Pulmonary Circulation最新文献

Resting heart rate has been incorporated in REVEAL risk assessment. Rest and sleep heart rate variability (HRV) measured in the home setting could provide early insight into worsening physiology in patients with pulmonary arterial hypertension (PAH). We hypothesized continuous HRV monitoring in the home setting for 7 days would be a treatment responsive measure and be associated with outcomes in PAH. This was a prospective observational study completed at the University of Rochester. We recruited two groups, one with stable background therapy and another with therapy intensification during the study. MC10 Biostamp (continuous electrocardiogram heart rate monitoring) was worn for 7 days at baseline and follow up; stable patients completed monitoring twice within 4 weeks while treatment intensification patients were assessed 3 months later. HRV was calculated using MC10 proprietary algorithm. Baseline, follow up, and changes in heart rate and HRV (rest and sleep) were compared between the groups and correlated to clinical outcomes at 2 years. Periods of activity were excluded from analysis. Non-parametric testing was performed. Twenty-four (10 stable and 14 treatment intensification) PAH patients had paired monitoring sessions during sleep and rest. There were no statistical differences in heart rate or HRV values at baseline or follow-up within either stable PAH patients or those requiring treatment escalation. Additionally, the change in heart rate from baseline to follow-up did not differ significantly between the two groups. There was no difference in HRV between patients who had clinical worsening (parenteral therapy, hospitalization, or death) within 2 years, while elevated rest and sleep heart rate did predict clinical worsening at 2 years. Unlike left ventricular systolic failure, continuous HRV for 7 days in the home setting does not appear to improve assessment in PAH, and functional testing appears to be a better way to assess treatment response and risk for clinical worsening.

Although current guidelines recommend standard cardiopulmonary exercise testing (CPET) to evaluate symptomatic patients after pulmonary embolism (PE), CPET with simultaneous echocardiography could provide relevant information to evaluate right ventricular-pulmonary arterial coupling. The aim of this study was to investigate exercise-induced changes in echocardiographic variables of RV function or RV- arterial coupling in patients with residual thrombotic defects at 3 months after PE. This retrospective study investigated patients with residual thromboembolic disease on V/Q scintigraphy with persistent symptoms despite adequate anticoagulation after 3 months of acute PE, and resting echocardiography with a low probability of PH. At rest and during exercise, CPET and doppler echocardiography were performed following a standard protocol. Forty-five patients were included, completing a follow-up period of at least 24 months. The mean (standard deviation) age was 63 (15) years, and 24 (53%) patients were male. Four patients developed CTEPH after 2 years follow up. Correlation analyses showed that the peak TAPSE was significantly associated with peak workload (r = 0.454, p = 0.003), peak VO₂ (r = 0.558, p < 0.001), VE/VECO₂ (AT) (r = -0.531, p < 0.001), and oxygen pulse (r = 0.375, p = 0.02). TAPSE/PASP was only slightly associated with peak workload (r = 0.300, p = 0.045). By contrast, the change on TAPSE (from rest to peak) was significantly correlate with peak oxygen uptake (r = 0.491, p = 0.01). Also, reduced VO₂ at AT and TAPSE/PASP was seen in patients with CTEPH. CPET with synchronic echocardiography could be a useful tool in early assessment of symptomatic patients with perfusion defects on imaging after 3 months of correctly treated PE.

Treatment patterns of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) in Finland are unknown. Guidelines now recommend early escalation of treatment for PAH. We evaluated how well Finnish practice follows guidelines, and how treatment initiations and outcomes are related. The pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension patients in Finland cohort includes all PAH and CTEPH patients diagnosed between 2008 and 2020 in all Finnish university hospitals. Drug therapy was analysed in patients with medical/procedural history available, and changes in the 4-tier comparative, prospective registry of newly initiated therapies for pulmonary hypertension (COMPERA) 2.0 risk score were evaluated. PAH patients (n = 268) were initially treated with monotherapy (52%) or double therapy (24%). After year 2015, double therapy use increased to 39%. PAH treatment at 1 year after diagnosis included phosphodiesterase 5 inhibitors (71%), endothelin-receptor antagonist (48%), prostacyclin analogue (7%), calcium channel blocker (12%) and selexipag (1%). 35% achieved low risk at 1 year, increasing to 44% for patients diagnosed after 2015. Those remaining at intermediate-high (IH) or high risk (H) (28%) were not treated less aggressively than others but were older, had more comorbidities, and often history of smoking. CTEPH patients (n = 189) were treated with pulmonary endarterectomy (PEA) (27%), balloon pulmonary angioplasty (BPA) (11%) and medical therapy only (41%) within 1 year from diagnosis. 45% achieved low risk at 1 year. We present additional results on treatment of IH and H patients, patient characteristics preceding death, and treatment persistence. We found less treatment of PAH patients with double or triple therapies and of CTEPH patients with PEA and BPA than expected but with good results. Patients not reaching low or intermediate COMPERA 2.0 were old and had comorbidities.

Idiopathic pulmonary fibrosis (IPF) is a leading indication for lung transplantation. Pulmonary hypertension (PH), a common comorbidity in IPF, has gained renewed attention following the updated ESC/ERS guidelines, which redefine diagnostic thresholds for PH. This study evaluates the impact of the revised PH criteria on transplant waitlist outcomes among IPF patients. Specifically, we assessed the prevalence of PH under the new guidelines and its association with waitlist survival. We conducted a retrospective analysis using the OPTN/SRTR database, including 14,156 IPF candidates listed for lung transplantation. Survival analyses were performed using Kaplan-Meier and multivariate models to examine the influence of revised mPAP and PVR thresholds on waitlist mortality. The prevalence of PH, defined by the revised criteria, was significantly higher compared to the prior definition. Kaplan-Meier analysis demonstrated worse waitlist survival for patients with PH under both diagnostic thresholds. However, multivariate analysis revealed that mPAP and PVR thresholds were not independently predictive of mortality. Instead, clinical parameters, including 6MWD, functional status, BMI, FVC, PaCO2, and double lung transplant preference, were significant predictors of waitlist mortality. In conclusion, while the revised PH diagnostic criteria increase PH prevalence in IPF patients, their independent prognostic utility for waitlist survival is limited. This national transplant database study underscores the importance of comprehensive clinical evaluation and timely referral for transplantation in managing IPF with PH.

Chronic obstructive pulmonary disease (COPD) is a major challenge to global public health. Evidence showed that long noncoding RNA (lncRNA)-XIST/microRNA (miRNA)-200c-3p axis regulated apoptosis and inflammation in cigarette smoke extract (CSE)-exposed human bronchial epithelial cells. Wenshen Yiqi granule (WSYQG) is a Traditional Chinese medicine compound prescription and often used for treating COPD. However, the current understanding of the mechanism by which WSYQG improves COPD is still limited, which has somewhat restrained its widespread application. Therefore, this study aims to investigate the effects and biological mechanisms of WSYQG on CSE-exposed type II alveolar epithelial (AEC II) cells with cell transfection and miRNA mimics/inhibitors intervention. Cell counting kit-8, flow cytometry, Transwell, Western blot, real-time quantitative reverse transcription PCR, and fluorescence in situ hybridization assays were used. Results showed that WSYQG intervention increased cell viability and decreased levels of IFN-γ, TNF-α and apoptosis, also preventing cell migration in CSE-exposed ACE II cells. Additionally, expression of epithelial marker (ZO-1), Notch1/4 decreased, and mesenchymal markers (vimentin) and Notch2 expression increased in CSE-exposed ACE II cells, while WSYQG intervention antagonized them and also decreased N-cadherin and increased E-cadherin. Silencing lncRNA-XIST enhanced WSYQG's effects on CSE-exposed ACE II cells, while inhibiting miR-200c-3p reversed silencing lncRNA-XIST's effects. Furthermore, dual-luciferase reporter assay system and RNA immunoprecipitation assay proved that lncRNA-XIST acts as a miR-200c-3p sponge. This study highlights the importance of the lncRNA-XIST/miR-200c-3p axis in WSYQG improving COPD, providing a research basis for WSYQG to improve COPD and expanding the possibility of expanding its clinical application.

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.