Double-blind, placebo-controlled, randomized trial of prophylactic metoprolol for reduction of hospital length of stay after heart surgery: The β-Blocker Length Of Stay (BLOS) study

Connolly, Stuart J.; Cybulsky, Irene; Lamy, André; Roberts, Robin S.; O’Brien, Barbara C.; Carroll, Sandra; Crystal, Eugene; Thorpe, Kevin E.; Gent, Michael

doi:10.1067/mhj.2003.147

Cited by 141 publications

(99 citation statements)

References 28 publications

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“…The lack of mechanistic cellular insight into the genesis of oxidative AF hampered the development of effective pharmacological therapy to suppress and/or prevent the oxidative AF [11]. For example, beta-blockers [12] and Amiodarone, [13] considered first line preventive drugs against POAF, are only partially effective. Interestingly, both human and animal studies have shown increased atrial CaMKII activity as the molecular signal that couples oxidative stress with AF [10].…”

Section: Introductionmentioning

confidence: 99%

Atrial Fibrillation Initiated by Early Afterdepolarization-Mediated Triggered Activity during Acute Oxidative Stress: Efficacy of Late Sodium Current Blockade

Pezhouman¹,

Cao

Fishbein

et al. 2018

J Hear Health

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Background The mechanism of Atrial Fibrillation (AF) that emerges spontaneously during acute oxidative stress is poorly defined and its drug therapy remains suboptimal. We hypothesized that oxidative activation of Ca-calmodulin dependent protein kinase (CaMKII) promotes Early Afterdepolarization-(EAD)-mediated triggered AF in aged fibrotic atria that is sensitive to late Na current (INa-L) blockade. Method and Results High-resolution voltage optical mapping of the Left and Right Atrial (LA & RA) epicardial surfaces along with microelectrode recordings were performed in isolated-perfused male Fisher 344 rat hearts in Langendorff setting. Aged atria (23–24 months) manifested 10-fold increase in atrial tissue fibrosis compared to young/adult (2–4 months) atria (P<0001. Spontaneous AF arose in 39 out of 41 of the aged atria but in 0 out of 12 young/adult hearts (P<001) during arterial perfusion of with 0.1 mm of hydrogen peroxide (H2O2). Optical Action Potential (AP) activation maps showed that the AF was initiated by a focal mechanism in the LA suggestive of EAD-mediated triggered activity. Cellular AP recordings with glass microelectrodes from the LA epicardial sites showing focal activity confirmed optical AP recordings that the spontaneous AF was initiated by late phase 3 EAD-mediated triggered activity. Inhibition of CaMKII activity with KN-93 (1 μM) (N=6) or its downstream target, the enhanced INa-L with GS-967 (1 μM), a specific blocker of INa-L (N=6), potently suppressed the AF and prevented its initiation when perfused 15 min prior to H2O2 (n=6). Conclusions Increased atrial tissue fibrosis combined with acute oxidative activation of CaMK II Initiate AF by EAD-mediated triggered activity. Specific block of the INa-L with GS-967 effectively suppresses the AF. Drug therapy of oxidative AF in humans with traditional antiarrhythmic drugs remains suboptimal; suppressing INa-L offers a potential new strategy for effective suppression of oxidative human AF that remains suboptimal.

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Section: Introductionmentioning

confidence: 99%

Atrial Fibrillation Initiated by Early Afterdepolarization-Mediated Triggered Activity during Acute Oxidative Stress: Efficacy of Late Sodium Current Blockade

Pezhouman¹,

Cao

Fishbein

et al. 2018

J Hear Health

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“…The largest trial evaluating the effectiveness of beta-blocker therapy in postoperative AF is the Beta-Blocker Length of Stay (BLOS) study. 15 In this double-blind, placebo-controlled randomized trial of 1,000 patients undergoing cardiac surgery, metoprolol was associated with a 20% relative risk reduction in AF (31% versus 39%; p = 0.01).…”

Section: Beta-blockers and Calcium-channel Blockersmentioning

confidence: 99%

Amiodarone for Atrial Fibrillation Following Cardiac Surgery: Development of Clinical Practice Guidelines at a University Hospital

Khanderia¹,

Wagner²,

Walker³

et al. 2007

Clinical Cardiology

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SummaryAtrial fibrillation (AF) usually develops within the first 72 h following cardiac surgery, and is often selflimiting. Within 48 h of acute onset of symptoms, approximately 50% of patients spontaneously convert to normal sinus rhythm. Thus, the relative risks and benefits of therapy must be carefully considered. The etiology of AF following cardiac surgery is similar to that in nonsurgical patients except that pericardial inflammation and increased adrenergic tone play an increasingly important role. Further, AF after surgery may be associated with transient risk factors that resolve as the patient moves out from surgery, and the condition is less likely to recur compared with AF arising in other circumstances. Immediate heart rate control is important in preventing ischemia, tachycardia-induced cardiomyopathy, and left ventricular dilatation.At our institution, amiodarone is frequently used as a first-line drug for treating AF after cardiac surgery. Inconsistent prescribing practices, variable dosage regimens, and a lack of consensus regarding the appropriate use of amiodarone prompted the need for developing practice guidelines. Multidisciplinary collaboration between the departments of cardiac surgery, pharmacy, and anesthesiology led to the development of a protocol for postoperative AF. We review the clinical evidence from published trials and discuss our guidelines, defining amiodarone use for AF in the cardiac surgery setting.

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“…1 Numerous studies have demonstrated that postoperative atrial fibrillation (AF) is associated with prolonged length of hospital stay, greater risk of major morbidity, and increased overall costs. [2][3][4] More importantly, recent studies have found up to a 2.3-fold increased risk of stroke in patients with postoperative AF. 5 In terms of the effect of postoperative AF on survival, Villareal et al 6 recently published results of the long-term follow-up of patients with postoperative AF (mean 4 years).…”

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confidence: 99%

Prophylactic Intravenous Magnesium Sulphate in Addition to Oral β-Blockade Does Not Prevent Atrial Arrhythmias After Coronary Artery or Valvular Heart Surgery

et al. 2009

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Background-Atrial arrhythmias (AA) are an important cause of morbidity after cardiac surgery. Efforts at prevention of postoperative AA have been suboptimal. Perioperative beta-blocker administration is the standard of care at many centers. Although prophylactic administration of magnesium sulfate (MgSO 4 ) has been recommended, review of all previously published trials of MgSO 4 reveals conflicting results. This study was designed to address methodological shortcomings from previous studies and is the largest randomized, placebo-controlled trial of intravenous (IV) MgSO 4 for the prevention of AA after coronary artery bypass grafting or cardiac valvular surgery. Methods and Results-A total of 927 nonemergent cardiac surgery patients were stratified into 2 groups: isolated coronary artery bypass grafting (nϭ694), or valve surgery with or without coronary artery bypass grafting (nϭ233), and randomized to receive either 5g IV MgSO 4 or placebo on removal of the cross-clamp, followed by daily 4-hour infusions, from postoperative day 1 until postoperative day 4. All patients were treated according to an established oral ␤-blocker protocol. Postoperative serum Mg levels were checked and standard of care was to administer IV MgSO 4 for low serum levels. The primary end point was AA lasting Ն30 minutes or requiring treatment for hemodynamic compromise. There were no differences in the incidence of AA between patients who received IV MgSO 4 or placebo (26.4% versus 24.3%, respectively). The results were similar when broken down according to stratified groups. Conclusions-In patients treated with a protocol for postoperative oral ␤-blocker after nonemergent cardiac surgery, the addition of prophylactic IV MgSO 4 did not reduce the incidence of AA. (Circulation. 2009;120[suppl 1]:S163-S169.)

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Double-blind, placebo-controlled, randomized trial of prophylactic metoprolol for reduction of hospital length of stay after heart surgery: The β-Blocker Length Of Stay (BLOS) study

Cited by 141 publications

References 28 publications

Atrial Fibrillation Initiated by Early Afterdepolarization-Mediated Triggered Activity during Acute Oxidative Stress: Efficacy of Late Sodium Current Blockade

Atrial Fibrillation Initiated by Early Afterdepolarization-Mediated Triggered Activity during Acute Oxidative Stress: Efficacy of Late Sodium Current Blockade

Amiodarone for Atrial Fibrillation Following Cardiac Surgery: Development of Clinical Practice Guidelines at a University Hospital

Prophylactic Intravenous Magnesium Sulphate in Addition to Oral β-Blockade Does Not Prevent Atrial Arrhythmias After Coronary Artery or Valvular Heart Surgery

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