Cardiogenic shock is a high-acuity, potentially complex, and hemodynamically diverse state of end-organ hypoperfusion that is frequently associated with multisystem organ failure. Despite improving survival in recent years, patient morbidity and mortality remain high, and there are few evidence-based therapeutic interventions known to clearly improve patient outcomes. This scientific statement on cardiogenic shock summarizes the epidemiology, pathophysiology, causes, and outcomes of cardiogenic shock; reviews contemporary best medical, surgical, mechanical circulatory support, and palliative care practices; advocates for the development of regionalized systems of care; and outlines future research priorities. Cardiogenic shock (CS) is a low-cardiac-output state resulting in life-threatening end-organ hypoperfusion and hypoxia.1,2 Acute myocardial infarction (MI) with left ventricular (LV) dysfunction remains the most frequent cause of CS. 1,3 Advances in reperfusion therapy have been associated with improvements in survival, but significant regional disparities in evidence-based care have been reported, and in-hospital mortality remains high (27%-51%).1,4-9 Management recommendations are distributed between disease-specific statements and guidelines, and a dedicated and comprehensive clinical resource in this area is lacking. Thus, consolidating the evidence to define contemporary best medical and surgical CS practices for both MI-associated CS and other types of CS may be an important step in knowledge translation to help attenuate disparities in evidence-based care.Regional systems of care coupled with treatment algorithms have improved survival in high-acuity time-sensitive conditions such as MI, out-of-hospital cardiac arrest (OHCA), and trauma.10-12 Applying a similar framework to CS management may lead to similar improvements in survival, and CS systems of care are emerging within existing regional cardiovascular emergency care networks; however, guidance from a national expert group on structure and systems of care has not been available. 13,14 Accordingly, the purposes of this American Heart Association (AHA) scientific statement on CS are to summarize our contemporary understanding of the epidemiology, pathophysiology, and in-hospital best care practices into a single clinical resource document; to suggest a stepwise management algorithm that integrates medical, surgical, and mechanical circulatory support (MCS) therapies; and to propose a Mission: Lifelinesupported pathway for the development of integrated regionalized CS systems of care. DEFINITION OF CSAcute cardiac hemodynamic instability may result from disorders that impair function of the myocardium, valves, conduction system, or pericardium, either in isolation HISTORICAL PERSPECTIVESBefore the routine use of early revascularization, MIassociated CS had an in-hospital mortality exceeding 80%. A registry trial of 250 patients with acute MI described the association between bedside physical examination (Killip classification) for the as...

M ultiple medications are common in the treatment of adult patients. This is particularly true in elderly patients with chronic medical conditions such as atrial fibrillation (AF). The use of multiple medications in a single patient, called polypharmacy, is becoming more prevalent in contemporary, guidelinedriven practice. Continuing medical education (CME) credit is available for this article. Go to http://cme.ahajournals.org to take the quiz.

Non–vitamin K oral anticoagulants (NOACs) are now widely used as alternatives to warfarin for stroke prevention in atrial fibrillation and management of venous thromboembolism. In clinical practice, there is still widespread uncertainty on how to manage patients on NOACs who bleed or who are at risk for bleeding. Clinical trial data related to NOAC reversal for bleeding and perioperative management are sparse, and recommendations are largely derived from expert opinion. Knowledge of time of last ingestion of the NOAC and renal function is critical to managing these patients given that laboratory measurement is challenging because of the lack of commercially available assays in the United States. Idarucizumab is available as an antidote to rapidly reverse the effects of dabigatran. At present, there is no specific antidote available in the United States for the oral factor Xa inhibitors. Prothrombin concentrate may be considered in life-threatening bleeding. Healthcare institutions should adopt a NOAC reversal and perioperative management protocol developed with multidisciplinary input.

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Objective To determine whether the treatment effect of apixaban versus warfarin differs with increasing numbers of concomitant drugs used by patients with atrial fibrillation.Design Post hoc analysis performed in 2015 of results from ARISTOTLE (apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation)—a multicentre, double blind, double dummy trial that started in 2006 and ended in 2011.Participants 18 201 ARISTOTLE trial participants.Interventions In the ARISTOTLE trial, patients were randomised to either 5 mg apixaban twice daily (n=9120) or warfarin (target international normalised ratio range 2.0-3.0; n=9081). In the post hoc analysis, patients were divided into groups according to the number of concomitant drug treatments used at baseline (0-5, 6-8, ≥9 drugs) with a median follow-up of 1.8 years. Main outcome measures Clinical outcomes and treatment effects of apixaban versus warfarin (adjusted for age, sex, and country).Results Each patient used a median of six drugs (interquartile range 5-9); polypharmacy (≥5 drugs) was seen in 13 932 (76.5%) patients. Greater numbers of concomitant drugs were used in older patients, women, and patients in the United States. The number of comorbidities increased across groups of increasing numbers of drugs (0-5, 6-8, ≥9 drugs), as did the proportions of patients treated with drugs that interact with warfarin or apixaban. Mortality also rose significantly with the number of drug treatments (P<0.001), as did rates of stroke or systemic embolism (1.29, 1.48, and 1.57 per 100 patient years, for 0-5, 6-8, and ≥9 drugs, respectively) and major bleeding (1.91, 2.46, and 3.88 per 100 patient years, respectively). Relative risk reductions in stroke or systemic embolism for apixaban versus warfarin were consistent, regardless of the number of concomitant drugs (Pinteraction=0.82). A smaller reduction in major bleeding was seen with apixaban versus warfarin with increasing numbers of concomitant drugs (Pinteraction=0.017). Patients with interacting (potentiating) drugs for warfarin or apixaban had similar outcomes and consistent treatment effects of apixaban versus warfarin.Conclusions In the ARISTOTLE trial, three quarters of patients had polypharmacy; this subgroup had an increased comorbidity, more interacting drugs, increased mortality, and higher rates of thromboembolic and bleeding complications. In terms of a potential differential response to anticoagulation therapy in patients with atrial fibrillation and polypharmacy, apixaban was more effective than warfarin, and is at least just as safe.Trial registration ARISTOTLE trial, ClinicalTrials.gov NCT00412984.

Dronedarone is less effective than amiodarone for the maintenance of sinus rhythm, but has fewer adverse effects. For every 1,000 patients treated with dronedarone instead of amiodarone, we estimate approximately 228 more recurrences of AF in exchange for 9.6 fewer deaths and 62 fewer adverse events requiring discontinuation of drug.

2246Objective-To review the literature systematically to determine whether initiation of beta blockade within 45 days prior to noncardiac surgery reduces 30-day cardiovascular morbidity and mortality rates. Methods- PubMed (up to April 2013), Embase (up to April 2013), Cochrane Central Register of Controlled Trials (up to March 2013), and conference abstracts (January 2011 to April 2013) were searched for randomized controlled trials (RCTs) and cohort studies comparing perioperative beta blockade with inactive control during noncardiac surgery. Pooled relative risks (RRs) were calculated under the random-effects model. We conducted subgroup analyses to assess how the The American Heart Association requests that this document be cited as follows: Wijeysundera DN, Duncan D, Nkonde-Price C, Virani SS, Washam JB, Fleischmann KE, Fleisher LA. Perioperative beta blockade in noncardiac surgery: a systematic review for the 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130:2246-2264 This article has been copublished in the Journal of the American College of Cardiology.Copies: This document is available on the World Wide Web sites of the American College of Cardiology (www.cardiosource.org) and the American Heart Association (my.americanheart.org). A copy of the document is available at http://my.americanheart.org/statements by selecting either the "By Topic" link or the "By Publication Date" link. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@wolterskluwer.com.Expert peer review of AHA Scientific Statements is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelines development, visit http://my.americanheart.org/statements and select the "Policies and Development" link.Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at http://www.heart.org/HEARTORG/General/CopyrightPermission-Guidelines_UCM_300404_Article.jsp. A link to the "Copyright Permissions Request Form" appears on the right side of the page. Perioperative Beta Blockade in Noncardiac Surgery IntroductionPerioperative cardiac complications are an important concern for the 230 million individuals who undergo surgery worldwide every year.1 After surgery, 2% of these patients suffer major cardiac complications, 2 and 8% show evidence of significant myocardial injury.3 Perioperative beta blockade showed early promise as a means of preventing these complications, with enthusiasm driven by promising results in 2 RCTs. 4,5 Consequently, perioperative beta blockade was recommended for a fairly broad spectrum of surgical patients in initial versions of the American College of Cardiology (ACC)/ American Heart Associat...

Background: There is no randomized data evaluating the safety or efficacy of apixaban for stroke prevention in patients with end-stage kidney disease (ESKD) on hemodialysis and with atrial fibrillation (AF). Methods: The RENAL-AF trial was a prospective, randomized, open-label, blinded-outcome evaluation (PROBE) of apixaban versus warfarin in patients receiving hemodialysis with AF and CHA 2 DS 2 -VASc score ≥2. Patients were randomized 1:1 to apixaban 5mg twice daily (2.5mg twice daily with age ≥80 years and/or weight ≤60kg) or dose-adjusted warfarin. The primary outcome was time to major or clinically relevant non-major bleeding. Secondary outcomes included stroke, mortality, and apixaban pharmacokinetics. Pharmacokinetic sampling was day 1, day 3, and month 1. Results: From January 2017 through January 2019, 154 patients were randomized to apixaban (n=82) or warfarin (n=72). The trial stopped prematurely due to enrollment challenges. Time in therapeutic range (INR 2.0-3.0) for warfarin-treated patients was 44% (interquartile range; 23-59%). The 1-year rates for major or clinically relevant non-major bleeding were 32% and 26% in apixaban and warfarin groups, respectively (HR 1.20, 95% CI 0.63-2.30), while 1-year rates for stroke or systemic embolism were 3.0% and 3.3% in apixaban and warfarin groups, respectively. Death was the most common major event in the apixaban (21 patients [26%]) and warfarin (13 patients [18%]) arms. The pharmacokinetic substudy enrolled the target 50 patients. Median steady state 12-hour area under the curve (AUC0-12) was 2,475 ng-h/mL (10 th -90 th percentiles 1,342-3,285) for 5mg apixaban twice daily and 1,269 ng-h/mL (10 th -90 th percentiles 615-1,946) for 2.5mg apixaban twice daily. There was substantial overlap between minimum apixaban blood concentration, 12-hour AUC0-12, and maximum apixaban blood concentration for patients with and without a major or clinically relevant non-major bleeding events. Conclusions: There was inadequate power to draw any conclusion regarding rates of major or clinically relevant non-major bleeding comparing apixaban and warfarin in patients with AF and ESKD on hemodialysis. Clinically relevant bleeding events were approximately 10-fold more frequent than stroke or systemic embolism among this population on anticoagulation, highlighting the need for future randomized studies evaluating the risks versus benefits of anticoagulation among patients with AF and ESKD on hemodialysis.