Refer to: Robin ED, Abuabara F, Myers C, et al: Pectus excavatum and cardiopulmonary complications-Stanford University School of Medicine Pulmonary Rounds (Specialty Conference). West J Med 130:522-530, Jun 1979
* . .;Modarator:.
.EGENE D.
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FuAD ABUABARA:t The case for discussion this morning is that of a 64-year-old woman admitted to the cardiology service for evaluation of pericardial effusion, atrial fibrillation and mitral regurgitation. The cardiologists were perplexed by her extreme dyspnea on exertion and asked us to evaluate her case for possible pulmonary disease. The patient considered herself well until 1967, when there was an episode of paroxysmal atrial fibrillation (PAF) which was successfully treated with digoxin. There were similar episodes of PAF in 1968, 1969 and 1974. These were treated with digoxin and either propranolol or quinidine. Since 1974 there have been short episodes of palpitations and light headedness at least weekly. In January 1977 the patient was seen in Letterman Army Medical Center, San Francisco, with PAF. An echocardiogram indicated mitral valve prolapse. An electroc-ardiogram showed a 2-mm ST segment depression in the precordijal leads. *Director, Pulmonary Function Laboratory. tThird Year Medical Student at the time the paper was submitted. Reprint requests to: Eugene D. Robin, MD, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305.
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JUNE 1979 * 130 * 6
There was no evidence of shunt on a technetium Tc 99m shunt study. On August 10, 1977, the patient was seen at Stanford University Hospital with shortness of breath, fatigue, indigestion and a 9pound weight loss over three months. The diagnosis was atrial fibrillation and mitral regurgitation. She was treated initially with propranolol as an outpatient, and then with intermittent oxygen for extreme dyspnea. This was unsuccessful in relieving symptoms and she was admitted to hospital for examination. As a child she had had scarlet fever and Sydenham chorea (St. Vitus' dance). Subsequently a heart murmur developed and she was told to restrict her activities. She had a successful pregnancy without cardiac complications and obtained health insurance without difficulty. Moderate scoliosis and severe pectus excavatum were noted in childhood. She had had a tonsillectomy as a child. Saphenous vein stripping was done in 1959 and a benign right ovarian tumor was removed in 1967. On physical examination, the patient was found to be pleasant and in no distress at rest. The pulse
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rate was 78 per minute and regular. Blood pressure was 115/80 mm of. mercury. The respiratory rate was 16 per minute. Findings on chest examination were a pronounced pectus excavatum and scoliosis of the thoracic spine with concavity to the left. Excursion of the chest wall was moderately restricted. A systolic murmur consistent with mitral regurgitation was noted intermittently. Cardiac catheterization showed mitral valve prolapse. The left ventricular end diastolic pressure increased from 10 torr to 28 torr with exercise. Pulmonary artery wedge pressure rose from a mean of 10 to a mean of 18 torr with elevation of the legs. There was no cardiac shunt shown by hydrogen inhalation study. A sector scan showed a minimal apical pericardial effusion. Pulmonary angiography and coronary ateriography were normal. Pulmonary function tests showed mild obstructive disease. Results of exercise studies showed the bicarbonate value decreased from 27 to 21 mEq per liter with mild exercise while arterial oxygen pressure (Pao2) remained at 97 torr and arterial carbon dioxide pressure (Paco2) remained at 35 torr. These studies suggested that circulatory factors limited the degree of exercise.
EUGENE D. ROBIN, MD:* The patient had mitral regurgitation. Do you wish to speculate on the origin of that? MR. ABUABARA: She had had scarlet fever and St. Vitus' dance, both manifestations of streptococcal infection, and a murmur developed later. She was told to restrict her activities. Mitral regurgitation can result from rheumatic fever with carditis. I suppose it could also be congenital. DR. ROBIN: It is conceivable, therefore, that she had three abnormalities, all congenital in origin. What you would want to know, I suppose, would be the temporal relationships between the development of the spine and when scoliosis can develop, the development of the thoracic cage and when pectus excavatum can develop, and how soon in life the mitral valve is capable of being modified to produce regurgitation. I suspect that no one in this room knows the answer to that. I knowv that I don't, but it is at least conceivable that all three were manifestations of the same underlying process occurring during fetal
life. *Professor of Medicine and Physiology, Division of Respiratory
Medicine.
CHRISTOPHER MYERS, MD: t Do you think it is possible that a severe pectus excavatum and scoliosis, and the resulting impingement on the heart, produced a mitral insufficiency murmur? DR. ROBIN: Yes. That is not the most common cardiac manifestation of pectus excavatum, but presumably sufficient cardiac distortion can occur to produce mitral insufficiency. JAMES THEODORE, MD:t What percent of patients who have scoliosis also have mitral regurgitation? DR. ROBIN: Well, if you had asked what percentage of patients with scoliosis have murmurs, then I would have said not an insignificant percentage. I would guess at least 20 percent. It is possible for bizarre murmurs to develop, both systolic and diastolic, of loud intensity, which are innocent and merely related to distorted geometry within the thoracic cage. This is well described in the so-called straight back syndrome.' Could we go back just a bit? What was felt to be the cause of paroxysmal atrial fibrillation? MR. ABUABARA: I do not have any reference to that. DR. ROBIN: I see. Suppose you had been her physician then, what would you have thought? MR. ABUABARA: Well, after you have pointed out the association with all these other structural deformities, I would have thought of some congenital cause; maybe a second diagnosis would be rheumatic heart disease. PATRICK HAMMER, MD:§ I think the most logical approach would be to consider rheumatic heart disease; this seemed to be the leading candidate because of the patient's childhood illness; however, it does not rule out other possibilities. DR. ROBIN: Yes. In 1967 she was about 51 years old, so it would be a relatively long time between her birth and the development of paroxysmal atrial fibrillation. One would have to ask if this evidence of increasing atrial decompensation was related to mitral insufficiency or whether heart disease is developing independently. MR. ABUABARA: She was referred to Stanford University Hospital for a cardiology workup. She had increased shortness of breath and fatigue, tClinical Assistant Professor of Medicine. tAssociate Professor of Medicine. §Fellow in Respiratory Disease.
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with many episodes of indigestion. She was treated with digoxin and propranolol. Sector scan at this time showed a percardial effusion and right ventricular enlargement; however, no prolapse of the mitral valve was shown. DR. ROBIN: Prolapse was indicated by ultrasound but not by sector scan. What kind of analysis should we use? Either there was prolapse that the sector scan did not pick up; or there was no prolapse which the ultrasound picked up as an artifact; or there was prolapse that had reversed itself and was shown on ultrasound studies but not on sector scan. The decision one has to make, therefore, is which of those possibilities is more likely? That is to say, how often do prolapses reverse themselves, and how accurate is ultrasound versus sector scan in picking up prolapses? You know, if you get conflicting data, you cannot ignore the conflict. THOMAS RAFFIN, MD:* By sector scan you mean the new ultrasonic technique which shows a cross sectional image as compared with the old M modes. This new technique produces a much better resolution. DR. HAMMER: I would guess that the sector scan did not show the prolapse. DR. ROBIN: That would be my guess. I do not think that serious prolapse is readily reversed. Early ultrasound techniques are relatively inaccurate; in fact, there are some series that suggest everyone has prolapse of the mitral valve. As you know, there are all kinds of syndromes described as sudden death with prolapse, arrhythmia with prolapse, and the like. Many of these may have been based on cases of patients who really did not have prolapse-the technique used was too sensitive and not accurate. ALLAN HANCE, MD:t There is a situation in which one might expect prolapse to be reversed and that is in a person who had 2-mm ST depression, namely papillary muscle dysfunction on an ischemic basis. DR. RAFFIN: My impression would have to be that the sector scan is more accurate than the M mode echo. Could you tell us why propranolol was being given in the case of the woman we were discussing? Was it for chest pain or for
arrhythmia? *Fellow in Respiratory Disease. tFellow in Respiratory Disease.
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MR. ABUABARA: The reasons are not clear to us. DR. ROBIN: An additional fact, in terms of her cardiac history, is useful. You state that her history indicates the presence of lifelong disease, and she has had one of the best stress tests available for cardiac function-pregnancy. In treating a woman with heart disease, you should obtain, as carefully as you can, a history of occurrences during the patient's pregnancy. Dr. Raffin, what is the natural life history, for example, of valvular heart disease as related to pregnancy? DR. RAFFIN: Toward the second and third trimester, especially, women who are pregnant sometimes have problems with decompensation of the valvular heart disease. They need careful followup examination in a high-risk clinic because pregnancy may precipitate congestive heart failure. DR. ROBIN: Is there a logical explanation for the fact that the most difficulty occurs in about the seventh month? DR. RAFFIN: The blood volume goes up significantly during the last trimester.
DR. ROBIN: It is interesting that if the pregnant patient can be carried past the seventh or eighth month, the actual stress of childbirth can almost always be successfully managed. That is not the time at which the patients have extreme difficulty and die. The process of childbirth, by itself, is much less demanding, and as Dr. Raffin has intimated, difficulty with heart failure correlates well with the curve of plasma volume which rises progressively until the seventh month, and comes down in the last month or two. This is also true of total body water. So, plasma volwme, total body water and cardiac symptoms peak in about the seventh month, and then -decrease. The old dictum was that if you could carry the patient past the sixth or seventh month, then the patient would do well. MR. ABUABARA: The woman had anorexia and a weight change of nine pounds in the last three months. She had no symptoms of heat intolerance, tremors, nervousness, goiter or changes in blood pressure. DR. HANCE: I am curious about the appearance of the pulmonary artery on the x-ray film of the chest. I realize that there probably is rotation. I would have said that it seems less prominent on the left than on the right and would have inter-
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preted that bulge as the left atrium. I think the bulge you see on the left heart border is the left atrial appendage, which does come out relatively high. I just do not see a good pulmonary artery. DR. RAFFIN: Do you think there is pruning of the pulmonary vasculature? DR. ROBIN: Yes. DR. RAFFIN: I agree. I think the right side is rather remarkable. You can follow it only about two thirds of the way out. DR. ROBIN: Now, there is the other issue as to whether that is atrial appendage or not. It is much too high to be either a pulmonary artery or an atrial appendage. I think all you can say from the x-ray film of the chest is that the right ventricular shadow looks prominent, which is different from saying it is large because the chest is distorted. The left ventricular size appears to be normal and she does not have the aneurysmal dilatation of the left atrium which is associated with far advanced mitral insufficiency. In fact, I think the left atrial shadow is normal, which is almost surprising in view of the gross distortion of the chest. Dr. Newman, would you like to review the catheterization data? ANDREW NEWMAN, MD:* The wedge pressure is raised significantly from 10/9/7 (systolic/diastolic/mean) to 19/18/16 torr just on elevating the legs, and the pulmonary artery pressure changed from 25/6/12 to 32/29/26 torr with exercise. On that exercise, which was bicycle exercise on the table, she increased her minute ventilation to only 17 liters per minute. DR. THEODORE: There has been some increase in the wedge pressure. Do you think that the increase in pulmonary artery pressure is proportionate to the increase in wedge pressure, or do you think that the pulmonary artery pressure goes up higher than can be purely accounted for by the increase in wedge pressure? DR. NEWMAN: Wedge pressures were measured on leg elevation only. The pulmonary artery pressure is measured on exercise and the wedge pressure is measured just on leg elevation, so we do not have an exercise wedge, which would probably be higher. Anyway, they did selective coronary angiography. The rationale was that the patient had exercise tests with 2 and 3 mm ST *Fellow in Respiratory Disease.
segment depression. The coronary arteries were absolutely healthy looking. The left ventricle showed good contraction but early relaxation. DR. ROBIN: Were the rest and exercise studies done close to the time that propranolol therapy was stopped? Was it days, weeks or months away? DR. NEWMAN: Days.
DR. ROBIN: Well, there was a substantial increase in wedge pressure. I do not know what to make of it. I could easily visualize that people given propranolol, a myocardial depressant, who have a sudden increase in blood volume, would have a left ventricle that might not respond appropriately and would show an increase in wedge pressure. I think that is an important point. We know that propranolol produces functional impairment of the left ventricle. Once a patient has had propranolol and a change of this kind occurs, I think it is an open issue as to whether the change is due to the drug or due to structural changes in the left ventricle. Can we go back to the catheterization data before we proceed? Another finding in the patient's data which is very peculiar is that the left ventricular end diastolic pressure is zero, and then the pressure rebounds to 28 torr during diastole. I think you can make a pathophysiologic reconstruction of. events, especially because the right ventricle tracing shows no end diastolic pressure, with a rebound to only 4 torr. DR. RAFFIN: So the patient clearly has left ventricular dysfunction without evidence of right
ventricular dysfunction. DR. ROBIN: Yes, the tracing is said to show that the left ventricular pressure falls to zero and then rebounds to 28 torr instead of 4 or 5 torr. I think it is also important that this is not happening on the right side. I am going to interpret this as indicating altered compliance of the left ventricle. Similar compliance changes are occasionally seen in cardiac involvement with pectus excavatum or endocardial fibroelastosis, or in diffuse endomyocardial fibrosis or constrictive pericarditis. Generally this is found in both ventricles. My reconstruction is that a major effect of pectus excavatum in this case is to trap the left ventricle and therefore isolated left ventricular disease appears like a restrictive cardiomyopathy or constrictive pericarditis, but is limited to one side (the left). I have never seen that described before in pectus excavatum, so take my analysis with suspicion. Even THE WESTERN JOURNAL OF MEDICINE
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though the left ventricular end diastolic pressure is zero, a more pertinent finding is that there is a rebound of 28 torr, and if we look at the tracing (if this thesis is correct) then what will be shown is not only a rise to 28 torr, but a series of oscillations as the ventricle first exceeds its elastic limits and then begins to shudder as the blood fills it. Indeed, if this reconstruction is correct, one might go to the bedside and find a diastolic shudder, a prominent early third sound like a gallop, only much louder. Whether or not that is the mechanism of left ventricular abnormality can be debated. However, the results of catheterization do show one cause of dyspnea: increases in wedge pressure to levels that cause pulmonary edema. Consequently, the patient's dyspnea must stem partly from an abnormal left ventricle. DR. NEWMAN: The cardiologists did not make this reconstruction. They were concerned about the patient's extreme dyspnea on exertion and asked us to do pulmonary function studies. Flow rates and helium washout time were normal. We are uncertain whether the volume measurements were accurate.
DR. THEODORE: One thing missing is the diffusion
capacity. DR. HANCE: You said she just could not hold her breath for ten seconds. DR. THEODORE: Yes.
DR. NEWMAN: At this point, we brought her back for testing at various levels of exercise using the method recommended by the American Heart Association.2 Basically, exercise is done at four different levels beginning with Bruce 1, 2, 3 and 4. Bruce 0 is 1.2 percent grade at 0 miles per hour; Bruce 0.5 would be 1.7 at 5 miles per hour; Bruce 1 is 1.7 at 10 miles per hour; Bruce 2 is progressing up from that. Most people would reach Bruce 4 with some gasping. Athletes will usually go to Bruce 5. One would expect the patient to go at least to Bruce 1 or Bruce 2. We planned to have her walk or run for seven minutes, but after five minutes she was holding onto the railings with extreme shortness of breath and many complaints. She was unable to continue. At that point, the heart rate was 165 beats per minute and the bicarbonate value dropped to 21 mEq per liter with the pH dropping to 7.38, while Pao2 remained at 97 torr. At this point you have shown that the patient has been able to 526
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maintain oxygenation but circulatory limitation of exercise tolerance is indicated by acidosis. I think this is consistent with what Dr. Robin says about the patient's ventricle; and I think that her problems are, in fact, circulatory and not pulmonary. DR. RAFFIN: Would you use a pH of 7.38, Paco2 of 35 and a bicarbonate value of 21 mEq per liter as evidence for acidosis? DR. ROBIN: Although the change in pH is within measurement error, the change in bicarbonate value is 6 mEq per liter and is significant. DR. HANCE: Most people exercised to the point where they must stop because of circulatory limitation would show a greater degree of acidosis than 7.38. This would suggest that in this case there must be other factors stopping the patient, for instance, a rise in wedge pressure and dyspnea on some other basis.
DR. ROBIN: I do think there is a significant decrease in bicarbonate. DR. HANCE: But you and I would not stop exercising at this point. We would be able to go to another level or two. DR. ROBIN: Please speak only for yourself. DR. RAFFIN: If an increased left ventricular diastolic pressure and pulmonary capillary wedge pressure developed with exercise, it is quite remarkable. The patient's alveolar-arterial oxygen difference increases, but not notably. DR. ROBIN: What is more pertinent is that the arteriovenous/oxygen difference increases 5 volumes per dl, a large increase. Moreover hemodynamic measurements show increases in wedge and pulmonary artery diastolic pressure to levels associated with increased lung extravascular water. This implicates pulmonary edema as a factor in the dyspnea and indicates left ventricular disease for which I have supplied a logical (although possibly incorrect) explanation. DR. THEODORE: The question you all should ask is, "How do we know she does not have pulmonary limitations rather than circulatory limitations?" I think the point Dr. Newman was making was that although we can argue whether we really pushed her to the limits, there is no one here who would not agree that the drop in bicarbonate is significant and, at least by definition, this would appear to be circulatory limitation. The total
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oxygen consumption at that point was significantly less than one would expect for someone her age. Also she never reached two thirds of her maximum voluntary ventilation (MW). Was she stopped because of some kind of intrinsic lung disease? Is this why she could not reach her Mvv? When you look at this case, you see that the blood gas values certainly do not bear that out. If anything, the Paco2 dropped as the Pao2 increased. All we have is an increase in physiologic dead space, and that could certainly be consistent with some kind of abnormality within the pulmonary circulation. DR. RpBIN: People stop exercising for many different reasons. Patients with mild degrees of lactic acidosis, for example, may stop exercising be-cause they are neurotic, as well as having pulmonary edema develop. Poorly conditioned patients may show an early pulse from lactic acidosis. I suspect that patients treated with propranolol may show premature lactic acidosis. The latter possibility is important in this patient: biochemical evidence of circulatory impairment develops as a relatively early degree of increased oxygen consumption, and with our knowledge that should be interpreted as circulatory limitation. DR. RAFFIN: When the patient's ventilatory response to exercise changes from 3.14 to 33.5 liters per minute, about 25 percent to 30 percent of the MVV, do you think the response is inappropriate for that amount of exercise? Gradually some lactate acidosis was shown. DR. ROBIN: Dr. Lynne-Davies should comment and then I will give you my opinion. What percentage of the Mvv does one usually mobilize during peak exercise?
PATRICIA LYNNE-DAVIES, MD: * Well, allegedly 65 percent, something in that order, but there are one or two peculiarities in this case. First, the tidal volume at rest is extraordinarily low even for someone who is fairly small. Consequently, she has a spectacular increase in tidal volume with exercise. Second, although it may well be true that her lung volumes are normal, it is interesting that the ratio of residual volume to total lung capacity is elevated, and the functional residual capacity is mildly elevated. I think you also found a functional residual capacity that was high. So I think that there may well be some limitation. *Associate
Professor of Medicine.
There is no question that one does not function as well at 60 percent or 70 percent total lung capacity as you do at 50 percent, just in terms of mechanical ability to shift ventilation around. Having said all of that, I still do not think these are in any sense limiting factors. I am impressed, just as Dr. Robin has been, by factors like the increase in her arteriovenous oxygen pressure difference with exercise. These seem much more dramatic to me. DR. ROBIN: Given the general issue of lungs versus circulation, I do not think it is possible to say that the patient has perfectly normal lungs. Indeed, given mitral stenosis or coronary artery disease, which is hemodynamically significant, you will almost never find normal lungs. At times you will find problems we generally consider representative of obstructive lung disease. After all, the mucosae of the bronchi become edematous and bronchiolar changes occur with pulmonary edema. I believe the main focus of this patient's disorder is circulatory for two reasons; objective measurements show that the circulation is primarily impaired, and we can come up with a logical explanation for the impairment. A handle for discussing this case is to ask, "What happens in patients who have severe pectus excavatum, even without scoliosis?" In most patients, nothing happens. If you measure lung function and cardiac function not only when, for instance, the patient is young, but continue to make measurements, the interference of the pectus excavatum with the function of either the heart or the lungs is minimal or nonexistent. That brings up another point. If you look at 100 patients who have had a surgical operation for pectus excavatum the overwhelming indication is cosmetic. It is interesting that the surgical procedure for the disorder is bloody and complicated. In one way, pectus excavatum in most patients represents an imbalance between a surgical procedure for something cosmetically wrong with the patient and a surgical procedure for physiologic indications. In a small number of patients with the disorder restrictive'lung disease develops, and the restriction is pretty clearcut; it is not as tenuous as in this patient. The pectus excavatum is usually severe and notable reductions are seen in all lung volumes. Such patients have rapid, shallow breathing and the natural life history, as far as I know, is not progressive. Patients first present with comTHE WESTERN JOURNAL OF MEDICINE
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plaints of dyspnea, and there are examples in which surgical treatment relieves restrictive lung disease. Another complication more or less well documented in the literature is restrictive heart disease, and up until now my view is that it appears like chronic restrictive pericarditis, endomyocardial fibrosis or endocardial fibroelastosis. Both sides of the circulation are involved, with generally an equalization of pressure across both. When right ventricular catheterization is carried out in the patient there is a right ventricular diastolic dip (square root sign). Not uncommonly you hear the so-called pericardial knock, which is not necessarily pericardial in origin. These patients may have severe congestive heart failure. The biventricular heart disease can be treated by surgical operation, which corrects the pectus excavatum.3 Pulmonary hypertension may represent another complication. One patient with severe pulmonary hypertension and pectus excavatum made a profound impression on me. This was a woman in her late 20's who was married to an Army officer in Hawaii. Her husband went to see his physician each year for an examination that included an exercise test. She accompanied her husband to the physician's office and when the husband finished the exercise test she asked if she could try it. She mounted the treadmill, took about four steps and fainted. It was clear that she had severe heart disease. An x-ray film of the chest showed a pronounced pectus excavatum, and cardiac catheterization showed severe pulmonary hypertension with pulmonary artery pressures equal to systemic pressures. Findings on pulmonary angiograms were normal and the patient had the usual kind of workup for pulmonary hypertension, which showed nothing. Primary pulmonary hypertension was diagnosed. It occurred to me that there could well be a pathogenetic link between the pectus excavatum and the development of severe pulmonary hypertension. The pathogenetic link could be explained by what we have called the Goldblatt lung.4 Under several clinical circumstances, there is the development of pulmonary hypertension in patients who have reductions, without cessation, of regional pulmonary blood flow over a long period. In going back to the concept of primary pulmonary hypertension, there are two important features, one of which is not usually considered: increases in pulmonary artery pressure that occur without a known cause and the development of 528
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a disproportionate degree of pulmonary hypertension for any given degree of heart or lung
disease. If you go back to the basic relation between mean pulmonary artery pressure and flow in a normal lung, the flow must double to produce an increase in pressure. There are three or four conditions in which there is less than 50 percent of the pulmonary vasculature involved in disease of the lung or the pulmonary apparatus, but in which the patient has severe pulmonary hypertension that is disproportionate. This may occur in unilateral pleural fibrosis. We collected a series of four cases, and there now have been about three or four more reported in the literaturecases of unilateral pleural restriction with severe pulmonary hypertension.4 The question is, if the disease involves only one lung, why is the pulmonary artery pressure elevated? The second cdndition that fits this classification is multiple regional pulmonary coarctations. There are well described cases in which there are multiple small pulmonary artery coarcts as a congenital defect.5 The degree -that is, the number of vessels involved-is not of the magnitude which would generally occlude greater than 50 percent of the pulmonary vasculature. These patients may have striking pulmonary hypertension, in fact, that is one of the clinical features. The third condition is kyphoscoliosis; progressive pulmonary hypertension may develop in patients with this condition even if there are no overt difficulties with breathing.6 Dr. Liebow, impressed by this phenomenon, reported neural elements which he described as neuroepitheliomas in the lungs of these patients. He hypothesized that the neuropithelioma might be the site of the release of a humor that produced generalized pulmonary hypertension. Therefore, when I saw the patient with pectus excavatum and pulmonary hypertension, I wondered whether the disorders could possibly be related. On an intuitive level, it was convincing enough to suggest that the patient, at age 27, has pulmonary artery pressures equal to systemic pressures. The length of life she had left, at least statistically, was short and there was already, when I saw her, right ventricular failure and functional tricuspid insufficiency. One possible therapeutic approach was to correct the pectus excavatum. Two other experts (if I qualify as an expert) were consulted and they felt that my suggestion was outlandish. Nothing was done. If my reconstruction is correct, pectus excava-
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tum in this case represents a form of cardiac restrictive disease in which the anatomical restriction is largely localized to the left ventricle; therefore, the usual bilateral signs of restrictive cardiac disease related to the disorder are not shown. However, pectus excavatum does restrict her cardiac output during exercise, and gives her periods of pulmonary edema when she is exercising or has increases in blood volume. Her case, therefore, represents isolated left ventricular disease in which, conceivably, the prolapsed mitral valve might have an additional role. However, the major problem is related to mechanical restriction of the left ventricle. In addition, the patient is being treated with propranolol, which depresses myocardial contractility. If it is true that the problem is related to mechanical restriction (and it is easy to persuade yourself that a logical explanation is true) then this case represents another unusual complication of pectus excavatum. Then the question is what should be done? Clearly, therapy with propranolol should be stopped because it would render a noncompliant left ventricle even less compliant. If that failed, one might consider relieving the disorder surgically and freeing the left ventricle. I would argue against this for two reasons: The first is that the surgical operation is difficult and is usually a four- to five-hour procedure with major blood loss in which the sternal plate is unroofed by cutting the ribs and lifting the sternum. A prosthetic device is inserted and the sternal plate is sewed in place. The second reason is that the case makes clear physiological sense to me. This is dangerous; when a case fits into a neat package you should suspect the analysis. DR. HANCE: Another possible diagnosis is restrictive heart disease, also associated with unilateral signs that are left sided only. This is now referred to at the National Institutes of Health as asymmetrical septal hypertrophy, and I think it fits this case fairly well. The onset occurs when patients are in their 50's. In some cases, tachyrhythmia may be a problem and the kind of limitation would be highly suspicious of that. Prolapse of the valve may frequently be associated with it. This narrowing of the ventricular neck is highly suggestive. So, I would do a regular echo scan rather than a sector scan, and would look closely for that abnormality. DR. ROBIN: I do not object to that diagnosis, but I really think the problem is that the referring
physicians have used all their techniques, and cannot explain left ventricular disease on the basis of their data. Maybe the reason is that they (like we) are dealing with something that has not been described previously. DR. HANCE: Is asymmetrical septal hypertrophy a common diagnosis in the cardiology clinic here? That has not been my impression. This is a case in which you might have a pathologic abnormality without obstruction. DR. RAFFIN: Just as in most of Epstein's recent work in trying to study the epidemiology of prolapse, asymmetrical septal hypertrophy is a diagnosis made easily on just the A mode ultrasound. DR. ROBIN: My guess would be that septal hypertrophy or idiopathic hypertrophic subaortic stenosis could have been pulled out of the data had the data been suggestive; that does not necessarily mean that people have looked for it specifically. DR. RAFFIN: 1 would like Dr. Newman to get the pressure tracings. This case is fascinating if you really do have the classical square root sign of some types of restrictive cardiac abnormalities; if you do not, then the case is still interesting, but less elegant, I think. In the August 5, 1972, issue of the New England Journal of Medicine there is a report of a series of patients with pectus excavatum who were operated on for significant restrictive heart disease or symptoms due to the disorder. It is interesting that patients were more symptomatic when sitting than when supine, and this was thought to be the result of the heart dropping down further into the
pectus.7 DR. ROBIN: That form of dyspnea is called platypnea.8 DR. RAFFIN: It is not completely clear to me that surgical operation is inappropriate for this woman if her quality of life is zero. DR. ROBIN: The decision should not only be based on the quality of life. It should also be based on the security of feeling that your analysis is accurate. This is an important point because we are increasingly carrying out tests in patients because of insecure feelings that stem from inadequate knowledge. If I were certain that my analysis was correct, or that it had eight chances out of ten of being correct, then I might be enthusiastic THE WESTERN JOURNAL OF MEDICINE
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about using a surgical procedure. Confronted by a patient who is one in the world, and to come up then with an unprecedented indication for surgical operation would be arrogant. A bad guess might cost the patient some years of relatively happy life. I am certain I would begin by stopping the propranolol therapy. In swnmary, we have seen a patient with severe pectus excavatum and dyspnea. It seems unlikely that the manifestations are related to abnormal pulmonary mechanics, but rather to abnormal cardiac function. Pectus excavatum can produce restrictive lung disease, restrictive heart disease antd possibly pulmonary hypertension (by a Goldblatt mechanism). The hemodynamics suggest restrictive left ventricular disease that may have been intensified by the use of propranolol. After much soul-searching, the consensus would be to stop propranolol therapy and see what happens. FOLLOW UP: Review of the patient's cardiac tracings showed what seemed to be a square root sign with oscillations following the diastolic dip
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in the left ventricular tracing. This was considered by most (but not all) to indicate restrictive left ventricular disease. Propanolol therapy was stopped and the patient's condition has improved, but not to the point where she can tolerate normal exercise. However, she is considerably more comfortable. REFERENCES 1. Siegel J, Schecter G: The straight back syndrome. Am J Med 42:309-313, Feb 1967 2. Exercise Testing and Training of Apparently Healthy Individuals-A Handbook for Physicians, Amer Heart Assoc Committee on Exercise, Kattus AA, Chairman. New York, Am Heart Assoc, 1972 3. Chin EG: Surgery of funnel chest and congenital sternal prominence. Br J Surg 44:360-376, Jan 1957 4. Robin ED, Cross CE, Kroetz F, et al: Pulmonary hypertension and unilateral pleural constriction with speculations on pulmonary vasoconstrictive substance. Arch Intern Med 118:391400, Oct 1966 5. Arvidsson J, Karnell J, Moller T: Multiple stenosis of the pulmonary arteries associated with pulmonary hypertension diagnosed by selective angiocardiography. Acta Radiol 44:209-216, Sep 1955 6. Bergofsky EH, Turino GM, Fishman AP: Cardiorespiratory failure in kyphoscoliosis. Medicine 38:263-317, Sep 1959 7. Beiser G, Epstein S, Stampfer M, et al: Impairment of cardiac function in patients with pectus excavatum, with improvement after operative correction. N Engl J Med 287:267-272, Aug 10, 1972 8. Robin ED, Laman D, Horn B: Platypnea related to orthodeoxia caused by true vascular lung shunts. N Engl J Med 294: 941-943, Apr 22, 1976
* . .;Modarator:.
.EGENE D.
ROBIN, MD
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FuAD ABUABARA:t The case for discussion this morning is that of a 64-year-old woman admitted to the cardiology service for evaluation of pericardial effusion, atrial fibrillation and mitral regurgitation. The cardiologists were perplexed by her extreme dyspnea on exertion and asked us to evaluate her case for possible pulmonary disease. The patient considered herself well until 1967, when there was an episode of paroxysmal atrial fibrillation (PAF) which was successfully treated with digoxin. There were similar episodes of PAF in 1968, 1969 and 1974. These were treated with digoxin and either propranolol or quinidine. Since 1974 there have been short episodes of palpitations and light headedness at least weekly. In January 1977 the patient was seen in Letterman Army Medical Center, San Francisco, with PAF. An echocardiogram indicated mitral valve prolapse. An electroc-ardiogram showed a 2-mm ST segment depression in the precordijal leads. *Director, Pulmonary Function Laboratory. tThird Year Medical Student at the time the paper was submitted. Reprint requests to: Eugene D. Robin, MD, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305.
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JUNE 1979 * 130 * 6
There was no evidence of shunt on a technetium Tc 99m shunt study. On August 10, 1977, the patient was seen at Stanford University Hospital with shortness of breath, fatigue, indigestion and a 9pound weight loss over three months. The diagnosis was atrial fibrillation and mitral regurgitation. She was treated initially with propranolol as an outpatient, and then with intermittent oxygen for extreme dyspnea. This was unsuccessful in relieving symptoms and she was admitted to hospital for examination. As a child she had had scarlet fever and Sydenham chorea (St. Vitus' dance). Subsequently a heart murmur developed and she was told to restrict her activities. She had a successful pregnancy without cardiac complications and obtained health insurance without difficulty. Moderate scoliosis and severe pectus excavatum were noted in childhood. She had had a tonsillectomy as a child. Saphenous vein stripping was done in 1959 and a benign right ovarian tumor was removed in 1967. On physical examination, the patient was found to be pleasant and in no distress at rest. The pulse
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rate was 78 per minute and regular. Blood pressure was 115/80 mm of. mercury. The respiratory rate was 16 per minute. Findings on chest examination were a pronounced pectus excavatum and scoliosis of the thoracic spine with concavity to the left. Excursion of the chest wall was moderately restricted. A systolic murmur consistent with mitral regurgitation was noted intermittently. Cardiac catheterization showed mitral valve prolapse. The left ventricular end diastolic pressure increased from 10 torr to 28 torr with exercise. Pulmonary artery wedge pressure rose from a mean of 10 to a mean of 18 torr with elevation of the legs. There was no cardiac shunt shown by hydrogen inhalation study. A sector scan showed a minimal apical pericardial effusion. Pulmonary angiography and coronary ateriography were normal. Pulmonary function tests showed mild obstructive disease. Results of exercise studies showed the bicarbonate value decreased from 27 to 21 mEq per liter with mild exercise while arterial oxygen pressure (Pao2) remained at 97 torr and arterial carbon dioxide pressure (Paco2) remained at 35 torr. These studies suggested that circulatory factors limited the degree of exercise.
EUGENE D. ROBIN, MD:* The patient had mitral regurgitation. Do you wish to speculate on the origin of that? MR. ABUABARA: She had had scarlet fever and St. Vitus' dance, both manifestations of streptococcal infection, and a murmur developed later. She was told to restrict her activities. Mitral regurgitation can result from rheumatic fever with carditis. I suppose it could also be congenital. DR. ROBIN: It is conceivable, therefore, that she had three abnormalities, all congenital in origin. What you would want to know, I suppose, would be the temporal relationships between the development of the spine and when scoliosis can develop, the development of the thoracic cage and when pectus excavatum can develop, and how soon in life the mitral valve is capable of being modified to produce regurgitation. I suspect that no one in this room knows the answer to that. I knowv that I don't, but it is at least conceivable that all three were manifestations of the same underlying process occurring during fetal
life. *Professor of Medicine and Physiology, Division of Respiratory
Medicine.
CHRISTOPHER MYERS, MD: t Do you think it is possible that a severe pectus excavatum and scoliosis, and the resulting impingement on the heart, produced a mitral insufficiency murmur? DR. ROBIN: Yes. That is not the most common cardiac manifestation of pectus excavatum, but presumably sufficient cardiac distortion can occur to produce mitral insufficiency. JAMES THEODORE, MD:t What percent of patients who have scoliosis also have mitral regurgitation? DR. ROBIN: Well, if you had asked what percentage of patients with scoliosis have murmurs, then I would have said not an insignificant percentage. I would guess at least 20 percent. It is possible for bizarre murmurs to develop, both systolic and diastolic, of loud intensity, which are innocent and merely related to distorted geometry within the thoracic cage. This is well described in the so-called straight back syndrome.' Could we go back just a bit? What was felt to be the cause of paroxysmal atrial fibrillation? MR. ABUABARA: I do not have any reference to that. DR. ROBIN: I see. Suppose you had been her physician then, what would you have thought? MR. ABUABARA: Well, after you have pointed out the association with all these other structural deformities, I would have thought of some congenital cause; maybe a second diagnosis would be rheumatic heart disease. PATRICK HAMMER, MD:§ I think the most logical approach would be to consider rheumatic heart disease; this seemed to be the leading candidate because of the patient's childhood illness; however, it does not rule out other possibilities. DR. ROBIN: Yes. In 1967 she was about 51 years old, so it would be a relatively long time between her birth and the development of paroxysmal atrial fibrillation. One would have to ask if this evidence of increasing atrial decompensation was related to mitral insufficiency or whether heart disease is developing independently. MR. ABUABARA: She was referred to Stanford University Hospital for a cardiology workup. She had increased shortness of breath and fatigue, tClinical Assistant Professor of Medicine. tAssociate Professor of Medicine. §Fellow in Respiratory Disease.
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with many episodes of indigestion. She was treated with digoxin and propranolol. Sector scan at this time showed a percardial effusion and right ventricular enlargement; however, no prolapse of the mitral valve was shown. DR. ROBIN: Prolapse was indicated by ultrasound but not by sector scan. What kind of analysis should we use? Either there was prolapse that the sector scan did not pick up; or there was no prolapse which the ultrasound picked up as an artifact; or there was prolapse that had reversed itself and was shown on ultrasound studies but not on sector scan. The decision one has to make, therefore, is which of those possibilities is more likely? That is to say, how often do prolapses reverse themselves, and how accurate is ultrasound versus sector scan in picking up prolapses? You know, if you get conflicting data, you cannot ignore the conflict. THOMAS RAFFIN, MD:* By sector scan you mean the new ultrasonic technique which shows a cross sectional image as compared with the old M modes. This new technique produces a much better resolution. DR. HAMMER: I would guess that the sector scan did not show the prolapse. DR. ROBIN: That would be my guess. I do not think that serious prolapse is readily reversed. Early ultrasound techniques are relatively inaccurate; in fact, there are some series that suggest everyone has prolapse of the mitral valve. As you know, there are all kinds of syndromes described as sudden death with prolapse, arrhythmia with prolapse, and the like. Many of these may have been based on cases of patients who really did not have prolapse-the technique used was too sensitive and not accurate. ALLAN HANCE, MD:t There is a situation in which one might expect prolapse to be reversed and that is in a person who had 2-mm ST depression, namely papillary muscle dysfunction on an ischemic basis. DR. RAFFIN: My impression would have to be that the sector scan is more accurate than the M mode echo. Could you tell us why propranolol was being given in the case of the woman we were discussing? Was it for chest pain or for
arrhythmia? *Fellow in Respiratory Disease. tFellow in Respiratory Disease.
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MR. ABUABARA: The reasons are not clear to us. DR. ROBIN: An additional fact, in terms of her cardiac history, is useful. You state that her history indicates the presence of lifelong disease, and she has had one of the best stress tests available for cardiac function-pregnancy. In treating a woman with heart disease, you should obtain, as carefully as you can, a history of occurrences during the patient's pregnancy. Dr. Raffin, what is the natural life history, for example, of valvular heart disease as related to pregnancy? DR. RAFFIN: Toward the second and third trimester, especially, women who are pregnant sometimes have problems with decompensation of the valvular heart disease. They need careful followup examination in a high-risk clinic because pregnancy may precipitate congestive heart failure. DR. ROBIN: Is there a logical explanation for the fact that the most difficulty occurs in about the seventh month? DR. RAFFIN: The blood volume goes up significantly during the last trimester.
DR. ROBIN: It is interesting that if the pregnant patient can be carried past the seventh or eighth month, the actual stress of childbirth can almost always be successfully managed. That is not the time at which the patients have extreme difficulty and die. The process of childbirth, by itself, is much less demanding, and as Dr. Raffin has intimated, difficulty with heart failure correlates well with the curve of plasma volume which rises progressively until the seventh month, and comes down in the last month or two. This is also true of total body water. So, plasma volwme, total body water and cardiac symptoms peak in about the seventh month, and then -decrease. The old dictum was that if you could carry the patient past the sixth or seventh month, then the patient would do well. MR. ABUABARA: The woman had anorexia and a weight change of nine pounds in the last three months. She had no symptoms of heat intolerance, tremors, nervousness, goiter or changes in blood pressure. DR. HANCE: I am curious about the appearance of the pulmonary artery on the x-ray film of the chest. I realize that there probably is rotation. I would have said that it seems less prominent on the left than on the right and would have inter-
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preted that bulge as the left atrium. I think the bulge you see on the left heart border is the left atrial appendage, which does come out relatively high. I just do not see a good pulmonary artery. DR. RAFFIN: Do you think there is pruning of the pulmonary vasculature? DR. ROBIN: Yes. DR. RAFFIN: I agree. I think the right side is rather remarkable. You can follow it only about two thirds of the way out. DR. ROBIN: Now, there is the other issue as to whether that is atrial appendage or not. It is much too high to be either a pulmonary artery or an atrial appendage. I think all you can say from the x-ray film of the chest is that the right ventricular shadow looks prominent, which is different from saying it is large because the chest is distorted. The left ventricular size appears to be normal and she does not have the aneurysmal dilatation of the left atrium which is associated with far advanced mitral insufficiency. In fact, I think the left atrial shadow is normal, which is almost surprising in view of the gross distortion of the chest. Dr. Newman, would you like to review the catheterization data? ANDREW NEWMAN, MD:* The wedge pressure is raised significantly from 10/9/7 (systolic/diastolic/mean) to 19/18/16 torr just on elevating the legs, and the pulmonary artery pressure changed from 25/6/12 to 32/29/26 torr with exercise. On that exercise, which was bicycle exercise on the table, she increased her minute ventilation to only 17 liters per minute. DR. THEODORE: There has been some increase in the wedge pressure. Do you think that the increase in pulmonary artery pressure is proportionate to the increase in wedge pressure, or do you think that the pulmonary artery pressure goes up higher than can be purely accounted for by the increase in wedge pressure? DR. NEWMAN: Wedge pressures were measured on leg elevation only. The pulmonary artery pressure is measured on exercise and the wedge pressure is measured just on leg elevation, so we do not have an exercise wedge, which would probably be higher. Anyway, they did selective coronary angiography. The rationale was that the patient had exercise tests with 2 and 3 mm ST *Fellow in Respiratory Disease.
segment depression. The coronary arteries were absolutely healthy looking. The left ventricle showed good contraction but early relaxation. DR. ROBIN: Were the rest and exercise studies done close to the time that propranolol therapy was stopped? Was it days, weeks or months away? DR. NEWMAN: Days.
DR. ROBIN: Well, there was a substantial increase in wedge pressure. I do not know what to make of it. I could easily visualize that people given propranolol, a myocardial depressant, who have a sudden increase in blood volume, would have a left ventricle that might not respond appropriately and would show an increase in wedge pressure. I think that is an important point. We know that propranolol produces functional impairment of the left ventricle. Once a patient has had propranolol and a change of this kind occurs, I think it is an open issue as to whether the change is due to the drug or due to structural changes in the left ventricle. Can we go back to the catheterization data before we proceed? Another finding in the patient's data which is very peculiar is that the left ventricular end diastolic pressure is zero, and then the pressure rebounds to 28 torr during diastole. I think you can make a pathophysiologic reconstruction of. events, especially because the right ventricle tracing shows no end diastolic pressure, with a rebound to only 4 torr. DR. RAFFIN: So the patient clearly has left ventricular dysfunction without evidence of right
ventricular dysfunction. DR. ROBIN: Yes, the tracing is said to show that the left ventricular pressure falls to zero and then rebounds to 28 torr instead of 4 or 5 torr. I think it is also important that this is not happening on the right side. I am going to interpret this as indicating altered compliance of the left ventricle. Similar compliance changes are occasionally seen in cardiac involvement with pectus excavatum or endocardial fibroelastosis, or in diffuse endomyocardial fibrosis or constrictive pericarditis. Generally this is found in both ventricles. My reconstruction is that a major effect of pectus excavatum in this case is to trap the left ventricle and therefore isolated left ventricular disease appears like a restrictive cardiomyopathy or constrictive pericarditis, but is limited to one side (the left). I have never seen that described before in pectus excavatum, so take my analysis with suspicion. Even THE WESTERN JOURNAL OF MEDICINE
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though the left ventricular end diastolic pressure is zero, a more pertinent finding is that there is a rebound of 28 torr, and if we look at the tracing (if this thesis is correct) then what will be shown is not only a rise to 28 torr, but a series of oscillations as the ventricle first exceeds its elastic limits and then begins to shudder as the blood fills it. Indeed, if this reconstruction is correct, one might go to the bedside and find a diastolic shudder, a prominent early third sound like a gallop, only much louder. Whether or not that is the mechanism of left ventricular abnormality can be debated. However, the results of catheterization do show one cause of dyspnea: increases in wedge pressure to levels that cause pulmonary edema. Consequently, the patient's dyspnea must stem partly from an abnormal left ventricle. DR. NEWMAN: The cardiologists did not make this reconstruction. They were concerned about the patient's extreme dyspnea on exertion and asked us to do pulmonary function studies. Flow rates and helium washout time were normal. We are uncertain whether the volume measurements were accurate.
DR. THEODORE: One thing missing is the diffusion
capacity. DR. HANCE: You said she just could not hold her breath for ten seconds. DR. THEODORE: Yes.
DR. NEWMAN: At this point, we brought her back for testing at various levels of exercise using the method recommended by the American Heart Association.2 Basically, exercise is done at four different levels beginning with Bruce 1, 2, 3 and 4. Bruce 0 is 1.2 percent grade at 0 miles per hour; Bruce 0.5 would be 1.7 at 5 miles per hour; Bruce 1 is 1.7 at 10 miles per hour; Bruce 2 is progressing up from that. Most people would reach Bruce 4 with some gasping. Athletes will usually go to Bruce 5. One would expect the patient to go at least to Bruce 1 or Bruce 2. We planned to have her walk or run for seven minutes, but after five minutes she was holding onto the railings with extreme shortness of breath and many complaints. She was unable to continue. At that point, the heart rate was 165 beats per minute and the bicarbonate value dropped to 21 mEq per liter with the pH dropping to 7.38, while Pao2 remained at 97 torr. At this point you have shown that the patient has been able to 526
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maintain oxygenation but circulatory limitation of exercise tolerance is indicated by acidosis. I think this is consistent with what Dr. Robin says about the patient's ventricle; and I think that her problems are, in fact, circulatory and not pulmonary. DR. RAFFIN: Would you use a pH of 7.38, Paco2 of 35 and a bicarbonate value of 21 mEq per liter as evidence for acidosis? DR. ROBIN: Although the change in pH is within measurement error, the change in bicarbonate value is 6 mEq per liter and is significant. DR. HANCE: Most people exercised to the point where they must stop because of circulatory limitation would show a greater degree of acidosis than 7.38. This would suggest that in this case there must be other factors stopping the patient, for instance, a rise in wedge pressure and dyspnea on some other basis.
DR. ROBIN: I do think there is a significant decrease in bicarbonate. DR. HANCE: But you and I would not stop exercising at this point. We would be able to go to another level or two. DR. ROBIN: Please speak only for yourself. DR. RAFFIN: If an increased left ventricular diastolic pressure and pulmonary capillary wedge pressure developed with exercise, it is quite remarkable. The patient's alveolar-arterial oxygen difference increases, but not notably. DR. ROBIN: What is more pertinent is that the arteriovenous/oxygen difference increases 5 volumes per dl, a large increase. Moreover hemodynamic measurements show increases in wedge and pulmonary artery diastolic pressure to levels associated with increased lung extravascular water. This implicates pulmonary edema as a factor in the dyspnea and indicates left ventricular disease for which I have supplied a logical (although possibly incorrect) explanation. DR. THEODORE: The question you all should ask is, "How do we know she does not have pulmonary limitations rather than circulatory limitations?" I think the point Dr. Newman was making was that although we can argue whether we really pushed her to the limits, there is no one here who would not agree that the drop in bicarbonate is significant and, at least by definition, this would appear to be circulatory limitation. The total
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oxygen consumption at that point was significantly less than one would expect for someone her age. Also she never reached two thirds of her maximum voluntary ventilation (MW). Was she stopped because of some kind of intrinsic lung disease? Is this why she could not reach her Mvv? When you look at this case, you see that the blood gas values certainly do not bear that out. If anything, the Paco2 dropped as the Pao2 increased. All we have is an increase in physiologic dead space, and that could certainly be consistent with some kind of abnormality within the pulmonary circulation. DR. RpBIN: People stop exercising for many different reasons. Patients with mild degrees of lactic acidosis, for example, may stop exercising be-cause they are neurotic, as well as having pulmonary edema develop. Poorly conditioned patients may show an early pulse from lactic acidosis. I suspect that patients treated with propranolol may show premature lactic acidosis. The latter possibility is important in this patient: biochemical evidence of circulatory impairment develops as a relatively early degree of increased oxygen consumption, and with our knowledge that should be interpreted as circulatory limitation. DR. RAFFIN: When the patient's ventilatory response to exercise changes from 3.14 to 33.5 liters per minute, about 25 percent to 30 percent of the MVV, do you think the response is inappropriate for that amount of exercise? Gradually some lactate acidosis was shown. DR. ROBIN: Dr. Lynne-Davies should comment and then I will give you my opinion. What percentage of the Mvv does one usually mobilize during peak exercise?
PATRICIA LYNNE-DAVIES, MD: * Well, allegedly 65 percent, something in that order, but there are one or two peculiarities in this case. First, the tidal volume at rest is extraordinarily low even for someone who is fairly small. Consequently, she has a spectacular increase in tidal volume with exercise. Second, although it may well be true that her lung volumes are normal, it is interesting that the ratio of residual volume to total lung capacity is elevated, and the functional residual capacity is mildly elevated. I think you also found a functional residual capacity that was high. So I think that there may well be some limitation. *Associate
Professor of Medicine.
There is no question that one does not function as well at 60 percent or 70 percent total lung capacity as you do at 50 percent, just in terms of mechanical ability to shift ventilation around. Having said all of that, I still do not think these are in any sense limiting factors. I am impressed, just as Dr. Robin has been, by factors like the increase in her arteriovenous oxygen pressure difference with exercise. These seem much more dramatic to me. DR. ROBIN: Given the general issue of lungs versus circulation, I do not think it is possible to say that the patient has perfectly normal lungs. Indeed, given mitral stenosis or coronary artery disease, which is hemodynamically significant, you will almost never find normal lungs. At times you will find problems we generally consider representative of obstructive lung disease. After all, the mucosae of the bronchi become edematous and bronchiolar changes occur with pulmonary edema. I believe the main focus of this patient's disorder is circulatory for two reasons; objective measurements show that the circulation is primarily impaired, and we can come up with a logical explanation for the impairment. A handle for discussing this case is to ask, "What happens in patients who have severe pectus excavatum, even without scoliosis?" In most patients, nothing happens. If you measure lung function and cardiac function not only when, for instance, the patient is young, but continue to make measurements, the interference of the pectus excavatum with the function of either the heart or the lungs is minimal or nonexistent. That brings up another point. If you look at 100 patients who have had a surgical operation for pectus excavatum the overwhelming indication is cosmetic. It is interesting that the surgical procedure for the disorder is bloody and complicated. In one way, pectus excavatum in most patients represents an imbalance between a surgical procedure for something cosmetically wrong with the patient and a surgical procedure for physiologic indications. In a small number of patients with the disorder restrictive'lung disease develops, and the restriction is pretty clearcut; it is not as tenuous as in this patient. The pectus excavatum is usually severe and notable reductions are seen in all lung volumes. Such patients have rapid, shallow breathing and the natural life history, as far as I know, is not progressive. Patients first present with comTHE WESTERN JOURNAL OF MEDICINE
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plaints of dyspnea, and there are examples in which surgical treatment relieves restrictive lung disease. Another complication more or less well documented in the literature is restrictive heart disease, and up until now my view is that it appears like chronic restrictive pericarditis, endomyocardial fibrosis or endocardial fibroelastosis. Both sides of the circulation are involved, with generally an equalization of pressure across both. When right ventricular catheterization is carried out in the patient there is a right ventricular diastolic dip (square root sign). Not uncommonly you hear the so-called pericardial knock, which is not necessarily pericardial in origin. These patients may have severe congestive heart failure. The biventricular heart disease can be treated by surgical operation, which corrects the pectus excavatum.3 Pulmonary hypertension may represent another complication. One patient with severe pulmonary hypertension and pectus excavatum made a profound impression on me. This was a woman in her late 20's who was married to an Army officer in Hawaii. Her husband went to see his physician each year for an examination that included an exercise test. She accompanied her husband to the physician's office and when the husband finished the exercise test she asked if she could try it. She mounted the treadmill, took about four steps and fainted. It was clear that she had severe heart disease. An x-ray film of the chest showed a pronounced pectus excavatum, and cardiac catheterization showed severe pulmonary hypertension with pulmonary artery pressures equal to systemic pressures. Findings on pulmonary angiograms were normal and the patient had the usual kind of workup for pulmonary hypertension, which showed nothing. Primary pulmonary hypertension was diagnosed. It occurred to me that there could well be a pathogenetic link between the pectus excavatum and the development of severe pulmonary hypertension. The pathogenetic link could be explained by what we have called the Goldblatt lung.4 Under several clinical circumstances, there is the development of pulmonary hypertension in patients who have reductions, without cessation, of regional pulmonary blood flow over a long period. In going back to the concept of primary pulmonary hypertension, there are two important features, one of which is not usually considered: increases in pulmonary artery pressure that occur without a known cause and the development of 528
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a disproportionate degree of pulmonary hypertension for any given degree of heart or lung
disease. If you go back to the basic relation between mean pulmonary artery pressure and flow in a normal lung, the flow must double to produce an increase in pressure. There are three or four conditions in which there is less than 50 percent of the pulmonary vasculature involved in disease of the lung or the pulmonary apparatus, but in which the patient has severe pulmonary hypertension that is disproportionate. This may occur in unilateral pleural fibrosis. We collected a series of four cases, and there now have been about three or four more reported in the literaturecases of unilateral pleural restriction with severe pulmonary hypertension.4 The question is, if the disease involves only one lung, why is the pulmonary artery pressure elevated? The second cdndition that fits this classification is multiple regional pulmonary coarctations. There are well described cases in which there are multiple small pulmonary artery coarcts as a congenital defect.5 The degree -that is, the number of vessels involved-is not of the magnitude which would generally occlude greater than 50 percent of the pulmonary vasculature. These patients may have striking pulmonary hypertension, in fact, that is one of the clinical features. The third condition is kyphoscoliosis; progressive pulmonary hypertension may develop in patients with this condition even if there are no overt difficulties with breathing.6 Dr. Liebow, impressed by this phenomenon, reported neural elements which he described as neuroepitheliomas in the lungs of these patients. He hypothesized that the neuropithelioma might be the site of the release of a humor that produced generalized pulmonary hypertension. Therefore, when I saw the patient with pectus excavatum and pulmonary hypertension, I wondered whether the disorders could possibly be related. On an intuitive level, it was convincing enough to suggest that the patient, at age 27, has pulmonary artery pressures equal to systemic pressures. The length of life she had left, at least statistically, was short and there was already, when I saw her, right ventricular failure and functional tricuspid insufficiency. One possible therapeutic approach was to correct the pectus excavatum. Two other experts (if I qualify as an expert) were consulted and they felt that my suggestion was outlandish. Nothing was done. If my reconstruction is correct, pectus excava-
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tum in this case represents a form of cardiac restrictive disease in which the anatomical restriction is largely localized to the left ventricle; therefore, the usual bilateral signs of restrictive cardiac disease related to the disorder are not shown. However, pectus excavatum does restrict her cardiac output during exercise, and gives her periods of pulmonary edema when she is exercising or has increases in blood volume. Her case, therefore, represents isolated left ventricular disease in which, conceivably, the prolapsed mitral valve might have an additional role. However, the major problem is related to mechanical restriction of the left ventricle. In addition, the patient is being treated with propranolol, which depresses myocardial contractility. If it is true that the problem is related to mechanical restriction (and it is easy to persuade yourself that a logical explanation is true) then this case represents another unusual complication of pectus excavatum. Then the question is what should be done? Clearly, therapy with propranolol should be stopped because it would render a noncompliant left ventricle even less compliant. If that failed, one might consider relieving the disorder surgically and freeing the left ventricle. I would argue against this for two reasons: The first is that the surgical operation is difficult and is usually a four- to five-hour procedure with major blood loss in which the sternal plate is unroofed by cutting the ribs and lifting the sternum. A prosthetic device is inserted and the sternal plate is sewed in place. The second reason is that the case makes clear physiological sense to me. This is dangerous; when a case fits into a neat package you should suspect the analysis. DR. HANCE: Another possible diagnosis is restrictive heart disease, also associated with unilateral signs that are left sided only. This is now referred to at the National Institutes of Health as asymmetrical septal hypertrophy, and I think it fits this case fairly well. The onset occurs when patients are in their 50's. In some cases, tachyrhythmia may be a problem and the kind of limitation would be highly suspicious of that. Prolapse of the valve may frequently be associated with it. This narrowing of the ventricular neck is highly suggestive. So, I would do a regular echo scan rather than a sector scan, and would look closely for that abnormality. DR. ROBIN: I do not object to that diagnosis, but I really think the problem is that the referring
physicians have used all their techniques, and cannot explain left ventricular disease on the basis of their data. Maybe the reason is that they (like we) are dealing with something that has not been described previously. DR. HANCE: Is asymmetrical septal hypertrophy a common diagnosis in the cardiology clinic here? That has not been my impression. This is a case in which you might have a pathologic abnormality without obstruction. DR. RAFFIN: Just as in most of Epstein's recent work in trying to study the epidemiology of prolapse, asymmetrical septal hypertrophy is a diagnosis made easily on just the A mode ultrasound. DR. ROBIN: My guess would be that septal hypertrophy or idiopathic hypertrophic subaortic stenosis could have been pulled out of the data had the data been suggestive; that does not necessarily mean that people have looked for it specifically. DR. RAFFIN: 1 would like Dr. Newman to get the pressure tracings. This case is fascinating if you really do have the classical square root sign of some types of restrictive cardiac abnormalities; if you do not, then the case is still interesting, but less elegant, I think. In the August 5, 1972, issue of the New England Journal of Medicine there is a report of a series of patients with pectus excavatum who were operated on for significant restrictive heart disease or symptoms due to the disorder. It is interesting that patients were more symptomatic when sitting than when supine, and this was thought to be the result of the heart dropping down further into the
pectus.7 DR. ROBIN: That form of dyspnea is called platypnea.8 DR. RAFFIN: It is not completely clear to me that surgical operation is inappropriate for this woman if her quality of life is zero. DR. ROBIN: The decision should not only be based on the quality of life. It should also be based on the security of feeling that your analysis is accurate. This is an important point because we are increasingly carrying out tests in patients because of insecure feelings that stem from inadequate knowledge. If I were certain that my analysis was correct, or that it had eight chances out of ten of being correct, then I might be enthusiastic THE WESTERN JOURNAL OF MEDICINE
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about using a surgical procedure. Confronted by a patient who is one in the world, and to come up then with an unprecedented indication for surgical operation would be arrogant. A bad guess might cost the patient some years of relatively happy life. I am certain I would begin by stopping the propranolol therapy. In swnmary, we have seen a patient with severe pectus excavatum and dyspnea. It seems unlikely that the manifestations are related to abnormal pulmonary mechanics, but rather to abnormal cardiac function. Pectus excavatum can produce restrictive lung disease, restrictive heart disease antd possibly pulmonary hypertension (by a Goldblatt mechanism). The hemodynamics suggest restrictive left ventricular disease that may have been intensified by the use of propranolol. After much soul-searching, the consensus would be to stop propranolol therapy and see what happens. FOLLOW UP: Review of the patient's cardiac tracings showed what seemed to be a square root sign with oscillations following the diastolic dip
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in the left ventricular tracing. This was considered by most (but not all) to indicate restrictive left ventricular disease. Propanolol therapy was stopped and the patient's condition has improved, but not to the point where she can tolerate normal exercise. However, she is considerably more comfortable. REFERENCES 1. Siegel J, Schecter G: The straight back syndrome. Am J Med 42:309-313, Feb 1967 2. Exercise Testing and Training of Apparently Healthy Individuals-A Handbook for Physicians, Amer Heart Assoc Committee on Exercise, Kattus AA, Chairman. New York, Am Heart Assoc, 1972 3. Chin EG: Surgery of funnel chest and congenital sternal prominence. Br J Surg 44:360-376, Jan 1957 4. Robin ED, Cross CE, Kroetz F, et al: Pulmonary hypertension and unilateral pleural constriction with speculations on pulmonary vasoconstrictive substance. Arch Intern Med 118:391400, Oct 1966 5. Arvidsson J, Karnell J, Moller T: Multiple stenosis of the pulmonary arteries associated with pulmonary hypertension diagnosed by selective angiocardiography. Acta Radiol 44:209-216, Sep 1955 6. Bergofsky EH, Turino GM, Fishman AP: Cardiorespiratory failure in kyphoscoliosis. Medicine 38:263-317, Sep 1959 7. Beiser G, Epstein S, Stampfer M, et al: Impairment of cardiac function in patients with pectus excavatum, with improvement after operative correction. N Engl J Med 287:267-272, Aug 10, 1972 8. Robin ED, Laman D, Horn B: Platypnea related to orthodeoxia caused by true vascular lung shunts. N Engl J Med 294: 941-943, Apr 22, 1976
