SPECIAL ARTICLE
The Year in Cardiothoracic and Vascular Anesthesia: Selected Highlights From 2014 Jacob T. Gutsche, MD,* Prakash A. Patel, MD,* Frederick C. Cobey, MD, MPH,† Harish Ramakrishna, MD, FASE,‡ Emily K. Gordon, MD,* Hynek Riha, MD, DEAA, FCCP,§ Aris Sophocles, MD,* Kamrouz Ghadimi, MD,¶ Michael Fabbro, MD,* Lourdes Al-Ghofaily, MD,* Sy-Yeu S. Chern, MD,* Sophia Cisler, MD,* Gurmukh S. Sahota, MD,* Elizabeth Valentine, MD,* Stuart J. Weiss, MD, PhD,* Michael Andritsos, MD,║ George Silvay, MD, PhD,** and John G.T. Augoustides, MD, FASE, FAHA*
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HIS ARTICLE IS THE SEVENTH in the annual series for the Journal of Cardiothoracic and Vascular Anesthesia.1 The authors thank the editor-in-chief, Dr. Kaplan, and the editorial board for the opportunity to continue this series; namely, the research highlights of the year that pertain to the specialty of cardiothoracic and vascular anesthesia. The major themes selected for this past year will be outlined in this introduction and then each highlight will be reviewed in detail in the main body of the article. The literature highlights in the specialty for 2014 begin with the release of the new guidelines about perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery.2 A pervasive theme throughout this important guideline is the detection and prevention of myocardial injury after noncardiac surgery that is explored in detail in this article because it is a common cause of perioperative mortality. The second major theme in our specialty for 2014 is the explosion of new therapeutic options for the management of atrial fibrillation (AF). The importance of these paradigm shifts for this common arrhythmia is reflected by the recent publication of comprehensive guidelines in both Europe and North America. The third major theme for the specialty is the revolution in adult aortic arch repair due to innovations such as moderate hypothermic circulatory arrest and hybrid aortic arch repair. The themes selected for this seventh highlights article only sample the advances in the specialty for 2014. The patient care processes identified in these highlights will further improve important perioperative outcomes for patients with cardiovascular disease in both cardiac and noncardiac surgery. MYOCARDIAL INJURY AFTER NONCARDIAC SURGERY
The Detection of Myocardial Injury After Noncardiac Surgery The recent guidelines from the American College of Cardiology (ACC) and American Heart Association (AHA) on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery have 9 sections, more than 100 pages of text and figures, and 490 references.2 Although a detailed summary of this landmark document is beyond the scope of this highlights article, the emphasis on myocardial ischemia is pervasive throughout this important document. A dominant theme in these perioperative guidelines is myocardial ischemia, given that it is a leading cause of
perioperative mortality worldwide.3,4 The importance of perioperative myocardial ischemia in the Journal is evidenced by the fact that more than 150 articles published in the past 2 years are related to this topic (electronic search in ScienceDirect for the Journal of Cardiothoracic and Vascular Anesthesia conducted on September 20, 2014, key word: Myocardial ischemia). Although the universal definition of myocardial infarction typically includes an elevated troponin in combination with an ischemic symptom and/or an ischemic electrocardiographic tracing, defining factors such as symptoms and electrocardiographic changes frequently may not accompany the presentation of myocardial ischemia in the perioperative setting.5,6 The question is whether there is a better way to detect this lifethreatening complication, given these limitations. A recent analysis (n = 15,065) from the large international prospective Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) study developed diagnostic criteria for myocardial injury after noncardiac surgery (MINS) as a primary objective.6 The secondary objectives of this analysis
From the *Cardiovascular and Thoracic Section, Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, †Tufts University School of Medicine, Boston, Massachusetts, ‡Mayo Clinic, Scottsdale, Arizona; §Cardiothoracic Anesthesiology and Intensive Care, Department of Anesthesiology and Intensive Care Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic, ¶Department of Anesthesiology and Critical Care, Duke University, Durham, North Carolina, ║Department of Anesthesiology, Ohio State University, Columbus, Ohio; and **Department of Anesthesiology and Critical Care, Icahn School of Medicine, Mount Sinai Hospital, New York, New York. Address reprint requests to John G. T. Augoustides, MD, FASE, FAHA, Cardiothoracic Section, Anesthesiology and Critical Care, Dulles 680, HUP, 3400 Spruce Street, Philadelphia, PA, 19104-4283. E-mail: [email protected] © 2014 Elsevier Inc. All rights reserved. 1053-0770/2601-0001$36.00/0 http://dx.doi.org/10.1053/j.jvca.2014.10.002 Key words: perioperative cardiovascular evaluation, guidelines, VISION study, myocardial injury after noncardiac surgery, troponins, aspirin, clonidine, POISE-2 study, atrial fibrillation, stroke, bleeding, risks scores, dabigatran, factor Xa inhibitors, left atrial appendage occlusion, surgical ablation, aortic arch, moderate hypothermic circulatory arrest, antegrade cerebral perfusion, hybrid aortic arch repair, paradigm shifts
Journal of Cardiothoracic and Vascular Anesthesia, Vol 29, No 1 (February), 2015: pp 1–7
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were to determine the characteristics, predictors, and perioperative outcomes of MINS at 30 days (full details of the ongoing VISION study are available at www.clincialtrials.gov, trial identifier NCT00512109).6 The principal finding from the VISION clinical registry was that MINS was diagnosed best by a peak perioperative troponin T level Z0.03 ng/mL that was not attributable to a nonischemc etiology. This definition of MINS does not require an ischemic presentation with respect to clinical symptoms, signs, and electrocardiographic features.6 In fact, only 41.8% of patients with MINS fulfilled the universal definition of myocardial infarction; the remaining 51.2% who did not rule in for myocardial infarction by classic criteria had a 30-day mortality rate of 7.7%.5,6 Furthermore, according to this definition, MINS had an incidence of 8.0% and was associated significantly with cardiovascular complications and mortality at 30 days; it explained 34% of all deaths in adults in the first 30 days after noncardiac surgery.6 The VISION trial data have highlighted that MINS is common and important. The global impact of these observations is staggering; about 8 million adults suffer MINS worldwide each year, assuming that that the annual volume of adult noncardiac surgery is about 100 million cases.6 Given this massive caseload, MINS likely accounts for more than 2 million deaths after noncardiac surgery worldwide every year.6,7 Further trials are, therefore, essential to identify strategies to prevent and manage the serious complication of MINS.6,8,9 The consequences of perioperative myocardial ischemia have been realized globally, as evidenced by the recent large trials in Europe and Asia.8,9 A large single-center analysis from China (n = 117,856: 2003-2011) found that perioperative myocardial infarction after adult noncardiac surgery had an incidence of 5.2 per 10,000, although it significantly increased with age to an incidence of 40.4 per 10,000 for adults aged Z75 years (p o 0.001).9 The mortality rate for patients with myocardial ischemia was 36.1%, which was more than 100 times higher than patients with no perioperative myocardial ischemia (36.1% v 0.32%; p o 0.001).9 Furthermore, in this study myocardial infarction typically occurred within 72 hours after surgery without chest pain and with non-ST segment changes on the electrocardiogram.9 Taken collectively, these perioperative trials also have highlighted the gaps in the current universal definition of myocardial infarction with respect to perioperative practice; this definition at times may not be clinically relevant. This lack of clinical relevance not only has resulted in the VISION registry but also has led to recent consideration of a new definition of clinically relevant myocardial infarction after coronary revascularization, whether due to percutaneous coronary intervention or coronary artery bypass grafting.10 Given these gaps in the current definition of myocardial infarction, it is likely that the universal definition of myocardial infarction will be revised in the near future. The 2014 ACC/AHA guidelines deal with MINS in section 8 entitled “perioperative surveillance.”2 In the setting of signs and symptoms suggestive of perioperative myocardial ischemia, the guidelines strongly recommend the analysis of an electrocardiogram (Class I recommendation; Level of Evidence B) and the measurement of troponins (Class I recommendation;
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Level of Evidence A).2 The routine measurement of troponins in patients at high risk for MINS was recommended less strongly in the absence of a defined management strategy with known risks and benefits (Class IIb recommendation; Level of Evidence B).2 The routine postoperative measurement of troponins in unselected patients was not recommended (Class III recommendation; level of Evidence B).2 The VISION trials have, through perioperative surveillance, facilitated the discovery of a gap in perioperative care, namely the detection and management of MINS.4–6 Although a troponin-based definition has refined the identification of MINS in at-risk patients, the question now becomes what interventions are available to prevent this serious complication. The Prevention of Myocardial Injury After Noncardiac Surgery The perioperative therapy for MINS is reviewed in detail in section 6 of the recent ACC/AHA guidelines.2 The first subsection deals with recommendations for coronary revascularization before noncardiac surgery, including surgical timing in patients who have undergone previous percutaneous coronary intervention.2 The second subsection deals with perioperative medical therapy, including beta-blockers, alpha2-agonists, and antiplatelet agents.2 The recommendations for perioperative beta-blockade in these guidelines are based on a recent systematic review of the evidence that was specially commissioned to address the scientific misconduct in the work by Dr. Poldermans.2,11 The issue of research misconduct has been reviewed previously in this article series.12 The key findings of the ACC/AHA systematic review were not affected significantly by the exclusion of the relevant published studies by Dr. Poldermans. Full details of this evidence analysis are provided both in the guidelines and the separately published metaanalysis.2,12 The first strong recommendation in the new guidelines is that betablockers should be continued in patients undergoing surgery who have been on these agents chronically (Class I recommendation; Level of Evidence B).2 The second strong recommendation is that beta-blockade should not be commenced on the day of surgery (Class III recommendation; Level of Evidence B).2 The remaining 5 recommendations about betablockers in this guideline are Class II and are discussed comprehensively in section 6.2 (subsection 1).2 The roles of this group of pharmacologic agents, in both cardiac and noncardiac surgery, continue to be explored vigorously and debated in the Journal: 73 articles were devoted to this topic in the Journal within the past 2 years, including a recent metaanalysis (electronic search in ScienceDirect for the Journal of Cardiothoracic and Vascular Anesthesia conducted on September 22, 2014, key word: beta-blockers).13 The guidelines also have strongly recommended against apha2-agonists for prevention of myocardial events in patients undergoing noncardiac surgery (Class III recommendation; Level of Evidence B).2 The recent international randomized Perioperative Ischemic Evaluation-2 (POISE-2) trial evaluated the effects of low-dose clonidine (0.2 mg/day) in patients with or at risk for atherosclerotic disease who underwent noncardiac surgery (n ¼ 10,010: 135 centers in 23 countries).14,15 In this
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landmark trial, low-dose clonidine was started just before surgery and continued for 72 hours. The primary trial outcome was defined as a composite of death or nonfatal myocardial infarction at 30 days. Clonidine did not reduce this primary outcome (hazard ratio 1.08; 95% confidence interval 0.93-1.26; p = 0.29).15 Furthermore, exposure to clonidine significantly increased the risks of clinically important hypotension (hazard ratio 1.32; 95% confidence interval 1.24-1.40; p o 0.001) and nonfatal cardiac arrest (hazard ratio 3.20; 95% confidence interval 1.17-8.73; p ¼ 0.02).15 The adverse outcomes of clonidine in noncardiac surgery explain the Class III recommendation for this agent in the ACC/AHA perioperative guidelines.2,15 The POISE-2 investigators also investigated the effects of aspirin in adult noncardiac surgery.16 Patients at risk for vascular events were stratified according to previous aspirin exposure. The initiation stratum (n ¼ 5,628), consisting of patients who were not previously on aspirin, were randomized to aspirin (initial dose 200 mg followed by 100 mg daily) placebo that began on the day of surgery and continued for 30 days. The continuation stratum (n ¼ 4,382), consisting of patients already on aspirin, also were randomized to aspirin (initial dose 200 mg followed by 100 mg daily) or placebo on the day of surgery for 7 days, after which patients returned to their usual aspirin regimen. Patients were excluded if within 6 weeks from placement of a bare metal coronary stent or if within 12 months from placement of a drug-eluting coronary stent.16 The defined primary trial outcome was a composite of death or nonfatal myocardial infarction at 30 days. Aspirin exposure did not decrease the incidence of the primary outcome (hazard ratio 0.99; 95% confidence interval 0.86-1.15; p ¼ 0.92).16 Furthermore, aspirin exposure significantly increased the risk of major bleeding (hazard ratio 1.23; 95% confidence interval 1.01-1.49; p ¼ 0.04).16 These adverse outcomes largely explain the strong recommendation in the 2014 ACC/ AHA guidelines against routine aspirin therapy in noncardiac surgery patients who have not had previous coronary stenting (Class III recommendation; level of Evidence B) unless the risks of ischemic events exceed the risks of surgical bleeding (Class III recommendation; Level of Evidence C).2 On the other hand, when the risks of ischemic cardiac events outweigh the risks of bleeding, the 2014 ACC/AHA guidelines do recommend consideration be given to continuation of aspirin for elective noncardiac surgery in adults who have not undergone coronary stenting (Class IIb recommendation; Level of Evidence B).2 In the setting of recent percutaneous coronary intervention, the guidelines have the following 3 strong recommendations, given the high risk of perioperative stent thrombosis in this patient population.17,18 In urgent noncardiac surgery within 6 weeks after coronary stent implantation, dual antiplatelet therapy should be continued regardless of stent type, unless the risks of bleeding exceed the risks of stent thrombosis (Class I recommendation; Level of Evidence C).2 In patients with coronary stents undergoing surgical procedures that mandate the cessation of the P2Y12 platelet blocker, the aspirin should be continued if possible and the P2Y12 blocker be restarted as soon as possible in the postoperative period (Class I recommendation; Level of Evidence C).2,19 In patients who have undergone coronary
stenting, management of perioperative antiplatelet therapy should be based on a consensus of the surgeon, anesthesiologist, cardiologist, and patient with consideration of the risks of bleeding versus the risks of stent thrombosis (Class I recommendation; Class of Evidence C).2 For a complete discussion of the management of patients with coronary stents undergoing noncardiac surgery, please refer to the 2014 ACC/AHA guideline.2 Recent evidence from a large noncardiac surgery registry (n ¼ 41,989: 2000-2010) suggests that the risk of major adverse cardiovascular events was associated most strongly with the following 3 factors: Emergency hospital admission (odds ratio 4.77; 95% confidence interval 4.07-5.59); myocardial infarction within preceding 6 months (odds ratio 2.63; 95% confidence interval 2.32-2.98); and, a revised cardiac risk index score 42 (odds ratio 2.13; 95% confidence interval 1.85-2.44).20 In this perioperative trial, cardiovascular mortality and morbidity were not dependent on stent type or timing of surgery beyond 6 months after stent implantation.20 These findings challenge the current guidelines’ emphasis on stent type and timing of surgery.20,21 Although further trials are indicated, the multiple advances in stent design over the past decade will continue to make the risks of stent thrombosis in the perioperative period recede.22,23 In cardiac surgery, the debate continues about the optimal perioperative management of platelet blockers. Recent evidence from metaanalysis suggests that, although continuation of platelet blockade increases bleeding, it has no adverse effects on major clinical outcomes and is associated with a low risk for mediastinal exploration.24 Furthermore, aspirin therapy may reduce acute kidney injury and mortality after cardiac surgery in patients with chronic kidney disease.25 The risks and benefits of this perioperative platelet blockers have to be individualized both in cardiac and noncardiac surgery. PARADIGM SHIFTS IN THE MANAGEMENT OF ATRIAL FIBRILLATION
The Medical Management of Atrial Fibrillation The global incidence of AF has been increasing steadily with adverse effects on major clinical outcomes.26 Perioperative AF is common and clinically important in cardiothoracic and vascular practice.27–30 Consequently, there is considerable imperative to reduce mortality and morbidity from this common arrhythmia, as reflected by the recent guidelines from Europe and North America.31,32 This imperative also applies to subclinical AF, given that in a large randomized controlled trial (n = 2,580) it significantly increased the risk of ischemic stroke and/or systemic embolism (hazard ratio 2.50; 95% confidence interval 1.28-4.89; p = 0.008).33 The recent multisociety guidelines review the management options for AF.31,32 Although anticoagulation should be considered routinely in AF, this must be balanced against the risks of bleeding.31,32 The classic technique for chronic anticoagulation in this setting was supervised oral anticoagulation with a vitamin K antagonist such as warfarin with the international normalized ratio in the 2.0 to 3.0 range.31,32 Recently, novel oral anticoagulants such as a direct thrombin inhibitor (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban) also have been approved for anticoagulation in AF.31,32 These
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new pharmacologic arrivals already have been reviewed in detail earlier in the Journal, including their perioperative implications due to paucity of reversal agents.34,35 In selected cases, dual-platelet blockade with aspirin and clopidogrel is reasonable for stroke prophylaxis.31,32 The clinical application of novel platelet P2Y12 inhibitors such as prasugrel and ticagrelor for stroke prophylaxis in AF require further adequately powered clinical trials.31,32,36 Risk stratification for stroke in AF recently has been standardized to an extent by the introduction of clinical scoring systems such as the CHA2DS2-VASc score (congestive heart failure/left ventricular dysfunction; age Z75 years [doubled]; diabetes; stroke [doubled]; vascular disease; age 65-74 years; sex [female]).31,32,37,38 Each risk factor in this scheme is given at least a score of 1; the additive total represents the total score. The CHA2DS2-VASc score has been validated in multiple trials and has become an accepted standard risk score tool in this setting.31,32,39,40 In a similar fashion, clinical scoring systems also have evolved for predicting the risk of serious bleeding from thromboprophylaxis in AF.31,32 The AF guidelines have recommended the HAS-BLED score (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly) for assessment of bleeding risk in AF, because it has been validated in multiple trials.31,32,41,42 Each risk factor in this scheme is given at least a score of 1; the additive total represent the total score. The use of scoring systems such as the CHA2DS2-VASc score and the HAS-BLED score could further optimize the risk/ benefit ratio for oral anticoagulation in adult AF.31,32 The 2014 ACC/AHA AF guidelines also have a section dedicated to AF after cardiothoracic and vascular surgery.32 The treatment of AF in this setting with beta-blockade has been recommended strongly in the absence of contraindications such as significant hypotension (Class I recommendation; Level of Evidence A).32 Furthermore, a nondihydroperidine calcium channel blocker, such as diltiazem, has been recommended strongly when beta-blockers are contraindicated or ineffective (Class I recommendation; Level of Evidence B).32 Preoperative amiodarone also was deemed as a reasonable medical intervention for prophylaxis of perioperative AF in patients at high risk (Class IIa recommendation; Level of Evidence A).32 Both pharmacologic and electrical cardioversion of AF in this setting were considered reasonable interventions, as recommended for medical patients (Class IIa recommendation; Level of Evidence B).32 The application of anticoagulation with or without rate control also was considered reasonable, as recommended for medical patients (Class IIa recommendation; Level of Evidence B). Perioperative administration of sotalol or colchicine was considered a reasonable possibility for reduction of AF in this setting (Class IIb recommendation; Level of Evidence B).32 Although earlier studies have suggested that colchicine may reduce perioperative AF in cardiovascular practice, the latest randomized trial (n ¼ 360: 11 Italian cardiac surgery centers from 2012-2014) found that, although colchicine significantly reduced the incidence of postpericardiotomy syndrome, it did not reduce the risk of AF after cardiac surgery.43 This landmark trial was published after the ACC/AHA AF guideline but did not include AF as a primary clinical outcome. Further trials are indicated to further explore the perioperative utility of colchicine in cardiothoracic and vascular practice.
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The paradigm shifts in the medical management of AF include mature clinical outcome scoring systems and new drugs for oral anticoagulation. Although these advances likely will further improve overall health for patients with AF, they also may complicate perioperative management, especially in the setting of novel oral anticoagulants that are not readily reversible. The multicenter Cardiothoracic Surgical Trials Network also currently is investigating, in a large randomized trial (n ¼ 470), whether control of rhythm is superior to rate control for AF after cardiac surgery, The hypothesis of this trial is that the strategy of rhythm control for in-hospital postoperative AF will reduce hospital days within 2 months of the initial episode of AF. The trial design includes amiodarone for rhythm control and drugs such as beta-blockers, calcium channel blockers, and digoxin for rate control. Full details of this ongoing trial at 23 centers across the United States and Canada are available at www.clincialtrials.gov, trial identifier NCT02132767). The Interventional Management of Atrial Fibrillation Mechanical approaches to reduce stroke risk in AF remain relevant, because not all patients with AF qualify for anticoagulation due to reasons such as excessive bleeding risk, personal preference, and poor medication compliance.31,32 Given that the left atrial appendage (LAA) remains a principal thromboembolic source in AF, catheter-based and surgical approaches to LAA occlusion continue to receive considerable attention.44 A multicenter cross-sectional clinical trial (n ¼ 1,889) found that LAA occlusion can be performed safely at the time of cardiac surgery with no increase in adverse events (relative risk 0.71; 95% confidence interval 0.19-2.66; p ¼ 0.61).45 These pilot data have provided the basis for a large randomized multicenter trial (n ¼ 4,700) in patients with AF undergoing on-pump surgical procedures who will be randomized to LAA occlusion or no LAA occlusion.46 The primary outcome has been defined as a first occurrence of stroke or systemic arterial embolism over a mean follow-up period of 4 years. Secondary outcomes include total mortality, perioperative bleeding, heart failure, and myocardial infarction.46 The 2014 ACC/AHA AF guidelines recommend surgical ligation of the LAA as a consideration in adult cardiac surgery (Class IIb Recommendation; Level of Evidence C).32 Catheter-based interventions for LAA occlusion recently have been evaluated. There are currently 2 device platforms that are still in randomized clinical trials.31,32 Both of these percutaneous devices reach the LAA by crossing the interatrial septum from the right atrium after septal puncture. The first platform is the Watchman LAA system (Boston Scientific, Natick, MA).47 A noninferiority randomized trial (n ¼ 707) found that LAA closure with this percutaneous system, as compared with oral anticoagulation, did not significantly increase the primary efficacy event rate, defined as a composite endpoint of stroke, cardiovascular death, and systemic embolism).47 The results from the Watchman continued-access registry show a significant learning curve that typically is a feature of a novel clinical intervention.48 The second percutaneous system for LAA occlusion is the Amplatzer Cardiac Plug (St Jude Medical, St Paul, MN).49 The feasibility and safety study (n ¼ 143) found a technical success rate of 96%, with a
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serious complication rate of 7.0%.49 Although further trials are required to define the full clinical application of these current devices, it is likely that transcatheter occlusion of the LAA will become a mainstream therapeutic option in selected patients with AF.31,32 The surgical management of atrial fibrillation also has experienced major innovations.31 The Cox-Maze procedure first was performed in 1987 and demonstrated the feasibility of this strategy for AF.50 The clinical advent of linear ablation lines generalized this technically challenging procedure throughout cardiac surgery with preserved clinical efficacy.51,52 Recent meta-analyses have shown that AF ablation during concomitant cardiac surgery significantly increased the likelihood of durable sinus rhythm.53,54 The advent of thorascopic approaches for the management of AF may extend the therapeutic application of these techniques even further.55 The multicenter Cardiothoracic Surgical Trials Network also currently is investigating, in a randomized trial (n ¼ 260 patients with AF undergoing mitral valve surgery), whether concurrent surgical ablation of AF significantly increases the rate of freedom from AF in the first year after surgery. The trial has just completed patient enrollment and now has entered the phase of data analysis (full details of this trial are available at www.clincialtrials.gov, trial identifier NCT00903370). The hybrid approach to AF ablation aims for transmural ablation by combining minimally invasive surgical epicardial lesions with percutaneous catheter-based endocardial lesions.56,57 The hybrid procedure typically is performed in a stepwise fashion. The surgical procedure is performed first via a thoracoscopic approach without cardiopulmonary bypass. The electrophysiologist then completes the procedure in a catheter-based fashion; detailed electrical mapping facilitates the identification of lesion gaps, the connection of lesions that are not transmural, and the induction of additional lesions.56,57 The recent results of this hybrid approach to AF ablation are favorable.56,57 Further trials are currently in progress to define its overall niche in the management of AF. These procedures could be performed in hybrid operating rooms, where the heart rhythm team consisting of surgeons, electrophysiologists, and anesthesiologists would work together in close cooperation.
The Aortic Arch Revolution There is currently a paradigm shift in adult aortic arch repair.58 Recent data have shown a gradual trend away from deep hypothermia toward moderate hypothermic circulatory arrest with routine antegrade cerebral perfusion with adequate pressure and monitoring.59,60 This paradigm appears safe and effective; it offers the opportunity for reduced exposure to cardiopulmonary bypass due to less time for cooling and rewarming. Furthermore, the maturation of hybrid aortic arch repair with endovascular stenting has begun to challenge the idea that circulatory arrest is required for extensive aortic arch procedures.58,61,62 These aspects of the revolution in adult aortic arch repair will be explored further in the near future, with a dedicated series of expert reviews dealing with these new frontiers in aortic therapy. CONCLUSIONS
The literature highlights in the specialty for 2014 begin with the recent comprehensive guidelines about perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery. Myocardial injury after noncardiac surgery is a dominant theme in this important document, because it remains a leading cause of perioperative mortality and major morbidity. Recent trials suggest that measurement of troponins in high-risk patients can improve significantly the detection of this complication. Further trials are indicated to define management strategies based on this clinical intervention. The second major theme in the specialty for 2014 is the profusion of new therapeutic options for the management of atrial fibrillation. The importance of these paradigm shifts for this common arrhythmia is reflected by the recent publication of comprehensive guidelines in both Europe and North America. The third major theme for the specialty is the revolution in adult aortic arch repair due to innovations such as moderate hypothermic circulatory arrest and hybrid aortic arch repair. The themes selected for this seventh highlights article only sample the advances in the specialty for 2014. The patient care processes identified in these highlights will further improve important perioperative outcomes for patients with cardiovascular disease in both cardiac and noncardiac surgery.
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establishing diagnostic criteria, characteristics, predictors and 30-day outcomes. Anesthesiology 120:564-578, 2014 7. Weiser TG, Regenbogen SE, Thompson KD, et al: An estimation of the global volume of surgery: A modeling strategy based on available data. Lancet 372:139-144, 2008 8. van Waes JA, Nathoe HM, de Graat JC, et al: Myocardial injury after noncardiac surgery and its association with short-term mortality. Circulation 127:2264-2271, 2013 9. Li SL, Wang DX, Wu XM, et al: Perioperative acute myocardial infarction increases mortality following noncardiac surgery. J Cardiothorac Vasc Anesth 27:1277-1281, 2013 10. Moussa ID, Klein LW, Shah B, et al: Consideration of a new definition of clinically relevant myocardial infarction after coronary revascularization: An expert consensus document from the Society for Cardiovascular Angiography and Interventions (SCAI). J Am Coll Cardiol 62:1563-1570, 2013 11. Wijeysundera DN, Duncan D, Nkonde-Price C, et al: Perioperative beta blockade in noncardiac surgery: A systematic review for the
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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. J Am Coll Cardiol 2014 Jul 29 [Epub ahead of print]. 12. Ramakrishna H, Reidy C, Riha H, et al: The year in cardiothoracic and vascular anesthesia: selected highlights from 2012. J Cardiothorac Vasc Anesth 27:86-91, 2013 13. Guay J, Ochroch EA: β-blocking agents for surgery: Influence on mortality and major outcomes. A meta-analysis. J Cardiothorac Vasc Anesth 27:834-844, 2013 14. Devereaux PJ, POISE-2 Investigators. Rationale and design of the PeriOperative ISchemic Evaluation-2 (POISE-2) trial: An international 2 2 factorial randomized controlled trial of acetyl-salicyclic acid vs. placebo and clonidine vs. placebo in patients undergoing noncardiac surgery. Am Heart J 167:804-809, 2014 15. Devereaux PJ, Sessler DI, Leslie K, et al: Clonidine in patients undergoing noncardiac surgery. N Engl J Med 370:1504-1513, 2014 16. Devereaux PJ, Mrkobrada M, Sessler DI, et al: Aspirin in patients undergoing noncardiac surgery. N Engl J Med 370: 1494-1503, 2014 17. Brilakis ES, Patel VG, Banerjee S: Medical management after coronary stent implantation: A review. JAMA 310:189-198, 2013 18. Trentman TL, Rosenfeld DM, Danielson DR, et al: Drug-eluting stents: Patient understanding of the risks of premature cessation of antiplatelet drugs. J Cardiothorac Vasc Anesth 22:806-810, 2008 19. Patel PA, Lane B, Augoustides JG: Progress in platelet blockers: The target is the P2Y12 receptor. J Cardiothorac Vasc Anesth 27: 620-624, 2013 20. Hawn MT, Graham LA, Richman JS, et al: Risk of major adverse cardiac events following noncardiac surgery in patients with coronary stents. JAMA 310:1462-1472, 2013 21. Brilakis ES, Banerjee S: Patient with coronary stents needs surgery: What to do? JAMA 310:1451-1452, 2013 22. Patel PA, Augoustides JG: Progress in platelet medicine: Focus on stent thrombosis and drug resistance. J Cardiothorac Vasc Anesth 24:722-727, 2010 23. Escárcega RO, Baker NC, Lipinski MJ, et al: Current application and bioavailability of drug-eluting stents. Expert Opin Drug Deliv 11: 689-709, 2014 24. Guay J, Ochroch EA: Continuing antiplatelet therapy before cardiac surgery with cardiopulmonary bypass: A meta-analysis on the need for reexploration and major outcomes. J Cardiothorac Vasc Anesth 28:90-97, 2014 25. Yao L, Young N, Liu H, et al: Evidence for preoperative aspirin improving major outcomes in patients with chronic kidney disease undergoing cardiac surgery: A cohort study. Ann Surg 90:1-6, 2014 26. Rahman F, Kwan GF, Benjamin EJ: Global epidemiology of atrial fibrillation. Nat Rev Cardiol 11:639-654, 2014 27. Augoustides JG, Szeto W, Ochroch EA, et al: Atrial fibrillation after aortic arch repair requiring deep hypothermic circulatory arrest: Incidence, clinical outcome, and clinical predictors. J Cardiothorac Vasc Anesth 21:388-392, 2007 28. Ghadimi K, Patel PA, Gutsche JT, et al: Perioperative conduction disturbances after transcatheter aortic valve replacement. J Cardiothorac Vasc Anesth 27:1414-1420, 2013 29. Murphy GS, Whitlock RP, Gutsche JT, et al: Steroids for adult cardiac surgery with cardiopulmonary bypass: Update on dose and key randomized trials. J Cardiothorac Vasc Anesth 27:1053-1059, 2013 30. Rostagno C, La Meir C, Gelsomino S, et al: Atrial fibrillation after cardiac surgery: incidence, risk factors, and economic burden. J Cardiothorac Vasc Anesth 24:952-958, 2010 31. Camm AJ, Lip GY, De Caterina R, et al: 2012 focused update of the ESC guidelines for the management of atrial fibrillation: An update
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of the 2010 ESC guidelines for the management of atrial fibrillation— Developed with the special contribution of the European Heart Rhythm Association. Europace 14:1385-1413, 2012 32. January CT, Wann LS, Alpert JS, et al: 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and Heart Rhythm Society. J Am Coll Cardiol 2014 Mar 28 [Epub ahead of print]. 33. Healey JS, Connolly SJ, Gold MR, et al: Subclinical atrial fibrillation and the risk of stroke. New Engl J Med 366:120-129, 2012 34. Augoustides JG: Advances in anticoagulation: Focus on dabigatran, an oral direct thrombin inhibitor. J Cardiothorac Vasc Anesth 25: 1208-1212, 2011 35. Augoustides JG: Breakthroughs in anticoagulation: Advent of the oral direct factor Xa inhibitors. J Cardiothorac Vasc Anesth 26: 740-745, 2012 36. McNeice AH, McAleavey NM, Menown IB: Advances in clinical cardiology. Adv Ther 31:837-860, 2014 37. Lip GY, Nieuwlaat R, Pisters R, et al: Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: The Euro Heart Survey on Atrial Fibrillation. Chest 137:263-272, 2010 38. Camm AJ, Kirchof P, Lip GY, et al: Guidelines for the management of atrial fibrillation: The task force for the management of atrial fibrillation of the European Society of Cardiology (ESC). Europace 12:1360-1420, 2010 39. Olesen JB, Torp-Pedersen C, Hansen ML, et al: The value of the CHA2DS2-VASc score for refining stroke risk stratification in patients with atrial fibrillation with a CHADS2 – a nationwide cohort study. Thromb Haemost 107:1172-1179, 2012 40. Boriani G, Botto GL, Padeletti L, et al: Improving stroke risk stratification using the CHADS2 and CHA2DS2-VASc risk scores in patients with paroxysmal atrial fibrillation by continuous arrhythmia burden monitoring. Stroke 42:1768-1770, 2011 41. Pisters R, Lane DA, Nieuwlaat R, et al: A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 138:1093-1100, 2010 42. Lip GY, Frison L, Halperin JL, et al: Comparative validation of a novel risk score in anticoagulated patients with atrial fibrillation: The HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly) score. J Am Coll Cardiol 57:173-180, 2011 43. Imazio M, Brucato A, Ferrazzi I, et al: Colchicine for prevention of postpericardiotomy syndrome and postoperative atrial fibrillation: The COPPS-2 randomized clinical trial. JAMA 312:1016-1023, 2014 44. Holmes DR Jr, Lakkireddy DR, Whitlock RP, et al: Left atrial appendage occlusion: Opportunities and challenges. J Am Coll Cardiol 63:291-298, 2014 45. Whitlock RP, Vintcent J, Blakall MH, et al: Left Atrial Appendage Occlusion Study II (LAAOS II). Can J Cardiol 29: 1443-1447, 2013 46. Whitlock R, Healey J, Vintcent J, et al: Rationale and design of the left atrial appendage occlusion study (LAAOS) III. Ann Cardiothorac Surg 3:45-54, 2014 47. Holmes DR, Reddy VY, Turi ZG, et al: Percutaneous closure of the left atrial appendage vs warfarin therapy for prevention of stroke in patients with atrial fibrillation: A randomized non-inferiority trial. Lancet 37:534-542, 2009 48. Reddy VY, Holmes D, Doshi SK, et al: Safety of percutaneous left atrial appendage closure: Results from the Watchman left atrial appendage system for embolic protection in patients with AF (PROTECT AF) clinical trial and the Continued Access Registry. Circulation 123:417-424, 2011
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49. Park JW, Bethencourt A, Sievert H, et al: Left atrial appendage closure with Amplatzer cardiac plug in atrial fibrillation: Initial European experience. Catheter Cardiovasc Interv 77:700-706, 2011 50. Pinho-Gomes AC, Amorim MJ, Oliviera SM, et al: Surgical treatment of atrial fibrillation: An updated review. Eur J Cardiothorac Surg 46:167-178, 2014 51. Weimar T, Bailey MS, Watanabe Y, et al: The Cox-maze IV procedure for lone atrial fibrillation: A single center experience in 100 consecutive patients. J Interv Card Electrophysiol 31:47-54, 2011 52. Weimar T, Schena S, Bailey MS, et al: The cox-maze procedure for lone atrial fibrillation: A single-center experience over 2 decades. Circ Arrhythm Electrophysiol 5:8-14, 2012 53. Cheng DC, Ad N, Martin J, et al: Surgical ablation for atrial fibrillation in cardiac surgery: A meta-analysis and systematic review. Innovations (Phila) 5:84-96, 2010 54. Phan K, Xie A, La Meir M, et al: Surgical ablation for treatment of atrial fibrillation in cardiac surgery: A cumulative meta-analysis of randomized controlled trials. Heart 100:722-730, 2014 55. La Meir M, Gelsomino S, Luca F, et al: Minimal invasive surgery for atrial fibrillation: An updated review. Europace 15:170-182, 2013 56. Mahapatra S, LaPar DJ, Kamath S, et al: Initial experience of sequential surgical epicardial-catheter endocardial ablation for
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persistent and long-standing persistent atrial fibrillation with longterm follow-up. Ann Thorac Surg 1890-1898, 2011 57. Pison L, La Meir M, van Opsatl J, et al: Hybrid thoracoscopic surgical and transvenous catheter ablation of atrial fibrillation. J Am Coll Cardiol 60:54-61, 2012 58. Gutsche JT, Ghadimni K, Patel PA, et al: New frontiers in aortic therapy: Focus on deep hypothermic circulatory arrest. J Cardiothorac Vasc Anesth 2014 Aug 28 [Epub ahead of print]. 59. Gutsche JT, Feinman J, Silvay G, et al: Practice variations in the conduct of hypothermic circulatory arrest for adult aortic arch repair: Focus on an emerging European paradigm. Heart Lung Vessel 6: 43-51, 2014 60. Augoustides JG, Patel P, Ghadimi K, et al: Current conduct of deep hypothermic circulatory arrest in China. HSR Proc Intensive Care Cardiovasc Anesth 5:25-32, 2013 61. Augoustides JG, Andritsos M: Innovations in aortic disease: The ascending aorta and aortic arch. J Cardiothorac Vasc Anesth 24: 198-207, 2010 62. Cao P, Rango P, Czerny M, et al: Systematic review of clinical outcomes in hybrid procedures for aortic arch dissections and other arch diseases. J Thorac Cardiovasc Surg 144:1286-1300, 2012
The Year in Cardiothoracic and Vascular Anesthesia: Selected Highlights From 2014 Jacob T. Gutsche, MD,* Prakash A. Patel, MD,* Frederick C. Cobey, MD, MPH,† Harish Ramakrishna, MD, FASE,‡ Emily K. Gordon, MD,* Hynek Riha, MD, DEAA, FCCP,§ Aris Sophocles, MD,* Kamrouz Ghadimi, MD,¶ Michael Fabbro, MD,* Lourdes Al-Ghofaily, MD,* Sy-Yeu S. Chern, MD,* Sophia Cisler, MD,* Gurmukh S. Sahota, MD,* Elizabeth Valentine, MD,* Stuart J. Weiss, MD, PhD,* Michael Andritsos, MD,║ George Silvay, MD, PhD,** and John G.T. Augoustides, MD, FASE, FAHA*
T
HIS ARTICLE IS THE SEVENTH in the annual series for the Journal of Cardiothoracic and Vascular Anesthesia.1 The authors thank the editor-in-chief, Dr. Kaplan, and the editorial board for the opportunity to continue this series; namely, the research highlights of the year that pertain to the specialty of cardiothoracic and vascular anesthesia. The major themes selected for this past year will be outlined in this introduction and then each highlight will be reviewed in detail in the main body of the article. The literature highlights in the specialty for 2014 begin with the release of the new guidelines about perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery.2 A pervasive theme throughout this important guideline is the detection and prevention of myocardial injury after noncardiac surgery that is explored in detail in this article because it is a common cause of perioperative mortality. The second major theme in our specialty for 2014 is the explosion of new therapeutic options for the management of atrial fibrillation (AF). The importance of these paradigm shifts for this common arrhythmia is reflected by the recent publication of comprehensive guidelines in both Europe and North America. The third major theme for the specialty is the revolution in adult aortic arch repair due to innovations such as moderate hypothermic circulatory arrest and hybrid aortic arch repair. The themes selected for this seventh highlights article only sample the advances in the specialty for 2014. The patient care processes identified in these highlights will further improve important perioperative outcomes for patients with cardiovascular disease in both cardiac and noncardiac surgery. MYOCARDIAL INJURY AFTER NONCARDIAC SURGERY
The Detection of Myocardial Injury After Noncardiac Surgery The recent guidelines from the American College of Cardiology (ACC) and American Heart Association (AHA) on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery have 9 sections, more than 100 pages of text and figures, and 490 references.2 Although a detailed summary of this landmark document is beyond the scope of this highlights article, the emphasis on myocardial ischemia is pervasive throughout this important document. A dominant theme in these perioperative guidelines is myocardial ischemia, given that it is a leading cause of
perioperative mortality worldwide.3,4 The importance of perioperative myocardial ischemia in the Journal is evidenced by the fact that more than 150 articles published in the past 2 years are related to this topic (electronic search in ScienceDirect for the Journal of Cardiothoracic and Vascular Anesthesia conducted on September 20, 2014, key word: Myocardial ischemia). Although the universal definition of myocardial infarction typically includes an elevated troponin in combination with an ischemic symptom and/or an ischemic electrocardiographic tracing, defining factors such as symptoms and electrocardiographic changes frequently may not accompany the presentation of myocardial ischemia in the perioperative setting.5,6 The question is whether there is a better way to detect this lifethreatening complication, given these limitations. A recent analysis (n = 15,065) from the large international prospective Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) study developed diagnostic criteria for myocardial injury after noncardiac surgery (MINS) as a primary objective.6 The secondary objectives of this analysis
From the *Cardiovascular and Thoracic Section, Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, †Tufts University School of Medicine, Boston, Massachusetts, ‡Mayo Clinic, Scottsdale, Arizona; §Cardiothoracic Anesthesiology and Intensive Care, Department of Anesthesiology and Intensive Care Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic, ¶Department of Anesthesiology and Critical Care, Duke University, Durham, North Carolina, ║Department of Anesthesiology, Ohio State University, Columbus, Ohio; and **Department of Anesthesiology and Critical Care, Icahn School of Medicine, Mount Sinai Hospital, New York, New York. Address reprint requests to John G. T. Augoustides, MD, FASE, FAHA, Cardiothoracic Section, Anesthesiology and Critical Care, Dulles 680, HUP, 3400 Spruce Street, Philadelphia, PA, 19104-4283. E-mail: [email protected] © 2014 Elsevier Inc. All rights reserved. 1053-0770/2601-0001$36.00/0 http://dx.doi.org/10.1053/j.jvca.2014.10.002 Key words: perioperative cardiovascular evaluation, guidelines, VISION study, myocardial injury after noncardiac surgery, troponins, aspirin, clonidine, POISE-2 study, atrial fibrillation, stroke, bleeding, risks scores, dabigatran, factor Xa inhibitors, left atrial appendage occlusion, surgical ablation, aortic arch, moderate hypothermic circulatory arrest, antegrade cerebral perfusion, hybrid aortic arch repair, paradigm shifts
Journal of Cardiothoracic and Vascular Anesthesia, Vol 29, No 1 (February), 2015: pp 1–7
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were to determine the characteristics, predictors, and perioperative outcomes of MINS at 30 days (full details of the ongoing VISION study are available at www.clincialtrials.gov, trial identifier NCT00512109).6 The principal finding from the VISION clinical registry was that MINS was diagnosed best by a peak perioperative troponin T level Z0.03 ng/mL that was not attributable to a nonischemc etiology. This definition of MINS does not require an ischemic presentation with respect to clinical symptoms, signs, and electrocardiographic features.6 In fact, only 41.8% of patients with MINS fulfilled the universal definition of myocardial infarction; the remaining 51.2% who did not rule in for myocardial infarction by classic criteria had a 30-day mortality rate of 7.7%.5,6 Furthermore, according to this definition, MINS had an incidence of 8.0% and was associated significantly with cardiovascular complications and mortality at 30 days; it explained 34% of all deaths in adults in the first 30 days after noncardiac surgery.6 The VISION trial data have highlighted that MINS is common and important. The global impact of these observations is staggering; about 8 million adults suffer MINS worldwide each year, assuming that that the annual volume of adult noncardiac surgery is about 100 million cases.6 Given this massive caseload, MINS likely accounts for more than 2 million deaths after noncardiac surgery worldwide every year.6,7 Further trials are, therefore, essential to identify strategies to prevent and manage the serious complication of MINS.6,8,9 The consequences of perioperative myocardial ischemia have been realized globally, as evidenced by the recent large trials in Europe and Asia.8,9 A large single-center analysis from China (n = 117,856: 2003-2011) found that perioperative myocardial infarction after adult noncardiac surgery had an incidence of 5.2 per 10,000, although it significantly increased with age to an incidence of 40.4 per 10,000 for adults aged Z75 years (p o 0.001).9 The mortality rate for patients with myocardial ischemia was 36.1%, which was more than 100 times higher than patients with no perioperative myocardial ischemia (36.1% v 0.32%; p o 0.001).9 Furthermore, in this study myocardial infarction typically occurred within 72 hours after surgery without chest pain and with non-ST segment changes on the electrocardiogram.9 Taken collectively, these perioperative trials also have highlighted the gaps in the current universal definition of myocardial infarction with respect to perioperative practice; this definition at times may not be clinically relevant. This lack of clinical relevance not only has resulted in the VISION registry but also has led to recent consideration of a new definition of clinically relevant myocardial infarction after coronary revascularization, whether due to percutaneous coronary intervention or coronary artery bypass grafting.10 Given these gaps in the current definition of myocardial infarction, it is likely that the universal definition of myocardial infarction will be revised in the near future. The 2014 ACC/AHA guidelines deal with MINS in section 8 entitled “perioperative surveillance.”2 In the setting of signs and symptoms suggestive of perioperative myocardial ischemia, the guidelines strongly recommend the analysis of an electrocardiogram (Class I recommendation; Level of Evidence B) and the measurement of troponins (Class I recommendation;
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Level of Evidence A).2 The routine measurement of troponins in patients at high risk for MINS was recommended less strongly in the absence of a defined management strategy with known risks and benefits (Class IIb recommendation; Level of Evidence B).2 The routine postoperative measurement of troponins in unselected patients was not recommended (Class III recommendation; level of Evidence B).2 The VISION trials have, through perioperative surveillance, facilitated the discovery of a gap in perioperative care, namely the detection and management of MINS.4–6 Although a troponin-based definition has refined the identification of MINS in at-risk patients, the question now becomes what interventions are available to prevent this serious complication. The Prevention of Myocardial Injury After Noncardiac Surgery The perioperative therapy for MINS is reviewed in detail in section 6 of the recent ACC/AHA guidelines.2 The first subsection deals with recommendations for coronary revascularization before noncardiac surgery, including surgical timing in patients who have undergone previous percutaneous coronary intervention.2 The second subsection deals with perioperative medical therapy, including beta-blockers, alpha2-agonists, and antiplatelet agents.2 The recommendations for perioperative beta-blockade in these guidelines are based on a recent systematic review of the evidence that was specially commissioned to address the scientific misconduct in the work by Dr. Poldermans.2,11 The issue of research misconduct has been reviewed previously in this article series.12 The key findings of the ACC/AHA systematic review were not affected significantly by the exclusion of the relevant published studies by Dr. Poldermans. Full details of this evidence analysis are provided both in the guidelines and the separately published metaanalysis.2,12 The first strong recommendation in the new guidelines is that betablockers should be continued in patients undergoing surgery who have been on these agents chronically (Class I recommendation; Level of Evidence B).2 The second strong recommendation is that beta-blockade should not be commenced on the day of surgery (Class III recommendation; Level of Evidence B).2 The remaining 5 recommendations about betablockers in this guideline are Class II and are discussed comprehensively in section 6.2 (subsection 1).2 The roles of this group of pharmacologic agents, in both cardiac and noncardiac surgery, continue to be explored vigorously and debated in the Journal: 73 articles were devoted to this topic in the Journal within the past 2 years, including a recent metaanalysis (electronic search in ScienceDirect for the Journal of Cardiothoracic and Vascular Anesthesia conducted on September 22, 2014, key word: beta-blockers).13 The guidelines also have strongly recommended against apha2-agonists for prevention of myocardial events in patients undergoing noncardiac surgery (Class III recommendation; Level of Evidence B).2 The recent international randomized Perioperative Ischemic Evaluation-2 (POISE-2) trial evaluated the effects of low-dose clonidine (0.2 mg/day) in patients with or at risk for atherosclerotic disease who underwent noncardiac surgery (n ¼ 10,010: 135 centers in 23 countries).14,15 In this
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2014 HIGHLIGHTS
landmark trial, low-dose clonidine was started just before surgery and continued for 72 hours. The primary trial outcome was defined as a composite of death or nonfatal myocardial infarction at 30 days. Clonidine did not reduce this primary outcome (hazard ratio 1.08; 95% confidence interval 0.93-1.26; p = 0.29).15 Furthermore, exposure to clonidine significantly increased the risks of clinically important hypotension (hazard ratio 1.32; 95% confidence interval 1.24-1.40; p o 0.001) and nonfatal cardiac arrest (hazard ratio 3.20; 95% confidence interval 1.17-8.73; p ¼ 0.02).15 The adverse outcomes of clonidine in noncardiac surgery explain the Class III recommendation for this agent in the ACC/AHA perioperative guidelines.2,15 The POISE-2 investigators also investigated the effects of aspirin in adult noncardiac surgery.16 Patients at risk for vascular events were stratified according to previous aspirin exposure. The initiation stratum (n ¼ 5,628), consisting of patients who were not previously on aspirin, were randomized to aspirin (initial dose 200 mg followed by 100 mg daily) placebo that began on the day of surgery and continued for 30 days. The continuation stratum (n ¼ 4,382), consisting of patients already on aspirin, also were randomized to aspirin (initial dose 200 mg followed by 100 mg daily) or placebo on the day of surgery for 7 days, after which patients returned to their usual aspirin regimen. Patients were excluded if within 6 weeks from placement of a bare metal coronary stent or if within 12 months from placement of a drug-eluting coronary stent.16 The defined primary trial outcome was a composite of death or nonfatal myocardial infarction at 30 days. Aspirin exposure did not decrease the incidence of the primary outcome (hazard ratio 0.99; 95% confidence interval 0.86-1.15; p ¼ 0.92).16 Furthermore, aspirin exposure significantly increased the risk of major bleeding (hazard ratio 1.23; 95% confidence interval 1.01-1.49; p ¼ 0.04).16 These adverse outcomes largely explain the strong recommendation in the 2014 ACC/ AHA guidelines against routine aspirin therapy in noncardiac surgery patients who have not had previous coronary stenting (Class III recommendation; level of Evidence B) unless the risks of ischemic events exceed the risks of surgical bleeding (Class III recommendation; Level of Evidence C).2 On the other hand, when the risks of ischemic cardiac events outweigh the risks of bleeding, the 2014 ACC/AHA guidelines do recommend consideration be given to continuation of aspirin for elective noncardiac surgery in adults who have not undergone coronary stenting (Class IIb recommendation; Level of Evidence B).2 In the setting of recent percutaneous coronary intervention, the guidelines have the following 3 strong recommendations, given the high risk of perioperative stent thrombosis in this patient population.17,18 In urgent noncardiac surgery within 6 weeks after coronary stent implantation, dual antiplatelet therapy should be continued regardless of stent type, unless the risks of bleeding exceed the risks of stent thrombosis (Class I recommendation; Level of Evidence C).2 In patients with coronary stents undergoing surgical procedures that mandate the cessation of the P2Y12 platelet blocker, the aspirin should be continued if possible and the P2Y12 blocker be restarted as soon as possible in the postoperative period (Class I recommendation; Level of Evidence C).2,19 In patients who have undergone coronary
stenting, management of perioperative antiplatelet therapy should be based on a consensus of the surgeon, anesthesiologist, cardiologist, and patient with consideration of the risks of bleeding versus the risks of stent thrombosis (Class I recommendation; Class of Evidence C).2 For a complete discussion of the management of patients with coronary stents undergoing noncardiac surgery, please refer to the 2014 ACC/AHA guideline.2 Recent evidence from a large noncardiac surgery registry (n ¼ 41,989: 2000-2010) suggests that the risk of major adverse cardiovascular events was associated most strongly with the following 3 factors: Emergency hospital admission (odds ratio 4.77; 95% confidence interval 4.07-5.59); myocardial infarction within preceding 6 months (odds ratio 2.63; 95% confidence interval 2.32-2.98); and, a revised cardiac risk index score 42 (odds ratio 2.13; 95% confidence interval 1.85-2.44).20 In this perioperative trial, cardiovascular mortality and morbidity were not dependent on stent type or timing of surgery beyond 6 months after stent implantation.20 These findings challenge the current guidelines’ emphasis on stent type and timing of surgery.20,21 Although further trials are indicated, the multiple advances in stent design over the past decade will continue to make the risks of stent thrombosis in the perioperative period recede.22,23 In cardiac surgery, the debate continues about the optimal perioperative management of platelet blockers. Recent evidence from metaanalysis suggests that, although continuation of platelet blockade increases bleeding, it has no adverse effects on major clinical outcomes and is associated with a low risk for mediastinal exploration.24 Furthermore, aspirin therapy may reduce acute kidney injury and mortality after cardiac surgery in patients with chronic kidney disease.25 The risks and benefits of this perioperative platelet blockers have to be individualized both in cardiac and noncardiac surgery. PARADIGM SHIFTS IN THE MANAGEMENT OF ATRIAL FIBRILLATION
The Medical Management of Atrial Fibrillation The global incidence of AF has been increasing steadily with adverse effects on major clinical outcomes.26 Perioperative AF is common and clinically important in cardiothoracic and vascular practice.27–30 Consequently, there is considerable imperative to reduce mortality and morbidity from this common arrhythmia, as reflected by the recent guidelines from Europe and North America.31,32 This imperative also applies to subclinical AF, given that in a large randomized controlled trial (n = 2,580) it significantly increased the risk of ischemic stroke and/or systemic embolism (hazard ratio 2.50; 95% confidence interval 1.28-4.89; p = 0.008).33 The recent multisociety guidelines review the management options for AF.31,32 Although anticoagulation should be considered routinely in AF, this must be balanced against the risks of bleeding.31,32 The classic technique for chronic anticoagulation in this setting was supervised oral anticoagulation with a vitamin K antagonist such as warfarin with the international normalized ratio in the 2.0 to 3.0 range.31,32 Recently, novel oral anticoagulants such as a direct thrombin inhibitor (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban) also have been approved for anticoagulation in AF.31,32 These
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new pharmacologic arrivals already have been reviewed in detail earlier in the Journal, including their perioperative implications due to paucity of reversal agents.34,35 In selected cases, dual-platelet blockade with aspirin and clopidogrel is reasonable for stroke prophylaxis.31,32 The clinical application of novel platelet P2Y12 inhibitors such as prasugrel and ticagrelor for stroke prophylaxis in AF require further adequately powered clinical trials.31,32,36 Risk stratification for stroke in AF recently has been standardized to an extent by the introduction of clinical scoring systems such as the CHA2DS2-VASc score (congestive heart failure/left ventricular dysfunction; age Z75 years [doubled]; diabetes; stroke [doubled]; vascular disease; age 65-74 years; sex [female]).31,32,37,38 Each risk factor in this scheme is given at least a score of 1; the additive total represents the total score. The CHA2DS2-VASc score has been validated in multiple trials and has become an accepted standard risk score tool in this setting.31,32,39,40 In a similar fashion, clinical scoring systems also have evolved for predicting the risk of serious bleeding from thromboprophylaxis in AF.31,32 The AF guidelines have recommended the HAS-BLED score (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, Drugs/alcohol concomitantly) for assessment of bleeding risk in AF, because it has been validated in multiple trials.31,32,41,42 Each risk factor in this scheme is given at least a score of 1; the additive total represent the total score. The use of scoring systems such as the CHA2DS2-VASc score and the HAS-BLED score could further optimize the risk/ benefit ratio for oral anticoagulation in adult AF.31,32 The 2014 ACC/AHA AF guidelines also have a section dedicated to AF after cardiothoracic and vascular surgery.32 The treatment of AF in this setting with beta-blockade has been recommended strongly in the absence of contraindications such as significant hypotension (Class I recommendation; Level of Evidence A).32 Furthermore, a nondihydroperidine calcium channel blocker, such as diltiazem, has been recommended strongly when beta-blockers are contraindicated or ineffective (Class I recommendation; Level of Evidence B).32 Preoperative amiodarone also was deemed as a reasonable medical intervention for prophylaxis of perioperative AF in patients at high risk (Class IIa recommendation; Level of Evidence A).32 Both pharmacologic and electrical cardioversion of AF in this setting were considered reasonable interventions, as recommended for medical patients (Class IIa recommendation; Level of Evidence B).32 The application of anticoagulation with or without rate control also was considered reasonable, as recommended for medical patients (Class IIa recommendation; Level of Evidence B). Perioperative administration of sotalol or colchicine was considered a reasonable possibility for reduction of AF in this setting (Class IIb recommendation; Level of Evidence B).32 Although earlier studies have suggested that colchicine may reduce perioperative AF in cardiovascular practice, the latest randomized trial (n ¼ 360: 11 Italian cardiac surgery centers from 2012-2014) found that, although colchicine significantly reduced the incidence of postpericardiotomy syndrome, it did not reduce the risk of AF after cardiac surgery.43 This landmark trial was published after the ACC/AHA AF guideline but did not include AF as a primary clinical outcome. Further trials are indicated to further explore the perioperative utility of colchicine in cardiothoracic and vascular practice.
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The paradigm shifts in the medical management of AF include mature clinical outcome scoring systems and new drugs for oral anticoagulation. Although these advances likely will further improve overall health for patients with AF, they also may complicate perioperative management, especially in the setting of novel oral anticoagulants that are not readily reversible. The multicenter Cardiothoracic Surgical Trials Network also currently is investigating, in a large randomized trial (n ¼ 470), whether control of rhythm is superior to rate control for AF after cardiac surgery, The hypothesis of this trial is that the strategy of rhythm control for in-hospital postoperative AF will reduce hospital days within 2 months of the initial episode of AF. The trial design includes amiodarone for rhythm control and drugs such as beta-blockers, calcium channel blockers, and digoxin for rate control. Full details of this ongoing trial at 23 centers across the United States and Canada are available at www.clincialtrials.gov, trial identifier NCT02132767). The Interventional Management of Atrial Fibrillation Mechanical approaches to reduce stroke risk in AF remain relevant, because not all patients with AF qualify for anticoagulation due to reasons such as excessive bleeding risk, personal preference, and poor medication compliance.31,32 Given that the left atrial appendage (LAA) remains a principal thromboembolic source in AF, catheter-based and surgical approaches to LAA occlusion continue to receive considerable attention.44 A multicenter cross-sectional clinical trial (n ¼ 1,889) found that LAA occlusion can be performed safely at the time of cardiac surgery with no increase in adverse events (relative risk 0.71; 95% confidence interval 0.19-2.66; p ¼ 0.61).45 These pilot data have provided the basis for a large randomized multicenter trial (n ¼ 4,700) in patients with AF undergoing on-pump surgical procedures who will be randomized to LAA occlusion or no LAA occlusion.46 The primary outcome has been defined as a first occurrence of stroke or systemic arterial embolism over a mean follow-up period of 4 years. Secondary outcomes include total mortality, perioperative bleeding, heart failure, and myocardial infarction.46 The 2014 ACC/AHA AF guidelines recommend surgical ligation of the LAA as a consideration in adult cardiac surgery (Class IIb Recommendation; Level of Evidence C).32 Catheter-based interventions for LAA occlusion recently have been evaluated. There are currently 2 device platforms that are still in randomized clinical trials.31,32 Both of these percutaneous devices reach the LAA by crossing the interatrial septum from the right atrium after septal puncture. The first platform is the Watchman LAA system (Boston Scientific, Natick, MA).47 A noninferiority randomized trial (n ¼ 707) found that LAA closure with this percutaneous system, as compared with oral anticoagulation, did not significantly increase the primary efficacy event rate, defined as a composite endpoint of stroke, cardiovascular death, and systemic embolism).47 The results from the Watchman continued-access registry show a significant learning curve that typically is a feature of a novel clinical intervention.48 The second percutaneous system for LAA occlusion is the Amplatzer Cardiac Plug (St Jude Medical, St Paul, MN).49 The feasibility and safety study (n ¼ 143) found a technical success rate of 96%, with a
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2014 HIGHLIGHTS
serious complication rate of 7.0%.49 Although further trials are required to define the full clinical application of these current devices, it is likely that transcatheter occlusion of the LAA will become a mainstream therapeutic option in selected patients with AF.31,32 The surgical management of atrial fibrillation also has experienced major innovations.31 The Cox-Maze procedure first was performed in 1987 and demonstrated the feasibility of this strategy for AF.50 The clinical advent of linear ablation lines generalized this technically challenging procedure throughout cardiac surgery with preserved clinical efficacy.51,52 Recent meta-analyses have shown that AF ablation during concomitant cardiac surgery significantly increased the likelihood of durable sinus rhythm.53,54 The advent of thorascopic approaches for the management of AF may extend the therapeutic application of these techniques even further.55 The multicenter Cardiothoracic Surgical Trials Network also currently is investigating, in a randomized trial (n ¼ 260 patients with AF undergoing mitral valve surgery), whether concurrent surgical ablation of AF significantly increases the rate of freedom from AF in the first year after surgery. The trial has just completed patient enrollment and now has entered the phase of data analysis (full details of this trial are available at www.clincialtrials.gov, trial identifier NCT00903370). The hybrid approach to AF ablation aims for transmural ablation by combining minimally invasive surgical epicardial lesions with percutaneous catheter-based endocardial lesions.56,57 The hybrid procedure typically is performed in a stepwise fashion. The surgical procedure is performed first via a thoracoscopic approach without cardiopulmonary bypass. The electrophysiologist then completes the procedure in a catheter-based fashion; detailed electrical mapping facilitates the identification of lesion gaps, the connection of lesions that are not transmural, and the induction of additional lesions.56,57 The recent results of this hybrid approach to AF ablation are favorable.56,57 Further trials are currently in progress to define its overall niche in the management of AF. These procedures could be performed in hybrid operating rooms, where the heart rhythm team consisting of surgeons, electrophysiologists, and anesthesiologists would work together in close cooperation.
The Aortic Arch Revolution There is currently a paradigm shift in adult aortic arch repair.58 Recent data have shown a gradual trend away from deep hypothermia toward moderate hypothermic circulatory arrest with routine antegrade cerebral perfusion with adequate pressure and monitoring.59,60 This paradigm appears safe and effective; it offers the opportunity for reduced exposure to cardiopulmonary bypass due to less time for cooling and rewarming. Furthermore, the maturation of hybrid aortic arch repair with endovascular stenting has begun to challenge the idea that circulatory arrest is required for extensive aortic arch procedures.58,61,62 These aspects of the revolution in adult aortic arch repair will be explored further in the near future, with a dedicated series of expert reviews dealing with these new frontiers in aortic therapy. CONCLUSIONS
The literature highlights in the specialty for 2014 begin with the recent comprehensive guidelines about perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery. Myocardial injury after noncardiac surgery is a dominant theme in this important document, because it remains a leading cause of perioperative mortality and major morbidity. Recent trials suggest that measurement of troponins in high-risk patients can improve significantly the detection of this complication. Further trials are indicated to define management strategies based on this clinical intervention. The second major theme in the specialty for 2014 is the profusion of new therapeutic options for the management of atrial fibrillation. The importance of these paradigm shifts for this common arrhythmia is reflected by the recent publication of comprehensive guidelines in both Europe and North America. The third major theme for the specialty is the revolution in adult aortic arch repair due to innovations such as moderate hypothermic circulatory arrest and hybrid aortic arch repair. The themes selected for this seventh highlights article only sample the advances in the specialty for 2014. The patient care processes identified in these highlights will further improve important perioperative outcomes for patients with cardiovascular disease in both cardiac and noncardiac surgery.
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