Relationship Between Proximal Aorta Morphology and Progression Rate of Aortic Stenosis.

BACKGROUND: The aim of this study was to examine the association between abnormal morphology of the proximal aorta and aortic stenosis (AS) progression rate. The main hypothesis was that morphologic changes of the proximal aorta, such as effacement of the sinotubular junction (STJ), result in increased biomechanical stresses and contribute to calcification and progression of AS. METHODS: Between 2010 and 2012, 426 patients with mild to moderate AS were included in this study. Proximal aortic dimensions were measured at three different levels (i.e., sinus of Valsalva, STJ, and ascending aorta), and sinuses of Valsalva/STJ and ascending aorta/STJ ratios were used to determine degree of aortic deformity. AS progression rate was assessed by annualized increase in mean gradient (median follow-up time, 3.1 years; interquartile range, 2.6-3.9 years). The degree of aortic flow turbulence was examined in 18 matched patients with and without STJ effacement using cardiac magnetic resonance phase-contrast imaging. RESULTS: Patients' mean age was 71 ± 13 years, and 64% were men. Patients with low ratios had greater AS progression (P < .05). After comprehensive adjustment, sinuses of Valsalva/STJ (P = .025) and ascending aorta/STJ (P = .027) ratios were independently associated with greater AS progression rate. Compared with patients without STJ effacement, those with effacement of the STJ had higher degrees of aortic flow turbulence (24.4% vs 17.2%, P = .038). CONCLUSIONS: Effacement of the STJ is independently associated with greater AS progression, regardless of arterial hemodynamics, aortic valve phenotype, or baseline AS severity. Patients with abnormal proximal aortic geometry had disturbed aortic flow patterns. These findings suggest an interrelation between proximal aorta morphology and stenosis progression.

Economic Evaluation of Teledentistry in Cleft Lip and Palate Patients.

OBJECTIVE: To assess the use of Teledentistry (TD) in delivering specialist dental services at the Royal Children's Hospital (RCH) for rural and regional patients and to conduct an economic evaluation by building a decision model to estimate the costs and effectiveness of Teledental consultations compared with standard consultations at the RCH. METHODS: A model-based analysis was conducted to determine the potential costs of implementing TD at the RCH. The outcome measure was timely consultations (whether the patient presented within an appropriate time according to the recommended schedule). Dental records at the RCH of those who presented for orthodontic or pediatric dental consultations were assessed. A cost-effectiveness analysis (CEA), comparing TD with the traditional method of consultation, was conducted. One-way sensitivity analysis was performed to test the robustness of the results. Results and Materials: A total of 367 TD appropriate consultations were identified, of which 241 were timely (65.7%). The mean cost of a RCH consultation was A$431.29, with the mean TD consult costing A$294.35. This represents a cost saving of A$136.95 per appointment. The CEA found TD to be a dominant option, with cost savings of A$3,160.81 for every additional timely consult. The model indicated that 36.7 days of clinic time may be freed up at the RCH to treat other patients and expand capacity. These results were robust when performing one-way sensitivity analysis. CONCLUSION: When taking a societal perspective, the implementation of TD is likely to be a cost-effective alternative compared with the standard practice of face-to-face consultation at the RCH.

Effect of growth hormone treatment on diastolic function in patients who have developed growth hormone deficiency after definitive treatment of acromegaly.

OBJECTIVE: Although growth hormone (GH) replacement is prescribed for patients with hypopituitarism due to many etiologies, it is not routinely prescribed for patients with GH deficiency (GHD) after cure of acromegaly (acroGHD). This study was designed to investigate the effect of GH replacement on cardiac parameters in acroGHD. DESIGN: We prospectively evaluated for 12months 23 patients with acroGHD: 15 subjects on GH replacement and eight subjects not on GH replacement. Main outcome measures included LV mass corrected for body surface area (LVM/BSA) and measures of diastolic dysfunction (E/A ratio and deceleration time), as assessed by echocardiography. RESULTS: After 12months of follow-up, there were no differences between the GH-treated group and the untreated group in LVM/BSA (GH: 74.4±22.5g/m(2) vs untreated: 72.9±21.3g/m(2), p=0.89), E/A ratio (GH: 1.21±0.39 vs untreated: 1.08±0.39, p=0.50) or deceleration time (GH: 224.5±60.1ms vs untreated: 260±79.8ms, p=0.32). The overall degree of diastolic function was similar between the groups with 42.9% of untreated subjects and 50% of GH-treated subjects (p=0.76) classified as having normal diastolic function at follow-up. CONCLUSIONS: There were no significant differences in LVM/BSA or parameters of diastolic function in patients with a history of acromegaly treated for GHD as compared to those who were untreated. These data are reassuring with respect to cardiovascular safety with GH use after treatment for acromegaly, although further longer term study is necessary to evaluate the safety and efficacy of GH treatment in this population.

Mitral valve and papillary muscle abnormalities in hypertrophic obstructive cardiomyopathy.

PURPOSE OF REVIEW: This section reviews abnormalities of the mitral valve apparatus that are associated with hypertrophic obstructive cardiomyopathy. RECENT FINDINGS: Mitral valve abnormalities in hypertrophic obstructive cardiomyopathy include leaflet elongation and thickening and hypertrophy with anterior displacement of the papillary muscles. This combination contributes to the development of systolic anterior motion. The resultant flow forces during systolic anterior motion pulling the leaflets into the left ventricular outflow tract also result in reduced leaflet coaptation and a posteriorly directed mitral regurgitant jet. Additional mitral valve abnormalities include degenerative leaflet changes, aberrant chordal attachments and papillary muscle anomalies. SUMMARY: Mitral valve abnormalities are common in hypertrophic obstructive cardiomyopathy and play an important role in the pathophysiology of dynamic left ventricular outflow tract obstruction.

Erythropoietin increases neuronal NDPKA expression, and NDPKA up-regulation as well as exogenous application protects cortical neurons from in vitro ischemia-related insults.

Using proteomics, we identified nucleoside diphosphate kinase A (NDPKA; also known as NME/NM23 nucleoside diphosphate kinase 1: NME1) to be up-regulated in primary cortical neuronal cultures by erythropoietin (EPO) preconditioning. To investigate a neuroprotective role of NDPKA in neurons, we used a RNAi construct to knock-down and an adenoviral vector to overexpress the protein in cortical neuronal cultures prior to exposure to three ischemia-related injury models; excitotoxicity (L-glutamic acid), oxidative stress (hydrogen peroxide), and in vitro ischemia (oxygen-glucose deprivation). NDPKA down-regulation had no effect on neuronal viability following injury. By contrast, NDPKA up-regulation increased neuronal survival in all three-injury models. Similarly, treatment with NDPKA recombinant protein increased neuronal survival, but only against in vitro ischemia and excitotoxicity. These findings indicate that the NDPKA protein may confer a neuroprotective advantage following injury. Furthermore, as exogenous NDPKA protein was neuroprotective, it suggests that a cell surface receptor may be activated by NDPKA leading to a protective cell-signaling response. Taken together both NDPKAs intracellular and extracellular neuroprotective actions suggest that the protein is a legitimate therapeutic target for the design of drugs to limit neuronal death following stroke and other forms of brain injury.