Determination of optimal atrioventricular delay for cardiac resynchronization therapy using acute non-invasive blood pressure.

AIMS: In this study, we apply non-invasive blood pressure (BP) monitoring, by continuous finger photoplethysmography (Finometer), to detect directly haemodynamic responses during adjustment of the atrioventricular (AV) delay of cardiac resynchronization therapy (CRT), at different heart rates. METHODS AND RESULTS: Twelve patients were studied with six re-attending for reproducibility assessment. At each AV delay, systolic BP relative to a reference AV delay of 120 ms (SBPrel) was calculated. We found that at higher heart rates, altering the AV delay had a more pronounced effect on BP (average range of SBPrel=17.4 mmHg) compared with resting rates (average range of SBPrel=6.5 mmHg), P<0.0001. Secondly, peak AV delay differed between patients (minimum 120 ms, maximum 200 ms). Thirdly, small changes in AV delay had significant BP effects: programming AV delay 40 ms below the peak AV delay reduced SBPrel by 4.9 mmHg (P<0.003); having it 40 ms above the peak decreased SBPrel by 4.4 mmHg (P<0.0005). Finally, the peak AV delay is highly reproducible both on the same day and at 3 months (Bland-Altman difference: 3+/-8 ms). CONCLUSIONS: Continuous non-invasive arterial pressure monitoring demonstrates that even small changes in AV delay from its haemodynamic peak value have a significant effect on BP. This peak varies between individuals, is highly reproducible, and is more pronounced at higher heart rates than resting rates.     

Comparison of different invasive hemodynamic methods for AV delay optimization in patients with cardiac resynchronization therapy: Implications for clinical trial design and clinical practice

Background

Reproducibility and hemodynamic efficacy of optimization of AV delay (AVD) of cardiac resynchronization therapy (CRT) using invasive LV dp/dt_max are unknown.

Method and results

25 patients underwent AV delay (AVD) optimisation twice, using continuous left ventricular (LV) dp/dt_max, systolic blood pressure (SBP) and pulse pressure (PP). We compared 4 protocols for comparing dp/dt_max between AV delays:

Immediate absolute: mean of 10 s recording of dp/dt_max acquired immediately after programming the tested AVD,

Delayed absolute: mean of 10 s recording acquired 30 s after programming AVD,

Single relative: relative difference between reference AVD and the tested AVD,

Multiple relative: averaged difference, from multiple alternations between reference and tested AVD.

We assessed for dp/dt_max, LVSBP and LVPP, test–retest reproducibility of the optimum.Optimization using immediate absolute dp/dt_max had poor reproducibility (SDD of replicate optima = 41 ms; R² = 0.45) as did delayed absolute (SDD 39 ms; R² = 0.50). Multiple relative had better reproducibility: SDD 23 ms, R² = 0.76, and (p < 0.01 by F test).Compared with AAI pacing, the hemodynamic increment from CRT, with the nominal AV delay was LVSBP 2% and LVdp/dt_max 5%, while CRT with pre-determined optimal AVD gave 6% and 9% respectively.

Conclusions

Because of inevitable background fluctuations, optimization by absolute dp/dt_max has poor same-day reproducibility, unsuitable for clinical or research purposes. Reproducibility is improved by comparing to a reference AVD and making multiple consecutive measurements. More than 6 measurements would be required for even more precise optimization — and might be advisable for future study designs. With optimal AVD, instead of nominal, the hemodynamic increment of CRT is approximately doubled.     

Randomized prospective trial of atrioventricular delay programming for cardiac resynchronization therapy

OBJECTIVES: The purpose of this study was to determine if AV delay optimization with continuous-wave Doppler aortic velocity-time integral (VTI) is clinically superior to an empiric program in patients treated with cardiac resynchronization therapy (CRT) for severe heart failure. BACKGROUND: The impact of AV delay programming on clinical outcomes associated with CRT is unknown. METHODS: A randomized, prospective, single-blind clinical trial was performed to compare two methods of AV delay programming in 40 patients with severe heart failure referred for CRT. Patients were randomized to either an optimized AV delay determined by Doppler echocardiography (group 1, n = 20) or an empiric AV delay of 120 ms (group 2, n = 20) with both groups programmed in the atriosynchronous biventricular pacing (VDD) mode. Optimal AV delay was defined as the AV delay that yielded the largest aortic VTI at one of eight tested AV intervals (between 60 and 200 ms). New York Heart Association (NYHA) functional classification and quality-of-life (QOL) score were compared 3 months after randomization. RESULTS: Immediately after CRT initiation with AV delay programming, VTI improved by 4.0 +/- 1.7 cm vs 1.8 +/- 3.6 cm (P < .02), and ejection fraction (EF) increased by 7.8 +/- 6.2% vs 3.4 +/- 4.4% (P < .02) in group 1 vs group 2, respectively. After 3 months, NYHA classification improved by 1.0 +/- 0.5 vs 0.4 +/- 0.6 class points (P < .01), and QOL score improved by 23 +/- 13 versus 13 +/- 11 points (P < .03) for group 1 vs group 2, respectively. CONCLUSIONS: Echocardiography-guided AV delay optimization using the aortic Doppler VTI improves clinical outcomes at 3 months compared to an empiric AV delay program of 120 ms.     

A prospective comparison of AV delay programming methods for hemodynamic optimization during cardiac resynchronization therapy

Introduction: There are several methods for programming the optimal AV delay (AVD) during cardiac resynchronization therapy (CRT). These include Doppler echocardiographic measurements of mitral inflow or aortic outflow velocities, an arbitrarily fixed AVD, and calculations based on intracardiac electrogram (EGM) intervals. The present study was designed to compare the acute effects of AVD programming methods during CRT.
Methods and Results: We studied 28 patients at CRT implant with invasive measurements of LV dP/dt to determine the effect of AVD during atrial sensed (AS) and atrial paced (AP) modes. The optimal AVD, defined as that resulting in the maximal LV dP/dt, was then compared with that predicted by several noninvasive methods. CRT increased LV dP/dt 11%± 11% during AS (heart rate: 73 ± 14 bpm) and 17%± 12% during AP (heart rate: 86 ± 12 bpm) (P < 0.001 vs AS). There was an excellent correlation between the EGM method and the maximum achievable LV dP/dt (AS: R²= 0.99, P < 0.0001, AP: R²= 0.96, P < 0.0001) and this method performed better than other techniques.
Conclusions: An electrogram-based optimization method accurately predicts the optimal AVD among patients over a wide range of QRS intervals during CRT in both AS and AP modes. This simple technique may obviate the need for echocardiography for AVD programming.     

Left univentricular pacing for cardiac resynchronization therapy using rate-adaptive atrioventricular delay

Objective To evaluate left univentricular (LUV) pacing for cardiac resynchronization therapy (CRT) using a rate-adaptive atrioventricular delay (RAAVD) algorithm to track physiological atrioventricular delay (AVD). Methods A total of 72 patients with congestive heart failure (CHF) were randomized to RAAVD LUV pacing versus standard biventricular (BiV) pacing in a 1: 1 ratio. Echocardiography was used to optimize AVD for both groups. The effects of sequential BiV pacing and LUV pacing with optimized A-V (right atrio-LV) delay using an RAAVD algorithm were compared. The standard deviation (SD) of the S/R ratio in lead V1 at five heart rate (HR) segments (R_S/R-SD5), defined as the “tracking index,” was used to evaluate the accuracy of the RAAVD algorithm for tracking physiological AVD. Results The QRS complex duration (132 ± 9.8 vs. 138 ± 10 ms, P < 0.05), the time required for optimization (21 ± 5 vs. 50 ± 8 min, P < 0.001), the mitral regurgitant area (1.9 ± 1.1 vs. 2.5 ± 1.3 cm2, P < 0.05), the interventricular mechanical delay time (60.7 ± 13.3 ms vs. 68.3 ± 14.2 ms, P < 0.05), and the average annual cost (13,200 ± 1000 vs. 21,600 ± 2000 RMB, P < 0.001) in the RAAVD LUV pacing group were significantly less than those in the standard BiV pacing group. The aortic valve velocity-time integral in the RAAVD LUV pacing group was greater than that in the standard BiV pacing group (22.7 ± 2.2 vs. 21.4 ± 2.1 cm, P < 0.05). The R_S/R-SD5 was 4.08 ± 1.91 in the RAAVD LUV pacing group, and was significantly negatively correlated with improved left ventricular ejection fraction (LVEF) (?LVEF, Pearson’s r = ?0.427, P = 0.009), and positively correlated with New York Heart Association class (Spearman’s r= 0.348, P = 0.037). Conclusions RAAVD LUV pacing is as effective as standard BiV pacing, can be more physiological than standard BiV pacing, and can decrease the average annual cost of CRT.     

Left bundle branch–optimized cardiac resynchronization therapy (LOT-CRT): Results from an international LBBAP collaborative study group

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Determination of the optimal atrioventricular and interventricular delays in cardiac resynchronization therapy

Objective In order to provide the maximum benefit of cardiac resynchronization therapy (CRT), we tried to use an echocardiography method to optimize the atrioventricular and interventricular delay. Methods The study included 6 patients who underwent implantation of biventricular pacemakers for drug-resistant heart failure. Two-dimensional echocardiography and tissue Doppler imaging were carried out before and after the pacemaker implantation. The optimal AV delay was defined as the AV delay resulting in maximum time-velocity integral (TVI) of transmitral filling flow, the longest left ventricular filling time (LVFT) and the minimum mitral regurgitation (MR). The optimal VV delay was defined as the VV delay producing the maximum LV synchrony and the largest aortic TVI. Results CRT was successfully performed in all patients. After pacemaker implantation, an acute improvement in left ventricular ejection fraction (LVEF) was observed from 26.5% to 35%. Meanwhile, the QRS duration decreased from 170ms to 150ms. The optimal AV delay was programmed at 130, 120, 120, 120, 150 and 110ms respectively with heart rate corrected, LVFT significantly lengthened and TVI of MR decreased (non-optimal vs optimal AV delay: LVFT: 469ms vs 523ms; TVI of MR: 16.43cm vs 13.06cm, P<0.05). The optimal VV delay was programmed at 4, 4, 4, 8, 12 and 8ms with LV preactivation respectively. Programming the optimal VV delay increased the aortic TVI from 17.33cm up to 21.42cm (P<0.05). In the septal and lateral wall, peak systolic velocities improved from 2.70cm/s to 3.02cm/s (P>0.05) and froml.31cm/s to 2.50cm/s (P<0.05) respectively. The septal-to-lateral delay in peak velocity improved from 56.4ms to 13.3ms after CRT (P<0.01). Conclusions Optimization of AV and VV delays may further enhance the efficacy of CRT. However, there was interindividual variability of optimal values, warranting individual patient examination.     

Doppler echocardiographic methods for optimization of the atrioventricular delay during cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) is beneficial for a majority of patients with medically refractory heart failure due to severe left ventricular (LV) systolic dysfunction and prolonged interventricular conduction to improve symptoms and LV performance. An optimally programmed atrioventricular delay (AVD) during CRT can be also important to maximize the response in left ventricular function. Several Doppler echocardiographic methods have been reported to be useful for determination of the optimal AVD. This review will discuss the various Doppler-based approaches to program the AVD in patients that receive CRT.     

Temporal variation in optimal atrioventricular and interventricular delay during cardiac resynchronization therapy

BackgroundTailored atrioventricular delay (AVd) and interventricular delay (VVd) combination improves hemodynamics in patients treated with cardiac resynchronization therapy (CRT). Whether tailored AVd-VVd combination changes over time is not known.Methods and ResultsTwenty-two patients (18 M, aged 69.9 ± 12.5 years, New York Heart Association class III, QRS ≥ 130 ms, ejection fraction 29.6 ± 8.8%) were implanted with a biventricular device with programmable VVd. Myocardial performance index (MPI) was evaluated during pacing at different VVds and AVds at baseline and after 6 and 12 months. The optimal AVd-VVd combination was identified by the minimum MPI. After optimization, the appropriate AVd-VVd combination was programmed in each patient. MPI at 6-month follow-up after optimization was significantly higher compared with baseline (.79 ± .21 vs. .59 ± .15, P < .05). Re-optimization of AVd-VVd combination was required after 6 months in 21 of 22 (95%) patients. Re-optimization significantly reduced MPI compared with the value prior to re-optimization (.56 ± .15 vs. .79 ± .21, P < .05). The MPI remained unchanged at 12-month compared with 6-month follow-up (.59 ± .19 vs. .56 ±.15, P = NS). Clinical symptoms and reverse left ventricular remodeling were sustained at 6-month and 12-month follow-up.ConclusionOptimal AVd and VVd combination changes over time in patients with heart failure. Sustained improvement in clinical symptoms and reverse left ventricular remodeling after CRT are not temporally associated with improvement in MPI.     

Calculation of effective VV interval facilitates optimization of AV delay and VV interval in cardiac resynchronization therapy

BACKGROUND: In hearts with left bundle branch block (LBBB), both atrioventricular (AV) delay and interventricular (VV) interval determine left ventricular (LV) pump function in cardiac resynchronization therapy (CRT). The optimal combination of AV delay and VV interval currently is determined by extensive hemodynamic testing. OBJECTIVES: The purpose of this study was to investigate whether the effective VV interval (VV(eff)) can be used to optimize AV delay and VV interval. METHODS: In eight canine hearts with chronic LBBB, LV pacing was performed at various AV delays as well as biventricular pacing at multiple AV delays and VV intervals. LV pump function was assessed from LVdP/dt(max) and stroke volume (conductance catheter). Interventricular asynchrony was calculated from the timing difference between upslope of LV and RV pressure curves. VV(eff) was defined as the time delay between activation of the RV apex and LV lateral wall, irrespective of the source of RV activation (RV pacing or intrinsic conduction). VV(eff) was determined from pacemaker settings and surface ECGs recorded during biventricular pacing at various AV delays (positive values denote LV preexcitation). RESULTS: For all animals, the relationship between VV(eff) and LVdP/dt(max) as well as LV stroke work was parabolic. Maximal improvement in LVdP/dt(max) was similar during LV pacing, simultaneous biventricular pacing, and sequential biventricular pacing and was obtained at similar values of VV(eff). VV(eff) was strongly correlated with interventricular asynchrony (R = 0.97 +/- 0.03). Optimum LVdP/dt(max) occurred at VV(eff) ranging from -24 to 12 ms (mean -6 +/- 13 ms). For each experiment, the optimal VV(eff) was virtually equal to the value halfway between its minimum (during LV pacing at short AV delay) and maximum (during LBBB) value (R = 0.91). CONCLUSION: Use of VV(eff) facilitates determination of the best combination of AV delay and VV interval during biventricular pacing. For each individual heart, VV(eff), resulting in optimum LV pump function, can be estimated using surface ECGs recorded during biventricular pacing.     

Lack of clinical predictors of optimal V-V delay in patients with cardiac resynchronization devices

Introduction  Cardiac resynchronization therapy (CRT) is a well-established therapy for patients with moderate-to-severe heart failure (HF), left ventricular dysfunction with an ejection fraction ≤ 35% and a QRS on the surface electrocardiogram of ≥130 msec. Device optimization is often performed, adjusting the timing of RV and LV stimulation to produce a pacing sequence that yields the best global cardiac performance. However, no standard guidelines exist for optimization and many invasive and non-invasive techniques have been employed with mixed results. The aim of the present study was to determine whether there are any clinical predictors of the optimal V-V settings in patients implanted with CRT devices. Methods and results  We prospectively evaluated 47 consecutive patients with HF who were referred to our device optimization clinic. The mean patient age was 64.9 ± 12.7 years. Patients were in both sinus rhythm (83%) and atrial fibrillation. Prior to device implant, 51% of patients had left bundle branch block (LBBB), 17% had intra-ventricular conduction delay (IVCD) and 21% were RV paced. Sixty-two percent were male, the mean QRS duration was 152 ± 29 ms, mean LVEF 26 ± 8% and 60% had a non-ischemic cardiomyopathy. Overall, 82% of patients required sequential pacing with 69% requiring LV pre-excitation to produce the best global cardiac function as determined by aortic velocity time integrals (VTI). In our cohort, none of the clinical characteristics evaluated, including etiology of the cardiomyopathy, QRS duration, LVEF, pre-implant rhythm or AV delay were predictive of an optimal simultaneous or sequential V-V setting. Conclusions  None of the clinical variables tested in our analysis predicted optimal RV-LV settings. Our results suggest that individual optimization and programming of V-V settings is necessary. The inability to predict optimal settings likely reflects the unique characteristics of each patient and supports the need for individualized programming of each device.     

Comparison of different approaches for optimization of atrioventricular and interventricular delay in biventricular pacing

Aims: It has been shown that optimizing atrioventricular (AV) andinterventricular (VV) delay improves cardiac performance inpatients with biventricular pacemakers. However, there is nostandard method for optimization available yet. The aim of thisstudy was to compare echocardiographic parameters—displacementimaging, A wave duration, and aortic velocity time integral(VTI)—and acoustic cardiography derived electromechanicalactivation time (EMAT) using different approaches of AV andVV delay optimization. We tested whether the initial optimizationof the AV interval followed by VV optimization at that optimalAV interval or initial optimization of the VV interval followedby AV optimization at the determined optimal VV interval wasaccurate and consistent, and how this compared to testing everyconceivable combination of AV and VV intervals available. Methods and results: A group of 20 patients with biventricular pacemakers was included.Displacement imaging, A wave duration, and aortic VTI were determinedat different combinations of AV (100, 150, 200, 250 ms) andVV (RV40, 0, LV40 ms) intervals. If AV duration was determinedfirst, displacement imaging identified the best setting in 8/20,aortic VTI in 10/20, A duration in 13/20, and EMAT in 18/20patients. With VV duration determined first, the best settingwas more difficult to identify regardless of the method used.There was a poor agreement in optimal AV and VV delays of thedifferent methods, and there was no single patient in whom allfour methods yielded the same delay combination. Conclusion: It is advisable to measure a full grid of AV and VV delays toidentify optimal settings rather than optimizing one of thetwo delays first. Different techniques for delay optimizationresulted in different optimal delay combinations.     

动态优化AV／VV间期的心脏再同步治疗对慢性心力衰竭的疗效评价

目的评价AV／VV间期动态优化的心脏再同步治疗（CRT）对慢性心力衰竭的疗效。方法26例因心力衰竭接受CRT的患者分别于植入术后1周,6个月以及12～18个月在超声指导下行AV／VV间期优化。同时行超声心动图以及组织多普勒、心电图、6min步行距离试验（6MHW）、血浆脑钠肽（BNP）值以及x线胸片（心胸比）检查。结果本文最佳优化AV间期在100～140（120．77±8．91）ms之间,最佳优化VV间期在4～24（12．92±5．34）ms之间。CRT植入后最佳AV间期在±10ms之间波动,最佳VV间期在±4ms之间波动。植入后1周同植入前相比左心室射血分数（LVEF）由0．30±0．04增加至0．31±0．03,舒张期二尖瓣反流速度时间积分（VTImr）由（18．97±3．81）cm降至（16．04±3．64）cm;间隔对后壁的运动延迟（SPWMD）由植入前（125．06±7．47）ms降至（105．06±12．06）ms;QRS时限由植入前（144．35±10．76）ms降歪（129．00±6．65）ms;6MHW由植入前（278．46±12．55）m增加至（324．62±25．49）m;血浆BNP值由植入前（672．79±98．36）pg／ml降至（484．03±106．02）pg／ml。12～18个月AV／VV间期优化后同优化前相比：LVEF值由0．32±0．03增至0．40±0．03,VTImr由（16．04±3．64）cm降至（8．67±1．18）cm;SPWMD由（105．06±12．06）ms降至（101．00±7．56）ms;QRS时限无明显变化;6MHW由（324．62±25．49）m增加至（347．12±15．24）m;血浆BNP值由（484．03±106．02）pg／ml降至（98．41±8．57）pg／ml。左心室舒张末期内径（LVEDD）由（71．73±7．07）mm降至（64．46±4．95）mm;心胸比由（71±5）％降至（63±4）％。结论动态程控AV／VV间期可以提高CRT对慢性心力衰竭的短、中、远期疗效。     

Sustained benefit of cardiac resynchronization therapy

Introduction: Most data on cardiac resynchronization therapy (CRT) are from trials with highly selected patients, with limited long-term echocardiographic data. This study was performed to evaluate long-term echocardiographic remodeling after CRT in daily practice.
Methods and Results: A biventricular pacemaker was implanted in 130 patients with advanced heart failure who met the general accepted criteria for CRT or in heart failure patients with a conventional pacemaker indication. Two years echocardiographic follow-up was available. Mean age (73 years) was higher than in the randomized trials. Forty-one patients (32%) died during the 2 year follow-up period. Mortality was higher in males, in patients with increased NT-proBNP, renal dysfunction, or left atrial dilatation before implantation. Echocardiographic response (LVEF improvement of 5% or more) was documented in 69, 88, and 91% of the survivors, after 3 months, 1 year, and 2 years, respectively. Echocardiographic response after 3 months was associated with a significantly higher long-term survival (P = 0.04). Mean LVEF was 22% at baseline compared to 31.8, 38.3, and 39.7% after 3 months, 1 year, and 2 years, respectively (P < 0.01). Reverse remodeling (a reduction of LV end systolic volume of more than 10%) was observed in 70.7, 81.0, and 91.7% of the survivors after 3 months, 1 year, and 2 years, respectively. Long-term LV improvement was more pronounced in patients with nonischemic cardiomyopathy.
Conclusion: LV reverse remodeling and beneficial echocardiographic changes were sustained during 2 years follow-up. A 5% or more increase in LVEF after 3 months was associated with a better long-term survival.