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Key words: cardiac, ablation, arrhythmia
Radiofrequency (RF) catheter ablation is a commonly used procedure for the treatment of cardiac arrhythmias. In this procedure, high frequency energy is delivered to the interior wall of the heart (myocardium) through a catheter electrode creating a thermal lesion. The lesion eliminates abnormal electrical pathways that are responsible for creating circuitous rhythms. One reason for its popularity is that, unlike other treatments for cardiac arrhythmias, cardiac ablation is a curative procedure that does not require the implantation of a device or the adherence to a specified drug regimen. From 1989 to 1993, the number of cardiac ablation procedures in the U.S. increased from 450 to 14,975. In 1994, it was estimated that a million people in the U.S. alone suffered from conditions that are treatable with catheter ablation. Until recently, success of this procedure has been limited to supraventricular tachyarrhythmias (SVT). These are circuitous patterns that exist around the atrioventricular node. Ablation of atrial fibrillation and ventricular tachycardia have become new areas of concern. In the case of atrial fibrillation, the primary issue is the prevalence of the pathologic disorder. In ventricular tachycardia, it is the pathology itself. Ventricular tachycardia is widely noted for being a precursor to the "Sudden Death Syndrome."
Although the RF ablation procedure has been widely used, only recently have there been approved devices, and there are still some unanswered questions regarding safety and efficacy. One of the efficacy concerns for cardiac ablation is the optimal temperature for lesion formation. The move towards temperature monitoring being an important aspect of ablation is heralded in the literature. Previous research has shown that steady state temperature is a better predictor of lesion size than power, current, voltage, or energy delivered. The range of useful temperatures has been established to be between 48°C and 100°C. Neither previous research, nor industry performance testing, however, has established the optimum temperature for cardiac ablation. Therefore, CDRH is concerned about the relationship between the steady state tip temperature and the duration of treatment on lesion size. This is necessary to enable the Center to perform scientific reviews to ensure that ablation devices are truly safe.
OST is currently studying the safety of excessive tissue damage during ablation. This is an especially important research area as the tools required to treat the newer clinical indications involve electrodes of higher power and larger size. A second safety aspect to be studied with this system is the nonuniform distribution of energy from an ablation electrode. To this end, OST scientists constructed a specialized system to simulate ablation in and near coronary vessels and around heart valves. They will use this system to determine the maximum proximity allowable before an intended ablation results in unwanted lesions.
An in vitro ablation electrode evaluation system has been designed, tested, and used to perform preliminary studies of RF ablation catheters. The ablation evaluation system consists of an RF signal source, power meters, an ablation catheter, and an array of several thermocouple sensors. Specially designed solid and liquid phantom materials were developed to simulate the electrical properties of blood and tissue. A large linear tank was constructed to allow for predictable blood flow velocity profiles around an ablation electrode. Stable vortices can be generated as well by shaping the surface of the solid phantom. This allows for the study of heat transfer processes with complex geometries. By performing specific absorption rate (SAR) measurements, OST engineers are able to generate a power distribution profile for the catheter. Preliminary studies have been conducted on a number of ablation electrodes. These studies show that the proximal edge of the catheter electrodes generates a local "hot spot." These "hot spots" have the potential to form coagulum and char tissue. Detailed evaluations of a variety of ablation catheters is planned by OST for FY 97. [PreME]
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Key words: neurology, cardiology, stimulator, defibrillator, Implantable cardiac defibrillator, biomaterials
OST performs safety studies on medical devices implanted in electrically excitable tissues of the nervous system and heart. This work applies to a large number of devices which include the classic cardiac defibrillators (both implanted and external), brain stimulators, spinal cord stimulators, and peripheral nerve stimulators. The classic devices use electrical stimulation to restore function or treat symptoms. Laboratory studies concentrate on the possible deleterious effects of these devices upon live cells and how these harmful effects can be avoided.
Over the past fiscal year, work continued to focus on the safety of the electroshock delivered by defibrillators. In addition, new studies were performed to investigate the fundamental issues of safety and effectiveness associated with a new class of electrical stimulation medical devices. These implanted devices claim to promote directed growth of nerve tissue for the restoration of neurological function or for better electrical connection between nerve tissues and implanted electrodes. This new area of study evaluates the survival and electrical excitability of nerve cells grown on tissue-engineered artificial biopolymers.
The defibrillator research involved performing studies on isolated heart cells, cultured in vitro. These studies demonstrated that damage can be produced in the heart by implantable and external defibrillators. This cellular damage is related to the production of secondary arrhythmias seen clinically following defibrillator shocks. Because cellular calcium is a key regulator of cell activity, contraction, rhythm and excitability, studies focused on some of the details of intracellular calcium elevation following the shock. Time-resolved analysis of optical measurement of intracellular calcium showed two events following the shock (figure 7). The first event resembles normal activity of heart cells. It is fixed in duration, and its magnitude is independent of shock strength or waveform. The second event is related to cellular damage. It is a slow elevation in calcium whose magnitude and duration are related to defibrillator shock strength, and it occurs when shock strength exceeds 18 V/cm around the cell. This field strength can be reached in the heart from implanted defibrillators or from high-energy DC defibrillators. The damage-related event is also sensitive to defibrillator waveform. It is longer with biphasic than monophasic shocks.
Most recent efforts have been directed toward understanding the mechanism behind this damage. The possibilities include microlesions to cell membranes, alteration of calcium channels on the plasma membrane, and changes in intracellular calcium cycling by sarcoplasmic reticulum. Understanding the mechanism will permit prediction of the conditions that are most likely to produce secondary arrhythmias and other untoward effects in patients that are treated with ICDs. These results have served to establish premarket review criteria for a number of medical devices, and were used in formulating a guidance document on the regulation of ICDs.
The new study of electrically stimulating nerve growth on tissue-engineered surfaces deals with a new generation of medical devices. These devices will use coatings and surfaces designed to interface an electrical stimulation device with the nervous system. Hence, OST scientists are performing a collaborative study with the National Institutes of Health which involves the growth and survival of explanted neurons from mouse brain on surfaces coated with the laminin biopolymer. This coating is useful in medical devices for obtaining nerve growth across injury sites and for obtaining infiltration into the devices to help restore neural function. Certain nerve cell types grow well on this biopolymer while other types (e.g., cerebellar granule cells from the weaver mouse) do not grow well and die. Experimental results suggest that agents which lower neuronal intracellular calcium levels rescue the weaver cerebellar neurons growing on this surface. The surface, therefore, affects selectivity for neural survival and growth, and this selectivity is regulated by intracellular calcium modulators. Such experiments proactively study the mechanism and factors governing the neural growth which is necessary for the safety and effectiveness for a new generation of tissue-engineered medical implants. [PreME]
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Key words: implantable cardiac defibrillator, ICD, ablation, cardiac
Scientists and engineers in OST have developed a computer-controlled system to measure the rate of energy deposition around the electrodes of a variety of cardiac electrical therapy devices. This Specific Absorption Rate (SAR) is directly proportional to the current density induced in heart tissues by an implantable cardioverter defibrillator (ICD) or a cardiac ablation system and, therefore, directly equal to the rate of temperature rise in the tissue. The OST system for the evaluation of SAR uses special temperature probe scanning and allows a quantitative spatial mapping of energy deposited in cardiac and other tissues. With these data, a comparison can be made between the safety and effectiveness of various models of the same class of cardiac device.
The results of these measurements are obtained in a rectangular tank filled with physiological saline. Data are obtained throughout the entire three dimensional volume of the tank. The system consists of a high speed personal computer, a 16-bit A/D and D/A converter board, high-current power amplifier, three-dimensional positioning system with submillimeter resolution, and a specially designed, fast-response thermal probe. These probes are tapered glass tubes containing a carefully calibrated glass-encapsulated micro thermistor bead embedded in the tip and are designed to produce minimal interference with current conduction paths in the testing tank. Special software was written to control the measurement system and record all data.
While the system can be used with a wide variety of electrical stimulation devices, initial tests concentrated on implantable cardioverter defibrillator (ICD) leads and cardiac ablation catheters. In one study, SAR was computed at each point by applying a high current shock from a simulated ICD generator to the saline in the tank. Figure 8 shows the SAR around an ICD lead measured at 1-mm resolution. The instantaneous rate of change in temperature due to the electrical shock was measured and computed at each point. After the SAR was calculated at a particular point in space, the thermal probe was moved, thermal gradients were allowed to decay, and the process was repeated. [PreME]
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Key words: implantable cardioverter defibrillator, cardiac, defibrillator
Scientists and engineers in OST are working on a laboratory bench test system to supplement clinical trials of implantable cardioverter defibrillator (ICDs). This system utilizes a broad array of recordings of cardiac electrical waveforms, known as electrograms. The electrograms were measured by cardiologists at the Philadelphia Heart Institute (PHI) in patients with problems in the electrical conduction system of their hearts. These problems, termed "arrhythmias," have unique electrogram waveforms. These waveforms can be used to functionally test ICDs in the laboratory through connection to a simulated patient, the OST bench test system. OST plans to use the system to enhance reviewer confidence in premarket clinical data on the safety and effectiveness of sample devices.
The OST bench test system is illustrated in figure 9. Use of the system occurs in two phases. The first phase involves data acquisition and interpretation. As illustrated, electrograms were obtained from patients during standard ICD implant procedures by cardiologists at PHI. During these procedures, arrhythmias were purposely induced to ensure proper operation of the ICD. The electrograms that were detected during the induction of arrhythmias were electronically recorded from the ICD sensing leads implanted in the patients' hearts during the functional testing. Upon returning to the laboratory, these analog data were digitized by CDRH/OST using an analog/digital converter. Cardiologists from ODE reviewed each electrogram and interpreted the arrhythmias. Data from over 30 patients receiving ICDs were collected and stored in digital form on the OST bench testing system.
The second phase of use of the bench test system involves testing ICDs. This testing is done to determine if sample defibrillators provide the appropriate therapy when various recorded electrograms are applied. A digital-to-analog converter is used to deliver voltages directly to the sensing leads of an ICD. The voltages are precise replicas of the clinically recorded electrograms. The ICD's output leads are monitored to determine the specific events in the electrogram waveform that cause the ICD to fire. The occurrence of under-sensing (not firing during an arrhythmia) as well as inappropriate firing can also be determined. The following table shows preliminary results for bench tests from one ICD.
Arrhythmia Type Correct Response ___________________________________________________________ Monomorphic Ventricular Tachycardia (VT) 82% Polymorphic VT 0% Self Terminating Monomorphic VT 0% Ventricular flutter (VF) and VT 0% VF 56% VT / VF 25% Coarse VF 55% Fine VF 33% Torsade VT 40% Torsade VF 33% Normal Sinus rhythm 80%
These preliminary studies show that bench testing can produce data that can be useful for the development of standardized procedures for the preclinical testing of new ICDs designs. A refined and expanded version of this system may be used by CDRH and device manufacturers to improve the quality of the device premarket review process and, perhaps, reduce the necessity for extensive clinical trials. Bench testing with this standardized electrogram library may also reduce the number of FDA-approved ICDs that deliver inappropriate therapy to patients in a postmarket approval setting. [PreME]