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What's new in cardiovascular medicineFind Print Email

What's new in cardiovascular medicineAuthorsGordon M Saperia, MD, FACCSusan B Yeon, MD, JD, FACCBrian C Downey, MD, FACCDisclosures

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Jan 2013. | This topic last updated: Jan 31, 2013.

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.

ARRHYTHMIAS AND ELECTROCARDIOGRAPHY

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Apixaban for prevention of embolic events in atrial fibrilllation — Apixaban has been approved by the US Food and Drug Administration and the European Medicines Agency for use in patients with atrial fibrillation to reduce the

risk of stroke and systemic embolization [1,2]. Approval was based on the results of the large randomized ARISTOTLE trial, which found that apixaban was non-inferior to warfarin in terms of efficacy and superior in terms of

safety [3]. In patients with atrial fibrillation who meet criteria for anticoagulation, we prefer either a factor Xa inhibitor (apixaban or rivaroxaban) or a direct thrombin inhibitor (dabigatran) to warfarin. (See "Antithrombotic therapy to

prevent embolization in atrial fibrillation", section on 'Apixaban' and "Antithrombotic therapy to prevent embolization in atrial fibrillation", section on 'Indications for and choice of therapy'.)

Radiofrequency catheter ablation as primary therapy for atrial fibrillation — For most patients with paroxysmal atrial fibrillation who wish to pursue a rhythm rather than a rate control strategy, radiofrequency catheter ablation

(RFA) is performed after antiarrhythmic drug therapy has failed. The MANTRA-PAF trial evaluated the potential role of RFA as first-line therapy and found that it was as safe and as effective as antiarrhythmic drug therapy for the long-

term maintenance of sinus rhythm [4]. In addition, patients had fewer symptomatic episodes. While promising, we believe that the evidence is not strong enough to warrant a recommendation to prefer RFA as primary therapy. (See

"Radiofrequency catheter ablation to prevent recurrent atrial fibrillation", section on 'Comparison to antiarrhythmic therapy'.)

Bleeding rates with warfarin and dabigatran — Despite favorable results in the initial randomized trials, post-marketing reports have raised concerns that patients with atrial fibrillation may have a higher rate of serious bleeding

with dabigatran than warfarin. In November 2012, the US Food and Drug Administration issued a statement that a review of information from insurance claims and administrative data sources suggested that the rate of bleeding with

dabigatran did not appear to be higher than with warfarin in patients who were using either drug for the first time [5]. (See "Antithrombotic therapy to prevent embolization in atrial fibrillation", section on 'Studies of anticoagulant

monotherapy'.)

Optimal programming for primary prevention ICDs — The optimal strategy for implantable cardioverter-

defibrillator (ICD) programming, until now, has been to deliver antitachycardia therapy (either pacing or shocks) with minimal delay for any sustained ventricular arrhythmia. In MADIT-RIT, 1500 patients receiving an ICD for primary

prevention were randomly assigned to one of three different ICD programming and therapy strategies [6]:

"Conventional" therapy programming – 2.5 second delay at rates of 170 to 199 beats per minute; 1

second delay at rates of 200 or more beats per minute.

Delayed therapy programming – 60 second delay at rates of 170 to 199 beats per minute; 12 second

delay at rates of 200 to 249 beats per minute; 2.5 second delay at rates of 250 or more beats per minute.

High-rate therapy programming – No therapy at rates of 170 to 199 beats per minutes; 2.5 second

delay at rates of 200 or more beats per minute.

Both high-rate and delayed therapy programming led to significant reductions in the primary outcome of inappropriate

ICD therapies; reduced mortality was also seen with both strategies but was statistically significant only with high-rate programming. In patients receiving an ICD for primary prevention, we recommend strategies that delay therapy or

only institute therapy for very high heart rates, rather than a "conventional" ICD strategy that rapidly administers therapy with minimal delay. For the two alternative strategies investigated in MADIT-RIT, we suggest using the high-

rate therapy programming strategy rather than the delayed therapy programming strategy. (See "General principles of the implantable cardioverter-defibrillator", section on 'Optimal ICD programming'.)

Ivabradine for symptomatic inappropriate sinus tachycardia — Inappropriate sinus tachycardia (IST) may continue for months or years, may produce troublesome symptoms (eg, palpitations, dizziness, shortness of breath),

and is frequently refractory to medical therapy with standard heart rate (HR) controlling medications. Ivabradine, a drug that decreases the depolarizing current in the sinoatrial node, thereby decreasing HR, has been associated with

reductions in HR in a large cohort of patients with coronary heart disease as well as in two small cohorts of patients with IST. In a double-blind, placebo-controlled study of 21 patients with IST, patients treated with ivabradine (5 mg

twice daily) had significant reductions in resting HR and symptoms along with a significant increase in exercise time [7]. When available, we suggest ivabradine (5 mg twice daily) for patients with symptomatic IST. The medication is

not currently available in the United States or Canada. (See "Sinus tachycardia", section on 'Inappropriate sinus tachycardia'.)

Short-term versus long-term antiarrhythmic therapy in atrial fibrillation — The concept that short-term might be as effective and safer than long-term antiarrhythmic drug therapy for the maintenance of sinus rhythm in patients with

a history of atrial fibrillation (AF) has been based on concerns about drug-related arrhythmias and a plausible physiologic mechanism. However, the Flec SL non-inferiority trial, which randomly assigned patients with persistent

AF to either four weeks or six months of flecainide, found that short-term therapy was not non-inferior to long-term therapy for the primary outcomes of time to persistent AF or death [8]. (See "Antiarrhythmic drugs to maintain sinus

rhythm in patients with atrial fibrillation: Recommendations", section on 'Short- versus long-term therapy'.)

Right precordial T-wave inversion — T-wave inversion in the right precordial leads (V1-V3) is seen commonly as a

normal variant in children and adolescents and this pattern may persist into early adulthood. In a population-based study of over 10,000 middle-aged Finnish citizens who were followed for 30 years, right precordial T-wave inversion

was found at baseline in 0.5 percent and its presence did not predict increased mortality compared to individuals without this electrocardiographic pattern [9]. (See "ECG tutorial: ST and T wave changes", section on 'Persistent

juvenile T wave pattern'.)

Epinephrine for out-of-hospital cardiac arrest — Epinephrine is frequently used as a vasopressor in patients with

out-of-hospital cardiac arrest, although data showing improved outcomes with epinephrine are sparse. In a prospective observational study of over 417,000 adults with out-of-hospital cardial arrest that compared return of

spontaneous circulation (ROSC), survival, and neurologic outcome in patients who did (15,030 patients, 3.6 percent) or did not (402,158 patients, 96.4 percent) receive epinephrine, there was significantly greater ROSC in the

epinephrine group [10]. However, this improvement in ROSC did not translate into improved survival, as patients receiving epinephrine had significantly lower rates of overall and neurologically intact survival. Although this study is

limited by its observational nature, the results call into question the routine use of epinephrine in the treatment of out-of-hospital cardiac arrest and should serve as an impetus for randomized controlled trials of this issue. (See

"Supportive data for advanced cardiac life support in adults with sudden cardiac arrest", section on 'VF or VT arrest and vasopressors'.)

CORONARY HEART DISEASE

Bilateral internal thoracic artery grafting in patients with diabetes — While all patients with diabetes undergoing

coronary artery bypass grafting should receive an internal thoracic (mammary) artery (ITA) graft to improve survival, it has been uncertain whether bilateral ITA grafting would add further benefit. Based on the results of two observational

studies, which demonstrated significantly higher rates of long-term survival for bilateral ITA grafts compared with single grafts, we suggest that bilateral ITA grafting be performed in many patients with diabetes who require coronary

revascularization, particularly those younger than age 70 to 75 years [11,12]. (See "Coronary artery revascularization in patients with diabetes mellitus and multivessel coronary artery disease", section on 'Internal thoracic artery grafts'.)

Time to first cardiac rehabilitation visit — Despite the benefits of cardiac rehabilitation programs for patients with coronary heart disease, including those who have had a myocardial infarction or have undergone revascularization,

participation rates are low. A single-blind trial randomly assigned 148 patients to an appointment for cardiac rehabilitation orientation either within the initial 10 days or at 35 days of a nonsurgical qualifying CAD diagnosis [13].

The median time to orientation was 8.5 and 42 days and the attendance rate was significantly higher in the group that received appointments in the shorter time frame (77 versus 59 percent, respectively). We suggest that early

appointments for cardiac rehabilitation be arranged for qualifying patients. (See "Components of cardiac rehabilitation and exercise prescription", section on 'Timing of first visit'.)

PCI versus medical therapy for stable angina — For patients with stable angina who do not meet criteria for revascularization, the available evidence supports the use of optimal medical therapy as the initial strategy rather

than percutaneous coronary intervention (PCI). However, this issue is widely debated, in part because of significant weaknesses in the relevant randomized trials. Similar to an earlier meta-analysis, a 2013 meta-analysis found no

significant difference in the rate of all-cause MI between these two strategies [14]. However, medical therapy was associated with a significantly higher incidence of spontaneous, non-procedural myocardial infarction (MI) with a

lower incidence of procedural MI. This issue is important, since outcomes are worse after spontaneous compared to procedural MI. Our suggestion for optimal medical therapy rather than PCI as the initial strategy for most patients with

stable angina remains unchanged. (See "Medical therapy versus revascularization in the management of stable angina pectoris", section on 'PCI versus medical therapy'.)

Blood transfusion thresholds for acute upper GI bleeding — The decision to initiate blood transfusions in patients with acute upper gastrointestinal bleeding is based on the rapidity of bleeding and the patients' comorbid conditions.

A randomized trial of patients with and without cardiovascular disease suggests that in patients who are not at increased risk for complications from anemia, outcomes are improved if a lower hemoglobin threshold (<7 g/dL rather

than <9 g/dL) is used for initiating blood transfusion [15]. Patients transfused when the hemoglobin was <7 g/dL had lower mortality rates, were less likely to have further bleeding, and were less likely to suffer complications.

We recommend giving blood transfusions to maintain the hemoglobin at ≥7 g/dL, rather than ≥9 g/dL, for the majority of patients with acute upper gastrointestinal bleeding who do not have significant comorbid illnesses. However,

patients with active bleeding and hypovolemia may require blood transfusion despite an apparently normal hemoglobin. Additionally, we suggest transfusing to maintain the hemoglobin at ≥9 g/dL for patients at increased risk

of adverse events in the setting of significant anemia, such as those with unstable coronary artery disease. (See "Approach to acute upper gastrointestinal bleeding in adults", section on 'Blood transfusions' and "Overview of the

non-acute management of unstable angina and non-ST elevation myocardial infarction", section on 'Blood transfusion'.)

New stable ischemic heart disease guidelines — A multisociety guideline for the diagnosis and management of patients with stable ischemic heart disease has been published and is referenced in multiple topics [16,17]. The

guideline includes recommendations, with which we agree, that most patients with suspected stable ischemic heart disease undergo stress testing to confirm the diagnosis and to gain prognostic information and that beta blockers are

first line therapy to reduce anginal episodes and improve exercise tolerance. (See "Overview of the care of patients with stable ischemic heart disease".)

Stenting versus CABG in patients with diabetes and multivessel coronary artery disease — The evidence to guide the choice of revascularization between percutaneous intervention (PCI) with stenting and coronary artery

bypass graft surgery (CABG) in patients with diabetes and multivessel coronary artery disease was limited prior to the publication of the FREEDOM trial [18]. In FREEDOM, 1900 such patients were randomly assigned to either PCI with

drug-eluting stents or CABG. The primary composite outcome of death from any cause, nonfatal myocardial infarction, or nonfatal stroke occurred significantly more often in the PCI group at five years. We prefer CABG to PCI

with stenting in most patients with diabetes and multivessel disease based on these findings as well as consistent results from older balloon angioplasty and bare metal stent trials. (See "Coronary artery revascularization in patients

with diabetes mellitus and multivessel coronary artery disease", section on 'Stenting versus CABG in multivessel disease'.)

Duration of beta blocker after myocardial infarction — Although beta blocker therapy reduces mortality in patients with recent myocardial infarction (MI), the optimal duration of beta blocker therapy after MI is unknown. Many patients

are continued on this therapy indefinitely based on studies performed in the 1980s and 1990s. A more contemporary evaluation of the potential benefit from long-term beta blocker use was made in a 2012 observational study of over

14,000 patients with a history of prior MI enrolled in the international REACH registry [19]. There was no significant difference in the primary composite outcome of cardiovascular death, nonfatal MI, or nonfatal stroke between those

taking and those not taking beta blocker after nearly four years. This study raises the possibility that indefinite beta blocker therapy after MI may not be necessary in patients who have no other reason for such therapy, such as left

ventricular systolic dysfunction with heart failure. We now give a weak recommendation for indefinite beta blocker therapy. (See "Beta blockers in the management of acute coronary syndrome", section on 'Duration of therapy'.)

Antiplatelet therapy for patients with NSTEACS — All patients with a non-ST elevation acute coronary syndrome (NSTEACS) should receive dual antiplatelet therapy with aspirin and a P2Y12 receptor blocker. For these patients

who are managed with a noninvasive approach, ticagrelor is preferred to clopidogrel. The TRILOGY ACS trial directly compared prasugrel to clopidogrel in this patient population and found no statistically significant difference in the rate

of the primary composite outcome of death from cardiovascular causes, myocardial infarction, or stroke [20]. Potential advantages to clopidogrel compared with prasugrel include a lower cost, greater familiarity by health care providers,

and a trend toward a lower rate of bleeding. Based on TRILOGY ACS, we suggest clopidogrel rather than prasugrel in NSTEACS patients being managed noninvasively who cannot take ticagrelor. (See "Antiplatelet agents in acute

non-ST elevation acute coronary syndromes", section on 'Patients not undergoing PCI'.)

Intraaortic balloon pump in acute MI with cardiogenic shock — Placement of an intraaortic balloon pump (IABP)

in patients with acute myocardial infarction (MI) complicated by cardiogenic shock is routine in many institutions in North America and Europe. However, the randomized IABP-SHOCK II trial, which compared use of the device or no

device in 600 patients with cardiogenic shock complicating acute MI (STEMI and NSTEMI), found no difference in the rate of all-cause mortality at 30 days [21]. We suggest not routinely placing an IABP in patients with acute MI and

cardiogenic shock in whom percutaneous coronary intervention is intended.

However, placement of an IABP may be a reasonable option for carefully selected patients with MI who have specific

indications, including rapidly deteriorating hemodynamic parameters and clinical status despite vasopressor and inotropic support, or hemodynamically compromising mechanical defects. (See "Prognosis and treatment of

cardiogenic shock complicating acute myocardial infarction", section on 'Intraaortic balloon pump'.)

Endoscopic vein graft harvesting for CABG — Endoscopic harvesting of the saphenous vein prior to coronary

artery bypass graft surgery (CABG) has been used in preference to conventional (open) harvesting to lessen postoperative discomfort. In an observational study of outcomes of CABG surgery in over 235,000 US Medicare

patients, the use of endoscopic vein-graft harvesting was also associated with a significant reduction in the rate of harvest site wound complications compared to open procedures [22]. (See "Early noncardiac complications of

coronary artery bypass graft surgery", section on 'Leg wound complications'.)

Universal definition of myocardial infarction — An updated version of the universal definition of myocardial infarction (MI) was published by a joint committee of the European Society of Cardiology/American College of

Cardiology Foundation/American Heart Association/World Health Organization [23]. Although there were no major changes to either the criteria necessary for a diagnosis of MI or to the clinical classification of MI based on the

proximate cause of myocardial ischemia, practitioners caring for patients with possible acute MI should be familiar with both the criteria and classification of MI types. (See "Criteria for the diagnosis of acute myocardial infarction",

section on 'Acute MI'.)

Spontaneous coronary artery dissection — Spontaneous coronary artery dissection is a rare cause of acute

myocardial infarction (MI). The best available study of the clinical presentation, angiographic findings, and prognosis of this entity is a single-center report from the Mayo Clinic of 87 patients who presented over three decades [24].

Spontaneous coronary artery dissection should be considered in the differential diagnosis of any young woman who presents with acute MI, particularly if traditional risk factors for coronary heart disease are absent. (See "Clinical

features and diagnosis of coronary heart disease in women", section on 'Spontaneous coronary artery dissection'.)

Inflammation and CHD risk — While the association between inflammation and the development of atherosclerotic

disease is well-known, proving causation for any particular biomarker of inflammation has been difficult. Interleukin-6 (IL-6) signals a downstream proinflammatory response by activating membrane-bound receptors on the cell surface.

Two large studies looking at single nucleotide polymorphisms (SNPs) in the IL6R gene have confirmed the crucial role played by IL-6 and its receptor in the generation of inflammation and the associated risk of coronary heart

disease (CHD) [25,26]. Inherited copies of a variant allele of the IL6R gene were associated with increased IL-6 and soluble IL-6R levels, leading to decreased downstream inflammation as measured by decreased C-reactive protein

levels and a 3 to 5 percent decreased risk of CHD. Additionally, there was no association between the presence of the variant allele and traditional cardiac risk factors. Increased IL-6 appears to have a direct causal role in the

development of CHD and may be a future target for therapeutic interventions to prevent CHD. (See "Overview of the risk equivalents and established risk factors for cardiovascular disease", section on 'Interleukin-6'.)

Risk of major bleeding with aspirin — Aspirin is recommended for most patients with established cardiovascular disease (CVD), as the benefit (prevention of CVD events) outweighs the risk (major bleeding). The decision to

recommend aspirin for the primary prevention of CVD requires a reasonable estimate of the risk of major bleeding, since the benefit and risk are of similar magnitude. Concerns have been raised that rates of major bleeding seen in

randomized trials might differ from those in patients in the general population. In a population-based study of almost 200,000 Italian citizens, the rate of major bleeding at 5.7 years was significantly higher in aspirin users compared to

aspirin non-users (5.6 versus 3.6 per 1000 person-years) [27]. This study probably represents the best available data to be used in calculating the risk/benefit ratio of the use of aspirin for primary prevention. (See "Benefits and risks of

aspirin in secondary and primary prevention of cardiovascular disease", section on 'Bleeding risk'.)

Coronary CT angiography — The value of coronary computed tomographic angiography (CCTA) as compared to

traditional care for the management of low to intermediate risk patients with possible acute coronary syndrome presenting to the emergency department was evaluated in a multicenter randomized trial enrolling 1370 patients [28].

Lengths of stay were shorter, rates of discharge from the emergency department were higher and there was a higher rate of detection of coronary disease in patients undergoing CCTA. One percent of patients in each group had a

myocardial infarction and there were no cardiac deaths within 30 days after presentation. (See "Noninvasive imaging and stress testing in patients with suspected acute coronary syndrome", section on 'Coronary computed tomographic

angiography'.)

Vorapaxar as adjunctive antiplatelet therapy in stable patients — Long-term antiplatelet therapy with aspirin reduces the risk of cardiovascular events in patients with stable and unstable coronary artery disease. The

addition of a second antiplatelet agent reduces the risk in patients with unstable disease or those who have undergone percutaneous coronary intervention with stenting. In the PRA 2P-TIMI 50 trial of patients with stable

cardiovascular disease, the addition of vorapaxar (a competitive inhibitor of a major thrombin receptor on platelets) to at least one other antiplatelet drug lowered the combined rate of cardiovascular death, MI, or stroke at three years

compared to placebo [29]. However, the rate of moderate or severe bleeding occurred significantly more often with vorapaxar. Vorapaxar is not available for clinical use. (See "Secondary prevention of cardiovascular disease", section

on 'Vorapaxar'.)

Glucose-insulin-potassium in patients with acute coronary syndromes — Although there has been no

conclusive evidence of benefit from the infusion of a glucose-insulin-potassium (GIK) solution in patients with suspected or diagnosed acute coronary syndromes (ACS), concerns have persisted that, in the relevant studies, the

infusion had not been given early enough. The issue of timing was addressed in the IMMEDIATE trial, which randomly assigned 871 patients with suspected ACS to intravenous GIK or 5 percent glucose placebo; study drug

was administered by paramedics in the pre-hospital setting [30]. There was no difference in the rate of progression to MI at 24 hours or the rate of death at 30 days between the two groups. (See "Overview of the acute management of

unstable angina and non-ST elevation myocardial infarction", section on 'Intravenous glucose-insulin-potassium'.)

HEART FAILURE

Ultrafiltation in acute decompensated heart failure — The efficacy and safety of ultrafiltration in patients with acute decompensated heart failure has been evaluated in a few randomized trials. In CARRESS-HF, 188 patients

with acute decompensated heart failure, worsened renal function, and persistent congestion were randomly assigned to stepped pharmacologic therapy or ultrafiltration [31]. Ultrafiltration was an effective method for fluid volume

removal that provided similar amounts of weight loss to stepped pharmacologic therapy, but it was inferior to stepped pharmacologic therapy for preservation of renal function at 96 hours and was associated with a higher rate of adverse

events. (See "Treatment of acute decompensated heart failure: Components of therapy", section on 'Ultrafiltration'.)

Angiotensin II receptor blocker therapy for heart failure — A systematic review found that angiotensin II receptor

blocker (ARB) therapy compared to placebo produced a borderline statistically significant reduction in mortality in patients with systolic heart failure [32]. Given the established mortality benefit of angiotensin converting enzyme

inhibitor (ACE inhibitor) therapy in such patients, ACE inhibitor therapy continues to be a first line therapy for systolic heart failure. ARB therapy is recommended as an alternative to ACE inhibitor therapy only in selected patients

intolerant of ACE inhibitor therapy due to symptoms such as cough and angioedema. (See "Angiotensin II receptor blockers in heart failure due to systolic dysfunction: Therapeutic use", section on 'Comparison to placebo'.)

Antithrombotic therapy in heart failure — Although patients with systolic heart failure have an increased risk of thromboembolic events, data are inconclusive on the utility of antithrombotic therapy to reduce thromboembolic

events or mortality in patients who are in sinus rhythm. The WARCEF trial found no significant difference in the primary endpoint (ischemic stroke, intracerebral hemorrhage, or death from any cause) for patients in sinus rhythm

with an LVEF ≤35 percent who were assigned to receive either warfarin or aspirin [33]. Warfarin significantly reduced the rate of ischemic stroke, but increased the rate of major hemorrhage, compared to aspirin. (See "Indications for

antithrombotic therapy in heart failure", section on 'Comparison of aspirin to warfarin'.)

INTERVENTIONAL CARDIOLOGY

Platelet monitoring to adjust antiplatelet therapy at PCI — It is unknown whether testing of platelet function and adjustment of antiplatelet therapy as needed, before and after percutaneous coronary intervention (PCI) with stenting,

improves clinical outcomes. The ARCTIC trial randomly assigned patients scheduled for coronary stenting and receiving dual antiplatelet therapy to a strategy of platelet-function monitoring (before and after PCI) or no monitoring

[34]. Patients with high platelet reactivity were administered clopidogrel, prasugrel, or aspirin and glycoprotein IIb/IIIa inhibitors during the PCI. No significant difference in the rate of the primary composite end point (death, myocardial

infarction, stent thrombosis, stroke, or urgent revascularization at one year) was found, supporting our recommendation to not routinely perform platelet-function testing in patients undergoing PCI. (See "Nonresponse and

resistance to clopidogrel".)

Drug-coated balloon angioplasty for restenosis following drug-eluting stent — The optimal treatment for

restenosis following implantation of drug-eluting stents (DES) is uncertain. The efficacy of drug-eluting balloon angioplasty for patients with DES restenosis was evaluated in the ISAR-DESIRE 3 trial, which found no significant

difference between treatment with a paclitaxel-eluting balloon and a paclitaxel-eluting stent in the rate of the primary end point of diameter stenosis at six- to eight-month angiographic follow-up [35]. Both of these interventions were

superior to balloon angioplasty alone. (See "Intracoronary stent restenosis", section on 'Drug-coated balloon angioplasty'.)

Selection of stent type in acute STEMI — Drug-eluting stents (DES) are used in preference to bare-metal stents (BMS) in many stable patients undergoing percutaneous coronary intervention (PCI) because they reduce the need

for repeat target vessel revascularization without a significant increase in the cumulative rate of adverse outcomes. Similar findings have been found in studies of patients undergoing primary PCI for ST-elevation myocardial infarction

(STEMI); most of these studies compared first generation DES to BMS.

The EXAMINATION and COMFORTABLE AMI trials randomly assigned STEMI patients to one of two second generation DES (an everolimus-eluting or a biolimus–eluting stent, respectively) or a BMS [36,37]. Both studies found

a lower rate of the need for target vessel/lesion revascularization and suggested a lower rate of definite stent thrombosis with the DES. (See "Primary percutaneous coronary intervention in acute ST elevation myocardial

infarction: Periprocedural management", section on 'Selection of stent type'.)

Periprocedural anticoagulant in patients taking an oral anticoagulant — The optimal periprocedural

anticoagulant strategy for patients taking therapeutic doses of an oral anticoagulant at the time of percutaneous coronary intervention (PCI) has not been established. In an observational study of stable and unstable patients, there

was no significant difference in the rates of major adverse cardiac and cerebrovascular events or major bleeding between those who did or did not receive additional periprocedural anticoagulation with heparin [38]. However, there

was a significantly higher rate of access site complications in those receiving heparin. (See "Antithrombotic therapy for percutaneous coronary intervention: General use", section on 'Patients taking oral anticoagulants'.)

Multivessel versus culprit only PCI in NSTEACS — In patients with a non-ST elevation acute coronary syndrome (NSTEACS) who are found to have multivessel disease on coronary arteriography and for whom percutaneous

coronary intervention (PCI) is chosen as the revascularization strategy, a decision must be made between complete or incomplete (culprit-only) revascularization. Evidence that can be used to decide between the two strategies is

limited. Support for multivessel intervention comes from a substudy of the ACUITY trial, in which complete revascularization was associated with a lower rate of the composite primary end point of death, myocardial infarction,

or additional revascularization [39]. (See "Coronary arteriography and revascularization for unstable angina or non-ST elevation acute myocardial infarction", section on 'Multivessel versus culprit only PCI'.)

Switching from heparin to bivalirudin in acute myocardial infarction — Anticoagulation with bivalirudin is preferred to heparin in patients with acute coronary syndromes and planned percutaneous coronary intervention, as it

has a comparable efficacy profile but is associated with lower rates of major bleeding. (See "Anticoagulant therapy in acute ST elevation myocardial infarction", section on 'Summary and recommendations'.)

In a prespecified analysis of the HORIZONS AMI trial, bivalirudin maintained its efficacy and safety profile, compared to heparin, in the subgroup of patients who were initially treated with heparin [40]. (See "Anticoagulant therapy in

acute ST elevation myocardial infarction", section on 'Switching from heparin to bivalirudin'.)

LIPID DISORDERS

Lomitapide for homozygous familial hypercholesterolemia — Lomitapide is a microsomal triglyceride transfer protein, which transfers triglycerides onto apolipoprotein B as part of the assembly of very low density lipoprotein

within the liver. Small studies in differing populations have shown that the drug lowers low density lipoprotein cholesterol (LDL-C) by approximately 20 to 50 percent [41,42]. It has been approved by the US Food and Drug

Administration for patients with homozygous familial hypercholesterolemia (FH). We suggest using lomitapide in patients with homozygous FH who have not achieved their LDL-C target after optimal drug therapy and either LDL-

apheresis or liver transplantation. (See "Treatment of drug-resistant hypercholesterolemia", section on 'Lomitapide'.)

Monoclonal antibody to PCSK9 in patients with drug-resistant hypercholesterolemia — Proprotein convertase

subtilisin kexin 9 (PCKS9) is a serine protease that leads to the degradation of low density lipoprotein (LDL) receptors and increased LDL-cholesterol levels. In four independent, new randomized trials, differing patient groups with

hypercholesterolemia were randomly assigned to receive a human monoclonal antibody to PCSK9 (AMG 145) or placebo [43-46]. LDL-cholesterol levels were lowered by as much as 40 to 60 percent with AMG 145 compared to

placebo, including in patients on maximal tolerated doses of statin therapy. Phase III trials with several years of follow-up are needed to evaluate the impact of treatment with AMG 145 on clinical outcomes and long-term safety.

(See "Treatment of drug-resistant hypercholesterolemia", section on 'Monoclonal antibody to PCSK9'.)

CETP inhibition in patients at high risk for cardiovascular disease — Inhibition of cholesteryl ester transfer

protein (CETP) function with torcetrapib, anacetrapib, evacetrapib, or dalcetrapib leads to a rise in HDL-cholesterol(C) levels as well as other favorable effects on lipids. However, such an effect on HDL-C has not yet been

shown to lower the risk of cardiovascular disease events in individuals at increased risk. The dal-OUTCOMES trial, which randomly assigned acute coronary syndrome patients to dalcetrapib or placebo, was terminated early for futility

as there was no significant difference in the two groups with regard to the primary composite end point of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, unstable angina, or cardiac arrest with

resuscitation [47]. (See "HDL metabolism and approach to the patient with abnormal HDL-cholesterol levels", section on 'Dalcetrapib'.)

MYOPERICARDIAL DISEASE

Pericardiectomy for recurrent pericarditis — Recurrent pericarditis, a recurrence or persistence of the symptoms

of acute pericarditis thought to be autoimmune in nature, typically requires a prolonged course of medical therapy. While treatment with pericardiectomy is available for patients with refractory symptoms, the surgery is not universally

successful and has been considered as high risk for morbidity and mortality. Among a cohort of 184 patients with chronic recurrent pericarditis (mean six to seven relapses) treated at a single referral center and followed for an

average of 5.5 years, the 58 patients who underwent pericardiectomy fared well post-operatively (no immediate deaths, only two major complications) and had significantly fewer relapses (9 versus 29 percent in the medical

treatment group) and similar survival as the 126 medically treated patients. Pericardiectomy does appear to be a safe

and frequently effective treatment option when performed by experienced surgeons in a high-volume center, and it should be considered in persons with ongoing symptoms of recurrent pericarditis in spite of medical therapy. (See

"Recurrent pericarditis", section on 'Role of pericardiectomy'.)

Beta blockers in hypertrophic cardiomyopathy — Beta blockers may play an important role in the treatment of left

ventricular outflow tract (LVOT) obstruction induced by exercise in patients with hypertrophic cardiomyopathy (HCM). In a cohort study of 27 patients without resting LVOT obstruction but an exercise-provoked LVOT gradient of 30

mmHg or greater, beta blocker treatment for one year resulted in significantly lower post-exercise LVOT gradients (36 mmHg versus 87 mmHg at baseline) [48]. While encouraging, additional studies are needed to confirm these results

and investigate whether this reduction in provocable LVOT obstruction translates to improved outcomes. (See "Medical therapy in hypertrophic cardiomyopathy", section on 'Beta blockers'.)

VALVULAR HEART DISEASE

Early anticoagulation after implantation of a bioprosthetic aortic valve — The use of short-term vitamin

K antagonist therapy early after bioprosthetic valve implantation in patients without thromboembolic risk factors is controversial. An observational study of data from the Danish National Patient Registry found an association between

discontinuation of warfarin within six months after bioprosthetic aortic valve implantation and thromboembolic events and cardiovascular death [49]. However, a causal relationship was not established. Given the available evidence, the

role of warfarin therapy during the first few months after bioprosthetic valve placement (in patients without other indications for anticoagulation) is uncertain. (See "Antithrombotic therapy in patients with prosthetic heart valves",

section on 'Early anticoagulation after bioprosthetic valve replacement or mitral valve repair'.)

Avoid dabigatran with prosthetic heart valves — Based upon interim data from the European RE-ALIGN trial, a

safety communication warning was issued in the United States by the Food and Drug Administration regarding increased rates of stroke, myocardial infarction, thrombosis, and major bleeding in patients with mechanical

prosthetic heart valves who received anticoagulation with dabigatran compared to those receiving dose-adjusted warfarin [50-52]. We recommend against use of direct thrombin inhibitors such as dabigatran in patients with

prosthetic heart valves. A vitamin K antagonist is the preferred anticoagulant in patients with prosthetic valves. (See "Antithrombotic therapy in patients with prosthetic heart valves", section on 'Direct thrombin inhibitors'.)

Systolic duration of mitral regurgitation and outcome — In patients with chronic mitral regurgitation, the magnitude of mitral regurgitation is a predictor of outcome. The regurgitant volume is determined by the size of the

regurgitant orifice (estimated by the effective orifice area [ERO]), the size of the systolic pressure gradient across the mitral valve, as well as the duration of regurgitation within the cardiac cycle. A study comparing patients with mid to

late systolic MR to patients with holosystolic MR found greater regurgitant volumes in the later group despite similar EROs [53]. Adverse outcomes were more frequent in patients with holosystolic MR. Regurgitant volume, but not

ERO, was an independent predictor of cardiac events. (See "Natural history of chronic mitral regurgitation in mitral valve prolapse and flail mitral leaflet", section on 'Clinical outcome'.)

Timing of surgery for native valve endocarditis — The optimal timing of surgery for native valve endocarditis in the absence of heart failure is uncertain. A randomized trial compared early surgery versus conventional therapy in

patients with native valve endocarditis, large vegetations (>10 mm), and severe valve regurgitation or stenosis [54]. The endpoint of in-hospital death and embolic events was significantly less frequent in the early surgery group

compared with the conventional treatment group, due to a lower embolic event rate in the early surgery group. Given these results, we suggest early surgery as a means of reducing the risk of embolism in patients with vegetations >10

mm who have severe valve disease and no coexisting major embolic stroke. (See "Surgery for native valve endocarditis", section on 'Vegetation size'.)

Mitral valve surgery at the time of CABG — In 2011, the Surgical Treatment for Ischemic Heart Failure (STICH) trial was the first randomized trial to compare surgical revascularization with medical therapy in patients with LVEF of

35 percent or less and coronary artery disease amenable to coronary artery bypass graft (CABG) surgery [55]. In a post hoc analysis of patients in the STICH trial with moderate or severe mitral regurgitation, those who had

concurrent mitral valve surgery and CABG had better survival compared to those undergoing CABG alone [56]. Unlike the primary component of STICH where patients were randomized to CABG or medical therapy, mitral valve

surgery was nonrandomized and performed at the surgeon’s discretion. Therefore, these results should be considered to be hypothesis generating for a future randomized trial. (See "Diagnosis and management of ischemic

cardiomyopathy", section on 'Improvement in survival'.)

Transcatheter aortic valve replacement — Transcatheter aortic valve replacement (TAVR) has been developed as

a treatment for patients with severe symptomatic aortic stenosis with high risk for surgical aortic valve replacement. Benefits and limitations of TAVR are illustrated by results from the following two trials:

Data on two-year outcomes from a randomized trial comparing TAVR to medical therapy (often

including balloon aortic valvotomy) in patients with inoperable severe aortic stenosis showed that TAVR improved survival rates and symptoms [57]. However, TAVR did not improve survival in patients with a

Society of Thoracic Surgeons (STS) score of ≥15 percent. (See "Transcatheter aortic valve replacement", section on 'Comparison to medical therapy in inoperable patients'.)

Data on two-year outcomes from a randomized trial comparing TAVR to surgical aortic valve

replacement in high risk patients with aortic stenosis showed similar survival rates and improvement in symptoms [58]. Paravalvular regurgitation was more frequent after TAVR and was associated with an

increased risk of late mortality. (See "Transcatheter aortic valve replacement", section on 'Comparison to surgical therapy' and "Transcatheter aortic valve replacement", section on 'Paravalvular

regurgitation'.)