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The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
Implantable cardioverter-defibrillators (ICDs) for primary prevention in nonischemic cardiomyopathy (July 2017)
Several trials have shown reduced arrhythmia-related mortality among patients with nonischemic cardiomyopathy who receive an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden death, but no individual trial has shown a benefit in total mortality. Four meta-analyses that included patients receiving a primary prevention ICD from the same six trials (CAT, AMIOVIRT, DEFINITE, SCD-HeFT, COMPANION, and DANISH), demonstrate a significant benefit for all-cause mortality compared with medical therapy alone (19 to 24 percent hazard reduction) [1-4]. ICDs should be used in conjunction with optimal medical therapy to reduce mortality in patients with nonischemic cardiomyopathy. (See "Primary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Meta-analyses of ICD trials in nonischemic cardiomyopathy'.)
ACC/AHA/HRS guideline for the evaluation and management of syncope (July 2017)
In 2017 the American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) published guidelines on evaluation and management of patients with syncope, the first major new syncope guidelines in eight years . The guidelines present an approach to the evaluation and management of patients with syncope that is consistent with the approach advocated by UpToDate experts. Both UpToDate and the ACC/AHA/HRS guidelines emphasize the importance of a detailed medical history, physical examination, and review of an electrocardiogram as the initial evaluation in all patients. An echocardiogram should be performed in patients with known or suspected structural heart disease, with selected additional testing directed by the results of the initial evaluation. (See "Syncope in adults: Clinical manifestations and diagnostic evaluation", section on 'Initial evaluation'.)
Management of dabigatran in the periprocedural period prior to catheter ablation for AF (June 2017)
Most patients scheduled to undergo catheter ablation for atrial fibrillation (AF) receive effective oral anticoagulation weeks before the procedure. When warfarin is used as the anticoagulant, it is given without interruption up to the procedure. The newer oral anticoagulants (NOAC), such as dabigatran, are most often held the day prior to the procedure. In the RE-CIRCUIT trial, 704 patients scheduled for catheter ablation were randomly assigned to take dabigatran 150 mg twice daily (without interruption prior to catheter ablation) or warfarin (target INR 2.0-3.0) for 4 to 8 weeks prior to the procedure . There were significantly fewer episodes of major bleeding in the dabigatran group but no significant difference in the rate of thromboembolism. UpToDate authors continue to advise discontinuing dabigatran before catheter ablation, but suggest that uninterrupted dabigatran may be reasonable for the patient who is at very high risk of a periprocedural stroke. (See "Catheter ablation to prevent recurrent atrial fibrillation: Anticoagulation", section on 'Choice of anticoagulant'.)
CORONARY ARTERY BYPASS GRAFT SURGERY
Five-year survival worse with off-pump compared with on-pump CABG (August 2017)
We perform off-pump coronary artery bypass graft surgery (CABG) in a small minority of patients as the evidence to support its use has been eroding. In the large ROOBY trial, the rate of death at five years was significantly higher with off-pump, compared with on-pump, CABG (15.2 versus 11.9 percent) . (See "Off-pump and minimally invasive direct coronary artery bypass graft surgery: Outcomes", section on 'Comparison to on-pump CABG'.)
CORONARY HEART DISEASE, ACUTE
Targeting inflammation to reduce adverse cardiac events in patients with a recent ACS and elevated CRP (September 2017)
Inflammation is believed to be a central component in the pathogenesis of atherosclerosis. An elevated level of C-reactive protein (CRP), an inflammatory biomarker, is an independent predictor of adverse events from atherosclerosis, but no therapy specifically targeting inflammation has previously been shown to reduce atherosclerotic events. The CANTOS trial randomly assigned over 10,000 patients with a recent acute coronary syndrome and CRP ≥2 mg/L to receive placebo or one of three doses of canakinumab, a monoclonal antibody targeting interleukin-1 beta. At a median follow-up of over three years, canakinumab dosed at 150 or 300 mg subcutaneously every three months reduced the primary composite endpoint of cardiac death, nonfatal myocardial infarction, and nonfatal stroke, with no significant impact on lipid levels, but was associated with an increased risk of fatal infections . This is the first study to show that an anti-inflammatory drug with no effect on lipid levels improves the outcome of patients with ACS and systemic evidence of inflammation. However, the role, if any, of anti-inflammatory therapy for patients following ACS remains to be determined. (See "C-reactive protein in cardiovascular disease", section on 'Monoclonal antibodies'.)
No benefit from supplemental oxygen in normoxemic AMI patients (September 2017)
The value of supplemental oxygen in normoxemic patients (oxygen saturation ≥90 percent) with suspected acute myocardial infarction (AMI) has been debated for years. In the DETO2X-AMI trial, over 6500 such patients were randomly assigned to receive supplemental oxygen (delivered through an open face mask) or ambient air . There was no benefit or harm from supplemental oxygen. We do not treat normoxemic AMI patients with supplemental oxygen. (See "Overview of the acute management of ST-elevation myocardial infarction", section on 'Oxygen'.)
Timing of coronary angiography in patients with NSTEACS (August 2017)
Unlike patients with ST-elevation myocardial infarction who should undergo coronary angiography and revascularization within a few hours of symptom onset, the optimal timing of angiography in patients with non-ST elevation acute coronary syndromes (NSTEACS) is not known. A 2017 meta-analysis evaluated mortality in eight randomized trials that compared early to delayed invasive treatment . There was no difference in mortality between the two strategies. However, subgroup analysis suggested benefit from early intervention in patients at high risk. We generally perform coronary angiography in most NSTEACS patients within 24 hours of presentation. (See "Coronary angiography and revascularization for unstable angina or non-ST elevation acute myocardial infarction", section on 'Timing'.)
Rapid aspirin desensitization in patients with acute coronary syndrome (April 2017)
There are well-established protocols for elective desensitization to aspirin, but fewer studies of approaches in patients needing urgent treatment. In a multicenter observational study of 330 consecutive patients with acute coronary syndrome and past hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs), 95 percent were successfully desensitized to low-dose aspirin using a protocol that could be completed within six hours . The procedure was aborted in 5 percent because symptoms developed during the protocol. While useful, we prefer our own approach because it does not exclude patients who react during the protocol. (See "Diagnostic challenge and desensitization protocols for NSAID reactions", section on 'Our approach'.)
Urgency of diuretic therapy in patients with acute heart failure (August 2017)
Only retrospective data have been available, until now, to evaluate the importance of time to initiation of diuretic therapy for management of acute heart failure. A multicenter, prospective observational study of 1291 patients with acute heart failure treated with intravenous furosemide within 24 hours of arrival in an emergency department found that treatment within one hour was associated with a lower in-hospital mortality than later treatment . Thus, the expeditious initiation of an intravenous loop diuretic regimen may improve in-hospital outcomes, in addition to controlling symptoms of volume overload. (See "Treatment of acute decompensated heart failure: Components of therapy", section on 'Diuretics'.)
Vitamin D and all-cause mortality in patients with advanced heart failure (August 2017)
Some, but not all, observational studies suggest that low 25-hydroxyvitamin D levels (especially <10 to 20 ng/mL [25 to 50 nmol/L]) are associated with higher mortality. There are few randomized trials of vitamin D supplementation with mortality as a primary endpoint. In one such trial, vitamin D supplementation (4000 international units daily for three years) compared with placebo did not reduce overall mortality in patients with advanced heart failure and baseline vitamin D levels <30 ng/dL (75 nmol/L) . (See "Vitamin D and extraskeletal health", section on 'Mortality'.)
Declining rate of sudden death in heart failure with reduced ejection fraction (July 2017)
Evidence-based medical therapy for heart failure with reduced ejection fraction (HFrEF) reduces both overall mortality rates and risk of sudden death. The trend in risk of sudden death was examined by an analysis of data from over 40,000 patients with HFrEF enrolled in 12 clinical trials of medical therapy with study periods spanning 1995 through 2014 . There was a significant decline in the rate of sudden death across the trials. The cumulative incidence of sudden death at 90 days after trial randomization was 2.4 percent in the earliest trial and 1.0 percent in the most recent trial. (See "Prognosis of heart failure", section on 'Cause of death'.)
Ularitide does not improve outcomes for acute heart failure (May 2017)
Early vasodilator therapy has been proposed as a means of improving outcomes for acute heart failure. However, in a randomized trial comparing a 48-hour infusion of ularitide (a synthetic analogue of the renal vasodilatory peptide urodilatin) with placebo in over 2000 patients presenting with acute heart failure, ularitide led to greater reductions in systolic blood pressure but no difference in clinical outcomes at 48 hours based upon a composite endpoint . Cardiovascular mortality rates at 15 months were similar for both groups. Thus, ularitide caused short-term hemodynamic effects but did not improve clinical outcomes. (See "Treatment of acute decompensated heart failure: Components of therapy".)
Adaptive servoventilation in adults with central sleep apnea and heart failure (April 2017)
A previous randomized trial (SERVE-HF) found that adaptive servoventilation (ASV), a modified method of positive airway pressure ventilation, increased cardiovascular mortality in patients with central sleep apnea (CSA) due to symptomatic heart failure with reduced ejection fraction. In the CAT-HF trial, 126 hospitalized patients with heart failure and moderate-to-severe CSA were randomly assigned to ASV plus optimized medical therapy or medical therapy alone . While the trial showed no difference between the groups in a combined endpoint (death, cardiovascular hospitalizations, and timed walk distance), the confidence intervals were wide and there was a suggestion of increased harm in the ASV group (HR 1.06, 95% CI 0.75-1.51). The trial was stopped early, in part due to results of SERVE-HF. Although this limits interpretation of the CAT-HF results, we continue to recommend against use of ASV in patients with CSA and heart failure with reduced ejection fraction. (See "Sleep-disordered breathing in heart failure", section on 'Adaptive servoventilation' and "Central sleep apnea: Treatment", section on 'Patients with ejection fraction ≤45 percent'.)
Anacetrapib, a CETP inhibitor, improves cardiovascular outcomes (September 2017)
Cholesteryl ester transfer protein (CETP) inhibitors raise high density lipoprotein cholesterol (HDL-C) and lower low density lipoprotein cholesterol (LDL-C). However, previous randomized clinical trials of four different CETP inhibitors, for the most part, have found no benefit and some potential harm. In the recent REVEAL trial, over 30,000 adults with atherosclerotic vascular disease who were receiving intensive statin therapy were randomly assigned to receive the CETP inhibitor anacetrapib once daily or placebo . During a median follow-up of over four years, fewer cardiovascular events occurred in the treatment group and there was no evidence of serious adverse events with anacetrapib. Most of the benefit could be attributed to LDL-C lowering. Further investigation is required to determine the role of CETP inhibitors in the management of dyslipidemia. (See "HDL cholesterol: Clinical aspects of abnormal values", section on 'CETP inhibition'.)
Statin awareness and reported muscle-related adverse events (August 2017)
In clinical practice, side effects with statins are common, which could be related in part to a heightened awareness of adverse reactions traditionally attributed to the drugs. In a randomized double-blind, placebo-controlled trial involving over 10,000 patients, atorvastatin therapy did not increase the rate of muscle-related adverse events (AEs) . By contrast, in the non-randomized, non-blinded extension of the study, muscle-related AEs were reported more often in patients taking atorvastatin compared with placebo. These results suggest that some muscle-related AEs attributed to atorvastatin are not causally linked to the drug. (See "Statins: Actions, side effects, and administration", section on 'Side effects'.)
Fulminant myocarditis associated with adverse outcomes (August 2017)
Fulminant myocarditis is defined as myocarditis with new onset severe heart failure requiring parenteral inotropic or mechanical circulatory support. Older reports have suggested that patients with fulminant myocarditis may have better outcomes than those with acute nonfulminant myocarditis. In contrast, a new study of 187 patients with acute myocarditis found that individuals with a fulminant presentation had lower rates of heart transplant-free survival both during their initial hospitalization and at nine years compared with patients with nonfulminant myocarditis . The differences in study results are likely due to inclusion of milder cases in the later study as the diagnostic evaluation of acute myocarditis has evolved. (See "Treatment and prognosis of myocarditis in adults", section on 'Fulminant myocarditis'.)
Methamphetamine use and cardiomyopathy (June 2017)
Cardiovascular complications, particularly cardiomyopathy, are the leading causes of death among individuals using methamphetamine, yet there are few data on cardiomyopathy outcomes among methamphetamine users. In a study of 30 methamphetamine users with reduced left ventricular ejection fraction (LVEF) who were followed for a mean of nearly three years, cessation of use compared with continuing use was associated with better cardiac function and a trend toward reduced cardiac symptoms . The extent of myocardial fibrosis was associated with the duration of methamphetamine use and may serve as a marker of irreversible ventricular changes. (See "Methamphetamine use disorder: Epidemiology, clinical manifestations, course, assessment, and diagnosis", section on 'Cardiovascular disease'.)
PERIPHERAL VASCULAR DISEASE
Enhanced MRI does not improve prediction of AAA outcomes (September 2017)
Progression of abdominal aortic aneurysm (AAA) is associated with infiltration of inflammatory cells into the wall of the aorta. Such inflammation can be identified by ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI). In a multicenter study of 342 individuals with AAA ≥4 cm, USPIO uptake was present in 42.7 percent and was associated with increased rates of aneurysm expansion (3.1 versus 2.5 mm per year) and aneurysm rupture/repair (47.3 versus 35.6 percent) . However, baseline AAA diameter and current smoking also predicted aneurysm rupture/repair, and the addition of USPIO uptake did not improve prediction of adverse AAA-related events over clinical features alone. (See "Epidemiology, risk factors, pathogenesis, and natural history of abdominal aortic aneurysm", section on 'Inflammation and the Th2 response'.)
Small interfering RNA molecules to lower PCSK9 and LDL-C (April 2017)
The profound ability of monoclonal antibodies to proprotein convertase subtilisin/kexin type 9 (PCSK9) to lower low-density lipoprotein-cholesterol (LDL-C) has prompted research into other ways of lowering PCSK9. Small interfering RNA molecules (siRNA) offer the potential to lower PCSK9 at a decreased dose frequency compared with monoclonal antibodies. One siRNA inhibitor of PCSK9 synthesis (inclisiran) has undergone phase 2 (dose-finding) evaluation. A randomized trial compared several doses of inclisiran with placebo in 501 patients at high cardiovascular disease risk receiving maximal possible dose of statin therapy . At the highest dose, inclisiran reduced LDL-C by approximately 50 percent from baseline and there were no serious adverse events. (See "PCSK9 inhibitors: Pharmacology, adverse effects, and use", section on 'Ongoing investigation'.)
Instantaneous wave-free ratio versus fractional flow reserve for coronary artery stenosis evaluation (May 2017)
For patients with coronary artery stenoses of intermediate severity, measurement of fractional flow reserve (FFR) with adenosine-induced hyperemia may be used to assess the functional significance of the lesion. However, patients often complain of significant chest pain, attributable to the adenosine, which limits its use. Two randomized non-inferiority trials have compared clinical outcomes for low-risk patients evaluated by FFR with a newer method, instantaneous wave-free ratio (iFR), which does not require adenosine [23,24]. The rate of a composite clinical outcome (death, myocardial infarction, or unplanned revascularization within 12 months) was similar in both groups, but the frequency of adenosine-induced chest discomfort was less with iFR and the duration of the procedure was shorter. We choose either iFR or FFR for evaluation of intermediate lesions. (See "Clinical use of coronary artery pressure flow measurements", section on 'iFR compared with FFR'.)
Increased risk of stent thrombosis with bioresorbable intracoronary scaffolds (April 2017)
Bioresorbable intracoronary stents were developed to overcome limitations of metallic intracoronary stents, such as the inability to subsequently place a bypass graft. However, early trials of these new stents have suggested an increased risk of stent thrombosis compared with commonly used drug-eluting stents. In a preliminary analysis of the AIDA trial, which randomly assigned over 1800 patients to a bioresorbable or metallic stent, there was an increased risk of definite or probable device thrombosis in the scaffold group at two years and there was no evidence of benefit . We do not advocate the routine use of bioresorbable intracoronary drug-eluting stents. (See "Bioresorbable polymer or scaffold drug-eluting coronary artery stents", section on 'Bioresorbable stents or scaffolds'.)
Exercise-based rehabilitation in heart transplant recipients (June 2017)
Most cardiac transplant recipients experience improvement in functional capacity post transplant compared with their preoperative condition, but exercise capacity generally remains below normal. The effect of exercise-based rehabilitation post cardiac transplantation was assessed by a systematic review of 10 randomized controlled trials with a total of 300 participants and median 12 weeks of follow-up . Exercise-based rehabilitation improved exercise capacity compared with no exercise but had no effect on health-related quality of life (HRQoL). We continue to recommend exercise-based cardiac rehabilitation for cardiac transplant recipients, although further studies are needed to determine its long-term effects. (See "Rehabilitation after cardiac transplantation", section on 'Exercise capacity and rehabilitation post-transplantation'.)
VALVULAR HEART DISEASE
An investigational transcatheter mitral valve repair system (September 2017)
Many patients with severe mitral regurgitation do not meet anatomic criteria for transcatheter mitral valve repair with the widely available MitraClip device. The investigational PASCAL transcatheter mitral valve repair system was developed to reduce the anatomical requirements for transcatheter valve repair. The feasibility of PASCAL mitral valve repair was evaluated in 23 patients with symptomatic severe mitral regurgitation, most of whom were not candidates for MitraClip repair . Among the 20 patients alive at 30 days of follow-up, nearly all had improved functional status. (See "Transcatheter mitral valve repair", section on 'Investigational technologies'.)
Embolic protection devices during transcatheter aortic valve implantation (April 2017)
Transcatheter aortic valve implantation (TAVI) has an evolving role as an alternative to surgical aortic valve replacement in treating patients with symptomatic severe aortic stenosis. However, TAVI is associated with an increased risk of stroke and risk of subclinical ischemic brain lesions on magnetic resonance imaging (MRI). Embolic protection devices (EPDs) have been studied as potential means of reducing this risk of stroke. A meta-analysis included 16 studies involving 1170 patients who underwent TAVI, the majority treated with EPD . Analyses comparing EPD versus no EPD strategies could not confirm or exclude differences in clinically evident stroke or mortality at 30 days. While there was no significant difference in numbers of new lesions, use of EPD was associated with a significantly smaller total volume of ischemic lesions. Further study is needed to determine whether EPDs can improve clinical outcomes. (See "Transcatheter aortic valve implantation: Complications", section on 'Stroke and subclinical brain injury'.)
Updated guidelines for management of coronary artery abnormalities in Kawasaki disease (September 2017)
The American Heart Association (AHA) updated its guidelines for management of Kawasaki disease (KD) . New recommendations for evaluating and managing coronary artery abnormalities (CAAs) include an updated risk stratification schema based on CAA size (table 1), which is used to guide antithrombotic therapy and long-term follow-up. The guidelines panel concluded that patients with KD and no history of CAAs are probably not at increased risk for cardiovascular disease compared with the general pediatric population and can be managed with routine preventive counseling alone. Our recommendations for management of cardiovascular sequelae of KD are generally consistent with the 2017 AHA guidelines. (See "Cardiovascular sequelae of Kawasaki disease: Management and prognosis", section on 'Management'.)
High sensitivity cardiac troponin test results in the general population (August 2017)
The blood test for cardiac troponin (cTn) is used most commonly to evaluate patients who may have acute myocardial infarction. With the development of increasingly sensitive troponin tests, it has become clear that many presumably healthy individuals in the general population have an elevated cTn level. The best available data on the prevalence of elevated troponin in the general population and the impact on prognosis comes from a large 2017 observational study . High-sensitivity cTn was detectable in 80 percent of individuals, and the relative risks of major adverse cardiovascular outcomes were significantly increased in a comparison of patients in the top and bottom tertiles for troponin level. However, we do not interpret these findings as evidence in support of screening healthy individuals. (See "Elevated cardiac troponin concentration in the absence of an acute coronary syndrome", section on 'Prognosis'.)
Confirmatory data on idarucizumab for dabigatran reversal (July 2017)
Idarucizumab (pronounced "I-dare-you-cizumab") is a monoclonal antibody fragment against dabigatran that can reverse the anticoagulant effect within minutes. A preliminary report suggested good efficacy in patients with dabigatran-associated bleeding or those undergoing emergency surgery. In a new report of over 500 patients treated with idarucizumab, most had cessation of bleeding or underwent surgery without abnormal bleeding . We continue to suggest idarucizumab for clinically significant bleeding or emergency surgery in patients on dabigatran with a history or laboratory testing that suggest they are actively anticoagulated. (See "Management of bleeding in patients receiving direct oral anticoagulants", section on 'Dabigatran reversal'.)
Radiation for nonmetastastic breast cancer and cardiovascular risk (June 2017)
Many women treated for nonmetastatic breast cancer receive radiation therapy after surgical resection. In a meta-analysis of 39 studies involving almost 1.2 million patients with breast cancer, the risk of coronary artery disease and cardiac death was somewhat increased (relative risk 1.3 and 1.38, respectively) for those who received radiotherapy relative to those who did not . However, absolute risks for these complications were low (76 and 126 cases, respectively, per 100,000 person-years). For appropriately selected patients, adjuvant radiation remains a safe and effective treatment for nonmetastatic breast cancer. (See "Cardiotoxicity of radiation therapy for breast cancer and other malignancies", section on 'Meta-analyses and randomized trials'.)
Routine prophylactic antibiotics do not improve clinically important outcomes in survivors of out-of-hospital cardiac arrest (April 2017)
Many survivors of out-of-hospital cardiac arrest (OHCA) go on to develop pneumonia, but the value of prophylactic antibiotics is unproven. In a single-center clinical trial involving 60 comatose OHCA patients without obvious evidence of tracheobronchial aspiration on admission, random assignment to prophylactic antibiotics versus clinically-driven antibiotic therapy reduced the number of positive broncho-alveolar lavage cultures on hospital day 3, but did not improve survival or other patient-important outcomes . We do not suggest routine prophylactic treatment with antibiotics in these patients. (See "Post-cardiac arrest management in adults", section on 'Antibiotic therapy and prophylaxis'.)
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- Wykrzykowska JJ, Kraak RP, Hofma SH, et al. Bioresorbable Scaffolds versus Metallic Stents in Routine PCI. N Engl J Med 2017.
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