Pulmonary Circulation最新文献

Interstitial lung disease (ILD) can lead to pulmonary hypertension (ILD-PH), worsening prognosis and increasing mortality. Diagnosing ILD-PH is challenging due to the limitations of imaging methods. Right heart catheterization (RHC) is the gold standard for diagnosing PH but is limited to ILD patients considered for lung transplantation. This study assessed the usefulness of RHC in diagnosing ILD-PH in a large cohort of 105 patients followed for at least 72 months, examining hemodynamic parameters for survival analysis. We conducted an ambispective cohort study, diagnosing PH as mean pulmonary artery pressure ≥ 20 mmHg, pulmonary arterial wedge pressure < 15 mmHg, and pulmonary vascular resistance > 2 Wood units by RHC. We registered demographic, biochemical, echocardiographic, respiratory, and hemodynamic parameters for survival analyses. Using RHC, we found a PH prevalence of 84.7% among ILD patients who previously exhibited an intermediate-to-high probability of PH by echocardiography. Thirty-nine ILD-PH patients died, yielding a 5-year survival rate of 35%, whereas ILD patients without PH had a survival rate of 100%. Connective tissue disease-associated ILD and interstitial pneumonia with autoimmune features were the predominant ILD subtypes in ILD-PH patients. The ILD-PH group had worse pulmonary function, lower forced vital capacity, and more severe hypoxemia. Kaplan-Meier analyses showed significantly lower survival rates in ILD-PH patients with a 6-min walking distance < 360 m, tricuspid annular plane systolic excursion/pulmonary artery systolic pressure ratio < 0.35 mm/mmHg, venous oxygen saturation < 65%, and pulmonary artery compliance < 2.2 mm/mmHg. RHC accurately characterizes ILD-PH and provides long-term survival predictors.

The therapeutic value of lipid-lowering drugs in pulmonary vascular disease remains uncertain due to insufficient studies and evidence. This study aims to investigate the causal effects of lipid-lowering drugs (specifically, inhibitors of APOB, CETP, HMGCR, NPC1L1, and PCSK9) on pulmonary vascular diseases using a Mendelian randomization (MR) approach. We utilized summary-level statistics from genome-wide association studies (GWAS) to simulate the exposure to low-density lipoprotein cholesterol (LDL-C) and its outcomes on pulmonary arterial hypertension (PAH), pulmonary embolism (PE), and pulmonary heart disease (PHD). Single-nucleotide polymorphisms (SNPs) within or near drug target-associated LDL-C loci were selected as proxies for the lipid-lowering drugs. Data from the FinnGen cohort and UK Biobank (UKB) were incorporated to enhance the robustness and generalizability of the findings. The inverse variance weighted (IVW) and MR-Egger methods were employed to estimate MR effects. Our MR analysis indicated that LDL-C mediated by NPC1L1 (odds ratio [OR] = 104.76, 95% confidence interval [CI] = 2.01-5457.01, p = 0.021) and PCSK9 (OR = 10.20, 95% CI = 3.58-29.10, p < 0.001) was associated with an increased risk of PAH. In contrast, LDL-C mediated by APOB was associated with a decreased risk of PE (FinnGen: OR = 0.74, 95% CI = 0.60-0.91, p = 0.005; UKB: OR = 0.998, 95% CI = 0.996-1.000, p = 0.031) and PHD (FinnGen: OR = 0.73, 95% CI = 0.59-0.91, p = 0.004). However, LDL-C mediated by CETP and HMGCR did not show significant associations with the risks of PAH, PE, or PHD. This MR study revealed the causal effects of NPC1L1 and PCSK9 inhibitors on increased PAH risk, while APOB inhibitors appear to reduce the risks of PE and PHD. These findings enhance our understanding of the potential roles of lipid-lowering drugs in pulmonary vascular disease.

Right ventricular heart failure (RV HF) is the leading cause of death in pulmonary arterial hypertension (PAH). Relevance of the low-risk status assessment using available diagnostic tools requires a reliable confirmation. The study aimed to evaluate right ventricular perfusion and glucose metabolism using positron emission tomography (PET)/computed tomography (CT) with [13N]-ammonia and [18F]-fluorodeoxyglucose ([18F]-FDG) in 30 IPAH patients (33.8 ± 9.4 years) according to ESC/ERS 2022 risk status. The ratio of SUVmax_RV/LV metabolism and SUVmax_RV/LV perfusion showed significant positive correlation with pulmonary artery pressure, right heart dilatation, NT-proBNP level and negative correlation with the RV ejection fraction. The SUVmax_RV/LV perfusion and SUVmax_RV/LV metabolism ratios differed significantly according to risk status. Low risk patients had a SUVmax_RV/LV metabolism comparable to the controls without PH. The SUVmax_RV/LV perfusion ratio was elevated in low-risk IPAH patients compared with controls. Increased SUVmax_RV/LV perfusion may be an early marker of coronary flow adaptation to RV pressure overload in low-risk IPAH patients and requires further evaluation. Further long-term studies are needed to determine the clinical relevance and cut-off values for the RV/LV PET/CT with [13N]-ammonia and [18F]-fluorodeoxyglucose ([18F]-FDG) uptake in different IPAH risk groups.

The pulmonary vasculature plays a pivotal role in the development and progress of chronic lung diseases. Due to limitations of conventional two-dimensional histological methods, the complexity and the detailed anatomy of the lung blood circulation might be overlooked. In this study, we demonstrate the practical use of optical serial block face imaging (SBFI), ex vivo microcomputed tomography (micro-CT), and nondestructive optical tomography for visualization and quantification of the pulmonary circulation's 3D architecture from macro- to micro-structural levels in murine lung samples. We demonstrate that SBFI can provide rapid, cost-effective, and label-free visualization of mouse lung macrostructures and large pulmonary vessels. Micro-CT offers high-resolution imaging and captures microvascular and (pre)capillary structures, with microstructural quantification. Optical microscopy techniques such as optical projection tomography (OPT) and light sheet fluorescence microscopy, allows noninvasive, mesoscopic imaging of optically cleared mouse lungs, still enabling 3D microscopic reconstruction down to the precapillary level. By integrating SBFI, micro-CT, and nondestructive optical microscopy, we provide a framework for detailed and 3D understanding of the pulmonary circulation, with emphasis on vascular pruning and rarefaction. Our study showcases the applicability and complementarity of these techniques for organ-level vascular imaging, offering researchers flexibility in selecting the optimal approach based on their specific requirements. In conclusion, we propose 3D-directed approaches for a detailed whole-organ view on the pulmonary vasculature in health and disease, to advance our current knowledge of diseases affecting the pulmonary vasculature.

In patients with chronic thromboembolic pulmonary hypertension (CTEPH) who undergo balloon pulmonary angioplasty (BPA), pretreatment with PH-targeted medical therapy may be beneficial to improve clinical parameters and pulmonary hemodynamics. This study aims to describe clinical results of PH-targeted therapy prior to BPA. All consecutive patients with CTEPH who underwent BPA treatment were selected from our CTEPH database. Medical treatment strategy, clinical parameters, and pulmonary hemodynamics at time of diagnosis and at the first BPA were analyzed. In total 92 CTEPH patients who started BPA treatment (64.1% women; 60.4 ± 14.1 years of age; 62.0% NYHA FC III/IV) were included. Most patients received dual oral PH-targeted medical therapy (68.5%) prior to BPA. Between diagnosis and first BPA (median time 13.9 [7.5-30.7] months) significant improvements were observed in patients treated with PH-targeted medical therapy for both clinical (6MWD: +28.2 m [5.1-51.3], log NTproBNP: -0.4 pg/ml [-0.8 to -0.1]) as well as pulmonary hemodynamic parameters (mPAP: -6.5 mmHg [-8.5 to -4.5], CO: +0.6 L/min [0.2-1.0] and PVR: -2.8 WU [-3.5 to -2.1]). The overall complication rate per BPA (out of a total of 441 procedures) was 15.0% for patients on monotherapy and 14.9% for those on dual/triple PH-targeted medical therapy. No severe complications occurred. In conclusion, pretreatment with PH-targeted medical therapy prior to BPA results in an improvement in clinical- and pulmonary hemodynamic parameters.

Pulmonary vein stenosis (PVS) is an insidious diagnosis associated with morbidity and mortality. Pharmacologic therapy may suffice initially, but advanced stages demand mechanical intervention. Pulmonary stent implantation (PSI) and pulmonary balloon angioplasty (PBA) are common strategies, both carrying restenosis risks. This meta-analysis compares PSI and PBA to determine the superior revascularization strategy. We systematically searched databases until November 2023, identifying 11 studies with 780 patients. Studies, including those involving patients undergoing balloon angioplasty (BA) or stent angioplasty (SA) for PVS, were selected. Case reports, editorials, and cross-sectional studies were omitted. Primary outcomes included restenosis requiring reintervention, 5-year freedom from restenosis, and procedure-related complications. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Meta-regression analysis assessed factors like age and stent size. Study quality was evaluated using the Newcastle-Ottawa scale. This Systematic review and meta-analysis incorporated 11 observational studies. PSI exhibited a lower risk of restenosis requiring reintervention (OR 0.34, 95% CI 0.13, 0.87, p = 0.02) and significantly higher 5-year freedom from restenosis (OR 4.42, 95% CI 1.11, 17.62, p = 0.04) compared to PBA, with no significant difference in procedure-related complications. Meta-regression analysis showed age and stent size insignificantly affecting restenosis risk. Our review supports PSI as the preferred revascularization strategy for PVS due to superior patency benefits, emphasizing its role as the initial treatment choice. Further research is warranted for validation, considering individual patient factors in treatment selection.

Health disparities in patients with pulmonary arterial hypertension (PAH) have not been extensively reported in the United States. The aim of this project was to characterize the extent of demographic and socioeconomic disparities in clinical outcomes within a large, diverse PAH patient population. A retrospective, population-based study of electronic health record data from the OneFlorida Data Trust was completed. Adult patients seeking care within one of the 12 OneFlorida Network partner healthcare systems with a documented diagnosis of any form of pulmonary hypertension (PH), including PAH, via ICD-10 code were included. Social deprivation index and healthcare provider access scores were calculated from population-based centroids derived from patient home addresses. The primary outcome was all-cause mortality, with secondary outcomes including hospitalization, emergency department (ED) visits, and similar clinical outcomes in a combined cohort of patients with other forms PH. A total of 6379 patients were included in the PAH cohort, and 37,412 patients were included in the nonspecific PH cohort. PAH patients with the greatest social deprivation exhibited increased rates of ED visits and hospitalizations. Despite having similar rates of ED visits and hospitalizations compared to non-Hispanics, Hispanic PAH patients had markedly lower mortality rates. Similar associations were also observed in the combined cohort of 37,412 patients with other forms of PH. In conclusion, healthcare disparities exist in PAH outcomes across both demographic and socioeconomic boundaries. Patients identifying as Hispanic appear to have decreased rates of mortality compared to other races/ethnicities.

Pulmonary arteriovenous malformations (PAVMs) cause cerebral abscess and ischemic stroke due to paradoxical emboli, risks that are increasingly recognized. We report the evolving placement of thoracic surgery in multi-disciplinary team management of PAVMs that were sporadic or associated with hereditary hemorrhagic telangiectasia. From 1983 to 2006, all patients receiving elective treatment had embolization. Between January 2006 and July 2022, 24 of 714 (3%) patients reviewed at our institution underwent elective surgical resection of one or more PAVMs. Initially, the bar for elective surgery had been set very high, and only patients with persistent symptoms of cerebral ischemia after maximal embolization and medical therapy were referred. As PAVM natural history, follow-up radiation exposures for residual PAVMs, and good surgical outcomes were appreciated, PAVM resection became part of the discussion for highly localized, very complex PAVMs which we consider are best treated surgically. Elective surgical intervention may be considered for other selected patients.