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Introduction: We aimed to investigate the impact of the 2021 European Society of Cardiology (ESC) guideline changes in left bundle branch block (LBBB) definition on cardiac resynchronization therapy (CRT) patient selection and outcomes. Methods: The MUG (Maastricht, Utrecht, Groningen) registry, consisting of consecutive patients implanted with a CRT device between 2001 and 2015 was studied. For this study, patients with baseline sinus rhythm and QRS duration ≥ 130ms were eligible. Patients were classified according to ESC 2013 and 2021 guideline LBBB definitions and QRS duration. Endpoints were heart transplantation, LVAD implantation or mortality (HTx/LVAD/mortality) and echocardiographic response (LVESV reduction ≥15%). Results: The analyses included 1.202, typical CRT patients. The ESC 2021 definition resulted in considerably less LBBB diagnoses compared to the 2013 definition (31.6% vs. 80.9%, respectively). Applying the 2013 definition resulted in significant separation of the Kaplan–Meier curves of HTx/LVAD/mortality (p <.0001). A significantly higher echocardiographic response rate was found in the LBBB compared to the non‐LBBB group using the 2013 definition. These differences in HTx/LVAD/mortality and echocardiographic response were not found when applying the 2021 definition. Conclusion: The ESC 2021 LBBB definition leads to a considerably lower percentage of patients with baseline LBBB then the ESC 2013 definition. This does not lead to better differentiation of CRT responders, nor does this lead to a stronger association with clinical outcomes after CRT. In fact, stratification according to the 2021 definition is not associated with a difference in clinical or echocardiographic outcome, implying that the guideline changes may negatively influence CRT implantation practice with a weakened recommendation in patients that will benefit from CRT. [ABSTRACT FROM AUTHOR]

Introduction: Recent studies have shown that the baseline QRS area is associated with the clinical response after cardiac resynchronization therapy (CRT). In this study, we investigated the association of QRS area reduction (∆QRS area) after CRT with the outcome. We hypothesize that a larger ∆QRS area is associated with a better survival and echocardiographic response. Methods and Results: Electrocardiograms (ECG) obtained before and 2–12 months after CRT from 1299 patients in a multi‐center CRT‐registry were analyzed. The QRS area was calculated from vectorcardiograms that were synthesized from 12‐lead ECGs. The primary endpoint was a combination of all‐cause mortality, heart transplantation, and left ventricular (LV) assist device implantation. The secondary endpoint was the echocardiographic response, defined as LV end‐systolic volume reduction ≥ of 15%. Patients with ∆QRS area above the optimal cut‐off value (62 µVs) had a lower risk of reaching the primary endpoint (hazard ratio: 0.43; confidence interval [CI] 0.33–0.56, p <.001), and a higher chance of echocardiographic response (odds ratio [OR] 3.3;CI 2.4–4.6, p <.0001). In multivariable analysis, ∆QRS area was independently associated with both endpoints. In patients with baseline QRS area ≥109 µVs, survival, and echocardiographic response were better when the ∆QRS area was ≥62 µVs (p <.0001). Logistic regression showed that in patients with baseline QRS area ≥109 µVs, ∆QRS area was the only significant predictor of survival (OR: 0.981; CI: 0.967–0.994, p =.006). Conclusion: ∆QRS area is an independent determinant of CRT response, especially in patients with a large baseline QRS area. Failure to achieve a large QRS area reduction with CRT is associated with a poor clinical outcome. [ABSTRACT FROM AUTHOR]

Aims: Various strain parameters and multiple imaging techniques are presently available including cardiovascular magnetic resonance (CMR) tagging (CMR‐TAG), CMR feature tracking (CMR‐FT), and speckle tracking echocardiography (STE). This study aims to compare predictive performance of different strain parameters and evaluate results per imaging technique to predict cardiac resynchronization therapy (CRT) response. Methods and results: Twenty‐seven patients were prospectively enrolled and underwent CMR and echocardiographic examination before CRT implantation. Strain analysis was performed in circumferential (CMR‐TAG, CMR‐FT, and STE‐circ) and longitudinal (STE‐long) orientations. Regional strain values, parameters of dyssynchrony, and discoordination were calculated. After 12 months, CRT response was measured by the echocardiographic change in left ventricular (LV) end‐systolic volume (LVESV). Twenty‐six patients completed follow‐up; mean LVESV change was −29 ± 27% with 17 (65%) patients showing ≥15% LVESV reduction. Measures of dyssynchrony (SD‐TTPLV) and discoordination (ISFLV) were strongly related to CRT response when using CMR‐TAG (R2 0.61 and R2 0.57, respectively), but showed poor correlations for CMR‐FT and STE (all R2 ≤ 0.32). In contrast, the end‐systolic septal strain (ESSsep) parameter showed a consistent high correlation with LVESV change for all techniques (CMR‐TAG R2 0.60; CMR‐FT R2 0.50; STE‐circ R2 0.43; and STE‐long R2 0.43). After adjustment for QRS duration and QRS morphology, ESSsep remained an independent predictor of response per technique. Conclusions: End‐systolic septal strain was the only parameter with a consistent good relation to reverse remodelling after CRT, irrespective of assessment technique. In clinical practice, this measure can be obtained by any available strain imaging technique and provides predictive value on top of current guideline criteria. [ABSTRACT FROM AUTHOR]

Aims Some, but not all, studies have shown that patient-reported health status, including symptoms, functioning, and healthrelated quality of life, provides additional information to traditional clinical factors in predicting prognosis in heart failure patients. To evaluate the overall evidence, the association of disease-specific health status on mortality in heart failure was examined through a systematic review and meta-analysis. Methods and results Prospective cohort studies that assessed the independent association of disease-specific health status with mortality in heart failure were selected. Searching PubMed (until March 2013) resulted in 17 articles in the systematic review and 17 studies in the meta-analysis. About half of the studies reported a significant relationship between diseasespecific health status and mortality in heart failure, while the remainder found no association. A larger sample size increased the chance of identification of a significant association. The results of the meta-analysis (including studies using a dichotomized heart failure-specific health status variable as predictor) showed that heart failure patients reporting poor disease-specific health status had a 39% increased risk of dying [hazard ratio 1.39 (1.25-1.54)] when compared with patients experiencing moderate or good disease-specific health status. Conclusion Patient-reported health status was an independent risk indicator for mortality in heart failure patients and may facilitate the identification of patients at high risk for poor prognosis above and beyond traditional risk variables. These findings suggest that patient-reported health status should be routinely assessed in determining prognosis, as this information cannot be captured from patients' medical records. [ABSTRACT FROM AUTHOR]

Aims The current study examined the degree of agreement between echocardiographic and patient-reported health status response to CRT 6 months after implantation, and evaluated the differences in pre-implantation characteristics of patients with concordant and discordant echocardiographic and health status responses. Methods and results Consecutively implanted CRT-defibrillator patients ( n = 109, mean age = 65.4 ± 10.1 years, 74 men) were recruited from the University Medical Center Utrecht, The Netherlands. Prior to implantation and 6 months post-implantation, all patients underwent echocardiography and completed the Kansas City Cardiomyopathy Questionnaire ( KCCQ). Echocardiographic response was defined as a relative reduction of ≥15% in LV end-systolic volume; an improvement of ≥10 points in KCCQ score indicated a health status response. In the 54 patients with discordant responses, 25 (22.9%) had an echocardiographic response but no health status response and 29 (26.6%) had a health status response but no echocardiographic response. Patients with concordant and discordant responses differed on various pre-implantation characteristics, including sex, employment status, LV volumes, and pre-implantation KCCQ score. In multivariable analysis, pre-implantation KCCQ score [odds ratio ( OR) = 0.91, 95% confidence interval ( CI) = 0.88-0.95, P < 0.001] and QRS duration ( OR = 1.03, 95% CI = 1.01-1.06, P = 0.009) were the only characteristics associated with health status response to CRT. Conclusions Our results show a large discrepancy between echocardiographic and patient-reported health status response to CRT. The most important predictor of health status response was the pre-implantation health status score. These results emphasize that disease-specific health status measures may have additional value over 'objective' measures of CRT response and should be incorporated in clinical practice. [ABSTRACT FROM AUTHOR]

Background In cardiac resynchronization therapy (CRT) devices, the interventricular (VV) delay denotes the time interval between left (LV) and right ventricular (RV) pacing. This study aimed to determine the proportion of patients in whom the effective VV delay (VVeff, delay between LV and RV depolarization, being induced either by pacing or intrinsic conduction) is different from the programmed VV delay during a standard VV delay optimization procedure. Methods Thirty-three patients with heart failure and left bundle branch block configuration without total atrioventricular (AV) block receiving CRT were prospectively included. VVeff was calculated from intrinsic AV intervals, programmed optimal AV delay, and programming system. Intrinsic AV intervals were measured on intracardiac electrograms. The optimal AV and VV delays were determined by highest increase in maximum rate of LV pressure rise (dP/dtmax). VV delays of 20-80 ms LV and RV preactivation were tested. Results Calculated maximum possible VVeff was shorter than 80 ms LV preactivation in up to 46% of patients and shorter than 40 ms LV preactivation in up to 3% of the patients. These proportions were 6% and 0% during 80 and 40 ms RV preactivation, respectively. Conclusions In CRT patients with left bundle branch block without total AV block, the effective VV delay is shorter than the programmed VV delay during a standard optimization procedure in approximately half of the patients and this phenomenon is encountered predominantly during LV preactivation by 40 ms or more. Calculation of the individual maximum VVeff in advance can shorten the VV delay optimization procedure. [ABSTRACT FROM AUTHOR]

Influence of Preactivation on the ECG in CRT. Introduction: The aims of this study were to compare ECG signs of biventricular electrical resynchronization during cardiac resynchronization therapy (CRT) with various interventricular (VV) delays and to correlate these and other ECG characteristics with the acute hemodynamic benefit of CRT. Methods and Results: Thirty-four patients with heart failure and a left bundle branch block (LBBB) pattern were prospectively enrolled. A 12-lead surface ECG and the relative improvement in left ventricular (LV) dP/dtmax (the maximum rate of pressure rise) were recorded at baseline and during CRT with VV delays varying from 80 ms LV preactivation to 40 ms right ventricular (RV) preactivation. Rightward QRS-axis shift occurred in 71-80% among all VV delays. Activation reversal to dominant negative in leads I/aVL was progressively observed at increasing LV preactivation (53-65%) and less (18-22%) during RV preactivation. Activation reversal to dominant positive in leads V1/V2 was observed in 21-27% during LV preactivation and in 6-15% during RV preactivation. Higher acute response to CRT was independently predicted by a complete LBBB at baseline (regression coefficient B = 7.7 [0.3-15.0], P = 0.042), later timing of LV depolarization within the QRS at baseline (Q-LVsense: B = 0.2 [0.1-0.3], P = 0.002), and biventricular electrical resynchronization during CRT as evidenced by activation reversal in leads I/aVL (B = 9.9 [3.2-16.6], P = 0.005). Conclusion: ECG signs of biventricular electrical resynchronization are present over a wide range of LV preactivated VV delays but to a lesser extent during RV preactivation. The presence of complete LBBB and longer Q-LVsense at baseline and signs of biventricular electrical resynchronization during CRT predict higher acute hemodynamic response. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1237-1245, November 2012) [ABSTRACT FROM AUTHOR]

Aims The maximum rate of left ventricular (LV) pressure rise (dP/dtmax) has been used to assess the acute haemodynamic effect of cardiac resynchronization therapy (CRT). We tested the hypothesis that LV dP/dtmax predicts long-term clinical outcome after initiation of CRT. Methods and results This was a retrospective observational multicentre study in 285 patients in whom dP/dtmax was measured invasively following implantation of a CRT device. The minimum required follow-up was 1 year. We analysed the relationship between dP/dtmax and time to the composite endpoint, consisting of all-cause mortality, heart transplantation (HTX), or LV assist device (LVAD) implantation within the first year of CRT. Thirty-four events occurred after a mean follow-up of 160 days (range 21–359). Patients with an event had lower dP/dtmax than patients without an event both at baseline (705 ± 194 vs. 800 ± 222 mmHg/s, P= 0.018) and during CRT (894 ± 224 vs. 985 ± 244 mmHg/s, P= 0.033), but the acute increase in dP/dtmax was similar in patients with and without an event (190 ± 133 vs. 185 ± 115 mmHg/s, P= n.s.). Left ventricular dP/dtmax-level at baseline and during CRT both predicted the clinical outcome after adjustment for gender, aetiology and New York Heart Association class: hazard ratio (HR) 0.791 [95% confidence interval (CI) 0.658–0.950, P= 0.012] and HR 0.846 (95% CI 0.723–0.991, P= 0.038), respectively. Conclusion Left ventricular dP/dtmax measured at baseline and during CRT are predictors of 1-year survival free from all-cause mortality, HTX, or LVAD implantation, but the acute improvement in dP/dtmax is not correlated to clinical outcome. [ABSTRACT FROM AUTHOR]

Cardiac resynchronization therapy aims at diminishing cardiac dyssynchrony in patients with heart failure. The effect of cardiac resynchronization therapy can be improved by optimization of the atrioventricular (AV) and interventricular (VV) delays. Currently, optimization of these pacing settings is mainly performed during resting conditions. This paper aims to objectively review the current literature about a rate-adaptive AV and VV delay in cardiac resynchronization therapy. The current evidence for a rate-adaptive AV and VV delay comprises only small nonrandomized studies on acute effects. The effect of exercise on the optimal AV delay was heterogeneous between studies. The optimal VV delay was influenced by exercise conditions in some, but not all patients. Possible explanations lie in the heterogeneous electrical and mechanical responses to exercise in patients with a complex disease such as heart failure with asynchronous contraction. Current evidence is insufficient to show the superiority of a rate-adaptive AV or VV delay in all CRT patients. Individualized exercise programming may be warranted in selected patients. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1307-1316, November 2010) [ABSTRACT FROM AUTHOR]

Background: Cardiac resynchronization therapy (CRT) is a promising treatment for a subgroup of patients with advanced congestive heart failure and a prolonged QRS interval. Despite the majority of patients benefiting from CRT, 10–40% of patients do not respond to this treatment and are labeled as nonresponders. Given that there is a lack of consensus on how to define response to CRT, the purpose of this viewpoint is to discuss currently used definitions and their shortcomings, and to provide recommendations as to how an expansion of the criteria for CRT response may be useful to clinicians. Methods and Results: Analysis of the literature and case reports indicates that the majority of established measures of CRT response, including New York Heart Association functional class and echocardiographic, hemodynamic, and neurohormonal parameters, are poor associates of patient-reported symptoms and quality of life. Moreover, the potential moderating role of psychological factors in determining health outcomes after CRT has largely been neglected. Conclusions: It is recommended to routinely assess health status after CRT with a disease-specific questionnaire in standard clinical practice and to examine its determinants, including psychological factors such as personality traits and depression. This may lead to improved (secondary) treatment and prognosis in CHF patients treated with CRT. [ABSTRACT FROM AUTHOR]

Aims: To develop a novel myocardial deformation index that is highly sensitive to the effect of cardiac resynchronization therapy (CRT) and that can be used to predict response to CRT. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Recent, conflicting results about the use of tissue Doppler imaging derived (TDI-) asynchrony indices to predict reverse remodelling after cardiac resynchronisation therapy (CRT) have raised questions about their physiological meaning and methodological limitations. Methods: In 41 patients, baseline TDI-derived septal to lateral delays of peak velocities (TDI-SL), standard deviation of peak velocities over 12 segments (Ts-SD), and peak 2D longitudinal strain (strain-SL) were compared with volumetric response (reduction in end-systolic volume of ≥15%) after at least 6 months of CRT. Timing of peak TDI velocities was compared to timing of 2DS velocities and strain-SL. Influence of sample position, transverse motion, and interobserver inconsistency of the chosen peak velocities was assessed. Diagnostic accuracy of TDI-based delays was compared to accuracy of visual and 2D strain-based assessment. Results: After 7.0±3.2 months of CRT, 24 patients were classified as responders. TDI-SL and Ts-SD were similar between responders and nonresponders at baseline, did not predict response, and were unaffected by CRT. Visual asynchrony scoring and strain-SL were better predictors of response than TDI-SL and Ts-SD. TDI measurements were highly susceptible to sample location and transverse motion components and poorly correlated with the timing of longitudinal contraction. There was a considerably poor agreement between observers with regard to scoring of TDI-SL and Ts-SD. Conclusion: TDI-based measurements of asynchrony do not appear robust predictors of volume response to CRT. [Copyright &y& Elsevier]

The evaluation of the heart rate response to exercise is important for the diagnosis of chronotropic incompetence and the assessment of a rate responsive algorithm of sensor-controlled pacemakers. The aim of the present study was to examine a classification of the chronotropic response at an individually moderate exercise level. Sixteen pacemaker patients (patient group, age 62.9 ± 7.6 years) with sick sinus syndrome and 15 age-matched healthy subjects (control group, age 57.6 ± 9.4 years) underwent a maximum cardiopulmonary exercise test on a treadmill after a protocol with individually selected incremental steps. To analyze the patients' intrinsic heart rate response, the rate responsive mode of the pacemaker was switched off. Chronotropic incompetence was diagnosed in eight patients whose maximal heart rate was < 80% of the age-predicted heart rate. The heart rate at the anaerobic threshold was significantly lower in the chronotropically incompetent subgroup than in the chronotropically competent patients and the healthy subjects (85.9 ± 6.6 beats/min vs 100.3 ± 9.9 beats/min and 112.9 ± 11.7 beats/min, respectively). The chronotropic slope of the heart rate reserve as a function of the metabolic reserve was significantly higher in the control group than in the patient groups with either mild or severe chronotropic incompetence (0.94 ± 0.17 vs 0.64 ± 0.08 and 0.43 ± 0.14, respectively). Furthermore, the chronotropically incompetent response could be divided into a linear type with and without a threshold, an exponential, and a logarithmic type. The anaerobic threshold was an objectively detectable breakpoint at an individually moderate exercise level that could be used for characterization of chronotropic function. At the anaerobic threshold, a physiological heart rate response was about 220 — age — 50 beats/min. A deviation of more than 10 beats/min below this physiological value characterized chronotropic incompetence. [ABSTRACT FROM AUTHOR]

The dromotropic pacemaker concept needs a rate responsive algorithm in which the pacing rate is controlled by the atrioventricular conduction time (AVCT). To develop basic concepts for such a rate responsive algorithm, the influence of the pacing rate on the AVCT was investigated. Seven patients (62 ± 7.8 years) with sick sinus syndrome and intact atrioventricular conduction underwent two cardiopulmonary exercise tests (CPX) on a treadmill. According to the determination of the anaerobic threshold (AT) and the patients maximum capacity in the first incremental CPX the work rate for two exercise levels below and above the AT were chosen for the second constant workload CPX. The calculation of the optimal pacing rate (HRopt) was based on the oxygen uptake (VO2) during exercise after reaching steady-state conditions. According to the increase of the VO2 from 14.8 ± 2.3 mL/min per kilogram during aerobic work (38.3 ± 16.0 W) to 19.4 ± 4.7 mL/min per kilogram during anaerobic work (80.6 ± 32.3 W), the HRopt was calculated to be 98.6 ± 6.9 beats/min and 116.4 ± 4.7 beats/min. Starting from HRopt, the pacing rate was increased (overpacing) and decreased (underpacing) by about 5 beats/min every minute. At optimal pacing rate the AVCT decreased significantly from 233.0 ± 30.5 ms during aerobic work and to 226.4 ± 27.3 ms during anaerobic work (P < 0.05). Whereas overpacing induced a significant prolongation of the AVCT during aerobic work (4.17 ± 1.78 ins per 10 beats/min) and anaerobic work (3.84 ± 1.60 ms per 10 beats/min), underpacing yielded a significant shortening of the AVCT by about 4.49 ± 2.64 ms per 10 beats/min during aerobic work and 4.75 ± 1.87 ms per 10 beats/min during anaerobic work (P < 0.01). The slopes of the regression lines of the relationship between A VCT and pacing rate were not significantly... [ABSTRACT FROM AUTHOR]

To develop a dromotropic-controlled rate adaptive algorithm for patients with sick sinus syndrome (SSS) and intact AV conduction, 14 pace-maker patients with SSS underwent cardiopulmonary exercise testing (CPX). During exercise, the pacemaker was programmed in an AAT mode without rate adaptation, whereby 3 patients developed supraventricular arrhythmia and 11 patients kept sinus rhythm. Chronotropic incompetence (CI) at heart rate (HR) < 95 beats/min at the anaerobic threshold (AT) was found in five patients. In patients with chronotropic competence (CC), the HR increase was significantly greater than in CI patients (rest: 73.2 ± 12.6 vs. 64.2 ± 4.0 beats/min; AT:101.2 ± 6.2 vs. 82.0 ±5.1 beats/min;peak: 135.2 ± 10.7 vs. 103.2 ± 10.9 beats/min). There was no significant difference in the AVD between CC and CI patients (rest; 167.7 ± 38.6 vs. 170.8 ± 22.5 ms, AT; 156.2 ± 30.7 vs. 163.6 ± 21.6 ms, peak: 144.7 ± 29.0 vs. 152.4 ± 15.0 ms). The correlation coefficient between HR increase and V02 was +1.0 and between AVD decrease and VO2 - 1.0 in both groups. An increase in pacing rate from 75 beats/min to 120 beats/min without exercise (overpacing) led to a prolongation of the AV interval of about 30.6 ± 14.2 ms. Based on this closed loop control with negative feedback, a dromotropic rate adaptive algorithm for patients with SSS and intact AV conduction could be developed. [ABSTRACT FROM AUTHOR]

Determination of the optimal interventricular (VV) delay in cardiac resynchronization therapy currently relies on costly, time-consuming echocardiographic (ECHO) methods. This study evaluated the performance of a new intracardiac electrogram (IEGM)-based VV method compared to the aortic velocity time integral (AVTI) method of VV delay optimization. The study included two patient groups. Eleven patients enrolled by a single center in the Rhythm II ICD trial underwent prospective comparisons of the AVTI at the VV interval determined by the IEGM VV method versus the maximum AVTI at the echocardiographically determined optimal VV delay. In 61 patients enrolled in the RHYTHM VV trial, the same testing methods were compared retrospectively. In the prospective study, the maximum AVTI by the ECHO-based method (24.3 ± 7.9 cm), was closely correlated with maximum AVTI by the IEGM-based method (23.9 ± 7.9 cm; concordance correlation coefficient = 0.99; 95% confidence, lower limit of 98%. Likewise, in the retrospective analysis, the ECHO-determined maximum AVTI (22.1 ± 8.2 cm) was similar to that determined by the IEGM-based method (20.9 ± 8.3 cm; concordance correlation coefficient = 0.98; 95% confidence, lower limit of 97%). [ABSTRACT FROM AUTHOR]