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[Dr. Shapiro] This is Dr. Samantha Shapiro, executive editor of Harrison's Principles of Internal Medicine. Harrison's Podclass is brought to you by McGraw Hill's AccessMedicine, the online medical resource that delivers the latest trusted content from the best minds in medicine. And now onto the episode.
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[Dr. Handy] Hi everyone, welcome back to Harrison's Podclass. We're your co-hosts. I'm Dr. Cathy Handy.
[Dr. Wiener] And I'm Dr. Charlie Wiener and we're joining you from the Johns Hopkins School of Medicine. Welcome to episode 108, a 70-year-old with fatigue. Cathy, your patient today is a 70-year-old non-smoker who until recently was an avid gardener and squash player. However, over the last year, he's noticed increase in fatigue while gardening and exerting himself. He tells you that he often poops out during long tennis rallies and this is notably different than a year ago. His past history is only notable for hyperlipidemia for which he takes atorvastatin. He denies any weight loss, night sweats, cough, wheezing, or chest pains. His resting vital signs and physical examination are normal. You obtain a chest X-ray, chemistries, and hematology and all of those studies are normal. His baseline ECG is also normal. You subsequently order an echocardiogram and that shows normal biventricular systolic and diastolic function, normal atrial size, and no valvular abnormalities. Any thoughts so far?
[Dr. Handy] Interesting, so really, he only has symptoms with exertion and so far none of his initial examinations, and you even did an even more extensive cardiac workup, and that has not yielded any abnormalities. I most definitely don't want to write this off as just normal aging, so I think my next steps would be pulmonary function tests and an exercise stress test. He does have two cardiac risk factors being his age and hyperlipidemia.
[Dr. Wiener] Great. Well, his pulmonary function test includes spirometry, lung volumes, and a diffusion capacity, and all of those are within normal limits.
[Dr. Handy] What about the stress tests? There has to be some question here somewhere or it's going to be a very short episode.
[Dr. Wiener chuckles] Yeah, on his exercise ECG test, which he does to exhaustion, his peak heart rate is 96 and there are no ST segment alterations. The question asks, based on the above data, you suspect his symptoms are due to which of the following? Option A. is chronotropic incompetence; option B. is heart failure; option C. is lung disease; option D. is normal aging; or option E. is psychosomatic complaints.
[Dr. Handy] All right, well, we can rule out a few things here based on our workup. Option B. is heart failure and we should be more precise with our wording here. Traditionally, heart failure was defined only by systolic dysfunction characterized by a reduced ejection fraction or HFrEF. In the past 25 years, we've learned that abnormal diastolic relaxation may also cause symptoms and signs of heart failure. Those patients have a normal or even high ejection fraction but have diastolic dysfunction. Those patients are referred to as having heart failure with preserved ejection fraction or HFpEF.
[Dr. Wiener] But our patient has neither of those based on the echo, right?
[Dr. Handy] Yes, the echo specifically reported no abnormality of either systolic or diastolic function.
[Dr. Wiener] Okay, well what about the other options then?
[Dr. Handy] The normal pulmonary function tests do not rule out all lung disorders. Remember, patients with asthma that are not having an attack will typically have normal PFTs, but he gives no story of asthma so I'm moving that down on the list. And as I mentioned before, normal aging should not cause these symptoms and I'm not ready to ascribe this all to psychosomatic complaints because his exercise test was not normal.
[Dr. Wiener] But he had no ST changes on the exercise stress test.
[Dr. Handy] Right, but he only achieved a peak heart rate of 96 and was apparently really trying. So I think he may have option A. chronotropic incompetence.
[Dr. Wiener] Okay, well now we have something to talk about. Tell me more.
[Dr. Handy] So let's start with the SA node. So the sinoatrial or SA node serves as the natural pacemaker of the heart and has variable rates in response to parasympathetic and sympathetic stimulation. Symptoms of sinus node dysfunction can vary, but typically present as fatigue, exercise intolerance, or dyspnea. Now importantly, the SA node determines the resting heart rate, but also responds to sympathetic stimuli such as during exercise to raise the heart rate and cardiac output. So failure to do that is called chronotropic incompetence.
[Dr. Wiener] Okay, I've really not experienced that term before, tell me more about chronotropic incompetence.
[Dr. Handy] So it's broadly defined as the inability of the heart to increase its rate to meet activity or demand. Compared to an increased stroke volume, the increase in heart rate is a stronger contributor to the increase in oxygen uptake or VO2 during aerobic exercise. It's alternatively defined as failure to reach 85% of the predicted maximal heart rate at peak exercise, or failure to achieve a heart rate over 100 beats per minute with exercise, or a maximal heart rate with exercise less than two standard deviations below that of an age-matched control population. Now, chronotropic incompetence can be associated with severe exercise intolerance and increased cardiovascular events, and overall mortality.
[Dr. Wiener] So that would fit with our gentleman's symptoms. Remind me, how do we calculate the target heart rate during a maximal exercise test? You said his was inadequate.
[Dr. Handy] Maximum heart rate is 208 minus 0.7 times age or for this patient, it'd be 159 so he should have achieved 85% of that or that would be a heart rate of 135, and we heard that his was less than 100. Chronotropic incompetence may be insidious and hard to diagnose, and again, many people will just ascribe it to age. In addition to exercise testing, ambulatory heart rate monitoring along with a diary can be helpful to correlate symptoms with abnormally slow heart rates.
[Dr. Wiener] Okay, before we finish with how to help this man, what else should we think about in a patient that we suspect might have sinus node dysfunction?
[Dr. Handy] Well, there are some reversible causes of sinus bradycardia or chronotropic incompetence, and that would include hypothyroidism and medications with beta-blockers and calcium channel blockers at the top of that list. Also, cannabis use has been associated with sinus node dysfunction. Obviously, structural heart disease may involve the sinus node as can many systemic illnesses such as sarcoid, Lyme disease, myocarditis, COVID-19, or amyloidosis. And finally, while I said normal aging should not cause these symptoms, it is true that with aging, there may be fibrosis of the SA node and that may eventually result in the so-called sick sinus syndrome.
[Dr. Wiener] Okay, well, back to our gentleman who is a vigorous gardener and squash player. What can we do to help him?
[Dr. Handy] Well, the mainstay of treatment for patients with symptomatic bradycardia or chronotropic incompetence is a pacemaker. Chronotropic medications such as methylxanthines do not typically work well or sometimes they just have significant side effects. So if this man's ambulatory monitoring shows his symptoms are due to chronotropic incompetence, he'd benefit from a pacemaker.
[Dr. Wiener] Before we close, given my interest, I'd also like to highlight that in patients with symptomatic breathlessness or dyspnea on exertion that is unexplained, a cardiopulmonary exercise test with collection of exhaled gases may help distinguish between cardiac and respiratory exercise limitation. These tests may be performed in most pulmonary function testing units and may be helpful in distinguishing the causes of breathlessness.
[Dr. Handy] Maybe a topic for a future Podclass episode.
[Dr. Wiener] Ha! good idea. Okay, so the teaching points in today's case are that a functional sinus node is necessary to augment cardiac output during exercise. Sinus node dysfunction may be insidious and hard to diagnose, but exercise and ambulatory monitoring may be helpful. In cases of symptomatic bradycardia, a pacemaker may be necessary.
[Dr. Handy] And you can learn more about this in the Harrison's chapter on disorder of the sinus node.
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[Dr. Shapiro] Thanks for listening to Harrison's Podclass. You can listen to this episode and more on AccessMedicine.com which includes the complete Harrison's Principles of Internal Medicine text, Harrison's Review Questions, which complement and expand upon the questions in this episode, and much more. AccessMedicine.com may already be available to you via your academic institution. Check it out!
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