Intramyocardial Electrograms Research Articles

EDEN (Electrocardiographic Radial Depth Navigation): A Novel Approach to Navigate Inside Heart Muscle

BackgroundIntramyocardial guidewire navigation is a novel technique that allows free transcatheter movement within ventricular muscle. Guidewire radial depth, between endocardial and epicardial surfaces, is ambiguous by x-ray and echocardiography. ObjectivesThe aim of this study was to develop a simple tool, EDEN (Electrocardiographic Radial Depth Navigation), to indicate radial depth during intramyocardial guidewire navigation. Combined with routine imaging, EDEN facilitates a new family of intramyocardial catheter procedures to slice, reshape, pace, and ablate the heart. MethodsWe mapped intramyocardial electrograms of left and right ventricular walls and septum during open- and closed-chest swine procedures (N = 53), including MIRTH (Myocardial Intramural Remodeling by Transvenous Tether) ventriculoplasty. We identified radial depth–dependent features on unipolar electrograms. We developed a machine learning–based classifier to indicate categorical position, and modeled the findings in silico to test understanding of the physiology. ResultsEDEN signatures distinguished 5 depth zones throughout left and right ventricular free walls and interventricular septum. Relative ST-segment elevation magnitude best discriminated position and was maximum (40.1 ± 6.5 mV) in the midmyocardium. Subendocardial positions exhibited dominant Q waves with lower-amplitude ST segments (16.8 ± 5.8 mV), whereas subepicardial positions exhibited dominant R waves with lower-amplitude ST segments (15.7 ± 4.8 mV). EDEN was unaffected by pacing-induced left bundle branch block. ST-segment elevation declined over minutes and reappeared after submillimeter guidewire manipulation. Modeling recapitulated EDEN features. The machine learning–based classifier was 97% accurate. EDEN successfully guided MIRTH ventriculoplasty. ConclusionsEDEN provides a simple and reproducible real-time reflection of categorical guidewire-tip radial depth during intramyocardial guidewire navigation. Used in tandem with x-ray, EDEN enables novel, transcatheter, intramyocardial therapies such as MIRTH, SESAME (Septal Surfing Along Midline Endocardium), and cerclage ventriculoplasty.

Melatonin Prevents Early but Not Delayed Ventricular Fibrillation in the Experimental Porcine Model of Acute Ischemia.

Antiarrhythmic effects of melatonin have been demonstrated ex vivo and in rodent models, but its action in a clinically relevant large mammalian model remains largely unknown. Objectives of the present study were to evaluate electrophysiological and antiarrhythmic effects of melatonin in a porcine model of acute myocardial infarction. Myocardial ischemia was induced by 40-min coronary occlusion in 25 anesthetized pigs. After ischemia onset, 12 animals received melatonin (4 mg/kg). 48 intramyocardial electrograms were recorded from left ventricular wall and interventricular septum (IVS). In each lead, activation time (AT) and repolarization time (RT) were determined. During ischemia, ATs and dispersion of repolarization (DOR = RTmax − RTmin) increased reaching maximal values by 3–5 and 20–25 min, respectively. Ventricular fibrillation (VF) incidence demonstrated no relations to redox state markers and was associated with increased DOR and delayed ATs (specifically, in an IVS base, an area adjacent to the ischemic zone) (p = 0.031). Melatonin prevented AT increase in the IVS base, (p < 0.001) precluding development of early VF (1–5 min, p = 0.016). VF occurrence in the delayed phase (17–40 min) where DOR was maximal was not modified by melatonin. Thus, melatonin-related enhancement of activation prevented development of early VF in the myocardial infarction model.

Using intramyocardial electrograms combined with other noninvasive methods for monitoring acute rejection following human heart transplantation

Background Acute allograft rejection in heart transplantation remains as one of the major complications. Obligatory graft surveillance is still achieved with the invasive and expensive endomyocardial biopsy (EMB). Our study aimed to study the use of intramyocardial electrograms combined with other noninvasive methods for the monitoring of acute rejection after human heart transplantation. Methods Permanent pacemakers were implanted in 58 patients undergoing heart transplantations. Intramyocardial electrograms (IMEG) were recorded periodically and the results were compared with those from EMBs. The R wave amplitude of the IMEG was used as the index value, the average R wave amplitude at the third week following transplantation was considered as the baseline, and a reduction of &gt;20% compared with the baseline was regarded as a positive result. EMB was performed in cases of positive IMEG results and also at other times. Other noninvasive methods were used to help the diagnosis. Acute rejection (AR) was defined as International Society of Heart-Lung Transplantation grade IIIA or higher. Results We obtained 1231 IMEG records and 127 EMBs. Of the total 127 EMBs, 53 were positive, in which there were 42 IMEG positive results and 11 negative, while in the rest 74 negative EMBs, there were 9 IMEG positive results and 65 negative. The sensitivity of IMEG for the diagnosis of AR was 79.2%, and the specificity was 87.8%. The positive predictive value was 82.4% and the negative predictive value was 85.5%. Of the total of 1231 IMEG records, 51 were positive and 1180 were negative. Excluding 11 proved by EMB to be false negative, if the other 1169 were considered as no evidence of rejection, through the other noninvasive methods, AR diagnosed by this noninvasive monitoring strategy, the sensitivity was 79.2%, and the specificity was 99.2%. The positive predictive value was 82.4% and the negative predictive value was 99.1%. Conclusions IMEG can be used as a noninvasive method for monitoring AR following heart transplantation. It is a continuous, safe and inexpensive method, and could reduce the need for EMB combined with other noninvasive methods, without reducing the detection of rejection.

Ventricular Intramyocardial Electrograms and Their Expected Potential for Cardiac Risk Surveillance, Telemonitoring, and Therapy Management

Ventricular intramyocardial electrograms are recorded with electrodes directly from the heart either in intraventricular or epimyocardial position and may be acquired either from the spontaneously beating or from the paced heart. The morphology of these signals differs significantly from that of body surface ECG recordings. Although the morphology shows general characteristics, it additionally depends on different individual impacts. This problem of individual evaluation is briefly discussed. As an appropriate methodology for its solution, personalized referencing based on similarity averaging has been employed. A more general approach may be model-based signal interpretation, which is still under investigation. The preliminary results reveal a promising potential of intramyocardial electrograms for cardiac risk surveillance, e.g., for arrhythmia detection, recognition of rejection events in transplanted hearts, and assessment of hemodynamic performance. Employing implants with telemetric capabilities may render possible permanent and even continuous cardiac telemonitoring. Furthermore, the signals can be utilized for supporting therapy management, e.g., in patients with different kinds of cardiomyopathies. This paper shall demonstrate some preliminary results and discuss the expected potential.

Identifying coronary artery flow reduction and ischemia using quasistationary QT/RR-interval hysteresis measurements

Because myocardial ischemia induces QT/RR hysteresis, a correlation was hypothesized to exist between the extent of myocardial flow reduction and the magnitude of QT/RR hysteresis. Graded reductions in regional myocardial perfusion in the distribution of the left anterior descending coronary artery in open-chest pigs were used to model 1-vessel coronary artery disease. At each reduced level of left anterior descending coronary artery flow, the heart was electrically paced at progressively higher and lower rates between an initial control and maximum heart rate values. Digitized surface and intramyocardial electrograms and aortic pressure were used to measure QT/RR hysteresis, QT-interval adaptation, ST- and TQ-segment depression, and cardiac contractility. Intraexperimental blood samples were analyzed to assess inflammatory response (interleukin 6), oxidative stress (protein carbonyls), and myocyte injury (creatine kinase). Higher values of QT/RR hysteresis correlated with the severity of ischemia as assessed by TQ-segment depression in intramyocardial electrograms ( P = .002). Lower flow rates were strongly associated with higher values of QT/RR hysteresis and slower QT-interval adaptation ( P ≤ .004), and were less correlated with the magnitude of ST- and TQ-segment depression ( P ≥ .02). Significant increases in systemic measures of inflammation, oxidative stress, and cardiac myocyte injury and major decrease in cardiac contractility preceded the most severe stages of flow reduction (30% and 20% of normal flow). We determined QT/RR hysteresis index thresholds corresponding to these mechanical and immunochemical responses. QT/RR hysteresis is a strong indicator of reduced myocardial perfusion and may provide information for noninvasive assessment of mechanical and immunochemical changes associated with early stages of coronary artery disease.

The Prognostic Validity of the Ventricular Evoked Response (VER) Signals in Cardiac Transplantation

Computerized heart allograft rejection monitoring (CHARM) used for non-invasive rejection monitoring in heart transplant recipients is based on the analysis of ventricular evoked response (VER) signals. The aim of this study was to evaluate the prognostic validity of the Tslew(C), a parameter calculated from the VER. During orthotopic heart transplantation, 2 unipolar fractally coated screw-in leads were implanted epimyocardially, one to the left and one to the right ventricle, and connected to a telemetric pacemaker. Recordings of intramyocardial electrograms were performed routinely at the hospital. Data processing was done, artifacts were eliminated, and trend curves of the patients were displayed. Tslew(C) was calculated from the tangent of VER and evaluated from 105 patients. The patients were divided into survivor and non-survivor groups. For statistical analysis, the 2-tailed t-test was performed. Patients in the non-survivors group compared with the control group showed a significantly lower Tslew(C) in the final follow-up (p < 0.001). The differences were even more impressive in patients with recorded intramyocardial electrograms 30 days before death or with a cardiac reason for death. Tests were performed to find an optimal prognostic threshold of the Tslew(C), and the value of 26 mV was finally found. Tslew(C) can function as prognostic factor after orthotopic heart transplantation. Further studies should be initiated to provide the prognostic threshold so that patients would not be forced to show up routinely every 4 weeks for follow-up visits. Patients would only have to be admitted to the hospital if the Tslew(C) were less than this prognostic threshold.

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.

Model-based interpretation of intramyocardial electrograms for cardiac risk assessment and surveillance

Model-based interpretation of intramyocardial electrograms for cardiac risk assessment and surveillance

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.

Influence of antiarrhythmic drugs on telemetrically recorded, paced intramyocardial electrograms — Preliminary results

Influence of antiarrhythmic drugs on telemetrically recorded, paced intramyocardial electrograms — Preliminary results

Influence of antiarrhythmic drugs on telemetrically recorded, paced intramyocardial electrograms — Preliminary results

Influence of antiarrhythmic drugs on telemetrically recorded, paced intramyocardial electrograms — Preliminary results

Multi-channel data collection and visualization system for intramyocardial electrograms

The aim of the project was to develop a multichannel data acquisition system for the recording and visualisation of intramyocardial electrograms (IEGM) from both the spontaneously beating and the artificially paced heart. Signal processing comprises multi-step amplification, filtering (0.05-800 Hz), and AD conversion (12 Bit max. 6.25 kHz). IEGMs can be obtained either in unipolar or bipolar mode. Stimulation of the heart is achieved by an incorporated programmable dual-chamber pacemaker that can be selectively switched to the input channels. A LabView-based graphical user interface permits the programming of all system parameters via a microcontroller, and supports data acquisition and visualisation. The system can be used in animal experiments to monitor the spread of excitation across the heart, to measure propagation velocity, or to measure the impact of drugs and pathological changes on the morphology of IEGMs.

Non-invasive Rejection Monitoring with a New Implantable Multisensor Device.

1041 Following cardiac transplantation, allograft rejection is a serious complication which demands particular attention. Assessment of the biopsy histology is the gold standard method used to monitor rejection, but it has well-known limitations. Complementary echocardiography is frequently used as an important functional non-invasive tool. As we previously reported, the analysis of amplitude of intramyocardial electrograms (IMEG) is another non-invasive method which derives the IMEG data via commercially available pacemakers. The success of this method led us to develop an implantable multisensor (MUSE) system capable of measuring the uni- and bipolar intramyocardial electrogram (1), the impedance (2) of the myocardium of both ventricles, and the thickening (3) of the left ventricular free wall. All three parameters are known to be highly sensitive indicators of very early rejection-evoked changes of the myocardium. Whereas a drop in IMEG QRS-complex amplitude is a known parameter of rejection which cannot be reliably interpreted prior to 10 postoperative days, however, the impedance shows a different behaviour. Immediately postoperatively, an impedance increase represents the phase of reperfusion injury followed by a continuous decrease which represents a period of recovery from ischemia. An additional increase represents myocyte swelling which is a typical sign of the beginning of rejection (figure). From the wall thickening curve different parameters can be extracted and their changes observed daily such as maximal contraction and relaxation velocity, amplitude of wall thickening and duration of systole and diastole (figure). So, the MUSE device detects non-invasively the electrophysiological (IMEG), morphological (myocyte swelling; impedance), and functional (wall thickening) changes of incipient rejection. The device is equipped with a telemetric capability so that the patients are monitored at night when asleep in hospital or at home. The first six placements of MUSE devices in patients showed an impressive accuracy of data, since three rejection episodes were detected at a very early stage thus enabling treatment which could be limited to a temporary increase of their maintenance immunosuppression. This new device reduces the number and significance of endomyocardial biopsies, the frequency of echocardiographic examinations, follow-up costs, and improves the reliability of rejection monitoring and the quality of life of the transplanted patients.Figure: Course of intramyocardial impedance (left ventricular myocardium)Figure: Thickening of left ventricular wall five months postoperatively

Noninvasive detection of cardiac transplant rejection using electronic monitoring.

Cardiac transplantation has become the therapy of choice for the treatment of end-stage congestive heart failure. One of the major problems after cardiac transplantation is acute cellular rejection. The diagnosis of rejection is crucial to the management of transplant patients because rejection must be successfully diagnosed and reversed. Endomyocardial biopsy is the major method for detecting cardiac transplant rejection; however, this approach is invasive and is associated with morbidity and mortality. One noninvasive approach for detecting rejection is to monitor changes in the intramyocardial electrograms using pacemakers. Changes in the ventricular evoked response amplitude (VERA) obtained during ventricular pacing have been correlated with the presence of acute cellular rejection in both single center studies in Europe and a multicenter trial in five transplant centers in the United States. Given the high negative predictive value for the VERA, this approach may provide a screen to determine if individual patients require more invasive procedures such as endomyocardial biopsy and may aid in reducing the number of biopsies needed.

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.

Intramyocardial electrograms for non-invasive rejection monitoring: initial experience with an infection-specific parameter

Non-invasive rejection monitoring based on the analysis of paced intramyocardial electrograms enables repeated or even daily graft surveillance. The rejection-sensitive parameter is calculated from the maximum slope of the descending part of the t wave. Biopsy-proven rejection grade 2 or higher (ISHLT classification) can safely be detected. Nevertheless, infection influences the rejection-sensitive parameter in the same manner as does rejection (99% negative predictive value for rejection grade 2 or higher, 17% positive predictive value). We defined the infection-specific parameter as the time on the O line between the pacemaker stimulus and the crossover with the maximum slope of the descending part of the t wave. Patients were classified prospectively according to infection status: patients without infection and those with clinically apparent infection. Patients with clinically apparent infections had a significantly longer infection-specific parameter. A simultaneous decrease of the rejection-sensitive parameter and an increase in the infection-specific parameter was observed during clinical infection: a decrease in the rejection-sensitive parameter and no changes in the infection-specific parameter were observed during rejection. This preliminary analysis revealed that discrimination of rejection and infection might be possible by the analysis of intramyocardial electrograms.

Intramyocardial electrograms for non-invasive rejection monitoring: initial experience with an infection-specific parameter

Abstract Non-invasive rejection monitoring based on the analysis of paced intramyocardial electrograms enables repeated or even daily graft surveillance. The rejection-sensitive parameter is calculated from the maximum slope of the descending part of the t wave. Biopsy-proven rejection grade 2 or higher (ISHLT classification) can safely be detected. Nevertheless, infection influences the rejection-sensitive parameter in the same manner as does rejection (99% negative predictive value for rejection grade 2 or higher, 17 % positive predictive value). We defined the infection-specific parameter as the time on the O line between the pacemaker stimulus and the crossover with the maximum slope of the descending part of the t wave. Patients were classified prospectively according to infection status: patients without infection and those with clinically apparent infection. Patients with clinically apparent infections had a significantly longer infection-specific parameter. A simultaneous decrease of the rejection-sensitive parameter and an increase in the infection-specific parameter was observed during clinical infection; a decrease in the rejection-sensitive parameter and no changes in the infection-specific parameter were observed during rejection. This preliminary analysis revealed that discrimination of rejection and infection might be possible by the analysis of intramyocardial electrograms.

Introducing a New Clinical Method for Noninvasive Rejection Monitoring After Heart Transplantation to Clinical Practice: Analysis of Paced Intramyocardial Electrograms

Introducing a New Clinical Method for Noninvasive Rejection Monitoring After Heart Transplantation to Clinical Practice: Analysis of Paced Intramyocardial Electrograms

Monitorização de transplante cardíaco usando análises do eletrograma intracavitário

Uma série de registros do eletrograma intracavitário tem sido utilizada para monitorização não invasiva da rejeição em pacientes transplantados usando um marcapasso de dupla câmara e eletrodos endocavitários revestidos com estrutura fractal. Os sinais têm sido avaliados usando o sistema CHARM (Computerized Heart Acute Rejection Monitoring _ sistema computadorizado para monitorização da rejeição cardíaca aguda). Os relatórios obtidos com este sistema contêm curvas com parâmetros sensíveis à rejeição, que demonstram uma boa correlação com a clínica e os resultados das biópsias convencionais. A monitorização a longo prazo, usando estas análises, mostrou ser uma ferramenta valiosa no acompanhamento destes pacientes.