Key words: implantable defibrillator, cardiac
Scientists and engineers in OST are working on a laboratory testing system to augment clinical trials of inplantable cardioverter defibrillators (ICDs). This system will enable exhaustive bench testing of ICDs. This testing can utilize a broader array of arrhythmias and artifacts than those encountered by a few hundred patients over the course of a premarket trial. Also, the laboratory tests can be completed in a much shorter time than clinical trials and can enhance CDRH's confidence in premarket clinical studies of safety and effectiveness. Finally, bench testing may be able to ensure that fewer individuals with an FDA-approved ICD will fail to receive the intended therapy. In the development of this system, OST is collaborating with several clinical cardiologists whose efforts are aimed at compiling a computer-readable library of clinical electrograms composed of clinically induced arrhythmias. These electrograms are being obtained from patients during actual ICD implantations. The electrograms detected during arrhythmias are recorded from the actual ICD sensing leads implanted in the patients' hearts during the functional testing that is a part of the clinical implantation process for all ICD recipients.
The bench testing system illustrated in figure 07 uses a personal computer with analog and digital converters to deliver recorded electrograms to an ICD's sensing leads. The ICD's output (defibrillation) leads, normally implanted in the myocardium, are monitored to determine the specific events in the electrogram that cause the ICD to fire. The occurrence of undersensing (not firing during an arrhythmia) as well as inappropriate firing can also be determined. The test system evaluates the following subsystems of the ICD under test: 1) sensing leads (electrodes) in contact with the heart wall; 2) the electrical sensing circuit that detects the electrograms and determines when the ICD should fire; 3) the pulse generator that delivers an external stimulation pulse, when needed, to resuscitate the heart from fibrillation, or to convert ventricular tachycardia to normal sinus rhythm; and 4) the stimulating leads electrodes that deliver the resuscitation pulse from the ICD electronics unit to the heart.
This system uses a personal computer with analog and digital converters to deliver recorded electrograms to the sensing leads of an ICD.
In a feasibility study, recorded data from the actual implanted transvenous leads of over 20 patients undergoing ICD implantation were collected. These data were stored in a digital computer database. The purpose of the tests was to determine if the defibrillator could provide the appropriate therapy when a recorded electrogram of ventricular fibrillation was presented to its sensing leads. In addition, the testing insured that no inappropriate firing occurred when a wide range of non-fibrillation electrograms was presented to the sensing leads. Preliminary tests of the ICD test system indicated that it can indeed perform its intended functions.
Exhaustive computerized lab testing with the OST electrogram database can improve the device review process. It may also reduce the number of FDA-approved ICDs that fail to deliver the appropriate therapy to patients in a postmarket approval setting. During the next fiscal year, a large (< 50) number of recorded electrograms representing many normal and abnormal electrograms, including artifacts, will be tested with samples of ICDs that have been approved by FDA. These lab test results will be compared with clinical results presented in the PMAs for each device, as well as with postmarket records from several clinical centers. If results are positive, premarket lab testing may be recommended using a broad array of arrhythmias and artifacts in the OST database. [PreME]
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Key words: cardiac, ablation
Radiofrequency (RF) cardiac ablation is becoming a commonly used procedure for the treatment of cardiac arrhythmias. It is a procedure in which high frequency energy is delivered to the myocardium via an electrode catheter to create thermal lesions, thereby, eliminating arrhythmia pathways. One reason for its popularity is that, unlike other treatments for cardiac arrhythmias, cardiac ablation provides a cure for the patient instead of simply treating the patient's symptoms. From 1989 to 1993, the number of cardiac ablation procedures in the U.S. went from approximately 450 to 14,975. Although this procedure is 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. Several of the FDA-approved ablation devices automatically adjust their power output to maintain a constant temperature at the target site. This move toward temperature monitoring being an important aspect of ablation is also 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 also been established. The lower limit begins at approximately 48° C, where irreversible myocardial injury occurs. The upper limit is defined at the temperature where coagulum formation occurs with its associated large impedance rise at temperatures of 100° C or more. However, neither the previous research nor the industry has established the optimum temperature for cardiac ablation. Furthermore, ODE recognized the need for the optimal choice of target temperature to be objectively studied following a recent Circulatory Systems Device Panel meeting. Therefore in FY 95, OST performed laboratory studies of the relationship between the steady state tip temperature and the duration of treatment on lesion size.
The in vitro experimental setup consisted of an RF signal source, power meters, and an ablation catheter with a thermocouple sensor in its tip. Also, a thermocouple meter, a water bath, and plastic container (tank) were used. A butchered beef heart was the test material. To control for variables that can affect the lesion size, such as tissue contact force, fluid flow, and electrode catheter size, each of these variables was held constant.
Two experimental protocols were run: one in which the duration of the experiment was held constant at 60 seconds and the steady state tip temperature was varied, and the second protocol called for the steady state temperature to be held constant and the duration was varied. During both protocols, the power of the RF signal was varied to hold the steady state tip temperature constant. After lesion formation, the tissue was stained using a tetrazolium solution, which stains normal tissue red, giving a good contrast to the lesion and surrounding tissue. Finally, the lesion size was measured using calipers.
The temperature and power were recorded over time for each ablation. It took, on average, 3 to 4 seconds for the temperature to reach its steady state temperature. As the duration increased, the amount of power needed to maintain the steady state temperature decreased. The power needed to reach and maintain a steady state temperature of 60° C was, on average, 12.6 Watts. To maintain 70° C was an average of 20.7 Watts. To maintain 90° C, it took an average of 40.3 Watts, respectively.
The first protocol, in which duration was held constant at 60 seconds, found a linear relationship between lesion size and the steady state tip temperature. The steady state temperature was varied from 50° C to 90° C in steps of five degrees. Lesion depth was directly proportional to the temperature and varied from 1 mm at 50° C to 7.5 mm at 90° C. Lesion widths varied from 3.5 mm at 50° C to 9 mm at 90° C. For the second protocol, temperature was held constant and the time duration was varied. For each steady state temperature, an exponential curve was fitted to the data. A plateau in lesion depth was reached after 120 - 180 seconds seconds for both lesion depth and width.
The use of temperature-sensing catheters and temperature control increases the safety of cardiac ablation, because it prevents the tip temperature from reaching 100° C where coagulum is formed on the tip. Temperature sensing can also increase the efficacy of cardiac ablation because it is a good predictor of lesion size. Finally, steady state tip temperature and lesion size have a linear relationship, which supports the industry's move toward temperature-controlled ablation generators. [PreME]
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Key words: cardiac, defibrillation
Because of both increased patient use and FDA regulatory responsibility, OST has continued its proactive research program on the safety of cardiac electrostimulation devices. The automatic implantable cardioverter defibrillator (ICD) is a critical lifesaving device, and it continues to undergo revision by industry with options added for different varieties and combinations of electric shocks. Reports in the literature demonstrate that certain combinations of shock waveforms and voltages are capable of producing cardiac dysfunction which may induce additional fibrillation or block electrical pacing of the heart. One important aspect of the OST research program on ICD's has, therefore, been to assess dysfunction in heart cells caused by various shock waveforms and voltages.
The system employed by OST uses cultured cardiac cells exposed to electric fields that would be encountered during defibrillation. A unique feature of the OST program is theability to optically measure calcium in heart cells during the process of shocking. Calcium ions signal cardiac contraction, so when calcium levels are elevated, cells remain in a contracted state. The effect of certain high voltage shocks is to cause a prolonged elevation in intracellular calcium ion concentration, lasting a few seconds to a minute. Cells during this state are unexcitable and remain contracted. Concerning specific shock waveforms, symmetric biphasic shocks (equal phase amplitudes) were found to be more damaging than asymmetric shocks with a second phase of 20% of the first phase amplitude. For a 5 msec phase duration the damage threshold was a field strength of 50 volts/cm.
The results of this type of experiment are illustrated by the calcium recordings in figure 08a. In the upper trace, a normal rhythm is interrupted for 6 seconds by a 2.5 millisecond asymmetric biphasic shock. In the lower trace, the same strength shock with a symmetric biphasic waveform caused the interruption for 16 seconds. The differential effect of shock waveform is illustrated by figure 08b, which shows the recovery times from paired asymmetric and symmetric biphasic shocks. This work has correlates in animal studies and is relevant to the clinical situation where electric field strengths can exceed 100 volts/cm. Shock-induced dysfunction, therefore, is a possible side effect of defibrillatory therapy, and the key determinants of risk are shock voltage, waveform and duration.
Effect of symmetric and asymmetric defibrillator shock waveform on calcium recovery time in single heart cells. A: optical recordings of intracellular calcium concentration during applications of shocks; B: calcium recovery from paired shocks in isolated cells.
The results of OST experimental work on possible deleterious effects of defibrillatory shocks, a survey of relevant literature, and a set of recommendations for reviewers were drafted in a memorandum for reviewers in the ODE. [ProA]
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