Myocardial Viability

Presence of myocardial viability is another important predictor of response to CRT and has not been well evaluated. Limited studies have shown that detection of a significant amount of myocardial scar despite the presence of mechanical asynchrony predicts lack of response to cardiac resynchronization.²³

Pacemaker Programming

Atrioventricular and Interventricular Delays

Another important parameter that is often overlooked is whether or not the biventricular pacemaker is appropriately programmed.²⁴ Optimal atrioventricular (AV) delay was determined by earlier studies from diastolic filling time of mitral inflow. Nominal settings for pacemaker devices include typically short AV delays of 100–120ms. These data come from good biventricular capture at short AV delays, and also show that echo-derived diastolic mitral inflow filling time is the longest at short AV delays. However, short AV delays often lead to premature mitral valve closure. This reduces forward atrial contribution in late diastole and leads to pulmonary vein atrial flow reversal and, in turn, increased pulmonary venous pressure. Thus, longest diastolic mitral inflow filling time is not necessarily associated with best cardiac output. In the author’s experience, patients have needed AV delays between 30ms and 290ms. Therefore, programming of AV delay needs to be performed on an individual basis.

Despite the availability of interventricular or sequential ventricular programming capability, the devices are often left in simultaneous pacing mode following implantation. While studies have shown that the majority of patients need LV pre-excitation for better cardiac output, at least one-third of patients have better hemodynamics with simultaneous LV and right ventricular (RV) pacing or even RV pre-excitation.²⁵ Unless tested, optimal interventricular timing in a patient cannot be predicted based on ECG.

Atrial Pacing versus Sensing

Some patients who might be better off with atrial sensing are often inappropriately atrially paced at relatively higher heart rates such as 70bpm. Programming a lower back-up atrial pacing rate down to, for example, 50bpm often allows intrinsic atrial rhythm and heart rate variability during exercise.

Pacemaker Response to Exercise

Although advantage is often taken of the capability of current generation pacemakers to increase heart rate in response to exercise in chronotropically incompetent patients, it is not uncommon that patients continue to have markedly limited heart rate variability and hence get symptomatic after minimal exercise. Except in truly sedentary patients, this often results from lack of device sensitivity to detect mechanical activity. In some patients referred for optimization who are chronotropically incompetent or atrially paced, exercise-induced increase in heart rate function is turned ‘off.’ Sometimes slope of activation timing depending on lower rate limit may delay increase in heart rate upon commencement of exercise and hence results in inappropriate early quitting of exercise. Simple adjustment of pacemaker sensitivity and/or slope may overcome this problem. Change in the exercise-induced change in AV delay is another area where little investigation has been carried out. Currently, all devices allow decrease in AV delay with increases in heart rate, however the magnitude of AV delay change for a given increase in heart rate is too little, hence the pacemaker algorithm of AV shortening in the current generation pacemakers may not be appropriate for all patients.

Sleep Apnea

Another ignored factor that leads to lack of response to CRT or worsening of symptoms after initial response is the presence of sleep apnea in a significant number of CHF patients post-CRT. It is known that sleep apnea leads to worsening of heart failure. Our evaluation has suggested potential mechanisms of worsening of heart failure symptoms with sleep apnea. These include marked tachycardia compromising diastolic filling, worsening of mitral regurgitation and exaggerated ventricular interdependence during the hyperpneic phase of the sleep apnea cycle,²⁶ and ventricular ectopy during the bradypneac phase.

Experience at the Author’s Institution

At the author’s center, potential patients for CRT are evaluated for the presence of mechanical dyssynchrony irrespective of presence of electrical asynchrony by means of tissue Doppler imaging echocardiography and twodimensional strain imaging by speckle tracking. All published criteria that have evaluated mechanical dyssynchrony are used. There is often a lack of concordance between different parameters in the majority of patients except those with the most severe mechanical dyssynchrony. An algorithm has therefore been developed to report dyssynchrony based on the author’s experience in evaluating over 600 tissue Doppler studies (see Table 1). Mechanical dyssynchrony is reported as present if there are three major, two major and two intermediate; one major and three intermediate; four intermediate, two intermediate and two minor; or one intermediate and three minor positive criteria.