Cardiac memory studies in two human models

Background Cardiac memory is a form of electrical remodeling of the ventricles, where the T vector follows ("remembers') a previously altered QRS vector. On the electrocardiogram (ECG), it presents as T-wave inversions. It has been observed after periods of ventricular pacing, ventricular tachycardia, intermittent bundle branch block and after periods of preexcitation in patients with the Wolff-Parkinson-White (WPW) syndrome. Aims To study the occurrence, development and dissipation of cardiac memory in two human models, ventricular pacing and WPW ablation. In addition to conventional ECG analysis, the spatial vectorcardiogram (VCG) was analyzed in 3 dimensions, including T-vector loop morphology. Studies I-II Twenty patients who received DDD-R pacemakers due to symptomatic sinus bradycardia were followed daily for 1 week (n=6) or weekly for 5-8 weeks (n=14). A baseline ECG and VCG were recorded prior to pacemaker implantation. The patients were all paced endocardially in the right ventricle and the pacemakers were programmed to a short AV delay to achieve maximum ventricular stimulation. At each follow-up, the pacemakers were temporarily programmed to AM mode to re-establish normal ventricular activation and an ECG and VCG were recorded. After this protocol, the 14 patients who were studied weekly had their pacemakers reprogrammed to individually optimized AV delays and, after 4-5 weeks, they were seen at one last follow-up. Repolarization changes assessed by Tvector amplitude and morphology changes were already present within 24 hours after the initiation of pacing. Cardiac memory was fully developed within one week and the VCG revealed a backward and upward rotation of the maximum T vector. After the cessation of ventricular pacing, cardiac memory disappeared within 4 weeks. When ventricular pacing was continued, cardiac memory was preserved in proportion to the percentage of ventricular pacing. After the abrupt termination of ventricular pacing, the prolongation of repolarization time (QTc) and changes in T-loop morphology suggested unfavorable effects on repolarization. During continuous ventricular pacing, the repolarization time decreased. Study III The effects of ventricular pacing on repolarization and cardiac memory were compared in 15 patients with hypertrophic obstructive cardiomyopathy (HOCM) and the patients from Studies I and II. A baseline ECG was recorded prior to pacemaker implantation. The HOCM patients were evaluated after 3 months of right ventricular endocardial pacing with a short AV delay. An ECG was first recorded during DDD pacing and then during sinus rhythm after pacing was temporarily switched off. T-wave inversions consistent with cardiac memory were observed in all HOCM patients and similar to controls. In contrast to sick sinus patients, there was no change in repolarization time in the HOCM group. Baseline myocardial structure and function thus make a difference to the repolarization response related to cardiac memory. Studies IV- V The occurrence and dissipation of cardiac memory after an accessory pathway ablation in WPW patients were studied retrospectively (Study IV) and prospectively (Study V). In Study IV, T-wave inversions in leads II, aVF and III were evaluated on ECGs from 125 patients ablated due to a posteroseptal (PS) accessory pathway. Within one day after ablation, 123 (98%) of the patients showed cardiac memory (T-wave inversions). In most patients, cardiac memory disappeared within 3 months. In Study V, ECGs and VCGs were used to compare the occurrence of cardiac memory after the ablation of PS (n=11) and left lateral (LL) (n=6) accessory pathways. Cardiac memory in the form of T-wave inversions on ECG was only seen in the PS group. Evaluation by VCG, however, revealed T-vector changes in the transverse plane in the LL group and vertical T-vector changes in the PS group. In 82% of the patients, cardiac memory disappeared within 3-4 weeks. Conclusions In humans, cardiac memory developed and reached steady state within 1 week after the onset of right ventricular endocardial pacing. After WPW ablation, cardiac memory was present, independent of accessory pathway site. Cardiac memory is probably an adaptation mechanism of the heart, involving a gradual change in repolarization when the activation sequence (depolarization) is altered. VCG including T-vector loop morphology is a useful and sensitive method for evaluating repolarization changes

Networked multielectrode left ventricular pacing lead for avoidance of phrenic nerve stimulation in a canine model

BACKGROUND: In cardiac resynchronization therapy, left ventricular stimulation may lead to concomitant phrenic nerve stimulation (PNS). OBJECTIVE: To evaluate a new networked multielectrode lead with 16 electrode segments (SEGs) configured into groups of 4, forming a virtual band (VBAND) around the lead. Each electrode is individually programmable using an embedded integrated circuit. METHODS: In 8 anesthetized dogs, the lead was positioned in a left ventricular coronary vein. The voltage thresholds for cardiac stimulation and PNS were measured for different electrode configurations, including "VBAND-VBAND" (∼conventional bipolar pacing), "SEG-VBAND", and "SEG-SEG" (anode and cathode within the same VBAND). The measurements were performed (1) with closed chest and (2) after opening the chest and repositioning the phrenic nerve to above the lead, simulating a worst-case scenario. RESULTS: Compared with the conventional VBAND-VBAND stimulation, the SEG-SEG stimulation increased the PNS threshold and raised the difference between phrenic and cardiac thresholds from 6.2 ± 2.3 to 9.5 ±0.3 V in the closed chest condition and from 1.4 ± 1.6 to 9.0 ± 1.0 V in the worst-case scenario (both P < .001). Both SEG-VBAND and SEG-SEG stimulations reduced the cardiac threshold and increased pacing impedance, thus reducing the required cardiac pacing power by 77%-80% (P <.001 and P <.01 for closed and open chest, respectively). CONCLUSION: This novel multielectrode pacing lead achieves low cardiac and high extracardiac stimulation thresholds during left ventricular pacing in a canine model. The virtual elimination of PNS may facilitate and improve the application of cardiac resynchronization therapy

Vectorcardiographic QRS area as a novel predictor of response to cardiac resynchronization therapy

AbstractBackgroundQRS duration and left bundle branch block (LBBB) morphology are used to select patients for cardiac resynchronization therapy (CRT). We investigated whether the area of the QRS complex (QRSAREA) on the 3-dimensional vectorcardiogram (VCG) can improve patient selection.MethodsVCG (Frank orthogonal lead system) was recorded prior to CRT device implantation in 81 consecutive patients. VCG parameters, including QRSAREA, were assessed, and compared to QRS duration and morphology. Three LBBB definitions were used, differing in requirement of mid-QRS notching. Responders to CRT (CRT-R) were defined as patients with ≥15% reduction in left ventricular end systolic volume after 6months of CRT.ResultsFifty-seven patients (70%) were CRT-R. QRSAREA was larger in CRT-R than in CRT non-responders (140±42 vs 100±40 μVs, p<0.001) and predicted CRT response better than QRS duration (AUC 0.78 vs 0.62, p=0.030). With a 98μVs cutoff value, QRSAREA identified CRT-R with an odds ratio (OR) of 10.2 and a 95% confidence interval (CI) of 3.4 to 31.1. This OR was higher than that for QRS duration >156ms (OR=2.5; 95% CI 0.9 to 6.6), conventional LBBB classification (OR=5.5; 95% CI 0.9 to 32.4) or LBBB classification according to American guidelines (OR=4.5; 95% CI 1.6 to 12.6) or Strauss (OR=10.0; 95% CI 3.2 to 31.1).ConclusionQRSAREA is an objective electrophysiological predictor of CRT response that performs at least as good as the most refined definition of LBBB.Condensed abstractIn 81 candidates for cardiac resynchronization therapy (CRT) we measured the area of the QRS complex (QRSAREA) using 3-dimensional vectorcardiography. QRSAREA was larger in echocardiographic responders than in non-responders and predicted CRT response better than QRS duration and than simple LBBB criteria. QRSAREA is a promising electrophysiological predictor of CRT response

The value of the 12-lead ECG for evaluation and optimization of cardiac resynchronization therapy in daily clinical practice

Based on existing literature and some new data we propose a simple three-step strategy using the standard 12-lead ECG for patient selection and optimal delivery of cardiac resynchronization therapy (CRT). (1) Complete LBBB with regard to the indication for CRT can probably best be identified by a QRS duration of a &gt;= 130 ms for women and &gt;= 120 ms for men with the presence of mid-QRS notch-/slurring in &gt;= 2 contiguous leads of V-1, V-2, V-5, V-6, I and aVL. (2) Left ventricular (LV) free wall pacing should result in a positive QRS complex in lead V-1, with estimation of the exact LV lead position in the circumferential and apico-basal direction using lead aVF and the precordial leads, respectively. Wide and fractionated LV-paced QRS complexes may indicate pacing in scar tissue. (3) Atrioventricular and interventricular stimulation intervals may be optimized by adjusting them until precordial leads show fusion patterns between left and right ventricular activation wavefronts in the QRS complex

Synchronization of repolarization after cardiac resynchronization therapy: A combined clinical and modeling study

INTRODUCTION: The changes in ventricular repolarization after cardiac resynchronization therapy (CRT) are poorly understood. This knowledge gap is addressed using a multimodality approach including electrocardiographic and echocardiographic measurements in patients and using patient-specific computational modeling. METHODS: In 33 patients electrocardiographic and echocardiographic measurements were performed before and at various intervals after CRT, both during CRT-ON and temporary CRT-OFF. T-wave area was calculated from vectorcardiograms, and reconstructed from the 12-lead electrocardiography (ECG). Computer simulations were performed using a patient-specific eikonal model of cardiac activation with spatially varying action potential duration (APD) and repolarization rate, fit to a patient's ECG. RESULTS: During CRT-ON T-wave area diminished within a day and remained stable thereafter, whereas QT-interval did not change significantly. During CRT-OFF T-wave area doubled within 5 days of CRT, while QT-interval and peak-to-end T-wave interval hardly changed. Left ventricular (LV) ejection fraction only increased significantly increased after 1 month of CRT. Computer simulations indicated that the increase in T-wave area during CRT-OFF can be explained by changes in APD following chronic CRT that are opposite to the change in CRT-induced activation time. These APD changes were associated with a reduction in LV dispersion in repolarization during chronic CRT. CONCLUSION: T-wave area during CRT-OFF is a sensitive marker for adaptations in ventricular repolarization during chronic CRT that may include a reduction in LV dispersion of repolarization

Vectorcardiography for optimization of stimulation intervals in cardiac resynchronization therapy

Current optimization of atrioventricular (AV) and interventricular (VV) intervals in cardiac resynchronization therapy (CRT) is time consuming and subject to noise. We aimed to prove the principle that the best hemodynamic effect of CRT is achieved by cancelation of opposing electrical forces, detectable from the QRS morphology in the 3D vectorcardiogram (VCG). Different degrees of left (LV) and right ventricular (RV) pre-excitation were induced, using variation in AV intervals during LV pacing in 20 patients with left bundle branch block (LBBB) and variation in VV intervals during biventricular pacing in 18 patients with complete AV block or atrial fibrillation. The smallest QRS vector area identified stimulation intervals with minimal systolic stretch (median difference [IQR] 20 ms [-20, 20 ms] and maximal hemodynamic response (10 ms [-20, 40 ms]). Reliability of VCG measurements was superior to hemodynamic measurements. This study proves the principle that VCG analysis may allow easy and reliable optimization of stimulation intervals in CRT patients