A Medical Device Daily

A late-breaking clinical trials session held on Saturday, the final day of this year’s Heart Rhythm 2005 meeting in New Orleans, focused in large part on studies involving implantable cardioverter-defibrillators (ICDs), a hot topic for those attending the annual meeting of the Heart Rhythm Society (HRS; Washington).

Medtronic (Minneapolis) said that findings from the EMPIRIC clinical trial showed that in people with an ICD, physician use of a prescribed set of sophisticated ICD heart rhythm detection and therapy parameters can help reduce the proportion of fast heart rhythm episodes shocked with high-energy electrical therapy.

EMPIRIC compared the proportion of fast heart rhythm episodes shocked using a strategically chosen (empiric) collection of parameters intended to leverage Medtronic device features, or a patient-by-patient, physician-tailored programming approach.

The study demonstrated that an empiric set of sophisticated shock-reduction features is equally effective as customized physician programming for minimizing patient shocks.

The company said the study is the first ICD trial with a primary endpoint focused on the proportion of shocks for both true ventricular tachycardia (VT)/ventricular fibrillation (VF) and true supraventricular tachycardia (SVT) episodes.

Medtronic said the dual-chamber ICD used in the study – the Marquis DR– includes advanced features designed to reduce shocks by terminating VT/VF heart rhythm episodes with painless pacing therapy (anti-tachycardia pacing or ATP) and by accurately detecting rhythm abnormalities like SVT that do not require shock therapy.

It said the study is one element of the company’s clinical strategy targeting the reduction of ICD shocks to improve care of ICD patients.

“Because shocks are major causes of anxiousness for many ICD patients, reducing shocks while delivering effective treatment is critical to patient acceptance of ICD therapy,” said Bruce Wilkoff, director of cardiac pacing and tachyarrythmia devices at the Cleveland Clinic Foundation and EMPIRIC primary investigator.

“I expect these results will surprise many physicians, but it’s important we consider this study as we implant future ICDs,” Wilkoff said. “Device manufacturers have developed highly sophisticated technologies that can minimize ICD shocks, and now we also have a proven, optimal programming approach to simplify therapy prescription and improve patient outcomes.”

Among the findings:

• In the empiric arm, 22.3% of true VT/VF episodes were shocked, resulting from the high efficacy of ATP, compared to 28.7% in the physician-tailored arm.
• In the empiric arm, 11.9% of all true SVT episodes were shocked, compared to 26.1% of all true SVT episodes shocked in the physician-tailored arm.
• The empiric strategy resulted in a significant reduction of unscheduled hospital visits.
• The two programming strategies were equivalent in time to first all-cause shock.
• There was no statistical difference in mortality, adverse events or ATP accelerations between the two treatment groups.

EMPIRIC investigators followed 900 patients at 54 centers in the U.S., Canada, UK, Austria, Saudi Arabia and Kuwait.

“This study gives us hope that some standardization in ICD settings may be feasible and not result in under-detection and therapy of heart rhythm disorders,” said Dwight Reynolds, MD, first vice president of the Heart Rhythm Society and program chair of the 2005 meeting.

In other studies reported on during the late-breaking trials session:

• A comparison of defibrillation efficacy of a standard transvenous ICD (TV-ICD) system with a totally subcutaneous ICD system (the S-ICD System) had the objective of comparing defibrillation thresholds for a S-ICD to that of a standard TV-ICD at surgery.

An ICD that does not require transvenous leads may alter adult and pediatric ICD practice patterns by eliminating lead complications and procedural barriers, but it remains unproven whether defibrillation is possible for the subcutaneous-only ICD at technically feasible energy levels and how those levels compare to TV-ICDs.

As anticipated, the findings showed that a S-ICD defibrillates at higher energy levels than a TV-ICD. However, the researchers involved, who are from the UK, New Zealand, Italy and the U.S., reported that energy levels “are much lower than typical external transthoracic requirements” and that “S-ICD energies are within the range of what is technically feasible for a device specifically geared for easy subcutaneous-only insertion.”

The subcutaneous ICD does not require fluoroscopy, has potential for very short insertion times, and did not require lead repositioning, as the TV-ICD does. The researchers said the S-ICD “may well serve as a viable alternative to TV-ICDs in many patients.”

Reynolds said, “This trial is an initial report of a revolutionary technology involving an ICD that can be implanted under the skin without the use of electrodes that are traditionally placed inside the heart.” He added that “while the verdict is not in on this, the heart rhythm management world is watching closely.”

• Another trial focused on whether patients with recently diagnosed non-ischemic cardiomyopathy benefit from ICD implantation.

The trial randomized 458 patients with non-ischemic dilated cardiomyopathy, left ventricle ejection fraction of less than 36% and an arrhythmia marker to receive standard medical therapy with or without an ICD. Patients were randomized regardless of the duration of cardiomyopathy as long as a reversible cause of LV dysfunction was not present. Patients were divided into recently and remotely diagnosed cardiomyopathy groups based on the time from diagnosis to randomization.

To categorize patients, cut-points of three and nine months were used. Patients with recently diagnosed cardiomyopathy who received an ICD had better survival than those treated with standard therapy at both cut-points. The difference in survival was significant at three months and was borderline at nine months.

The findings indicate that ICD therapy appears to benefit patients with recently diagnosed cardiomyopathy and should be considered in such patients as soon as they are identified.

• Steven Singh, MD, of VA Medical Center (Washington), noted that it remains controversial whether restoration of sinus rhythm in older patients with persistent atrial fibrillation (AF) improves quality of life and exercise capacity. The purpose of his analysis was to compare changes in quality of life and exercise performance in patients with persistent AF cardioverted to sinus rhythm to those in or reverting to AF.

The data were derived from the Sotalol Amiodarone Fibrillation Efficacy Trial (SAFE-T), in which 665 patients with persistent AF were randomly assigned double-blind to amiodarone, sotalol or placebo. Patients not achieving sinus rhythm by day 28 were electrically cardioverted.

Singh said there was a “marginal improvement” in AFSS general well-being score at one year. Exercise duration increased from baseline in SR patients vs. AF patients at eight weeks and at one year, while resting and peak heart rates were significantly decreased for patients in SR compared to those in AF.

In patients with persistent AF, restoration of sinus rhythm is associated with both short- and long-term improvements in generic quality of life, disease-specific quality of life measures, exercise performance and heart rate.

Singh said these observations “may have a major impact on the controversy regarding the rhythm or rate control approach to management of patients with AF.”

Reynolds added, “This study indicates what many of us have observed anecdotally, that most patients who have normal rhythm tend to feel better than those who are in atrial fibrillation.”