Acute Cardiac Resynchronization Therapy Research Articles

Pulse arrival time variation as a non-invasive marker of acute response to cardiac resynchronization therapy.

Successful cardiac resynchronization therapy (CRT) shortens the pre-ejection period (PEP) which is prolonged in the left bundle branch block (LBBB). In a combined animal and patient study, we investigated if changes in the pulse arrival time (PAT) could be used to measure acute changes in PEP during CRT implantation and hence be used to evaluate acute CRT response non-invasively and in real time. In six canines, a pulse transducer was attached to a lower limb and PAT was measured together with left ventricular (LV) pressure by micromanometer at baseline, after induction of LBBB and during biventricular pacing. Time-to-peak LV dP/dt (Td) was used as a surrogate for PEP. In twelve LBBB patients during implantation of CRT, LV and femoral pressures were measured at baseline and during five different pacing configurations. PAT increased from baseline (277 ± 9 ms) to LBBB (313 ± 16 ms, P < 0.05) and shortened with biventricular pacing (290 ± 16 ms, P < 0.05) in animals. There was a strong relationship between changes in PAT and Td in patients (r2 = 0.91). Two patients were classified as non-responders at 6 months follow-up. CRT decreased PAT from 320 ± 41 to 298 ± 39 ms (P < 0.05) in the responders, while PAT increased by 5 and 8 ms in the two non-responders. This proof-of-concept study indicates that PAT can be used as a simple, non-invasive method to assess the acute effects of CRT in real time with the potential to identify long-term response in patients.

Synchronization of repolarization after cardiac resynchronization therapy: time course and relation to reverse remodeling

Abstract Funding Acknowledgements Type of funding sources: None. Background The changes in ventricular repolarization after cardiac resynchronization therapy (CRT) are poorly understood. Objective Address this knowledge gap using a multimodality approach including electrocardiographic and echocardiographic measurements in patients and patient-specific computational modeling. Methods In a cohort of consecutive CRT 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, reconstructed from the 12-lead ECG. Computer simulations were performed using a patient-specific eikonal model of cardiac activation with spatially varying action potential duration (APD) and repolarization rate, based on a patient’s ECG and MRI-based chest and cardiac anatomy. Results In 33 patients T-wave area during CRT-OFF doubled within 5 days of CRT (left figure) while other repolarization markers like QT-interval and peak-to-end T-wave interval hardly changed. Patients with T-wave area increase above the median increase showed a significantly larger increase in left ventricular ejection fraction than those with smaller T-wave area increase (+11±8% vs. +6±6%, respectively; p&amp;lt;0.05, n=76). Computer simulations (figure, right) show the sequence of depolarization and repolarization before CRT, obtained by the patient-specific model (BL LBBB) and following Acute CRT. Repolarization after chronic CRT-OFF was obtained by matching the measured CRT-OFF ECG with that provided by the model. The best match was obtained by changes in APD following chronic CRT that are opposite to the change in CRT-induced activation time. Such APD changes were associated with a reduction in right and left ventricular dispersion in repolarization during chronic CRT-ON compared with acute CRT-ON. Conclusions T-wave area during CRT-OFF is a sensitive marker for adaptations in ventricular repolarization after CRT that are related to CRT-induced reverse remodeling and may involve an inverse relation between activation time and APD, coinciding with lower right and left ventricular dispersion of repolarization and with larger increases in LV ejection fraction during chronic CRT.

Non-invasive hemodynamic determination of patient-specific optimal pacing mode in cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) devices have multiple programmable pacing parameters. The purpose of this study was to determine the best pacing mode, i.e., associated with the greatest acute hemodynamic response, in each patient. Patients in sinus rhythm and intact atrioventricular conduction were included within 3 months of implantation of devices featuring SyncAV and multipoint pacing (MPP) algorithms. The effect of nominal biventricular pacing using the latest activated electrode (BiV-Late), optimized atrioventricular delay (AVD), nominal and optimized SyncAV, and anatomical MPP was determined by non-invasive measurement of systolic blood pressure (SBP). CRT response was defined as SBP increase > 10% relative to baseline. Thirty patients with left bundle branch block (LBBB) were included. BiV-Late increased SBP compared to intrinsic rhythm (128 ± 21 mmHg vs. 121 ± 22 mmHg, p = 0.0002). The best pacing mode further increased SBP to 140 ± 19 mmHg (p < 0.0001 vs. BiV-Late). The proportion of CRT responders increased from 40% with BiV-Late to 80% with the best pacing mode (p = 0.0005). Compared to BiV-Late, optimized AVD and optimized SyncAV increased SBP (to 134 ± 21 mmHg, p = 0.004, and 133 ± 20 mmHg, p = 0.0003, respectively), but nominal SyncAV and MPP did not. The best pacing mode was variable between patients and was different from nominal BiV-Late in 28 (93%) patients. Optimized AVD was the most frequent best mode, in 14 (47%) patients. In patients with LBBB, the best pacing mode was patient-specific and doubled the magnitude of acute hemodynamic response and the proportion of acute CRT responders compared to nominal BiV-Late pacing. ClinicalTrials.gov : NCT03779802.

Impact of paced left ventricular dyssynchrony on left ventricular reverse remodeling after cardiac resynchronization therapy.

We investigated whether pacing-induced electrical dyssynchrony at the time of cardiac resynchronization therapy (CRT) device implantation was associated with chronic CRT response. We included a total of 69 consecutive heart failure patients who received a CRT device. Left (LVp-RVs) and right (RVp-LVs) pacing-induced interlead delays were measured intraoperatively and used to determine if there was paced left ventricular (LV) dyssynchrony, defined as present when LVp-RVs is larger than RVp-LVs. CRT response was defined as a reduction in LV end-systolic volume ≥15%, 6 months after implantation. Paced left ventricular dyssynchrony (PLVD) was associated with ischemic cardiomyopathy (ICM) (χ2 : 8; P = .005) but not with QRS morphology nor with pacing lead positions. In a univariate analysis, PLVD (odds ratio [OR], 6.53; 95% confidence interval [CI], 2.2-18.9; P = .001), atypical left bundle branch block (LBBB) (OR, 3.3; 95% CI, 1.2-9.4; P = .022), and ICM (OR, 5.2; 95% CI, 1.6-17; P = .006) were associated with nonresponse. In a multivariate analysis, both PLVD (OR, 9.74; 95% CI, 2.8-33.9; P < .0001) and atypical LBBB (OR, 5.6; 95% CI, 1.5-20.3; P = .009) were independently associated with nonresponse. Adding PLVD to a model based on QRS morphology provided a significant and meaningful incremental value to predict LV reverse remodeling after CRT (χ2 to enter: 8; P < .005). Computer simulations corroborate these findings by showing that, while intrinsic electrical dyssynchrony is a prerequisite, the level of pacing-induced dyssynchrony modulates acute CRT response. In addition to the intrinsic electrical substrate, PLVD is strongly associated with less LV reverse remodeling, demonstrating that measuring the electrical substrate during pacing has additional value for prediction of CRT response in an already well-selected patient population.

Septal contraction predicts acute haemodynamic improvement and paced QRS width reduction in cardiac resynchronization therapy.

Three distinct septal contraction patterns typical for left bundle branch block may be assessed using echocardiography in heart failure patients scheduled for cardiac resynchronization therapy (CRT). The aim of this study was to explore the association between these septal contraction patterns and the acute haemodynamic and electrical response to biventricular pacing (BIVP) in patients undergoing CRT implantation. Thirty-eight CRT candidates underwent speckle tracking echocardiography prior to device implantation. The patients were divided into two groups based on whether their septal contraction pattern was indicative of dyssynchrony (premature septal contraction followed by various amount of stretch) or not (normally timed septal contraction with minimal stretch). CRT implantation was performed under invasive left ventricular (LV) pressure monitoring and we defined acute CRT response as ≥10% increase in LV dP/dtmax. End-diastolic pressure (EDP) and QRS width served as a diastolic and electrical parameter, respectively. LV dP/dtmax improved under BIVP (737 ± 177 mmHg/s vs. 838 ± 199 mmHg/s, P < 0.001) and 26 patients (68%) were defined as acute CRT responders. Patients with premature septal contraction (n = 27) experienced acute improvement in systolic (ΔdP/dtmax: 18.3 ± 8.9%, P < 0.001), diastolic (ΔEDP: -30.6 ± 29.9%, P < 0.001) and electrical (ΔQRS width: -23.3 ± 13.2%, P < 0.001) parameters. No improvement under BIVP was observed in patients (n = 11) with normally timed septal contraction (ΔdP/dtmax: 4.0 ± 7.8%, P = 0.12; ΔEDP: -8.8 ± 38.4%, P = 0.47 and ΔQRS width: -0.9 ± 11.4%, P = 0.79). Septal contraction patterns are an excellent predictor of acute CRT response. Only patients with premature septal contraction experienced acute systolic, diastolic, and electrical improvement under BIVP.

Acute Modifications of Left Ventricular Torsional Mechanics Induced by Cardiac Resynchronization Therapy Affect Short-Term Reverse Remodeling.

Left ventricular (LV) torsion is an important aspect of cardiac mechanics and is altered in heart failure patients. Cardiac resynchronization therapy (CRT) has a positive effect on LV function, but the exact mechanisms through which it works are not completely depicted. Our aim was to investigate (1) the acute CRT effect on LV torsional mechanics in heart failure patients using 3D speckle tracking echocardiography (3DSTE) and (2) its effect on short-term LV remodeling. We considered 48 patients (age 72±11 years, 35 men) who received CRT. They underwent 3DSTE during CRT-on (biventricular stimulation) vs. CRT-off (intrinsic conduction/right atrial/ventricular stimulation alone), in a random fashion. Patients were classified as CRT responders based on LV systolic volume reduction ≥15% at 6 months (final population: 31 responders, 17 non-responders). Acute CRT positively affected responders in terms of LV torsion (from 0.32±0.06°/cm CRT-off to 0.41±0.06°/cm CRT-on), but adversely affected non-responders (from 0.54±0.08°/cm CRT-off to 0.28±0.08°/cm CRT-on, interaction P=0.02). A similar trend was confirmed for apical (interaction P<0.04), but not for basal torsion (interaction P=0.351). CRT has a positive role in acute recovery of LV torsion (particularly in its apical component) in responders, likely modulating the improvement in LV remodeling at early follow-up.

A minimally invasive hybrid approach for cardiac resynchronization of the systemic right ventricle.

Patients with systemic right ventricle (RV) often develop progressive heart failure and may benefit from cardiac resynchronization therapy (CRT); however, the optimal strategy for CRT has not been defined. A retrospective review of all the patients with systemic RV failure undergoing a hybrid transcatheter-surgical approach was performed. Procedural technique and outcomes are reported. Six patients underwent detailed electroanatomical mapping of the systemic RV followed by a new hybrid approach targeting latest endocardial activation, which was followed by focused epicardial mapping. The exact site of latest endocardial activation was variable but localized to the basolateral RV in all cases. Sites of latest activation tended to be more superior during contralateral ventricular pacing versus intact atrioventricular conduction (P=0.06). Latest endocardial activation at the targeted site occurred at 157ms (interquartile range [IQR]=120-181ms) and corresponding epicardial activation at 174ms (IQR=140-198ms), after the onset of the QRS complex. Following the hybrid CRT, the QRS duration decreased from a median of 193 to 147ms and the fractional area of change increased from a median of 15.5% to 30% (P<0.001). Patients were discharged to home after a median of 4 days. Of the three patients who were initially referred for transplant evaluation, two (66%) of them no longer met the criteria following CRT. Whereas latest endocardial activation for the systemic RV appears to localize to the basolateral region, the optimal lead position may be variable. An approach utilizing endocardial mapping followed by a limited surgical incision and confirmation of latest activation may result in minimally invasive surgery and a favorable acute CRT response.

Left ventricular end-systolic volume is a more sensitive marker of acute response to cardiac resynchronization therapy than contractility indices: insights from an experimental study.

There are conflicting data and no consensus on how to measure acute response to cardiac resynchronization therapy (CRT). This study investigates, which contractility indices are best markers of acute CRT response. In eight anaesthetized dogs with left bundle branch block, we measured left ventricular (LV) pressure by micromanometer and end-diastolic volume (EDV) and end-systolic volume (ESV) by sonomicrometry. Systolic function was measured as LV ejection fraction (EF), peak rate of LV pressure rise (LV dP/dtmax) and as a gold standard of contractility, LV end-systolic elastance (Ees), and volume axis intercept (V0) calculated from end-systolic pressure-volume relations (ESPVR). Responses to CRT were compared with inotropic stimulation by dobutamine. Both CRT and dobutamine caused reduction in ESV (P < 0.01) and increase in LV dP/dtmax (P < 0.05). Both interventions shifted the ESPVR upwards indicating increased contractility, but CRT which reduced V0 (P < 0.01), caused no change in Ees. Dobutamine markedly increased Ees, which is the typical response to inotropic stimulation. Preload (EDV) was decreased (P < 0.01) by CRT, and there was no change in EF. When adjusting for the reduction in preload, CRT increased EF (P = 0.02) and caused a more marked increase in LV dP/dtmax (P < 0.01). Increased contractility by CRT could not be identified by Ees, which is a widely used reference method for contractility. Furthermore, reduction in preload by CRT attenuated improvement in contractility indices such as EF and LV dP/dtmax. These results suggest that changes in LV volume may be more sensitive markers of acute CRT response than conventional contractility indices.

Effect of Cardiac Resynchronization Therapy on Exercise-Induced Pulmonary Hypertension and Right Ventricular-Arterial Coupling.

Background Acute and chronic effects of cardiac resynchronization therapy (CRT) on pulmonary pressures, right ventricular function, and ventricular-vascular coupling during exercise are insufficiently understood. Yet, these factors are strongly associated with functional status and outcome. Methods and Results Heart failure patients with reduced ejection fraction indicated for CRT were prospectively included to undergo exercise echocardiography simultaneously with cardiopulmonary exercise testing before (pre_CRT), 1 day after (post_CRT), and 6 months (post6_CRT) after CRT implant. Right ventricular-arterial coupling was assessed by the tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (SPAP) ratio. A total of 31 heart failure patients with reduced ejection fraction (age=66±13 years) were prospectively included. CRT resulted in an immediate reduction in rest SPAP (pre_CRT=32±16 versus post_CRT=23±16 mm Hg; P=0.006) and rest effective regurgitant orifice (pre_CRT=0.32±0.1 versus post_CRT=0.18±0.2; P=0.001) without changes in exercise mitral regurgitation or exercise SPAP indexed for cardiac output. Six months after CRT, in parallel with left ventricular reverse remodeling and a reduction in exercise mitral regurgitation and exercise E/e' ratio, the exercise SPAP/cardiac output significantly improved (post_CRT=5.6±3.1 versus post6_CRT=4.3±2.9 mm Hg·L-1·min-1; P=0.039), which was also illustrated by a reduced slope of ΔSPAP/Δcardiac output (post_CRT=5.2±3.7 versus post6_CRT=2.9±2.7 mm Hg·L-1·min-1; P=0.002). CRT did not result in an acute or chronic effect on TAPSE or TAPSE/SPAP ratio at rest. However, exercise revealed the presence of right ventricular-arterial uncoupling which was not affected by an acute CRT effect ( P=0.396) but only improved by a chronic CRT effect ( P<0.001; TAPSE/SPAP ratio: pre_CRT= 0.39±0.6 mm/mm Hg; post_CRT=0.42±0.5 mm/mm Hg; post6_CRT =0.84±0.12 mm/mm Hg). Of all exercise echocardiography variables, the TAPSE/SPAP ratio demonstrated the strongest correlation with Vo2 peak ( r=0.475), VE/Vco2 ( r=-0.585), and workload ( r=0.476) during cardiopulmonary exercise testing ( P<0.05 all). Multivariate predictors affecting exercise ventricular-arterial coupling after CRT included metrics of residual exercise mitral regurgitation and systolic and diastolic left ventricular function. Conclusions Chronic CRT beneficially influences pulmonary pressures and right ventricular-arterial coupling during exercise, which strongly relates to functional status. These findings are mechanistically linked to reverse remodeling with improved interventricular dependence and reduction in exercise mitral regurgitation.

Response to cardiac resynchronization therapy is determined by intrinsic electrical substrate rather than by its modification

BackgroundElectrocardiographic mapping (ECM) expresses electrical substrate through magnitude and direction of the activation delay vector (ADV). We investigated to what extent the response to cardiac resynchronization therapy (CRT) is determined by baseline ADV and by ADV modification through CRT and optimization of left ventricular (LV) pacing site. MethodsECM was performed in 79 heart failure patients (4 RBBB, 12 QRS < 120 ms, 23 non-specific conduction delay [NICD] and 40 left bundle branch block [LBBB]). 67 patients (QRS ≥ 120 ms) underwent CRT implantation and in 26 patients multiple LV pacing site optimization was performed. ADV was calculated from locations/depolarization times of 2000 virtual epicardial electrodes derived from ECM. Acute response was defined as ≥10% LVdP/dtmax increase, chronic response by composite clinical score at 6 months. ResultsDuring intrinsic conduction, ADV direction was similar in patients with QRS < 120 ms, NICD and LBBB, pointing towards the LV free wall, while ADV magnitude was larger in LBBB (117 ± 25 ms) than in NICD (70 ± 29 ms, P < 0.05) and QRS < 120 ms (52 ± 14 ms, P < 0.05). Intrinsic ADV accurately predicted the acute (AUC = 0.93) and chronic (AUC = 0.90) response to CRT. ADV change by CRT only moderately predicted response (highest AUC = 0.76). LV pacing site optimization had limited effects: +3 ± 4% LVdP/dtmax when compared to conventional basolateral LV pacing. ConclusionThe baseline electrical substrate, adequately measured by ADV amplitude, strongly determines acute and chronic CRT response, while the extent of its modification by conventional CRT or by varying LV pacing sites has limited effects.

Cardiac resynchronization therapy when no lateral pacing option exists: vectorcardiographic guided non-lateral left ventricular lead placement predicts acute hemodynamic response.

A difficult cardiac resynchronization therapy (CRT) implantation scenario emerges when no lateral pacing option exists. The aim of this study was to explore the effect of biventricular pacing (BIVP) on vectorcardiographic parameters in patients with a non-lateral left ventricular (LV) lead position. We hypothesized that perimeter and area reduction for both the QRS complex and T-wave would predict acute CRT response. Twenty-six patients (14 ischaemic) with a mean age of 63 ± 10 years and standard CRT indication underwent device implantation with continuous LV pressure registration. The LV lead was placed in either an anterior or apical position. Biventricular pacing was performed at a rate 10% above intrinsic rhythm with acute CRT response defined as LV ΔdP/dtmax >10%. Using this criterion 12 patients were identified as acute CRT responders (responders: 16.7 ± 4.8% vs. non-responders: 1.9 ± 5.3%, P < 0.001). Vectorcardiographic assessment of the QRS complex and T-wave were performed at baseline and under BIVP. Based on the observed changes in three-dimensional area and perimeter, ΔQRS-area (responders: -46.7 ± 39.6% vs. non-responders: 1.1 ± 50.9%, P = 0.006) was considered as the preferred parameter. Receiver operating characteristic curve analysis identified -40% as the optimal cut-off value (sensitivity 67% and specificity 93%) for prediction of acute CRT response (AUC = 0.81, P < 0.01). A significant correlation was observed between LV ΔdP/dtmax and ΔQRS-area (R2 = 0.37, P = 0.001). ΔQRS-area is correlated to LV ΔdP/dtmax and predicts acute CRT response in patients with a non-lateral LV lead position. Assessment of ΔQRS-area might be a useful tool for patient specific LV lead placement when no lateral pacing option exists.

Echocardiographic Prediction of Cardiac Resynchronization Therapy Response Requires Analysis of Both Mechanical Dyssynchrony and Right Ventricular Function: A Combined Analysis of Patient Data and Computer Simulations

Pronounced echocardiographically measured mechanical dyssynchrony is a positive predictor of response to cardiac resynchronization therapy (CRT), whereas right ventricular (RV) dysfunction is a negative predictor. The aim of this study was to investigate how RV dysfunction influences the association between mechanical dyssynchrony and left ventricular (LV) volumetric remodeling following CRT. One hundred twenty-two CRT candidates (mean LV ejection fraction, 19±6%; mean QRS width, 168±21msec) were prospectively enrolled and underwent echocardiography before and 6months after CRT. Volumetric remodeling was defined as percentage reduction in LV end-systolic volume. RV dysfunction was defined as RV fractional area change<35%. Mechanical dyssynchrony was assessed as time to peak strain between the septum and LV lateral wall, interventricular mechanical delay, and septal systolic rebound stretch. Simulations of heart failure with an LV conduction delay in the CircAdapt computer model were used to investigate how LV and RV myocardial contractility influence LV dyssynchrony and acute CRT response. In the entire patient cohort, higher baseline septal systolic rebound stretch, time to peak strain between the septum and LV lateral wall, and interventricular mechanical delay were all associated with LV volumetric remodeling in univariate analysis (R=0.599, R=0.421, and R=0.410, respectively, P<.01 for all). The association between septal systolic rebound stretch and LV volumetric remodeling was even stronger in patients without RV dysfunction (R=0.648, P<.01). However, none of the mechanical dyssynchrony parameters were associated with LV remodeling in the RV dysfunction subgroup. The computer simulations showed that low RV contractility reduced CRT response but hardly affected mechanical dyssynchrony. In contrast, LV contractility changes had congruent effects on mechanical dyssynchrony and CRT response. Mechanical dyssynchrony parameters do not reflect the negative impact of reduced RV contractility on CRT response. Echocardiographic prediction of CRT response should therefore include parameters of mechanical dyssynchrony and RV function.

Prediction of optimal cardiac resynchronization by vectors extracted from electrograms in dyssynchronous canine hearts.

Proper optimization of atrioventricular (AV) and interventricular (VV) intervals can improve the response to cardiac resynchronization therapy (CRT). It has been demonstrated that the area of the QRS complex (QRSarea) extracted from the vectorcardiogram can be used as a predictor of optimal CRT-device settings. We explored the possibility of extracting vectors from the electrograms (EGMs) obtained from pacing electrodes and of using these EGM-based vectors (EGMVs) to individually optimize acute hemodynamic CRT response. Biventricular pacing was performed in 13 dogs with left bundle branch block (LBBB) of which five also had myocardial infarction (MI), using 100 randomized AV- and VV-settings. Settings providing an acute increase in LV dP/dtmax ≥ 90% of the highest achieved value were defined as optimal. The prediction capability of QRSarea derived from the EGMV (EGMV-QRSarea) was compared with that of QRS duration. EGMV-QRSarea strongly correlated to the change in LV dP/dtmax (R = -0.73 ± 0.19 [LBBB] and -0.66 ± 0.14 [LBBB + MI]), while QRS duration was more poorly related to LV dP/dtmax changes (R = -0.33 ± 0.25 [LBBB] and -0.47 ± 0.39 [LBBB + MI]). This resulted in a better prediction of optimal CRT-device settings by EGMV-QRSarea than by QRS duration (LBBB: AUC = 0.89 [0.86-0.93] vs. 0.76 [0.69-0.83], P < 0.01; LBBB + MI: AUC = 0.91 [0.84-0.99] vs. 0.82 [0.59-1.00], P = 0.20, respectively). In canine hearts with chronic LBBB with or without MI, the EGMV-QRSarea predicts acute hemodynamic CRT response and identifies optimal AV and VV settings accurately. These data support the potency of EGM-based vectors as a noninvasive, easy and patient-tailored tool to optimize CRT-device settings.

Biventricular Paced QRS Area Predicts Acute Hemodynamic CRT Response Better Than QRS Duration or QRS Amplitudes.

Vectorcardiographic (VCG) QRS area of left bundle branch block (LBBB) predicts acute hemodynamic response in cardiac resynchronization therapy (CRT) patients. We hypothesized that changes in QRS area occurring with biventricular pacing (BV) might predict acute hemodynamic CRT response (AHR). VCGs of 624 BV paced electrocardiograms (25 LBBB patients with 35 different pacing configurations) were calculated according to Frank's orthogonal lead system. Maximum QRS vector amplitudes (XAmpl , YAmpl , ZAmpl , and 3DAmp ) and QRS areas (XArea , YArea , ZArea , and 3DArea ) in the orthogonal leads (X, Y, and Z) and in 3-dimensional projection were measured. Volume of the 3D vector loop and global QRS duration (QRSD) on the surface electrocardiogram were assessed. Differences (Δ) in VCG parameters between BV paced and LBBB QRS complexes were calculated. An increase of 10% in dP/dt max was considered as AHR. LBBB conduction is characterized by a large ZArea (109 μVs, interquartile range [IQR]:75;135), significantly larger than XArea (22 μVs, IQR:10;57) and YArea (44 μVs, IQR:32;62, P < 0.001). Overall, QRS duration, amplitudes, and areas decrease significantly with BV pacing (P < 0.001). Of all VCG parameters, 3DAmpl , Δ3DAmpl , ZArea, ΔZArea , Δ3DArea , and ΔQRSD differentiate AHR response from nonresponse (P < 0.05). ΔZArea predicted best positive AHR (area under the curve = 0.813) and outperformed any other VCG parameter or QRSD measurement. Of all VCG parameters, reduction in QRS area, calculated in Frank's Z lead, predicts acute hemodynamic response best. This method mightbe an easy, noninvasive tool to guide CRT implantation and optimization.

169-08: Electrical drivers of hemodynamic response to cardiac resynchronization therapy

Introduction: The drivers of cardiac resynchronization therapy (CRT) response remain unclear. We combined clinical electrocardiographic imaging (ECGi) data with cardiovascular model simulations (CircAdapt) to investigate how inter- and intra-ventricular dispersion of activation influences acute hemodynamic CRT response. Results: Computed changes of LVdP/dtmax based on both VEU and DISP data showed good agreement with measurements (FIG.A). High baseline VEU appeared to be both essential and sufficient for acute CRT response (FIG.A&B). When the VEU substrate was absent, response to CRT varied from worsening to slight improvement of hemodynamic function, depending on DISP. Consequently, including DISP as an input parameter in CircAdapt improved response prediction for the NICD and NARROW patient groups (FIG.A). Conclusion: Combining electrical activation from ECGi with computer simulations predicts hemodynamic improvement following CRT. VEU, representing interventricular dispersion of activation, is the dominant driver of CRT response. In patients with low baseline values for VEU, intraventricular dispersion of activation, characterized by DISP, is a strong determinant of baseline hemodynamic function and thereby additive as a predictor of response to CRT.

Myocardial motion and deformation patterns in an experimental swine model of acute LBBB/CRT and chronic infarct

In cardiac resynchronization therapy (CRT), specific changes in motion/deformation happen with left-bundle-branch-block (LBBB) and following treatment. However, they remain sub-optimally studied. We propose a two-fold improvement of their characterization. This includes controlling them through an experimental model and using more suitable quantification techniques. We used a swine model of acute LBBB and CRT with/without chronic infarct (pure-LBBB: N = 11; LBBB + left-anterior-descending infarct: N = 11). Myocardial displacement, velocity and strain were extracted from short-axis echocardiographic sequences using 2D speckle-tracking. The data was transformed to a single spatiotemporal system of coordinates to perform subject comparisons and quantify pattern changes at similar locations and instants. Pure-LBBB animals showed a specific intra-ventricular dyssynchrony pattern with LBBB (11/11 animals), and the recovery towards a normal pattern with CRT (10/11 animals). Pattern variability was low within the pure-LBBB population, as quantified by our method. This was not correctly assessed by more conventional measurements. Infarct presence affected the pattern distribution and CRT efficiency (improvements in 6/11 animals). Pattern changes correlated with global cardiac function (global circumferential strain) changes in all the animals (corrected: (pLBBBvsBaseline) < 0.001, (pCRTvsBaseline) = NS; non-corrected: (pLBBBvsBaseline) = NS, (pCRTvsBaseline) = 0.028). Our LBBB/CRT experimental model allowed controlling specific factors responsible for changes in mechanical dyssynchrony and therapy. We illustrated the importance of our quantification method to study these changes and their variability. Our findings confirm the importance of myocardial viability and of specific LBBB-related mechanical dyssynchrony patterns.

Assessing reverse remodeling in heart failure patients treated with cardiac resynchronization therapy and its impact on prognosis

Cardiac resynchronization therapy (CRT) has become an alternative for patients with systolic dysfunction and persistence of heart failure symptoms despite optimal medical therapy. The role of noninvasive cardiac imaging before device implantation still remains controversial, but they are essential to provide an objective evidence of reverse remodeling of the heart which is, in turn, also related to the outcome of patients treated with CRT. The objective of this review is to highlight the acute and long-term CRT benefits as assessed by imaging, with special focus in cardiac reverse remodeling and its impact on prognosis.

Effect of cardiac resynchronization therapy on regional left ventricular function: a speckle tracking strain analysis

The mechanisms associated with cardiac resynchronization therapy (CRT) benefits have been elucidated in part, however little is known about the effects of biventricular pacing (BVP) on regional myocardial contractility. Twenty patients with conventional CRT criteria were studied before and after device implantation. Speckle tracking strain analysis was performed from standard bidimensional acquisitions during different pacing configurations. Longitudinal and transverse strains were measured for the six basal left ventricular (LV) segments. Acute CRT improved LV end-diastolic and end-systolic volumes without significantly modifying LV ejection fraction. Moreover, CRT produced significant changes in regional strain. When compared with spontaneous rhythm, simultaneous BVP caused a significant increase in longitudinal septal strain (-4.8 vs. -7.3%, P = 0.003) and a significant decrease in longitudinal lateral strain (-8.2 vs. -5.9%, P = 0.03). Simultaneous BVP also induced a significant decrease in transverse lateral strain from 17.9 to 10.9% (P = 0.004). In this acute echocardiographic study, BVP decreased lateral wall deformation while improving septal wall contraction, thus potentially improving LV contractile pattern.

Pacemaker optimization guided by echocardiography in cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) or biventricular pacing is a contemporary treatment in the management of advanced heart failure. Echocardiography plays an evolving and important role in patient selection for CRT, follow-up of acute and chronic CRT effects and optimization of device settings after biventricular pacemaker implantation. In this paper we illustrate usefulness of echocardiography for successful AV and VV timing optimization in patients with CRT. A review of up-to-date literature concerning rationale for AV and VV delay optimization, echocardiographic protocols and current recommendations for AV and VV optimization after CRT are also presented. The first case is of successful AV delay optimization guided by echocardiography in a patient with dilated cardiomyopathy treated with CRT is presented. Pulsed blood flow Doppler was used to detect mitral inflow while programming different duration of AV delay. The AV delay with optimal transmittal flow was established. The optimal mitral flow was the one with clearly defined E and A waves and maximal velocity time integral (VTI) of the mitral flow. Improvement in clinical status and reverse left ventricle remodelling with improvement of ejection fraction was registered in our patient after a month. The second case presents a patient with heart failure caused by dilated cardiomyopathy; six months after CRT implantation the patient was still NYHA class III and with a significantly depressed left ventricular ejection fraction. Optimization of VV interval guided by echocardiography was undertaken measuring VTI of the left ventricular outflow tract (LVOT) during programming of different VV intervals. The optimal VV interval was determined using a maximal LVOT VTI. A month after VV optimization our patient showed improvement in LV ejection fraction. Optimal management of patients treated with CRT integrate both clinical and echocardiographic follow-up with, if needed, echocardiographically guided optimization of AV and VV delays, which offers the possibility of additional clinical improvement in such patients.

Noninvasive Imaging in Cardiac Resynchronization Therapy—Part 2: Follow‐up and Optimization of Settings

Cardiac resynchronization therapy (CRT) has become a therapeutic option for drug-refractory heart failure. Several noninvasive imaging techniques play an increasingly important role before and after device implantation. This review highlights the acute and long-term CRT benefits after implantation as assessed with echocardiography and nuclear imaging. Furthermore, optimization of CRT settings, in particular atrioventricular and interventricular delay, will be discussed using echocardiography and other (device-based) techniques.