8- Use of the Instantaneous Wave-free Ratio or Fractional Flow Reserve in PCI (Justin E. Davies, M.D., Ph.D.,...,Javier Escaned, M.D., Ph.D. March 18, 2017/NEJ)

Coronary revascularization guided by fractional flow reserve (FFR) is associated with better patient outcomes after the procedure than revascularization guided by angiography alone. It is unknown whether the instantaneous wave-free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR.

METHODS: We randomly assigned 2492 patients with coronary artery disease, in a 1:1 ratio, to undergo either iFR-guided or FFR-guided coronary revascularization.

CONCLUSIONS: Coronary revascularization guided by iFR was noninferior to revascularization guided by FFR with respect to the risk of major adverse cardiac events at 1 year. The rate of adverse procedural signs and symptoms was lower and the procedural time was shorter with iFR than with FFR.

 

7- Fractional Flow Reserve–Guided Multivessel Angioplasty in Myocardial Infarction (Pieter C. Smits, M.D., Ph.D.,..., Elmir Omerovic, M.D., Compare-Acute Investigators, March 18, 2017/NEJ)

In patients with STEMI, the use of PCI to restore blood flow in an infarct-related coronary artery improves outcomes. The use of PCI in non–infarct-related coronary arteries remains controversial.

METHODS: We randomly assigned 885 patients with STEMI and multivessel disease who had undergone primary PCI of an infarct-related coronary artery in a 1:2 ratio to undergo complete revascularization of non–infarct-related coronary arteries guided by fractional flow reserve (FFR) (295 patients) or to undergo no revascularization of non–infarct-related coronary arteries (590 patients). Clinically indicated elective revascularizations performed within 45 days after primary PCI were not counted as events in the group receiving PCI for an infarct-related coronary artery only.

RESULTS: The primary outcome occurred in 23 patients in the complete-revascularization group and in 121 patients in the infarct-artery-only group that did not receive complete revascularization, a finding that translates to 8 and 21 events per 100 patients, respectively. Death occurred in 4 patients in the complete-revascularization group and in 10 patients in the infarct-artery-only group (1.4% vs. 1.7%), myocardial infarction in 7 and 28 patients, respectively (2.4% vs. 4.7%), revascularization in 18 and 103 patients (6.1% vs. 17.5%), and cerebrovascular events in 0 and 4 patients (0 vs. 0.7%). An FFR-related serious adverse event occurred in 2 patients (both in the group receiving infarct-related treatment only).

 

6- Levosimendan in Patients with Left Ventricular Dysfunction Undergoing Cardiac Surgery (Rajendra H. Mehta, M.D.,... John H. Alexander, M.D., M.H.S., LEVO-CTS Investigators, March 19, 2017/NEJ)

In a multicenter, randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of levosimendan in patients with a left ventricular ejection fraction of 35% or less who were undergoing cardiac surgery with the use of cardiopulmonary bypass. Patients were randomly assigned to receive either intravenous levosimendan (at a dose of 0.2 μg per kilogram of body weight per minute for 1 hour, followed by a dose of 0.1 μg per kilogram per minute for 23 hours) or placebo, with the infusion started before surgery. A total of 882 patients underwent randomization, 849 of whom received levosimendan or placebo.

CONCLUSIONS: Prophylactic levosimendan did not result in a rate of the short-term composite end point of death, renal-replacement therapy, perioperative myocardial infarction, or use of a mechanical cardiac assist device that was lower than the rate with placebo among patients with a reduced left ventricular ejection fraction who were undergoing cardiac surgery with the use of cardiopulmonary bypass. 

 

5- Uninterrupted Dabigatran versus Warfarin for Ablation in Atrial Fibrillation (Hugh Calkins, M.D., ..., Massimo Grimaldi, M.D., Ph.D., RE-CIRCUIT Investigators, March 19, 2017, NEJM)

Catheter ablation of atrial fibrillation is typically performed with uninterrupted anticoagulation with warfarin or interrupted non–vitamin K antagonist oral anticoagulant therapy. Uninterrupted anticoagulation with a non–vitamin K antagonist oral anticoagulant, such as dabigatran, may be safer; however, controlled data are lacking. We investigated the safety of uninterrupted dabigatran versus warfarin in patients undergoing ablation of atrial fibrillation.

RESULTS: The trial enrolled 704 patients across 104 sites; 635 patients underwent ablation. Baseline characteristics were balanced between treatment groups. The incidence of major bleeding events during and up to 8 weeks after ablation was lower with dabigatran than with warfarin (5 patients [1.6%] vs. 22 patients [6.9%]. Dabigatran was associated with fewer periprocedural pericardial tamponades and groin hematomas than warfarin. The two treatment groups had a similar incidence of minor bleeding events.

CONCLUSIONS: In patients undergoing ablation for atrial fibrillation, anticoagulation with uninterrupted dabigatran was associated with fewer bleeding complications than uninterrupted warfarin.

 

4- Implantable Cardioverter–Defibrillators in Nonischemic Cardiomyopathy (Rebecca E. Berger, M.D., N Engl J Med December 8, 2016)

CASE VIGNETTE: A Man with Nonischemic Cardiomyopathy Who Is Considering an ICD

Mr. Gregory is a 68-year-old man with nonischemic cardiomyopathy who has come to your office to discuss possible placement of an implantable cardioverter–defibrillator (ICD). Six months ago, he was admitted to the hospital with progressive exercise intolerance and new onset of edema in his legs. He has a history of heavy alcohol use but has been abstinent for the past 5 years. During his hospital stay, an echocardiogram showed an ejection fraction of 30%; cardiac catheterization revealed no clinically significant coronary artery disease. He received a diagnosis of nonischemic cardiomyopathy, which was presumed to be due to alcohol use. At discharge, medical therapy was prescribed that included lisinopril (20 mg daily), carvedilol (25 mg twice daily), spironolactone (25 mg daily), and furosemide.

At the office visit today, Mr. Gregory reports good adherence to the medications. He is asymptomatic at rest but has dyspnea when he walks one city block or climbs a flight of stairs. Electrocardiography shows normal sinus rhythm with a QRS duration of 90 msec. A repeat transthoracic echocardiogram performed 1 week before this visit is unchanged from the prior one. He is otherwise in good health, with no other major medical problems.

TREATMENT OPTIONS

In addition to continuing medical therapy, which of the following treatment options would you recommend for this patient? 1. Undergo placement of an ICD. 2. Do not undergo placement of an ICD.

Mr. Gregory has concerns about possible side effects of device therapy. The risk of inappropriate shocks from ICDs can be reduced to less than 2% per year with programming available today. The risk of complications from device implantation, including serious infection or hematoma, is typically 2 to 3%, and such complications generally occur shortly after device implantation. In the National ICD Registry, the risk of a major adverse event was 1.56%.

The results of the DANISH trial showed that among patients with nonischemic cardiomyopathy, the rate of sudden death was lower among those who had ICDs than among those who received usual clinical care, but there was no significant difference between the groups in overall survival. So with current medical management of Mr. Gregory’s cardiomyopathy, the likelihood that an ICD will terminate a cardiac arrest is probably less than 1% per year, and even if an ICD does prevent a cardiac arrest, his survival may not be meaningfully extended.

Trial participants comprise some patients who benefit and some who do not. Are there any factors that might suggest that Mr. Gregory is more likely to benefit? At 68 years of age, he is older than the mean age of patients enrolled in ICD trials. A prespecified subgroup analysis in the DANISH trial showed benefit in patients younger than 68 years of age, but not in older patients. This finding is consistent with the recognition that rates of death from noncardiac and nonarrhythmic cardiac causes increase with age, whereas rates of death from arrhythmia may not.

Are there other beneficial effects of an ICD that should be considered? If Mr. Gregory had left bundle-branch block, implanting a device for cardiac resynchronization therapy (CRT), which could potentially ameliorate his heart failure and reduce his risk of death, would be a consideration. More than half the patients in both groups of the DANISH trial were eligible for and received CRT, which probably contributed to the lower mortality than that seen in earlier trials. In patients who are candidates for CRT, a combined-function device with CRT and ICD (CRT-D) is often recommended. However, the QRS duration in Mr. Gregory is not prolonged, so he would not be a candidate for CRT.

NO ICD AT THIS TIME

A common dilemma in clinical practice. Primary prevention ICD for NICMY is a class I (B) indication for those with EF<35% and NYHA class II or III. Our patient probably has class II symptoms and has 6 month echocardiogram with EF of 30%. He should be transitioned to maximally tolerated ARNI and reevaluated in 3 months. I think ARNI will make it to Class I (A) indication in the next heart failure guidelines (whenever they come out) and should be a part of the ideal guideline recommended medical strategy. DANISH trial results are reassuring. If, at a 3 month reassessment on maximally tolerated ARNI, BB, Spironolactone he continues to be NYHA II/III - I will recommend primary prevention ICD. He buys himself an ICD sooner, if develops palpitations, syncope or NSVTs.

 

3- Everolimus-Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease (Gregg W. Stone, M.D.,...,A. Pieter Kappetein, M.D., Ph.D., for the EXCEL Trial Investigators, N Engl J Med December 8, 2016)

We randomly assigned 1905 eligible patients with left main coronary artery disease of low or intermediate anatomical complexity to undergo either percutaneous coronary intervention (PCI) with fluoropolymer-based cobalt–chromium everolimus-eluting stents (PCI group, 948 patients) or CABG (CABG group, 957 patients). Anatomic complexity was assessed at the sites and defined by a Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score of 32 or lower. The primary end point was the rate of a composite of death from any cause, stroke, or myocardial infarction at 3 years. Major secondary end points included the rate of a composite of death from any cause, stroke, or myocardial infarction at 30 days and the rate of a composite of death, stroke, myocardial infarction, or ischemia-driven revascularization at 3 years.

Results: At 3 years, a primary end-point event had occurred in 15.4% of the patients in the PCI group and in 14.7% of the patients in the CABG group. The secondary end-point event of death, stroke, or myocardial infarction at 30 days occurred in 4.9% of the patients in the PCI group and in 7.9% in the CABG group. The secondary end-point event of death, stroke, myocardial infarction, or ischemia-driven revascularization at 3 years occurred in 23.1% of the patients in the PCI group and in 19.1% in the CABG group.

Conclusion: In patients with left main coronary artery disease and low or intermediate SYNTAX scores by site assessment, PCI with everolimus-eluting stents was noninferior to CABG with respect to the rate of the composite end point of death, stroke, or myocardial infarction at 3 years.

 

2- Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI (C. Michael Gibson, M.D.,...,Keith A. Fox, M.B., Ch.B, N Engl J Med December 22, 2016)

In patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) with placement of stents, standard anticoagulation with a vitamin K antagonist plus dual antiplatelet therapy (DAPT) with a P2Y12 inhibitor and aspirin reduces the risk of thrombosis and stroke but increases the risk of bleeding. The effectiveness and safety of anticoagulation with rivaroxaban plus either one or two antiplatelet agents are uncertain.

Methods: We randomly assigned 2124 participants with nonvalvular atrial fibrillation who had undergone PCI with stenting to receive, in a 1:1:1 ratio, low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor for 12 months (group 1), very-low-dose rivaroxaban (2.5 mg twice daily) plus DAPT for 1, 6, or 12 months (group 2), or standard therapy with a dose-adjusted vitamin K antagonist (once daily) plus DAPT for 1, 6, or 12 months (group 3). The primary safety outcome was clinically significant bleeding.

Results: The rates of clinically significant bleeding were lower in the two groups receiving rivaroxaban than in the group receiving standard therapy (16.8% in group 1, 18.0% in group 2, and 26.7% in group 3). The rates of death from cardiovascular causes, myocardial infarction, or stroke were similar in the three groups (Kaplan–Meier estimates, 6.5% in group 1, 5.6% in group 2, and 6.0% in group 3).

Conclusion: In participants with atrial fibrillation undergoing PCI with placement of stents, the administration of either low-dose rivaroxaban plus a P2Y12inhibitor for 12 months or very-low-dose rivaroxaban plus DAPT for 1, 6, or 12 months was associated with a lower rate of clinically significant bleeding than was standard therapy with a vitamin K antagonist plus DAPT for 1, 6, or 12 months. The three groups had similar efficacy rates, although the observed broad confidence intervals diminish the surety of any conclusions regarding efficacy.

 

1- Fibromuscular Dysplasia of the Brachial Artery (Mistyann-Blue Miller, M.D., and Demetrio R. Flores III, M.D. N Engl J Med January 12, 2017)

A 68-year-old woman presented with exertional dyspnea and chest pain, symptoms that suggested unstable angina. She had undergone coronary-artery bypass grafting 5 years earlier. Vascular examination revealed palpable radial pulses on both sides of the body. The results of Allen’s test, conducted with the use of plethysmography, were normal. Transradial coronary angiography was attempted, but there was difficulty advancing the guidewire and diagnostic catheter past the level of the elbow. Right brachial angiography revealed a “string of beads” pattern (arrows) that was consistent with fibromuscular dysplasia, a noninflammatory, nonatherosclerotic disorder of the blood vessels. Fibromuscular dysplasia is most commonly seen in the carotid and renal arteries but has been observed in nearly every arterial bed. Although many patients are asymptomatic, some have symptoms related to the affected arterial bed, such as hypertension, renal failure, stroke, abdominal pain, or claudication of the legs.