Cause-Specific Mortality in Patients With Advanced Chronic Kidney Disease in the ISCHEMIA-CKD Trial.

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).

Guideline-Directed Medical Therapy Attainment and Outcomes in Dialysis-Requiring Versus Nondialysis Chronic Kidney Disease in the ISCHEMIA-CKD Trial.

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·1.73m2]). 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.

Periprocedural myocardial damage during percutaneous coronary intervention: a point-of-care platelet testing and intravascular ultrasound/virtual histology study.

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.

Clinical presentation, treatment, and long-term outcomes in patients with takotsubo cardiomyopathy. Experience of a single cardiology center.

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.