Faculty Bibliography

Background The role of invasive management compared with medical management in patients with non-ST-segment-elevation myocardial infarction (NSTEMI) and advanced chronic kidney disease (CKD) is uncertain, given the increased risk of procedural complications in patients with CKD. We aimed to compare clinical outcomes of invasive management with medical management in patients with NSTEMI-CKD. Methods and Results We identified NSTEMI and CKD stages 3, 4, 5, and end-stage renal disease admissions using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes from the Nationwide Readmission Database 2016 to 2018. Patients were stratified into invasive and medical management. Primary outcome was mortality (in-hospital and 6 months after discharge). Secondary outcomes were in-hospital postprocedural complications (acute kidney injury requiring dialysis, major bleeding) and postdischarge 6-month safety and major adverse cardiovascular events. Out of 141 052 patients with NSTEMI-CKD, 85 875 (60.9%) were treated with invasive management, whereas 55 177 (39.1%) patients were managed medically. In propensity-score matched cohorts, invasive strategy was associated with lower in-hospital (CKD 3: odds ratio [OR], 0.47 [95% CI, 0.43-0.51]; P<0.001; CKD 4: OR, 0.79 [95% CI, 0.69-0.89]; P<0.001; CKD 5: OR, 0.72 [95% CI, 0.49-1.06]; P=0.096; end-stage renal disease: OR, 0.51 [95% CI, 0.46-0.56]; P<0.001) and 6-month mortality. Invasive management was associated with higher in-hospital postprocedural complications but no difference in postdischarge safety outcomes. Invasive management was associated with a lower hazard of major adverse cardiovascular events at 6 months in all CKD groups compared with medical management. Conclusions Invasive management was associated with lower mortality and major adverse cardiovascular events but minimal increased in-hospital complications in patients with NSTEMI-CKD compared with medical management, suggesting patients with NSTEMI-CKD should be offered invasive management.

Percutaneous coronary intervention (PCI) of coronary artery bifurcation lesions entails technical challenges and carries a higher risk of adverse events on follow-up, driven by repeat revascularisation and stent thrombosis. While most bifurcations can be tackled with a provisional (single-stent) approach, more complex lesions involving both branches (true bifurcation lesions) require a two-stent approach. In the latter context, several techniques have been proposed. Among them, the crush technique has dramatically evolved in recent years, and its more recent iterations have been shown to provide excellent and durable results, both for left main and non-left main bifurcations. The aim of the present work is to discuss the technical aspects and outcomes of the variants of the crush technique from the first description in the early 2000s to the present day.

BACKGROUND:Patients with atrial fibrillation (AF) and oral anticoagulation (OAC) failure may benefit from left atrial appendage closure (LAAC), however, the evidence is scarce. We report outcomes of LAAC in patients with OAC failure compared to those with classic indications of OAC contraindications. METHODS:Prospective registry of LAAC with Amplatzer or WATCHMAN device followed by dual antiplatelet therapy (DAPT) was analyzed (05.2014-11.2019). The study group included patients with OAC failure defined as stroke/TIA/PE/LAA thrombus (n = 39) during OAC, whereas the control group consisted of patients with OAC contraindications (n = 156). Structured follow-up at 3, 6, and 12 months was done. RESULTS:-VASc predicted to observed annual stroke/TIA/PE rate was markedly smaller in the study vs control group (14% vs 77%) with 10.3% vs 1.9% stroke/TIA/PE respectively (P = 0.031). The reduction from HAS-BLED predicted to observed annual major nonprocedural bleeding rate was higher (100% vs 7.4%) with 0.0% vs 5.1% major bleedings respectively (P = 0.361). The device-related thrombosis remained similar (13.2% vs 11.3%, P = 0.778). CONCLUSIONS:Patients after LAAC for OAC failure and unremarkable prior bleeding history presented with high residual stroke and low bleeding risks. Therefore concomitant long-term OAC or prolonged DAPT should strongly be considered in this population.

BACKGROUND:ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) compared an initial invasive treatment strategy (INV) with an initial conservative strategy in 5179 participants with chronic coronary disease and moderate or severe ischemia. The ISCHEMIA research program included a comprehensive quality-of-life (QOL) substudy. METHODS:In 1819 participants (907 INV, 912 conservative strategy), we collected a battery of disease-specific and generic QOL instruments by structured interviews at baseline; at 3, 12, 24, and 36 months postrandomization; and at study closeout. Assessments included angina-related QOL (19-item Seattle Angina Questionnaire), generic health status (EQ-5D), depressive symptoms (Patient Health Questionnaire-8), and, for North American patients, cardiac functional status (Duke Activity Status Index). RESULTS:Median age was 67 years, 19.2% were female, and 15.9% were non-White. The estimated mean difference for the 19-item Seattle Angina Questionnaire Summary score favored INV (1.4 points [95% CI, 0.2-2.5] over all follow-up). No differences were observed in patients with rare/absent baseline angina (SAQ Angina Frequency score >80). Among patients with more frequent angina at baseline (SAQ Angina Frequency score <80, 744 patients, 41%), those randomly assigned to INV had a mean 3.7-point higher 19-item Seattle Angina Questionnaire Summary score than conservative strategy (95% CI, 1.6-5.8) with consistent effects across SAQ subscales: Physical Limitations 3.2 points (95% CI, 0.2-6.1), Angina Frequency 3.2 points (95% CI, 1.2-5.1), Quality of Life/Health Perceptions 5.3 points (95% CI, 2.8-7.8). For the Duke Activity Status Index, no difference was estimated overall by treatment, but in patients with baseline SAQ Angina Frequency scores <80, Duke Activity Status Index scores were higher for INV (3.2 points [95% CI, 0.6-5.7]), whereas patients with rare/absent baseline angina showed no treatment-related differences. Moderate to severe depression was infrequent at randomization (11.5%-12.8%) and was unaffected by treatment assignment. CONCLUSIONS:In the ISCHEMIA comprehensive QOL substudy, patients with more frequent baseline angina reported greater improvements in the symptom, physical functioning, and psychological well-being dimensions of QOL when treated with an invasive strategy, whereas patients who had rare/absent angina at baseline reported no consistent treatment-related QOL differences. REGISTRATION/BACKGROUND:URL: https://www. CLINICALTRIALS/RESULTS:gov; Unique identifier: NCT01471522.

BACKGROUND:Patients with significant (≥50%) left main disease (LMD) have a high risk of cardiovascular events, and guidelines recommend revascularization to improve survival. However, the impact of intermediate LMD (stenosis, 25%-49%) on outcomes is unclear. METHODS:Randomized ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) participants who underwent coronary computed tomography angiography at baseline were categorized into those with (25%-49%) and without (<25%) intermediate LMD. The primary outcome was a composite of cardiovascular mortality, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. The primary quality of life outcome was the Seattle Angina Questionnaire summary score. RESULTS: CONCLUSIONS:In the ISCHEMIA trial, there was no meaningful heterogeneity of treatment benefit from an invasive strategy regardless of intermediate LMD status except for a greater absolute risk reduction in nonprocedural MI with invasive management in those with intermediate LMD. An invasive strategy increased procedural MI, reduced nonprocedural MI, and improved angina-related quality of life. REGISTRATION/BACKGROUND:URL: https://www. CLINICALTRIALS/RESULTS:gov; Unique identifier: NCT01471522.

Background In participants with concomitant chronic coronary disease and advanced chronic kidney disease (CKD), the effect of treatment strategies on the timing of dialysis initiation is not well characterized. Methods and Results In ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease), 777 participants with advanced CKD and moderate or severe ischemia were randomized to either an initial invasive or conservative management strategy. Herein, we compare the proportion of randomized participants with non-dialysis-requiring CKD at baseline (n=362) who initiated dialysis and compare the time to dialysis initiation between invasive versus conservative management arms. Using multivariable Cox regression analysis, we also sought to identify the effect of invasive versus conservative chronic coronary disease management strategies on dialysis initiation. At a median follow-up of 23 months (25th-75th interquartile range, 14-32 months), dialysis was initiated in 18.9% of participants (36/190) in the invasive strategy and 16.9% of participants (29/172) in the conservative strategy (P=0.22). The median time to dialysis initiation was 6.0 months (interquartile range, 3.0-16.0 months) in the invasive group and 18.2 months (interquartile range, 12.2-25.0 months) in the conservative group (P=0.004), with no difference in procedural acute kidney injury rates between the groups (7.8% versus 5.4%; P=0.26). Baseline clinical factors associated with earlier dialysis initiation were lower baseline estimated glomerular filtration rate (hazard ratio [HR] associated with 5-unit decrease, 2.08 [95% CI, 1.72-2.56]; P<0.001), diabetes (HR, 2.30 [95% CI, 1.28-4.13]; P=0.005), hypertension (HR, 7.97 [95% CI, 1.09-58.21]; P=0.041), and Hispanic ethnicity (HR, 2.34 [95% CI, 1.22-4.47]; P=0.010). Conclusions In participants with non-dialysis-requiring CKD in ISCHEMIA-CKD, randomization to an invasive chronic coronary disease management strategy (relative to a conservative chronic coronary disease management strategy) is associated with an accelerated time to initiation of maintenance dialysis for kidney failure. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01985360.

Aim/UNASSIGNED:inhibitor or aspirin monotherapy for secondary prevention in patients with atherosclerotic cardiovascular disease (ASCVD). Methods and results/UNASSIGNED:inhibitor used. Conclusion/UNASSIGNED:inhibitor monotherapy for secondary prevention is associated with a significant reduction in atherothrombotic events compared with aspirin alone without an increased risk of major bleeding.

BACKGROUND:Detection of ≥50% diameter stenosis left main coronary artery disease (LMD) has prognostic and therapeutic implications. Noninvasive stress imaging or an exercise tolerance test (ETT) are the most common methods to detect obstructive coronary artery disease, though stress test markers of LMD remain ill-defined. OBJECTIVES:The authors sought to identify markers of LMD as detected on coronary computed tomography angiography (CTA), using clinical and stress testing parameters. METHODS:This was a post hoc analysis of ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), including randomized and nonrandomized participants who had locally determined moderate or severe ischemia on nonimaging ETT, stress nuclear myocardial perfusion imaging, or stress echocardiography followed by CTA to exclude LMD. Stress tests were read by core laboratories. Prior coronary artery bypass grafting was an exclusion. In a stepped multivariate model, the authors identified predictors of LMD, first without and then with stress testing parameters. RESULTS:Among 5,146 participants (mean age 63 years, 74% male), 414 (8%) had LMD. Predictors of LMD were older age (P < 0.001), male sex (P < 0.01), absence of prior myocardial infarction (P < 0.009), transient ischemic dilation of the left ventricle on stress echocardiography (P = 0.05), magnitude of ST-segment depression on ETT (P = 0.004), and peak metabolic equivalents achieved on ETT (P = 0.001). The models were weakly predictive of LMD (C-index 0.643 and 0.684). CONCLUSIONS:In patients with moderate or severe ischemia, clinical and stress testing parameters were weakly predictive of LMD on CTA. For most patients with moderate or severe ischemia, anatomical imaging is needed to rule out LMD. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).