Serial 6-month change in forced vital capacity predicts subsequent decline and mortality in Japanese patients with newly diagnosed idiopathic pulmonary fibrosis

BackgroundThe clinical course of idiopathic pulmonary fibrosis (IPF) is characterized by a progressive decline in lung function; however, predicting changes in lung function is difficult. We sought to determine whether the prior 6-month trend in forced vital capacity (FVC) could predict mortality and the subsequent 6-month trend in FVC.MethodsWe retrospectively analyzed consecutive patients with newly diagnosed IPF who underwent serial pulmonary function tests. The immediate two years after the initial evaluation were divided into four terms of six months each and stratified on the basis of presence or absence of a ≥10% relative decline in FVC at six months (declined and stable groups, respectively).ResultsWe included 107 patients with %predicted FVC of 80.8% and %predicted diffusing capacity of the lung for carbon monoxide of 58.9%. In multivariate analysis, a decline in %predicted FVC in the initial six months was found to be an independent prognostic factor (hazard ratio 4.45, 95% confidence interval 2.62–7.56, p < 0.01). Among the 46 terms in which the FVC declined during the initial 1.5-year study period, a decline in FVC was exhibited in 23 (50.0%) of the subsequent terms. Among 231 terms in which FVC remained stable, a decline was observed in 32 (13.9%) of the subsequent terms (relative risk 3.61, p < 0.01). The frequency of FVC decline in each term was 16–27%. FVC was stable or declined in all four terms in 50.5% and 15.9% of cases, respectively.ConclusionsSix-month decline in FVC predicts subsequent FVC change and mortality in IPF patients in the era of antifibrotic agents.     

Predictive factors for the long-term use of pirfenidone in patients with fibrosing interstitial lung disease

BackgroundPirfenidone is an anti-fibrotic agent approved for idiopathic pulmonary fibrosis (IPF), and long-term treatment data and the effect of continuation after disease progression have been reported. The efficacy and safety of pirfenidone in fibrosing interstitial lung disease (ILD) patients without IPF have been recently reported in clinical trials; therefore, the benefits of long-term treatment are also expected. This study aims to analyze the long-term treatment data of pirfenidone and clarify the predictive factors for long-term use of pirfenidone in non-IPF patients.MethodsWe retrospectively reviewed the records of consecutive fibrosing ILD patients who started using pirfenidone between 2008 and 2014.ResultsOf the 266 fibrosing ILD patients, 167 patients had IPF, and 99 had non-IPF. Despite the non-significant differences in body size and pulmonary function between IPF and non-IPF patients, the non-IPF patients had better overall survival than the IPF patients (median 4.06 years vs. 2.09 years, p < 0.0001). In addition, the non-IPF patients had a significantly longer time to treatment discontinuation than the IPF patients (median 2.20 years vs. 1.20 years, p = 0.002). Multivariate logistic regression analysis for ≥2 years of use of pirfenidone showed that the percent predicted forced vital capacity (%FVC) and age were predictive factors common to both IPF and non-IPF patients.ConclusionsOur results indicate that non-IPF patients can continue using pirfenidone for longer durations than IPF patients. Initiation of pirfenidone for fibrosing ILD patients with higher %FVC and younger age would lead to long-term use of pirfenidone.     

Impact of SYNTAX Score on 10-Year Outcomes After Revascularization for Left Main Coronary Artery Disease

ObjectivesThe aim of this study was to investigate the long-term impact of SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (SS) on differential outcomes after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for left main coronary artery (LMCA) disease.BackgroundThe very long term prognostic effect of SS on mortality and major cardiovascular events after LMCA revascularization is still undetermined.MethodsIn the MAIN-COMPARE (Ten-Year Outcomes of Stents Versus Coronary-Artery Bypass Grafting for Left Main Coronary Artery Disease) registry, patients with baseline SS measurements were analyzed. The 10-year rates of all-cause mortality, the composite of death, Q-wave myocardial infarction, or stroke, and target vessel revascularization after PCI or CABG were compared according to baseline SS.ResultsAmong 1,580 patients with baseline SS, 547 patients (34.6%) had low SS (≤22), 350 (22.2%) had intermediate SS (23 to 32), and 683 (43.2%) had high SS (≥33). In patients with low to intermediate SS, the adjusted 10-year risks for death and serious composite outcome were similar between the PCI group and the CABG group. However, in patients with high SS, PCI with stenting, compared with CABG, was associated with a higher risk for death (hazard ratio: 1.39; 95% confidence interval: 1.00 to 1.92; p = 0.048) and serious composite outcome (hazard ratio: 1.27; 95% confidence interval: 0.94 to 1.74; p = 0.123). In each revascularization group, conventional tertiles of SS had a differential prognostic impact on 10-year clinical outcomes in the PCI arm but not in the CABG arm.ConclusionsIn this 10-year extended follow-up of patients undergoing LMCA revascularization, CABG showed a clear prognostic benefit over PCI in patients with high anatomic complexity measured by SS at baseline. The discriminative capacity of SS on long-term outcomes was relevant in the PCI group but not in the CABG group. (Ten-Year Outcomes of Stents Versus Coronary-Artery Bypass Grafting for Left Main Coronary Artery Disease [MAIN-COMPARE]; NCT02791412)     

Impact of Pulmonary Artery Dilatation on Clinical Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement

ObjectivesThe aim of this study was to evaluate the clinical impact of computed tomography (CT)–derived pulmonary artery dilatation (PAD) in patients undergoing transcatheter aortic valve replacement (TAVR).BackgroundSeveral studies have reported an association between pulmonary hypertension and cardiovascular events, but the prognostic value of PAD in patients undergoing TAVR remains unclear.MethodsThe preprocedural computed tomographic studies of patients who underwent TAVR at Cedars-Sinai Medical Center between November 2013 and December 2017 were analyzed. Patients were divided into 2 groups according to the presence of PAD assessed on CT (pulmonary artery [PA] diameter ≥29 mm). The primary endpoint was all-cause mortality at 2 years.ResultsA total of 895 patients were included (mean age 81.3 ± 8.5 years), with a mean Society of Thoracic Surgeons score of 4.8%. The median PA diameter was 28.0 mm, and PAD was observed in 369 patients (41.2%). Compared with the no-PAD group, the PAD group had higher Society of Thoracic Surgeons scores and higher rates of atrial fibrillation, chronic kidney disease, and chronic obstructive pulmonary disease. The PAD group had higher 2-year all-cause mortality than the no-PAD group (28.9% vs 12.8%; P < 0.001), and PAD was independently associated with mortality (adjusted HR: 2.21; 95% CI: 1.44-3.39; P < 0.001). Furthermore, PAD had strong prognostic power in the subgroup analysis, stratified according to PA pressure (>36 mm Hg).ConclusionsCT-derived PAD is a significant prognostic factor in patients undergoing TAVR.     

Characteristics and association with survival of respiratory-related hospitalization in Japanese idiopathic pulmonary fibrosis patients

BackgroundThe characteristics and significance of respiratory-related hospitalization in patients with idiopathic pulmonary fibrosis (IPF) in Asian countries remain unknown. The purpose of this study was to define the characteristics of respiratory-related hospitalization and to inspect the relationship between respiratory-related hospitalization and subsequent survival in patients with IPF in Japanese general practice.MethodsPatients with IPF who underwent clinical evaluation between February 2008 and August 2017 were screened. Only those who had undergone evaluation within 1 year after the diagnosis of IPF were included in the study. The post-diagnosis pulmonary function tests were considered the registration point. We then performed a 6-month landmark analysis including only patients who were alive 6 months after the registration. The characteristics of respiratory-related hospitalizations during the 6 months after registration and the association between respiratory-related hospitalization and survival were investigated.ResultsA total of 106 patients with IPF were included in the study. The mean forced vital capacity (FVC) at registration was 80.2 ± 25.1% predicted. Seventeen patients (16.0%) had respiratory-related hospitalization during the 6 months after registration. Pneumonia was the most frequent reason for hospitalization (47.0%), followed by acute exacerbation of IPF (29.4%). In multivariate analysis, % predicted FVC (hazard ratio: 0.98, 95% confidence interval: 0.96–0.99, p = 0.004), 6-month decrease in % predicted FVC (1.05, 1.02–1.08, 0.005), and respiratory-related hospitalization (2.45, 1.24–4.85, 0.009) were significantly associated with survival.ConclusionsPneumonia is the most frequent cause of respiratory-related hospitalization in Japanese IPF patients. Furthermore, respiratory-related hospitalization is significantly associated with subsequent poor survival.     

Human epididymis protein 4 is a new biomarker to predict the prognosis of progressive fibrosing interstitial lung disease

BackgroundThe clinical course and prognosis of progressive fibrosing interstitial lung diseases (PF-ILDs) vary between individuals. Notably, predictive serum biomarkers for disease management are needed. Serum human epididymis protein 4 (HE4) is reportedly elevated in patients with idiopathic pulmonary ?brosis (IPF); however, its clinical utility remains unknown. We evaluated the potential of serum HE4 as a biomarker for patients with PF-ILD.MethodsSerum HE4 was measured in a retrospective study consisting of 34 patients with PF-ILD and 40 healthy volunteers. The relationship between serum HE4 levels and clinical parameters or prognosis was investigated. To validate the significance of results obtained, a prospective observational study was performed in 37 patients presenting PF-ILD and 40 control patients without PF-ILD.ResultsSerum HE4 levels were higher in patients with PF-ILD than in healthy volunteers (P < 0.01). Moreover, serum HE4 levels correlated with the extent of honeycombing on chest high-resolution computed tomography (r = 0.41, P = 0.015). In multivariate analysis using the Cox proportional hazard model, higher HE4 levels (>238 pmol/L) were associated with an elevated mortality risk; hazard ratio (HR) 7.27, 95% CI 1.56–34.0, P = 0.01 in the derivation cohort; HR 44.3, 95% CI 4.19–468, P < 0.01 in validation cohort.ConclusionsSerum HE4 levels may serve as a new diagnostic and prognostic biomarker for patients with PF-ILD.     

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.     

Extent of pulmonary fibrosis on high-resolution computed tomography is a prognostic factor in patients with pleuroparenchymal fibroelastosis

BackgroundSeveral prognostic factors for pleuroparenchymal fibroelastosis (PPFE) have recently been reported. However, detailed high-resolution computed tomography (HRCT) findings have not yet been evaluated as prognostic factors. This study retrospectively investigated whether HRCT findings are prognostic factors in patients with PPFE compared to those with idiopathic pulmonary fibrosis (IPF).MethodsPatients with PPFE and IPF diagnosed at our hospital between January 2008 and December 2016 were enrolled. Clinical and HRCT characteristics were obtained. In addition to our patients, we also analyzed data of PPFE patients whose cause of death had been identified in previous studies.ResultsWe enrolled 15 patients with PPFE and 75 patients with IPF. Consolidation and maximum pleural thickening were significantly higher in patients with PPFE than in those with IPF (both P < .001). Fibrosis score, honeycomb area, and traction bronchiectasis were not significantly different between these patient groups but were significant prognostic factors in patients with PPFE in univariate analysis (P = .021, P = .017, and P = .014, respectively). The proportions of deaths by acute exacerbation or lung cancer were significantly lower in patients with PPFE than in those with IPF (P < .001 and P = .001, respectively), whereas death by respiratory failure was significantly more frequent in PPFE patients (P < .001).ConclusionsHRCT findings, such as fibrosis score, honeycomb area, and traction bronchiectasis, were independent prognostic factors in patients with PPFE. Respiratory failure, but not acute exacerbation and lung cancer, was the main cause of death in patients with PPFE.     

Predictors of acute exacerbation in biopsy-proven idiopathic pulmonary fibrosis

BackgroundAcute exacerbation (AE) is a major cause of death in patients with idiopathic pulmonary fibrosis (IPF). Current evidence on AE-IPF has been largely based on clinical, rather than pathological, analyses.MethodsWe investigated AE incidence and its predictors using clinical, radiological, and pathological data of patients diagnosed with IPF by multi-disciplinary discussion.This study, a secondary analysis of previous research, included 155 patients with IPF who underwent surgical lung biopsy (SLB). Cumulative AE incidence was evaluated by the Kaplan–Meier method. Predictors of AE-IPF were analyzed with a Fine-Gray sub-distribution hazard model. Sub-analysis was performed using propensity score-matching analysis.ResultsIn this cohort, the median age of the patients was 66 years and the median percent-predicted forced vital capacity was 82.8%. The cumulative AE incidence rates at 30 days and one year post SLB were 1.9% and 7.6%, respectively. On multivariable analysis, a lower percent-predicted diffusing capacity of the lung for carbon monoxide (%DL_CO) (hazard ratio 0.98 per 1% increase, P = 0.02) and fibroblastic foci (FF)-present (vs. absent; hazard ratio 3.01, P = 0.04) were independently associated with a higher incidence of AE. The propensity score-matching analysis with adjustment for age, gender, and %DL_CO revealed that the cumulative AE incidence rate was significantly higher in the FF-present subgroup than in the FF-absent subgroup (1-year incidence rate, 10.5% vs. 0%, respectively; P = 0.04 by Gray's test).ConclusionsFF and %DL_CO were independent predictors of AE in patients with biopsy-proven IPF. FF may be associated with the pathogenesis of AE-IPF.     

Role of serum surfactant protein-D as a prognostic predictor in fibrotic hypersensitivity pneumonitis

BackgroundSerum Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) are candidate diagnostic and activity markers for fibrotic hypersensitivity pneumonitis (HP), although their correlation with prognosis remains unclear. We aimed to evaluate the prognostic usefulness of serum KL-6 and SP-D in patients with fibrotic HP.MethodsThis was a retrospective medical record review of 185 patients with fibrotic HP at a single center from 2005 to 2019. The baseline and minimum serum KL-6 and SP-D levels over two years were recorded. The contribution of KL-6 and SP-D levels to the incidence of progressive fibrosing interstitial lung disease (PF-ILD) and mortality were evaluated using multivariate analysis.ResultsThe respective baseline and minimum levels were 1441 and 808 U/ml for KL-6 and 254 and 132 ng/mL for SP-D. A high minimum SP-D level was significantly associated with a high incidence of PF-ILD by logistic regression, independent of baseline forced vital capacity and honeycombing. Similarly, a high minimum SP-D level was significantly associated with high mortality by Cox proportional hazard model analysis. The stratified minimum SP-D levels of <100, 100–200, and >200 revealed significantly distinct groups in the entire cohort, with PF-ILD incidence rates of 28%, 48%, and 74% and median survival times of 120, 74, and 45 months, respectively.ConclusionsHigh minimum SP-D levels over two years were correlated with an unfavorable prognosis in our cohort. Patient with consistently high SP-D levels during the clinical course may have a poor prognosis and be a candidate for early treatment intensification.     

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.     

Prognostic Value of SYNTAX Score in Patients With Infarct-Related Cardiogenic Shock: Insights From the CULPRIT-SHOCK Trial

ObjectivesThis study sought to evaluate the prognostic value of the SYNTAX (SYNergy between PCI with TAXUS and Cardiac Surgery) scores in patients undergoing percutaneous coronary intervention (PCI) for multivessel coronary disease with infarct-related cardiogenic shock (CS).BackgroundThe prognostic value of the SYNTAX score in this high-risk setting remains unclear.MethodsThe CULPRIT-SHOCK (Culprit Lesion Only PCI versus Multivessel PCI in Cardiogenic Shock) trial was an international, open-label trial, where patients presenting with infarct-related CS and multivessel disease were randomized to a culprit-lesion-only or an immediate multivessel PCI strategy. Baseline SYNTAX score was assessed by a central core laboratory and categorized as low SYNTAX score (SS ≤22), intermediate SYNTAX score (22<SS≤32) and high SYNTAX score (SS>32). Adjudicated endpoints of interest were the 30-day risk of death or renal replacement therapy (RRT) and 1-year death. Associations between baseline SYNTAX score and outcomes were assessed using multivariate logistic regression.ResultsPre-PCI SYNTAX score was available in 624 patients, of whom 263 (42.1%), 207 (33.2%) and 154 (24.7%) presented with low, intermediate and high SYNTAX score, respectively. A stepwise increase in the incidence of adverse events was observed from low to intermediate and high SYNTAX score for the 30-day risk of death or RRT and the 1-year risk of death (p < 0.001, for all). After multiple adjustments, intermediate and high SYNTAX score remained strongly associated with 30-day risk of death or renal replacement therapy and 1-year risk of all-cause death. There was no significant interaction between SYNTAX score and the coronary revascularization strategy for any outcomes.ConclusionsIn patients presenting with multivessel disease and infarct-related CS, the SYNTAX score was strongly associated with 30-day death or RRT and 1-year mortality.     

Machine-Learning Score Using Stress CMR for Death Prediction in Patients With Suspected or Known CAD

BackgroundIn patients with suspected or known coronary artery disease, traditional prognostic risk assessment is based on a limited selection of clinical and imaging findings. Machine learning (ML) methods can take into account a greater number and complexity of variables.ObjectivesThis study sought to investigate the feasibility and accuracy of ML using stress cardiac magnetic resonance (CMR) and clinical data to predict 10-year all-cause mortality in patients with suspected or known coronary artery disease, and compared its performance with existing clinical or CMR scores.MethodsBetween 2008 and 2018, a retrospective cohort study with a median follow-up of 6.0 (IQR: 5.0-8.0) years included all consecutive patients referred for stress CMR. Twenty-three clinical and 11 stress CMR parameters were evaluated. ML involved automated feature selection by random survival forest, model building with a multiple fractional polynomial algorithm, and 5 repetitions of 10-fold stratified cross-validation. The primary outcome was all-cause death based on the electronic National Death Registry. The external validation cohort of the ML score was performed in another center.ResultsOf 31,752 consecutive patients (mean age: 63.7 ± 12.1 years, and 65.7% male), 2,679 (8.4%) died with 206,453 patient-years of follow-up. The ML score (ranging from 0 to 10 points) exhibited a higher area under the curve compared with Clinical and Stress Cardiac Magnetic Resonance score, European Systematic Coronary Risk Estimation score, QRISK3 score, Framingham Risk Score, and stress CMR data alone for prediction of 10-year all-cause mortality (ML score: 0.76 vs Clinical and Stress Cardiac Magnetic Resonance score: 0.68, European Systematic Coronary Risk Estimation score: 0.66, QRISK3 score: 0.64, Framingham Risk Score: 0.63, extent of inducible ischemia: 0.66, extent of late gadolinium enhancement: 0.65; all P < 0.001). The ML score also exhibited a good area under the curve in the external cohort (0.75).ConclusionsThe ML score including clinical and stress CMR data exhibited a higher prognostic value to predict 10-year death compared with all traditional clinical or CMR scores.     

The interaction between hyperuricemia and low-density lipoprotein cholesterol increases the risk of 1-year post-discharge all-cause mortality in ST-segment elevation myocardial infarction patients

Background and aimsHyperuricemia is a known risk factor for cardiovascular diseases, but little is known on whether the association between hyperuricemia and poor outcomes in ST-segment elevation myocardial infarction (STEMI) is modified by low-density lipoprotein cholesterol (LDL-c). This study aimed to investigate the effect of the interaction between hyperuricemia and LDL-c on the risk of 1-year post-discharge all-cause mortality in STEMI patients.Methods and resultsA total of 1396 STEMI patients were included. Cox proportional hazards models were used to determine the association between hyperuricemia and 1-year all-cause mortality in the overall population and subgroups stratified based on LDL-c levels (<3.0 mmol/L or ≥3.0 mmol/L). Multivariate analysis indicated that hyperuricemia was associated with 1-year mortality (HR: 2.66; 95% CI: 1.30–5.47; p = 0.008). However, the prognostic effect of hyperuricemia was only observed in patients with LDL-c level ≥3.0 mmol/L (HR: 12.90; 95% CI: 2.98–55.77; p < 0.001), but not in those with LDL-c level <3.0 mmol/L (HR: 0.91, 95% CI: 0.30–2.79, p = 0.875). The interaction between hyperuricemia and LDL-c levels had a significant effect on 1-year mortality.ConclusionHyperuricemia was associated with increased 1-year post-discharge mortality in patients with LDL-c level≥ 3.0 mmol/L, but not in those with LDL-c level< 3.0 mmol/L.     

Association of Life's Essential 8 with all-cause and cardiovascular mortality among US adults: A prospective cohort study from the NHANES 2005–2014

Background and aimsThis study aims to investigate the association of Life's Essential 8 (LE8), the recently updated algorithm for quantifying cardiovascular health (CVH) by the American Heart Association (AHA), with long-term outcomes among US adults.Methods and resultsThis population-based prospective cohort study analyzed data of 23,110 participants aged 20 years or older from the National Health and Nutrition Examination Survey from 2005 to 2014 and their linked mortality data through December 2019. LE8 score (range 0–100) was measured according to AHA definitions and was categorized into low (0–49), moderate (50–79), and high (80–100) CVH. The weighted mean age of the study population was 47.0 years (95% confidence interval [CI], 46.4–47.5 years), and 11,840 were female (weighted percentage, 51.5%; 95% CI, 50.9–52.1%). During a median follow-up period of 113 months (up to 180 months), 2942 all-cause deaths occurred, including 738 CVD deaths. The LE8 score was significantly and inversely related to mortality from all causes (adjusted hazard ratio [HR] for per 10-score increase in LE8 score, 0.86; 95% CI, 0.82–0.90) and cardiovascular disease (adjusted HR for per 10-score increase in LE8 score, 0.81; 95% CI, 0.75–0.87). Compared with participants having low CVH, those having high CVH had a reduction of 40% (adjusted HR, 0.60; 95% CI, 0.48–0.75) in the risk for all-cause mortality and 54% (adjusted HR, 0.46; 95% CI, 0.31–0.68) in the risk for cardiovascular mortality.ConclusionsHigher LE8 score was independently associated with lower risks of all-cause and cardiovascular mortality among US adults.     

Clinical significance and safety of combined treatment with chemotherapy and pulmonary rehabilitation regarding health-related quality of life and physical function in nontuberculous mycobacterial pulmonary disease

BackgroundIn the treatment of patients with nontuberculous mycobacterial pulmonary disease (NTM-PD), pulmonary rehabilitation (PR) has been recommended as a non-pharmacological therapy. However, no study has validated the combination of chemotherapy and PR in this context. This study investigated the effect of chemotherapy and supervised PR on health-related quality of life (HRQoL) and physical function in NTM-PD patients.MethodsThis prospective cohort study included patients diagnosed with NTM-PD who had a planned hospitalization of at least 3 weeks for chemotherapy and PR. HRQoL (Leicester Cough Questionnaire [LCQ] and chronic obstructive pulmonary disease assessment test [CAT]), physical function (incremental shuttle walk distance [ISWD], quadriceps force), and C-reactive protein levels were assessed before and after treatment, and the corresponding data were analyzed in conjunction with clinical data. The adverse events of PR were also investigated.ResultsForty-two patients who met the study criteria were included in the analysis. After treatment, all LCQ item scores, total CAT score and sub-item scores related to respiratory symptoms, ISWD, quadriceps force, and C-reactive protein levels were found to have improved significantly. In the chronic cough with excessive sputum production (CCS) group, the proportions of responders who showed improvements in LCQ and CAT scores and ISWD greater than the corresponding minimal clinically important difference were significantly greater than those in the non-CCS group. No PR-related adverse events were reported.ConclusionsCombined treatment with chemotherapy and PR may improve HRQoL and physical function, and supervised PR can be provided safely.     

Association between monocyte count to high-density lipoprotein cholesterol ratio and mortality in patients undergoing peritoneal dialysis

Background and aimsPrevious studies had demonstrated that elevated monocyte count to high-density lipoprotein cholesterol ratio (MHR), a novel marker of inflammation, was associated with higher cardiovascular events and mortality in patients with pre-dialysis chronic kidney disease, diabetes, and coronary heart disease. However, the association between MHR and mortality in patients undergoing peritoneal dialysis (PD) has received little attention. The aim of this study was to investigate the association between MHR and all-cause and cardiovascular mortality in PD patients.Methods and resultsIn this single center retrospective cohort study, PD patients who had catheter insertion in our PD center from January 1, 2006 to December 31, 2016 were enrolled. All patients were divided into three groups according to the tertiles of baseline MHR levels and followed up until December 31, 2018. The associations of MHR levels with all-cause and cardiovascular mortality were assessed by using Cox proportional hazards models. Of 1584 patients, mean age was 46.02 ± 14.65 years, 60.1% were male, and 24.2% had diabetes. The mean MHR level was 0.39 ± 0.23. During a median follow up time of 45.6 (24.6–71.8) months, 349 patients died, and 181 deaths were caused by cardiovascular disease. After adjusting for confounders, the highest MHR tertile was significantly associated with all-cause and cardiovascular mortality with a hazard ratio of 1.43 (95%CI = 1.06–1.93, P = 0.019), 1.54 (95%CI = 1.01–2.35, P = 0.046), respectively.ConclusionHigher MHR level was an independent risk factor for all-cause and cardiovascular mortality in PD patients.     

Cardiopulmonary Hemodynamic Profile Predicts Mortality After Transcatheter Tricuspid Valve Repair in Chronic Heart Failure

ObjectivesThis study was designed to assess hemodynamic changes in response to transcatheter tricuspid valve edge-to-edge repair (TTVR) and to identify hemodynamic predictors associated with mortality.BackgroundSevere tricuspid regurgitation (TR) is associated with high mortality. TTVR effectively alleviates heart failure symptoms, but comprehensive hemodynamic characterization of patients undergoing TTVR is currently lacking.MethodsThis international, multicenter study included 236 patients undergoing TTVR. Data from clinical assessment, echocardiography, intraprocedural right heart catheterization, and noninvasive cardiac output measurement were analyzed. Hemodynamic predictors for mortality were identified using linear Cox regression analysis and were used for stratification of patients with subsequent analysis of survival time.ResultsPatients (median age 78 years, 53% women) were symptomatic (89% in New York Heart Association functional class III or IV) because of severe TR (grade ≥3+ in 100%). TTVR significantly reduced TR at discharge (grade ≥3+ in 16%; p < 0.001), with a corresponding 19% reduction of the right atrial v wave (21 mm Hg vs. 16 mm Hg; p < 0.001) and an improvement in cardiac output (from 3.5 to 4.0 l/min; p < 0.01). Invasive mean pulmonary artery pressure, transpulmonary gradient, pulmonary vascular resistance, and right ventricular stroke work were significant predictors of 1-year mortality (p < 0.05 for all). Hemodynamic stratification by mean pulmonary artery pressure and transpulmonary gradient best predicted 1-year survival (p < 0.001). Although patients with pre-capillary dominant pulmonary hypertension showed an unfavorable prognosis (1-year survival 38%), patients without or with post-capillary pulmonary hypertension had favorable outcome (1-year survival 92% or 78%, respectively).ConclusionsInvasive assessment of cardiopulmonary hemodynamic status predicts survival after TTVR. Invasive hemodynamic characterization may help identify patients profiting most from TTVR.     

Incidence and changes in treatment of acute exacerbation of idiopathic pulmonary fibrosis in Japan: A claims-based retrospective study

BackgroundAcute exacerbation is an essential prognostic factor in idiopathic pulmonary fibrosis (IPF) and is the leading cause of death in Japanese patients with IPF. Its epidemiology, treatment status, and effect on IPF progression have been insufficiently investigated. We examined the incidence of acute exacerbation and treatment status before and after the onset of acute exacerbation in Japanese patients with IPF to provide basic information for treatment strategies.MethodsA Japanese claims database (April 2008–March 2019) from acute-care hospitals was analyzed. Incidence of acute exacerbation, time to the next event, and percentages of patients who received each treatment by the year before and after the onset of acute exacerbation were examined in patients diagnosed with IPF at least once. Acute exacerbation was defined according to the use of steroid pulse therapy.ResultsWe identified 9961 patients with IPF and 2629 acute exacerbations (average age at the time of acute exacerbation: 74.8 years, percentage of men: 79%). The annual incidence of acute exacerbation was approximately 10% between 2010 and 2018. The time to the next acute exacerbation shortened with increasing number of these events. The percentage of patients receiving antifibrotic drugs remained constant (30%–40%) throughout the period. The percentages of patients receiving steroid therapy, immunosuppressive drugs, and oxygen therapy increased after the onset of acute exacerbation compared with before the onset.ConclusionsThe annual incidence of acute exacerbation was approximately 10% in recent years. It is suggested that acute exacerbation worsens respiratory function in patients with IPF.