A CDU

A late-breaking clinical trials session held on 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 Heart Rhythm Society (HRS; Washington) members.

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 epi-sodes 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 Veterans Affairs 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.”

Also at the Heart Rhythm 2005 meeting:

Biophan Technologies (West Henrietta, New York) reported the results of its recent scientific studies that it said help explain what it termed “the widely varying reports on the MRI safety of implanted medical devices such as pacemakers, defibrillators, neurostimulators and other devices.”

CEO Michael Weiner noted that Biophan was founded five years ago to solve the problems of pacemaker heating, “which have precluded millions of pacemaker patients from undergoing MRI, including for critical needs such as preparation for cancer treatment.”

He said that over the last several years, the worldwide scientific community has been divided over whether there is or is not a real safety problem. “Biophan has identified a major inconsistency in the method of testing used by the industry to assess pacemaker heating during MRI, which helps to account for the wide variation of results observed in lead heating,” Weiner said.

The company’s study results indicate that some of the unintentional variance seen in testing is “due to limitations in the methods of testing and the very complicated physics associated with MRI.”

Biophan said its scientists have characterized a wide array of variables related to devices, patients, MRI scan parameters and temperature measurement techniques that can affect lead heating. “For example, testing has determined that maximum heating occurs slightly into the tissue and not at the tip of the electrode where heating is typically measured, and that different types of approved temperature measurement probes can significantly understate actual heating due to their design.”

When more accurate and more precise temperature measurement protocols are used, the company said “physiologically significant” temperature increases well in excess of currently allowable limits are observed.

The company’s data released include studies of the temperature generated by a device and its dependence upon the location of the patient and device within the MRI scanner. Moving the pacemaker lead as little as 3 inches to 4.3 inches within the scanner can result in an increase in temperature at the tip of the lead of more than 10 degrees C, enough, Biophan said, to cause significant tissue damage. “This could occur clinically as a result of shifting a patient off center in the MRI bore to better image other tissues,” it added.

Additional data show the effect of two different temperature probe designs, both of which are acceptable according to the current ASTM testing standard. “This information is significant,” Biophan said, “since it also affects the way MRI-induced heating is measured in other devices, such as the safety testing of surgical tools used in the emerging field of MRI-guided interventional medicine.”

GE Healthcare (Waukesha, Wisconsin) reported that it to date has the largest global installed base of 64-detector volume computed tomography (CT) systems. The company said that installations of its next-generation system, the LightSpeed VCT, in 2005 would number in the hundreds.

In a single rotation, the LightSpeed VCT creates 64 submillimeter images, totaling 40 mm of anatomical coverage, which are combined to form a 3-D view of the patient’s anatomy for the physician to analyze. “These highly detailed images can provide critical information to a physician analyzing less-invasive treatment options,” GE said.

Laura King, global vice president, interventional, cardiology and surgery at GE Healthcare, said the speed and accuracy of the LightSpeed VCT “has put GE at the forefront of diagnostic cardiovascular care.”

She said that installations of LightSpeed VCT in general hospitals, cardiac centers, physician offices, children’s hospitals and other facilities around the world “are revolutionizing imaging and transforming the delivery of healthcare.”

GE Healthcare said its AW Card EP software option, available to cardiologists using the LightSpeed VCT, allows for greater precision in pre-planning for electrophysiology procedures (EP), even in the most complex anatomy. The company said the AW Card EP software provides cardiologists “a tool for quick and easy 3-D processing of CT images used in EP ablation planning and biventricular lead placement procedures.”

The 3-D images obtained with the LightSpeed VCT system also can be processed with the Carto XP EP Navigation System manufactured by Biosense Webster (Diamond Bar, California), a Johnson & Johnson (New Brunswick, New Jersey) company, resulting, GE said, in “more accurate anatomical registration with 3-D map for greater confidence in navigation.”

LightSpeed VCT, which GE introduced last year as the world’s first volume CT system, also enables cardiologists to capture images of the heart in just five heartbeats – something no other CT system can offer, according to the company.

“Cardiologists and [other] customers told us that imaging the heart in five or fewer beats was an urgent clinical need,” said King. “The LightSpeed VCT is the only technology capable of five-beat cardiac imaging.”

Impulse Dynamics (USA) (Orangeburg, New York) reported data highlights from two poster presentations and one oral presentation and also hosted a satellite symposium to discuss device-based treatment options for those who suffer from chronic heart failure, with special attention on patients with a normal QRS duration.

One poster presentation, presented by lead author Hani Sabbah of Henry Ford Health System (Detroit), was titled “Cardiac Contractility Modulation with Non-Excitatory Electrical Signals Normalizes Expression of the Transcriptional Factor GATA-4 in Dogs with Chronic Heart Failure.” Sabbah also made an oral presentation on “Chronic Therapy With Non-Excitatory Cardiac Contractility Modulation Electric Signals Improves Left Ventricular Function, Reduces Myocardial Oxygen Consumption and Increases Myocardial Mechanical Efficiency.”

Another poster presentation, “Effects of Cardiac Contractility Modulation Signal Delivery on Left Ventricular Contractility,” was conducted by Thomas Lawo, of Bergmannsheil Klinikum Bochum in Germany.

The satellite symposium, titled “Device-Based Treatments for CHF: Options for patients with narrow QRS,” was moderated by William Abraham, director of the division of cardiovascular medicine at Ohio State University (Columbus).

Impulse Dynamics’ Optimizer technology stems from a scientific discovery regarding the electrical control of tissue function. The company’s research and development efforts are focused on refining the principle and practice of modifying tissue properties and function through the predictable and reproducible delivery of electrical signals.

Impulse Dynamics (USA) is a wholly owned subsidiary of Impulse Dynamics NV, located in the Netherlands Antilles.

ELA Medical (Arvada, Colorado), a business of the Sorin Group (Milano, Italy) that develops cardiac rhythm management and diagnostic systems, bannered FDA clearance for its AAIsafeR 2 pacing mode, a second-generation technology designed to prevent unnecessary ventricular pacing. ELA terms the AAIsafeR 2 “the first therapeutic pacing alternative available in the U.S.” and said that its Symphony pacemakers with AAIsafeR 2 limit unnecessary ventricular stimulation to 0.1% in patients while they are not in heart block, meaning an electrical disturbance that blocks the heart’s in-sync pumping.

“Conventional pacemakers unnecessarily pace these same individuals 50% to 80% of the time,” ELA said, adding that recent studies indicate that unnecessary right ventricular pacing increases the risk of developing heart failure and AF. The company said the new pacing mode potentially could benefit more than 300,000 people in the U.S. who receive a dual-chamber pacemaker, or about 60% of the pacemaker population. “No other pacemaker can treat such a large patient population,” it said.

ELA’s first-generation AAIsafeR technology was launched in its Symphony pacing systems in Europe in September 2003, and the company received CE marking for its AAIsafeR 2 technology earlier this year.

Malcolm Bersohn, MD, PhD, electrophysiologist and professor of medicine at the University of California Los Angeles Medical Center, said, “AAIsafeR 2 will offer a dramatic reduction in ventricular pacing for a high percentage of patients” and comes “remarkably close” to achieving the goal of zero-percent unnecessary pacing.

The AAIsafeR 2 pacing mode already is incorporated in previously implanted Symphony pacemakers. A software change to the pacemaker programmer unlocks this feature in patients who already have these devices implanted.

ELA held a satellite symposium discussing the AAIsafeR pacing mode during the HRS meeting.

Siemens Medical Solutions (Erlangen, Germany/Malvern, Pennsylvania) highlighted the launch of enhancements to its Axiom Sensis hemodynamic and electrophysiological (EP) recording system. Customers already using the Axiom Sensis for EP, Siemens said, will automatically receive the software upgrades which feature several new applications, such as: vital signs logging, non-invasive blood pressure (NIBP) measurements, arrhythmia detection and recording, examination archiving, and Axiom Sensis data transfer between two systems.

Siemens also featured the AcuNav 8F catheter, enabling improved access in all patients, particularly smaller patients and for left heart applications in EP and interventional cardiology. The new catheter is sized at 8 Fr and is 33% smaller in the cross sectional area than the existing Acuson AcuNav 10F catheter.

According to clinical evaluators, Siemens said, “the smaller size coupled with the same performance as the AcuNav 10F catheter is a significant improvement and allows access to a wider range of patients.”

Additionally, the company is showcasing the Acuson CV70 cardiovascular ultrasound system with Doppler sensitivity, color flow sensitivity and spatial resolution. Featuring foursight transesophageal (TEE) view for integrated 3-D TEE imaging, and P9-4 transducer for pediatric cardiac imaging, the system enables easier access to 3-D/4-D images through simple acquisition, review, manipulation and display capabilities of 3-D datasets using the V5Ms TEE transducer.