Visual LV motion and invasive LVdP/dtmax for selection and optimisation of cardiac resynchronisation therapy

Abstract

Echocardiography shows that multiphasic septal movement and a septal to lateral apical systolic left ventricular (LV) motion have a high predictive value for dyssynchrony and the response to cardiac resynchronisation therapy (CRT). Presence of dyssynchrony is also the major marker for CRT response in the presence of scar tissue, provided the interventricular (V-V) pacing interval is optimalised. For atrioventricular (AV) interval optimisation, the velocity-time integral of the transmitral flow has an excellent correlation with invasive LVdP/dt_max. In acute haemodynamic measurements, LVdP/dt_max shows strongly the effect of AV and V-V optimisation. It also illustrates that the haemodynamic effect of LV pacing when associated with intrinsic conduction over the right bundle is equal to or better than biventricular pacing. We found that once AV and V-V interval were optimised, QRS morphology could be used as a template for optimal therapy. Automated continuous optimisation of the pacing intervals will be the big challenge for the future. (Neth Heart J 2008;16(Suppl1):S32-S35.).

Cardiac resynchronisation therapy (CRT) has become an essential part in the treatment of selected patients with left ventricular (LV) systolic heart failure and intraventricular (V-V) conduction delay.

However, despite the remarkable clinical results, the percentage of non-responders is still between 25 and 35%.^1,2 Non-responsiveness can be attributed to absence of LV dyssynchrony despite presence of the prevailing selection criteria or extensive scar tissue, especially in the posterolateral area of the left ventricle.³ Apart from anatomical limitations in positioning the LV lead close to the preferred posterolateral area, complications such as lead dislocation, failure to capture, and phrenic nerve stimulation may occur.¹ To obtain the full benefit from CRT the atrioventricular (AV) and V-V stimulation intervals should be optimised.^4,5 In this paper we will demonstrate the importance of optimisation of the devices by echocardiography or by invasive measurement of LVdP/dt_max to maximise CRT benefits.

Echocardiography

Dyssynchrony: visual LV motion characteristics

Increasing evidence suggests that mechanical dyssynchrony determined by echocardiography is superior to QRS duration in predicting response to CRT.^6-8 However, recently, preliminary data from the multi-centre PROSPECT study shed doubt on the predictive value of echocardiographic indices and lack of inter-observer agreement.⁹ Indeed, the heterogeneity of the pattern of ventricular activation in patients with heart failure and V-V conduction delay demands investigation of multiple LV segments to increase the accuracy of predicting response to CRT.^7,8 However, V-V dyssynchrony obtained by different echocardiographic techniques usually requires specialised equipment and expertise. Unfortunately, at the moment, no ideal approach exists.

In this respect, the simplicity of the visual echocardiographic assessment of LV dyssynchrony seems promising. Left bundle branch block can produce a multiphasic septal movement and a septal to lateral apical systolic LV motion also described as the ‘shuffle’. Recently, in a study involving five cardiologists from different institutions observation of one or both LV motion characteristics could predict LV reverse remodelling after CRT with a sensitivity and specificity of 87 to 92% and 69 to 81%, respectively. The observations were highly reproducible between different observers.¹⁰

Lead position

Several echocardiography studies have suggested the significance of identification of the LV site of latest mechanical activation. Concordance of LV lead placement with the site of latest activation by tissue Doppler was associated with a more favourable response to CRT.¹¹ The influence of pacing at the site of left ventricle scar tissue on the response to CRT is equivocal. Bleeker et al. showed an influence on CRT response of the posterolateral scar that was not related to the presence of LV dyssynchrony.³ However, we demonstrated that in patients with an optimised V-V pacing interval and LV dyssynchrony investigated in six LV segments instead of only two, the latter predicts response to CRT better than the presence of posterolateral scar.¹² Optimisation of the paced V-V interval is necessary to obtain maximal haemodynamic benefit from CRT. Further, the mean optimal V-V pacing interval (LV first) was greater in the patients with posterolateral and remote scar than in patients with no scar (49±28 ms, 52±22 ms and 36±30 ms, respectively). There was no significant difference in optimal V-V interval for patients with scar tissue in the posterolateral region as compared with remote scar (p=0.88). The total group with scar tissue, posterolateral and remote, had a significantly longer optimal V-V interval than the patients without scar tissue (p=0.05). This reflects the need to correct for the slower myocardial conduction velocity in patients with ischaemic cardio-myopathy. Therefore, presence of scar tissue in the posterolateral area does not preclude a positive effect on LV remodelling after CRT, provided significant LV dyssynchrony is present and the V-V pacing interval is optimalised.

Optimisation of the pacing intervals

Optimisation of the AV and V-V intervals plays an important role in obtaining the maximal CRT benefit. When the velocity-time integral of the transmitral flow is used, there is a very good correlation for AV interval optimisation between invasive LVdP/dt_max and Doppler echocardiography.⁴ Other methods, including E-A duration and Ritter's formula, yielded sub-optimal results. The velocity-time interval of the aortic flow is less clearly defined or less easily obtained than the transmitral flow and therefore optimisation of the paced V-V interval is less accurate.

Optimisation by invasive measurement of LVdP/dt_max

LVdP/dt_max is not only a measure of contractility but also dependent on preload and LV synchrony and therefore very suitable for optimisation of CRT post-implant. For this purpose a 0.014' hi-fidelity pressure wire (RADI Medical, Uppsala, Sweden) is introduced into the left ventricle via the femoral artery and a 4 French multipurpose catheter. It is important to maintain a constant heart rate as LVdP/dt_max is influenced by heart rate through the force-frequency response. Therefore, after determination of the baseline LVdP/dt_max, the atrium is paced at a rate 5 to 10 beats above the intrinsic rate during the whole protocol which includes RV, LVand biventricular (BiV) pacing. The following parameters are investigated: the paced atrioventricular interval (PAV), the sensed atrio-ventricular interval (SAV) and the V-V interval. Four different AV intervals are assessed. Once the optimal AV interval is determined, the optimal V-V interval is determined in BiV pacing in steps of 20 ms from +80 ms (LV first) to -80 ms (RV first).⁵

Simultaneous BiV pacing increases LVdP/dt_max in patients in sinus rhythm (SR) and atrial fibrillation (AF) by 20.9 and 16.9%, respectively. Optimising the V-V interval increased LVdP/dt_max to 26.2% for patients in SR and 21.4% for patients in AF. This indicates that the contribution of V-V optimisation is similar for AF as for SR. Of note, the average V-V interval for patients in AF was +36 ms and for patients in SR +41 ms, which was not statistically different (figure 1). In the majority of patients (81.5%), the highest LVdP/dt_max was achieved with LV pacing preceding RV pacing. Simultaneous BiV pacing was the best in 12% and RV pacing first in 6.5%.

Figure 1.

Diagram showing the percentage increase in LVdP/dt_max from left ventricular, biventricular simultaneous and optimised biventricular pacing in patients in atrial fibrillation (AF) and sinus rhythm (SR). The relative increase in LVdP/dt_max by optimising the V-V interval is 26.6% for patients in AF and 25.3% in SR.

Investigating LVdP/dt_max with different heart rates can demonstrate a negative force-frequency response in some patients at still physiological heart rates. This can be of use in programming the upper rate in pacing-dependent patients.¹³

We further demonstrated that QRS morphology could be useful in CRT. After optimising the paced AV interval, adjusting the sensed AV interval until an identical QRS morphology was obtained coincided with the optimal sensed LVdP/dt_max. This may open perspectives for algorithms to adapt the AV interval during exercise (figure 2).¹⁴

Figure 2.

Example of a 12-lead ECG that shows the QRS morphology at the optimal paced AV (PAV) interval of 150 ms. At a sensed AV (SAV) interval of 110 ms there is an identical QRS morphology, which differs from the morphology at a SAV interval of 130 ms and 90 ms, respectively. The corresponding values of LVdP/dt_max are mentioned.

LVdP/dt_max may become a useful tool in the determination of optimal pacing sites during implant. It is relatively easy to implement, can be continuously monitored on line and the results are unequivocal. However, optimisation of CRT is still limited to optimisation at rest and there are no devices able to control for continuous optimisation under changing physical conditions in daily life. Also the effect of reverse remodelling on optimal pacing parameters is unknown, although it can be anticipated that changing ventricular dimensions due to reverse remodelling will at least affect optimal V-V timing. A sensor-controlled closed loop system adapting optimal settings for changing acute and chronic conditions will be the challenge for the future.¹⁵

Left ventricular or biventricular pacing?

In patients in sinus rhythm with left ventricular dys-synchrony, LV pacing alone is superior to BiV pacing. Generally, the optimal LVdP/dt_max is obtained at longer AV intervals where intrinsic conduction over the right bundle is still present. This shows that intrinsic conduction over the right bundle is haemodynamically superior to right ventricular pacing in this category of patients. In contrast to patients with AF, who are stimulated above the intrinsic heart rate to assure capture, or patients with complete AV block, BiV pacing is superior to LV pacing alone as no contribution of right bundle branch conduction is present.¹⁶

Conclusion

Currently, there is no ideal approach for selecting patients for CRT and to optimise CRT after device implantation. Because imaging techniques to quantify V-V dyssynchrony require training and expertise, the shuffle motion of the left ventricle based on multiphasic septal motion or the septal to lateral apical LV motion looks simple and promising.

Acute haemodynamic measurements of LVdP/dt_max have shown that AV and V-V optimisation contribute strongly to the effect of CRT. The development of CRT devices with an automated continuous optimisation of the pacing intervals is a great challenge to improve the cost-effectiveness of this electrotherapy.