Tolerance of High-Dose Oral Amiodarone for Cardioversion of Atrial Flutter.

In atrial arrhythmias, amiodarone is usually given either intravenously for acute management, requiring in-hospital monitoring, or orally for chronic control, as doses given 60 times per half-life, requiring weeks to reach full effect. A high-risk, 245-kg male with heart failure exacerbated by atrial flutter was successfully cardioverted using an atypically large, 8000-mg oral amiodarone dose. The only adverse effect was transient sinus arrest, which did not require intervention, only 24 hours of inpatient monitoring. Amiodarone's unique pharmacokinetics, including its long elimination half-life and its extensive distribution into a large volume of adipose tissue, make high-dose oral amiodarone boluses a reasonable strategy for cardioversion of atrial arrhythmias.

En présence d'arythmie auriculaire, l'amiodarone est généralement administrée par voie intraveineuse dans la phase aiguë de la prise en charge, ce qui nécessite une surveillance du patient en milieu hospitalier, ou encore par voie orale dans le cadre d'un traitement au long cours à des doses représentant 60 fois la demi-vie, le plein effet du médicament n'étant obtenu qu'au bout de plusieurs semaines. Un homme de 245 kg à haut risque souffrant d'insuffisance cardiaque aggravée par un flutter auriculaire a subi avec succès une cardioversion médicamenteuse faisant appel à une dose exceptionnellement élevée d'amiodarone ­ 8000 mg ­ administrée par voie orale. Le seul effet indésirable a été une pause sinusale n'ayant pas nécessité d'intervention, seulement 24 heures de surveillance en milieu hospitalier. Vu la pharmacocinétique particulière de l'amiodarone, notamment sa longue demi-vie d'élimination et sa distribution étendue dans un grand volume de tissu adipeux, l'administration perorale de ce médicament en dose de charge constitue une stratégie raisonnable de cardioversion en cas d'arythmie auriculaire.

Treatment Decisions in Geriatric Cardiac Lymphoma Facilitated by Serial Cardiac Magnetic Resonance Imaging and Positron Emission Tomography.

A tumour encasing the right coronary was identified on computed tomography pulmonary embolism protocol in an 81-year-old man. Concerns regarding tolerability of chemotherapy in an octogenarian were addressed using cardiac magnetic resonance imaging to monitor a trial of modified-chemotherapy for his primary cardiac B-cell lymphoma. Residual activity on positron emission tomography computed tomography mandated consolidation with radiotherapy to achieve a tumor-free return to health. Despite advanced age, successful therapy in this, the oldest case of primary cardiac lymphoma reported, was facilitated by monitoring treatment effectiveness with advanced cardiac imaging and the use of standardized frailty scores in communicating his appropriate level of robustness for tolerating chemotherapy.

Une tumeur enveloppant l'artère coronaire droite a été décelée lors du protocole de tomodensitométrie à la recherche d'une embolie pulmonaire chez un homme de 81 ans. Les préoccupations relatives à la tolérance à la chimiothérapie chez un octogénaire ont été prises en considération lors de l'imagerie cardiaque par résonance magnétique pour surveiller l'essai d'une chimiothérapie modifiée de son lymphome cardiaque primitif à cellules B. L'activité résiduelle à la tomographie par émission de positons associée à la tomodensitométrie a rendu nécessaire la consolidation par radiothérapie pour un retour à la santé sans tumeur. En dépit de son âge avancé, la réussite du traitement de cet homme, le cas signalé le plus ancien de lymphome cardiaque primitif, a été facilitée par la surveillance de l'efficacité du traitement par une technique avancée d'imagerie cardiaque et l'utilisation des scores de fragilité standardisés pour connaître son degré de robustesse approprié pour tolérer la chimiothérapie.

Personalized Anticoagulation: Guided Apixaban Dose Adjustment to Compensate for Pharmacokinetic Abnormalities Related to Short-Bowel Syndrome.

A 45-year-old woman who required lifelong anticoagulation for recurrent thrombosis had her therapeutic choices limited by heparin-induced thrombocytopenia and abnormal pharmacokinetics (greatly reduced absorption) resulting from short gut syndrome from extensive gut resection after mesenteric thrombosis. As an alternative to inconvenient and expensive injections of fondaparinux, personalized dosing of a direct oral anticoagulant was sought using clinical pharmacology techniques. Enteral absorption was ascertained with small test doses of apixaban, and the ability of supraconventional doses to deliver effective concentrations was verified.

A liquid chromatography-mass spectrometry method for nicotine and cotinine; utility in screening tobacco exposure in patients taking amiodarone.

A liquid chromatographic mass spectrometric (LC-MS) assay for the quantification of nicotine and cotinine in human specimens was developed. Human serum and urine (100 µL) were subjected to liquid-liquid extraction. For glucuronidated cotinine, serum was alkalinized and hydrolyzed before extraction. The dried samples were reconstituted and run using gradient flow reverse-phase liquid chromatography with MS detection. The ions utilized for quantification of nicotine, cotinine and milrinone (internal standard) were 162.8, 176.9 and 211.9 m/z, respectively. The mean recoveries were over 80% for cotinine and nicotine with excellent linearity between nominal concentrations and peak area ratios, over a wide concentration range. The percentage coefficient of variation and mean error of the inter- and intra-day validations were <15% for nicotine and cotinine. Analysis of serum from cardiac patients receiving amiodarone suggested that a number of patients were either active smokers or exposed to second-hand smoke. Significant concentrations of nicotine and cotinine were measured in the urine of a known smoking volunteer. The method was highly specific, sensitive and applicable as a tool in detecting and monitoring the passive exposure to tobacco smoke using small specimen volumes (0.1 mL).

Influence of peroxisome proliferator-activated receptor-alpha (PPARα) activity on adverse effects associated with amiodarone exposure in mice.

Although amiodarone is the most effective antiarrhythmic agent currently available, concerns regarding adverse effects, including liver, lung and thyroid toxicity, often limit its use. Previously, we reported that amiodarone-induced hepatic steatosis in mice was associated with an upregulation of target genes modulated by peroxisome proliferator-activated receptor-alpha (PPARα). Because amiodarone does not directly stimulate PPARα, target gene induction may reflect a compensatory reaction countering some adverse effects of amiodarone. To test this, we examined co-treatment with the PPARα agonist, fenofibrate, and amiodarone in both PPARα(+/+) and PPARα(-/-) mice. Amiodarone treated PPARα(-/-) mice exhibited significantly greater weight loss and higher serum aspartate aminotransferase (AST) compared to PPARα(+/+) mice. Fenofibrate co-treatment reduced weight loss in amiodarone treated PPARα(-/-) mice, but not PPARα(+/+) mice. Fenofibrate stimulation of PPARα reduced serum amiodarone concentrations in normal mice. Serum amiodarone concentrations were higher in mice without PPARα expression given at 40-80 mg/kg amiodarone doses. These results are consistent with a protective influence of PPARα in reducing amiodarone-induced hepatic toxicity. In addition to PPARα-dependent effects, fenofibrate also demonstrated PPARα-independent actions that suggest a complex interaction modulating both hepatic lipid metabolism and amiodarone disposition. Further studies of the beneficial effect of fenofibrate and the interplay between lipid metabolism and amiodarone pharmacokinetics are required.

Amiodarone hepatotoxicity.

Potential hepatotoxicity related to amiodarone therapy is often a concern when deciding whether to initiate or continue treatment with this medication. While mostly associated with long-term oral administration of the drug, toxicity has also been reported early during intravenous administration and months after discontinuation of therapy. In the majority of patients, it is discovered incidentally during routine testing of liver biochemistry and rarely do the hepatic effects develop into symptomatic liver injury or failure. Despite the widespread use of amiodarone, prospective clinical studies have been sparse and there has been little consensus among experts in the field regarding optimum monitoring for adverse effects in patients receiving this drug. In order to examine the current state of knowledge surrounding the incidence, pathogenesis and mechanism of liver effects associated with amiodarone, the existing literature was reviewed, with particular emphasis on clinical recommendations for monitoring.

Treating the right patient at the right time: an innovative approach to the management of atrial fibrillation.

The Canadian Cardiovascular Society Access to Care Working Group recently published a series of commentaries on access to cardiovascular care in Canada. These commentaries included proposed minimally acceptable wait times for patients with atrial fibrillation (AF) to be assessed by a cardiologist or an electrophysiologist. To improve access to medical care for the patient with AF, a nurse clinician-based AF clinic was established in the Calgary Health Region (Alberta) in 2005. More than 330 patients had been referred at the time of writing. The time from referral to initial nurse assessment was 38+/-31 days, to physician review and establishment of a management plan was 66+/-49 days and to in-person specialist physician assessment was 80+/-55 days. These wait times are markedly shorter than historical wait times to see an arrhythmia specialist in the Calgary Region. As experience increased, wait times continued to shorten significantly. Preliminary data suggest that early assessment and patient education may reduce emergency department visits and hospitalizations for AF. This experience suggests that a nurse clinician-based AF clinic may provide earlier access to medical care and may improve health outcomes in the long term.