Vitamin D Status and Exercise Capacity in Older Patients with Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Older patients with heart failure with preserved ejection fraction have severe exercise intolerance. Vitamin D may play a role in cardiovascular and skeletal muscle function, and may therefore be implicated in exercise intolerance in heart failure with preserved ejection fraction. However, there are few data on vitamin D status and its relationship to exercise capacity in heart failure with preserved ejection fraction patients. METHODS: Plasma 25-hydroxyvitamin D (25[OH]D) and exercise capacity (peak oxygen consumption, [VO2], 6-minute walk distance) were measured in 112 older heart failure with preserved ejection fraction patients (mean ± SD age = 70 ± 8 years) and 37 healthy age-matched controls. General linear models were used to compare 25(OH)D between heart failure with preserved ejection fraction patients and healthy controls, and to determine the cross-sectional association between 25(OH)D and exercise capacity. The association between 25(OH)D and left ventricular function was evaluated secondarily in heart failure with preserved ejection fraction patients. RESULTS: 25(OH)D concentrations were significantly lower in heart failure with preserved ejection fraction vs healthy controls (11.4 ± 0.6 ng/mL vs 19.1 ± 2.1 ng/mL; P = .001, adjusted for age, race, sex, body mass index, season). More than 90% of heart failure with preserved ejection fraction patients had 25(OH)D insufficiency (<20 ng/mL) and 30% had frank 25(OH)D deficiency (<10 ng/mL). In heart failure with preserved ejection fraction patients, but not healthy controls, 25(OH)D was significantly correlated with peak VO2 (r = 0.26; P = 0.007) and 6-minute walk distance (r = 0.34; P < .001). CONCLUSIONS: More than 90% of heart failure with preserved ejection fraction patients had 25(OH)D insufficiency, and 30% were frankly deficient. Lower 25(OH)D was associated with lower peak VO2 and 6-minute walk distance in heart failure with preserved ejection fraction, suggesting that 25(OH)D insufficiency could contribute to exercise intolerance in this patient population. These findings provide the data and rationale for a future randomized trial designed to test the potential for vitamin D supplementation to improve exercise intolerance in heart failure with preserved ejection fraction.

His-Bundle Pacing for Identifying Optimal Ablation Sites in Patients Undergoing Atrioventricular Junction Ablation: Teaching an Old Dog a New Trick.

BACKGROUND: Atrioventricular (AV) junction (AVJ) ablation is conventionally performed by localizing the His-bundle electrogram (HBE). Identification of HBE in the presence of atrial fibrillation (AF) can be difficult, and can make this simple procedure challenging. In this study, we describe our experience with an alternative approach to localize optimal ablation sites using His-bundle pacing (HBP). METHODS: Between 1/1/2014 and 12/31/2015, we performed 13 AVJ ablations using the standard electrogram-guided approach and 11 ablations using HBP. All cases utilized a long femoral guiding sheath and an 8-mm-tip electrode radiofrequency (RF) energy ablation catheter. Pacing was performed at high output (10 mA at 2 ms) to initially achieve right bundle branch capture. The catheter was withdrawn until a narrow QRS morphology and increased stim-to-QRS time were observed. HBP was confirmed when paced and native QRS were identical in morphology. RF energy was applied at the site of HBP capture until AV block was observed. RESULTS: Baseline characteristics of patients in each arm were not significantly different. Compared with the standard approach, HBP was associated with trends toward lower RF applications (3 vs. 2, P = 0.16) and shorter mean RF time (208 seconds vs. 128 seconds, P = 0.19). CONCLUSION: HBP is an effective technique to identify optimal ablation sites during AVJ ablation and may shorten procedure time. HBP can be used to identify the AV node during AF without recording the His potential. Future studies with larger sample size are needed to better characterize the utility of this technique.

Cell cycle inhibition and apoptosis induced by curcumin in Ewing sarcoma cell line SK-NEP-1.

Curcumin is a naturally occurring polyphenolic compound found in the turmeric, which is used as food additive in Indian cooking and as a therapeutic agent in traditional Indian medicine. Curcumin is currently under investigation as a chemotherapeutic and chemopreventive agent in adult cancer models at both pre-clinical and clinical levels. In this preliminary study, we show that curcumin is effective in causing cell cycle arrest, inducing apoptosis, and suppressing colony formation in the Ewing sarcoma cell line SK-NEP-1. Curcumin causes upregulation of cleaved caspase 3 and downregulation of phospho-Akt, producing apoptosis in Ewing sarcoma cells at an inhibitory concentration 50% (IC50) of approximately 4 µM. Our findings indicate a need for further evaluation of curcumin in chemotherapy and chemoprevention of Ewing sarcoma.

The Yin and Yang of lactosylceramide metabolism: implications in cell function.

Although lactosylceramide (LacCer) plays a pivotal role in the biosynthesis of nearly all the major glycosphingolipids, its function in regulating cellular function has begun to emerge only recently. Our current opinion is that several physiologically critical molecules such as modified/oxidized LDL, growth factors, pro-inflammatory cytokines and fluid shear stress converge upon and activate lactosylceramide synthase to generate LacCer. In turn, LacCer activates an "oxygen-sensitive" signaling pathway involving superoxides, nitric oxide, p21 Ras GTP loading, kinase cascade, PI3kinase/Akt activation, nuclear factor up-regulation ultimately contributing to phenotypic changes such as cell proliferation, adhesion, migration and angiogenesis. Since dys-regulation of such phenotypic changes constitute a hallmark in several diseases of the cardiovascular system, proliferative disorders such as cancer, polycystic kidney disease and inflammatory diseases, LacCer synthase and LacCer provide novel targets for the development of therapeutics aimed at these health conditions.