Implantable cardioverter–defibrillators (ICDs) are being implanted in an ever-increasing number of patients at risk for sudden cardiac death. To ensure the efficacy of the defibrillation system, step-down defibrillation threshold (DFT) testing has traditionally been used to ensure that the ICD can appropriately detect and terminate clinical ventricular fibrillation (VF).
Currently, the most widely accepted method of ‘device testing’ at the time of ICD implantation requires at least two VF inductions, with subsequent demonstration of two conversion successes with shock energies of 10J less than the maximum energy delivered by the ICD. While VF conversion testing is a relatively safe procedure, in rare cases the repeated induction of VF, particularly in patients with marked heart failure, may result in serious complications such as myocardial depression or ischemia, cerebral hypoperfusion, intractable VF, or even death.1–3 A retrospective analysis from the Low Energy Safety Study (LESS) showed that one low-energy VF conversion success at 14J was sufficient to ensure the adequacy of an ICD system at the time of implantation when programming all shocks to the maximum energy of the device at 31J.4,5 Based on these findings and the concern of potential patient cardiac decompensation with repeated VF inductions during ICD implantation, many centers have adopted a single VF induction approach.
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Testing for the upper limit of vulnerability (ULV) is an alternative method that may be used to estimate the DFT without the repeated VF inductions required with traditional DFT testing. It is well known that a vulnerable period exists in the cardiac cycle and that a single shock of appropriate strength can induce VF. If the strength of the shock delivered during the vulnerable period is gradually increased, the ventricle will eventually become ‘non-vulnerable’ and VF will not be induced. The ULV is defined as the weakest shock delivered during the vulnerable phase of the cardiac cycle (which correlates to the peak of the T wave) at which VF is not induced. The basis of the ULV approach is that the ULV closely correlates with the DFT and that ICDs programmed on the basis of the ULV reliably defibrillate VF. Thus, the purpose of the Arrhythmia Single Shock Defibrillation Threshold Testing versus Upper Limit of Vulnerability: Risk Reduction Evaluation with Implantable Cardioverter Defibrillator Implantations (ASSURE) Study was, for the first time, to prospectively evaluate in a randomized, controlled, large multicenter study the efficacy of a potentially inductionless ULV screening approach versus a single low-energy VF conversion test at the time of ICD implantation.
Results of the ASSURE Study
The ASSURE Study was a large, multicenter, randomized study to evaluate the efficacy of ULV versus a single VF conversion test in relation to standard defibrillation testing to ensure a 10J safety margin. The results of this study were recently published in Circulation.6
The ASSURE Study enrolled 426 patients who underwent implantation of an ICD or cardiac resynchronization therapy defibrillator (CRT-D) and were followed for a mean duration of 9.5±4.5 months. Seventy-one percent of the patients had a left ventricular ejection fraction ≤30% and more than half of the patients (54%) were NYHA class III or IV heart failure. All of the patients received a left-sided pectoral implantation with a dual-coil shocking lead implanted in the right ventricular apex. In this study, patients were randomized to undergo ICD/CRT-D implant testing consisting of either low-energy ULV screening at 14J or a single VF conversion test at 14J. Confirmatory testing of two successful VF conversions at 21J or lower was also performed (10J safety margin) regardless of their randomized testing strategy. A 21J shock for fast clinical ventricular tachycardia (VT) or VF of 200bpm or faster was programmed if patients passed their randomized testing strategy. The ULV screening protocol consisted of three T-wave shocks at 14J timed to the peak of the latest peaking monophasic T-wave as determined by a standard 12-lead electrocardiogram (ECG). The three T-wave shocks were timed to 20msec before the peak of the T-wave, at the peak of the T-wave, and 20msec after the peak of the T-wave. Successfully passing ULV screening at 14J meant that VF was not induced with any of the three T-wave shocks. Proper determination of the latest peaking monophasic T-wave was independently validated at an ECG core laboratory.
To increase the statistical power of the study, all patients underwent both 14J ULV screening and a single VF conversion test at 14J. However, final shock programming was determined by whether or not patients passed their randomized testing strategy at implantation. Of the 420 patients who underwent 14J ULV screening, 322 (76.7%) passed. Of these, 317 (98.4%) also passed their 21J confirmatory tests (see Table 1). Of the 416 patients who underwent a single VF conversion test at 14J, 343 (82.5%) passed. Of these, 338 (98.5%) also passed their 21J confirmatory tests (see Table 1). There was no difference in the positive predictive accuracy of passing either the 14J ULV screening or a single VF conversion test at 14J based on whether the device was an ICD or a CRT-D.
Overall, 6.2% of the patients failed initial confirmatory VF conversion testing at 21J and thus a 10J safety margin could not be achieved. Of note, only 4.4% of the ICD patients had an elevated initial defibrillation energy requirement, which is in contrast to 7.6% of the CRT-D patients having a high initial defibrillation energy requirement (p=0.16). In all cases, subsequent revisions to the shock vector or upgrade to a high-energy device resulted in a 10J safety margin. Most clinical fast VT/VF episodes (32 of 37; 86%) were terminated by the first shock with no difference in the first shock success and with shock programming based on the randomized testing strategy. In all observed cases where the first shock was unsuccessful, subsequent shocks terminated VT/VF without complication.
Inductionless Implantable Cardioverter–Defibrillator Implantations and Clinical Implications of the ASSURE Study
While the assessment of the DFT has long been the standard of ICD shock testing at the time of implantation, it is certainly not without additional procedural time and risk to the patient. Many authors have suggested that DFT testing at the time of implantation may no longer be needed given the significant advances in device and lead technology.7 While it is relatively uncommon to encounter a high DFT patient with current ICD/CRT-D technology, there is still a small sub-group of patients, especially those with more advanced heart failure, for whom an adequate DFT cannot be achieved by standard methods. Thus, ideally at implantation a safe and reliable testing method could be employed to identify those patients with increased defibrillation energy requirements.
In rare cases, repeated induction of VF, especially in patients with advanced heart failure, may result in myocardial depression or ischemia, cerebral hypoperfusion, immediate cardiac dilation, acute pulmonary edema, elevation of cardiac enzymes, intractable VF, or even death. Fortunately, in the ASSURE Study we did not observe any complications from shock testing at the time of implantation. We did, however, observe that in patients monitored utilizing a standardized anesthesia protocol and continuous arterial blood pressure monitoring, prolonged hypotension was more commonly observed following VF induction than ULV assessment in sinus rhythm. These findings are consistent with our previously reported findings of a study of 194 patients who underwent device testing, in which prolonged hypotension was observed in 2 and 8% of patients after ULV and DFT testing, respectively (p=0.006).8
In the ASSURE Study, 6.2% of the patients had an elevated defibrillation energy requirement (10J safety margin not achieved) during VF conversion testing in the initial shock configuration. A trend toward higher initial defibrillation energy requirements was observed in patients receiving a CRT-D device, which is likely a manifestation of more advanced underlying heart disease. This is consistent with our finding of an elevated defibrillation energy requirement of 3.9%, which was observed from 1,530 patients in the INTRINSIC RV Study.9,10 Thus, as high defibrillation energy requirements are rarely encountered with modern ICD/CRT-D systems, ideally a simple and safe testing method could be used to quickly identify those patients who may have higher defibrillation energy requirements at the time of implantation.
Moreover, in the ASSURE Study ULV or a single VF conversion test at 14J resulted in a similar positive predictive accuracy of successfully defibrillating the patients at an energy level 10J below the maximum energy of the device (98.4 and 98.5%, respectively; p<0.0001). These findings are consistent with the results of LESS, which reported that one successful VF conversion at 14J was associated with a 99.1% positive predictive accuracy of the clinically accepted testing criteria of two successful VF shock conversions at 10J below the maximum energy of the device.11,12 While both screening methods (ULV testing at 14J or a single VF conversion test at 14J) appear to provide a similar degree of safety with regard to first clinical shock success by programming a device based on these screening methods, ULV screening at 14J could have avoided intentional VF induction at the time of implantation in 76.7% of the patients.
Two criticisms of ULV testing are that this testing method is difficult to learn and adds significant time to the entire ICD implantation procedure. Based on our findings, ULV screening added 2.1 minutes to the total case time. Moreover, even though most investigators in this study had not previously performed ULV testing, evaluation of ULV measurements by the ECG Core Lab demonstrated uniformity among investigators. While there was no statistical difference in first shock efficacy between the randomized implant testing methods, it is possible that the first clinical shock success rate for fast VT/VF in this study could have been higher than the observed first clinical shock success of 84%, had the devices been programmed to deliver the first clinical shock at a maximal energy of 31J rather than the lower-energy 21J shock. A lower-energy first clinical shock of 21J was selected at the time of protocol development to minimize device charge time and potentially avoid post-shock mechanical dysfunction and electromechanical dissociation, which may occur with higher-energy shocks.13
Since the development of the ASSURE protocol, the ICD/CRT-D devices currently available on the market have very short charge times for shocks at any energy strength. Thus, the potential risks of a higher first energy shock may be offset by an increased first clinical shock success rate for spontaneously occurring fast VT/VF. Among all observed cases where the first shock was unsuccessful, subsequent shocks terminated fast VT/VF without complication. Moreover, of the reported deaths that occurred during follow-up or post mortem device evaluation, none were due to failure of programmed shocks to terminate a ventricular arrhythmia.
Based on the results of the ASSURE Study, we now routinely perform either low-energy ULV screening at 14 or 15J or a single VF conversion test at 14 or 15J, depending on the manufacturer device-specific shock output of the ICD/CRT-D. Patients who pass this simple screening test are then programmed to have their first clinical shock delivered at the maximum energy of the device. In our experience of using this implant testing approach in more than 3,000 ICD/CRT-D implantations, it has dramatically reduced implantation time, decreased the risk for potential cardiovascular decompensation during implantation, and resulted in reliable clinical defibrillation of spontaneously occurring fast VT or VF.
Conclusion
As high defibrillation energy requirements are not commonly encountered in modern ICD/CRT-D systems, a safe and effective testing method is needed at implantation to identify which patients may or may not require additional testing. Low-energy ULV or a single VF conversion screening provide a reasonable balance between identifying those patients who do not require significant implant testing and those who may have an increased defibrillation energy requirement and may require more formal DFT testing. In this large, multicenter, randomized trial, either ULV screening at 14J or a single VF conversion test at 14J predicted that 98.4 and 98.5% of the patients, respectively, would subsequently pass standard confirmatory testing with a 10J safety margin. Furthermore, this type of minimal screening approach with low-energy ULV testing or a single VF conversion test may prevent unnecessary additional VF inductions and potential procedural complications during implantation in most patients.