Since the 1970s, only a few studies have evaluated the accuracy of noninvasive screening exercise tests for detecting coronary artery disease (CAD) in symptomatic individuals with mitral valve prolapse (MVP). The present systematic review has been designed to summarize the main findings of these studies and to assess the overall pooled estimates of sensivity and specificity of exercise ECG, exercise myocardial perfusion scintigraphy (MPS) and exercise stress echocardiography (ESE) in diagnosing CAD among MVP individuals.

All studies examining the specificity and sensitivity of exercise ECG and/or exercise MPS and/or ESE in detecting obstructive CAD in symptomatic MVP patients, selected from PubMed and EMBASE databases, were included. There was no limitation of time period. The risk of bias was assessed by using the National Institutes of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.

The full texts of 11 studies with 840 MVP individuals were analyzed. True obstructive CAD was documented in 11.1% of MVP individuals (range 0-31.2%). When used in MVP patients with suspected CAD, exercise ECG, exercise MPS and ESE showed a pooled specificity of 61.9% (range 25-91.7%), 82.3% (range 25-100%) and 89% (range 80.5-97.6%), respectively, and a pooled sensitivity of 80% (range 50-100%), 96.7% (range 90-100%) and 91% (range 82-100%), respectively. The pooled positive predictive value was 33.2% (range 23.1-44.8%) for exercise ECG, 100% for exercise MPS and 80.2% (range 75.8-84.6%) for ESE, whereas the pooled negative predictive value was 80% (range 50-100%) for exercise ECG, 97% for exercise MPS and 99% (range 97.6-100%) for ESE.

ESE appears to be the first-choice screening method for CAD detection in symptomatic MVP individuals. It allows true CAD in symptomatic MVP individuals with false-positive exercise ECG results to be ruled out, without ionizing radiation exposure.

Mitral valve prolapse (MVP) is the most common mitral valve disorder affecting 2%-3% of the general population. Two histological forms for the disease exist: Myxomatous degeneration and fibroelastic disease. Pathological evidence suggests the disease is not confined solely to the valve tissue, and accumulation of proteoglycans and fibrotic tissue can be seen in the adjacent myocardium of MVP patients. MVP is diagnosed by demonstrating valve tissue passing the annular line into the left atrium during systole. In this review we will discuss the advantages and limitations of various imaging modalities in their MVP diagnosis ability as well as the potential for demonstrating extra associated valvular pathologies.

The possibility of exercise-induced myocardial ischemia due to mitral valve prolapse (MVP) in the absence of coronary artery disease was evaluated with single-photon emission computed tomographic analysis using thallium-201 and technetium-99m sestamibi in 72 patients with MVP. Exercise electrocardiography was positive in 5 patients (8%), but single-photon emission computed tomography was found to be normal in all patients, and exercise-induced chest pain, electrocardiographic changes, and arrhythmias were found not to be related to myocardial ischemia in patients with MVP.

Mitral valve prolapse is sometimes associated with chest pain, but this symptom may also be caused by coexisting coronary disease. The accuracy of exercise echocardiography in diagnosing coronary disease in these patients and the most cost-efficient diagnostic approach are unclear. We studied 96 patients (aged 59 +/- 12 years; 70 men) with mitral valve prolapse who underwent exercise electrocardiography, exercise echocardiography, and coronary angiography. The accuracies of seven diagnostic strategies based on the current and expected use of exercise electrocardiography and exercise echocardiography in patients with mitral valve prolapse were examined, with the costs calculated based on Medicare reimbursement. Thirteen (13.5%) patients had significant coronary artery disease. The sensitivity and specificity of exercise electrocardiography in the 71 patients with interpretable electrocardiograms were 50% and 72%, respectively. For the 73 patients who achieved >85% of maximal heart rate, 52 had interpretable exercise electrocardiograms (sensitivity 50%; specificity 69%). Exercise echocardiography had a sensitivity of 69% and a specificity of 98% in the 96 patients and a sensitivity of 82% and a specificity of 96% in patients who achieved >85% of maximal heart rate. Approaches adopting Bayes' theorem and restricting further investigation to patients with at least intermediate pretest probability of coronary disease were the least costly. When combined with exercise echocardiography as the initial test, clinical stratification was associated with a false-negative rate of 21%. The utility of exercise electrocardiography is limited by the high prevalence of resting electrocardiographic abnormalities and suboptimal sensitivity and specificity. The best balance of cost and diagnostic accuracy is to perform exercise echocardiography in patients with at least intermediate probability of coronary artery disease.

Mitral valve prolapse is a common cardiac disorder that can readily be diagnosed by characteristic auscultatory and echocardiographic criteria. Although many diseases have been associated with mitral valve prolapse, most affected individuals have the primary form of the disorder. Mitral valve prolapse is an inherited condition commonly associated with myxomatous degeneration of the mitral valve and its support structures. Complications of mitral valve prolapse, including cardiac arrhythmias, sudden death, infective endocarditis, severe mitral regurgitation (with or without chordae tendineae rupture), and cerebral ischemic events, occur infrequently considering the wide prevalence of the disorder. Panic disorder is a specific type of anxiety disorder characterized by at least three panic attacks within a 3-week period or one panic attack followed by fear of subsequent panic attacks for at least 1 month. It too is a common condition with a prevalence and age and gender distribution similar to that of mitral valve prolapse. Panic disorder and mitral valve prolapse share many nonspecific symptoms, including chest pain or discomfort, palpitations, dyspnea, effort intolerance, and pre-syncope. Chest pain is the symptom in both conditions that most commonly brings the patient to medical attention. The clinical description of chest pain in patients with mitral valve prolapse is highly variable, possibly reflecting multiple etiologies. Chest pain in panic disorder is usually characterized as atypical angina pectoris and as such bears resemblance to the chest pain commonly described by patients with mitral valve prolapse. Multiple investigative attempts to elucidate the mechanism of chest pain in both conditions have failed to identify a unifying cause. Review of the literature leaves little doubt that mitral valve prolapse and panic disorder frequently co-occur. Given the similarities in their symptomatology, a high rate of co-occurrence is, in fact, entirely predictable. There is, however, no convincing evidence of a cause-effect relationship between the two disorders, nor has a single pathophysiologic or biochemical mechanism been identified that unites these two common conditions. Until specific biologic markers for these disorders are identified, it may be impossible to do so. The lack of a proven cause-and-effect relationship between mitral valve prolapse and panic disorder and the absence of a unifying mechanism do not diminish the clinical significance of the high rate of co-occurrence between the two conditions. Primary care physicians and cardiologists frequently encounter patients with mitral valve prolapse and nonspecific symptoms with no discernible objective cause who fail to respond to beta-blockade. Panic disorder should be considered as a possible explanation for symptoms in such patients.(ABSTRACT TRUNCATED AT 400 WORDS)

We performed a retrospective study in order to study the ability of thallium-201 exercise scintigraphy to detect and to localize coronary artery perfusion defects (in comparison with a recent coronary angiogram). We studied 81 patients (67 males); their average age was 52.3 years (men 50.5 and women 54.1 years). They performed a pulse-conducted cycle exercise test, and 2 min before end of exercise 75 MBq of thallium-201 was infused intravenously, and tomographic images were reconstructed by using a Siemens-Rota SPECT gamma camera immediately and 4 h after exercise. The thallium-201 uptake defects were attributed to different coronary arteries, and the results were compared with a coronary angiogram made afterwards in 48 patients. The groups of one-, two- and three-vessel disease were 27, 21, and 21 patients, and only 12 patients did not have significant (over 50%) stenoses. The latter had the highest ejection fraction and working capacity. Sensitivity of thallium-201 exercise scintigraphy was 65%, whereas that of exercise ECG was 41% in patients with a low ejection fraction, while in the whole material the sensitivity of thallium-201 scintigraphy was 91% and that of exercise ECG was 54%. A stenosis in the right coronary artery was best localized by the thallium-201 scintigram (86% correctly); a stenosis in the left anterior descending artery was localized correctly in 75% of the cases, but a stenosis in left circumflex artery was localized correctly only in 44%. We conclude that exercise thallium-201 scintigraphy is a useful method not only in detecting but also in localizing coronary artery disease.

Mitral valve prolapse is a common mitral valve disorder manifested clinically as a midsystolic click and/or a late systolic murmur (the click-murmur syndrome) and pathologically as billowing or prolapsing mitral leaflets (the floppy valve syndrome). Not only is it one of the two most common congenital heart diseases and the most common valve disorder diagnosed in the United States, but it is also prevalent throughout the world. Mitral valve prolapse may be associated with a variety of other conditions or diseases. Diagnosis of mitral valve prolapse should be made on clinical grounds and, if necessary, supported by echocardiography. The majority of patients with mitral valve prolapse suffer no serious sequelae. However, major complications such as disabling angina-like chest pains, progressive mitral regurgitation, infective endocarditis, thromboembolism, serious arrhythmias, and sudden death may occur. Unless these serious complications occur, most of the patients with mitral valve prolapse need no treatment other than reassurance, including those with atypical chest pain or palpitation unconfirmed by objective data. Therapy with a beta-blocker for disabling chest pain and/or arrhythmias and antiplatelet therapy for cerebral embolic events may be indicated. In occasional patients with significant mitral regurgitation surgery may be necessary.

In patients with valvar heart disease detection of coronary artery disease by conventional non-invasive methods may be difficult. The usefulness of thallium-201 exercise scintigraphy for detecting coronary artery disease was evaluated in 16 patients with aortic stenosis, 17 with aortic regurgitation, nine with mitral stenosis, and six with mitral regurgitation who were investigated by coronary angiography. Only two of 21 patients with greater than or equal to 50% coronary artery obstruction had normal thallium images. Three patients without angiographic evidence of coronary artery stenoses had perfusion defects demonstrated by thallium scintigraphy. Only one patient with greater than or equal to 75% coronary stenosis had a normal thallium scan. Angina pectoris or ST segment depression evoked by exercise test were not useful in distinguishing patients with coronary artery disease from those with normal coronary vessels. These data suggest that thallium exercise scintigraphy may be a useful non-invasive test for detecting coronary artery disease in patients with valvar heart disease.

Patients with mitral valve prolapse (MVP) frequently have chest pain, which may be difficult to differentiate from angina pectoris in coronary artery disease (CAD). We performed resting and exercise ECGs, pulmonary arterial pressure measurements, radionuclide ventriculography (99mtechnetium), and perfusion scintigrams (201thallium) in 56 patients with angiographically proven MVP and no CAD. Pathological results were obtained in 31% of exercise ECGs, 33% of pulmonary arterial pressure measurements during exercise, 22% of radionuclide ventriculographies, and in 75% of thallium perfusion scintigrams. A significant correlation in pathological results was found only between exercise ECG and both radionuclide ventriculography and pulmonary arterial pressure measurements. Because of the high prevalence of false-positive perfusion scintigrams in patients with typical or atypical chest pain, the use of exercise 201Tl imaging as a screening method to separate patients with MVP from those with CAD will not be appropriate. The variability of cardiac abnormalities in our patients with MVP and angiographically normal coronary arteries suggests that the MVP syndrome may represent a variable combination of metabolic, ischemic, or myopathic disorders.

Mitral valve prolapse is a very common condition. It occurs in 4-5% of the population. It may be idiopathic or associated with a number of other conditions. Myxomatous degeneration is the underlying mechanism of mitral valve prolapse. Most patients with mitral valve prolapse have no symptoms. When symptoms do occur, palpitations, chest pain and dyspnea are the major complaints. The midsystolic click occasionally followed by the late systolic murmur are the typical physical findings. The echocardiogram plays a big role in the diagnosis of mitral valve prolapse. The beta blockers are used in the treatment of the symptomatic patient.

Six patients with angina pectoris had reversible perfusion defects on stress and redistribution thallium imaging. Three patients had a positive electrocardiographic response to exercise. No significant coronary artery lesions were seen on coronary arteriography in any of the six patients. All had mild to moderate hypoxemia at rest and physiologic evidence of chronic obstructive pulmonary disease as defined by the decrease in the ratio of forced expiratory volume at 1 second to forced vital capacity (FEV1/FVC X 100) or decrease in the forced midexpiratory flow rate (FEF25-75), or both. None had clinical findings suggestive of any of the reported causes of positive thallium scans in patients with normal coronary arteriograms. Cellular dysfunction produced by hypoxemia affecting the uptake of thallium seems to be the most likely mechanism of this abnormality.

We reviewed the exercise thallium-201 (TI-201) scans and clinical data of 41 patients with chest pain and normal coronary arteries to identify clinical factors associated with "false-positive" studies. Exercise TI-201 studies were performed before angiography and often precipitated referral. Sex, beta-blocker therapy, anginal pattern, and results of exercise electrocardiography were evaluated and compared with TI-201 imaging. A negative TI-201 study was the most common finding (p less than 0.005). Of the 41 patients, 11 (27%) had abnormal exercise TI-201 scans. No clinical factor was significantly associated with a false-positive TI-201 scans. Of the 11 patients with abnormal scans, 9 had greater than or equal to 1 cardiac abnormality: right bundle branch block in 2, mitral valve prolapse in 3, paroxysmal atrial fibrillation in 2, abnormal left ventricular diastolic pressure in 3, and left bundle branch block in 1. Thus, (1) when results of exercise TI-201 imaging are used to refer patients for angiography, "false-positive" TI-201 studies are common; (2) sex, beta blockade, anginal pattern, and results of exercise electrocardiogram are not useful predictors of a false-positive TI-201 study; and (3) patients with chest pain, normal coronary arteries, and abnormal TI-201 scans frequently have other cardiac abnormalities.

In brief The mitral valve prolapse syndrome is prevalent in apparently normal people, including athletes. Symptoms, when present, range from chest pain and palpitations to anxiety neurosis. The typical finding on auscultation of the heart is a midsystolic click and/or a mid-to-late systolic high-frequency murmur. Cardiac arrhythmias are common and often do not require therapy. The exercise ECG shows ST segment depression in up to one fourth of patients. When drug therapy is necessary, beta blockers are usually selected. The overall prognosis is excellent. Sudden death, infectious endocarditis, and cerebral thromboembolic events are relatively rare.

The diagnostic accuracy of 14-lead exercise electrocardiography was evaluated in 112 women who had no history of myocardial infarction and underwent coronary angiography. The sensitivity of ST-segment displacement of 0.1 mV or more in any of 14 ECG leads was 0.79 for coronary artery stenosis of at least 70%; the specificity was 0.66. Results were similar using bipolar ECG leads CC5 and CM5 or 11 standard ECG leads. The ST-segment shifts that occurred only during exercise were associated with a 77% false-positive rate (10 of 13). Downsloping ST-segment depression did not provide more diagnostic information than horizontal ST-segment depression in the three clinical subsets of women. In women with typical angina pectoris, ST-segment depression of at least 0.15 mV for 0.08 second after the J point or a final treadmill time less than 360 seconds was predictive of proximal left or multivessel coronary artery disease. In the women with probable angina or nonspecific chest pain, this finding was not of diagnostic value. ST-segment elevation of 0.1 mV or more in leads V1-2 or a VL predicted proximal stenosis of at lest 80% in the left anterior descending coronary artery in all six women with typical angina pectoris. Maximal exercise testing in women with typical angina provides important diagnostic information when 11 standard ECG leads are recorded. In women with probable angina or nonspecific chest pain, diagnostic exercise testing is less useful and bipolar leads CC5 and CM5 are sufficient for most clinical purposes.

Twenty-four patients with mitral valve prolapse underwent cardiac catheterization, exercise testing, and exercise 201thallium scintigraphy. Of 10 patients with coronary artery disease, six had abnormal scintigrams. Two of these six had exercise-induced reversible defects, two had defects that persisted during redistribution, and two had both reversible and persistent defects. Of 14 patients with normal coronary arteries, five had negative scintigrams. Of the remaining nine patients, two had exercise-induced defects, and seven (50%) had defects involving the inferior or posterior wall that persisted during redistribution. Possible mechanisms for this latter finding are discussed. In contrast to previous reports, exercise 201thallium scintigraphy was not entirely successful in identifying patients with coronary artery disease in our patients with mitral valve prolapse.

The clinical features of mitral valve prolapse syndrome and ischemic coronary disease overlap, making differentiation of the two conditions difficult. Furthermore, many patients have both conditions. This study assessed changes in ventricular function during rest and exercise in patients with mitral valve prolapse alone and in patients with prolapse and concomitant coronary artery disease. Twelve patients with angiographically documented mitral valve prolapse and normal coronary anatomy and 11 patients with normal coronary anatomy and no mitral valve prolapse had increased ejection fraction and demonstrated no wall motion abnormality during exercise. Changes in ventricular function during exercise in 11 additional patients with mitral valve prolapse demonstrated on echocardiography were similar to those in the group with mitral valve prolapse and normal coronary anatomy seen on angiography. In contrast, 6 of 11 patients with mitral valve prolapse and coronary arterial stenosis demonstrated on angiography had a decreased ejection fraction and exhibited wall motion abnormalities during exercise. These results suggest that mitral valve prolapse alone has no detrimental effect on ventricular function during rest and exercise and that exercise-induced abnormalities in ventricular function are related to the presence and severity of coronary artery disease and not to mitral valve prolapse.

Abnormalities of left ventricular contraction in patients with mitral valve prolapse have suggested a myocardial factor in this disease. To determine systolic left ventricular function in mitral valve prolapse, technetium-99m gated equilibrium radionuclide cineangiography was performed in 47 patients with this diagnosis. In 39 patients without mitral regurgitation the average ejection fraction was normal at rest (average [+/- standard error of the mean] 57 +/- 3 percent, normal 57 +/- 1 percent, difference not significant) and exceeded the lower limits of normal in all but 1 patient, whose ejection fraction was 41 percent. However, ejection fraction during maximal exercise was lower for the group of patients with mitral prolapse without mitral regurgitation than for normal subjects (average 64 +/- 2 percent, normal 71 +/- 2 percent, p < 0.005). In eight patients with mitral prolapse and mitral regurgitation, the average ejection fraction was normal at rest but was diminished with exercise in comparison with both normal subjects and patients with mitral valve prolapse without mitral regurgitation. Chest pain, arrhythmia and the pattern or extent of mitral valve prolapse on echocardiography were not independently associated with impaired left ventricular functional reserve. We conclude that, although many patients with mitral valve prolapse have normal left ventricular function, there is a subgroup without mitral regurgitation in whom diminished left ventricular functional reserve is suggestive of a cardiomyopathic process.

Exercise thallium-201 myocardial imaging and exercise radionuclide angiography are the two techniques of nuclear cardiology most widely used for the diagnosis of coronary artery disease. EAch of these tests provides information of diagnostic and functional value. The diagnostic accuracy and clinical utility of these two tests for the detection of coronary artery disease are compared. The strengths and weaknesses of each approach are discussed. A clinical approach to the detection and evaluation of coronary artery disease using these radionuclide exercise techniques is presented.

The mitral valve prolapse syndrome may present with a variety of clinical manifestations and has proved to be a common cause of nonspecific cardiac symptoms in clinical practice. Primary and secondary forms must be distinguished. Myxomatous degeneration appears to be the common denominator of the primary form. The diagnostic standard of this form has not previously been defined because the detection of mitral leaflet tissue in the left atrium (prolapse) on physical examination or angiography is nonspecific. M mode echocardiography has greatly enhanced the recognition of this syndrome but has not proved to be the best diagnostic standard because of its limited view of mitral valve motion. The advent of two dimensional echocardiography has provided the potential means for specific identification of the mitral leaflet motion in systole and can be considered the diagnostic standard for this syndrome. Primary myxomatous degeneration with leaflet prolapse is not localized to the mitral valve. Two dimensional echocardiography has detected in preliminary studies tricuspid valve prolapse in up to 50 percent and aortic valve prolapse in about 20 percent of patients with idiopathic mitral valve prolapse.

Mitral valve prolapse is a common cardiac anomaly in which diagnosis is generally made by auscultation. In a typical case, a midsystolic click followed by a late systolic murmur is heard, although this pattern can vary. Selected pharmacologic agents (vasopressors and vasodilators) may be useful in diagnosis, and echocardiography can be helpful in cases without auscultatory signs. In the majority of cases, mitral valve prolapse is benign and no specific treatment is needed except reassurance and perhaps endocarditis prophylaxis. Patients with chest pain and symptomatic arrhythmias may benefit from propranolol, those with ventricular tachycardia should receive antiarrhythmic therapy, and those with abnormal resting ECGs or frequent ventricular premature beats should be further tested because of increased risk of sudden death or possibility of associated ischemic heart disease.

Thirty patients with angiographically documented mitral valve prolapse but without associated coronary artery disease, underwent exercise 201thallium myocardial scintigraphy. The resting ECG demonstrated ST segment abnormalities in 15 patients (50 percent). The exercise ECGs were abnormal in two patients (6.7 percent), normal in four (13.3 percent), and inconclusive in 24 patients (80 percent). Two patients (6.7 percent) had abnormal exercise myocardial scintigraphy (both patients had abnormal exercise ECGs). Two additional patients (6.7 percent) had perfusion abnormalities in the rest images that did not change with exercise. Twenty-six patients (86.4 percent) had normal scans. We conclude that the majority of patients with mitral valve prolapse have normal exercise 201thallium images in the absence of associated coronary artery disease and exercise electrocardiography is of limited value in patients with mitral valve prolapse because the results are frequently (80 percent) inconclusive.