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Researchers report results of studies on atrial fibrillation management
Childhood obesity causes subtle changes in heart, arteries
Four Late-Breaking Clinical Trial results presented
Ablation techniques better than antiarrhythmic drug therapy in treating AF patients
Novel agent for hypertension in development
Researchers report results of studies on atrial fibrillation management
Ventricular rate control is more effective in atrial fibrillation (AF) management and valsartan does not reduce AF recurrence, researchers said Tuesday in oral abstract presentations on therapy for AF. Ensuring a stable sinus rhythm was once thought to boost survival in AF and congestive heart failure (CHF). But in a trial involving 1,376 AF and CHF patients, researchers found that AF does not predict mortality when symptom severity and mitral regurgitation have been established.
The findings suggest that rate control could be applied to all patients, Mario Talajic, M.D, said in his presentation, “Maintenance of Sinus Rhythm is Not Associated with Improved Survival in Patients with Atrial Fibrillation and Heart Failure.”
Eighty-two percent of study patients were male; average age was 67. Almost half had coronary disease and nearly a third had New York Heart Association stage 3-4 CHF. Average EF was 27 (+/- 6 percent).
After a mean patient follow-up of 37 months, 445 patients died — 357 from cardiovascular disease. The median proportion of time spent in AF was 39 percent for the entire cohort. In these patients, AF did not predict mortality.
“This doesn’t preclude ‘maintenance’ of sinus rhythm,” said Talajic, J.C. Edwards professor of medicine at the University of Montreal. However, “it appears that rate control is as good as sinus-rhythm control.”
The findings also suggest beta blockers are an appropriate first-line treatment in this patient group, he said. Valsartan was not associated with any significant reduction in AF recurrence (51.4 percent vs. 52.1 percent placebo) in the largest trial to date, GISSI-AF, on renin angiotensin aldosterone system blockers in patients with AF. The study followed 1,442 patients (median age 68, about two-thirds men) treated at 114 Italian cardiology centers. Valsartan was used in conjunction with ACE inhibitors and amiodarone, and researchers observed no AF rate reduction at one year among patients at risk for recurrence.
AF occurred in 371 of the 722 patients in the valsartan group versus 375 of the 720 patients in the placebo group, Aldo Maggioni, M.D., said in his presentation, “The Role of Valsartan in the Prevention of Atrial Fibrillation Recurrence: The GISSI-AF Results.”
The number of patients who had more than one AF episode was 194 (26.9 percent) in the valsartan group and 201 (27.9 percent) in the placebo group, he said. The regimen was well tolerated and only two patients in the valsartan group had serious adverse effects (one with hypotension and one with renal dysfunction plus hyperkalemia).
The GISSI-AF investigation appears to counter previous studies and long-standing clinical assumptions about the drug’s probable benefits for AF and associated heart disease. In fact, such findings suggest the pathology of atrial fibrillation might need re-examination, said Maggioni, chief cardiologist at ANMCO Research Center in Firenze, Italy.
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Childhood obesity causes subtle changes in heart, arteries
Recent studies in children demonstrate that childhood obesity and overweight are not innocuous and that overweight children are beginning to show subtle but important changes in the heart and arteries, researchers noted during a Tuesday news conference.
“We already see trends in risk factors among children that are cause for concern; higher blood pressure across the childhood population, changes in waist circumference and changes in triglycerides are all going in the wrong direction,” said Stephen Daniels, M.D., Ph.D., chair, Department of Pediatrics, University of Colorado, Denver. He moderated a Tuesday news conference highlighting three new studies that associate obesity in childhood with risk of heart disease in adults.
LA size increases with BMI
Researchers from the University of Sydney, Australia, report that left atrial size increases with body mass index (BMI) in children. In adults, this raises the risk of acute MI, stroke and AF.
In a community-based study, 991 children attending a cardiology clinic but with no heart abnormalities were classified by BMI as “healthy weight,” “overweight” or “obese.”
Julian G. Ayer, M.D., a pediatric cardiologist, said the children’s left atrial diameter was determined by ultrasound and indexed to height to account for the effect of statural growth.
The 777 children with healthy weight had a mean LA diameter of 19.75 mm/m; 136 overweight children had a mean LA diameter of 20.54 mm/m; and 78 obese children had a mean diameter of 21.89 mm/m.
“These small differences may be an important public health issue for future cardiovascular disease, given the scope of the disease and the persistence of the problem,” Ayer said.
‘Vascular age’ of children increases with obesity
Obesity and dyslipidemia in children are associated with an increased “vascular age,” according to researchers from the University of Missouri-Kansas City School of Medicine.
Geetha Raghuveer, M.D., associate professor, Department of Cardiology, said percentile tables are available that plot carotid intima media thickness for 45-year-olds in the population, categorized by race and gender.
There are no tables for children so Raghuveer and colleagues arbitrarily designated advanced childhood vascular age as having a thickness above the first quartile for a child matched to a 45-year-old in the table by sex and race.
“Vascular age is advanced in children with risk factors such as obesity and dyslipidemia,” reported Raghuveer. She said carotid artery ultrasound and estimation of vascular age may help stratify children with risk factors who may be at greater risk and who may need intensive management including pharmacological management of risk factors.
Diastolic untwisting velocity influenced by BMI
Another Australian group reported here that increased BMI in children has an “adverse” influence on left ventricular (LV) untwisting velocity, a measurement of the wringing motion made by the heart in transition between LV relaxation and suction. Walter Abhayaratna, M.D., senior lecturer, Australian National University, said LV untwisting velocity is a sensitive marker of LV function.
In this study, twist mechanics were quantitated in 150 children with a mean BMI of 18.2 by two-dimensional speckle-tracking imaging of the LV base and apex in short axis.
Abhayaratna reported that increasing BMI correlated with a decreasing twist velocity, which could ultimately lead to deterioration in LV mechanics and function.
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Four Late-Breaking Clinical Trial results presented
Exercise training is safe in people with stable heart failure (HF) and is associated with better clinical outcomes even in patients already receiving optimal medical care, suggest results of the randomized, phase III Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) trial.
This U.S.-government-funded study enrolled 2,331 heart failure patients at 82 sites in the United States, Canada and Europe. The patients, average age 59, were randomized to an exercise training program aimed at increasing workout intensity and duration or to usual care, in which they were encouraged to exercise without any specific program.
The researchers found no excess risk for heart attack, arrhythmia, angina or fractures in the exercise training group.
After 2.5 years, there was a nonsignificant trend toward improved outcomes with exercise vs. usual care in the primary endpoint – a composite of all-cause mortality and all-cause hospitalization. However, after adjusting for differences in more than two dozen important prognostic characteristics, the exercise training group had a significant 11 percent reduction (p-value = 0.03) in the same endpoint and a 15 percent (p-value = 0.03) reduction in the secondary endpoint of cardiovascular mortality and heart failure hospitalization compared to the usual care group.These findings “support a structured exercise training program for patients with reduced LV [left ventricular] function and HF symptoms in addition to evidence-based therapy,” said Christopher M. O’Connor, M.D., co-principal investigator and director of the Heart Center and professor of medicine at Duke University Medical Center in Durham, N.C.
The exercise group received a multi-stage, guided program that began with 36 supervised training sessions with a goal of 40 minutes of exercise three times a week. At the 18th session, patients were given a treadmill or exercise bicycle for home use, taught how to monitor their heart rate during exercise and encouraged to complete five weekly exercise sessions of similar intensity and duration.
The 36 supervised exercise sessions in this study were modeled on the cardiac rehabilitation sessions provided to heart attack survivors, which are usually covered by insurance. Patients in the usual care group received instructions based on the American College of Cardiology/American Heart Association recommendation to perform 30 minutes of moderate-intensity exercise most days of the week.
Heart failure patients with normal left ventricular ejection fraction don’t benefit from angiotensin II receptor blocker
For patients with preserved ejection fraction heart failure, the angiotensin II receptor blocker irbesartan is no better than usual care after 4.5 years, according to results of the Irbesartan in Heart Failure with Preserved Systolic Function (I-PRESERVE) study.
In the world’s largest randomized, placebo-controlled trial of an angiotensin II receptor blocker (ARB), 4,128 participants at least 60 years of age with current heart failure symptoms and a left ventricular ejection fraction of at least 45 percent were randomized to receive the ARB irbesartan titrated up to a dose of 300 mg per day or placebo.
The study found no differences in the primary outcome – a composite of death or hospitalization for heart failure, myocardial infarction, unstable angina, stroke or arrhythmia – or in the secondary endpoints of cardiovascular mortality or death/hospitalization due to heart failure.
“Unfortunately, for this large group of patients, there is no specific evidence-based therapy,” said Barry M. Massie, M.D., co-principal investigator of the study, professor of medicine at the University of California, San Francisco, and chief of the cardiology division at the San Francisco Veterans Administration Medical Center. He added that a better understanding of molecular mechanisms is needed to develop effective therapies for this syndrome, which affects approximately half of heart failure patients.
Interferon reduces, eliminates viral infections in heart failure patients with chronic viral cardiomyopathy
In heart failure patients with chronic viral cardiomyopathy, interferon-beta treatment appears to safely reduce or eliminate viral load and improves cardiac function and quality of life, suggest results of the randomized, double-blind, placebo-controlled phase II Betaferon In Chronic Viral Cardiomyopathy (BICC) Trial.
In this largest study of its kind in inflammatory/viral heart disease, 143 patients with chronic heart failure and biopsy-proven adenovirus, enterovirus, and/or parvovirus received interferon beta-1b (IFNb-1b) or placebo every other day for 24 weeks.
After a 12-week follow-up period, interferon-treated patients were significantly more likely than placebo-treated patients to attain a reduction or elimination of any of the three viruses. Analyses of responses against individual infections were not statistically significant due to the small number of patients.
In a stratified analysis, patients who received IFNb-1b were three times as likely as placebo-treated patients to have improved symptoms 12 weeks after treatment ended. In the overall analysis, 40.2 percent of interferon-treated patients improved at least one New York Heart Association (NYHA) functional class from baseline to 12 weeks after treatment compared to 19.0 percent of those in the placebo group.
Interferon-treated patients were more than twice as likely as the placebo group to improve at least one class from baseline to 24 weeks after treatment (p-value = .073).
Quality-of-life improvements from baseline to 24 weeks after treatment were also significantly greater with interferon vs. placebo (p-value = .032), as measured by the Minnesota Living with Heart Failure Questionnaire.
“These results from our randomized trial provide the first evidence that interferon beta-1b (IFNb-1b) treatment eliminates cardiotropic viruses and improves the clinical outcomes of patients with chronic enteroviral and adenoviral heart disease,” said Heinz Peter Schultheiss, M.D., lead author of the study and professor of medicine in the Department of Cardiology and Pneumology at Charite – University Medicine of Berlin, Campus Benjamin Franklin, in Berlin, Germany.
New blood test better identifies heart failure patients in ER
A new blood test identifies the sickest heart failure patients better than tests now used in emergency departments, according to results of the Biomarkers in the Assessment of Congestive Heart Failure multinational trial (BACH).
In the study, researchers followed 1,641 patients having difficulty breathing upon arrival at the emergency department. They were from 15 investigational centers around the globe, including eight from the United States.
BACH is the first randomized comparison of two tests considered the gold standard for evaluating possible heart failure patients in the emergency setting versus the new test approved for use in the European Union as of Oct. 1.
The MR-proADM (Mid-Regional pro-Adrenomedullin) test accurately predicted 90-day mortality 73.5 percent of the time, making it significantly superior to both the B-Natriuretic peptide (BNP) test (60.8 percent) and the NT-proBNP test (63.6 percent), which measures a biological fragment associated with BNP.
Patients with the highest levels of MR-proADM were over three times more likely than other patients to die within 3 months.
MR-proADM indirectly measures a hormone called adrenomedullin, which regulates the blood vessels’ dilation and plays a key role in many cardiac and infectious diseases. The test indicates dysfunction in the lining of the blood vessels.
This technology could “help identify patients who should ‘move to the front of the line’ of medical care,” noted Stefan D. Anker, M.D., Ph.D., co-principal investigator of the study and professor of cardiology and cachexia research at Campus Virchow-Klinkum (Virchow Hospital) of the Charité Medical School, Berlin, Germany. However, the practical application of this test for the treatment and management of patients is not yet clear, and good clinical judgment is still paramount.
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Ablation techniques better than antiarrhythmic drug therapy in treating AF patients
The ThermoCool ablation catheter system is superior to continued
antiarrhythmic drug (AAD) therapy in atrial fibrillation patients refractory to at least one AAD, according to final outcomes of The ThermoCool AF Trial presented Tuesday in the session on “New Trials in Electrophysiology and Pacing.”David J. Wilber, M.D., director of the Cardiovascular Institute in the Division of Cardiology at Loyola University Medical Center in Maywood, Ill., said patients who underwent ablation experienced a dramatic reduction in recurrence over a year compared to patients who did not.
In the prospective, multicenter randomized trial, scientists tested the effectiveness of the Navistar ThermoCool Radiofrequency Ablation Catheter compared with antiarrhythmic drug therapy in 167 patients presenting with paroxysmal atrial fibrillation. Study participants had a mean age of 56 years and 34 percent were female.
The median number of symptomatic AF episodes in the six months prior to randomization was 28 for the 106 patients randomly assigned to ablation, and 24 for the 61 AAD control patients. All study participants experienced failure with at least one AAD or AV nodal blocking agent. Patients with AF episodes greater than 30 days in duration, under age 18, or with an LVEF less than 40 percent, were excluded from the study.
AAD control patients received a class I or III AAD not previously administered. All patients were followed for one year. With 159 patients completing the trial, 75 percent of the 103 ablation patients had freedom from documented occurrence of symptomatic AF after one year, compared with 21 percent of the 56 AAD patients, Wilber said.
Microwave ablation effective in restoring sinus rhythm
Microwave ablation in left and right atria in conjunction with mitral valve surgery is safe and effectively restores sinus rhythm (SR) in patients with long-lasting permanent AF as compared to mitral valve surgery alone, a scientist told attendees in the second presentation of this session.
Anders Jonsson, M.D., a consultant at University Hospital of Linköping in Sweden, presented his findings on “Microwave Ablation in Mitral valve surgery for Atrial fibrillation (MAMA).”
In the randomized, double-blind study, 64 patients with permanent AF were randomly assigned to mitral valve surgery and left and right atrial microwave ablation (31 patients) or mitral valve surgery alone (33 patients). The primary endpoint was the presence of SR at six and 12 months. Secondary endpoints were the occurrence of predefined serious adverse events and the use of antiarrhythmic drugs (class I or III).
The mean duration of permanent AF before surgery was 53 months in the ablation group compared to 34 months in the control group, while the median durations were 12 months and 11 months respectively.
At 12 months, SR was restored in 81 percent in the ablation group vs. 36 percent in the control group. Corresponding figures at six months were 78 percent vs. 41 percent, respectively.
There was no significant difference between the groups in the in-hospital period, he said.
“Sixteen percent of patients randomized to ablation were on antiarrhythmic drugs compared to 6 percent in the control group after one year,” Jonsson said.
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Novel agent for hypertension in development
A new class of drug can effectively manage hypertension, according to a study reported Tuesday.
PS433540 is the first compound in a novel class of agents called Dual Acting Receptor Antagonists (DARA) that selectively blocks angiotensin (AT1) and endothelin (ETA) receptors. The drug is in clinical trials. “This is the first stage in the development of a drug that may be useful in managing hypertension, especially in patients with difficult-to-control systolic hypertension,” said Joel M. Neutel, M.D., who discussed the results of the study in his presentation, “Hypertension: Emerging Treatment Strategies.”
In a prospective, randomized, double-blind, placebo-controlled study, 234 men and women with a mean age of 56 years entered a three- to four-week single-blind placebo run-in period.
Qualifying stage I or stage II hypertensive patients were randomized in a 1:1:1 ratio to either PS433540 200 mg, 500 mg or matching placebo for four weeks. Researchers performed ambulatory BP monitoring (ABPM) at the start of the study and again after the treatment period.
In the study, PS433540 lowered 24-hour systolic blood pressure and diastolic blood pressure and mean office SBP and DBP more than placebo did. The study also found that PS433540 was well tolerated with two reported serious adverse events in the placebo group and placebo lead-in period. Three patients (all from the placebo group) were discontinued from the study for adverse events. There were no significant laboratory abnormalities and other adverse events among these two treatment and placebo groups.
“We demonstrated highly significant blood pressure reduction with this compound — really a lot greater than we see with typical monotherapies,” said Neutel, associate professor of medicine at the University of California, Irvine, and director of research at the Orange County Research Center, in Tustin, Calif. “It also had a safety profile that was very good.”
Neutel said PS433540 “may prove to be a very important addition to our armamentarium for the management of hypertension.”
“I think it is important that we realize management of hypertension here in the United States hasn’t been quite as successful as we would have hoped,” he said. “There is a lot of room for improvement. This new drug will provide us with another alternative in normalizing systolic blood pressure.”
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