The following represent additions to UpToDate since the last version that were considered by the authors and editors to be of particular interest. The new material described below represents a small subset of the updating that has been performed, since approximately 40 percent of the topic reviews are updated during each four-month cycle.

ARRHYTHMIAS

The optimal rate goal for patients with AF, in whom a rate control strategy has been chosen, has been uncertain. The randomized RACE II trial, compared strategies of lenient rate control strategy (resting heart rate <110 beats per minute) or strict rate-control strategy (resting heart rate <80 beats per minute and heart rate during moderate exercise <110 beats per minute) [1]. There was no significant difference between the two groups in the primary composite outcome (cardiovascular death, hospitalization for heart failure, and stroke, systemic embolism, bleeding, and life-threatening arrhythmic events) at three years. However, there were nearly nine times as many visits to achieve rate the control target(s) in those assigned to strict control. (See "Control of ventricular rate in atrial fibrillation: Pharmacologic therapy".)

Arterial hyperoxia early after sudden cardiac arrest (SCA) may have deleterious effects, perhaps due to oxidative injury. Analysis using a multicenter database found that patients with hyperoxia (PaO2 ≥300 mmHg) within 24 hours after ICU arrival following cardiac arrest had higher in-hospital mortality compared with those with normoxia and hypoxia (PaO2 <60mmHg) (63 percent versus 45 and 57 percent) [2]. In a multivariable model, hyperoxia and hypoxia were independent risk factors for death. Further data are needed to determine the impact of oxygen titration during and after resuscitation. (See "Outcome of sudden cardiac arrest", section on 'Impact of arterial oxygen level'.)

CORONARY HEART DISEASE

The optimal blood pressure goal for hypertensive patients with established cardiovascular disease is not known. Two studies have added to the evidence from which recommendations are made (see "Blood pressure management in patients with atherosclerotic cardiovascular disease", section on 'Clinical trials':

• The ACCORD BP trial randomly assigned over 4700 patients with type 2 diabetes who had cardiovascular disease or at least two additional risk factors for cardiovascular disease to systolic blood pressure targets of either less than 120 or less than 140 mmHg [3]. After a mean follow up of 4.7 years, there was no significant difference in the annual rate of the primary composite endpoint of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes (1.87 versus 2.09 percent). Significant adverse events occurred in more patients in the group assigned to the lower blood pressure goal (3.3 versus 1.3 percent).
• In the NAVIGATOR trial, over 9000 patients with impaired glucose tolerance and either established cardiovascular disease or one or more risk factors for cardiovascular disease were randomly assigned to valsartan (160 mg/day) or placebo [4]. After a median follow-up of five years, there was no significant difference in the incidence of either an extended composite outcome (death from cardiovascular causes, nonfatal MI, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina) or a core composite outcome that excluded unstable angina and revascularization.

A hypertensive response during treadmill testing, particularly at peak exercise, is not associated with increased mortality in patients with baseline hypertension, but whether this is true for normotensive patients at baseline as been less clear. In a study of over 4800 asymptomatic individuals with baseline BP <140/90 mmHg who underwent submaximal Bruce treadmill tests and were followed for 20 years [5]. Bruce stage 2 BP >180/90 compared to ≤180/90 mmHg was associated with a significant increase in risk of cardiovascular death after adjustment for rest BP and other risk factors. (See "Performance of exercise ECG testing", section on 'BP measurements'.)

Patients with extremely elevated low density lipoprotein-cholesterol (LDL-C) levels cannot reach their therapeutic goals even on maximal statin dose. The addition of other lipid lowering agents neither reduces LDL-C more than additional 10-20 percent, nor improves cardiovascular outcomes. Two studies found that mipomersen, a second generation antisense oligonucleotide inhibitor of apolipoprotein B100 synthesis, significantly lowers plasma concentration of LDL-C in such patients [6,7]. (See "Primary disorders of LDL-cholesterol metabolism", section on 'Management' and "Treatment of drug-resistant hypercholesterolemia", section on 'Mipomersen'.)

The time from hospital arrival to reperfusion (the door-to-balloon time) has, in most studies, been predictive of in-hospital mortality. However early studies of the relationship between the time from symptom onset to primary percutaneous coronary intervention (PPCI) with stenting were conflicting. This issue was reevaluated in a study of 70 patients with STEMI successfully treated with PPCI and stenting within 12 hours of symptom onset and who subsequently underwent cardiac magnetic resonance imaging [8]. Longer time to PPCI after symptom onset was associated with worsened outcomes (increased mean infarct size and decreased percent of myocardium salvaged). (See "Primary percutaneous coronary intervention in acute ST elevation myocardial infarction: Therapeutic use", section on 'Time to primary PCI' and "Clinical utility of cardiovascular magnetic resonance imaging", section on 'CMR after myocardial infarction'.)

In the general population, coronary artery bypass graft surgery (CABG) is preferred to percutaneous coronary intervention (PCI) in many patients with multivessel coronary disease who require revascularization. The evidence to guide the choice between PCI with stenting and CABG in diabetic patients with stable multivessel disease is limited and does not demonstrate clear superiority to either strategy. The CARDia trial randomly assigned 510 patients with diabetes and symptomatic, multivessel, or complex single vessel CAD to stenting (31 percent were bare metal stents) or CABG [9]. At a mean follow up of one year, stenting was not found to be non-inferior to CABG for the primary composite outcome of all-cause mortality, MI, and stroke (13.0 versus 10.5 percent respectively). (See "Coronary artery revascularization in patients with diabetes mellitus", section on 'Stenting versus CABG in multivessel disease'.)

HEART FAILURE AND CARDIOMYOPATHY

Cardiac resynchronization therapy (CRT) is an effective therapy in selected patients with systolic HF and prolonged QRS interval. Response to therapy is difficult to predict although a number of predictors have been identified. Disparity in response criteria leads to inability to compare study outcomes, as indicated in a review of published CRT trials that found poor agreement across 15 criteria that were reported and compared [10]. These results indicate a need for adaptation of standardized clinically relevant response criteria. (See "Cardiac resynchronization therapy in heart failure: Implantation and other considerations", section on 'Lack of standard response criteria'.)

Experimental evidence and case reports have suggested that prolactin blockade with bromocriptine can have a beneficial effect in peripartum cardiomyopathy (PPCM). The efficacy of prolactin blockade with bromocriptine in peripartum cardiomyopathy (PPCM) was evaluated in an open-label randomized trial of 20 women with PPCM with follow-up at six months [11]. The 10 women receiving bromocriptine demonstrated significantly greater improvement in left ventricular ejection fraction as compared to the 10 women receiving standard care. Fewer patients in the bromocriptine group reached the composite end-point of death, NYHA functional class III or IV heart failure or left ventricular ejection fraction <35 percent as compared to patients in the standard care group (1 versus 8). Further studies are needed to determine the safety and efficacy of bromocriptine therapy for PPCM. (See "Peripartum cardiomyopathy", section on 'Bromocriptine'.)

The 1994 Task Force Criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) were based upon clinical experience with severe disease and are highly specific but lack sensitivity for early and familial disease. The 2010 revised Task Force Criteria were selected based on analysis of data from 108 probands with newly diagnosed ARVC and data from normal subjects [12]. They include quantitative measures for improved diagnostic sensitivity with preserved specificity (table 1 and table 2). (See "Diagnosis of arrhythmogenic right ventricular cardiomyopathy", section on '2010 revision'.)

CARDIAC TRANSPLANTATION

Gene expression profiling of mononuclear cells in peripheral blood specimens has been studied as an alternative to endomyocardial biopsy to detect cellular rejection. The Invasive Monitoring Attenuation through Gene Expression (IMAGE) trial was a noninferiority comparison between a commercially available gene-expression profiling test and routine biopsies [13]. There was no significant difference in two-year cumulative rates of the composite outcome (rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation) although the wide confidence intervals were consistent with up to a 68 percent increase in risk using the gene-expression profiling strategy. Further evidence will be needed to determine the utility of this molecular diagnostic assay as a potential replacement for routine biopsies. (See "Acute cardiac allograft rejection: Diagnosis", section on 'Gene expression profiling'.)

INTERVENTIONAL CARDIOLOGY

In patients with drug-eluting stents (DES), it is not known whether extending the duration of dual antiplatelet therapy with a thienopyridine and aspirin beyond 12 months is beneficial. This issue was addressed in a study that combined data from almost 2700 patients in the REAL-LATE and ZEST-LATE randomized trials [14]. Patients who had received DES and had been free of major adverse cardiac of cerebrovascular events and major bleeding for at least twelve months while on dual antiplatelet therapy (DAT) were randomly assigned to clopidogrel plus aspirin or aspirin alone. The risk of the primary composite outcome of MI or death from cardiac causes did not differ significantly between the two groups at a median follow up of 19.2 months. (See "Coronary artery stent thrombosis: Prevention and management", section on 'Duration of dual antiplatelet therapy'.)

Four randomized trials comparing second generation to first generation drug-eluting stents are summarized as follows (see "Clinical trials of drug-eluting intracoronary stents: Second generation":

• In the SPIRIT IV trial nearly 3700 patients with more complex coronary disease than previously studied, were randomized to everolimus or paclitaxel-eluting stents (EES or PES) [15]. The primary endpoint of target vessel failure at one year was significantly lower in the EES group (4.2 percent versus 6.8 percent), owing to significant reductions in target lesion revascularization and MI.
• In COMPARE, EES were compared to PES in 1800 unselected, real-world patients. The primary endpoint of death, MI and target vessel revascularization at 12 months occurred significantly less often with EES (6.2 versus 9.1 percent) [16].
• The ENDEAVOR IV trial randomly assigned over 1500 patients with single coronary lesions to either zotarolimus-eluting stent (ZES) or PES [17]. ZES was found to be noninferior to PES for the primary end point of nine-month target vessel failure (cardiac death, myocardial infarction, or target vessel revascularization) with rates of 6.6 percent and 7.1 percent for ZES and PES respectively.
• SORT OUT III randomly assigned over 2300 patients to ZES or sirolimus-eluting stents) SES [18]. The primary endpoint, a composite of cardiac death, MI, and TVR, occurred significantly more often in ZES than SES at nine months (6 percent versus 3 percent) and 18 months (10 percent versus 5 percent).

VALVULAR HEART DISEASE

A retrospective study found that statin therapy is associated with slower progression of rheumatic mitral stenosis (MS) [19]. During mean six year follow-up, the rates of decline in mitral valve area, increase in mean transmitral gradient, and increase in pulmonary artery systolic pressure were lower in the statin group (n=35) compared with the untreated group (n=280). Further study in randomized controlled trials is required to determine whether statins have a beneficial impact in this setting. (See "Medical management and indications for intervention in mitral stenosis", section on 'Statin therapy'.)

The primary indication for aortic valve replacement for aortic stenosis (AS) is symptomatic disease. However, improved outcomes with aortic valve replacement for asymptomatic very severe AS was suggested by an observational study [20]. Very severe AS was defined as an aortic valve area of ≤0.75 cm2 accompanied by a peak aortic jet velocity ≥4.5 m/sec or a mean transaortic pressure gradient ≥50 mmHg. In a nonrandomized prospective study, early surgery was performed on 102 patients and a conventional treatment strategy (surgery for symptomatic AS) was followed in 95 patients with a median 4 year follow-up. The early surgery had no operative mortalities, no cardiac deaths, and three noncardiac deaths while the conventional treatment group had 18 cardiac and 10 noncardiac deaths These results suggest that early surgery can be beneficial in patients with very severe AS with low operative risk, but are limited by nonrandomized assignment to early surgery or conventional therapy. (See "Indications for valve replacement in aortic stenosis in adults", section on 'Very severe AS'.)

NONINVASIVE CARDIAC IMAGING

Uptake of metaiodobenzylguanidine (mIBG), an analog of norepinephrine, is decreased in heart failure (HF). A prospective multicenter study evaluated the predictive value of mIBG imaging in subjects with NYHA functional class II or III HF and LVEF ≤35 percent [21]. The heart/mediastinal uptake ratio (H/M) on mIBG imaging was compared to time to first occurrence of NYHA functional class progression, potentially life-threatening arrhythmic event, or cardiac death. The two-year event rate was 15 percent for an H/M ≥ 1.6 as compared to 37 percent for an H/M ≤1.6. In a multivariable model, H/M, left ventricular ejection fraction, brain natriuretic peptide level, and NYHA functional class were independent predictors for time to cardiac events. (See "Predictors of survival in heart failure due to systolic dysfunction", section on 'mIBG imaging'.)

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