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.

The synthesized vectorcardiogram resembles the measured vectorcardiogram in patients with dyssynchronous heart failure.

BACKGROUND: The use of vectorcardiography (VCG) has regained interest, however, original Frank-VCG equipment is rare. This study compares the measured VCGs with those synthesized from the 12-lead electrocardiogram (ECG) in patients with heart failure and conduction abnormalities, who are candidate for cardiac resynchronization therapy (CRT). METHODS: In 92 CRT candidates, Frank-VCG and 12-lead ECG were recorded before CRT implantation. The ECG was converted to a VCG using the Kors method (Kors-VCG) and the two methods were compared using correlation and Bland-Altman analyses. RESULTS: Variables calculated from the Frank- and Kors-VCG showed correlation coefficients between 0.77 and 0.90. There was a significant but small underestimation by the Kors-VCG method, relative bias ranging from -1.9% ± 4.6% (QRS-T angle) to -9.4% ± 20.8% (T area). CONCLUSION: The present study shows that it is justified to use Kors-VCG calculations for VCG analysis, which enables retrospective VCG analysis of previously recorded ECGs in studies related to CRT.

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.

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

BACKGROUND: QRS 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. METHODS: VCG (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. RESULTS: Fifty-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). CONCLUSION: QRSAREA is an objective electrophysiological predictor of CRT response that performs at least as good as the most refined definition of LBBB. CONDENSED ABSTRACT: In 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.

Early repolarization in middle-age runners: cardiovascular characteristics.

PURPOSE: This study aimed to assess the prevalence and patterns of early repolarization (ER) in middle-age long-distance runners, its relation to cardiac structure and function, and its response to strenuous physical activity. METHODS: Male first-time cross-country race participants >45 yr were assessed pre- and postrace by medical history and physical examination, 12-lead ECG, vectorcardiography, blood tests, and echocardiography. ER was defined either as ST elevation or J wave and categorized according to localization and morphology. RESULTS: One hundred and fifty-one subjects (50 ± 5 yr) were evaluated before the race, and 47 subjects were evaluated after the race. Altogether, 67 subjects (44%) had ER. Subjects with versus without ER had a lower resting HR (56 ± 8 vs 69 ± 9 bpm, P = 0.02), lower body mass index (24 ± 2 vs 25 ± 3 kg·m(-2), P < 0.001), higher training volume (3.0 ± 2.6 vs 2.1 ± 2.7 h·wk(-1), P = 0.03), and faster 30-km running times (194 ± 28 vs 208 ± 31 min, P = 0.01). Vectorcardiography parameters in subjects with ER showed more repolarization heterogeneity: vector gradient (QRS-T(area)) (120 ± 25 vs 92 ± 29 µVs, P < 0.001), T(area) (105 ± 18 vs 73 ± 23 µVs, P < 0.001), and T(amplitude) (0.63 ± 0.13 vs 0.53 ± 0.16 mm, P < 0.001); these parameters were inversely related to HR (r = -0.37 to -0.48, P < 0.001). ER disappeared in 15 (75%) of 20 subjects after the race. CONCLUSIONS: ER is a common finding in middle-age male runners. This ECG pattern, regardless of morphology and localization, is associated with normal cardiac examinations including noninvasive electrophysiology, features of better physical conditioning, and disappears after strenuous exercise in most cases. These findings support that ER should be regarded as a common and training-related finding also in middle-age physically active men.

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 ≥ 130 ms for women and ≥ 120 ms for men with the presence of mid-QRS notch-/slurring in ≥ 2 contiguous leads of V1, V2, V5, V6, I and aVL. (2) Left ventricular (LV) free wall pacing should result in a positive QRS complex in lead V1, 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.

Vectorcardiography shows cardiac memory and repolarization heterogeneity after ablation of accessory pathways not apparent on ECG.

BACKGROUND: Pacing induced cardiac memory is an established phenomenon, but following successful WPW ablation, cardiac memory was present on ECG in variable proportions of patients depending on accessory pathway (AP) location. We hypothesized that vectorcardiography (VCG), which is more sensitive than ECG, would show cardiac memory after WPW ablation independent of AP location. METHODS: Thirty-six patients were followed after successful AP ablation, 11 with overt posteroseptal (PS), 13 with overt left-sided (LS) and 12 with concealed APs (controls). VCGs were recorded the day before and after the procedure, ≥ once/week for 6-8 weeks and after ≥ 3 months. T vector and T-vector loop parameters were analyzed and compared. RESULTS: After ablation of overt APs, there was a correlation between the directions of the preexcited maximum QRS-vector and the post-ablation maximum T-vector, confirming the presence of cardiac memory. Ablation of overt APs was followed by cardiac memory apparent in different directions. Thus, ablation of PS APs was followed by most pronounced changes in T-vector elevation and LS APs with significant changes only in T-vector azimuth. Cardiac memory disappeared within a month in > 80% of cases. Furthermore, T-vector loop morphology changes suggested a period of repolarization heterogeneity immediately after ablation of overt APs. CONCLUSIONS: According to VCG analysis cardiac memory was present after ablation of overt APs independent of location as consistently as after ventricular pacing, and disappeared within a similar time frame during normal ventricular activation. In addition, signs of transient repolarization heterogeneity were observed after ablation of overt APs.

Vectorcardiography as a tool for easy optimization of cardiac resynchronization therapy in canine left bundle branch block hearts.

BACKGROUND: In cardiac resynchronization therapy (CRT), optimization of left ventricular (LV) stimulation timing is often time consuming. We hypothesized that the QRS vector in the vectorcardiogram (VCG) reflects electric interventricular dyssynchrony, and that the QRS vector amplitude (VAQRS), halfway between that during left bundle branch block (LBBB) and LV pacing, reflects optimal resynchronization, and can be used for easy optimization of CRT. METHODS AND RESULTS: In 24 canine hearts with LBBB (12 acute, 6 with heart failure, and 6 with myocardial infarction), the LV was paced over a wide range of atrioventricular (AV) delays. Surface ECGs were recorded from the limb leads, and VAQRS was calculated in the frontal plane. Mechanical interventricular dyssynchrony (MIVD) was determined as the time delay between upslopes of LV and right ventricular pressure curves, and systolic function was assessed as LV dP/dtmax. VAQRS and MIVD were highly correlated (r=0.94). The VAQRS halfway between that during LV pacing with short AV delay and intrinsic LBBB activation accurately predicted the optimal AV delay for LV pacing (1 ms; 95% CI, -5 to 8 ms). Increase in LV dP/dtmax at the VCG predicted AV delay was only slightly lower than the highest observed LV dP/dtmax (-2.7%; 95% CI, -3.6 to -1.8%). Inability to reach the halfway value of VAQRS during simultaneous biventricular pacing (53% of cases) was associated with suboptimal hemodynamic response, which could be corrected by sequential pacing. CONCLUSIONS: The VAQRS reflects electric interventricular dyssynchrony and accurately predicts optimal timing of LV stimulation in canine LBBB hearts. Therefore, VCG may be useful as a reliable and easy tool for individual optimization of CRT.

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.

Repolarization changes in patients with heart failure receiving cardiac resynchronization therapy-signs of cardiac memory.

BACKGROUND AND PURPOSE: Cardiac memory is known as T-wave inversions and other repolarization changes after a period of altered ventricular activation, previously mainly studied in structurally normal hearts. We investigated repolarization changes in failing hearts undergoing cardiac resynchronization therapy (CRT). METHODS: Electrocardiogram and vectorcardiogram were recorded before and 1 day and 2 weeks after initiation of CRT in 23 patients with heart failure and left bundle-branch block. RESULTS: After 1 day of CRT, the T vector during intrinsic conduction (left bundle-branch block) had rotated toward the direction of the paced QRS vector; T-vector size had increased with further increase after 2 weeks (T-vector amplitude, 889 ± 277 vs 651 ± 225 µV; T area, 169 ± 70 vs 102 ± 39 µVs; P < .01) accompanied by prolonged repolarization (T peak-to-end, 174 ± 34 vs 127 ± 16; QT interval corrected for heart rate, 541 ± 59 vs 493 ± 33 milliseconds; P < .01). CONCLUSIONS: Repolarization changes are present in patients with heart failure, although less pronounced compared with after right ventricular pacing in structurally normal hearts.

Maximal aerobic power versus performance in two aerobic endurance tests among young and old adults.

BACKGROUND: Aerobic fitness is of great value for reducing risk of mortality and cardiovascular diseases. OBJECTIVE: This study evaluated the performance in and correlations between a new test (five-minute pyramid test, 5MPT), the six-minute walk-test (6MWT) and maximal oxygen uptake (VO2max) among old and young adults. METHODS: Forty-four habitually active adults (females and males), 23 old (64-79 years) and 21 young (20-32 years) participated. In the 5MPT, the participants moved back and forth along a short walkway (5.5 m) over boxes (height: 'old people' 0.42 m, 'young people' 0.62 m) arranged like an elongated step pyramid for 5 min. Power in the pyramid test (5MPT(power)) was calculated as the product of numbers of laps, body weight, gravity and highest box level divided by time. A 6MWT and a maximal cycle ergometer test for direct measurements of VO2max were also performed. In all tests heart rate, with on-line electrocardiography, and perceived exertion were recorded. RESULTS: There was a strong correlation between the 5MPT(power) and VO2max for the entire group studied (r = 0.98), and each of the four subgroups old and young females and males separately (r = 0.78-0.98). Contrary to several earlier studies, especially involving people with various diseases, the present data showed that 6MWT cannot be used to predict VO2max among old females and young adults. The correlation with VO2max was weaker for the 6MWT than for the 5MPT(power). The relative performance values for the old compared to the young (ratio old/young × 100) were considerably lower in 5MPT(power) and VO2max (47-55%) than in distance and 'work' in the 6MWT (82-86%). CONCLUSIONS: The results, with age and gender variations, can be valuable information in health-fitness contexts, since measuring physical aerobic capacity is very significant in connection with risk evaluations of mortality and various diseases. The 5MPT is a rapid, functional, easy and inexpensive tool for predicting assessed maximal aerobic power.

Right ventricular pacing-induced electrophysiological remodeling in the human heart and its relationship to cardiac memory.

BACKGROUND: Right ventricular apical (RVA) pacing induces electrophysiological and structural remodeling. Cardiac memory (CM) evolves during the course of pacing and is readily apparent on electrocardiography (ECG) or vectorcardiography (VCG) when normal ventricular activation resumes. OBJECTIVE: This study sought to assess ventricular repolarization (VR) changes during pacing and intermittent normal ventricular conduction by ECG and VCG and to determine the temporal and conformational evolution of CM. METHODS: Twenty sick sinus patients received a dual-chamber rate-adaptive (DDD-R) pacemaker and were paced from the RVA endocardium. The pacemakers were programmed to a short AV delay to maximize ventricular preexcitation. The ECG and VCG were recorded before and 1 day after implantation, and then daily for the first week (n=6) or weekly for 5 to 8 weeks (n=14), with the pacemakers temporarily programmed to AAI (normal ventricular activation). RESULTS: The first parameters to change were T-vector amplitude, T(area), and T(peak)-T(end) (T(p-e)), which decreased within 1 day after initiating pacing. CM became apparent between day 1 and day 3, was fully established after 1 week, and then remained stable. Signs of increased VR heterogeneity were observed as the T loop became more circular (decreased T(egenv)) and distorted (increased T(avplan)), which have previously been observed in conditions with increased risk for arrhythmias. Over weeks, VR duration was prolonged (increased QTc). In contrast, during ventricular pacing, a gradual shortening of the repolarization time was observed, suggesting a stabilizing adaptive process. CONCLUSION: In sick sinus syndrome patients in whom ventricular pacing is indicated, switching between normal AV conduction and ventricular pacing should be minimized to avoid periods of repolarization instability.

T wave inversions following ablation of 125 posteroseptal accessory pathways.

BACKGROUND: Cardiac memory, electrophysiological remodeling induced by periods of altered ventricular activation, has been observed after resumption of normal activation following ablation of overt accessory pathways. We studied the occurrence and temporal characteristics of cardiac memory (inferior T wave inversions) after ablation of overt posteroseptal accessory pathways. METHODS: T wave changes were assessed in the frontal plane (leads II, aVF, and III) up to one year after the ablation in 125 consecutive patients. T wave polarity immediately after ablation was compared with the pre ablation delta wave polarity and the dominant QRS force in each lead. The number of inferior leads (0-3) with post ablation T wave changes (estimate of degree of cardiac memory) was analyzed in relation to estimates of the degree of preexcitation (accessory pathway refractoriness and QRS duration) prior to ablation. RESULTS: Electrocardiogram (ECG) signs of cardiac memory were present in 123 (98%) of the patients within one day after ablation. The post ablation T wave vector had the same direction as the vector of the pre-excited QRS complex (and delta wave) creating inferior T wave inversions. There was no correlation between the degree of preexcitation pre ablation and the extent of cardiac memory post ablation. A majority (about 90%) of ECGs recorded 3-6 months after the procedure, showed complete or almost complete normalization. CONCLUSIONS: T wave inversions were present in the vast majority of patients, persisted in some patients beyond 3 months, and might be misinterpreted as inferior wall ischemia.

Pacing-induced electrophysiological remodeling in hypertrophic obstructive cardiomyopathy--observations on cardiac memory.

BACKGROUND: Hypertrophic cardiomyopathy carries an increased risk for sudden cardiac death. While pacing therapy reduces the left ventricular outflow tract gradient and improves symptoms in a subgroup of hypertrophic obstructive cardiomyopathy (HOCM) patients, its electrophysiological consequences are unknown and were therefore assessed in this prospective study. METHODS AND RESULTS: Fifteen consecutive HOCM patients were studied and compared with 14 patients without HOCM paced because of sinus bradycardia. ECG intervals were measured before pacemaker implantation and after > or =3 months of DDD pacing in HOCM patients and > or =5 weeks in controls. Both groups showed similar ECG signs of cardiac memory development. In HOCM patients, with baseline QTc 447 +/- 33 ms, cardiac memory development was not associated with any significant changes in ECG intervals. In contrast, baseline repolarization in control patients was significantly prolonged by 6% (QTc 429 +/- 33 vs 454 +/- 46 ms; P < 0.05). Furthermore, in HOCM patients repolarization was 7% shorter during DDD pacing compared to sinus rhythm (JTc 329 +/- 25 vs 353 +/- 21 ms; P < 0.05), despite a significantly prolonged ventricular activation time (QRS duration 155 +/- 16 vs 91 +/- 9 ms; P < 0.01). CONCLUSIONS: Importantly, the development of cardiac memory-induced different repolarization responses depending on baseline structure and electrophysiology. In HOCM patients repolarization was shorter during right ventricular apical pacing than during normal activation despite prolonged activation time.

Temporal characteristics of cardiac memory in humans: vectorcardiographic quantification in a model of cardiac pacing.

OBJECTIVES: The purpose of this study was to assess the temporal characteristics of cardiac memory in a human pacing model. BACKGROUND: Cardiac memory is induced by periods of altered ventricular activation and in the canine pacing model develops in 2 to 3 weeks. METHODS: Cardiac memory development (phase 1) and resolution (phase 2) was followed qualitatively (ECG) and quantitatively (vectorcardiography [VCG]) in 20 patients with symptomatic sinus bradycardia receiving DDD-R pacing at physiologic rates. During phase 1, maximum ventricular pacing in the right ventricular apical endocardium was achieved by short AV delay. ECG and VCG were recorded during normal ventricular activation prior to implantation (sinus rhythm), 1 day after and then weekly for 5 to 8 weeks during AAI pacing (n = 14, "long-term"), and daily during 1 week (n = 6, "short-term"). In phase 2, the remaining cardiac memory was related to the amount of ventricular pacing. A long AV delay was chosen to reduce ventricular pacing, and 14 patients were seen once after 4 to 5 weeks. RESULTS: ECG and VCG showed marked changes in all patients within 1 week's pacing and remained stable during phase 1. Of the 14 long-term patients, 13 showed significant change in T vector azimuth (mean -150 degrees ) and 11 in T vector elevation (mean 63 degrees ). At the end of phase 2, a linear relation existed between remaining cardiac memory (%) and amount (%) of delivered ventricular pacing. CONCLUSIONS: Cardiac memory developed and reached steady state within 1 week of right ventricular endocardial pacing at physiologic rates in man, was preserved in proportion to delivered ventricular pacing, and completely resolved within 1 month in its absence.

T vector and loop characteristics in coronary artery disease and during acute ischemia.

OBJECTIVE: Three-dimensional characterization of the ventricular repolarization by the T vector and T vector loop morphology in coronary artery disease (CAD), and their response to short-term (no flow) ischemia induced by coronary occlusion during a percutaneous intervention (PCI). BACKGROUND: The risk for sudden cardiac death is increased in conditions of acute or permanently heterogeneous ventricular repolarization, for which ischemia is a risk factor. METHODS: Fifty-six CAD patients without visible collateral circulation were studied during an elective single-vessel PCI, and 10 healthy controls twice at rest. T vector parameters (Televation, Tazimuth, and QRS-T angle), and T loop parameters (Tarea, Tavplan, and Teigenv) were measured by vectorcardiography. ST vector magnitude (ST-VM) and its change (STC-VM) were used for reference. RESULTS: At rest, T vector loop morphology (Tarea, Teigenv) was significantly different in CAD patients and controls, while T vector angles did not separate the groups. Ischemia induced significant changes in T loop parameters in the entire CAD group, whereas in the LAD subgroup significant changes were seen also in T vector angle. The T loop morphology was significantly different at baseline and a more pronounced response to ischemia (Tarea) was seen in patients with, than in those without, a history of hypertension. CONCLUSION: T loop morphology, rather than the T vector angle, separated CAD patients from healthy controls. Coronary occlusion had significant impact on ventricular repolarization, as assessed by T vector and morphology analysis, and most prominently in the LAD group. Hypertensive patients appeared especially vulnerable to ischemia.