Telemetric Pacemakers Research Articles

Noninvasive monitoring of rejection therapy based on intramyocardial electrograms after orthotopic heart transplantation. Initial experience with 14 cases

Despite the use of increasingly specific immunosuppressive therapy, rejection remains the leading cause of death in cardiac transplant patients. Endomyocardial biopsy (EMB) is the gold standard for early detection and monitoring of cardiac transplant rejection. However, this approach is invasive and not suitable for routine use. A noninvasive alternative for monitoring cardiac transplant patients uses the analysis of the ventricular evoked response (VER) obtained by programmed electrical stimulation. Rejection-sensitive parameters (RSP) and infection-specific parameters (ISP) are extracted from changes in the slope of the T-wave and from the duration of repolarization, respectively. For the analysis of intramyocardial electrograms, separate left and right ventricular pacing at a rate of 100 beats/min and lasting 60 s is required, following the same protocol. From year 2000, telemetric pacemakers were implanted in 14 patients undergoing heart transplantation at this institution. A total of 95 endomyocardial biopsies and 275 ventricular evoked response measurements were carried out. Five out of 6 cases with significant rejection were correctly identified by RSP values below a threshold of 98% (sensitivity=80%, specifity=50%, negative predictive value=97%, positive predictive value=11%; P<0.002). Of the EMBs, 45% could have been saved if the diagnosis model had been used to indicate need for EMB. Noninvasive cardiac graft monitoring can reduce the need for surveillance biopsies and may offer a tool to optimize immunosupressive therapy after heart transplantation. Rejection grade 2 or higher can safely be detected.

Computerized heart allograft-recipient monitoring: a multicenter study.

Computerized heart allograft recipient monitoring (CHARM) is a unique concept of patient surveillance after heart transplantation (HTx), based on the evaluation of intramyocardial electrograms (IEGMs) recorded non-invasively with telemetric pacemakers. Previous open, single-center studies had indicated a high correlation between CHARM results and clinical findings. The present study was initiated to assess the suitability of CHARM for monitoring the absence of rejection in a blind, multicenter context. During the HTx procedure, telemetric pacemakers and two epimyocardial leads were implanted in 44 patients at four European HTx centers. IEGMs during pacing were recorded and transferred via the Internet to the CHARM computer center, for automatic data processing and extraction of diagnostically relevant information, i.e., the maximum slew rate of the descending part of the repolarization phase of the ventricular evoked response (VER T-slew). The study period comprised the first 6 months after HTx, during which the transplant centers were blind to the CHARM results. A single threshold diagnosis model was prospectively defined to assess the ability of the VER T-slew to indicate clinically significant rejection, which was defined as an endomyocardial biopsy (EMB) grade greater than or equal to 2, according to the grading system of the International Society for Heart and Lung Transplantation. All EMB slides from three centers were reviewed blind by the pathologist of the fourth center in order that agreement among the histological diagnoses at the various centers could be assessed. Totals of 839 follow-ups and 366 EMBs were obtained in 44 patients. Thirty-seven patients were alive at the end of the study period. Age at HTx, EMB grade distribution, and rejection prevalence varied significantly between the centers. Review of the EMB results showed considerable differences with respect to classification of significant rejection. Comparison of average VER T-slew values with and without rejection in the 15 patients who exhibited both states revealed significantly lower values under the influence of rejection (97+/-13% vs 79+/-15%, P<0.0001). Twenty out of the 25 cases with significant rejection were correctly identified by VER T-slew values below a threshold of 98% (sensitivity =80%, specificity =50%, negative predictive value =97%, positive predictive value =11%; P<0.0005). Of the EMBs, 48% could have been saved if the diagnosis model had been used to indicate the need for EMB. A high negative predictive value for the detection of cases with significant rejection has been obtained in a prospective, blind, multicenter study. The presented method can, therefore, be used to supplement patient monitoring after HTx non-invasively, in particular to indicate the need for EMBs. In centers with patient management similar to the ones who participated in the study, this may allow a reduction in the number of surveillance EMBs.

Computerized heart allograft recipient monitoring (CHARM) - a multicenter study

Computerized Heart Allograft Recipient Monitoring (CHARM) is a unique concept of patient surveillance after HTX based on intramyocardial electrograms (IEGM’s). Previous open, single center studies indicated a high correlation with clinical findings. The present study was initiated to assess the suitability of CHARM for monitoring the absence of rejection in the framework of a blinded, multicenter context. During the HTX procedure, telemetric pacemakers and two epimyocardial leads were implanted in 44 patients/4centers. IEGM’s during pacing were recorded and transfered via the Internet to the central workstation for automatic data processing and extracting the diagnostically relevant information, i.e. the maximum slew rate of the descending part of the repolarization phase of the ventricular evoked response (VER T-slew). A single threshold diagnosis model was prospectively defined in order to assess the ability of the VER T-slew to indicate clinically significant rejection (EMB grade = 2, according to the ISHLT grading). A total of 839 follow-ups and 366 EMBs have been obtained. 37 patients were alive at the end of the study period (6 months). Age at HTX, EMB grade distribution, and rejection prevalence varied significantly between the centers. Review of the EMB results showed considerable differences. Comparison of average VER T-slew values with and without rejection in the 15 patients who exhibited both states revealed significantly lower values under the influence of rejection (97 ± 13% versus 79 ± 15%, p < 0.0001). 20 out of the 25 cases with significant rejection were correctly identified by VER T-slew values below a threshold of 98% (SENS=80%, SPEC=50%, NPV=97%, PPV=11%, p < 0.0005). 48% of the EMBs could have been saved, if the diagnosis model would have been used to indicate the need for EMB. A high NPV for the detection of cases with significant rejection has been obtained in a prospective, blinded, multicenter study. The presented method can, therefore, be used to noninvasively supplement patient monitoring after HTX, in particular to reduce the number of EMBs.

Non-invasive cardiac allograft monitoring: the Graz experience

Background 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. Methods 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. Results 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%. Conclusions 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

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

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.

Long term bradycardia by electrical pacing: a new method for studying heart rate reduction.

The aim was to develop a method of inducing bradycardia on a chronic basis by electrical pacing and to study its effect upon myocardial capillarity in pigs. Farm pigs were instrumented with Medtronic dual chamber telemetric pacemakers and two leads, either both atrial or one atrial and one ventricular. Bradycardia was achieved by linking pacing stimuli to endogenous atrial or ventricular events for the different electrode positions respectively, and monitored postoperatively for 4-5 weeks by implanted telemetric ECG devices. Myocardial capillary supply (lectin staining) and myocyte cross sectional areas were then estimated in sections of the left ventricle. Heart rates were reduced by 40-50 beats.min-1 at operation from a resting rate of 110(SEM 3) beats.min-1 in eight animals and bradycardia maintained upon recovery from anaesthesia for up to five weeks, with no obvious limitations for the animals. After this time, heart rates measured under anaesthesia were found to remain low for up to 2 h after pacing had been switched off. There was no evidence of myocyte hypertrophy, yet mean capillary density.mm-2 was significantly increased by pacing, from 1470(50) to 1734(82), p < 0.02. It is possible to produce primary heart rate reduction in the pig by a novel means of pacing on a chronic basis, leading to increased myocardial capillary supply without myocyte hypertrophy. This method can provide a basis for future investigations of the beneficial effects of heart rate reduction in the vascularly compromised heart.