A randomized trial of intravenous heparin in conjunction with anistreplase (anisoylated plasminogen streptokinase activator complex) in acute myocardial infarction: the Duke University Clinical Cardiology Study (DUCCS) 1.

OBJECTIVES: We designed a randomized trial to evaluate the effects of heparin administration in conjunction with anistreplase (anisoylated plasminogen streptokinase activator complex [APSAC]) on arterial patency and clinical end points. BACKGROUND: The role of conjunctive intravenous heparin therapy with APSAC has not been tested despite the recommendations that intravenous heparin should be used. METHODS: Four hours after APSAC administration, 250 patients with acute myocardial infarction were randomly assigned to receive 325 mg of either aspirin alone or aspirin and a continuous infusion of heparin (15 IU/kg body weight per h). Clinical ischemic events and bleeding complications were monitored. On hospital day 5, coronary arteriography and left ventriculography were performed. RESULTS: The primary end point of the trial (the combined outcome of death, reinfarction, recurrent ischemia and occlusion of the infarct-related artery) occurred in 42% of the heparin-treated group versus 43% of the group treated without heparin (p = 0.94). A patent infarct-related artery was present in 80% of the patients treated with heparin and in 73% of those treated without heparin (p = 0.26). Left ventricular function, as measured by ejection fraction, was well preserved in both groups (52% vs. 50.5%, respectively, p = 0.29). The overall bleeding rate was higher in patients with (32%) than without (17.2%) heparin (p = 0.006). CONCLUSIONS: Weight-adjusted intravenous heparin therapy after APSAC in acute myocardial infarction does not reduce the combined incidence of death, reinfarction, recurrent ischemia and occlusion of the infarct-related artery. Furthermore, withholding intravenous heparin therapy is associated with a 46% reduction in bleeding complications. Our findings do not support the addition of intravenous heparin after APSAC therapy, as currently recommended, and suggest that a strategy of withholding heparin is simpler and safer and does not place the patient at increased risk for ischemic complications after myocardial infarction.

Failure of alpha-methyltyrosine to prevent hypertensive crisis in pheochromocytoma.

Sudden onset of a hypertensive crisis occurred shortly after induction of anesthesia in a patient with malignant pheochromocytoma, despite preoperative medical preparation with alpha-methyltyrosine (alpha-methyl-p-tyrosine) and propranolol hydrochloride. Other investigators have advocated alpha-methyltyrosine as the medical therapy of choice in the preoperative preparation of patients with pheochromocytoma. This case emphasizes the caution that should be exercised when using alpha-methyltyrosine preoperatively, without concurrent alpha-adrenergic blocking agents, to prevent intraoperative hypertensive crisis.

Antihypertensive therapy in the elderly. Effects on blood pressure and cerebral blood flow.

Antihypertensive therapy significantly reduces cardiovascular morbidity and mortality in the rapidly growing population of elderly patients. However, the desire to treat more of these patients is dampened by the concern that a reduction in blood pressure may compromise cerebral blood flow, causing untoward consequences. This study evaluated the therapeutic effect of titrated doses of prazosin, an alpha-adrenergic blocking agent, on systemic blood pressure and cerebral blood flow in elderly patients with chronic stable hypertension. Prazosin alone or co-administered with hydrochlorothiazide significantly lowered mean systolic and diastolic blood pressures in 31 elderly hypertensive patients. At the same time, however, there was no significant change in cerebral blood flow, which was measured in eight patients. Neither harmful biochemical changes nor treatment-related adverse effects were observed in any patients. Prazosin therapy alone or in combination with low-dose diuretic therapy was effective in the treatment of hypertension in this elderly population. Furthermore, blood pressure reduction with prazosin therapy was accomplished without compromising cerebral blood flow and without unfavorably altering lipid profiles.

Detection, characterization and functional assessment of reperfused Q-wave acute myocardial infarction by cine magnetic resonance imaging.

The capability of dynamic gradient-refocused magnetic resonance imaging (cine MRI) to detect, localize and functionally assess acute myocardial infarction (AMI) in 25 patients at a mean time interval of 7 days after AMI was evaluated. Fifteen asymptomatic volunteers were also examined to determine the specificity of the observations. Upon presentation, each patient received intravenous thrombolytic therapy, underwent immediate cardiac catheterization and had percutaneous transluminal coronary angioplasty performed when coronary reperfusion was absent. Twenty-four of the patients had documented coronary reperfusion at a mean interval of 259 +/- 129 minutes. Global ejection fraction and regional wall motion abnormalities were evaluated at 7 days by cine MRI, left ventriculography and radionuclide angiography. Twenty patients with both an absolute decrease in myocardial signal and a matched regional wall motion abnormality had AMI properly identified by cine MRI. In contrast, the finding of both decreased signal intensity and a matched regional wall motion abnormality was absent in the group of asymptomatic volunteers. The ejection fraction by cine MRI correlated better with the ejection fraction by left ventriculography (r = 0.94, standard error of the estimate = 3.6) than did the ejection fraction by radionuclide angiography (r = 0.82, standard error of the estimate = 5.8). The regional wall motion concordance rate in comparison to left ventriculography was similar for both cine MRI (69%) and radionuclide angiography (65%). These findings suggest that cine MRI may play an important role in the future detection and functional characterization of AMI.

A randomized factorial trial of reperfusion strategies and aspirin dosing in acute myocardial infarction. The DUCCS-II Investigators.

The focus of new research efforts to improve the morbidity and mortality associated with acute myocardial infarction (AMI) has turned to adjuvant agents that show promise of improving outcomes following coronary thrombolysis. We enrolled 162 patients with AMI in a randomized trial comparing front-loaded tissue-plasminogen activator (t-PA) plus weight-adjusted heparin with anisoylated plasminogen streptokinase activator complex (APSAC) without heparin as well as standard-dose (325 mg) and low-dose (81 mg) aspirin. The primary end point was an in-hospital morbidity profile; secondary end points were clinical and angiographic potency and hemorrhagic events. Selected sites performed an electrocardiographic substudy to determine the time to 50% ST-segment recovery and the time to steady state. Although the trial was terminated when the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries-I trial showed that t-PA had a significant mortality advantage over streptokinase, important trends were evident. Patients given t-PA and heparin were better anticoagulated (p = 0.001), yet AP-SAC-treated patients had more bleeding complications. The primary end point favored t-PA (25.4% vs 31.3%), and the secondary end points were similar in both groups. In the electrocardiographic substudy, the t-PA group achieved both 50% ST-segment recovery and steady-state recovery sooner than the APSAC group. Patients taking low-dose aspirin had lower in-hospital mortality and less recurrent ischemia but more strokes than the standard-dose aspirin group. Thus, this trial demonstrated trends favoring front-loaded t-PA with weight-adjusted heparin over APSAC without heparin in the treatment of AMI. The use of low-dose aspirin did not appear to impose a loss of protection from adverse events, nor did standard-dose aspirin increase serious bleeding.

Heterogeneous signal intensity in magnetic resonance images of hypertrophied left ventricular myocardium.

Left ventricular hypertrophy is associated with decreased longevity and often leads to congestive heart failure. An exploratory study of magnetic resonance imaging in human left ventricular hypertrophy was performed. First, 13 patients with left ventricular hypertrophy and 7 controls of similar ages were studied using electrocardiogramgated end-diastolic images. Visual inspection suggested that low-intensity zones were frequently found within the hypertrophied myocardium. To verify this observation, the images were processed with semi-automatic edge detection and a derivative-based tissue characterization algorithm, yielding tissue heterogeneity indices (THI-A and THI-V) which objectively measured the low-intensity zones. THI-A and THI-V were both significantly greater in left ventricular hypertrophy patients than in controls (THI-A: 0.111 vs 0.038, p = 0.009). THI was also significantly correlated with duration of disease and electrocardiographic abnormalities. To validate these initial findings prospectively, the same quantitative analysis was applied to magnetic resonance images of an additional 20 left ventricular hypertrophy patients and 12 controls from two institutions, using different imaging systems and different acquisition parameters. Again, THI was significantly greater in patients than in controls. Analysis of end-systolic images yielded similar results. In four dogs with left ventricular hypertrophy induced by aortic banding, THI showed a statistically significant increase as left ventricular hypertrophy developed. Hypertrophied myocardium thus shows reproducible differences from normal tissue with magnetic resonance imaging; hence, quantitative magnetic resonance tissue characterization may be useful in assessing pathologic changes in LVH.

The inconsistent effects of calcium supplements upon blood pressure in primary hypertension.

The effects of 800 mg of elemental calcium per day (calcium carbonate or calcium citrate) on blood pressure were compared with a placebo in a controlled randomized, crossover, double-blinded trial involving 26 patients with uncomplicated primary hypertension. Each patient took two of the three forms of therapy orally for 8-week intervals with a 2-week washout period in between. Standing mean blood pressure rose an average of 5.7 mm Hg on placebo, rose an average of 0.5 mm Hg on calcium carbonate, and fell an average of 2.2 mm Hg on calcium citrate. Changes in sitting mean pressures averaged +1.9 mm Hg on placebo, -0.4 mm Hg on calcium carbonate, and -0.4 mm Hg on calcium citrate. Some patients had a fall, others had a rise in blood pressure on each form of calcium. Similarly, inconsistent responses were noted among the nine patients who took both forms of calcium. Neither initial nor post-treatment biochemical measures nor patient characteristics were predictive of the blood pressure response. Combinations of various measures and characteristics analyzed by the multiple regression technique explained only 30% of the overall variability in blood pressure. Therefore, until ways can be found to predict the response, calcium supplements should not be routinely prescribed for the treatment of hypertension and, if given for any indication, blood pressure should be monitored.

The calcium deficiency hypothesis of hypertension: a critique.

Primary (essential) hypertension has recently been related to calcium deficiency, rather than excess. The evidence used to support this hypothesis includes surveys showing lesser dietary intake of calcium, lower levels of ionized calcium in the blood, and reduction of blood pressure with calcium supplements. This critique examines each of these points and the theoretical construct used to explain the hypothesis. We conclude that the theoretical construct is based on the use of only a portion of available experimental data and the clinical evidence remains inconclusive. Until the hypothesis is supported further, calcium deficiency should not be accepted as a mechanism responsible for hypertension and calcium supplements should be used with caution.