Efficacy of signal-averaged electrocardiography in the young orthotopic heart transplant patient to detect allograft rejection.

Endomyocardial biopsy is the gold standard survey for cardiac graft rejection. Signal-averaged electrocardiography (SAECG) identifies slowly conducting, diseased myocardium. We sought to determine whether SAECG is a sensitive, noninvasive transplant surveillance method in the young.Ninety-four SAECGs recorded prior to biopsy in 20 young transplant (OHT) patients and those from 15 healthy age-matched controls (CTL) were analyzed. In the OHT group, 56 no-rejection (NOREJ) (ISHLT grades 0 or 1 A) and 37 acute rejection (REJ) (ISHLT grades IB, 2, and 3A) SAECGs were compared, SAECGs were filtered at 40-255 Hz. Total QRS duration (QRSd), duration of terminal low amplitude of QRS under 40 microV (LAS), and root mean square amplitude of terminal 40 msec of QRS (RMS40) were compared.SAECGs were significantly different in CTL vs NOREJ but not in NOREJ vs REJ: QRSd, 81.7 +/- 8, 107.2 +/- 18.4, and 112.3 +/- 21.6 msec, respectively; LAS, (18 +/- 5.8, 23.6 +/- 10.7, and 27 +/- 14.8 msec, respectively; and RMS40, (169.3 +/- 100.4, 68 +/- 48.8, and 57.5 +/- 45.6 microV, respectively. Children following OHT exhibited significant differences in the SAECG compared to controls. Differences between the NOREJ and REJ groups were negligible. Therefore, SAECG may not be effective in detecting OHT rejection in the young.

A MULTICHANNEL FIBER-OPTIC MAPPING SYSTEM FOR INTRAMURAL RECORDING OF CARDIAC ACTION POTENTIALS.

Measuring cardiac action potentials at many sites within the ventricular wall is important for understanding cardiac arrhythmias; however, recording in the depth of the heart wall presents many difficulties. We have developed a multichannel optical mapping system for recording cardiac action potentials transmurally. Each channel uses a single small-diameter optical fiber to transmit and collect light from the cardiac tissue. Excitation light is supplied by low-power green lasers. Wavelength separation is performed with a dichroic mirror, and fluorescence is detected with a photodiode. We have recorded action potentials with an unfiltered signal-to-noise ratio (SNR) as high as 60:1 and a temporally filtered SNR as high as 200:1. The collection of fluorescence is optimized so that low excitation light intensity can be used, which increases the available recording time. Channels are modular and compact, and the system can be easily expanded to include additional channels, ratiometry or dual-dye mapping. In addition, the system is highly flexible and can be used for virtually any experiment from single cell recording to surface and transmural mapping of the whole heart.

Real-time three-dimensional intracardiac echocardiography.

Using catheter-mounted 2-D array transducers, we have obtained real-time 3-D intracardiac ultrasound (US) images. We have constructed several transducers with 64 channels inside a 12 French catheter lumen operating at 5 MHz. The transducer configuration may be side-scanning or beveled, with respect to the long axis of the catheter lumen. We have also included six electrodes to acquire simultaneous electrocardiograms. Using an open-chest sheep model, we inserted the catheter into the cardiac chambers to study the utility of in vivo intracardiac 3-D scanning. Images obtained include a cardiac four-chamber view, mitral valve, pulmonic valve, tricuspid valve, interatrial septum, interventricular septum and ventricular volumes. We have also imaged two electrophysiological interventional devices in the right atrium, performed an in vitro ablation study, and viewed the pulmonary veins in vitro.

Effect of pacing site on ventricular fibrillation initiation by shocks during the vulnerable period.

The critical point hypothesis for the upper limit of vulnerability (ULV) states that the site of S1 pacing should not affect the ULV S2 shock strength for a single S2 shock electrode configuration but may affect the S1-S2 interval at which sub-ULV shocks induce ventricular fibrillation (VF). Furthermore, early post-S2 activations leading to VF should arise in areas with low potential gradients of similar magnitude, regardless of the S1 site. This hypothesis was tested in 10 pigs by determining ULVs for three S1 sites [left ventricular apex (LVA), LV base (LVB), and right ventricular outflow tract (RVOT)] with one S2 configuration (LVA patch to superior vena cava catheter). T-wave scanning was performed with biphasic S2 shocks incremented from 60 V in 40-V steps and stepped up or down in 20- and 10-V steps. Activations and S2 potential gradients were recorded at 528 epicardial sites. Although shocks just below the ULV induced VF significantly earlier in the T wave when the S1 site was the RVOT than when it was the LVA or LVB, ULVs were not significantly different for the three S1 pacing sites. Early post-S2 activations arose closer to the S2 electrode for weak S2s but moved to distant low potential gradient areas as the S2 strengthened. Just below the ULV, early post-S2 activations arose in the RVOT when the S1 site was the LVA or LVB but arose along the RV base when the S1 site was the RVOT. Early site potential gradients were not significantly different just below the ULV (LVA: 8.2 +/- 4.1 V/cm; LVB: 8.6 +/- 4. 9 V/cm; RVOT: 8.7 +/- 4.4 V/cm). At the ULV, early post-S2 activations arose from the same areas but did not induce VF. The results support the critical point hypothesis for the ULV. For this S2 configuration, no single point in the T wave could be used to determine the ULV for all S1 sites.

Influence of epicardial patches on defibrillation threshold with nonthoracotomy lead configurations.

BACKGROUND: In previous studies, epicardial patch electrodes decreased transthoracic defibrillation efficacy. We studied the effects of two inactive epicardial 14-cm2 titanium mesh patches on defibrillation energy requirements with nonthoracotomy internal lead configurations. METHODS AND RESULTS: A 6/6-millisecond biphasic shock wave-form was delivered via several electrode configurations 10 seconds after ventricular fibrillation was initiated with a 60-Hz generator. In two series, a total of 16 dogs (weight, 23.3 +/- 2.4 kg) underwent an up-down defibrillation protocol. In the first series, the defibrillation threshold (DFT) was determined for each electrode configuration in the presence of two inactive epicardial patches. In the second series, DFTs were determined in the presence of an inactive right ventricular (RV) or left ventricular (LV) patch alone. For several nonthoracotomy lead configurations tested in the first 8 dogs, the mean +/- SD DFT energy increased 49% to 97% with two inactive patches on the heart compared with no patches on the heart as follows: RV to superior vena caval (SVC) electrode, from 8.9 +/- 2.6 to 18.0 +/- 14.3 J; RV to SVC plus subcutaneous array electrode, from 7.0 +/- 2.4 to 10.7 +/- 5.3 J; RV to subcutaneous pectoral plate electrode, from 6.2 +/- 1.3 to 11.4 +/- 4.0 J (P < or = .05). The lowest DFT was achieved by defibrillating between the epicardial patches (3.8 +/- 3.3 J). The second series showed that DFT voltage requirements increased significantly for all three nonthoracotomy lead configurations with the inactive LV patch alone (P < or = .05) but not with the inactive RV patch alone. CONCLUSIONS: Inactive epicardial patches can significantly increase the defibrillation energy requirements for nonthoracotomy lead configurations. This negative impact may be due to an insulating effect of the patches and to a disturbance of the potential gradient field under the patches. If the same holds true in patients, these results have clinical implications. Functioning epicardial patch leads should be incorporated in the defibrillation lead system if already present. If the LV patch is nonfunctioning, such as because of a lead fracture, the marked increase in DFT due to an inactive LV patch calls for thorough DFT testing during surgery and, in selected patients, may necessitate patch removal to produce an effective transvenous-based system.

Effect of rapid pacing and T-wave scanning on the relation between the defibrillation and upper-limit-of-vulnerability dose-response curves.

BACKGROUND: The critical-point and upper-limit-of-vulnerability (ULV) hypotheses predict that the ULV dose-response curve should be steeper and to the right of the defibrillation (DF) curve. Yet, some recent experimental data contradict this prediction. Two studies are presented that test two explanations for the contradiction: (1) Testing at a single point in the T wave underestimates the ULV dose-response curve and (2) ULV testing at normal heart rates does not mimic the mechanical or electrical state of the heart in ventricular fibrillation (VF). METHODS AND RESULTS: A nonthoracotomy lead system with a biphasic waveform was used throughout. In eight dogs, the dose-response curve widths (a measure of steepness) were compared between DF data and ULV data gathered at the peak (ULVPK), middownslope (ULVDWN), midupslope (ULVUP), and all times (scanning or ULVSCN) in the T wave. In another eight dogs, ULV data (ULVRAP) were gathered by scanning the T wave after 15 rapidly paced beats (166- to 198-ms pacing interval). The rapid pacing interval was chosen to more closely mimic the hemodynamics and activation rate of early VF. ULV data (ULVSTD) at normal heart rates were gathered for all animals. In the first study, scanning significantly reduced the ULV curve width (ULVSCN, 63.5 +/- 29.7 V; ULVPK, 81.9 +/- 45.2 V; ULVDWN, 116 +/- 36.5 V; DF, 105 +/- 22.0 V; P < .03) and significantly shifted the ULV curve to the right (ULV80 SCN, 410 +/- 62.6 V; ULV80 PK, 266 +/- 35.3 V; ULV80 DWN, 355 +/- 80.4 V; DF80, 427 +/- 60.9 V; P < .001). The subscript 80 signifies that the subject was left in normal sinus rhythm 80% of the time after that stimulus strength was delivered. In the second study, the ULVRAP curve was shifted dramatically to the right, the average ULV50 RAP being greater than the average DF90. Furthermore, 92% of the ULVRAP VF inductions occurred between 10 ms before and 50 ms after the peak of the T wave, suggesting that scanning of the entire T wave may not be necessary. CONCLUSIONS: With a single rapidly paced ULV sequence with limited T-wave scanning, it may be possible to estimate highly effective defibrillation doses with few VF episodes and high-voltage stimuli.

Predicting the potential gradient field in ventricular fibrillation from shocks delivered in paced rhythm.

A method of defibrillation threshold determination that utilizes low-strength shocks delivered in a benign rhythm would be desirable. Because the two-dimensional epicardial potential gradient (PG) is a shock parameter that is linked to defibrillation, we examined whether the epicardial PG measured for shocks delivered in paced rhythm could be used to predict the PG for defibrillation-strength shocks delivered in ventricular fibrillation (VF). In six open-chest pentobarbital-anesthetized pigs with left ventricular apex and right atrial internal defibrillation patches, we measured the epicardial PG field for shocks delivered in paced rhythm and during VF. We determined that there was a linear relationship between epicardial PG and shock strength for shocks delivered in paced rhythm. However, prediction of the PG measured for shocks in VF from those measured in paced rhythm resulted in a statistically significant overestimation of the PG in VF. We conclude that, for equivalent strength shocks, the epicardial PG field is weaker for shocks delivered in VF. This change in the potential gradient field can have an effect on defibrillation threshold estimates that are based on shocks delivered in paced rhythm.

Comparison of defibrillation probability of success curves for an endocardial lead configuration with and without an inactive epicardial patch.

OBJECTIVES: This study sought to assess the effect of passive "bystander" epicardial electrodes on defibrillation efficacy. BACKGROUND: We hypothesized that an inactive epicardial patch placed in an area of low potential gradient from an endocardial electrode shock might affect defibrillation efficacy through its effects on the shock field and the underlying potential gradient. METHODS: We studied the effects of an inactive 18-cm2 titanium mesh patch placed on the anterolateral left ventricular epicardium on the 50% probability of successful defibrillation. A biphasic shock with both phases 6 ms in duration was delivered between superior vena cava and right ventricular catheter electrodes 10 s after the electrical induction of ventricular fibrillation. Six dogs underwent an up/down defibrillation protocol randomized with or without the patch on the heart. RESULTS: Mean 50% (+/-) probability point for energy doubled with the conductive patch on the heart, from 8.0 +/- 3.2 to 16.8 +/- 7.0 J (p < 0.01), and leading-edge voltage increased from 334 +/- 64 to 477 +/- 98 V (p < 0.01). Mean 50% probability points for energy and leading-edge voltage were not significantly changed when the procedure was repeated using a nonconductive patch in another six dogs as a control group. In a saline-saturated foam model, measurements from electrodes placed around and under the patch revealed a 72% mean decrease in the potential gradient in the foam under the conductive patch. CONCLUSIONS: A passive defibrillator patch can markedly increase the energy requirements for defibrillation, probably by decreasing the potential gradient under the patch. These results suggest the use of caution when passive electrodes are present, for example, when a patient receives a nonthoracotomy defibrillator system while epicardial electrodes from a previously implanted system are left in place.

The effect of cardiac compression on defibrillation efficacy and the upper limit of vulnerability.

INTRODUCTION: We determined the effects of decreasing the ventricular blood volume and altering cardiac geometry on defibrillation, the upper limit of vulnerability (ULV), and the relationship between them. METHODS AND RESULTS: In six pigs, fibrillation/defibrillation trials were performed with a left ventricular apex patch to a superior vena cava catheter electrode configuration and a biphasic waveform. Thirty trials each were performed on a compressed versus noncompressed (normal) heart. Compression was achieved using direct mechanical ventricular actuation. Dose-response curves were constructed, and the 50% probability points (ED50) were compared for leading edge voltage (LEV), leading edge current (LEI), and total energy (TE). In another 12 pigs, triplicate defibrillation thresholds (DFTs) and ULVs were determined for each heart state. The T wave was scanned with shocks in 10-msec steps for determining the ULV. Compression resulted in decreased ED50s for LEV (delta = 138 +/- 77 V, P < 0.05, mean +/- SD), LEI (delta = 1.57 +/- 0.7 A, P < 0.05), and TE (delta = 4.9 +/- 3.6 J, P < 0.05) compared to normal. In the second study, compression significantly reduced DFT (P < 0.02) and ULV (P < 0.02) for LEV, LEI, and TE compared to normal. The ULV tended to be lower than the DFT for the normal heart state (delta = 23 +/- 46 V LEV: P = NS). However, the ULV was significantly greater than the DFT for the compressed heart state (delta = 19 +/- 25 V LEV; P < 0.03). CONCLUSIONS: Shock delivery during cardiac compression improves defibrillation efficacy. Additionally, cardiac compression decreases both DFT and ULV, which supports the ULV hypothesis of defibrillation. Finally, maintaining the heart's geometric and volumetric state during ULV testing in paced rhythm and DFT testing in ventricular fibrillation moves the ULV higher than the DFT-the position predicted by the ULV hypothesis for defibrillation.

Efficient electrode spacing for examining spatial organization during ventricular fibrillation.

Spatial organization has been observed during episodes of ventricular fibrillation (VF) by recording epicardial unipolar electrograms on a grid of electrodes. In such studies, the choice of spacing between electrodes is an important decision, affecting the resolution and the size of the domain to be studied. A basic tenet of sampling theory, the Nyquist criterion, states that an electrode spacing smaller than half the smallest significant wavelength is required to capture the important details of a spatially sampled process. In this paper, we suggest a method to choose a practical interelectrode spacing by examining wavenumber power spectra of high-resolution VF data recorded from a square 11 x 11 array of electrodes spaced 0.28 mm apart. The plaque was sutured on the epicardium near the left ventricular apex in seven anesthetized pigs. VF was induced with ac simulation. Unipolar extracellular electrograms were simultaneously recorded from each channel for 2 s after the induction of VF. Each signal was sampled in time at 1000 Hz. Wavenumber power spectra were calculated for 100 ms segments using the zero-delay wavenumber spectrum method, for a total of 140 power spectra. All spectra had dominant peaks at the origin and fell off rapidly with increasing wavenumber (decreasing wavelength). In all the spectra, every wavelength shorter than 1.4 mm contributed insignificant power. Furthermore, in 134 of 140 spectra (96%), insignificant power levels were associated with every wavelength shorter than 2.8 mm. These results suggest that, for unipolar extracellular electrodes, an intersensor spacing on the order of 1 mm is appropriate to study organization during early VF.