The contribution of gastroesophageal reflux to chest pain in patients with coronary artery disease.

OBJECTIVE: To describe the effectiveness of investigating and treating the cause of refractory chest pain in patients with coronary artery disease who are receiving optimal antianginal therapy. DESIGN: Cohort study. SETTING: Tertiary referral center. PATIENTS: Between January 1988 and December 1989, 34 patients were identified as having angiographically proven coronary artery disease and atypical chest pain symptoms despite their having received aggressive medical or surgical antianginal therapy, or both. INTERVENTION: Patients with confirmed acid-related symptoms were treated with high-dose histamine-2 (H2) blockers or omeprazole for 8 weeks in an open-label study. MEASUREMENTS: Esophageal manometry and simultaneous 24-hour pH and Holter studies; global improvement in or disappearance of chest pain. RESULTS: Of the 34 patients, 30 (88%) experienced their identical chest pain symptoms during the study. A total of 164 pain episodes was recorded: 38 (23.2%) correlated with acid reflux; 6 (3.7%) were related to cardiac ischemia; and the remaining 120 (73.2%) had no identifiable cause. Of these 30 patients, 20 (67%) had some of their episodes of chest pain (range, 14% to 100%) secondary to acid reflux. After 8 weeks of vigorous acid suppression, 13 of these 20 patients had marked improvement or resolution of chest pain. Four other patients had ischemia-related episodes of chest pain that responded to more aggressive antianginal therapy. No episodes of acid reflux were clearly followed by ischemic chest pain. One patient had both acid- and ischemic-related episodes of chest pain that were indistinguishable. Overall, 24 of 34 (71%) patients had a definite cause of chest pain identified by combined pH and Holter monitoring. CONCLUSIONS: Gastroesophageal reflux disease is a common, treatable cause of chest pain in patients with coronary artery disease who have atypical symptoms and remain symptomatic despite aggressive antianginal therapy. Combined Holter and 24-hour esophageal pH studies are complementary investigations for elucidating the cause of chest pain in these patients.

Excluding heart disease in the patient with chest pain.

Angina pectoris is chest discomfort associated with myocardial ischemia. When coronary blood flow is inadequate to meet myocardial tissue demand, lactate accumulates, resulting in diastolic and systolic left ventricular dysfunction. This leads to ST-segment abnormalities and eventually to angina pectoris. Angina, most commonly a pressure-type sensation in the midanterior chest precipitated by exercise, stress, or cold, typically lasts 1-5 minutes and is alleviated by rest or nitroglycerin. Diagnostic studies to assess myocardial ischemia include treadmill exercise testing, Holter monitoring, and coronary angiography. Treadmill exercise testing has a relatively low accuracy for diagnosing coronary artery disease. This can be improved by combining exercise with thallium-201 imaging, two-dimensional echocardiography, or positron emission tomography (PET). Thallium-201 scintigraphy and exercise echocardiography have reported sensitivities of 70-85% and specificities of 50-60% when applied to low-risk, asymptomatic populations. PET scanning has a high predictive accuracy (sensitivity 90%, specificity 90-95%) and is more useful as a screening test; it can also assess the functional significance of coronary artery stenoses and differentiate viable myocardium from infarcted tissue. Holter monitoring is too insensitive and nonspecific to be used as a screening test for coronary artery disease; it can, however, assess the total ischemic burden in patients with known coronary artery disease and correlate symptoms and ST-segment abnormalities during episodes of pain at rest. Coronary angiography has been the gold standard for diagnosing coronary artery stenoses. Quantitative angiography has improved the assessment of coronary artery narrowing but is still limited in evaluating coronary blood flow. Doppler flow studies provide useful information regarding coronary flow reserve. Myocardial ischemia as a cause of chest pain is determined by evaluating the clinical characteristics consistent with angina, correlating electrocardiographic abnormalities with perfusion defects or wall motion abnormalities, and determining the extent and functional significance of coronary artery stenoses by coronary angiography.

The prevalence of abnormal esophageal test results in patients with cardiovascular disease and unexplained chest pain.

The purpose of our study was to assess the prevalence of esophageal test abnormalities in patients with known cardiovascular disease and persistent chest pain. We performed a retrospective review of symptoms, manometry, and provocative test results performed on patients with undiagnosed chest pain. The 220 patients with angiographically determined cardiac disease and persistent chest pain were divided into three groups: coronary artery disease (125 patients), mitral valve prolapse (38 patients), and coronary bypass/angioplasty (57 patients). A comparison group consisted of 159 patients with noncardiac chest pain. All patients underwent esophageal manometry and placebo-controlled provocative testing (acid perfusion test and edrophonium chloride test). The prevalence of esophageal motility disorders in the noncardiac chest pain group (27%) was similar to that in the coronary artery disease (24%), mitral valve prolapse (37%), and coronary bypass/angioplasty (30%) groups. The frequency of nutcracker esophagus (11% to 16%) and diffuse esophageal spasm (2% to 7%) was remarkably constant. The prevalence of any positive provocative result in the noncardiac chest pain group (27%) was similar to that in the coronary artery disease (19%), mitral valve prolapse (32%), and coronary bypass/angioplasty (20%) groups. Furthermore, completely negative results of esophageal investigation occurred in 55%, 62%, 42%, and 59% of the respective patient groups.

Acute Epstein-Barr virus myocarditis simulating myocardial infarction with cardiogenic shock.

We have reported the case of a 38-year-old white woman with substernal chest pain, hypotension, and ECG changes suggesting acute anterior myocardial infarction. Cardiac catheterization revealed no coronary artery pathology, but severe global hypokinesia was noted on left ventriculogram and endomyocardial biopsy revealed myocytic degeneration and mononuclear cell infiltration consistent with acute viral myocarditis. Viral serologies confirmed a recent Epstein-Barr virus infection.

Cardiac transplantation in a patient with muscular dystrophy and cardiomyopathy.

A 17-year-old boy with muscular dystrophy developed a cardiomyopathy. His brother died of a cardiomyopathy, and muscle enzyme levels were elevated in asymptomatic family members. Examination revealed cardiomegaly, hepatomegaly, proximal muscle atrophy and weakness, and calf hypertrophy. Skeletal muscle and endomyocardial biopsy specimens were consistent with Becker's muscular dystrophy. Because of intractable heart failure, orthotopic cardiac transplantation was performed. Two years after transplantation, the patient has returned to work and regained previous exercise tolerance. Heart transplantation can be an acceptable treatment of patients who have muscular dystrophy, with preserved ambulation and favorable life expectancy, and also life-threatening cardiomyopathy refractory to medical management.

Short- and long-acting angiotensin-converting enzyme inhibitors: a randomized trial of lisinopril versus captopril in the treatment of congestive heart failure. The Multicenter Lisinopril-Captopril Congestive Heart Failure Study Group.

A randomized, parallel, double-blind study was performed with lisinopril, a long-acting angiotensin-converting enzyme inhibitor, versus captopril, a shorter-acting angiotensin-converting enzyme inhibitor, in the treatment of congestive heart failure. All patients were in New York Heart Association class II, III or IV and had remained symptomatic despite therapy with digoxin and diuretics. After a 4 to 14 day placebo baseline period, patients were randomized to receive either lisinopril, 5 mg orally once per day (n = 94), or captopril, 12.5 mg orally three times per day (n = 95), in addition to continuation of digoxin and diuretics. The dose of study drug could be doubled at 4 week intervals for a total of 12 weeks of double-blind therapy. The maximal dose was 20 mg once per day of lisinopril or 50 mg three times per day of captopril. The addition of either lisinopril or captopril to a regimen of diuretics or digoxin, or both, caused an increase in exercise duration as assessed on a motorized treadmill. When protocol violators were excluded, patients receiving lisinopril had a statistically greater increase in exercise duration than that of patients receiving captopril. In patients with renal impairment (serum creatinine greater than 1.6 mg/dl at baseline), lisinopril was superior to captopril in improving exercise duration. Lisinopril, but not captopril, increased left ventricular ejection fraction in patients with moderately to severely (less than 35%) decreased function (p less than 0.05). Improvement in functional capacity and quality of life, as assessed by the Yale Scale dyspnea/fatigue index, was significantly greater for the lisinopril group.(ABSTRACT TRUNCATED AT 250 WORDS)

Diastolic mitral regurgitation in acute but not chronic aortic regurgitation: implications regarding the mechanism of mitral closure.

In acute aortic regurgitation, left ventricular pressure rises rapidly during diastole, which produces presystolic mitral valve closure. This does not occur in chronic aortic regurgitation. Since normal, nonregurgitant mitral valve closure may depend on properly coordinated atrial and ventricular contractions, we hypothesized that abnormal mitral valve closure occurring before systole in acute aortic regurgitation may produce diastolic mitral regurgitation detectable by Doppler echocardiography. Accordingly, we performed ultrasonic Doppler examination of seven patients with acute aortic regurgitation and 12 patients with chronic aortic regurgitation. Regurgitant aortic flow was severe in all cases. Doppler sampling within the left atrium demonstrated regurgitant mitral flow in late diastole in all patients with acute aortic regurgitation. The onset of diastolic mitral regurgitation coincided with mitral valve preclosure in patients with acute aortic regurgitation and occurred regardless of the position of the mitral leaflets at the initiation of closure. In contrast, none of the 12 patients with chronic aortic regurgitation had mitral valve preclosure or diastolic mitral regurgitation (p less than 0.05 versus acute aortic regurgitation). We conclude that diastolic mitral regurgitation accompanies mitral valve preclosure, which occurs in acute but not chronic aortic regurgitation. Thus diastolic mitral regurgitation may be a Doppler sign of acute aortic regurgitation, in the absence of a markedly prolonged PR interval. Furthermore, this observation suggests that normal, nonregurgitant mitral closure requires more than an increase in left ventricular pressure above left atrial pressure, regardless of the position of the mitral leaflets before closure.

Long-term follow-up of symptomatic status of patients with noncardiac chest pain: is diagnosis of esophageal etiology helpful?

Questionnaires were sent to 119 patients with noncardiac chest pain, all of whom had previous detailed esophageal evaluations in which 63 were diagnosed as having pain from the esophagus. Mean follow-up period was 21.8 months. Patients diagnosed as having an esophageal etiology of their noncardiac chest pain usually continued to have recurrent pain. Furthermore, a specific diagnosis did not significantly increase the likelihood of pain resolution. However, patients who understood that the esophagus was the source of their pain were significantly less likely to feel disabled by their pain and to require continued physician evaluation. This finding was independent of any treatment program. This study emphasizes the importance of a careful evaluation of the esophagus as a potential source of pain and clearly communicating this information to the patient.

A double-blind comparison of lisinopril with captopril in patients with symptomatic congestive heart failure.

Angiotensin-converting enzyme (ACE) inhibition with captopril is accepted therapy for the treatment of symptomatic congestive heart failure. In this trial, we compared the new ACE inhibitor, lisinopril, to captopril during a 12-week randomized double-blind study. One hundred twenty-nine patients with New York Heart Association class II, III, or IV congestive heart failure were randomized to receive either lisinopril 5 mg/day (n = 64) or captopril 37.5 mg/day (n = 65) in 15 centers. Drug doses could be titrated upwards every 4 weeks. The primary measure of drug efficacy was improvement in treadmill exercise time using a modified Naughton protocol. Secondary measures of efficacy and the development of adverse effects were also examined. Lisinopril improved exercise time (following 12 weeks of therapy) more than captopril [from 500 +/- 30 to 682 +/- 34 sec (mean +/- SEM) with lisinopril versus 480 +/- 26 to 600 +/- 35 sec with captopril; difference between groups, p less than 0.05]. Adverse drug effects were unusual and similar in frequency in the two groups, although an increase in blood urea nitrogen was more common with lisinopril than with captopril (p less than 0.05). These results indicate that using the doses and treatment regimens studied, lisinopril is more effective than captopril for the treatment of symptomatic congestive heart failure. Adverse experiences with lisinopril were infrequent and similar in incidence to those observed with captopril.

Edrophonium: a useful provocative test for esophageal chest pain.

Esophageal motility disorders may be an important cause of noncardiac chest pain. To improve our diagnostic yield, we studied the use of edrophonium as a provocative test for inducing esophageal chest pain in 50 symptomatic patients without coronary artery disease and in 25 age-matched controls. Edrophonium (80 micrograms/kg of body weight, intravenous bolus) induced chest pain in 15 (30%) patients and in no controls. Edrophonium increased esophageal amplitude and repetitive contractions to a similar degree in all subjects, but the change in duration (101 +/- 13% [SE] was significantly greater (p less than 0.02) in patients in whom chest pain was induced. Drug specificity was assessed in 9 patients during cardiac catheterization, but no significant change was seen in coronary artery diameter, blood pressure, or heart rate. Further clinical testing using a placebo control confirmed a positivity rate of 28% in 125 unselected patients with chest pain referred to our laboratory; false-positive tests were infrequent (5.6%). No important side effects were seen. Edrophonium is useful for provoking esophageal chest pain.

Spasm of the aortocoronary venous graft.

Two cases of spasm of the coronary artery bypass graft are reported, and the angiographic and clinical findings are discussed. Few previous reports of this entity were found in a search of the literature. The therapeutic implications are also presented.

Venous thrombosis as a cause of superior vena cava syndrome. Rapid response to streptokinase.

Venous thrombosis, resulting in superior vena cava syndrome, developed in a patient with two permanent transvenous pacemaker wires. Therapy with streptokinase resulted in prompt relief of the obstruction, with no complications. In properly selected patients, streptokinase may be the treatment of choice for this potentially life-threatening problem.

Coronary artery thrombus: rapid resolution shown by serial coronary arteriography.

Resolution of a coronary artery thrombus within two weeks was demonstrated by serial coronary arteriography in a man with atherosclerotic coronary artery disease. This observation indicates that subtotal coronary artery thrombosis does not invariably progress to complete occlusion of the affected vessel and that the resolution of coronary artery thrombus can occur rapidly.

Comparison of Tc-99m pyrosphosphate and Tc-99m hydroxymethylene diphosphonate in acute myocardial infarction: concise communication.

A clinical comparison between a new bone seeking radiopharmaceutical, Tc-99m hydroxymethylene diphosphonate (TcHMDP) and the standard agent, Tc-99m pyrophosphate (TcPPi), was performed in 18 patients with acute myocardial infarction. Each patient was imaged initially with either TcHMDP or TcPPi, and imaged 24 hr later with the other tracer. All 18 patients had images positive for acute myocardial infarction with TcPPi, whereas 16 of 18 patients (89%) had positive studies with TcHMDP. The TcPPi images were graded significantly superior to those obtained with TcHMDP in 61% of the patients, and they were equal in 33%. In only one patient (6%) was TcHMDP better. The results indicate that compared with TcHMDP, TcPPi not only has a superior sensitivity for acute myocardial infarction but also has a significantly increased intensity of uptake in positive areas. TcPPi remains the agent of choice for myocardial infarct imaging.

Comparison of Tc-99m pyrophosphate and Tc-99m methylene diphosphonate in acute myocardial infarction: concise communication.

This study compared Tc-99m pyrophosphate (PPi) and Tc-99m methylene diphosphonate (MDP) for myocardial infarct imaging in 24 patients with diagnosed acute myocardial infarction. The radiopharmaceuticals were administered randomly and interpreted without knowledge of the sequence used. Twenty-three patients (96%) had positive Tc-99m PPi scintigrams, but only 17 (71%) had a positive Tc-99m MDP study (P less than 0.05). In addition, a comparison of the relative intensity with each agent revealed greater intensity with Tc-99m in 21 cases, equal intensity in two cases, and less intensity in only one case (p less than 0.001). These findings support the superiority of Tc-99m PPi as the agent of choice for myocardial scintigraphy in acute infarction.