Effects of Cognitive Behavioral Stress Management on Negative Mood and Cardiac Autonomic Activity in ICD Recipients.

BACKGROUND: Behavioral intervention studies in patients with an implantable cardioverter-defibrillator (ICD) show promise in improving psychosocial outcomes but inconclusive effects on cardiovascular outcome. We assessed the effects of cognitive behavioral stress management (CBSM) on mood state and potentially arrhythmogenic cardiovascular responses to mental stress in ICD patients, in support of further larger scale arrhythmia trials. METHODS: A total of 103 ICD recipients were randomly assigned to 10-week programs of CBSM or "Patient Education" (ED). Of these, 83 patients continued to either CBSM (n = 44) or ED (n = 39) intervention. Study end points were mood change, heart rate variability (HRV), double product elevation (DP = heart rate × systolic blood pressure) by math and anger-recall stress, and arrhythmia up to 6 months follow-up. RESULTS: Adjusting for multiple testing, CBSM was associated with moderate effect size reductions in tension/anxiety (P = 0.010), anger/hostility (P = 0.020), perceived stress (P = 0.037), and total mood disturbance (P = 0.025), greatest immediately following intervention (P < 0.05), and partially attributable to increased negative mood following ED (P < 0.01). No significant intervention effects on high frequency or low frequency spectral power of HRV, DP responses, or cardiac arrhythmias were demonstrated. CONCLUSIONS: CBSM intervention in ICD recipients resulted in reduced anxiety, anger, and perceived stress, not sustained at 6 months follow-up, and without conclusive effect on cardiac autonomic or hemodynamic responses to mental stress, or arrhythmia. Findings support conduct of larger behavioral intervention arrhythmia trial, with consideration of reinforcement training and targeting of subgroup responders to therapy.

Role of arachidonic acid, lipoxygenase, and mitochondrial depolarization in reperfusion arrhythmias.

We have sought evidence that arachidonic acid (AA) induces mitochondrial depolarization in isolated myocytes by a lipoxygenase (LOX)-dependent mechanism and that such depolarization might contribute to arrhythmogenesis following ischemia-reperfusion injury. A method was developed for measuring mitochondrial depolarization in isolated adult rat myocytes in suspension, using tetramethylrhodamine ethyl ester. The addition of AA to myocytes resulted in mitochondrial depolarization that was inhibited by the LOX inhibitor baicalein, by the reactive oxygen species (ROS) scavenger mercaptoproprionylglycine, and by the anion channel inhibitor diisothiocyanatostilbene-disulfonic acid (DIDS). AA induced mitochondrial uncoupling and mitochondrial ATPase activity in myocytes, but both were insensitive to baicalein. We conclude that the metabolic effect of AA in myocytes puts mitochondria into an energetically compromised state where membrane potential is easily changed by the DIDS-sensitive LOX/ROS-mediated opening of an inner membrane anion channel. In an in vivo anesthetized rat model of coronary artery occlusion, baicalein was found to strongly inhibit arrhythmias induced by ischemia-reperfusion injury. Arrhythmias following ischemia-reperfusion injury have been previously associated with DIDS-sensitive ROS-mediated mitochondrial depolarization, and free fatty acids including AA were previously found to accumulate during such injury. We therefore conclude that arrhythmias following ischemia-reperfusion injury might originate from mitochondrial depolarization mediated by LOX and AA.

Randomized Placebo-Controlled Withdrawal Study of Amlodipine in Agina Pectoris.

OBJECTIVES: To assess the antianginal and antiischemic efficacy, safety, and the potential for tolerance or withdrawal effects of amlodipine. BACKGROUND: The slow onset of action and long half-life of amlodipine may help avoid withdrawal effects such as the exacerbation of angina and precipitation of myocardial seen with beta-blockers. METHODS: After a 2-week single-blind placebo run-in period, 226 patients with stable exertional angina pectoris were given amlodipine (starting at 5 mg day(minus sign1) and titrated to 10 mg day(minus sign1)) in a single-blind fashion for 8 weeks. One hundred seventy-two responders (greater-than-or-equal7% improvement in symptom-limited exercise time) entered a 4-week double-blind withdrawal phase and randomly received continued treatment with amlodipine (n = 91) or placebo (n = 81). RESULTS: Treatment with amlodipine increased the exercise capacity by 14% and improved time to angina onset by 25% and time to 1-mm ST segment deviation by 18%. These variables remained essentially unchanged at the end of the 4-week withdrawal phase for the group continued on amlodipine (+0.8%, +3.2%, and +2.0%, respectively) but decreased for the group on placebo (minus sign5.8%, minus sign9.8%, and minus sign11.0%, respectively) (p < 0.001 between groups, all assessments) to values similar to those obtained during the initial placebo run-in period. Approximately one-third of the patients responded to 5 mg amlodipine during single-blind therapy and according to "usual clinical practice" remained on this dose. The results of randomized withdrawal in the subgroup receiving 5 mg also favored amlodipine over placebo. Side effects were reported by 47% of patients on amlodipine and by 22% of patients receiving placebo. The most frequently reported side effects for

Coronary arteriomegaly in a patient with Ehlers-Danlos syndrome and multiple aneurysms--a case report.

The authors report a case of coronary arteriomegaly in a patient with Ehlers-Danlos syndrome and multiple aneurysms who presented with myocardial infarction. Coronary arteriography revealed distal "pruning" of vessels without occlusive disease. Fibroblast cultures excluded Ehlers-Danlos syndrome types IV and VII. Literature review suggests this may represent a previously unidentified vascular syndrome.

The effects of a forgiveness intervention on patients with coronary artery disease.

This research assesses the effects of a psychology of forgiveness pilot study on anger-recall stress induced changes in myocardial perfusion, forgiveness and related variables. Thirty-two patients were administered baseline rest and anger-recall stress imaging studies, and 17 of these participants who demonstrated anger-recall stress induced myocardial perfusion defects (forgiveness group, n = 9; control group, n = 8) were randomly assigned to a series of 10 weekly interpersonal forgiveness or control therapy sessions with a trained psychologist, and underwent additional anger-recall stress myocardial perfusion nuclear imaging studies post-test and at 10-week follow-up. Patients assigned to the forgiveness group showed significantly fewer anger-recall induced myocardial perfusion defects from pre-test to the 10-week follow-up as well as significantly greater gains in forgiveness from pre-test to post-test and from pre-test to follow-up compared to the control group. Forgiveness intervention may be an effective means of reducing anger-induced myocardial ischemia in patients with coronary artery disease.