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Author: Dr. Hassan Gargoum

Clinical Professor of Medicine, University of Saskatchewan Consultant, Cardiovascular Diseases

Colchicine post-ablation reduces early atrial fibrillation recurrences

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.

How safe is catheter ablation of atrial fibrillation in patients 65 years or older?

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

Beta-Blockers May Not Be Associated With Lower Event Rates in Patients With CAD

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.

Scarring seen on MRI may predict ICD benefit better than assessment of LVEF

 

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.

 

New Recommendations on Stroke Prevention in Atrial Fibrillation

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

Case Series Associates Olmesartan with Spruelike Disease

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

 

First-in-human transcatheter mitral-valve implant (TMVI)

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.

New guidance for management of asymptomatic young people with Wolff-Parkinson-White (WPW) syndrome

A consensus statement on the management of asymptomatic patients with Wolff-Parkinson-White (WPW) syndrome has been presented at The Heart Rhythm Society (HRS) 2012 Scientific Sessions. This statement should help clarify which young people should undergo catheter ablation. While there is a small chance that an asymptomatic young person could end up having a life-threatening arrhythmia, the number is not zero. Yet, catheter ablation for every young individual who has ever had a WPW pattern on his/her electrocardiogram (ECG) is also not the answer.

Cohen and colleagues released the statement on May 18, 2012 at the Heart Rhythm Society Scientific Sessions.

The guidance is explicitly directed at physicians treating young patients with WPW and defines young people as between eight and 21. At the crux of the document is the question of just when physicians should intervene—and when they shouldn’t—in young people found, on ECGs, to have the signature electrocardiographic WPW pattern. These are increasingly important questions, given increased emphasis on pre-participation screeningfor sports in young people.

The expert consensus statement, a joint effort of the Pediatric and Congenital Electrophysiology Society (PACES) and the HRS, estimates that from one to three young people per 1000 likely have WPW, although many—around 65%—are asymptomatic.

The guideline writers recommend the following:

  • If a child is old enough to comply, an exercise stress test to look for persistent preexcitation is “reasonable.” Clear loss of preexcitation at physiologic heart rates is associated with lower risk of sudden death due to accessory pathways.
  • Where noninvasive testing shows persistent or uncertain loss of preexcitation, diagnostic transesophageal or intracardiac electrophysiology studies are warranted. Recommendations, based on test results, include ablation or continued awareness and observation for symptoms.
  • Ablation is a “reasonable” consideration in young people with a shortest preexcited RR interval (SPERRI) <250 ms. Young people with SPERRI >250 ms are lower risk, and ablation may be deferred.
  • Patients deemed low risk who subsequently develop symptoms like syncope or palpitations may be eligible for ablation.
  • WPW in the setting of structural heart disease increases risk for both atrial tachycardia and atrioventricular (AV) reciprocating tachycardia. Patients can be considered for ablation.
  • Ablation may also be considered in asymptomatic patients with WPW who have ventricular dysfunction secondary to dyssynchronous contractions.

 

 

Source: The heart.org

 

 

Exercise Testing in Asymptomatic Patients After Revascularization: Does it worth the effort?

Exercise Testing in Asymptomatic Patients After Revascularization: Worth the Effort?

Exercise echocardiography in asymptomatic patients after revascularization can identify those at high risk, but these patients do not necessarily benefit from repeat revascularization, according to a retrospective study in the Archives of Internal Medicine.

Researchers studied some 2100 asymptomatic patients who underwent exercise echocardiography roughly 4 years after percutaneous coronary intervention or coronary artery bypass grafting. Of 13% of patients with ischemia on exercise testing, one third had a subsequent revascularization during nearly 6 years of follow-up. While patients with ischemia had a greater mortality risk, repeat revascularization of these patients did not improve survival.

A commentator points out that “routine periodic stress testing in asymptomatic patients following coronary revascularization is associated with high rates of resource utilization and high costs.” He concludes: “Until well-supported data become available supporting such a strategy, routine testing in asymptomatic patients is probably not worth the effort.”

Source: Archives of Internal Medicine.

 

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)


What is Catecholaminergic Polymorphic Ventricular Tachycardia?

CPVT is a rare condition that affects the heart of otherwise fit and healthy people. It causes the heart to beat abnormally quickly, usually at times of exercise (particularly swimming) or times of high emotion, and can result in dizziness, sudden loss of consciousness or even death. It most commonly occurs in children and young adults typically in the first or second decade of life. It was first recognised in 1975.

In at least a third of cases, it is familial, (inherited) being passed down through the generations.

It is a difficult condition to diagnose, because all of the tests taken at a time of rest are normal including the electrocardiogram (ECG), and the echocardiogram (ultrasound of the heart).

The diagnosis is usually made by detecting extra beats, or runs of fast rhythm arising from the bottom part of the heart, (ventricles), during an exercise test or on a 24 hour ECG.

 How does CPVT get its name?

The heart is a pump that initiates its own electrical signals, causing it to beat between at between 50 and 180 beats per minute depending on whether you are resting, exercising or under some form of emotional/physical stress.

In response to stress the body releases adrenaline and noradrenaline (also called epinephrine and norepinephrine). Adrenaline and noradrenaline are chemical messengers that are collectively known as catecholamines that have a direct action on the heart. During exercise or emotional stimulation these catecholamines cause the heart to beat faster and the blood pressure to increase, thus enabling blood and oxygen to reach the exercising muscles and other vital organs.

This response to stress is how the body copes and allows us to flee from danger or run to catch the bus, however it also works the same if the body is emotionally or physically challenged in some other way, such as severe illness.

People with CPVT have hearts that respond abnormally to catecholamines, such that the heartbeat becomes rapid, chaotic and irregular at times of stress. A rapid heart rhythm is known as a “tachycardia”, and since this particular tachycardia arises from the main pumps or ventricles, it is known as a “ventricular tachycardia”. The word “polymorphic” literally means lots of different shapes- referring to the varying beats seen on the ECG. If such a rhythm sustains for more than a few seconds, insufficient blood reaches the brain, leading to a faint, collapse, or even death.

 How does it present?

CPVT typically presents with sudden collapse or severe dizziness, usually associated with exercise (or just after exercise stops) or intense emotional stress. First symptoms appear usually in the first or second decade of life, and may often be mistaken for epilepsy in children. It can also present quite out of the blue with sudden death.

 How can doctors make the diagnosis?

Symptoms may be reproduced by exercise test, and a 24-hour holter ECG (Holter) test can be useful. These tests are always performed in hospital under specialist supervision. Increasingly doctors use a long-term implanted digital loop recorder, or “Reveal” device, which records the ECG continuously, and documents the heart rhythm during a collapse.

Sudden collapse or severe dizziness may be associated with heart rhythm disturbance such as CPVT. Typically these  symptoms may occur with little or no warning, and are usually associated with exercise (or just after exercise stops) or   intense emotional stress. Typically cases present in the first or second decade of life, and may often be mistaken for epilepsy in children. Symptoms of the disease may be reproduced by exercise test or by using other forms of adrenergic stimulation such as drugs that increase the heartbeat. These tests are always performed in hospital under Specialist supervision.

Familial incidence of the condition has been manifest in 30% of cases to date.

 Treatment:

CPVT usually responds well to beta-blockers. Beta-blocker medications work to stop adrenaline and other catecholamines from speeding the heart up and therefore keep the heart rate under control. More recently, Flecainide has been found very effective in preventing this arrhythmia. In some cases beta-blockers are usually used in combination with implantable defibrillators (implantable cardioverter defibrillator “ICD”) that stop the fast chaotic heart rhythm by treating it with a small electric shock

 Genetic Diagnosis of CPVT:

At this time 3 genes are thought to be responsible for CPVT. Ryanodine (RYR2) mutations (abnormalities in the gene sequence), are thought to be responsible for the autosomal dominant (this means that each child born has a 50% chance of inheriting the mutation). In the heart ryanodine is located in the working part of the heart muscle cells that are responsible for making the heartbeat.

The role of ryanodine is to release calcium inside the cell in order for each heartbeat to occur, however this does not work properly as in the case of the abnormal ryanodine, then calcium may build up and not be realised as it should. When adrenaline is present and the heart rate speeds up the working cells are likely not able to cope with the increased workload and this throw the heart into the chaotic heart rhythm.

Calsequestrin CASQ2 binds to calcium inside the working areas of the cardiac muscle cells (sarcoplastic reticulum), it is thought that mutations in the calsequestrin prevent adequate binding occurring particularly when the cell is having to work hard in the presence of catecholamines such as adrenaline. The buildup of calcium because it cannot adequately attach itself to calsequestrin for transport is thought to cause the chaotic heart rhythm.

Ankyrin B mutations have also been implicated in CPVT, and these may also be linked to LQT (Long QT type 4). Work is still being done to establish this link.