Determination of sensed and paced atrial-ventricular delay in cardiac resynchronization therapy.

BACKGROUND: Optimization of atrial-ventricular delay (AVD) during atrial sensing (SAVD) and pacing (PAVD) provides the most effective cardiac resynchronization therapy (CRT). We demonstrate a novel electrocardiographic methodology for quantifying electrical synchrony and optimizing SAVD/PAVD. METHODS: We studied 40 CRT patients with LV activation delay. Atrial-sensed to RV-sensed (As-RVs) and atrial-paced to RV-sensed (Ap-RVs) intervals were measured from intracardiac electrograms (IEGM). LV-only pacing was performed over a range of SAVD/PAVD settings. Electrical dyssynchrony (cardiac resynchronization index; CRI) was measured at each setting using a multilead ECG system placed over the anterior and posterior torso. Biventricular pacing, which included multiple interventricular delays, was also conducted in a subset of 10 patients. RESULTS: When paced LV-only, peak CRI was similar (93 ± 5% vs. 92 ± 5%) during atrial sensing or pacing but optimal PAVD was 61 ± 31 ms greater than optimal SAVD. The difference between As-RVs and Ap-RVs intervals on IEGMs (62 ± 31 ms) was nearly identical. The slope of the correlation line (0.98) and the correlation coefficient r (0.99) comparing the 2 methods of assessing SAVD-PAVD offset were nearly 1 and the y-intercept (0.63 ms) was near 0. During simultaneous biventricular (BiV) pacing at short AVD, SAVD and PAVD programming did not affect CRI, but CRI was significantly (p < .05) lower during atrial sensing at long AVD. CONCLUSIONS: A novel methodology for measuring electrical dyssynchrony was used to determine electrically optimal SAVD/PAVD during LV-only pacing. When BiV pacing, shorter AVDs produce better electrical synchrony.

Electrical Dyssynchrony in Cardiac Amyloidosis: Prevalence, Predictors, Clinical Correlates, and Outcomes.

BACKGROUND: Conduction-system involvement in cardiac amyloidosis (CA) is common. The prevalence, clinical correlates and impact on outcome related to ventricular electrical dyssynchrony in CA remain insufficiently elucidated. METHODS: Data from a prospectively maintained registry of patients with CA diagnosed in the Cleveland Clinic's amyloidosis clinic was used to determine the frequency of electrical dyssynchrony (defined as a QRS > 130 msec). The relation with the clinical profile and clinical outcome was assessed. To determine the impact of hypertrophy on QRS prolongation, a QRS-matched cohort without CA was used for comparison of cardiac magnetic resonance imaging. RESULTS: A total of 1140 patients with CA (39% AL, 61% TTR) were evaluated, of whom 230 (20%) had electrical dyssynchrony. The type of conduction block was predominantly a right bundle branch block (BBB, 48%) followed by left BBB (35%) and intraventricular conduction delay (17%). Presence of transthyretin amyloidosis (ATTR-CA), older age, male gender, white race, and coronary artery disease were independently (P< 0.05 for all) associated with electrical dyssynchrony, and patients were more commonly prescribed a mineralocorticoid receptor antagonist. In ATTR-CA, specifically, every increase in ATTR-CA disease stage was associated with a 1.55-fold (1.23--1.95; P< 0.001) increased odds for electrical dyssynchrony. In a subset of patients with CA who underwent cardiac magnetic resonance imaging (n = 41), left ventricular mass index was unrelated to the QRS duration (r = 0.187; P = 0.283) in CA, in contrast to a non-CA QRS-matched cohort (r = 0.397; P< 0.001). Patients with electrical dyssynchrony were more symptomatic at initial presentation, as illustrated by a higher New York Heart Association class (P= 0.041). During a median follow-up of 462 days (IQR:138--996 days), a higher proportion of patients with electrical dyssynchrony died from all-cause death (P= 0.037) or developed a permanent pacing indication (3% vs 10.4%; P< 0.001) during follow-up. CONCLUSION: Electrical dyssynchrony is common in CA, especially in ATTR-CA, and is associated with worse functional status and clinical outcome. Given the high rate of permanent pacing indications at follow-up, additional studies are necessary to determine the best monitoring and pacing strategies in CA.

Relationship between QRS duration and resynchronization window for CRT optimization: Implications for CRT in narrow QRS patients.

AIMS: Cardiac resynchronization therapy (CRT) response is proportional to QRS duration (QRSd). We hypothesize that this is, in part, due to slower conduction velocity and hence wider range of programmed device settings that produce adequate electrical wavefront fusion and resynchronization in wider QRSd patients. METHODS: CRT patients (n = 122) with left ventricular (LV) conduction delay, sinus rhythm and intact atrioventricular node conduction were studied. Patients were categorized by QRSd: narrow (<120 ms; n = 20); moderate (120-150 ms, n = 37); and prolonged (≥150 ms; n = 65). Electrocardiographic data was acquired during native rhythm and LV-only pacing at varying atrioventricular delays (AVDs). Electrical synchrony was quantified as cardiac resynchronization index (CRI) using multi­lead electrocardiographic systems and a proprietary algorithm that quantified wavefront fusion. A Gaussian distribution equation was fitted to CRI response. RESULTS: Peak CRI was high (87.6 ± 6.3%) and similar (p = 0.716) across QRSd groups. The standard deviation of the Gaussian distribution significantly correlated with QRSd (R = 0.614, p < 0.001), and progressively and significantly (p < 0.001) increased as QRSd increased from narrow (34.8 ± 10.0 ms), to moderate (50.6 ± 8.4 ms), to prolonged (67.6 ± 18.3 ms). At AVDs 20 and 40 ms from optimal, CRI differed significantly (p < 0.001) between groups, with progressively higher CRI values as native QRSd increased. CONCLUSION: Electrical resynchronization with optimally programmed LV-only pacing was similar between patients with varying QRSd, including patients with narrow QRSd. The resynchronization window that corresponded with optimal electrical resynchronization decreased as native QRSd decreased. This finding provides one potential explanation for the lack of significant benefit of CRT in narrow QRSd patients in previous studies.

Electrical dyssynchrony mapping and cardiac resynchronization therapy.

PURPOSE: There is no clinical methodology for quantification or display of electrical dyssynchrony over a wide range of atrial-ventricular delays (AVD) and ventricular-ventricular delays (VVD) in patients with cardiac resynchronization therapy (CRT). This study aimed to develop a new methodology, based on wavefront fusion, for mapping electrical synchrony. METHODS: A cardiac resynchronization index (CRI) was measured at multiple device settings in 90 patients. Electrical dyssynchrony maps (EDM) were constructed for each patient to display CRI at any combination of AVD and VVD. An optimal synchrony line (OSL) depicted the AVD/VVD combinations producing the highest CRIs. Fusion of right ventricular paced (RVp), left ventricular paced (LVp), and native wavefront offsets were calculated. RESULTS: CRI significantly increased (p < 0.0001) from 58.0 ± 28.1% at baseline to 98.3 ± 1.7% at optimized settings. EDMs in patients with high-grade heart block (n = 20) had an OSL parallel to the simultaneous biventricular pacing (BiVPVV-SIM) line with leftward shift across all AVDs (RVp-LVpOFFSET = 50.5 ± 29.8 ms). EDMs in patients with intact AV node conduction (n = 64) had an OSL parallel to the BiVPVV-SIM line with leftward shift at short AVDs (RVp-LVpOFFSET = 33.4 ± 23.3 ms), curvilinear at intermediate AVDs (triple fusion), and vertical at long AVDs (native-LVpOFFSET = 85.2 ± 22.8 ms) in all patients except those with poor LV lead position (n = 6). CONCLUSION: A new methodology is described for quantifying and graphing electrical dyssynchrony over a physiologic range of AVDs/VVDs. This methodology offers a noninvasive, practical, clinical approach for measuring electrical synchrony that could be applied to optimization of CRT devices.

Usefulness of ventricular sense response in last-generation cardiac resynchronization therapy devices.

OBJECTIVES: High percentages of pacing were associated to maximal symptomatic and mortality benefit from cardiac resynchronization therapy (CRT). Loss of CRT pacing is linked to intrinsic ventricular activation preceding biventricular pacing (BiV), as it occurs in patients with atrial fibrillation (AF). Last generation CRT devices incorporate the ventricular sense response (VSR) mechanism to maintain biventricular pacing in patients with atrial arrhythmias. This work aimed to characterize electrical dyssynchrony differences among baseline, BiV and VSR pacing, and determine whether the VSR mode is as beneficial as the BiV mode in terms of electrical dyssynchrony. METHODS: Thirty-two patients implanted with CRT devices were retrospectively studied. All patients presented non-ischemic dilated myocardiopathy and complete left bundle branch block (LBBB). Every patient went through baseline, BiV and VSR pacing while recording the 12­lead ECG. Electrical dyssynchrony was assessed by a dyssynchrony index (DIn) obtained from correlation analysis on the 12­lead ECG. RESULTS: When comparing with baseline, VSR pacing improved QRS duration (178 ± 22 ms vs 158 ± 43 ms, baseline vs VSR, p < 0.05) and so did BiV pacing (178 ± 22 ms vs 142 ± 20 ms, baseline vs BiV, p < 0.05). However, electrical dyssynchrony only improved at BiV pacing (2.86±0.6 vs 0.54±0.8, baseline vs BiV, p < 0.05) while VSR showed average DIn values similar to those at baseline. CONCLUSIONS: VSR pacing did not improve the electrical synchrony while did shorten QRS duration in this sample population. Therefore, VSR paced beats would fall in the category of inefficient BiV and may not be the preferred alternative in patients with CRT and AF.

Prognostic value of integrative analysis of electrical and mechanical dyssynchrony in patients with acute heart failure.

BACKGROUND: Left ventricular mechanical dyssynchrony has been shown to provide significant clinical values for chronic heart failure (HF) and cardiac resynchronization therapy (CRT). The purpose of this study was to evaluate whether electrical dyssynchrony combined with mechanical dyssynchrony has an incremental benefit over electrical dyssynchrony or mechanical dyssynchrony alone to predict clinical events in patients with acute heart failure (AHF). METHODS: Ninety-six AHF patients who received standard 12-lead ECG, gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), and echocardiography were enrolled. Thirty-two normal subjects were collected as the control group to get the normal database of mechanical dyssynchrony. The end point is the composite of all-cause death and heart transplantation. Electrical dyssynchrony was defined as QRS duration > 120 ms. Mechanical dyssynchrony was defined as > mean + 2 × SD phase standard deviation (PSD) or phase bandwidth (PBW) based on our normal database. RESULTS: During the follow-up of 28 ± 10 months, complete data were obtained in 92 patients. 26 (28.3%) Patients who reached the end point were classified into the event group. There were no significant differences in PSD or PBW between the event and non-event groups. However, PBW > 77.76° was independently associated with the end point in the univariate and multivariate analysis (hazard ratio 2.92, 95% confidence interval 1.00-8.47, P = .049; hazard ratio 3.89, 95% confidence interval 1.01-14.97, P = .048). The Kaplan-Meier curve with a log-rank test showed that the end point rate was significantly higher in the patients with PBW > 77.76° (log-rank P = .039). Moreover, the ROC curve analysis showed that the area under the curve (AUC) for predicting end point events by the integrative analysis of QRS > 120 ms and PBW > 77.76° was significantly improved compared to QRS duration > 120 ms (AUC: 0.75 vs 0.68, P = .001) or PBW > 77.76° (AUC: 0.75 vs 0.62, P = .049), respectively. The model of combined electrical and mechanical dyssynchrony yielded a further significantly improved risk prediction for adverse events in the global χ2. CONCLUSIONS: The combination of QRS duration > 120 ms and PBW > 77.76° was an independent predictor of all-cause death and heart transplantation in AHF patients. The integrative analysis of electrical and mechanical dyssynchrony provides incremental prognostic value for clinical use.

Structural heart disease, not the right ventricular pacing site, determines the QRS duration during right ventricular pacing.

Right ventricular (RV) pacing causes changes in the heart's electrical and mechanical activation patterns. The QRS duration is a useful surrogate marker of electrical dyssynchrony; a longer QRS duration during RV pacing indicates poor prognosis. However, the mechanisms underlying a longer QRS duration during RV pacing remain unclear; hence, we investigated factors predicting QRS prolongation during RV pacing. We enrolled 211 patients who underwent catheter ablation for supraventricular tachyarrhythmia and showed no bundle branch block. Three-dimensional mapping for the QRS duration during RV pacing from the RV outflow to RV apex was performed, and differences in the QRS duration were analyzed. The predisposing factors causing QRS > 160 ms during RV apical pacing were also analyzed. The QRS durations at baseline and during RV pacing from the RV outflow and at the RV apex were 85.0 ± 7.5 ms, 163.7 ± 17.1 ms, and 156.2 ± 16.1 ms, respectively. With respect to the QRS duration, there was a significant correlation between RV outflow and RV apical pacing (r = 0.658, p < 0.001). Difference in the QRS duration between the RV outflow and RV apex in each patient was only 12.5 ± 10.4 ms. Logistic multivariable regression analysis identified baseline QRS duration [odds ratio (OR) 1.24, 95% confidence interval (CI) 1.15-1.33, p < 0.01], interventricular septum thickness (OR 1.20, 95% CI 1.02-1.40, p = 0.025), left atrial diameter (OR 1.08, 95% CI 1.01-1.16, p = 0.024), and E/e' (OR 1.23, 95% CI 1.12-1.35, p < 0.01) as significant predictors of QRS prolongation during RV apical pacing. The QRS duration during RV pacing largely depends not on the pacing site, but on the underlying structural heart diseases.

Novel ultra-high-frequency electrocardiogram tool for the description of the ventricular depolarization pattern before and during cardiac resynchronization.

INTRODUCTION: The present study introduces a new ultra-high-frequency 14-lead electrocardiogram technique (UHF-ECG) for mapping ventricular depolarization patterns and calculation of novel dyssynchrony parameters that may improve the selection of patients and application of cardiac resynchronization therapy (CRT). METHODS: Components of the ECG in sixteen frequency bands within the 150 to 1000 Hz range were used to create ventricular depolarization maps. The maximum time difference between the UHF QRS complex centers of mass of leads V1 to V8 was defined as ventricular electrical dyssynchrony (e-DYS), and the duration at 50% of peak voltage amplitude in each lead was defined as the duration of local depolarization (Vd). Proof of principle measurements was performed in seven patients with left (left bundle branch block) and four patients with right bundle branch block (right bundle branch block) before and during CRT using biventricular and His-bundle pacing. RESULTS: The acquired activation maps reflect the activation sequence under the tested conditions. e-DYS decreased considerably more than QRS duration, during both biventricular pacing (-50% vs -8%) and His-bundle pacing (-77% vs -13%). While biventricular pacing slightly increased Vd, His-bundle pacing reduced Vd significantly (+11% vs -36%), indicating the contribution of the fast conduction system. Optimization of biventricular pacing by adjusting VV-interval showed a decrease of e-DYS from 102 to 36 ms with only a small Vd increase and QRS duration decrease. CONCLUSIONS: The UHF-ECG technique provides novel information about electrical activation of the ventricles from a standard ECG electrode setup, potentially improving the selection of patients for CRT and application of CRT.

Electrical wavefront fusion in heart failure patients with left bundle branch block and cardiac resynchronization therapy: Implications for optimization.

BACKGROUND: Novel metrics of electrical dyssynchrony based on multi-electrode mapping and ECG-based markers of fusion are better predictors of cardiac resynchronization therapy (CRT) response than QRS duration. OBJECTIVE: To describe a new methodology for measuring electrical synchrony based on wavefront fusion and electrocardiographic cancellation in patients with CRT and its potential for CRT optimization. METHODS: Patients with left bundle branch block (LBBB) type conduction and CRT (n = 84) were studied at multiple device settings using an ECG belt (53 anterior and posterior electrodes). The area between combinations of anterior and posterior curves (AUC) was calculated and cardiac resynchronization index (CRI) defined as percent change in AUC compared to LBBB. RESULTS: In 14 patients with complete heart block or atrial fibrillation, CRI at optimal ventriculo-ventricular delay (VVD) (40 ± 19 ms) was significantly higher than with simultaneous biventricular pacing (BiVp) (90 ± 8.6% vs. 54.2 ± 24.2%, p < 0.001). In all 70 patients paced LV-only, LV-paced wavefront was ahead of native wavefront at short atrio-ventricular delay (AVD) and CRI increased with increase in AVD, peaked, and then decreased. Optimal CRI during LV-only pacing was significantly better than optimal CRI with simultaneous BiVp (89.6 ± 8% vs. 64.4 ± 22%, p < 0.001), and occurred at AVD 68 ± 22 ms less than the atrial-RV sensed interval. With sequential BiVp, best CRI was 83.9 ± 13% (with LV preactivation of 40 ± 20 ms). Best CRI at any setting was markedly better than CRI at standard setting (91.6 ± 7.7% vs. 52.7 ± 23.3, p < 0.001). CONCLUSION: We describe a novel non-invasive investigational tool that quantifies wavefront fusion and electrical dyssynchrony, and may allow for individualized CRT optimization.

Body surface activation mapping of electrical dyssynchrony in cardiac resynchronization therapy patients: Potential for optimization.

BACKGROUND: Electrical synchronization is likely improved by cardiac resynchronization therapy (CRT), but is difficult to quantify with 12-lead ECG. We aimed to quantify changes in electrical synchrony and potential for optimization with CRT using a body-surface activation mapping (BSAM) system. METHODS: Standard deviation of activation times (SDAT) was calculated in 94 patients using BSAM at baseline CRT (CRTbl), native, and different CRT configurations. RESULTS: SDAT decreased 20% from native to CRTbl (p<0.01) and an additional 26% (p<0.01) at optimal CRT (CRTopt), the minimal SDAT setting. Patients with LBBB and patients with QRS duration ≥150ms had higher native SDAT and greater decrease with CRTbl (p<0.01); however, the improvement from CRTbl to CRTopt was similar in all four groups (range: 24-28%). CRTopt was achieved with biventricular pacing in 52% and LV-only pacing in 44%. We propose that improved wavefront fusion demonstrated by BSAMs contributed substantially to the improved electrical synchrony. CONCLUSION: Optimization potential is similar regardless of pre-CRT QRS morphology or duration. BSAM could possibly improve CRT response by individualizing device programming to minimize electrical dyssynchrony.

Improved acute haemodynamic response to cardiac resynchronization therapy using multipoint pacing cannot solely be explained by better resynchronization.

BACKGROUND: The recently developed quadripolar left ventricular (LV) leads have been developed to increase the benefit of cardiac resynchronization therapy (CRT). These leads offer the option to stimulate the LV on multiple sites (multipoint pacing, MPP). Invasive haemodynamic measurements have shown that MPP increases haemodynamic response. PURPOSE: To investigate whether the beneficial effect of MPP can be explained by better electrical resynchronization. METHODS: Different LV lead locations were tested during biventricular (BiV) pacing and MPP in 29 CRT candidates. The 12-lead electrocardiogram (ECG) and the invasive LV pressure curves were measured simultaneously. The Kors matrix was used to convert the ECG into a vectorcardiogram (VCG). The acute haemodynamic benefit of MPP was compared with the reduction in QRS duration and VCG-derived QRS area. RESULTS: Out of the 29 patients, three patients were excluded due to missing LV pressures or ECG measurements. In the remaining 26 patients MPP resulted in a significant haemodynamic improvement compared to BiV pacing without a significant change in QRS duration and QRS area. In only 5 out of the 26 patients the QRS area decreased during MPP compared to BiV pacing. In 17 patients MPP did not change QRS duration and significantly increased QRS area but moved the direction of the maximal QRS vector (azimuth) more opposite from baseline compared to BiV pacing. In 4 patients the QRS area was small during baseline, indicating limited electrical dyssynchrony. CONCLUSION: The acute haemodynamic benefit of MPP over BiV pacing is achieved by either electrical resynchronization (reduction in QRS area) or by a rotation of the maximal QRS vector, indicating a more LV dominated activation sequence. The latter property was found in two-thirds of the cohort studied.

Prognostic Implications of QRS Duration in Third-Degree Atrioventricular Block Patients with Heart Failure Treated with Cardiac Resynchronization Therapy.

Cardiac resynchronization therapy (CRT) improves heart function and prognosis in third-degree atrioventricular block (AVB) patients with heart failure (HF). However, it is still unclear how to screen for appropriate patients before implantation. This study aimed to evaluate the value of using QRS duration to predict CRT efficacy.This study enrolled a total of 72 third-degree AVB patients with HF who received CRT implantation. The patients were divided into Groups A (QRS duration < 120 ms, 33 cases), B (120 ms ≤ QRS duration < 150 ms, 22 cases), and C (QRS duration ≥ 150 ms, 17 cases) according to their baseline QRS duration. The effects of different QRS durations on CRT efficacy were analyzed.The CRT response rate were 30.3%, 50.0%, and 76.5% in Groups A, B, and C, respectively (P = 0.008). The patients in the 3 groups showed significant changes in left ventricular (LV) end-diastolic volume, LV end-systolic volume, and LV ejection fraction over the baseline values at 12 months after the implantation (P < 0.05), with the greatest change observed in Group C. Survival analysis indicated statistically significant differences among Groups A, B, and C (P = 0.024). Multivariate logistic regression analysis suggested that QRS duration was an independent prognostic factor for CRT efficacy. Baseline QRS duration was associated with improved myocardial remodeling and reductions in the incidence rates of primary endpoint events.QRS ≥ 150 ms is an effective predictor of postoperative outcome in patients with third-degree AVB and HF treated with CRT.

Deleterious acute and chronic effects of bradycardic right ventricular apex pacing: consequences for arrhythmic outcome.

In the chronic complete atrioventricular (AV) block dog (CAVB) model, both bradycardia and altered ventricular activation due to the uncontrolled idioventricular rhythm contribute to ventricular remodeling and the enhanced susceptibility to Torsade de Pointes (TdP) arrhythmias. We investigated the effect of permanent bradycardic right ventricular apex (RVA) pacing on mechanical and electrical remodeling and TdP. In 23 anesthetized dogs, serial experiments were performed at sinus rhythm (SR), acutely after AV block (AAVB) and 3 weeks of remodeling CAVB at a fixed pacing rate of 60/min. ECG, and left (LV) and right ventricular (RV) monophasic action potentials durations (MAPD) were recorded; activation time (AT) and activation recovery interval (ARI) were determined from ten distinct LV electrograms; interventricular mechanical delay (IVMD) and time-to-peak strain (TTP) of the LV septal and lateral wall (ΔTTP: lateral wall minus septal wall) were obtained echocardiographically. Dofetilide (25 µg/kg/5 min) was infused to study TdP inducibility. In baseline AAVB, in comparison to SR, RVA bradypacing acutely increased QT interval, LV, and RVMAPD. Echocardiographic IVMD and ΔTTP were initially increased, which was partially corrected after 3 weeks of RVA pacing (IVMD: 22 ± 13 vs. 42 ± 11 vs. 31 ± 6 ms; ΔTTP: -2 ± 47 vs. -114 ± 38 vs. -36 ± 22 ms). QT interval (362 ± 23 vs. 373 ± 29 ms), LVMAPD (245 ± 18 vs. 253 ± 22 ms), RVMAPD (226 ± 26 vs. 238 ± 31 ms), and mean LV-ARI (268 ± 5 vs. 267 ± 6 ms) were not significantly changed after 3 weeks of RVA pacing. During AAVB, dofetilide increased mean LV-ARI (381 ± 11 ms) with largest increases in the later activated basal areas (slope AT-ARI: +0.96). In contrast with acute RVA pacing, 3 week pacing increased TdP inducibility (0/13 vs. 11/21) and mean LV-ARI (484 ± 18 ms), while the slope of AT-ARI responded differently on dofetilide (-2.37), with larger APD increases in the early region. The latter was supported at the molecular level: reduced RNA expressions of three repolarization-related ion channel genes in early (KCNQ1, KCNH2, and KCNJ2) versus two in late regions (KNCQ1 and KCNJ2). In conclusion, bradycardic RVA pacing acutely induced LV intra- and interventricular mechanical dyssynchrony, which was partially reversed after 3 weeks of pacing (remodeling). The latter occurred without apparent baseline electrical effects. However, dofetilide clearly unmasked (region-specific) arrhythmic consequences of remodeling.

Dual-site right ventricular pacing in patients undergoing cardiac resynchronization therapy: Results of a multicenter propensity-matched analysis.

BACKGROUND: Dual-site right ventricular pacing (Dual RV) has been proposed as an alternative for patients with heart failure undergoing cardiac resynchronization therapy (CRT) with a failure to deliver a coronary sinus (CS) lead. Only short-term hemodynamic and echocardiographic results of Dual RV are available. We aimed to assess the long-term results of Dual RV and its impact on survival. METHODS: Multicenter retrospective assessment of all CRT implants during a 12-year period. Patients with failed CS lead implantation, treated with Dual RV, were followed and assessed for the primary endpoint of all-cause mortality and/or heart transplant. A control group was obtained from contemporary patients using propensity matching for all available baseline variables. RESULTS: Ninety-three patients were implanted with Dual RV devices and compared with 93 matched controls. During a median of 1,273 days (interquartile range 557-2,218), intention-to-treat analysis showed that all-cause mortality and/or heart transplant was higher in the Dual RV group (adjusted hazard ratio [HR] = 1.66, 95% confidence interval [CI] 1.12-2.47, P = 0.012). As-treated analysis yielded similar results (HR = 1.97, 95% CI 1.31-2.96, P = 0.001). Cardiac device-related infections occurred seven times more frequently in the Dual RV site group (HR = 7.60, 95% CI 1.51-38.33, P = 0.014). Among Dual RV nonresponders, four had their apical leads switched off, five required an epicardial LV lead insertion, a transseptal LV lead was implanted in two, and in nine patients, after reviewing the CS venogram, a new CS lead insertion was successfully attempted. CONCLUSION: Dual RV pacing is associated with worse clinical outcomes and higher complication rates than conventional CRT.

Predicting Ventricular Arrhythmias in Cardiac Resynchronization Therapy: The Impact of Persistent Electrical Dyssynchrony.

BACKGROUND: Although response to cardiac resynchronization therapy (CRT) has been conventionally assessed with left ventricular volume reduction, ventricular arrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]) are of critical importance associated with unfavorable outcomes even in the "superresponders" to therapy. We evaluated the predictors of VT/VF and the association of residual dyssynchrony during follow-up. METHODS: Ninety-five patients receiving CRT were followed-up for 9 ± 3 months. Post-CRT dyssynchrony was defined as a prolonged QRS duration (QRSd) for persistent electrical dyssynchrony (ED), and a Yu index ≥ 33 ms for persistent mechanical dyssynchrony. The first VT/VF episode, including nonsustained VT detected on device interrogation and/or appropriate antitachycardia pacing or shock for VT/VF, were the end points of the study. RESULTS: Forty-five patients who reached the study end points had significantly lower mean ΔQRS (baseline QRSd - post-CRT QRSd) values than those without VT/VF (-20.8 ± 28.9 ms vs -6.6 ± 30.7 ms, P = 0.022). Both the baseline and post-CRT QRSds, along with the Yu index values, were not different in two groups. Patients with VT/VF were statistically more likely to have persistent ED (38% vs 9%, P = 0.021). Kaplan-Meier curves showed that a negative ΔQRS was associated with a higher incidence of VT/VF during follow-up (P = 0.016). A multivariate Cox model revealed that QRS prolongation was an independent predictor of VT/VF after CRT (P = 0.029). CONCLUSIONS: A negative ΔQRS, also called persistent ED, is associated with VT/VF. Narrowest possible QRSd might be a reliable goal of both implantation and optimization of devices to reduce arrhythmic events after CRT.

Measurements of electrical and mechanical dyssynchrony are both essential to improve prediction of CRT response.

INTRODUCTION: Predicting reverse remodeling after cardiac resynchronization therapy (CRT) remains challenging and different etiologies of heart failure might hamper identification of predictors. OBJECTIVE: Assess the incremental value of mechanical dyssynchrony besides electrical dyssynchrony for predicting CRT response. METHODS: 227 patients (51% ischemic) received CRT. Response was defined as ≥15% left ventricular end systolic volume decrease after six months. Prediction models were developed comprising clinical parameters and electrical dyssynchrony (Model A), subsequently complemented with mechanical dyssynchrony (Model B). Models were compared by area under the receiver-operating curve (AUC), net reclassification index (NRI) and integrated discrimination improvement (IDI) for the complete cohort, ischemic (ICM) and non-ischemic (NICM) subpopulations. RESULTS: Model B performed significantly better than Model A supported by AUC, NRI and IDI. Furthermore, model B significantly better predicted response for NICM than ICM. CONCLUSION: Electrical dyssynchrony and mechanical dyssynchrony are essential to predict CRT response. Nevertheless, response prediction for ICM remains challenging.

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.

Cardiac resynchronization therapy: past, present, and future.

Cardiac resynchronization therapy (CRT), or biventricular pacing, has become a standard therapeutic modality for patients with symptomatic heart failure (HF), depressed left ventricular (LV) function, and electrical dyssynchrony. Despite the overall success of CRT in improving morbidity and mortality in selected patients with HF, a significant minority demonstrates nonresponse. This review describes the electrical and physiologic rationale for biventricular pacing therapy, summarizes landmark clinical trials assessing CRT efficacy, highlights strategies to optimize the response to CRT, and frames future challenges in the use, delivery, and care of patients undergoing CRT.

Long-term impact of cardiac resynchronization therapy in mild heart failure: 5-year results from the REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) study.

BACKGROUND: The benefit of cardiac resynchronization therapy (CRT) among patients with mild heart failure (HF), reduced left ventricular (LV) function and wide QRS is well established. We studied the long-term stability of CRT. METHODS: REVERSE was a randomized, double-blind study on CRT in NYHA Class I and II HF patients with QRS ≥120 ms and left ventricular ejection fraction (LVEF) ≤40%. After the randomized phase, all were programmed to CRT ON and prospectively followed through 5 years for functional capacity, echocardiography, HF hospitalizations, mortality, and adverse events. We report the results of the 419 patients initially assigned to CRT ON. FINDINGS: The mean follow-up time was 54.8 ± 13.0 months. After 2 years, the functional and LV remodelling improvements were maximal. The 6-min hall walk increased by 18.8 ± 102.3 m and the Minnesota and Kansas City scores improved by 8.2 ± 17.8 and 8.2 ± 17.2 units, respectively. The mean decrease in left ventricular end-systolic volume index and left ventricular end-diastolic volume index was 23.5 ± 34.1 mL/m(2) (P < 0.0001) and 25.4 ± 37.0 mL/m2 (P < 0.0001) and the mean increase in LVEF 6.0 ± 10.8% (P < 0.0001) with sustained improvement thereafter. The annualized and 5-year mortality was 2.9 and 13.5% and the annualized and 5-year rate of death or first HF hospitalization 6.4, and 28.1%. The 5-year LV lead-related complication rate was 12.5%. CONCLUSION: In patients with mild HF, CRT produced reverse LV remodelling accompanied by very low mortality and need for heart failure hospitalization. These effects were sustained over 5 years. Cardiac resynchronization therapy in addition to optimal medical therapy produces long-standing clinical benefits in mild heart failure. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00271154.

The left ventricular lead electrical delay predicts response to cardiac resynchronisation therapy.

Up to one-third of patients who undergo cardiac resynchronisation therapy (CRT) are not responders. To identify potential responders to CRT may be sometimes difficult and time-consuming. Forty-five patients who had undergone CRT implantation for standard indications were evaluated. Electrical left ventricular (LV) lead location was assessed by left ventricular activation time (LVAT), LV lead electrical delay (LVLED), and RV-LV interlead electrical delay (RVsense-LVsense). Anatomic LV pacing location was assessed as basal or mid-ventricular between 3:00 to 5:00 (traditionally optimal site), and all the other positions (traditionally non-optimal site). CRT response was defined as a decrease in LV end-systolic volume (LVESV) exceeding 15% at six months. LVLED was larger in the responder group than that in the non-responder group (67.3 ± 8.5% vs. 55.3 ± 8.1%, P< 0.001). In the multivariate analysis, LVLED and cLBBB morphology were the two independent predictors of positive echocardiographic response to CRT (OR=1.180, P=0.003; OR=7.497, P=0.04, respectively). A cutoff value of LVLED> 54.82% predicted responders with 96.3% sensitivity and 75.2% specificity and the area under the receiver operating characteristic (ROC) curve was 0.844 for LVLED (P=0.002). No relationship was found between the anatomic LV pacing sites and response to CRT (P=0.188). The larger left ventricular lead electrical delay may predict response to cardiac resynchronisation therapy.