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Improving Clinical Outcomes in Chronotropic Incompetence: Case Studies

  • Authors: Kenneth Ellenbogen, MD; Karoly Kaszala, MD, PhD
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Target Audience and Goal Statement

This activity is intended for cardiologists, electrophysiologists, and other healthcare professionals involved in the management of patients with pacemakers.

The goal of this activity is to update clinicians on the implications of chronotropic incompetence (CI) and provide the latest management strategies for patients who have existing pacemakers and are who are experiencing CI.

Upon completion of this activity, participants will be able to:

  1. Define the incidence of CI and its implications
  2. Describe the characteristics of an ideal sensor for rate-responsive pacing
  3. Discuss how rate-adaptive pacing may improve patients' quality of life


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  • Kenneth Ellenbogen, MD

    Professor and Vice-Chair of Cardiology and Director of Clinical Cardiac Electrophysiology and Pacing at the Virginia Commonwealth University School of Medicine in Richmond, VA


    Disclosure: Kenneth Ellenbogen, MD, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: Medtronic, Inc.; Boston Scientific; St. Jude Medical; Biotronik
    Served as a speaker or a member of a speakers bureau for: Medtronic, Inc.; Boston Scientific; St. Jude Medical; Biotronik
    Received grants for clinical research from: Medtronic, Inc.; Boston Scientific; St. Jude Medical

    Dr. Ellenbogen does not intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics approved by the FDA for use in the United States.

    Dr. Ellenbogen does not intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics not approved by the FDA for use in the United States.

  • Karoly Kaszala, MD, PhD

    Assistant Professor of Cardiology, Virginia Commonwealth University School of Medicine, Richmond, VA


    Disclosure: Karoly Kaszala, MD, PhD, has disclosed the following relevant financial relationships:
    Served as Principal Investigator for: Boston Scientific; St. Jude Medica; Sorin Group

    Dr. Kaszala does intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics approved by the FDA for use in the United States.

    Dr. Kaszala does intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics not approved by the FDA for use in the United States.


  • Caroline M. Fisher, B.Pharm

    Senior Scientific Director, Medscape, LLC


    Disclosure: Caroline M. Fisher has disclosed no relevant financial relationships

    John F. Kross, MSc, DMD

    Lincoln University, PA

    Disclosure: John F. Kross, MSc, DMD, has disclosed no relevant financial relationships.

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  • Laurie E. Scudder, DNP, NP

    Accreditation Coordinator, Continuing Professional Education Department, Medscape, LLC; Clinical Assistant Professor, School of Nursing and Allied Health, George Washington University, Washington, DC; Nurse Practitioner, School-Based Health Centers, Baltimore City Public Schools, Baltimore, Maryland


    Disclosure: Laurie E. Scudder, DNP, NP, has disclosed no relevant financial relationships.

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Improving Clinical Outcomes in Chronotropic Incompetence: Case Studies

Authors: Kenneth Ellenbogen, MD; Karoly Kaszala, MD, PhDFaculty and Disclosures


Patient Image

A 55-year-old man is seen for a follow-up appointment in the pacemaker clinic. Before he presented to the clinic with near-syncope and fatigue during exertion, he was a long-distance runner and competitive athlete with peak performance of a 6-minute mile. He underwent Holter monitoring that showed evidence of sinus node dysfunction and sinus pauses of over 4.5 seconds. He underwent a dual-chamber, dual-sensor, rate-modulated pacemaker implantation.

Following pacemaker implantation, he has not had further episodes of syncope but his lifestyle has been severely limited as his exercise tolerance declined due to sinus node dysfunction. He underwent multiple treadmill exercise tests and sensor parameters were successfully re-programmed to mimic normal intrinsic chronotropic function. His symptoms have markedly improved and at present, he runs a 7-minute mile and his only complaint is difficulty running on humid days and occasional Achilles tendon problems.

Most physicians who evaluate and treat patients with exercise intolerance, and fatigue or dyspnea on exertion, have faced similar clinical situations. While these symptoms are nonspecific and require consideration of a very wide list of differential diagnoses, chronotropic incompetence should be part of this differential diagnosis. The aim of this 2-part program is to discuss the pathophysiologic background, diagnosis, and treatment of chronotropic incompetence including pacemaker technology and sensors. We will also discuss several case studies from our pacemaker clinic to help understand some of the challenges we face in everyday practice.

First, however, it is important to review some of the basics of exercise physiology in order to better understand the pathophysiologic consequences, options and limitations of current therapy.

  • Kenneth Ellenbogen, MD: Hello. I’m Dr. Kenneth Ellenbogen. I am a Professor of Cardiology from the Virginia Commonwealth University (VCU) School of Medicine. I am here today with Dr. Kaszala who is an Assistant Professor of Cardiology at the VCU School of Medicine in Richmond, Virginia.

    We’re here today to talk about sensors in cardiac pacing. I thought what we’d do today is present several clinical cases of patients who have pacemakers where programming the pacemaker, and particularly, using the appropriate sensors made a substantial difference in how the patient was able to function and their quality of life.

  • Slide 1.

    Slide 1.

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  • I’ll start off by presenting these patients, and then we’ll have a general discussion about the role of rate-adaptive cardiac pacing.

    The first patient is a 55-year-old man who was evaluated in device clinic for routine follow-up. His pacemaker was implanted 7 years ago for syncope. At that time, he was found to have severe sick sinus syndrome (SSS) and 4-second pauses and had a pacemaker implanted. Prior to that, the patient had been racing competitively for over 30 years. His peak performance was a 6-minute mile. Currently, with his pacemaker, he’s able to easily run a 7-minute mile. He states his only limitation is difficulty running on very humid days.

  • Slide 2.

    Slide 2.

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  • I’ll start off by presenting these patients, and then we’ll have a general discussion about the role of rate-adaptive cardiac pacing.

    The first patient is a 55-year-old man who was evaluated in device clinic for routine follow-up. His pacemaker was implanted 7 years ago for syncope. At that time, he was found to have severe sick sinus syndrome (SSS) and 4-second pauses and had a pacemaker implanted. Prior to that, the patient had been racing competitively for over 30 years. His peak performance was a 6-minute mile. Currently, with his pacemaker, he’s able to easily run a 7-minute mile. He states his only limitation is difficulty running on very humid days.

  • Slide 3.

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  • This is a picture of his histograms and counters from an interrogation of his pacemaker, and you can see that he is atrially paced a substantial portion of the time.

  • Slide 4.

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  • When one delves further and looks in further detail about the patient's rate response, we can see how, with programming a dual-sensor mode here, there is a substantial increase in heart rate, as one can see by the peak heart rate that goes toward the top of the page with running.

  • Slide 5.

    Slide 5.

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  • Here we have a 2-hour trending, and again, you can see the very dynamic response of this patient's paced heart rate to exercise. It has really allowed this patient to run at a very good rate and continue his very active exercise schedule.

  • Slide 6.

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  • The next patient is a 66-year-old man who was evaluated in the device clinic. This patient had a pacemaker implanted 6 years ago. At that point, the patient's problem was complete heart block. Over the ensuing time, progressive sinus bradycardia developed that required both atrial and ventricular pacing.

  • Slide 7.

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  • As you can see on his histogram counter, once again, in this case, the patient is predominately atrially and ventricularly paced.

  • Slide 8.

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  • He has a very nice response to exercise, as is shown in the following slide, where with a combination of an accelerometer and minute ventilation, this patient is able to obtain a very appropriate response to exercise and to chores of daily activity.

  • Slide 9.

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  • The final patient I'd like to talk about is a 74-year-old woman who was evaluated in our device clinic. Unfortunately, she was lost to follow-up after her dual-chamber pacemaker was implanted 4 years earlier for SSS. She complained of shortness of breath with exertion.

  • Slide 10.

    Slide 10.

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  • Here, her histograms and counters show that she is predominately sensed and not getting a pacing response with exertion.

  • Slide 11.

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  • As I said, the patient complained of shortness of breath with exertion. When she came in, her rate response was programmed to an accelerometer only. Her minute ventilation sensor was initialized. The patient performed a hallwalk and trending data were re-evaluated.

  • Slide 12.

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  • As you can see with an accelerometer, only after a hallwalk, there is an inadequate response to exercise. Additionally, her heart rate decreases abruptly after the termination of exercise.

  • Slide 13.

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  • With a dual sensor and a minute ventilation response factor of 4, one can see a much more appropriate, and now, a sustained heart rate response to exercise that does not dissipate immediately after the termination of exercise.

    I've presented 3 patients in whom the sensor response was critical in providing them with an appropriate quality of life and an ability to perform both exercise and chores of daily living.

  • Slide 14.

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  • Dr. Kaszala, would you review the basic physiology and the importance of the heart rate in providing adequate stroke volume in response to exercise?

    Karoly Kaszala, MD, PhD: Thank you, Ken. These are very interesting cases, and I think it will be very important to understand some of the basics of exercise physiology, so we may be able to better evaluate the patients who have SSS or chronotropic incompetence (CI) and require rate-sensitive and rate-responsive pacing.

  • Slide 15.

    Slide 15.

    (Enlarge Slide)
  • Aerobic exercise requires adequate transport of oxygen from the lungs to the peripheral tissues. In this process, there is a key role for the cardiovascular and pulmonary systems. Failure of either of these systems will result in a decline in the metabolic supply, and may result in fatigue, shortness of breath, or exercise intolerance.

  • Slide 16.

    Slide 16.

    (Enlarge Slide)
  • In this talk, I will mostly focus on the heart and heart rate response. As the metabolic demand increases, the heart responds with an increased cardiac output, which is determined by the stroke volume and heart rate. The stroke volume depends on the preload, afterload, and inotropy.

    In a normal heart, the stroke volume may increase by approximately 50% as a result of exercise. This increase, however, occurs mostly in the initial phase of exercise, and in the later stages, the stroke volume plateaus or may even decline. On the other hand, the heart rate increase may play a much more significant role, especially in submaximal and maximal exercise, and result in an increase in cardiac output of 2- to 3-fold.

  • Slide 17.

    Slide 17.

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  • If either of these parameters is deficient, such as there’s a reduced inotropic reserve—such as in heart failure or post-MI—or there’s a suboptimal increase in heart rate, the patient may develop exercise intolerance.

  • Slide 18.

    Slide 18.

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  • In normal hearts, the heart rate is modulated by the effects of the sympathetic and parasympathetic systems. At the initiation of exercise, there is an immediate increase in heart rate that is related to the withdrawal of parasympathetic tone.

  • Slide 19.

    Slide 19.

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  • A further increase in heart rate is related to changes in the neuronal and circulating catecholamine levels, but it is also important to understand the great flexibility in the cardiovascular system. At the start of vigorous exercise, the heart rate and cardiac output may reach a plateau as quickly as 45 to 90 seconds. On the other hand, during a more graded exercise, change in heart rate, cardiac output, and minute ventilation remain proportional to work load.

  • Slide 20.

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  • Dr. Ellenbogen: Let me ask you to define CI and talk about how important that is. It's such a common cause for an indication for pacemaker implantation. Depending on the series, 40%-60% of patients who get a pacemaker have CI, so tell us what it is.

  • Slide 21.

    Slide 21.

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  • Dr. Kaszala: It is rather easy to define CI. The definition is attenuated heart rate response to exercise. However, to make the diagnosis is not as straightforward, especially in cases wthat are not as obvious. Defining maximal heart rate is not very easy because there are several confounding factors, such as age, resting heart rate, or physical fitness, among others, that have a strong influence. In fact, we use an age-predicted maximal heart rate as a goal or as a maximal heart rate for each patient, which is defined by subtracting the age from 220.

  • Slide 22.

    Slide 22.

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  • There are different causes for CI. These include sinus node disease, autonomic dysfunction, arthrosclerosis, myocardial ischemia, heart failure, or drug therapy.

  • Slide 23.

    Slide 23.

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  • As you mentioned, the prevalence of CI is substantial. Up to 20% of patients in the Framingham study, which excluded patients with known coronary disease or heart disease, have been identified as having CI. On the other hand, if you look at a sicker population, such as patients with heart failure, up to 70% may present with CI. The importance is that there is a reduced exercise tolerance in these patients, and on top of that there is also an association with adverse cardiac events, even in otherwise healthy patients, which has been shown in the Framingham study as illustrated in the slide.

  • Slide 24.

    Slide 24.

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  • Looking at a chronotropic response index, which is one of the most precise ways to evaluate chronotropic dysfunction, has shown that patients in the lowest level with this index have an increased mortality.

  • Slide 25.

    Slide 25.

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  • Dr. Ellenbogen: So one of the purposes of cardiac pacing, therefore, is to try to mimic the normal heart rate response to exercise, which as you said, is important for submaximal and maximal exercise. To do that in patients who have SSS and sinus node impairment, we need to use some sort of sensor. What I'd like you to describe are the currently available clinical sensors and a little bit about their role in cardiac pacing.

  • Slide 26.

    Slide 26.

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  • Dr. Kaszala: At this time, the only available treatment option for us to treat CI is a sensor-driven or rate-motivated pacing. These devices use some form of sensor to estimate the metabolic load or activity level of the patient. An ideal sensor that we could use would mimic completely a normal sinus node function. This would have a rapid sensitive and specific way to identify an increased metabolic demand. It would allow a proportionate response to exercise. It would be able to accommodate short, as well as prolonged activities, and potentially, it would also allow response to other nonexercise-related increased demands, such as those seen in fever or mental stress.

  • Slide 27.

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  • Currently there are 5 different sensors commonly used in clinical practice. Activity sensors are probably the most commonly-used sensors. These are tertiary sensors, which means that they measure parameters that are nonphysiologic. These sensors measure changes in acceleration, vibration, or motion. They are relatively simple and require little energy. However, they are more prone to have interference from the environment, and they are not able to estimate any physiologic demand.

    The rest of the sensors are physiologic sensors. The next most commonly used sensor is the minute ventilation sensor. Minute ventilation, as I mentioned earlier, changes proportionately to the work load and heart rate, and it has been shown to be a very good marker to estimate the heart rate response. There is a change in transthoracic impedance as the air moves in the thorax, and this change may be measured through a pacemaker can and a pacemaker lead. These changes have been correlated with minute ventilation very accurately. The advantage of these sensors is that they may be used with any lead. The disadvantage is that they may be slow at the beginning of the exercise, and they may be limited in certain populations, such as children or patients with severe lung disease.

  • Slide 28.

    Slide 28.

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  • The other types of sensors include a QT interval sensor, which is not very widely used, but has been shown to be an accurate measure of physiologic changes. QT interval changes as the circulating catecholamines change within the body, and has been shown to be a good estimate of a heart rate response. They may respond to mental stress too. The disadvantages are that it requires ventricular pacing and T-wave sensing may be variable in certain patients.

    Two other sensors, which I want to talk about in more detail because they’re not as widely available, measure contractility, either by an impedance-based or an activity sensor-based mechanism, and they have been shown to be appropriate measures and proportional rate sensors for exercise.

  • Slide 29.

    Slide 29.

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  • Kenneth Ellenbogen, MD: That’s very useful in terms of the basic physiology of sensors. In the patients I showed you, it was very important to be able to provide not only a very proportional exercise response, a very proportional heart rate response to exercise, one that’s proportional to the metabolic demand, but also in some of these people, to get their sensor going, and that’s something that we often do in clinical practice. A combination of sensors is often very important in young patients and in older patients. You may only need one sensor. You may need both. You may want to blend them. Can you talk about the blend of sensors and sensor combinations?

  • Slide 30.

    Slide 30.

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  • Karoly Kaszala, MD: There is the availability to mix more than one sensor within one device. Most commonly used is a combination of an activity sensor with either an evoked QT sensor or a minute ventilation sensor. The advantage of an activity sensor is that its response is very rapid, and therefore, it is a sensitive marker for the start of exercise, especially aerobic exercise. On the other hand, a minute ventilation or an evoked QT sensor is much more appropriate to estimate how much pacing a patient would need doing that exercise and how long that pacing would be needed.

    By using a combination of sensors, you may blend the advantages of each sensor by using specialized algorithms that, for example, allow a rapid initiation of pacing, based on the activity sensor and then further pacing according to the level of exercise. That would be determined by a minute ventilation sensor. These sensors may also allow crosschecking. For example, if there is a false-positive sensing on the activity sensor because of a bumpy ride or some kind of an environmental effect, then a minute ventilation or QT sensor would be able to identify that and cut back on the pacer rate, and reduce inappropriate pacing.

  • Slide 31.

    Slide 31.

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  • Kenneth Ellenbogen, MD: Certainly, that’s very, very clinically useful. I’d like to end our discussion of sensor-based pacing by having you briefly tell us what we’ve learned from clinical trials.

  • Slide 32.

    Slide 32.

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  • Karoly Kaszala, MD: Many clinical trials were carried out in the early 1960s and 1970s looking at the hemodynamic benefits of rate-modulation and rate-reductive pacing, and almost exclusively, all of these studies have shown that the cardiac index, the cardiac exercise duration, exercise capacity increases with rate-modulated pacing. These were, however, smaller studies.

  • Slide 33.

    Slide 33.

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  • More recently, larger studies were performed to look at, in a larger scale, how these sensors perform, and these are illustrated in the following slide.

    Kenneth Ellenbogen, MD: It looks like the results show, in some cases, an improvement in quality of life, but it’s been disappointing that the trials have not been unanimous at all in showing a clear cut benefit in terms of rate-adaptive pacing. Based upon the trial data from this slide, for me, the take-home message from this is that choice of pacing modes really needs to be individualized to the particular patient. I think one of the criticisms of a lot of these studies is that they had very heterogenous groups of patients and that some of the patient groups probably didn’t need rate-adaptive pacing and some of them did. Do you think there are other take-home messages from these clinical studies?

  • Slide 34.

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  • Karoly Kaszala, MD: Yes, I think there are several factors that may be considered, how optimal the programming of these devices where. These were large, multicenter studies, and sometimes, the programming was not very aggressive. There is also a possibility that many of these patients were limited for reasons other than chronotropic incompetence. Finally, it is also possible that, after all, reaching a maximal heart rate is not as important as we think.

    Kenneth Ellenbogen, MD: So based upon what you’ve explained to us about the physiology of rate-adaptive pacing, about the different types of sensors, but also, particularly about the sensor blends, I think it’s clear to me, and as I illustrated in that third patient, programing the pacemakers in some patients still requires listening to what the patient has to say, programming the rate-adaptive sensors. And then seeing how the patient does: having the patient do a hall walk, having the patient come back in 10 or 15 minutes and see how they feel, see how their symptoms improve, and interrogate their device and see what their heart rate does. I think that’s one of the advantages of having sensor blends and having multiple sensors, you can figure out what works best for a patient. As you pointed out, in an elderly patient, it may not be critical to reach their maximal heart rate.

    In the young patient that I presented—the first patient—here is a guy who in his fifties is still running 5, 7, 8 miles a day, and he needs to get his heart rate to 150-160 beats a minute. There a physiologic sensor or blend of sensors, for example, the accelerometer when he begins to exercise, followed by the minute ventilation sensor, really gives him a spectacular quality of life. I think the take-home message is that medicine still requires individualizing the therapy that we deliver to patients, whether that therapy is programming a pacemaker or deciding about the dose of a drug to give patients.

  • Slide 35.

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Supported by an independent educational grant from Boston Scientific.

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