Embolic myocardial infarction in a patient with a Fontan circulation.

Coronary artery embolism is an uncommon cause of acute myocardial infarction (MI). We present a patient with pulmonary atresia and severe right heart hypoplasia who underwent a lateral tunnel Fontan procedure in childhood and presented with an acute ST-segment elevation MI at 19 years of age. In addition to the known risk of thrombotic complications associated with a Fontan circulation, potential predisposing factors to thromboembolism in this patient included a right ventricle to left anterior descending coronary connection and a Fontan baffle leak. The patient was treated with device closure of the baffle leak and anticoagulation. This is one of the first reports of an embolic MI in a patient with a Fontan circulation. The optimal method of reducing thromboembolic risk in this patient, and those with a Fontan circulation in general, is complicated and no consensus exists.

Effect of late revascularization of a totally occluded coronary artery after myocardial infarction on mortality rates in patients with renal impairment.

Renal dysfunction is an independent predictor of cardiovascular events and a negative prognostic indicator after myocardial infarction (MI). Randomized data comparing percutaneous coronary intervention to medical therapy in patients with MI with renal insufficiency are needed. The Occluded Artery Trial (OAT) compared optimal medical therapy alone to percutaneous coronary intervention with optimal medical therapy in 2,201 high-risk patients with occluded infarct arteries >24 hours after MI with serum creatinine levels ≤2.5 mg/dl. The primary end point was a composite of death, MI, and class IV heart failure (HF). Analyses were carried out using estimated glomerular filtration rate (eGFR) as a continuous variable and by eGFR categories. Long-term follow-up data (maximum 9 years) were used for this analysis. Lower eGFR was associated with development of the primary outcome (6-year life-table rates of 16.9% for eGFR >90 ml/min/1.73 m(2), 19.2% for eGFR 60 to 89 ml/min/1.73 m(2), and 34.9% for eGFR <60 ml/min/1.73 m(2); p <0.0001), death, and class IV HF, with no difference in rates of reinfarction. On multivariate analysis, eGFR was an independent predictor of death and HF. There was no effect of treatment assignment on the primary end point regardless of eGFR, and there was no significant interaction between eGFR and treatment assignment on any outcome. In conclusion, lower eGFR at enrollment was independently associated with death and HF in OAT participants. Despite this increased risk, the lack of benefit from percutaneous coronary intervention in the overall trial was also seen in patients with renal dysfunction and persistent occlusion of the infarct artery in the subacute phase after MI.

Abdominal pain in the ED: a 35 year retrospective.

OBJECTIVE: Research published in 1972 and 1993 has detailed the demographics, diagnoses, and diagnostic test utilization of adult patients presenting with nontraumatic abdominal pain to the emergency department (ED) at the University of Virginia Hospital. This is an update of those studies, designed to examine the present state of diagnosis and management of abdominal pain, as well as to look at trends during the 35-year span of the investigations. METHODS: One thousand consecutive adult patients presenting in the year 2007 with abdominal pain as their chief complaint were included in the analysis. Demographic data, discharge diagnosis, disposition, ED length of stay, charges, and diagnostic test utilization information were gathered and analyzed using electronic databases. RESULTS: These patients represented 6.5% of the total ED census. Sixty-five percent were female, 24.7% hospitalized, and 21% diagnosed with undifferentiated abdominal pain. Relative to 1993, there were more patients receiving specific diagnoses, (79% versus 75%) and a higher rate of hospitalization (24.7% versus 18.3%). Use of diagnostic testing has markedly increased in frequency, most notably computed tomography and ultrasound, which have risen 6-fold. One of these imaging modalities is now used in 42% of patient encounters. Visit times were longer and patient charges higher. There were 2 cases of missed surgical disease in 2007 compared with 1 in 1993 and 8 in 1972. CONCLUSION: Over the past 35 years, ED management of atraumatic abdominal pain has become time, money, and resource intense. Widespread use of sophisticated imaging has had a small impact on diagnostic specificity but has not produced lower admission rates or fewer cases of missed surgical illness.

Brain serotonin transporter binding in depressed patients with bipolar disorder using positron emission tomography.

CONTEXT: Depression in bipolar disorder is clinically indistinguishable from that observed in major depressive disorder. As in major depression, selective serotonin reuptake inhibitors targeting brain serotonin transporters are first-line treatments for bipolar depression. Associations of serotonin transporter promoter polymorphisms and bipolarity have been reported; however, research on alterations in serotonergic neurotransmission in bipolar depression remains scant. OBJECTIVES: To assess in vivo brain serotonin transporter binding potential (BP(1), proportional to serotonin transporter number) in patients with bipolar depression and controls and to examine the relationship between serotonin transporter binding and genotype. DESIGN: Case-control study. SETTING: University hospital. PARTICIPANTS: A sample of 18 medication-free patients with bipolar depression and 41 controls. MAIN OUTCOME MEASURES: In vivo brain serotonin transporter binding was measured using positron emission tomography and radiolabeled trans-1,2,3,5,6,10-beta-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]-isoquinoline ([(11)C](+)-McNeil 5652). Participants were genotyped assessing biallelic and triallelic 5-HTTLPR polymorphisms. RESULTS: Patients with bipolar disorder had 16% to 26% lower serotonin transporter BP(1) in the midbrain, amygdala, hippocampus, thalamus, putamen, and anterior cingulate cortex. Triallelic 5-HTTLPR genotypes were unrelated to serotonin transporter BP(1). CONCLUSIONS: Lower serotonin transporter BP(1) in bipolar depression overlaps with that observed in major depression and suggests that serotonergic dysfunction is common to depressive conditions.

Effect of a triallelic functional polymorphism of the serotonin-transporter-linked promoter region on expression of serotonin transporter in the human brain.

OBJECTIVE: The authors examined effects of a triallelic functional polymorphism of the human serotonin-transporter-linked promoter region (5-HTTLPR) on in vivo expression of serotonin transporter in the brain in healthy volunteers and subjects with major depressive disorder. METHOD: Twenty-five medication-free subjects with DSM-IV major depressive disorder during a major depressive episode and 42 healthy volunteers were clinically evaluated and genotyped. Serotonin transporter binding potential (f(1)B(max)/K(d)) was determined by using positron emission tomography with the radiotracer [(11)C]McN 5652 and metabolite-corrected arterial input functions. RESULTS: There was no difference in serotonin transporter binding potential by genotype in healthy volunteers or in subjects with major depressive disorder. Allelic frequencies did not differ between subjects with major depressive disorder and healthy volunteers. CONCLUSIONS: Associations of the 5-HTTLPR polymorphism to clinical phenotypes appear to be due to developmental effects of 5-HTTLPR on expression and not due to its direct effect on serotonin transporter binding in adulthood.

Lower serotonin transporter binding potential in the human brain during major depressive episodes.

OBJECTIVE: CSF analysis, neuroendocrine challenges, serotonin depletion studies, and treatment studies implicate the serotonergic system in the pathophysiology of major depressive disorder. On the basis of postmortem and imaging studies, the authors hypothesized that subjects with major depressive disorder in a major depressive episode have fewer serotonin transporter sites, compared with healthy subjects. METHOD: Serotonin transporter binding potential (f(1)B(max)/K(d)) was determined using positron emission tomography with [(11)C]McN 5652 in six brain regions in 25 medication-free subjects with DSM-IV major depressive disorder during a major depressive episode and in 43 healthy volunteer comparison subjects. All subjects had arterial lines placed to determine metabolite-corrected arterial input functions. RESULTS: Serotonin transporter binding potential differed significantly by brain region and group. Post hoc analysis revealed lower binding potential in subjects with major depressive disorder, relative to the comparison subjects, in the amygdala and midbrain. The lower binding potential was more pronounced in the depressed subjects who had never received antidepressants. No correlation was found between binding potential in the midbrain and severity of depression or number of days without medication. Binding potential did not differ between suicide attempters and nonattempters. CONCLUSIONS: Subjects in a major depressive episode have lower serotonin transporter binding potential in the amygdala and midbrain, compared to healthy subjects.

Volumetric analysis of the prefrontal cortex, amygdala, and hippocampus in major depression.

Magnetic resonance imaging (MRI) studies in depressed subjects report smaller volumes of amygdala, hippocampus, inferior anterior cingulate, and the orbital prefrontal cortex (OPFC), components of the limbic-cortico-thalamic circuit. Major depression occurs more commonly in women, raising the possibility of an additional psychopathological process affecting women and not men. We sought to determine whether volumetric differences related to mood disorders are dependent on sex. Eight male and 10 female depressed subjects, meeting DSM III R criteria for a major depressive episode, and eight male and 10 female healthy volunteers had MRI scans on a 1.5 T GE Signa Advantage scanner. The regions of interest included amygdala, hippocampus, inferior anterior cingulate, and OPFC. In all analyses, regional volumes were normalized for total cerebral volume. Volumetric changes in the ROIs showed a significant sex by diagnosis interaction, indicating a different pattern of volumetric changes in depressed males compared with females relative to controls. Relative to sex-matched controls, the left inferior anterior cingulate was smaller in depressed males (23%) compared with depressed females (11%). Depressed females but not depressed males had smaller amygdala compared with controls (F-value = 4.946, p = 0.033). No significant volumetric differences were noted in the hippocampus or OPFC. No volumetric correlations were noted with clinical variables, depression subtypes, or a reported history of sexual or physical abuse. Sex may affect volumetric deficits in amygdala and anterior cingulate cortex in mood disorders, but no effects were found in the hippocampus or OPFC. The biology of mood disorders in females may differ in some aspects from males, and may contribute to the higher rate of depression in women.