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Objectives: The purpose of this study was to determine the efficacy and safety of intravenous RSD1235 in terminating recent onset atrial fibrillation (AF)., Background: Anti-arrhythmic drugs currently available to terminate AF have limited efficacy and safety. RSD1235 is a novel atrial selective anti-arrhythmic drug., Methods: This was a phase II, multi-centered, randomized, double-blinded, step-dose, placebo-controlled, parallel group study. Fifty-six patients from 15 U.S. and Canadian sites with AF of 3 to 72 h duration were randomized to one of two RSD1235 dose groups or to placebo. The two RSD1235 groups were RSD-1 (0.5 mg/kg followed by 1 mg/kg) or RSD-2 (2 mg/kg followed by 3 mg/kg), by intravenous infusion over 10 min; a second dose was given only if AF was present. The primary end point was termination of AF during infusion or within 30-min after the last infusion. Secondary end points included the number of patients in sinus rhythm at 0.5, 1, and 24 h post-last infusion and time to conversion to sinus rhythm., Results: The RSD-2 dose showed significant differences over placebo in: 1) termination of AF (61% vs. 5%, p < 0.0005); 2) patients in sinus rhythm at 30 min (56% vs. 5%, p < 0.001); 3) sinus rhythm at 1 h (53% vs. 5%, p = 0.0014); and 4) median time to conversion to SR (14 vs. 162 min, p = 0.016). There were no serious adverse events related to RSD1235., Conclusions: RSD1235, a new atrial-selective anti-arrhythmic agent, appears to be efficacious and safe for converting recent onset AF to sinus rhythm.

Objectives: This study compared the effects of amlodipine, atenolol and their combination on ischemia during treadmill testing and 48-h ambulatory monitoring., Background: It is not known whether anti-ischemic drugs exert similar effects on ischemia during ambulatory monitoring and exercise treadmill testing., Methods: Patients with stable coronary artery disease and ischemia during treadmill testing and ambulatory monitoring were randomized to receive amlodipine (n = 51) or atenolol (n = 49). Each group underwent a counterbalanced, crossover evaluation of single drug and placebo, followed by evaluation of the combination., Results: Amlodipine and the combination prolonged exercise time to 0.1-mV ST segment depression by 29% and 34%, respectively (p < 0.001) versus 3% for atenolol (p = NS). During ambulatory monitoring, the frequency of ischemic episodes decreased by 28% with amlodipine (p = 0.083 [NS]), by 57% with atenolol (p < 0.001) and by 72% with the combination (p < 0.05 vs. both single drugs; p < 0.001 vs. placebo). Suppression of ischemia during exercise testing and ambulatory monitoring was similar in patients with and without exercise-induced angina. Exercise time to angina improved by 29% with amlodipine (p < 0.01), by 16% with atenolol (p < 0.05) and by 39% with the combination (p < 0.005 vs. placebo, atenolol and amlodipine). In patients with angina, total exercise time improved by 16% with amlodipine (p < 0.001), by 4% with atenolol (p = NS) and by 19% with the combination (p < 0.05 vs. placebo and either single drug). In those patients without angina, no therapy significantly improved total exercise time., Conclusions: Ischemia during treadmill testing was more effectively suppressed by amlodipine, whereas ischemia during ambulatory monitoring was more effectively suppressed by atenolol. The combination was more effective than either single drug in both settings.

Objectives: This study was conducted to compare the influence of psychologic traits versus ischemia severity on the occurrence of angina during treadmill exercise., Background: Some studies suggest that angina is associated with certain psychologic traits, whereas others show an association with more severe ischemia. The relative influence of these two factors and the extent to which they interact are not known., Methods: Off-drug treadmill exercise testing and a battery of psychologic tests were performed on 122 patients with known coronary artery disease. Psychologic tests measured sensitivity to physical symptoms, denial and deception, type A behavior, anger, hostility, depression, marital adjustment and amount of external stress. Stepwise logistic regression was used to determine the independent association of psychologic traits, ischemic threshold and exercise tolerance with the occurrence of angina., Results: Angina during treadmill exercise was reported by 66 of 122 patients. On univariate testing, angina was positively associated with sensitivity to physical symptoms (p < 0.001), type A behavior (p = 0.021) and depression (p = 0.032) and was negatively associated with exercise tolerance (p < 0.001) and work load threshold for ischemia (p < 0.01). Multivariate analysis revealed independent and additive associations of angina with sensitivity to physical symptoms (p = 0.003), exercise capacity (p = 0.003) and work load threshold for ischemia (p = 0.018). Once these were included in a logistic model, depression and type A behavior were no longer significant. Other psychologic traits showed no association with angina., Conclusions: Sensitivity to physical symptoms, ischemic threshold and exercise tolerance are independently associated with angina, with sensitivity to physical symptoms having the stronger influence. The physiologic and psychologic mechanisms underlying symptom perception have an influence on angina that is independent of and additive to the severity of underlying ischemia.

Patients with New York Heart Association functional class II or III heart failure stabilized on furosemide therapy were entered into a randomized controlled trial comparing enalapril (n = 72) and digoxin (n = 73). End points were clinical outcome, treadmill exercise capacity and echocardiographic left ventricular dimensions. Improvement in clinical outcome was defined as a reduction of at least one functional class or withdrawal because of an adverse clinical event. After 4 weeks, 13 patients receiving enalapril showed improvement, 55 had no change and 9 manifested deterioration compared with 7, 49 and 17, respectively, in the digoxin group (p less than 0.01). After 14 weeks, 13 patients receiving enalapril showed improvement, 50 had no change and 9 manifested deterioration, compared with 14, 37 and 22, respectively, in the digoxin group (p less than 0.025). More patients in the digoxin group were withdrawn because of an adverse clinical event (p less than 0.05). Exercise time and percent fractional shortening improved in both groups (p less than 0.001 and less than 0.05, respectively), with no significant difference between groups (p greater than 0.50). Both rate-pressure product and subjectively evaluated exertion during submaximal exercise were reduced only in the enalapril group. Although the majority of patients in both groups did well, those receiving enalapril experienced fewer adverse clinical events and had less fatigue during submaximal exercise.

Although the diagnostic utility of thallium-201 myocardial imaging after dipyridamole infusion is well established, the intravenous form of the drug is not yet commercially available in North America. Fifty patients referred for coronary angiography were prospectively studied. Within a 2 week period, each patient underwent cardiac catheterization and thallium-201 myocardial imaging after both oral and intravenous dipyridamole administration. For the oral protocol, patients were randomly assigned to treatment with either 200 or 400 mg of dipyridamole in tablet form. Coronary artery stenoses of 70% or greater were considered significant. For the 25 patients who received a 200 mg oral dose of dipyridamole, the scintigraphic study showed perfusion defects in 65% of patients with significant coronary artery disease after the oral dose and in 85% of patients after the intravenous dose. For the 25 patients who received a 400 mg oral dose, the sensitivity of the scintigram was 84% after the oral dose and 79% after the intravenous dose. Except for headache and nausea, side effects were less severe and less frequent with oral (either 200 or 400 mg) than with intravenous dipyridamole. Because of the delayed and variable absorption of dipyridamole tablets, the oral studies required a longer period of medical supervision (45 to 60 minutes), and aminophylline was empirically administered after completion of the first set of thallium-201 images. It is concluded from this study that thallium-201 myocardial imaging after coronary vasodilation with a 400 mg oral dose of dipyridamole is a safe, widely available and reliable alternative for the evaluation of coronary artery disease in patients unable to achieve an adequate exercise level on stress testing.