High-resolution, real-time, and nonfluoroscopic 3-dimensional cardiac imaging and catheter navigation in humans using a novel dielectric-based system.

BACKGROUND: Catheter navigation and 3-dimensional (3D) cardiac mapping are essential components of minimally invasive electrophysiological procedures. OBJECTIVE: The purpose of this study was to develop a novel 3D mapping system (KODEX - EPD, EPD Solutions, Best, The Netherlands) that measures changing electric field gradients induced on intracardiac electrodes to enable catheter localization and real-time 3D cardiac mapping. METHODS: We first validated the accuracy of the system's measurement and localization capabilities by comparing known and KODEX - EPD-measured distances and locations at 12 anatomical landmarks in both the atria and ventricles of 4 swine. Next, in vivo images of 3D porcine cardiac anatomy generated by KODEX - EPD and widely used CARTO 3 system (Biosense Webster, Inc., Diamond Bar, CA) were compared with gold standard computed tomography images acquired from the same animals. Finally, 3D maps of atrial anatomy were created for 22 patients with paroxysmal atrial fibrillation (Dielectric Unravelling of Radiofrequency ABLation Effectiveness trial). RESULTS: First, the mean error between known and measured distances was 1.08 ± 0.11 mm (P < .01) and the overall standard deviation between known and measured locations in 12 areas of the porcine heart was 0.35 mm (P < .01). Second, an expert comparison of 3D image quality revealed that KODEX - EPD is noninferior to CARTO 3. Third, the system enabled 3D imaging of atrial anatomy in humans, provided real-time images of atrioventricular valves, and detected important anatomical variations in a subset of patients. CONCLUSION: The KODEX - EPD system is a novel 3D mapping system that accurately detects catheter location and can generate high-resolution images without the need for preacquired imaging, specialty catheters, or a point-by-point mapping procedure.

High-speed myocardial perfusion imaging initial clinical comparison with conventional dual detector anger camera imaging.

OBJECTIVES: The purpose of this study was to compare myocardial perfusion imaging (MPI) with high-speed single-photon emission computed tomography (SPECT) with conventional SPECT imaging for the evaluation of myocardial perfusion in patients with known or suspected coronary artery disease. BACKGROUND: A novel technology has been developed for high-speed SPECT MPI by employing a bank of independently controlled detector columns with large-hole tungsten collimators and multiple cadmium zinc telluride crystal arrays. METHODS: A total of 44 patients (39 men) underwent same-day Tc-99m sestamibi stress/rest MPI. High-speed SPECT images were performed within 30 min after conventional SPECT. Stress and rest acquisition times were 16 and 12 min for conventional imaging and 4 and 2 min for high-speed SPECT, respectively. Myocardial counts/min (cpm) were calculated for both conventional SPECT and high-speed SPECT. Images were visually analyzed, and the summed stress score (SSS) and summed rest score (SRS) were calculated. Image quality and diagnostic confidence were qualitatively assessed. RESULTS: High-speed SPECT SSS and SRS correlated linearly with conventional SPECT respective scores (r = 0.93, p < 0.0001 for SSS, and r = 0.93, p < 0.0001 for SRS). Image quality was rated good and higher in 17 (94%) cases for high-speed SPECT and 16 (89%) cases for conventional SPECT. Of the 44 patients studied, 36 (81.8%) and 35 (79.5%) were diagnosed definitely normal or abnormal by conventional and high-speed SPECT, respectively (p = NS). Myocardial count rate was significantly higher in high-speed versus conventional SPECT (384 x 10(-3) +/- 134 x 10(-3) cpm/min vs. 47 x 10(-3) +/- 14 x 10(-3) cpm/min, respectively, p < 0.0001) for stress and (962 x 10(-3) +/- 426 x 10(-3) cpm/min vs. 136 x 10(-3) +/- 37 x 10(-3) cpm/min, respectively, p < 0.001) for rest. CONCLUSIONS: High-speed SPECT provides fast MPI with high image quality and up to 8 times increased system sensitivity. The amount of perfusion abnormality visualized by high-speed SPECT is highly correlated to conventional SPECT, with an equivalent level of diagnostic confidence.

Therapy with cardiac contractility modulation electrical signals improves left ventricular function and remodeling in dogs with chronic heart failure.

OBJECTIVES: This study examined the effects of long-term delivery of cardiac contractility modulation (CCM) electric signals on left ventricular (LV) function and global, cellular, and molecular remodeling in dogs with chronic heart failure (HF). BACKGROUND: Acute studies in dogs with experimentally induced HF showed that CCM signals applied to the failing myocardium during the absolute refractory period improved LV function without increasing myocardial oxygen consumption. METHODS: In one study, dogs with intracoronary microembolization-induced HF were randomized to 3 months of active CCM monotherapy or to a sham-operated control group. In another study, 19 HF dogs were randomized to 3 months chronic monotherapy with extended release metoprolol succinate (MET-ER), MET-ER with CCM, or no therapy at all (control group). RESULTS: In CCM-only treated dogs, LV ejection fraction (EF) increased (27 +/- 1% vs. 33 +/- 1%, p < 0.0001) compared with a decrease in sham-operated control animals (27 +/- 1% vs. 23 +/- 1%, p < 0.001). The increase in EF seen with CCM-treated dogs was accompanied by reduced LV volumes, improved myocardial structure, reversal of the maladaptive fetal gene program, and an improvement in sarcoplasmic reticulum calcium cycling proteins. Dogs treated with a combination of MET-ER and CCM showed a greater increase in LV EF and a greater reversal of LV global, structural, and biochemical remodeling compared with dogs treated with MET-ER alone. CONCLUSIONS: In dogs with HF, long-term CCM therapy improves LV systolic function. The improvements are additive to those seen with beta-blockers. These findings are further strengthened by the concomitant benefits of CCM therapy on LV global, cellular, and biochemical remodeling.

Cardiac contractility modulation by non-excitatory currents: studies in isolated cardiac muscle.

BACKGROUND: Myocardial contractility can be altered using voltage clamp techniques by modulating amplitude and duration of the action potential resulting in enhanced calcium entry in the cell of isolated muscle strips (Non-Excitatory Currents; NEC). Extracellular electrical stimuli delivered during the absolute refractory period (Cardiac Contractility Modulation; CCM) have recently been shown to produce inotropic effects in-vivo. AIM: Understanding the cellular mechanism, underlying the CCM effect, is essential for evaluating its clinical potential. We tested the hypothesis that NEC and CCM modulate contractility via similar cellular mechanisms. METHODS: Square wave electric currents were applied in the organ bath to isometrically contracting rabbit RV papillary muscle and human failing trabecular muscle during the absolute refractory period (ARP). RESULTS: These currents, which did not initiate new action potentials or contractions, modulated action potential duration (shortened or lengthened) and contractility (enhanced or depressed) in a manner that depended upon their amplitude, duration and delay from the pacing stimulus. The contractility modulation effect in the rabbit RV papillary muscle was markedly blunted after exposure to ryanodine, indicating that the sarcoplasmic reticulum plays an important role in the contractility modulation. CONCLUSION: Like voltage clamping, extracellular currents applied during the ARP can similarly modulate action potential duration in-vitro and modulate myocardial contractility by similar intracellular mechanisms. This concept provides the potential of a therapeutic strategy in patients with heart failure to enhance contractility.

Ventricular mapping during atrial and right ventricular pacing: relation of electrogram parameters to ventricular tachycardia reentry circuits after myocardial infarction.

INTRODUCTION: Ventricular tachycardia (VT) late after myocardial infarction is usually due to reentry in the border zone of the infarct area. Identification of critical parts of the VT reentry circuit by catheter mapping without needing to induce VT is a desirable goal for VT ablation. The aim of this study was to develop a model to predict reentry circuit locations based on characteristics of sinus or paced electrograms and pace mapping (PM) recorded from the infarct region. METHODS: Left ventricular electroanatomic mapping with the CARTO mapping system was performed in 16 male patients with recurrent VT late after myocardial infarction. A total of 1072 left ventricular sites were recorded during atrial pacing (AP) and right ventricular pacing (RVP), and the corresponding electrograms were analyzed for their local activation time (LAT), onset (ONS), end (END), duration (DUR), and amplitude (AMP) in each pacing sequence. At 1041 of these sites, PM was performed; the resulting stimulus to QRS intervals (S-QRS) was determined at 931 sites, the remaining 110 sites did not capture. All the obtained parameters were compared with the location of 18 ablation target areas with a radius of 2 cm defined by success of radiofrequency (RF) ablation or entrainment during VT, or both. RESULTS: Of 1072 sites, 227 (21%) were in the target and 845 (79%) were outside the target. All parameters were significantly different (p < 0.05) in AP and in RVP between inside and outside the target in a univariate analysis. In a multivariate analysis LAT, END, DUR, and AMP in AP, END and AMP in RVP, and S-QRS were independent predictors for the target (p < 0.05). A combination of selected parameters of these predictors (DUR in AP, AMP in RVP, and S-QRS) had a specificity of 64% with a sensitivity of 80% for the target. CONCLUSION: The observations suggest that ablation guided by a combination of abnormal electrograms in different rhythms can be useful to ablate VT and reduce the necessity of VT induction. Anatomically fixed regions of block may be important for reentry and be identifiable during sinus rhythm.

Use of novel nonfluoroscopic three-dimensional electroanatomic mapping system to monitor and analyze heart surgery in animal models.

BACKGROUND: The new method of three-dimensional (3D) electroanatomic mapping was presented as an important tool for cardiac imaging and intervention. We present herein the first use of this technology for the monitoring, analysis, and development of cardiac surgery at the preclinical stage. METHODS: The method is based on utilizing a locatable catheter connected to an endocardial mapping and navigating system, to accurately establish the location and orientation of the tip of the mapping catheter and simultaneously record its local electrogram. The 3D geometry of the beating cardiac chamber is reconstructed in real time. The system was tested on six goats that underwent dynamic cardiomyoplasty. Two maps of each animal were performed: preoperative and postoperative during the stimulation protocol of the skeletal muscle. RESULTS: The electroanatomic mapping system provided detailed maps of the left ventricle during the stimulation protocol, which demonstrated a striking geometric difference between the assisted and the unassisted beats. These geometric changes are best described by referring to left ventricular long-axis movements (22.3 +/- 3.8 degrees vs 3.4 +/- 1.6 degrees, p < 0.001), center-of-mass movements (10.4 +/- 3.0 mm vs 3.9 +/- 1.6 mm, p < 0.005), and the changes in upward movement viewed along the base (7.9 +/- 1.9 mm vs 3.6 +/- 1.7 mm, p < 0.01), middle (13.8 +/- 4.0 mm vs 7.3 +/- 1.8 mm, p < 0.005), and the apex of the heart (28.1 +/- 4.5 vs 5.3 +/- 2.3 mm, p < 0.001) [mean +/- SD]. CONCLUSIONS: The 3D electroanatomic mapping system allows detailed reconstruction of the left ventricular geometry and a clear view of the difference between the assisted and the unassisted beats. This novel monitoring system may serve as an important tool for the analysis and development of new techniques in cardiac surgery.

First human chronic experience with cardiac contractility modulation by nonexcitatory electrical currents for treating systolic heart failure: mid-term safety and efficacy results from a multicenter study.

INTRODUCTION: Conventional electrical therapies for heart failure (HF) encompass defibrillation and ventricular resynchronization for patients at high risk for lethal arrhythmias and/or with inhomogeneous ventricular contraction. Cardiac contractility modulation (CCM) by means of nonexcitatory electrical currents delivered during the action potential plateau has been shown to acutely enhance systolic function in humans with HF. The aim of this multicenter study was to assess the chronic safety and preliminary efficacy of an implantable device delivering this novel form of electrical therapy. METHODS AND RESULTS: Thirteen patients with drug-resistant HF (New York Heart Association [NYHA] class III) were consecutively implanted with a device (OPTIMIZER II) delivering CCM biphasic square-wave pulses (20 ms, 5.8-7.7 V, 30 ms after detection of local activation) through two right ventricular leads screwed into the right aspect of the interventricular septum. CCM signals were delivered 3 hours daily over 8 weeks (3-hour phase) and 7 hours daily over the next 24 weeks (7-hour phase). Safety and feasibility of this novel therapy were regarded as primary endpoints. Preliminary clinical efficacy, -as expressed by changes in ejection fraction (EF), NYHA class, 6-minute walking test (6-MWT), peak O(2) uptake (peak VO(2)), and Minnesota Living with HF Questionnaire (MLWHFQ), was assessed at baseline and at the end of each phase. At the end of follow-up (8.8 +/- 0.2 months), all patients were alive, without heart transplantation or need for left ventricular assist device. Serial 24-hour Holter analysis revealed no proarrhythmic effect. No devices malfunctioned or failed for any reason other than end-of-battery life. Throughout the two study phases, EF improved from 22.7 +/- 7% to 28.7 +/- 7% and 37 +/- 13% (P = 0.004), 6-MWT from 418 +/- 99 m to 477 +/- 96 m and 510 +/- 107 m (P = 0.002), MLWHFQ from 36 +/- 21 to 18 +/- 12 and 7 +/- 6 (P = 0.002), peak VO(2) from 13.7 +/- 1.1 to 14.9 +/- 1.9 to 16.2 +/- 2.4 (P = 0.037), and NYHA class from 3 to 1.8 +/- 0.4 to 1.5 +/- 0.7 (P < 0.001). CONCLUSION: CCM therapy appears to be safe and feasible. Proarrhythmic effects of this novel therapy seem unlikely. Preliminary data indicate that CCM gradually and significantly improves systolic performance, symptoms, and functional status. CCM therapy for 7 hours per day is associated with greater dispersion near the mean, emphasizing the need to individually tailor CCM delivery duration. The technique appears to be attractive as an additive treatment for severe HF. Controlled randomized studies are needed to validate this novel concept.

Chronic electrical stimulation during the absolute refractory period of the myocardium improves severe heart failure.

AIM: In experimental studies, nonexcitatory electrical stimulation delivered at the time of absolute myocardial refractoriness resulted in cardiac contractility modulation (CCM) with improved systolic function. This study reports the initial experience with CCM in patients with chronic heart failure. METHODS AND RESULTS: Twenty-five patients, 23 males, with a mean age of 62+/-9 years and drug-refractory NYHA class III heart failure were assigned to CCM-generator implantation. The underlying heart disease was idiopathic dilated cardiomyopathy in 12 patients and coronary heart disease in 13 patients. Acute efficacy of CCM with 7.73-V stimuli delivered via two right ventricular leads was evaluated by measuring the time derivative of left ventricular pressure (dP/dt). After implantation, the CCM generator was activated for 3 h daily over 8 weeks. In 23/25 patients the CCM system was implanted successfully. Heart failure significantly improved from NYHA class III to class II in 15 patients and to class I in 4 patients (p < 0.000001), left ventricular ejection fraction improved from 22+/-7% to 28+/-8% (p = 0.0002), and the Minnesota Living with Heart Failure Score improved from 43+/-22 to 25+/-18 (p = 0.001). The 6-min walk test increased from 411+/-86 to 465+/-81 m (p= 0.02). Nine patients (39%) had intermittent sensations associated with CCM delivery. There were two (8%) non-device-related deaths during follow-up. CONCLUSIONS: These preliminary data indicate that CCM by delivery of intermittent nonexcitatory electrical stimuli is a promising technique for improving ventricular systolic function and symptoms in patients with drug-refractory NYHA class III heart failure.

Long-term effects of non-excitatory cardiac contractility modulation electric signals on the progression of heart failure in dogs.

OBJECTIVE: We previously showed that acute delivery of non-excitatory cardiac contractility modulation (CCM) electric signal during the absolute refractory period improved LV function in dogs with chronic heart failure (HF). In the present study we examined the long-term effects of CCM signal delivery on the progression of LV dysfunction and remodeling in dogs with chronic HF. METHODS: Chronic HF was produced in 12 dogs by multiple sequential intracoronary microembolizations. The CCM signal was delivered using a lead implanted in the distal anterior coronary vein. A right ventricular and a right atrial lead were implanted and used for timing of CCM signal delivery. In six dogs, CCM signals were delivered continuously for 6 h daily with an average amplitude of 3.3 V for 3 months. Six HF dogs did not have leads implanted and served as controls. RESULTS: In control dogs, LV end-diastolic volume (EDV) and LV end-systolic volume (ESV) increased (64+/-5 ml vs. 75+/-6 ml, P=0.003; 46+/-4 ml vs. 57+/-4 ml, P=0.003; respectively), and ejection fraction (EF) decreased (28+/-1% vs. 23+/-1%, P=0.001) over the course of 3 months of follow-up. In contrast, CCM-treated dogs showed a smaller increase in EDV (66+/-4 vs. 73+/-5 ml, P=0.01), no change in ESV, and an increase in EF from 31+/-1 to 34+/-2% (P=0.04) after 3 months of therapy. CONCLUSIONS: In dogs with HF, long-term CCM therapy prevents progressive LV dysfunction and attenuates global LV remodeling. These findings provide compelling rationale for exploring the use of CCM for the treatment of patients with chronic HF.

Enhancement of antral contractions and vagal afferent signaling with synchronized electrical stimulation.

Gastric filling activates vagal afferents involved in peripheral signaling to the central nervous system (CNS) for food intake. It is not known whether these afferents linearly encode increasing contractions of the antrum during antral distension (AD). The aim of this study was to investigate effects of AD and electrically enhanced antral contractions on responses of vagal afferents innervating the antrum. Single-fiber recordings were made from the vagal afferents in anesthetized male Long-Evans rats. Antral contractions were measured with a solid-state probe placed in the antrum. A nonexcitatory electrical stimulation (NES) inducing no smooth muscle contractions was applied during the ascending phase of antral contractions to enhance subsequent antral contractions. Fifty-six fibers identified during AD (1 ml for 30 s) were studied through different types of mechanical stimuli. Under normal conditions, one group of fibers exhibited rhythmic firing in phase with antral contractions. Another group of fibers had nonrhythmic spontaneous firing. Responses of 15 fibers were tested with NES during multiple-step distension (MSD). NES produced a mean increase in antral contraction amplitude (177.1 +/- 35.3%) and vagal afferent firing (21.6 +/- 2.6%). Results show that both passive distension and enhanced antral contractions activate distension-sensitive vagal afferents. Responses of these fibers increase linearly to enhanced antral contraction induced by NES or MSD up to a distending volume of 0.6 ml. However, responses reached a plateau at a distending volume >0.8 ml. We concluded that enhanced contraction of the antrum can activate vagal afferents signaling to the CNS.

Relationship of slow conduction detected by pace-mapping to ventricular tachycardia re-entry circuit sites after infarction.

OBJECTIVES: This study sought to characterize the relationship of conduction delays detected by pace-mapping, evident as a stimulus to QRS interval (S-QRS) delay >or=40 ms, to ventricular tachycardia (VT) re-entry circuit isthmuses defined by entrainment and ablation. BACKGROUND: Areas of slow conduction and block in old infarcts cause re-entrant VT. METHODS: In 12 patients with VT after infarction, pace-mapping was performed at 890 sites. Stimulus to QRS intervals were measured and plotted in three-dimensional reconstructions of the left ventricle. Conduction delay was defined as >or=40 ms and marked delay as >80 ms. The locations of conduction delays were compared to the locations of 14 target areas, defined as the region within a radius of 2 cm of a re-entry circuit isthmus. RESULTS: Pacing captured at 829 sites; 465 (56%) had no S-QRS delay, 364 (44%) had a delay >or=40 ms, and 127 (15%) had a delay >80 ms. Sites with delays were clustered in 14 discrete regions, 13 of which overlapped target regions. Only 1 of the 14 target regions was not related to an area of S-QRS delay. Sites with marked delays >80 ms were more often in the target (52%) than sites with delays 40 to 80 ms (29%) (p < 0.0001). CONCLUSIONS: Identification of abnormal conduction during pace-mapping can be used to focus mapping during induced VT to a discrete region of the infarct. Further study is warranted to determine if targeting regions of conduction delay may allow ablation of VT during stable sinus rhythm without mapping during VT.

Cardiac contractility modulation with nonexcitatory electric signals improves left ventricular function in dogs with chronic heart failure.

BACKGROUND: Nonexcitatory electrical, signals termed cardiac contractility modulation (CCM) have been shown to improve contractile force of isolated papillary muscles. In this study, we examined the effects of CCM signal delivery on left ventricular function in dogs with chronic heart failure (HF). METHODS AND RESULTS: Chronic HF (ejection fraction

Electric currents applied during refractory period enhance contractility and systolic calcium in the ferret heart.

We investigated the mechanism of positive inotropism of electric currents applied during the absolute refractory period. Ten Langendorff-perfused ferret hearts were instrumented to measure isovolumic left ventricular pressure (LVP) and the aequorin luminescence. Biphasic square-wave electric currents (+/-20 mA, total duration 30 ms) were delivered between pairs of electrodes. Six hearts were perfused at different extracellular Ca(2+) concentrations ([Ca(2+)](o); 1, 2, 4, and 8 mM). These signals increased LVP from 50.0 +/- 9.4 to 70.1 +/- 14.7, from 67.5 +/- 11.0 to 79.0 +/- 15.6, from 79.3 +/- 21.0 to 87.1 +/- 22.8, and from 84.6 +/- 24.0 to 91.8 +/- 28.5 mmHg at the respective [Ca(2+)](o) (P < 0.05). Peak free intracellular [Ca(2+)] ([Ca(2+)](i)) increased from 0.52 +/- 0.13 to 1.37 +/- 0.23, from 0.76 +/- 0.23 to 1.73 +/- 0.14, from 1.10 +/- 0.24 to 2.05 +/- 0.33, and from 1.41 +/- 0.36 to 2.24 +/- 0.36 microM/ml, respectively (P < 0.001). With the use of 1 mg/l propranolol with 1 mM [Ca(2+)](o), LVP and [Ca(2+)](i) were increased significantly from 48.7 +/- 8.18 to 56.3 +/- 6.11 mmHg and from 0.61 +/- 0.11 to 1.17 +/- 0.20 microM, respectively (P < 0.05). In conclusion, positive inotropism of such electrical currents was due to increased peak [Ca(2+)](i) and Ca(2+) responsiveness of the myofilaments did not change significantly.

Temporal changes in the endocardial ST segment during the evolution of myocardial infarction in dogs.

Acute coronary occlusion causes ST-segment elevation on the body surface ECG and on the epicardial electrogram in the territory supplied by that artery. The occurrence and significance of endocardial ST changes have not been studied. The NOGA electromechanical mapping was performed on eight anesthetized dogs at baseline, immediately after occlusion of the LAD, and again at 5 hours to assess regional changes in the ST segment. At 3 days and 4 weeks the ventricles were remapped for comparison. Regional unipolar ST-segment elevation was measured for each zone from NOGA maps at 0, 80, and 120 ms after the J point. ST segments rose immediately in the infarct zones, as demarcated by echocardiography, compared to remote zones, but by 3 days had dropped below, and at 4 weeks returned to baseline values. Immediately postocclusion, ST elevation at 120 ms best differentiated between normal versus abnormal echo scores (concordance = 0.80), probably by correcting for pressure induced ST elevation. In conclusion, acute endocardial ST-segment changes occur in the infarct zone in the dog, showing a distinctive temporal evolution.

Cardiac contractility modulation by electric currents applied during the refractory period in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

We assessed the feasibility of cardiac contractility modulation (CCM) by electric currents applied during the refractory period in patients with heart failure (HF). Extracellular electric currents modulating action potential and calcium transients have been shown to potentiate myocardial contractility in vitro and in animal models of chronic HF. CCM signals were biphasic square-wave pulses with adjustable amplitude, duration, and time delay from sensing of local electric activity. Signals were applied to the left ventricle through an epicardial vein (in 12 patients) or to the right ventricular (RV) aspect of the septum endocardially (in 6 patients). Simultaneous left ventricular (LV) and aortic pressure measurements were performed using a Millar catheter (Millar Instruments, Houston, Texas). Hemodynamics during RV temporary dual-chamber pacing was regarded as the control condition. Both LV and RV CCM stimulation increased dP/dt(max) to a similar degree (9.1 +/- 4.5% and 7.1 +/- 0.8%, respectively; p <0.01 vs controls), with associated aortic pulse pressure changes of 10.3 +/- 7.2% and 10.8 +/- 1.1% (p <0.01 vs controls). Regional systolic wall motion assessed quantitatively by color kinesis echocardiography was markedly enhanced near the CCM electrode, and the area of increased contractility involved 4.6 +/- 1.2 segments per patient. In 6 patients with HF with left bundle branch block, CCM signals delivered during biventricular pacing (BVP) produced an additional 16.1 +/- 3.7% increase in dP/dt(max) and a 17.0 +/- 7.5% increase in pulse pressure compared with BVP alone (p <0.01). CCM stimulation in patients with HF enhanced regional and global measures of LV systolic function, regardless of the varied delivery chamber or whether modulation was performed during RV pacing or BVP.

Evaluation of inotropic changes in ventricular function by NOGA mapping: comparison with echocardiography.

Assessment of left ventricular (LV) function in the catheterization laboratory is important to optimize treatment decisions and guide catheter-based local therapies. NOGA electromechanical mapping was developed to assess LV contraction during catheterization; however, quantitative analysis of its "local shortening" (LS) algorithm and direct comparison with conventional methods are lacking. We evaluated the accuracy of NOGA-based regional and global function by examining its ability to detect pharmacologically induced changes in contractility compared with echocardiography. Ten anesthetized pigs were paced to ensure a constant heart rate throughout the experiment. Electromechanical maps of the LV and short-axis echocardiograms were obtained 1) at baseline, 2) during intravenous dobutamine, and 3) after intravenous propranolol. NOGA LS and ejection fraction (EF) consistently increased under dobutamine and decreased after propranolol. NOGA LS and NOGA and echocardiography circumferential shortening correlated highly with one another (r > 0.80), as did NOGA EF with echocardiography EF (r = 0.92), although absolute values differed somewhat. Thus NOGA-based global and regional function correlates closely with echocardiography and is sensitive to changes in contractility, but, at the upper end of the scale, LV function is underestimated.

Cardiac contractility modulation by electric currents applied during the refractory period.

Inotropic effects of electric currents applied during the refractory period have been reported in cardiac muscle in vitro using voltage-clamp techniques. We investigated how electric currents modulate cardiac contractility in normal canine hearts in vivo. Six dogs were instrumented to measure regional segment length, ventricular volume (sonomicrometry), and ventricular pressure. Cardiac contractility modulating (CCM) electric currents (biphasic square pulses, amplitude +/-20 mA, total duration 30 ms) were delivered during the refractory period between pairs of electrodes placed on anterior and posterior walls. CCM significantly increased index of global contractility (E(es)) from 5.9 +/- 2.9 to 8.3 +/- 4.6 mmHg/ml with anterior CCM, from 5.3 +/- 1.8 to 8.9 +/- 4.0 mmHg/ml with posterior CCM, and from 6.1 +/- 2.6 to 11.0 +/- 7.0 mmHg/ml with combined CCM (P < 0.01, no significant change in volume axis intercept). End-systolic pressure-segment length relations showed contractility enhancement near CCM delivery sites, but not remotely. Relaxation was not influenced. CCM increased mean aortic pressure, but did not change peripheral resistance. Locally applied electrical currents enhanced global cardiac contractility via regional changes in myocardial contractility without impairing relaxation in situ.

Technical delivery of myogenic cells through an endocardial injection catheter for myocardial cell implantation.

BACKGROUND: The next clinical frontier in the therapeutics of ischemic heart disease may involve the development and delivery of specific molecules and cells into the myocardium. The aim of the present study was to evaluate the efficiency and safety of the MyoStar injection catheter (Biosense-Webster Inc.) that has recently been developed to deliver molecules and cells to the myocardium. The 8 Fr (110 cm length) catheter comprises a navigation sensor with a 27 gauge needle at the distal tip. METHODS: Mouse myogenic cells (C2) were delivered to a tissue culture dish through different modalities: a standard laboratory pipette, a syringe needle (27 gauge) and the injection catheter. The cells were counted and monitored for growth and differentiation in the tissue culture immediately after delivery and two, three and six days later. Cells that were injected through a regular syringe needle or through the injection catheter demonstrated the same capacity to proliferate in tissue culture up to six days. RESULTS: The behavior of the cells in culture (fusion) was identical for the cells delivered to the tissue culture by a pipette or by the injection catheter. CONCLUSION: The results of the present study indicate that delivery of cells through the MyoStar injection catheter is a method with no significant loss or adverse effects to the cells along the path of the catheter. The catheter, which possesses both injection and navigation capabilities, can be used to deliver cell therapy to patients with ischemic heart disease.