And Resynchronization Therapy

Because of the potential detrimental effects of ventricular pacing on hemodynamics, alternative methods to ensure more physiological pacing are important, particularly in the pres ence of severe left ventricular dysfunction. Components of such physiological pacing include: (1) appropriate chronotropic response (rate responsive pacing); (2) preservation of atrial function (atrioventricular sequential pacing); (3) maintenance of optimal atrioventricular synchrony (atrioventricular delay); and (4) maintenance of normal ventricular activation sequences (His pacing or biventricular pacing).

Like controlling heart rate as a means to improve cardiac output, modulating atrioventricular synchrony is also important for more normal hemodynamics response. For example, loss of atrial contraction may reduce cardiac output by up to one-third (15 to 30%). Furthermore, the spatiotemporal distribution of contraction is considered to affect ventricular function significantly (7).

The importance of synchronized ventricular activation (and contraction) as manifested by a narrow QRS complex has been demonstrated by Schwaab and colleagues (8). In this acute study in 14 patients with third-degree atrioventricular block, the atrioventricular delay was individually optimized. Right ventricular pacing with decreased QRS duration obtained by alternate pacing sites on the septum was found to be correlated significantly with homogenization of left ventricular contraction and with increased systolic function.

Figure 1 shows the maximal dp/dt during high right atrial, single ventricular, and biventricular pacing in normal dogs (5). In particular, these data indicated that ventricular pacing, particularly right ventricular apical pacing, is associated with reduced maximal dp/dt (an index of cardiac contractility). The importance of maintaining atrioventricular synchrony and normal ventricular activation sequences is further presented in Fig. 2. Figure 2 shows the relative cardiac outputs associated with differant pacing modes during exercise in patients with sinus node dysfunction and normal atrioventricular node function without bundle branch block (9). AAI pacing represents a pacing protocol associated with normal ventricular activation sequence and atrioventricular conduction. DDD pacing maintains atrioventricular synchrony, but is associated with disturbed ventricular activation sequence. VVI pacing has neither normal ventricular activation sequence nor atrioventricular synchrony. In general, cardiac output was significantly lower during VVI pacing compared with AAI and DDD pacing. Interestingly, at rest and during the initial phase of exercise with a lower workload, there was no significant difference in cardiac output between DDD and AAI pacing. However, AAI pacing was significantly better in maintaining the required performance as the exercise duration increased. Proposed mechanisms for the adverse effects of right ventricular pacing include: (1) paradoxical septal motions; (2) altered ventricular activation sequences; (3) impaired mitral or tricuspid apparatus functions; (4) altered diastolic function; (5) diminished diastolic filling times; and (6) increased serum catecholamine concentrations.

Conduction delays in the atrioventricular node or in the ventricles associated with dilated cardiomyopathy are considered to contribute to left ventricular dysfunction by impairing atrioventricular synchrony, uniformity of ventricular contraction, or relaxation of the left ventricle. It is noteworthy that approx 30% of patients with severe congestive heart failure have intraven-tricular conduction disturbances, characterized electrically by a widened QRS complex and mechanically by discoordination of ventricular contraction and relaxation patterns (10). A widened QRS duration has been associated with increased mortality in patients with congestive heart failure.

Subsequently, it has been estimated that 10-20% of a generalized heart failure population may be eligible for biven-tricular pacing (11,12). Again, ventricular dyssynchrony is associated with abnormal motion of the interventricular septum, reduced dp/dt, reduced diastolic filling time, and prolonged mitral regurgitation duration.

The two primary therapeutic mechanisms underlying resyn-chronization therapy via biventricular pacing are (1) improvement in coordinated contraction and (2) atrioventricular optimization (Table 1). Increased left ventricular filling time, decreased septal dyskinesis, and reduced mitral regurgitation are also considered beneficial in biventricular pacing for the congestive heart failure patient.

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