A new randomized Danish study, published online October 9, 2012 in BMJ, showed that hormone-replacement therapy (HRT) in postmenopausal women, with a mean age of 50, significantly reduced the risk of the combined end point of mortality, myocardial infarction, or heart failure.

Healthy 1006 women aged 45 to 58 who were recently postmenopausal or had perimenopausal symptoms were randomized to receive HRT (n=502) or no treatment (n=504).

The participants of this study, who used HRT for more than 10 years, had a 52% reduction in cardiovascular endpoints without significant increase in risk of breast cancer or stroke.

This is considered the longest randomized trial with hard end points. The participants were also followed for a further 6 years after discontinuation of randomized treatment.

In 2002, the Women’s Health Study Initiative (WHI) showed no cardiovascular benefit from HRT and, even an indication that HRT may be harmful. However, subsequent analysis of WHI and data from other studies has suggested that the time at which HRT is first started is the key.  The women in the Danish study were 13 years younger, on average, than women in WHI (mean age 63 years). Therefore, it is important to initiate the treatment at menopause and not many years later.

The administration of colchicine in patients who underwent pulmonary vein isolation helps to prevent early recurrences of atrial fibrillation, research shows. The reduction in event recurrences appears to be mediated through a reduction in inflammation following the radiofrequency catheter-ablation procedure, with investigators showing significant reductions in inflammatory mediators such as interleukin-6 (IL-6) and C-reactive protein (CRP).

The idea of fighting inflammation after ablation treatment for atrial fibrillation is not new. One study also showed that the administration of corticosteroids following ablation reduced immediate atrial fibrillation by 77%. However, corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended for prolonged use due to unwanted adverse effects. Colchicine, on the other hand—a low-cost medicine that has been around for long time—possesses a unique combination of features: anti-inflammatory action, antiproliferative action, and no adverse effects on the cardiovascular system.
Given the potent anti-inflammatory action of colchicine and that it can be administered without serious cardiovascular adverse effects for a relatively prolonged time period, the researchers assessed the safety and efficacy of the agent in the setting of atrial-fibrillation ablation.
In the study, published online October 3, 2012 in the Journal of the American College of Cardiology, the researchers randomized 81 patients with paroxysmal atrial fibrillation to a three-month course of colchicine 0.5 mg twice daily and 80 patients to placebo.
After three months of treatment, atrial-fibrillation recurrence was observed in 33.5% of patients treated with placebo and in 16% of patients treated with colchicine (a 62% reduction). The number needed to treat to prevent one recurrence was 5.6. The mean recurrence-free time in the placebo-treated patients was 68.9 days, compared with 82.2 days in the colchicine-treated patients.
In addition to reducing the risk of atrial-fibrillation recurrence, colchicine significantly reduced CRP and IL-6 levels, compared to placebo.
Researchers state that a few more steps are needed before colchicine can be used regularly in clinical practice. While the dose and duration of treatment are not firmly established, they warn that because the primary rationale for catheter ablation of atrial fibrillation is to improve quality of life, physicians should not replace one problem, atrial fibrillation, with another, gastrointestinal upset caused by colchicine use.
Also long-term studies are needed to determine whether the reduction in short-term atrial-fibrillation recurrence translates into long-term success.

Source: Deftereos S, Giannopoulos G, Kossyvakis C, et al. Colchicine for prevention of early atrial fibrillation recurrence after pulmonary vein isolation. J Am Coll Cardiol 2012.

This was a retrospective analysis of the US Centers for Medicare and Medicaid Services database, by Piccini et al (published in Circulation 2012; Sep 26).
All patients 65 years or older who underwent CA of AF in 2007-2009 were included. The sample size was 15,423 patients, with a mean age of 72 years. Outcomes were tracked for 1 year post-CA.

The mortality rate at 30 days was 0.8%. The 30-day rates of post procedure events were as follows: myocardial infarction (0.3%), pericardial effusion (1.7%), stroke (0.8%), and vascular complications requiring surgery (0.5%).
The mortality rate at 1 year was 3.8%. The 1-year rates of events were as follow: heart failure (2.5%), stroke (2.1%), hospitalization (43%), and repeat CA (11%).
Renal impairment, age >80 years, and heart failure were independent risk factors for death at 1 year.
The mortality rate was 5 times higher in patients older than 80 years than in patients 69 years or younger. Older age independently was predictive of all major complications.
Conclusions:
The overall risk of death and major complications after CA of AF is relatively low in Medicare beneficiaries, but the risk increases with advanced age. The redo CA rate of only 11% is considerably lower than the atrial fibrillation recurrence rate.

Source: Cardiosource.org

β-Blockers remain the standard of care after a myocardial infarction (MI). However, the benefit of β-blocker use in patients with coronary artery disease (CAD) but no history of MI, those with a remote history of MI, and those with only risk factors for CAD is unclear.
S. Bangalore, et al, analysed data on 44,708 patients enrolled in the international REACH registry with a known prior MI (n=14,043), CAD without a history of MI (n=12,012) and patients with risk factors for CAD (n=18,653), to assess the association of β-blocker use with cardiovascular events in stable patients with a prior history of MI, in those with CAD but no history of MI, and in those with only risk factors for CAD.

The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke. The secondary outcome was the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure.
With a median follow-up of 44 months (range, 35-45 months), event rates were not significantly different in patients with β-blocker use compared with those without β-blocker use for any of the outcomes tested, even in the prior MI cohort (489 [16.93%] vs 532 [18.60%], respectively. In the CAD without MI cohort, the associated event rates were not significantly different in those with β-blocker use for the primary outcome (391 [12.94%]) vs without β-blocker use (405 [13.55%]). In the cohort with CAD risk factors only, the event rates were higher for the primary outcome with β-blocker use (467 [14.22%]) vs without β-blocker use (403 [12.11%]). However, in those with recent MI (≤1 year), β-blocker use was associated with a lower incidence of the secondary outcome (OR, 0.77 [95% CI, 0.64-0.92]).
The study authors concluded that among patients enrolled in the international REACH registry, beta-blocker use was not associated with a lower event rate of cardiovascular events at 44-month follow-up, even among patients with prior history of MI. They suggest further research is warranted to identify subgroups that benefit from beta-blocker therapy and the optimal duration of beta-blocker therapy.

Source: JAMA. 2012;308(13):1340-1349.

Myocardial scarring assessed by MRI is an independent predictor of poor outcomes in implantable cardioverter defibrillator (ICD) candidates with low left ventricular ejection fraction (LVEF), new trial results show.

Currently, measuring LVEF is the most common method for identifying which patients are most likely to need an implantable defibrillator to prevent sudden cardiac death, but sudden cardiac death is usually caused by ventricular tachyarrhythmia, so LVEF is only an indirect measure sudden cardiac death risk. About 70% of patients suffering sudden cardiac death have a preserved LVEF, and studies show that only one death is prevented for every 14 to 18 patients with ventricular dysfunction receiving an ICD, according to the principle investigator of this new trial,  Dr Igor Klem (Duke University) and colleagues.

Klem and colleagues used MRI to evaluate myocardial scarring in 137 patients being evaluated for possible ICD placement for prevention of sudden cardiac death. Results of their study are published in the July 31, 2012 issue of the Journal of the American College of Cardiology.

Over a median follow-up of two years, 39 of the patients died and/or had an appropriate ICD discharge for a sustained ventricular tachyarrhythmia.  As previous trials have shown, the rate of adverse events increased steadily with decreasing LVEF, but there was a big difference in risk between those with a scar greater than 5% of left ventricular mass and those with less scarring (hazard ratio 5.2). A multivariable Cox proportional analysis showed that scar size was an independent predictor of adverse outcomes.

Among patients with LVEFs >30%, those with scarring over 5% of the left ventricle were 6.3 times as likely to die or suffer a sustained ventricular tachyarrhythmia as those with scarring under 5%. Among patients with an LVEF <30%, those with scarring greater than 5% were 3.9 times as likely to die or suffer a sustained ventricular tachyarrhythmia as those with minimal or no scarring.

Patients with an LVEF >30% but significant scarring had the same risk as all patients with an LVEF <30%. Patients with an LVEF <30% and minimal or no scarring had a similar risk to all patients with an LVEF >30%.

Klem I, Weinsaft J, Bahnson T, et al. Assessment of myocardial scarring improves risk stratification in patients evaluated for cardiac defibrillator implantation. J Am Coll Cardiol 2012; 60:408-20.

The American Heart Association (AHA)/American Stroke Association (ASA) advisory on stroke prevention in atrial fibrillation has released a new scientific advisory on use of the new oral antithrombotic agents to prevent stroke in patients with nonvalvular atrial fibrillation.

The update recommends that, along with warfarin and dabigatran (Pradaxa, Boehringer Ingelheim), already recommended for this indication, rivaroxaban (Xarelto, Bayer/Johnson & Johnson), and apixaban (Eliquis, Pfizer/Bristol-Myers Squibb) are also indicated to prevent a first or recurrent stroke in patients with nonvalvular AF.

Some of the new recommendations include:

• Warfarin, dabigatran, apixaban, and  rivaroxaban are all indicated for the prevention of first and recurrent  stroke in patients with nonvalvular AF. “The selection of an agent  should be individualized on the basis of risk factors, cost, tolerability,  patient preference, potential for drug interactions, and other clinical  characteristics, including time in INR therapeutic range if the patient   has been taking warfarin.”
• Dabigatran 150 mg twice daily is an  “efficacious alternative” to warfarin for the prevention of  first and recurrent stroke in patients with nonvalvular AF and at least  one additional risk factor who have creatinine clearance (CrCl) >30      mL/min.
• Use of dabigatran 75 mg twice daily may be  considered in patients with AF and at least one additional risk factor who  have a low CrCl, in the range of 15 to 30 mL/min. Dabigatran is not  recommended in patients with more severe renal failure (CrCl <15  mL/min).
• Apixaban 5 mg twice daily is an  “efficacious alternative” to aspirin in patients with nonvalvular AF deemed unsuitable for vitamin-K-antagonist therapy who have  at least one additional risk factor and no more than one of the following      characteristics: age >80 years, weight <60 kg, or serum creatinine   >1.5 mg/dL.
• Apixaban 2.5 mg twice daily may be considered      as an alternative to aspirin in patients with nonvalvular AF deemed  unsuitable for vitamin-K-antagonist therapy who have at least one  additional risk factor and more than two of the following criteria: age  >80 years, weight <60 kg, or serum creatinine >1.5 mg/dL.
• Apixaban 5 mg twice daily is a  “relatively safe and efficacious alternative” to warfarin in  patients with nonvalvular AF deemed appropriate for vitamin-K-antagonist  therapy who have at least one additional risk factor and no more than one  of the following characteristics: age >80 years, weight <60 kg, or serum creatinine >1.5 mg/dL.
• Although its safety and efficacy have not been  established, apixaban 2.5 mg twice daily may be considered as an alternative to warfarin in patients with nonvalvular AF deemed appropriate for vitamin-K-antagonist therapy who have at least one additional risk factor and more than two of the following criteria: age >80 years,  weight <60 kg, or serum creatinine >1.5 mg/dL. Apixaban should not      be used if the CrCl is <25 mL/min.
• In patients with nonvalvular AF who are at moderate to high risk of stroke (prior history of transient ischemic attack [TIA], stroke, or systemic embolization or more than two additional risk factors), rivaroxaban 20 mg/day “is reasonable” as an alternative  to warfarin.
• In patients with renal impairment and  nonvalvular AF who are at moderate to high risk of stroke (prior history  of TIA, stroke, or systemic embolization or more than two additional risk  factors), with a CrCl of 15 to 50 mL/min, 15 mg of rivaroxaban daily may  be considered, but its safety and efficacy have not been established.   Rivaroxaban should not be used if the CrCl is <15 mL/min.
• The safety and efficacy of combining  dabigatran, rivaroxaban, or apixaban with an antiplatelet agent have not  been established.

 Source: The Heart.Org

The antihypertensive olmesartan seems to have played a role in the development of otherwise unexplained spruelike enteropathy in 22 patients, according to a report in the Mayo Clinic Proceedings.

The patients, all of whom were taking olmesartan, were seen at the Mayo Clinic for evaluation of chronic severe diarrhea that had been present for a median of 18 months. Nausea and vomiting were present in two thirds, as was fatigue; abdominal pain was present in half. Treatment with a gluten-free diet and corticosteroids was ineffective. When olmesartan was withdrawn, the diarrhea resolved, and changes seen on intestinal biopsies also resolved.

The authors speculate that the delay between starting olmesartan and the onset of enteropathy (average, 3 years) suggests some effect of olmesartan on cell-mediated immunity rather than a type I hypersensitivity reaction. Their case series does not prove causality, they write, but they encourage physicians to consider medications as a cause when evaluating diarrheal syndromes.

Source: May Clinic Proceedings article

A team of interventional cardiologists at the Rigshopitalet University Hospital in Copenhagen, Denmark    have become the first to implant a new bioprosthetic mitral valve into a person via a transcatheter approach. They implanted the valve as a compassionate treatment into an 86-year-old male suffering from severe mitral regurgitation (MR 4+).  Currently, percutaneous valve replacement, increasingly done in the aortic and pulmonary valves, but has remained elusive for the mitral valve.     The valve used in Denmark was the CardiAQ prosthesis (CardiAQ Valve Technologies, Winchester, MA). The company says its technology, which it describes as “self-conforming and self-anchoring,” is designed to make nonsurgical mitral heart valve replacement a future alternative to open heart surgical replacement and repair.

If it proves successful, this could boost the entire field of percutaneous options for the treatment of mitral-valve disease.