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.).

Inotrope versus placebo therapy in cardiogenic shock: Rationale and study design of the CAPITAL DOREMI2 trial.

BACKGROUND: Cardiogenic shock (CS) is a state of end-organ hypoperfusion related to cardiac dysfunction. Current guidelines recommend consideration of inotrope therapy in patients with CS, however no robust data support their use. The purpose of the CAPITAL DOREMI2 trial is to examine the efficacy and safety of inotrope therapy against placebo in the initial resuscitation of patients with CS. METHODS AND DESIGN: This is a multi-center, double-blind, randomized, placebo-controlled trial comparing single-agent inotrope therapy to placebo in patients with CS. A total of 346 participants with Society for Cardiovascular Angiography and Interventions class C or D CS will be randomized in a 1:1 fashion to inotrope or placebo therapy, which will be administered over a 12-hour period. After this period, participants will continue open-label therapies at the discretion of the treating team. The primary outcome is a composite of all-cause in-hospital death, and, as measured during the 12-hour intervention period, any of: sustained hypotension or high dose vasopressor requirements, lactate greater than 3.5 mmol/L at 6 hours or thereafter, need for mechanical circulatory support, arrhythmia leading to emergent electrical cardioversion, and resuscitated cardiac arrest. All participants will be followed for the duration of their hospitalization, and secondary outcomes will be assessed at the time of discharge. IMPLICATION: This trial will be the first to establish the safety and efficacy of inotrope therapy against placebo in a population of patients with CS and has the potential to alter the standard care provided to this group of patients.

Outcomes in cardiogenic shock: the role of surrogate endpoints.

PURPOSE OF REVIEW: Early revascularization, invasive hemodynamic profiling, and initiation of temporary mechanical circulatory support (MCS) have all become routine components of cardiogenic shock (CS) management. Despite this evolution in clinical practice, patient selection and timing of treatment initiation remain a significant barrier to achieving sustained improvement in CS outcomes. Recent efforts to standardize CS management, through the development of treatment algorithms, have relied heavily on surrogate endpoints to drive therapeutic decisions. The present review aims to provide an overview of the basis of evidence for those surrogate endpoints commonly employed in clinical trials and CS management algorithms. RECENT FINDINGS: Recent publications from both observational and randomized cohorts have demonstrated the utility of surrogate endpoints in risk stratifying patients with CS. In particular, invasive hemodynamics using pulmonary artery catheters to guide initiation and weaning of MCS, biochemical markers that portend imminent end-organ failure, and clinical risk scores that combine multiple hemodynamic and laboratory parameters have demonstrated an ability to prognosticate outcomes in patients with CS. SUMMARY: Although further validation is necessary, multiple clinical, hemodynamic, and biochemical markers have demonstrated utility as surrogate endpoints in CS, and will undoubtedly assist physicians in clinical decision-making.

Acute kidney injury after radial or femoral artery access in ST-segment elevation myocardial infarction: AKI-SAFARI.

BACKGROUND: Acute kidney injury (AKI) complicating primary percutaneous coronary intervention (PCI) is an independent predictor of short- and long-term outcomes in patients presenting with ST-elevation myocardial infarction (STEMI). Prior studies suggest a lower incidence of AKI in patients undergoing PCI through radial artery compared to femoral artery access; however, no randomized clinical trials have specifically investigated this question in patients presenting with STEMI. METHODS: To determine whether radial access (RA) is associated with a reduced frequency of AKI following primary PCI, we performed a substudy of the SAFARI-STEMI trial. The SAFARI-STEMI trial was an open-label, multicenter trial, which randomized patients presenting with STEMI to RA or femoral access (FA), between July 2011 and December 2018. The primary outcome of this post hoc analysis was the incidence of AKI, defined as an absolute (>0.5 mg/dL) or relative (>25%) increase in serum creatinine from baseline. RESULTS: In total 2,285 (99.3%) of the patients enrolled in SAFARI-STEMI were included in the analysis-1,132 RA and 1,153 FA. AKI occurred in 243 (21.5%) RA patients and 226 (19.6%) FA patients (RR: 0.91, 95% CI: 0.78-1.07, P = .27). An absolute increase in serum creatinine >0.5 mg/dL was seen in 49 (4.3%) radial and 52 (4.5%) femoral patients (RR: 1.04, 95% CI: 0.71-1.53, P = .83). AKI was lower in both groups when the KDIGO definition was applied (RA 11.9% vs FA 10.8%; RR: 0.90, 95% CI: 0.72-1.13, P = .38). CONCLUSIONS: Among STEMI patients enrolled in the SAFARI-STEMI trial, there was no association between catheterization access site and AKI, irrespective of the definition applied. These results challenge the independent association between catheterization access site and AKI noted in prior investigations.

Lactate Clearance Is Associated With Improved Survival in Cardiogenic Shock: A Systematic Review and Meta-Analysis of Prognostic Factor Studies.

OBJECTIVE: Elevated blood lactate levels are strongly associated with mortality in patients with cardiogenic shock. Recent evidence suggests that the degree and rate at which blood lactate levels decrease after the initiation of treatment may be equally important in patient prognosis. We performed a systematic review and meta-analysis to evaluate the usefulness of lactate clearance as a prognostic factor in cardiogenic shock. METHODS AND RESULTS: We performed searches of Ovid MEDLINE, Elsevier EMBASE, EBM Reviews-Cochrane Central Register of Controlled Trials, and Web of Science to identify studies comparing lactate clearance between survivors and nonsurvivors at one or more timepoints. Both prospective and retrospective studies were eligible for inclusion. Two study investigators independently screened, extracted data, and assessed the quality of all included studies. Twelve studies were included in the meta-analysis. The median lactate clearance at 6-8 hours was 21.9% (interquartile range [IQR] 14.6%-42.1%) in survivors and 0.6% (IQR -3.7% to 14.6%) in nonsurvivors. At 24 hours, the median lactate clearance was 60.7% (IQR 58.1%-76.3%) and 40.3% (IQR 30.2%-55.8%) in survivors and nonsurvivors, respectively. Accordingly, the pooled mean difference in lactate clearance between survivors and nonsurvivors at 6-8 hours was 17.3% (95% CI 11.6%-23.1%, P < .001) at 6-8 hours and 27.9% (95% CI 14.1%-41.7%, P < .001) at 24 hours. CONCLUSIONS: Survivors had significantly greater lactate clearance at 6-8 hours and at 24 hours compared with nonsurvivors, suggesting that lactate clearance is an important prognostic marker in cardiogenic shock.

Temporary mechanical circulatory support devices: updates from recent studies.

PURPOSE OF REVIEW: Over the past several years, the role of short-term mechanical circulatory support (MCS) devices has become the dominant focus in efforts to improve outcomes in patients with cardiogenic shock (CS). Alongside these efforts, temporary MCS devices have been increasingly used to support patients prior to cardiac surgery, during high-risk percutaneous coronary intervention, awaiting cardiac transplantation, and in the setting of refractory cardiac arrest. The present review aims to provide an update on the recent literature evaluating the evolving role of temporary MCS devices, and to provide insights into the current challenges and future directions of MCS research. RECENT FINDINGS: Recent observational data have demonstrated potential roles for intra-aortic balloon pump preoperatively in high-risk patients awaiting coronary artery bypass grafting, and advanced heart failure patients awaiting transplantation. Impella continues to demonstrate promising results as part of an early MCS strategy in CS, as a temporary bridge to transplantation, and as a mechanism for left ventricular unloading in patients on venoarterial extracorporeal membrane oxygenation (ECMO). Finally, the first randomized trial of ECMO facilitated resuscitation in the United States demonstrated improved survival in patients with refractory out of hospital cardiac arrest. SUMMARY: Though randomized data remains limited, observational data continue to support the role of temporary MCS devices in a variety of clinical settings.

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.

Radial access first for PCI in acute coronary syndrome : Are we propping up a straw man?

Coronary angiography and percutaneous coronary intervention (PCI) represent the recommended revascularization strategy for patients presenting with acute coronary syndrome (ACS). However, periprocedural bleeding events, of which up to 50% are related to the access site, remain an important complication of PCI and are associated with higher costs, prolonged hospital stays, and increased mortality. Several randomized trials have demonstrated that PCI performed via radial artery (RA) access is associated with a reduction in bleeding events, and perhaps a reduction in mortality compared with femoral artery (FA) access. As a result, current practice guidelines from the European Society of Cardiology and the Canadian Cardiovascular Society recommend that RA be the default strategy for PCI in patients presenting with ACS. The recently published Safety and Efficacy of Femoral Access vs. Radial Access in ST-Segment Elevation Myocardial Infarction (SAFARI-STEMI) trial challenges the benefits of a default RA approach in a contemporary setting where additional bleeding-reduction strategies (i.e., avoidance of glycoprotein IIb/IIIa inhibitors, routine use of bivalirudin for procedural anticoagulation, and vascular closure devices) were employed. In order to better understand the evidence that has shaped the current recommendations, we present a review of the background studies and major randomized trials comparing RA with FA in patients presenting with ACS.

Comparative Accuracy of Focused Cardiac Ultrasonography and Clinical Examination for Left Ventricular Dysfunction and Valvular Heart Disease: A Systematic Review and Meta-analysis.

Background: Incorporating focused cardiac ultrasonography (FoCUS) into clinical examination could improve the diagnostic yield of bedside patient evaluation. Purpose: To compare the accuracy of FoCUS-assisted clinical assessment versus clinical assessment alone for diagnosing left ventricular dysfunction or valvular disease in adults having cardiovascular evaluation. Data Sources: English-language searches of MEDLINE, Embase, and Web of Science from 1 January 1990 to 23 May 2019 and review of reference citations. Study Selection: Eligible studies were done in patients having cardiovascular evaluation; compared FoCUS-assisted clinical assessment versus clinical assessment alone for the diagnosis of left ventricular systolic dysfunction, aortic or mitral valve disease, or pericardial effusion; and used transthoracic echocardiography as the reference standard. Data Extraction: Three study investigators independently abstracted data and assessed study quality. Data Synthesis: Nine studies were included in the meta-analysis. The sensitivity of clinical assessment for diagnosing left ventricular dysfunction (left ventricular ejection fraction <50%) was 43% (95% CI, 33% to 54%), whereas that of FoCUS-assisted examination was 84% (CI, 74% to 91%). The specificity of clinical assessment was 81% (CI, 65% to 90%), and that of FoCUS-assisted examination was 89% (CI, 85% to 91%). The sensitivities of clinical assessment and FoCUS-assisted examination for diagnosing aortic or mitral valve disease (of at least moderate severity) were 46% (CI, 35% to 58%) and 71% (CI, 63% to 79%), respectively. Both the clinical assessment and the FoCUS-assisted examination had a specificity of 94% (CI, 91% to 96%). Limitation: Evidence was scant, persons doing ultrasonography had variable skill levels, and most studies had unclear or high risk of bias. Conclusion: Clinical examination assisted by FoCUS has greater sensitivity, but not greater specificity, than clinical assessment alone for identifying left ventricular dysfunction and aortic or mitral valve disease; FoCUS-assisted examination may help rule out cardiovascular pathology in some patients, but it may not be sufficient for definitive confirmation of cardiovascular disease suspected on physical examination. Primary Funding Source: None. (PROSPERO: CRD42019124318).

In-hospital outcomes of STEMI patients on warfarin undergoing primary PCI.

OBJECTIVES: We sought to describe the safety and efficacy outcomes of patients on warfarin presenting with ST-elevation myocardial infarction (STEMI). BACKGROUND: Limited data exist on the outcomes and optimal management of STEMI patients on warfarin undergoing primary percutaneous coronary intervention (PCI). METHODS: Baseline characteristics and outcomes were prospectively collected for 2,390 consecutive STEMI patients referred for primary PCI. Patients were stratified based on warfarin use at baseline. The primary safety endpoint was the rate of in-hospital bleeding (a composite of major bleeding or minor bleeding) according to the thrombolysis in myocardial infarction (TIMI) classification. Efficacy endpoints included major adverse cardiovascular events (MACE), defined as death, myocardial infarction, or stroke, as well as intracranial bleeding, cardiogenic shock, and length of stay. Multiple logistic regression was used to determine if warfarin was independently associated with bleeding and MACE. RESULTS: Warfarin patients (n = 59 vs. n = 2,331) were significantly older (73.2 years vs. 61.7 years; P < 0.01), and more likely to present as Killip Class IV (13.6% vs. 2.7%; P < 0.01). TIMI major/minor bleeding occurred in 30.4% of the warfarin patients and 14.2% of the control patients (P < 0.01). After adjustment warfarin was independently associated with an increased risk of bleeding (OR 2.08; P = 0.04). Warfarin patients also had an increased frequency of MACE (20.3% vs. 5.9%; P < 0.01), though this was not significant after adjustment (OR 2.00; P = 0.10). CONCLUSIONS: STEMI patients on warfarin referred for primary PCI are more likely to experience bleeding. New strategies are needed to optimize the management and minimize bleeding in this high-risk population.

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.

Pharmacogenetics in the Development of Lipid Lowering Medications: Lomitapide & Mipomersen in Clinical Practice.

INTRODUCTION: The familial hypercholesterolemias (FH) are a group of undertreated genetically inherited disorders of lipid metabolism that lead to severely elevated cholesterol levels and early onset cardiovascular disease. Aggressive lifestyle modifications and lipid-lowering medications such as statins and bile acid sequestrants are the backbone of current treatment. Despite these interventions, homozygous FH (HoFH) patients are unable to reach LDL-C targets and remain at significantly increased risk of cardiovascular disease. Recently, two novel lipid-lowering medications, lomitapide and mipomersen, have been approved for the treatment of HoFH. CASE DESCRIPTIONS: We present two patients with HoFH who have been unable to reach target LDL-C goals on standard therapy. Patient A is a 41-year-old male and patient B is a 64-year-old female, both of whom have complex histories of multi-vessel coronary artery disease. In attempt to improve their LDL-C levels and lower their cardiovascular risk, lomitapide and mipomersen were initiated in patient A and B, respectively. DISCUSSION/CONCLUSION: Through inhibition of the microsomal triglyceride transfer protein, lomitapide prevents the formation of triglyceride rich lipoproteins. Mipomersen is an antisense oligonucleotide that inhibits the translation of apolipoprotein B-100. Both medications employ novel mechanisms developed through advances in pharmacogenetic technology and achieve unprecedented LDL-C reductions.

Mitral Regurgitation Complicated by Cardiogenic Shock: Reassessing Risk Stratification and Therapeutic Strategies.

Mitral regurgitation complicated by cardiogenic shock creates a unique and devastating risk profile for patients and poses significant difficulties for physicians who lack a comprehensive range of effective management strategies. Supportive measures such as intravenous vasodilators, intra-aortic balloon pumps, and percutaneous ventricular assist devices are often necessary to stabilize patients prior to definitive treatment with surgical mitral valve replacement or trans-catheter edge-to-edge repair. This review evaluates the evidence for the available supportive and definitive management strategies in patients with mitral regurgitation complicated by cardiogenic shock and presents a framework to aid clinicians in navigating the complex clinical decision-making process. Additionally, the authors review emerging transcatheter mitral valve replacement technologies that hold promise for expanding the therapeutic armamentarium and improving patient outcomes.

Efficacy of Milrinone and Dobutamine in Cardiogenic Shock: An Updated Systematic Review and Meta-Analysis.

OBJECTIVES: Inotropic support is commonly used in patients with cardiogenic shock (CS). High-quality data guiding the use of dobutamine or milrinone among this patient population is limited. We compared the efficacy and safety of these two inotropes among patients with low cardiac output states (LCOS) or CS. DATA SOURCES: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched up to February 1, 2023, using key terms and index headings related to LCOS or CS and inotropes. DATA EXTRACTION: Two independent reviewers included studies that compared dobutamine to milrinone on all-cause in-hospital mortality, length of ICU stay, length of hospital stay, and significant arrhythmias in hospitalized patients. DATA SYNTHESIS: A total of eleven studies with 21,084 patients were included in the meta-analysis. Only two randomized controlled trials were identified. The primary outcome, all-cause mortality, favored milrinone in observational studies only (odds ratio [OR] 1.19 (95% CI, 1.02-1.39; p = 0.02). In-hospital length of stay (LOS) was reduced with dobutamine in observational studies only (mean difference -1.85 d; 95% CI -3.62 to -0.09; p = 0.04). There was no difference in the prevalence of significant arrhythmias or in ICU LOS. CONCLUSIONS: Only limited data exists supporting the use of one inotropic agent over another exists. Dobutamine may be associated with a shorter hospital LOS; however, there is also a potential for increased all-cause mortality. Larger randomized studies sufficiently powered to detect a difference in these outcomes are required to confirm these findings.

Diagnostic accuracy of point-of-care ultrasound with artificial intelligence-assisted assessment of left ventricular ejection fraction.

Focused cardiac ultrasound (FoCUS) is becoming standard practice in a wide spectrum of clinical settings. There is limited data evaluating the real-world use of FoCUS with artificial intelligence (AI). Our objective was to determine the accuracy of FoCUS AI-assisted left ventricular ejection fraction (LVEF) assessment and compare its accuracy between novice and experienced users. In this prospective, multicentre study, participants requiring a transthoracic echocardiogram (TTE) were recruited to have a FoCUS done by a novice or experienced user. The AI-assisted device calculated LVEF at the bedside, which was subsequently compared to TTE. 449 participants were enrolled with 424 studies included in the final analysis. The overall intraclass coefficient was 0.904, and 0.921 in the novice (n = 208) and 0.845 in the experienced (n = 216) cohorts. There was a significant bias of 0.73% towards TTE (p = 0.005) with a level of agreement of 11.2%. Categorical grading of LVEF severity had excellent agreement to TTE (weighted kappa = 0.83). The area under the curve (AUC) was 0.98 for identifying an abnormal LVEF (<50%) with a sensitivity of 92.8%, specificity of 92.3%, negative predictive value (NPV) of 0.97 and a positive predictive value (PPV) of 0.83. In identifying severe dysfunction (<30%) the AUC was 0.99 with a sensitivity of 78.1%, specificity of 98.0%, NPV of 0.98 and PPV of 0.76. Here we report that FoCUS AI-assisted LVEF assessments provide highly reproducible LVEF estimations in comparison to formal TTE. This finding was consistent among senior and novice echocardiographers suggesting applicability in a variety of clinical settings.

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.

Treatment Intensity for the Management of Cardiogenic Shock: Comparison Between STEMI and Non-STEMI.

Background: Cardiogenic shock is a leading cause of mortality in patients with acute myocardial infarction. Objectives: The authors sought to compare clinical characteristics, hospital trajectory, and drug and device use between patients with ST-segment elevation myocardial infarction-related cardiogenic shock (STEMI-CS) and those without (non-ST-segment elevation myocardial infarction complicated by cardiogenic shock [NSTEMI-CS]). Methods: We analyzed data from 1,110 adult admissions with cardiogenic shock complicating acute myocardial infarction (AMI-CS) across 17 centers within Cardiogenic Shock Working Group. The primary end point was in-hospital mortality. Results: Our study included 1,110 patients with AMI-CS, of which 731 (65.8%) had STEMI-CS and 379 (34.2%) had NSTEMI-CS. Most patients were male (STEMI-CS: 71.6%, NSTEMI-CS: 66.5%) and White (STEMI-CS: 53.8%, NSTEMI-CS: 64.1%). In-hospital mortality was 41% and was similar among patients with STEMI-CS and NSTEMI-CS (43% vs 39%, P = 0.23). Patients with out-of-hospital cardiac arrest had higher in-hospital mortality in patients with NSTEMI-CS (63% vs 36%, P = 0.006) as compared to patients with STEMI-CS (52% vs 41%, P = 0.16). Similar results were observed for in-hospital cardiac arrest in patients with STEMI-CS (63% vs 33%, P < 0.001) and NSTEMI-CS (60% vs 32%, P < 0.001). Only 27% of patients with STEMI-CS and 12% of NSTEMI-CS received both a drug and temporary mechanical circulatory support device during the first 24 hours, which increased to 78% and 61%, respectively, throughout the course of the hospitalization (P < 0.001 for both). Conclusions: Despite increasing use of inotropic and vasoactive support and mechanical circulatory support throughout the hospitalization, both patients with STEMI-CS and NSTEMI-CS remain at increased risk for in-hospital mortality. Randomized controls trials are needed to elucidate whether timing and sequence of escalation of support improves outcomes in patients with AMI-CS.

Left Ventricular Unloading Before Percutaneous Coronary Intervention is Associated With Improved Survival in Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock: A Systematic Review and Meta-Analysis.

BACKGROUND: Left ventricular unloading with Impella may improve survival outcomes in patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS). However, the optimal timing to initiate left ventricular unloading has yet to be established. Therefore, we conducted a systematic review and meta-analysis to compare survival in patients with AMI-CS who were supported with Impella prior to PCI (pre-PCI) to those in whom support was initiated following PCI (post-PCI). METHODS: All studies that evaluated the impact of pre-PCI versus post-PCI Impella placement in patients with AMI-CS were included. Primary endpoints included in-hospital, 30-day, and 6-month survival rates. RESULTS: We identified five observational studies comparing outcomes in 432 patients with AMI-CS, of which 173 patients were treated with Impella pre-PCI and 259 patients post-PCI. Patients in the pre-PCI group had lower in-hospital mortality compared to patients in the post-PCI group (RR 0.62, 95% CI: 0.50-0.76, I2 = 0%). The lower mortality rate in the pre-PCI group remained evident at 30 days (HR 0.60, 95% CI: 0.47-0.78, I2 = 0%) and at 6 months (HR 0.66, 95% CI: 0.44-0.97, I2 = 0%). There was no difference in the risk of adverse events including reinfarction, stroke, major bleeding, acute ischemic limb, access site bleeding, and hemolysis. CONCLUSIONS: In this meta-analysis of studies evaluating survival among AMI-CS patients with left ventricular unloading initiated pre- versus post-PCI, Impella placement prior to PCI was associated with improved survival.

Strategies to reduce limb ischemia in peripheral venoarterial extracorporeal membrane oxygenation: A systematic review and Meta-analysis.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides cardiovascular and respiratory support for patients in cardiogenic shock; yet, complications are a frequent source of morbidity and mortality. Limb ischemia can be potentially mitigated by limp perfusion protection strategies (LPPS). We performed a systematic review and meta-analysis to evaluate the safety and efficacy of two LPPS in patients treated with peripheral VA-ECMO - prophylactic insertion of a distal perfusion catheter (DPC) and small bore (<17 Fr) arterial return cannula. Among 22 included studies, limb ischemia was reduced in patients receiving a small arterial cannula (OR 0.40, 95% CI 0.24-0.65; p < 0.001) and in patients receiving a prophylactic DPC (OR 0.31, 95% CI 0.21-0.47; p < 0.001). Mortality was not significantly reduced with either a small arterial cannula (OR 0.70, 95% CI 0.23-2.18; p = 0.54) or prophylactic DPC strategy (OR 0.89, 95% CI 0.67-1.17; p = 0.40). As such, prophylactic insertion of a DPC or smaller bore arterial return cannula appear to reduce the risk of lower limb ischemia in this analysis. Further data are needed to confirm these findings. Registration: Registered in PROSPERO Database (Registration CRD42020215677).