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Designed as a systematic review and meta-analysis to better understand the role of lactate in the prognosis of patients presenting with cardiogenic shock

Systematic review and network meta-analysis with the objective of evaluating the comparative efficacy of epinephrine dosing in out-of-hospital cardiac arrest.

Systematic review and network meta-analysis with the objective of evaluating the comparative efficacy of four temperature targets for targeted temperature management in comatose survivors of out-of-hospital cardiac arrest.

Federal agencies such as CIHR are responsible for funding health and medical research. Since its inception, research productivity following successful grants have not been analyzed. Given the large dedication of taxpayer dollars towards public research, we will seek to quantify research efficiency by calculating the number of dollars required per publication, per citation, and per journal impact factor. This remains important for both clinicians and the public to better understand the public investment in healthcare research.

Cardiogenic shock is a state of low cardiac output resulting in end-organ hypoperfusion. Mortality in cardiogenic shock remains as high as 40-50% and has been unchanged for several decades. Little has been shown to improve outcomes in cardiogenic shock apart from urgent revascularization in the setting of acute coronary syndrome, and we rely primarily on expert consensus to guide management. One therapeutic target that remains unclear is the optimal mean arterial pressure (MAP) to target during initial resuscitation. Clinicians selecting an optimal MAP target must take into consideration both the risks of low MAP, including impaired renal perfusion and associated impairment in diuresis, decreased coronary perfusion pressure, and decreased cerebral perfusion pressure, as well as the risks of increased MAP including increased left ventricular afterload and myocardial oxygen demand. We seek to evaluate existing evidence on MAP targets in cardiogenic shock.

Background: Device-related thrombus (DRT) has been considered an Achilles’ heel of left atrial appendage occlusion (LAAO). However, data on DRT prediction remain limited. Objectives: This study constructed a DRT registry via a multicenter collaboration aimed to assess outcomes and predictors of DRT. Methods: Thirty-seven international centers contributed LAAO cases with and without DRT (device-matched and temporally related to the DRT cases). This study described the management patterns and mid-term outcomes of DRT and assessed patient and procedural predictors of DRT. Results: A total of 711 patients (237 with and 474 without DRT) were included. Follow-up duration was similar in the DRT and no-DRT groups, median 1.8 years (interquartile range: 0.9-3.0 years) versus 1.6 years (interquartile range: 1.0-2.9 years), respectively (P = 0.76). DRTs were detected between days 0 to 45, 45 to 180, 180 to 365, and >365 in 24.9%, 38.8%, 16.0%, and 20.3% of patients. DRT presence was associated with a higher risk of the composite endpoint of death, ischemic stroke, or systemic embolization (HR: 2.37; 95% CI, 1.58-3.56; P < 0.001) driven by ischemic stroke (HR: 3.49; 95% CI: 1.35-9.00; P = 0.01). At last known follow-up, 25.3% of patients had DRT. Discharge medications after LAAO did not have an impact on DRT. Multivariable analysis identified 5 DRT risk factors: hypercoagulability disorder (odds ratio [OR]: 17.50; 95% CI: 3.39-90.45), pericardial effusion (OR: 13.45; 95% CI: 1.46-123.52), renal insufficiency (OR: 4.02; 95% CI: 1.22-13.25), implantation depth >10 mm from the pulmonary vein limbus (OR: 2.41; 95% CI: 1.57-3.69), and non-paroxysmal atrial fibrillation (OR: 1.90; 95% CI: 1.22-2.97). Following conversion to risk factor points, patients with ≥2 risk points for DRT had a 2.1-fold increased risk of DRT compared with those without any risk factors. Conclusions: DRT after LAAO is associated with ischemic events. Patient- and procedure-specific factors are associated with the risk of DRT and may aid in risk stratification of patients referred for LAAO.

To compare the relative efficacy of supportive therapies (inotropes, vasopressors, and mechanical circulatory support [MCS]) for adult patients with cardiogenic shock complicating acute myocardial infarction.We conducted a systematic review and network meta-analysis and searched six databases from inception to December 2021 for randomized clinical trials (RCTs). We evaluated inotropes, vasopressors, and MCS in separate networks. Two reviewers performed screening, full-text review, and extraction. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to rate the certainty in findings. The critical outcome of interest was 30-day all-cause mortality.We included 17 RCTs. Among inotropes (seven RCTs, 1,145 patients), levosimendan probably reduces mortality compared with placebo (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.33 to 0.87; moderate certainty), but primarily in lower severity shock. Milrinone (OR, 0.52; 95% CI, 0.19 to 1.39; low certainty) and dobutamine (OR, 0.67, 95% CI, 0.30 to 1.49; low certainty) may have no effect on mortality compared with placebo. With regard to MCS (eight RCTs, 856 patients), there may be no effect on mortality with an intra-aortic balloon pump (IABP) (OR, 0.94; 95% CI, 0.69 to 1.28; low certainty) or percutaneous MCS (pMCS) (OR, 0.96; 95% CI, 0.47 to 1.98; low certainty), compared with a strategy involving no MCS. Intra-aortic balloon pump use was associated with less major bleeding compared with pMCS. We found only two RCTs evaluating vasopressors, yielding insufficient data for meta-analysis.The results of this systematic review and network meta-analysis indicate that levosimendan reduces mortality compared with placebo among patients with low severity cardiogenic shock. Intra-aortic balloon pump and pMCS had no effect on mortality compared with a strategy of no MCS, but pMCS was associated with higher rates of major bleeding.Center for Open Science ( https://osf.io/ky2gr ); registered 10 November 2020.RéSUMé: OBJECTIF: Comparer l’efficacité relative des thérapies de soutien (inotropes, vasopresseurs et assistance circulatoire mécanique [ACM]) chez les patients adultes atteints d’un choc cardiogénique compliquant un infarctus aigu du myocarde.Nous avons réalisé une revue systématique et une méta-analyse en réseau et effectué des recherches dans six bases de données depuis leur création jusqu’à décembre 2021 pour en tirer les études randomisées contrôlées (ERC). Nous avons évalué les inotropes, les vasopresseurs et les ACM dans des réseaux distincts. Deux réviseurs ont effectué la recherche, l’évaluation du texte intégral et l’extraction. Nous avons utilisé le système de notation GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pour évaluer la certitude des résultats. Le critère d’évaluation d’intérêt était la mortalité toutes causes confondues à 30 jours.Nous avons inclus 17 ERC. Parmi les inotropes (sept ERC, 1145 patients), le lévosimendan a probablement réduit la mortalité par rapport au placebo (rapport de cotes [RC], 0,53; intervalle de confiance [IC] à 95 %, 0,33 à 0,87; certitude modérée), mais principalement en cas de choc de sévérité moindre. La milrinone (RC, 0,52; IC 95 %, 0,19 à 1,39; certitude faible) et la dobutamine (RC, 0,67, IC 95 %, 0,30 à 1,49; certitude faible) pourraient n’avoir aucun effet sur la mortalité par rapport au placebo. En ce qui concerne l’ACM (huit ERC, 856 patients), il pourrait n’y avoir aucun effet sur la mortalité avec un ballon intra-aortique (IABP) (RC, 0,94; IC 95 %, 0,69 à 1,28; certitude faible) ou un ACM percutané (ACMp) (RC, 0,96; IC 95 %, 0,47 à 1,98; certitude faible), par rapport à une stratégie sans ACM. L’utilisation d’un ballon intra-aortique était associée à moins de saignements majeurs par rapport à une ACMp. Nous n’avons trouvé que deux ERC évaluant les vasopresseurs, ce qui n’a pas fourni suffisamment de données pour la méta-analyse.Les résultats de cette revue systématique et de la méta-analyse en réseau indiquent que le lévosimendan réduit la mortalité par rapport au placebo chez les patients présentant un choc cardiogénique de faible gravité. Le ballon intra-aortique et l’ACMp n’ont eu aucun effet sur la mortalité par rapport à une stratégie sans ACM, mais l’ACMp était associée à des taux plus élevés de saignements majeurs. ENREGISTREMENT DE L’éTUDE: Center for Open Science ( https://osf.io/ky2gr ); enregistrée le 10 novembre 2020.

Background Assessment of the case-fatality rate (CFR) of major bleeding on dual antiplatelet therapy (DAPT) may improve balancing risks and benefits of different durations of DAPT following percutaneous coronary intervention (PCI). Objectives To determine the CFR of major bleeding in patients on DAPT after PCI and to compare rates among different durations of DAPT. Methods Medline, Embase, and CENTRAL were searched from inception to August 2021 for randomized trials that reported fatal bleeding among patients who were randomized to ≥1 month of DAPT following PCI. Summary estimates for CFRs of major bleeding were calculated using the random-effects inverse-variance method. Statistical heterogeneity was evaluated using the I 2 statistic. Results Of 2777 citations obtained by the search, 15 (48%) of 31 potentially eligible studies were excluded because fatal bleeding was not reported, leaving 16 studies that were included in the analysis. Overall, there were 823 major bleeding events including 91 fatal events in 48,884 patients who were assigned to receive DAPT during study follow-up. The CFR of major bleeding was 10.8% (95% confidence interval [CI], 7.1-16.2; I 2 = 50%) in the entire study population, and 13.8% (95% CI, 6.5-27.1; I 2 = 28%), 11.2% (95% CI, 6.7-18.0; I 2 = 0%), and 5.8% (95% CI, 3.0-11.1; I 2 = 0%) in those on short-term (≤6 months; n = 16,553), standard-term (12 months; n = 19,453), and long-term DAPT (>12 months; n = 10,238), respectively. Conclusion Fatal bleeding is not reported in many studies evaluating DAPT after PCI. The CFR of major bleeding on DAPT is substantial and may be higher in the first 12 months of DAPT than during long-term DAPT.

Additional file 4 : Table S4. Multivariable Logistic Regression Model for hospital mortality for entire study cohort (n = 15,014), including interaction terms. Multivariable Logistic Regression Model for hospital mortality for entire study cohort (n = 15,014), including interaction terms.

Additional file 3 : Table S3. Multivariable Logistic Regression Model for hospital mortality for patients with septic shock (n = 1286). Multivariable Logistic Regression Model for hospital mortality for patients with septic shock (n = 1286).

Additional file 1 : Table S1. Multivariable Logistic Regression Model for hospital mortality for entire study cohort (n = 15,014). Multivariable Logistic Regression Model for hospital mortality for entire study cohort (n = 15,014).

Additional file 7 : Table S7. Generalized Linear Model with gamma distribution and log link for total cost for patients with new-onset atrial fibrillation (n = 15,014). Generalized Linear Model with gamma distribution and log link for total cost for patients with new-onset atrial fibrillation (n = 15,014).

Additional file 5 : Table S5. Multivariable Logistic Regression Model for hospital mortality among patients with new-onset atrial fibrillation (n = 1541). Multivariable Logistic Regression Model for hospital mortality among patients with new-onset atrial fibrillation (n = 1541).

Additional file 2 : Table S2. Multivariable Logistic Regression Model for hospital mortality for patients with sepsis (n = 1944). Multivariable Logistic Regression Model for hospital mortality for patients with sepsis (n = 1944).

Additional file 6 : Table S6. Generalized Linear Model with gamma distribution and log link for total cost for entire study cohort (n = 15,014). Generalized Linear Model with gamma distribution and log link for total cost for entire study cohort (n = 15,014).

Supplemental material, Supplemental_Tables_for_PAI-1_RTR for Performance of plasminogen activator inhibitor-1 as a biomarker in patients undergoing coronary angiography: Analytical and biological considerations by Richard G Jung, Trevor Simard, Pietro Di Santo, Alisha Labinaz, Robert Moreland, Anne-Claire Duchez, Kamran Majeed, Pouya Motazedian, Rebecca Rochman, Young Jung and Benjamin Hibbert in Diabetes & Vascular Disease Research

Association between plasminogen activator inhibitor-1 and cardiovascular events: a systematic review and meta-analysis. (DOCX 4410 kb)

Association between plasminogen activator inhibitor-1 and cardiovascular events: a systematic review and meta-analysis. (DOCX 4410 kb)