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.     

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.     

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.     

Deterioration of high-resolution computed tomography findings predicts disease progression after initial decline in forced vital capacity in idiopathic pulmonary fibrosis patients treated with pirfenidone

BackgroundPirfenidone suppresses the decline of forced vital capacity (FVC) in patients with idiopathic pulmonary fibrosis (IPF). However, IPF progresses in some patients despite treatment. We analyzed patients with meaningful FVC declines during pirfenidone treatment and explored the factors predictive of disease progression after FVC decline.MethodsThis study was a retrospective, multicenter, observational study conducted by the Okayama Respiratory Disease Study Group. We defined initial decline in %FVC as 5% or greater per 6-month period during pirfenidone treatment. IPF patients who were treated with pirfenidone and experienced an initial decline from December 2008 to September 2017 were enrolled.ResultsWe analyzed 21 patients with IPF. After the initial decline, 4 (19.0%) patients showed improvement in disease, 11 (52.4%) showed stable disease, and 6 (28.6%) showed progressive disease. There was no significant correlation between %FVC reduction on initial decline and subsequent %FVC change (p = 0.475). Deterioration of high-resolution computed tomography (HRCT) findings on initial decline was observed significantly more often in the progressive versus improved/stable disease groups (100% vs 20.0%, p = 0.009).ConclusionsWe revealed that deterioration of HRCT findings may predict disease progression after the initial decline in %FVC in IPF patients treated with pirfenidone.     

A modified GAP model for East-Asian populations with idiopathic pulmonary fibrosis

BackgroundThe easy-to-calculate gender, age, and lung physiology (GAP) model shows good predictive and discriminative performance in the prognosis of idiopathic pulmonary fibrosis (IPF). However, the GAP model was not effective in predicting the prognosis accurately in previous Japanese and Korean IPF cohort studies. Therefore, we developed a modified GAP model for the East-Asian populations by weighing the GAP variables. The validity of the modified GAP model was subsequently evaluated in East-Asian IPF patients.MethodsThe derivation cohort comprised 326 patients with IPF. Weights of the variables were adjusted on the basis of coefficients derived from Cox regression models. The total points were distributed to the three stages of the disease so that the number of patients included in each stage was appropriate. The validity of the modified model was analyzed in another Japanese cohort of 117 patients with IPF and a nationwide cohort of Korean patients with IPF.ResultsPredicted survival rates differed significantly in the derivation cohort using the modified GAP model for each stage of IPF (log-rank test: stage I vs. stage II, p < 0.001; stage II vs. stage III, p < 0.001). Model performance improved according to Harrell's C-index (at three years: 0.696 in the original GAP model to 0.738 in the modified model). The performance of the modified model was validated in the Japanese validation and Korean national cohorts.ConclusionsOur modification of the original GAP model showed improved performance in East-Asian IPF patient populations.     

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.     

Serum S100A8 and S100A9 as prognostic biomarkers in acute exacerbation of idiopathic pulmonary fibrosis

BackgroundAcute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a devastating and life-threatening condition during its clinical course. Biomarkers for precisely anticipating the prognosis of AE-IPF remain to be fully established. The objective of this study was to clarify whether S100A8 and S100A9, which are calcium-binding proteins mainly produced by activated neutrophils, are significant prognostic biomarkers in AE-IPF.MethodsThirty-seven patients with AE-IPF who were diagnosed and treated at our hospital were retrospectively evaluated. The serum levels of S100A8 and S100A9 were measured using enzyme-linked immunosorbent assay, and the relationships between these levels and clinical parameters or prognosis were evaluated.ResultsThe serum levels of S100A8 (median 386.5 ng/mL) and S100A9 (median 60.2 ng/mL) in patients with AE-IPF were significantly higher than those in age-matched healthy controls and in patients at IPF diagnosis (p < 0.001 for all combinations). The serum levels of S100A8 negatively correlated with percent forced vital capacity (r = −0.356, p = 0.049) and positively correlated with peripheral white blood cell number (r = 0.509, p = 0.002). Immunohistochemical staining of autopsy lung specimens showed that neutrophils, present mainly in the alveolar septum, were positive for S100A8 and S100A9. Patients with AE-IPF with higher levels of S100A8 or S100A9 showed significantly worse 3-month survival than those with lower levels (log-rank test, both p = 0.028). Finally, in multivariate analysis, the serum levels of both S100A8 and S100A9 were significant prognostic factors (hazard ratio 4.032, p = 0.023 and hazard ratio 4.327, p = 0.012).ConclusionThe serum levels of S100A8 and S100A9 at AE were significant prognostic biomarkers in patients with AE-IPF.     

12-Month Results From the Unblinded Phase of the RADIANCE-HTN SOLO Trial of Ultrasound Renal Denervation

ObjectivesThis study reports the 12-month results of the RADIANCE-HTN (A Study of the ReCor Medical Paradise System in Clinical Hypertension) SOLO trial following unblinding of patients at 6 months.BackgroundThe blood pressure (BP)–lowering efficacy and safety of endovascular ultrasound renal denervation (RDN) in the absence (2 months) and presence (6 months) of antihypertensive medications were previously reported.MethodsPatients with daytime ambulatory BP ≥135/85 mm Hg after 4 weeks off medication were randomized to RDN (n = 74) or sham (n = 72) and maintained off medication for 2 months. A standardized medication escalation protocol was instituted between 2 and 5 months (blinded phase). Between 6 and 12 months (unblinded phase), patients received antihypertensive medications at physicians’ discretion. Outcomes at 12 months included medication burden, change in daytime ambulatory systolic BP (dASBP) and office or home systolic BP (SBP), visit-to-visit variability in SBP, and safety.ResultsSixty-five of 74 RDN patients and 67 of 72 sham patients had 12-month dASBP measurements. The proportion of patients on ≥2 medications (27.7% vs. 44.8%; p = 0.041), the number of medications (1.0 vs. 1.4; p = 0.015), and defined daily dose (1.4 vs. 2.2; p = 0.007) were less with RDN versus sham. The decrease in dASBP from baseline in the RDN group (−16.5 ± 12.9 mm Hg) remained stable at 12 months. The RDN versus sham adjusted difference at 12 months was −2.3 mm Hg (95% confidence interval [CI]: −5.9 to 1.3 mm Hg; p = 0.201) for dASBP, −6.3 mm Hg (95% CI: −11.1 to −1.5 mm Hg; p = 0.010) for office SBP, and −3.4 mm Hg (95% CI: −6.9 to 0.1 mm Hg; p = 0.062) for home SBP. Visit-to-visit variability in SBP was smaller in the RDN group. No renal artery injury was detected on computed tomographic or magnetic resonance angiography.ConclusionsDespite unblinding, the BP-lowering effect of RDN was maintained at 12 months with fewer prescribed medications compared with sham.     

Effect of Ticagrelor on Left Ventricular Remodeling in Patients With ST-Segment Elevation Myocardial Infarction (HEALING-AMI)

ObjectivesThe aim of this study was to evaluate the effect of ticagrelor versus clopidogrel on left ventricular (LV) remodeling after reperfusion of ST-segment elevation myocardial infarction (STEMI) in humans.BackgroundAnimal studies have demonstrated that ticagrelor compared with clopidogrel better protects myocardium against reperfusion injury and improves remodeling after myocardial infarction.MethodsIn this investigator-initiated, randomized, open-label, assessor-blinded trial performed at 10 centers in Korea, patients were enrolled if they had naive STEMI successfully treated with primary percutaneous coronary intervention (PCI) and at least 6-month planned duration of dual-antiplatelet treatment. The coprimary endpoints were LV remodeling index (LVRI) (a relative change of LV end-diastolic volume) measured on 3-dimensional echocardiography and N-terminal pro–B-type natriuretic peptide level at 6 months.ResultsAmong initially enrolled patients with STEMI (n = 336), 139 in each group completed the study. LVRI at 6 months was numerically lower with ticagrelor versus clopidogrel (0.6 ± 18.6% vs. 4.5 ± 16.5%; p = 0.095). Ticagrelor significantly reduced the 6-month level of N-terminal pro–B-type natriuretic peptide (173 ± 141 pg/ml vs. 289 ± 585 pg/ml; p = 0.028). These differences were prominent in patients with pre-PCI TIMI (Thrombolysis In Myocardial Infarction) flow grade 0. By multivariate analysis, ticagrelor versus clopidogrel reduced the risk for positive LV remodeling (LVRI >0%) (odds ratio: 0.56; 95% confidence interval: 0.33 to 0.95; p = 0.030). The LV end-diastolic volume index remained unchanged during ticagrelor treatment (from 54.7 ± 12.2 to 54.2 ± 12.2 ml/m²; p = 0.629), but this value increased over time during clopidogrel treatment (from 54.6 ± 11.3 to 56.4 ± 13.9 ml/m²; p = 0.056) (difference −2.3 ml/m²; 95% confidence interval: −4.8 to 0.2 ml/m²; p = 0.073). Ticagrelor reduced LV end-systolic volume index (from 27.0 ± 8.5 to 24.7 ± 8.4 ml/m²; p < 0.001), whereas no reduction was seen with clopidogrel (from 26.2 ± 8.9 to 25.6 ± 11.0 ml/m²; p = 0.366) (difference −1.8 ml/m²; 95% confidence interval: −3.5 to −0.1 ml/m²; p = 0.040).ConclusionsTicagrelor was superior to clopidogrel for LV remodeling after reperfusion of STEMI with primary PCI. (High Platelet Inhibition With Ticagrelor to Improve Left Ventricular Remodeling in Patients With ST Segment Elevation Myocardial Infarction [HEALING-AMI]; NCT02224534)     

Interstitial pneumonia with autoimmune features and histologic usual interstitial pneumonia treated with anti-fibrotic versus immunosuppressive therapy

BackgroundTherapeutic strategies in patients with interstitial pneumonia with autoimmune features (IPAF) and histological usual interstitial pneumonia (UIP) pattern (IPAF-UIP) have not been thoroughly evaluated. We compared the therapeutic efficacy of anti-fibrotic therapy with that of immunosuppressive treatment for patients with IPAF-UIP.MethodsIn this retrospective case series, we identified consecutive IPAF-UIP patients treated with anti-fibrotic therapy or immunosuppressive therapy. Clinical characteristics, one-year treatment response, acute exacerbation, and survival were studied. We performed a stratified analysis by the pathological presence or absence of inflammatory cell infiltration.ResultsTwenty-seven patients with anti-fibrotic therapy and 29 with immunosuppressive treatment were included. There was a significant difference in one-year forced vital capacity (FVC) change between patients with anti-fibrotic treatment (4 in 27 improved, 12 stable, and 11 worsened) and those with immunosuppressive treatment (16 in 29 improved, eight stable, and five worsened) (p = 0.006). There was also a significant difference in one-year St George's Respiratory Questionnaire (SGRQ) change between patients with anti-fibrotic therapy (2 in 27 improved, ten stable, and 15 worsened) and those with immunosuppressive treatment (14 in 29 improved, 12 stable, and worsened) (p < 0.001). There was no significant difference in survival between the groups (p = 0.32). However, in the subgroup with histological inflammatory cell infiltration, survival was significantly better with immunosuppressive therapy (p = 0.02).ConclusionIn IPAF-UIP, immunosuppressive therapy seemed to be superior to anti-fibrotic treatment in terms of therapeutic response, and provided better outcomes in the histological inflammatory subgroup. Further prospective studies are needed to clarify the therapeutic strategy in IPAF-UIP.     

Optimal Strategy for Antiplatelet Therapy After Endovascular Revascularization for Lower Extremity Peripheral Artery Disease

ObjectivesThe aim of this study was to investigate the optimal strategy for antiplatelet therapy in patients with lower extremity peripheral artery disease (PAD) after endovascular revascularization.BackgroundThe optimal strategy for antiplatelet therapy in patients with PAD after endovascular revascularization has not been established.MethodsFrom March 2008 to February 2013, 693 patients with lower extremity PAD treated with different antiplatelet therapies, such as mono-antiplatelet therapy (MAPT) and dual-antiplatelet therapy (DAPT), of various durations after endovascular revascularization were analyzed. They were classified into 2 groups (DAPT <6 months or MAPT vs. DAPT ≥6 months). The primary outcomes were major adverse cardiovascular events and major adverse limb events. The safety outcome was major bleeding.ResultsDuring 5-year follow-up, major adverse cardiovascular events occurred less frequently in the DAPT ≥6-month group than the DAPT <6-month or MAPT group (17.3% vs. 31.3%; hazard ratio: 0.44; 95% confidence interval: 0.30 to 0.65; p < 0.001). Major adverse limb events also occurred less frequently in the DAPT ≥6-month group than the DAPT <6-month or MAPT group (21.5% vs. 43.7%; hazard ratio: 0.42; 95% CI: 0.30 to 0.58; p < 0.001). However, major bleeding events were infrequent, with no signal toward harm with DAPT ≥6 months. Results were consistent after inverse probability-weighted adjustment and propensity score matching.ConclusionsFollowing endovascular revascularization for lower extremity PAD, DAPT ≥6 months was associated with decreased 5-year major adverse cardiovascular events and major adverse limb events.     

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.     

Titanium-Nitride-Oxide–Coated Versus Everolimus-Eluting Stents in Acute Coronary Syndrome: The Randomized TIDES-ACS Trial

ObjectivesThis study sought to compare next-generation cobalt-chromium–based titanium-nitride-oxide (TiNO)–coated stents with a platinum-chromium–based biodegradable polymer everolimus-eluting stent (EES) in patients with acute coronary syndrome (ACS).BackgroundPrevious generation TiNO-coated stents showed acceptable performance in patients with ACS.MethodsIn a multicenter, randomized trial, we randomly assigned 1,491 ACS patients (2:1) to receive either a TiNO-coated stent (n = 989) or EES (n = 502). The primary endpoint was the rate of a composite of cardiac death, myocardial infarction (MI), or ischemia-driven target lesion revascularization at 12-month follow-up. The co-primary endpoint was a composite of cardiac death, MI, or major bleeding at 18 months.ResultsA primary endpoint event occurred in 6.3% of patients in the TiNO-coated stent group versus in 7.0% in the EES group (hazard ratio: 0.93; 95% confidence interval: 0.71 to 1.22; p = 0.66 for superiority; p < 0.001 for noninferiority). A co-primary endpoint event occurred in 3.7% of the patients in the TiNO group and in 7.8% in the EES group (hazard ratio: 0.64; 95% confidence interval: 0.51 to 0.80; p = 0.001). TiNO-coated stents were associated with lower rates of cardiac death (0.6% vs. 2.6%; p = 0.002) and MI (2.2% vs. 5.0%; p = 0.007) at 18 months of follow-up. Rates of target lesion revascularization were not significantly different at 18 months (5.8% vs. 4.4%; p = 0.27).ConclusionsIn patients with ACS, cobalt-chromium–based TiNO-coated stents were noninferior to platinum-chromium–based biodegradable polymer EES for major cardiac events at 12 months, and were superior for the co-primary endpoint of cardiac death, MI, and bleeding at 18 months. (Comparison of Titanium-Nitride-Oxide-Coated Bio-Active-Stent (Optimax™) to the Drug (Everolimus) -Eluting Stent (Synergy™) in Acute Coronary Syndrome [TIDES-ACS]; NCT02049229)     

Prospective Cohort Study of Infective Endocarditis in People Who Inject Drugs

BackgroundInfective endocarditis (IE) in people who inject drugs (PWID) is an emergent public health problem.ObjectivesThe purpose of this study was to investigate IE in PWID and compare it with IE in non-PWID patients.MethodsTwo prospective cohort studies (ICE-PCS and ICE-Plus databases, encompassing 8,112 IE episodes from 2000 to 2006 and 2008 to 2012, with 64 and 34 sites and 28 and 18 countries, respectively). Outcomes were compared between PWID and non-PWID patients with IE. Logistic regression analyses were performed to investigate risk factors for 6-month mortality and relapses amongst PWID.ResultsA total of 7,616 patients (591 PWID and 7,025 non-PWID) were included. PWID patients were significantly younger (median 37.0 years [interquartile range: 29.5 to 44.2 years] vs. 63.3 years [interquartile range: 49.3 to 74.0 years]; p < 0.001), male (72.5% vs. 67.4%; p = 0.007), and presented lower rates of comorbidities except for human immunodeficiency virus, liver disease, and higher rates of prior IE. Amongst IE cases in PWID, 313 (53%) episodes involved left-side valves and 204 (34.5%) were purely left-sided IE. PWID presented a larger proportion of native IE (90.2% vs. 64.4%; p < 0.001), whereas prosthetic-IE and cardiovascular implantable electronic device-IE were more frequent in non-PWID (9.3% vs. 27.0% and 0.5% vs. 8.6%; both p < 0.001). Staphylococcus aureus caused 65.9% and 26.8% of cases in PWID and non-PWID, respectively (p < 0.001). PWID presented higher rates of systemic emboli (51.1% vs. 22.5%; p < 0.001) and persistent bacteremia (14.7% vs. 9.3%; p < 0.001). Cardiac surgery was less frequently performed (39.5% vs. 47.8%; p < 0.001), and in-hospital and 6-month mortality were lower in PWID (10.8% vs. 18.2% and 14.4% vs. 22.2%; both p < 0.001), whereas relapses were more frequent in PWID (9.5% vs. 2.8%; p < 0.001). Prior IE, left-sided IE, polymicrobial etiology, intracardiac complications, and stroke were risk factors for 6-month mortality, whereas cardiac surgery was associated with lower mortality in the PWID population.ConclusionsA notable proportion of cases in PWID involve left-sided valves, prosthetic valves, or are caused by microorganisms other than S. aureus.     

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.     

Combination of F-ASO and Targeted Medical Therapy in Patients With Secundum ASD and Severe PAH

ObjectivesThis study was conducted to investigate the combined use of fenestrated atrial septal occluder (F-ASO) and targeted medical therapy (TMT) in patients with secundum atrial septal defect (ASD) and severe pulmonary arterial hypertension (PAH).BackgroundTreatment of patients with ASD and severe PAH is still challenging.MethodsAfter ethical approval was obtained, 56 consecutive patients with ASD with severe PAH were included (7 men, 49 women; median age 50.5 years; mean ASD size 26.9 ± 4.6 mm). After 3 months of TMT, transcatheter closure was performed using F-ASO in patients with ratios of pulmonary to systemic blood flow ≥1.5. TMT was continued post-operatively together with 6 months of dual-antiplatelet therapy. The hemodynamic variables during baseline, TMT alone, and combined treatment with F-ASO were compared.ResultsAfter only TMT, systolic pulmonary arterial pressure (−14.5 mm Hg; p < 0.001), pulmonary vascular resistance (−3.9 Wood units; p < 0.001), and exercise capacity (+72.0 m; p < 0.001) improved. Ratio of pulmonary to systemic blood flow increased by 0.9 (p < 0.001), with adverse cardiac remodeling (right ventricular dimension +3.5 mm; p < 0.001). Closure with F-ASO (median size 34.0 mm) led to further decrease in systolic pulmonary artery pressure (−6.0 mm Hg; p < 0.001). Follow-up (median duration 10 months) revealed further improvement in exercise capacity (+60.5 m; p < 0.001), with favorable cardiac remodeling (right ventricular dimension −9.9 mm; p < 0.001). In addition, all fenestrations were stable (p = 0.699), with negligible shunt (median ratio of pulmonary to systemic blood flow 1.1) and no complications. One year later, pulmonary artery pressure was normalized in 8 of 19 patients, and PAH recurred in 5 patients after discontinuation of TMT.ConclusionsIn patients with ASD and severe PAH, combination of F-ASO and TMT was a safe and effective procedure. Compared with TMT alone, the combined treatment further improved exercise capacity, with favorable cardiac remodeling.     

Drug-Coated Balloon Versus Drug-Eluting Stent for Small Coronary Vessel Disease: PICCOLETO II Randomized Clinical Trial

ObjectivesThis study sought to compare the performance of a novel drug-coated balloon (DCB) (Elutax SV, Aachen Resonance, Germany), with an everolimus-eluting stent (EES) (Abbott Vascular, Santa Clara, California) in patients with de novo lesions.BackgroundSmall vessel coronary artery disease (SVD) represents one of the most attractive fields of application for DCB. To date, several devices have been compared with drug-eluting stents in this setting, with different outcomes.MethodsThe PICCOLETO II (Drug Eluting Balloon Efficacy for Small Coronary Vessel Disease Treatment) trial was an international, investigator-driven, multicenter, open-label, prospective randomized controlled trial where patients with de novo SVD lesions were randomized to DCB or EES. Primary study endpoint was in-lesion late lumen loss (LLL) at 6 months (independent core laboratory), with the noninferiority between the 2 arms hypothesized. Secondary endpoints were minimal lumen diameter, percent diameter stenosis at angiographic follow-up, and the occurrence of major adverse cardiac events at 12 months.ResultsBetween May 2015 and May 2018, a total of 232 patients were enrolled at 5 centers. After a median of 189 (interquartile range: 160 to 202) days, in-lesion LLL was significantly lower in the DCB group (0.04 vs. 0.17 mm; p = 0.001 for noninferiority; p = 0.03 for superiority). Percent diameter stenosis and minimal lumen diameter were not significantly different. At 12-month clinical follow-up, major adverse cardiac events occurred in 7.5% of the DES group and in 5.6% of the DCB group (p = 0.55). There was a numerically higher incidence of spontaneous myocardial infarction (4.7% vs. 1.9%; p = 0.23) and vessel thrombosis (1.8% vs. 0%; p = 0.15) in the DES arm.ConclusionsIn this multicenter randomized clinical trial in patients with de novo SVD lesions, a new-generation DCB was found superior to EES in terms of LLL as the angiographic pattern and comparable in terms of clinical outcome. (Drug Eluting Balloon Efficacy for Small Coronary Vessel Disease Treatment [PICCOLETO II]; NCT03899818)     

3-Year Outcomes of Transcatheter Mitral Valve Repair in Patients With Heart Failure

BackgroundIn the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, transcatheter mitral valve repair (TMVr) resulted in fewer heart failure hospitalizations (HFHs) and lower mortality at 24 months in patients with heart failure (HF) with mitral regurgitation (MR) secondary to left ventricular dysfunction compared with guideline-directed medical therapy (GDMT) alone.ObjectivesThis study determined if these benefits persisted to 36 months and if control subjects who were allowed to cross over at 24 months derived similar benefit.MethodsThis study randomized 614 patients with HF with moderate-to-severe or severe secondary MR, who remained symptomatic despite maximally tolerated GDMT, to TMVr plus GDMT versus GDMT alone. The primary effectiveness endpoint was all HFHs through 24-month follow-up. Patients have now been followed for 36 months.ResultsThe annualized rates of HFHs per patient-year were 35.5% with TMVr and 68.8% with GDMT alone (hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.37 to 0.63; p < 0.001; number needed to treat (NNT) = 3.0; 95% CI: 2.4 to 4.0). Mortality occurred in 42.8% of the device group versus 55.5% of control group (HR: 0.67; 95% CI: 0.52 to 0.85; p = 0.001; NNT = 7.9; 95% CI: 4.6 to 26.1). Patients who underwent TMVr also had sustained 3-year improvements in MR severity, quality-of-life measures, and functional capacity. Among 58 patients assigned to GDMT alone who crossed over and were treated with TMVr, the subsequent composite rate of mortality or HFH was reduced compared with those who continued on GDMT alone (adjusted HR: 0.43; 95% CI: 0.24 to 0.78; p = 0.006).ConclusionsAmong patients with HF and moderate-to-severe or severe secondary MR who remained symptomatic despite GDMT, TMVr was safe, provided a durable reduction in MR, reduced the rate of HFH, and improved survival, quality of life, and functional capacity compared with GDMT alone through 36 months. Surviving patients who crossed over to device treatment had a prognosis comparable to those originally assigned to transcatheter therapy. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation [COAPT]; NCT01626079)     

Biventricular Physiology of Iatrogenic Atrial Septal Defects Following Transcatheter Mitral Valve Edge-to-Edge Repair

ObjectivesThe study sought to assess the acute hemodynamic effects of iatrogenic atrial septal defect (iASD) closure following transcatheter mitral valve edge-to-edge repair (TMVR).BackgroundThe potential hemodynamic and clinical consequences of an iASD following TMVR are currently subject to controversial debates.MethodsIn 21 patients with relevant left-to-right shunt flow (50% [IQR: 38% to 60%] of systemic perfusion volume) across an iASD following TMVR, interventional closure was performed with recordings of left ventricular (LV) and right ventricular (RV) pressure-volume loops during iASD occlusion.ResultsiASD occlusion led to a volume shift from the RV (RV end-diastolic volume index: pre 102 [IQR: 80 to 120] ml/m², post 92 [IQR: 70 to 111] ml/m²; p < 0.001) to the LV (LV end-diastolic volume index: pre 91 [IQR: 74 to 124] ml/m², post 97 [IQR: 77 to 127] ml/m²; p < 0.001) with reduced RV (3.49 [IQR: 2.07 to 3.58] l/min/m² vs. 2.68 [IQR: 2.07 to 3.58] l/min/m²; p < 0.001) but increased LV cardiac index (2.25 [IQR: 1.80 to 3.28] l/min/m² vs. 2.77 [IQR: 1.90 to 3.34] l/min/m²; p = 0.039). Although RV end-diastolic pressure decreased (pre 5.0 [IQR: 4.0 to 8.5] mm Hg, post 4.5 [IQR: 3.0 to 8.3] mm Hg; p = 0.024), LV end-diastolic pressure remained unchanged (pre 11.0 [IQR: 9.5 to 14.0] mm Hg, post 13.0 [IQR: 9.0 to 15.5] mm Hg; p = 0.142). LV transmural pressure increased (7.0 [IQR: 4.0 to 11.0] mm Hg vs. 11.0 [IQR: 7.0 to 15.0] mm Hg; p = 0.001) and LV eccentricity index decreased (p < 0.001). The change in LV transmural pressure correlated significantly with the change in LV-to-RV end-diastolic volume ratio (r = 0.674; p = 0.018). Right heart failure symptoms declined at 1-month follow-up (71% vs. 35%; p = 0.003) as did New York Heart Association functional class (≥III: 48% vs. 25%; p < 0.001).ConclusionsiASD closure following TMVR leads to a volume shift from the RV to the LV with reduced pulmonary but increased systemic cardiac index and with favorable biventricular interaction at maintained LV filling pressure, resulting in a decline in heart failure symptoms at 1-month follow-up.