Biomechanical Stress Profiling of Coronary Atherosclerosis: Identifying a Multifactorial Metric to Evaluate Plaque Rupture Risk

ObjectivesThe purpose of this study was to derive a biomechanical stress metric that was based on the multifactorial assessment of coronary plaque morphology, likely related to the propensity of plaque rupture in patients.BackgroundPlaque rupture, the most frequent cause of coronary thrombosis, occurs at locations of elevated tensile stress in necrotic core fibroatheromas (NCFAs). Finite element modeling (FEM), typically used to calculate tensile stress, is computationally intensive and impractical as a clinical tool for locating rupture-prone plaques. This study derived a multifactorial stress equation (MSE) that accurately computes peak stress in NCFAs by combining the influence of several morphological parameters.MethodsIntravascular ultrasound and optical frequency domain imaging were conducted in 30 patients, and plaque morphological parameters were defined in 61 NCFAs. Multivariate regression analysis was applied to derive the MSE and compute a peak stress metric (PSM) that was based on the analysis of plaque morphological parameters. The accuracy of the MSE was determined by comparing PSM with FEM-derived peak stress values. The ability of the PSM in locating plaque rupture sites was tested in 3 additional patients.ResultsThe following parameters were found to be independently associated with peak stress: fibrous cap thickness (p < 0.0001), necrotic core angle (p = 0.024), necrotic core thickness (p < 0.0001), lumen area (p < 0.0001), necrotic core including calcium areas (p = 0.017), and plaque area (p = 0.003). The PSM showed excellent correlation (R = 0.85; p < 0.0001) with FEM-derived peak stress, thus confirming the accuracy of the MSE. In only 56% (n = 34) of plaques, the thinnest fibrous cap thickness was a determining parameter in identifying the cross section with highest PSM. In coronary segments with plaque ruptures, the MSE precisely located the rupture site.ConclusionsThe MSE shows potential to calculate the PSM in coronary lesions rapidly. However, further studies are warranted to investigate the use of biomechanical stress profiling for the prognostic evaluation of patients with atherosclerosis.     

Clinical Impact of High-Sensitivity Cardiac Troponin T Implementation in the Community

BackgroundLimited U.S. data exist regarding high-sensitivity cardiac troponin (cTn) implementation.ObjectivesThis study sought to evaluate the impact of high-sensitivity cardiac troponin T (cTnT) implementation.MethodsObservational U.S. cohort study of emergency department (ED) patients undergoing measurement of cTnT during the transition from 4th (pre-implementation March 12, 2018, to September 11, 2018) to 5th generation (Gen) cTnT (post-implementation September 12, 2018, to March 11, 2019). Diagnoses were adjudicated following the Fourth Universal Definition of Myocardial Infarction (MI). Resources evaluated included length of stay, hospitalizations, and cardiac testing.ResultsIn this study, 3,536 unique patients were evaluated, including 2,069 and 2,491 ED encounters pre- and post-implementation. Compared with 4th Gen cTnT, encounters with ≥1 cTnT >99th percentile increased using 5th Gen cTnT (15% vs. 47%; p < 0.0001). Acute MI (3.3% vs. 8.1%; p < 0.0001) and myocardial injury (11% vs. 38%; p < 0.0001) increased. Although type 1 MIs increased (1.7% vs. 2.9%; p = 0.0097), the overall MI increase was largely due to more type 2 MIs (1.6% vs. 5.2%; p < 0.0001). Women were less likely than men to have MI using 4th Gen cTnT (2.3% vs. 4.4%; p = 0.008) but not 5th Gen cTnT (7.7% vs. 8.5%; p = 0.46). Overall length of stay and stress testing were reduced, and angiography was increased (all p < 0.05). Among those without cTnT increases, there were more ED discharges and a reduction in length of stay, echocardiography, and stress tests (all p < 0.05).ConclusionsHigh-sensitivity cTnT implementation resulted in a marked increase in myocardial injury and MI, particularly in women and patients with type 2 MI. Despite this, except for angiography, overall resource use did not increase. Among those without cTnT increases, there were more ED discharges and fewer cardiac tests.     

Gastroesophageal reflux-like symptoms are associated with hyposalivation and oropharyngeal problems in patients with asthma

BackgroundPrevious studies have suggested a significant relationship between hyposalivation and inhalation therapy-induced oropharyngeal problems. However, salivary secretion tests are not widely performed in daily clinical practice. In fact, xerostomia, the complaint of dry mouth, may not indicate hyposalivation. Therefore, we determined the clinical factors associated with hyposalivation in patients with asthma.MethodsThis study is a post-hoc analysis of our previous studies. Adult patients with asthma on maintenance inhalation therapy were enrolled. The participants completed questionnaires on oropharyngeal symptoms and underwent a salivary secretion test. Symptom severity was evaluated using a numerical rating scale (NRS), and salivary secretion was measured using the modified cotton roll method. Using logistic regression analysis, we identified the clinical factors associated with hyposalivation.ResultsIn total, 531 patients completed the questionnaire (43.8 ± 16.9 years and male/female = 171/360), and 234 patients successfully performed a salivary secretion test, of which 126 (53.8%) were diagnosed with hyposalivation (<0.25 g/min). The patients with hyposalivation were significantly older (p < 0.0001) and had severe xerostomia and/or gastroesophageal reflux-like symptoms (GERLS) (p < 0.0001). Many of these patients had also used inhaled long-acting beta agonists (p = 0.012) and high-dose inhaled corticosteroids (p = 0.024). Multivariate analysis revealed that advanced age (odds ratio [OR] 1.05, p < 0.0001), severe xerostomia (OR 1.02, p = 0.0006) and severe GERLS (OR 1.02, p = 0.001) were independently and significantly associated with hyposalivation.ConclusionsAge, xerostomia, and GERLS were significantly related to hyposalivation in patients with asthma. To identify oropharyngeal problems in these patients, a careful assessment of the suspected symptoms of gastroesophageal reflux may be useful.     

High prevalence of airway obstruction and pulmonary emphysema in urothelial (renal pelvis,ureter, and bladder) cancer patients

BackgroundCigarette smoking is a major cause of COPD, with patients also presenting complications that stem from other smoking-related diseases, including urothelial cancer. However, the prevalence of COPD or airflow obstruction in urothelial cancer patients has not been well studied.MethodsWe investigated the prevalence of airflow obstruction (FEV1/FVC < 70%) in newly diagnosed urothelial cancer patients and identified the risk factors for airflow obstruction in existing urothelial cancer patients. Additionally, we compared the characteristics of subjects who had been diagnosed with both airflow obstruction and urothelial cancer, and subjects whose airflow obstruction was discovered during health screenings.ResultsA total of 217 patients were newly diagnosed with urothelial cancer during the study period at our institution. Among all patients, 210 (96.8%) underwent an evaluable lung function test, in which 38.6% (81 patients) displayed airflow obstruction defined as FEV1/FVC < 70%. In urothelial cancer patients, age, smoking index (pack-years), and BMI proved to be significant risk factors for airflow obstruction in multivariate logistic regression (p = 0.007, p < 0.0001, and p = 0.035, respectively). Gender, cancer stage, and cancer location were not significant risk factors. Patients with both airflow obstruction and urothelial cancer showed a more advanced emphysematous change than subjects presenting with airflow obstruction alone (unpaired t-test, p = 0.0003).ConclusionsAirflow obstruction was identified in 38.6% of urothelial cancer patients. Age, smoking index (pack-years), and BMI were significant risk factors. A significantly higher emphysematous score was observed in subjects with urothelial cancer than in subjects with airway obstruction alone.     

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.     

Effect of pulmonary rehabilitation programs including lower limb endurance training on dyspnea in stable COPD: A systematic review and meta-analysis

Pulmonary rehabilitation (PR) is recommended as an effective treatment for patients with chronic obstructive pulmonary disease (COPD). Previous meta-analyses showed that PR improves exercise capacity and health-related quality of life (HRQOL). However, they did not evaluate the effect of PR on the sensation of dyspnea.We searched six databases in May 2019 for randomized controlled trials (RCTs) that examined PR, including supervised lower limb endurance training as a minimal essential component that was continued for 4–12 weeks, in patients with stable COPD, with changes from baseline dyspnea as a primary outcome. Secondary outcomes were changes in exercise capacity, HRQOL, activity of daily life (ADL), physical activity (PA), and adverse events. We calculated the pooled weighted mean difference (MD) using a random effects model. We identified 42 studies with 2150 participants. Compared with the control, PR improved dyspnea, as shown using the British Medical Research Council (MRC) questionnaire (MD, −0.64; 95% CI, −0.99 to −0.30; p = 0.0003), transitional dyspnea index (MD, 1.95; 95% CI, 1.09 to 2.81; p = 0.0001), modified Borg score during exercise (MD, −0.62; 95% CI, −1.10 to −0.14; p = 0.01), and Chronic Respiratory Questionnaire (CRQ) dyspnea score (MD, 0.91; 95% CI, 0.39 to 1.44; p = 0.0007). PR significantly increased exercise capacity measured by the 6 min walking distance time, peak workload, and peak VO₂. It improved HRQOL measured by the St. George's Respiratory Questionnaire and CRQ, but not on PA or ADL. These results indicated that PR programs including lower limb endurance training improve dyspnea, HRQOL, and exercise capacity in patients with stable COPD.     

Is the Leicester Cough Questionnaire useful for nontuberculous mycobacterial lung disease?

BackgroundAlthough the incidence of nontuberculous mycobacterial lung disease (NTM-LD) is increasing worldwide, there is no established standard of care leading to eradication. Therefore, research on health-related quality of life (HRQOL) is important for patients with NTM-LD. HRQOL is commonly evaluated using the St. George's Respiratory Questionnaire (SGRQ), developed for chronic obstructive pulmonary disease (COPD). However, NTM-LD differs from COPD in that few patients complain of dyspnea or wheezing, and cough and sputum are their main symptoms. The Leicester Cough Questionnaire (LCQ) is an HRQOL questionnaire dedicated to cough, but few studies have used it for NTM-LD. This study evaluated HRQOL in patients with NTM-LD using the SGRQ and LCQ and clarified the usefulness of the LCQ.MethodsInformation on age, height, weight, lung function, percent ideal body weight, laboratory data, radiological scores, exercise capacity, SGRQ, and LCQ were collected from the medical records of 81 patients. Correlations between SGRQ and LCQ domains were assessed using Spearman's rank correlation coefficients. Multivariate analysis was performed with SGRQ and LCQ total scores.ResultsStatistically significant correlations were observed between all domains, and the correlation between the total scores was ?0.67 (p < 0.01). Multivariate analysis with total scores as the dependent variable showed that the explanatory variables were lung function (p < 0.05) and radiological score (p < 0.05) in the SGRQ, and radiological score (p < 0.05) and C-reactive protein level (p < 0.05) in the LCQ.ConclusionThe LCQ, which evaluates an inflammatory response involved in the diagnosis of NTM-LD, may be useful to assess HRQOL in patients with NTM-LD.     

Comparison Between the Performance of Quantitative Flow Ratio and Perfusion Imaging for Diagnosing Myocardial Ischemia

ObjectivesThis study compared the performance of the quantitative flow ratio (QFR) with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) myocardial perfusion imaging (MPI) for the diagnosis of fractional flow reserve (FFR)−defined coronary artery disease (CAD).BackgroundQFR estimates FFR solely based on cine contrast images acquired during invasive coronary angiography (ICA). Head-to-head studies comparing QFR with noninvasive MPI are lacking.MethodsA total of 208 (624 vessels) patients underwent technetium-⁹⁹m tetrofosmin SPECT and [¹⁵O]H₂O PET imaging before ICA in conjunction with FFR measurements. ICA was obtained without using a dedicated QFR acquisition protocol, and QFR computation was attempted in all vessels interrogated by FFR (552 vessels).ResultsQFR computation succeeded in 286 (52%) vessels. QFR correlated well with invasive FFR overall (R = 0.79; p < 0.001) and in the subset of vessels with an intermediate (30% to 90%) diameter stenosis (R = 0.76; p < 0.001). Overall, per-vessel analysis demonstrated QFR to exhibit a superior sensitivity (70%) in comparison with SPECT (29%; p < 0.001), whereas it was similar to PET (75%; p = 1.000). Specificity of QFR (93%) was higher than PET (79%; p < 0.001) and not different from SPECT (96%; p = 1.000). As such, the accuracy of QFR (88%) was superior to both SPECT (82%; p = 0.010) and PET (78%; p = 0.004). Lastly, the area under the receiver operating characteristics curve of QFR, in the overall sample (0.94) and among vessels with an intermediate lesion (0.90) was higher than SPECT (0.63 and 0.61; p < 0.001 for both) and PET (0.82; p < 0.001 and 0.77; p = 0.002), respectively.ConclusionsIn this head-to-head comparative study, QFR exhibited a higher diagnostic value for detecting FFR-defined significant CAD compared with perfusion imaging by SPECT or PET.     

Progression of Myocardial Fibrosis in Hypertrophic Cardiomyopathy: A Cardiac Magnetic Resonance Study

ObjectivesThis study examined fibrosis progression in hypertrophic cardiomyopathy (HCM) patients, as well as its relationship to patient characteristics, clinical outcomes, and its effect on clinical decision making.BackgroundMyocardial fibrosis, as quantified by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR), provides valuable prognostic information in patients with HCM.MethodsA total of 157 patients with HCM were enrolled in this study, with 2 sequential CMR scans separated by an interval of 4.7 ± 1.9 years.ResultsAt the first CMR session (CMR-1), 70% of patients had LGE compared with 85% at CMR-2 (p = 0.001). The extent of LGE extent increased between the 2 CMR procedures, from 4.0 ± 5.6% to 6.3 ± 7.4% (p < 0.0001), with an average LGE progression rate of 0.5 ± 1.0%/year. LGE mass progression was correlated with higher LGE mass and extent on CMR-1 (p = 0.0017 and p = 0.007, respectively), greater indexed left ventricular (LV) mass (p < 0.0001), greater LV maximal wall thickness (p < 0.0001), apical aneurysm at CMR-1 (p < 0.0001), and lower LV ejection fraction (EF) (p = 0.029). Patients who were more likely to have a higher rate of LGE progression presented with more severe disease at baseline, characterized by LGE extent >8% of LV mass, indexed LV mass >100 g/m², maximal wall thickness ≥20 mm, LVEF ≤60%, and apical aneurysm. There was a significant correlation between the magnitude of LGE progression and future implantation of insertable cardioverter-defibrillators (p = 0.004), EF deterioration to ≤50% (p < 0.0001), and admission for heart failure (p = 0.0006).ConclusionsMyocardial fibrosis in patients with HCM is a slowly progressive process. Progression of LGE is significantly correlated with a number of clinical outcomes such as progression to EF ≤50% and heart failure admission. Judicious use of serial CMR with LGE can provide valuable information to help patient management.     

Baseline Functional Capacity and Transcatheter Mitral Valve Repair in Heart Failure With Secondary Mitral Regurgitation

ObjectivesThe aim of this study was to determine the prognostic utility of baseline functional status and its impact on the outcomes of transcatheter mitral valve repair (TMVr) in patients with heart failure (HF) with secondary mitral regurgitation (SMR).BackgroundThe COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial demonstrated that TMVr with the MitraClip in patients with HF with moderate to severe or severe SMR improved health-related quality of life. The clinical utility of a baseline assessment of functional status for evaluating prognosis and identifying candidates likely to derive a robust benefit from TMVr has not been previously studied in patients with HF with SMR.MethodsThe COAPT study was a multicenter, randomized, controlled, parallel-group, open-label trial of TMVr with the MitraClip plus guideline-directed medical therapy (GDMT) versus GDMT alone in patients with HF, left ventricular ejection fraction 20% to 50%, and moderate to severe or severe SMR. Baseline functional status was assessed by 6-min walk distance (6MWD).ResultsPatients with 6MWD less than the median (240 m) were older, were more likely to be female, and had more comorbidities. After multivariate modeling, age (p = 0.005), baseline hemoglobin (p = 0.007), and New York Heart Association functional class III/IV symptoms (p < 0.0001) were independent clinical predictors of 6MWD. Patients with 6MWD <240 m versus ≥240 m had a higher unadjusted and adjusted rate of the 2-year composite of all-cause death or HF hospitalization (64.4% vs. 48.6%; adjusted hazard ratio: 1.53; 95% confidence interval: 1.19 to 1.98; p = 0.001). However, there was no interaction between baseline 6MWD and the relative effectiveness of TMVr plus GDMT versus GDMT alone with respect to the composite endpoint (p = 0.633).ConclusionsBaseline assessment of functional capacity by 6MWD was a powerful discriminator of prognosis in patients with HF with SMR. TMVr with the MitraClip provided substantial improvements in clinical outcomes for this population irrespective of baseline functional capacity.     

Fractal dimension in CT low attenuation areas is predictive of long-term oxygen therapy initiation in COPD patients: Results from two observational cohort studies

BackgroundSome chronic obstructive pulmonary disease (COPD) patients develop hypoxemia with disease progression, with some even requiring long-term oxygen therapy (LTOT). Lung function, especially diffusing capacity, and the annual decline in PaO₂, are reported to be predictive factors of chronic respiratory failure. However, the association between lung morphometry evaluated using computed tomography (CT) images and LTOT initiation is unknown.MethodsWe retrospectively evaluated the relationship between clinical indices, including pulmonary function, body mass index (BMI), and CT parameters, at baseline and LTOT initiation in two prospective COPD cohorts. In the Nara Medical University cohort (n = 76), the low attenuation area (LAA) and its fractal dimension (fractal D) were adapted as the indices for parenchymal destruction in CT images. The association between these CT measurements and LTOT initiation was replicated in the Kyoto University cohort (n = 130).ResultsIn the Nara Medical University cohort, lower BMI (hazard ratio [HR]:0.70, p = 0.006), lower % diffusing capacity (%DLCO) (HR: 0.92, p = 0.006), lower %DLCO/VA (HR, 0.90, p = 0.008), higher RV/TLC (HR, 1.26, p = 0.012), higher LAA% (HR: 1.18, p = 0.001), and lower fractal D (HR: 3.27 × 10^?8, p < 0.001) were associated with LTOT initiation. Multivariate analysis in the Kyoto University cohort confirmed that lower %DLCO and lower fractal D were independently associated with LTOT initiation, whereas LAA% was not.ConclusionFractal D, which is the index for morphometric complexity of LAA in CT analysis, is predictive of LTOT initiation in COPD patients.     

Surgical approach and short-term outcomes in adults and children undergoing total pancreatectomy with islet autotransplantation: A report from the Prospective Observational Study of TPIAT

BackgroundTotal pancreatectomy with islet autotransplantation (TPIAT) is a viable option for treating debilitating recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) in adults and children. No data is currently available regarding variation in approach to operation.MethodsWe evaluated surgical techniques, islet isolation and infusion approaches, and outcomes and complications, comparing children (n = 84) with adults (n = 195) enrolled between January 2017 and April 2020 by 11 centers in the United States in the Prospective Observational Study of TPIAT (POST), which was launched in 2017 to collect standard history and outcomes data from patients undergoing TPIAT for RAP or CP.ResultsChildren more commonly underwent splenectomy (100% versus 91%, p = 0.002), pylorus preservation (93% versus 67%; p < 0.0001), Roux-en-Y duodenojejunostomy reconstruction (92% versus 35%; p < 0.0001), and enteral feeding tube placement (93% versus 63%; p < 0.0001). Median islet equivalents/kg transplanted was higher in children (4577; IQR 2816-6517) than adults (2909; IQR 1555-4479; p < 0.0001), with COBE purification less common in children (4% versus 15%; p = 0.0068). Median length of hospital stay was higher in children (15 days; IQR 14–22 versus 11 days; IQR 8–14; p < 0.0001), but 30-day readmissions were lower in children (13% versus 26%, p = 0.018). Rate of portal vein thrombosis was significantly lower in children than in adults (2% versus 10%, p = 0.028). There were no mortalities in the first 90 days post-TPIAT.ConclusionsPancreatectomy techniques differ between children and adults, with islet yields higher in children. The rates of portal vein thrombosis and early readmission are lower in children.     

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.     

Association between low mean corpuscular hemoglobin and prognosis in patients with exacerbation of chronic obstructive pulmonary disease

BackgroundSeveral studies have demonstrated the association between mean corpuscular hemoglobin concentration (MCHC), a hematological index used for the assessment of anemia, and the prognosis of patients with heart disease. While the red cell distribution width (RDW) is known to be related to the prognosis of patients with chronic obstructive pulmonary disease (COPD), few studies have focused on the association between the MCHC and COPD. Therefore, we examined the association between the MCHC and prognosis in patients with exacerbation of COPD.MethodsWe examined the association between the 30-day mortality and clinical findings in patients with COPD exacerbation who were hospitalized between October 2008 and December 2018.ResultsWe enrolled 195 patients with COPD exacerbation (average age: 76.4 years; 181 men, 14 women). The MCHC was significantly lower, while the RDW was significantly higher in the 27 patients (13.8%) who died during the 30-day observation period compared to those in the patients who survived. Multivariate logistic regression analysis revealed that the MCHC was independently associated with 30-day mortality. The area under the curve calculated from the MCHC obtained from peripheral blood was 0.688 and the cutoff value was 31.6 g/dL, with a sensitivity of 0.593 and specificity of 0.810 (p = 0.0001).ConclusionThe MCHC might be a valuable biomarker for evaluating the prognosis of patients with COPD exacerbation.     

Aortic Stenosis Progression,Cardiac Damage,and Survival: Comparison Between Bicuspid and Tricuspid Aortic Valves

ObjectivesThis study sought to compare aortic stenosis (AS) progression rates, AS-related cardiac damage (AS-CD) indicator incidence and determinants, and survival between patients with tricuspid aortic valve (TAV)-AS and those with bicuspid aortic valve (BAV)-AS.BackgroundDifferences in AS progression and AS-CD between patients with BAV and patients with TAV are unknown.MethodsWe retrospectively studied consecutive patients with baseline peak aortic valve velocity (peakV) ≥2.5 m/s and left ventricular ejection fraction ≥50%. Follow-up echocardiograms (n = 4,818) provided multiparametric AS progression rates and AS-CD.ResultsThe study included 330 BAV (age 54 ± 14 years) and 581 patients with TAV (age 72 ± 11 years). At last echocardiogram (median: 5.9 years; interquartile range: 3.9 to 8.5 years), BAV-AS exhibited similar peakV and mean pressure gradient (MPG) as TAV-AS, but larger calculated aortic valve area due to larger aortic annulus (p < 0.0001). Multiparametric progression rates were similar between BAV-AS and TAV-AS (all p ≥ 0.08) and did not predict age-/sex-adjusted survival (p ≥ 0.45). Independent determinants of rapid progression were male sex and baseline AS severity for TAV (all p ≤ 0.024), and age, baseline AS severity, and cardiac risk factors (age interaction: p = 0.02) for BAV (all p ≤ 0.005). At 12 years, patients with TAV-AS had a higher incidence of AS-CD than BAV-AS patients (p < 0.0001), resulting in significantly worse survival compared to BAV-AS (p < 0.0001). AS-CD were independently determined by multiple factors (MPG, age, sex, comorbidities, cardiac function; all p ≤ 0.039), and BAV was independently protective of most AS-CD (all p ≤ 0.05).ConclusionsIn this cohort, TAV-AS and BAV-AS progression rates were similar. Rapid progression did not affect survival and was determined by cardiac risk factors for BAV-AS (particularly in patients with BAV <60 years of age) and unmodifiable factors for TAV-AS. AS-CD and mortality were significantly higher in TAV-AS. Independent determinants of AS-CD were multifactorial, and BAV morphology was AS-CD protective. Therefore, the totality of AS burden (cardiac damage) is clinically crucial for TAV-AS, whereas attention to modifiable risk factors may be preventive for BAV-AS.     

Impact of Pulmonary Hypertension Hemodynamic Status on Long-Term Outcome After Transcatheter Aortic Valve Replacement

ObjectivesThe aim of this study was to investigate the prognostic impact and development of pulmonary hypertension (PH) in the different hemodynamic subtypes of PH in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR).BackgroundPH is a frequent finding in patients with severe AS and predicts outcome after TAVR. Nevertheless, outcomes among PH subtypes and the impact of residual PH after TAVR are controversial.MethodsA total of 1,400 patients with symptomatic AS and full invasive hemodynamic assessment before and after TAVR were included. Patients were stratified into 4 groups: no PH (n = 658); isolated pre-capillary PH (n = 139), isolated post-capillary PH (Ipc-PH; n = 534), and combined post-capillary and pre-capillary PH (n = 69).ResultsThe mean overall patient age was 81.5 ± 6.8 years, and 46.3% were men. Acute device success was achieved in 94.9%. Patients without PH showed significantly lower mortality rates compared with patients with PH (1 year, 13.8% vs. 22.4% [p < 0.001]; 4 years, 37.2% vs. 51.5% [p < 0.001]). Patients with pre-capillary PH showed 1.9-fold increased 1-year mortality and those with Ipc-PH showed 1.5-fold increased 1-year mortality compared with patients without pH (p = 0.001). No differences regarding survival were found among the subgroups. Only in patients with Ipc-PH, residual PH was associated with 2.1-fold increased mortality (p = 0.010). All patients benefited in terms of functional capacity after TAVR.ConclusionsPatients with pre-capillary PH and those with Ipc-PH showed significantly higher risk for death after TAVR compared with those without PH. Reversible PH had no benefit for survival except in patients with Ipc-PH. Hemodynamic stratification of PH is helpful for risk and response prediction in patients with AS undergoing TAVR.     

In-Stent CTO Percutaneous Coronary Intervention: Individual Patient Data Pooled Analysis of 4 Multicenter Registries

ObjectivesThe authors sought to examine the outcomes of percutaneous coronary intervention (PCI) for in-stent restenosis (ISR) chronic total occlusions (CTOs).BackgroundThe outcomes of PCI for ISR CTOs have received limited study.MethodsThe authors examined the clinical and angiographic characteristics and procedural outcomes of 11,961 CTO PCIs performed in 11,728 patients at 107 centers in Europe, North America, Latin America, and Asia between 2012 and 2020, pooling patient-level data from 4 multicenter registries. In-hospital major adverse cardiovascular events (MACE) included death, myocardial infarction, stroke, and tamponade. Long-term MACE were defined as the composite of all-cause death, myocardial infarction, and target vessel revascularization.ResultsISR represented 15% of the CTOs (n = 1,755). Patients with ISR CTOs had higher prevalence of diabetes (44% vs. 38%; p < 0.0001) and prior coronary artery bypass graft surgery (27% vs. 24%; p = 0.03). Mean J-CTO (Multicenter CTO Registry in Japan) score was 2.32 ± 1.27 in the ISR group and 2.22 ± 1.27 in the de novo group (p = 0.01). Technical (85% vs. 85%; p = 0.75) and procedural (84% vs. 84%; p = 0.82) success was similar for ISR and de novo CTOs, as was the incidence of in-hospital MACE (1.7% vs. 2.2%; p = 0.25). Antegrade wiring was the most common successful strategy, in 70% of ISR and 60% of de novo CTOs, followed by retrograde crossing (16% vs. 23%) and antegrade dissection and re-entry (15% vs. 16%; p < 0.0001). At 12 months, patients with ISR CTOs had a higher incidence of MACE (hazard ratio: 1.31; 95% confidence interval: 1.01 to 1.70; p = 0.04).ConclusionsISR CTOs represent 15% of all CTO PCIs and can be recanalized with similar success and in-hospital MACE as de novo CTOs.     

Abundant TNF-LIGHT expression in the airways of patients with asthma with persistent airflow limitation: Association with nitrative and inflammatory profiles

BackgroundThe role of the inflammatory secretory protein TNF-LIGHT (LIGHT) in the molecular mechanisms underlying persistent airflow limitation (PAL) in asthma remains unclear. We hypothesized that high airway LIGHT expression may be a feature of asthma with PAL associated with specific expression patterns of inflammatory molecules.MethodsThis hypothesis was tested in 16 patients with asthma on inhaled corticosteroid treatment. Induced sputum was collected, the expression of LIGHT and 3-nitrotyrosine (NT), which reflects the footprint of reactive nitrogen species content, was measured using immunohistochemical staining, and the inflammatory molecules in the sputum supernatant were analyzed using a magnetic bead array.ResultsLIGHT staining in the cells had a significantly higher intensity in participants with PAL than in participants without PAL (47.9 × 10⁴/ml vs. 5.4 × 10⁴/ml; p < 0.05). The array analysis indicated that IL-8, IL-19, matrix metalloproteinase 2, and osteopontin, were associated with high LIGHT immunoreactivity. The fractionation of 3-NT-positive cells was positively correlated with that of LIGHT-positive cells (r = 0.57, p < 0.05) and the TGF-β1 level (r = 0.61, p < 0.05). LIGHT- and 3-NT-positive cells showed significant positive correlation with the differential cell counts of neutrophils, macrophages, and eosinophils in the induced sputum. Intense immunoreactivities of LIGHT (r = −0.54, p < 0.05) and 3-NT (r = −0.42, p = 0.1) were negatively associated with decreased forced expiratory volume in 1/forced vital capacity ratio.ConclusionsThe findings suggest that LIGHT is a key component in the association between airway inflammation and airflow limitation in patients with asthma, and its expression may be persistently correlated with the abundance of inflammatory cells and inflammatory and profibrogenic radical/molecules.     

Predicting the presence and severity of obstructive sleep apnea based on mandibular measurements using quantitative analysis of facial profiles via three-dimensional photogrammetry

BackgroundIn obstructive sleep apnea (OSA), the upper airway is obstructed during sleep due to obesity and/or posterior collapse of the tongue root. Maxillofacial morphological abnormalities increase the risk of OSA in the Asian population. This study sought to elucidate whether three-dimensional (3D) photogrammetry measurements correlate with the severity of OSA irrespective of sex and degree of obesity.MethodsA prospective pilot study was performed, in which 37 consecutive adult patients (M/F = 28/9) underwent polysomnography and 3D photogrammetry in the supine position for the diagnosis of OSA. Measurements obtained from 3D photogrammetry included mandibular width (Mw), mandibular length (Ml), mandibular depth (Md), mandibular width–length angle (Mwla), and mandibular area (Ma). The effects of sex and body mass index (BMI) on the measurements and their association with the apnea–hypopnea index (AHI) were statistically analyzed. The inter-rater reliability of the measurements was evaluated using intraclass correlation coefficients (ICC).ResultsMwla (R = 0.73, p < 0.01), Mw (R = 0.39, p < 0.05), and Md (R = ?0.34, p < 0.05) were significantly correlated with the severity of OSA. On multivariate analysis, Mwla (p < 0.01) and Md (p < 0.05) remained independent factors for AHI after adjusting for sex, age, BMI, and neck circumference. In addition, diagnosability analysis revealed that Mwla was useful for identifying the presence of OSA (AHI ≥5) (cutoff: 78.6°, sensitivity: 0.938, specificity: 0.800, area under the curve: 0.931). The ICC was >0.9, showing high reliability.ConclusionsThis study suggests that Mwla measured using 3D photogrammetry can predict the presence of OSA and correlates with the severity of OSA, independent of obesity and sex.     

Systolic Blood Pressure and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction

BackgroundNational guidelines recommend that systolic blood pressure (SBP) in patients with heart failure with reduced ejection fraction (HFrEF) and hypertension be maintained below 130 mm Hg.ObjectivesThis study sought to determine associations of SBP <130 mm Hg with outcomes in patients with HFrEF.MethodsOf the 25,345 patients in the Medicare-linked OPTIMIZE-HF registry, 10,535 had an ejection fraction (EF) ≤40%. Of these, 5,615 had stable SBP (≤20 mm Hg admission to discharge variation), and 3,805 (68%) had a discharge SBP <130 mm Hg. Propensity scores for SBP <130 mm Hg, estimated for each of the 5,615 patients, were used to assemble a matched cohort of 1,189 pairs of patients with SBP <130 versus ≥130 mm Hg, balanced on 58 baseline characteristics (mean age 76 years; mean EF 28%, 45% women, 13% African American). This process was repeated in 3,946 patients, after excluding 1,669 patients (30% of 5,615) with a discharge SBP <110 mm Hg and assembled a second matched balanced cohort of 1,099 pairs of patients with SBP 110 to 129 mm Hg versus ≥130 mm Hg.ResultsThirty-day all-cause mortality occurred in 7% and 4% of matched patients with SBP <130 mm Hg versus ≥130 mm Hg, respectively (hazard ratio [HR]: 1.76; 95% confidence interval [CI]: 1.24 to 2.48; p = 0.001). HRs (95% CIs) for all-cause mortality, all-cause readmission, and HF readmission at 1 year, associated with SBP <130 mm Hg, were 1.32 (1.15 to 1.53; p < 0.001), 1.11 (1.01 to 1.23; p = 0.030), and 1.24 (1.09 to 1.42; p = 0.001), respectively. HRs (95% CIs) for 30-day and 1-year all-cause mortality associated with SBP 110 to 129 mm Hg (vs. ≥130 mm Hg) were 1.50 (1.03 to 2.19; p = 0.035), and 1.19 (1.02 to 1.39; p = 0.029), respectively.ConclusionsAmong hospitalized older patients with HFrEF, SBP <130 mm Hg is associated with poor outcomes. This association persisted when the analyses were repeated after excluding patients with SBP <110 mm Hg. There is an urgent need for randomized controlled trials to evaluate optimal SBP reduction goals in patients with HFrEF.