Ventricular mapping during atrial and ventricular pacing. Relationship of multipotential electrograms to ventricular tachycardia reentry circuits after myocardial infarction.

AIMS: Conduction through separated myocyte bundles causes multipotential electrograms and reentrant ventricular tachycardia. We hypothesized that without initiating tachycardia, the reentry region could be detected by analysing the change in multipotential electrograms during two different activation sequences. METHODS AND RESULTS: During catheter mapping and ablation in 16 patients with ventricular tachycardia late after infarction ventricular electrograms were recorded from 1072 sites during atrial and right ventricular paced ventricular activation. Multipotential electrograms were present during both activation sequences at 285 (27%) sites, during atrial pacing only at 159 (15%) sites and during right ventricular pacing only at 152 (14%) sites. Sites with multipotential electrograms during both activation sequences were more often related to a ventricular tachycardia circuit isthmus (43%) as compared to sites where such electrograms were present during one activation sequence (20%). Multipotential electrograms with >2 low amplitude deflections and a >100 ms difference in duration between the two activation sequences were infrequent but highly predictive of the reentry circuit. CONCLUSION: Regions with fixed multipotentials consistent with conduction block might be useful guides for ablation approaches that target large regions of the infarct, but are not sufficiently specific to be the sole guide for focal ablation approaches.

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.

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.

Long-term effect of low energy laser irradiation on infarction and reperfusion injury in the rat heart.

Low-energy laser irradiation (LELI) has been found to modulate biological processes. The present study investigated the effect of LELI on infarct size after chronic myocardial infarction (MI) and ischemia-reperfusion injury in rats. The left anterior descending (LAD) coronary artery was ligated in 83 rats to create MI or ischemia-reperfusion injury. The hearts of the laser-irradiated (LI) rats received irradiation after LAD coronary artery occlusion and 3 days post-MI. At 14, 21, and 45 days post-LAD coronary artery permanent occlusion, infarct sizes (percentage of left ventricular volume) in the non-laser-irradiated (NLI) rats were 52 +/- 12 (SD), 47 +/- 11, and 34 +/- 7%, respectively, whereas in the LI rats they were significantly lower, being 20 +/- 8, 15 +/- 6, and 10 +/- 4%, respectively. Left ventricular dilatation (LVD) in the chronic infarcted rats was significantly reduced (50-60%) in LI compared with NLI rats. LVD in the ischemia-reperfusion-injured LI rats was significantly reduced to a value that did not differ from intact normal noninfarcted rats. Laser irradiation caused a significant 2.2-fold elevation in the content of inducible heat shock proteins (specifically HSP70i) and 3.1-fold elevation in newly formed blood vessels in the heart compared with NLI rats. It is concluded that LELI caused a profound reduction in infarct size and LVD in the rat heart after chronic MI and caused complete reduction of LVD in ischemic-reperfused heart. This phenomenon may be partially explained by the cardioprotective effect of the HSP70i and enhanced angiogenesis in the myocardium after laser irradiation.

Cardiac contractility modulation with the impulse dynamics signal: studies in dogs with chronic heart failure.

The intravenous use of positive inotropic agents, such as sympathomimetics and phosphodiesterase inhibitors, in heart failure is limited by pro-arrhythmic and positive chronotropic effects. Chronic use of these agents, while eliciting an improvement in the quality of life of patients with advanced heart failure, has been abandoned because of marked increase in mortality when compared to placebo. Nevertheless, patients with advanced heart failure can benefit from long-term positive inotropic support if the therapy can be delivered 'on demand' and in a manner that is both safe and effective. In this review, we will examine the use of a novel, non-stimulatory electrical signal that can acutely modulate left ventricular (LV) contractility in dogs with chronic heart failure in such a way as to elicit a positive inotropic support. Cardiac contractility modulation (CCM) with the Impulse Dynamic(trade mark) signal was examined in dogs with chronic heart failure produced by intracoronary microembolizations. Delivery of the CCM signal from a lead placed in the great coronary vein for periods up to 10 minutes resulted in significant improvements in cardiac output, LV peak+dP/dt, LV fractional area of shortening and LV ejection fraction measured angiographically. Discontinuation of the signal resulted in a return of all functional parameters to baseline values. In cardiomyocytes isolated from dogs with chronic heart failure, application of the CCM signal resulted in improved shortening, rate of change of shortening and rate of change of relengthening suggesting that CCM application is associated with intrinsic improvement of cardiomyocyte function. The improvement in isolated cardiomyocyte function after application of the CCM signal was accompanied by an increase in the peak and integral of the Ca(2+) transient suggesting modulation of calcium cycling by CCM application. In a limited number of normal dogs, intermittent chronic delivery of the CCM signal for up to 7 days showed chronic maintenance of LV functional improvement. In conclusion, pre-clinical results to date with the Impulse Dynamics CCM signal indicate that this non-pharmacologic therapeutic modality can provide short-term positive inotropic support to the failing heart and as such, may be a useful adjunct in the treatment of advanced heart failure. Additional, long-term studies in dogs with heart failure are needed to establish the safety and efficacy of this therapeutic modality for the chronic treatment of this disease syndrome.

Electrical modulation of cardiac contractility: clinical aspects in congestive heart failure.

Heart failure is a highly prevalent disease in western society. Drug therapies aimed at increasing myocardial contractility have been associated with decreased survival. Several short and mid term clinical studies have suggested adjuvant or alternative therapies to congestive heart failure using modified pacing techniques that were aimed to increase contractility (e.g. Paired pacing) or restore synchrony of contraction (biventricular pacing). While delivery of paired pacing was abandoned during the early 70's, biventricular pacing has recently emerged as an adjuvant treatment to limited group of congestive heart failure patients with aberrant left ventricular conduction. In this brief review, we describe our initial safety and efficacy experience in patients with heart failure using a novel non-stimulatory electrical approach to the delivery of positive inotropic therapy to the failing myocardium. The study suggests that unlike modified pacing techniques, delivery of the signal to the left ventricle during the refractory period resulted in a rapid increase in myocardial contractility and improved hemodynamic performance. The near instantaneous contractility improvement achieved by this type of stimulus was shown to be safe and effective independently of the primary cause of heart failure or the function of the conduction system. Unlike pharmacologic treatments, which have a relatively constant effect, use of electrical stimuli may prove useful as a new therapeutic modality in the treatment of heart failure with which contractility can be improved when and as needed.

Assessment of NOGA catheter stability during the entire cardiac cycle by means of a special needle-tipped catheter.

The NOGA system maps regional myocardial function and delivers local catheter-based therapeutics, requiring stability and precise localization of the catheter tip throughout the cardiac cycle. A special catheter having a retractable needle at its tip was used to compare tip stability with and without needle insertion into the myocardium, assuming this prevents catheter slippage. For multiple sites in seven pig left ventricles, we recorded sets of three consecutive point locations: pre-, post-, and during needle insertion. In-point location stability (LocStab), defined as the mean displacement between catheter tip trajectories of two consecutive cardiac cycles at a specific point, did not differ among the three groups of points (mean, 1.33 +/- 0.61 mm; P = 0.37 by ANOVA), indicating that trajectories are equally stable and repeatable with or without needle insertion. Between-point LocStab(p1,p2), i.e., displacement between the trajectories of two different points (p1 and p2) at the same location, was not increased when p1 = a needle insertion point and p2 = a noninsertion point, compared to both p1,p2 = noninsertion points, suggesting that slippage of noninsertion points is negligible. In conclusion, catheter tip trajectories at any location are highly stable throughout the cardiac cycle.

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.

Recovery from sarafotoxin-b induced cardiopathological effects in mice following low energy laser irradiation.

OBJECTIVE: Low energy laser irradiation has been shown to accelerate various biological processes, including regeneration of injured tissues. In the present work we studied the effect of low energy laser irradiation on ischemic mice hearts, following administration of sarafotoxin-b, a powerful vasoconstrictor peptide of the endothelin/sarafotoxin family. METHODS: Immediately after injection of the toxin and two days later, hearts were exposed to low energy laser irradiation. Eight days after the injection the mice were sacrificed and their hearts were processed for light and electron microscopy. RESULTS: Sarafotoxin-b induced an approximate 2-fold increase in the relative cavity volume of the left ventricle. Low energy laser irradiation of the sarafotoxin-injected mice caused a significant decrease (62%) in the left ventricular dilatation. Electron microscopy of the sarafotoxin-injected mice hearts revealed that the extent of formation of large vacuoles in the cytoplasm of the cardiomyocytes as well as disorganization of the myofibrils were much higher than in the laser irradiated mice. CONCLUSIONS: Our study indicates that low energy laser irradiation enhanced recovery of the damaged cardiomyocytes from the ischemia induced by sarafotoxin-b.

Electromechanical mapping of regional left ventricular function in humans: comparison with echocardiography.

A catheter-based method of mapping left ventricular electromechanical regional function may be used to optimize application of local myocardial therapies by demarcating zones of ischemia or infarction. We thus performed a detailed comparison between electromechanical parameters and segmental function as assessed by echocardiography in 10 patients (3 with normal ventricles and 7 with old infarcts). Using a 16-segment model, unipolar voltage and local shortening were significantly and independently related to echo score by multivariate analysis, having a concordance with echo score of 73% for shortening and 79% for voltage. Area under ROC curves, expressing the ability to differentiate normal from abnormal segments, had values of 0.75 and 0.81 for local shortening and unipolar voltage, respectively. In conclusion, automatic assessment of regional ventricular function can be achieved independently by electrical and mechanical parameters, compared with echocardiography, permitting an integrated approach to the evaluation of ventricular function and aiding localization of catheter-based therapies.

The correlation dimension of rat hearts in an experimentally controlled environment.

The electric response of several isolated rat hearts in a controlled environment was studied experimentally. The correlation dimension D(2) was estimated and was found to be between 4 and 6.5 when the response was nearly periodic. The variation of D(2) with the concentration of calcium was studied and a general trend of its increase with increasing concentration was found. Two types of ventricular fibrillation (VF) were observed, one that corresponds to a stochastic signal where D(2) is unbounded and the other to a low dimensional dynamical system with 3.5

Catheter ablation of paroxysmal atrial fibrillation using a 3D mapping system.

BACKGROUND: We treated paroxysmal recurrent atrial fibrillation (AF) with radiofrequency (RF) catheter ablation by creating long linear lesions in the atria. To achieve line continuity, a 3D electroanatomic nonfluoroscopic mapping system was used. METHODS AND RESULTS: In 27 patients with recurrent AF, a catheter incorporating a passive magnetic field sensor was navigated in both atria to construct a 3D activation map. RF energy was delivered to create continuous linear lesions: 3 lines (intercaval, isthmic, and anteroseptal) in the right atrium and a long line encircling the pulmonary veins in the left atrium. After RF application, the atria were remapped to validate completeness of the block lines, demonstrated by late activation of the areas circumscribed by the lines. The mean procedure duration was 312+/-103 minutes (range, 187 to 495), with mean fluoroscopy time of 107+/-44 minutes (range, 32 to 185 minutes). No acute complications occurred, but 1 patient experienced early prolonged sinus pauses and received a pacemaker. During the first day, 17 patients (63%) had AF episodes, but at discharge, 25 patients were in sinus rhythm. After a follow-up of 6. 0 to 15.3 months (average, 10.5+/-3.0 months), 16 patients are asymptomatic, 3 have an almost complete disappearance of symptoms, 1 patient is improved, and 7 patients have their AF attacks unchanged. CONCLUSIONS: Paroxysmal recurrent drug-refractory AF can be treated by RF catheter ablation. Creation of long continuous linear lesions necessary to compartmentalize the atria is facilitated by a nonfluoroscopic electroanatomic mapping system.

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.

Nonfluoroscopic endocardial catheter mapping of atrial fibrillation.

The treatment of drug-refractory atrial fibrillation (AF) remains one of the unsolved problems in cardiology. Surgical interventions have demonstrated that AF can be prevented by multiple incisions within both atria. Recently, this strategy has been translated into a catheter procedure. So far, the ablation approach is not based on individual electrophysiologic data, but constitutes only an anatomic approach. Further insight into the spatial and temporal distribution of the local electrograms during AF is needed. Electroanatomic maps acquired by sequential mapping over 45 seconds at each site during AF in six patients with paroxysmal AF were analyzed off-line. Electrograms were sampled at a mean of 36 +/- 12 sites in the left atrium of each patient. A total of 217 sites were sampled, of which 27.3% (59) represented type A (regular) AF, 9.7% (21) represented type B (totally irregular), and 63.1% (137) represented type C (mixture of type A and B) electrograms. The distribution was analyzed in 20 different segments of the left atrium, and a significantly higher incidence of type A electrograms was found in area 3 (upper lateral pulmonary vein) than at all other sites (P < 0.005). This observation needs further confirmation before any conclusion with regard to catheter ablation can be drawn, particularly because the analysis was based on bipolar recordings from a 4-mm tip electrode.

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.