Hemodynamic Aspects of Cardiac Pacing

Chapter 35 Hemodynamic Aspects of Cardiac Pacing

Since the implantation of the first permanent pacemaker in 1958, the understanding of the hemodynamic principles and consequences of cardiac pacing has steadily progressed. Instead of merely supporting chronotropic function, cardiac stimulation aims at closely emulating normal physiology. The progresses made are attributable to technologic advances and, in particular, to a deeper understanding of cardiovascular physiology during stimulation. In permanently paced patients, the ideal “physiological stimulator” should preserve or restore three main functions: (1) chronotropy, by adapting the pacing rate to the patient’s activity, (2) atrial function and atrioventricular (AV) synchrony, to optimize ventricular filling, and (3) ventricular activation sequence, to optimize the synchrony and performance of ventricular contraction. The adverse consequences of right ventricular (RV) apical stimulation are notorious and justify the avoidance of optional ventricular capture. Cardiac resynchronization plays an important role, particularly in patients presenting with congestive heart failure (HF) and electromechanical dyssynchrony. Therefore, the aims of physiological cardiac pacing are to (1) instantaneously optimize cardiac function according to the patient’s activity status, and (2) preserve atrial and ventricular mechanical and electrical (prevention of arrhythmias) functions in the long term. This chapter reviews hemodynamic principles, which have prompted the development of physiological cardiac stimulation.

Heart Rate: Restoration of Normal Chronotropic Function

Cardiovascular Physiology

Cardiac output (CO) is the product of heart rate (HR) and stroke volume (SV), calculated as the difference between left ventricular (LV) end-diastolic (ED) and end-systolic (ES) volumes. HR is mainly under the influence of the autonomic nervous system and circulating catecholamines. LVED volume depends on the (1) circulating volume, (2) cardiac filling pressures, (3) contributions of atrial systole, and (4) ventricular relaxation, and LVES volume depends on (1) cardiac afterload and (2) ventricular contractility (Figure 35-1). The Frank-Starling law correlates the ventricular filling pressures with ventricular systolic ejection volumes as a function of the LV systolic performance (Figure 35-2).1 The respective contributions of these variables to cardiovascular performance are influenced by age; physical fitness; the presence, type, and severity of underlying heart disease; and the prescription of pharmaceuticals. In healthy individuals, during exercise, up to a 300% increase in CO is mostly contributed by an increase in HR and more modestly to an increase in stroke volume (SV).2 On the one hand, the contribution of the increase in SV is more important in endurance athletes. In the presence of LV systolic dysfunction, on the other hand, the increase in SV during exercise is limited by a reduced contractile reserve, and the increase in CO is even more dependent on variations in HR.

Chronotropic Dysfunction

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.

Optimal Heart Rate

The optimal lowest ventricular pacing rate at rest and the highest ventricular pacing rate during exercise vary among patients as a function of age, physical conditioning, and underlying cardiovascular status.

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.

Preserving Atrial Function and Atrioventricular Synchrony

Atrioventricular Synchrony

A proper AV synchronization is key for the efficacious hemodynamic contribution of atrial systole. Conversely, complete AV dissociation is hemodynamically detrimental. Atrial systole occurring when the mitral valve is closed activates (1) atrial and pulmonary neurohumoral stretch receptors, (2) vagal activity, and (3) the production of atrial natriuretic peptide. These effects may cause a fall in systemic arterial pressure and a variety of manifestations known as pacemaker syndrome when occurring in permanently paced patients. It has been described in approximately 20% of patients paced in the VVI/VVIR mode, whose atrial activity is sinus, though it may occur in any pacing mode in the presence of AV dyssynchronization. AV synchronization is electrical and mechanical, left and right. While electrical and mechanical dyssynchronies usually coexist, their correlation is not systematic (see Atrial Conduction Delay). “Electrical” AV dyssynchrony manifests as an abnormal PR interval or AV dissociation on surface ECG, and “mechanical” AV dyssynchrony is defined as a LV diastolic filling time less than 40% of the cardiac cycle, accompanied by an abnormal transmitral Doppler profile. In the case of cardiac pacing, left AV mechanical synchrony is hemodynamically the most important and is preserved by programming an appropriate AV delay. The main determinants of the AV delay are AV conduction time, intra-atrial and inter-atrial conduction times, and intraventricular and interventricular (VV) conduction times.

Atrial Conduction Delay

The intra-atrial and inter-atrial conduction delays are measured from the onset of the P wave to (1) the para-Hisian atrial ECG (normally 30 to 60 ms), and (2) to the distal coronary sinus atrial ECG (normal 60 to 90 ms), respectively. Prolonged atrial conduction delays may cause left AV dyssynchrony with a foreshortened mechanical AV delay, apparent on mitral Doppler as a short LV filling period and truncated A wave. The main causes of prolonged atrial conduction delays—apparent on surface ECG as a more than 120-ms P-wave duration, notching of the P wave, and a foreshortened segment between the end of the P wave and the onset of QRS (Figure 35-4)—are (1) slowing of intra-atrial conduction due to heart disease, and (2) a latency of paced atrial capture. The latter is responsible for greater conduction delays than is apparent during sinus rhythm and mandates the routine programming of a 30 ms to 40-ms longer paced than sensed AV delay. The latency of atrial capture can be considerably amplified by several factors, including type and location of the pacing lead and its interface with the myocardium, pacing rate, abnormal electrolyte or metabolic status, the effect of medications, and myocardial disease. Heart diseases most often associated with anomalous atrial conduction are valvular (rheumatic mitral disease, in particular), hypertrophic, ischemic, and hypertensive. Programmers allow a choice of separate AV intervals for sensed P waves versus paced P waves in order to offset this phenomenon. While left atrial dilation is often associated with prolonged atrial conduction time, this correlation is low, except in the case of rheumatic mitral valve disease.9

In the majority of patients, prolonged intra-atrial conduction is associated with slowing of AV conduction, probably due to atrial lesions similar to those found in SND; this association is found in 30% of patients. PR prolongation compensates for the delayed atrial conduction and limits its effects on left AV synchrony. In the presence of normal AV conduction and major intra-atrial and inter-atrial conduction delays, left atrial contraction is delayed, sometimes to the point of encountering a closed mitral valve. The main consequences are (1) a decreased LV SV, and (2) the activation of neurohumoral responses due to atrial distension. On the one hand, programming of the AV delay based on surface ECG alone is unlikely to remedy this situation. On the other hand, the echocardiographic transmitral filling pattern enables the optimization of left AV synchrony (see Atrioventricular Optimization Methods).

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:

1. DDD pacing with a paced AV delay up to 250 ms to 300 ms to restore the atrial contribution concealed by shorter AV delays (Figure 35-5). However, this option, which lengthens the TARP and limits exercise capacity by lowering the 2 : 1 Wenckebach point, is acceptable mainly in inactive patients.

2. Bi-atrial synchronous DDD pacing. In addition to its probable antiarrhythmic effect, this pacing mode confers significant hemodynamic benefits in difficult situations, verified during temporary pacing. By preempting left atrial systole by 30 ms to 75 ms, it restores normal left AV synchrony (Figure 35-6) and enables the programming of conventional AV delays. When conventional DDD pacing was compared with DDD bi-atrial pacing by using different AV delays and a fixed pacing rate, DDD bi-atrial pacing was shown to increase CO by a mean of 23% ± 6% and lower pulmonary capillary wedge pressure by a mean of 27% ± 13%. The benefit decreased as the AV delay increased.10

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.

Atrioventricular Optimization in DDD/DDDR Pacing

The purpose of an optimal AV delay is to guarantee (1) the maximal contribution of the atrium to the diastolic LV filling, (2) a long diastolic filling period, (3) a short isovolumetric contraction period, and (4) the maximal SV. Empirical programming is suboptimal because of the wide variability among patients in optimal AV delay, caused by marked interindividual differences in electrical and electromechanical intervals in the atria (intra-atrial and inter-atrial conduction times) and ventricles (VV conduction delay, in particular). In case of an excessively long AV delay, LV contraction occurs well after atrial systole, while the mitral valve is passively semi-closed, causing (1) fusion of E and A waves of the filling transmitral Doppler flow and (2) diastolic mitral regurgitation (Figure 35-9). An excessively short AV delay causes the LV contraction to close the mitral valve before the end of ventricular filling (truncated A wave). AV delay is optimized mostly in recipients of CRT systems, whereas in dual-chamber pacing, it is reserved for the rare patients presenting with symptoms attributed to AV dyssynchrony. Several methods are applicable, depending on the choices and practices of the various centers (Table 35-1). Echocardiography and programming algorithms are most often used because of their wide availability, ease of use, and low cost. Other methods are mostly investigative and will not be discussed in detail in this chapter (see Table 35-1).

Table 35-1 AV Optimization Methods

Methods Description
Optimization of Left Ventricular Filling

Optimization of Left Ventricular Systole



Vopt, Optimal AV delay; AV, AV delay; long QA, interval between Q of the electrocardiogram to end of mitral Doppler A wave with long AV delay; short QA, interval between Q of the electrocardiogram to end of mitral Doppler A wave with short AV delay; VTI, velocity-time integral.

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Aug 12, 2016 | Posted by in CARDIOLOGY | Comments Off on Hemodynamic Aspects of Cardiac Pacing

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