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1576 JACC Vol. 25, No. 7 June 1995:1576-83 Clinical Predictors of the Defibrillation Threshold With the Unipolar Implantable Defibrillation System MERRITT H. R A I T T , M D , G E O R G E JOHNSON, B S E E , G. L E E D O L A C K , M D , F A C C , J E A N N E E. P O O L E , M D , F A C C , P E T E R J. K U D E N C H U K , M D , F A C C , G U S T H. B A R D Y , M D , F A C C Seattle, Washington Objectives. The purpose of this study was to determine the relation between clinical variables and the defibrillation threshold by using a standardized testing protocol and a uniform implantable defibrillator system. Background. Past studies have not revealed useful correlations between clinical variables and the energy required to terminate ventricular fibrillation. Most of these studies did not use a uniform implantable defibrillator system or a standardized protocol to measure the defibrillation threshold and, thus, did not control for the influence of these technical influences. We postulated that defibrillator and defibrillation threshold measurement-based sources of variability overshadowed important clinical predictors. Methods. The defibrillation threshold was measured by using a standardized protocol in 101 consecutive patients. We used a transvenons unipolar pectoral defibrillation system that employed a single endocardial right ventricular defibrillation coil as the anode and the shell of an 80-cm3 pulse generator as the cathode to deliver a 65% tilt biphasic pulse. Results. Several clinical variables were found to be significantly associated with the defibrillation threshold: patient gender, height, weight, body surface area, heart rate at rest, QRS and corrected QT (QTc) intervals, left ventricular mass and several measures of heart and chest size by chest roentgenogram. None of these variables had a correlation coefficient >0.45 with the defibrillation threshold. On multivariate analysis, left ventricular mass and heart rate at rest were the only independent predictors of the defibrillation threshold and explained only 25% of the observed variability. Conclusions. Despite the use of a uniform transvenous defibrillation system and a standardized protocol to measure the defibrillation threshold, no clinically relevant correlation was found between clinical variables and the defibrillation threshold. The defibrillation threshold is probably a function of a complex interaction of anatomic, physiologic and cellular variables that are not adequately represented by easily obtainable clinical information. It is probably not possible to predict defibrillation outcome from standard clinical variables. Past efforts to relate the minimal energy required to terminate ventricular fibrillation to clinical variables in patients undergoing defibrillator implantation have revealed poor correlations (1-5). If the defibrillation threshold could be predicted on the basis of clinical data, such information could be useful in planning patient care. Many device and lead system factors are known to effect the defibrillation threshold, including the number of electrodes utilized, electrode position, electrode polarity, pulsing technique and shock waveform (4,6-17). It is common practice to test a variety of combinations of these variables at the time of defibrillator implantation in an attempt to optimize the defibrillation threshold of an individual patient (1-5,18,19). It was our hypothesis that the wide patient to patient variation in defibrillation technique in previous studies may have overshadowed the role of clinical variables in determining the defibrillation threshold. Furthermore, not all past investigators (2-5) have used a standardized protocol to determine the defibrillation threshold and many (2,4,5) simply examined whether a clinical variable predicted whether the defibrillation threshold was above or below a predetermined arbitrary energy level. This lack of precision in determining the defibrillation threshold, the variation in defibrillator systems and the use of an arbitrary energy level instead of the defibrillation threshold as an end point may have clouded the effect of clinical variables on the defibrillation threshold. Thus, it was the purpose of this study to determine the relation of clinical variables to the defibrillation threshold in a large group uf patients by using a uniform defibrillation protocol, lead system, lead location, electrode polarity and shock waveform. From the Division of Cardiology,Department of Medicine, Universityof Washington, Seattle, Washington.This work was supported in part by a grant from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland;MedtronicCorporation,Minneapolis,Minnesota; and the TachycardiaResearch Foundation, Seattle, Washington.Dr. Bardyis a consultant for Medtronics, Inc., Minneapolis. Manuscript receivedOctober3, 1994;revised manuscriptreceivedDecember 30, 1994,acceptedFebruary2, 1995. Address for correspondence:Dr. Merritt H. Raitt, PortlandVeteransAffairs Medical Center, 3710SW US Veterans Road, P.O. Box 1034(IllB), Portland, Oregon 97207. ©1995 by the AmericanCollegeof Cardiology (J Am CoU Cardiol 1995;25:1576-83) Methods Patients. After providing informed verbal and written consent, 101 consecutive patients with a history of syncopal ventricular tachycardia, ventricular fibrillation, or both, under0735-1097/95/$9.50 0735-1097(95)00093-J JACC Vol. 25, No. 7 June 1995:1576-83 went defibrillation threshold testing with a unipolar single lead transvenous defibrillation system during implantation of a standard transvenous defibrillator. Unipolar defibrillation system. The unipolar defibrillation system utilized in this study has been described previously (20). The anodal electrode is a 5-cm long coil on a 10.5F transvenous lead (Medtronic model 6966) positioned in the right ventricular apex. The cathode is an active titanium shell with a volume of 80 cm3 and a surface area of 108 cm2 (Medtronic model 7219C) placed in a left infraclavicular pocket (19). This unipolar defibrillation system utilizes a 120-~F capacitor to deliver a 65% tilt asymmetric biphasic defibrillation pulse (15). All defibrillation pulse characteristics were measured from oscilloscopic recordings of waveform, voltage and current, as previously described (13). Defibrillation threshold testing. The defibrillation threshold of the unipolar system was determined before testing and implantation of a standard system that utilized two transvenous electrodes and a left infraclavicular subcutaneous patch. Standard antiarrhythmic medications were stopped at least 5 half-lives before testing, and amiodarone was stopped 1 to 2 weeks before testing. The energy was delivered 10 s after the onset of ventricular fibrillation, including the time period during which alternating current was applied to induce the rhythm. If the transvenous pulse delivered was unsuccessful, a 100- to 200-J transthoracic rescue pulse was delivered immediately by means of a precharged external defibrillator (PhysioControl LifePak 6s). A minimal rest period of 3 min was observed between inductions of ventricular fibrillation. Before reinduction of ventricular fibrillation, care was taken to ensure that the ST segments, T waves and arterial pressure had returned to baseline level. The initial energy level tested was 10 J. The pulse energy was increased after a failed shock and decreased after a successful shock. Testing then continued in 5-J steps between energy levels of 10 and 30 J, in 2.5-J steps between 5 and 10 J and in 1.25-J steps at <5 J. If a shock was successful the energy was decreased two steps for each retest until a failure occurred, after which the next highest previously skipped energy level was tested. Similarly, if the initial 10-J energy level failed, it was increased two steps after each ensuing failure and then reduced one step to the last skipped step after a success. This skip method was used to minimize the number of episodes of ventricular fibrillation needed to determine the defibrillation threshold. The defibrillation threshold was defined as the lowest pulse amplitude that successfully terminated ventricular fibrillation. Determining this defibrillation threshold required 2 to 5 (mean + SD 3.4 _+ 0.9) inductions of ventricular fibrillation. All patients completed the protocol without significant complications. Clinical data. For each patient the clinical data available included age, gender, height, weight, body surface area, clinical arrhythmia history, underlying cardiac disease, chronic therapy with amiodarone within the last month, past cardiac surgical history, ejection fraction by radionuclide ventriculogram and electrocardiographic (ECG) data including QRS interval, corrected QT (QTc) interval and heart rate at rest. A postero- RAITT ET AL. DEFIBRILLATION THRESHOLD PREDICTION 1577 Table 1. BaselinePatient Characteristics (n = 101) Age (yr) Male Coronary artery disease History of ventricular tachycardia Past heart surgery Past amiodarone therapy Left ventricular ejection fraction 57 + 13 73% 68% 54% 47% 21% 0.38 + 0.16 Data are expressed as mean value _+ SD or percent of patients. anterior chest roentgenogram performed after defibrillator implantation was examined and several measures of heart size and the relative positions of the pectoral and right ventricular electrodes were recorded. These measurements included the horizontal heart and chest diameters at the level of the cardiac apex, the distance from the right ventricular electrode to the center of the pectoral patch (which occupies the same pectoral pocket occupied by the active can during testing for this study), the distance along the line between the two defibrillation electrodes and from the middle of the right ventricular coil to the superior heart border, and the horizontal distance from the chest midline to the center of the pectoral pocket (position of the can electrode during testing). In 86 patients, left ventricular end-diastolic diameter, septal wall thickness and left ventricular free wall thickness were measured from echocardiograms performed as part of the patients' evaluation before defibrillator implantation. Left ventricular mass was calculated (21) from these measured variables. Statistical analysis. The two-tailed t test and linear regression were used to analyze the statistical significance of correlations between the defibrillation threshold and clinical variables. Stepwise multiple linear regression (SPSS version 6.0) with a probability of F to enter of 0.05 and 0.10 to remove was used to determine independent predictors of the defibrillation threshold. Results The baseline characteristics of the 101 patients in the study group are shown in Table 1. The mean defibrillation threshold was 9.3 _+ 6.5, with 98% of patients having a defibrillation threshold <25 J. The correlation coefficients for the clinical, chest X-ray and echocardiographic variables with the defibrillation threshold are shown in Table 2. Figures 1 to 4 show graphs of the defibrillation threshold as a function of each of the individual clinical variables. A statistically significant correlation was present between the defibrillation threshold and several variables including patient gender, weight, body surface area, heart rate at rest, QRS interval, QTc interval, chest diameter, heart diameter, ejection fraction, left ventricular end-diastolic diameter and left ventricular mass. Despite the significance of the relation between these clinical variables and the defibrillation threshold, the correlation coefficients were poor, with none >0.45. Furthermore, when the data from the two outlier patients with the highest defibrillation thresholds 1578 RAITI" ET AL. DEFIBRILLATION T H R E S H O L D PREDICTION JACC Vol. 25, No. 7 June 1995:1576-83 Table 2. Correlation Between Clinical Variables and the Defibrillation Threshold, Univariate Analysis were removed from the analysis, the QTc interval and ejection fraction no longer had a significant association with the defibrillation threshold. Left ventricular mass had the best correlation with the defibrillation threshold (R = 0.45). There were no significant associations between the defibrillation threshold and patient age, history of heart surgery, history of myocardial infarction, history of ventricular tachycardia, recent amiodarone therapy, cardiothoracic ratio, the distance between the two electrodes on the posteroanterior chest roentgenogram, posterior and septal wall thickness on echocardiography and the resistance between the coil and can electrode. Stepwise multiple linear regression was performed using the variables with a significant association with the defibrillation threshold on univariate testing; 17 patients were excluded because of missing data. Only two clinical variables were found to be independent predictors of the defibrillation threshold: left ventricular mass and heart rate at rest. The model containing both these variables nevertheless was a poor predictor of the defibrillation threshold. The correlation coefficient was only 0.50 and together these variables explained only 25% of the observed variability in the defibrillation threshold. Figure 1. Plots of the defibrillation threshold (DFF) as a function of (A) gender, (B) previous history of coronary artery disease (CAD), (C) previous history of myocardial infarction (MI), (D) previous history of ventricular tachycardia (VT), (E) recent amiodarone therapy and (F) previous open heart surgery. The p values are shown for a two-tailed t test comparing the groups. • A) p = 0 . 0 0 4 40 B) p = 0 . 0 4 Clinical Characteristic Regression Coefficient p Value Age Female Height Body weight Body surface area History of myocardial infarction History of coronary artery disease History of ventricular tachycardia Past heart surgery Recent amiodarone therapy Heart rate at rest QRS interval QTc interval PA chest width on chest roentgenogram PA heart width on chest roentgenogram Cardiothoracic ratio Distance from RV coil to can electrode Distance from RV coil to heart border Distance from spine to can electrode Ejection fraction Posterior wall thickness Septal wall thickness Left ventricular end-diastolic diameter Left ventricular mass Shock resistance +0.04 -0.28 +0.29 +0.33 +0.35 +0.14 +0.20 +0.15 +0.01 +0.12 +0.24 +0.26 +0.20 +0.29 +0.36 +0.09 +0.10 +0.29 +0.15 -0.25 +0.13 +0.03 +0.40 +0.45 +0.03 0.66 0.004 0.003 0.0008 0.0004 0.17 0.04 0.14 0.93 0.24 0.015 0.009 0.04 0.004 0.0003 0.38 0.34 0.004 0.13 0.01 0.24 0.78 0.0001 < 0.0001 0.75 PA = posteroanterior; QTc = corrected QT interval; RV = right ventricular. • 4O a5 35 35 25 25 25 ~2o ~ 2o 15 15 10 10 5 5 ! Male Female o 5 No Yes Sex 40 D) p = 0 . 1 4 4o 35 30 3o 25 25 15 ! ~ 20 | is ,o 10 5 0 • No Yes I ! No Yes o Histor/of MI E) p = 0 . 2 4 4o F) p = 0 . 9 3 35 25 15 1- ,o 5 History of VT ;! !i History of CAD 35 ~ 2o 0 C) p = 0.17 • I • No Yes Recent Amiodarone Therapy 5 o i! ! ! No Yes Past Heart Surgery JACC Vol. 25, No. 7 June 1995:1576-83 DEFIBRILLATION 4o A) R = 0.04 p - 0.66 B) R = 0.33 p - 0.0008 40 • 35 4o 35 30 • 30 • 25 "20 • • • 25 O O 20 oil,• eleo 0 % t 15 o,,,o • 15 lo 8 • • 5 " IP.• .,o']J'~B ••••el f~n~Oe~• ~o Ildl~ qlo • • O~O • • 10 40 o• n i i 20 30 40 lo • 5 • go i u 50 60 Age (yr$) D) R = 0.24 p = 0,015 -- i u u 70 80 90 80 • oa,0° • 120 • i 15 ~ • i • i i t 240 i i 40 15 • el•• el • oOO ~ • o~00 qt• ~ • ~O 5 • i i 2.6 I • 30 25 10 5 • 1.6 1.8 2 2.2 2.4 Body Surface Area (m2) C,r~ R - 0.20 p - 0.04 • • 15 ° °o "q~Jog° " °° ° " 1.4 35 20 °°° gob " i 1.2 25 2o ,~:.'! 0 280 30 25 "~. • 35 3O ,. "•- . ~ ~ . ' . 'L0 • • 160 200 Weight (Ibs) E) R = 0.26 p = 0.009 4o o o • o go ••olin• 8 • w I n n ~ e'•o• Q O0 • i 0 • 35 • 35 3O 25 C) R - 0 3 5 p - 0.0004 • 1579 RAITF ET AL. PREDICTION THRESHOLD 1- •alp IOlo ~ 20 15 • "o-oh'0 • • o o• • OOo • "l lO ;,," i • 0 5 ° • Oil ° • ° ~ 0o•o0• 0 o 0 4O 50 60 70 80 90 100 Resting Heart Rate (bprn) 110 120 Discussion Several previous investigators (1-5) have reviewed their clinical experience and found a significant but poor correlation between a variety of clinical variables and the defibrillation threshold or the likelihood of successful defibrillator implantation. Kelly et al. (1) reviewed the results of epicardial defibrillator implantation in 42 of 62 patients receiving a spring and large patch electrode configuration. A standardized defibrillation threshold protocol was followed, but the surgical technique and waveform polarity were not controlled. Patients taking amiodarone at the time of implantation had a higher defibrillation threshold than that of patients who had never taken amiodarone. Patient age, gender, cardiac diagnosis, ejection fraction, the presence or absence of a left ventricular aneurysm and antiarrhythmic drug therapy other than amiodarone had no significant association with the defibrillation threshold. Leitch et al. (3) reviewed a manufacturer's data base to determine predictors of the defibrillation threshold in patients undergoing epicardial defibrillator implantation. A defibrillation threshold was not determined in 137 of the 375 patients available for study. In the remaining 238 patients the defibrillation threshold was determined but the defibrillation threshold protocol, pulsing technique, number of electrodes, electrode position and electrode polarity varied among patients. Male gender, lower ejection fraction, higher functional class, the use of two instead of three patches and the use of 60 80 100 120 140 160 QRS Interval (ms) 180 200 360 400 440 480 QTc Interval (ms) 520 560 Figure 2. Plots of the defibrillationthreshold (DFT) as a function of (A) patient age, (B) bodyweight, (C) bodysurface area, (D) heart rate at rest, (E) QRS intervaland (F) corrected QT (QTc) interval.The R value and the p value of the linear correlation are shown, bpm beats/rain. simultaneous rather than sequential shocks were significantly associated with a higher defibrillation threshold on univariate analysis. Patient age, body surface area, presence of coronary artery disease and the use of amiodarone were not significant predictors of the defibrillation threshold. On multivariate analysis, patient gender, ejection fraction, and pulsing technique were independent but weak predictors of the defibrillation threshold. More recently, Brooks et al. (4) examined the determinants of successful nonthoracotomy defibrillator implantation (defibrillation threshold _>10 J below the maximal device output, not the actual defibrillation threshold) in 101 patients. In their study, defibrillators and lead systems produced by two manufacturers were utilized, and multiple lead system configurations, polarities and pulsing techniques were tested at the discretion of the implanting physician. Significant univariate predictors of successful implantation included smaller cardiac diameter on chest roentgen•gram, QRS duration <120 ms, absence of left bundle branch block, ventricular fibrillation as the presenting arrhythmia, smaller left ventricular diastolic diameter on echocardiogram and the absence of antiarrhyth- 1580 R A I T T ET AL. DEFIBRILLATION T H R E S H O L D PREDICTION o36 p = 0,0003 olBo • P = 0.004 35 30 • 25 ~20 " 15 5 • • ' t p = 0,38 35 30 30 25 25 ~20 . • t • 5 T . "~'- ;: :," 40 12 14 16 18 20 PA CXR Heart Width (cm) D) R = 0,29 p = 0.004 24 22.5 40 51 27.5 32.5 37.5 42.5 47.5 ...,,,.,, .35 .4 .45 E) R = 0 . 1 0 p = 0.34 • .5 .55 .6 .65 .7 .75 CardiothoracicRatio 40 F) R - 0.15 p - 0.13 e • 35 35 30 • 25 • • • 253° 25 2o • • o• 15 • O O O ~ o°O 15 15 J• 10 _ _ j....r'rl j• o I o • • • • 0 • ..,..'2.. ~20 • ooJoooo 5 • "': ".- " PA CXR ChestWidth (cm) 35 0 • • i l , '' i 7 8 9 10 11 12 Distancefrom RV Coil to Heart Border(cm) Ooi• ooo 0 13 O • o • O o • i • O •o 10 • 5 • l'": 10 o| •00•=%0 • .Io 5 "1 o o •:81.* 0 " 0 22 • 30 • 8 °eee ~ • _ :" 10 • 15 "'" • • ~20 15 ";.;... •OR0 • 35 .... . JACC Vol. 25, No. 7 June 1995:1576-83 " 12 14 16 18 20 22 Distance from RV Coil to Can Electrode(cm) Figure 3. Plots of the defibrillationthreshold (DFT) as a function of (A) heart width on a posteroanterior chest roentgenogram (PACXR), (B) chest width on a posteroanterior chest roentgenogram, (C) cardiothoracic ratio, (D) distance from the middle of the right ventricular (RV) electrode to the superior heart border along the line connecting the centers of the two electrodes, (E) distance between the right ventricular and can electrodes and (F) horizontal distance from the spine to the can electrode. The R value and the p value of the linear correlation are shown. mic drugs at the time of implantation. Patient age, height, weight, body surface area, presence of coronary artery disease and ejection fraction were not significantly associated with the likelihood of successful implantation. On multivariate analysis only smaller cardiac diameter on chest roentgen•gram and female gender were significant independent predictors of successful implantation. Even the most powerful predictor, cardiac diameter, showed significant overlap between patients with and without successful implantation (16.2 _+ 1.7 cm vs. 18.3 _+ 1.1 cm). In these studies and in others, the investigators (1-5,18,19) found significant correlations between certain clinical variables and the defibrillation threshold, but the correlations were poor and of little clinical value. They tested multiple electrode positions, polarities, pulsing techniques and, in some cases, different waver•tins until a configuration with an acceptable defibrillation threshold was found. In addition, a standardized protocol for determination of the defibrillation threshold was 4" " o 5 10 15 20 25 30 DistancefromSpine to Can Electrode (cm) not always followed (2-5). It was our hypothesis that these system-dependent sources of variability and the lack of a uniform method to determine the defibrillation threshold obscured the role of clinical variables in determining the defibrillation threshold. Our findings, however, indicate that a poor correlation between the defibrillation threshold and clinical variables persists despite use of a uniform defibrillation system and defibrillation threshold protocol. Predictors of the defibrillation threshold. Our use of a uniform defibrillation lead system, lead location, way•form, polarity, and pulsing technique, as well as a standard protocol to determine the defibrillation threshold, allowed identification of more clinical variables that were significantly associated with the defibrillation threshold at a higher level of statistical significance than that reported by past investigators. Clinical variables significantly associated with a higher defibrillation threshold in our patients included male gender, increased patient height, weight and body surface area, several measures of increased heart and chest size by chest roentgen•gram and echocardiography, longer QTc and QRS intervals, faster heart rate at rest and increased left ventricular mass. The results of the multivariate analysis suggest that most of the predictive value of these variables is related to their representation of the same underlying property, increased heart and body size as reflected in left ventricular mass. This correlation between left ventricular mass and the defibrillation threshold has been shown in one small previous study involving 11 patients (22). The role played by heart and body size in defibrillation is J A C C V o l . 25, N o . 7 June 1995:1576-83 DEFIBRILLATION A) R - 0.13 p = 0.24 40 B) R - 0.03 p - 0.78 • THRESHOLD • 40 35 35 • 30 1581 RAITr ET AL. PREDICTION C) R n 0 . ~ p - 0.0001 • 35 30 25 25 • 20 • • ,::. ~20 • 15 • 10 • 5 • 8 0 0 | 0 i .5 40 = • • • • • i i i J • n • • i n 0 .6 .7 .8 .9 1 1.1 1.2 1.3 1.4 Posterior Wall 111icknes$ (cm) D) R = 0,45 p <0.0001 • .4 i .6 .8 1 u 1.2 : 1.4 u 1.6 • • E) R = 0.25 p = 0.013 4O • • .. 6 7 8 9 10 F) R - 0.03 p - 0.75 • 30 25 2o 5 35 30 25 4 LV End Diastolic Diameter (cm) 35 30 i i 1.8 $ep(al Wall Thickness (cm) 40 35 o, /me o• 0 0 oo • Iljooo~i o• • • 5 • o ~ ~,o*,,t, lfi j 25 ".. j,..::'.- • o. o d l p , O e 15 •L ~ O LO10 "n • ~a n • o •~ 15 ~ 10 o• • OO • • 15 10 • . 5 • 0 r - , " : _ ' , 50 150 250 350 Left Ventrictdar Mass (g) , 450 , 550 o understandable given the requirement that an electric field of a certain threshold gradient (approximately 5 V/cm2) must be applied to >90% of the myocardium to terminate ventricular fibrillation (16). The larger the patient and the larger the heart, the more the electric field is likely to diminish in intensity to below this threshold at a particular pulse strength. Thus, larger hearts and larger patients are likely to require higher delivered energy levels to accomplish defibrillation. Heart rate at rest was the only other independent predictor of the defibrillation threshold: A faster heart rate at rest was associated with a higher defibrillation threshold. The mechanism of this association is not clear, but a higher heart rate at rest may simply be a marker for more severe heart disease that is associated with physiologic or cellular abnormalities that raise the defibrillation threshold. A m i o d a r o n e . Recent amiodarone therapy was not found to be a significant predictor of the defibrillation threshold. This finding is unexpected because past studies (23-26) have suggested that amiodarone results in significant elevation of the defibrillation threshold. A likely explanation is that the withholding of amiodarone for 1 to 2 weeks before testing reduced the impact of the drug on the defibrillation threshold. Kelly et al. (1) observed a similar phenomenon: The defibrillation threshold of patients who had never taken amiodarone was not different from that of patients who had stopped taking the drug >1 month before device implantation. Patients who continued to take amiodarone up to the time of device implantation had significantly higher defibrillation thresholds than those of 0 .1 .2 -" " .3 .4 .5 Ejection Fraction "'-" .6 .7 o ,8' i 35 40 t • • t,, J.-,,'- •o•0 i• •° • *'e* ~ f . . . . • • ~ Q qP • o,o 000o0% • u = e , 60 65 70 75 Resistance (ohms) 80 85 45 50 i 55 e u e -- 4. Plots of the defibrillationthreshold (DFT) as a function of (A) posterior wall thickness on echocardiography, (B) septal wall thickness on echocardiography,(C) left ventricular (LV) end-diastolic diameter on echocardiography, (I)) left ventricular mass calculated from echocardiographic data, (E) ejection fraction and (F) shock resistance. The R value and the p value of the linear correlation are shown. Figure patients who had never taken the medication or who had stopped taking it for >1 month. Why such an effect would occur over a period of time significantly shorter than the half-life of the drug is unclear. However, the finding may reflect differences in the short- and long-term distribution of amiodarone. Alternatively, our results may reflect the current practice of using lower doses of the drug than had been customary at the time of some of the earlier studies. C l i n i c a l utility of identified p r e d i c t o r s . Despite our identification of highly significant correlations between several clinical variables and the defibrillation threshold there is remarkable scatter present when the defibrillation threshold of individual patients is considered in relation to these variables (Fig. 1 to 4). The multivariate model in fact explained only 25% of the observed variability in the defibrillation threshold. Thus, despite controlling for all device, lead system, lead location, waveform, polarity and defibrillation threshold measurement sources of variability in the defibrillation threshold, we were unable to identify a set of clinical variables that could in any reliable way predict the defibrillation threshold of an 1582 RAITT ET AL. DEFIBRILLATION THRESHOLD PREDICTION individual patient. These findings indicate that defibrillation is a complex interaction of anatomy and physiology, not well reflected in easily obtained clinical measurements, that determines the distribution of current and the excitability and the refractoriness of cardiac membranes during ventricular fibrillation. It is possible that sophisticated methods such as finite element analysis by means of patient-specific thoracic computed tomographic models may improve the predictability of the defibrillation threshold in individual patients (27). Limitations. A limitation inherent in all human studies of defibrillation is the precision with which the defibrillation threshold can be measured. Defibrillation is in part a statistical phenomenon such that at any one energy level there is a probability of defibrillation rather than a certainty of success or failure (28). In animal studies the defibrillation threshold is often defined as the energy level with a 50% likelihood of defibrillation, in human studies it is neither practical nor safe to perform a large enough number of defibrillations so that this energy level can be precisely determined. Thus, in any one patient chance may lead to significant under- or overestimation of the defibrillation threshold. Our defibrillation threshold measurement protocol minimized this effect by using an initial energy level near the expected mean defibrillation threshold of the entire study group. In addition, the energy step-skipping protocol allows relatively small increments in energy to be tested near the defibrillation threshold while minimizing the overall number of inductions of ventricular fibrillation. Nevertheless, it is possible that the inherent variability in the defibrillation threshold measurement obtained with this method and other methods reasonable in human studies and clinical practice may account for a significant proportion of the 75% of the defibrillation threshold not accounted for by clinical variables. Nevertheless, it is the results of this type of defibrillation threshold testing that physicians would like to be able to predict. A second potential limitation of this study is the concern that the result may be relevant only to the specific lead configuration, pulsing method and waveform tested. This limitation is, of course, inherent in any study that controls these factors. This issue is made less important because our results suggest that there is not an inherent determination of the defibrillation threshold by easily measured clinical factors but, instead, a significant but minimal influence. Testing a different waveform or electrode configuration may increase or decrease the modest influence of individual clinical variables, but it is unlikely to change the basic finding that something other than these clinical measures accounts for the preponderance of the observed variability in the defibrillation threshold in clinical practice. Conclusions. The defibrillation threshold cannot be reliably predicted for individual patients from standard clinical variables. Though certain clinical variables are associated with a higher or lower defibrillation threshold, the predictive value is low. We do not advocate withholding an attempt at transvenous defibrillator implantation on the basis of a clinical variable such as increased left ventricular mass or patient JACC Vol. 25, No. 7 June 1995:1576-83 weight that tends to be associated with an increased defibrillation threshold. The defibrillation threshold is probably a function of a complex interaction of anatomic, physiologic and cellular variables that are not adequately represented by easily obtainable clinical information. We thank Charles Troutman, RN and Jill Anderson, RN for nursing care of the patients, Joan McDaniel for secretarial assistance and Susan Shattuc, MS for preparation of the figures. References 1. Kelly PA, Cannom DS, Garan H, et al. The automatic cardioverterdefibrillator: efficacy, complications and survival in patients with malignant ventricular arrhythmias. J Am Coil Cardiol 1988;11:1276-86. 2. Epstein AE, Ellenbogen KA, Kirk KA, Kay GN, Dailey SM, Plumb VJ, and the High Defibrillation Threshold Investigators. Clinical characteristics and outcome of patients with high defibrillation thresholds: a multicenter study. Circulation 1992;86:1206-16. 3. Leitch JW, Yee R, and the Multicenter Pacemaker-CardioverterDefibrillator (PCD) Investigators Group. 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