Pulmonary Circulation最新文献

Right ventricular (RV) (dys)function determines outcomes in pulmonary hypertension (PH). We previously found that asymmetric RV myocardial work (MW) corresponds with inefficient RV function in experimental PH models. We therefore aimed to investigate regional distribution of RV MW and its correlation with catheter hemodynamics in children with PH. RV MW was calculated by longitudinal strain and simultaneous catheter pressure measurements in 14 patients with PH. Wasted MW was defined as the ratio of inappropriate myocardial lengthening to favorable shortening work. Segment-wise and averaged MW and wasted MW were evaluated at baseline and during pulmonary vasodilation therapy with oxygen and nitric oxide, and their relationship to hemodynamic measurements was analyzed. We found that MW was higher for the lateral wall than the septum: 1013 ± 374 mmHg · % versus 532 ± 190 mmHg · % at baseline. Wasted MW ratio did not differ significantly between wall regions. Pulmonary vasodilators slightly reduced mean pulmonary artery pressure and was accompanied by a more symmetrical MW distribution. Averaged MW correlated with the rate of RV pressure development (dP/dt maximum) and decay (dP/dt minimum) at all conditions (p  $\le$  0.047). The results suggest that MW contribute to, and may be used as a marker of, systolic and diastolic efficiency in the PH RV.

Our prospective study investigates the 3-year trajectory of disease-specific quality of life (QoL) using the PEmb-QoL questionnaire, functional performance via 6-min walk tests, and the 5-year survival following acute pulmonary embolism (PE) and explores their association with patient demographics and clinical characteristics. We highlight that PE-specific QoL improves over time despite no significant changes in cardiopulmonary performance.

Activation of the sympathetic nervous system is observed in pulmonary arterial hypertension patients. This study investigates whether inhibiting the conversion of dopamine into noradrenaline by dopamine β-hydroxylase (DβH) inhibition with BIA 21-5337 improved right ventricular (RV) function or remodeling in pressure overload-induced RV failure. RV failure was induced in male Wistar rats by pulmonary trunk banding (PTB). Two weeks after the procedure, PTB rats were randomized to vehicle (n = 8) or BIA 21-5337 (n = 11) treatment. An additional PTB group treated with ivabradine (n = 11) was included to control for the potential heart rate-reducing effects of BIA 21-5337. A sham group (n = 6) received vehicle treatment. After 5 weeks of treatment, RV function was assessed by echocardiography, magnetic resonance imaging, and invasive pressure-volume measurements before rats were euthanized. RV myocardium was analyzed to evaluate RV remodeling. PTB caused a fourfold increase in RV afterload which led to RV dysfunction, remodeling, and failure. Treatment with BIA 21-5337 reduced adrenal gland DβH activity and 24-h urinary noradrenaline levels confirming relevant physiological response to the treatment. At end-of-study, there were no differences in RV function or RV remodeling between BIA 21-5337 and vehicle-treated rats. In conclusion, treatment with BIA 21-5337 did not have any beneficial-nor adverse-effects on the development of RV failure after PTB despite reduced adrenal gland DβH activity.

Data from invasive CPET (iCPET) revealed long COVID patients have impaired systemic oxygen extraction (EO₂), suggesting impaired mitochondrial ATP production. However, it remains uncertain whether the initial severity of SARS-CoV-2 infection has implications on EO₂ and exercise capacity (VO₂) nor has there been assessment of anerobic ATP generation in long COVID patients. iCPET was performed on 47 long COVID patients (i.e., full cohort; n = 8 with severe SARS-CoV-2 infection). In a subset of patients (i.e., metabolomic cohort; n = 26) metabolomics on venous and arterial blood samples during iCPET was performed. In the full cohort, long COVID patients exhibited reduced peak EO₂ with reduced peak VO₂ (90 ± 17% predicted) relative to cardiac output (118 ± 23% predicted). Peak VO₂ [88% predicted (IQR 81% - 108%) vs. 70% predicted (IQR 64% - 89%); p = 0.02] and EO₂ [0.59(IQR 0.53-0.62) vs. 0.53(IQR 0.50-0.48); p = 0.01) were lower in severe versus mild infection. In the metabolomic cohort, 12 metabolites were significantly consumed, and 41 metabolites were significantly released (p-values < 0.05). Quantitative metabolomics demonstrated significant increases in inosine and succinate arteriovenous gradients during exercise. Peak VO₂ was significantly correlated with peak venous succinate (r = 0.68; p = 0.0008) and peak venous lactate (r = 0.49; p = 0.0004). Peak EO₂ and consequently peak VO₂ impact long COVID patients in a severity dependent manner. Exercise intolerance associated with long COVID is defined by impaired aerobic and anaerobic energy production. Peak venous succinate may serve as a potential biomarker in long COVID.

Leveraging the potential of virtual platforms in the post-COVID-19 era, the Infection and Pulmonary Vascular Diseases Consortium (iPVDc), with the support of the Pulmonary Vascular Research Institute (PVRI), launched a globally accessible educational program to highlight top-notch research on inflammation and infectious diseases affecting the lung vasculature. This innovative virtual series has already successfully brought together distinguished investigators across five continents - Asia, Europe, South and North America, and Africa. Moreover, these open global forums have contributed to a comprehensive understanding of the complex interplay among immunology, inflammation, infection, and cardiopulmonary health, especially concerning pulmonary hypertension and related pulmonary disorders. These enlightening discussions have not only heightened awareness about the impact of various pathogenic microorganisms, including fungi, parasites, and viruses, on the onset and development of pulmonary vascular diseases but have also cast a spotlight on co-infections and neglected illnesses like schistosomiasis - a disease that continues to impose a heavy socioeconomic burden in numerous regions worldwide. Thus, the overall goal of this review article is to present the most recent breakthroughs from infectious PVDs as well as bring to light the scientific and educational insights from the 2023 iPVDc/PVRI virtual symposium series, shaping our understanding of these crucial health issues in this more than ever interconnected world.

Delta-like ligand 4 (DLL-4) inhibitor drugs are an emerging cancer treatment. In clinical trials for solid organ malignancies, intravenous administration of monoclonal antibodies that inhibit DLL-4 is associated with development of pulmonary hypertension, in the absence of left ventricular dysfunction. Analysis of 13 clinical trials showed that pulmonary hypertension is a complication of DLL-4 inhibition.

Current methods for quantifying perfusion from computed tomography pulmonary angiography (CTPA) often rely on semi-quantitative scoring systems and requires an experienced evaluator. Few studies report on absolute quantitative variables derived from the images, and the methods are varied with mixed results. Dual-energy CTPA (DE-CTPA) enables automatic quantification of lung and lobar perfusion with minimal user interaction by utilizing machine learning based software. We aimed to evaluate differences in DE-CTPA derived quantitative perfusion variables between patients with acute pulmonary embolism (PE) and chronic thromboembolic pulmonary hypertension (CTEPH). This retrospective, single-center, observational study included 162 adult patients diagnosed with PE (n = 81) or CTEPH (n = 81) and scanned using dual-energy CT between 2020 and 2023. Mann-Whitney U tests and permutational analysis of variance (PERMANOVA) were used for comparative analyses. We found whole lung perfusion blood volume to be lower (p < 0.001) in PE patients (median 3399 mL [2554, 4284]) than in CTEPH patients (median 4094 mL [3397, 4818]). The same was observed at single lung and lobar level. PERMANOVA encompassing all perfusion variables showed a difference between the two groups (F-statistic = 13.3, p = 0.002). Utilizing logistic regression, right and left lower lobe perfusion blood volume showed some ability to differentiate between PE and CTEPH with area under the receiver operation characteristics curve values of 0.71 (95% CI: 0.56; 0.84) and 0.72 (95% CI: 0.56; 0.86). Pulmonary perfusion is lower in patients with PE than patients with CTEPH, highlighted by differences in DECT-derived perfusion blood volume. Quantitative perfusion variables might be useful to differentiate between the two diseases.

Current risk assessment of pulmonary embolism (PE) stratifies patients based on hemodynamic stability, clinical parameters of severity, right ventricular dysfunction and cardiac injury but fails to integrate a wide variety of comorbid conditions. The Charlson Comorbidity Index (CCI) predicts mortality based on patients' diseases and provides a system to quantify disease burden. The National Inpatient Sample (NIS) database (2016-2018) was used to identify patients with PE and calculate CCI score groups of 0, 1-2, 3-5, and ≥6 and stratify them by outcome. Of 561,625 patients with PE, 176,460 (31.4%) had CCI score of 0, 223,870 (39.8%) had CCI of 1-2, 102,305 (18.2%) had CCI of 3-5, and 58,990 (10.5%) had CCI ≥ 6. Higher CCI scores were associated with increased mortality: CCI 1-2 (adjusted odds ratio [aOR] 2.09), CCI 3-5 (aOR 3.12), CCI ≥ 6 (aOR 5.44) compared to CCI 0, along with stepwise increases in shock and mechanical ventilation with each increase in CCI score group. CCI scores ≥3 had increased length of stay (1.4-1.72 days) and increased total hospital costs ($3651-$4265) compared to CCI0. Patients with CCI ≥ 3 were less likely to receive systemic thrombolysis, catheter directed thrombolysis and mechanical thrombectomy. Acute PE in patients with elevated comorbidity scores is associated with higher morbidity and mortality, increased hospital resource utilization, and decreased usage of advanced therapies in a large cohort reflective of patients across the United States. Integration of comorbidities in risk assessment profiles identifies patients with higher short-term mortality which may guide management strategy.