Canadian VIGOUR Centre

Vranckx, P (corresponding author), Jessa Ziekenhuis, Dept Cardiol & Crit Care Med, Stadsomvaart 11, B-3500 Hasselt, Belgium.; Vranckx, P (corresponding author), Univ Hasselt, Fac Med & Life Sci, Martelarenlaan 42, B-3500 Hasselt, Belgium.

To identify factors associated with short-term mortality among patients receiving microaxial flow pump (mAFP) therapy for acute myocardial infarction-related cardiogenic shock (AMI-CS). We searched four databases (MEDLINE, Embase, CENTRAL, and Scopus) from January 1, 2004, to January 1, 2025. We selected English-language studies that included adults with AMI-CS receiving mAFP and evaluated factors associated with short-term mortality. We excluded patients receiving concurrent venoarterial extracorporeal membrane oxygenation, as well as studies that solely included patients presenting with out-of-hospital cardiac arrest. Two authors performed citation screening and data extraction. For each factor evaluated in at least two studies, we performed meta-analyses of adjusted odds ratios (aORs) using a random-effects model. Risk of bias was evaluated using the Quality in Prognosis Studies tool, and the certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations methodology. Our primary analysis included 18 studies, encompassing 20,617 patients. Median short-term mortality across studies was 50.7% (interquartile range 38.4-55.3%). Factors associated with short-term mortality based on high-certainty evidence included: increased age (aOR, 1.04 per year [95% CI, 1.03-1.05 per year] or ≥ 65 yr (aOR, 2.42 yr [95% CI, 0.77-7.64 yr]), female sex (aOR, 1.26 [95% CI, 1.09-1.45]), higher body mass index (aOR, 1.05 per point [95% CI, 1.04-1.07 per point]), higher heart rate (aOR, 1.02 per beats/min [95% CI, 1.01-1.02 per beats/min]), higher serum creatinine (aOR, 1.35 per mg/dL [95% CI, 1.08-1.70 per mg/dL]), mechanical ventilation (aOR, 2.53 [95% CI, 1.82-3.53]), vasopressors (aOR, 1.52 [95% CI, 1.11-2.08] for any vasopressors and aOR, 1.37 [95% CI, 1.18-1.58] per each vasopressor), presentation with ST-elevation myocardial infarction (aOR, 1.59 [95% CI, 1.11-2.26]), cardiac arrest (aOR, 2.85 [95% CI, 2.22-3.64]), and hypoxic-ischemic brain injury (aOR, 5.36 [95% CI, 3.03-9.47]). We identified several prognostic factors associated with short-term mortality in AMI-CS patients receiving mAFP support. This work may help inform clinicians, patients, and families regarding utilization of mAFP in AMI-CS.

Ex-situ heart perfusion (ESHP) is an innovative technology that has the power to greatly improve donor heart utilization and may eventually provide a platform for improvement of suboptimal hearts. However, its impact is limited by functional decline whilst on the platform, which is characterized by the development of oxidative stress and inflammation. Pathologic metabolism during normothermic ESHP may be an underlying factor in the development of such characteristics, however it is understudied within the context of machine perfusion. In the following review article, we discuss the limitations of the current metabolic substrate provision approach during ESHP (analogous to post-prandial glucose and insulin) from a mechanistic standpoint. We discuss alternative approaches and substrates that may be more conducive to physiologic preservation and recovery on the platform. We advocate for a support strategy mimicking fasting insulin and glucose, and alternative substrates such as free fatty acids and ketone bodies, which may be more adapted to the non-physiologic state encountered during ESHP. Throughout, we outline research gaps yet to be explored that would enable substrate provision approaches during machine perfusion of the donor heart to be further optimized.

BackgroundZalunfiban is a glycoprotein IIb/IIIa (integrin αIIbβ3) inhibitor designed for subcutaneous administration on first medical contact with patients with suspected ST-segment elevation myocardial infarction (STEMI).MethodsAn international, double-blind, placebo-controlled trial randomly assigned patients with STEMI in a 1:1:1 ratio to receive a single subcutaneous injection of zalunfiban (0.11 mg/kg or 0.13 mg/kg) or placebo. The primary efficacy end point was a hierarchical proportional odds model ranking seven end points from worst to best: all-cause death, stroke, recurrent myocardial infarction, acute stent thrombosis, new-onset or rehospitalization for heart failure, larger infarct size, or no end point through 30 days. The primary safety end point was the occurrence of severe or life-threatening bleeding as per the global use of strategies to open occluded coronary arteries (GUSTO) criteria.ResultsThe trial randomly assigned 2467 patients (853 to zalunfiban 0.11 mg/kg, 818 to zalunfiban 0.13 mg/kg, and 796 to placebo). The primary efficacy end point was significantly improved by zalunfiban (adjusted odds ratio 0.79; 95% confidence interval, 0.65 to 0.98; P=0.028). GUSTO severe bleeding was similar between those who received zalunfiban versus placebo (1.2% vs. 0.8%; P=0.40), but GUSTO mild to moderate bleeding was increased (6.4% vs. 2.5%; P<0.001). Angiography showed faster coronary blood flow with zalunfiban versus placebo (corrected frame count of the infarct-related artery 109 [interquartile range 35 to 176] vs. 176 [interquartile range 40 to 176]; P=0.012).ConclusionsIn patients with STEMI, zalunfiban administered at first medical contact significantly improved preintervention infarct-related patency and reduced the likelihood of a worse 30-day multicomponent hierarchical clinical end point. Zalunfiban was not associated with increased severe or life-threatening bleeding but was associated with increased mild to moderate bleeding. (Funded by CeleCor Therapeutics; CELEBRATE ClinicalTrials.gov number, NCT04825743.)

The long-term effects of catheter ablation (CA) compared with medical therapy on cardiovascular outcomes for atrial fibrillation (AF) remain undetermined. Using a population-based cohort, we sought to determine what the association between CA and medical therapy was on these outcomes. By use of Alberta administrative data, patients with AF as the primary diagnosis during hospitalization, emergency department visit, or physician visit were included between October 1, 2008, and March 31, 2018. Based on therapy received, patients were assigned to categories of CA, rate control, or rhythm control with medication. The association of treatment with the primary composite outcome of all-cause death, hospitalization for heart failure, or stroke was examined after adjustment for age, sex, comorbidities, and baseline medications. Of 39,966 treated AF patients, 2077 (5.2%), 29,467 (73.7%), and 8422 (21.1%) were treated with CA, rate control, and rhythm control with medication, respectively. Patients in the CA group had a lower incidence of the primary outcome (4.0/100 person-years) compared with the rate control group (8.7/100 person-years) or the rhythm control with medication group (6.8/100 person-years) during a median follow-up of 6.3 years. In multivariable analysis, compared with CA, both rate control (hazard ratio, 1.28; 95% confidence interval, 1.09-1.50) and rhythm control with medication (hazard ratio, 1.21; 95% confidence interval, 1.03-1.43) were associated with a higher risk of the primary outcome. In this cohort study, patients who received CA demonstrated a reduction in the risk of long-term adverse cardiovascular outcomes compared with medical therapy in patients with AF, providing some data to indicate the effects of CA in the long-term.

Chronic kidney disease is common in patients with atrial fibrillation (AF) and is associated with higher rates of bleeding with anticoagulation. In the AZALEA-TIMI 71 randomized clinical trial, abelacimab, a novel factor XI inhibitor, reduced rates of major or clinically relevant nonmajor (CRNM) bleeding compared with rivaroxaban in patients with AF. To examine the safety of abelacimab vs rivaroxaban across a range of kidney function. The AZALEA-TIMI 71 study randomized patients with AF to 1 of 2 abelacimab doses (150 mg or 90 mg monthly) or to rivaroxaban, with stratification by creatinine clearance (CrCl). Patients with CrCl less than 15 mL/min or receiving dialysis were excluded. This secondary analysis of AZALEA-TIMI 71 examines outcomes by randomized treatment and CrCl at randomization. Patients randomized to rivaroxaban with a CrCl greater than 50 mL/min received rivaroxaban, 20 mg, daily, and those with a CrCl of 50 mL/min or less received rivaroxaban, 15 mg, daily. Patients randomized to abelacimab received the assigned dose irrespective of CrCl. The primary outcome was major bleeding or CRNM bleeding. Among 1284 patients, median (IQR) age was 74 (69-78) years and 572 patients (44.5%) were female. Median (IQR) CrCl was 71 (54-90) mL/min, with 264 patients (20.6%) having a CrCl of 50 mL/min or less. In the rivaroxaban group, patients with CrCl of 50 mL/min or less experienced higher rates of major or CRNM bleeding compared with those with CrCl greater than 50 mL/min despite dose reduction (incidence rates, 13.6 vs 7.0 per 100 person-years). Abelacimab reduced major or CRNM bleeding vs rivaroxaban irrespective of CrCl (CrCl ≤50 mL/min: hazard ratio [HR], 0.26; 95% CI, 0.12-0.54; >50 mL/min: HR, 0.40; 95% CI, 0.26-0.62; P value for interaction = .33), with absolute risk reductions of 10.1 vs 4.2 per 100 person-years in those with CrCl of 50 mL/min or less vs greater than 50 mL/min, respectively (P value for interaction = .09). This risk reduction was consistent for major bleeding alone and for a broader composite inclusive of major, CRNM, and minor bleeding. Results were similar when comparing the individual abelacimab doses to rivaroxaban. In this secondary analysis of the AZALEA-TIMI 71 randomized clinical trial, abelacimab consistently reduced the risk of bleeding relative to rivaroxaban irrespective of kidney function. These findings suggest that abelacimab may offer a particularly favorable safety profile among those with chronic kidney disease; however, larger studies are necessary to characterize the efficacy of abelacimab for stroke prevention in AF.