Deven J. Patel

Comparison of the effect of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina.

OBJECTIVES This study compared the effects of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina. BACKGROUND Transient myocardial ischemia occurring in patients with unstable angina is associated with an adverse prognosis. Heparin and aspirin are two drugs used frequently in the treatment of this condition, but the effect of combination therapy versus aspirin alone on transient myocardial ischemia is unknown. METHODS Two hundred eighty-five consecutive patients with unstable angina were randomized to receive either intravenous heparin plus oral aspirin (150 mg once daily) (Group H + A) or aspirin alone (Group A). Patients also received a beta-adrenergic blocking agent, diltiazem and intravenous nitrates. ST segment monitoring was performed for the 1st 48 h of treatment. Patients were followed up for the duration of their in-hospital stay. RESULTS One hundred fifty-four patients (30 women, mean [+/- SEM] age 58.3 +/- 0.8 years) received heparin and aspirin (Group H + A), and 131 patients (26 women, mean age 60.6 +/- 0.8 years) received aspirin only (Group A). ST segment monitoring (11,622 h) yielded 244 episodes of transient myocardial ischemia of a total duration of 7,819 min. There were no significant differences between the two treatment arms in the number of patients with transient myocardial ischemia (27 [18%] in Group H + A vs. 31 [24%] in Group A), number of episodes (96 in Group H + A vs. 148 in Group A) or total duration of transient myocardial ischemia (2,911 min in Group H + A vs. 4,908 min in Group A). The incidence of in-hospital myocardial infarction or death was significantly higher in patients with transient myocardial ischemia (53% vs. 22%, p < 0.0001). Five of the six deaths occurred in patients with transient myocardial ischemia. Event-free survival from myocardial infarction or death was similar in both treatment groups. Preadmission therapy with aspirin was associated with a lower in-hospital infarction rate (19% vs. 34%, p = 0.01). CONCLUSIONS The presence of transient myocardial ischemia in patients with unstable angina is associated with a significantly higher incidence of myocardial infarction or death in hospital. Combined therapy with heparin and aspirin compared with aspirin alone makes no difference in the development of these events, nor does it reduce the development of transient myocardial ischemia.

Different Effects of Calcium Antagonists, Nitrates, and β-Blockers on Platelet Function Possible Importance for the Treatment of Unstable Angina

BACKGROUND The three major classes of antianginal drug all inhibit platelet aggregation at high concentrations in vitro, but detecting clinically relevant effects has proved to be more difficult. We used whole-blood flow cytometry, a sensitive method that allows direct measurement of activation antigens on the surface of individual platelets in whole unfixed blood, to evaluate the effect of representative antianginal drugs on platelet function in vivo in healthy volunteers. METHODS AND RESULTS The effects of glyceryl trinitrate (GTN), amlodipine, and atenolol were studied in nine normal volunteers. Fibrinogen binding to activated GP IIb/IIIa and expression of P-selectin, GP Ib, and GP IIb/IIIa on the platelet surface were measured. In addition, fibrinogen binding and P-selectin expression were measured in response to ex vivo stimulation with the agonists ADP and thrombin. The three drugs had very different effects on platelets. GTN inhibited platelet fibrinogen binding and expression of P-selectin at rest and in response to agonist stimulation, whereas amlodipine enhanced P-selectin expression and atenolol increased fibrinogen binding in response to agonists. Atenolol did not block the stimulatory effects of epinephrine on ADP-induced platelet activation. GTN neutralized the proactivatory effects of amlodipine, whereas the effects of atenolol and amlodipine were not additive. CONCLUSIONS The three main classes of antianginal medication have different and possible clinically relevant effects on platelet behavior in vivo, nitrates causing inhibition of aggregation (fibrinogen binding) and degranulation (P-selectin expression), calcium antagonists enhancing degranulation, and beta-blockers enhancing aggregation.Background The three major classes of antianginal drug all inhibit platelet aggregation at high concentrations in vitro, but detecting clinically relevant effects has proved to be more difficult. We used whole-blood flow cytometry, a sensitive method that allows direct measurement of activation antigens on the surface of individual platelets in whole unfixed blood, to evaluate the effect of representative antianginal drugs on platelet function in vivo in healthy volunteers. Methods and Results The effects of glyceryl trinitrate (GTN), amlodipine, and atenolol were studied in nine normal volunteers. Fibrinogen binding to activated GP IIb/IIIa and expression of P-selectin, GP Ib, and GP IIb/IIIa on the platelet surface were measured. In addition, fibrinogen binding and P-selectin expression were measured in response to ex vivo stimulation with the agonists ADP and thrombin. The three drugs had very different effects on platelets. GTN inhibited platelet fibrinogen binding and expression of P-selectin at rest...

Pathophysiology of Transient Myocardial Ischemia in Acute Coronary Syndromes Characterization by Continuous ST-Segment Monitoring

BACKGROUND Transient ischemia in stable coronary disease peaks in the morning, reflecting increased myocardial oxygen demand and coronary vasomotor tone after walking. In acute coronary syndromes, however, ischemia may result from transient thrombus formation or coronary spasm at the site of a ruptured plaque. We report on the pathophysiological mechanisms underlying transient ischemia in acute coronary syndromes despite optimal therapy, on the basis of analysis of heart rate changes preceding ischemia and its circadian variation. METHODS AND RESULTS Two hundred fifty-six patients with unstable angina or non-Q-wave myocardial infarction underwent continuous ST-segment monitoring for 48 hours while receiving maximal medical therapy. All ischemic episodes were characterized by their timing, duration, association with pain, and heart rate changes before the onset of ischemia. During 10,629 hours of monitoring, 44 patients (17.2%) had 176 episodes of transient ischemia. The mean heart rate at onset of ischemia was 68 +/- 12.8 bpm, and > 55% of ischemic episodes were not preceded by a significant increase in heart rate. Ischemic activity had a single nocturnal peak, with 64% of all episodes occurring between 10 PM and 8 AM, this nocturnal preponderance being evident for episodes with or without a preceding increase in heart rate. The characteristics and timing of transient ischemia were similar in unstable angina and non-Q-wave myocardial infarction, but transient ischemia was more frequent (27.3% versus 15.1%; P < .05) and prolonged (median, 20 versus 13.5 minutes; P < .01) in non-Q-wave myocardial infarction. CONCLUSIONS In acute coronary syndromes, transient ischemia has a low threshold, occurs predominantly without an increase in myocardial oxygen demand, and is present mainly at night rather than in the morning. These findings in patients receiving maximal medical therapy suggest significant pathophysiological differences underlying transient ischemia compared with stable coronary disease.

Objective assessment of the response to treatment of severe heart failure using a 9-minute walk test on a patient-powered treadmill*

BACKGROUND No previous studies have demonstrated the changes in exercise capacity that occur during treatment of decompensated severe heart failure. The authors assessed the efficacy and safety of using a patient-powered treadmill to objectively measure exercise capacity and its relationships, if any, to symptom scores and body weight. METHODS AND RESULTS Changes in time-limited exercise capacity on a patient-powered treadmill were assessed during inpatient treatment of 12 patients with decompensated chronic heart failure (New York Heart Association classes III and IV). Patients performed a 9-minute walk test daily for 7 days and again at the 6-week follow-up examination. They also completed a 24-item symptom score questionnaire. After treatment, there was a rapid, significant increase in total distance walked, with the increase beginning as early as the second day after admission (mean distance walked +/- SEM, 54 +/- 27 m and 174 +/- 54 m on admission and on day 2, respectively, P < .05). Improvement was maintained throughout the period in the hospital and at 6 weeks (P < .001). Patients reported symptomatic improvement, but this did not reach significance until 4 days after admission (P < .05). Weight loss was not significant. Improved exercise capacity correlated with reduced symptoms and weight loss, but preceded these by several days. CONCLUSIONS In patients with decompensated chronic heart failure, this exercise test provides a safe, practical, inexpensive, and objective assessment of functional capacity, providing certain advantages over other indices of response to therapy, such as symptom scores and weight loss. Improvement of exercise capacity does not occur concurrently with relief of symptoms and weight loss.

Asynchronous left ventricular wall motion in unstable angina.

The objective of the study was to assess the nature of left ventricular wall motion disturbances in patients with unstable angina and the relative contributions of the severity of symptoms and the severity of coronary artery disease (CAD) to their genesis. A prospective examination was performed on 30 patients with unstable angina (UA) with triple CAD, 34 matched patients with chronic stable angina (CSA) (20 with triple CAD and 14 with isolated left anterior descending (LAD) artery disease), and compared to 21 normals. LV cavity size was normal in all three groups. Twenty-two of 30 patients with UA had marked (>3 mm) abnormal long axis shortening during isovolumic relaxation time (IVRT), 65% of LV sites being abnormal. In CSA, minor (<3 mm) shortening during IVRT occurred in 7 patients with triple CAD, and in 5 with LAD disease, with 12% of LV sites involved in both groups, P<0.001 vs. UA. The incidence of other long axis abnormalities, including reduced extent and peak rate of shortening and lengthening as well as the delay in the onset of shortening and lengthening was increased between patients with CSA and triple CAD compared with LAD but not between the two groups of patients with triple CAD, CSA and UA. Transmitral E/A ratio was also reduced in the two groups with triple vessel disease, CSA and UA. Thus, the incidence of minor long axis abnormalities is similar in CSA and UA and is related to the severity of CAD. However, abnormal shortening during IVRT is more severe and generalised in UA but not in CSA with triple vessel disease. We suggest that these abnormalities of wall motion bear a close relation to the development of instability within the setting of CAD.

Tenuous link between ischaemic threshold and both ambulatory ischaemia and symptom status over time in stable angina : a 5-year follow-up study

This study evaluates changes in ischaemic threshold over a 5-year period in patients with stable angina pectoris, who did not suffer any intervening cardiac event. Changes in ischaemic threshold are related to alterations in symptomatic status and ambulatory ischaemia. Over long-term follow-up, there is a significant fall in ischaemic threshold in such patients (mean heart rate at onset of ischaemia fell from 104 +/- 17.8 to 97 +/- 17.4 bpm: P < 0.001), but this is not matched by a worsening of either symptoms or ischaemia during daily life. In the 68% of patients that had a reduction in ischaemic threshold of > or = 5 bpm, 68% had either definite reduction or no change in symptoms and 84% had either reduction, abolition or no change in transient ischaemic activity. The dissociation between ischaemic threshold, ambulatory ischaemia and symptoms has implications for long-term monitoring and management of the patient with stable angina.