New blog policy

From now onwards, we will be posting table of contents from major cardiology journals as soon as they are published. This way you can keep track of interesting developments in the field of Cardiology.

2006 Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death (SCD) released

The 2006 Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death (SCD) were released by the American College of Cardiology (ACC), American Heart Association (AHA), and the European Society of Cardiology (ESC) in collaboration with the European Heart Rhythm Association EHRA) and the Heart Rhythm Society (HRS)on 21st August. ESC.

The executive summary will be published in the September 5, 2006 issues of the Journal of the American College of Cardiology, and Circulation: Journal of the American Heart Association, and the first September issue of the European Heart Journal (Eur Heart J 2006;27:2099–2140). The full-text guideline is published in Europace and e-published in the same issue of the journals noted above, as well as posted on the ACC (www.acc.org), AHA www.americanheart.org), and ESC (www.escardio.org) sites.

Is Angioplasty a form of Surgery?

Recently, 93 year old Former US President Ford underwent angioplasty with stenting to two of his coronary arteries which supply blood to the heart. Most of the media carried reported that Ford had a surgery. Can one really call angioplasty as surgery?

People with significant blocks in coronary atreries generally need one of two treatments - bypass surgery or angiplasty. Bypass surgery is a surgical procedure that involves oening up the chest.

However, angioplasty is a minimally invasive procedure that involves passing a catheter through an artery in the leg or arm. Through the catheter, a thin metal wire is passed across the block in the coronary artery. A special balloon is tracked along the wire, placed at the level of the block and carefully inflated at the site to relieve the narrowing. Actually this balloon inflation is called balloon angioplasty. After this, generally a metallic mesh like stent os placed to keep the artery open.

As angioplasty does not involve cutting open or any surgical wounds, I would not call it a surgery. It may just be a matter of semantics.

FDA calls for strong warning labels on ADHD Drugs about cardiovascular side effects

Food and Drug Administration (FDA) says that drugs used for ADHD (Attention Deficit Hyperactivity Disorder) must carry warning labels that state that these drugs may cause suppression of growth, psychosis, aggression and serious cardiovascular side effects

In February, an FDA advisory committee had strongly recommended that the FDA require all ADHD drugs come with a black box warning, linking the drugs to serious side cardiovascular side effects. In March, a different committee was convened which recommended additional warnings about psychological side effects.

The warnings state in part, "Sudden deaths, strokes and myocardial infaction have been reported in adults taking stimulant drugs at usual doses." These warnings caution about an increased risk of strokes and heart attacks that come after scattered reports of children dropping dead suddenly while taking the drugs.

"It's appropriately worded," says Steven Nissen, president of the American College of Cardiology and chairman of cardiology at the Cleveland Clinic regarding the warnings. He says, "It basically lets physicians and patients know that these drugs to have serious cardiovascular side effects."

New ACC AHA ESC guidelines for Atrial fibrillation released

According to the revised ACC AHA ESC guidelines for the Management of Patients with Atrial Fibrillation released today, risk factors for stroke should be used to determine whether anticoagulation therapy is given to people with atrial fibrillation.

Atrial fibrillation (AF) is the most common heart rhythm disturbance and it increases the risk of stroke, heart failure and all-cause death. It affects more
than 2 million Americans and 4.5 million Europeans. The number of patients with atrial fibrillation is expected to increase even more due to an aging population, a rising number of people with chronic heart disease and improved diagnosis.

During AF, two upper chambers of the heart (the atria) quiver instead of beating effectively. Blood is not pumped completely out of them, so it may pool and clot. If a piece of a blood clot in the atria leaves the heart and lodges in an artery in the brain, a stroke results. Moreover, when the very rapid electrical signals from the atria reach the lower chambers of the heart (the ventricles) they start to beat quickly and irregularly causing palpitations and decreased blood pumping leading to
tiredness and breathlessness.

Previous guidelines published in 2001 recommended using several patient characteristics – age, gender, heart disease risk and concurrent conditions – to decide proper anti-clotting therapy for these patients. The new approach recommends that the risk for stroke should be the main factor, said Valentin Fuster, M.D., Ph.D., co-chair of the guidelines writing committee.

"We focused on stroke risk because AF is associated with increased long-term risk for stroke", he said. "About 15 percent to 20 percent of strokes occur in people with AF, and those strokes are especially large and disabling, Incorporating existing recommendations on anti-clotting therapy from the stroke primary
prevention guidelines will streamline patient care and make recommendations clearer for physicians", he added.

AF is expensive, with total costs approaching €13.5 billion in the European Union alone, according to the statement.

The revised guidelines also recommend daily aspirin therapy (81–325 mg) to guard against blood clots in AF patients with no stroke risk factors. Aspirin or warfarin is recommended for those with one “moderate” risk factor (over age 75, high blood pressure, heart failure, impaired left ventricular systolic function or diabetes). Warfarin is recommended for people with any “high” risk factor (previous stroke, transient ischemic attack [TIA], systemic embolism or prosthetic heart valve) or more than one moderate risk factor.

According to co-chair Lars E. Rydén, the guidelines help physicians prioritize the objectives of patient care according to the following steps:
1) controlling heart rate,
2) preventing clots, and, if possible,
3) correcting the rhythm disturbance.

Rate control usually involves achieving a ventricular rate (pulse) of 60 to 80 beats per minute at rest and between 90 and 115 beats per minute during moderate exercise. Also new in the guidelines, catheter ablation — a procedure that corrects irregular heartbeat with radiofrequency energy — is considered “a reasonable alternative to drug therapy to treat AF in patients with little or no left atrial enlargement, and in whom drug treatments did not stop the rhythm disturbance,” Fuster said.

Depending on symptoms, controlling the heart rate may be the reasonable therapy in elderly patients with persistent AF who have hypertension or heart disease, according to the joint statement.

For people under age 70, especially those with recurrent AF and no evidence of underlying heart disease, rhythm control may be the preferred approach, starting with drugs and by means of catheter ablation if medication fails to stop the attacks.

Both Fuster and Rydén emphasized that regardless of the approach, the need for anti-clotting therapy should still be based on stroke risk and not on whether proper heart rhythm is maintained

Full guidelines are available at many websites including ACC page for scientific statements

Drug Eluting Stents and Stent Thrombosis

Blockages in coronary arteries (coronary stenoses) reduce blood flow to the heart and may result in symptoms of anginal chest pain, heart attack (myocardial infarction), heart failure and even sudden death. Many patients with these conditions require treatment to relieve the blockages. Traditionally this has been done by coronary bypass surgery. From 1980's, interventional cardiology techniques like angioplasty and stenting has overtaken bypass surgery as the treatment of choice as they offer good results without the morbidity of major surgery. However, patients treated with these techniques have greater chances of recurrence of blockages. This is due to the development of restenosis at the site of stenting or angioplasty.

The introduction of drug eluting stents (DES) in the late 1990's was a major landmark in coronary interventions. They could reduce restenosis due to the effects of the drug, the Achilles heel of coronary stents, thus reducing the need for repeat intervention. However, a new problem has surfaced with their use - an increased rate of late stent thrombosis. Stent thrombosis refers to the development of clots within the stent blocking blood flow suddenly and this almost invariably results in a heart attack.

All stents are to some degree thrombogenic, ie, they promote clotting. This tendency is overcome by antiplatelet therapy to reduce clotting at least till the stented part heals by endothelialization. Drug eluting stents appear to be more thrombogenic than bare stents. Stent thrombosis is often a catastrophic event leading to acute myocardial infarction or even death. Delayed reendothelialization of the stented segment due to the effects of the drug has been thought as the mechanism for stent thrombosis. Particularly disturbing are the reports of late stent thrombosis more than a year after stent implantation. Such events are generally associated with stoppage of antiplatelet therapy.

A recently reported study by Kuchulakanti et al in Circulation is one of the first to evaluate the correlates of stent thrombosis. They found that stent thrombosis was significantly higher in patients with diabetes, acute postprocedural renal failure, and chronic renal failure. There were more bifurcation lesions, type C lesions, and a trend for smaller-diameter stents. Discontinuation of clopidogrel was higher in these patients (36.8% versus 10.7%). Multivariate analysis detected cessation of clopidogrel therapy, renal failure, bifurcation lesions, and in-stent restenosis as significant correlates of stent thrombosis. The follow up period in this study was 12 months.

The current best practice to reduce the incidence of stent thrombosis in patients treated with DES (sirolimus and paclitaxel) is to give dual antiplatelet therapy with aspirin and clopidogrel for at least 12 months. Thereafter, patient should be on aspirin lifelong. Aspirin should never be stopped even if the patient is undergoing surgery. As one cardiologist put it: "In the current era, there is no surgery which cannot be done without stopping aspirin". One should still recognize that there may still be instances where aspirin need to be withheld as in intracranial surgery or bleeding. In such situations, time off antiplatelets should be minimized.

Newer drug eluting stents which have a biopolymer coating are claimed not to interfere with endothelial healing. One might hope that they will reduce the risks of late stent thrombosis, while still maintaining low restenosis rates.

Drugs for ADHD and heart risk

The cardiac risk of the drugs for ADHD have attracted interest recently following the recommendation by the Drug Safety and Risk Management Advisory Committee of the FDA to include a black-box warning describing the cardiovascular risks of stimulant drugs used to treat this condition. However, this recommendation has subsequently been toned down by the Pediatric Advisory Committee of the FDA.

ADHD (attention deficit hyperactivity disorder) is a disorder mainly diagnosed in school age children. It is characterized by increased activity, an inability to concentrate and poor school performance. Stimulant drugs have been the mainstay of treatment of ADHD. These include amphetamine and related drugs like methamphetamine and methylphenidate (Ritalin). One popular drug is Adderall, a mixture of amphetamine salts.

It is estimated that 2.5 million children now take stimulants for ADHD in the USA. A growing number of adults also take the drug, with a diagnosis of "adult ADHD", which has recently come into vogue. However, the numbers are quite small in Europe and elsewhere.

Now let us come to the crux of the matter. Why are these drugs supposed to cause heart problems?

These stimulant drugs belong to the class of sympathomimetic amines. Cardiovascular
effects of these compounds have been well studied. They act by stimulating the sympathetic nervous system and increase heart rate and blood pressure significantly. One study with a commercially marketed formulation showed an increase in systolic BP by about 5 mm Hg in treated adults. Such a rise of BP, argues the Drug Safety and Risk Management Advisory committee, can cause definite adverse effects on long term therapy.

The induced increase in heart rate also has well-described adverse effects on the heart. Persistent increase in heart rate may induce chronic heart failure as demonstrated in animal models of dilated cardiomyopathy.

The Committee also cites the examples of Ephedra (ma huang), marketed as a dietary supplement and phenylpropanolamine, an over the counter nasal decongestant, which belong to the same class. They have been known to have caused several well publicized adverse effects. Studies have reported that ephedra containing supplements accounted for 64% of the serious adverse reactions to supplements reported to the Centers for Disease Control and Prevention, although their sales represented less than 1% of all dietary-supplement sales. A 16-fold increase in the risk of stroke has been reported among women taking phenylpropanolamine as a weight loss drug.

Drug Safety and Risk Management Advisory committee studied cases of myocardial infarction, stroke and sudden death in children and adults taking ADHD stimulants which have been reported to the FDA's Adverse Event Reporting System (AERS). This could represent only a tip of the iceberg as only 1 to 10 percent of serious adverse events are actually reported. Some had evidence of undiagnosed heart disease on autopsy and the documentation was frequently incomplete.

Despite these difficulties, the advisory committee decided to recommend strong preemptive action. Factors which the committee cited as the reason for the action included the tendency of these drugs to raise blood pressure and heart rate, the history of serious adverse effects associated with two drugs of the class (ephedra and phenylpropanolamine) and the rapid increase in exposure,particularly among adults. Though the committee noted important potential benefits of these drugs for
certain highly affected children, they felt that the administration of these potent sympathomimetic agents to millions of Americans is inappropriate. The recommendations emphasize more selective and restricted use of these drugs while increasing the awareness of potential hazards.

However, FDA's Pediatric Advisory Committee was of the opinion that adding strong black-box warnings could cause more harm than good and may frighten patients. They, on the other hand, called for new information about health risks on the labels of attention deficit drugs. This would benefit doctors, patients and parents. They said that patients and parents should know about the reports even though it is unclear if the drugs contributed to the problems.

Now, the FDA has to decide on the difficult problem of how to communicate the potential risks associated with ADHD drugs. The FDA will consider both panels' recommendations before making a final labeling decision.

Fondaparinux as effective as enoxaparin in acute coronary syndromes

Acute coronary syndromes require treatment with multiple drugs which reduce blood clotting to prevent recurrent ischemia. However, this is attained at a cost of mild increase in bleeding episodes.

Here we report the findings of a new study which assessed whether fondaparinux would preserve the anti-ischemic benefits of the low molecular weight heparin, enoxaparin, while reducing bleeding. Fondaprinux is direct thrombin inhibitor.

Results of the study showed that Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days in patients with acute coronary syndromes, but it substantially reduces major bleeding and improves long term mortality and morbidity.

The full study will be published in NEJM on April 6th.

Abstract link