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Background: In ISCHEMIA-CKD, 777 patients with advanced chronic kidney disease and chronic coronary disease had similar all-cause mortality with either an initial invasive or conservative strategy (27.2% vs 27.8%, respectively)., Objectives: This prespecified secondary analysis from ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease) was conducted to determine whether an initial invasive strategy compared with a conservative strategy decreased the incidence of cardiovascular (CV) vs non-CV causes of death., Methods: Three-year cumulative incidences were calculated for the adjudicated cause of death. Overall and cause-specific death by treatment strategy were analyzed using Cox models adjusted for baseline covariates. The association between cause of death, risk factors, and treatment strategy were identified., Results: A total of 192 of the 777 participants died during follow-up, including 94 (12.1%) of a CV cause, 59 (7.6%) of a non-CV cause, and 39 (5.0%) of an undetermined cause. The 3-year cumulative rates of CV death were similar between the invasive and conservative strategies (14.6% vs 12.6%, respectively; HR: 1.13, 95% CI: 0.75-1.70). Non-CV death rates were also similar between the invasive and conservative arms (8.4% and 8.2%, respectively; HR: 1.25; 95% CI: 0.75-2.09). Sudden cardiac death (46.8% of CV deaths) and infection (54.2% of non-CV deaths) were the most common cause-specific deaths and did not vary by treatment strategy., Conclusions: In ISCHEMIA-CKD, CV death was more common than non-CV or undetermined death during the 3-year follow-up. The randomized treatment assignment did not affect the cause-specific incidences of death in participants with advanced CKD and moderate or severe myocardial ischemia. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease [ISCHEMIA-CKD]; NCT01985360)., Competing Interests: Funding Support and Author Disclosures This project was supported by grants from the National Institutes of Health grants U01H117904 and U01HL117905; Arbor Pharmaceuticals, LLC; and AstraZeneca Pharmaceuticals, LP. Devices or medications were provided by Abbott Vascular (previously St. Jude Medical, Inc); Medtronic, Inc; Phillips (previously Volcano Corporation); Omron Healthcare, Inc; Arbor Pharmaceuticals, LLC; AstraZeneca Pharmaceuticals, LP; Espero Pharmaceuticals; Merck Sharp and Dohme Corp; and Sunovion Pharmaceuticals. The manuscript contents are solely the responsibility of the authors and do not necessarily represent official views of the National Heart, Lung, and Blood Institute, the National Institutes of Health, or the United States Department of Health and Human Services. Dr Sidhu has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; and has received personal fees from AstraZeneca and Sanofi-Regeneron outside the submitted work. Dr Alexander has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Mr Huang has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Mathew has received grants from National Heart, Lung, and Blood Institute, during the conduct of the study. Dr Newman has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr O’Brien has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Pellikka has received grants from National Heart, Lung, and Blood Institute during the conduct of the study. Dr Bockeria has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Briguori has received grants from the National Heart, Lung, and Blood Institute, during the conduct of the study. Dr Kretov has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Mazurek has received grants from the National Heart, Lung, and Blood Institute, during the conduct of the study. Dr Orso has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Roik has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Sajeev has received grants from National Heart, Lung, and Blood Institute, during the conduct of the study. Dr Shutov has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Rockhold reports grants from the National Institutes of Health, the Patient-Centered Outcomes Research Institute, Bristol Myers Squibb, AstraZeneca, American Regent, Gates Foundation, and Eidos during the conduct of the study; has received consulting fees from Janssen, Clover, Doctor Evidence, and Intercept; and equity ownership in GlaxoSmithKline, Clover, Athira, Doctor Evidence, DataVant, Spencer Health Solutions, and Adaptic Health. Dr Borrego has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Balter has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Stone has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; has received speaker honoraria from Pulnovo and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Vascular Dynamics, Shockwave, V-Wave, Cardiomech, Gore, and Amgen; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Dr Stone’s daughter is an employee at Medtronic. Dr Stone’s employer, Mount Sinai Hospital, receives research support from Abbott, Bioventrix, Cardiovascular Systems Inc, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, and V-wave. Dr Chaitman has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; and has received personal fees from Merck, NovoNordisk, Sanofi, Lilly, Johnson and Johnson, Daiichi Sankyo, Tricida, Relypsa, Imbria, and Xylocor outside the submitted work. Dr Goodman has received grants and personal fees from the National Heart, Lung, and Blood Institute during the conduct of the study; has received grants and personal fees from Amgen; AstraZeneca, Bayer, Boehringer Ingelheim/Eli Lilly, Bristol Myers Squibb/Pfizer, CSL Behring/PERFUSE, Daiichi Sankyo/American Regent/DCRI, Ferring, Novartis, and Regeneron/Sanofi; and has received personal fees from Esperion/C5, GlaxoSmithKline, HLS Therapeutics, Merck, NovoNordisk, and Servier outside the submitted work. Dr Fleg has reports employment by the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Reynolds has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; and has received nonfinancial support from Abbott Vascular, Siemens, and BioTelemetry outside the submitted work. Dr Maron has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Hochman is the principal investigator for the ISCHEMIA trial for which, in addition to support by the National Heart, Lung, and Blood Institute grant, devices and medications were provided by Abbott Vascular; Medtronic, Inc; Abbott Laboratories (formerly St. Jude Medical, Inc); Royal Philips NV (formerly Volcano Corporation); Arbor Pharmaceuticals, LLC; AstraZeneca Pharmaceuticals, LP; Merck Sharp and Dohme Corp; Omron Healthcare, Inc, Sunovion Pharmaceuticals, Inc Espero BioPharma; and Amgen, Inc; and has received financial donations from Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. Dr Bangalore has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; has received grants and personal fees from Abbott Vascular; and has received personal fees from Biotronik, Pfizer, Amgen, and Reata outside the submitted work. Dr Lyubarova has reported that she has no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. All rights reserved.)

Background: Patients with chronic kidney disease (CKD) on dialysis (CKD G5D) have worse cardiovascular outcomes than patients with advanced nondialysis CKD (CKD G4-5: estimated glomerular filtration rate <30 mL/[min·1.73m 2 ]). Our objective was to evaluate the relationship between achievement of cardiovascular guideline-directed medical therapy (GDMT) goals and clinical outcomes for CKD G5D versus CKD G4-5., Methods: This was a subgroup analysis of ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease) participants with CKD G4-5 or CKD G5D and moderate-to-severe myocardial ischemia on stress testing. Exposures included dialysis requirement at randomization and GDMT goal achievement during follow-up. The composite outcome was all-cause mortality or nonfatal myocardial infarction. Individual GDMT goal (smoking cessation, systolic blood pressure <140 mm Hg, low-density lipoprotein cholesterol <70 mg/dL, statin use, aspirin use) trajectory was modeled. Percentage point difference was estimated for each GDMT goal at 24 months between CKD G5D and CKD G4-5, and for association with key predictors. Probability of survival free from all-cause mortality or nonfatal myocardial infarction by GDMT goal achieved was assessed for CKD G5D versus CKD G4-5., Results: A total of 415 CKD G5D and 362 CKD G4-5 participants were randomized. Participants with CKD G5D were less likely to receive statin (-6.9% [95% CI, -10.3% to -3.7%]) and aspirin therapy (-3.0% [95% CI, -5.6% to -0.6%]), with no difference in other GDMT goal attainment. Cumulative exposure to GDMT achieved during follow-up was associated with reduction in all-cause mortality or nonfatal myocardial infarction (hazard ratio, 0.88 [95% CI, 0.87-0.90]; per each GDMT goal attained over 60 days), irrespective of dialysis status., Conclusions: CKD G5D participants received statin or aspirin therapy less often. Cumulative exposure to GDMT goals achieved was associated with lower incidence of all-cause mortality or nonfatal myocardial infarction in participants with advanced CKD and chronic coronary disease, regardless of dialysis status., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT01985360.

Background: Recent studies have implied that platelet reactivity as well as certain lesion morphology may be linked to myocardial injury during percutaneous coronary intervention (PCI). However, to date the abovementioned features have not been investigated simultaneously in one population., Aim: To determine if and how high on-treatment platelet reactivity, different lesion morphology, and plaque components are associated with increased risk of periprocedural myocardial injury in patients referred for elective coronary stenting., Methods: Sixty patients pretreated with aspirin and clopidogrel and undergoing elective PCI with stent(s) implantation were included. On-treatment platelet reactivity was measured with VerifyNow Aspirin and P₂Y₁₂ assays (Accumetrics, USA) before PCI. Grey-scale intravascular ultrasound (IVUS) and virtual histology were performed before stent(s) implantation (Volcano, USA). Two levels of myocardial injury were considered: any elevation of troponin I (periprocedural myocardial damage, PMD) and/or > 3 times the upper normal limit (periprocedural myocardial infarction, PMI)., Results: By receiver-operating characteristics analysis, the following factors, ranked from strongest to weakest, were able to distinguish between patients with and without PMD: remodelling index (RI), fibrous tissue, fibro-fatty tissue volume (FFT), plaque and media cross-sectional area, and external elastic membrane cross-sectional area (EEM CSA). Only platelet count and RI could differentiate patients with and without PMI. PMD as well as PMI could not be predicted either by VerifyNow Aspirin or P₂Y₁₂ assay. Likewise, there was no association between necrotic core volume and PMD or PMI. In logistic regression analysis, after adjusting for possible clinical and procedural confounding factors, only EEM CSA > 14.6 mm² (OR 23.7, 95% CI 1.9-302, p = 0.015), RI > 1.044 (OR 12.3, 95% CI 1.2-121.9, p = 0.032) and FFT > 11.2 mm³ (OR 13.6, 95% CI 1.1-160.9, p = 0.038) were independent predictors of PMD. Only RI > 1.044 was identified as an independent predictor of PMI (OR 7.5, 95% CI 1.92-29.6, p = 0.004)., Conclusions: Greater total vessel area, positive remodelling at the lesion site, and high volume of FFT in the coronary plaque are independently associated with increased risk of myocardial injury. Only positive RI was an independent predictor of PMI. Simple lesion morphology, rather than more complex VH-IVUS analysis or platelet reactivity, seems to predict myocardial injury after elective PCI.

Introduction: Takotsubo cardiomyopathy (TTC) is a rare transient cardiomyopathy mimicking acute coronary syndrome (ACS)., Objectives: The aim of the study was to retrospectively analyze the clinical course, treatment strategies, and follow-up of patients with TTC., Patients and Methods: Among all patients hospitalized in the department between January 2005 and January 2010, we identified a group of patients who were fulfilling the modified Mayo Clinic criteria for the diagnosis of TTC. Clinical presentation, hospital course, and clinical outcomes were analyzed., Results: A total of 31 patients with TTC were included into the study; women comprised 93.5% of the study population. The most common symptoms included chest pain and dyspnea caused by emotional or physical stress. Cardiogenic shock was present in 2 subjects and life-threatening ventricular arrhythmias in 3 other patients. Twenty-four patients had ST-segment elevation on the electrocardiogram. A mean left ventricular ejection fraction was 42 +/-8.6% during contractility abnormalities, and it increased to 58 +/-7.9% during recovery. Troponin I was positive in 30 cases with a mean peak level of 2.7 +/-5.1 ng/ml. Follow-up data were available in 23 patients and a mean follow-up was 955 +/-502.8 days. We did not observe a recurrence of TTC., Conclusions: TTC is observed mainly in postmenopausal women. Clinical presentation of TTC is almost indistinguishable from ACS, but its course is milder and the outcomes are better.