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.     

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.     

Rivaroxaban Plus Aspirin in Obese and Overweight Patients With Vascular Disease in the COMPASS Trial

BackgroundDirect oral anticoagulants are administered in fixed doses irrespective of body weight, but guidelines recommend against their use in patients with extremes of body weight.ObjectivesThis study determined the effects of dual-pathway inhibition antithrombotic regimen (rivaroxaban 2.5 mg twice daily plus aspirin 100 mg/day) compared with aspirin Halone across a range of patient body mass indexes (BMIs) and body weights.MethodsThis was a secondary analysis of the COMPASS (Cardiovascular OutcoMes for People using Anticoagulation StrategieS) trial, which included patients with chronic coronary artery disease or peripheral artery disease. Efficacy and safety outcomes were studied in relation to BMI: (normal 18.5 ≤BMI <25 kg/m², overweight 25 ≤BMI <30 kg/m², obese ≥30 kg/m²) and body weight (≤70 kg, 70 < weight ≤90 kg, and >90 kg; as well as ≤120 kg vs. >120 kg).ResultsAmong 27,395 randomized patients, 6,459 (24%) had normal BMI, 12,047 (44%) were overweight, and 8,701 (32%) were obese. The combination of rivaroxaban and aspirin compared with aspirin produced a consistent reduction in the primary outcome of cardiovascular death, stroke, or myocardial infarction, irrespective of BMI or body weight. For 18.5 ≤BMI <25 kg/m²: 3.5% vs. 5.0%; hazard ratio (HR): 0.73 (95% credible interval [CrI]: 0.58 to 0.90); 25 ≤ BMI <30 kg/m²: 4.3% vs. 5.1%; HR: 0.80 (95% CrI: 0.66 to 0.96); BMI ≥30 kg/m²: 4.2% vs. 6.1%; HR: 0.71 (95% CrI: 0.57 to 0.86). For body weight ≤70 kg: 4.1% vs. 5.3%; HR: 0.75 (95% CrI: 0.62 to 0.91); 70 < weight ≤90 kg: 4.1% vs. 5.3%; HR: 0.76 (95% CrI: 0.65 to 0.89); >90 kg: 4.2% vs. 5.7%; HR: 0.74 (95% CrI: 0.61 to 0.90). Effects on bleeding, mortality, and net clinical benefit were consistent irrespective of BMI or bodyweight.ConclusionsThe effects of dual-pathway antithrombotic therapy are consistent irrespective of BMI or body weight, suggesting no need for dose adjustments in the ranges of weights and BMI of patients enrolled in the COMPASS trial. Further studies need to address this problem in relation to greater extremes of body weight. (Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease [COMPASS]; NCT01776424)     

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)     

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.     

Stress-Associated Neurobiological Pathway Linking Socioeconomic Disparities to Cardiovascular Disease

BackgroundLower socioeconomic status (SES) associates with a higher risk of major adverse cardiac events (MACE) via mechanisms that are not well understood.ObjectivesBecause psychosocial stress is more prevalent among those with low SES, this study tested the hypothesis that stress-associated neurobiological pathways involving up-regulated inflammation in part mediate the link between lower SES and MACE.MethodsA total of 509 individuals, median age 55 years (interquartile range: 45 to 66 years), underwent clinically indicated whole-body ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography imaging and met pre-defined inclusion criteria, including absence of known cardiovascular disease or active cancer. Baseline hematopoietic tissue activity, arterial inflammation, and in a subset of 289, resting amygdalar metabolism (a measure of stress-associated neural activity) were quantified using validated ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography methods. SES was captured by neighborhood SES factors (e.g., median household income and crime). MACE within 5 years of imaging was adjudicated.ResultsOver a median 4.0 years, 40 individuals experienced MACE. Baseline income inversely associated with amygdalar activity (standardized β: −0.157 [95% confidence interval (CI): −0.266 to −0.041]; p = 0.007) and arterial inflammation (β: −0.10 [95% CI: −0.18 to −0.14]; p = 0.022). Further, income associated with subsequent MACE (standardized hazard ratio: 0.67 [95% CI: 0.47 to 0.96]; p = 0.029) after multivariable adjustments. Mediation analysis demonstrated that the path of: ↓ neighborhood income to ↑ amygdalar activity to ↑ bone marrow activity to ↑ arterial inflammation to ↑ MACE was significant (β: −0.01 [95% CI: −0.06 to −0.001]; p < 0.05).ConclusionsLower SES: 1) associates with higher amygdalar activity; and 2) independently predicts MACE via a serial pathway that includes higher amygdalar activity, bone marrow activity, and arterial inflammation. These findings illuminate a stress-associated neurobiological mechanism by which SES disparities may potentiate adverse health outcomes.     

5-Year Prognostic Value of Quantitative Versus Visual MPI in Subtle Perfusion Defects: Results From REFINE SPECT

ObjectivesThis study compared the ability of automated myocardial perfusion imaging analysis to predict major adverse cardiac events (MACE) to that of visual analysis.BackgroundQuantitative analysis has not been compared with clinical visual analysis in prognostic studies.MethodsA total of 19,495 patients from the multicenter REFINE SPECT (REgistry of Fast Myocardial Perfusion Imaging with NExt generation SPECT) study (64 ± 12 years of age, 56% males) undergoing stress Tc-99m-labeled single-photon emission computed tomography (SPECT) myocardial perfusion imaging were followed for 4.5 ± 1.7 years for MACE. Perfusion abnormalities were assessed visually and categorized as normal, probably normal, equivocal, or abnormal. Stress total perfusion deficit (TPD), quantified automatically, was categorized as TPD = 0%, TPD >0% to <1%, ≤1% to <3%, ≤3% to <5%, ≤5% to ≤10%, or TPD >10%. MACE consisted of death, nonfatal myocardial infarction, unstable angina, or late revascularization (>90 days). Kaplan-Meier and Cox proportional hazards analyses were performed to test the performance of visual and quantitative assessments in predicting MACE.ResultsDuring follow-up examinations, 2,760 (14.2%) MACE occurred. MACE rates increased with worsening of visual assessments, that is, the rate for normal MACE was 2.0%, 3.2% for probably normal, 4.2% for equivocal, and 7.4% for abnormal (all p < 0.001). MACE rates increased with increasing stress TPD from 1.3% for the TPD category of 0% to 7.8% for the TPD category of >10% (p < 0.0001). The adjusted hazard ratio (HR) for MACE increased even in equivocal assessment (HR: 1.56; 95% confidence interval [CI]: 1.37 to 1.78) and in the TPD category of ≤3% to <5% (HR: 1.74; 95% CI: 1.41 to 2.14; all p < 0.001). The rate of MACE in patients visually assessed as normal still increased from 1.3% (TPD = 0%) to 3.4% (TPD ≥5%) (p < 0.0001).ConclusionsQuantitative analysis allows precise granular risk stratification in comparison to visual reading, even for cases with normal clinical reading.     

Sex-Specific Risks of Major Cardiovascular and Limb Events in Patients With Symptomatic Peripheral Artery Disease

BackgroundPatients with peripheral artery disease (PAD) have a higher risk of major adverse cardiovascular events (MACE) compared with those without PAD.ObjectivesThe aim of this post hoc analysis was to evaluate sex-specific differences in MACE and limb events in the EUCLID (Examining Use of Ticagrelor in PAD) trial.MethodsCox proportional hazards models were used to compare time-to-event outcomes stratified by sex. Covariates were introduced after adjusted model selection.ResultsEUCLID enrolled 13,885 patients with PAD (28% women [n = 3,888]). PAD severity and medical treatment were comparable between sexes, whereas prior lower extremity revascularization was reported less frequently in women (54.8% vs. 57.3%; p = 0.006). Women were older (mean ± SD age: 67.8 ± 8.9 vs. 66.1 ± 8.2 years; p < 0.001) and more likely to have diabetes mellitus (p = 0.004), hypertension, hyperlipidemia, and chronic kidney disease (all p < 0.001). Over a mean follow-up of 30 months, women had a lower risk of MACE (9.5% vs. 11.2%; adjusted hazard ratio: 0.77; 95% confidence interval: 0.68 to 0.88; p < 0.001) and all-cause-mortality (7.6% vs. 9.7%; adjusted hazard ratio: 0.61; 95% confidence interval: 0.53 to 0.71; p < 0.001). In contrast, risk for major adverse limb events (2.6% vs. 3.0%) and hospitalization for acute limb ischemia (1.6% vs. 1.7%) were not different by sex.ConclusionsAlthough women with PAD are at lower risk for MACE and all-cause mortality, risk for limb events was similar between sexes over a mean follow-up of 30 months. Understanding sex-specific differences and dissociation between baseline cardiovascular risk and subsequent cardiovascular events requires further investigation. (A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease [EUCLID]; NCT01732822)     

Randomized Comparison Between Everolimus-Eluting Bioresorbable Scaffold and Metallic Stent: Multimodality Imaging Through 3 Years

ObjectivesThe aim of this study was to investigate the vascular responses and fates of the scaffold after bioresorbable vascular scaffold (BVS) implantation using multimodality imaging.BackgroundSerial comprehensive image assessments after BVS implantation in the context of a randomized trial have not yet been reported.MethodsIn the ABSORB Japan trial, 400 patients were randomized to a BVS (n = 266) or a cobalt-chromium everolimus-eluting stent (n = 134). Through 3 years, patients underwent serial angiography and intravascular ultrasound or optical coherence tomography (OCT).ResultsLuminal dimension at 3 years was consistently smaller with the BVS than with the cobalt-chromium everolimus-eluting stent (mean angiographic minimal luminal diameter 2.04 ± 0.63 mm vs. 2.40 ± 0.56 mm, mean difference −0.37 mm [95% confidence interval: −0.50 to −0.24 mm]; p < 0.001), mainly because of smaller device area (6.13 ± 2.03 mm² vs. 7.15 ± 2.16 mm², mean difference −1.04 mm² [95% confidence interval: −1.66 to −0.42 mm²]; p < 0.001), and larger neointimal area (2.10 ± 0.61 mm² vs. 1.86 ± 0.64 mm², mean difference 0.24 mm² [95% confidence interval: 0.06 to 0.43 mm²]; p = 0.01) by OCT. BVS-treated vessels did not show previously reported favorable vessel responses, such as positive vessel remodeling, late luminal enlargement, and restoration of vasomotion, although the OCT-based healing score was on average zero (interquartile range: 0.00 to 0.00). At 3 years, intraluminal scaffold dismantling (ISD) was observed in 14% of BVS. On serial OCT, ISD was observed in 6 lesions at 2 years, where the struts had been fully apposed at post-procedure, while ISD was observed in 12 lesions at 3 years, where 8 lesions were free from ISD on 2-year OCT. In 5 cases of very late scaffold thrombosis, strut discontinuities were detected in all 4 cases with available OCT immediately before reintervention.ConclusionsIn this multimodality serial imaging study, luminal dimension at 3 years was smaller with the BVS than with the cobalt-chromium everolimus-eluting stent. ISD, suspected to be one of the mechanisms of very late BVS thrombosis, was observed in a substantial proportion of cases at 3 years, which developed between post-procedure and 2 years and even beyond 2 years. (AVJ-301 Clinical Trial: A Clinical Evaluation of AVJ-301 [Absorb™ BVS] in Japanese Population [ABSORB JAPAN]; NCT01844284)     

Invasive Approaches in the Management of Cocaine-Associated Non–ST-Segment Elevation Myocardial Infarction

ObjectivesThe aim of this study was to determine the impact of invasive approaches and revascularization in patients with cocaine-associated non–ST-segment elevation myocardial infarction (NSTEMI).BackgroundThe role of invasive approaches in cocaine-associated NSTEMI is uncertain.MethodsThis retrospective cohort study identified 3,735 patients with NSTEMI and history of cocaine use from the Nationwide Readmissions Database from 2016 to 2017. Invasive approaches were defined as coronary angiography, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). Revascularization was defined as PCI and CABG. The primary efficacy outcome was major adverse cardiac events (MACE), and the primary safety outcome was emergent revascularization. Nonadherence was identified using appropriate International Classification of Diseases-Tenth Revision codes. Two propensity-matched cohorts were generated (noninvasive vs. invasive and noninvasive vs. revascularization) through multivariate logistic regression.ResultsIn the propensity score–matched cohorts, an invasive approach (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.56 to 0.92; p = 0.008) and revascularization (HR: 0.54; 95% CI: 0.40 to 0.73; p < 0.001) (compared with a noninvasive approach) were associated with a lower rate of MACE, without an increase in emergent revascularization. On stratification, PCI and CABG individually were associated with a lower rate of MACE. Emergent revascularization was increased with PCI (HR: 1.78; 95% CI: 1.12 to 2.81; p = 0.014) but not with CABG. Nonadherent patients after PCI and CABG did not have significant difference in rate of MACE. PCI in nonadherent patients was associated with an increase in emergent revascularization (HR: 4.45; 95% CI: 2.07 to 9.57; p < 0.001).ConclusionsInvasive approaches and revascularization for cocaine-associated NSTEMI are associated with lower morbidity. A history of medical nonadherence was not associated with a difference in morbidity but was associated with an increased risk for emergent revascularization with PCI.     

Indexing Left Atrial Volumes: Alternative Indexing Methods Better Predict Outcomes in Overweight and Obese Populations

BackgroundLeft atrial volume (LAV) is often adjusted for body surface area (BSA). In overweight individuals this may result in underestimation of left atrial (LA) dilation. The authors investigated whether alternative indexing techniques better predict mortality and cardiovascular (CV) events.ObjectivesThe purpose of this study was to evaluate the efficacy of different methods of indexing LAV in predicting mortality and CV events across a range of body sizes.MethodsLAV was adjusted for BSA, idealized BSA (iBSA), height, and height-squared (H²) in patients aged over 50 years who underwent outpatient echocardiography and longitudinal follow-up at our institution. LA dilation was categorized using published criteria. Mortality and CV events were assessed via medical records.ResultsLAVs were calculated in 17,454 individuals. In this study, 71.2% were overweight or obese. Indexing using iBSA, height, and H² resulted in reclassification of LA size in up to 28.4% (P < 0.001) compared with indexing using BSA. In severely obese individuals (body mass index [BMI] ≥40 kg/m²), LA dilation indexed for BSA no longer predicted mortality (P = 0.70). Other indexing methods remained predictive of mortality. Height, H², and iBSA all had greater performance, compared with BSA, for prediction of mortality and CV events in all overweight patients with H² showing the best overall performance (P < 0.001). Net reclassification index for mortality was significant for all alternative indexing techniques (P < 0.001) and patients whose LA was reclassified from normal to dilated had increased risk of mortality (P < 0.001) and CV events (P < 0.001) across all BMI categories.ConclusionsLA dilation based on standard indexing using BSA is nondiscriminatory for prediction of mortality in the severely obese. Indexing using height, H², or iBSA to diagnose LA dilation better predicts mortality in this population and has better overall predictive performance across all overweight and obese populations. Using BSA indexing may lead to underappreciation of LA dilation and underestimation of patients at increased risk.     

Impact of Obesity on Outcomes of Pregnancy in Women With Heart Disease

BackgroundWomen with heart disease are at risk for complications during pregnancy. This study sought to examine the effect of maternal obesity on pregnancy complications in women with heart disease.ObjectivesThe objective was to determine the incidence of adverse cardiac events (CE) in pregnant women with heart disease and obesity.MethodsAdverse CE during pregnancy were examined in a prospective cohort of women with heart disease. CE were a composite of the following: cardiac death/arrest, arrhythmias, heart failure, myocardial infarction, stroke, aortic dissection, and thromboembolic events. Pre-eclampsia and post-partum hemorrhage were also studied. Outcomes were examined according to body mass index (BMI). To identify additional predictors of CE, a baseline risk score (CARPREG [Canadian Cardiac Disease in Pregnancy Study] II score) for predicting cardiac complications was calculated for all pregnancies and included in a multivariable logistic regression model.ResultsOf 790 pregnancies, 19% occurred in women with BMI ≥30 kg/m² (obesity), 25% in women with BMI 25 to 29.9 kg/m² (overweight), 53% in women with BMI 18.5 to 24.9 kg/m² (normal weight), and 3% in women with BMI <18.5 kg/m² (underweight). Women with obesity were at higher risk of CE when compared with women with normal weight (23% vs. 14%; p = 0.006). In a multivariable model, obesity (odds ratio: 1.7; 95% confidence interval: 1.0 to 2.7) and higher CARPREG II risk scores (odds ratio: 1.7; 95% confidence interval: 1.5 to 1.9) predicted CE. Pre-eclampsia was more frequent in women with obesity compared with those with normal weight (8% vs. 2%; p = 0.001).ConclusionsObesity increases the risk of maternal cardiovascular complications in pregnant women with heart disease. This modifiable risk factor should be addressed at the time of preconception counseling.     

Dual Antiplatelet Therapy Discontinuation,Platelet Reactivity,and Adverse Outcomes After Successful Percutaneous Coronary Intervention

ObjectivesThe purpose of this study was to assess the extent to which the association between premature dual antiplatelet therapy (DAPT) discontinuation and excess risk of thrombotic events varies according to the reason and timing of DAPT discontinuation and whether high on-treatment platelet reactivity (HPR) influences the risk of thrombotic events after premature DAPT discontinuation.BackgroundDAPT after percutaneous coronary intervention (PCI) suppresses platelet reactivity, and HPR on clopidogrel after PCI is associated with an increased risk of thrombotic events.MethodsADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective, multicenter registry of 8,582 patients successfully treated with coronary drug-eluting stents that assessed HPR on clopidogrel. For patients who discontinued aspirin or clopidogrel at any time during the study, the reasons for discontinuation were systematically categorized.ResultsPlanned DAPT discontinuation occurred within 2 years in 3,203 (37.3%) patients. One thousand four hundred eighteen (16.5%) patients discontinued DAPT for unplanned reasons, including surgery or trauma (n = 768 [8.9%]), patient nonadherence (n = 321 [3.7%]), bleeding complications (n = 264 [3.1%]), and drug allergy or hypersensitivity (n = 113 [1.3%]). Unplanned but not planned DAPT discontinuation was associated with an increased risk of a major adverse cardiac event (MACE, defined as the composite of cardiac death, myocardial infarction, or stent thrombosis); with highest risk within 3 months after PCI (adjusted HR: 7.65, 95% CI: 2.77-21.10 vs adjusted HR: 2.47, 95% CI: 1.70-3.58 for unplanned DAPT discontinuation ≥3 months after PCI). MACE risk after DAPT discontinuation was not moderated by HPR (P_interaction = 0.91).ConclusionsIn this large-scale all-comers registry, premature DAPT discontinuation for unplanned reasons occurred in approximately 1 of 6 patients after DES implantation and was associated with a markedly increased risk of MACEs. (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents [ADAPT-DES]; NCT00638794)     

Long-Term Outcomes in Women and Men Following Percutaneous Coronary Intervention

BackgroundStudies examining sex-related outcomes following percutaneous coronary intervention (PCI) have reported conflicting results.ObjectivesThe purpose of this study was to examine the sex-related risk of 5-year cardiovascular outcomes after PCI.MethodsThe authors pooled patient-level data from 21 randomized PCI trials and assessed the association between sex and major adverse cardiac events (MACE) (cardiac death, myocardial infarction [MI], or ischemia-driven target lesion revascularization [ID-TLR]) as well as its individual components at 5 years.ResultsAmong 32,877 patients, 9,141 (27.8%) were women. Women were older and had higher body mass index, more frequent hypertension and diabetes, and less frequent history of surgical or percutaneous revascularization compared with men. By angiographic core laboratory analysis, lesions in women had smaller reference vessel diameter and shorter lesion length. At 5 years, women had a higher unadjusted rate of MACE (18.9% vs. 17.7%; p = 0.003), all-cause death (10.4% vs. 8.7%; p = 0.0008), cardiac death (4.9% vs. 4.0%; p = 0.003) and ID-TLR (10.9% vs. 10.2%; p = 0.02) compared with men. By multivariable analysis, female sex was an independent predictor of MACE (hazard ratio [HR:]: 1.14; 95% confidence interval [CI:]: 1.01 to 1.30; p = 0.04) and ID-TLR (HR: 1.23; 95% CI: 1.05 to 1.44; p = 0.009) but not all-cause death (HR: 0.91; 95% CI: 0.75 to 1.09; p = 0.30) or cardiac death (HR: 0.97; 95% CI: 0.73 to 1.29; p = 0.85).ConclusionsIn the present large-scale, individual patient data pooled analysis of contemporary PCI trials, women had a higher risk of MACE and ID-TLR compared with men at 5 years following PCI.     

Mortality After Repeat Revascularization Following PCI or CABG for Left Main Disease: The EXCEL Trial

ObjectivesThe aim of this study was to investigate the incidence and impact on mortality of repeat revascularization after index percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for left main coronary artery disease (LMCAD).BackgroundThe impact on mortality of the need of repeat revascularization following PCI or CABG in patients with unprotected LMCAD is unknown.MethodsAll patients with LMCAD and site-assessed low or intermediate SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) scores randomized to PCI (n = 948) or CABG (n = 957) in the EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial were included. Repeat revascularization events were adjudicated by an independent clinical events committee. The effect of repeat revascularization on mortality through 3-year follow-up was examined in time-varying Cox regression models.ResultsDuring 3-year follow-up, there were 346 repeat revascularization procedures among 185 patients. PCI was associated with higher rates of any repeat revascularization (12.9% vs. 7.6%; hazard ratio: 1.73; 95% confidence interval: 1.28 to 2.33; p = 0.0003). Need for repeat revascularization was independently associated with increased risk for 3-year all-cause mortality (adjusted hazard ratio: 2.05; 95% confidence interval: 1.13 to 3.70; p = 0.02) and cardiovascular mortality (adjusted hazard ratio: 4.22; 95% confidence interval: 2.10 to 8.48; p < 0.0001) consistently after both PCI and CABG (p_int = 0.85 for both endpoints). Although target vessel revascularization and target lesion revascularization were both associated with an increased risk for mortality, target vessel non–target lesion revascularization and non–target vessel revascularization were not.ConclusionsIn the EXCEL trial, repeat revascularization during follow-up was performed less frequently after CABG than PCI and was associated with increased mortality after both procedures. Reducing the need for repeat revascularization may further improve long-term survival after percutaneous or surgical treatment of LMCAD. (EXCEL Clinical Trial; NCT01205776)     

Impact of Diabetes on Outcome With Drug-Coated Balloons Versus Drug-Eluting Stents: The BASKET-SMALL 2 Trial

ObjectivesThe study sought to evaluate the impact of diabetes mellitus on 3-year clinical outcome in patients undergoing drug-coated balloon (DCB) or drug-eluting stent (DES) treatment for de novo lesions.BackgroundFor treatment of de novo coronary small vessel disease, DCBs are noninferior to DES.MethodsIn this prespecified analysis of a multicenter, randomized, noninferiority trial, including 758 patients with de novo lesions in coronary vessels <3 mm who were randomized 1:1 to DCB or DES and followed over 3 years for major adverse cardiac events (MACE) (cardiac death, nonfatal myocardial infarction [MI], and target vessel revascularization [TVR]), outcome was analyzed regarding the presence or absence of diabetes mellitus.ResultsIn nondiabetic patients (n = 506), rates of MACE (DCB 13.0% vs DES 11.5%; hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 0.73-2.09; P = 0.43), cardiac death (2.8% vs 2.9%; HR: 0.97; 95% CI: 0.32-2.92; P = 0.96), nonfatal MI (5.1% vs 4.8%; HR: 1.00; 95% CI: 0.44-2.28; P = 0.99), and TVR (8.8% vs 6.1%; HR: 1.64; 95% CI: 0.83-3.25; P = 0.16) were similar. In diabetic patients (n = 252), rates of MACE (19.3% vs 22.2%; HR: 0.82; 95% CI: 0.45-1.48; P = 0.51), cardiac death (8.8% vs 5.9%; HR: 2.01; 95% CI: 0.76-5.31; P = 0.16), and nonfatal MI (7.1% vs 9.8%; HR: 0.55; 95% CI: 0.21-1.49; P = 0.24) were similar in DCB and DES. TVR was significantly lower with DCBs vs DES (9.1% vs 15.0%; HR: 0.40; 95% CI: 0.17-0.94; P = 0.036; P = 0.011 for interaction).ConclusionsThe rates of MACE are similar in DCBs and DES in de novo coronary lesions of diabetic and nondiabetic patients. In diabetic patients, need for TVR was significantly lower with DCB versus DES. (Basel Stent Kosten Effektivitäts Trial Drug Eluting Balloons vs Drug Eluting Stents in Small Vessel Interventions [BASKET-SMALL2]; NCT01574534)     

Sex Differences in Coronary Computed Tomography Angiography–Derived Fractional Flow Reserve: Lessons From ADVANCE

ObjectivesThis study is to determine the management and clinical outcomes of patients investigated with coronary computed tomography angiography (CCTA)–derived fractional flow reserve (FFR_CT) according to sex.BackgroundWomen are underdiagnosed with conventional ischemia testing, have lower rates of obstructive coronary artery disease (CAD) at invasive coronary angiography (ICA), yet higher mortality compared to men. Whether FFR_CT improves sex-based patient management decisions compared to CCTA alone is unknown.MethodsSubjects with symptoms and CAD on CCTA were enrolled (2015 to 2017). Demographics, symptom status, CCTA anatomy, coronary volume to myocardial mass ratio (V/M), lowest FFR_CT values, and management plans were captured. Endpoints included reclassification rate between CCTA and FFR_CT management plans, incidence of ICA demonstrating obstructive CAD (≥50% stenosis) and revascularization rates.ResultsA total of 4,737 patients (n = 1,603 females, 33.8%) underwent CCTA and FFR_CT. Women were older (age 68 ± 10 years vs. 65 ± 10 years; p < 0.0001) with more atypical symptoms (41.5% vs. 33.9%; p < 0.0001). Women had less obstructive CAD (65.4% vs. 74.7%; p < 0.0001) at CCTA, higher FFR_CT (0.76 ± 0.10 vs. 0.73 ± 0.10; p < 0.0001), and lower likelihood of positive FFR_CT ≤ 0.80 for the same degree stenosis (p < 0.0001). A positive FFR_CT ≤0.80 resulted in equal referral to ICA (n = 510 [54.5%] vs. n = 1,249 [56.5%]; p = 0.31), but more nonobstructive CAD (n = 208 [32.1%] vs. n = 354 [24.5%]; p = 0.0003) and less revascularization (n = 294 [31.4%] vs. n = 800 [36.2%]; p < 0.0001) in women, unless the FFR_CT was ≤0.75 where revascularization rates were similar (n = 253 [41.9%] vs. n = 715 [46.4%]; p = 0.06). Women have a higher V/M ratio (26.17 ± 7.58 mm³/g vs. 24.76 ± 7.22 mm³/g; p < 0.0001) that is associated with higher FFR_CT independent of degree stenosis (p < 0.001). Predictors of revascularization included stenosis severity, FFR_CT, symptoms, and V/M ratio (p < 0.001) but not female sex (p = 0.284).ConclusionsFFR_CT differs between the sexes, as women have a higher FFR_CT for the same degree of stenosis. In FFR_CT-positive CAD, women have less obstructive CAD at ICA and less revascularization, which is associated with higher V/M ratio. The findings suggest that CAD and FFR_CT variations by sex need specific interpretation as these differences may affect therapeutic decision making and clinical outcomes. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care [ADVANCE]; NCT02499679)     

Sex Differences in LV Remodeling and Hemodynamics in Aortic Stenosis: Sex-Specific Criteria for Severe Stenosis?

BackgroundThe current criteria for aortic stenosis (AS) severity have not incorporated sex-related differences.ObjectivesThe authors investigated sex-related serial changes in left ventricular (LV) structure/function and hemodynamics in AS.MethodsSerial echocardiograms of patients with severe AS (time 0; aortic valve area [AVA] ≤1 cm²) and ≥1 previous echocardiogram were compared between sexes.ResultsOf 927 patients (time 0: AVA 0.87 ± 0.11 cm², peak velocity 4.03 ± 0.65 m/s, mean Doppler systolic pressure gradient [MG] 40.6 ± 13.1 mm Hg), 393 (42%) were women. Women had smaller body surface area (BSA) (1.77 ± 0.22 m² vs 2.03 ± 0.20 m²; P < 0.001), lower stroke volume (SV) (81.1 ± 17.2 mL vs 88.3 ± 18.6 mL; P < 0.001), and more frequent low-gradient severe AS (n = 196 [50%] vs n = 181 [34%]; P < 0.001). Women consistently had smaller AVA, indexed AVA (AVAi), peak velocity, and MG than men. The difference in aortic valve gradient lessened when AVAi ≤0.6 cm²/m² was applied as severe AS (n = 694, women 43%, AVA 0.95 ± 0.17 cm², AVAi 0.50 ± 0.07 cm²/m²). Peak velocity (3.83 ± 0.66 m/s) and MG (36.5 ± 13.2 mm Hg) were lower based on AVAi severity criteria compared to those based on AVA. Men had a lower left ventricular ejection fraction (LVEF) (55.8% ± 14.8% vs 61.1% ± 11.7%; P < 0.001) and greater reduction in SV (?13.3 ± 19.6 mL vs ?7.4 ± 16.4 mL; P < 0.001) as AS progressed from moderate to severe. Concentric LV hypertrophy was more common and E/e? higher in women (21.2 ± 10.9 vs 18.8 ± 9.1; P < 0.001). SV, LVEF, AVA, peak velocity, and MG became precipitously worse when AVA reached 1.2 cm² in both sexes.ConclusionsSmaller BSA in women yields lower SV, resulting in lower aortic valve gradient than men. Indexed parameters by BSA are thus important in sex-related differences of aortic valve hemodynamics, but AVAi ≤0.6 cm²/m² includes individuals with moderate AS. Elevated filling pressure is more common in women. Men experience a larger reduction in SV and LVEF as AS progresses. The definition of AS severity may require different criteria between sexes.     

Effect of Coronary CTA on Chronic Total Occlusion Percutaneous Coronary Intervention: A Randomized Trial

ObjectivesThe purpose of this study was to test whether the success rate of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) increased with pre-procedural coronary computed tomography angiography (CTA).BackgroundCoronary CTA provides valuable information before and during CTO-PCI. However, there are no randomized data that explore whether coronary CTA increases its success rate.MethodsIn this multicenter, randomized trial, a total of 400 patients with CTO were randomized to receive PCI with pre-procedural coronary CTA (coronary CTA–guided group; n = 200) or without coronary CTA (angiography-guided group; n = 200) between January 2014 and September 2019. The primary endpoint was the successful recanalization rate, a final TIMI (Thrombolysis In Myocardial Infarction) grade ≥2, and ≤30% residual stenosis on the final angiogram.ResultsA total of 10 operators performed PCI. Successful recanalization was achieved in 187 patients (93.5%) in the coronary CTA–guided group and in 168 patients (84.0%) in the angiography-guided group (absolute difference, 9.5% [95% confidence interval: 3.4% to 15.6%]; p = 0.003). When comparing the success rates according to the Multicenter CTO Registry of Japan score (J-CTO), the coronary CTA guidance was favored over the angiography-guidance in the subset of J-CTO ≥2 versus in the subset of J-CTO <2 (p interaction = 0.035). Coronary perforations occurred in 2 (1%) and 8 patients (4%) in the coronary CTA- and angiography-guided groups, respectively (p = 0.055). Periprocedural myocardial infarction was not observed in the coronary CTA–guided group, whereas it occurred in 4 patients (2%) in the angiography-guided group (p = 0.123). Total procedure and fluoroscopic times were not different. There were no differences between the groups in the occurrences of cardiac death, target vessel–related myocardial infarction, or target-vessel revascularization at 1 year.ConclusionsPre-procedural coronary CTA-guidance for CTO resulted in higher success rates with numerically fewer immediate periprocedural complications such as coronary perforations or periprocedural myocardial infarction than angiography guidance. Higher success rates were more prominently observed in patients with CTO who had a high J-CTO score than those who did not. (Role of CT Scan for the Successful Recanalization of Chronic Total Occlusion; a Randomized Comparison Between 3D CT-guided PCI vs. Conventional Treatment [CT-CTO Trial]; NCT02037698)