Dale C. Wortham

Percutaneous closure of the small (< 2.5 mm) patent ductus arteriosus using coil embolization

Persistently patent ductus arteriosus (PDA) is a common form of congenital heart disease, occurring between 0.01 to 0.08% of live births.1 Surgical ligation by lateral thoracotomy is effective, yet carries procedural risks (potential bleeding, recurrent laryngeal nerve injury, exposure to general anesthesia and death [<1%]).2 In 1971, Porstmann et al3 described the first nonsurgical PDA closure with an Ivalon plug with an 18Fr arterial conduit. More recently, the Rashkind PDA double disc occlusion system has undergone extensive evaluation, with flow occlusion accomplished in 72 to 88% of cases attempted.4–6 The smaller Rashkind occluder requires an 8Fr delivery system. Rao et al7 described an occluder which may be introduced through a 7Fr catheter and reduces the crossing profile required. Nevertheless, technical limitations persist in patients whose PDA internal diameter is <2.5 mm. Techniques to facilitate cannulation of the very small ductus by the Rashkind delivery system, involving arterial cannulation and rendezvous of an exchange wire from femoral vein to contralateral artery,8 and ductal dilation with balloon angioplasty,9 have been described. These techniques require additional manipulations and procedural time, and may potentially increase patient morbidity. This report describes experience with an alternative technique for transcatheter closure of the very small ductus arteriosus using stainless steel coil embolization.

Itraconazole Affects Single‐Dose Terfenadine Pharmacokinetics and Cardiac Repolarization Pharmacodynamics

The object of this study was to examine prospectively the effects of itraconazole on the pharmacokinetics and electrocardiographic repolarization pharmacodynamics (QTc intervals) of single‐dose terfenadine in six healthy volunteers. It was designed as a prospective cohort study with each subject serving as his own control, set in an outpatient cardiology clinic. The participants were six healthy volunteers (two men, four women; ages 24–35) not taking any prescription or over‐the‐counter medications. Single‐dose terfenadine administration (120 mg) was accompanied by pharmacokinetic profiles and serial determination of the QTc interval for 12 hours. The subjects then began daily oral itraconazole (200 mg each morning) for 7 days. Repeat pharmacokinetic and pharmacodynamic determinations were made after administration of a second dose (120 mg) of terfenadine while receiving itraconazole. The main outcome measures were terfenadine and acid metabolite serum concentrations; corrected QT intervals as determined by 12‐lead electrocardiogram (ECG); and presence or absence of late potentials as determined by signal‐averaged ECGs over 150 cardiac cycles. There were significant changes in the pharmacokinetic parameters of acid metabolite after treatment with itraconazole. All subjects had detectable levels of unmetabolized terfenadine after addition of itraconazole, which was associated with QT prolongation. There was no evidence of late depolarization as manifested by an increase in QRS duration found using signal‐averaged electrocardiography. Itraconazole influences the metabolism of terfenadine in normal volunteers and results in the accumulation of unmetabolized parent drug associated with altered cardiac repolarization. This drug combination should be avoided.

Comparison of the Effect of the Macrolide Antibiotics Erythromycin, Clarithromycin and Azithromycin on Terfenadine Steady-State Pharmacokinetics and Electrocardiographic Parameters

SummaryTerfenadine is a nonsedating histamine H1-antagonist that, when given with ketoconazole, results in accumulation of parent terfenadine and altered cardiac repolarisation in susceptible individuals. This prospective cohort study, designed to assess macrolide effects on terfenadine pharmacokinetics and electrocardiogram (ECG) parameters, evaluated 18 healthy male and female volunteers who received terfenadine to steady-state. Equal numbers (6) were randomised to receive either erythromycin, clarithromycin or azithromycin at recommended doses while continuing terfenadine. Macrolide monotherapy effects on the ECG were also investigated. Pharmacokinetic profiles for terfenadine were performed before and after the addition of macrolide therapy, and ECGs were obtained at baseline and predose on days of blood sampling.Erythromycin and clarithromycin significantly affected the pharmacokinetics of terfenadine. Three of 6 volunteers receiving erythromycin and 4 of 6 receiving clarithromycin demonstrated accumulation of quantifiable unmetabolised terfenadine that was associated with altered cardiac repolarisation. Azithromycin had no effect on terfenadine pharmacokinetics or cardiac pharmacodynamics.

Grapefruit juice alters the systemic bioavailability and cardiac repolarization of terfenadine in poor metabolizers of terfenadine.

A prospective cohort study was conducted to examine the effects of double‐strength grapefruit juice on the pharmacokinetics and electrocardiographic repolarization pharmacodynamics of terfenadine in poor metabolizers of terfenadine. Six healthy volunteers who were previously found to be poor metabolizers of terfenadine were studied, with each participant serving as his or her own control. In phase I of the study, terfenadine was given to participants at recommended dosages until steady state was achieved (60 mg twice daily for 7 days). In phase II, participants began receiving concomitant twice‐daily, double‐strength servings of grapefruit juice for 7 days. Serial pharmacokinetic and pharmacodynamic determinations were made after each phase of the study. The main outcome measures were serum concentrations of terfenadine and terfenadine acid metabolite, and corrected QT intervals as determined by 12‐lead electrocardiogram. Significant changes occurred in time to maximum concentration (tmax) and area under the concentration‐time curve (AUC) of terfenadine and terfenadine acid metabolite after addition of grapefruit juice. All participants had detectable concentrations of unmetabolized terfenadine at the end of Phase I, which were quantified in three of the six participants. Further, all participants had increased and quantifiable levels of unmetabolized terfenadine after addition of grapefruit juice that were associated with prolongation of the QT interval relative to the baseline control period without terfenadine. Grapefruit juice did not alter the elimination half‐life (t1/2) of terfenadine acid metabolite. Because of the intraindividual variability in the pharmacokinetics of terfenadine, further study is needed to confirm these results.

Coronary arterial ectasia: Increased prevalence in patients with abdominal aortic aneurysm as compared to occlusive atherosclerotic peripheral vascular disease

Coronary artery ectasia (CAE) is the saccular or fusiform dilatation of a coronary artery. CAE is found in 1.2% to 4.9% of patients at autopsy or during angiographic studies, with a similar prevalence of CAE found in patients with atherosclerotic peripheral vascular disease (PVD). Abdominal aortic aneurysm (AAA) and CAE are similar in pathogenesis and histology. To determine whether CAE occurs more frequently in patients with AAA than in occlusive forms of atherosclerotic PVD, a review of coronary angiograms was performed in patients who underwent cardiac catheterization and vascular reconstruction for AAA or occlusive atherosclerotic PVD of the lower extremities. Of 72 patients with AAA, 15 had CAE (20.8%) compared with only 2 of 69 patients with atherosclerotic PVD (2.9%) (p < 0.003). CAE was predominantly discrete, located in the left coronary system, and associated with significant coronary atherosclerosis. CAE may be more prevalent in patients with AAA resulting from a similar pathogenetic process.

Effect of concomitant administration of cimetidine and ranitidine on the pharmacokinetics and electrocardiographic effects of terfenadine

SummaryTerfenadine is a widely prescribed non-sedating antihistamine which undergoes rapid and almost complete first pass biotransformation to an active carboxylic acid metabolite. It is unusual to find unmetabolised terfenadine in the plasma of patients taking the drug. Terfenadine in vitro is a potent blocker of the myocardial potassium channel. Overdose, hepatic compromise and the coadministration of ketoconazole and erythromycin result in the accumulation of terfenadine, which is thought to be responsible of QT prolongation and Torsades de Pointes ventricular arrhythmia in susceptible individuals. Cimetidine and ranitidine are two popular H2 antagonists which are often taken with terfenadine. The effects of cimetidine and ranitidine on terfenadine metabolism were studied in two cohorts of 6 normal volunteers given the recommended dose of terfenadine (60 mg every 12 h) for 1 week prior to initiation of cimetidine 600 mg every 12 h or ranitidine 150 mg every 12 h. Pharmacokinetic profiles and morning pre-dose electrocardiograms were obtained whilst the patients were on terfenadine alone and after the addition of cimetidine or rantidine.One of the subjects in each cohort had a detectable plasma level of parent compound after 1 week of terfenadine therapy alone; it did not accumulate further after addition of the H2 antagonist. The pharmacokinetics of the carboxylic acid metabolite of terfenadine (Cmax, tmax, AUC) were not significantly changed after co-administration of either H2 antagonist. None of the remaining 5 subjects in either cohort demonstrated accumulation of unmetabolised terfenadine after addition of the respective H2 antagonist and electrocardiographic QT intervals and T-U morphology in them was not changed during the course of the study.We conclude that cimetidine and ranitidine in the dosages used in this study did not affect the metabolism of terfenadine, and that patients exposed to these drug combinations are not at increased risk of altered cardiac repolarisation.

Unruptured sinus of Valsalva aneurysm presenting with embolization.

15. Hiatt .JR, Yeatman LA, Child +JS. The value of echocardiopraphy in blunt chest trauma. J Trauma 1988:28:914-P?. King RM, Mucha P, Seward .JB. Cardiac contusion: a new diagnostic approach utilizing two-dimensional echocardiography. J Trauma 1983:23:610-X3. Wisner DH, Reed WH, Riddick RS. Suspected myocardial contusion. Ann Surg 1990;213:82-6. Kertes P, Westlake G, Luxton M. Multiple peripheral emholi after cardiac trauma. Br Heart J 1983;49:187-9. Pomerantz M, Delgado F. Eiseman B. Unsuspected depressed cardiac output following blunt thoracic or abdominal trauma. Sureerv 1971:70:8&i-71. ” “-~ ,

Side-branch occlusion with directional coronar atherectomy: Incidence and risk factors☆

Side-branch occlusion is a recognized complication of directional coronary atherectomy (DCA). To evaluate the incidence, risk factors, and clinical outcome of side-branch compromise, we analyzed our first 100 consecutive atherectomies of native coronary arteries. Seventy-eight patients had 122 side branches at risk, 21 (17%) of which demonstrated compromised flow after DCA. Origin of the side branch from the culprit atheroma and preexisting side-branch ostial stenosis were highly predictive of this complication in 20 of 55 (p < 0.05) and 14 of 31 (p < 0.05) lesions, respectively. There was one non-Q-wave myocardial infarction, no emergency surgeries, and no deaths. In conclusion, side-branch loss after DCA occurs with a frequency similar to balloon angioplasty and was well tolerated in our patient population. Side branches that originate directly from culprit lesions or that have significant ostial narrowing have a higher incidence of this complication.

Spring coil embolization of a patent ductus arteriosus in an adult.

To date, coil embolization has been reserved for occlusion of the small patent ductus arteriosus (PDA) because of potential dislodgement of the coils. We report a case of a larger, hemodynamically significant PDA in an adult which was successfully closed by two spring coils using a “crossed catheter” technique for coil delivery.