P. Kastner

Intramyocardial Electrogram Variability in the Monitoring of Graft Rejection After Heart Transplantation

The ventricular evoked response is a well‐standardized electrophysiological signal that can be used for noninvasive, long‐term cardiac transplant monitoring. Rejection‐sensitive and infection‐specific parameters extracted from intramyocardial electrograms correlate with clinical results. The influences of pacing rate, transition from intrinsic to paced rhythm and positional changes on the diagnostic parameters were studied. Increasing the pacing rate shortened the ventricular evoked response and directly influenced the infection specific parameter. The rejection‐sensitive parameter remained stable at pacing rates between 100 and 120 beats/min. Measurements made immediately after the patient assumed a supine position and after switching to paced rhythm showed a decrease in the rejection‐sensitive parameter. A change in position from supine to upright did not influence the rejection‐sensitive parameter, but higher values were measured after returning to the supine position. In conclusion, noninvasive recordings of the ventricular evoked response for monitoring of cardiac allograft should be done at the same time of day, at the same pacing rate, and with the patient resting for at least 5 minutes before measurements are made.

Non-invasive cardiac allograft monitoring: the Graz experience

Based on previous reports by our group, initial studies on non-invasive cardiac graft monitoring have been presented recently. In this study we define new parameters to monitor rejection and infection after heart transplantation (HTX) the ventricular evoked response (VER) T-slew rate parameter is defined as the maximum negative slope in the descending part of the repolarization phase of the VER. We calculated the VER duration parameter in milliseconds and defined it as the time between the pacemaker spike and the cross-over of the baseline, with the slope line used to calculate the VER T-slew rate. During the HTX procedure, we implant wide-band telemetric pacemakers and fractally coated, epimyocardial electrodes (Physios CTM 01 and ELC 54-UP, Biotronik; Berlin, Germany). During each follow-up and on biopsy days, intramyocardial electrogram sequences were obtained and sent via the Internet to the central data-processing unit in Graz. We scored the infection status of the patients before data acquisition. The VER parameters were automatically calculated and send back within a few minutes. We prospectivly compared 1,613 follow-ups from 42 patients with biopsy (International Society of Heart and Lung Transplantation grading) and infection classification. The VER duration parameter did not change during rejection; however, we found an increase during clinically apparent infection. The VER T-slew rate parameter was lower during rejection grade 2 or higher, as well as during clinically apparent infection. The negative predictive value to rule out rejection was 99%. Our results indicate that rejection and infection cause different, reproducible effects on the electrical activity of the transplanted heart. Non-invasive cardiac graft monitoring may reduce the need for surveillance biopsies and may offer a tool to optimize immunosuppressive therapy after HTX.

Non-invasive graft monitoring after heart transplantation: rationale to reduce the number of endomyocardial biopsies.

Abstract The endomyocardial biopsy is invasive, reduces quality of life and cannot be repeated daily. Initial studies on noninvasive cardiac graft monitoring have been presented recently. During the heart transplant procedure, we implanted wideband telemetric pacemakers and fractally coated, epimyocardial electrodes. On biopsy days and during each follow‐up, intramyocardial electrogram sequences were obtained. The maximum T‐slew rate from the ventricular evoked response (VER) was automatically calculated and compared to the biopsy results (n = 331, ISHLT grading). The VER T‐slew rate was significantly lower during rejection grade 2 or higher. The negative predictive value to exclude rejection was 98%. Using a single threshold diagnosis model, 74% of the biopsies could have been avoided. Noninvasive cardiac graft monitoring can reduce the need for surveillance biopsies and may offer a tool to optimize immunosuppressive therapy after heart transplantation

Hemodynamic assessment by evaluation of intramyocardial electrograms

The influence of hemodynamic variation on intramyocardial electrograms was investigated by combining clinical intramyocardial electrogram recordings with computerized modeling of the heart. Paced intramyocardial electrograms were recorded in heart transplant patients using telemetric pacemakers. Different hemodynamic filling states of the heart have been achieved by variation of the pacing rate. The results of the regression analysis between the pacing rate and parameters of the depolarization phase were used to set the parameters of the computer model that allows to simulate the origination of the ventricular evoked response and to consider influences of geometric variation. The experimental and theoretical results show a distinct and comparable impact of the hemodynamic state of the heart on the depolarization phase of paced intramyocardial electrograms.

Correlation between paced epimyocardial electrograms and stroke volume in heart transplants

In 10 heart transplant patients different hemodynamic states have been forced by randomized changes of pacing rate (PR) and postural variations (overall 40, 4/spl plusmn/1 per patient). Cardiac output assessed with thermodilution technique was compared to the ventricular evoked response (VER) recorded with telemetric pacemakers from epimyocardial leads. Linear regression analysis between the negative extremum during the depolarization phase of the VER (R/sub amp/) and the stroke volume (SV=CO/PR) resulted in the equation: R/sub amp/[%]=140-0.4*SV[%] with r=0.89 and p<0.00001. This result confirms previously reported results of a distinct relation between the negative extremum of paced epimyocardial ECGs and geometrical variations of the heart.

The influence of infectious disease on ventricular evoked responses from heart transplants

Telemetric recording and subsequent analysis of intramyocardial electrograms offer a noninvasive method for patient monitoring after heart transplantation. Decreasing electrical activity indicates both episodes of rejection and infection. Analysis of the duration of the ventricular evoked response recorded during pacing reveals a significant increase of this parameter only during infection. In many cases, this additional information can be used to differentiate between the two pathological effects and to enhance the specificity of the method.

Intramyocardial electrograms from spontaneous and paced heart beats, telemetrically recorded from different right ventricular positions

Intramyocardial electrograms from the spontaneously beating and the paced heart were recorded in 8 heart transplants for rejection monitoring, using telemetric dual chamber pacemakers and two epimyocardial leads, located at two different right ventricular positions. Linear regression analysis of the rejection sensitive parameters showed that the correlation between the two electrodes was significantly higher for the paced than for the spontaneous heart beats.

Correlation between amplitude and RR interval of premature QRS complexes from intramyocardial electrograms

Intramyocardial electrograms have been recorded noninvasively via telemetric pacemakers from spontaneously beating heart transplants. The amplitudes of premature QRS complexes have been compared to those of normal QRS complexes. Linear regression analysis revealed increased amplitudes, which are assumed to be due to the reduced filling pattern of the premature beats. Hence, intramyocardial electrograms contain haemodynamic information.

Noninvasive assessment of cardiac conduction velocity using telemetric pacemakers and two ventricular electrodes

Intramyocardial electrograms were recorded noninvasively in 20 heart transplants using telemetric pacemakers and two epimyocardial leads, located at two different ventricular positions. One electrode was used to stimulate and the other electrode was used to sense the electrical activity of the heart and vice versa. Linear regression analysis of the time from the stimulus to the steepest negative slope of the electrograms revealed increasing values with increasing anatomical distance and a symmetrical behavior with respect to the two leads. This indicates the close relationship of this parameter to ventricular conduction velocity.

Monitorização de transplante cardíaco usando análises do eletrograma intracavitário

Serial intramyocardial electrogram recordings have been performed for noninvasive rejection monitoring in patients after heart transplantation using implanted telemetric dual-chamber pacemaker and fractally coated endocardial loads. The signals have been evaluated using the CHARM (Computerized Heart Acute Rejection Monitoring) system. The reports containing the trend curves of the rejection sensitive parameters show good correlation with the patients clinical course and the results of endomyocardial biopsy. Long-term cardiac transplant monitoring using intramyocardial electrograms is a valuable tool for clinical patient management.