COX-2 inhibitor may disrupt heart rhythm

MedWire News - Cardiology - COX-2 inhibitor may disrupt heart rhythm

Gene Linked To Increased Risk Of Developing Inflammatory Arthritis May Also Increase Patients' Risk Of Dying From Cardiovascular Disease

Ventricular Arrhythmias During Clinical Treadmill Testing and Prognos

Ventricular Arrhythmias During Clinical Treadmill Testing and Prognosis


Frederick E. Dewey, BA; John R. Kapoor, MD, PhD; Ryan S. Williams, MD; Michael J. Lipinski, MD; Euan A. Ashley, MRCP, DPhil; David Hadley, PhD; Jonathan Myers, PhD; Victor F. Froelicher, MD

Arch Intern Med. 2008;168(2):225-234.

Background Although exercise-associated ventricular arrhythmias are frequently observed during exercise testing, their prognostic significance remains uncertain. Therefore, we aimed to evaluate the clinical correlates and prognostic significance of exercise-associated premature ventricular complexes (PVCs) during and after exercise testing.

Methods We studied 1847 heart failure–free patients who underwent clinical treadmill testing between March 13, 1997, and January 15, 2004, in the Veterans Affairs Palo Alto Health Care System. Logistic regression was used to evaluate the clinical and exercise test associations of exercise and recovery PVCs. Propensity score–adjusted Cox survival analyses were used to evaluate the prognostic significance of exercise-associated PVCs.

Results Of the 1847 subjects, 850 (46.0%) developed exercise PVCs (median rate, 0.43 per minute) and 620 (33.6%) had recovery PVCs (median rate, 0.60 per minute). Resting PVCs, age, and systolic blood pressure were key predictors of both exercise and recovery PVCs. Whereas exercise PVCs were related to the heart rate increase with exercise, recovery PVCs were related to coronary disease (previous myocardial infarction, coronary revascularization procedure, or pathological Q waves on resting electrocardiogram) and ST-segment depression. During a 5.4-year mean follow-up, 161 subjects (8.7%) died, and 53 of these deaths (32.9%) were due to cardiovascular causes. Recovery PVCs, but not exercise PVCs, were associated with 71% to 96% greater propensity-adjusted mortality rates (hazard ratio, 1.96 [95% confidence interval, 1.31-2.91] for infrequent PVCs; hazard ratio, 1.71 [95% confidence interval, 1.07-2.73] for frequent PVCs compared with subjects without PVCs), and occurrence of recovery PVCs reclassified 33.2% of subjects with intermediate-risk Duke Treadmill Scores into higher-risk subgroups.

Conclusion In our heart failure–free population, recovery PVCs were associated with increased mortality and augmented established risk markers.

Cardiovascular Effects of Haloperidol

FDA Issues Warning on Cardiovascular Effects of Haloperidol


The FDA is warning clinicians about the risks for cardiovascular side effects and sudden death from haloperidol.


The agency says there are "at least 28 case reports" of QT prolongation and Torsades de Pointes in the literature associated with the antipsychotic drug, "especially when given intravenously"; some cases have been fatal. A 2005 postmarketing study conducted for the Italian drug authority, but only recently submitted to the FDA by Johnson & Johnson, found 13 additional cases. The FDA notes that the drug is often used intravenously off-label, especially in intensive care units, to treat severe agitation.


Label warnings will be strengthened, the FDA says, and it recommends ECG monitoring if the drug is used intravenously. The FDA urges particular caution in patients with other QT-prolonging conditions, such as electrolyte imbalance (especially hypokalemia and hypomagnesemia).


FDA alert (Free)

Heart Palpitations Are Usually Not Dangerous, Reports The Harvard Heart Letter

29 Aug 2007

Palpitations the sensation that the heart has started to race or pound, or feels like it has skipped a beat are usually caused by a harmless hiccup in the heart's rhythm.

Sometimes, though, palpitations reflect a problem in the heart or elsewhere in the body. Sorting out worrisome palpitations from harmless ones isn't always easy, reports the September 2007 issue of the Harvard Heart Letter.

Palpitations are extremely common. Different people experience them in different ways. You might feel as though your heart is fluttering, throbbing, flip-flopping, or pounding, or that it has missed a beat. Palpitations can appear out of the blue and disappear just as suddenly. Or they might be linked with certain activities, events, or feelings. Some of the most important pieces of information that can help your doctor in pinning them down is how palpitations feel, how often they strike, and when they occur.

Some palpitations result from premature contractions of the heart's chambers or malfunctions of a heart valve. But a physical exam and electrocardiogram often don't turn up any problems, which can be frustrating to the patient.

If your palpitations aren't accompanied by dizziness or other symptoms and if you don't have a valve disorder or other structural problem with your heart, that usually means palpitations are benign.

The Harvard Heart Letter suggests that if you have unexplained palpitations, start with simple steps to help alleviate them. Cut back on caffeine, smoking, and alcohol; avoid over-the-counter decongestants, eat and drink regularly, get enough sleep, and find a way to relax if you are stressed.

In some cases, your doctor may recommend medications or a procedure to correct errant electrical signals in the heart.

Harvard Heart Letter

http://www.health.harvard.edu/heart

Electrocardiographic abnormalities in patients with cluster headache on verapamil therapy

Electrocardiographic abnormalities in patients with cluster headache on verapamil therapy


NEUROLOGY 2007;69:668-675© 2007 American Academy of Neurology

Anna S. Cohen, MRCP, PhD, Manjit S. Matharu, MRCP, PhD and Peter J. Goadsby, MD, PhD, DSc
From the Headache Group (A.S.C., M.S.M., P.J.G.), Institute of Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; and Department of Neurology (P.J.G.), University of California, San Francisco.

Background: High dose verapamil is an increasingly common preventive treatment in cluster headache (CH). Side effects include atrioventricular block and bradycardia, although their incidence in this population is not clear.

Method: This audit study assessed the incidence of arrhythmias on high dose verapamil in patients with cluster headache.

Results: Of three hundred sixty-nine patients with cluster headache, 217 outpatients (175 men) received verapamil, starting at 240 mg daily and increasing by 80 mg every 2 weeks with a check electrocardiogram (EKG), until the CH was suppressed, side effects intervened, or to a maximum daily dose of 960 mg. One patient had 1,200 mg/day. Eighty-nine patients (41%) had no EKGs. One hundred eight had EKGs in the hospital notes, and a further 20 had EKGs done elsewhere. Twenty-one 108 patients (19%) had arrhythmias. Thirteen (12%) had first-degree heart block (PR > 0.2 s), at 240 to 960 mg/day, with one requiring a permanent pacemaker. Four patients had junctional rhythm, and one had second-degree heart block. Four patients had right bundle branch block. There was bradycardia (HR <>0.2 s. The incidence of arrhythmias on verapamil in this patient group is 19%, and bradycardia 36%.

Conclusion: We therefore strongly recommend EKG monitoring in all patients with cluster headache on verapamil, to observe for the potential development of atrioventricular block and symptomatic bradycardia.

Inherited Arrhythmic Disorders

Inherited Arrhythmic Disorders


Tex Heart Inst J. 2007; 34(1): 67–75.
Copyright © 2007 by the Texas Heart® Institute, Houston
Inherited Arrhythmic Disorders
Long QT and Brugada Syndromes

Inherited arrhythmic disorders comprise a group of syndromes with unique genetic abnormalities and presentations but with very similar clinical outcomes and complications, the most terrifying of which are life-threatening arrhythmias and sudden cardiac death. Advances in molecular biology have enabled us to define and pinpoint many such disorders, which were previously labeled as idiopathic, to specific genes on various chromosomes. The current trend in the management of these potentially deadly disorders is to use pharmacotherapy (antiarrhythmic agents) and defibrillators for the prevention of sudden death; however, targeted therapy at a molecular level appears to be the path of the future. Herein, we review long QT and Brugada syndromes and focus on the genetics, pathophysiology, and clinical manifestations of these inherited arrhythmogenic disorders that affect patients with structurally normal hearts.

New York Times takes a look at uncertainties in catheter ablation of atrial fibrillation

New York Times takes a look at uncertainties in catheter ablation of atrial fibrillation

July 9, 2007

Michael O'Riordan

New York, NY - Catheter ablation of atrial fibrillation is in the national spotlight this week as a new report in the New York Times (NYT) highlights the rapid growth of the procedure and its associated costs [1]. With limited long-term clinical data and the use of equipment in an off-label manner, coupled with the expected increase in the prevalence of AF as the population ages, the newspaper says catheter ablation is testing "the ability of regulators to keep up with medical treatments being carried out with scant evidence of long-term effectiveness."

Written by Barnaby Feder, the article, which appeared in the July 7, 2007 issue of the NYT, notes that the FDA has not yet approved the devices used in the catheter ablation of AF, and with this, hospital and doctors struggle to be fully reimbursed for the procedure. "This is one of those areas where the practice of medicine has moved faster than the approval process," Dr Daniel G Schultz (Food and Drug Administration, Rockville, MD) told the NYT. "This is very high on our list of areas that need concerted attention."

Dr Carolyn Clancy, director of the Agency for Healthcare Research and Quality, noted that any situation where off-label therapies are used as frequently as they are in AF "spotlights where we lack good evidence of which patients can benefit from which therapies." Although such off-label use is legal, doctors and hospitals often run into roadblocks with reimbursement (payments fall short of full compensation), and insurance companies are sometimes reluctant to cover it, mainly because healthcare providers might have less legal protection should something go wrong, writes Feder.

In addition, although clinical trials have shown ablation to be effective in eliminating AF in the short term, long-term evidence is scant, Feder writes. Still, despite what's missing, a consensus statement, developed by the Heart Rhythm Society, the European Heart Rhythm Association (EHRA), and the European Cardiac Arrhythmia Society (ECAS), in collaboration with the American College of Cardiology, the American Heart Association, and the Society of Thoracic Surgeons, has been drafted to standardize the procedure and define patient indications [2].

Feder reports that estimates of the potential market for AF devices in the next decade range from $1.5 to $5 billion, with projections including the cost of various diagnostic and mapping technologies. The number of ablation procedures would surge if the time needed could be reduced and insurance coverage were easier to obtain, he adds. Even with the uncertainties, many electrophysiologists are not hurting for work. Dr Andrea Natale (Cleveland Clinic, OH) told the NYT that he is booked into 2008 and there is a waiting list of four to six months for other electrophysiologists working at the hospital.

The report goes on to highlight the drawbacks of drug therapy for AF, with Dr Mark Connolly telling the paper that the "medications to control it are nasty drugs. Many patients don't tolerate them well, especially if they are active."

Sources

Feder BJ. Heart therapy strains efforts to limit costs. New York Times, July 7, 2007. Available at http://www.theheart.org/viewDocument.do?document=http%3A%2F%2Fwww.nytimes.com.
Calkins H, Brugada J, Packer DL, et al. HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: Recommendations for personnel, policy, procedures, and follow-up. Heart Rhythm Society 2007. Available at www.hrsonline.org/News/Media/press-releases/upload/HR-and-Euro-Copy-for-Print.pdf.


Related links

Heart rhythm societies develop consensus statement on catheter and surgical ablation of AF [HeartWire > News; May 10, 2007]
Late symptomatic recurrence observed in AF patients "cured" with pulmonary-vein isolation [HeartWire > News; Nov 23, 2006]
ACC/AHA/ESC updates guidelines for AF management [HeartWire > News; Aug 04, 2006]
Ablation superior to drug therapy in patients who have already failed one antiarrhythmic drug [HeartWire > News; May 22, 2006]
Ablation better than drug therapy for restoring sinus rhythm in paroxysmal AF patients [HeartWire > News; Mar 12, 2006]
Experts say time has come for AF ablation RCTs: "Only thing missing is the data" [HeartWire > Features; Sep 01, 2005]
New York Times takes a look at uncertainties in catheter ablation of atrial fibrillation

Reclast and Aledronate found to cause abnormal heart rhythms

Reclast (Zoledronic Acid ) found to cause abnormal heart rhythms

An osteoporosis drug with the potential to cut the risk of spine fractures by 70 percent and the chance of hip fractures by 41 percent, has been found to have an adverse side effect on some women.

Researchers say the drug Reclast which is produced by Novartis, which is given once a year, reduces the risk of broken bones for three years but it may spark an abnormal heart rhythm in some patients.

The study leader Dr. Dennis Black of the "http://www.ucsf.edu/" University of California San Francisco,says Reclast represents an excellent alternative for those who cannot or do not want to take oral drugs; however serious atrial fibrillation, an abnormal heart rhythm that can increase the risk of stroke, was found to be nearly three times more common among women taking Reclast.

Of 3,889 volunteers using the drug and 3,876 given placebo injections, one in 77 Reclast patients developed the problem.

Dr. Black says for the first time, women have the option of being treated once a year for osteoporosis, instead of having to remember to take a weekly pill.

Reclast represents an excellent alternative for those who cannot or do want to take oral drugs and is already approved in more than 50 countries to treat the abnormal bone growth of Paget's disease.

One injection of Reclast has been shown in studies to increase bone density for a year, whereas conventional oral drugs as a rule produce a 40 to 50 percent reduction in spine bone breakage.

Reclast is currently under review in the U.S. for osteoporosis; outside the United States it is called as Aclasta.

Reclast also produced other side-effects with 31.6 percent of recipients experiencing fever, joint and muscle pain, headache, or flu-like symptoms after their injections, compared to 6.2 percent who got placebo injections.

But the chance of having any of those symptoms dropped to 6.6 percent with the second yearly injection, and 2.8 percent with the third.

A once-a-year treatment for osteoporosis is preferred by doctors because patients do not always take other medication regularly.

A similar effect has been seen with Merck's equivalent Fosamax which is the same class of drug but is taken in an oral form.

Fosamax, is used by an estimated 1.8 million American women but a study by Dr. Steven Cummings of http://www.cpmc.org/California Pacific Medical Center Research Institute has found a 50 percent higher risk of the serious heart rhythm in women who took the daily pill.

The study involving 6,459 women, half of whom took Fosamax while the other didn't, found there appeared to be 50 percent more risk of the serious heart rhythm in women taking the pill than among those who didn't take it; about half of the 6,459 women took Fosamax, and 47 developed atrial fibrillation, compared to just 31 cases among the other women.

Experts say this is a cause for concern and must be given serious consideration, while the researchers say it is unclear if the side-effects are a random event or the true effects of the drug or if the risk applies to other drugs in the class known as biphosphonates.

Osteoporosis affects millions of women worldwide, with more than 50 million women in the United States, Europe and Japan suffering from the ailment.

The two reports are published in the current issue of The New England Journal of Medicine


Abstract: Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis

Dennis M. Black, Ph.D., Pierre D. Delmas, M.D., Ph.D., Richard Eastell, M.D., Ian R. Reid, M.D., Steven Boonen, M.D., Ph.D., Jane A. Cauley, Dr.P.H., Felicia Cosman, M.D., Péter Lakatos, M.D., Ph.D., Ping Chung Leung, M.D., Zulema Man, M.D., Carlos Mautalen, M.D., Peter Mesenbrink, Ph.D., Huilin Hu, Ph.D., John Caminis, M.D., Karen Tong, B.S., Theresa Rosario-Jansen, Ph.D., Joel Krasnow, M.D., Trisha F. Hue, M.P.H., Deborah Sellmeyer, M.D., Erik Fink Eriksen, M.D., D.M.Sc., Steven R. Cummings, M.D., for the HORIZON Pivotal Fracture Trial


A single infusion of intravenous zoledronic acid decreases bone turnover and improves bone density at 12 months in postmenopausal women with osteoporosis. We assessed the effects of annual infusions of zoledronic acid on fracture risk during a 3-year period.

In this double-blind, placebo-controlled trial, 3889 patients (mean age, 73 years) were randomly assigned to receive a single 15-minute infusion of zoledronic acid (5 mg) and 3876 were assigned to receive placebo at baseline, at 12 months, and at 24 months; the patients were followed until 36 months. Primary end points were new vertebral fracture (in patients not taking concomitant osteoporosis medications) and hip fracture (in all patients). Secondary end points included bone mineral density, bone turnover markers, and safety outcomes.

Treatment with zoledronic acid reduced the risk of morphometric vertebral fracture by 70% during a 3-year period, as compared with placebo (3.3% in the zoledronic-acid group vs. 10.9% in the placebo group; relative risk, 0.30; 95% confidence interval [CI], 0.24 to 0.38) and reduced the risk of hip fracture by 41% (1.4% in the zoledronic-acid group vs. 2.5% in the placebo group; hazard ratio, 0.59; 95% CI, 0.42 to 0.83). Nonvertebral fractures, clinical fractures, and clinical vertebral fractures were reduced by 25%, 33%, and 77%, respectively P<0.001>

Conclusions

A once-yearly infusion of zoledronic acid during a 3-year period significantly reduced the risk of vertebral, hip, and other fractures.