Patients suffering from dysautonomia often find the pathway to a diagnosis to be an ordeal. Many patients who have the audacity to complain of severe symptoms without providing the objective physical or laboratory findings to back them up are written off as being merely anxious or hysterical. This can make finding a doctor who will make the right diagnosis quite difficult.

After patients with one of these conditions have seen a doctor or two, and have had a couple of major workups which have yielded no objective findings, and after their doctors have expressed frustration with these results and have begun broaching (overtly or by hints) the idea of a psychogenic illness, or malingering, or some other such condition in which their psychological inadequacy is offered as the root cause, they actually do often become depressed and anxious—even if they began their quest with well-adjusted self-control and a sense of abiding optimism.

Patients lucky enough to be taken seriously by their primary care physician are likely to be sent to a specialist. The particular specialist they will see depends on the predominant symptoms they complain about.

Making the correct diagnosis requires the doctor to be alert to the possibility of dysautonomia in anyone presenting with one or more of the typical symptoms and a general sparsity of objective findings. In general, the most important key to the diagnosis is a history of good health, followed by some potentially triggering event, followed by unremitting (though often waxing and waning) symptoms compatible with dysautonomia.

Some of the dysautonomia conditions present next to nothing in the way of objective findings. These include CFS, fibromyalgia, and IBS. These diagnoses are made on purely clinical grounds, with heavy reliance on the medical history.

Other dysautonomias do indeed present objective findings. These generally are the conditions that include a strong component of vasomotor instability which can be objectively documented: POTS, vasovagal syncope, and IST. Fortunately for the electrophysiologist, these are the patients with dysautonomia most likely to be referred to them.

Often, in the course of working up a patient with dysautonomia, an echocardiogram is obtained, and the echo will show evidence of mild MVP. Given the high resolution achieved with today’s echocardiographic equipment, at least some evidence of MVP can be identified in 25–30% of normal patients, and this finding is all the more likely to be called out on a final report if the reason given for the examination is to “rule out MVP.” Consequently, these patients are likely to be diagnosed with “MVP syndrome.” There is actually little if any evidence that the symptoms of dysautonomia are any more likely if MVP is present than if it is not. So in the vast majority of cases, the “MVP” (if it is actually present at all) is an incidental finding. There’s probably nothing terrible about making the superfluous diagnosis of MVP syndrome, as long as the physician understands that what’s actually going on is dysautonomia. But to the extent that this diagnosis steers the doctor away from recognizing dysautonomia and treating it appropriately, it is indeed a problem.

Whichever of the dysautonomia conditions a patient might have, the doctor should be alert to the likelihood of symptom overlap. So, for instance, the patient with CFS may have some orthostatic instability, or the patient with fibromyalgia may have a mild resting sinus tachycardia or a history of vasovagal syncope. These kinds of clue can provide important corroboratory evidence as to the real nature of the patient’s condition.

Whether they like it or not, electrophysiologists end up seeing many patients with dysautonomia. Typically, these patients will be referred for palpitations, for episodes of syncope, or for tachycardia. Frequently, neither the patient nor the referring doctor will realize that dysautonomia is the real problem. Likely the referring doctor will believe, and the patient will be afraid, that they are just crazy.

So the electrophysiologist will be doing a very good thing if he or she not only provides the assessment of the symptom for which the patient is being referred, but also is able to point the referring doctor and the patient in the right direction, so they can begin taking the steps necessary to get the underlying dysautonomia under control.

Dysautonomia and Palpitations

Typically, the work-up of palpitations is pretty straightforward. You simply arrange for the patient to have cardiac monitoring for whatever period of time seems necessary to capture an ECG during an episode of palpitations. Sometimes that’s a 24-hour Holter study, and sometimes it’s two or more 4-week event-recorder studies. But once you have recorded an ECG that tells you what the heart rhythm is at the moment the patient is experiencing their typical palpitations, you generally have your diagnosis. If there’s an arrhythmia, you deal with that. If the palpitations are not associated with an arrhythmia then they are likely to be due to muscle spasms or esophageal gas or some other benign noncardiac cause, and the treatment is reassurance.

It may not be so simple in the patient with dysautonomia. These patients very often have several different symptoms, which may include actual palpitations from cardiac arrhythmias, as well as other transient sensations which they may perceive in the region of the chest. And only the rare patient with dysautonomia can reliably differentiate among the various upper-body sensations they experience when they say they are having “palpitations.”

Because the patient may be experiencing several types of symptom they call “palpitations,” it becomes relatively easy to write off their symptoms when they are found not to be associated with specific cardiac arrhythmias. This may cause the physician to miss symptomatic episodes of tachycardia or bradycardia, both of which are also fairly common in patients with autonomic instability. Patients with dysautonomia are typically relatively young and (except for their dysautonomia) reasonably healthy, so missing sinus bradycardia or sinus tachycardia is not likely to have devastating consequences. But capturing those heart rhythms, and correlating them with symptoms, may turn out to be an important clue that dysautonomia with a certain degree of hemodynamic instability is present. And this knowledge carries treatment implications.

So, when evaluating palpitations in a patient who is suspected of having dysautonomia, the clinician ought to be a little more circumspect than usual in declaring that there is no correlation between the symptoms and the heart rhythm. Often, this is best accomplished by continuing the monitoring for a long enough period of time to record electrograms during multiple episodes of palpitations.

Dysautonomia and Syncope

Chapter 10 discussed the evaluation of syncope in detail. As we saw, by far the most common cause of syncope is vasodepressor syncope. And vasodepressor syncope, at least when it is a recurrent problem, is often a form of dysautonomia.

In the majority of patients who have vasodepressor syncope, the syncopal episodes themselves are the only sign of dysautonomia. In contrast to the kinds of dysautonomia we are talking about in this chapter (in which symptoms tend to be multiple, and, with varying degrees of intermittency, relatively persistent), patients with vasodepressor syncope most typically will present with a single episode, or perhaps a short cluster of episodes—and will be entirely normal at all other times. That is, their susceptibility to syncope is usually intermittent and fairly transient.

However, some patients with vasodepressor syncope will have a more chronic condition, in which syncope is likely almost any time a potential “triggering event” happens to occur. These patients quite often, on questioning, will describe other symptoms consistent with dysautonomia, including a definitive precipitating event that first heralded the onset of their condition. Tilt-table testing (see Chapter 10), which helps to estimate a person’s relative susceptibility to vasodepressor syncope, is much more likely to be strikingly positive in these patients. These patients, not surprisingly, are typically more difficult to treat than those with only rare and sporadic syncopal events.

One additional observation might help to clarify the nature of the symptoms patients sometimes experience with dysautonomia. After a vasodepressor syncopal episode, patients will often feel extremely weak, lightheaded, and fatigued for several minutes to several hours. During this post-syncopal period, they can do little more than lie down, feeling miserable; if they try to get up, they become orthostatic and dizzy. What these patients are experiencing during this interval is a transient case of acute and fairly striking dysautonomia. Patients who are symptomatic with many of the dysautonomia conditions discussed in this chapter feel more or less just like that, much of the time.

Chapter 10 describes in more detail the evaluation and treatment of patients with vasodepressor syncope.

Dysautonomia and Tachycardia

Tachycardia is fairly common in patients with dysautonomia. Generally, the fast heart rate is sinus tachycardia, and presumably it is caused by autonomic imbalance in the direction of increased sympathetic tone.

In some patients the sinus tachycardia is quite remarkable and persistent and is the most striking feature. These patients are said to have inappropriate sinus tachycardia (IST).

Patients with IST have sinus rates that are abnormally high at rest (usually around 100 beats/min, though during sleep the rates may drop to the mid 80s, or even lower) and invariably increase rapidly with even minimal exertion. They have no identifiable reason for secondary sinus tachycardia, such as anemia, infection, hyperthyroidism, pheochromocytoma, substance abuse, or cardiopulmonary disease. Their sinus tachycardia is therefore “inappropriate.”

While IST can occur in anybody, the typical sufferer is a woman in her 20s or 30s who has been having symptoms for months to years. Prior to the onset of IST, which often follows a viral illness or physical trauma, most of these patients will have been in excellent health, both physically and emotionally. In addition to the most common symptoms of palpitations, fatigue, and especially exercise intolerance, IST can be associated with a host of other issues, including orthostatic hypotension, blurred vision, dizziness, tingling, gastrointestinal disturbances, shortness of breath, and sweating. In other words, they often suffer from the constellation of symptoms typical for patients with dysautonomia.

Symptoms with IST can be quite severe, sometimes to the point of being disabling. All these symptoms occur with a paucity of physical findings or laboratory abnormalities. The only consistent finding is tachycardia.

IST has been a recognized clinical condition only since 1979, and while electrophysiologists by now are very familiar with it, many other doctors remain blissfully unaware that it exists. By the time the sufferer of IST gets to an electrophysiologist, if they are lucky enough to be referred, they will have been told by at least one doctor that the culprit is “anxiety.” If the IST itself isn’t enough to make the patient crazy, then being told it’s all “in your head” may be: by the time he or she sees an electrophysiologist, anxiety often is indeed an issue.

The cause of IST, like all the dysautonomias, is unknown. And in fact, while the author obviously classifies this condition as a dysautonomia, many electrophysiologists disagree, and believe it is a primary disorder of the SA node.

Indeed there are several lines of evidence that point to IST being a primary SA nodal disorder. First, the intrinsic heart rate (see Chapter 5) in patients with IST tends to be elevated, suggesting that even in the absence of autonomic influence the SA node displays enhanced automaticity. Second, patients with IST tend to have an abnormally enhanced heart-rate response to epinephrine, similar to their exercise response. And third, at least some evidence exists that the SA node in patients with IST is structurally abnormal.

It is important to know whether IST is a primary SA nodal disorder because if it is, ablation of the SA node ought to cure the condition. Accordingly, electrophysiologists have tested this theory by performing SA nodal ablations in hundreds of patients with IST. The outcome is very interesting. The immediate response is usually quite favorable—over 90% of patients no longer have IST immediately after SA nodal ablation. Unfortunately, in about 80% of patients who have such “successful” ablations, the IST recurs within 6–9 months.

Repeat electrophysiologic testing usually shows regeneration of SA nodal function, complete with its IST-like behavior, though this regenerated SA nodal activity is often found inferior to the original site of ablation, along the crista terminalis. Repeated ablations usually yield the same results: early success and late failure.

Thus, something—this “something” being external to the SA node itself—appears to be stimulating regeneration of SA nodal tissue, complete with its inappropriate rate of firing, after ablation. This is an important piece of evidence against the “primary SA nodal disorder” hypothesis.

There is actually quite a bit of evidence that IST may often be one of the dysautonomias. It shares many of the characteristics of dysautonomia, including that its onset is frequently preceded by a viral illness or trauma and that the patient profile is typical, and “extra” symptoms frequently occur which are consistent with other forms of dysautonomia (indeed, many IST patients might have been labeled as suffering from IBS, POTS, or CFS if they had seen someone other than an electrophysiologist). Then, of course, there’s the fact that something stimulates the successfully ablated SA nodes to regenerate, suggesting a more systemic problem than intrinsic SA nodal disease. Finally, even during transiently successful SA nodal ablations, the other symptoms consistent with dysautonomia typically persist.

The treatment of IST would be straightforward if SA nodal ablation offered permanent relief from symptoms. Unfortunately, however, this is usually not the case. The mainstay of therapy for IST therefore is pharmacologic therapy with β-blockers, calcium blockers, type Ic antiarrhythmic agents, and—in countries where it is available—ivabradine (a drug that slows the automaticity of the SA node). Usually, a combination of drugs is required to achieve an adequate slowing of the heart rate. Patients also often respond to the more general measures used for dysautonomia (see next section), especially long-term aerobic-exercise training.

In patients who remain largely disabled by symptoms of IST despite noninvasive efforts at control, SA nodal ablation should be strongly considered despite its drawbacks.

Finally, simply waiting may be an option for some patients. The natural history of this disorder has not been well documented, but it seems likely that IST tends to improve over time in most individuals, as is the case with most of the dysautonomias. “Doing nothing” may not be an option for patients who are severely symptomatic, but many patients with IST can tolerate their symptoms once they are assured that they do not have a life-threatening cardiac disorder, told that the problem is likely to improve on its own eventually, and enlightened as to the other treatment options.

Treating a patient with dysautonomia, like making the diagnosis, is often a challenge. The keys to treatment are reassurance and patience.

The physician should keep in mind that, despite the fact that dysautonomia is an honest-to-goodness, actual medical (as opposed to psychological) condition, by the time the patient has seen two or three doctors and has been told there’s actually nothing wrong, or that they’re crazy, it is the rule for the patient to compound their underlying dysautonomia with a state of real anxiety and/or depression. This secondary neurosis almost always greatly exacerbates their symptoms.

So a critical step in the treatment of dysautonomia is reassurance. First, the patient needs to be told that they’re actually not nuts, that they have a legitimate and well-recognized medical problem—and that there’s a name for it. They should be told about the concept of autonomic imbalance, and that this state of imbalance is usually triggered by some distinct event (which most often the patient will be able to identify). They should be told that, in general, dysautonomia is seen in young, healthy patients with robust autonomic nervous systems, and that over time the dysautonomia usually goes away or improves substantially (this improvement, however, may take several years). Finally, they should be told that there are several things that can be done to help minimize their symptoms while their autonomic nervous system “resets” itself.

Just telling the patient this much often provides an immediate sense of relief. They are not crazy. They have a real medical problem, and they have a doctor who understands it. It is likely to get better, and there’s something they can do about it in the meantime. These facts provide the patient with a sense of control over their own destiny, and this sense of control will often relieve a lot of their anxiety, diminish the severity of their symptoms, and help them cope with the symptoms that remain.

The “patience” component of treating dysautonomia is important because there is no direct treatment for this condition. Rather, there are a host of therapies that help relieve one symptom or another in one patient or another—and so adequately treating dysautonomia often requires a prolonged period of trial-and-error therapeutics. Recognizing this fact up front will help both the doctor and the patient avoid frustration (and symptom-exacerbating anxiety) during what is likely to be a long process of optimizing therapy.

Non-Drug Therapy for Dysautonomia

Underlying Causes

In addition to the “idiopathic” varieties of dysautonomia we are discussing here, autonomic dysfunction can also be caused by numerous underlying medical conditions. These include a host of neurological conditions (including multiple sclerosis, Shy–Drager syndrome, Parkinson’s disease, Huntington’s disease, and Guillain–Barré syndrome), systemic diseases (including diabetes and amyloidosis), active infectious diseases (including HIV/AIDS, diphtheria, and Chagas disease), connective tissue diseases, hepatic disease, renal failure, and many others. So an early step in diagnosing and treating dysautonomia should be to do a thorough medical evaluation looking for potential underlying causes, and if one is found, to treat it aggressively.

Exercise

It is well known that chronic exercise training produces changes in autonomic balance. Further, it has been shown that in patients with dysautonomia—particularly patients with hemodynamic instability (POTS), IST, or frequent vasovagal syncope—aerobic training can significantly reduce elevated resting heart rates, improve orthostatic symptoms, and in general improve hemodynamic stability. In these patients, however, beginning an exercise program can be a challenge, since being upright can precipitate symptoms or cause excessive elevations in heart rate.

Recently, however, investigators have reported that patients with autonomic hemodynamic instability can achieve excellent results if they begin their exercise program using a “non-upright” form of exercise, such as a recumbent bicycle, a rowing machine, or swimming (Fu Q et al., Hypertension 2011; DOI: 10.1161/hypertensionaha.111.172262). The exercise has to begin slowly, a few minutes at a time, a few times per week, depending on what the patient can tolerate. But generally, after a month or two, a “training effect” becomes noticeable, whereby the patient can exercise more frequently and for longer periods of time. Most patients can eventually begin upright exercise activities such as walking, jogging, or bicycling. As their fitness improves, these patients usually experience a marked improvement in their baseline symptoms.

As a bonus, the fact that the patient is actively doing something that will lead to an improvement in their often-disabling symptoms gives them a sense of control over their own destiny that is therapeutic in itself. So an exercise program, with the physician’s ongoing supervision and advice, should be the “baseline” therapeutic approach to many varieties of dysautonomia—but in particular, those varieties marked by hemodynamic instability. In contrast to the older patients for whom doctors usually prescribe exercise, the much younger patients with dysautonomia—who quite often seem to have been athletes prior to their illness—are more often highly motivated to gain control over their medical condition and their lives. Typically, they will dedicate themselves to an exercise program if one is encouraged by a doctor.

Fluid Management and Daily Precautions

Patients whose dysautonomia includes orthostatic symptoms, inappropriate tachycardia, or vasovagal syncope ought to be coached in maintaining good hydration. They generally should not be placed on salt restriction, and in some cases might benefit from increasing sodium consumption. Patients with orthostatic symptoms must take appropriate precautions when arising from a seated or lying position. This is especially important first thing in the morning, when fluid balance is typically as negative as it ever gets. Such precautions might include sitting on the side of the bed for a few minutes and drinking a glass of water before standing, immediately walking upon arising (instead of standing in place), and wearing ankle weights for the first few minutes after getting up (to stimulate muscular action in order to improve blood return). Other “tricks” that sometimes help with hemodynamic instability include elevating the head of the bed 12 inches or so at night, taking showers while sitting down, and scheduling most daily activities in the afternoon (when symptoms tend to diminish), instead of in the morning.

Other Nonpharmacologic Measures

Patients with dysautonomia have responded favorably to biofeedback techniques, meditation, yoga, and other similar practices known to alter autonomic tone. Doctors taking care of these individuals should try to keep an open mind about such nontraditional options.

Drug Therapy for Dysautonomia

Several types of medication can help alleviate symptoms associated with dysautonomia. To a large extent, these medications are used on a trial-and-error basis, and very often several drug trials are needed before a drug or drug combination is found that provides satisfactory symptom relief without producing intolerable side effects.

Drugs that seem to offer some help, at least occasionally, include β-blockers (especially carvedilol and labetalol, which provide both α and β blockade), selective serotonin reuptake inhibitors, fludrocorisone, midodrine, methyldopa, ibuprophen, clonidine, and (in patients with severe POTS) erythropoetin.

Patients with gastrointestinal symptoms often benefit from eating frequent small meals, increasing dietary fiber, avoiding foods that seem to have caused particular problems, and using anticholinergic medication.

The Bottom Line on Treating Dysautonomia

The bottom line is that treating dysautonomia is not by any means a “once and done” affair. The right therapy always needs to be individualized, and virtually always requires establishing a long-term and trusting doctor–patient relationship. The end result, however, is often very rewarding for both parties.

Electrophyiologists, given the nature of their field, will end up seeing a lot of patients with dysautonomia, and in many cases they will be the ones who actually make the diagnosis. The electrophysiolgist who is unwilling to develop the kind of long-term relationship with these patients that adequate treatment will require ought at least to feel obligated to identify a few trusted colleagues who understand this family of conditions and are able and willing to give these patients the attention they need in order to return them to a happy and functional life.

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