Heart Failure Study of Multi-site Pacing Effects on Ventriculoarterial Coupling

Given that the main function of the cardiovascular system is to provide sufficient blood supply to tissues in order to ensure their normal and effective function, combined with the most efficient possible use of energy produced by ATP degradation, there has been a keen interest in elucidating the interplay between heart and vessels, critically affecting both.

In order to achieve these goals, it is thought that in healthy humans the cardiovascular system as a unity operates at a unique combination of parameters (arterial elastance, heart rate and left ventricular end systolic elastance) so as to:

1. Maximize stroke work (SW) for a given left ventricular contractility. This is related to the fact that adequate tissue perfusion is dependent both on stroke volume and on pressure and in fluid dynamics W=∆P×∆V (thus maximizing SW leads to optimal perfusion), OR
2. Optimize energy efficiency of the heart, in terms of energy transferred to the arterial bed to total mechanical energy.

Ventriculoarterial coupling (VAC) is a composite parameter, defined as the ratio of arterial elastance (Ea) to end systolic left ventricular elastance (Ees). Thus: VAC=Ea/Ees . It is a fundamental property of the cardiovascular system, integrating and assessing the interaction of all individual parameters of the ventricle (pump) and the arterial tree (afterload). Furthermore, VAC may assess both whether SW produced is maximal for a given contractility of the left ventricle (condition for maximization: VAC=1) and whether mechanical efficiency of the ventricle is optimal (optimization condition: VAC=0.5-0.7). Consequently, simultaneous optimization is not possible, and the cardiovascular system operates either at maximal output (as in healthy individuals at rest) or at optimal efficiency (healthy individuals at exercise). Multi-site pacing (MSP) of the left ventricle is a recently introduced technique with excellent studies' findings concerning echocardiographic parameters of ventricular function. Recently, the MultiPoint Pacing (MPP) IDE study showed that a specific choice of electrical dipole for the first left ventricular pulse and a close to simultaneous application of the two left ventricular pulses achieves a very high percent of clinical response (87%), with excellent patient safety. Subsequent studies confirmed these findings, reporting even higher NYHA response rates (95% vs 78% for conventional cardiac resynchronization therapy - CRT).

The underlying rationale lies in the better approximation of the normal sequence of left ventricular activation, through use of two, instead of a single, pulses. According to trial results, one can achieve, compared to conventional CRT, improved coordination between left ventricular segments, improved cardiac output and, possibly, tissue perfusion, and potentially reduction of arrhythmia propensity (mechanism similar to that of CRT). Thus, it would be interesting to study whether these can be independently confirmed by changes in VAC values. In heart failure, VAC values increase considerably due to increases in Ea as a result of the feedback loop regarding pressure (but not volume) maintenance. As a consequence, any reduction would move them closed to both 1 and the 0.5-0.7 area, yielding improvement in both SW maximization and efficiency optimization.

However, there are objective difficulties in achieving lege artis MSP (according to MPP-IDE study standards) given that two prerequisites must be met: 1. Interpolar distance for the first left ventricular pulse >30mm (i.e. non-sequential poles used), 2. Nearly simultaneous (Δt=5msec) left ventricular pulses and 3. Threshold of ≤3.5V@0.5msec.

Moreover, the first pulse should, ideally, be directed to the most delayed, compared to the normal activation sequence, viable myocardial segment, a feat not always possible due to electrode placing constraints. Obviously, presence of scar could alter the course and shape of the activation front and thus diminish its effects (similar to issues already discussed in the case of CRT).

Objective:

To perform a comparative study of multi-site left ventricular pacing and cardiac resynchronization therapy effects on ventriculoarterial coupling and energy efficiency of the failing heart

Hypothesis:

VAC values are improved (shift closer to unity/0.5-0.7 area) and work/efficiency increase with patients on MSP as compared to CRT pacing.