Isolated TR can be severe and is associated with excess mortality and morbidity, warranting heightened attention to diagnosis and quantitation. Quantitative assessment of TR, particularly ERO measurement, is a powerful independent predictor of outcome, superior to standard qualitative assessment.

Background-Fibro-elastic deficiency (FED) and diffuse myxomatous degeneration (DMD) are phenotypes of degenerative mitral valve disease defined morphologically. Whether physiological differences in annular and valvular dynamics exist between these phenotypes remains unknown. Methods and Results-We performed triple quantitation of cardiac remodeling and of mitral regurgitation severity and of annular and valvular dimensions by real-time 3-dimensional-transesophageal-echocardiography. Forty-nine patients with degenerative mitral valve disease classified as FED (n=31)

A wide variety of drugs and chemicals elicit neurobehavioral teratogenesis. Surprisingly, however, despite the obvious differences among unrelated compounds, the behavioral outcomes often display striking similarities, such as cognitive and attentional deficits. Recent studies of drugs of abuse (heroin, nicotine, barbiturates) and environmental toxins (environmental tobacco smoke, pesticides, metals) suggest that, regardless of the originating mechanism for perturbation of brain development, disparate neuroteratogens converge downstream on common families of alterations, characterized by changes in the expression and/or activity of the cell‐signaling molecules that are essential to neuronal differentiation and synaptic communication. Identification of these common targets may help in the design of pharmacologic interventions that, administered in adulthood, can reverse the impact of exposure to neurobehavioral teratogens.

Objectives Cleft-like indentations (CLI) are deep separations between scallops of the mitral posterior leaflet observed in myxomatous mitral valve disease (MMVD), but their diagnosis, mechanisms and implications are unknown. Using 3D transoesophageal echocardiography (3DTOC), we aimed at assessing diagnostic accuracy and defining mechanisms of CLI in patients undergoing surgery for MMVD.

Opioid drugs act primarily on the opiate receptors; they also exert their effect on other innervations resulting in non-opioidergic behavioural deficits. Similarly, opioid neurobehavioural teratogenicity is attested in numerous behaviours and neural processes which hinder the research on the mechanisms involved. Therefore, in order to be able to ascertain the mechanism we have established an animal (mouse) model for the teratogenicity induced by opioid abuse, which focused on behaviours related to specific brain area and innervation. Diacetylmorphine (heroin) and not morphine was applied because heroin exerts a unique action, distinguished from that of morphine. Pregnant mice were exposed to heroin (10 mg/kg per day) and the offspring were tested for behavioural deficits and biochemical alterations related to the septohippocampal cholinergic innervation. Some studies employing the chick embryo were concomitantly added as a control for the confounding indirect variables. Prenatal exposure to heroin in mice induced global hyperactivation both pre- and post-synaptic along the septohippocampal cholinergic innervation, including basal protein kinase C (PKC) activity accompanied by a desensitization of PKC activity in response to cholinergic agonist. Functionally, the heroin-exposed offspring displayed deficits in hippocampus-related behaviours, suggesting deficits in the net output of the septohippocampal cholinergic innervation. Grafting of cholinergic cells to the impaired hippocampus reversed both pre- and post-synaptic hyperactivity, resensitized PKC activity, and restored the associated behaviours to normality. Consistently, correlation studies point to the relative importance of PKC to the behavioural deficits. The chick model, which dealt with imprinting related to a different brain region, confirmed that the effect of heroin is direct. Taken together with studies by others on the effect of prenatal exposure to opioids on the opioidergic innervation and with what is known on the opioid regulation of the cholinergic innervation, it appears that heroin exerts its neuroteratogenicity by inducing alterations in the opioidergic innervation, which by means of its regulatory action, attenuates the functional output of the cholinergic innervation. In our model, there was hyperactivity mostly of the post-synaptic components of the cholinergic innervation. However, the net cholinergic output is decreased because PKC is desensitized to the effect of the cholinergic agonist, and this is further evidenced by the extensive deficits in the related behaviours.

<b><i>Background:</i></b> Percutaneous device closure was shown to effectively prevent recurrent strokes in patients with patent foramen ovale (PFO). Whether this protective effect is relevant for patients with hypercoagulable states (HCSs) is unknown as they were not represented in prior studies. <b><i>Methods:</i></b> Data on 136 consecutive patients with a PFO and clinically significant HCS were retrospectively collected. PFO closure and antithrombotic regimen were decided on an individual basis by the treating physicians, and adherence to therapy was routinely evaluated. The outcome was the occurrence of cerebrovascular accident (CVA) or transient ischemic attack (TIA). <b><i>Results:</i></b> HCS types consisted of antiphospholipid syndrome (31%), factor-5 Leiden mutation (22%), prothrombin mutation (18%), protein S deficiency (15%), protein C deficiency (7%), methyl-tetra-hydro folate reductase mutation (5%), and essential thrombocytosis (2%). 102 patients (75%) were maintained on anticoagulants and the remaining on antiplatelet therapy. PFO closure was undertaken in 85 (63%); antithrombotic therapy was not interrupted prior to or after the procedures. At a mean follow-up of 46 ± 8 months, 23 patients (17%; 95% confidence interval, 9.3–22%) experienced an outcome event, mainly in the form of CVAs (<i>n</i> = 15, 65%). In multivariable analysis, PFO closure was associated with a 5-fold decrease in the risk of CVA/TIA (<i>p</i> = 0.02). This effect was independent of the type of HCS or antithrombotic therapy. <b><i>Conclusions:</i></b> Among patients with HCSs maintained on anticoagulant or antiplatelet therapies, PFO closure was associated with a significantly lower risk of CVA or TIA.

Objective To assess the diagnostic capability of handheld echocardiography (HHE) compared with transthoracic echocardiography (TTE) performed and evaluated by experienced sonographers and expert echocardiographers. Patients and Methods We conducted a prospective study of adult outpatients undergoing comprehensive TTE from July 9, 2012, through April 3, 2013. Experienced sonographers performed a detailed, standardized examination with a handheld ultrasound device (Vscan; GE Healthcare) that included 2-dimensional and color Doppler images from standard imaging windows. TTE and HHE images were independently interpreted by expert echocardiographers to whom the other study was masked. Agreement between the standard TTE and the HHE reports was analyzed. Results The study group contained 190 patients (mean [SD] age, 62 [17] years; 49% male). κ Values were 0.52 for left ventricular (LV) enlargement, 0.52 for right ventricular enlargement, 0.62 for regional wall motion abnormalities, 0.73 for aortic stenosis, and 0.61 for mitral regurgitation. Lin concordance correlation coefficients ranged from 0.89 for LV end-systolic diameter to 0.78 for LV end-diastolic diameter. In 51 patients (27%), echocardiographic findings were discordant between HHE and standard TTE. The most common discordant finding was the presence vs absence of any regional wall motion abnormalities. In discordant cases, HHE tended to underestimate, rather than overestimate, the severity of abnormal findings. Conclusion HHE in experienced hands shows moderate correlation with standard TTE, but discordant findings were present in 27% of patients. HHE, even when performed and interpreted by experienced operators, should not be used as a surrogate for standard TTE.

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