Impact of Tricuspid Valve Regurgitation on Early Outcomes after Transcatheter Aortic Valve Replacement.

BACKGROUND AND AIM OF THE STUDY: Tricuspid valve regurgitation (TR) is often not taken into consideration in the prognostication of patients undergoing transcatheter aortic valve replacement (TAVR). Accordingly, its impact on such patients remains relatively poorly defined. The study aim was to explore the effect of TR and parameters of right ventricular (RV) function on outcomes in patients undergoing TAVR. METHODS: Baseline demographic and echocardiographic data were collected for 460 consecutive patients undergoing TAVR at the authors' institution between 2012 and 2015. A retrospective analysis was performed to determine the association of TR with all-cause mortality in these patients. The primary endpoint was 30-day rate of all-cause mortality and/or hospital re-admission. RESULTS: Among 460 patients included in the study analysis there were 25 deaths and 40 re-admissions. Univariate analysis showed that a higher Society of Thoracic Surgeons (STS) score, severe preoperative mitral and tricuspid regurgitation were associated with statistically significant higher 30-day mortality and/or re-admission rates. On multivariate analysis, STS score (OR 1.07, 95% CI 1.012-1.126), moderate TR (OR 3.24, 95% CI 1.52-6.87) and severe TR (OR 2.5, 95% CI 1.04-6.04) were identified as significant independent predictors of all-cause mortality. CONCLUSIONS: The severity of TR is a strong independent parameter predictive of death at 30 days. Therefore, parameters of RV function such as TR should be incorporated into predictive models for patients undergoing TAVR.

Cortical development of AMPA receptor trafficking proteins.

AMPA-receptor trafficking plays a central role in excitatory plasticity, especially during development. Changes in the number of AMPA receptors and time spent at the synaptic surface are important factors of plasticity that directly affect long-term potentiation (LTP), long-term depression (LTD), synaptic scaling, and the excitatory-inhibitory (E/I) balance in the developing cortex. Experience-dependent changes in synaptic strength in visual cortex (V1) use a molecularly distinct AMPA trafficking pathway that includes the GluA2 subunit. We studied developmental changes in AMPA receptor trafficking proteins by quantifying expression of GluA2, pGluA2 (GluA2serine880), GRIP1, and PICK1 in rat visual and frontal cortex. We used Western Blot analysis of synaptoneurosome preparations of rat visual and frontal cortex from animals ranging in age from P0 to P105. GluA2 and pGluA2 followed different developmental trajectories in visual and frontal cortex, with a brief period of over expression in frontal cortex. The over expression of GluA2 and pGluA2 in immature frontal cortex raises the possibility that there may be a period of GluA2-dependent vulnerability in frontal cortex that is not found in V1. In contrast, GRIP1 and PICK1 had the same developmental trajectories and were expressed very early in development of both cortical areas. This suggests that the AMPA-interacting proteins are available to begin trafficking receptors as soon as GluA2-containing receptors are expressed. Finally, we used all four proteins to analyze the surface-to-internalization balance and found that this balance was roughly equal across both cortical regions, and throughout development. Our finding of an exquisite surface-to-internalization balance highlights that these AMPA receptor trafficking proteins function as a tightly controlled system in the developing cortex.