Late-Breaking Clinical Trials Presented at Heart Rhythm 2011

Session Chairs: Karl-Heinz Kuck, MD, FHRS. Asklepios Klinik St. Georg, Hamburg, Germany Laurence M. Epstein, MD. Brigham and Women’s Hospital, Boston, MA Abstract Commentator: Michael R. Gold, MD, PHD, FHRS. Medical University of South Carolina, Charleston, SC

Five late-breaking clinical trial abstracts unveiled new research results from around the world. New findings included survival following shock therapy, symptomatic and asymptomatic atrial fibrillation following radiofrequency ablation, newly developed risk factors for Brugada syndrome, a novel ablation system for atrial fibrillation, and data that could extend the indications for CRT. Read a summary of the science presented at this session (see below) or Download Late-Breaking Clinical Trials Abstracts Brochure (PDF, 172K).

Survival After Shock Therapy in ICD and CRT-D Recipients According to Rhythm Shocked: The ALTITUDE Study Group

The initial study presented new results from the Altitude Study Group showing that in patients with ICD and CRT-D, it is the underling arrhythmia that kills, not inappropriate shocks. “We know that patients who receive inappropriate shocks are at higher risk of death,” said lead author Brian Powell, MD, Mayo Clinic, Rochester, MN. “Patients who receive appropriate shocks are also at higher risk. The question has been whether the risk lies with the shock or the underlying arrhythmia.”

Researchers analyzed the first shock rhythm episodes in 3,814 patients enrolled in the Latitude remote monitoring system. Within each rhythm category, patients who received a shock were matched to patients who did not receive a shock. Patients were matched by age at implantation, implant year, gender, and type of device implanted. All patients were followed for a mean of 25 months.

The most common type of rhythm shocked was sustained monomorphic ventricular tachycardia (SMVT, 36%). VF/polymorphic ventricular tachycardia (PMVT) accounted for 16% of shocks and combined SMVT/ PMVT accounted for 7%. Shocks were administered for atrial fibrillation/ flutter (AF) in 18% of patients, sinus tachycardia/SVT in 17%, noise/artifact/ oversensing 5%, and non-sustained ventricular tachycardia (NSVT) 1%.

There were distinct differences in outcome based on the type of underlying rhythm, Dr. Powell reported. Compared to patients who received no shocks, patients who received a shock for SMVT, VF/PMVT, SMVT and PMVT, NSVT, and AF had a lower survival rate. Patients who received shocks for sinus tachycaradia/ DVT and noise/artifact/oversensing had a similar survival rate compared to patients who received no shocks.

“This is the first study large enough to do subgroup analysis,” Dr. Powell said. “The adverse prognosis of some of these groups may be correlated to the underlying arrhythmia, not to the shock itself.”

Discerning The Incidence Of Symptomatic And Asymptomatic Episodes Of Atrial Fibrillation Pre- And Post-Radiofrequency Ablation (DISCERN AF): A Prospective, Multicenter Study

New data from Canada suggest that radiofrequency ablation for atrial fibrillation is less effective than generally believed. A total of 50 patients in eight centers were fitted with implanted loop recorders (ILR) three months before a planned radiofrequency ablation for AF and followed for at least 18 months after ablation.

In addition to the ILR data, patients agreed to complete daily diaries recording any symptoms of AF. Patient follow-up visits were scheduled every three months to enable physicians to download ILR data and collect diaries. “Patients were blinded to ILR data so as not to influence their own diary recording,” said lead author Atul Verman, MD, FRCPC, of Southlake Regional Health Centre, Newmarket, Ontario, Canada. “However, physicians were allowed to use the data for clinical decision-making.”

ILR recorded 2,355 episodes of possible arrhythmia during the study period, but patients recorded more than 5,000 diary entries of perceived symptoms. Fewer than half of diary entries correlated with recorded arrhythmias, Dr. Verman reported.

Within ILR-documented arrhythmias, 59.9% were asymptomatic before ablation and 78.7% were asymptomatic post ablation. Based on the ratio of symptomatic and asymptomatic arrhythmias pre and post ablation, researchers concluded that about 12% of patients have only asymptomatic arrhythmias.

Novel Scheme For Risk Stratification And Therapy Selection In Brugada Syndrome: Results Of The PRELUDE Study

Italian researchers proposed novel risk stratification factors for Brugada syndrome. Current understanding clearly distinguishes low risk patients, individuals with negative baseline ECG and no syncope. High risk patients are also easily defined, individuals with both spontaneous type 1 ECG and syncope. But about 41% of the population is indeterminate, with spontaneous type 1 ECG but no syncope.

“When there is no previous cardiac arrest, the indications for ICD are ill-defined,” said lead author Carlo Napolitano, MD, Ph.D., IRCCS Fondzaione Salvatore Maugeri, Pavia, Italy and New York University School of Medicine. “There is conflicting data in the literature.” Researchers enrolled 308 patients with a type 1 ECG in 41 electrophysiology centers and followed them for an average of 34 months in the PRELUDE registry. Of the group, 14 patients had an arrhythmic event, with 13 receiving ICD and one being resuscitated. Only five of the 13 were inducible, suggesting the VT/VF inducibility during electrical stimulation is not predictive.

Multivariate analysis confirmed that type 1 ECG with syncope is predictive of cardiac events. Researchers also found that a ventricular refractory period of less than 200 ms conferred a hazard ratio of 4.2 for arrhythmic events and QRS fragmentation carried a hazard ratio of 4.9.

“These two markers could be effective to improve predictability of patients who need an ICD to save their lives,” Dr. Napolitano said.

Conventional Ablation For Atrial Fibrillation With Or Without Focal Impulse And Rotor Modulation (the CONFIRM Trial)

Researchers in the United States have developed a new computational mapping system that identifies a novel target for ablation in atrial fibrillation. The technology has been commercialized and is currently being used in trials, reported Sanjiv Narayan, MD, Ph.D., FHRS, University of California and VA Medical Center, San Diego. The CONFIRM trial suggests that the new ablation target can greatly improve AF-free survival. “Animal studies have shown that atrial fibrillation is driven by localized electrical rotors or focal drivers,” Dr. Narayan explained. “This new technology allows rotors to be visualized in humans and targeted for local ablation.”

The CONFIRM trial compared conventional ablation and focal impulse and rotor modulation (FIRM) guided ablation followed by conventional ablation. Rotors, or focal drivers of AF, were seen in 97% of patients. FIRM either terminated acute AF or slowed it substantially in 88% of patients, Dr. Narayan reported, typically within minutes. Two years after treatment, 84.3% of FIRM patients were free of AF compared to 50.5% of conventional ablation patients (p=0.004). “This trial confirms a new paradigm for the treatment of AF,” he concluded. “The fundamental approach used to treat AF needs to be reevaluated.”

Cardiac Resynchronization Therapy In Patients Undergoing AV Junction Ablation For Permanent Atrial Fibrillation: A Randomized Trial

The final abstract presented data suggesting that cardiac resynchronization therapy is more widely useful than believed. Current guidelines recommend CRT only for patients an ejection fraction of 35% or less, New York Heart Association grade III or higher, and QRS of 120 ms or greater. A prospective trial with 186 patients across 19 centers in Italy, Spain, and Greece compared CRT with RV apical pacing in patients who had successful AV junction ablation and CRT implantation. The two patient groups were well matched, said lead author Michele Brignole, MD, Ospedali del Tigullio, Lavagna, Italy. About 25% of patients met CRT guidelines and 75% did not meet guidelines.

After a median of 20 months of follow up, the CRT group had lower mortality from heart failure (hazard ratio 0.37), less worsening of heart failure (HR 0.27), and fewer hospitalizations for heart failure (HR 0.20). Overall mortality was similar in the two groups.

“CRT showed a consistent benefit both in patients who met guidelines and those who did not meet guidelines,” Dr. Brignole said. “If these experimental data are confirmed, they support the extension of CRT to a larger population of heart failure patients.”