After my recent post, "POTS - Who's The Real Grinch," I was contacted by Dr. Benjamin Levine, whose study I critiqued in that post. Dr. Levine made some excellent points, so I offered to publish a response from him if he was interested in submitting one. Here it is. (I have edited his response for brevity, and added my own comments at the end.)
Dear Dr. Fogoros,
Thank you for your blog post about our research on patients with POTS - I appreciate the opportunity to provide a few points of clarification regarding the study you specifically discussed, and some of the interpretations of the implications from this research.
1) Promotion of Research Findings. First of all, let me reassure you that I have never "promoted" our work in any media outlets, and neither has anyone else in my institution. Frankly, I am not a big fan of media reporting of scientific data, and although I will speak to reporters when they call if I can provide any unique expertise, I do not search it out. As I am sure you know, we have no control over what reporters say about our work. [Here Dr. Levine included a vignette describing how the news media routinely distorts scientific studies, a common problem with which I have had my own personal experiences. RF] Our audience for our papers is other physicians and scientists, who must interpret the data in light of their own experience and read of the literature. I caution you, and all patients who must get their information from the media not to over interpret what they read in the press or see on TV...
2) POTS is not caused by "laziness." The story told by many of the respondents to your article is quite typical of our POTS patients as well. Most of the patients I see were very high functioning (like our astronauts, upon whom we modeled our POTS training program) prior to something happening - for some it is a viral infection; others an injury or other illness; some it is pregnancy, or the complications of delivering a baby. This "sentinel event" causes one common thing to happen - it puts people to bed.
It is important to emphasize that even 20 hours of bed rest can induce loss of plasma volume, impaired baroreflex function, and orthostatic light headedness in many people. These symptoms are quickly relieved by lying back down and induces a very rapid downward spiral of orthostatic intolerance, hypovolemia (loss of plasma from the blood), cardiac atrophy (about 1% loss of heart muscle per week in bed) progressive bedrest deconditioning and ultimately incapacitation. After only 2 weeks of bedrest or spaceflight, nearly 2/3 of people can't stand for 10 minutes!
It is also worth noting that earlier studies from our site showed that it was the most athletic subjects who were most impaired by even short duration (3 weeks) bed rest, with very long recovery periods. In fact, the volunteers who were least fit before going to bed, recovered relatively quickly in response to subsequent controlled training, generally within 2 weeks. On the other hand, the most athletic volunteers, after 3 weeks of bed rest and 2 months of intensive training, still had not recovered to their baseline fitness. Intriguingly, we studied the same subjects 30 years after the original study, and found that, amazingly, not a single person was in worse shape 30 years later, than they were after 3 weeks of bedrest in their 20s. In other words, 3 weeks of bedrest was worse for the body's ability to physical work than 30 years of aging! (see McGuire et al Circulation 2001).
Regardless of what caused the initiating event however, by the time the illness (or whatever happened) has run its course, the patients are left with profound disability (one patient in our study had not been able to even sit upright for more than 2 years) that seems to get better with our dedicated, focused, gradual exercise program beginning in the semi-recumbent position. The latter nuance is perhaps the key new wrinkle we have brought to the table in taking care of POTS patients. Most POTS cannot tolerate the upright posture so starting sitting down or even reclining backwards is critical to their success. And it is hard! Many patients struggle to complete the first few weeks of the training program, which by the way begins with only 30 minutes per day, 3 days per week. But if they push through the initial discomfort, they usually find themselves gradually feeling better and stronger.
This highlights a critical point -- We have never felt that a single POTS patient was lazy or irresponsible -- if it were easy to treat POTS with exercise, everyone would do it!! However when we apply a highly specific training program focused on making the heart bigger, the vast majority of patients feel dramatically better and many are "cured", meaning only that they no longer meet the criteria for POTS. I should emphasize though that maintaining fitness is a life-long goal for our POTS patients and we encourage them to consider exercise as part of their personal hygiene. For those patients who have heard me speak, either privately to them as patients, or publically in lectures, they know that I STRONGLY emphasize that "cardiovascular deconditioning" is a real and well described process that has nothing whatsoever to do with laziness.
Please note that patients with POTS do NOT have autonomic failure. This is not to say that the autonomic nervous system is never compromised at some point in the process of progression of POTS. However in the chronic phase, the hemodynamics are dominated by the physiology of cardiovascular deconditioning - and the evidence is that when we reverse this pathophysiology, by increasing the amount of blood the heart contains and can pump with each heart beat, that HR goes down, sympathetic nervous activity goes down, and the patients feel better.
Let me re-emphasize this point: CARDIOVASCULAR DECONDITIONING IS NOT THE SAME AS "JUST BEING OUT OF SHAPE"!!!!! Anyone who interprets our data that way is misinterpreting our findings and our therapy. I have great sympathy for our patients many of whom are extraordinarily debilitated, and I have been frustrated for much of my career trying to find therapies that work consistently.
3) On selecting patients for research studies on POTS. For our studies, we used standard definitions according to guidelines established by national and international organizations involved in autonomic disorders. [Here Dr. Levine offers a detailed discussion of the various medical conditions associated with POTS, and of the inherent difficulty all investigators face when determining the selection criteria for clinical studies on POTS. With these difficulties in mind I am convinced they followed accepted "best practices" at recruiting patients for their clinical trial. RF]
I know this may not be very satisfying to patients with these conditions, but reflects the reality of clinical research. As you can imagine, the more restrictive the enrollment criteria are, the better the investigators will be at teasing out the specifics of their hypothesis, though the less generalizable the conclusions may be. As you and many of your readers may know, we are currently engaged in a much larger registry study out in the community, where >200 patients will be studied with many fewer restrictions in enrollment. We hope that this study will answer the questions that we and others have about referral bias.
In our published studies, we enrolled a consecutive series of patients referred to my tertiary autonomic function clinic with a diagnosis of POTS. In practice, we excluded very few patients with underlying disorders, in part because as you suggested in your review, most of these patients had seen many other doctors before being referred to me, similar to the patient populations at the Mayo Clinic or Vanderbilt. From discussing our patient population with those of other experts (and we often see each others' patients...) in the field, I am confident that our population is representative of the broad referral population of POTS patients.
4) Regarding "Grinch Syndrome." Finally, let me finish with a few words about the Grinch. The vast majority of our patients who hear the term "The Grinch Syndrome" laugh and take comfort in the spirit in which it is presented. On the other hand, I understand that some patients who don't know me, and are concerned with being labeled by a name that is associated with being mean spirited, object to the use of the term Grinch Syndrome, and I respect those concerns. Frankly, if I had to do it over again, I probably would have been more reluctant to use the term, and I want all POTS patients to know that we mean them no ill will. There is no "fame and fortune" associated with this name and I get no personal benefit from using this term. However I have seen how it is very effective at calling attention to what we have observed as the primary pathophysiology associated with the extreme incapacitation of these patients. As I often tell my patients, the term "POTS" simply puts a label on the fact that the patient's heart beats fast when they stand up. The "Grinch Syndrome" focuses attention upstream, on WHY the standing heart rate is so high -- namely that the heart is "two sizes too small."
Based on simple population statistics, 2.5% of all the women in the world will have a heart that is more than two standard deviations below the mean -- the definition of "normal" in medicine. We believe that it is these women who are most at risk of getting POTS symptoms which can be induced incredibly quickly by even a brief period of bedrest.
Ultimately though, I would like to emphasize that humor is a powerful tool for healing, not only for patients with POTS, but almost any disease. We treat all our patients with the deepest respect, and are acutely aware of how debilitated they are, which we take very seriously. Mark Twain once said that "Humor is mankind's greatest blessing"; we believe it is an essential part of the healing process and hope that all of our patients smile when they think of The Grinch, and then go off to exercise!
- Benjamin D. Levine, MD
COMMENT: Dr. Levine is a dedicated and careful researcher, and his body of work on POTS has advanced our knowledge of this condition significantly, and as a result thousands of people with this condition are being helped. In addition, judging from some of the comments that appeared following my previous post, patients with POTS who have been under his care think extremely highly of him, and praise him for the respect, concern, and dedication he has shown them personally.
I still think it is too easy for a non-expert on POTS (like me) to interpret the study in question as indicating that POTS is somehow a self-induced disease, and judging from the comments my post received, that misinterpretation is indeed all too common among physicians. Dr. Levine's elaboration on that point (above) clearly indicates that it was never his intention to suggest that POTS is self-induced. Rather, his findings indicate that a relatively brief period of bed rest, perhaps especially in in some highly active people (usually women), may be enough to bring on this condition.
In any case, people with POTS who need to convince their doctors and family that their condition is not something they brought on themselves, now do not have to rely on a document written by me to do so (as several of them indicated they would in their comments). They now have documentation to that effect written by Dr. Levine himself.
I would like to thank Dr. Levine for his collegial attitude regarding this exchange, and for the effort he has made in clearing the air.