Positional desaturation due to persistent left superior vena cava draining into the left atrium.

Persistent left superior vena cava (PLSVC) is a rare congenital anomaly whose prevalence is 0.3 % of general population. The majority of PLSVC drain into right atrium (RA) through the coronary sinus without clinical harm. However, in about 10 % of patients with PLSVC, it drains into left atrium (LA) causing right-to-left shunt. Here, we present a 60-year-old male patient with a PLSVC draining into LA, who developed dyspnea and desaturation depending on the body position after trans-catheter coil embolization of coronary to pulmonary artery fistulas. PLSVC draining into LA should be included in the differential diagnosis of positional desaturation.

Prognostic value of pre-procedural left ventricular strain for clinical events after transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an alternative therapy for surgically high-risk patients with severe aortic stenosis (AS). Although TAVI improves survival of patients with severe AS, the mechanism of this effect remains to be clarified. We investigated the effects of TAVI on left ventricular (LV) function and identified the predictive parameters for cardiac events after TAVI. METHODS AND RESULTS: We studied 128 patients with severe symptomatic AS who underwent TAVI. Echocardiographic assessments were performed before and after TAVI. In addition to the conventional echocardiographic parameters such as LV ejection fraction (LVEF) and LV mass index (LVMI), the LV global longitudinal strain (GLS) and early diastolic peak strain rate (SR_E) using two-dimensional speckle tracking echocardiography were also evaluated. All patients were assessed for clinical events including major adverse cardiac events and stroke according to Valve Academic Research Consortium-2 criteria. GLS, early diastolic peak velocity (e'), aortic regurgitation (AR) severity, and SR_E were significantly improved after TAVI. Thirteen patients had an event during the observational period of 591 days (median). Patients with events had higher LVMI, more severe AR, and worse GLS compared to those without events. Furthermore, receiver-operating curve analysis revealed that GLS was the strongest predictor for clinical events (p = 0.009; area under the curve, 0.73). CONCLUSION: Preoperative LV geometric deformation and dysfunction, as a consequence of the cumulative burden of pressure overload, improved after TAVI and could predict cardiac events after TAVI.

Intramolecular control of protein stability, subnuclear compartmentalization, and coactivator function of peroxisome proliferator-activated receptor gamma coactivator 1alpha.

Peroxisome proliferator-activated receptor gamma coactivator (PGC)-1 is a critical transcriptional regulator of energy metabolism. Here we found that PGC-1alpha is a short lived and aggregation-prone protein. PGC-1alpha localized throughout the nucleoplasm and was rapidly destroyed via the ubiquitin-proteasome pathway. Upon proteasome inhibition, PGC-1alpha formed insoluble polyubiquitinated aggregates. Ubiquitination of PGC-1alpha depended on the integrity of the C terminus-containing arginine-serine-rich domains and an RNA recognition motif. Interestingly, ectopically expressed C-terminal fragment of PGC-1alpha was autonomously ubiquitinated and aggregated with promyelocytic leukemia protein. Cooperation of the N-terminal region containing two PEST-like motifs was required for prevention of aggregation and targeting of the polyubiquitinated PGC-1alpha for degradation. This region thereby negatively controlled the aggregation properties of the C-terminal region to regulate protein turnover and intranuclear compartmentalization of PGC-1alpha. Exogenous expression of the PGC-1alpha C-terminal fragment interfered with degradation of full-length PGC-1alpha and enhanced its coactivation properties. We concluded that PGC-1alpha function is critically regulated at multiple steps via intramolecular cooperation among several distinct structural domains of the protein.