Quantitative analysis of left ventricular dyssynchrony using cardiac computed tomography versus three-dimensional echocardiography.

OBJECTIVES: We investigated whether cardiac computed tomography (CCT) can determine intraventricular dyssynchrony in comparison to real-time three-dimensional echocardiography (RT3DE) in patients who are considered for cardiac resynchronisation therapy (CRT). METHODS: 35 patients considered for CRT were examined. Left ventricular (LV) dyssynchrony was quantified by calculating the standard deviation index (SDI) of 17 myocardial LV segments by RT3DE and ECG-gated contrast-enhanced 64-slice dual-source CCT. For both analyses the same software algorithm (4D LV-Analysis) was used. RESULTS: Close correlations were observed for end-systolic volume, end-diastolic volume and LV ejection fraction between the two techniques (r = 0.94, r = 0.92 and r = 0.95, respectively, P < 0.001 for all). For the global dyssynchrony index SDI, a high correlation was found between RT3DE and CCT (r = 0.84, P < 0.001), which further increased after exclusion of segments with poor image quality by echocardiography (r = 0.90, P < 0.001). The required time for quantitative analysis was significantly shorter (162 ± 22 s vs. 608 ± 112 s per patient, P < 0.001) and reproducibility was significantly higher for CCT compared with RT3DE (interobserver variability of 4.5 ± 3.1% vs. 7.9 ± 6.1%, P < 0.05). CONCLUSION: Quantitative assessment of LV dyssynchrony is feasible by CCT. Owing to its higher reproducibility and faster analysis time compared with RT3DE, this technique may represent a valuable alternative for dyssynchrony assessment. KEY POINTS: • Quantitative assessment of left ventricular dyssynchrony is feasible by cardiac computed tomography (CCT). • This technique has been compared with real-time three-dimensional echocardiography (RT3DE). • Reproducibility is significantly higher for CCT compared with RT3DE. • Time spent for analysis is significantly shorter for CCT. • Computed tomography may represent a valuable alternative to ultrasound for dyssynchrony assessment.

Atrioventricular delay programming in cardiac resynchronization therapy devices: fixed or adaptive? A randomized monocenter trial.

INTRODUCTION: Cardiac resynchronization therapy devices are routinely programmed on fixed atrioventricular delays (AVD) under resting conditions based on echocardiographic techniques. Whether this AVD also ensures optimal exercise hemodynamics, is unclear. METHODS: In order to compare fixed-AVD with rate-adaptive AVD, 100 patients with cardiac resynchronization therapy systems and sinus rhythm were randomized to fixed-AVD or adaptive-AVD. The patients then underwent bicycle ergometry with noninvasive hemodynamic monitoring. At rest and at peak exercise, stroke volume, cardiac output, and cardiac index were determined using "electrical velocimetry." RESULTS: There were no significant differences in clinical characteristics and baseline hemodynamic parameters between fixed or adaptive AVD. In patients randomized to adaptive AVD, a trend towards higher stroke volume, cardiac output, and cardiac index at peak exercise was encountered. CONCLUSIONS: Based on the trend towards better exercise hemodynamics demonstrated by this pilot study, a randomized follow-up study with clinical end points appears to be justified to clarify this issue.

Determination of myocardial infarct size by noncontact mapping.

BACKGROUND: Once chamber geometry is determined, the EnSite 3000 noncontact mapping system can create a voltage map during a single cardiac cycle. The EnSite uses an inverse solution to the Laplace equation to process the amplified far-field signals from the noncontact catheter. This process creates a three-dimensional endocardial potential map from a single cardiac cycle. Dynamic substrate mapping (DSM) is an algorithm designed to identify conduction boundaries, such as myocardial scars based on voltage distribution within the corresponding chamber. OBJECTIVE: The purpose of this study was to investigate the correlation between DSM- and magnetic resonance imaging (MRI)-determined scar areas and to identify a suitable DSM voltage threshold. METHODS: A total of eight dogs were studied. Four healthy foxhounds underwent ligation of the left anterior descending coronary artery. Evidence of myocardial infarction, including ECG changes and elevated cardiac troponin T levels, was noted in all animals. Cardiac MRI scan was performed 29 +/- 2 days after ligation of the left anterior descending coronary artery. Subsequently, noncontact mapping of the left ventricle was obtained in each dog, and myocardial infarction size was determined using DSM at different filter settings. As a control group, another four foxhounds underwent sham thoracotomy/pericardiotomy. RESULTS: A significant linear correlation of infarction size using DSM compared with MRI measurements was found at the filter setting "peak negative 34%" (P = .001, r = 0.99). Mean relative infarction size was 15.9% +/- 4.5% with DSM and 16.0% +/- 4.2% with MRI. Compared with the sham group, a significant reduction in left ventricular ejection fraction was found after ligation of the left anterior descending coronary artery (51.0% +/- 3.8% vs 69.2% +/- 5.9%, P = .002). Pathoanatomic studies were performed to confirm the measured infarct dimensions. No scars were detectable in sham-operated dogs using DSM or MRI. CONCLUSION: Noncontact mapping allows identification of scar tissue within the left ventricle. An excellent correlation was observed between DSM-scar surface and MRI-determined scar size. Identifying and marking these areas can be useful when planning an ablation strategy in the clinical setting of ischemic heart disease.

Effects of protein kinase C activation on cardiac repolarization and arrhythmogenesis in Langendorff-perfused rabbit hearts.

AIMS: Cardiac arrhythmias are still a major cause of mortality in western countries. Currently available antiarrhythmic drugs are limited by a low efficacy and proarrhythmic effects. The role of the protein kinase C (PKC) signalling pathway in arrhythmogenesis is still unclear. The goal of the present study was to test the effects of PKC stimulation on whole heart electrophysiology and its pro-/antiarrhythmic activity. METHODS AND RESULTS: Left ventricular (LV) action potential duration (APD 90%) was determined in 27 Langendorff-perfused rabbit hearts, using Tyrode solution plus the PKC agonist phorbol-12-myristate-13-acetate (PMA; 100 nM) alone (nine rabbits), Verapamil alone (n = 6), or PMA in combination with Verapamil (0.25 mg/L, six rabbits), or bisindolylmaleimide (0.5 microM, n = 6). Intermittent programmed extra-stimulation was performed to induce ventricular arrhythmias. Administration of PMA alone led to a significant shortening of repolarization (APD 90%, 157 +/- 8 vs. 128 +/- 5 ms, P<0.05). Non-sustained ventricular fibrillation (VF) could be induced in seven out of nine animals. After perfusion of Verapamil (156 +/- 6 vs. 169 +/- 4 ms, P>0.05) or bisindolylmaleimide, a selective inhibitor of PKC (136 +/- 4 vs. 146 +/- 4 ms, P>0.05), PMA-induced shortening of repolarization could be inhibited, and induction of VF failed. Verapamil alone did not affect APD and VF could not be induced. CONCLUSIONS: Activation of PKC facilitates induction of VF, which is most likely due to a shortening of repolarization and a prominent calcium influx. These findings demonstrate involvement of the PKC-signalling pathway in arrhythmogenesis.

Safety of symptom-limited exercise testing in a big cohort of a modern ICD population.

BACKGROUND: Exercise may predispose to ventricular arrhythmias especially in patients with congestive heart failure. As therapy with implanted cardioverter-defibrillators (ICDs) has become standard medical care, there is an emerging number of exercise tests that need to be performed in patients with ICDs. In contrast, little is known about the safety of symptom-limited exercise testing in these patients. METHODS AND RESULTS: 400 ICD patients performed symptom-limited exercise treadmill testing. 200 patients performed a ramp protocol with an initial workload of 0 W increased by 15 W every minute. Another 200 ICD patients did a slightly modified ramp protocol with again an initial workload of 0 W but with an increased capacity of 15 W every 2 min. The study population consists mainly of patients with ischemic (63%) and non-ischemic (34%) heart disease. Atrial fibrillation was present in 16% of the subjects. The mean ejection fraction was 28 ± 8, and 78% of the patients had an ejection fraction below 30%. In this cohort of patients, no sustained ventricular arrhythmias and no deaths occurred during or after exercise testing. No inappropriate shock delivery was observed. The modified ramp protocol resulted in a prolonged exercise time with equal exercise capacity but does not result in an enhanced susceptibility for ventricular arrhythmias. CONCLUSIONS: Symptom-limited exercise treadmill testing in heart failure patients with ICDs is a safe procedure. The use of a ramp protocol is sufficient in terms of safety and is easy to perform in general practice. The exercise duration in heart failure patients with ICDs does not predict serious adverse events.

Patient alert in implantable cardioverter defibrillators: toy or tool?

OBJECTIVES: The purpose of this study was to analyze the utility of patient-alert features in implantable cardioverter defibrillators (ICDs). BACKGROUND: Various alert features producing acoustic warning signals have been implemented in newer generation ICDs, but their role in early detection of system-related complications has not been systematically evaluated. METHODS: In 240 patients implanted with Medtronic ICD devices, the following alert features were routinely activated: pacing lead impedance <200 or >2,000 Omega, high-voltage lead impedance <10 or >200 Omega, low battery voltage (elective replacement indicator), long charge time (>18 s), >3 shocks delivered per episode, and all therapies in a zone delivered. Alert events occurring during follow-up were assessed in relation to actual findings (hospital charts, chest X-rays, ICD printouts including sensing/pacing/defibrillation threshold tests, episode data) to determine incidence, sensitivity, and specificity of the alert function. RESULTS: During 12.2 +/- 8.9 months, 24 alert events occurred in the 240 patients (pacing lead impedance, n = 4; high-voltage lead impedance, n = 7; low battery voltage, n = 1; >3 shocks, n = 6; all therapies, n = 6). A total of 22 serious complications (necessitating reprogramming or device/lead replacement) were observed, 14 of which were primarily identified through a patient alert (lead fracture, n = 11; connector defect, n = 1; T-wave oversensing, n = 1; battery depletion, n = 1). This reflects a sensitivity of 64% and a specificity of 96% of the alert function for serious complications. With 14 of 24 patient alerts being caused by serious complications, the positive predictive value reached 58%. CONCLUSIONS: Patient-alert features are a useful additional tool facilitating early detection of serious ICD complications, but they do not substitute for regular ICD follow-up, because of their low sensitivity.

Suppression of atrial fibrillation by multisite and septal pacing in a novel experimental model.

OBJECTIVES: To evaluate the preventive efficacy of multisite and septal atrial pacing in an experimental model. METHODS: Sterile right atrial pericarditis was induced in 12 foxhounds to provide an anatomical substrate for atrial fibrillation (AF). As a trigger mechanism, atrial extrasystoles were simulated by constant asynchronous pacing at a cycle length of 1000 ms from randomly selected right or left atrial electrodes, using a biatrial epicardial multielectrode with 128 bipoles. Additionally, a transvenous pacing lead was screwed into the interatrial septum. Four electrodes located in the high and low right (HRA/LRA) and left atrium (HLA/LLA) were selected for preventive multisite stimulation. Constant pacing at a cycle length 30 ms below sinus rate was applied from the following site(s): HRA, septal, HRA+LRA, HRA+LLA, HRA+LRA+LLA and HRA+LRA+HLA+LLA (order randomized). Number and duration of AF episodes were studied during 10 min intervals, separated by 5 min pauses, respectively. To validate the model, the protocol was repeated 10 min after i.v. bolus administration of D,L-sotalol (1 mg/kg body weight). RESULTS: The number of AF episodes decreased with increasing number of pacing sites, reaching statistical significance compared to HRA stimulation for quadruple-site and single-site septal pacing only (P<0.05). Single-site septal was as efficient as quadruple-site pacing in suppressing AF. The duration of AF episodes was not significantly affected by the pacing configuration. D,L-sotalol almost completely suppressed AF irrespective of the pacing configuration used. CONCLUSIONS: In this novel experimental model, quadruple-site and septal pacing effectively suppress paroxysmal AF.

Pro- and antiarrhythmic effects of fast cardiac pacing in a canine model of acquired long QT syndrome.

Increasing the heart rate is one option for suppressing bradycardia-dependent polymorphic ventricular tachycardias (PVTs). The mechanisms underlying preventive pacing in acquired forms of the long QT syndrome (LQTs) are still not fully understood. Using two needle electrodes, local effective refractory periods (ERPs) were determined in the left (LV) and right ventricle (RV) in 20 dogs with acute AV node ablation before continuous pacing, during a 20-min period of continuous fast pacing (Cl 300 ms, fastpac) and during a 35-min recovery period with slow (Cl 500 ms) pacing. This protocol was applied to control dogs (5 dogs) and dogs with pretreatment of the IKs blocking agent chromanol 293b (5 dogs, LQTs1), the IKr-blocking agent dofetilide (5 dogs, LQTs2) or a combination thereof (5 dogs). Fastpac resulted in a significant abbreviation of ERPs in control dogs and dogs receiving dofetilide or chromanol 293b. During recovery, shortening of ERPs persisted in the control group, but diminished in dogs with acquired LQTs. In dogs with LQTs2 fastpac could not suppress inhomogeneity of refractoriness during recovery. With pretreatment of dofetilide and chromanol 293b in combination, MAP duration during fastpac significantly increased (first beat: 256+/-6 ms vs. sixth beat: 278+/-9 ms, p<0.05) and fastpac-induced PVTs were evident. ERP shortening and reduced inhomogeneity of refractoriness might be one antiarrhythmic action of fastpac in dogs with acute AV-block. However, in the acquired LQTs1 and 2 beneficial effects of fastpac diminished and in a combination thereof fastpac-induced PVTs are likely.

Effects of acute ischemia, early extrabeats and propafenone on complex activation patterns in intact and ischemic canine hearts.

Although, sodium channel blockers have the ability to suppress nonsustained ventricular arrhythmias, an excessive drug-associated arrhythmic death rate has been reported in patients with coronary heart disease (CHD). Sodium channel blockers should prevent initiation of reentry activation by reducing directional differences in cardiac conduction (anisotropy). However, in vitro data demonstrated, that reduction of membrane excitability, e.g. by lowering the inward Na+ current, increases the risk for conduction failure and associated reentry arrhythmias. In 11 dogs the effects of myocardial ischemia, premature epicardial stimulation (PES) and propafenone on anisotropic conduction properties were tested using three-dimensional mapping techniques. The epicardial (longitudinal and transverse to fiber orientation) and transmural (oblique and straight) spread of activation was reconstructed during constant and PES. At baseline, conduction velocities (CV) were higher along (1.20 +/- 0.41 m/s) than across (0.91 +/- 0.19 m/s; p < 0.05) epicardial muscle fibers as well as along oblique (1.77 +/- 0.75 m/s) compared to straight (0.39 +/- 0.09 m/s, p < 0.05) transmural pathways. Acute ischemia did not significantly reduce tissue anisotropy. PES and additional administration of propafenone epicardially eliminated and transmurally profoundly reduced tissue anisotropy (longitudinal 0.58 +/- 0.09 m/s, transverse 0.69 +/- 0.08 m/s, oblique 0.69 +/- 0.28 m/s, straight 0.27 +/- 0.07 m/s). However, reduced anisotropy was associated with a higher probability for conduction block along myocardial fibers in the epicardium and along oblique transmural pathways. Our data show, that propafenone exhibits both potential pro- and antiarrhythmic effects in dogs with acute myocardial ischemia. These results possibly provide more insights in mechanisms underlying the excessive drug-associated arrhythmic death rate in patients with CHD.

Usefulness of heart rate to predict one-year mortality in patients with atrial fibrillation and acute myocardial infarction (from the OMEGA trial).

In the setting of acute myocardial infarction and sinus rhythm, the heart rate (HR) has been demonstrated to correlate closely with mortality. In patients presenting with acute myocardial infarction and atrial fibrillation (AF) on admission, however, the prognostic relevance of the HR has not yet been systematically addressed. A post hoc subgroup analysis of the data from the OMEGA trial was conducted to analyze whether the admission HR determines the 1-year mortality in patients presenting with AF in the setting of acute myocardial infarction. Of 3,851 patients enrolled in the OMEGA study, 211 (6%) presented with AF on admission. This subgroup was dichotomized according to the admission HR (cutoff 95 beats/min). Multiple regression analysis revealed that an admission HR of ≥95 beats/min independently determined the 1-year mortality in patients with AF (odds ratio 4.69, 95% confidence interval 1.47 to 15.01; p = 0.01). In conclusion, this is the first study demonstrating that a high HR (≥95 beats/min) on admission in patients with AF and acute myocardial infarction is associated with an almost fivefold mortality risk.

Effect of cardiac resynchronization therapy on conversion of persistent atrial fibrillation to sinus rhythm.

BACKGROUND: Spontaneous conversion of persistent atrial fibrillation to sinus rhythm (SR) has anecdotally been reported following cardiac resynchronisation therapy. OBJECTIVE: This monocenter observational study was designed to estimate the incidence of spontaneous conversion of persistent atrial fibrillation to SR in consecutive patients implanted with a cardiac resynchronisation device. METHODS AND RESULTS: A total of 46 patients with persistent atrial fibrillation (> or =4 weeks pre-implant), left bundle branch block (QRS > 130 ms), left ventricular ejection fraction <0.35 and NYHA III or IV heart failure were implanted with a cardiac resynchronisation pacemaker or defibrillator and followed for at least 6 months between 6/2000 to 12/2006. During 22 +/- 9 (7-34) months of follow-up, eight out of 46 patients (17%) converted to SR. Spontaneous conversion was encountered in seven cases, whereas one patient converted due to an ICD shock delivered for ventricular tachycardia; in the latter patient, previous ICD shocks had not converted atrial fibrillation. The time interval from device implantation to conversion was 12 +/- 11 (3-31) months. In patients converting to SR, the duration of atrial fibrillation before device implantation was significantly shorter than in patients remaining in atrial fibrillation (15 +/- 13 vs. 53 +/- 58 months, P = 0.001). Echocardiographic parameters such as left ventricular ejection fraction, left ventricular end-diastolic diameter, left atrial diameter did not differ significantly between converting and non-converting patients. However, patients converting to SR showed a significant reduction in systolic pulmonary artery pressure on CRT vs. before CRT (45 +/- 13 vs. 29 +/- 5 mmHg, P = 0.008). CONCLUSIONS: This pilot study suggests that CRT favors spontaneous conversion of persistent AF to SR in a minority of patients. If confirmed by larger clinical studies, atrial lead implantation would be encouraged in these patients, in order to provide AV synchronous pacing in case of spontaneous conversion or successful cardioversion to SR on cardiac resynchronisation therapy.

The basic pacing rate in CRT patients: the higher the better?

BACKGROUND: To maximize the hemodynamic benefit of cardiac resynchronization therapy (CRT), echocardiographic AV interval optimization is routinely performed, complemented by VV interval optimization especially in non-responders. Programming of the basic pacing rate, however, is largely empirical in these patients. Therefore, the present study aimed to systematically evaluate the impact of basic pacing rate on hemodynamic parameters in CRT patients with sinus bradycardia. METHODS AND RESULTS: We included 70 consecutive patients with moderate to severe heart failure, LV ejection fraction 120 ms combined with echocardiographic evidence of ventricular dyssynchrony. All patients were on optimal heart failure medication, with CRT-ICD devices implanted at least 6 months before inclusion into the study. All patients were in sinus rhythm with a spontaneous heart rate <40 bpm. In all patients, cardiac output (CO) and stroke volume (SV) were determined using electrical velocimetry (EV) (Aesculon, Osypka Medical, Berlin, Germany). EV provides a new algorithm to calculate CO based on variations in thoracic electrical bioimpedance, which has been recently validated. Hemodynamic measurements were performed at four different pacing rates ranging from 40 to 70 bpm. A stepwise increase in CO was encountered with increasing heart rates, reaching statistical significance when comparing 70 with 40 bpm. SV remained unchanged throughout all pacing rates. CONCLUSIONS: In the range between 40 and 70 bpm, an increase in basic pacing rate enhances CO without reducing SV. According to this pilot study, a basic pacing rate between 60 and 70 bpm would appear reasonable.

There is no transmural heterogeneity in an index of action potential duration in the canine left ventricle.

BACKGROUND: Transmural heterogeneity in ventricular repolarization demonstrated in vitro has been difficult to confirm in vivo. Whether this discrepancy reflects a physiological phenomenon or a methodological problem remains a vivid matter of debate despite a plethora of experimental work. Therefore, we have measured the relevant electrophysiological parameters first in vivo and repeated these in the same heart and at identical sites in vitro. Methodological issues were tackled by using both unipolar and bipolar recordings. Physiological issues were explored by measuring both local and functional electrophysiological parameters. METHODS: In 10 healthy dogs, 2 high-resolution needle electrodes were inserted into the left ventricle. Effective refractory periods (ERP) as well as activation recovery intervals (ARI) were determined at each electrode along both needles at basic cycle lengths (BCL) of 850 and 300 ms, respectively. After excision of the heart, ERP and ARI measurements were repeated in the arterially perfused wedge preparations. RESULTS: First, we observed that ERPs and ARIs were significantly shorter in vivo than in vitro. Mean ERPs and ARIs of all muscle layers were relatively uniform throughout the ventricular wall in vivo. The transition from the in vivo to the in vitro preparation was associated with a significant albeit small increase of mean ARIs in the subendocardium, whereas interlayer differences in mean ERPs did not reach statistical significance as in vivo. CONCLUSION: In the intact canine left ventricular wall, a more or less homogeneous distribution in transmural ERP and ARI is present.

"Home monitoring" for early detection of implantable cardioverter-defibrillator failure: a single-center prospective observational study.

BACKGROUND: Telemedical ICD monitoring has the potential to enhance patient safety. The "home-monitoring" (HM) feature transmits selected device-related data to a service-center via mobile phone network. In case of a potential emergency situation, event reports are generated automatically. This prospective observational study was designed to test whether HM is effective and reliable in early detection of device failure. METHODS: Consecutive patients receiving ICD, CRT-D or CRT pacemaker systems with HM feature were included. Regular follow-up visits were performed 1, 3, 6, 9 and 12 months after implantation in the first year, and every 6 months thereafter. All event reports transmitted by HM were analyzed and severe device-related events (serious lead or device dysfunction, hospitalization, death) were documented including timing, type and mode of detection. RESULTS: Sixty-nine patients were included and followed for 18 +/- 9 months. A total of 206 event reports were transmitted, prompted by VF/VT-episodes (n = 193), ineffective ICD shocks (n = 7), abnormal pacing impedance (n = 4) or battery depletion (n = 2). 8 SAEs were observed (RV lead fracture; n = 5, connector defect; n = 1, sensing defect, n = 1, RV lead dislodgement, n = 1). There was no device-related death. 6 out of 8 SAEs were discovered by HM (sensitivity, 75%). Without HM, these events would have been detected with a theoretical delay of 1.9 +/- 0.5 months in the first year (3 monthly FU) and 4.9 +/- 0.5 months in the following years (6 monthly FU). CONCLUSIONS: This pilot study demonstrates that HM enables early detection of ICD failure and appears to enhance patient safety.

Can noncontact mapping distinguish between endo- and epicardial foci?

OBJECTIVES: Noncontact mapping has been demonstrated to facilitate RF ablation of ventricular arrhythmias, but the reproducibility in the localization of endocardial exit sites during focal ventricular tachycardia ("VT") originating from defined myocardial layers has not been systematically studied. Furthermore, it remains unclear whether noncontact mapping can distinguish between endo- and epicardial foci. METHODS: In six dogs, constant pacing was applied through octopolar needle electrodes in the left ventricle to mimic VT of subendocardial, midmyocardial (mid1; mid2) or subepicardial origin. Using noncontact mapping, the site of origin was determined for each of 50 consecutive beats of all "VTs" and the variation between respective exit sites was measured. Exit sites were reconstructed for 50 consecutive beats of each "VT" and the time span between site of origin and exit site was measured as a parameter of intramural conduction. RESULTS: While subendocardial and midmyocardial (mid1, mid2) foci were pinpointed with a variation of

Elevated B-type natriuretic peptide levels in patients with nonischemic cardiomyopathy predict occurrence of arrhythmic events.

BACKGROUND: Patients with nonischemic cardiomyopathy (DCM) are at high risk for sudden cardiac death (SCD). However, the predictive value of prophylactic implantation of implantable cardioverter defibrillators (ICD) in this patient cohort is yet unclear. METHODS AND RESULTS: Whether NT pro BNP levels and/or reproducible non sustained ventricular tachycardias (NSVTs) are predictive for SCD was prospectively tested in 30 patients with DCM and LVEF

Role of KATP channels in repetitive induction of ventricular fibrillation.

AIM: Patients with sustained ventricular tachyarrhythmias are at high risk for sudden cardiac death. The mechanisms leading to multiple temporally related episodes of ventricular fibrillation (VF) are not yet fully elucidated, and treatment options are limited. We investigated whether K(ATP)-channels could be involved in triggering VF. METHODS: We determined postarrhythmic changes of monophasic action potentials (MAP) after repetitive induction of VF in 32 Langendorff-perfused rabbit hearts. RESULTS: Postarrhythmic action potential duration (APD) was significantly shorter compared with baseline (100 +/- 12 ms vs. 140 +/- 8 ms, P < 0.05). With increasing numbers of VF and shortening of recovery intervals between VF episodes (2 min) inducibility of VF increased, and abbreviation of APD became more prominent (90 +/- 5 ms vs. 130 +/- 4 ms, P < 0.05). Pre-treatment with the selective K(ATP) blocking agent HMR 1883 led to a significant increase of postarrhythmic APDs compared with control hearts (100 +/- 12 ms vs. 118 +/- 3 ms, P = 0.0013). Moreover, HMR 1883 significantly reduced inducibility of VF and increased the rate of successful defibrillation. CONCLUSIONS: Repetitive episodes of VF result in postarrhythmic abbreviation of APDs, a phenomenon thought to be of potential relevance for incessant tachyarrhythmias in patients. Prevention of postarrhythmic MAP-shortening by HMR 1883 might be useful in suppressing VF.

Atrial-radiofrequency catheter ablation mediated targeting of mesenchymal stromal cells.

Sinus node dysfunction and high-degree heart block are the major causes for electronic pacemaker implantation. Recently, genetically modified mesenchymal stromal cells (MSCs, also known as "mesenchymal stem cells") were demonstrated to generate pacemaker function in vivo. However, experimental approaches typically use open thoracotomy for direct cell injection into the myocardium. Future clinical implementation, however, essentially requires development of more gentle methods to precisely and efficiently apply specified stem cells at specific cardiac locations. In a "proof of concept" study, we performed selective power-controlled radiofrequency catheter ablation (RFCA) with eight ablation pulses (30 W, 60 seconds each) to induce heat-mediated lesions at the auricles of the cardiac right atrium of four healthy foxhounds. The next day, allogeneic MSCs (4.3 x 10(5) cells per kilogram of body weight) labeled with superparamagnetic iron oxide particles (SPIOs) were infused intravenously. Hearts were explanted 8 days later. High numbers of SPIO-labeled cells were identified in areas surrounding the RFCA-induced lesions by Prussian blue staining. Antibody staining revealed SPIO-labeled cells being positive for the typical MSC surface antigen CD44. In contrast, low levels of calprotectin, an antigen found on monocytes and macrophages, indicated negligible infiltration of monocytes in MSC-positive areas. Thus, RFCA allows targeting of MSCs to the cardiac right atrium, adjacent to the sinoatrial node, providing an opportunity to rescue or generate pacemaker function without open thoracotomy and direct injection of MSCs. This method presents a new strategy for cardiac stem cell application leading to an efficient guidance of MSCs into the myocardium. Disclosure of potential conflicts of interest is found at the end of this article.