First derivate of left ventricular pressure pulse
The ultimate way to determine contractile properties is measuring the force that is generated by a muscle; however, it not possible to measure this in clinical practice. As an alternative, the rate of left ventricular pressure change (LV dP/dt) has been proposed [
59,
60]. Pressure is defined as force per unit area and is thus related to wall force. The rate of pressure development is influenced by the contractile properties of the LV. Changes in contractility alter the slope of the pressure curve resulting in an increased or decreased peak rise in intraventricular pressure (d
P/d
t
max) during isovolumetric contraction [
61]. However, LV d
P/d
t is a complex function that is not only dependent on contractility, but also dependent on preload, afterload and heart rate [
62,
63]. However, within physiological limits, LV d
P/d
t
max shows mainly dependence on contractility and preload [
64]. This properties make LV d
P/d
t
max a useful instrument to evaluate the effect of both AV and VV delays on myocardial performance.
LV d
P/d
t is optimally derived from a left ventricular pressure curve obtained by a micromanometer that is introduced endovascular into the LV [
65]. We have previously described an alternative method using a 0.014 high-fidelity pressure wire (Radiwire, St. Jude Medical Inc., St. Paul, MN, USA) introduced either retrogradely or transseptally into the LV [
40]. In order to adequately determine the effect of different pacing settings on LV d
P/d
t
max, different protocols have been described [
65,
66].
In order to overcome the influence of heart rate on LV dP/dt, the atrium is paced at 5–10 beats above the intrinsic rate. In patients with atrial fibrillation, ventricular stimulation is performed above the intrinsic rate to ensure continuous capture. First, a baseline LV dP/dt
max is measured and averaged out over several heart beats or seconds, excluding premature and post-extrasystolic beats from analysis. After baseline measurement, AV optimization is performed first during simultaneous biventricular pacing. The optimal AV delay with the highest LV dP/dt
max is selected to perform the subsequent VV optimization. The optimization procedure should proceed under stable conditions to minimize any influence on LV dP/dt measurement.
This method has the advantage that it is easily implemented, even during the implantation procedure. Interpretation is not dependent on operator skills or technical limitations as with echocardiography. Also, it allows the evaluation of multiple pacing sites in a short time frame. Due to these characteristics, it is a suitable method to evaluate the acute hemodynamic effect of different pacing sites, either epicardially or even endocardially as has been demonstrated in a recent case report [
67]. As an example, we implanted a left endocardial lead in a patient who showed no clinical or echocardiographic response to standard CRT. The definite LV pacing site was determined with optimal LV d
P/d
t
max during a temporary pacing study of different endocardial sites. At long-term follow-up, there were both clinical and echocardiographic improvements.
A disadvantage of the LV dP/dt
max optimization method is its invasive nature. However, as only a 4-French guiding is needed, no more complications than with standard angiography are to be expected. Nevertheless, in our opinion, the advantages of this invasive technique outweigh the relatively low risk. Alternatively, the pressure wire can be introduced via the radial artery or even via transseptal puncture.
The use of continuous wave Doppler imaging of the mitral regurgitation signal is advocated as a non-invasive alternative to determine LV d
P/d
t
max [
68]. Importantly, this method does not measure the true
maximal LV d
P/d
t, but an averaged slope of the left ventricular pressure curve between 4 mmHg and 36 mmHg. This measure has not been validated in an experimental physiological set-up, as has been in case of invasively measured LV d
P/d
t
max [
61,
63,
64]. Further, it requires the presence of a detectable mitral regurgitation signal which is not always present [
69], has a lower temporal resolution than the invasive method and is more laborious to average over multiple heart beats.
Both PATH-CHF and PATH-CHF II trials used invasive LV d
P/d
t
max to optimize the AV delay [
30,
65]. So far, there are no randomized controlled trials evaluating the long-term outcome of CRT optimization by LV d
P/d
t
max.
Pressure–volume loops
LV pressure–volume loops can be used to calculate stroke work defined as the integrated area within the pressure–volume loop (in mmHg mL). This index is mainly dependent on contractility and preload with little effect of changes in afterload [
64].
To acquire pressure–volume curves, a 6-French or 7-French pressure-conductance catheter is inserted in the LV via the femoral artery. The signals are digitized and transformed to pressure–volume loops by dedicated software [
64,
70].
Except for its invasiveness, there are other disadvantages to the use of pressure–volume loops. The relatively inaccurate measurement of LV volume in dilated hearts combined with a low signal-to-noise ratio make it difficult to acquire a reliable signal in heart failure patients [
71]. Also, the pressure-conductance catheter needs calibrating, has a larger size and is more expensive compared to the micromanometer used for left ventricular pressure measurements [
72].
In contrary to LV d
P/d
t
max measurement, the pressure–volume loop covers both the systolic and the diastolic phases of the cardiac cycle and incorporates both pressure and volume changes. This makes stroke work more sensitive to measure CRT-induced volume changes caused by alteration in mitral regurgitation. Further, the internal flow fraction derived from the conductance signals can be used to quantify LV mechanical dyssynchrony [
73]. In selected cases, this dyssynchrony index could be used to support the indication for resynchronization therapy [
74].
Compared to LV d
P/d
t
max, pressure–volume loops have been used only limited in early cardiac resynchronization studies [
71]. Interestingly, when evaluating the acute hemodynamic response to CRT by both LV d
P/d
t
max and stroke work, both measures do not match in up to 50% of the cases when using a cutoff value of 10% change to define response to CRT [
72]. A sustained long-term hemodynamic response at 6 months has been demonstrated in a small-scale trial [
70].