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Background The purpose of this study was to evaluate the rate and domains of cognitive impairment in out-of-hospital cardiac arrest (OHCA) survivors, as compared to patients who experienced a myocardial infarction (MI), and to explore mechanisms and predictors of this impairment. Methods and results OHCA survivors with “good” neurological recovery (i.e., Cerebral Performance Categories Scale ≤ 2) (n = 79), as well as a control group of MI patients (n = 69), underwent a comprehensive neuropsychological assessment. Forty-three percent of OHCA survivors were cognitively impaired (in the lowest decile on a global measure of cognitive functioning). Rates of impairment were approximately six times higher in the OHCA group than the MI group. Attention, memory, language and executive function were affected. Downtime was a significant predictor of cognitive impairment; the interaction between downtime and immediate intervention was significant such that, at short downtimes, receiving cardiopulmonary resuscitation (CPR) or defibrillation within 1 min of collapse predicted less cognitive impairment. Conclusions OHCA survivors – even those with seemingly good neurological recovery – are at risk for cognitive impairment. Cognitive rehabilitation may be an important consideration post-OHCA.

Introduction: Comatose survivors of OHCA develop a post cardiac arrest syndrome (PCAS) characterized by myocardial dysfunction and cerebrovascular dysregulation. Hemodynamic derangements related to PCAS can jeopardize cerebral oxygen delivery and therefore impair neurologic recovery. However, optimal hemodynamic targets to ensure adequate cerebral oxygen delivery following OHCA remain undefined. Accordingly, we examined the relationship between cardiac index (CI), mean arterial pressure (MAP), and regional cerebral oxygen saturation (rO 2 %) following OHCA. Methods: CAPITAL-RETURN was a prospective, single-center observational study examining hemodynamics in comatose survivors of OHCA undergoing targeted temperature management after an initial shockable rhythm. Between August 2016 and December 2017, comatose survivors of OHCA underwent continuous, blinded, non-invasive monitoring of CI and rO 2 % using bioimpedance (Cheetah Medical, Portland, OR, USA) and near-infrared spectroscopy (Covidien, Boulder, CO, USA), respectively, for 96 hours after intensive care unit admission. In the present study, we examined the relationship between CI, MAP, and rO 2 % using multivariable linear regression. Results: In 56 patients in this analysis, the mean CI and MAP during the first 96 hours of intensive care unit admission were 3.2±0.5 L/min/m 2 and 76±6 mmHg, respectively (Figure). The mean rO 2 % was 63±9% and increased over time (+0.1% per hour; p2 % (+3.2% per L/min/m2 increase in CI; p2 % (p=0.42). After adjustment for MAP, the association between CI and rO 2 % remained significant (+3.1% per L/min/m2 increase in CI; p Conclusion: In comatose survivors of OHCA with an initial shockable rhythm, a higher CI is associated with improved rO 2 %. Further studies are needed to determine whether CI targets improve rO2% and neurologic outcomes following OHCA.

Introduction: Comatose survivors of out-of-hospital cardiac arrest (OHCA) have decreased cardiac index (CI) following return of spontaneous circulation. Although reversible, a reduced CI can contribute to cerebral hypoperfusion and impaired neurologic outcomes. We sought to examine the relationship between CI and clinical outcomes following OHCA. Methods: CAPITAL-RETURN was a prospective study examining hemodynamics in comatose survivors of OHCA undergoing targeted temperature management. Between August 2016 and December 2017, comatose survivors of OHCA with an initial shockable rhythm underwent continuous, blinded monitoring of CI using bioimpedance (Cheetah Medical, Portland, OR, USA) for 96 hours after intensive care unit (ICU) admission. In the present study, we examined the association between CI and the composite of death or severe neurologic dysfunction at 6 months (primary outcome) using logistic regression. Severe neurologic dysfunction was defined as a modified Rankin Scale score ≥4. We excluded patients who died or had withdrawal of advanced life support within 72 hours of ICU admission. Results: In 53 patients in this analysis (mean age 59±13 years, downtime 24±13 minutes, STEMI 35%), the rate of the primary outcome was 25%. The mean CI was lower in patients with (3.0±0.5 L/min/m 2 ) versus without (3.3±0.5 L/min/m 2 ) the primary outcome (p=0.018). A higher mean CI during the first 96 hours of ICU admission was associated with lower rates of the primary outcome (OR 0.85 per 0.1L/min/m 2 increase in CI; p=0.025). This association persisted after adjusting for age and downtime (OR 0.78 per 0.1L/min/m2 increase in CI; p=0.014). Cardiac index was similar in patients with versus without the primary outcome at the end of the 96-hour monitoring period (Figure). Conclusion: In comatose survivors of OHCA with an initial shockable rhythm, a higher CI during the first 96 hours of ICU admission is associated with lower rates of death or severe neurologic dysfunction.

Background: The optimal blood glucose target during the early hospitalisation of comatose survivors of out-of-hospital cardiac arrest (OHCA) has not been established. Methods: In a retrospective cohort study, we examined clinical outcomes in relation to mean blood glucose during the first 96 hours of hospital admission in comatose survivors of OHCA with an initial shockable rhythm. Mean blood glucose was assessed as a continuous (primary analysis) and categorical variable: Results: Among 122 eligible patients, death and severe neurological dysfunction occurred in 29 (24%) and 40 (33%) patients, respectively. Higher mean blood glucose levels during the first 96 hours of admission were associated with increased odds of death (odds ratio (OR): 1.50; 95% confidence interval (CI): 1.17–1.92; p = 0.001) and severe neurological dysfunction (OR: 1.42; 95% CI: 1.11–1.80; p = 0.004). The associations between mean blood glucose and the odds of death (OR: 1.35; 95% CI: 1.04–1.76; p = 0.02) and severe neurological dysfunction (OR: 1.28; 95% CI: 1.00–1.64; p = 0.05) persisted after adjusting for age, time from cardiac arrest to return of spontaneous circulation (ROSC) and vasoactive agent use. There was no interaction between age, time from cardiac arrest to ROSC or a history of diabetes mellitus and the relationship between mean blood glucose and co-primary outcomes. Conclusions: In comatose survivors of OHCA with initial shockable rhythms, higher mean blood glucose levels during the first 96 hours of admission are associated with increased rates of death and severe neurological dysfunction.

Objectives This study investigated the safety and efficacy of a pharmacoinvasive strategy compared with a primary percutaneous coronary intervention (PCI) strategy for ST-segment elevation myocardial infarction (STEMI) in the context of a real-world system. Background Primary PCI continues to be the optimal reperfusion therapy; however, in areas where PCI centers are not readily available, a pharmacoinvasive strategy has been proposed. Methods The University of Ottawa Heart Institute regional STEMI system provides a primary PCI strategy for patients presenting within a 90-km radius from the PCI center, and a pharmacoinvasive strategy for patients outside this limit. We included all confirmed STEMI patients between April 2009 and May 2011. The primary efficacy outcome was a composite of mortality, reinfarction, or stroke and the primary safety outcome was major bleeding. Results We identified 236 and 980 consecutive patients enrolled in pharmacoinvasive and primary PCI strategies, respectively. The median door-to-needle time was 31 min in the pharmacoinvasive group and the median door-to-balloon time was 95 min in the primary PCI group. In a multivariable model, there was no significant difference in the primary efficacy outcome (odds ratio: 1.54; p = 0.21); however, the propensity for more bleeding with a pharmacoinvasive strategy approached statistical significance (odds ratio: 2.02; p = 0.08). Conclusions Within the context of a STEMI system, a pharmacoinvasive strategy was associated with similar rates of the composite of mortality, reinfarction, or stroke as compared with a primary PCI strategy; however, there was a propensity for more bleeding with a pharmacoinvasive strategy.

Medical care in Canadian cardiac units has changed considerably over the past 3 decades in response to an increasingly complex and diverse patient population admitted with acute cardiac pathology. To maintain the highest level of care for these patients, there is a pressing need to evolve traditional coronary care units into contemporary cardiac intensive care units. In this article we aim to highlight the current variations in Canadian units, develop approaches to overcome logistical and infrastructural obstacles, and propose staffing and training recommendations that would allow for the establishment of contemporary cardiac intensive care units.

Importance Among patients with ST-segment elevation myocardial infarction (STEMI) referred for primary percutaneous coronary intervention (PCI), a survival benefit associated with radial access compared with femoral access remains controversial. Objective To assess whether there is a survival benefit when radial access is used instead of femoral access among patients with STEMI referred for primary PCI. Design, Setting, and Participants This multicenter, open-label, randomized clinical trial was conducted at 5 PCI centers in Canada. In total, 2292 patients with STEMI referred for primary PCI were enrolled between July 2011 and December 2018, with a 30-day follow-up. The primary analyses were conducted based on the intention-to-treat population. Interventions Patients were randomized to radial access (n = 1136) or to femoral access (n = 1156) for PCI. Main Outcomes and Measures Initially, the primary outcome was bleeding, but this outcome was modified to 30-day all-cause mortality following the recommendation of the granting agency. Secondary outcomes included recurrent myocardial infarction, stroke, and Thrombolysis in Myocardial Infarction–defined major or minor bleeding. Results Among the 2292 patients enrolled, the mean (SD) age of the patients randomized to radial access was 61.6 (12.3) years and to femoral access was 62.0 (12.1) years, with 883 male patients in the radial access and 901 male patients in the femoral access group. The trial was stopped early following a futility analysis. Primary PCI was performed in 1082 of 1136 patients (95.2%) in the radial access group and 1109 of 1156 patients (95.9%) in the femoral access group. Bivalirudin was administered to 1001 patients (88.1%) in the radial access group and to 1068 patients (92.4%) in the femoral access group, whereas glycoprotein IIb/IIIa inhibitors were administered in only 69 patients (6.1%) in the radial access group and 68 patients (5.9%) in the femoral access group. A vascular closure device was used in 789 patients (68.3%) in the femoral group. The primary outcome, 30-day all-cause mortality, occurred in 17 patients (1.5%) assigned to radial access and in 15 patients (1.3%) assigned to femoral access (relative risk [RR], 1.15; 95% CI, 0.58-2.30;P = .69). There were no significant differences between patients assigned to radial and femoral access in the rates of reinfarction (1.8% vs 1.6%; RR, 1.07; 95% CI, 0.57-2.00;P = .83), stroke (1.0% vs 0.4%; RR, 2.24; 95% CI, 0.78-6.42;P = .12), and bleeding (1.4% vs 2.0%; RR, 0.71; 95% CI, 0.38-1.33;P = .28). Conclusions and Relevance No significant differences were found for survival or other clinical end points at 30 days after the use of radial access vs femoral access in patients with STEMI referred for primary PCI. However, small absolute differences in end points cannot be definitively refuted given the premature termination of the trial. Trial Registration ClinicalTrials.gov identifier:NCT01398254

OBJECTIVES We sought to describe the safety and efficacy outcomes of patients on warfarin presenting with ST-elevation myocardial infarction (STEMI). BACKGROUND Limited data exist on the outcomes and optimal management of STEMI patients on warfarin undergoing primary percutaneous coronary intervention (PCI). METHODS Baseline characteristics and outcomes were prospectively collected for 2,390 consecutive STEMI patients referred for primary PCI. Patients were stratified based on warfarin use at baseline. The primary safety endpoint was the rate of in-hospital bleeding (a composite of major bleeding or minor bleeding) according to the thrombolysis in myocardial infarction (TIMI) classification. Efficacy endpoints included major adverse cardiovascular events (MACE), defined as death, myocardial infarction, or stroke, as well as intracranial bleeding, cardiogenic shock, and length of stay. Multiple logistic regression was used to determine if warfarin was independently associated with bleeding and MACE. RESULTS Warfarin patients (n = 59 vs. n = 2,331) were significantly older (73.2 years vs. 61.7 years; P

To determine the optimal mean arterial pressure (MAP) during the early-to-intermediate phase care of comatose survivors of out-of-hospital cardiac arrest (OHCA).We identified consecutive comatose survivors of OHCA with an initial shockable rhythm. Using blood pressure-over-time plots, we calculated the area below pre-specified MAP thresholds (ABT; mmHg*hours) during the first 96 h of admission. We used incremental MAP thresholds ranging between 65 and 85 mmHg. Logistic regression analyses were used to examine the association between ABT and clinical outcomes for each MAP threshold and to adjust for age, duration of cardiac arrest, and bystander CPR. The primary outcome was severe neurological dysfunction as defined by a cerebral performance category (CPC) ≥3.We identified 122 consecutive OHCA patients meeting inclusion criteria. The rate of the primary outcome was 33%. There was a significant association between ABT and the rate of the primary outcome when MAP thresholds of 60 (p = 0.01), 65 (p 0.01), 70 (p 0.01), 75 (p 0.01), and 80 mmHg (p 0.01) were used. This association was lost once a MAP threshold of 85 mmHg was reached (p = 0.63). In the adjusted analysis, the association between ABT and the primary outcome was no longer present when the MAP threshold reached 75 mmHg.In comatose survivors of OHCA with an initial shockable rhythm, higher ABT is associated with increased rates of severe neurological dysfunction when MAP thresholds75 mmHg are used. The current findings support the hypothesis that higher MAP targets (≥75 mmHg) may be indicated in this patient population.

Current guidelines suggest that patients undergoing percutaneous coronary intervention (PCI) receive dual-antiplatelet therapy. There are limited data on the pharmacodynamics of P2Y12 inhibitors in patients with cardiac arrest and return of spontaneous circulation (ROSC) undergoing PCI and therapeutic hypothermia (TH). Accordingly, we compared inhibition of platelet reactivity in patients undergoing TH receiving clopidogrel or ticagrelor. Notably, clopidogrel was ineffective in lowering platelet reactivity, with ticagrelor providing a more rapid (within 4 hours) and sustained reduction (6 days) in platelet reactivity. Pending outcome-based studies, ticagrelor should be used preferentially in patients who have ROSC and are undergoing PCI and TH.

Aim of the study We sought to assess the relationship between mean arterial pressure (MAP) and clinical outcomes in comatose survivors of out-of-hospital cardiac arrest (OHCA). Methods We identified consecutive comatose survivors of OHCA with an initial shockable rhythm treated with targeted temperature management. We examined clinical outcomes in relation to mean MAP (measured hourly) during the first 96h of hospitalization. Co-primary outcomes were the rates of death and severe neurological dysfunction at discharge. Results In 122 patients meeting inclusion criteria, death occurred in 29 (24%) and severe neurological dysfunction in 39 (32%). Higher mean MAPs were associated with lower odds of death (OR 0.55 per 5mmHg increase; 95%CI 0.38–0.79; p=0.002) and severe neurological dysfunction (OR 0.66 per 5mmHg increase; 95%CI 0.48–0.90; p=0.01). After adjustment for differences in patient, index event, and treatment characteristics, higher mean MAPs remained associated with lower odds of death (OR 0.60 per 5mmHg increase; 95%CI 0.40–0.89; p=0.01) but not severe neurological dysfunction (OR 0.73 per 5mmHg increase; 95%CI 0.51–1.03; p=0.07). The relationship between mean MAP and the odds of death (p-interaction=0.03) and severe neurological dysfunction (p-interaction=0.03) was attenuated by increased patient age. Conclusion In comatose survivors of OHCA treated with target temperature management, a higher mean MAP during the first 96h of admission is associated with increased survival. The association between mean MAP and clinical outcomes appears to be attenuated by increased age.

Background Therapeutic hypothermia improves neurologic outcome and survival in patients following out-of-hospital cardiac arrest (OHCA). Endovascular cooling devices are commonly used to rapidly achieve and maintain hypothermia. The use of these devices may be associated with catheter related thrombosis. The objective of this study was to determine the risk of catheter related thrombosis associated with the use of an endovascular cooling catheter in patients referred for therapeutic hypothermia following OHCA. Methods and results We conducted a retrospective cohort study on consecutive patients, referred for therapeutic hypothermia following OHCA, between February 2012 and May 2013. Of 80 patients initially treated with therapeutic hypothermia, 61 completed the cooling protocol using an endovascular cooling device. The primary outcome was catheter related thrombosis defined as evidence of thrombus in the inferior vena cava, deep vein thrombosis or pulmonary embolism during the index hospitalization. We further evaluated the incidence of the primary outcome between patients on dose adjusted intravenous unfractionated heparin compared to those on a subcutaneous prophylactic regimen alone. Catheter related thrombosis was observed in 9/61 (14.7%), with nine events in the prophylaxis group compared to none in the full dose unfractionated heparin group (22.0% vs. 0.0%, p =0.02). Conclusions The use of endovascular catheters for induction of therapeutic hypothermia is associated with a high rate of catheter related thrombosis. This risk appears to be abrogated with dose adjusted unfractionated heparin infusion.

Bivalirudin for primary percutaneous coronary interventions in patients with cardiogenic shock: Outcome Assessment in the CAPITAL STEMI registry. BACKGROUND: Data from randomized clinical trials have demonstrated superiority of bivalirudin to heparin with or without routine use of glycoprotein (GP) IIb/IIIa inhibitors in patients undergoing primary percutaneous coronary intervention (PPCI). However the performance of bivalirudin in PPCI without the use GPIIb/IIIa inhibitors, in patients with cardiogenic shock remains unknown. METHODS AND RESULTS: We screened 2536 patients who underwent PPCI for ST elevation myocardial infarction (STEMI) at the University of Ottawa Heart Institute between June 2004 to June 2011. From this cohort, we identified 91 patients who developed cardiogenic shock and who received either bivalirudin (n1⁄434) or Heparin (n1⁄457), with no GP IIb/IIIa inhibitors. The primary outcome was a composite of cardiovascular death, myocardial infarction and stroke. The secondary endpoints were the rate non-coronary artery bypass graft related TIMI major bleeding, any major bleeding, reinfarction and stent thrombosis and in-hospital mortality. The primary outcome was similar in both groups, occurring in 44% of patients receiving bivalirudin vs. 58% in patients treated with heparin alone (OR 0.76 CI 0.36 to 1.60, P1⁄40.47). Compared with the heparin group, a reduction in non-CABG related TIMI major bleeding (18% vs. 16%, P1⁄40.72), any major bleeding (18% vs. 19%, P1⁄40.87) or inhospital mortality (38% vs. 52%, P1⁄40.18) with bivalirudin could not be demonstrated. Notably, the use of bivalirudin was associated with a 6.8 fold increased risk of stent thrombosis and re-infarction (11.7% vs. 1.7%, P1⁄40.043). CONCLUSION: In patients with cardiogenic shock, undergoing PPCI with dual antiplatelet therapy with no GP IIb/IIIa inhibitors, the use of bivalirudin appears to be a safe anticoagulation strategy when compared to heparin. Bivalirudin was however associated with a potential risk of increased stent thrombosis and re-infarction in the setting of cardiogenic shock. Larger clinical studies are needed to either confirm or refute these findings.