Hibbert, Benjamin

Background Recent studies have shown improved outcomes in cardiogenic shock through protocols directed toward early identification and initiation of mechanical circulatory support. However, objective therapeutic targets—based on clinical and/or laboratory data—to guide real‐time clinical decision making are lacking. Lactate clearance has been suggested as a potential treatment target because of its independent association with mortality. Methods and Results In a post hoc analysis of the DOREMI (Dobutamine Compared to Milrinone in the Treatment of Cardiogenic Shock) trial—a randomized, double‐blind, controlled trial comparing milrinone to dobutamine in the treatment of cardiogenic shock—we used prospectively collected lactate data to evaluate lactate clearance as a surrogate marker for in‐hospital mortality. In total, 82 (57.7%) patients survived to hospital discharge (survivors). In multivariate logistic regression analysis, complete lactate clearance, percentage lactate clearance, and percentage lactate clearance per hour were independently associated with survival beginning as early as 8 hours after enrollment. Complete lactate clearance was the strongest predictor of survival at all time points, with odds ratios ranging between 2.46 (95% CI, 1.09–5.55; P =0.03) at 8 hours to 5.44 (95% CI, 2.14–13.8; P <0.01) at 24 hours. Conclusions Complete lactate clearance is a strong and independent predictor of in‐hospital survival in patients with cardiogenic shock. Together with previously published data, these results further support the validity of lactate clearance as an appropriate surrogate for mortality and as a potential therapeutic target in future cardiogenic shock trials. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03207165.

Abstract Objective We sought to evaluate the association between the institutional volume of catheter‐directed thrombolysis (CDT) for pulmonary embolism and in‐hospital mortality. Background CDT is an increasingly utilized therapy in patients with intermediate/high‐risk PE. However, data on the relationship between hospital volume and clinical outcomes remain limited. Methods Patients who underwent CDT between October 1, 2015, and March 31, 2021, were identified in the Vizient Clinical Database. The primary outcome was in‐hospital mortality. Secondary outcome were major complications, length of stay, and cost. Hospitals were dichotomized into <8 and 8 cases/year following restricted cubic spline analysis. Results A total of 6741 CDT procedures at 171 hospitals were included with a median annual hospital volume of 4.1 cases (IQR = 1.9–8.3). A total of 44 hospitals (25.7%) were classified as high‐volume (8 cases/year) and performed 60.9% of all CDT cases. CDT at high‐volume centers was associated with lower in‐hospital mortality (6.0% vs. 11.3%; p < 0.0001). Stroke and bleeding rates were similar, but pulmonary complications were more frequent at low‐volume centers. CDT at high volume centers was associated with a significantly shorter length of stay and lower cost. The association between high CDT volume and in‐hospital mortality persisted after adjustment for demographics (odds ratio [OR] = 0.49, [0.41–0.58]), demographics and risk factors (OR = 0.52 [0.44–0.62]), and demographics, risk factors, and troponin elevation (OR = 0.51 [0.40–0.66]). Conclusion In a large contemporary cohort of patients undergoing CDT in the United States, low annual institutional volume of CDT was associated with higher in‐hospital mortality.

Background The randomized DOREMI (Dobutamine Compared to Milrinone) clinical trial evaluated the efficacy and safety of milrinone and dobutamine in patients with cardiogenic shock. Whether the results remain consistent when stratified by acute myocardial infarction remains unknown. In this substudy, we sought to evaluate differences in clinical management and outcomes of acute myocardial infarction complicated by cardiogenic shock (AMICS) versus non‐AMICS. Methods and Results Patients in cardiogenic shock (n=192) were randomized 1:1 to dobutamine or milrinone. The primary composite end point in this subgroup analysis was all‐cause in‐hospital mortality, cardiac arrest, non‐fatal myocardial infarction, cerebrovascular accident, the need for mechanical circulatory support, or initiation of renal replacement therapy (RRT) at 30‐days. Outcomes were evaluated in patients with (n=65) and without (n=127) AMICS. The primary composite end point was significantly higher in AMICS versus non‐AMICS (hazard ratio [HR], 2.21; 95% CI, 1.47–3.30; P =0.0001). The primary end point was driven by increased rates of all‐cause mortality, mechanical circulatory support, and RRT. No differences in other secondary outcomes including cardiac arrest or cerebrovascular accident were observed. AMICS remained associated with the primary composite outcome, 30‐day mortality, and RRT after adjustment for age, sex, procedural contrast use, multivessel disease, and inotrope type. Conclusions AMI was associated with increased rates of adverse clinical outcomes in cardiogenic shock along with increased rates of mortality and initiation of mechanical circulatory support and RRT. Contrast administration during revascularization likely contributes to increased rates of RRT. Heterogeneity of outcomes in AMICS versus non‐AMICS highlights the need to study interventions in specific subgroups of cardiogenic shock. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03207165.

AbstractAimsCardiogenic shock (CS) is a state of low cardiac output resulting in end-organ hypoperfusion. Despite high in-hospital mortality rates, little evidence exists regarding the optimal mean arterial pressure (MAP) target in CS. We therefore evaluated the relationship between achieved MAP and clinical outcomes in patients with CS.Methods and resultsWe performed a post hoc analysis of the CAPITAL DOREMI trial: a randomized, double-blind trial comparing dobutamine to milrinone in patients with CS. We divided patients into a high MAP group (average MAP ≥ 70 mmHg over the 36 h following randomization), and a low MAP group (average MAP &lt; 70 mmHg). Our primary outcome included in-hospital all-cause mortality, resuscitated cardiac arrest, need for cardiac transplantation or mechanical circulatory support, non-fatal myocardial infarction, transient ischaemic attack or stroke, or initiation of renal replacement therapy. In total, 71 (37.0%) patients achieved an average MAP &lt; 70 mmHg, and 121 (63.0%) achieved an average MAP ≥ 70 mmHg. The primary outcome occurred in 48 (67.6%) patients in the low MAP group and 51 (42.2%) patients in the high MAP group [adjusted relative risk (aRR) 0.70; 95% confidence interval (CI) 0.53–0.92; P = 0.01]. All-cause mortality occurred in 41 (57.8%) and 35 (28.9%) patients in the low and high MAP groups, respectively (aRR 0.56; 95% CI 0.40–0.79; P &lt; 0.01). There were no significant differences in any secondary outcomes between each group.ConclusionsIn patients with CS treated with inotrope therapy, low MAP is associated with worse clinical outcomes. Randomized data evaluating optimal MAP targets in CS is needed to guide medical therapy.

Background Elective percutaneous coronary intervention (PCI) is performed to relieve symptoms of angina. Identifying patients who will benefit symptomatically after PCI would be clinically advantageous but robust predictors of symptom resolution are ill-defined. Methods Prospective indexing of baseline angina status, clinical, and procedural characteristics were collected over a 5-year period in a regional revascularization registry. At 1-year follow-up, angina resolution was assessed. We performed a stepwise selection algorithm to identify predictors of persistent angina at 1 year. Results A total of 777 patients were included in the analysis and the median follow-up was 387 days. Mean age of the cohort was 66.6 years, 23.8% were female and 23.3% had baseline Canadian Cardiovascular Society class 3 or 4 angina. Overall, 13.1% had persistent angina. The only predictor of persistent angina was the presence of a residual chronic total occlusion after PCI with odds ratio of 3.06 (95% confidence interval, 1.81–5.17). Residual stenoses 50–69%, 70–89%, and 90–99% were not associated with residual angina after PCI. Conclusion Most patients achieved symptom resolution with PCI and optimal medical therapy. A residual chronic total occlusion after PCI was associated with persistent angina. Other degrees of stenoses were not associated with persistent angina.

AbstractBackgroundSex‐based differences in transcatheter aortic valve replacement (TAVR) outcomes have been previously documented. However, whether these differences persist with contemporary third generation transcatheter heart valves (THVs) is unknown.MethodsWe utilized Vizient's clinical database/resource manager (CDB/RM™) to identify patients who underwent TAVR between January 1, 2018 and March 31, 2020 to compare in‐hospital outcomes between males and females. The primary endpoint was in‐hospital mortality. Secondary endpoints included key in‐hospital complications, length of stay, discharge disposition, and cost. Unadjusted, propensity‐score matched and risk‐adjusted analyses of outcomes were performed.ResultsDuring the study period, 44,280 patients (24,842 males, 19,438 females) underwent TAVR. The primary endpoint of in‐hospital mortality was higher in females than in males (1.6 vs. 1.1% p < .001) in unadjusted analysis and persisted following propensity matching (1.6 vs. 0.9%, p < .001) and multivariable logistic regression with various risk‐adjustment models. In the most comprehensive model adjusting for age, race, and clinical comorbidities, female sex was associated with 34% greater odds of in‐hospital death (95% CI 20–50%, p < .001). Unadjusted and risk‐adjusted rates of post‐TAVR stroke, vascular complication, and blood transfusion were higher in females. Moreover, females demonstrated longer hospitalizations, higher costs and reduced rates of independent discharge home.ConclusionSex‐based differences in TAVR in‐hospital outcomes persist in contemporary practice with third generation transcatheter heart valves. Further research is needed to assess the reasons for these observed disparities and to identify effective mitigation strategies.

Adenosine boasts promising preclinical and clinical data supporting a vital role in modulating vascular homeostasis. Its widespread use as a diagnostic and therapeutic agent have been limited by its short half‐life and complex biology, though adenosine‐modulators have shown promise in improving vascular healing. Moreover, circulating adenosine has shown promise in predicting cardiovascular (CV) events. We sought to delineate whether circulating plasma adenosine levels predict CV events in patients undergoing invasive assessment for coronary artery disease. Patients undergoing invasive angiography had clinical data prospectively recorded in the Cardiovascular and Percutaneous ClInical TriALs (CAPITAL) revascularization registry and blood samples collected in the CAPITAL Biobank from which adenosine levels were quantified. Tertile‐based analysis was used to assess prediction of major adverse cardiovascular events (MACE; composite of death, myocardial infarction, unplanned revascularization, and cerebrovascular accident). Secondary analyses included MACE subgroups, clinical subgroups and adenosine levels. There were 1,815 patients undergoing angiography who had blood collected with adenosine quantified in 1,323. Of those quantified, 51.0% were revascularized and 7.3% experienced MACE in 12 months of follow‐up. Tertile‐based analysis failed to demonstrate any stratification of MACE rates (log rank, P = 0.83), when comparing low‐to‐middle (hazard ratio (HR) 1.10, 95% confidence interval (CI) 0.68–1.78, P = 0.70) or low‐to‐high adenosine tertiles (HR 0.95, 95% CI 0.56–1.57, P = 0.84). In adjusted analysis, adenosine similarly failed to predict MACE. Finally, adenosine did not predict outcomes in patients with acute coronary syndrome nor in those revascularized or treated medically. Plasma adenosine levels do not predict subsequent CV outcomes or aid in patient risk stratification.