Signal-averaged isoharmonic body surface maps of patients with ischemic cardiomyopathy.

INTRODUCTION: Prevention of sudden arrhythmic cardiac death depends on accurate identification of individuals at high risk. Previous studies of signals recorded directly from arrhythmogenic tissue suggested that the predictive value of the signal-averaged ECG could be enhanced by expanded temporal, spectral, and spatial analysis. Accordingly, we performed a prospective study of 192-lead signal-averaged body surface maps from 43 patients with ischemic cardiomyopathy referred for electrophysiologic study. Three groups were included: 15 patients with clinical ventricular tachycardia (VT), 12 patients with inducible VT, and 16 patients with non-VT. METHODS AND RESULTS: The patients were well matched with regard to age, gender, infarct location, ejection fraction (28% +/- 9%), QRS duration, and incidence of nonsustained VT (96%). Isoharmonic maps of the entire cardiac cycle were constructed for each patient. The peaks of the 1-7 Hz isoharmonic maps distinguished patients with clinical VT from non-VT and inducible VT patients (1,152 +/- 273, 852 +/- 283, and 808 +/- 272, respectively; P = 0.003). After prospective observation for 22 +/- 16 months, the combined endpoint of spontaneous sustained VT, ventricular fibrillation, appropriate defibrillator therapy, and death was predicted by inducibility of VT (relative risk 3.8, P = 0.008) and by the signal-averaged isoharmonic body surface map (relative risk 3.1, P = 0.02). CONCLUSION: These results confirm the diagnostic utility of signal-averaged isoharmonic body surface maps in a rigorously defined patient population.

The effect of procainamide on T wave alternans.

INTRODUCTION: The measurement of microvolt level T wave alternans (TWA) is a technique for detecting arrhythmia vulnerability. Previous studies demonstrated that the magnitude of TWA is dependent on heart rate. However, the effects of antiarrhythmic drugs on TWA are unknown. METHODS AND RESULTS: This was a prospective evaluation of intravenous procainamide on TWA in 24 subjects with inducible sustained ventricular tachycardia (VT). Measurements of TWA were performed at baseline in the drug-free state and after procainamide loading (1,204+/-278 mg). Recordings were made in normal sinus rhythm, and during atrial pacing at 100 beats/min and 120 beats/min. The magnitude of TWA in the vector magnitude lead was decreased by procainamide at all heart rates: 0.6+/-0.8 to 0.3+/-0.4 microV in sinus rhythm, 2.0+/-1.6 to 0.7+/-0.7 microV at 100 beats/min, and 3.0+/-2.0 to 1.7+/-1.8 microV at 120 beats/min (P<0.001 by analysis of variance). The sensitivity of TWA for the induction of VT at baseline was 5% in sinus, 60% at 100 beats/min, and 87% at 120 beats/min, while it decreased with procainamide to 5%, 19%, and 60%, respectively. Decreases in TWA in response to procainamide were independent of the antiarrhythmic effects on VT inducibility. CONCLUSIONS: These results indicate that the magnitude of TWA decreases with acute procainamide loading and this effect decreases the sensitivity of TWA for the induction of sustained VT.

Intravenous amiodarone suppression of electrical storm refractory to chronic oral amiodarone.

We report the case of an electrical storm in a cardiac arrest survivor with an ICD, in whom chronic oral amiodarone failed to suppress ventricular arrhythmias, and in whom intravenous amiodarone resulted in stability for 6 weeks prior to successful cardiac transplantation. Intravenous amiodarone can be successful in suppressing life-threatening ventricular arrhythmias, even when chronic oral amiodarone is unsuccessful.

Effect of heart rate on T wave alternans.

INTRODUCTION: T wave alternans (TWA) is a promising technique for detecting arrhythmia vulnerability. Previous studies in animals demonstrated that the magnitude of TWA is dependent on heart rate. However, the effects of heart rate on TWA in humans and the clinical relevance of this effect remain controversial. METHODS AND RESULTS: This was a prospective evaluation of pacing rate and monitoring lead configuration on TWA in subjects undergoing electrophysiologic study. Measurements of TWA were performed on 45 patients in the absence of antiarrhythmic drugs. Recordings were made in normal sinus rhythm and during atrial pacing at 100 and 120 beats/min. Sustained monomorphic ventricular tachycardia (VT) was induced in 29 patients with programmed stimulation. TWA in the vector magnitude lead increased with heart rate, independent of VT inducibility (0.4 +/- 0.7 microV, 1.6 +/- 1.9 microV, and 2.4 +/- 2.1 microV in sinus rhythm and at 100 and at 120 beats/min, respectively; P < 0.001). In addition, the diagnostic performance of TWA for inducible VT was dependent on heart rate (sensitivity 4%, 42%, and 65%, and specificity 100%, 93%, and 63% at 77, 100, and 120 beats/min, respectively). By analyzing orthogonal leads rather than the vector magnitude lead, the sensitivity is increased from 42% to 59% at 100 beats/min, but the specificity is reduced from 93% to 72%. CONCLUSION: These results indicate that TWA in humans is strongly dependent on heart rate with regard to both magnitude and diagnostic performance. The optimal heart rate for the measurement of TWA is between 100 and 120 beats/min and multiple leads should be monitored.

A comparison of pectoral and abdominal transvenous defibrillator implantation: analysis of costs and outcomes.

Traditionally cardioverter-defibrillator implantation was performed by surgeons under general anesthesia. However, with advances in lead and pulse generator technology, the surgical implantation technique has been simplified and routine pectoral pulse generator placement without general anesthesia is now possible. To assess the economic benefit of pectoral implantation, we analyzed 43 consecutive initial transvenous defibrillator implantations. The patients were grouped according to whether the implant was abdominal by a surgeon in the operating room (n = 23) or pectoral by an electrophysiologist in a laboratory (n = 20). The duration of hospitalization was significantly longer in the operating room than in the laboratory group (8.1 +/- 3.4 vs 5.8 +/- 2.4 days, p = 0.01), which was due primarily to the postoperative stay which averaged 1.9 days longer. Total costs were $40,274 +/- 6,861 for the operating room cohort and $32,546 +/- 3,634 for the lab group (p < 0.001). This reduction was due to a 32% lowering of professional costs and an 18% lowering of facility costs. We conclude that pectoral defibrillator implantation is cost effective and results in significant reductions of hospital stay.

Comparison of power- and temperature-guided radiofrequency modification of the atrioventricular node. Polaris Investigator Group.

The purpose of this study was to compare the performance and clinical outcome of radiofrequency ablation of the substrate of atrioventricular (AV) nodal reentrant tachycardia (AVNRT) when guided by power output or temperature monitoring. Two sequential multicenter studies of power-controlled and open-loop, temperature-controlled radiofrequency ablation were analyzed in 171 patients undergoing AV node modification for the treatment of AVNRT. After successful ablation of AVNRT, complete elimination of slow AV node pathway function was accomplished more often with than without temperature monitoring (92% vs 69%, p = 0.005). Greater power was delivered to each patient with than without temperature monitoring (median 47 W, range 10 to 57, vs median 35 W, range 5 to 68, p = 0.001). Acute elimination of tachycardia (100% vs 96%), 3-month recurrence (6% vs 8%), procedural times (162 vs 170 minutes), fluoroscopy times (24.6 vs 29.5 minutes), complications (6% vs 3%), and catheter removals to check for coagulum (8% vs 6%) did not differ between patients treated with and without temperature monitoring, respectively. Power- and temperature-controlled radiofrequency techniques are highly successful with low complication rates for slow pathway ablation. Temperature monitoring may allow the safe delivery of more power, and the more complete elimination of slow AV node pathway function.

Effect of biphasic waveforms on transvenous defibrillation thresholds in patients with coronary artery disease.

This study is a prospective, randomized comparison of monophasic and biphasic defibrillation thresholds in 19 patients with a single transvenous lead. Despite using reverse polarity and optimal tilts for the monophasic waveform, the defibrillation threshold was reduced with biphasic shocks from 15.8 +/- 11.3 to 11.5 +/- 6.1 (p <0.05) with comparable reductions of leading edge voltage and current.

Biphasic waveforms prevent the chronic rise of defibrillation thresholds with a transvenous lead system.

OBJECTIVES: The purpose of this study was to compare chronic changes in monophasic and biphasic defibrillation thresholds using a uniform transvenous lead system and testing protocol. BACKGROUND: Defibrillation thresholds increase over time in patients with nonthoracotomy lead systems. This increase can result in an inadequate chronic defibrillation safety margin and could limit the safety of smaller pulse generators, which have a reduced maximal output. However, previous studies of the temporal changes of defibrillation thresholds evaluated complex lead systems or monophasic shock waveforms, neither of which are used with current technology. METHODS: This study was a prospective, randomized assessment of the effects of shock waveforms on the changes of transvenous defibrillation thresholds over time. Paired monophasic and biphasic thresholds were measured both at implantation and at follow-up (250 +/- 105 days) in 24 consecutive patients who were not receiving antiarrhythmic drugs. The lead system was a dual-coil Endotak C lead, and reverse polarity shocks (distal coil = anode) were delivered. RESULTS: Monophasic defibrillation thresholds increased from (mean +/- SD) 13.7 +/- 6.0 J to 16.8 +/- 6.7 J (p = 0.02), whereas biphasic thresholds were unchanged (10.4 +/- 4.3 J to 10.2 +/- 4.8 J, p = 0.86) in the same patients. Shock impedance chronically increased (47.0 omega to 50.5 omega, p = 0.02) and was unaffected by waveform. CONCLUSIONS: These results indicate that biphasic shocks prevent the chronic increase in defibrillation thresholds with a transvenous lead system.

Clinical predictors of transvenous biphasic defibrillation thresholds.

Transvenous lead systems have become routine for defibrillator placement. However, previous studies of clinical predictors of an adequate nonthoracotomy defibrillation threshold (DFT) evaluated monophasic waveforms or more complex lead systems, including subcutaneous patches. Accordingly, this study is a prospective evaluation of the predictors of an adequate biphasic DFT in 114 consecutive patients undergoing cardioverter-defibrillator implantation with a single transvenous lead. For each subject, 38 parameters were assessed, including standard demographic, electrocardiographic, echocardiographic, and radiographic measurements. An adequate DFT (< or =20 J) was achieved in 92% of patients. Multivariable analysis revealed 2 independent factors predictive of a high threshold: echocardiographic measurements of left ventricular dilation (odds ratio = 0.16, 95% confidence interval 0.05 to 0.53, p = 0.003) and body size (odds ratio = 0.36, 95% confidence interval 0.17 to 0.73; p = 0.005). No patient with a normal left ventricular end-diastolic dimension had a high DFT, whereas 14% (9 of 66) of those with left ventricular dilation had elevated thresholds. When the DFT cutoff was lowered to 15 J, as is necessary with some downsized pulse generators, an adequate threshold was observed in 84% of patients and the same 2 independent predictors of high thresholds were found. These results indicate that an adequate transvenous DFT can be predicted from simple clinical parameters.

Chronic rise in monophasic defibrillation thresholds with a transvenous lead system.

This study was a prospective evaluation of chronic changes of defibrillation thresholds in 31 clinically stable patients with a single transvenous lead, optimal shock polarity, and uniform testing protocol. At a mean follow-up of 273 +/- 146 days, defibrillation thresholds increased 26%, from 13.2 +/- 5.6 J to 17.1 +/- 6:0 J (p < 0.001), and shock impedance increased from 46.2 +/- 7.0 omega to 51.2 +/- 6.2 omega (p < 0.001).

Clinical predictors of transvenous defibrillation energy requirements.

Nonthoracotomy and, more recently, transvenous lead systems have become routine for initial implantable cardioverter-defibrillator (ICD) placement. Previous studies of clinical predictors of nonthoracotomy defibrillation energy requirements evaluated multiple complex lead systems that included subcutaneous patches. However, the predictors of an adequate transvenous defibrillation threshold (DFT) have not been assessed previously. Accordingly, the present study is a prospective evaluation of DFT using a uniform testing protocol in 119 consecutive patients undergoing ICD implantation with a single transvenous lead. For each patient, 38 parameters were assessed including standard clinical, echocardiographic, and radiographic measures. An adequate monophasic DFT (< or =20 J) was achieved in 76% of patients. Multivariable analysis revealed 3 independent factors predictive of a high threshold: preoperative amiodarone use (odds ratio = 5.8, p < or =0.002), echocardiographic measures of left ventricular dilation (odds ratio = 0.47, p < or =0.005) and body size (odds ratio = 0.51, p < or =0.006). Patients receiving amiodarone who also had left ventricular dilation constitute a group at considerable (69%) risk for having a high DFT. In contrast, patients with neither of these risk factors have only an 11% chance of having a high threshold. We conclude that an adequate transvenous DFT can be predicted from simple clinical parameters.

Phase and group-delay characteristics of signal-averaged electrocardiograms from patients with ventricular tachycardia.

Fourier analysis of the signal-averaged ECG (SAECG) has previously revealed significant differences in magnitude spectra that differentiate patients with ventricular tachycardia (VT) from those without VT. To determine additional distinguishing features in the frequency domain, we analyzed phase spectra of SAECG's of sinus beats from 57 patients with VT, 65 without VT, and 20 normal controls. Unwrapped phase spectra from SAECG's of the entire cardiac cycle were calculated with respect to three fiducial points: onset of the P and Q waves, and the negative of the slope of the phase (group delay) for frequencies in the band, which accounted for 97.5% of the energy in the vector magnitude of the Frank SAECG leads. Phase spectra of SAECG's from patients with VT differed from the non-VT patients at frequencies > or = 21 Hz (p = 0.000039) for the P-wave fiducial, at frequencies > or = 60 Hz (p = 0.00085) for the Q-wave fiducial, and at frequencies < or = 62 Hz (p = 0.0035) for the 97.5% energy fiducial. Group delays in SAECG's from patients with and without VT differed from 10 to 26 Hz (p = 0.000016) for the P-wave fiducial, and from 14 to 24 Hz (p = 0.00000070) for the Q-wave fiducial. Group delays with respect to the Q-wave fiducial in the VT patients in the 14-24 Hz band were, on average, 9 ms and 5 ms longer than those of the non-VT's and normals, respectively. Thus, phase spectra of SAECG's contain previously undetected features that together with magnitude may be helpful in improving methods for stratifying the risk of VT.

Enhanced detection of distinguishing features in signal-averaged electrocardiograms from patients with ventricular tachycardia by combined spatial and spectral analyses of entire cardiac cycle.

BACKGROUND: Signals generated by myocardium responsible for ventricular tachycardia (VT) contribute to the entire QRS complex, ST segment, and T wave and are spatially distributed over the entire torso. However, current methods of signal-averaged ECG analysis restrict interrogation to the terminal QRS complex, do not include data on the body surface distributions of the distinguishing features detected, and have a limited clinical value because of a low positive predictive accuracy. Accordingly, we tested the hypothesis that frequency analysis of the entire cardiac cycle of spatially selected ECGs based on isoharmonic maps of the body surface enhance the detection of the unique spectral features in signal-averaged ECGs that differentiate patients with from those without VT. METHODS AND RESULTS: Isoharmonic maps of the body surface were calculated during sinus rhythm with the use of forward problem solutions for 32 patients with sustained VT, 30 without VT, and 10 healthy subjects and analyzed over a bandwidth of 0.05 to 470 Hz. Spectra of ECGs at the maximum and minimum of each patient's isoharmonic map of 1 to 7 Hz demonstrated a broadened bandwidth of significant separation (P < .05) for patients with from those without VT compared with the separation achieved with the use of Frank ECGs alone. Furthermore, the statistical significance within the bands of separation was greater for spatially selected ECGs compared with the Frank leads. Frank leads separated patients over the band from 11 to 84 Hz with a mean value of P = .0094. ECGs at the maximum of 1-to-7-Hz isoharmonic maps separated patients over the 8-to-111-Hz band with a mean value of P = .0062 (range, P < .05 to P < .0000001). ECGs at the minimum of 1-to-7-Hz isoharmonic maps extended the low-frequency end of the band of separation, which covered 0 to 69 Hz with a mean value of P = .0039 (range, P < .05 to P < .0000001). Subgroup analysis verified that results were independent of QRS duration. CONCLUSIONS: Spectral analysis of ECGs that are spatially selected for each patient is superior to orthogonal ECGs and augments detection of distinguishing features in ECGs that identify risk of VT. The new data acquired from analysis of spatially selected ECGs from individual patients provide the information on the specific frequency bands and an improved ECG-lead system required to refine methods of analysis of the signal-averaged ECG.

Spectral analysis of the cardiac cycle of signal-averaged Frank leads from patients with ventricular tachycardia.

Identification of the spectral features in electrocardiograms that distinguish patients prone to ventricular tachycardia (VT) is a prerequisite to increasing the diagnostic power of the signal-averaged electrocardiogram (SAECG). To determine distinguishing features of the magnitude spectrum, the spectra of SAECGs of sinus beats were analyzed over the entire cardiac cycle from 32 patients with VT, 30 without VT, and 10 normal control subjects. The magnitude spectra of the Frank SAECGs separated patients with VT from those without VT over the band from 7 to 140 Hz with a P value of .000000047. To determine distinguishing features of phase and group-delay spectra, SAECGs of sinus beats over the entire cardiac cycle were analyzed from 57 patients with VT, 65 without VT, and 20 normal control subjects. Unwrapped phase spectra from SAECGs of the entire cardiac cycle were calculated with respect to the onset of the Q wave. Phase spectra of SAECGs from patients with VT differed from those from non-VT patients at frequencies of 60 Hz or greater (P = .00085). Average group delays in SAECGs from patients with and without VT differed (P = .00000069) from 14 to 24 Hz. Group delays in the VT patients in the 14-24-Hz band were on average 9 ms and 5 ms longer than those of the non-VTs and normal subjects, respectively. Time-domain reconstructions demonstrated that distinguishing frequency bands were detectable throughout the QRS complex, ST-segment, and T wave in SAECGs from each group. Thus, the spectra of SAECGs over the cardiac cycle contain features that together with temporal features from throughout the cardiac cycle are essential in improving methods for stratifying risk of VT.

The combined toxicity of azidothymidine and antimycobacterial agents. A retrospective study.

Eight patients being treated for tuberculosis prior to starting azidothymidine therapy (study group) were compared with 56 patients who were treated with azidothymidine but not with antimycobacterial agents (control group). Toxicity was assessed 12 wk after the initiation of treatment with azidothymidine. Study group patients were more likely than control subjects to be either black or Hispanic (75% versus 30%, p = 0.02). There were no other statistically significant demographic differences. Seven study patients, and 20 control subjects experienced a fall in leukocyte count greater than 10% (88% versus 36%, p = 0.01). Within each group, patients with acquired immune deficiency syndrome (AIDS) were more likely to experience this degree of hematologic toxicity than were patients with AIDS-related complex (p = 0.03). However, analysis of covariance showed no significant differences between the groups after 12 wk of azidothymidine with regard to mean leukocyte or platelet counts, hemoglobin levels, or values for tests of liver function. The groups were similar in transfusion requirements and frequency of changes in azidothymidine dosage. Although this study was limited in power by the number of patients and the nonrandomized, retrospective design, the data suggest that patients can tolerate concurrent therapy with azidothymidine and antimycobacterial agents without unacceptable toxicity.