Replacing carmustine by thiotepa and cyclophosphamide for autologous stem cell transplantation in Hodgkin's and non-Hodgkin's B-cell lymphoma.

This study aimed to compare the real-life results of TECAM, a thiotepa-based conditioning regimen consisting of thiotepa (40 mg/m2 days -5 to -2), etoposide (200 mg/m2 days -6 to -3), cytarabine (200 mg/m2 days -4 to -1), cyclophosphamide (60 mg/kg day -3), and melphalan (60 mg/m2 days -2 to -1) with that of the conventional carmustine-based regimen BEAM. We reviewed 125 consecutive patients who underwent a first autologous transplantation (ASCT) for B-cell lymphomas at a large tertiary transplantation center between 1999 and 2014. TECAM (n=65) and BEAM (n=60) had comparable results (3yPFS 49 vs 62%, P=0.16; 3yOS 64 vs 71%, P=0.44; TRM 1.6 vs 5%, P=0.35) without a difference in toxicity or time to engraftment. Notably, comparable outcomes were observed even though patients treated with TECAM were older (55 vs 44) and had a trend towards more prior lines of therapy (>2 prior lines: 43 vs 27%, P=0.08). In this regard, 23% of TECAM patients were over the age of 65 yet could withstand therapy with similar results to younger patients. We conclude that, replacing carmustine by thiotepa and cyclophosphamide for ASCT conditioning, has comparable efficacy and safety profiles with a possible advantage in older patients.

Pluripotent Stem Cell-Based Platforms in Cardiac Disease Modeling and Drug Testing.

The ability to generate patient/disease-specific human pluripotent stem cell (hPSC)-derived cardiomyocytes (hPSC-CMs) brings a unique value to the fields of cardiac disease modeling, drug testing, drug discovery, and precision medicine. Further integration of emerging innovative technologies such as developmental-biology inspired differentiation into chamber-specific cardiomyocyte subtypes, genome-editing, tissue-engineering, and novel functional phenotyping methodologies should facilitate even more advanced investigations. Here, we review cornerstone concepts and recent highlights of hPSC-based cardiac disease modeling and drug testing.

Electroanatomic mapping of arrhythmogenic right ventricular dysplasia.

OBJECTIVES: We tested the hypothesis that spatial association of low-amplitude intracardiac electrograms can identify the presence, location and extent of dysplastic regions in arrhythmogenic right ventricular dysplasia (ARVD). BACKGROUND: Arrhythmogenic right ventricular dysplasia is a right ventricular (RV) cardiomyopathy characterized pathologically by fibrofatty infiltration and clinically by a spectrum of arrhythmias, sudden cardiac death and RV failure. Diagnosis of ARVD still remains a clinical challenge. METHODS: A three-dimensional electroanatomic mapping technique was used to map the RV of two groups of patients: 1) those with ARVD presenting with typical clinical, electrocardiographic and echocardiographic or magnetic resonance imaging (MRI) findings; and 2) those with structurally normal ventricles. RESULTS: The dysfunctional RV area could be identified only in the first group and was characterized by the presence of discrete areas of abnormally low-amplitude electrograms. Hence, the normal voltage values observed in the control group (unipolar: 11.9 +/- 0.3 mV; bipolar: 4.6 +/- 0.2 mV [mean +/- SEM]) and in the nonaffected zones in the ARVD group (unipolar: 10.4 +/- 0.2 mV; bipolar: 4.6 +/- 0.2 mV) were reduced significantly (p < 0.05) in the dysplastic areas (unipolar: 3.3 +/- 0.1 mV; bipolar: 0.5 +/- 0.1 mV). The pathologic process mainly involved the RV anterolateral free wall, apex and inflow and outflow tracts and ranged from patchy areas to uniform and extensive involvement. Concordance between electroanatomic findings and MRI or echocardiographic findings was noted in all patients. CONCLUSIONS: The pathologic substrate in ARVD can be identified by spatial association of low-amplitude endocardial electrograms, reflecting replaced myocardial tissue. The ability to accurately identify the presence, location and extent of the pathologic substrate may have important diagnostic, prognostic and therapeutic implications.

Characterisation of acute myocardial ischaemia in a canine model based on principal component analysis of unipolar endocardial electrograms.

The study presents a method for identifying endocardial electrical features relevant to local ischaemia detection at rest. The method consists of, first, normalisation of electrograms to a uniform representation; secondly, the use of principal component analysis to reduce the dimensionality of the electrogram vector space; and, thirdly, a search for a classification axis that matches the degree of ischaemia present in the tissue. Left ventricular myocardial states were assessed by echocardiography and NOGA mapping in eight dogs at baseline and then immediately after, 5h after and 3 days after occlusion of the left anterior descending coronary artery. Five principal components were required to approximate electrograms with an average error of less than 10% of the peak-to-peak amplitude. Correlations of 0.77, 0.80 and 0.84 were obtained between the principal component-based parameters and the echocardiography scores at the three ischaemic stages, respectively. Expression of these parameters in the time domain showed that the major changes occurred in the depolarisation segment of the endocardial electrogram as well as in the ST-segment. In conclusion, the proposed method provides a suitable alternative co-ordinate system for the classification of ischaemic regions and highlights signal segments that change as a result of pathology.

Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes.

The study of human cardiac tissue development is hampered by the lack of a suitable in vitro model. We describe the phenotypic properties of cardiomyocytes derived from human embryonic stem (ES) cells. Human ES cells were cultivated in suspension and plated to form aggregates termed embryoid bodies (EBs). Spontaneously contracting areas appeared in 8.1% of the EBs. Cells from the spontaneously contracting areas within EBs were stained positively with anti-cardiac myosin heavy chain, anti--alpha-actinin, anti-desmin, anti--cardiac troponin I (anti-cTnI), and anti-ANP antibodies. Electron microscopy revealed varying degrees of myofibrillar organization, consistent with early-stage cardiomyocytes. RT-PCR studies demonstrated the expression of several cardiac-specific genes and transcription factors. Extracellular electrograms were characterized by a sharp component lasting 30 +/- 25 milliseconds, followed by a slow component of 347 +/- 120 milliseconds. Intracellular Ca(2+) transients displayed a sharp rise lasting 130 +/- 27 milliseconds and a relaxation component lasting 200--300 milliseconds. Positive and negative chronotropic effects were induced by application of isoproterenol and carbamylcholine, respectively. In conclusion, the human ES cell--derived cardiomyocytes displayed structural and functional properties of early-stage cardiomyocytes. Establishment of this unique differentiation system may have significant impact on the study of early human cardiac differentiation, functional genomics, pharmacological testing, cell therapy, and tissue engineering.

Online myocardial viability assessment in the catheterization laboratory via NOGA electroanatomic mapping: Quantitative comparison with thallium-201 uptake.

BACKGROUND: The aim of this prospective study was to investigate the concordance between quantitative resting (201)Tl uptake as an established myocardial viability index and the electrical activity of the heart, determined by NOGA nonfluoroscopic electroanatomic mapping. METHODS AND RESULTS: The myocardial resting and late resting thallium uptakes of 384 myocardial segments from 32 patients (27 males aged 65+/-8 years) with previous myocardial infarction and chronic stable angina were compared with unipolar voltage potentials and local shortening of the left ventricle as assessed by electroanatomic mapping. The quantitative thallium uptake data were analyzed by polar map analysis by division into 12 comparable myocardial segments, as represented in electroanatomic mapping images. Unipolar voltage potentials exhibited a significant logarithmic correlation with both resting and late resting thallium uptake (attenuation corrected: r=0.660 and r=0.744; non-attenuation corrected: r=0.623 and r=0.721). Receiver operator characteristic analyses revealed unipolar voltage cutoff points of 12.0 mV (predictive accuracy 0.853, P< 0.001; sensitivity/specificity 81%) for normal myocardium and 6.4 mV (predictive accuracy 0.901, P< 0.001; sensitivity/specificity 82%) for nonviable myocardium assessed by attenuation-corrected (201)Tl late resting images and of 12.7 mV (predictive accuracy 0.822, P<0.001; sensitivity/specificity 75%) and 6.5 mV (predictive accuracy 0.808, P<0.001; sensitivity/specificity 73%) for non-attenuation-corrected late resting (201)Tl images. CONCLUSIONS: These results indicate that the unipolar voltage potentials obtained by electroanatomic mapping correlate well with standard quantitative late resting (201)Tl imaging for the evaluation of myocardial viability; thus, NOGA endocardial mapping provides useful "online" data at the time of catheterization, especially when information from other methods for viability assessment is unavailable.

Detailed endocardial mapping accurately predicts the transmural extent of myocardial infarction.

OBJECTIVES: This study delineates between infarcts varying in transmurality by using endocardial electrophysiologic information obtained during catheter-based mapping. BACKGROUND: The degree of infarct transmurality extent has previously been linked to patient prognosis and may have significant impact on therapeutic strategies. Catheter-based endocardial mapping may accurately delineate between infarcts differing in the transmural extent of necrotic tissue. METHODS: Electromechanical mapping was performed in 13 dogs four weeks after left anterior descending coronary artery ligation, enabling three-dimensional reconstruction of the left ventricular chamber. A concomitant reduction in bipolar electrogram amplitude (BEA) and local shortening indicated the infarcted region. In addition, impedance, unipolar electrogram amplitude (UEA) and slew rate (SR) were quantified. Subsequently, the hearts were excised, stained with 2,3,5-triphenyltetrazolium chloride and sliced transversely. The mean transmurality of the necrotic tissue in each slice was determined, and infarcts were divided into <30%, 31% to 60% and 61% to 100% transmurality subtypes to be correlated with the corresponding electrical data. RESULTS: From the three-dimensional reconstructions, a total of 263 endocardial points were entered for correlation with the degree of transmurality (4.6 +/- 2.4 points from each section). All four indices delineated infarcted tissue. However, BEA (1.9 +/- 0.7 mV, 1.4 +/- 0.7 mV, 0.8 +/- 0.4 mV in the three groups respectively, p < 0.05 between each group) proved superior to SR, which could not differentiate between the second (31% to 60%) and third (61% to 100%) transmurality subgroups, and to UEA and impedance, which could not differentiate between the first (<30%) and second transmurality subgroups. CONCLUSIONS: The degree of infarct transmurality extent can be derived from the electrical properties of the endocardium obtained via detailed catheter-based mapping in this animal model.

Attenuation of infarct size in rats and dogs after myocardial infarction by low-energy laser irradiation.

BACKGROUND AND OBJECTIVE: The aim of the present study was to investigate the possibility that low-energy laser irradiation attenuates infarct size formation after induction of chronic myocardial infarction (MI) in small and large experimental animals. STUDY DESIGN/MATERIALS AND METHODS: Laser irradiation was applied to the infarcted area of rats and dogs at various power densities (2.5 to 20 mW/cm(2)) after occlusion of the coronary artery. RESULTS: In infarcted laser-irradiated rats that received laser irradiation immediately and 3 days after MI at energy densities of 2.5, 6, and 20 mW/cm(2), there was a 14%, 62% (significant; P < 0.05), and 2.8% reduction of infarct size (14 days after MI) relative to non--laser-irradiated rats, respectively. In dogs, a 49% (significant; P < 0.01) reduction of infarct size was achieved. CONCLUSION: The results of the present study indicate that delivery of low-energy laser irradiation to infarcted myocardium in rats and dogs has a profound effect on the infarct size after MI.

Low-energy laser irradiation reduces formation of scar tissue after myocardial infarction in rats and dogs.

BACKGROUND: Low-energy laser irradiation (LELI) has been found to attenuate various biological processes in tissue culture and experimental animal models. The aim of the present study was to investigate the effect of LELI on the formation of scar tissue in experimentally induced chronic infarct in rats and dogs. METHODS AND RESULTS: Myocardial infarction (MI) was induced in 50 dogs and 26 rats by ligation of the left anterior descending coronary artery. After induction of MI, the laser-irradiated (LI) group received laser irradiation (infrared laser, 803-nm wavelength) epicardially. Control MI-induced non-laser irradiated (NLI) dogs were sham-operated, and laser was not applied. All dogs were euthanized at 5 to 6 weeks after MI. Infarct size was determined by TTC staining and histology. The laser treatment (P:<0.05) lowered mortality significantly, from 30% to 6.5%, after induction of MI. The infarct size in the LI dogs was reduced significantly (P:<0.0001) (52%) compared with NLI dogs. Histological observation of the infarct revealed a typical scar tissue in NLI dogs and cellularity in most of the LI dogs. Only 14+/-3% of the mitochondria in the cardiomyocytes in the ischemic zone (4 hours after MI) of LI MI-induced rats were severely damaged, compared with 36+/-1% in NLI rats. Accordingly, ATP content in that zone was 7.6-fold (significantly) higher in LI than in NLI rats. CONCLUSIONS: Our observations indicate that epicardial LELI of rat and dog hearts after chronic MI caused a marked reduction in infarct size, probably due to a cardioprotective effect of the LELI.

Three-dimensional endocardial impedance mapping: a new approach for myocardial infarction assessment.

Precise identification of infarcted myocardial tissue is of importance in diagnostic and interventional cardiology. A three-dimensional, catheter-based endocardial electromechanical mapping technique was used to assess the ability of local endocardial impedance in delineating the exact location, size, and border of canine myocardial infarction. Electromechanical mapping of the left ventricle was performed in a control group (n = 10) and 4 wk after left anterior descending coronary artery ligation (n = 10). Impedance, bipolar electrogram amplitude, and endocardial local shortening (LS) were quantified. The infarcted area was compared with the corresponding regions in controls, revealing a significant reduction in impedance values [infarcted vs. controls: 168.8 +/- 11. 7 and 240.7 +/- 22.3 Omega, respectively (means +/- SE), P < 0.05] bipolar electrogram amplitude (1.8 +/- 0.2 mV, 4.4 +/- 0.7 mV, P < 0. 05), and LS (-2.36 +/- 1.6%, 11.9 +/- 0.9%, P < 0.05). The accuracy of the impedance maps in delineating the location and extent of the infarcted region was demonstrated by the high correlation with the infarct area (Pearson's correlation coefficient = 0.942) and the accurate identification of the infarct borders in pathology. By accurately defining myocardial infarction and its borders, endocardial impedance mapping may become a clinically useful tool in differentiating healthy from necrotic myocardial tissue.

Accurate linear radiofrequency lesions guided by a nonfluoroscopic electroanatomic mapping method during atrial fibrillation.

Catheter-based continuous linear lesions may become a curative procedure for AF. The accuracy of guiding the application of continuous RF lesions by a nonfluoroscopic mapping system (NFM) during AF in goats was tested. The NFM system (Carto) uses magnetic fields to determine, in real time, the location and orientation of a 7 Fr ablation catheter tip. AF was induced in nine goats by intravenous infusion of methacholine (3-4 microg x kg(-1) min(-1)) and burst pacing. The three-dimensional atrial geometry was reconstructed using the median location of the mapping catheter tip during 30 seconds when in contact with each endocardial site. Sequential RF energy (60 seconds in a temperature-controlled mode [60 degrees C]) was delivered along a predetermined path to create longitudinal lesions in both atria. Sites to which RF energy was applied were tagged on the NFM map, enabling the operator to accurately navigate the catheter tip to the adjacent sites. In all cases (n = 14) the location, shape, length, and continuity of the linear lesions on the electroanatomic maps highly correlated with the autopsy findings. Average line length on the reconstructed maps was 32.3+/-4.1 mm, which highly correlated (r = 0.98, P<.001) with the lesions created in the pathological specimen (31.7+/-3.9 mm). The NFM system can guide the application of RF linear lesions in a highly accurate manner during AF. Moreover, the ability to tag the ablation sites on the three-dimensional maps together with real-time monitoring of the ablation catheter tip location enables delivery of RF energy to create reproducible, continuous, longitudinal lesions without the use of fluoroscopy.

Atrial linear ablations in pigs. Chronic effects on atrial electrophysiology and pathology.

BACKGROUND: Generation of long and continuous linear ablations is required in a growing number of atrial arrhythmias. However, deployment and assessment of these lesions may be difficult, and there are few data regarding their short- and long-term effects on atrial electrophysiology and pathology. METHODS AND RESULTS: A nonfluoroscopic mapping and navigation technique was used to generate 3-dimensional (3D) electroanatomic maps of the right atrium in 8 pigs. The catheter was then used to deliver sequential radiofrequency (RF) applications (power output gradually increased until 80% reduction in the amplitude of the unipolar electrogram) to generate a continuous lesion between the superior and inferior venae cavae. The animals were remapped 4 weeks after ablation during septal pacing. Lesion continuity was confirmed in all cases by the following criteria: (1) activation maps indicating conduction block [significant disparities in activation times (52.0+/-16.0 ms) and opposite orientation of the activation wave front on opposing sides of the lesion], (2) evidence of double potentials (interspike time difference of 52.3+/-17.1 ms), and (3) low peak-to-peak amplitude of the bipolar electrograms (0.7+/-0.6 mV) along the lesion. At autopsy, all lesions were continuous and transmural, averaged 50.5+/-6.7 mm, and were characterized histologically by transmural fibrosis throughout the length of the lesion. CONCLUSIONS: Long linear atrial ablation, created by sequential RF applications (using unipolar amplitude attenuation as the end point for energy delivery), results in long-term continuous and transmural lesions. Lesion continuity is associated with evidence of conduction block in the 3D activation maps and the presence of double potentials and low electrogram amplitude along the lesion.

Electromechanical characterization of chronic myocardial infarction in the canine coronary occlusion model.

BACKGROUND: Defining the presence, extent, and nature of the dysfunctional myocardial tissue remains a cornerstone in diagnostic cardiology. A nonfluoroscopic, catheter-based mapping technique that can spatially associate endocardial mechanical and electrical data was used to quantify electromechanical changes in the canine chronic infarction model. METHODS AND RESULTS: We mapped the left ventricular (LV) electromechanical regional properties in 11 dogs with chronic infarction (4 weeks after LAD ligation) and 6 controls. By sampling the location of a special catheter throughout the cardiac cycle at multiple endocardial sites and simultaneously recording local electrograms from the catheter tip, the dynamic 3-dimensional electromechanical map of the LV was reconstructed. Average endocardial local shortening (LS, measured at end systole and normalized to end diastole) and intracardiac bipolar electrogram amplitude were quantified at 13 LV regions. Endocardial LS was significantly lower at the infarcted area (1.2+/-0.9% [mean+/-SEM], P<0.01) compared with the noninfarcted regions (7.2+/-1.1% to 13. 5+/-1.5%) and with the same area in controls (15.5+/-1.2%, P<0.01). Average bipolar amplitude was also significantly lower at the infarcted zone (2.3+/-0.2 mV, P<0.01) compared with the same region in controls (10.3+/-1.3 mV) and with the noninfarcted regions (4. 0+/-0.7 to 10.2+/-1.5 mV, P<0.01) in the infarcted group. In addition, the electrical maps could accurately delineate both the location and extent of the infarct, as demonstrated by the high correlation with pathology (Pearson's correlation coefficient=0.90) and by the precise identification of the infarct border. CONCLUSIONS: Chronic myocardial infarcted tissue can be characterized and quantified by abnormal regional mechanical and electrical functions. The unique ability to assess the regional ventricular electromechanical properties in various myocardial disease states may become a powerful tool in both clinical and research cardiology.

Preliminary animal and clinical experiences using an electromechanical endocardial mapping procedure to distinguish infarcted from healthy myocardium.

BACKGROUND: A catheter-based left ventricular (LV) endocardial mapping procedure using electromagnetic field energy for positioning of the catheter tip was designed to acquire simultaneous measurements of endocardial voltage potentials and myocardial contractility. We investigated such a mapping system to distinguish between infarcted and normal myocardium in an animal infarction model and in patients with coronary artery disease. METHODS AND RESULTS: Measurements of LV endocardial unipolar (UP) and bipolar (BP) voltages and local endocardial shortening were derived from dogs at baseline (n=12), at 24 hours (n=6), and at 3 weeks (n=6) after occlusion of the left anterior descending coronary artery. Also, 12 patients with prior myocardial infarction (MI) and 12 control patients underwent the LV endocardial mapping study for assessment of electromechanical function in infarcted versus healthy myocardial regions. In the canine model, a significant decrease in voltage potentials was noted in the MI zone at 24 hours (UP, 42. 8+/-9.6 to 29.1+/-12.2 mV, P=0.007; BP, 11.6+/-2.3 to 4.9+/-1.2 mV, P<0.0001) and at 3 weeks (UP, 41.0+/-8.9 to 13.9+/-3.9 mV, P<0.0001; BP, 11.2+/-2.8 to 2.4+/-0.4 mV, P<0.0001). No change in voltage was noted in zones remote from MI. In patients with prior MI, the average voltage was 7.2+/-2.7 mV (UP)/1.4+/-0.7 mV (BP) in MI regions, 17.8+/-4.6 mV (UP)/4.5+/-1.1 mV (BP) in healthy zones remote from MI, and 19.7+/-4.4 mV (UP)/5.8+/-1.0 mV (BP) in control patients without prior MI (P<0.001 for MI values versus remote zones or control patients). In the canine model and patients, local endocardial shortening was significantly impaired in MI zones compared with controls. CONCLUSIONS: These preliminary data suggest that infarcted myocardium could be accurately diagnosed and distinguished from healthy myocardium by a reduction in both electrical voltage and mechanical activity. Such a diagnostic electromechanical mapping study might be clinically useful for accurate assessment of myocardial function and viability.

Electroanatomical mapping of the heart: basic concepts and implications for the treatment of cardiac arrhythmias.

The CARTO electroanatomical mapping system represents a paradigm shift in the ability to map the three-dimensional anatomy of the heart and determine the cardiac electrical activity at any given mapped point. The system associates anatomical structure and electrophysiological data and displays the combined information in an easily readable, visual fashion. The system consists of a roving mapping catheter with small magnetic sensors in the tip, a fixed sensor that acts as a reference point, a low magnetic field generating pad, and a data acquisition and display system. When the roving catheter is moved in three-dimensional space, its location in relation to the fixed sensor is monitored by the system, with a resolution of < 1 mm. By gating the acquisition of points in space to the cardiac electrical activity, points that represent both location and electrical activity at that location can be acquired and displayed on a computer screen. After acquiring a number of points, a three-dimensional representation is constructed, and may be displayed from any viewing projection. Clinical applications of the system include defining the mechanisms of arrhythmias, designing ablation strategies, guiding ablations, and improving the safety of mapping and ablation procedures by allowing localization of critical cardiac structures such as the atrioventricular node and His bundle. The system holds the potential to both further our understanding of arrhythmias and increase the safety, efficacy, and efficiency of catheter ablation.

Hemodynamic evaluation of the heart with a nonfluoroscopic electromechanical mapping technique.

BACKGROUND: Clinical cardiac volumetric measurement techniques are essential for assessing cardiac performance but produce significant inaccuracies in extrapolation of the volume of a three-dimensional (3D) object from two-dimensional images and lack the ability to associate cardiac electrical and mechanical activities. In this study, we tested the accuracy of cardiac volumetric measurements using a new catheter-based system. METHODS AND RESULTS: The system uses magnetic technology to accurately locate a special catheter at a frequency of 125 Hz and is currently used in the field of electrophysiology, in which activation maps are superimposed on the 3D geometry of the cardiac chamber. The mapping procedure is based on sequentially acquiring the location of the tip and local electrogram while in contact with the endocardium. The 3D geometry of the chamber is reconstructed in real time, and its volume could be calculated at every time step (8 ms). The volumetric measurements of the system were found to be highly accurate for simple phantoms (mean+/-SEM deviation, 2.3+/-1.1%), left ventricular casts (9.6+/-1.3%), and a dynamic test jig. In addition, left ventricular volumes of 12 swine were measured. Intraobserver and interobserver variabilities were found to be minimal (ejection fraction, 6.5+/-1.9% and 7.1+/-2.0%; stroke volume, 4.5+/-1.0% and 11.3+/-2.4%). Comparison with the thermodilution method for measuring stroke volume showed an average deviation of 8.1+/-2.2%. Typical pressure-volume loops were also obtained. CONCLUSIONS: The new mapping image provides, for the first time, simultaneous information regarding cardiac mechanics, hemodynamics, and electrical properties. Furthermore, all this information is achieved without the use of fluoroscopy, contrast medium, or complicated image processing.

Activation-repolarization coupling in the normal swine endocardium.

BACKGROUND: While abnormalities of activation and repolarization play an important role in arrhythmogenesis, little information is available on the interaction between their spatial dispersions in the heart. This study examined the effects of activation spread on the spatial distribution of the repolarization properties during different depolarization patterns. METHODS AND RESULTS: Left ventricular (LV) endocardial activation and repolarization patterns were mapped in 13 healthy pigs. LV local activation, repolarization, and activation-recovery interval (ARI) times were determined from the intracardiac unipolar electrograms, color-coded, and superimposed on a three-dimensional anatomic map of the ventricle generated with a nonfluoroscopic mapping system. ARI values correlated with the duration of monophasic activation potential recorded from onset of activation to time of 90% repolarization (r=.97, P<.01). Activation time range of the left ventricle was 42+/-5 ms (mean+/-SEM) during sinus rhythm and 54+/-5 ms during right ventricular septal pacing. ARI inversely correlated with the corresponding activation times during both sinus (r2=.76+/-.03) and paced (r2=.77+/-.02) rhythms. The longest ARIs were located at the sites of earliest activation and shortest at the latest activation areas, with gradual shortening between them. CONCLUSIONS: The spatial distribution of repolarization is dependent on the activation pattern. Repolarization dispersion in the healthy swine heart is relatively small as the result of tight coupling of the action potential duration to the activation process, assigning longer ARIs to sites activated earlier. This coupling reduces global and regional dispersion of repolarization and may serve as an important antiarrhythmic mechanism present in normal myocardium.

Guidance of radiofrequency endocardial ablation with real-time three-dimensional magnetic navigation system.

BACKGROUND: Ablation therapy for certain arrhythmias requires the formation of complex lesions based on electrical and anatomic mapping. We tested the accuracy and reproducibility of a nonfluoroscopic mapping and navigation (NFM) system to guide delivery of radiofrequency (RF) energy in the right atrium (RA) of swine. METHODS AND RESULTS: The NFM system uses an ultralow magnetic field to measure the real-time three-dimensional (3D) location of the tip of the locatable catheter. While in stable contact with the endocardium, between 30 and 40 consecutive tip locations were sampled and used for the 3D reconstruction of the RA geometry. The location of the catheter tip was presented in real time, superimposed over the RA geometry. We selected a point on the 3D reconstruction and delivered RF energy to that site via the tip of the locatable catheter. The catheter was then completely withdrawn and renavigated twice to the same point, at which RF energy was delivered again. At autopsy, the distance between the centers of the three ablation points (mean+/-SEM) was 2.3+/-0.5 mm (n=27). Similarly, we used the NFM system to guide the generation of linear lesions. The measured length of the linear lesions on the NFM 3D view was close to the actual lesion length measured at autopsy (correlation coefficient, .96; P=.002; n=6). Furthermore, the location, shape, and continuity of the linear lesions corresponded to the autopsy findings. CONCLUSIONS: We conclude that the NFM system can guide the application of RF energy without the use of fluoroscopy in a highly accurate and reproducible manner.

A novel method for nonfluoroscopic catheter-based electroanatomical mapping of the heart. In vitro and in vivo accuracy results.

BACKGROUND: Cardiac mapping is essential for understanding the mechanisms of arrhythmias and for directing curative procedures. A major limitation of the current methods is the inability to accurately relate local electrograms to their spatial orientation. The objective of this study was to present and test the accuracy of a new method for nonfluoroscopic, catheter-based, endocardial mapping. METHODS AND RESULTS: The method is based on using a new locatable catheter connected to an endocardial mapping and navigating system. The system uses magnetic technology to accurately determine the location and orientation of the catheter and simultaneously records the local electrogram from its tip. By sampling a plurality of endocardial sites, the system reconstructs the three-dimensional geometry of the chamber, with the electrophysiological information color-coded and superimposed on the anatomy. The accuracy of the system was tested in both in vitro and in vivo studies and was found to be highly reproducible (SD, 0.16 +/- 0.02 [mean +/- SEM] and 0.74 +/- 0.13 mm) and accurate (mean errors, 0.42 +/- 0.05 and 0.73 +/- 0.03 mm). In further studies, electroanatomical mapping of the cardiac chambers was performed in 34 pigs. Both the geometry and activation sequence were repeatable in all pigs. CONCLUSIONS: The new mapping method is highly accurate and reproducible. The ability to combine electrophysiological and spatial information provides a unique tool for both research and clinical electrophysiology. Consequently, the main shortcomings of conventional mapping-namely, prolonged x-ray exposure, low spatial resolution, and the inability to accurately navigate to a predefined site-can all be overcome with this new method.

3D cardiac imaging of electromechanical coupling.

A novel method for three dimensional (3D) electromechanical mapping of the heart is presented. The new method is based on utilizing special magnetically locatable catheters connected to a mapping and navigation system. The 3D electromechanical map of the chamber is reconstructed by sampling the location of the catheter tip throughout the cardiac cycle at a plurality of endocardial sites together with their local electrograms. The ability to spatially combine electrical and mechanical information may provide a useful tool for both research and clinical cardiology.