Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock.

BACKGROUND: 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. METHODS: We randomly assigned patients with cardiogenic shock to receive milrinone or dobutamine in a double-blind fashion. The primary outcome was a composite of in-hospital death from any cause, resuscitated cardiac arrest, receipt of a cardiac transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic attack or stroke diagnosed by a neurologist, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary composite outcome. RESULTS: A total of 192 participants (96 in each group) were enrolled. The treatment groups did not differ significantly with respect to the primary outcome; a primary outcome event occurred in 47 participants (49%) in the milrinone group and in 52 participants (54%) in the dobutamine group (relative risk, 0.90; 95% confidence interval [CI], 0.69 to 1.19; P = 0.47). There were also no significant differences between the groups with respect to secondary outcomes, including in-hospital death (37% and 43% of the participants, respectively; relative risk, 0.85; 95% CI, 0.60 to 1.21), resuscitated cardiac arrest (7% and 9%; hazard ratio, 0.78; 95% CI, 0.29 to 2.07), receipt of mechanical circulatory support (12% and 15%; hazard ratio, 0.78; 95% CI, 0.36 to 1.71), or initiation of renal replacement therapy (22% and 17%; hazard ratio, 1.39; 95% CI, 0.73 to 2.67). CONCLUSIONS: In patients with cardiogenic shock, no significant difference between milrinone and dobutamine was found with respect to the primary composite outcome or important secondary outcomes. (Funded by the Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario; ClinicalTrials.gov number, NCT03207165.).

Inotropes, vasopressors, and mechanical circulatory support for treatment of cardiogenic shock complicating myocardial infarction: a systematic review and network meta-analysis.

PURPOSE: 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. SOURCE: 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. PRINCIPAL FINDINGS: 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. CONCLUSION: 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. STUDY REGISTRATION: 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. SOURCES: 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. CONSTATATIONS PRINCIPALES: 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. CONCLUSION: 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.

Outcomes of retrograde chronic total occlusion percutaneous coronary intervention: A report from the OPEN-CTO registry.

OBJECTIVES: We sought to assess in-hospital and long-term outcomes of retrograde compared with antegrade-only percutaneous coronary intervention for chronic total occlusion (CTO PCI). BACKGROUND: Procedural and clinical outcomes following retrograde compared with antegrade-only CTO PCI remain unknown. METHODS: Using the core-lab adjudicated OPEN-CTO registry, we compared the outcomes of retrograde to antegrade-only CTO PCI. Primary endpoints included were in-hospital major adverse cardiac and cerebrovascular events (MACCE) (all-cause death, stroke, myocardial infarction [MI], emergency cardiac surgery, or clinically significant perforation) and MACCE at 1-year (all-cause death, MI, stroke, target lesion revascularization, or target vessel reocclusion). RESULTS: Among 885 single CTO procedures from the OPEN-CTO registry, 454 were retrograde and 431 were antegrade-only. Lesion complexity was higher (J-CTO score: 2.7 vs. 1.9; p < .001) and technical success lower (82.4 vs. 94.2%; p < .001) in retrograde compared with antegrade-only procedures. All-cause death was higher in the retrograde group in-hospital (2 vs. 0%; p = .003), but not at 1-year (4.9 vs. 3.3%; p = .29). Compared with antegrade-only procedures, in-hospital MACCE rates (composite of all-cause death, stroke, MI, emergency cardiac surgery, and clinically significant perforation) were higher in the retrograde group (10.8 vs. 3.3%; p < .001) and at 1-year (19.5 vs. 13.9%; p = .03). In sensitivity analyses landmarked at discharge, there was no difference in MACCE rates at 1 year following retrograde versus antegrade-only CTO PCI. Improvements in Seattle Angina Questionnaire Quality of Life scores at 1-year were similar between the retrograde and antegrade-only groups (29.9 vs 30.4; p = .58). CONCLUSIONS: In the OPEN-CTO registry, retrograde CTO procedures were associated with higher rates of in-hospital MACCE compared with antegrade-only; however, post-discharge outcomes, including quality of life improvements, were similar between technical modalities.

Revisiting the Evidence for Dipyridamole in Reducing Restenosis: A Systematic Review and Meta-analysis.

ABSTRACT: 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.

Impact of baseline beta-blocker use on inotrope response and clinical outcomes in cardiogenic shock: a subgroup analysis of the DOREMI trial.

BACKGROUND: Cardiogenic shock (CS) is associated with significant morbidity and mortality. The impact of beta-blocker (BB) use on patients who develop CS remains unknown. We sought to evaluate the clinical outcomes and hemodynamic response profiles in patients treated with BB in the 24 h prior to the development of CS. METHODS: Patients with CS enrolled in the DObutamine compaREd to MIlrinone trial were analyzed. The primary outcome was a composite of all-cause mortality, resuscitated cardiac arrest, need for cardiac transplant or mechanical circulatory support, non-fatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary composite and hemodynamic response profiles derived from pulmonary artery catheters. RESULTS: Among 192 participants, 93 patients (48%) had received BB therapy. The primary outcome occurred in 47 patients (51%) in the BB group and in 52 (53%) in the no BB group (RR 0.96; 95% CI 0.73-1.27; P = 0.78) throughout the in-hospital period. There were fewer early deaths in the BB group (RR 0.41; 95% CI 0.18-0.95; P = 0.03). There were no differences in other individual components of the primary outcome or in hemodynamic response between the two groups throughout the remainder of the hospitalization. CONCLUSIONS: BB therapy in the 24 h preceding the development of CS did not negatively influence clinical outcomes or hemodynamic parameters. On the contrary, BB use was associated with fewer deaths in the early resuscitation period, suggesting a paradoxically protective effect in patients with CS. Trial registration ClinicalTrials.gov Identifier: NCT03207165.

Outcomes with retrograde versus antegrade chronic total occlusion revascularization.

OBJECTIVES: The aim of the study was to evaluate the outcomes of retrograde versus antegrade approach in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). BACKGROUND: The retrograde approach has increased the success rate of CTO PCI but has been associated with a higher risk for complications. METHODS: We conducted a meta-analysis of studies published between 2000 and August 2019 comparing the in-hospital and long-term outcomes with retrograde versus antegrade CTO PCI. RESULTS: Twelve observational studies (10,240 patients) met our inclusion criteria (retrograde approach 2,789 patients, antegrade approach 7,451 patients). Lesions treated with the retrograde approach had higher J-CTO score (2.8 vs. 1.9, p < .001). Retrograde CTO PCI was associated with a lower success rate (80.9% vs. 87.4%, p < .001). Both approaches had similar in-hospital mortality, urgent revascularization, and cerebrovascular events. Retrograde CTO PCI was associated with higher risk of in-hospital myocardial infarction (MI; odds ratio [OR] 2.37, 95% confidence intervals [CI] 1.7, 3.32, p < .001), urgent pericardiocentesis (OR 2.53, 95% CI 1.41-4.51, p = .002), and contrast-induced nephropathy (OR 2.12, 95% CI 1.47-3.08; p < .001). During a mean follow-up of 48 ± 31 months retrograde crossing had similar mortality (OR 1.79, 95% CI 0.84-3.81, p = .13), but a higher incidence of MI (OR 2.07, 95% CI 1.1-3.88, p = .02), target vessel revascularization (OR 1.92, 95% CI 1.49-2.46, p < .001), and target lesion revascularization (OR 2.08, 95% CI 1.33-3.28, p = .001). CONCLUSIONS: Compared with antegrade CTO PCI, retrograde CTO PCI is performed in more complex lesions and is associated with a higher risk for acute and long-term adverse events.

Improvement in left ventricular function following higher-risk percutaneous coronary intervention in patients with ischemic cardiomyopathy.

BACKGROUND: Surgical revascularization is associated with improved ventricular function and clinical outcomes among patients with ischemic cardiomyopathy. There are less extensive data on changes in ventricular function among patients with ischemic cardiomyopathy undergoing percutaneous coronary intervention (PCI). Accordingly, we sought to assess the extent and predictors of change in left ventricular ejection fraction (ΔLVEF) among patients undergoing hemodynamically-supported PCI. METHODS: We assessed ΔLVEF following hemodynamically-supported PCI (with Impella or intra-aortic balloon counterpulsation) among patients enrolled in the PROTECT II trial and cVAD registry. The ΔLVEF was compared among patients with paired echocardiography at baseline and at least 30 days of follow-up. Independent correlates of ΔLVEF (modeled continuously and with an absolute ΔLVEF≥5%) were assessed using multivariable models. RESULTS: Among the 689 patients with paired echocardiographic data included in the analysis, the mean LVEF improved from 24.8 ± 9.9% to 31.4 ± 13.3% after PCI, for a net increase of 6.5 ± 10.8% (p < .001). A total of 395 (57%) patients had ΔLVEF ≥ 5% following hemodynamically-supported PCI. The number of vessels treated was associated with ΔLVEF (ΔLVEF 5.5% with 1 vessel, 6.6% with 2 vessels, and 8.3% with 3 vessels, p for trend = .046). A lower baseline LVEF, absence of a history of congestive heart failure or aldosterone receptor antagonist use, and a greater number of vessels treated were independent correlates of LVEF improvement. CONCLUSIONS: Among patients with severe left ventricular systolic dysfunction and paired echocardiographic assessments, an improvement in LVEF was observed following hemodynamically-supported PCI.

Methodological Rigor in Preclinical Cardiovascular Studies: Targets to Enhance Reproducibility and Promote Research Translation.

RATIONALE: Methodological sources of bias and suboptimal reporting contribute to irreproducibility in preclinical science and may negatively affect research translation. Randomization, blinding, sample size estimation, and considering sex as a biological variable are deemed crucial study design elements to maximize the quality and predictive value of preclinical experiments. OBJECTIVE: To examine the prevalence and temporal patterns of recommended study design element implementation in preclinical cardiovascular research. METHODS AND RESULTS: All articles published over a 10-year period in 5 leading cardiovascular journals were reviewed. Reports of in vivo experiments in nonhuman mammals describing pathophysiology, genetics, or therapeutic interventions relevant to specific cardiovascular disorders were identified. Data on study design and animal model use were collected. Citations at 60 months were additionally examined as a surrogate measure of research impact in a prespecified subset of studies, stratified by individual and cumulative study design elements. Of 28 636 articles screened, 3396 met inclusion criteria. Randomization was reported in 21.8%, blinding in 32.7%, and sample size estimation in 2.3%. Temporal and disease-specific analyses show that the implementation of these study design elements has overall not appreciably increased over the past decade, except in preclinical stroke research, which has uniquely demonstrated significant improvements in methodological rigor. In a subset of 1681 preclinical studies, randomization, blinding, sample size estimation, and inclusion of both sexes were not associated with increased citations at 60 months. CONCLUSIONS: Methodological shortcomings are prevalent in preclinical cardiovascular research, have not substantially improved over the past 10 years, and may be overlooked when basing subsequent studies. Resultant risks of bias and threats to study validity have the potential to hinder progress in cardiovascular medicine as preclinical research often precedes and informs clinical trials. Stroke research quality has uniquely improved in recent years, warranting a closer examination for interventions to model in other cardiovascular fields.

Transcatheter Aortic Valve Implantation (TAVI) for Native Aortic Valve Regurgitation　- A Systematic Review.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has become the standard of care for management of high-risk patients with aortic stenosis. Limited data is available regarding the performance of TAVI in patients with native aortic valve regurgitation (NAVR).Methods and Results:We performed a systematic review from 2002 to 2016. The primary outcome was device success as per VARC-2 criteria. Secondary endpoints included procedural complications, and 30-day and 1-year mortality rates. A total of 175 patients were included from 31 studies. Device success was reported in 86.3% of patients - with device failure driven by moderate aortic regurgitation (AR ≥3+) and/or need for a second device. Procedural complications were rare, with no procedural deaths, myocardial infarctions or annular ruptures reported. Procedural safety was acceptable with a low 30-day incidence of stroke (1.5%). The 30-day and 1-year overall mortality rates were 9.6% and 20.0% (cardiovascular death, 3.8% and 10.1%, respectively). Patients receiving 2nd-generation valves demonstrated similar safety profiles with greater device success compared with 1st-generation valves (96.2% vs. 78.4%). This was driven by the higher incidence of second-valve implantation (23.4% vs. 1.7%) and significant paravalvular leak (8.3% vs. 0.0%). CONCLUSIONS: TAVI demonstrates acceptable safety and efficacy in high-risk patients with severe NAVR. Second-generation valves may afford a similar safety profile with improved device success. Dedicated studies are needed to definitively establish the efficacy of TAVI in this population.

Does renal function affect the efficacy or safety of a pharmacoinvasive strategy in patients with ST-elevation myocardial infarction? A meta-analysis.

BACKGROUND: The efficacy and safety of pharmacoinvasive strategy following fibrinolysis for ST-elevation myocardial infarction (STEMI) in relation to renal function have not been established. METHODS: Using patient-level data from 4 randomized controlled trials, we examined the efficacy and safety of pharmacoinvasive versus standard treatment after fibrinolysis for STEMI. Patients were stratified based on the estimated glomerular filtration rate (eGFR) on presentation (<60 mL/min/1.73 m2 vs ≥60 mL/min/1.73 m2). The primary outcome was the composite of death or reinfarction at 30 days. RESULTS: Of 2,029 patients, 457 (23%) had an eGFR<60 mL/min/1.73 m2. Patients with eGFR<60 mL/min/1.73 m2 were older and had higher Thrombolysis in Myocardial Infarction risk scores. Compared with patients with eGFR≥60 mL/min/1.73 m2, patients with renal dysfunction had higher rates of the primary outcome (5.3% vs 11.8%, respectively; P<.001). There was no significant heterogeneity in the treatment effect of pharmacoinvasive strategy on the primary outcome (P heterogeneity=.73) or the rate of death or reinfarction at 1 year (P heterogeneity=.64) in relation to eGFR. Patients with renal dysfunction had higher rates of in-hospital major bleeding compared with patients with eGFR ≥60 mL/min/1.73 m2 (7.7% vs 4.3%, respectively; P=.004); however, there was no difference in bleeding events between treatment arms in the overall cohort or in relation to eGFR (P heterogeneity=.67). CONCLUSIONS: Renal impairment is associated with increased rates of adverse events in STEMI patients treated with fibrinolysis. However, the safety and efficacy of pharmacoinvasive strategy are preserved in patients with renal impairment on presentation.

Predicting Acute Kidney Injury following Transcatheter Aortic Valve Replacement.

PURPOSE: Acute kidney injury occurs in up to a quarter of patients following transcatheter aortic valve replacement (TAVR) and has been associated with increased short and long-term mortality rates. A variety of patient characteristics predictive of post-TAVR acute kidney injury (AKI) have been identified, however discrepancies among studies exist almost uniformly. We investigated the hypothesis that the change in glomerular filtration rate (ΔGFR) in response to contrast administered during pre-TAVR coronary angiography is predictive of ΔGFR post-TAVR. METHODS: The study comprised 195 patients who underwent TAVR at a single center between August 2008 and June 2015 and were prospectively included in the CAPITAL TAVR registry. Multiple linear regression analysis was conducted to estimate the effect of independent variables on the change in renal function post-TAVR. RESULTS: There was no relationship identified between the ΔGFR post-angiogram and the ΔGFR post-TAVR (r=0.043, P=0.582). Multiple linear regression analysis revealed that a significant amount of the change in renal function post-TAVR can be explained by the patient's baseline creatinine (beta coefficient, -0.310, P.

Canadian Cardiovascular Society/Canadian Cardiovascular Critical Care Society/Canadian Association of Interventional Cardiology Clinical Practice Update on Optimal Post Cardiac Arrest and Refractory Cardiac Arrest Patient Care.

Survival to hospital discharge among patients with out-of-hospital cardiac arrest (OHCA) is low and important regional differences in treatment practices and survival have been described. Since the 2017 publication of the Canadian Cardiovascular Society's position statement on OHCA care, multiple randomized controlled trials have helped to better define optimal post cardiac arrest care. This working group provides updated guidance on the timing of cardiac catheterization in patients with ST-elevation and without ST-segment elevation, on a revised temperature control strategy targeting normothermia instead of hypothermia, blood pressure, oxygenation, and ventilation parameters, and on the treatment of rhythmic and periodic electroencephalography patterns in patients with a resuscitated OHCA. In addition, prehospital trials have helped craft new expert opinions on antiarrhythmic strategies (amiodarone or lidocaine) and outline the potential role for double sequential defibrillation in patients with refractory cardiac arrest when equipment and training is available. Finally, we advocate for regionalized OHCA care systems with admissions to a hospital capable of integrating their post OHCA care with comprehensive on-site cardiovascular services and provide guidance on the potential role of extracorporeal cardiopulmonary resuscitation in patients with refractory cardiac arrest. We believe that knowledge translation through national harmonization and adoption of contemporary best practices has the potential to improve survival and functional outcomes in the OHCA population.

Arrhythmic Events and Mortality in Patients With Cardiogenic Shock on Inotropic Support: Results of the DOREMI Randomized Trial.

BACKGROUND: Inotropic support is widely used in the management of cardiogenic shock (CS). Existing data on the incidence and significance of arrhythmic events in patients with CS on inotropic support is at high risk of bias. METHODS: The Dobutamine Compared to Milrinone (DOREMI) trial randomized patients to receive dobutamine or milrinone in a double-blind fashion. Patients with and without arrhythmic events (defined as arrhythmias requiring intervention or sustained ventricular arrhythmias) were compared to identify factors associated with their occurrence, and to examine their association with in-hospital mortality and secondary outcomes. RESULTS: Ninety-two patients (47.9%) had arrhythmic events, occurring equally with dobutamine and milrinone (P = 0.563). The need for vasopressor support at initiation of the inotrope and a history of atrial fibrillation were positively associated with arrhythmic events, whereas predominant right ventricular dysfunction, previous myocardial infarction, and increasing left ventricular ejection fraction were negatively associated with them. Supraventricular arrhythmic events were not associated with mortality (relative risk [RR], 0.97; 95% confidence interval [CI], 0.68-1.40; P = 0.879) but were positively associated with resuscitated cardiac arrests and hospital length of stay. Ventricular arrhythmic events were positively associated with mortality (RR, 1.66; 95% CI, 1.13-2.43; P = 0.026) and resuscitated cardiac arrests. Arrhythmic events were most often treated with amiodarone (97%) and electrical cardioversion (27%), which were not associated with mortality. CONCLUSIONS: Clinically relevant arrhythmic events occur in approximately one-half of patients with CS treated with dobutamine or milrinone and are associated with adverse clinical outcomes. Five factors may help to identify patients most at risk of arrhythmic events.

Milrinone vs Dobutamine for the Management of Cardiogenic Shock: Implications of Renal Function and Injury.

Background: Cardiogenic shock is associated with poor clinical outcomes. There is a paucity of prospective data examining the efficacy and safety of inotropic therapy in patients with cardiogenic shock and renal dysfunction. Objectives: This study sought to examine the treatment effect of milrinone compared to dobutamine in relation to renal function. Methods: In this post hoc analysis of the DOREMI (Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock) trial, we examined clinical outcomes with milrinone compared to dobutamine after stratification based on baseline estimated glomerular filtration rate (eGFR) 60 ml/min/1.73 m2 and acute kidney injury (AKI). The primary outcome was the composite of in-hospital death from any cause, resuscitated cardiac arrest, receipt of a cardiac transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. Results: Baseline eGFR <60 ml/min/1.73 m2 and AKI were observed in 78 (45%) and 124 (65%) of patients, respectively. The primary outcome and death from any cause occurred in 99 (52%) and 76 (40%) patients, respectively. eGFR <60 ml/min/1.73 m2 did not appear to modulate the treatment effect of milrinone compared to dobutamine. In contrast, there was a significant interaction between the treatment effect of milrinone compared to dobutamine and AKI with respect to the primary outcome (P interaction = 0.02) and death (P interaction = 0.04). The interaction was characterized by lower risk of primary outcome and death with milrinone compared to dobutamine in patients without, but not with, AKI. Conclusions: In patients requiring inotropic support for cardiogenic shock, baseline renal dysfunction and AKI are common. A modulating effect of AKI on the relative efficacy of milrinone compared to dobutamine was observed, characterized by attenuation of a potential clinical benefit with milrinone compared to dobutamine in patients who develop AKI.

Inhaled anaesthesia compared with conventional sedation in post cardiac arrest patients undergoing temperature control: A systematic review and meta-analysis.

INTRODUCTION: Patients admitted with return of spontaneous circulation (ROSC) following out of hospital cardiac arrest (OHCA) are often sedated to facilitate care. Volatile anaesthetics have been proposed as alternative sedatives because of their rapid offset. We performed a systematic review and meta-analysis comparing the use of volatile anaesthetics to conventional sedation in this population. MATERIALS: We searched four databases (MEDLINE, Embase, CENTRAL, and Scopus) from inception to January 6, 2022. We included randomized trials and observational studies evaluating patients admitted following ROSC. We pooled data and reported summary estimates using odds ratio (OR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, both with 95% confidence intervals (CIs). We assessed risk of bias using the Newcastle Ottawa Scale and certainty of evidence using GRADE methodology. RESULTS: Of 1,973 citations, we included three observational studies (n = 604 patients). Compared to conventional sedation, volatile agents had an uncertain effect on delirium (OR 0.96, 95% CI 0.68-1.37), survival to discharge (OR 0.66, 95% CI 0.17-2.61), and ICU length of stay (MD 1.59 days fewer, 95% CI 1.17-4.36, all very low certainty). Patients who received volatile anaesthetic underwent a shorter duration of mechanical ventilation (MD 37.32 hours shorter, 95% CI 7.74-66.90), however this was based on low-certainty evidence. No harms were described with use of volatile anesthetics. CONCLUSION: Volatile anaesthetics may be associated with a decreased duration of mechanical ventilation in patients admitted with ROSC however this is based on low-certainty evidence. Further data are needed to assess their role in this population.

Determinants of long-term dual antiplatelet therapy use in post myocardial infarction patients: Insights from the TIGRIS registry.

BACKGROUND: Patterns of dual antiplatelet therapy (DAPT) use beyond 1 year post-myocardial infarction (MI) have not been well studied. METHODS: TIGRIS (NCT01866904) was a prospective, multi-center (369 centers in 24 countries), observational study of patients 1 to 3 years post-MI. We sought to identify the prevalence and determinants of DAPT use ≥1 year post-MI in patients enrolled in TIGRIS. We used multivariable logistic regression to identify determinants of DAPT use at 396 days post-MI (365 days plus a 31day overrun period to account for intended DAPT discontinuation at 1 year). Patients treated with an oral anticoagulant were excluded. RESULTS: Of 7708 patients (median age 67 years, women 25%, ST-elevation MI 50%), 39% and 16% were on DAPT at 396 days and 5 years post-MI, respectively. DAPT use at 396 days post-MI was more prevalent in patients <65 years of age, treated with percutaneous coronary intervention (versus coronary artery bypass grafting or medical therapy), and with multivessel disease or a history of angina. Additional clinical determinants of ischemic and/or bleeding events following MI (diabetes, second prior MI, hypertension, peripheral artery disease, heart failure, smoking, and renal insufficiency) were not independently associated with DAPT use at 396 days. There were geographic variations in the use of DAPT at 396 days (p<0.001), with the lowest use in Europe and the highest in Asia and Australia. CONCLUSION: In a contemporary patient cohort, DAPT use beyond 1 year post MI was prevalent and associated with patient and index event characteristics. There were marked geographical variations in DAPT use beyond 1 year post MI.

Implications of Myocardial Infarction on Management and Outcome in Cardiogenic Shock.

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.

The association between mean arterial pressure and outcomes in patients with cardiogenic shock: insights from the DOREMI trial.

AIMS: Cardiogenic 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 RESULTS: We 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 < 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 < 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 < 0.01). There were no significant differences in any secondary outcomes between each group. CONCLUSIONS: In 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.

Performance of Plasma Adenosine as a Biomarker for Predicting Cardiovascular Risk.

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.