Methionine restores the venodilative response to nitroglycerin after the development of tolerance.

Depletion of sulfhydryl groups may contribute to nitroglycerin tolerance after long-term exposure. This study was performed to assess whether methionine, an amino acid capable of augmenting sulfhydryl availability, would restore the venodilative response to sublingual nitroglycerin once tolerance had developed. The venodilative response to organic nitrates was assessed with use of the equilibration technique of forearm plethysmography. Venous volume was measured before and after sublingual administration of 0.4 mg of nitroglycerin at baseline study and after 5 g of intravenous methionine. Retesting was performed 2 h after application of a 10 mg nitroglycerin patch and compared with the response after 74 h of nitroglycerin patch exposure before and after intravenous methionine. Methionine alone had no intrinsic venodilative action. Although the venous volume at rest was unchanged after methionine administration, the response to sublingual nitroglycerin was potentiated compared with baseline values (37 +/- 15% versus 32 +/- 13%, p less than 0.02). During nitroglycerin patch exposure, the response to sublingual nitroglycerin was significantly attenuated at 74 h compared with the response at 2 h of exposure (16 +/- 10% versus 31 +/- 13%, p less than 0.001). The venodilative response to sublingual nitroglycerin was restored at 74 h after methionine administration (35 +/- 14% versus 16 +/- 10%, p less than 0.001). Thus, methionine potentiates the venodilative effect of sublingual nitroglycerin both immediately and in the setting of nitrate tolerance.

Intravenous digital left ventriculography at rest and with atrial pacing as a screening procedure for coronary artery disease.

Digital subtraction left ventriculography using intravenous contrast injection was evaluated as a screening diagnostic method for coronary heart disease. Intravenous ventriculography was performed in 61 patients with 35 cc of contrast medium injected into a central vein (usually the inferior vena cava). Recognition of regional wall motion abnormalities by this technique was shown to be comparable with direct left ventriculography in 40 patients who underwent both imaging modalities at rest. If the rest digital ventriculogram was normal, it was repeated after incremental atrial pacing to the onset of chest pain or to a maximal heart rate of 150 beats/min. Forty-four of the 61 patients had significant coronary artery disease, of whom 10 had a wall motion abnormality at rest on intravenous ventriculography. With pacing, 28 of the 34 remaining patients developed a new wall motion abnormality. Thus, 38 (86%) of 44 patients with coronary heart disease were identified by wall motion abnormalities. One of the 17 patients without coronary artery disease had an abnormal rest study and was incorrectly assigned a diagnosis of coronary disease. Intravenous digital ventriculograms approximate those obtained by direct ventriculography. When combined with atrial pacing they are a sensitive and specific means of detecting coronary artery disease.

Temporal evolution of the human coronary collateral circulation after myocardial infarction.

An analysis of the coronary collateral circulation in a consecutive series of 116 postinfarction angiograms from patients with persistent 100% occlusion of their infarct artery is reported. Patients were classified into four groups according to the interval between acute infarction and angiography. Of 42 patients studied within 6 hours of infarction (Group I), 52% had no evidence of any coronary collateral development as compared with only 8% (1 of 16 patients) studied 1 day to 2 weeks after infarction (Group II). Virtually all patients studied beyond 2 weeks after myocardial infarction (14 to 45 days, Group III) and later than 45 days (Group IV) had visible collateral flow. Angiographically "well developed" collateral channels were seen in only 16% of Group I patients compared with 62, 75 and 84% of patients in Groups II to IV, respectively. Of six patients studied twice, on the day of the infarction and 2 weeks later, only one patient had collateral vessels on the day of infarction, whereas all six patients did at follow-up study. Group I patients were studied as part of a randomized acute myocardial infarction reperfusion trial, whereas the other patients were referred for angiography primarily because of post-infarction ischemia. Within the limitations imposed by the patient selection process, it is concluded that well developed coronary collateral vessels are rarely present at the time of infarction. After infarction, they develop rapidly and are generally demonstrable within 2 weeks. It may also be inferred that the preservation of ischemic myocardium by well developed coronary collateral vessels at the time of myocardial infarction may be an uncommon occurrence.

Patient selection for thrombolytic therapy.

Recent studies have shown that the use of thrombolytic therapy in patients with acute myocardial infarction can reduce mortality 20 to 52%. However, patient selection issues remain to be resolved. These issues include the time window for therapy, treatment based on the site of infarction, treatment based on electrocardiographic criteria and treatment of the elderly population.

Recurrent early ischemic events after thrombolysis for acute myocardial infarction.

Myocardium salvaged by early thrombolysis and then perfused through a residual stenosis may be at risk for ischemic events. To investigate this possibility, the short-term (2-week) clinical course of 81 consecutive patients managed within a randomized intracoronary thrombolysis trial was reviewed. All patients underwent coronary angiography within 5 hours of symptoms of acute myocardial infarction and were stratified into the following 3 outcome groups: patients with initially subtotal occlusion (subtotal group, n = 17), those with initial total occlusion and infarct artery reperfusion (reperfused group, n = 24) and those with continued infarct artery occlusion (occluded group, n = 40). Recurrent ischemic events were defined as spontaneous typical angina, provokable angina on predischarge exercise testing, and reinfarction. Eleven of 17 patients (65%) in the subtotal and 11 of 23 patients (48%) in the reperfused groups had an ischemic event (difference not significant). In contrast, 4 of 37 patients (11%) with occlusion had an ischemic event (p less than 0.01 compared with patients in the subtotal or reperfused groups). Four patients were excluded because of early (within 72 hours) elective coronary bypass surgery or death from pump failure. To eliminate the impact of multivessel coronary artery disease (CAD), 39 patients with 1-vessel CAD were analyzed separately. Five of 9 patients (56%) in the subtotal group, 3 of 10 (30%) in the reperfused group and only 2 of 20 (10%) in the occluded group had an ischemic event. These observations suggest the need for a more definitive revascularization strategy for acute myocardial infarction.

Lipoprotein and apolipoprotein levels in angiographically defined coronary atherosclerosis.

Recent studies suggest that apolipoproteins and subfractions of high-density lipoprotein (HDL) cholesterol may be better predictors of atherosclerotic coronary artery disease (CAD) than are plasma cholesterol and total HDL cholesterol. To examine this hypothesis, plasma cholesterol and triglyceride, cholesterol of low-density lipoprotein, HDL and its subfractions 2 and 3, apolipoprotein A-I, the apolipoprotein B of low-density lipoprotein, the ratio of apolipoprotein EII to EIII, and ratios of several of these variables were measured in a selected series of 126 patients (83 men and 43 women) who underwent coronary angiography for suspected CAD. Mean values of many of these variables differed significantly between the men with CAD and the men without significant CAD, when controlled for age, use of beta blockers and diuretic drugs. Using multivariate logistic regression analysis, the only variable that made a significant independent contribution in predicting CAD in men was the ratio of HDL cholesterol to total plasma cholesterol (p less than 0.0001). The mean of this ratio was 0.17 +/- 0.01 mg/dl in the men with CAD and 0.23 +/- 0.02 mg/dl in the male controls. All men with ratios of less than 0.15 mg/dl had significant CAD, defined as 50% or greater luminal diameter narrowing of 1 or more of the major coronary arteries. No measurement was a significant univariate or multivariate predictor of CAD in the women, but the power to detect such predictors was reduced because of small group sizes. In conclusion, the ratio of HDL cholesterol to plasma cholesterol may be superior to many of the more recently described lipoprotein and apolipoprotein-derived predictors of CAD.

Clinical and hemodynamic significance of left ventricular diastolic volume changes by exercise radionuclide ventriculography in coronary artery disease.

Recent studies have suggested that left ventricular (LV) dilatation during exercise radionuclide ventriculography may identify coronary artery disease (CAD). Coronary anatomy and LV end-diastolic pressure at catheterization were compared with results of supine exercise radionuclide ventriculography in 66 patients evaluated for chest pain. Forty-six patients had significant CAD (greater than 75% diameter stenosis) and 20 patients were normal. Radionuclide ventriculography was performed within 18 hours of catheterization, at rest and at peak exercise. Relative LV end-diastolic volumes were extrapolated from end-diastolic counts. LV end-diastolic counts increased during exercise in 19 of 20 normal subjects. In patients with CAD, LV end-diastolic counts increased in 35 (group A) and decreased in 11 (group B). The percent change in LV end-diastolic counts from rest to exercise, rest ejection fraction, exercise ejection fraction and rest LV end-diastolic pressure for each group were 20 +/- 23%, 60 +/- 13%, 67 +/- 13% and 8 +/- 3 mm Hg in normal subjects; 20 +/- 20%, 50 +/- 12%, 47 +/- 13% and 12 +/- 4 mm Hg in group A; and -9 +/- 8%, 54 +/- 21%, 49 +/- 18% and 21 +/- 7 mm Hg in group B (mean +/- standard deviation). An increase in LV end-diastolic counts was unrelated to ejection fraction response or presence of underlying CAD but only correlated to rest LV end-diastolic pressure (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized, angiographically controlled trial of intracoronary streptokinase in acute myocardial infarction.

Fifty-five patients with acute myocardial infarction evaluated within 4 hours of the onset of symptoms were entered into an angiographically controlled trial of intracoronary streptokinase (IC STK). Forty-three patients with total occlusion of their infarct artery were randomized to either IC STK or intracoronary nitroglycerin (IC NTG), and 12 patients with less-than-complete occlusion received only IC NTG. Reperfusion of a totally occluded vessel was achieved in 69% of STK patients and 17% of IC NTG patients. Time from onset of symptoms to peak CK activity was significantly shorter in reperfused patients and patients with subtotal occlusion on initial angiography than in patients with total occlusion who were not reperfused (p less than 0.0001). Comparison of radionuclide ejection fractions (EF) determined acutely and 10 to 14 days after infarction failed to show improvement in either the STK or IC NTG group (mean decrease of 2.8% and 0.4%, respectively). In contrast, patients with subtotal occlusion on baseline angiography demonstrated a significant (p = 0.05) spontaneous improvement in EF over 2 weeks (7.3% increase).

Detection of left ventricular wall motion abnormalities for the diagnosis of coronary artery disease: a comparison of exercise radionuclide and pacing intravenous digital ventriculography.

Intravenous digital ventriculography before and after pacing was compared with equilibrium gated nuclear ventriculography at rest and after exercise. Specifically, the relative abilities of the 2 techniques to detect resting and stress-related wall motion abnormalities were tested. Twelve normal patients and 28 patients with coronary artery disease (CAD) were tested. Neither technique produced a new wall motion abnormality in a patient with normal coronary arteries. Six patients with CAD had a history of a myocardial infarction (MI); an abnormality at rest was present in all 6 by both techniques. Of the 22 patients with CAD and a normal baseline ventriculogram, a wall motion abnormality developed in 18 during digital ventriculography with pacing; a wall motion abnormality developed in 15 with exercise nuclear ventriculography. Wall motion abnormalities by nuclear ventriculography (performed in the left anterior oblique projection) tended to be apical; digital ventriculography (performed in the right anterior oblique projection) more often produced an abnormality of the anterior or inferior wall, which could be predictive of coronary anatomy. Thus, the 2 techniques are substantially equivalent for the detection of wall motion abnormalities in CAD.

Congenital aneurysm of the left sinus of Valsalva. Report of a patient with 19-year survival without surgery.

An unruptured aneurysm of the left sinus of Valsalva was diagnosed by angiography in a 16-year-old male subject 19 years ago. A recent repeated angiographic study documented no change in the aneurysm over the 19-year interval, and the patient has remained asymptomatic. We are aware of no other long-term follow-up reports of patients with this lesion who have not had surgical correction. This case emphasizes the controversy regarding the need for prophylactic surgical correction of an unruptured aneurysm.

Exercise-induced ST-segment depression and elevation in the same patient. A case for mixed angina.

A patient with significant left anterior descending coronary disease is presented who developed significant ST segment elevation and depression at different times under similar testing conditions. Currently proposed explanations for exercise-induced ST segment elevation are discussed. This patient likely represents a case of spasm superimposed on significant obstructive disease, so-called mixed angina.

Multiple cardiac myxomas with multiple recurrences: unusual presentation of a "benign" tumor.

A 20-year-old woman with a two-week history of palpitations and constitutional symptoms was found to have right atrial and left ventricular myxomas. The myxomas were excised, but the patient had two recurrences of the tumor in the left atrium four and a half years after the initial presentation. The recurrent myxoma was locally aggressive, and removal required excision of the aortic valve. This patient demonstrates the need for careful follow-up for recurrences of myxoma.

Radionuclide ventriculography for evaluation and prevention of doxorubicin cardiotoxicity.

Chemotherapy with doxorubicin often leads to congestive heart failure, particularly after cumulative doses of 550 mg/m2 have been reached. Certain risk factors, however, may predispose the patient to development of cardiomyopathy at lower doses. Radionuclide ventriculography with determinations of resting and exercise ejection fractions has emerged as the most reliable noninvasive screening procedure to detect subclinical cardiotoxicity. Before embarking on a course of doxorubicin therapy, patients should be stratified into low-risk and high-risk groups. Those in the high-risk group should undergo frequent monitoring by means of radionuclide ventriculography. For patients in the low-risk group, such monitoring could be postponed until they are ready to cross into the high-risk group by virtue of cumulative doxorubicin dose. Doxorubicin should be discontinued if the ejection fraction drops to less than or equal to 45% at rest or fails to increase with exercise.

Measuring contributions to the clinical mission of medical schools and teaching hospitals.

This is the final report of a panel convened as part of the Association of American Medical College's (AAMC's) Mission-based Management Program to examine the use of metrics (i.e., measures) in assessing faculty and departmental contributions to the clinical mission. The authors begin by focusing on methods employed to estimate clinical effort and calculate a "clinical full-time equivalent," a prerequisite to comparing productivity among faculty members and departments. They then identify commonly used metrics, including relative-value units, total patient-care gross charges, total net patient fee-for-service revenue, total volume per CPT (current procedural terminologies) code by service category and number of patients per physician, discussing their advantages and disadvantages. These measures reflect the "twin pillars" of measurement criteria, those based on financial or revenue information, and those based on measured activity. In addition, the authors urge that the assessment of quality of care become more highly developed and integrated into an institution's measurement criteria. The authors acknowledge the various ways users of clinical metrics can develop standards against which to benchmark performance. They identify organizations that are sources of information about external national standards, acknowledge various factors that confound the interpretation of productivity data, and urge schools to identify and measure secondary service indicators to assist with interpretation and provide a fuller picture of performance. Finally, they discuss other, non-patient-care, activities that contribute to the clinical mission, information about which should be incorporated into the overall assessment. In summary, the authors encourage the use of clinical productivity metrics as an integral part of a comprehensive evaluation process based upon clearly articulated and agreed-upon goals and objectives. When carefully designed, these measurement systems can provide critical information that will enable institutional leaders to recognize and reward faculty and departmental performance in fulfillment of the clinical mission.

The role of thrombolytic therapy for acute myocardial infarction.

Thrombolytic therapy is widely available and easily administered and can restore IRA flow. IRA patency restored by thrombolysis salvages ventricular function and reduces mortality rates, albeit with an increased risk of hemorrhagic stroke. The risk of coronary reocclusion after t-PA administration can be reduced with concomitant use of intravenous heparin given in therapeutic doses. It appears that, in terms of mortality reduction and myocardial salvage, the greatest benefit is achieved when early IRA perfusion is normal (TIMI grade 3). Unfortunately, only 50% of patients treated with the most aggressive regimens will achieve normal flow when assessed 90 min after initiating thrombolysis. New strategies using currently available agents given in different dosing regimens, combinations of strategies, and new antithrombotic agents hold the promise of increasing early patency and further reducing both mortality and ventricular dysfunction.