Cardiogenic shock is associated with substantial morbidity and mortality. Although inotropic support is a mainstay of medical therapy for cardiogenic shock, little evidence exists to guide the selection of inotropic agents in clinical practice.
Background: Clinical outcomes in acute coronary syndrome patients treated with P2Y 12 inhibitors who require urgent coronary artery bypass grafting (CABG) have not been well studied. Methods: We examined clinical outcomes in acute coronary syndrome patients in relation to the timing of CABG following P2Y 12 inhibitor discontinuation (<72 h, 72 h to five days, >5 days). The primary ischemic outcome was a composite of death, reinfarction, need for revascularization, or stroke. The primary safety outcome was bleeding of at least moderate severity as defined by a Universal Definition of Perioperative Bleeding class ≥2. Results: Among 508 patients (95 ticagrelor, 413 clopidogrel), the timing of CABG following P2Y 12 inhibitor discontinuation was <72 h in 32.1%, 72 h to five days in 23.2% and >5 days in 44.7%. Compared with CABG within 72 h, CABG 72 h to five days (adjusted odds ratio (OR) 0.35; 95% confidence interval (CI) 0.14–0.85; p=0.02) but not >5 days (adjusted OR 0.62; 95% CI 0.33–1.16; p=0.14) after P2Y 12 inhibitor discontinuation was associated with lower odds of the primary ischemic outcome. Compared with CABG within 72 h, CABG 72 h to five days (adjusted OR 0.38; 95% CI 0.22–0.66; p=0.001) and >5 days (adjusted OR 0.33; 95% CI 0.20–0.53; p<0.001) after P2Y 12 inhibitor discontinuation were associated with lower rates of Universal Definition of Perioperative Bleeding class ≥2 bleeding. Conclusions: CABG within 72 h after P2Y 12 inhibitor discontinuation is associated with excess ischemia and bleeding. The rates of ischemic and bleeding events were comparable in patients undergoing CABG 72 h to five days compared with >5 days after P2Y 12 inhibitor discontinuation.
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; p<0.001). Higher CI was associated with improved rO 2 % (+3.2% per L/min/m2 increase in CI; p<0.0001). There was no association between MAP and rO 2 % (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<0.0001). 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.
nsuring that women are adequately represented in clinical trials is recognized as essential for sex equity in health.However, the use of female animal models and sex-based reporting have not been equally enforced in preclinical stages of research, which often precede and inform clinical trials.In 2014, the National Institutes of Health announced that it would require that sex be considered as a biological variable in applications for preclinical research funding, 1 yet a reluctance to include female animal models in preclinical experiments persists.Inappropriately inferring experimental findings to both sexes when a single sex is studied or when sex is not specified has the potential to disadvantage women by skewing our understanding of disease processes toward male-predominant patterns and by reducing the likelihood of female-specific therapeutics advancing to the clinical realm.We therefore systematically examined all preclinical cardiovascular studies published in American Heart Association journals with archives spanning at least 10 years (Circulation, Circulation Research, Hypertension, Stroke, and Arteriosclerosis, Thrombosis, and Vascular Biology [ATVB]) for evidence of sex bias.Full articles published between July 2006 and June 2016 and reporting original data from in vivo experiments in nonhuman mammals on pathophysiology, genetics, or therapeutic interventions directly relevant to a specific cardiovascular disorder in humans were included.Studies on physiological or genetic characteristics were included if they proposed potential therapeutic applications or implications of the study findings.Each journal article was independently reviewed and prespecified data were extracted by using standardized case report forms by 2 authors, including the cardiovascular disease investigated, animal model(s) used and their sex, whether study samples were sex matched (in studies using both sexes), whether at least 1 study result was reported by sex, and whether the use of a single sex was reported as a limitation (in single-sex studies).Interrater agreement was calculated using the Cohen κ-statistic and percentage agreement.Discrepancies were resolved by consensus or independent adjudication.Categorical variables were compared via χ 2 tests.Temporal patterns were evaluated via Pearson correlation or Cochrane-Armitage trend tests.All analyses were performed by using SAS 9.4 (SAS Institute Inc) with the use of an α-level of 0.05 to define statistical significance.Of 28 636 articles screened, 3396 met inclusion criteria and were analyzed.Interrater agreement for study inclusion before resolution was 94.5% (κ=0.72;95% confidence interval, 0.70-0.73).The sex of the animals used was not reported in 20.0% of studies.Males were exclusively used in 71.6% of studies in which sex was reported, whereas females were exclusively used in 12.9% and both sexes in 15.5%.Sex matching of animals was reported in 17.1% of studies that included both sexes.Restricting this analysis to the 988 studies of therapeutic interventions did not appreciably change these distributions.When stratified by the cardiovascular disease studied, males were exclusively used significantly more often than females or both sexes in all cases, with the exception of atherosclerosis and arrhythmia.When stratified by the animal model
The optimal blood glucose target during the early hospitalisation of comatose survivors of out-of-hospital cardiac arrest (OHCA) has not been established.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: <6 mmol/L, 6 to <8 mmol/L and ⩾8 mmol/L. Co-primary outcomes were the rates of death during the index hospitalisation and severe neurological dysfunction at discharge. We used multivariable logistic regression analyses to adjust for baseline differences in patient and index event characteristics.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.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.
Patients with acute coronary syndromes (ACS) may require immediate or urgent coronary artery bypass grafting (CABG). Ticagrelor is a potent P2Y12 receptor antagonist increasingly used in the management of ACS. Although current guidelines suggest discontinuing ticagrelor at least 5 days prior to CABG, the optimal timing of CABG following ticagrelor administration has not been well established. We sought to assess in-hospital clinical outcomes in ACS patients following CABG in relation to the duration of ticagrelor discontinuation prior to surgery. We identified consecutive ACS patients who underwent CABG after having received ticagrelor. Patients were divided into 3 groups based on the timing of surgery after discontinuation of ticagrelor (<48 hours, 48 hours to <5 days, 5 or more days). We then compared clinical outcomes following CABG in relation to the duration of ticagrelor discontinuation. Clinical variables evaluated included postoperative bleeding, need for surgical reopening or blood transfusions, and length of stay in the intensive care unit (ICU). Of 336 patients undergoing CABG following ACS between January 2012 and December 2013, 38 received ticagrelor prior to CABG. Ticagrelor had been discontinued <48 hours prior to CABG in 14 patients (37%); 48 hours to <5 days in 14 (37%); and 5 days or more in 10 (26%). Baseline characteristics were comparable between ticagrelor discontinuation strata. CABG was deemed to be needed immediately in 21% of patients; within 24 hours in 11%; and on an urgent basis in the remaining 68%. Patients who underwent CABG <48 hours after ticagrelor discontinuation had more preoperative intra-aortic balloon pump use, and were more likely to require blood transfusions and a prolonged ICU stay (defined as >3 days). In addition, they had numerically higher, but non-statistically significant, rates of postoperative bleeding. Patients who underwent CABG 48 hours to <5 days after ticagrelor discontinuation had similar rates of postoperative bleeding and duration of ICU stay compared to patients who waited at least 5 days. A significant proportion of ACS patients who require CABG undergo surgery before the guideline recommended ticagrelor discontinuation period of 5 days. Patients who undergo CABG <48 hours after ticagrelor discontinuation are more like to require postoperative blood transfusions and a prolonged ICU stay. Notably, patients who undergo CABG 48 hours to <5 days after ticagrelor discontinuation have similar postoperative outcomes compared to patients who undergo CABG after 5 days of ticagrelor discontinuation. Large prospective series are needed to corroborate these findings.View Large Image Figure ViewerDownload (PPT)
Background: Health-care associated pneumonia is a common complication in comatose survivors of out-of-hospital cardiac arrest (OHCA). However, the effect of pneumonia on the hospital course and cli...
Atherosclerosis remains a leading cause of morbidity and mortality, with revascularization remaining a cornerstone of management. Conventional revascularization modalities remain challenged by target vessel reocclusion-an event driven by mechanical, thrombotic, and proliferative processes. Despite considerable advancements, restenosis remains the focus of ongoing research. Adjunctive agents, including dipyridamole, offer a multitude of effects that may improve vascular homeostasis. We sought to quantify the potential therapeutic impact of dipyridamole on vascular occlusion. We performed a literature search (EMBASE and MEDLINE) examining studies that encompassed 3 areas: (1) one of the designated medical therapies applied in (2) the setting of a vascular intervention with (3) an outcome including vascular occlusion rates and/or quantification of neointimal proliferation/restenosis. The primary outcome was vascular occlusion rates. The secondary outcome was the degree of restenosis by neointimal quantification. Both human and animal studies were included in this translational analysis. There were 6,839 articles screened, from which 73 studies were included, encompassing 16,146 vessels followed up for a mean of 327.3 days (range 7-3650 days). Preclinical studies demonstrate that dipyridamole results in reduced vascular occlusion rates {24.9% vs. 48.8%, risk ratio 0.53 [95% confidence interval (CI) 0.40-0.70], I2 = 39%, P < 0.00001}, owing to diminished neointimal proliferation [standardized mean differences -1.13 (95% CI -1.74 to -0.53), I2 = 91%, P = 0.0002]. Clinical studies similarly demonstrated reduced occlusion rates with dipyridamole therapy [23.5% vs. 31.0%, risk ratio 0.77 (95% CI 0.67-0.88), I2 = 84%, P < 0.0001]. Dipyridamole may improve post-intervention vascular patency and mitigate restenosis. Dedicated studies are warranted to delineate its role as an adjunctive agent after revascularization.
