Bleeding and Ischemic Outcomes With Ticagrelor Monotherapy According to Body Mass Index

BackgroundThere is a paucity of data regarding the safety and efficacy of different antiplatelet regimens according to standardized body mass index (BMI) categories.ObjectivesThe aim of this study was to investigate bleeding and ischemic outcomes according to BMI in the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial.MethodsThe TWILIGHT trial randomized high-risk patients to ticagrelor plus aspirin or ticagrelor plus placebo at 3 months after percutaneous coronary intervention. In this secondary analysis, patients were stratified by standard BMI categories, as recommended by the European Society of Cardiology Working Group on Thrombosis (normal weight [BMI 18.5-24.99 kg/m²], overweight [BMI 25-29.99 kg/m²], and obese [BMI ≥30 kg/m²]) and by median BMI, as prespecified in the protocol.ResultsAmong 7,038 patients randomized and with available BMI, 1,807 (25.7%) were normal weight, 2,927 (41.6%) were overweight, and 2,304 (32.7%) were obese. In normal-weight, overweight, and obese patients, ticagrelor monotherapy, compared with ticagrelor plus aspirin, reduced the primary endpoint of Bleeding Academic Research Consortium type 2, 3, or 5 bleeding (normal weight: HR: 0.48 [95% CI: 0.32-0.73]; overweight: HR: 0.57 [95% CI: 0.41-0.78]; obese: HR: 0.63 [95% CI: 0.44-0.91]; P for interaction = 0.627), without any increase in the composite ischemic endpoint of all-cause death, myocardial infarction, or stroke (normal weight: HR: 1.36 [95% CI: 0.84-2.19]; overweight: HR: 0.92 [95% CI: 0.63-1.35]; obese: HR: 0.84 [95% CI: 0.56-1.25]; P for interaction = 0.290). These findings were consistent with the prespecified analysis by median BMI.ConclusionsAmong high-risk patients undergoing percutaneous coronary intervention, ticagrelor monotherapy, compared with ticagrelor plus aspirin, reduced bleeding events without any increase in ischemic risk across different BMI categories.     

Prevalence and Prognostic Significance of Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction

BackgroundThe pathophysiological and clinical significance of microvascular dysfunction (MVD) in patients with heart failure with preserved ejection fraction (HFpEF) remains uncertain.ObjectivesThe aim of this study was to use cardiovascular magnetic resonance to: 1) quantify coronary microvascular function; 2) examine the relationship between perfusion and fibrosis; and 3) evaluate the impact of MVD and fibrosis on long-term clinical outcomes.MethodsIn a prospective, observational study, patients with HFpEF and control subjects underwent multiparametric cardiovascular magnetic resonance (comprising assessment of left ventricular volumetry, perfusion, and fibrosis [focal by late gadolinium enhancement and diffuse by extracellular volume]). The primary endpoint was the composite of death or hospitalization with heart failure.ResultsOne hundred and one patients with HFpEF (mean age 73 ± 9 years, mean ejection fraction 56% ± 5%) and 43 control subjects (mean age 73 ± 5 years, mean ejection fraction 58% ± 5%) were studied. Myocardial perfusion reserve (MPR) was lower in patients with HFpEF versus control subjects (1.74 ± 0.76 vs 2.22 ± 0.76; P = 0.001). MVD (defined as MPR <2.0) was present in 70% of patients with HFpEF (vs 48% of control subjects; P = 0.014). There was no significant linear correlation between MPR and diffuse fibrosis (r = ?0.10; P = 0.473) and no difference in MPR between those with and without focal fibrosis (mean difference ?0.03; 95% CI: ?0.37 to 0.30). In the HFpEF group, during median follow-up of 3.1 years, there were 45 composite events. MPR was independently predictive of clinical outcome following adjustment for clinical, blood, and imaging parameters (1 SD increase: HR: 0.673 [95% CI: 0.463 to 0.978; P = 0.038]; HR: 0.694 [95% CI: 0.491 to 0.982; P = 0.039]; and HR: 0.690 [95% CI: 0.489 to 0.973; P = 0.034], respectively).ConclusionsMVD is highly prevalent among patients with HFpEF and is an independent predictor of prognosis. The lack of correlation between MVD and fibrosis may challenge the assertion of a direct causal link between these entities. (Developing Imaging and Plasma Biomarkers in Describing Heart Failure With Preserved Ejection Fraction [DIAMONDHFpEF]; NCT03050593)     

Prognostic Impact of High-Sensitivity C-Reactive Protein in Patients Undergoing Percutaneous Coronary Intervention According to BMI

ObjectivesThe aim of this study was to determine the prevalence and prognostic implications of elevated high-sensitivity C-reactive protein (hsCRP) in patients undergoing percutaneous coronary intervention (PCI) according to body mass index (BMI).BackgroundWhereas elevated hsCRP predicts adverse clinical outcome after PCI in the general population, the impact of BMI on its prognostic utility remains unclear.MethodsData from 14,140 patients who underwent PCI between January 2009 and June 2017 at a large tertiary care center were analyzed. Patients were divided into 4 BMI categories: normal (BMI 18.5 to <25 kg/m², n = 2,808), overweight (BMI 25 to <30 kg/m², n = 6,015), obese (BMI 30 to <35 kg/m², n = 3,490), and severely obese (BMI ≥35 kg/m², n = 1,827). Elevated hsCRP was defined as >3 mg/l. The primary endpoint of interest was the occurrence of major adverse cardiac events (MACE; defined as death, myocardial infarction, or target vessel revascularization) within 1 year after PCI.ResultsElevated hsCRP was present in 18.9%, 23.6%, 33.3%, and 47.7% of the normal, overweight, obese, and severely obese groups, respectively. MACE rates were consistently higher in patients with elevated hsCRP across all BMI categories (normal, 13.4% vs. 8.3%; overweight, 11.2% vs. 7.2%; obese, 10.6% vs. 7.5%; severely obese, 11.9% vs. 6.5%; p < 0.01 for all). After multivariate adjustment, hsCRP elevation remained significantly associated with MACE independent of BMI (hazard ratios: normal, 1.43 [95% confidence interval: 1.04 to 1.95]; overweight, 1.56 [95% confidence interval: 1.21 to 1.88]; obese, 1.40 [95% confidence interval: 1.06 to 1.84]; severely obese, 1.92 [95% confidence interval: 1.35 to 2.75]; p < 0.05 for all).ConclusionsAmong patients undergoing PCI, the prevalence of hsCRP elevation progressively increased with higher BMI. Measurement of hsCRP facilitates prognostic risk assessment for adverse outcome after PCI across a broad range of BMI.     

BMI,Infarct Size,and Clinical Outcomes Following Primary PCI: Patient-Level Analysis From 6 Randomized Trials

ObjectivesThe aim of this study was to examine the association between body mass index (BMI), infarct size (IS) and clinical outcomes.BackgroundThe association between obesity, IS, and prognosis in patients undergoing primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction is incompletely understood.MethodsAn individual patient-data pooled analysis was performed from 6 randomized trials of patients undergoing pPCI for ST-segment elevation myocardial infarction in which IS (percentage left ventricular mass) was assessed within 1 month (median 4 days) after randomization using either cardiac magnetic resonance (5 studies) or ^99mTc sestamibi single-photon emission computed tomography (1 study). Patients were classified as normal weight (BMI <25 kg/m²), overweight (25 kg/m² ≤BMI <30 kg/m²), or obese (BMI ≥30 kg/m²). The multivariable models were adjusted for age, sex, hypertension, hyperlipidemia, current smoking, left main or left anterior descending coronary artery infarct, baseline TIMI (Thrombolysis In Myocardial Infarction) flow grade 0 or 1, prior myocardial infarction, symptom–to–first device time, and study.ResultsAmong 2,238 patients undergoing pPCI, 644 (29%) were normal weight, 1,008 (45%) were overweight, and 586 (26%) were obese. BMI was not significantly associated with IS, microvascular obstruction, or left ventricular ejection fraction in adjusted or unadjusted analysis. BMI was also not associated with the 1-year composite risk for death or heart failure hospitalization (adjusted hazard ratio: 1.21 [95% confidence interval: 0.74 to 1.71] for overweight vs. normal [p = 0.59]; adjusted hazard ratio: 1.21 [95% confidence interval 0.74 to 1.97] for obese vs. normal [p = 0.45]) or for death or heart failure hospitalization separately. Results were consistent when BMI was modeled as a continuous variable.ConclusionsIn this individual patient-data pooled analysis of 2,238 patients undergoing pPCI for ST-segment elevation myocardial infarction, BMI was not associated with IS, microvascular obstruction, left ventricular ejection fraction, or 1-year rates of death or heart failure hospitalization.     

Coronary Flow Assessment Using 3-Dimensional Ultrafast Ultrasound Localization Microscopy

BackgroundDirect assessment of the coronary microcirculation has long been hampered by the limited spatial and temporal resolutions of cardiac imaging modalities.ObjectivesThe purpose of this study was to demonstrate 3-dimensional (3D) coronary ultrasound localization microscopy (CorULM) of the whole heart beyond the acoustic diffraction limit (<20 μm resolution) at ultrafast frame rate (>1000 images/s).MethodsCorULM was performed in isolated beating rat hearts (N = 6) with ultrasound contrast agents (Sonovue, Bracco), using an ultrasonic matrix transducer connected to a high channel–count ultrafast electronics. We assessed the 3D coronary microvascular anatomy, flow velocity, and flow rate of beating hearts under normal conditions, during vasodilator adenosine infusion, and during coronary occlusion. The coronary vasculature was compared with micro-computed tomography performed on the fixed heart. In vivo transthoracic CorULM was eventually assessed on anaesthetized rats (N = 3).ResultsCorULM enables the 3D visualization of the coronary vasculature in beating hearts at a scale down to microvascular structures (<20 μm resolution). Absolute flow velocity estimates range from 10 mm/s in tiny arterioles up to more than 300 mm/s in large arteries. Fitting to a power law, the flow rate–radius relationship provides an exponent of 2.61 (r² = 0.96; P < 0.001), which is consistent with theoretical predictions and experimental validations of scaling laws in vascular trees. A 2-fold increase of the microvascular coronary flow rate is found in response to adenosine, which is in good agreement with the overall perfusion flow rate measured in the aorta (control measurement) that increased from 8.80 ± 1.03 mL/min to 16.54 ± 2.35 mL/min (P < 0.001). The feasibility of CorULM was demonstrated in vivo for N = 3 rats.ConclusionsCorULM provides unprecedented insights into the anatomy and function of coronary arteries at the microvasculature level in beating hearts. This new technology is highly translational and has the potential to become a major tool for the clinical investigation of the coronary microcirculation.     

Clopidogrel Monotherapy After 1-Month Dual Antiplatelet Therapy in Patients With Diabetes Undergoing Percutaneous Coronary Intervention

BackgroundDiabetes was reported to be associated with an impaired response to clopidogrel.ObjectivesThe aim of this study was to evaluate the safety and efficacy of clopidogrel monotherapy after very short dual antiplatelet therapy (DAPT) in patients with diabetes undergoing percutaneous coronary intervention (PCI).MethodsA subgroup analysis was conducted on the basis of diabetes in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2) Total Cohort (N = 5,997) (STOPDAPT-2, n = 3,009; STOPDAPT-2 ACS [Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 for the Patients With ACS], n = 2,988), which randomly compared 1-month DAPT followed by clopidogrel monotherapy with 12-month DAPT with aspirin and clopidogrel after cobalt-chromium everolimus-eluting stent implantation. The primary endpoint was a composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) or bleeding (TIMI [Thrombolysis In Myocardial Infarction] major or minor) endpoints at 1 year.ResultsThere were 2,030 patients with diabetes (33.8%) and 3967 patients without diabetes (66.2%). Regardless of diabetes, the risk of 1-month DAPT relative to 12-month DAPT was not significant for the primary endpoint (diabetes, 3.58% vs 4.12% [HR: 0.87; 95% CI: 0.56-1.37; P = 0.55]; nondiabetes, 2.46% vs 2.49% [HR: 0.99; 95% CI: 0.67-1.48; P = 0.97]; P_interaction = 0.67) and for the cardiovascular endpoint (diabetes, 3.28% vs 3.05% [HR: 1.10; 95% CI: 0.67-1.81; P = 0.70]; nondiabetes, 1.95% vs 1.43% [HR: 1.38; 95% CI: 0.85-2.25; P = 0.20]; P_interaction = 0.52), while it was lower for the bleeding endpoint (diabetes, 0.30% vs 1.50% [HR: 0.20; 95% CI: 0.06-0.68; P = 0.01]; nondiabetes, 0.61% vs 1.21% [HR: 0.51; 95% CI: 0.25-1.01; P = 0.054]; P_interaction = 0.19).ConclusionsClopidogrel monotherapy after 1-month DAPT compared with 12-month DAPT reduced major bleeding events without an increase in cardiovascular events regardless of diabetes, although the findings should be considered as hypothesis generating, especially in patients with acute coronary syndrome, because of the inconclusive result in the STOPDAPT-2 ACS trial. (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 [STOPDAPT-2], NCT02619760; Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 for the Patients With ACS [STOPDAPT-2 ACS], NCT03462498)     

Association of Sex,Reduced Myocardial Flow Reserve,and Long-Term Mortality Across Spectrum of Atherosclerotic Disease

BackgroundCoronary vasomotor dysfunction (defined by reduced myocardial blood flow reserve [MBFR]) is associated with high cardiac risk in both men and women in absence of significant coexisting epicardial disease. Whether there is a sex-specific difference in prognostic value of reduced MBFR in patients with a greater burden of coexisting epicardial atherosclerotic disease is not well understood.ObjectivesThe purpose of this study was to examine the association of sex, MBFR, and mortality in consecutive patients with suspected or known coronary artery disease undergoing positron emission tomography myocardial perfusion imaging.MethodsUnique consecutive patients undergoing rubidium (Rb)-82 rest/stress positron emission tomography myocardial perfusion imaging from 2010-2016 were followed for a median of 3.2 years. Multivariable Cox models were built to describe the interaction of sex and MBFR on all-cause and cardiac death for the overall population and stratified by extent of calcified atherosclerosis (none: coronary artery calcium score = 0, subclinical: coronary artery calcium >0, clinical: prior myocardial infarction/percutaneous coronary intervention) and abnormal perfusion (no significant obstructive disease: summed stress score = 0, 1%-9.9%, and ≥10%) at baseline.ResultsAmong 12,594 patients, 52.8% were women. Compared with men, women had a lower prevalence of known coronary artery disease (16.5% vs 29.5%; P < 0.001) and were less likely to undergo revascularization after myocardial perfusion imaging (4.9% vs 9.7%; P < 0.001), but were more likely to have a reduced MBFR of <2 (56.2% vs 50.6%; P < 0.001). There were 1,699 (13.5%) all-cause and 490 (3.9%) cardiac deaths. In fully adjusted Cox models, reduced MBFR was independently associated with higher risk of death (HR per 0.1-U decrease: 1.09 [95% CI: 1.08-1.10]; P < 0.001), but female sex was not (HR: 0.95 [95% CI: 0.85-1.05]; P = 0.27). There was no significant interaction between sex and MBFR on death (P = 0.22) and cardiac death (P = 0.35) overall or in subgroups of patients with clinical, subclinical, and no atherosclerosis or across categories of perfusion abnormality at baseline.ConclusionsThe association between reduced MBFR and higher risk of all-cause and cardiac death did not differ by sex, regardless of extent of coexisting atherosclerosis or perfusion abnormality.     

Genetic prediction of age at menarche,age at natural menopause and type 2 diabetes: A Mendelian randomization study

Background and aimsThe relationship between reproductive factors and type 2 diabetes (T2D) is controversial; therefore, we explored the causal relationship of age at menarche (AAM), age at natural menopause (ANM), with the risk of T2D and glycemic traits using two-sample Mendelian randomization.Methods and resultsWe used publicly available data at the summary level of genome-wide association studies, where AAM (N = 329,345), ANM (N = 69,360), T2D (N = 464,389). The inverse variance weighting (IVW) method was employed as the primary method. To demonstrate the robustness of the results, we also conducted various sensitivity analysis methods including the MR-Egger regression, the weighted median (WM) and the MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. After excluding IVs associated with confounders, we found a causal association between later AAM and reduced risk of T2D (OR 0.81 [95% CI 0.75, 0.87]; P = 2.20 × 10⁻⁸), lower levels of FI (β −0.04 [95% CI -0.06, −0.01]; P = 2.19 × 10⁻³), FPG (β −0.03 [95% CI -0.05, −0.007]; P = 9.67 × 10⁻⁵) and HOMA-IR (β −0.04 [95% CI -0.06, −0.01]; P = 4,95 × 10⁻³). As for ANM, we only found a causal effect with HOMA-IR (β −0.01 [95% CI -0.02, −0.005]; P = 1.77 × 10⁻³), but not with T2D.ConclusionsOur MR study showed a causal relationship between later AAM and lower risk of developing T2D, lower FI, FPG and HOMA-IR levels. This may provide new insights into the prevention of T2D in women.     

Diagnostic and Prognostic Value of Myocardial Work Indices for Identification of Cancer Therapy–Related Cardiotoxicity

BackgroundEchocardiographic global longitudinal strain (GLS) is a useful measure for detection of cancer treatment–related cardiac dysfunction (CTRCD) but is influenced by blood pressure changes. This limitation may be overcome by assessment of myocardial work (MW), which incorporates blood pressure into the calculation.ObjectivesThis work aims to determine whether myocardial work indices (MWIs) can help diagnose or prognosticate CTRCD.MethodsIn this prospective cohort study, 136 women undergoing anthracycline and trastuzumab treatment for HER2+ breast cancer, underwent serial echocardiograms and cardiac magnetic resonance pre- and post-anthracycline and every 3 months during trastuzumab. GLS, global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency were measured. CTRCD was defined with cardiac magnetic resonance. Generalized estimating equations quantified the association between changes in GLS and MWIs and CTRCD at the current (diagnosis) and subsequent visit (prognosis). Regression tree analysis was used to explore the combined use of GLS and MW for the diagnostic/prognostic assessment of CTRCD.ResultsBaseline left ventricular ejection fraction (LVEF) was 63.2 ± 4.0%. Thirty-seven (27.2%) patients developed CTRCD. An absolute change in GLS (standardized odds ratio [sOR]: 1.97 [95% CI: 1.07-3.66]; P = 0.031) and GWI (sOR: 1.73 [95% CI: 1.04-2.85]; P = 0.033) were associated with concurrent CTRCD. An absolute change in GLS (sOR: 1.79 [95% CI: 1.22-2.62]; P = 0.003), GWI (sOR: 1.67 [95% CI: 1.20-2.32]; P = 0.003), and GCW (sOR: 1.65 [95% CI: 1.17-2.34]; P = 0.005) were associated with subsequent CTRCD. Change in GWI and GCW demonstrated incremental value over GLS and clinical factors for the diagnosis of concurrent CTRCD. In a small group with a GLS change <3.3% (absolute), and a >21 mm Hg reduction in systolic blood pressure, worsening of GWI identified patients with higher probability of concurrent CTRCD (24.0% vs 5.2%). MWIs did not improve identification of subsequent CTRCD beyond knowledge of GLS change.ConclusionsGLS can be used to diagnose and prognosticate cardiac magnetic resonance (CMR) defined CTRCD, with additional value from MWIs in selected cases. (Evaluation of Myocardial Changes During Breast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI [EMBRACE-MRI]; NCT02306538)     

Budesonide Oral Suspension Improves Outcomes in Patients With Eosinophilic Esophagitis: Results From a Phase 3 Trial

Background & AimsEosinophilic esophagitis (EoE) is a chronic, immune-mediated disease for which there is currently no pharmacologic therapy approved by the U.S. Food and Drug Administration.MethodsIn this double-blind, placebo-controlled, phase 3 trial, patients 11–55 years of age with EoE and dysphagia were randomized 2:1 to receive budesonide oral suspension (BOS) 2.0 mg twice daily or placebo for 12 weeks at academic or community care practices. Co-primary endpoints were the proportion of stringent histologic responders (≤6 eosinophils/high-power field) or dysphagia symptom responders (≥30% reduction in Dysphagia Symptom Questionnaire [DSQ] score) over 12 weeks. Changes in DSQ score (key secondary endpoint) and EoE Endoscopic Reference Score (EREFS) (secondary endpoint) from baseline to week 12, and safety parameters were examined.ResultsOverall, 318 patients (BOS, n = 213; placebo, n = 105) were randomized and received ≥1 dose of study treatment. More BOS-treated than placebo-treated patients achieved a stringent histologic response (53.5% vs 1.0%; Δ53% [95% confidence interval (CI), 43.8%–59.5%]; P < .001) or symptom response (52.6% vs 39.1%; Δ13% [95% CI, 1.6%–24.3%]; P = .024) over 12 weeks. BOS-treated patients also had greater improvements in least-squares mean DSQ scores and EREFS over 12 weeks than placebo-treated patients: DSQ, –13.0 (SEM 1.2) vs –9.1 (SEM 1.5) (Δ–3.9 [95% CI, –7.1 to –0.8]; P = .015); EREFS, –4.0 (SEM 0.3) vs –2.2 (SEM 0.4) (Δ–1.8 [95% CI, –2.6 to –1.1]; P < .001). BOS was well tolerated; most adverse events were mild or moderate in severity.ConclusionsIn patients with EoE, BOS 2.0 mg twice daily was superior to placebo in improving histologic, symptomatic, and endoscopic outcomes over 12 weeks. BOS 2.0 mg twice daily was well tolerated. ClinicalTrials.gov number: NCT02605837.     

Effect of intermittent and continuous caloric restriction on Sirtuin1 concentration depends on sex and body mass index

Background & aimsThe favorable effect of caloric restriction (CR) on health span is well known and partly mediated by the sirtuin system. Sirtuin1, a regulator of energy homeostasis in response to nutrient availability, is activated by CR. We therefore investigated effects of two different CR regimens on Sirtuin1 concentrations.Methods & resultsThe study included 112 abdominally obese subjects, randomized to intermittent or continuous CR for 1 year. Blood samples and anthropometric measures were collected at baseline and after 12 months. Sirtuin1 concentrations were measured by ELISA. Sirtuin1 correlated significantly to BMI at baseline (r = .232, p = 0.019). Mean reduction in body-weight was 8.0 and 9.0 kg after intermittent and continuous CR, respectively. After 1 year, no significant between-group differences in Sirtuin1 levels were observed according to regimen (p = 0.98) and sex (p = 0.41). An increase in median Sirtuin1 concentrations (pg/mL) [25, 75 percentiles] from baseline was observed after intermittent CR in the total population (884 [624, 1285] vs.762 [530, 1135]; p = 0.041), most marked in men (820 [623, 1250] vs. 633 [524, 926]; p = 0.016). Improvement in BMI after 1 year correlated to Sirtuin1 changes, but varied according to sex. In women, Spearman's rho = .298, p = 0.034, with stronger correlation in the intermittent CR group (r = .424, p = 0.049). In men, there was an inverse relation to Sirtuin1 changes, only in the intermittent CR group (r = ?.396, p = 0.045).ConclusionsEffects on Sirtuin1 concentrations after 1 year of CR are sex and BMI-related. Intermittent CR regimen affected Sirtuin1 to a stronger extent than continuous CR, suggesting individualized dietary intervention.     

Incident Clinical and Mortality Associations of Myocardial Native T1 in the UK Biobank

BackgroundCardiac magnetic resonance native T1-mapping provides noninvasive, quantitative, and contrast-free myocardial characterization. However, its predictive value in population cohorts has not been studied.ObjectivesThe associations of native T1 with incident events were evaluated in 42,308 UK Biobank participants over 3.17 ± 1.53 years of prospective follow-up.MethodsNative T1-mapping was performed in 1 midventricular short-axis slice using the Shortened Modified Look-Locker Inversion recovery technique (WIP780B) in 1.5-T scanners (Siemens Healthcare). Global myocardial T1 was calculated using an automated tool. Associations of T1 with: 1) prevalent risk factors (eg, diabetes, hypertension, and high cholesterol); 2) prevalent and incident diseases (eg, any cardiovascular disease [CVD], any brain disease, valvular heart disease, heart failure, nonischemic cardiomyopathies, cardiac arrhythmias, atrial fibrillation [AF], myocardial infarction, ischemic heart disease [IHD], and stroke); and 3) mortality (eg, all-cause, CVD, and IHD) were examined. Results are reported as odds ratios (ORs) or HRs per SD increment of T1 value with 95% CIs and corrected P values, from logistic and Cox proportional hazards regression models.ResultsHigher myocardial T1 was associated with greater odds of a range of prevalent conditions (eg, any CVD, brain disease, heart failure, nonischemic cardiomyopathies, AF, stroke, and diabetes). The strongest relationships were with heart failure (OR: 1.41 [95% CI: 1.26-1.57]; P = 1.60 × 10^-9) and nonischemic cardiomyopathies (OR: 1.40 [95% CI: 1.16-1.66]; P = 2.42 × 10^-4). Native T1 was positively associated with incident AF (HR: 1.25 [95% CI: 1.10-1.43]; P = 9.19 × 10^-4), incident heart failure (HR: 1.47 [95% CI: 1.31-1.65]; P = 4.79 × 10^-11), all-cause mortality (HR: 1.24 [95% CI: 1.12-1.36]; P = 1.51 × 10^-5), CVD mortality (HR: 1.40 [95% CI: 1.14-1.73]; P = 0.0014), and IHD mortality (HR: 1.36 [95% CI: 1.03-1.80]; P = 0.0310).ConclusionsThis large population study demonstrates the utility of myocardial native T1-mapping for disease discrimination and outcome prediction.     

Prognostic Value of Radiotracer-Based Perfusion Imaging in Critical Limb Ischemia Patients Undergoing Lower Extremity Revascularization

ObjectivesThe purpose of this study was to evaluate the prognostic value of single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging of angiosome foot perfusion for predicting amputation outcomes in patients with critical limb ischemia (CLI) and diabetes mellitus (DM).BackgroundRadiotracer imaging can assess microvascular foot perfusion and identify regional perfusion abnormalities in patients with critical limb ischemia CLI and DM, but the relationship between perfusion response to revascularization and subsequent clinical outcomes has not been evaluated.MethodsPatients with CLI, DM, and nonhealing foot ulcers (n = 25) were prospectively enrolled for SPECT/CT perfusion imaging of the feet before and after revascularization. CT images were used to segment angiosomes (i.e., 3-dimensional vascular territories) of the foot. Relative changes in radiotracer uptake after revascularization were evaluated within the ulcerated angiosome. Incidence of amputation was assessed at 3 and 12 months after revascularization.ResultsSPECT/CT detected a significantly lower microvascular perfusion response for patients who underwent amputation compared with those who remained amputation free at 3 (p = 0.01) and 12 (p = 0.01) months after revascularization. The cutoff percent change in perfusion for predicting amputation at 3 months was 7.55%, and 11.56% at 12 months. The area under the curve based on the amputation outcome was 0.799 at 3 months and 0.833 at 12 months. The probability of amputation-free survival was significantly higher at 3 (p = 0.002) and 12 months (p = 0.03) for high-perfusion responders than low-perfusion responders to revascularization.ConclusionsSPECT/CT imaging detects regional perfusion responses to lower extremity revascularization and provides prognostic value in patients with CLI (Radiotracer-Based Perfusion Imaging of Patients With Peripheral Arterial Disease; NCT03622359)     

Decreased intracellular histamine concentration and basophil activation in anaphylaxis

BackgroundHistamine is a crucial mediator in the development of anaphylaxis. Although histamine is promptly degraded because of its short half-life in plasma, basophils, which release histamine, remain in the blood for days. To explore basophils as a potential marker and their involvement in the pathogenesis of anaphylaxis, we evaluated the intracellular histamine concentration and the degree of basophil activation in anaphylaxis patients.MethodsWe conducted a case–control study enrolling anaphylaxis patients and healthy controls. Basophil activation was evaluated by flow cytometry using up-regulation of CD203c expression.ResultsWe enrolled 23 patients and measured their blood histamine concentration. Basophil activation was analyzed in seven of 23 patients. The median intracellular histamine concentrations at admission were significantly lower in patients compared with controls (16.4 ng/mL [interquartile range {IQR}, 2.70 to 34.0] vs. 62.3 ng/mL [IQR, 46.0 to 85.1]; p < 0.0001). The median basophil number at admission was also significantly lower in patients compared with controls (2.21 cell/μL [IQR, 0.75 to 12.3] vs. 21.0 cell/μL [IQR, 19.5 to 28.9]; p = 0.027). CD203c expression was not up-regulated in any of the seven patients in vitro, but it was up-regulated in response to anti-IgE stimulation in vitro in two patients at admission and four patients at follow-up.ConclusionsAnaphylaxis is associated with a decrease in intracellular histamine, and a reduced number and reactivity of peripheral basophils. Impaired basophil function and a decrease in their number and intracellular histamine levels in the circulation may reflect the underlying mechanism, suggesting that basophils may be a marker of anaphylaxis.     

Prognostic Value of Right Ventricular Function in Patients With Suspected Myocarditis Undergoing Cardiac Magnetic Resonance

BackgroundRisk-stratification of myocarditis is based on functional parameters and tissue characterization of the left ventricle (LV), whereas right ventricular (RV) involvement remains mostly unrecognized.ObjectivesIn this study, the authors sought to analyze the prognostic value of RV involvement in myocarditis by cardiac magnetic resonance (CMR).MethodsPatients meeting the recommended clinical criteria for suspected myocarditis were enrolled at 2 centers. Exclusion criteria were the evidence of coronary artery disease, pulmonary artery hypertension or structural cardiomyopathy. Biventricular ejection fraction, edema according to T2-weighted images, and late gadolinium enhancement (LGE) were linked to a composite end point of major adverse cardiovascular events (MACE), including heart failure hospitalization, ventricular arrhythmia, recurrent myocarditis, and death.ResultsAmong 1,125 consecutive patients, 736 (mean age: 47.8 ± 16.1 years) met the clinical diagnosis of suspected myocarditis and were followed for 3.7 years. Signs of RV involvement (abnormal right ventricular ejection fraction [RVEF], RV edema, and RV-LGE) were present in 188 (25.6%), 158 (21.5%), and 92 (12.5%) patients, respectively. MACE occurred in 122 patients (16.6%) and was univariably associated with left ventricular ejection fraction (LVEF), LV edema, LV-LGE, RV-LGE, RV edema, and RVEF. In a series of nesting multivariable Cox regression models, the addition of RVEF (HR_adj: 0.974 [95% CI: 0.956-0.993]; P = 0.006) improved prognostication (chi-square test = 89.5; P = 0.001 vs model 1; P = 0.006 vs model 2) compared with model 1 including only clinical variables (chi-square test = 28.54) and model 2 based on clinical parameters, LVEF, and LV-LGE extent (chi-square test = 78.93).ConclusionsThis study emphasizes the role of RV involvement in myocarditis and demonstrates the independent and incremental prognostic value of RVEF beyond clinical variables, CMR tissue characterization, and LV function. (Inflammatory Cardiomyopathy Bern Registry [FlamBER]; NCT04774549; CMR Features in Patients With Suspected Myocarditis [CMRMyo]; NCT03470571)     

Center Valve Preference and Outcomes of Transcatheter Aortic Valve Replacement: Insights From the AMTRAC Registry

BackgroundData on outcomes of transcatheter aortic valve replacement (TAVR) using balloon-expandable valves (BEVs) or self-expandable valves (SEVs) as well as the impact of center valve preference on these outcomes are limited.ObjectivesThe aim of this study was to compare outcomes of TAVR procedures using third-generation BEVs and SEVs stratified by center valve preference.MethodsIn a multicenter registry (n = 17), 13 centers exhibited valve preference (66.6%-90% of volume) and were included. Outcomes were compared between BEVs and SEVs stratified by center valve preference.ResultsIn total, 7,528 TAVR procedures (3,854 with SEVs and 3,674 with BEVs) were included. The mean age was 81 years, and the mean Society of Thoracic Surgeons score was 5.2. Baseline characteristics were similar between BEVs and SEVs. Need for pacemaker implantation was higher with SEVs at BEV- and SEV-dominant centers (17.8% vs 9.3% [P < 0.001] and 12.7% vs 10.0% [P = 0.036], respectively; HR: 1.51; P for interaction = 0.021), risk for cerebrovascular accident was higher with SEVs at BEV-dominant but not SEV-dominant centers (3.6% vs 1.1% [P < 0.001] and 2.2% vs 1.4% [P = 0.162]; HR: 2.08; P for interaction < 0.01). Aortic regurgitation greater than mild was more frequent with SEVs at BEV-dominant centers and similar with BEVs regardless of center dominance (5.2% vs 2.8% [P < 0.001] and 3.4% vs 3.7% [P = 0.504], respectively). Two-year mortality was higher with SEVs at BEV-dominant centers but not at SEV-dominant centers (21.9% vs 16.9% [P = 0.021] and 16.8% vs 16.5% [P = 0.642], respectively; HR: 1.20; P for interaction = 0.032).ConclusionsPeriprocedural outcomes, aortic regurgitation greater than mild, and 2-year mortality are worse when TAVR is performed using SEVs at BEV-dominant centers. Outcomes are similar regardless of valve type at SEV-dominant centers. The present results stress the need to account for this factor when comparing BEV and SEV outcomes. (The Aortic+Mitral Transcatheter [AMTRAC] Valve Registry; NCT04031274)     

Exposure to cold airflow alters skin pH and epidermal filaggrin degradation products in children with atopic dermatitis

BackgroundWe aimed to evaluate the influence of cold airflow from the air conditioner on skin barrier function and filaggrin degradation products (FDPs) in children with atopic deramtitis (AD).MethodsIn a case-control study, 28 children with AD and 12 normal children without AD were exposed to one of two air conditioner modes (conventional or wind-free) for 2 h. Skin temperature, transepidermal water loss (TEWL), and skin pH were measured on right cheek and forearm at pre- and post-exposure time points. We also measured filaggrin and FDPs from the volar surface of the forearm.ResultsIn AD patients, skin temperature on the forearm decreased after exposure to the conventional and wind-free modes (P < 0.001 and P = 0.026), and TEWL on the cheek and the forearm decreased in the wind-free mode (P = 0.037 and 0.002). Skin pH on the cheek increased only after exposure to the conventional mode in AD group (P = 0.002). However, no changes in TEWL and skin pH were found after exposure to either the conventional or the wind-free mode in the control group. In AD children, the levels of pyrrolidone carboxylic acid (PCA) and cis-urocanic acid (UCA) were reduced only after exposure to the conventional mode (all P = 0.033). The percent changes of PCA and cis-UCA were higher in the AD group than those in the control group after exposure to conventional mode (P = 0.029 and 0.046).ConclusionsSkin barrier function in children with AD may be altered by the exposure to cold airflow from a conventional air conditioner.     

Association Between Changes in Perivascular Adipose Tissue Density and Plaque Progression

BackgroundThe association between the change in vessel inflammation, as quantified by perivascular adipose tissue (PVAT) density, and the progression of coronary atherosclerosis remains to be determined.ObjectivesThe purpose of this study was to explore the association between the change in PVAT density and the progression of total and compositional plaque volume (PV).MethodsPatients were selected from a prospective multinational registry. Patients who underwent serial coronary computed tomography angiography studies with ≥2-year intervals and were scanned with the same tube voltage at baseline and follow-up were included. Total and compositional PV and PVAT density at baseline and follow-up were quantitatively analyzed for every lesion. Multivariate linear regression models using cluster analyses were constructed.ResultsA total of 1,476 lesions were identified from 474 enrolled patients (mean age 61.2 ± 9.3 years; 65.0% men). The mean PVAT density was ?74.1 ± 11.5 HU, and total PV was 48.1 ± 83.5 mm³ (19.2 ± 44.8 mm³ of calcified PV and 28.9 ± 51.0 mm³ of noncalcified PV). On multivariate analysis (adjusted for clinical risk factors, medication use, change in lipid levels, total PV at baseline, luminal HU attenuation, location of lesions, and tube voltage), the increase in PVAT density was positively associated with the progression of total PV (estimate = 0.275 [95% CI: 0.004-0.545]; P = 0.047), driven by the association with fibrous PV (estimate = 0.245 [95% CI: 0.070-0.420]; P = 0.006). Calcified PV progression was not associated with the increase in PVAT density (P > 0.050).ConclusionsIncrease in vessel inflammation represented by PVAT density is independently associated with the progression of the lipid component of coronary atherosclerotic plaques. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411)     

Association between food and nutrients intakes and coronary plaque vulnerability in patients with coronary heart disease: An optical coherence tomography study

Background and aimsDietary intakes play important roles in the prevention and treatment of coronary heart disease (CHD). Coronary plaque vulnerability is the key mechanism leading to CHD progression. We aimed to explore the association between dietary intakes and plaque vulnerability via optical coherence tomography (OCT).Methods and resultsA total of 314 CHD patients were included in this study. Dietary intake status was assessed by semi-quantitative food frequency questionnaire and plaque vulnerability was measured by OCT. The results showed that vegetables were negatively associated with macrophage infiltration, thin cap fibroatheroma (TCFA) and thrombus [odds ratio (OR) = 0.48, 0.38, 0.38, 95% confidence interval (95% CI) = 0.24–0.93, 0.17–0.84, 0.15–0.94, all P < 0.05]; fruits were negatively associated with lipid plaque, TCFA, rupture and thrombus (OR = 0.17, 0.11, 0.12, 0.20, 95% CI = 0.07–0.39, 0.04–0.29, 0.05–0.28, 0.08–0.55, all P < 0.05); salt was positively associated with lipid plaque and TCFA (OR = 2.59, 2.83, 95% CI = 1.14–5.90, 1.23–6.51, all P < 0.05). Regarding nutrients intakes, dietary fiber was negatively associated with macrophage infiltration (OR = 0.34, 95% CI = 0.14–0.85, P = 0.021); folate was negatively associated with lipid plaque, TCFA and rupture (OR = 0.22, 0.16, 0.20, 95% CI = 0.09–0.58, 0.06–0.41, 0.08–0.51, all P < 0.05); vitamin C was negatively associated with TCFA, rupture and thrombus (OR = 0.26, 0.22, 0.05, 95% CI = 0.07–0.95, 0.07–0.65, 0.01–0.25, all P < 0.05); sodium was positively associated with lipid plaque, TCFA, rupture and thrombus (OR = 3.43, 3.96, 2.73, 4.84, 95% CI = 1.51–7.80, 1.66–9.45, 1.18–6.27, 1.76–9.28, all P < 0.05).ConclusionSalt and sodium were dietary risk factors for plaque vulnerability, whereas vegetables, fruits, dietary fiber, folate and vitamin C were dietary protective factors for plaque vulnerability.