Table of Contents Preamblee79 Introductione81 Methodology and Evidence Reviewe81 Organization of the GWCe82 Document Review and Approvale82 Scope of the CPGe82 Definitions of Urgency and Riske83 ...Clinical Risk Factorse83 Coronary Artery Diseasee83 Heart Failuree85 Role of HF in Perioperative Cardiac Risk Indicese85 Risk of HF Based on Left Ventricular Ejection Fraction: Preserved Versus Reducede85 Risk of Asymptomatic Left Ventricular Dysfunctione85 Role of Natriuretic Peptides in Perioperative Risk of HFe86 Cardiomyopathye86 Valvular Heart Disease: Recommendationse87 Aortic Stenosis: Recommendatione87 Mitral Stenosis: Recommendatione88 Aortic and Mitral Regurgitation: Recommendationse88 Arrhythmias and Conduction Disorderse88 Cardiovascular Implantable Electronic Devices: Recommendatione89 Pulmonary Vascular Disease: Recommendationse90 Adult Congenital Heart Diseasee90 Calculation of Risk to Predict Perioperative Cardiac Morbiditye90 Multivariate Risk Indices: Recommendationse90 Inclusion of Biomarkers in Multivariable Risk Modelse91 Approach to Perioperative Cardiac Testinge91 Exercise Capacity and Functional Capacitye91 Stepwise Approach to Perioperative Cardiac Assessment: Treatment Algorithme93 Supplemental Preoperative Evaluatione95 The 12-Lead Electrocardiogram: Recommendationse95 Assessment of LV Function: Recommendationse96 Exercise Stress Testing for Myocardial Ischemia and Functional Capacity: Recommendationse97 Cardiopulmonary Exercise Testing: Recommendatione97 Pharmacological Stress Testinge97 Noninvasive Pharmacological Stress Testing Before Noncardiac Surgery: Recommendationse97 Radionuclide MPIe98 Dobutamine Stress Echocardiographye98 Stress Testing--Special Situationse99 Preoperative Coronary Angiography: Recommendatione99 Perioperative Therapye99 Coronary Revascularization Before Noncardiac Surgery: Recommendationse100 Timing of Elective Noncardiac Surgery in Patients With Previous PCI: Recommendationse115 Future Research Directionse116 Referencese117 Appendix 1 Author Relationships With Industry and Other Entities (Relevant)e129 Appendix 2 Reviewer Relationships With Industry and Other Entities (Relevant)e131 Appendix 3 Related Recommendations From Other CPGse136 Appendix 4 Abbreviationse137 Preamble The American College of Cardiology (ACC) and the American Heart Association (AHA) are committed to the prevention and management of cardiovascular diseases through professional education and research for clinicians, providers, and patients. Since 1980, the ACC and AHA have shared a responsibility to translate scientific evidence into clinical practice guidelines (CPGs) with recommendations to standardize and improve cardiovascular health.
Summary Background Tenofovir disoproxil fumarate can cause renal and bone toxic effects related to high plasma tenofovir concentrations. Tenofovir alafenamide is a novel tenofovir prodrug with a 90% ...reduction in plasma tenofovir concentrations. Tenofovir alafenamide-containing regimens can have improved renal and bone safety compared with tenofovir disoproxil fumarate-containing regimens. Methods In these two controlled, double-blind phase 3 studies, we recruited treatment-naive HIV-infected patients with an estimated creatinine clearance of 50 mL per min or higher from 178 outpatient centres in 16 countries. Patients were randomly assigned (1:1) to receive once-daily oral tablets containing 150 mg elvitegravir, 150 mg cobicistat, 200 mg emtricitabine, and 10 mg tenofovir alafenamide (E/C/F/tenofovir alafenamide) or 300 mg tenofovir disoproxil fumarate (E/C/F/tenofovir disoproxil fumarate) with matching placebo. Randomisation was done by a computer-generated allocation sequence (block size 4) and was stratified by HIV-1 RNA, CD4 count, and region (USA or ex-USA). Investigators, patients, study staff, and those assessing outcomes were masked to treatment group. All participants who received one dose of study drug were included in the primary intention-to-treat efficacy and safety analyses. The main outcomes were the proportion of patients with plasma HIV-1 RNA less than 50 copies per mL at week 48 as defined by the the US Food and Drug Adminstration (FDA) snapshot algorithm (pre-specified non-inferiority margin of 12%) and pre-specified renal and bone endpoints at 48 weeks. These studies are registered with ClinicalTrials.gov , numbers NCT01780506 and NCT01797445. Findings We recruited patients from Jan 22, 2013, to Nov 4, 2013 (2175 screened and 1744 randomly assigned), and gave treatment to 1733 patients (866 given E/C/F/tenofovir alafenamide and 867 given E/C/F/tenofovir disoproxil fumarate). E/C/F/tenofovir alafenamide was non-inferior to E/C/F/tenofovir disoproxil fumarate, with 800 (92%) of 866 patients in the tenofovir alafenamide group and 784 (90%) of 867 patients in the tenofovir disoproxil fumarate group having plasma HIV-1 RNA less than 50 copies per mL (adjusted difference 2·0%, 95% CI −0·7 to 4·7). Patients given E/C/F/tenofovir alafenamide had significantly smaller mean serum creatinine increases than those given E/C/F/tenofovir disoproxil fumarate (0·08 vs 0·12 mg/dL; p<0·0001), significantly less proteinuria (median % change −3 vs 20; p<0·0001), and a significantly smaller decrease in bone mineral density at spine (mean % change −1·30 vs –2·86; p<0·0001) and hip (−0·66 vs –2·95; p<0·0001) at 48 weeks. Interpretation Through 48 weeks, more than 90% of patients given E/C/F/tenofovir alafenamide or E/C/F/tenofovir disoproxil fumarate had virological success. Renal and bone effects were significantly reduced in patients given E/C/F/tenofovir alafenamide. Although these studies do not have the power to assess clinical safety events such as renal failure and fractures, our data suggest that E/C/F/tenofovir alafenamide will have a favourable long-term renal and bone safety profile. Funding Gilead Sciences.
Background The over-the-scope clip (OTSC) provides more durable and full-thickness closure as compared with standard clips. Only case reports and small case series have reported on outcomes of OTSC ...closure of GI defects. Objective To describe a large, multicenter experience with OTSCs for the management of GI defects. Secondary goals were to determine success rate by type of defect and type of therapy and to determine predictors of treatment outcomes. Design Multicenter, retrospective study. Setting Multiple, international, academic centers. Patients Consecutive patients who underwent attempted OTSC placement for GI defects, either as a primary or as a rescue therapy. Interventions OTSC placement to attempt closure of GI defects. Main Outcome Measurements Long-term success of the procedure. Results A total of 188 patients (108 fistulae, 48 perforations, 32 leaks) were included. Long-term success was achieved in 60.2% of patients during a median follow-up of 146 days. Rate of successful closure of perforations (90%) and leaks (73.3%) was significantly higher than that of fistulae (42.9%) ( P < .05). Long-term success was significantly higher when OTSCs were applied as primary therapy (primary 69.1% vs rescue 46.9%; P = .004). On multivariate analysis, patients who had OTSC placement for perforations and leaks had significantly higher long-term success compared with those who had fistulae (OR 51.4 and 8.36, respectively). Limitations Retrospective design and multiple operators with variable expertise with the OTSC device. Conclusion OTSC is safe and effective therapy for closure of GI defects. Clinical success is best achieved in patients undergoing closure of perforations or leaks when OTSC is used for primary or rescue therapy. Type of defect is the best predictor of successful long-term closure.
Food protein–induced enterocolitis (FPIES) is a non-IgE cell- mediated food allergy that can be severe and lead to shock. Despite the potential seriousness of reactions, awareness of FPIES is low; ...high-quality studies providing insight into the pathophysiology, diagnosis, and management are lacking; and clinical outcomes are poorly established. This consensus document is the result of work done by an international workgroup convened through the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology and the International FPIES Association advocacy group. These are the first international evidence-based guidelines to improve the diagnosis and management of patients with FPIES. Research on prevalence, pathophysiology, diagnostic markers, and future treatments is necessary to improve the care of patients with FPIES. These guidelines will be updated periodically as more evidence becomes available.
Recommendations2389 Future Research Directions2389 References2390 Appendix 1 Author Relationships With Industry and Other Entities (Relevant)2397 Appendix 2 Reviewer Relationships With Industry and ...Other Entities (Relevant)2399 Appendix 3 Related Recommendations From Other CPGs2404 Preamble The American College of Cardiology (ACC) and the American Heart Association (AHA) are committed to the prevention and management of cardiovascular diseases through professional education and research for clinicians, providers, and patients. Since 1980, the ACC and AHA have shared a responsibility to translate scientific evidence into clinical practice guidelines (CPGs) with recommendations to standardize and improve cardiovascular health. Harm B (187,211,218,219,224-227,238) Table A Left Main CAD Revascularization Recommendations From the 2011 CABG and PCI CPGs CABG indicates coronary artery bypass graft; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; COR, Class of Recommendation; CPG, clinical practice guideline; EF, ejection fraction; LAD, left anterior descending; LIMA, left internal mammary artery; LOE, Level of Evidence; LV, left ventricular; N/A, not applicable; PCI, percutaneous coronary intervention; SIHD, stable ischemic heart disease; STEMI, ST-elevation myocardial infarction; STS, Society of Thoracic Surgeons; SYNTAX, Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery; TIMI, Thrombolysis In Myocardial Infarction; UA/NSTEMI, unstable angina/non-ST-elevation myocardial infarction; UPLM, unprotected left main disease; and VT, ventricular tachycardia.
Background Left atrial enlargement, a sensitive integrator of left ventricular diastolic function, is associated with increased cardiovascular morbidity and mortality. Vitamin D is linked to lower ...cardiovascular morbidity, possibly modifying cardiac structure and function; however, firm evidence is lacking. We assessed the effect of an activated vitamin D analog on left atrial volume index (LAVi) in a post hoc analysis of the PRIMO trial (clinicaltrials.gov: NCT00497146). Methods and results One hundred ninety-six patients with chronic kidney disease (estimated glomerular filtration rate 15-60 mL/min per 1.73m2 ), mild to moderate left ventricular hypertrophy, and preserved ejection fraction were randomly assigned to 2 μg of oral paricalcitol or matching placebo for 48 weeks. Two-dimensional echocardiography was obtained at baseline and at 24 and 48 weeks after initiation of therapy. Over the study period, there was a significant decrease in LAVi (−2.79 mL/m2 , 95% CI −4.00 to −1.59 mL/m2 ) in the paricalcitol group compared with the placebo group (−0.70 mL/m2 95% CI −1.93 to 0.53 mL/m2 , P = .002). Paricalcitol also attenuated the rise in levels of brain natriuretic peptide (10.8% in paricalcitol vs 21.3% in placebo, P = .02). For the entire population, the change in brain natriuretic peptide correlated with change in LAVi ( r = 0.17, P = .03). Conclusions Forty-eight weeks of therapy with an active vitamin D analog reduces LAVi and attenuates the rise of BNP. In a population where only few therapies alter cardiovascular related morbidity and mortality, these post hoc results warrant further confirmation.
Coronary chronic total occlusions (CTOs) are frequently identified during coronary angiography and remain the most challenging lesion group to treat. Patients with CTOs are frequently left ...unrevascularized due to perceptions of high failure rates and technical complexity even if they have symptoms of coronary disease or ischemia. In this review, the authors describe a North American contemporary approach for percutaneous coronary interventions for CTO. Two guide catheters are placed to facilitate seamless transition between antegrade wire–based, antegrade dissection re-entry–based, and retrograde (wire or dissection re-entry) techniques, the “hybrid” interventional strategy. After dual coronary injection is performed, 4 angiographic parameters are assessed: 1) clear understanding of location of the proximal cap using angiography or intravascular ultrasonography; 2) lesion length; 3) presence of branches, as well as size and quality of the target vessel at the distal cap; and 4) suitability of collaterals for retrograde techniques. On the basis of these 4 characteristics, an initial strategy and rank order hierarchy for technical approaches is established. Radiation exposure, contrast utilization, and procedure time are monitored throughout the procedure, and thresholds are established for intraprocedural strategy conversion to maximize safety, efficiency, and effectiveness.
Summary Background For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued ...indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions. Methods TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4–16 years and had abnormal TCD flow velocities (≥200 cm/s) but no severe vasculopathy. After screening, eligible participants were randomly assigned 1:1 to continue standard transfusions (standard group) or hydroxycarbamide (alternative group). Randomisation was done at a central site, stratified by site with a block size of four, and an adaptive randomisation scheme was used to balance the covariates of baseline age and TCD velocity. The study was open-label, but TCD examinations were read centrally by observers masked to treatment assignment and previous TCD results. Participants assigned to standard treatment continued to receive monthly transfusions to maintain 30% sickle haemoglobin or lower, while those assigned to the alternative treatment started oral hydroxycarbamide at 20 mg/kg per day, which was escalated to each participant's maximum tolerated dose. The treatment period lasted 24 months from randomisation. The primary study endpoint was the 24 month TCD velocity calculated from a general linear mixed model, with the non-inferiority margin set at 15 cm/s. The primary analysis was done in the intention-to-treat population and safety was assessed in all patients who received at least one dose of assigned treatment. This study is registered with ClinicalTrials.gov , number NCT01425307. Findings Between Sept 20, 2011, and April 17, 2013, 159 patients consented and enrolled in TWiTCH. 121 participants passed screening and were then randomly assigned to treatment (61 to transfusions and 60 to hydroxycarbamide). At the first scheduled interim analysis, non-inferiority was shown and the sponsor terminated the study. Final model-based TCD velocities were 143 cm/s (95% CI 140–146) in children who received standard transfusions and 138 cm/s (135–142) in those who received hydroxycarbamide, with a difference of 4·54 (0·10–8·98). Non-inferiority (p=8·82 × 10−16 ) and post-hoc superiority (p=0·023) were met. Of 29 new neurological events adjudicated centrally by masked reviewers, no strokes were identified, but three transient ischaemic attacks occurred in each group. Magnetic resonance brain imaging and angiography (MRI and MRA) at exit showed no new cerebral infarcts in either treatment group, but worsened vasculopathy in one participant who received standard transfusions. 23 severe adverse events in nine (15%) patients were reported for hydroxycarbamide and ten serious adverse events in six (10%) patients were reported for standard transfusions. The most common serious adverse event in both groups was vaso-occlusive pain (11 events in five 8% patients with hydroxycarbamide and three events in one 2% patient for transfusions). Interpretation For high-risk children with sickle cell anaemia and abnormal TCD velocities who have received at least 1 year of transfusions, and have no MRA-defined severe vasculopathy, hydroxycarbamide treatment can substitute for chronic transfusions to maintain TCD velocities and help to prevent primary stroke. Funding National Heart, Lung, and Blood Institute, National Institutes of Health.
Background Statin intolerance limits many patients from achieving optimal low-density lipoprotein cholesterol (LDL-C) concentrations. Current options for such patients include using a lower but ...tolerated dose of a statin and adding or switching to ezetimibe or other non-statin therapies. Methods ODYSSEY ALTERNATIVE ( NCT01709513 ) compared alirocumab with ezetimibe in patients at moderate to high cardiovascular risk with statin intolerance (unable to tolerate ≥2 statins, including one at the lowest approved starting dose) due to muscle symptoms. A placebo run-in and statin rechallenge arm were included in an attempt to confirm intolerance. Patients (n = 361) received single-blind subcutaneous (SC) and oral placebo for 4 weeks during placebo run-in. Patients reporting muscle-related symptoms during the run-in were to be withdrawn. Continuing patients were randomized (2:2:1) to double-blind alirocumab 75 mg SC every 2 weeks (Q2W; plus oral placebo), ezetimibe 10 mg/d (plus SC placebo Q2W), or atorvastatin 20 mg/d (rechallenge; plus SC placebo Q2W) for 24 weeks. Alirocumab dose was increased to 150 mg Q2W at week 12 depending on week 8 LDL-C values. Primary end point was percent change in LDL-C from baseline to week 24 (intent-to-treat) for alirocumab vs ezetimibe. Results Baseline mean (standard deviation) LDL-C was 191.3 (69.3) mg/dL (5.0 1.8 mmol/L). Alirocumab reduced mean (standard error) LDL-C by 45.0% (2.2%) vs 14.6% (2.2%) with ezetimibe (mean difference 30.4% 3.1%, P < .0001). Skeletal muscle-related events were less frequent with alirocumab vs atorvastatin (hazard ratio 0.61, 95% confidence interval 0.38–0.99, P = .042). Conclusions Alirocumab produced greater LDL-C reductions than ezetimibe in statin-intolerant patients, with fewer skeletal-muscle adverse events vs atorvastatin.
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