/d). Both drugs mitigated PM_2.5-induced systolic blood pressure increases and partially prevented endothelial dysfunction, as reflected by a mixed effect on endothelial nitric oxide synthase phosphorylation. Both drugs ameliorated reactive oxygen species (ROS) formation and phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX-2) expression in the vasculature of PM_2.5-exposed mice. Pulmonary ROS levels showed a minor improvement by the treatments, whereas Nox2 mRNA expression was not diminished. Only captopril showed some anti-inflammatory effects in the heart and lung of PM_2.5-exposed mice, whereas both drugs failed to reduce systemic inflammation measured in plasma. These findings offer new insights into potential mitigation strategies for PM_2.5-induced cardiovascular complications, particularly for patients at higher cardiovascular risk, like those with coronary artery or ischemic heart disease or hypertension. Full article

The acute phase of pulmonary embolism (PE) may be a severe and potentially life-threatening condition. Moreover, long-term consequences following the acute phase can significantly impact a patient’s daily life. A systematic approach to PE follow-up can identify potential complications following acute PE. Post-PE syndrome (PPES) is a common occurrence among survivors experiencing persistent dyspnea and impaired functional status. While the exact definition is evolving, it encompasses a spectrum of disease phenotypes that may occur following an acute PE, which ranges from dyspnea, functional limitation, or cardiac impairment to chronic thromboembolic disease and chronic thromboembolic pulmonary hypertension. This review will describe the different PPES phenotypes, including their physiological basis, diagnosis and workup, and management following acute PE. Full article

Background: The tyrosine kinase inhibitors (TKIs) asciminib, bosutinib, dasatinib, imatinib, nilotinib, and ponatinib have been approved for chronic myelogenous leukemia (CML) therapy. However, pharmacovigilance reports associated with these drugs are neither consistent nor homogenous, with reports of pulmonary toxicity, which could limit their utilization. To better clarify TKIs’ pulmonary risk, we used the European database EudraVigilance to conduct a study on adverse events suspected to be caused by the TKIs asciminib, bosutinib, dasatinib, imatinib, nilotinib, and ponatinib when used for CML therapy. Methods: Suspected adverse reactions to TKIs in the EudraVigilance database (2020–2024) coming from European countries and the United Kingdom were analyzed and compared through a disproportionality analysis. Results: The most frequent alerts concerned the respiratory disorders “pleural effusion” (PE) and “pulmonary arterial hypertension” (PAH) in relation to dasatinib and bosutinib use. Among the TKIs, the prescription of dasatinib is associated with a higher occurrence of PE and PAH, while the prescription of bosutinib induces PE at a minor frequency that nonetheless carries a significant risk for PAH, occurring more often in women. Conclusions: The results indicate that respiratory disorders induced by the TKIs dasatinib and bosutinib need to be diagnosed in a timely manner, and suggest that caution should be taken when prescribing these TKIs to patients affected by CML and pulmonary comorbidities. Full article

Connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) is a severe form of pulmonary hypertension with poor prognosis. It most commonly arises in systemic sclerosis (SSc), followed by systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). Its pathogenesis involves a complex interplay of immune dysregulation, chronic inflammation, endothelial injury, vascular remodeling, and fibrosis. Although vasodilators targeting the endothelin, nitric oxide, and prostacyclin pathways remain the therapeutic backbone, newer agents—including the activin signal inhibitor sotatercept and inhaled treprostinil—have expanded treatment options. Immune-targeted therapies such as glucocorticoids, cyclophosphamide, mycophenolate mofetil, rituximab, and IL-6 receptor inhibitors may benefit inflammation-dominant PAH phenotypes, while fibrotic phenotypes continue to demonstrate limited responsiveness. In addition to brain natriuretic peptide (BNP), N-terminal (NT)-proBNP and disease-specific autoantibodies, emerging biomarkers show promise for early detection, risk stratification, and personalized treatment, though validation in CTD-PAH is lacking. Advances in animal models replicating immune-mediated vascular injury and fibrosis have further improved mechanistic understanding. Despite these developments, substantial unmet needs remain, including the absence of disease-specific therapeutic strategies, limited biomarker integration into clinical practice, and a scarcity of large, well-designed trials targeting individual CTD subtypes. Addressing these gaps will be essential for improving prognosis in patients with CTD-PAH. Full article

Pulmonary arterial hypertension (PAH) is a severe, progressive vasculopathy characterized by endothelial dysfunction, medial hypertrophy, and maladaptive vascular and cardiac remodelling that ultimately leads to right-heart failure and premature death. Despite advances in vasodilator therapies targeting endothelin, nitric oxide, and prostacyclin pathways, a substantial proportion of patients fail to achieve or maintain a low-risk profile, highlighting the need for disease-modifying strategies. Dysregulation of transforming growth factor-β (TGF-β) superfamily signalling, with excessive activin and growth differentiation factor activity and impaired bone morphogenetic protein signalling, plays a central role in PAH pathobiology. Sotatercept, a first-in-class activin signalling inhibitor, restores this imbalance by selectively trapping pro-proliferative ligands, thereby addressing a key molecular driver of pulmonary vascular remodelling. Evidence from pivotal phase II and III trials—PULSAR, STELLAR, ZENITH, and HYPERION—demonstrates that sotatercept significantly improves exercise capacity, haemodynamics, and risk status when added to background therapy. This review summarises the molecular mechanisms underlying sotatercept’s therapeutic effects, synthesises the current clinical evidence, and discusses its emerging role as a disease-modifying agent capable of promoting reverse pulmonary vascular remodelling within contemporary PAH management. Full article

Background: Cardiac amyloidosis (CA) is characterized by progressive myocardial infiltration leading to restrictive cardiomyopathy and heart failure. While left ventricular assessment has traditionally dominated prognostic evaluation, right ventricular (RV) dysfunction and RV–pulmonary artery (PA) coupling have emerged as critical determinants of outcomes. Objectives: This review synthesizes current evidence on RV–PA coupling as a prognostic marker in cardiac amyloidosis, examining measurement methodologies, prognostic significance, pathophysiological mechanisms, and clinical applications. Methods: We comprehensively reviewed the recent literature on RV–PA coupling in CA, focusing on studies published from 2020 to 2025, including both AL and ATTR subtypes. We analyzed data from multicenter cohorts, prospective registries, and validation studies examining the relationship between RV–PA coupling indices and clinical outcomes. Results: RV–PA coupling, most commonly assessed using the tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) ratio, consistently demonstrates strong independent prognostic value for mortality and heart failure outcomes in CA patients. Impaired coupling (TAPSE/PASP < 0.45 mm/mmHg) identifies high-risk patients with hazard ratios ranging from 1.98 to 4.17 for adverse outcomes. In a multicenter cohort of 283 patients, TAPSE/PASP < 0.45 mm/mmHg was independently associated with death or heart failure hospitalization (HR 1.98, 95% CI 1.32–2.96, p = 0.001) and significantly improved risk reclassification (NRI 0.46–0.49). In ATTR-specific populations receiving disease-modifying therapy, impaired coupling (TAPSE/PASP ≤ 0.382 mm/mmHg) predicted three-year mortality with an adjusted HR of 2.99. The coupling index provides incremental value over individual RV parameters by accounting for afterload conditions and demonstrates consistent prognostic performance across both AL and ATTR subtypes. Conclusions: RV–PA coupling represents a robust, easily obtainable prognostic marker that should be routinely assessed in CA patients for risk stratification and clinical decision-making. The TAPSE/PASP ratio can be calculated from standard echocardiographic examinations without additional cost or time, making it practical for widespread implementation. Future research should focus on standardizing measurement protocols, establishing disease-specific thresholds, evaluating coupling trajectories with novel therapies, and integrating coupling assessment into staging systems and management algorithms. The strong prognostic signal, pathophysiological relevance, and ease of measurement position RV–PA coupling as an essential component of comprehensive cardiac amyloidosis evaluation. Full article

Chronic thromboembolic pulmonary disease (CTEPD) is a severe long-term complication of acute pulmonary thromboembolism (PTE). Its pathogenesis is multifactorial, involving incomplete thrombus resolution, hemodynamic burden, comorbidities, and genetic factors. However, the contribution of inherited thrombophilic mutations to CTEPD development remains controversial. This retrospective cohort study included 204 patients diagnosed with acute PTE at a tertiary referral center between December 2023 and December 2024. Baseline demographic, clinical, laboratory, and echocardiographic data were collected. Genetic analysis assessed Factor II, Factor V Leiden, MTHFR C677T, MTHFR A1298C, Factor XIII V34L, and PAI-1 4G/5G polymorphisms. Patients were followed for at least 12 months for the development of CTEPD, defined according to guideline-based hemodynamic and imaging criteria. During follow-up, 17 patients (8.3%) developed CTEPD. Patients with CTEPD were significantly older and had higher baseline and follow-up systolic pulmonary artery pressure (sPAP) (p < 0.001), elevated NT-proBNP and troponin levels (both p < 0.001), and more frequent comorbidities, including cardiac and renal disease. Multivariate logistic regression identified comorbid diseases (HR: 0.17, 95% CI: 0.039–0.80, p = 0.025) and genetic thrombophilic factors (HR: 0.30, 95% CI: 0.10–0.91, p = 0.034) as independent predictors. Among genetic variants, only the PAI-1 4G/5G polymorphism was significantly associated with CTEPD (p = 0.001). Our study demonstrates that advanced age, comorbid diseases, elevated cardiac biomarkers, and genetic predisposition are associated with the development of CTEPD after acute PTE, while the PAI-1 4G/5G polymorphism may contribute to CTEPD susceptibility within a multifactorial context. Full article

Vascular remodeling and progressive lung vessel obliteration are a histopathological cornerstone for the onset of pulmonary arterial hypertension (PAH). However, the role of vascular endothelial growth factor (VEGF) signaling pathways in the development of histopathological vascular changes in PAH is still incompletely understood. This educational review aims to untangle the opposing and heterogeneous actions of VEGF and the receptors it engages in triggering lung angio-proliferative lesions, driving hemodynamic changes in PAH. A proposed ‘VEGF-oriented’ approach attempts to untangle some of the contrasting and complementary actions of VEGF in the pathogenesis of the disease. Experimental models provide a cogent explanation for dysfunctional angiogenesis and the paradox of VEGF-receptor-blockade-induced PAH. The multifaced properties of VEGF, whether angiogenic or nonangiogenic, vary depending on the nature of the ligand, receptor-dependent and -independent signaling pathways, and the duration of the ligand–receptor engagement. Further investigation is needed to translate the knowledge acquired to human subjects and to confirm the pathogenic mechanisms surrounding the phenotypic shift to apoptosis-resistant, hyperproliferative cellular subset and the development of angio-obliterative lesions in PAH. 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

Objectives: To develop and validate a transthoracic lung ultrasound (TLUS)-integrated clinical nomogram for predicting pulmonary arterial hypertension (PAH) in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). Methods: This multicenter retrospective study included 550 patients with CTD-ILD from the Second Affiliated Hospital of Fujian Medical University and 169 external cases from the Xijing Hospital, Fourth Military Medical University. Patients were randomly divided into a training cohort (n = 385) and an internal validation cohort (n = 165); the external dataset served as a testing cohort. Demographic, physiological, laboratory, pulmonary function, and TLUS data were collected. Univariate and multivariate logistic regression analyses identified independent predictors of PAH, which were used to construct a nomogram model. Discrimination was assessed using receiver operating characteristic (ROC) curves and area under the curve (AUC) values. Calibration, decision curve analysis (DCA), and clinical impact curves (CIC) were performed to evaluate model accuracy and clinical utility. Results: Five independent predictors were identified: respiratory rate, diffusing capacity of the lung for carbon monoxide (DLCO% predicted), TLUS score, red blood cell (RBC) count, and brain natriuretic peptide (BNP). The model achieved excellent discrimination with AUCs of 0.952 (95% confidence interval [CI]: 0.927–0.977) in the training cohort, 0.935 (95% CI: 0.885–0.985) in the validation cohort, and 0.874 (95% CI: 0.806–0.942) in the testing cohort, outperforming individual predictors. Calibration plots showed close agreement between predicted and observed probabilities, while DCA and CIC confirmed strong clinical benefit and applicability across all thresholds. Conclusions: This TLUS-integrated nomogram provides a noninvasive and reliable tool for individualized PAH risk assessment in CTD-ILD patients. By combining ultrasound findings with physiological and laboratory markers, the model enables accurate detection of high-risk cases and may assist clinicians in optimizing surveillance and management strategies. Full article

Background: Early identification of irreversible pulmonary vascular remodeling in congenital heart disease-associated pulmonary arterial hypertension (C-PAH) is critical for optimizing surgical timing. Current noninvasive diagnostic methods are inadequate, and the lung microbiome and metabolome may provide novel insights into disease progression. Methods: We analyzed bronchoalveolar lavage fluid (BALF) from 47 children, including those with C-PAH (n = 15), CHD without PAH (C-NPAH, n = 16), and healthy controls (n = 16), using 16S rRNA gene sequencing and untargeted metabolomics. Differential microbial taxa and metabolites were identified, and their interactions with clinical indicators were assessed via Random Forest (RF) and Mediation Analysis. Results: C-PAH patients exhibited airway microbial dysbiosis, characterized by an elevated Firmicutes/Bacteroidetes (F/B) ratio and increased abundance of g_Lactobacillus. Metabolomic profiling revealed 88 differential metabolites between C-PAH and controls, and 3 between C-PAH and C-NPAH. N1-methylnicotinamide (MNAM) and 2-piperidone emerged as potential biomarkers. Mediation analysis showed that g_Eikenella influenced PAH indirectly through 2-piperidone (β = −0.376, p = 0.026), indicating a microbe–metabolite–host interaction. Conclusions: Integrative microbiome–metabolome profiling of BALF reveals potential biomarkers for C-PAH. These findings provide exploratory evidence that microbial and metabolic biomarkers, particularly 2-piperidone and MNAM, hold potential for the early, noninvasive identification of irreversible pulmonary vascular remodeling, but require further validation in independent cohorts. Full article

Pulmonary hypertension is a progressive and life-threatening disorder affecting approximately 1% of the global population, with increasing prevalence among elderly individuals. Although it most commonly arises as a complication of chronic cardiac or pulmonary diseases, it may also develop in otherwise healthy individuals exposed to chronic hypoxia at high altitude. In this setting, sustained alveolar hypoxia triggers pulmonary vasoconstriction and vascular remodeling, key processes driving the elevation of pulmonary arterial pressure and highlighting the critical role of environmental stressors in disease pathogenesis. In this review, we examine the molecular mechanisms underlying the hypoxia-pulmonary hypertension axis, focusing on the complex and interconnected signaling networks involving redox imbalance, PI3K–Akt signaling, Na⁺/H⁺ exchange, nitric oxide bioavailability, autophagy, mitochondrial dynamics and mitophagy, metabolic reprogramming, inflammation, adventitial remodeling with particular emphasis on pulmonary arterial adventitial fibroblasts, and erythropoietin signaling. We also discuss current knowledge gaps and emerging therapeutic opportunities that may arise from a deeper understanding of these pathways. Collectively, while many of the signaling mechanisms implicated in hypoxia-induced pulmonary hypertension offer therapeutic promise, none have yet proven fully translatable, underscoring the multifactorial and tightly integrated nature of this disease. Full article

Background/Objectives: The diagnosis and risk stratification of valvular heart disease have traditionally relied on resting echocardiography. However, in a significant portion of patients, resting findings do not fully reflect the hemodynamic severity of the condition, particularly in asymptomatic individuals with severe valvular disease or those with nonspecific symptoms. In this context, stress echocardiography emerges as a vital imaging modality, providing a dynamic assessment of valvular, ventricular, and pulmonary function under hemodynamic load (from physical exercise or pharmacological agents). Methods: We conducted a comprehensive synthesis and critical evaluation of the current landscape, recent advancements, and future directions regarding the application of stress echocardiography in valvular heart disease. Results: This comprehensive review explores the incremental role of stress echocardiography in valvular heart disease, analyzing the evolution of its clinical applications, from low-flow, low-gradient aortic stenosis to the evaluation of contractile reserve and exercise-induced pulmonary hypertension in mitral stenosis and regurgitation. We discuss standardized protocols, key parameters to monitor, and the diagnostic and prognostic outcomes from major clinical trials and current guidelines. Attention is given to stress echocardiography’s ability to unmask the true severity of the disease and to identify patients at high risk for adverse events, thereby guiding crucial clinical decisions, such as the optimal timing for surgical or transcatheter intervention. Conclusions: The review evaluates the limitations of modality and outlines future research directions, including its integration with new technologies like 3D echocardiography and speckle tracking techniques, to further optimize the role of stress echocardiography as a decision-making tool in the multidisciplinary management of valvular heart disease. Full article

Background/Objectives: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic interstitial lung disease with high mortality and limited treatment options. Despite recent therapeutic advances, predicting survival remains challenging. Given the challenge of predicting disease progression in IPF, identifying reliable prognostic markers may support individualized treatment strategies, guide follow-up intensity, and improve clinical decision making. This study aimed to evaluate mortality rates and factors associated with poor prognosis in patients with IPF over a 10-year period at a tertiary care center. Methods: Medical records of 268 patients diagnosed with IPF between 2015 and 2024 were retrospectively reviewed. Demographic characteristics, comorbidities, radiological findings, pulmonary function test results, frequency of exacerbations and hospitalizations, treatment details, and survival outcomes were analyzed. Univariate and multivariate logistic regression analyses were performed to identify predictors of mortality. Results: This study included 268 patients (77.2% male; median age, 72 years). During a median follow-up of 24 months, 44% (n = 118) of patients died. Deceased patients were older (p < 0.001) and had higher rates of coronary artery disease, pulmonary embolism, pulmonary hypertension, and malignancy (all p < 0.05). A definite UIP pattern was more common among deceased patients (71.2% vs. 52.4%, p = 0.02). Acute exacerbations (23.3% vs. 8.1%) and hospitalizations (61.9% vs. 23.3%) were significantly more frequent in this group (p < 0.001). In multivariate analysis, GAP score (OR 11.68, p = 0.001), pulmonary hypertension (OR 15.39, p = 0.02), history of exacerbation (OR 56.2, p = 0.04), baseline FVC (OR 1.10, p = 0.02), mean platelet volume (OR 0.29, p = 0.01), and AST level (OR 1.12, p = 0.04) were independent predictors of mortality. Conclusions: Despite advances in management, IPF continues to carry a high mortality risk. This study represents one of the largest single-center IPF cohorts from our region with long-term real-life follow-up and additionally evaluates laboratory biomarkers such as MPV and AST, which have not been widely investigated as prognostic indicators in IPF. Advanced age, reduced pulmonary function, comorbidities, and acute exacerbations are major prognostic factors. Early recognition and proactive management of these parameters may help improve survival outcomes. Full article