The nature and prevalence of the abnormal exercise electrocardiogram in mitral valve prolapse

The nature and prevalence exercise electrocardiogram prolapse

of the abnormal in mitral valve

Peter J. Engel, Maj., USAF, MC Barry L. Alpert, Maj., USAF, MC James R. Hickman, Jr., Lt. Col., USAF, Brooks

AFB.

San Antonio,

MC

Texas

Mitral valve prolapse is a common disorder, many of whose features mimic those of coronary artery disease. The tendency for individuals with mitral valve prolapse to develop exercise-induced ECG repolarization abnormalities is one such feature, as has been previously recognized.‘-” The prevalence of an abnormal exercise ECG response in this syndrome is unknown. At the United States Air Force School of Aerospace Medicine (USAFSAM), military aircrew members are referred for evaluation of possible cardiac disorders, particularly those capable of producing sudden incapacitation in flight, such as coronary artery disease. This evaluation routinely includes a complete noninvasive cardiac assessment, including electrocardiogram, vectorcardiogram, chest x-ray, echocardiogram, phonocardiogram, ambulatory ECG monitoring, and maximal treadmill exercise stress testing. Those aircrew members receiving waivers for continued aviation duties are re-evaluated on an annual basis and thus may undergo multiple annual treadmill tests. All individuals with unexplained ST segment abnormalities on [readmill testing are offered coronary arteriography and left ventricular cineangiography. The observation that several subjects with abnormal treadmill tests had angiographic and other features of mitral valve prolapse in the absence of angioFrom the USAF School San Antonio. Texas.

of Aerospace

Received

for publication

Nov.

Accepted

for publication

March

Reprint requests: sity of Cincinnati Cincinnati. Ohio

716

December,

PeterJ. Medical 45267.

Medicine,

Brooks

Air Force

Base,

8, 1978. 6. 1979.

Engel, M.D., Division of Cardiology, UniverCenter, 231 Bethesda Ave., Room 3354,

1979,

Vol.

98. No.

6

graphically demonstrable coronary artery disease led us to explore retrospectively the relationship between mitral valve prolapse and ECG repolarization abnormalities on treadmill exercise testing. Material

and methods

The clinical records of all aircrew members referred to USAFSAM for medical evaluation since 1971 were reviewed in an effort to isolate individuals with mitral valve prolapse (MVP) as defined by the fulfillment of two of the three following criteria: (1) auscultatory and/or phonocardiographic evidence of mitral valve prolapse, namely midsystolic click, late systolic murmur, or both, with appropriate responses to physical and pharmacological interventions; (2) typical echocardiographic abnormalities, including systolic posterior buckling and holosytolic posterior “hammocking” of the mitral valve echo (with care taken to avoid caudad angulation of the ultrasound transducers); and (3) abnormal systolic ballooning or billowing of either leaflet of the mitral valve into the left atrium during a sinus beat visualized with right anterior oblique left ventricular cineangiography. All patients with mitral valve prolapse diagnosed on the basis of angiographic findings were so classified on the basis of quantitative angiographic criteria.“’ Echocardiography was performed on a commercially available Ekoline 20 ultrasonoscope interfaced with an Electronics for Medicine VR-6 strip chart recorded. Cardiac catheterization was performed utilizing standard techniques, including selective coronary arteriography by the techniques of either Judkins or Sones. All patients

0002.8703/79/120716

+ 09$00.90/O

g?:,1979

The

C. V. Mosby

Co

Abnormal

were maximally exercised utilizing a modification of the Balke-Ware protocol (USAFSAM Treadmill Protocol), reported previously.” An abnormal or positive repolarization response was defined as at least 0.1 mv. of horizontal or downsloping ST segment depression for 0.08 sec. after the inscription of the J point. Standard bipolar Leads X (CC-,) and CM-,, as well as an inferior Lead, Yh, and an inferior-posterior Lead, Z, were continuously monitored with the patient supine, during three minutes of quiet standing, during 30 seconds of supine hyperventilation, throughout treadmill exercise, and during an eight-minute supine recovery period. All signals were recorded continuously on hard copy and on magnetic tape for storage and playback. For the purposes of analysis, the first three minutes of the exercise period were defined as early exercise, the last three minutes as peak exercise, and the remainder of the exercise period was defined as mid exercise. Similarly, the first three minutes of recovery were defined as early recovery, the last three minutes as late recovery, and t.he mid portion as mid recovery. In addition to the data from patients with clinical evidence of mitral valve prolapse, the treadmill tests of 24 consecutive patients with abnormal treadmill tests presumably due to obstructive coronary artery disease found at catheterization (CAD group), and of 21 consecutive patients (normal group) with abnormal treadmill tests and no apparent cardiac disease (i.e., no evidence of coronary artery disease or mitral valve prolapse at cardiac catheterization), were examined. Statistical analysis was performed utilizing a two-tailed Student’s t test. Results Patient characteristics. Forty-three patients met our stated criteria for the diagnosis of mitral valve prolapse (Table I). Of the 43 patients in group P, 23 had phonocardiographic and echocardiographic evidence of mitral valve prolpase. Because of the absence of symptoms and ECG abnormalities, these 23 patients did not have angiography performed. Of the 20 patients with left ventricular angiogram (all of which demonstrated mitral valve prolapse), eight also had both abnormal echocardiogram and auscultatory abnormalities, and six others had phonocardiographic and/or auscultatory confirmation of mitral valve prolapse with normal echocardio-

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Heart

Journal

exercise ECG and mitral

value prolapse

gram. In the remaining six patients, no auscultatory or phonocardiographic evidence of mitral valve prolapse could be elicited despite repeated examination in supine, standing, squatting, and left lateral decubitus positions. These six patients had clear-cut echocardiographic and angiographit evidence of acoustically silent mitral valve prolapse. All patients were male (mean age, 36 years). Eighteen of 43 patients in group P were referred for evaluation of auscultatory abnormalities, 14 because of ECG abnormalities (four with complete right bundle branch block, two with first- or second-degree A-V block, two with ventricular premature beats, one with an isolated episode of atria1 fibrillation, and five with minor, nonspecific repolarization abnormalities), and eight patients were referred for reasons unrelated to the cardiovascular system. Only three patients were referred to USAFSAM because of an abnormal treadmill exercise test performed elsewhere. Thirty-nine of the 43 patients were completely asymptomatic; four had chest pain and/or palpitations, neither of which was considered disabling or requiring medical attention. Thirteen patients had musculoskeletal abnormalities detected radiologically or clinically, including pectus excavaturn, loss of normal thoracic dorsal kyphosis, and exaggerated thoracic scoliosis. In 42 of the 43 patients, mitral valve prolapse was the only cardiovascular abnormality; in one patient there was hemodynamically insignificant aortic regurgitation associated with a congentially bicuspid aortic valve. No patient was hypertensive or hypokalemic, and none was taking any regular medication. Of the 20 patients undergoing cardiac catheterization, 16 had selective coronary arteriography (including the three patients with chest pain); all coronary arteriograms were entirely normal. Analysis of treadmill tests At the time of initial treadmill stress testing, 35 patients had a normal resting electrocardiogram, seven had minor repolarization abnormalities, and one had complete right bundle branch block. None of the patients had resting ST segment abnormalities. A total of 82 treadmill exercise tests were available for review for the 43 patients. The peak heart rate achieved was 186 f 13 beats per minute (mean + 1 standard deviation). Only two of the efforts were submaximal and only four were associated with a hypertensive blood pressure

717

Engel,

Alpert,

and

Hickman

Table

I. Clinical characteristics of 43 patients with mitral valve prolapse MUSCUlO-

Angio-

AUSCUl-

Patient

Age

tation

Echo

1

33

MSC

2 3

28 37

MSC, MSC,

LSM LSM

Holosyst. Late syst.

4 5 6 7 8 9 10 11

34 34 42 49 30 36 39 27

MSC MSC, LSM LSM MSC, LSM Normal MSC MSC, LSM LSM

Holosyst. Late syst. Late syst. Late syst. Late syst. Holosyst. Holosyst. Late syst.

PPML PPML

12 13 14

35 39 24

MSC, LSM MSC Normal

Late syst. Late syst. Holosyst.

PPML PPML, PAML

15 16

31 33

HSM MSC. LSM

Late syst. Holosyst.

-

17 18

41 45

MSC, LSM MSC

Late syst. Normal

-

19 20

38 44

LSM Normal

Holosyst. Late syst.

Late

syst.

gwh

Symptoms

skeletal abnormalities

PPML

None

-

-

None None

-

None None None None None None None None

Pectus, straight back Pect,us, straight back -

-

PPML

Palpitations None None

None Chest pain, palpitations None None None None

Scoliosis -

ECG

TMT

Flat T v., v., Normal Flat T 2, 3aV Normal Normal Normal Normal Normal Normal Normal Normal

Abnormal

Abnormal Normal Normal Normal Abnormal Abnormal Normal Normal

Normal CRBBB Normal

Abnormal Abnormal Normal

Normal Normal

Normal Normal

Normal Flat T 2,3,aV, Normal Normal

Normal Abnormal

Normal Normal

Normal Abnormal

Abbreviations: MSC = midsystolic (nonejection) click; LSM = late systolic murmur; HSM = holosystolic murmur; Late Syst. = late systolic posterior buckling of mitral valve echo; Holosyst. = holosystolic “hammocking” of mitral valve echo; PPML = prolapse of posterior mitral leaflet: PAML = prolapse of anterior mitral leaflet; MR = mitral regurgitation; ECG = electrocardiogram; TMT = repolarization response to maximal treadmill testing; NA = not available.

response as judged by previously published heart rate and blood pressure criteria for normals utilizing the USAFSAM protocol.‘” Of the 43 patients with mitral valve prolapse, 12 (28%) had an abnormal initial treadmill exercise test. Of the nine patients with abnormal exercise repolarization responses who had more than one exercise test, six did not have reproducibly abnormal responses. None of the patients had chest pain at any time during exercise testing. Closer analysis of the data from abnormal exercise tests (Table II) revealed that in all 12 patients, the supine electrocardiogram was free of ST segment and T wave abnormalities. In ten of 12 (83%), ST segment and/or T wave changes developed with assumption of the standing position. These repolarization abnormalities did not

718

increase and usually regressed during and following the hyperventilation period. All exercise tests were definitely abnormal during t,he mid portion of exercise; greater than 2 mm. of ST depression was present in two of 12 patients. ST segment depression persisted through peak exercise in only 33% of patients, and through the immediate recovery period in only 8%. No specific pattern of lead positivity was demonstrated, with seven of 12 tests being positive in more than one lead. Only two of the 12 patients had an exercise test which was abnormal in Lead Yh only. No patient had ST depression in Lead Z. Analysis of the pattern of positivity of the treadmill tests in the CAD group and in the normal group (Table II) revealed that significantly fewer of the patients in these two groups developed ST segment or T wave abnormalities

Lkemher.

1979,

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Abnormal

Table

exercise ECG and mitral

llalrre prolapse

I. continued Auscultu tion

Echo

Angiographs

Patient

Age

21 22 23 24 25 26 27 28 29 30 31 32 33

34 44 55 47 44 26 26 41 43 28 43 30 27

MSC, LSM MSC MSC LSM MSC LSM Normal MSC LSM MSC LSM MSC MSC

Late syst. Late syst. Late Syst. NA Late syst. Holosyst. Holosyst. Late syst. Holosyst. Holosyst. Late syst. Holosyst. Holosyst.

PPML PPML, MR PPML, MR PPML -

.34 35 36

45 42 53

MSC. LSM MSC MSC

Late syst. Holosyst. Normal

PPML PPML

.r31

24

LSM

Late

syst.

PPML

38 39 40 41 42 43

40 40 25 40 40 37

MSC Normal Normal MSC MSC MSC. LSM

Normal Late syst. Holosyst. Late syst. Normal Late syst.

PPML PPML PPML PPML PPML PPML, PAML, MR

-

upon st,anding. In addition, the tendency towards normalization of the ST segment response during peak exercise and early recovery (Fig. 1) noted in the patients with mitral valve prolapse was considerably less common in the other two groups. Two additional trends were noted when the results of the treadmill test were examined in the light of auscultatory findings. Of the 43 patients (Table 11, 20 were found to have auscultatory or angiographic evidence of mitral regurgitation, while 23 patients had no such evidence. Of the 12 patients with abnormal treadmill tests, only one was found to occur in a patient with evidence of mitral regurgitation. The other 11 patients with abnormal repolarization responses to maximal treadmill exercise were among those without evidence of mitral regurgitation. Furthermore, four of these 11 patients were among the six patients in the entire group with angiographically

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Heart

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Symptoms None Chest None None None None None None None None None None None

pain

Musculoskeletal abnormalities

Scoliosis Scoliosis Scoliosis Scoliosis

None None Chest pain, Palpitations None None None None None None None

Pectus Pectus Pectus Pectus, Scoliosis Scoliosis P&us -

documented acoustically prolapse (Fig. 2).

ECG Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Inverted 2,3aV, Normal Normal Normal

TMT

T

Normal Normal Abnormal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal

Normal

Normal

Normal Normal Normal Normal Normal Normal

Normal Abnormal Abnormal Abnormal Normal Normal

silent

mitral

valve

Discussion Prevalence of abnormal treadmill tests. Previous investigations dealing with exercise testing in patients with mitral valve prolapse have emphasized the occurrence of exercise-induced arrhythmias in this condition. However, an association between mitral valve prolapse and “ischemic” ST segment responses to treadmill or bicycle exercise testing has been noted.‘-” Although the prevalence of abnormal treadmill test in these studies varied from 0 to 60R, of the 159 casesreported in these series in which exercise stress testing was performed, 52 were interpreted as positive, resulting in an over-all prevalence of abnormal exercise test of 33%. This figure is comparable to the 28% reported in the present study. In order to determine whether these find-

719

Engel,

Alpert,

and

Hickman

Table

II. Treadmill exercise test results

T

Number

(%)

of patients

MVP. ATM (n = 12) Standing changes Positive cise Positive Positive cise Positive fm Positive

ECG early

9 (43)*

4 (l’i)**

6 (28)

16 (67)* 18 (75)*

17 (81) 14 (67)

9 (38)

3 (14)

4 (33)

17 (71)

8 (38)

6 (50)

15 (63)

12 (57)

exer-

mid exercise peak exerearly

i (29)**

recov-

mid recov-

w Positive late recovery Standing ECG changes + positive early-mid exercise + negative peak exercise and early recovery >2 mm. ST depres-

12 (100) 4 (33) l(8)

i (58)

2 (15)

0 (o)***

11 (46)

Pathophysiology of exercise-induced ECG abnormalities. The mechanism of exercise-induced

1 (5)*‘*

9 (43)

sion Abbreviations:

CAD = coronary

disease; ATM

MVP = mitral valve prolapse: = abnormal treadmill exercise * = p < .05 vs. Group with MVP. ** = p < .Ol vs. Group with MVP. *** = p < .0025 vs. Group with MVP.

test.

art-q

ings reflected a true increase in the prevalence of positive treadmill tests in mitral valve prolapse, we reviewed the records of the USAFSAM Exercise Laboratory and found that over the period encompassed by the study, 2,171 asymptomatic, apparently healthy men (mean age 40 years) were exercised in our laboratory for the first time, 158 (7%) of whom had exercise-induced repolarization abnormalities. Thus, mitral valve prolapse results in at least a fourfold increase from the expected prevalence of false-positive treadmill tests in asymptomatic individuals. The results of the present study may actually underestimate the true prevalence of abnormal treadmill tests in patients with mitral valve prolapse, since the 2,171 patient,s mentioned above included those with resting ECG abnormalities, and since this study was restricted to male patients without resting ST segment abnormalities. Little is known regarding the true reproducibility of exercise-induced abnormalities. The fact

720

that only three of the nine patients with mitral valve prolapse and abnormal treadmill tests in this study who were retested had completely reproducible repolarization responses is not surprising, in view of what previous work has been done in normal subjects and in patients with coronary artery disease,‘,‘-” in which investigators have noted non-reproducible ST depression in from 10 to 60%
repolarization abnormalities in mitral valve prolapse has not been discussed extensively in the existing literature. Many of the features of the mitral valve prolapse syndrome, such as chest pain, ventricular arrhythmias, and resting T wave abnormalities, are felt to be ischemic in origin. Several theories explaining ischemia in mitral valve prolapse have been forwarded, but the concept which seems to have gained general acceptance postulates that the voluminous mitral leaflets, during their systolic excursion into the left atrium, produce abnormal tension within the chordae tendineae and the papillary muscles t,o which they are attached, as well as the surrounding myocardium. Although the existing data are inconclusive, several radionuclide studies have documented the presence of perfusion defects, at rest and following exercise in patients with mitral valve prolapse in the absence of coronary artery disease.“’ I; It is tempting to speculate that, in the exercising individual with mitral valve prolapse, positive inot,ropic influences and decreased left ventricle afterload lead to an increase in systolic emptying and to a more violent ventricular assault on the mitral valve. This, in turn, could lead to an increase in mitral valve prolapse and in the abnormal papillary tug” presumably responsible for myocardial ischemia. Of interest in this regard is the observation in the present study of a decreased prevalence of exercise-induced ECG repolarization abnormalities in patients with evidence of mitral regurgitation. Even severe mitral regurgitation is known to be compatible with a long asymptomatic period because of the tendency of this lesion to reduce tension developed by the left ventricular myocardium. It is

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Abnormal

exercise ECG and mitral

value prolapse

ttV

ME

Fig. 1. Portions of exercise ECG from patient No. 40, demonstrating the pattern of ECG abnormalities typical of our population. Note prominent T wave changes with assumption of standing position, ST depression at mid-exercise, with normalization during peak exercise and recovery. HV = hyperventilation; 2 MZN EX = second minute of exercise; 7 MZN EX = seventh minute of exercise; 11 MZN EX = eleventh minute of exercise: 3 MZN REC = third minute of recovery.

known that under experimental circumstances, even massive mitral regurgitation does little to increase total myocardial oxygen consumption”‘; therefore, it is not inconceivable that in the exercising human with mitral valve prolapse, the presence of mild mitral regurgitation might reduce myocardial oxygen consumption and lessen the tendency for the development of myocardial ischemia. Mitral valve abnormalities.”

prolapse

and

“vasoregulatory

An especially significant finding was that of the pattern of positivity of the abnormalities exercise-induced repolarization among our patients with mitral valve prolapse. The majority of our patients with both abnormal treadmill tests and mitral valve prolapse demonstrated ST segment and/or T wave changes with the assumption of the standing position, ST segment depression (usually less than 2 mm.) during the early and mid portion of the exercise period, absence of ST segment depression during peak exercise and immediate recovery, with or without reappearance of ST segment abnormalities during late recovery. This pattern was found in 58% of the study patients with mitral valve prolapse, and was found in only one of 45 other

American

Heart

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patients with abnormal treadmill tests without mitral valve prolapse. This pattern bears a striking resemblance to that found in a group of 40 patients with “vasoregulatory abnormalities” described by Friesinger and associates.‘” These investigators published a report concerning 40 patients, the majority of whom had either chest pain with normal coronary arteriograms or “neurocirculatory asthenia,” and in whom “ischemic” electrocardiographic changes were noted during standing and during the early portion of treadmill exercise tests. The patients were young (mean age 34 years) and were lacking in risk factors for coronary artery disease. The ischemic electrocardiographic changes were postulated to occur on the basis of an abnormal autonomic response to ordinary cardiovascular stress, as evidenced by a marked increase in heart rate upon standing. In view of the fact that all of Friesinger and colleagues’ patients were studied before 1967 and that echocardiographic, auscultatory, and angiographic findings were not reported upon in his patients, and based upon the findings of the present study, we feel there is a reasonable likelihood that many patients with “vasoregulatory abnormalities” have mitral valve prolapse. This

721

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Fig. 2. Echocardiogram (top) and end-diastolic (hottont Cefr) and end-systolic (hotlom right) frames of left ventricular cineangiogram from same patient as in Fig. I. Note holosystolic echographic mitral “hammocking” and angiographic evidence of posterior mitral leaflet prolapse (cr~owi. This patient was one of those with acoustical1.v silent mitral prolapse.

association is not surprising when certain facts are taken into consideration. First, as mentioned previously, many of the patients originally described by Friesinger and colleagues were felt to satisfy criteria for the diagnosis of neurocirculatory asthenia, a condition characterized by atypical chest pain, asthenic build, and neurotic symptoms. The similarity of these features with those found in mitral valve prolapse has been emphasized appropriately by Wooley,2’ and requires no further elaboration. Secondly, as mentioned previously, all of Friesinger and associates’ patients were studied over a decade ago, at which time general awareness of the mitral valve prolapse syndrome was lacking; the majority of the patients in the original description of Friesinger and co-workers did not have angiography performed and none had echocardiograms. The most important observation linking these groups of patients is that of the standing electrocardiographic changes. Orthostatic T wave

722

abnormalities in patients with mitral valve prolapse have been briefly commented upon by previous investigators.“. -’ :” Pharmacologic and physical interventions which decrease left ventricular volume are known to result in an increase in mitral valve prolapse,” and the assumption of the standing position is one of the purest examples of this phenomenon.” It seems reasonable, therefore, to assume that the standing T wave abnormalities observed in our patients are the consequence of increased tension on the papillary muscles brought about by the increase in ventriculovalvular disproportion which occurs with standing. The observation by Friesinger and associates that “ischemic” electrocardiographic responsesto exercise were corrected in many cases by maneuvers which increased left ventricular volume (the administration of propranolol, application of “body stockings,” and Valsalva maneuver) further supports the contention that vasoregulatory abnormalities may be a manifestation of

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1979, Vol. 98, No. 6

Abnormal

mitral valve prolapse. The retrospective nature of the present study prevented us from confirming these observations. The normalization of the ST response to treadmill exercise during the late or peak portion of the exercise period is less easily explained. Although definitive studies of alterations in ventricular volume and dynamics during treadmill exercise are lacking, it is interesting to note that Friesinger and colleagues” account foi this phenomenon on the basis’of an increase in left ventricular volume secondary to increased cardiac output and venous return during the later phases of exercise. This explanation is certainly acceptable in the present context as well. Silent mitral valve prolapse. The presence of mitral valve prolapse is difficult to substantiate in the absence of typical auscultatory abnormalities. The criteria for the diagnosis of mitral valve prolapse in the present study were intentionally stringent, so as to avoid the recent tendency toward overdiagnosis of this disorder.“’ In the present study, a case would not be accepted as silent mitral valve prolapse unless both echocardiographic and angiographic indications of this disorder were present. We do not believe that silent mitral valve prolapse can be diagnosed with certainty in the absence of either echocardiographic or angiographic features of this disorder. If the clinicopathological correlations presented by Roberts and co-workers’; are accepted, then silent mitral valve prolapse can be presumed to correspond to a minimal degree of mitral pathology. The graphic manifestations of such disease are therefore not likely to be flagrant. The opportunit,y to accurately diagnose silent mitral valve prolapse is probably more common in a laboratory in which cardiac catheterization is routinely performed in asymptomatic individuals. All six of our caseswere not only acoustically but also clinically silent, the indication for catheterization having been an abnormal treadmill test in four out of the six cases. These observations indicate that the suspicion of mitral valve prolapse in patients with an abnormal treadmill test must extend to asymptomatic patients without the auscultatory abnormalities typical of mitral valve prolapse. Clinical implications. With the recent increase in the use of treadmill exercise testing as a part of a health “screening” procedure in asymptomatic individuals, clinicians are increasingly confronted

American

Heart

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exercise ECG and mitral

value prolapse

with the problem of exercise-induced “ischemic” ECG changes in individuals without chest pain. Our findings imply that echocardiography is indicated in such casessince, even in the absence of symptoms or auscultatory abnormalities, mitral valve prolapse may herald its presence in the form of exercise-induced ECG repolarization abnormalities, particularly of the variety currently associated with vasoregulatory abnormalities. Summary

The maximal treadmill exercise tests in 43 subjects with mitral valve prolapse were retrospectively examined and compared to those of 24 consecutive patients with abnormal maximal treadmill tests and arteriographic evidence of obstructive coronary artery disease and 21 consecutive patients with abnormal treadmill tests with evidence of neither mitral valve prolapse nor coronary artery disease at catheterization. Twelve of 43 (28%) patients with mitral valve prolapse had greater than 0.1 mv. of flat or downsloping ST depression during or following treadmill exercise. Of these 12 patients, seven (58%) were found to have the pattern of abnormal treadmill test previously described as indicative of “vasoregulatory abnormalities”; four patients satisfied the diagnostic criteria for acoustically silent mitral valve prolapse, and only one had clinical or angiographic evidence of mitral regurgitation. The finding of the “vasoregulatory” pattern of abnormal ECG response was significantly less common in the groups with abnormal treadmill tests and coronary disease and with neither coronary diseasenor mitral valve prolapse (p < .0025). We conclude that the finding of- an abnormal treadmill test, particularly of the type associated with “vasoregulatory abnormalities,” should lead to the suspicion of mitral valve prolapse, even in the absence of symptoms and typical auscultatory abnormalities, The authors wish to thank Ms. Wienie Durkee for technical assistance, Ms. Rosie Rodriguez and Ms. Lorene Rutherford for secretarial assistance, and Dr. Victor Froelichrr for his helpful suggestions. REFERENCES

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