Faculty Bibliography

Although loperamide has been widely used for the treatment of diarrhea, there is growing popularity over its abuse potential in alleviating opioid-withdrawal symptoms and achieving euphoria. Toxic levels of loperamide have been associated with life-threatening ventricular tachyarrhythmias and cardiac arrest. We report a case of high-dose loperamide ingestion in a patient presenting initially with unstable bradycardia followed by episodes of polymorphic ventricular tachycardia, and an unmasked Brugada ECG pattern. This is the first such report of the Brugada pattern being unmasked on ECG with loperamide ingestion. The patient stabilized with supportive care without the need for inotropic support. We discuss potential mechanisms of toxicity leading to conduction abnormalities and provide a literature review of all published cases of loperamide toxicity to describe proposed treatment options. Recognition of the abuse potential and hazards of this over-the-counter anti-diarrheal therapy will alert the clinician of associated toxidromes and management strategies

OBJECTIVES: This study sought to evaluate variability in aortic measurements with multiple imaging modalities in clinical centers by comparing with a standardized measuring protocol implemented in a core laboratory. BACKGROUND: In patients with aortic disease, imaging of thoracic aorta plays a major role in risk stratifying individuals for life-threatening complications and in determining timing of surgical intervention. However, standardization of the procedures for performance of aortic measurements is lacking. METHODS: To characterize the diversity of methods used in clinical practice, we compared aortic measurements performed by echocardiography, computed tomography (CT), and magnetic resonance imaging (MRI) at the 6 GenTAC (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions) clinical centers to those performed at the imaging core laboratory in 965 studies. Each center acquired and analyzed their images according to local protocols. The same images were subsequently analyzed blindly by the core laboratory, on the basis of a standardized protocol for all imaging modalities. Paired measurements from clinical centers and core laboratory were compared by mean of differences and intraclass correlation coefficient (ICC). RESULTS: For all segments of the ascending aorta, echocardiography showed a higher ICC (0.84 to 0.93) than CT (0.84) and MRI (0.82 to 0.90), with smaller mean of differences. MRI showed higher ICC for the arch and descending aorta (0.91 and 0.93). In a mixed adjusted model, the different imaging modalities and clinical centers were identified as sources of variability between clinical and core laboratory measurements, whereas age groups or diagnosis at enrollment were not. CONCLUSIONS: By comparing core laboratory with measurements from clinical centers, our study identified important sources of variability in aortic measurements. Furthermore, our findings with regard to CT and MRI suggest a need for imaging societies to work toward the development of unifying acquisition protocols and common measuring methods.

BACKGROUND: There is a lack of uniformity across echocardiographic society guidelines as to how the diameter of the ascending aorta is to be measured. The aims of this study were to compare measurements done using the diastolic leading edge-to-leading edge and systolic inner edge-to-inner edge (SIE) techniques in a large cohort of healthy adult individuals and to report the normal values for adults using the SIE technique. METHODS: Aortic diameters obtained according to the two guideline recommendations at the aortic annuls, sinuses of Valsalva, sinotubular junction, and ascending aorta in 1,148 healthy adult volunteers were compared. Bland-Altman analysis, paired t tests, and intraclass correlation coefficients were evaluated at each segment. SIE values are reported as normative data, according to age, gender, and body surface area. RESULTS: The diastolic leading edge-to-leading edge convention yielded smaller diameters (compared with SIE) at the aortic annulus and ascending aorta and larger diameters at the sinus of Valsalva and sinotubular junction (P < .001 for all). There was excellent correlation between these techniques, with intraclass correlation coefficients of 0.88 to 0.96. Interobserver variability was minimal and similar for both techniques. Using the SIE technique, diameters were larger for men and increased with age and larger body surface area. CONCLUSIONS: Although there was a statistically significant difference in aortic diameter measures between the two conventions used, this difference was very small and correlations were excellent, suggesting that the difference has no clinical significance. The authors recommend that a standard convention be adopted within the American Society of Echocardiography and across all professional cardiovascular imaging societies for consistency and improved communication.

Atrial fibrillation (AF) is prevalent in patients with type 2 diabetes mellitus (DM) and is associated with markers of poor glycemic control; however, the impact of glycemic control on incident AF and outcomes is unknown. The aims of this study were to prospectively evaluate if intensive glycemic control in patients with DM affects incident AF and to evaluate morbidity and mortality in patients with DM and incident AF. A total of 10,082 patients with DM from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) cohort were studied in a randomized, double-blind fashion. Participants were randomized to an intensive therapeutic strategy targeting a glycated hemoglobin level of <6.0% or a standard strategy targeting a glycated hemoglobin level of 7.0% to 7.9%. Incident AF occurred in 159 patients (1.58%) over the follow-up period, at a rate of 5.9 per 1,000 patient-years in the intensive-therapy group and a rate of 6.37 per 1,000 patient-years in the standard-therapy group (p = 0.52). In a multivariate model, predictors of incident AF were age, weight, diastolic blood pressure, heart rate, and heart failure history. Patients with DM and new-onset AF had a hazard ratio of 2.65 for all-cause mortality (95% confidence interval 1.8 to 3.86, p <0.0001), a hazard ratio of 2.1 for myocardial infarction (95% confidence interval 1.33 to 3.31, p = 0.0015), and a hazard ratio of 3.80 for the development of heart failure (95% confidence interval 2.48 to 5.84, p <0.0001). In conclusion, intensive glycemic control did not affect the rate of new-onset AF. Patients with DM and incident AF had an increased risk for morbidity and mortality compared with those without AF.

p63, a p53 family member, is required for craniofacial and limb development as well as proper skin differentiation. However, p63 mutations associated with the ankyloblepharon-ectodermal dysplasia-clefting (AEC) syndrome (Hay-Wells syndrome) were found in the p63 carboxyl-terminal region with a sterile alpha-motif. By two-hybrid screen we identified several proteins that interact with the p63alpha carboxyl terminus and its sterile alpha-motif, including the apobec-1-binding protein-1 (ABBP1). AEC-associated mutations completely abolished the physical interaction between ABBP1 and p63alpha. Moreover the physical association of p63alpha and ABBP1 led to a specific shift of FGFR-2 alternative splicing toward the K-SAM isoform essential for epithelial differentiation. We thus propose that a p63alpha-ABBP1 complex differentially regulates FGFR-2 expression by supporting alternative splicing of the K-SAM isoform of FGFR-2. The inability of mutated p63alpha to support this splicing likely leads to the inhibition of epithelial differentiation and, in turn, accounts for the AEC phenotype.