Simonetta Dell’Orto, MD, Paolo Valli,
MD, Enrico Maria Greco, MD
Unità Operativa Cardiologia, Ospedale Uboldo, Azienda Ospedaliera
di Melegnano; Cernusco sul Naviglio, Milano, Italy
Address for correspondence:
Enrico Maria Greco, M.D., Unità Operativa Cardiologia, Ospedale
Uboldo, Via Uboldo, 21 Cernusco sul Naviglio, 20063 Milano, Italy.
Email:
enricomaria.greco@fastwebnet.it
Abstract:
Advances in pacemaker technology in the 1980s have
generated a wide variety of complex multiprogrammable pacemakers and pacing
modes. The aim of the present review is to address the different rate responsive
pacing modalities presently available in respect to physiological situations
and pathological conditions. Rate adaptive pacing has been shown to improve
exercise capacity in patients with chronotropic incompetence. A number of
activity and metabolic sensors have been proposed and used for rate control.
However, all sensors used to optimize pacing rate metabolic demands show typical
limitations. To overcome these weaknesses the use of two sensors has been
proposed. Indeed an unspecific but fast reacting sensor is combined with
a more specific but slower metabolic one. Clinical studies have demonstrated
that this methodology is suitable to reproduce normal sinus behavior during
different types and loads of exercise. Sensor combinations require adequate
sensor blending and cross checking possibly controlled by automatic algorithms
for sensors optimization and simplicity of programming. Assessment and possibly
deactivation of some automatic functions should be also possible to maximize
benefits from the dual sensor system in particular conditions. This is of
special relevance in patient whose myocardial contractility is limited such
as in subjects with implantable defibrillators and biventricular pacemakers.
The concept of closed loop pacing, implementing a negative feedback relating
pacing rate and the control signal, will provide new opportunities to optimize
dual-sensors system and deserves further investigation. The integration
of rate adaptive pacing into defibrillators is the natural consequence of
technical evolution.
Key words: rate responsive pacing, activity
sensors, metabolic sensors, physical activity, biventricular pacing, implantable
cardioverter defibrillator
The
advances in pacemaker technology in the 1980s have generated a wide variety
of complex multiprogrammable pacemakers and pacing modes. Pacing systems
can be classified as (1) single lead ventricular, such as VVI or ventricular
demand; (2) atrial based, single lead, such as AAI or atrial demand; or
dual chamber, such as DDD, which senses and paces from atrial and ventricular
chambers. These pacing modalities may or may not be rate adaptive or sensor-driven.
In the pacemaker code, rate adaptive pacemakers are designated with a fourth
letter R, for example a rate adaptive DDD becomes DDDR. Rate adaptive pacemakers
are useful for patients who cannot increase their heart rate appropriately
on exercise.
The goal of
new technologies is to come as close as possible to sinus node electrical
activity, combining the need of regular ventricular rate to a better quality
of life. In this context the clinical benefit of increasing ventricular
rate, and consequently cardiac output, during physical activity in patients
with “chronotropic incompetence” consequent to Sick Sinus Syndrome or advanced
AV block, has been established by different studies
1,2,3,4,5,6,7
The ACC/AHA
guidelines
8 define chronotropic
incompetence as failure to achieve a heart rate of 100 beats/min at maximal
exertion. From the practical standpoint heart rate at a given metabolic
load should mirror the line that describes the correlation of heart rate
to metabolic demand for age, sex, and weight matched control group
8. This definition avoids a fixed cutoff heart
rate as a criterion, and considers the trend of heart rate during different
intensity of exercise as the frame of reference
9,10,11.
Fixed rate versus rate responsive pacing
Many studies
have shown that during exercise, an increase in the pacing rate provided
by VVIR, VDD, DDD or DDDR modes augments the cardiac output, achieved workload,
and duration of exercise more than does fixed-frequency VVI pacing in patients
with both normal or impaired LV function
2,7,12,13,14,15. Beside superior hemodynamic effects, there
is an increase in maximum oxygen consumption, a reduction in arteriovenous
oxygen difference and an increase in subject well-being. Moreover, the
acute hemodynamic advantage is retained on a long term basis: by 6 and
12 months after implantation, dual chamber and rate adaptive pacemakers
may further augment LV function, reduce heart size and improve ventricular
performance compared with results in the immediate postoperative period
16,17
When patients
with complete AV block exercise, the sinus rate is significantly higher
with VVI pacing than during dual chamber or VVIR modes, a response possibly
reflecting the increased activity of the sympathetic nervous system when
pacing is set on VVI mode
18,19.
Indeed, coronary sinus norepinephrine is higher in patients with VVI pacemaker
during exercise. The increase in catecholamine on exercise during VVI pacing
is likely to be related to the need of improving contractility and therefore
cardiac output to compensate the lack of rate response. This enhanced cardiac
sympathetic activity may eventually produce an adverse effect on LV function,
with the possible development of congestive heart failure and arrhythmias.
In patients
with atrial chronotropic incompetence, VVIR and DDDR pacing modes are clearly
superior to the DDD mode in terms of exercise performance, because the sensor
increases the pacing rate according to metabolic needs. Most studies
20,21 on patients with atrial
chronotropic incompetence and DDDR pacemakers have shown superior hemodynamic
performance on exercise, and patients prefer the DDDR mode to the VVIR
mode.
Moreover, preliminary
data suggest that rate adaptive AAIR and DDDR modes may be more efficacious
in preventing atrial arrhythmias than their non rate adaptive counterparts
in Sick Sinus Syndrome
22,23,24. DDDR pacemakers may prevent arrhythmias
by eliminating the relative bradycardia noted during exercise in patients
with non-adaptive devices, when excessive catecholamine release may increase
the likelihood of atrial arrhythmias.
Rate responsiveness
Rate-adaptive
pacing has been designed to increase heart rate according to metabolic
needs during physical, mental or emotional activity. Rate responsive
pacemakers control heart rate by sensing physiological or nonphysiological
signals other than atrial rate.
Ideally the
rate adaptive sensors should reproduce the sinus node as close as possible;
therefore some definite properties must be accomplished: (1) the chronotropic
output should respond as promptly as the normal sinus node. (2) Sensors
should perform a highly specific and sensitive detection of the need of
increasing heart rate. (3) These latter have also to be proportional to
metabolic demand. (4) Rate decay during recovery after exercise should match
metabolic needs (i. e. fast after short exercise but prolonged after longer
and maximal exercise in response to an oxygen debt or in pathological conditions
like heart failure); (5) it should ideally operate in a closed loop system,
making rate adaptive pacing also insensitive to inputs not heart related.
Finally, (6) dedicated sensors should avoid undesiderable overpacing and
the need of complex programming.
Different parameters
have been investigated for controlling the pacemaker rate: oxygen saturation
25, venous pH
26,
QT interval
27,28,
body motion
28, respiratory
rate
29, stroke volume
30, central venous temperature
31,32,33,
minute ventilation
34, peak endocardial
acceleration
35, and changes of
the right ventricular impedance during the cardiac cycle (CLS, closed loop
stimulation)
36. Clinical studies
have outlined advantages and limitations of the different sensed parameters.
Finally complexity of implanting and programming, the evidence of instability
related to influence of external conditions or concomitant disease,
have defined the inadequacy of some parameters to the required characteristics,
and only some of these indicators are still used as single or dual sensor
technology.
Single sensor technology
Activity sensors
are the older and more widely used. The working modality is based on the
relationship between activity and heart rate. Activity may be acknowledged
either by a piezoelectric crystal, which recognizes the muscular pressure
waves, produced by physical activity and convert them to an electrical signal
sent to the pacemaker, or by an accelerometer that identifies the postural
changes and the body movements related to physical activity.
Activity sensors
offer rapid response to exercise by assessing body vibrations or movements.
A rapid response plays an important role in “burst activity” during daily
life. Fast reaction to termination of short exercise and technical simplicity
that allows for instance to tailor the rate response (RR) to the single
patient with proper treadmill protocols,
37
represent further advantages of this sensor type. However, after longer
exercise, an oxygen debt may require a sustained rate increase, which is
not provided by activity sensors during recovery because these sensors are
unable to recognize the oxygen debt. Moreover, low specificity with inappropriate
rate increase in conditions like laughing, coughing, driving, the fact that
activity sensors does not respond to activity not related to body movements
(isometric exercise, mental stress, or metabolic inadequacy consequent to
pathologic conditions), and the possible mismatch between exercise intensity
and rate increase, represent the main limitations of activity sensors.
Metabolic sensors,
based on QT interval, minute ventilation (MV) or peak endocardial acceleration,
provide pacing rates more closely and specifically related to physical
and mental stress requirements.
Minute ventilation,
the product of respiratory rate and tidal volume, is a physiological indicator
that has been shown to be correlated with metabolic demand
38,39. This parameter, which
also correlate linearly with heart rate
40,41, can be derived from variations in transthoracic
impedance signal. RR pacemakers, using impedance MV sensors, change the
pacing rate in response to the variations in the patients MV.
Limitations
of the MV sensor include the lower reliability in patients with obstructive
pulmonary disease, false positive reaction in hyperventilation or interference
with cardiac monitors
42 and posture
43.
Sensors using QT interval variations
27,44 are based on the finding that physical activity
and circulating catecholamine produce shortening of the QT interval. These
sensors are highly specific; furnish sustained increase of sensor-driven
heart rate during post-exercise recovery to compensate for an oxygen debt,
and are responsive to mental stress. However, measurement of evoked QT interval
may be unreliable in T wave undersensing; it can not be used in patients
with acute myocardial infarction, is affected by drugs, electrolyte disturbances
and increased circulating catecholamine, a common condition in patients
with congestive heart failure. Because it requires ventricular pacing, it
can not be used in AAIR mode.
More recently,
a sensor that assesses mechanical vibrations generated by the myocardium
during the isovolumetric contraction phase (peak endocardial acceleration
[PEA]), has been developed. A micro accelerometer is housed inside a rigid,
perfectly hermetic capsule inserted in the tip of a standard unipolar pacing
lead. The rigidity of the capsule prevents the generation of artifacts that
may arise from compression of the electrode by the cardiac muscle during contraction.
Therefore, the sensor is only sensitive to the inertial forces generated
by myocardium movements. An associated electronic circuit pre-processes the
signal to ensure its correct transmission trough the catheter.
Experimental
and clinical trials have shown that ∆PEA is correlated with dP/dT max
35,45,46
and is consequently related to contractile function. ∆PEA dynamic
monitoring has been shown to provide fast pacing rate responses with long
term performance of sensor lead and effective and rapid RR tailoring
35,47, also in patients with
heart failure and wide QRS
48.
Moreover Peak Endocardial Acceleration assessment allows AV delay automatic
optimization in DDDR pacing that can be calculated directly from the device
using a time saving procedure
49.
Experimental data in animals indicate that PEA monitoring is feasible also
during atrial fibrillation
50.
PEA sensor is
usually combined with activity sensors, however, in view of its rapid and
appropriate heart rate response in different conditions, the possibility
to use PEA sensor as a single sensor should also be considered.
Dual sensors pacemakers
As previously
described no single sensor can reproduce sinus node behavior in all the
different activities of daily life. To overcome these limitations a possible
option is to combine two different sensors. Rate modulation has to be considered
at three different levels: (1) short term response for effort or emotions;
(2) medium term adaptation for circadian variation of heart rate during
day- and night-time; and (3) long term regulation to obtain different rate
variations according to rest and activity periods
51.
Combining different
sensors might more closely mimic intrinsic heart rate, if the chosen sensors
are complementary. The most common combination include association of an
activity sensor giving a rapid response for light or for short duration
exercise, and a metabolic sensor, e.g. QT interval or minute ventilation
(MV) that provides a delayed but proportional and stable acceleration to
sustained exercise and deceleration during recovery
51. Another option in rate response devices
is to obtain circadian heart rate variation with two different hourly mean
rates during day and night. Physiologic sensors and activity sensors could
provide rate variations based on signal sensor solicitation. Two lower
heart rates are programmed for daytime and nighttime. When the sensor is
constantly solicited, the daytime lower rate is used. On the contrary,
when the signal sensor level is low for a consistent period of time, the
device switches on nighttime lower rate. Metabolic sensors could provide
a modulation of the algorithm curve slope according to the long term activity.
Sensors optimization
Independently
of the choice of sensors and mode of integration, algorithms for sensors
optimization determine the performance of dual sensor rate adaptive pacemakers.
Combining sensors with different rate responses requires adequate blending
of respective sensor activities. Blending can be performed at signal production.
The resulting signal transmitted to the algorithm is a mixture of a percentage
of activity sensor signals (0%.....10%) with an inverse percentage of non
activity sensor signals (100%....0%). This blending modality is used for
instance in the Vitatron device, combining QT interval and activity in 5
different possibility. This blended signal is transmitted to the algorithm
working with a variable automatic slope
51.
Another possibility
for sensor blending is priorization as in Medtronik Kappa 400: the activity
sensor initially accelerates from the lower rate to a plateau (programmable
90-95 b/min). The rate returns to the lower rate if activity stops, or
is proportionally increased from the plateau up to the sensor maximal programmed
rate, if the minute ventilation sensor activates. MV sensor is then in
charge during the recovery rate decrease.
Sensors cross
checking are used to avoid inappropriate rate increase. During crosscheck
both sensors can control each other and the pacing rate will only be changed
if both or a predominant sensor agrees. For example, after administration
of a drug that shortens the QT interval, a QT interval sensor would indicate
the need for rate increase, but the pacing rate would not change because
the activity sensor is not activated. Conversely, passively tapping on the
device would activate the activity sensor and indicate a rate increase, but
the pacing rate would not be modified because the QT-interval sensor would
not be activated by this manouver.
Algorithms for optimization of dual sensor performance
Algorithms for
sensors optimization determine the performance of dual-sensor rate-adaptive
pacing systems. Automatic setting has been developed in complex pacemakers
to simplify programming and optimize time. It is necessary for physicians
to be able to verify that rate adaptive pacemakers respond correctly, according
to the patient’s need. Nevertheless, even though these systems are generally
reliable
47, manual access to
sensor programmability is important and should be performed by physicians
with a thorough knowledge of the sensors capabilities. In addition, a specific
apparatus for O2 consumption measurement during physical exercise (cardiopulmonary
stress test) should be used. Alternatively an algorithm computing the best
correlation between heart rate and metabolic needs, such as Pacing Rate
Profile Software (PRPS), ought to be used
47.
Future devices
may provide the opportunity to use physiologic sensors to monitor cardiac
function and to adapt pacemaker function to assist therapy for associated
disorders. Multisensor devices can be used for cardiac rehabilitation in
pacemaker dependent patients, particularly the elderly and affected by cardiopulmonary
disease. These patients deserve a physically and psychologically autonomous
life style, which may be accomplished by using two rehabilitation methods:
(1) the set up of appropriate rate response; and (2) the institution of aerobic
training programs
52 for in-
and outpatients.
Moreover, the
integration of rate adaptive pacing into biventricular pacemakers and implantable
defibrillators is a natural consequence of technical evolution. The rationale
for the use of rate adaptive pacing in implantable defibrillators is the
same as for pacemaker. In normal heart, an increase in oxygen uptake
from 3 to 50 mL/kg per minute in a healthy subject is due to an increase
of oxygen extraction rate, stroke volume (by a factor of 1.5) and heart rate
(by a factor of 3). This allows a 4-5 fold increase in cardiac output compared
to resting values. In the large majority of patients receiving an implantable
defibrillator, the contractility reserve is limited. Therefore, an increase
in cardiac output is strictly related to the possibility of increasing heart
rate. Concomitant therapy with beta blockers, amiodarone or other antiarrhythmic
drugs may also impair the chronotropic response. This makes the issue of
chronotropic competence crucial in patients with biventricular stimulation
and implantable defibrillator despite the fact that only 20% of these latter
need primarily a cardiac pacing
8.
The concept
of closed loop pacing should be the next step in future technical developments.
Sensors that could be used in a closed loop system, indicating whether heart
rate is adequate to a given metabolic situation, are endocardial accelerometers
and sensors using impedance derived ventricular signals. It might take
some time to test technical feasibility and clinical reliability of those
closed loop systems before they will be implemented in cardiac pacemakers
and implantable defibrillators or biventricular pacemakers.
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