Mechanical ventilation for acute exacerbation of fibrosing interstitial lung diseases

BackgroundAcute exacerbation of fibrosing interstitial lung diseases, including idiopathic pulmonary fibrosis, is associated with poor prognosis. Accordingly, tracheal intubation and invasive mechanical ventilation are generally avoided in such patients. However, the efficacy of invasive mechanical ventilation for acute exacerbation of fibrosing interstitial lung diseases remains unclear. Therefore, we aimed to investigate the clinical course of patients with acute exacerbation of fibrosing interstitial lung diseases who were treated with invasive mechanical ventilation.MethodsWe retrospectively analyzed 28 patients with acute exacerbation of fibrosing interstitial lung diseases who underwent invasive mechanical ventilation at our hospital.ResultsOf the 28 included patients (20 men, 8 women; mean age, 70.6 years), 13 (46.4%) were discharged alive and 15 died. Ten patients (35.7%) had idiopathic pulmonary fibrosis. Univariate analysis revealed that longer survival was significantly associated with lower partial pressure of arterial carbon dioxide (hazard ratio [HR] 1.04 [1.01–1.07]; p = 0.002) and higher pH (HR 0.0002 [0–0.02] levels; p = 0.0003) and less severe general status according to the Acute Physiology and Chronic Health Evaluation II score (HR 1.13 [1.03–1.22]; p = 0.006) at the time of mechanical ventilation initiation. In addition, the univariate analysis indicated that patients without long-term oxygen therapy use had significantly longer survival (HR 4.35 [1.51–12.52]; p = 0.006).ConclusionsInvasive mechanical ventilation may effectively treat acute exacerbation of fibrosing interstitial lung diseases if good ventilation and general conditions can be maintained.     

Lobar distribution of non-emphysematous gas trapping and lung hyperinflation in chronic obstructive pulmonary disease

BackgroundLung hyperinflation in chronic obstructive pulmonary disease (COPD) is closely associated with emphysema and non-emphysematous gas trapping, termed functional small airway disease (fSAD), on inspiratory and expiratory computed tomography (CT). Because the cranial-caudal emphysema distribution affects pulmonary function and fSAD may precede emphysema on CT, we tested the hypothesis that lobar fSAD distribution would affect lung hyperinflation differently in COPD with minimal and established emphysema.MethodsThe volume percentages of fSAD and emphysema (fSAD% and Emph%) over the upper and lower lobes were measured using inspiratory and expiratory CT in 70 subjects with COPD. Subjects were divided into those with minimal and established emphysema (n = 36 and 34) using a threshold of 10% Emph% in the whole lung.ResultsIn the minimal emphysema group, fSAD% in the upper and lower lobes was positively correlated with functional residual capacity (FRC) and residual volume to total lung capacity ratio (RV/TLC), and the correlation of fSAD% with RV/TLC was greater in the lower lobes. Conversely, in the established emphysema group, fSAD% in the upper and lower lobes was correlated with RV/TLC, but not with FRC. In multivariate analysis, fSAD% in the lower lobes, but not in the upper lobes, was associated with RV/TLC in subjects with minimal emphysema after adjusting for age, smoking status, and bronchodilator use.ConclusionNon-emphysematous gas trapping in the upper and lower lobes has a distinct physiological effect, especially in COPD with minimal emphysema. This local evaluation might allow sensitive detection of changes in lung hyperinflation in COPD.     

Subclinical Pulmonary Congestion and Abnormal Hemodynamics in Heart Failure With Preserved Ejection Fraction

ObjectivesThe authors hypothesized that quantitative computed tomography (QCT) imaging would reveal subclinical increases in lung congestion in patients with heart failure and preserved ejection fraction (HFpEF) and that this would be related to pulmonary vascular hemodynamic abnormalities.BackgroundGross evidence of lung congestion on physical examination, laboratory tests, and radiography is typically absent among compensated ambulatory patients with HFpEF. However, pulmonary gas transfer abnormalities are commonly observed and associated with poor outcomes.MethodsPatients referred for invasive hemodynamic exercise testing who had undergone chest computed tomography imaging within 1 month were identified (N = 137). A novel artificial intelligence QCT algorithm was used to measure pulmonary fluid content.ResultsCompared with control subjects with noncardiac dyspnea, patients with HFpEF displayed increased mean lung density (–758 HU [–793, –709 HU] vs –787 HU [–828, –747 HU]; P = 0.002) and a higher ratio of extravascular lung water to total lung volume (EVLWV/TLV) (1.25 [0.80, 1.76] vs 0.66 [0.01, 1.03]; P < 0.0001) by QCT imaging, indicating greater lung congestion. EVLWV/TLV was directly correlated with pulmonary vascular pressures at rest, with stronger correlations observed during exercise. Patients with increasing tertiles of EVLWV/TLV demonstrated higher mean pulmonary artery pressures at rest (34 ± 11 mm Hg vs 39 ± 14 mm Hg vs 45 ± 17 mm Hg; P = 0.0003) and during exercise (55 ± 17 mm Hg vs 59 ± 17 mm Hg vs 69 ± 22 mm Hg; P = 0.0003).ConclusionsQCT imaging identifies subclinical lung congestion in HFpEF that is not clinically apparent but is related to abnormalities in pulmonary vascular hemodynamics. These data provide new insight into the long-term effects of altered hemodynamics on pulmonary structure and function in HFpEF.     

Comparison of the 22-gauge and 25-gauge needles for endobronchial ultrasound-guided transbronchial needle aspiration

BackgroundEndobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive hilar mediastinal node sampling technique used for lung cancer staging and diagnosis of lesions. Besides the conventional 22-gauge (G) and 21G needles, a 25G needle is now available for this procedure. The objective of this study was to evaluate the efficacy of the 25G EBUS-TBNA needle.MethodsWe retrospectively reviewed consecutive patients who underwent EBUS-TBNA using both 22G and 25G aspiration needles from January 2017 through December 2017 at St. Marianna University School of Medicine. We identified 10 patients and compared the diagnostic yield and the sample volume for each needle.ResultsSix patients were diagnosed with lung cancer and four with sarcoidosis. Total diagnostic yield was 80% (8/10) for the 22G and 60% (6/10) for the 25G (P = 0.31). In patients with lung cancer, the diagnostic yield was 67% (4/6) for the 22G and 83% (5/6) for the 25G (P = 0.50). In patients with sarcoidosis, the diagnostic yield was 100% (4/4) for the 22G and 25% (1/4) for the 25G (P = 0.07). In patients with lung cancer, the median tissue area was comparable for each needle; however, in patients with sarcoidosis, the sample area was smaller for the 25G than for the 22G. We did not encounter any major complications or bleeding during EBUS-TBNA procedures.ConclusionsAlthough histologic specimens obtained by the 25G needle are expected to be useful for the diagnosis of lung cancer, we found the 25G needle inadequate for diagnosing sarcoidosis due to insufficient sample size.     

Clinical characteristics,outcomes, and factors associated with mortality in Nocardia pneumonia: 18 years' real-world data from a tertiary care hospital in Karachi,Pakistan

BackgroundPulmonary nocardiosis is a rare pulmonary infection with high morbidity and mortality. Limited real-world data on pulmonary nocardiosis patients are available from developing countries like Pakistan.MethodsThis retrospective observational study was conducted at the Aga Khan University Hospital, Karachi, Pakistan, from August 2003 to June 2020. Demographics, immune status, underlying diseases, laboratory data, treatment, and outcomes of all nocardiosis patients were recorded in predesigned proforma.ResultsSixty-six patients with smear/culture-proven pulmonary nocardiosis were identified. Most patients (83.3%) were treated with trimethoprim-sulfamethoxazole alone or in combination with other medicines. The overall mortality rate in our study was 33.3% (n = 22/66). Factors significantly associated with mortality were respiratory failure (p < 0.001), raised procalcitonin levels (p = 0.01), concomitant fungal infections (p = 0.01), concomitant TB (p = 0.03), and patients on combination therapy (p < 0.001).Respiratory failure (odds ratio [OR] 46.94 [95% confidence intervals [CI]: 5.01–439.03] p < 0.001), concomitant fungal infection (OR 17.09 [95% CI: 1.47–197.88] p- = 0.02) and patients on combination therapy (OR 6.90 [95% CI: 1.23–38.61] p = 0.02) were also identified as independent risk factors for mortality on multivariate analysis.ConclusionsThis study provides essential information on the clinical characteristics and risk factors, outcomes, and factors associated with mortality for pulmonary nocardial infections.     

Clinical,radiological, and pathological features of anti-asparaginyl tRNA synthetase antibody-related interstitial lung disease

BackgroundMyositis and interstitial lung disease (ILD) frequently occur in patients with anti-aminoacyl-tRNA synthetase (ARS) antibodies. Nearly half of ARS-ILD patients have the acute or subacute form of the disease, and one-third of these patients show a deterioration in pulmonary function over the long-term course because of frequent recurrences and refractoriness to therapy. Several reports recently described different characteristics depending on the individual anti-ARS antibodies, and the anti-asparaginyl tRNA synthetase (KS) antibody was strongly linked to ILD rather than to myositis. We therefore hypothesized that KS-ILD may have clinical characteristics that differ from those of other ARS-ILDs. The aim of this study was to clarify the clinical, radiological, and pathological features of KS antibody-positive ILD.MethodsWe retrospectively analyzed 19 consecutive patients with KS-ILD who underwent initial clinical measurements and high-resolution computed tomography and pathological assessments. We also analyzed disease behavior based on pulmonary function test results during the follow-up period.ResultsOur KS-ILD cohort included patients with dermatomyositis (10.5%), primary Sjögren syndrome (5.3%), and idiopathic ILD (84.2%). Most patients presented with chronic onset (89.5%) and a nonspecific pattern of interstitial pneumonia at each radiological and pathological assessment (89.4% and 85.7%, respectively). The pulmonary function test results showed that the mean changes from the initial %forced vital capacity and %diffusing capacity of the lung for carbon monoxide at 3 years were 3.7% ± 2.9% and 9.35% ± 3.0%, respectively.ConclusionsMost KS-ILD patients showed a tendency for chronic disease onset and long-term stabilization of pulmonary function.     

Usefulness of new diagnostic criteria for chronic hypersensitivity pneumonitis established on the basis of a Delphi survey: A Japanese cohort study

BackgroundChronic hypersensitivity pneumonitis (CHP) is a fibrotic interstitial lung disease (ILD) caused by repeated exposure to a variety of organic particles. In November 2017, new criteria for CHP diagnosis were proposed by Morisset et al. based on a modified Delphi survey of ILD experts. However, it remains unclear whether these criteria are useful to accurately diagnose CHP. We aimed to evaluate the newly proposed CHP diagnostic criteria.MethodsWe retrospectively applied Morisset's CHP diagnostic criteria to consecutive Japanese patients who underwent surgical lung biopsy for diagnosis of ILD from 2008 to 2015. All patients underwent bronchoalveolar lavage and pulmonary function testing. Patients who had connective tissue disease complications or showed an acute or subacute disease onset were excluded.ResultsA total of 251 patients were included. The diagnoses based on multidisciplinary discussion (MDD) were CHP (n = 27), idiopathic pulmonary fibrosis (n = 117), unclassifiable interstitial pneumonia (IP) (n = 65), and other diagnoses (n = 42). Of the 27 MDD-CHP patients, 14 were classified as a CHP group with diagnostic confidence >50% and 13 were not categorized (sensitivity, 51.9%; specificity, 77.7%). Morisset's CHP diagnostic criteria could help avoid SLB for the diagnosis of CHP in seven patients. Of the 13 MDD-CHP patients who were not categorized in the CHP group with diagnostic confidence >50%, the reason for the exclusion was an inconsistent with UIP pattern without CHP features.ConclusionsHalf of the MDD-CHP patients were diagnosed with CHP using Morisset's CHP diagnostic criteria. Further investigation will be important for developing improved diagnostic criteria for CHP.     

Pathological and clinical relevance of selective recruitment of Langerhans cells in the respiratory bronchioles of smokers

BackgroundSmoking causes an influx of inflammatory cells including Langerhans cells (LCs) into the airways and lung parenchyma, thus inducing histological changes, such as emphysema and fibrosis. We examined the distribution and quantity of Langerhans cells in relation to clinical and pathological findings and explored the association between smoking and accumulation of Langerhans cells in the respiratory bronchioles.MethodsFifty-three patients who underwent lung resection for primary diseases, including lung cancer, were recruited. Histological and immunohistochemistry analyses were utilized to identify CD1a-positive Langerhans cells in peripheral lung specimens separated from primary lesions. Clinical characteristics, pathological changes, and distribution of CD1a-positive Langerhans cells distribution were assessed.ResultsOf the 53 patients, 35 were smokers and 18 were non-smokers. The number of Langerhans cells in the respiratory bronchioles was significantly increased in smokers as compared to that in non-smokers (p < 0.001). The number of Langerhans cells in smokers was significantly higher in patients with mild emphysema than in those without emphysema (p < 0.01). The high-LC group showed more frequent smoking-related histological changes, such as respiratory bronchiolitis, parenchymal fibrosis, accumulation of macrophages, and smoking-related interstitial fibrosis, than the low-LC group. However, there were no differences in the smoking indices and pulmonary functions of the groups.ConclusionsSelective accumulation of Langerhans cells in the respiratory bronchioles of smokers may lead to the development of smoking-related pathological changes.     

Pulmonary Artery Strain Predicts Prognosis in Pulmonary Arterial Hypertension

BackgroundCurrent cardiac magnetic resonance (CMR) imaging in pulmonary arterial hypertension (PAH) focuses on measures of ventricular function and coupling.ObjectivesThe purpose of this study was to evaluate pulmonary artery (PA) global longitudinal strain (GLS) as a prognostic marker in patients with PAH.MethodsThe authors included 169 patients with PAH from the ASPIRE (Assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre) and INITIATE (Integrated computatioNal modelIng of righT heart mechanIcs and blood flow dynAmics in congeniTal hEart disease) registries, and 82 normal controls with similar age and gender distributions. PA GLS was derived from CMR feature tracking. Right ventricular measurements including volumes, ejection fraction, and right ventricular GLS were also derived from CMR. Patients were followed up a median of 34 months with all-cause mortality as the primary endpoint. Other known risk scores were collected, including the REVEAL (Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management) 2.0 and COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension) 2.0 scores.ResultsOf 169 patients (mean age: 57 ± 15 years; 80% female), 45 (26.6%) died (median follow-up: 34 months). Mean PA GLS was 23% ± 6% in normal controls and 10% ± 5% in patients with PAH (P < 0.0001). Patients with PA GLS <9% had a higher risk of mortality than those with PA GLS ≥9% (P < 0.001), and this was an independent predictor of mortality in PAH on multivariable analysis after adjustment for known risk factors (HR: 2.93; P = 0.010). Finally, in patients with PAH, PA GLS provided incremental prognostic value over the REVEAL 2.0 (global chi-square; P = 0.001; C statistic comparison; P = 0.030) and COMPERA 2.0 (global chi-square; P = 0.001; C statistic comparison; P = 0.048).ConclusionsPA GLS confers incremental prognostic utility over the established risk scores for identifying patients with PAH at higher risk of death, who may be targeted for closer monitoring and/or intensified therapy.     

Limited efficacy of nintedanib for idiopathic pleuroparenchymal fibroelastosis

BackgroundThe antifibrotic agent nintedanib has been reported to effectively prevent the decline in forced vital capacity (FVC) in a broad range of interstitial lung diseases. However, the efficacy of nintedanib against idiopathic pleuroparenchymal fibroelastosis (iPPFE) remains unclear.MethodsWe retrospectively examined patients with idiopathic PPFE or idiopathic pulmonary fibrosis (IPF) who received nintedanib for more than 6 months. We evaluated annual changes in %FVC, radiological PPFE lesions, and body weight before and during nintedanib treatment. To investigate radiological PPFE lesions, we examined the fibrosis score, which was defined as the mean percentage of the high attenuation area in the whole lung parenchyma using three axial computed tomography images.ResultsOverall, 15 patients with iPPFE and 27 patients with IPF were included in the present study. In patients with IPF, the annual rate of decline in %FVC was significantly lower during nintedanib treatment than that before treatment (?2.01%/year [?7.64 to 3.21] versus ?7.64%/year [?10.8 to ?4.44], p = 0.031). Meanwhile, in patients with iPPFE, the annual rate of decline in %FVC during nintedanib treatment was higher than that before treatment (?18.0%/year [?21.6 to ?12.7] versus ?9.40%/year [?12.3 to ?8.23], p = 0.109). In addition, nintedanib treatment failed to inhibit the annual rate of increase in fibrosis score in patients with iPPFE (6.53/year [1.18–15.3] during treatment versus 2.70/year [0.27–12.2] before treatment, p = 0.175).ConclusionsNintedanib efficacy may be limited in patients with iPPFE.     

Lung function decline in sarcoidosis

BackgroundA decline in lung function is the basis of the definition of progressive fibrosing interstitial lung disease. This study aimed to evaluate the epidemiology and clinical relevance of lung function decline in sarcoidosis.MethodsThis retrospective observational study was conducted at a general sarcoidosis clinic. Lung function decline was defined as a relative 24-month decline in the percentage of predicted forced vital capacity (%FVC) of ≥10% or the percentage of predicted diffusion capacity for carbon monoxide (%DLco) of ≥15%. The frequency of lung function decline and its associations with the subsequent 24-month change in lung function and survival time were analyzed.ResultsOf the 201 patients, 14 (7.0%) exhibited a 24-month decline in %FVC of ≥10% and 28 (16.6%) exhibited a 24-month decline in %DLco of ≥15%. A 24-month decline in lung function was not associated with a subsequent 24-month lung function decline. Eleven patients died during the median observational time of 148.3 months; 4 of the 11 deaths were associated with sarcoidosis. A 24-month decline in lung function was associated with worse survival even after the adjustment for composite physiological index (CPI) and pulmonary hypertension (PH): 24-month decline in %FVC ≥10%, hazard ratio (HR) adjusted for CPI = 21.8, HR adjusted for PH = 19.3 and 24-month decline in %DLco ≥15%, HR adjusted for PH = 6.74.ConclusionsA 24-month decline in lung function can be a risk factor for mortality in sarcoidosis irrespective of CPI and PH.     

Serum cytokine changes induced by direct hemoperfusion with polymyxin B-immobilized fiber in patients with acute respiratory failure

BackgroundPolymyxin B-immobilized Fiber therapy (PMX-DHP) may improve the prognosis of patients with rapidly progressive interstitial lung diseases (ILDs). However, the mechanisms by which PMX-DHP ameliorates oxygenation are unclear. The present study aimed to clarify the changes in serum cytokine concentrations during PMX-DHP with steroid pulse therapy.MethodsPatients with acute respiratory failure (ARF) and rapidly progressive ILDs, acute exacerbation of idiopathic pulmonary fibrosis (IPF), or acute respiratory distress syndrome (ARDS), and treated with PMX-DHP were assessed, including patients with IPF. The serum concentrations of 38 cytokines were compared between the ARF and IPF groups before treatment. In the ARF group, cytokine levels were compared before, immediately after PMX-DHP, and the day after termination of steroid pulse therapy.ResultsFourteen ARF and eight IPF patients were enrolled. A comparison of the cytokine levels before treatment initiation revealed that EGF, GRO, IL-10, MDC, IL-12p70, IL-15, sCD40L, IL-7, IP-10, MCP-1, and MIP-1β were significantly different between the two groups. In the ARF group treated with PMX-DHP, the concentrations of MDC, IP-10, and TNF-α continuously decreased during treatment (P < 0.01). Further, the cytokine levels of GRO, IL-10, IL-1Ra, IL-5, IL-6, and MCP-1 decreased after the entire treatment period, with no change observed during the steroid-only period (P < 0.01, except GRO and MCP-1). Although PMX-DHP significantly reduced eotaxin and GM-CSF serum levels (P < 0.01 and P < 0.05), these levels did not change after treatment.ConclusionsPMX-DHP combined with steroid pulse therapy might reduce GRO, IL-10, IL-1Ra, IL-5, IL-6, and MCP-1 levels in ARF, contributing to better oxygenation in the disorder.     

Treatment efficacy of LAMA versus placebo for stable chronic obstructive pulmonary disease: A systematic review and meta-analysis

BackgroundFour long-acting muscarinic antagonists (LAMAs), tiotropium, glycopyrronium, aclidinium, and umeclidinium, are currently available for the treatment of stable chronic obstructive pulmonary disease (COPD). However, no integrated analysis has sought to determine the effectiveness of these LAMAs. Thus, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of LAMA versus placebo in patients with stable COPD.MethodsA literature search of relevant randomized control trials that administered LAMA to stable COPD patients was conducted, and the exacerbations, quality of life (QoL), dyspnea score, lung function, and adverse event of patients were evaluated.ResultsA total of 33 studies were included in this meta-analysis. LAMA significantly decreased the frequency of exacerbations compared to the placebo (OR 0.75; 95% CI 0.66 to 0.85; P < 0.001). The mean changes in the St George's Respiratory Questionnaire score (mean difference, ?3.61; 95% CI, ?4.27 to ?2.95; P < 0.00001), transitional dyspnea index score (mean difference 1.00; 95% CI 0.83 to 1.17; P < 0.00001), and trough FEV₁ (mean difference 0.12; 95% CI 0.11 to 0.13; P < 0.0001) indicated significantly greater improvement in the LAMA group than the placebo group. The number of withdrawals due to adverse events in the LAMA group was significantly fewer than that in the placebo group (OR -0.02; 95% CI -0.03 to ?0.01; P = 0.002).ConclusionLAMA is superior to placebo due to lower frequency of exacerbations and adverse events, as well as higher trough FEV₁, QoL, and dyspnea score for stable COPD.     

Characteristics of tobacco-related lung diseases in Fukuoka Prefecture,Japan: A prospective,multi-institutional,observational study

BackgroundTobacco smoking causes a variety of smoking-related diseases, death, and economic damage. Despite targeted anti-smoking campaigns, tobacco-related deaths are expected to increase in Japan. We investigated the current state of non-cancerous lung diseases such as idiopathic interstitial pneumonias (IIPs), chronic obstructive pulmonary disease (COPD), and combined pulmonary fibrosis and emphysema (CPFE), which are known to be highly related to tobacco smoking.MethodsThis prospective multi-institutional observational study involved 29 major hospitals within the Fukuoka Prefecture area (Fukuoka tobacco-related lung disease registry study group). Patients diagnosed with IIPs, including CPFE and COPD, registered from September 1, 2013 to April 30, 2016 were included. Clinical background information, laboratory and pulmonary function test results, findings of imaging tests, including chest radiography and chest computed tomography, and DNA isolated from peripheral blood were collected from each patient. Follow-up surveillance involved collection of data regarding the exacerbation of disease and death until 5 years of registration. In the present study, we report the baseline characteristics of the patients registered in this surveillance study.ResultsOverall, 1016 patients (524 with IIPs, including 145 CPFE and 492 with COPD) were enrolled. Among the patients with COPD, 96.8% were current or former smokers. Among the patients with IIPs, 69.9% were current or former smokers.ConclusionThis study revealed the current status of lung diseases potentially related to tobacco smoking in Fukuoka Prefecture. Both COPD and CPFE were highly related to tobacco smoking, whereas 30% of patients with IIPs had never smoked.     

The prognostic value of the COPD Assessment Test in fibrotic interstitial lung disease

BackgroundThe COPD Assessment Test (CAT) has been studied as a measure of health status in idiopathic pulmonary fibrosis (IPF) and interstitial lung disease associated with connective tissue disease. However, its prognostic value is unknown. The present study explored the association between CAT score and mortality in fibrotic interstitial lung disease (FILD), including IPF and other forms of ILD.MethodsWe retrospectively analyzed 501 consecutive patients with FILD who underwent clinical assessment, including pulmonary function test and CAT. The association between CAT score and 3-year mortality was assessed using Cox proportional hazard analysis, Kaplan–Meier plots, and the log-rank test for trend. To handle missing data, the imputed method was used.ResultsThe patients’ median age was 68 years, and 320 were male (63.9%). Regarding CAT severity, 203 patients had a low impact level (score <10), 195 had a medium level (10–20), 80 had a high level (21–30), and 23 had a very high level (31–40). During the 3-year study period, 118 patients died. After adjusting for age, sex, forced vital capacity, diffusion capacity for carbon monoxide, IPF diagnosis, and usual interstitial pneumonia pattern on high-resolution computed tomography, the CAT score was significantly associated with 3-year mortality (hazard ratio in increments of 10 points: 1.458, 95% confidence interval 1.161–1.830; p < 0.001). In addition, patients with high and very high impact levels had twofold and threefold higher mortality risk than those with low levels, respectively.ConclusionThe CAT has prognostic value in FILD.     

Various factors contribute to death in patients with different types of pulmonary hypertension: A retrospective pilot study from a single tertiary center

BackgroundA few studies have focused on the cause of death from different types of pulmonary hypertension (PH). This study aimed to systematically analyze the primary and secondary causes of death and compare the profiles between different PH groups.MethodsThe contribution of PH to death was assessed in precapillary PH (i.e., group 1 [pulmonary arterial hypertension], group 3 [PH associated with lung disease], and group 4 [chronic thromboembolic PH]) using specific criteria; death was classified into three categories: PH death (death due to PH only), PH-related death, and PH-unrelated death. Disorders other than PH that contributed to death were analyzed, and mortality profiles were compared between groups.ResultsEighty deceased patients with PH were examined (group 1, n = 28; group 3, n = 39; and group 4, n = 13). The contribution of PH to death was significantly different between the three groups. “PH death” was most common in group 1 (61%), “PH-related death” in group 3 (56%), and “PH-related death” and “PH-unrelated death” in group 4 (38% for both). The highest contributing factor to death other than PH was respiratory failure in group 3 and malignant disease in group 4.ConclusionsSignificant variations in the causes of death were observed in groups 1, 3, and 4 PH patients. In addition to PH, respiratory failure and malignant disease significantly contributed to death in group 3 and group 4 PH, respectively. Understanding the precise death cause may be important in achieving better outcomes in PH patients.     

Impact of obesity on adverse in-hospital outcomes in patients undergoing percutaneous mitral valve edge-to-edge repair using MitraClip® procedure - Results from the German nationwide inpatient sample

Background and aimThe number of percutaneous edge-to-edge mitral regurgitation (MR) valve repairs with MitraClip® implantations increased exponentially in recent years. Studies have suggested an obesity survival paradox in patients with cardiovascular diseases. We investigated the influence of obesity on adverse in-hospital outcomes in patients with MitraClip® implantation.Methods and resultsWe analyzed data on characteristics of patients and in-hospital outcomes for all percutaneous mitral valve repairs using the edge-to-edge MitraClip®-technique in Germany 2011–2015 stratified for obesity vs. normal-weight/over-weight.The nationwide inpatient sample comprised 13,563 inpatients undergoing MitraClip® implantations. Among them, 1017 (7.5%) patients were coded with obesity. Obese patients were younger (75 vs.77 years,P < 0.001), more often female (45.4% vs.39.5%,P < 0.001), had more often heart failure (87.1% vs.79.2%,P < 0.001) and renal insufficiency (67.0% vs.56.4%,P < 0.001). Obese and non-obese patients were comparable regarding major adverse cardiac and cerebrovascular events (MACCE) and in-hospital death. The combined endpoint of cardio-pulmonary resuscitation (CPR), mechanical ventilation and death was more often reached in non-obese than in obese patients with a trend towards significance (20.6%vs.18.2%,P = 0.066). Obesity was an independent predictor of reduced events regarding the combined endpoint of CPR, mechanical ventilation and death (OR 0.75, 95%CI 0.64–0.89,P < 0.001), but not for reduced in-hospital mortality (P = 0.355) or reduced MACCE rate (P = 0.108). Obesity class III was associated with an elevated risk for pulmonary embolism (OR 5.66, 95%CI 1.35–23.77,P = 0.018).ConclusionsWe observed an obesity paradox regarding the combined endpoint of CPR, mechanical ventilation and in-hospital death in patients undergoing MitraClip® implantation, but our results failed to confirm an impact of obesity on in-hospital survival or MACCE.     

Indigo Aspiration System for Treatment of Pulmonary Embolism: Results of the EXTRACT-PE Trial

ObjectivesThis study sought to prospectively evaluate the safety and efficacy of the Indigo aspiration system in submassive acute pulmonary embolism (PE).BackgroundPE treatment with thrombolytics has bleeding risks. Aspiration thrombectomy can remove thrombus without thrombolytics, but data are lacking.MethodsThis study was a prospective, single-arm, multicenter study that enrolled patients with symptomatic acute PE ≤14 days, systolic blood pressure ≥90 mm Hg, and right ventricular-to-left ventricular (RV/LV) ratio >0.9. The primary efficacy endpoint was change in RV/LV ratio from baseline to 48 h post-procedure on core lab–adjudicated computed tomography angiography. The primary safety endpoint was a composite of 48-h major adverse events: device-related death, major bleeding, and device-related serious adverse events (clinical deterioration, pulmonary vascular, or cardiac injury). All sites received Institutional Review Board approval.ResultsA total of 119 patients (mean age 59.8 ± 15.0 years) were enrolled at 22 U.S. sites between November 2017 and March 2019. Median device insertion to removal time was 37.0 (interquartile range: 23.5 to 60.0) min. Two (1.7%) patients received intraprocedural thrombolytics. Mean RV/LV ratio reduction from baseline to 48 h post-procedure was 0.43 (95% confidence interval: 0.38 to 0.47; p < 0.0001). Two (1.7%) patients experienced 3 major adverse events. Rates of cardiac injury, pulmonary vascular injury, clinical deterioration, major bleeding, and device-related death at 48 h were 0%, 1.7%, 1.7%, 1.7%, and 0.8%, respectively.ConclusionsIn this prospective, multicenter study the Indigo aspiration system was associated with a significant reduction in the RV/LV ratio and a low major adverse event rate in submassive PE patients. Intraprocedural thrombolytic drugs were avoided in 98.3% of patients. (Evaluating the Safety and Efficacy of the Indigo aspiration system in Acute Pulmonary Embolism [EXTRACT-PE]; NCT03218566)     

The REPAIR Study: Effects of Macitentan on RV Structure and Function in Pulmonary Arterial Hypertension

ObjectivesThe REPAIR (Right vEntricular remodeling in Pulmonary ArterIal hypeRtension) study evaluated the effect of macitentan on right ventricular (RV) and hemodynamic outcomes in patients with pulmonary arterial hypertension (PAH), using cardiac magnetic resonance (CMR) and right heart catheterization (RHC).BackgroundRV failure is the primary cause of death in PAH. CMR is regarded as the most accurate noninvasive method for assessing RV function and remodeling and CMR measures of RV function and structure are strongly prognostic for survival in patients with PAH. Despite this, CMR is not routinely used in PAH clinical trials.MethodsREPAIR was a 52-week, open-label, single-arm, multicenter, phase 4 study evaluating the effect of macitentan 10 mg, with or without phosphodiesterase type-5 inhibition, on RV remodeling and function and cardiopulmonary hemodynamics. Primary endpoints were change from baseline to week 26 in RV stroke volume, determined by CMR; and pulmonary vascular resistance, determined by RHC. Efficacy measures were assessed for all patients with baseline and week 26 data for both primary endpoints.ResultsAt a prespecified interim analysis in 42 patients, both primary endpoints were met, enrollment was stopped, and the study was declared positive. At final analysis (n = 71), RV stroke volume increased by 12 mL (96% confidence level: 8.4-15.6 mL; P < 0.0001) and pulmonary vascular resistance decreased by 38% (99% confidence level: 31%-44%; P < 0.0001) at week 26. Significant positive changes were also observed in secondary and exploratory CMR (RV and left ventricular), hemodynamic, and functional endpoints at week 26. Improvements in CMR RV and left ventricular variables and functional parameters were maintained at week 52. Safety (n = 87) was consistent with previous clinical trials.ConclusionsIn the context of this study, macitentan treatment in patients with PAH resulted in significant and clinically-relevant improvements in RV function and structure and cardiopulmonary hemodynamics. At 52 weeks, improvements in RV function and structure were sustained. (REPAIR: Right vEntricular remodeling in Pulmonary ArterIal hypeRtension [REPAIR]; NCT02310672)     

Pulmonary Artery Denervation for Pulmonary Arterial Hypertension: A Sham-Controlled Randomized PADN-CFDA Trial

BackgroundWorld Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH) is a progressive, debilitating disease. Previous observational studies have demonstrated that pulmonary artery denervation (PADN) reduces pulmonary artery pressures in PAH. However, the safety and effectiveness of PADN have not been established in a randomized trial.ObjectivesThe aim of this study was to determine the treatment effects of PADN in patients with group 1 PAH.MethodsPatients with WHO group 1 PAH not taking PAH-specific drugs for at least 30 days were enrolled in a multicenter, sham-controlled, single-blind, randomized trial. Patients were assigned to receive PADN plus a phosphodiesterase-5 inhibitor or a sham procedure plus a phosphodiesterase-5 inhibitor. The primary endpoint was the between-group difference in the change in 6-minute walk distance from baseline to 6 months.ResultsAmong 128 randomized patients, those treated with PADN compared with sham had a greater improvement in 6-minute walk distance from baseline to 6 months (mean adjusted between-group difference 33.8 m; 95% CI: 16.7-50.9 m; P < 0.001). From baseline to 6 months, pulmonary vascular resistance was reduced by ?3.0 ± 0.3 WU after PADN and ?1.9 ± 0.3 WU after sham (adjusted difference ?1.4; 95% CI: ?2.6 to ?0.2). PADN also improved right ventricular function, reduced tricuspid regurgitation, and decreased N-terminal pro–brain natriuretic peptide. Clinical worsening was less (1.6% vs 13.8%; OR: 0.11; 95% CI: 0.01-0.87), and a satisfactory clinical response was greater (57.1% vs 32.3%; OR: 2.79; 95% CI: 1.37-5.82) with PADN treatment during 6-month follow-up.ConclusionsIn patients with WHO group 1 PAH, PADN improved exercise capacity, hemodynamic status, and clinical outcomes during 6-month follow-up. (Safety and Efficacy of Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension [PADN-CFDA]; NCT03282266)