Chronic Cardiac Resynchronization Therapy Research Articles

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

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

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<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.

Optimization of Chronic Cardiac Resynchronization Therapy Using Fusion Pacing Algorithm Improves Echocardiographic Response

BackgroundWhether reprogramming of cardiac resynchronization therapy (CRT) to increase electrical synchrony translates into echocardiographic improvement remains unclear. SyncAV is an algorithm that allows fusion of intrinsic conduction with biventricular pacing. We aimed to assess whether reprogramming chronically implanted CRT devices with SyncAV is associated with improved echocardiographic parameters. MethodsPatients at a quaternary center with previously implanted CRT devices with a programmable SyncAV algorithm underwent routine electrocardiography-based SyncAV optimization during regular device clinic visits. This analysis included only patients who could be programmed to the SyncAV algorithm (i.e., in sinus rhythm with intrinsic atrioventricular conduction). Echocardiography was performed before and 6 months after CRT optimization. ResultsOf 64 consecutive, potentially eligible patients who underwent assessment, 34 who were able to undergo SyncAV programming were included. Their mean age was 74 ± 9 years, 41% were female, and 59% had ischemic cardiomyopathy. The mean time from CRT implant to SyncAV optimization was 17.8 ± 8.5 months. At 6-month follow-up, SyncAV optimization was associated with a significant increase in left ventricular ejection fraction (LVEF) (mean LVEF 36.5% ± 13.3% vs 30.9% ± 13.3%; P < 0.001) and a reduction in left ventricular end-systolic volume (LVESV) (mean LVESV 110.5 ± 57.5 mL vs 89.6 ± 52.4 mL; P < 0.001) compared with baseline existing CRT programming. ConclusionCRT reprogramming to maximize biventricular fusion pacing significantly increased LVEF and reduced LVESV in patients with chronic CRT devices. Further studies are needed to assess if a continuous fusion pacing algorithm improves long-term clinical outcomes and to identify which patients are most likely to derive benefit.

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.

Plasticity of left ventricular function with cardiac resynchronization therapy.

To evaluate the clinical and echocardiographic effects of prolonged cessation and resumption of left ventricular pacing among patients with chronic cardiac resynchronization therapy (CRT). This was a retrospective analysis of patients with long-term CRT who had loss of left ventricular pacing because of battery depletion. Clinical assessment and echocardiographic data were analyzed with comparisons between implant, chronic CRT, loss of CRT, and after resumption of CRT. There were 7 CRT responders who underwent 8 successful pulse generator replacements due to loss of CRT 6.3 ± 2.3months after reaching elective replacement interval. With initial CRT implantation, QRS duration decreased from 171 ± 25 to 145 ± 28ms (P < 0.001) and left ventricular ejection fraction increased from 27.6 ± 8.1 to 53.9 ± 9.6% (P < 0.001). At pulse generator replacement, worsening heart failure was present 6 of 7 patients with significant deterioration of left ventricular function and the left ventricular ejection fraction decreased to 43.4 ± 8.4%(P= 0.001). After resumption of CRT, clinical status and cardiac function recovered with left ventricular ejection fraction increasing to 53.7 ± 8.7% (P= 0.001). Prolonged loss of CRT is associated with significant deterioration of left ventricular function and functional status that is fully reversible with resumption of left ventricular pacing.

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.

Effect of Cardiac Resynchronization Therapy on Arterial-Ventricular Coupling during Exercise in Heart Failure with Reduced Ejection Fraction

Exercise intolerance in heart failure with reduced ejection fraction (HFrEF) is mediated, in part, by an impairment in arterial-ventricular coupling. Cardiac resynchronization therapy (CRT) improves resting and paced arterial-ventricular coupling. The effect of chronic CRT on arterial-ventricular coupling during exercise in HFrEF has not been studied. PURPOSE: To study the effects of 6 months of CRT on arterial-ventricular coupling during exercise in patients with HFrEF. METHODS: Seven patients with HFrEF (59 ± 9 yrs; m/f: 5/2; NYHA III/IV = 6/1; EF = 18 ± 3%; peak VO2 = 12.5 ± 3.6 ml/kg/min) were studied pre-CRT and 6 months following (post-CRT). After resting measurements, subjects performed cycle ergometry at 22 ± 8 W (70 ± 13% of peak VO2) for 4 min. Left ventricular volumes were determined using contrast enhanced echocardiography. Blood pressure was measured manually at the brachium. End-systolic pressure (ESP) was approximated as 0.9 × systolic blood pressure. Effective arterial elastance (Ea) was calculated as ESP/stroke volume and end-systolic elastance (Ees) was calculated as ESP/end-systolic volume. Arterial-ventricular coupling was calculated as Ea/Ees. Comparisons were made with a 2 (rest, exercise) × 2 (pre-CRT, post-CRT) repeated measures factorial ANOVA and t-tests. Data are mean ± SD and P < 0.05 was significant. RESULTS: There was a main effect of CRT on Ea, where the pre-CRT Ea increased 0.28 ± 0.45 mmHg/mL during exercise and the post-CRT Ea decreased 0.12 ± 0.25 mmHg/mL (P < 0.05). There was no main effect of CRT on Ees, as both the pre-CRT (0.04 ± 0.03 mmHg/mL) and post-CRT (0.08 ± 0.04 mmHg/mL) increase in Ees from rest to exercise was not significant (P > 0.05). However, resting and exercise Ees tended to be higher post-CRT. Lastly, there was a main effect of CRT on Ea/Ees, where Ea/Ees increased 0.40 ± 1.35 mmHg/mL from rest to exercise pre-CRT and Ea/Ees decreased 0.69 ± 0.35 mmHg/mL from rest to exercise post-CRT (P < 0.05). CONCLUSION: The improvement in arterial-ventricular coupling during exercise following chronic CRT in HFrEF can be attributed to improvements in arterial loading on the left ventricle, as contractility changes related to CRT were modest.

Improvement in left ventricular intrinsic dyssynchrony with cardiac resynchronization therapy.

Objective:Cardiac resynchronization therapy (CRT) has been shown to induce a structural and electrical remodeling; the data on whether left ventricle (LV) reverse remodeling is associated with restitution of intrinsic contraction pattern are unknown. In this study, we investigated the presence of improvement in left ventricular intrinsic dyssynchrony in patients with CRT.Methods:A total of 45 CRT recipients were prospectively studied. Dyssynchrony indexes including interventricular mechanical delay (IVMD) and tissue Doppler velocity opposing-wall delay (OWD) as well as QRS duration on 12-lead surface electrocardiogram were recorded before CRT device implantation. After 1 year, patients with chronic biventricular pacing were reprogramed to VVI 40 to allow the resumption of native conduction and contraction pattern. After 4–6 h of intrinsic rhythm, QRS duration and all echocardiographic measurements were recorded. Dyssynchrony was defined as IVMD >40 ms and OWD >65 ms. CRT response was defined by a ≥15% reduction in left ventricular end-systolic volume (LVESV) at a 12-month follow-up.Results:Thirty-two patients (71%) showed response to CRT. The native QRS duration reduced significantly from 150±12 ms to 138±14 ms (p<0.001), and dyssynchrony indexes showed a significant improvement only in responders. The mean OWD reduced from 86±37 ms to 50±29 ms (p<0.001), and the mean IVMD decreased from 55±22 ms to 28±22 ms (p<0.001) in responders. The reduction in LVESV was significantly correlated with ΔOWD (r=0.47, p=0.001), ΔIVMD (r=0.45, p=0.001), and ΔQRS (r=0.34, p=0.022).Conclusion:Chronic CRT significantly improves LV native contraction pattern and causes reverse remodeling in dyssynchrony.

178: Reverse electrical remodeling by cardiac resynchronization therapy: prevalence and clinical impact

Cardiac resynchronization Therapy (CRT) improves left ventricular ejection fraction (LVEF) in patients with congestive heart failure, LV systolic dysfunction and a wide QRS complex. Previous reports suggest that CRT may also induce electrical remodeling but the impact on clinical outcome remains unknown. We sought to determine 1) if chronic CRT induces a relevant shortening of the intrinsic QRS (iQRS), 2) whether changes in the native conduction system correlate with clinical or echocardiographic response to CRT and 3) to identify predictors of iQRS width shortening. We prospectively included 85 consecutive patients with left bundle branch block who received a CRT device in 3 French centers. NYHA class, iQRS duration, LVEF and left ventricular volumes were assessed before and one year after CRT implantation. Clinical and echocardiographic were defined respectively as NYHA class improvement >1 class without heart failure hospitalization and an increase of LVEF by ≥10% and/or a decrease in LVESV by ≥15%. Electrocardiographic responders were defined as a decrease in iQRS duration by ≥20 msec. Baseline and 1-year follow-up mean iQRS durations were respectively 168.0±19.7 ms and 149.6±31.6 ms (p<0.0001). Electrocardiographic response, observed in 43/85 patients (51%), was associated with a greater rate of clinical (p=0.035) and echocardiographic (p=0.023) response. Younger age, male gender and longer baseline QRS width were independent predictors of electrocardiographic response. CRT decreases iQRS duration. A reduction of at least 20 ms in iQRS duration is associated with better clinical and echocardiographic response.

Cardiac magnetic resonance-derived anatomy, scar, and dyssynchrony fused with fluoroscopy to guide LV lead placement in cardiac resynchronization therapy: a comparison with acute haemodynamic measures and echocardiographic reverse remodelling

Left ventricular (LV) lead positioning for cardiac resynchronization therapy (CRT) is largely empirical and operator-dependent. Our aim was to determine whether cardiac magnetic resonance (CMR)-guided CRT may improve the acute and the chronic response. CMR-derived anatomical models and dyssynchrony maps were created for 20 patients. The CMR targets (three latest activated segments with <50% scar) were overlaid on to live fluoroscopy. Acute haemodynamic response (AHR) to LV pacing was assessed using an intra-ventricular pressure wire. Chronic CRT response (end-systolic volume reduction ≥15%) was assessed 6 months post-implantation. All patients underwent successful CMR-guided LV lead placement. A CMR target segment was paced in 75% of patients. The mean change in LVdP/dtmax for the CMR target was +14.2 ± 12.5 vs. +18.7 ± 11.9% for the best AHR in any segment and +12.0 ± 13.8% for the segment based on coronary sinus (CS) venography. Using CMR guidance, the acute responder rate was 60 vs. 50% on the basis of venography. At 6 months 60% of patients were echocardiographic responders. Of the echocardiographic responders, 92% were successfully paced in a CMR target segment compared with only 50% of non-responders (P = 0.04). CMR guidance compared well when validated against the AHR. Lead placement was possible in the CMR target region in most patients with an AHR comparable with the best achieved in any CS branch. The chronic response was significantly better in patients paced in a CMR target segment. These results suggest that CMR guidance may represent a clinically useful tool for CRT.

Reverse Electrical Remodeling by Cardiac Resynchronization Therapy: Prevalence and Clinical Impact

Cardiac resynchronization therapy (CRT) improves left ventricular ejection fraction (LVEF) in patients with congestive heart failure, LV systolic dysfunction, and a wide QRS complex. Previous reports suggest that CRT may also induce electrical remodeling but the impact on clinical outcome remains unknown. We sought to determine (1) if chronic CRT induces a relevant shortening of the intrinsic QRS (iQRS), (2) whether changes in the native conduction system correlate with clinical or echocardiographic response to CRT, and (3) to identify predictors of iQRS width shortening. We prospectively included 85 consecutive patients with left bundle-branch block who received a CRT device in 3 French centers. NYHA class, iQRS duration, LVEF, and left ventricular volumes were assessed before and 1 year after CRT implantation. Clinical and echocardiographic CRT responders were defined respectively as NYHA class improvement >1 class without heart failure hospitalization and an increase of LVEF by ≥10% and/or a decrease in LVESV by ≥15%. Electrocardiographic responders were defined as a decrease in iQRS duration by ≥20 ms. Baseline and 1-year follow-up mean iQRS durations were, respectively, 168.0 ± 19.7 ms and 149.6 ± 31.6 ms (P < 0.0001). Electrocardiographic response, observed in 43/85 patients (51%), was associated with a greater rate of clinical (P = 0.035) and echocardiographic (P = 0.023) response. Younger age, male gender, and longer baseline QRS width were independent predictors of electrocardiographic response. CRT decreases iQRS duration. A reduction of at least 20 ms in iQRS duration is associated with better clinical and echocardiographic response.

Chronic right ventricular pacing, adverse remodelling, and CRT: an ounce of prevention?

This commentary refers to ‘Biventricular pacing is superior to right ventricular pacing in bradycardia patients with preserved systolic function: 2-year results of the PACE trial’[†][1], by J.Y.-S. Chan et al. , on page 2533 In medicine, it is encouraging when research yields results consistent with our understanding of the operative mechanisms, especially when there is a direct potential impact on clinical practice. Chan et al . have provided us with such a result and a clear message.1 The 2-year follow-up in the Pacing to Avoid Cardiac Enlargement (PACE) trial confirms that chronic right ventricular (RV) pacing in patients with bradycardia and preserved left ventricular (LV) function leads to sustained and progressive deterioration of LV ejection fraction (EF) and increases in LV volumes. This adverse remodelling process was prevented by pacing with cardiac resynchronization therapy (CRT). Adverse LV remodelling is a complex maladaptive process involving structural, haemodynamic, histopathological, and genetic changes.2 The process may be multifactorial and is frequently encountered in patients after loss of myocardium (myocardial infarction), volume overload (valvular insufficiency), or pressure overload (hypertension). It involves both LV hypertrophy and dilatation, and is initially an adaptive response that serves to maintain stroke volume. If persistent and progressive, the process becomes maladaptive and leads to further deterioration of LV function, LV dilatation, and eventually the typical symptoms of heart failure (HF). It is evident that substantial prolongation of the QRS interval, especially with a left bundle branch pattern, results in a delayed and dyssynchonous LV contraction.3 This dyssynchrony may be a major contributor that can both initiate and aggravate the process of adverse remodelling. In patients with symptomatic HF, systolic … [1]: #fn-2

Mechanical Dyssynchrony Assessed by Speckle Tracking Imaging as a Reliable Predictor of Acute and Chronic Response to Cardiac Resynchronization Therapy

Speckle tracking echocardiography (STE) has the potential to detect the heterogeneous initiation of active myocardial contraction, which is the primary cause of left ventricular (LV) systolic dysfunction in patients with mechanical dyssynchrony. This study was designed to assess the ability to predict response to cardiac resynchronization therapy (CRT) of STE-derived dyssynchrony parameters in comparison with invasive hemodynamic assessments. Thirty patients referred for CRT were studied. The time difference of first peak (Td-(first peak)) and the maximum peak (Td-(max peak)) on the radial strain-time curves of the earliest and the latest segments were measured as the dyssynchrony parameter. Peak positive dP/dt (dP/dt(max)) was measured as the indicator of global LV systolic performance. CRT responders were defined as patients with LV end-systolic volume reduction greater than 15% at 3 months after CRT. CRT increased the dP/dt(max) compared with the baseline study (P < .001). Percent changes in the dP/dt(max) (dP/dt(max)) were significantly correlated with Td-(first peak) (R = 0.743, P < .001), but weakly correlated with Td-(max peak) (R = 0.390, P = .03). Twenty patients (66%) were identified as chronic CRT responders. Receiver operating characteristics analysis revealed that Td-(first peak) shared a similar ability with dP/dt(max) to detect chronic responders (Td-(first peak) >167.0 ms, area under the curve [AUC] 0.945; dP/dt(max) >16.2%, AUC 0.934) compared with Td-(max peak) (>194.5 ms, AUC 0.820). STE-derived Td-(first peak) showed a reliable ability to predict the acute and chronic response to CRT as well as dP/dt(max).

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.

Endomyocardial Upregulation of β1 Adrenoreceptor Gene Expression and Myocardial Contractile Reserve Following Cardiac Resynchronization Therapy

Background Congestive heart failure (CHF) is associated with a blunted force-frequency relation (FFR) and myocardial contractile reserve (MCR) partially from a downregulation of β1-adrenoreceptors (β1-AR). We investigated whether acute and chronic cardiac resynchronization therapy (CRT) was capable of reversing the blunted FFR and MCR and if this was associated with upregulation of β1-AR. Methods and Results Left ventricle dP/dtmax was invasively measured in 10 CHF patients (New York Heart Association class ≥3; ejection fraction <25%) during incremental dual chamber (DDD)-CRT pacing at 70, 90, 110, and 130 beats/min, with and without continuous infusion of intravenous dobutamine, immediately after CRT implantation (BL) and 4 months later (FU). In a subgroup of 5 patients, serial left ventricle β1 and β2-AR gene expression was measured using reverse transcriptase-polymerase chain reaction. Four months after the initiation of resynchronization therapy, DDD-CRT pacing results in a significant upward shift of the heart rate versus LV dP/dtmax relationship ( P < .01) with force frequency amplification as evidenced by the steeper slope of the force frequency response ( P = .04). Infusion of dobutamine recruits myocardial contractile reserve and increases the heart rate versus LV dP/dtmax relationship at BL and at FU (both P < .05). However, only at follow-up was an additional force frequency amplification noticed ( P < .05) during dobutamine infusion. This observation was paralleled by a significant upregulation of β1-AR gene expression ( P = .02). Conclusions Chronic CRT is associated with a partial restoration of the FFR and with a recruitment in myocardial contractile reserve, which is paralleled by upregulation of β1-AR.

Chronic cardiac resynchronization therapy reverses cardiac remodelling and improves invasive haemodynamics of patients with severe heart failure on optimal medical treatment

The aim of this study was to assess chronic invasive haemodynamic effects of cardiac resynchronization therapy (CRT) in patients with severe heart failure. Seventeen patients with New York Heart Association (NYHA) class III or IV and QRS duration >120 ms on optimal treatments underwent CRT. Haemodynamic data were obtained by cardiac catheterization before and 1 month after CRT. Clinical parameters and exercise tolerance were also evaluated. Chronic CRT improved haemodynamics significantly; mean pulmonary capillary wedge pressure decreased from 15.9 +/- 6.1 to 10.2 +/- 5.3 mmHg (P < 0.05), systolic pulmonary artery pressure decreased from 36.5 +/- 13.2 to 26.7 +/- 11.9 mmHg (P < 0.05), left ventricular end-diastolic pressure decreased from 15.6 +/- 7.2 to 10.5 +/- 7.3 mmHg (P < 0.05), end-diastolic volume decreased from 358.8 +/- 84.6 to 322.9 +/- 99.0 mL (P < 0.05), end-systolic volume decreased from 264.1 +/- 67.6 to 219.2 +/- 74.3 mL (P < 0.05), left ventricular ejection fraction increased from 25.4 +/- 6.2 to 33.1 +/- 4.9% (P < 0.05), and cardiac index increased from 1.9 +/- 0.4 to 2.2 +/- 0.5 L/min/m(2) (P < 0.05). Chronic CRT significantly improved functional capacity such as NYHA classification, 6 min walk distance, and peak oxygen uptake. Chronic CRT improved not only symptoms and exercise tolerance but also invasive haemodynamics associated with reversed cardiac remodelling.

Abstract 1604: Response to Cardiac Resynchronization Therapy Differs Between Patients With and Without Previous Right Ventricular Pacing

Background: Previous large studies on the effects of cardiac resynchronization therapy (CRT) in patients with heart failure have generally excluded patients previously paced from the right ventricle (RV). Previously RV paced patients (RVp) can exhibit an iatrogenic cause of dyssynchrony and reduced systolic function and thus, may respond differently to CRT than patients not previously RV paced (nRVp). The purpose of this study was to test the hypothesis that RVp patients have greater improvements in left ventricular systolic function, volumes, and dyssynchrony in response to CRT than nRVp. Methods: Standard echocardiograms with tissue Doppler imaging were performed before and after chronic CRT in RVp (n = 21, 16 male) and nRVp (n = 70, 54 male) heart failure patients. Ejection fraction (EF), left ventricular end diastolic (LVEDV) and systolic (LVESV) volumes were calculated using the biplane Simpson’s method. Longitudinal dyssynchrony was calculated as the standard deviation of time to peak displacement (TT-12) of 12 segments in the apical views. Using mid-ventricular short axis views and speckle-tracking methods, radial dyssynchrony (Rad dys ) was calculated as the maximal time difference between six myocardial segments for peak radial strain. Echo response was defined as ≥ 15% reduction in LVESV. Results are reported as mean ± SD. Results: Significant baseline differences (p &lt; 0.05) were observed between groups (RVp vs. nRVp) for age (74 ± 13 vs. 67 ± 13 year), follow-up time (6.1 ± 1.8 vs. 4.6 ± 2.1 months), LVEDV (154.3±50.8 vs.185.3±56.9 mL), and a trend for LVESV (112.4 ± 40.6 vs. 134.9 ± 47 mL, p = 0 .05). No differences were observed for EF, etiology of heart failure, and dyssynchrony measures between groups at baseline. Echo response rate was significantly ( p &lt; 0.05) greater in RVp (76%) than nRVp (57%). After adjusting for baseline differences, RVp had greater improvement in EF (14 ± 9 vs. 8 ± 7%, p &lt; 0.05) and LVESV (−33 ± 18 vs. −20 ± 21%, p &lt; 0.05). After adjustment for follow-up time, no difference was observed for change in dyssynchrony between groups. Conclusion: RVp patients upgraded to CRT exhibit greater improvements in systolic function and ventricular remodeling as compared to nRVp patients.

Early and late effects of cardiac resynchronization therapy on force–frequency relation and contractility regulating gene expression in heart failure patients

Heart failure is associated with a reduction in left ventricular (LV) contractility as evidenced by a blunted force-frequency response (FFR) and downregulation of contractility regulating genes. This study sought to investigate whether cardiac resynchronization therapy (CRT) is capable of reversing the blunted FFR and the downregulation of contractility regulating genes. Twenty heart failure patients underwent echocardiographic examination during incremental AAI and DDD-CRT pacing at 70, 90, and 110 beats/min, immediately after and 4 months after CRT implantation. The FFR was determined from the ratio of the LV systolic pressure/end systolic volume index at given heart rate. In a subgroup of 6 patients with idiopathic dilated cardiomyopathy, serial LV dP/dtmax was invasively measured during both pacing modes and serial LV endomyocardial biopsies were taken to measure sarcoplasmatic reticulum calcium ATPase 2alpha (SERCA2alpha), phospholamban (PLN), sarcolemmal sodium calcium exchanger (NCX), beta1-adrenoreceptor (beta1-AR), and apelin (APL) gene expression using reverse-transcriptase polymerase chain reaction. Acutely, DDD-CRT pacing was associated with a decrease in dyssynchrony (P <.01) and increase in diastolic filling time (P <.01) at all heart rates paralleled by an upward shift of the FFR (P <.01) without force-frequency amplification. A greater upward shift of the FFR was noticed during DDD-CRT as compared with AAI (P <.01) after 4 months. In addition, CRT was associated with a significant force-frequency amplification at follow-up as evidenced from the steeper slope of the FFR relationship (P = .039). This was associated with a significant upregulation of SERCA2alpha P = .01), PLN (P = .01), their ratio (P = .01), ratio of SERCA/NCX (P = .02), beta1-AR (P = .03), and APL (P = .01) mRNA levels. CRT is associated with an acute upward shift in the FFR without force-frequency amplification related to restored synchronicity and increased filling time of the LV. Only chronic CRT is associated with force-frequency amplification in parallel to upregulation of contractility regulating genes.

Chronic Cardiac Resynchronization Therapy Reverses Cardiac Remodeling and Improves Invasive Hemodynamics of Patients with Severe Heart Failure on Optimal Medical Treatment

Chronic Cardiac Resynchronization Therapy Reverses Cardiac Remodeling and Improves Invasive Hemodynamics of Patients with Severe Heart Failure on Optimal Medical Treatment