Guillain-Barré syndrome as a cause of reversible cardiomyopathy.

Although autonomic dysfunction is a common manifestation of Guillain-Barré syndrome, cardiovascular involvement in this setting has rarely been reported in the literature. We describe a case of reversible left ventricular systolic dysfunction in a 60-year-old man with Guillain-Barré syndrome. Our patient had no history or signs of cardiac dysfunction on initial presentation. During the clinical manifestation of his autonomic dysfunction, he developed electrocardiographic changes accompanied by mildly elevated cardiac enzymes and severe left ventricular systolic dysfunction and segmental wall motion abnormality, which coincided with elevated urinary catecholamine and vanilmandelic acid levels. These abnormalities, and his symptoms, resolved rapidly once the acute episode was over. We believe the reversible left ventricular dysfunction was due to the toxic effect of increased catecholamines and to the transiently damaged sympathetic nerve endings in the myocardium, presumably a consequence of Guillain-Barré syndrome. We recommend that echocardiography be performed in patients with clinical signs of autonomic dysfunction, especially if they are associated with abnormal electrocardiographic findings, cardiac enzyme elevation, or hemodynamic instability, so that appropriate medical therapy can be instituted in a timely manner.

Effect of intensive versus moderate lipid-lowering therapy on epicardial adipose tissue in hyperlipidemic post-menopausal women: a substudy of the BELLES trial (Beyond Endorsed Lipid Lowering with EBT Scanning).

OBJECTIVES: This study sought to evaluate the effect of intensive and moderate statin therapy on epicardial adipose tissue (EAT). BACKGROUND: EAT has been associated with coronary artery disease severity and outcome. It is currently unknown whether EAT volume changes over time when patients are exposed to statin therapy. METHODS: Subanalysis of a randomized study of atorvastatin 80 mg/day versus pravastatin 40 mg/day for 1 year in a clinical trial designed to assess the progression of coronary artery calcium (CAC) in hyperlipidemic post-menopausal women. Patients underwent cardiac computed tomography scans at the start and end of the trial period. RESULTS: Of 420 patients, 194 received atorvastatin and 226 pravastatin; the median low-density lipoprotein change was -53.3% and -28.3% with atorvastatin and pravastatin, respectively (p < 0.001). Baseline EAT correlated with age, body mass index, hypertension, diabetes mellitus, high-density lipoprotein, triglyceride levels, and CAC (p < 0.001). At the end of follow-up, EAT regressed more in the atorvastatin than in the pravastatin group (median, -3.38% vs. -0.83%, p = 0.025). The EAT percent change from baseline was significant in the atorvastatin, but not the pravastatin group (p < 0.001 and p = 0.2, respectively). There was no correlation between lipid lowering and EAT regression. CAC progressed significantly in both groups from baseline. CONCLUSIONS: In hyperlipidemic post-menopausal women, statin therapy induced EAT regression, although intensive therapy was more effective than moderate-intensity therapy. This effect does not seem linked to low-density lipoprotein lowering and may be secondary to other actions of statins such as anti-inflammatory effects.

Randomized dose-ranging controlled trial of AQ-13, a candidate antimalarial, and chloroquine in healthy volunteers.

OBJECTIVES: To determine: (1) the pharmacokinetics and safety of an investigational aminoquinoline active against multidrug-resistant malaria parasites (AQ-13), including its effects on the QT interval, and (2) whether it has pharmacokinetic and safety profiles similar to chloroquine (CQ) in humans. DESIGN: Phase I double-blind, randomized controlled trials to compare AQ-13 and CQ in healthy volunteers. Randomizations were performed at each step after completion of the previous dose. SETTING: Tulane-Louisiana State University-Charity Hospital General Clinical Research Center in New Orleans. PARTICIPANTS: 126 healthy adults 21-45 years of age. INTERVENTIONS: 10, 100, 300, 600, and 1,500 mg oral doses of CQ base in comparison with equivalent doses of AQ-13. OUTCOME MEASURES: Clinical and laboratory adverse events (AEs), pharmacokinetic parameters, and QT prolongation. RESULTS: No hematologic, hepatic, renal, or other organ toxicity was observed with AQ-13 or CQ at any dose tested. Headache, lightheadedness/dizziness, and gastrointestinal (GI) tract-related symptoms were the most common AEs. Although symptoms were more frequent with AQ-13, the numbers of volunteers who experienced symptoms with AQ-13 and CQ were similar (for AQ-13 and CQ, respectively: headache, 17/63 and 10/63, p = 0.2; lightheadedness/dizziness, 11/63 and 8/63, p = 0.6; GI symptoms, 14/63 and 13/63; p = 0.9). Both AQ-13 and CQ exhibited linear pharmacokinetics. However, AQ-13 was cleared more rapidly than CQ (respectively, median oral clearance 14.0-14.7 l/h versus 9.5-11.3 l/h; p < or = 0.03). QTc prolongation was greater with CQ than AQ-13 (CQ: mean increase of 28 ms; 95% confidence interval [CI], 18 to 38 ms, versus AQ-13: mean increase of 10 ms; 95% CI, 2 to 17 ms; p = 0.01). There were no arrhythmias or other cardiac AEs with either AQ-13 or CQ. CONCLUSIONS: These studies revealed minimal differences in toxicity between AQ-13 and CQ, and similar linear pharmacokinetics.