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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.
ICDs for primary prevention of sudden cardiac death in nonischemic cardiomyopathy (September 2016)
Earlier studies, performed before use of cardiac resynchronization therapy (CRT) and current optimal medical therapy, have shown that implantable cardioverter-defibrillator (ICD) therapy reduced total mortality and sudden cardiac death (SCD) in patients with heart failure and nonischemic cardiomyopathy. A new trial (DANISH) in patients with symptomatic nonischemic systolic heart failure (LVEF ≤35 percent) treated with optimal medical therapy (including CRT in the majority of patients) found no reduction in the primary endpoint of total mortality for patients randomized to receive an ICD, compared with no ICD therapy . There was, however, a reduction in SCD, a pre-specified secondary outcome. Thus, although SCD is decreased, ICD therapy for this population does not appear to have an overall total mortality benefit in the setting of guideline-directed optimal medical therapy and cardiac resynchronization therapy. (See "Primary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'DANISH trial'.)
Radiofrequency catheter ablation for patients with an ICD and recurrent shocks (May 2016)
Patients with an implantable cardioverter-defibrillator (ICD) who have recurrent ICD shocks due to ventricular tachycardia (VT) experience significant discomfort and reduced quality of life, and the effectiveness of antiarrhythmic drug therapy to prevent VT is limited. In the VANISH trial, a multicenter, nonblinded trial of patients with prior myocardial infarction and an ICD who had at least one episode of VT within the preceding six months while on antiarrhythmic drug therapy, patients were randomized to radiofrequency catheter ablation (RFA) or escalated antiarrhythmic therapy . Over a mean follow-up of 28 months, patients in the RFA group had significant reduction in the composite primary outcome of death, VT storm, or appropriate ICD shocks, although there was no difference in mortality alone. RFA is an option for reducing the morbidity associated with recurrent ICD shocks in patients with ischemic cardiomyopathy who have recurrent VT despite antiarrhythmic drug therapy. (See "Sustained monomorphic ventricular tachycardia in patients with a prior myocardial infarction: Treatment and prognosis", section on 'Efficacy of catheter ablation'.)
Long QT syndrome mutations and sudden unexpected death in epilepsy (May 2016)
Sudden unexpected death in epilepsy (SUDEP) accounts for up to one-third of premature deaths in patients with epilepsy, and the pathophysiologic mechanisms are not well defined. A new study suggests that some patients may be predisposed to SUDEP due to congenital long QT syndrome (LQTS). In a study of 61 SUDEP cases for which whole blood was available at autopsy, exome sequencing identified pathogenic LQTS mutations in four patients . An additional nine patients had candidate pathogenic variants in dominant cardiac arrhythmia genes. Prospective studies are needed to determine whether electrocardiogram monitoring or other strategies can identify patients at risk for SUDEP and lead to interventions to reduce risk in patients with epilepsy. (See "Sudden unexpected death in epilepsy", section on 'Genetic factors'.)
Amiodarone versus lidocaine versus placebo for refractory out-of-hospital cardiac arrest (April 2016)
Out-of-hospital cardiac arrest is one of the leading causes of death worldwide. Antiarrhythmic therapy with amiodarone and lidocaine has been shown to increase survival to hospital arrival, but their effects on survival to hospital discharge and discharge with good neurologic function is unknown. In a randomized trial comparing amiodarone, lidocaine, and placebo in patients with pulseless ventricular tachycardia (VT) or ventricular fibrillation (VF) refractory to defibrillation and initial vasopressor therapy, there was no difference in the primary outcome (survival to hospital discharge) between the three groups, although there was a suggestion of improved survival in both the amiodarone and lidocaine groups compared with placebo . These data are consistent with the 2015 American Heart Association (AHA) guideline approach to therapy, in which amiodarone and lidocaine "may be considered" for patients with VF or pulseless VT that is refractory to initial treatments. Further studies are needed to identify patients who are more likely to benefit from antiarrhythmic drug therapy. (See "Supportive data for advanced cardiac life support in adults with sudden cardiac arrest", section on 'Comparison of amiodarone and lidocaine'.)
CORONARY ARTERY BYPASS GRAFT SURGERY
Preoperative statin therapy does not decrease the risk of perioperative AF (May 2016)
Perioperative atrial fibrillation (AF) is common with cardiac surgery. Statins have been prescribed as preventive therapy based on relatively weak evidence. In the STICS trial, 1922 patients in sinus rhythm scheduled for elective cardiac surgery were randomly assigned to receive perioperative rosuvastatin (20 mg daily) or placebo up to eight days before surgery . There was no difference in the rate of perioperative AF but a significant increase in the risk of acute kidney injury in the rosuvastatin group. Based on available evidence, we do not start statins before cardiac surgery in most cases. (See "Atrial fibrillation and flutter after cardiac surgery", section on 'Ineffective or possibly effective therapies'.)
Surgical revascularization in patients with coronary disease and left ventricular systolic dysfunction (April 2016)
Most observational studies suggest that surgical revascularization in patients with ischemic cardiomyopathy (left ventricular ejection fraction [LVEF] of 35 percent or less) improves survival compared with medical therapy. Previously reported five-year outcomes of the randomized Surgical Treatment for Ischemic Heart Failure (STICH) trial comparing surgical revascularization with medical therapy alone showed a trend toward reduced mortality following surgical revascularization, but this primary outcome did not achieve statistical significance. An updated report, the STICH Extension Study (STICHES), extended the follow-up to a median of 9.8 years and found a significant 7 percent absolute reduction in total mortality for patients who underwent surgical revascularization . On the basis of this new evidence, we have revised our previous suggestion for initial management with medical therapy alone for most patients with LVEF 35 percent or less and coronary artery disease amenable to coronary artery bypass graft (CABG) surgery. For such patients, we now suggest the combination of surgical revascularization and medical therapy rather than medical therapy alone. This suggestion is based primarily on the long-term absolute reduction in mortality over the 10 years following CABG surgery. Based on the small but nontrivial early mortality risk associated with CABG surgery as well as other post-CABG morbidities, patients may also reasonably choose medical therapy as the initial treatment option. (See "Diagnosis and management of ischemic cardiomyopathy", section on 'Randomized trials'.)
CORONARY HEART DISEASE, ACUTE
Management of a non-culprit chronic total occlusion after primary PCI in STEMI patients (October 2016)
The optimal management of non-culprit lesions, including chronic total occlusion (CTO), in patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) is not known. A randomized trial in 200 STEMI patients who underwent primary PCI compared additional PCI for a CTO within 7 days of the primary PCI with no PCI of the CTO . At four months, there was no difference in measures of cardiac function (left ventricular ejection fraction or left ventricular end diastolic volume). Nonetheless, we believe it is reasonable to perform PCI of CTO in STEMI patients with a significant area of potentially viable myocardium or persistent angina after primary PCI. (See "Primary percutaneous coronary intervention in acute ST-elevation myocardial infarction: Non-culprit lesions", section on 'Chronic total occlusions'.)
Diagnosis of left ventricular mural thrombus after STEMI (June 2016)
Although cardiac magnetic imaging (CMR) is considered the gold standard for the diagnosis of left ventricular (LV) thrombus after acute myocardial infarction (MI), it is not routinely employed due to issues of cost and availability. The role and limitations of contrast echocardiography as a screening test for mural thrombus was evaluated in a study of 201 patients who were evaluated with noncontrast and contrast echocardiography, and CMR, 7 to 30 days after ST-elevation myocardial infarction (STEMI) . The sensitivity of contrast echocardiography for mural thrombus was 64 percent. A high apical wall motion score, as a measure of apical dysfunction, correlated with the presence of LV thrombus. In patients where there remains uncertainty regarding the presence or absence of thrombus based on echocardiographic findings, it is reasonable to obtain CMR. (See "Left ventricular thrombus after acute myocardial infarction", section on 'Diagnosis'.)
Early, intravenous beta blocker not beneficial in patients with STEMI undergoing primary PCI (June 2016)
The early use of intravenous beta blocker in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) has not been extensively studied with large, rigorous trials evaluating hard clinical end points. In the EARLY-BAMI trial, 683 patients with STEMI were randomly assigned to intravenous metoprolol (two sequential 5 mg boluses) or placebo before PCI . No difference in the primary outcome of infarct size was found between the two groups. We do not recommend the routine use of early intravenous beta blocker in patients with STEMI undergoing primary PCI. (See "Acute myocardial infarction: Role of beta blocker therapy", section on 'Primary PCI'.)
CORONARY HEART DISEASE, STABLE
Combination inhaled glucocorticoid/long-acting beta agonists in patients with COPD and cardiovascular risk factors or disease (May 2016)
While the evidence has been generally reassuring about the safety of combination inhaled glucocorticoid plus long-acting beta agonist (ICS-LABA) inhalers in patients with chronic obstructive pulmonary disease (COPD), patients with known cardiovascular disease (CVD) were excluded from previous clinical trials. In the three-year randomized trial, Study to Understand Mortality and MorbidITy (SUMMIT), the effect of the fluticasone furoate-vilanterol combination inhaler was compared with the individual components and placebo in almost 17,000 patients with moderate COPD (FEV1 between 50 and 70 percent of predicted) and known or increased risk of CVD . Relative to placebo, the combination inhaler did not affect all-cause mortality or composite cardiovascular events. Thus, the presence of CVD should not affect the role of ICS-LABA inhalers in COPD. (See "Management of the patient with severe COPD and cardiovascular disease", section on 'Combination inhaled bronchodilator plus glucocorticoid'.)
Causes and prognosis of high-output heart failure (August 2016)
Limited information is available on contemporary causes and prognosis of high-output heart failure (HF). In a Mayo Clinic series of 120 consecutive patients referred for cardiac catheterization and diagnosed with high-output HF, the most common etiologies were morbid obesity (31 percent), liver disease (22.5 percent), arteriovenous shunts (22.5 percent), lung disease (16 percent), and myeloproliferative disorders (8 percent) . The mortality rate in patients with high-output HF was threefold that of controls without heart disease. High-output HF should be considered in the differential diagnosis when patients present with dyspnea, congestion, and a normal ejection fraction. (See "High-output heart failure", section on 'Causes of high-output failure'.)
Misclassification of genetic variants in minority populations (September 2016)
When an individual's genome is sequenced, the likelihood of an incidentally identified genetic variant is high. Genetic variants are classified for their pathogenicity based on data from population studies. However, many reference populations are heavily weighted to Caucasians and lack information from underrepresented minorities. In a recent study, five variants that are common in healthy African Americans were misclassified as pathogenic for hypertrophic cardiomyopathy . Clinicians must be aware of the potential for misclassification, especially in underrepresented minorities. (See "Incidental and secondary findings from genetic testing", section on 'Underrepresented ethnicities'.)
Mitral valve plication for symptomatic hypertrophic cardiomyopathy and LVOT obstruction (July 2016)
Patients with hypertrophic cardiomyopathy (HCM) and significant left ventricular outflow tract (LVOT) obstruction frequently develop heart failure symptoms and are initially treated medically. If significant heart failure symptoms persist despite maximal medical therapy, septal reduction therapy (surgical myectomy or alcohol septal ablation) can be effective. However, comorbidities may place some patients at high risk for procedural complications. Percutaneous mitral valve plication using the MitraClip device may be another option for such patients. In a prospective study, five patients at high risk for septal myectomy had this device successfully placed; the procedure was terminated for cardiac tamponade in a sixth patient . There was significant improvement in the LVOT gradient, mitral regurgitation, and cardiac output immediately following mitral valve plication, as well as a marked reduction in symptoms at 15-month follow-up. Additional data and longer-term follow-up are required to better assess the efficacy and safety of mitral valve plication in patients with HCM and refractory symptomatic LVOT obstruction. (See "Hypertrophic cardiomyopathy: Nonpharmacologic treatment of left ventricular outflow tract obstruction", section on 'Mitral valve intervention'.)
PERIPHERAL VASCULAR DISEASE
Bioresorbable drug-eluting iliac artery stenting for PAD (July 2016)
Metal stents are commonly used to treat suboptimal transluminal angioplasty, but restenosis remains a problem. Bioresorbable scaffolds have been used in the coronary circulation, but may increase stent thrombosis. A recent feasibility study reported the first clinical use of a drug-eluting (everolimus) bioresorbable vascular scaffold to treat 66 patients with symptomatic peripheral artery disease in the iliac or femoral arteries . At one and two years follow-up, binary restenosis rates (>50 percent) were 12.1 and 16.1 percent, respectively, and freedom from target lesion revascularization was 91.2 and 88.2 percent, respectively. There were no procedure-related amputations or deaths at two years follow-up. Although these results are encouraging, direct comparisons with drug-eluting balloons and drug-eluting polymer-coated metal stents are needed. (See "Percutaneous interventional procedures in the patient with lower extremity claudication", section on 'Aortoiliac occlusive disease'.)
Ticagrelor in patients with peripheral artery disease (July 2016)
Patients with a history of myocardial infarction and concomitant lower extremity peripheral artery disease (PAD) are at increased risk for both systemic and limb ischemic events. Long-term antiplatelet therapy with aspirin is recommended for these patients. Whether adding a second agent offers additional benefits in this population is unclear. A recent large multicenter trial randomly assigned over 21,000 patients with prior myocardial infarction (MI) to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo in addition to low-dose aspirin . Among the subset of patients with previously identified PAD (n = 1143), compared with placebo, use of ticagrelor reduced the absolute rate of major adverse cardiovascular events (MACE) by 4.1 percent and reduced the risk for peripheral revascularization for limb ischemia (hazard ratio [HR] 0.63; 95% CI 0.43-0.93), with a 0.12 percent absolute excess of major bleeding. Given methodologic issues with data ascertainment, further trials are needed to determine if the benefits of dual therapy outweigh the bleeding risk. We do not use dual antiplatelet therapy in patients with PAD in the absence of other indications (eg, drug-eluting stent). (See "Overview of lower extremity peripheral artery disease", section on 'Antithrombotic therapy'.)
CPAP in obstructive sleep apnea does not reduce cardiovascular events (August 2016)
Whether continuous positive airway pressure (CPAP) therapy can reduce the increased risk of cardiovascular morbidity and mortality associated with obstructive sleep apnea (OSA) is unknown. The largest trial to address this issue randomized 2717 patients with moderate to severe OSA and established cardiovascular disease to CPAP therapy plus usual care or usual care alone (eg, education, risk factor modification) and followed patients for 3.7 years . Despite adequate control of OSA, there was no difference in cardiovascular events (eg, cardiovascular deaths, myocardial infarction, or stroke). However, the exclusion of patients who are among the most likely to benefit from CPAP (eg, patients with “sleepy” OSA) and a low adherence rate to therapy (mean was 3.3 hours per night) may have limited the potential benefit from this therapy. While the cardiovascular benefits are unproven, CPAP should be administered for the associated noncardiovascular benefits (eg, improvement in symptoms and quality of life) and should remain the mainstay of therapy for patients with moderate to severe OSA. (See "Obstructive sleep apnea and cardiovascular disease", section on 'Cardiovascular events'.)
Comparison of outcomes with current generation drug-eluting and bare metal intracoronary stents (August 2016)
Improvements in the design of drug-eluting stents (DES) and bare metal stents (BMS) have lowered the rates of long-term cardiac death, stent thrombosis, and repeat revascularization. The NORSTENT trial, which randomly assigned over 9000 patients to percutaneous coronary intervention (PCI) with a DES or a thin-strut BMS, is the most recently published comparison of current generation intracoronary stents . In NORSTENT, there was no difference in the rate of the primary outcome of all-cause death or nonfatal myocardial infarction at six years. The rate of repeat revascularization was significantly lower with DES. We prefer contemporary DES to BMS in most cases. (See "Clinical use of intracoronary bare metal stents", section on 'Contemporary DES'.)
Hybrid coronary artery revascularization (July 2016)
Hybrid coronary artery revascularization (HCR) refers to complete or near complete revascularization using the combination of single vessel coronary artery bypass graft (CABG) with the left internal mammary artery (LIMA) placed to the left anterior descending coronary artery (LAD) and percutaneous coronary intervention (PCI) of significant coronary lesions in other vessels. The largest observational study compared 200 patients who underwent HCR with 98 patients who underwent multivessel PCI . At 12 months, there was no difference in the rate of major adverse cardiac and cerebrovascular events. Based on limited evidence, we believe HCR is a reasonable approach to multivessel coronary artery revascularization in selected patients at facilities with significant expertise. (See "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention", section on 'Hybrid coronary revascularization'.)
VALVULAR HEART DISEASE
Defects in von Willebrand factor function following transcatheter aortic valve replacement (August 2016)
Postprocedural aortic regurgitation (largely paravalvular) develops in approximately 10 to 20 percent of patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR) and is associated with worse outcomes, including an increased mortality rate at one year. A study of patients with aortic stenosis undergoing TAVR identified an association between presence of more than mild postprocedural aortic regurgitation and defects in von Willebrand factor function following TAVR . Defects in von Willebrand factor function following TAVR were also associated with mortality risk at one year. While these findings are intriguing, further data are needed to determine the utility of von Willebrand factor testing in patients undergoing TAVR. (See "Transcatheter aortic valve replacement: Overview of complications", section on 'Paravalvular regurgitation'.)
Genetically determined clopidogrel nonresponsiveness and DAPT outcomes (June 2016)
Dual antiplatelet therapy (DAPT), compared with aspirin alone, lowers the risk of subsequent ischemic events in patients with established atherosclerotic cardiovascular disease. However, many patients on DAPT experience ischemic events. One potential cause of treatment failure is failure to properly metabolize clopidogrel; the presence of the CYP2C19 loss of function allele has been correlated with clopidogrel resistance. The CHANCE trial of patients with transient ischemic attack or minor stroke found that DAPT was more effective in preventing subsequent stroke than aspirin alone. A 2016 subgroup analysis of 2933 individuals in CHANCE, who had genotyping for CYP2C19 genetic variants performed, found that the risk of stroke was lower among noncarriers of the CYP2C19 loss of function allele than those who carried the allele . While the evidence seems to be increasing that genetic variation may determine outcome with the use of clopidogrel, we do not recommend genotyping for clopidogrel loss of function genetic variants or testing for clopidogrel hypo/nonresponsiveness. (See "Clopidogrel resistance and clopidogrel treatment failure", section on 'Loss of function gene carriers'.)
Liraglutide and cardiovascular outcomes (June 2016)
Glucagon-like peptide-1 (GLP-1) receptor agonists improve glycemic control. However, there are few studies assessing clinically important cardiovascular health outcomes.
●In one trial, 9340 patients with type 2 diabetes (mean A1C 8.7 percent) and underlying cardiovascular disease (prior myocardial infarction or stroke) or risk factors were randomly assigned to liraglutide or placebo . Many patients were taking metformin (76 percent), sulfonylureas (50 percent), and/or insulin (44 percent). After a median follow-up of 3.8 years, the primary endpoint (time to first occurrence of a composite endpoint [death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke]) occurred in fewer patients in the liraglutide group (13 versus 14.9 percent).
●In another trial of liraglutide versus placebo in 300 patients (59 percent with type 2 diabetes) with established heart failure and reduced left ventricular ejection fraction who were recently hospitalized, liraglutide had no significant effect on the composite outcome (time to death, time to rehospitalization for heart failure, and time-averaged proportional change in N-terminal pro-B-type natriuretic peptide level) . In a prespecified subgroup analysis, there was no effect of liraglutide compared with placebo on heart failure outcomes in the subset of patients with diabetes.
The choice of additional therapy in metformin-treated patients with type 2 diabetes and persistent hyperglycemia should be individualized based upon patient characteristics, preferences, and costs. Among these considerations, a prior history of myocardial infarction or stroke might favor choosing liraglutide as the second drug to be added to metformin. (See "Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects'.)
Dosing of direct oral anticoagulants in obese patients (June 2016)
Limited data are available to guide dosing of direct oral anticoagulants (DOACs; dabigatran, apixaban, edoxaban, rivaroxaban) in patients with obesity. The International Society of Thrombosis and Hemostasis (ISTH) has issued guidance on this subject . The major recommendations include use of DOACs at standard doses for those with a body mass index (BMI) ≤40 kg/m2 or weight <120 kg, and avoidance of DOACs in individuals with a BMI >40 kg/m2 or weight ≥120 kg. (See "Direct oral anticoagulants: Dosing and adverse effects".)
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