805-1 Theophylline Reverses Myocardial Infarction-Related Brady and Tachy Arrhythmias: Role of Adenosine

Brady and tachyarrhythmias often complicate the early management of acute myocardial infarction (MI). Endogenously released adenosine (ADO) from ischemic cardiac cells has been proposed as a potential mediator of these arrhythmias. In order to test this hypothesis, theophylline (THEO), a competitive ADO receptor antagonist, was administered to nine patients who developed sustained or hemodynamically significant brady or tachyarrhythmias immediately following an acute inferior MI.MethodsOnce such an arrhythmia was detected, continuous ECG monitoring was begun. THEO was then administered i.v. at a rate of 100mg/min until the arrhythmia resolved or a maximum of 250mg THEO was infused. Patients were then monitored for 24 hours for recurrent arrhythmias.ResultsBradyarrhythmias were detected in 5 patients (3 with 3° AV block, 2 with 2° AV block). Tachyarrhythmias were detected in four patients (2 with atrial fibrillation, 2 with accelerated idioventricular rhythm). All patients converted to normal sinus rhythm within five minutes of the administration of THEO (178±57mg). No recurrent arrhythmia occurred in the follow-up period.ConclusionsMany of the brady and tachyarrhythmias which occur early after inferior MI are ADO-mediated. ADO receptor antagonism appears effective in converting these arrhythmias to normal sinus rhythm and may be considered as primary therapy

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Relationship Among Mental Stress-Induced Ischemia and Ischemia During Daily Life and During Exercise: The Psychophysiologic Investigations of Myocardial Ischemia (PIMI) Study

OBJECTIVES: The purposes of this database study were to determine: 1) the relationship between mental stress-induced ischemia and ischemia during daily life and during exercise; 2) whether patients who exhibited daily life ischemia experienced greater hemodynamic and catechol- amine responses to mental or physical stress than patients who did not exhibit daily life ischemia, and 3) whether patients who experienced daily life ischemia could be identified on the basis of laboratory-induced ischemia using mental or exercise stress testing. BACKGROUND: The relationships between mental stress- induced ischemia in the laboratory and ischemia during daily life and during exercise are unclear. METHODS: One hundred ninety-six stable patients with documented coronary disease and a positive exercise test underwent mental stress testing and bicycle exercise testing. Radionuclide ventriculography and electrocardiographic CECG) monitoring were performed during the mental stress and bicycle tests. Patients underwent 48 h of ambulatory ECG monitoring. Hemodynamic and catecholamine responses were obtained during mental stress and bicycle tests. RESULTS: Ischemia (reversible left ventricular dysfunction or ST segment depression ≥1 mm) developed in 106 of 183 patients (58%) during the mental stress test. There were no significant differences in clinical characteristics of patients with, compared with those without, mental stress-induced ischemia. Patients with mental stress ischemia more often had daily life ischemia than patients without mental stress ischemia, but their exercise tests were similar. Patients with daily life ischemia had higher ejection fraction and cardiac output, and lower systemic vascular resistance during mental stress than patients without daily life ischemia. Blood pressure and catecholamine levels at rest and during the mental stress tests were not different in patients with, compared with those without, daily life ischemia. Patients with daily life ischemia had a higher ejection fraction at rest and at peak bicycle exercise compared with patients without daily life ischemia, but there were no other differences in peak hemodynamic or catecholamine responses to exercise. The presence of ST segment depression during routine daily activities was best predicted by ST segment depression during mental or bicycle exercise stress, although ST segment depression was rare during mental stress. CONCLUSIONS: Patients with daily life ischemia exhibit a heightened generalized response to mental stress. ST segment depression in response to mental or exercise stress is more predictive of ST segment depression during routine daily activities than other laboratory-based ischemic markers. Therapeutic management strategies might therefore focus on patients with these physiologic responses to stress and on whether lessening such responses reduces ischemia