Background
In studies showing benefits of cardiac resynchronization therapy (CRT), individual atrioventricular (AV) delays have been optimized using echocardiography. However, the method for AV delay optimization remains controversial.
Methods
In 100 consecutive patients with CRT device implantation, AV delay was optimized using echocardiography. The optimal AV delay was determined by changing the interval in 20-ms increments while measuring displacement in 6 basal left ventricular segments (averaged and reported as left ventricular displacement [D LV ]) and other echocardiographic measures.
Results
A single optimal AV delay existed for each patient, and the associated highest D LV corresponded with the maximal velocity-time integral (VTI) in the left ventricular outflow tract (VTI LVOT ) and the E/e′ ratio. Significant increases in D LV and the VTI LVOT from before to after implantation with standard settings and from standard to optimal AV delay by displacement were found. Diastolic filling time corresponded poorly with D LV and the VTI LVOT .
Conclusion
Individual optimal AV delay programming provides significant improvement in left ventricular performance and hemodynamics. Displacement analysis and the VTI LVOT are interchangeable, whereas diastolic filling time cannot be recommended.
Cardiac resynchronization therapy (CRT) in patients with heart failure with left bundle branch block improves left ventricular (LV) function and reduces symptoms and mortality.
Several studies have reported high rates of nonresponse to CRT (24%-47%), and various factors may influence the individual effects of CRT. Atrioventricular (AV) delay optimization has been shown to be important for hemodynamic improvements and clinical response to CRT. In most large randomized studies of CRT, AV delays were optimized using echocardiography.
However, there is no conformity in the assessment of optimal AV delay. At present, optimization using the velocity-time integral (VTI) in the LV outflow tract (VTI LVOT ) is a frequently used technique to improve systolic performance, as this method is well correlated with cardiac output. However, there might be situations in which the measurement of the VTI LVOT may not be reliable or possible because of angle problems or severe valve disease. Diastolic filling measures using transmitral flow are also used for AV delay optimization, but these are preload dependent, and a clear truncation is often obscure.
Displacement by Doppler tissue imaging has been revealed as a simple and excellent marker of global systolic performance and correlates well with LV ejection fraction (LVEF). Accordingly, this method could be valuable performing AV delay optimization.
Our aim was to evaluate hemodynamic responses and correlations between different parameters of LV and right ventricular (RV) function during AV delay optimization in patients with newly implanted CRT devices. We hypothesized that displacement as a measure of LV systolic function would be associated with the VTI LVOT and would represent a valid method for the optimization of AV delay.
Methods
Study Population
The study population comprised 100 consecutive patients with sinus rhythm referred to our outpatient clinic for echocardiographically guided optimization of AV delay following the implantation (<1 week) of a CRT device. All patients fulfilled standard criteria for receiving a CRT device (ie, a dilated left ventricle with evidence of systolic LV dysfunction with an LVEF < 35%, New York Heart Association class III or IV heart failure, left bundle branch block, and optimal medical treatment). Patients with atrial fibrillation and patients with severe aortic or mitral valve disease or valve replacement were excluded.
Lead Positioning
During CRT implantation, the LV pacing lead was positioned in a coronary sinus tributary, with a preferred position in a lateral or posterolateral position and with as late sensed LV signal as possible compared with the surface electrocardiogram. A second lead was positioned in the right atrium and a third in the right ventricle. Sixty patients had RV leads positioned in the RV septum, and the remaining 40 patients had leads implanted in the RV apex. On the basis of left anterior oblique evaluations of coronary sinus venograms, LV lead positioning included 75 lateral or posterolateral leads, 10 true posterior leads, and 15 anterolateral leads.
After the completion of implantation and until the time of echocardiographic examination, all pacemakers were programmed to simultaneous pacing with a sensed AV delay of 120 ms.
AV Delay Programming During Optimization
Initially, the longest possible AV delay to provide biventricular capture was programmed and subsequently shortened in intervals of 20 ms to the shortest possible delay. Echocardiographic measurements were obtained initially, and after an equilibrium phase of 2 minutes, the AV delay was programmed.
Echocardiographic Protocol
During the echocardiographic examination (Vivid 7; GE Vingmed Ultrasound AS, Horten, Norway), all patients were in sinus rhythm and were examined during intrinsic conduction (ie, atrial-sensed biventricular pacing). Color-coded tissue Doppler recordings from the apical position were obtained during end-expiration covering the apical 4-chamber, 2-chamber, and long-axis views as well as a modified 4-chamber view for the evaluation of RV longitudinal systolic function. Frame rates ranged from 130 to 175 frames/s. Systolic longitudinal shortening of the 6 basal segments was evaluated using displacement, as previously described. Thus, the peak displacement within each annular segment was measured at the time of aortic valve closure to include only the summation of displacement that occurred between aortic valve opening and closure (ie, the ejection phase).
Systolic shortening within each segment was measured in 5 beats, and the average for each segment was used.
LV displacement (D LV ) was determined as the summation of the time integral in systole. Global systolic longitudinal D LV as presented was calculated by averaging systolic shortening for all 6 segments. Maximal D LV was used to define the optimal AV delay and used as reference for all comparisons.
From the modified 4-chamber view, basal systolic longitudinal shortening of the RV free wall was evaluated using displacement, and the average of these measurements in 5 beats is presented as RV displacement (D RV ).
The VTI LVOT was measured using pulsed-wave Doppler in the LVOT using a 2-mm sample volume positioned just proximal to the aortic valve. The VTI LVOT was measured for each AV delay, and data presented represent an average of 5 measurements in 5 different heartbeats.
Pulsed-wave Doppler recordings of transmitral flow were performed in the 4-chamber view with a 2-mm sample between the tips of the mitral leaflets. Diastolic filling time (DFT) was determined as the time interval from the onset of mitral inflow to the end of the mitral A-wave velocity relative to cycle length.
Peak early diastolic transmitral flow velocity (E) was evaluated 5 times for each AV delay and averaged. Pulsed-wave tissue Doppler in both the lateral and septal mitral annuli was obtained for each AV delay. Peak early diastolic myocardial velocity (e′) was measured 5 times at both sites and averaged. The E/e′ ratio was calculated using the average value of e′ from septal and lateral annuli. To minimize variability, all recordings were obtained by the same experienced echocardiographer (P.S.). Interobserver variability was tested in 15 random patients, and a Bland-Altman plot did not show any systematic bias (bias, 0.0 mm), and we found fine agreement (limits of agreement, ±0.21 mm).
Statistical Analysis
Baseline characteristics are presented as mean ± SD for continuous variables and as percentages for categorical variables. Comparison of echocardiographic parameters was performed at identical AV delays. Univariate linear regression analyses were performed using Pearson’s correlation coefficients to explore the relationship between the D LV measurements and the VTI LVOT , E/e′, and D RV measurements using raw data, because they satisfied the linear regression assumptions better than log-transformed data. P values < .05 were considered significant. All calculations were conducted using SAS version 9.1 (SAS Institute Inc, Cary, NC).
Results
Baseline characteristics are presented in Table 1 . The mean LVEF was 22%, all patients received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, 92% received β-blockers, and 50% received aldosterone inhibitors. The optimal AV delays were within 50% to 75% of intrinsic PR duration in 90% of patients. In the remaining 10%, the optimal AV delays ranged from 40% to 50% of intrinsic PR intervals.
| Variable | Value |
|---|---|
| Age (y) | 62 ± 11 |
| Men | 75% |
| Duration of heart failure (y) | 6 ± 2.5 |
| New York Heart Association class III | 85% |
| Ischemic etiology | 60% |
| QRS duration (ms) before CRT | 162 ± 17 |
| LVEF (%) | 22 ±4.8 |
| PR interval (ms) | 225 ±14 |
| Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers | 100% |
| β-blockers | 92% |
| Aldosterone inhibitors | 50% |
| Diuretics | 100% |
| Digoxin | 25% |
| Amiodarone | 10% |
We were able to estimate longitudinal displacement in all segments in all patients. Table 2 presents changes in the 5 echocardiographic parameters, showing significant improvements of all echocardiographic parameters from before to after implantation with standard settings for AV delay and from standard to optimal AV delay by D LV .
| Variable | Before CRT | Standard CRT (AV delay, 120 ms) | After AV optimization |
|---|---|---|---|
| D LV (mm) | 4.1 ± 1.2 | 4.9 ± 1.5 ∗ | 5.9 ± 1.1 † |
| VTI LVOT (cm) | 14.4 ± 1.7 | 15.5 ± 2.3 ∗ | 16.7 ± 2.6 † |
| E/e′ | 16.3 ± 2.1 | 13.3 ± 2.6 ‡ | 11.6 ± 1.6 § |
| DFT (%) | 34.7 ± 7.7 | 39.8 ± 7.9 | 43.9 ± 8.3 † |
| D RV (mm) | 16.6 ± 4.0 | 17.8 ± 3.6 ∗ | 18.9 ± 3.4 † |
† P < .05 versus standard CRT and P < .01 versus before CRT.
Displacement
In 87 patients, optimal D LV was related to the highest VTI LVOT , in 82 patients to the lowest E/e′ ratio, and in 61 patients to the highest DFT.
D LV values during AV delay optimization are shown in Table 3 with corresponding values of other echocardiographic parameters (VTI LVOT , E/e′, and D RV ) usable for AV delay optimization. The optimal AV delay obtained with D LV corresponded well with the maximal VTI LVOT and E/e′, but not with maximal D RV .
| AV delay (ms) | |||||||
|---|---|---|---|---|---|---|---|
| Less than optimal | Greater than optimal | ||||||
| −60 | −40 | −20 | Optimal ∗ | +20 | +40 | +60 | |
| Variable | (n = 96) | (n = 100) | (n = 100) | (n = 100) | (n = 100) | (n = 100) | (n = 88) |
| D LV (mm) | 4.7 ± 1.0 | 5.1 ± 1.0 | 5.3 ± 1.0 | 5.9 ± 1.1 | 5.5 ± 1.1 | 5.2 ± 1.1 | 5.0 ± 1.1 |
| VTI LVOT (cm) | 13.9 ± 2.4 | 14.9 ± 2.3 | 15.6 ± 2.5 | 16.7 ± 2.6 | 15.8 ± 2.7 | 15.1 ± 2.6 | 14.5 ± 2.6 |
| E/e′ | 13.5 ± 1.8 | 13.0 ± 1.8 | 12.3 ± 1.6 | 11.6 ± 1.6 | 12.3 ± 1.7 | 12.7 ± 1.7 | 13.1 ± 1.6 |
| DFT (%) | 38 ± 8 | 40 ± 8 | 43 ± 8 | 44 ± 8 | 43 ± 8 | 42 ± 8 | 38 ± 9 |
| D RV (mm) | 17.3 ± 3.5 | 18.3 ± 3.5 | 18.6 ± 3.5 | 18.9 ± 3.4 | 18.8 ± 3.4 | 18.8 ± 3.4 | 18.8 ± 3.5 |
During AV delay optimization, only one optimal time setting was found for each person, resulting in the highest D LV and VTI LVOT and lowest E/e′, as illustrated by mean values of the differences from optimal D LV in Figures 1 A to 1 C . The optimal AV delay using D LV was identical to the AV delay selected using the VTI LVOT in 87%, whereas a 20-ms longer AV delay was found in 8% and a 20-ms shorter AV delay in 5%. For E/e′, identical AV delay was found in 98%, and a 20-ms shorter AV delay was optimal in 2%. For D RV , identical AV delay was found in 40%, and optimal AV delays of −20, +20, +40, and +60 ms were found in 16%, 24%, 10%, and 10% of patients, respectively. However, overall D RV decreased with AV delays set lower than the optimal value by D LV . Correlations between optimal D LV and the 3 other echocardiographic parameters of interest (VTI LVOT , E/e′, and D RV ) are shown in Figures 2 and 3 and Table 4 .
| AV delay (ms) | |||||||
|---|---|---|---|---|---|---|---|
| Less than optimal | Greater than optimal | ||||||
| Variable | −60 | −40 | −20 | Optimal | +20 | +40 | +60 |
| VTI LVOT | 0.752 ∗ | 0.759 ∗ | 0.782 ∗ | 0.819 ∗ | 0.810 ∗ | 0.820 ∗ | 0.824 ∗ |
| E/e′ | −0.567 ∗ | −0.486 ∗ | −0.489 ∗ | −0.540 ∗ | −0.515 ∗ | −0.475 ∗ | −0.490 ∗ |
| D RV | 0.084 (.44) | 0.084 (.41) | 0.025 (.80) | 0.054 (.59) | 0.035 (.73) | 0.031 (.76) | 0.033 (.75) |
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