Chronotropic Incompetence

The term chronotropic incompetence (CI) describes an insufficient HR relative to the metabolic needs of the organism, during exercise or under stress caused by emotional disturbance, pain, and so on. The definition of CI has not been standardized. It has been defined as the inability to reach, during an exercise test, a maximal HR more than 75% to 80% of the theoretical maximal HR calculated by Astrand’s formula (220 – Age). Others consider that the absolute peak HR during exercise must be more than 100 or 120 beats/min.³ Wilkoff determined the HR response to exercise in a mathematical model, which includes age, resting HR, intensity of exercise, and functional capacity (FC) in the equation:

In contrast to others, this method is not limited to a single value of HR at peak exercise and takes the activity of the patient into consideration. It does, however, require the performance of a cardiorespiratory exercise test with measurements of expired gases during maximal exercise up to the anaerobic threshold to avoid underestimating CI. Because of the limited relevance of definitions based purely on statistics, a functional definition is usually adopted in clinical practice; this definition includes determining whether CI is symptomatic and whether it limits exercise capacity.

The incidence of CI varies with the definition applied, though it may reach 60% among permanently paced patients. Its origin is atrial or ventricular. Sinus node dysfunction (SND) is the most frequent cause of atrial CI, observed in 25% to 40% of cases, and the incidence increases with age.⁴ A few patients presenting with permanent atrial fibrillation maintain a normal chronotropic function during exercise. However, they have inappropriate tachycardia, bradycardia, or both in alternans. The severity of CI in patients presenting with high-degree AV block increases with age and with the increasingly distal location of a block along the His-Purkinje system. Rarely dissociated from disorders of impulse formation or propagation, CI may be associated with autonomic dysfunction, as well as with myocardial ischemia.⁵ Further investigation is warranted if myocardial ischemia is suggested by clinical presentation, particularly since its incidence is threefold higher among patients with coronary artery disease.

CI can be effectively managed using one of two main pacing modes: (1) In the presence of AV block without associated SND, the P-wave–synchronous VDD or DDD modes allow the synchronization of ventricular contraction with atrial systole with a programmable AV delay. The maximum tracking rate must be adapted to the patient’s characteristics, including habitual physical activities, age, and underlying cardiac status. In order to prevent the development of pseudo-Wenckebach periodicity or 2 : 1 AV block during exercise, the upper tracking rate must not exceed the total atrial refractory period (TARP), which is postventricular atrial refractory period (PVARP) plus AV delay. Most pacemakers allow fixed programming of these intervals or, using automatic adaptive algorithms, their variation in response to HR. The AV delay can also be modulated beat-by-beat in response to the preceding cycle. Adaptation of the AV delay is often preferred to modulate TARP, as a shortening of the PVARP gives rise to the risk of triggering pacemaker-mediated tachycardia (PMT) during exercise. State-of-the-art algorithms effectively prevent the onset of PMT. (2) Sensor-driven pacing allows the adaptation of HR to exercise in the atrium (AAIR), the ventricle (VVIR), or both chambers (DDDR, DDIR). Several sensors have been tested; however, a detailed description of each is beyond the scope of this chapter. Currently, the most frequently used sensors are accelerometers and motion sensors, minute ventilation sensors (which track variations in thoracic impedance), and QT interval sensors. Minute ventilation is less sensitive than motion sensing, though its performance is higher during sustained physical exercise. Some devices have combined these sensors. Much work is in progress to develop more physiological and automatically adaptive (closed-loop) sensors. Verification of the programming of the sensor adapted to the patient’s activity—by analysis of the stored histograms or by a 24-hour ambulatory electrocardiogram (ECG) or exercise test, if necessary—is important.

Hyperchronotropism

Excessively rapid atrial or ventricular pacing may be a source of LV dysfunction. In animal models, long-term, rapid ventricular pacing has been shown to cause a more rapid and severe deterioration of LV function than does atrial pacing. Therefore, all causes of excessively rapid permanent pacing must be identified and corrected to eliminate the risk of induced ventricular dysfunction. These causes include PMT, adverse effects of preventive algorithms against atrial arrhythmias, ventricular response to atrial tachycardias, sensing anomalies, poorly programmed sensors and, rarely, dysfunction of electronic internal circuits (runaway pacemaker). These complications are prevented or detected during programming or interrogation of the pulse generator. A proper programming of the PVARP at rest and during exercise and its extension after ventricular extrasystoles prevent the onset of PMT. If these measures fail, algorithms of PMT termination by atrial pacing or extension of the PVARP are helpful. Finally, all pacemaker models allow programming of mode switch at a selected atrial rate to prevent the tracking of supraventricular tachycardias by the ventricles.

Lower Ventricular Pacing Rate

In the early days of cardiac pacing, Sowton et al studied the optimal lowest pacing rate by measuring CO and left and right filling pressures in patients presenting with complete AV block.⁶ The highest CO and lowest filling pressures were associated with pacing rates between 55 and 90 beats/min and a mean of 71 beats/min. CO/ventricular pacing rate curves showed roughly two distinct profiles. Flat curves (Figure 35-3, left) were most often associated with normal myocardial contractility and a stable CO as HR increased. Peaking curves (see Figure 35-3, right) were often observed in the presence of LV dysfunction, showing greater variations in CO with changes in HR. At the fastest HR, CO levels fell, reflecting the shortened diastolic filling time and alteration in LV compliance.

Figure 35-3 Left, Flat curve. Right, Peaked curve.

(From Sowton E: Haemodynamic studies in patients with artificial pacemakers, Br Heart J 26;737–746, 1964.)

In clinical practice, the lowest pacing rate is often set between 50 and 70 beats/min, as observed on average in healthy individuals at rest. At less than 50 beats/min, CO decreases proportionally with HR, which must be avoided in the presence of HF. In patients with coronary artery disease or ventricular hypertrophy and diastolic dysfunction, excessively rapid pacing decreases coronary perfusion and ventricular filling. Furthermore, excessively rapid pacing shortens the life of the pulse generator.

Maximal Ventricular Pacing Rate

The upper ventricular pacing rate, whether atrial tracking driven or sensor driven, must also be tailored on the basis of the patient’s habitual activities and underlying cardiovascular status. An excessively slow upper pacing rate causes exercise-induced chronotropic insufficiency, and an excessively rapid pacing rate may be deleterious. Kindermann et al ascertained the theoretical, optimal, maximal pacing rate corresponding to the increase in maximum VO₂ (oxygen rate) measured during cardiorespiratory exercise testing in patients with a normal or less than 45% LV ejection fraction (EF), the majority of whom were paced in DDD mode.⁷ The mean optimal pacing rate was 86% of the theoretical maximal HR in patients with a normal LVEF, and 75% in patients with a depressed LVEF. It is noteworthy that programming of the upper pacing rate was excessively high in the majority of patients. Furthermore, in most patients, maximal VO₂ rapidly reached a plateau during exercise testing, regardless of systolic LV function. According to Fick’s principle, a VO₂ that remains stable despite an increase in HR (in presence of a stable arteriovenous O₂ difference) indicates a decrease in SV.

A decrease in CO along with an excessively rapid HR is associated with three main mechanisms: (1) development of myocardial ischemia, (2) decrease in LV diastolic filling, and (3) unfavorable force/HR ratio. The complex interaction of these mechanisms explains why one cannot predict the optimal ventricular pacing rate from measurements of baseline LVEF only. Likewise, the optimal pacing rate during exercise calculated as a percentage of the theoretical maximal HR must be interpreted cautiously. Under some conditions, including ongoing myocardial ischemia, arrhythmias, and so on, the optimal maximal HR estimated on the basis of the maximal CO may not be optimal for individual patients.

Heart Rate and Cardiac Resynchronization Therapy

The long-term effects of atrial pacing at a rate faster than the sinus rate in recipients of cardiac resynchronization therapy (CRT) devices programmed in DDD/DDDR mode are only indirectly understood. First, continuous atrial pacing might increase the inter-atrial conduction delay and accentuate the left heart AV dyssynchrony (see Atrial Conduction Delay). In addition, several studies have found a link between increased mortality and long-term elevation of HR in unpaced patients with or without HF. Finally, a slower HR may promote angiogenesis. For the time being, and pending additional information, the recommendation is to keep the backup atrial pacing rate below the sinus rate, except in the presence of chronotropic insufficiency.

Prevention and Management of Atrial Conduction Delay

In patients with long inter-atrial conduction times, different technical solutions may help prevent pacing-induced AV dyssynchrony in the left heart. This applies mainly to patients presenting with permanent, complete AV block or to those patients who need ventricular stimulation for hemodynamic indications such as hypertrophic obstructive cardiomyopathy. These patients may benefit from one of the following two choices:

Figure 35-5 Adverse hemodynamic consequences of major intra-atrial conduction delay in a patient permanently paced in the DDD mode for bradycardia. A standard AV delay of 150 ms results in a short filling time and single pulse mitral flow (left panel). Increasing the AV delay to 250 ms restores normal AV synchrony (right panel).

(From Daubert JC, Pavin D, Jauvert G, Mabo P: Intra- and interatrial conduction delay: Implications for cardiac pacing, Pacing Clin Electrophysiol 27:507–525, 2004.)

Figure 35-6 Instantaneous hemodynamic changes induced by bi-atrial synchronous DDD pacing versus standard DDD pacing in a patient with long inter-atrial conduction time. Left, Switch from standard to bi-atrial pacing instantaneously corrects the baseline atrioventricular dyssynchrony in the left heart. Right, Switch from biatrial to standard DDD causes a prominent decrease in aortic velocity-time integral.

(From Daubert JC, Pavin D, Jauvert G, Mabo P: Intra- and interatrial conduction delay: Implications for cardiac pacing, Pacing Clin Electrophysiol 27:507–525, 2004.)

It is generally possible to increase the programmed AV delay at the cost of a long TARP and a decrease in the maximal atrial tracking rate during exercise. Depending on the position of the lead and the distribution of intra-atrial morphologic abnormalities, atrial pacing might lengthen or shorten atrial conduction time, with a high interindividual variability. A septal implantation of the atrial lead often allows the shortening of conduction delays. If an atrial lead has already been implanted in the appendage, an alternative dual right atrial pacing, or bi-atrial stimulation, using a second lead placed at the coronary sinus ostium or within the coronary sinus, can be considered. One must also pay attention to the prolongation of the AV delay, which, during CRT, might compromise resynchronization by promoting spontaneous AV conduction.

Late Atrial Sensing and Cardiac Resynchronization Therapy

In the presence of major intra-atrial conduction delay between the sinus node and the atrial pacing site, atrial sensing is delayed. The interval between atrial sensing and ventricular sensing is foreshortened, with a risk of inhibited biventricular pacing or fusion beats. Repositioning the atrial lead or modulating or ablating the AV node may be necessary.

The clinical effects of fused spontaneous and paced QRS in recipients of CRT systems remain uncertain. Indirect arguments suggest that fusion complexes are not necessarily adverse.¹¹ In limited studies, at least a similar hemodynamic benefit was observed in patients at rest in whom resynchronization was achieved by LV stimulation alone, with fusion via the right bundle branch, or by biventricular stimulation.¹² Furthermore, the absence of first-degree AV block predicts a response to CRT. Either the presence of AV block is a prognostic factor associated with more severe heart disease or its absence is associated with a higher likelihood of fusion or “concealed resynchronization.”¹³ Nevertheless, pending further studies, the current recommendation is to avoid or limit biventricular simulation with fusion to the extent possible.

Atrioventricular Synchrony During Exercise

During exercise, sympathetic activity facilitates AV nodal conduction, and a shortening of AV delay that is inversely proportional to the HR is observed. Implantable pacemakers are able to reproduce this phenomenon in patients with AV block.¹⁴ The rate-adaptive AV delay shortens AV delay, usually linearly with acceleration of the HR, up to the shortest programmable value.¹⁵ This offers several benefits: (1) improvements in hemodynamic function and cardiopulmonary performance while preserving proper AV synchrony during exercise¹⁶; (2) ability to increase the maximal synchronous HR during exercise by shortening TARP; and (3) subjective improvement in the quality of life by the adaptation of the AV delay during exercise.¹⁷

Conflicting data have been reported regarding the programming of hemodynamically optimal AV delays in recipients of CRT systems during effort, probably reflecting heterogeneous patient characteristics, including degree and type of dyssynchrony, lead positions, and underlying heart disease.¹⁸ The current recommendation is to deactivate the rate-adaptive AV delay in the absence of AV conduction disorder.

Ventricular Conduction Delay and Atrioventricular Synchrony

An additional delay is inserted between left atrial and LV activation in cases of marked slowing of intraventricular or VV conduction with left bundle branch block morphology, most often observed in the context of advanced heart disease. Despite the absence of PR interval abnormality of surface ECG (Figure 35-7), unequivocal left AV mechanical dyssynchrony is present on ultrasound Doppler examination (Figure 35-8). Although conventional DDD pacing with a short AV delay can correct LV filling (transmitral Doppler), it should not be programmed in patients with HF because of the potential adverse effects of RV pacing. Moreover, this pacing increases only left heart filling, whereas biventricular stimulation restores AV synchrony on both sides of the heart (see Figure 35-17) as well as intraventricular synchrony and improves clinical outcomes.

Figure 35-7 Intracardiac recordings from four permanent leads at time of device implant. The P-R interval is normal on surface electrocardiogram (ECG). However, the intracardiac ECGs show marked VV conduction delay (140 ms) resulting in major left atrioventricular dyssynchrony (LA – LV = 240 ms). RA, Right atrium; LA, left atrium (distal coronary sinus); RV, right ventricle; LV, left ventricle (posterolateral vein); IEGM, intracardiac electrogram.

Figure 35-8 Effect of left bundle branch block (LBBB) on AV synchrony. Left ventricular outflow tract (orange triangles) and mitral Doppler (blue triangle, E wave; white triangle, A wave) are shown during the cardiac cycle. LBBB is responsible for an increased systolic and decreased diastolic interval (see also Figure 35-15) with fusion of A and E waves. The P-R interval is unchanged.

(Modified from Cazeau S, Gras D, Lazarus A, et al: Multisite stimulation for correction of cardiac asynchrony, Heart 84:579–581, 2000.)