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What's new in cardiovascular medicine
Official reprint from UpToDate® ©2017 UpToDate®
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What's new in cardiovascular medicine
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Dec 2016. | This topic last updated: Jan 23, 2017.

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.


Late gadolinium enhancement to risk stratify patients for primary prevention ICD placement (January 2017)

Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging appears to reflect myocardial fibrosis, which has been proposed as a pathogenic factor for ventricular arrhythmias. Risk stratification remains imperfect for identifying patients at highest risk of sudden cardiac death (SCD) who are most likely to benefit from an implantable cardioverter-defibrillator (ICD).

A systematic review and meta-analysis of 29 observational studies in patients with nonischemic dilated cardiomyopathy assessed the relationship between LGE on CMR imaging and ventricular arrhythmias, sustained ventricular arrhythmias [1]. Appropriate ICD intervention or sudden cardiac death (SCD) was significantly more likely in patients with LGE, with subgroup analysis revealing that LGE risk stratified patients at all levels of left ventricular ejection fraction (LVEF) (both above and below 35 percent).

In a meta-analysis, which included 2993 patients with hypertrophic cardiomyopathy from five cohorts, the presence of LGE on CMR imaging was associated with greater risk for total mortality, cardiovascular mortality, and SCD [2].

While not currently utilized in SCD risk stratification schemes , when the risk of SCD remains uncertain after assessment with conventional risk factors, LGE may help to guide decision-making with regard to implantation of a defibrillator for primary prevention of SCD. (See "Primary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Myocardial fibrosis on CMR' and "Hypertrophic cardiomyopathy: Assessment and management of ventricular arrhythmias and sudden cardiac death risk", section on 'Possible high-risk features'.)

Comparison of complications and efficacy between subcutaneous and transvenous ICDs (December 2016)

Transvenous implantable cardioverter-defibrillators (TV-ICDs) are associated with several complications related to the reliance on endovascular leads. The subcutaneous ICD (S-ICD) was developed to minimize some of the limitations of TV-ICD systems by avoiding endovascular access entirely. In a retrospective cohort study which propensity-matched S-ICD and TV-ICD recipients, the overall complication rate and efficacy was similar between the two groups [3]. S-ICD recipients experienced fewer lead-related complications but more nonlead-related complications, with a similar frequency of ICD shocks (both appropriate and inappropriate) between the two groups. While there are no defined guidelines for the selection of S-ICD over a TV-ICD system, our approach in deciding between the two for a specific patient is based on several clinical variables (algorithm 1). (See "Subcutaneous implantable cardioverter defibrillators", section on 'Comparison with TV-ICD'.)

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 [4]. 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'.)


Risk factors for mortality in Eisenmenger syndrome (December 2016)

Eisenmenger syndrome consists of the triad of congenital systemic-to-pulmonary cardiovascular communication, pulmonary arterial disease caused by increased pulmonary blood flow, and cyanosis. This syndrome is associated with high mortality rates but limited data are available on predictors of death in a contemporary population. In a multicenter study of 1098 patients with Eisenmenger syndrome followed for a median of three years, significant predictors of death on multivariable analysis included older age, presence of a pre-tricuspid shunt, lower oxygen saturation at rest, lack of sinus rhythm, and presence of pericardial effusion [5]. (See "Evaluation and prognosis of Eisenmenger syndrome", section on 'Prognosis'.)


Multiple rather than single arterial grafts in patients undergoing CABG (December 2016)

There is conflicting evidence as to whether survival is improved with placement of multiple arterial grafts, rather than one, in patients undergoing coronary artery bypass graft surgery (CABG). The 2016 ART trial, which randomly assigned 3102 patients scheduled to undergo CABG to bilateral or single internal thoracic artery grafting, found no significant difference in the rate of death at five years. [6]. Based on findings from earlier studies, and the relatively short-term follow-up of the ART trial, we consider placing multiple arterial grafts in patients with a predicted longevity of more than 10 years who are not at high risk of sternal wound infection (which occurs more frequently with multiple arterial grafts). (See "Coronary artery bypass graft surgery: Long-term clinical outcomes", section on 'Multiple arterial grafts'.)

M. chimaera infections associated with cardiac surgery (October 2016)

Clusters of disseminated infection with Mycobacterium chimaera in the United States and Europe have been linked to exposure to contaminated Stockert 3T heater-cooler devices during cardiac surgery [7]. In the United States, the Food and Drug Administration recommends retiring 3T heater-cooler devices and accessories that have tested positive for M. chimaera or that have been linked to known infections and refraining from using any 3T heater-cooler device manufactured before September 2014 except in emergency situations. Providers of patients who have undergone cardiac surgery should be aware of the possibility of M. chimaera infection, even months to years following the procedure. (See "Overview of nontuberculous mycobacterial infections in HIV-negative patients", section on 'Disseminated disease'.)


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 [8]. 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'.)

Testing for resistance to antiplatelet therapy in patients undergoing coronary stenting (August 2016)

Screening for clopidogrel responsiveness in patients treated with coronary artery stenting has not been shown to improve clinical outcomes. The possible benefit from such screening in patients who are treated with the more potent agent prasugrel was evaluated in the ANTARCTIC study, in which 877 elderly acute coronary syndrome patients who underwent coronary stenting and were treated with prasugrel 5 mg were randomly assigned to platelet function monitoring or no monitoring [9]. There was no difference between the groups in the rate of the primary composite cardiovascular outcome. We do not recommend routine testing of patients for antiplatelet therapy resistance. (See "Clopidogrel resistance and clopidogrel treatment failure", section on 'Screening'.)

Outcomes after PCI in patients with MI after noncardiac surgery (August 2016)

Mortality in patients who sustain a myocardial infarction (MI) after noncardiac surgery is known to be high. Outcomes were evaluated in a cohort of such individuals who were referred for coronary angiography and possible percutaneous coronary intervention (PCI) within seven days of surgery [10]. Among those who ultimately underwent PCI, the 30-day death rate was 31.2 percent in those with ST-elevation MI and 8.5 percent in those with non-ST elevation MI. The optimal management strategy for those patients who sustain an MI in the perioperative period is unknown. (See "Perioperative myocardial infarction after noncardiac surgery", section on 'Prognosis after MI'.)


J-shaped relationship between blood pressure and cardiovascular outcomes (November 2016)

There may be a blood pressure threshold below which tissue perfusion is reduced and risk is increased for cardiovascular and renal events and mortality (a J-shaped curve between blood pressure and event rate). In a large international prospective observational study of patients with stable coronary artery disease and treated hypertension, achieved diastolic pressures below 70 and above 80 mmHg were independently associated with increased risk for adverse outcomes (figure 1) [11]. Similarly, achieved systolic pressures below 120 and above 140 mmHg were independently associated with increased risk for adverse outcomes (figure 2). However, these data are observational, and other evidence disputes the importance of these J-shaped curves, particularly for systolic pressure. Based upon the available evidence and the physiology of coronary perfusion, we generally try to avoid lowering the diastolic blood pressure to a value of <60 mmHg in most patients. (See "What is goal blood pressure in the treatment of hypertension?", section on 'J-shaped diastolic curve'.)


Fully magnetically levitated centrifugal pump for advanced heart failure (November 2016)

Continuous flow left ventricular assist devices improve survival in selected patients with refractory heart failure, but these devices are subject to risk of pump thrombosis requiring surgical pump exchange. An unblinded randomized trial compared outcomes in patients receiving either an investigational fully magnetically levitated centrifugal pump, designed to reduce shear stress and thus avoid pump thrombosis, to a commercially available axial pump [12]. Rates of mortality and of stroke were similar in the two treatment groups, but there was a lower rate of reoperation for pump malfunction due to absence of confirmed pump thrombosis in the investigational pump group. (See "Intermediate- and long-term mechanical circulatory support", section on 'Heartmate 3'.)

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) [13]. 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'.)


Safety and efficacy of anakinra for refractory pericarditis (November 2016)

Nonsteroidal anti-inflammatory drugs and colchicine are the preferred initial therapy for acute pericarditis, with glucocorticoids as second-line treatment. Despite therapy, some patients have persistent or recurrent symptoms. A small preliminary randomized trial in patients with recurrent pericarditis and glucocorticoid dependence compared treatment with anakinra (an interleukin 1-beta recombinant receptor antagonist) or placebo for six months following initial treatment with anakinra for two months in both groups [14]. The group that continued anakinra had fewer recurrences and greater symptom-free survival, although prolonged anakinra use was associated with more frequent side effects (mostly nonlimiting local skin reactions). Larger studies are needed to determine safety and long-term efficacy. (See "Recurrent pericarditis", section on 'Other immune therapy'.)

Cardiotoxicity of checkpoint inhibitor immunotherapy (November 2016)

Checkpoint inhibitor immunotherapy for melanoma and other cancers may result in severe or fatal cardiotoxicity, even in the absence of a history of significant cardiac risk factors [15]. High-dose steroids are indicated to treat myositis and other cardiac complications, but symptoms may progress in some cases despite steroids. The early institution of more aggressive immunosuppressive therapy and monitoring should be considered for patients without an immediate response to high-dose steroids. (See "Toxicities associated with checkpoint inhibitor immunotherapy", section on 'Cardiotoxicity'.)

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 [16]. 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'.)


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 [17]. 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 [18]. 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'.)


Risk calculator for estimating cardiovascular disease risk in Chinese patients (January 2017)

A number of multivariate risk models have been developed for estimating the risk of initial cardiovascular disease (CVD) events in apparently healthy, asymptomatic individuals. The Predication for ASCVD Risk in China (China-PAR) project published a risk score which was developed and prospectively validated in two Chinese cohort groups [19]. China-PAR, the first risk estimator specific to Chinese populations, more accurately predicted the risk of future CVD events for Chinese patients than the ACC/AHA pooled cohort equations, which were developed and validated in North American populations. While all risk models have advantages and disadvantages and no single risk model is appropriate for all patients, clinicians should choose a risk calculator which is most appropriate based on the gender and ethnicity of the patient. (See "Estimation of cardiovascular risk in an individual patient without known cardiovascular disease", section on 'China-PAR risk predictor (2016)'.)

Inhibitors of PCSK9 synthesis (December 2016)

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 and require a lower dose frequency than monoclonal antibodies. One siRNA inhibitor of PCSK9 synthesis has undergone phase 1 evaluation [20]. In that trial, 24 patients were randomly assigned to a subcutaneous inclisiran, a long-acting RNA interference therapeutic agent, or placebo. Inclisiran reduced LDL-C without serious adverse events. (See "PCSK9 inhibitors: Pharmacology, adverse effects, and use", section on 'Current investigation'.)

Inadequate sleep and adverse cardiometabolic outcomes (December 2016)

The adverse health outcomes of inadequate sleep duration (<7 hours per night) and quality are increasingly recognized. A new scientific statement from the American Heart Association reviews data linking sleep restriction with adverse cardiometabolic outcomes and recommends that healthy sleep behavior be addressed in public health campaigns to promote ideal cardiac health, alongside blood pressure, cholesterol, diet, blood glucose, physical activity, weight, and smoking cessation [21]. (See "Insufficient sleep: Definition, epidemiology, and adverse outcomes", section on 'Cardiovascular morbidity'.)

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 [22]. 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'.)


CABG versus PCI for significant left main coronary artery disease (November 2016)

Most patients with significant left main coronary artery disease (LMCAD) are referred for revascularization, generally with coronary artery bypass graft surgery (CABG) rather than percutaneous coronary intervention (PCI) with drug eluting stents (DES). The EXCEL and NOBLE trials compared CABG and PCI with current generation DES in patients with LMCAD and low or intermediate disease complexity [23,24]. At long-term follow-up, CABG and PCI appear to have similar rates of death from any cause or myocardial infarction, while the rate of revascularization was higher with PCI. PCI may be an acceptable option for some patients with lower complexity left main coronary disease who can undergo PCI at a reasonable risk. (See "Management of left main coronary artery disease", section on 'Randomized trials'.)

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 [25]. 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 [26]. 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'.)


Cerebral protection device for transcatheter aortic valve implantation (December 2016)

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 risk of stroke and increased risk of subclinical ischemic brain lesions on magnetic resonance imaging (MRI). Cerebral protection devices have been studied as potential means of reducing this risk of stroke. The Sentinel transcatheter cerebral embolic protection device consists of two filters, which are positioned in the brachiocephalic and left common carotid arteries before TAVI and are removed after TAVI. A meta-analysis of three randomized controlled trials of the Sentinel device found that it reduced the total new lesion volume in protected brain regions on MRI [27]. In the largest included trial (with 363 patients), no significant effect on stroke rates or new lesion volume was found [28]. However, the trial was underpowered and the device was designed to protect only limited brain regions (given the dual blood supply of the posterior circulation). Further study is required to assess the clinical effectiveness of a cerebral protection device for TAVI. (See "Transcatheter aortic valve implantation: Complications", section on 'Stroke and subclinical brain injury'.)

Treatment options for symptomatic severe aortic stenosis with intermediate surgical risk (November 2016)

A meta-analysis of four randomized trials with over 3000 patients with symptomatic severe aortic stenosis (AS) at predominantly intermediate risk of perioperative death compared outcomes at two years for transcatheter aortic valve implantation (TAVI) versus surgical aortic valve replacement (SAVR) [29]. Transfemoral TAVI, but not alternative access (non-transfemoral) TAVI, reduced mortality compared with SAVR. TAVI compared with SAVR increased the risk for worsened heart failure symptoms, permanent pacemaker insertion, and moderate or severe aortic valve regurgitation. For patients with symptomatic severe AS and intermediate surgical risk, the Heart Valve Team should perform an individualized risk-benefit assessment of transfemoral TAVI versus SAVR if transfemoral TAVI is feasible; if transfemoral TAVI is not feasible, we recommend SAVR. (See "Choice of therapy for symptomatic severe aortic stenosis", section on 'In intermediate-risk patients'.)

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