Predictors of mortality in patients hospitalized for congestive heart failure with left ventricular ejection fraction ≥ 40%

Background: There are limited data regarding the predictors of mortality in patients with acute congestive heart failure (CHF) and left ventricular ejection fraction (LVEF) ≥ 40%. Methods: We evaluated clinical characteristics, mortality and prognostic factors in a sample of consecutive patients hospitalized for CHF with LVEF ≥ 40%. Multivariable Cox regression models were developed to predict mortality using baseline clinical characteristics and echocardiographic variables. Results: The study population consisted of 191 patients, mean age 70 ± 14.6 years (60% female) with average follow-up of 4.0 ± 2.8 years. Cumulative 5-year mortality was 58% in the entire population and it was 59% in men and 57% in women (p = 0.411). In multivariable analyses, predictors of mortality were the following: blood urea nitrogen (BUN) > 25 mg/dL (HR = 1.77; p = 0.002); absence of hypertension (HR = 1.58; p = 0.032), left ventricular end diastolic dimension (LVEDD) ≤ 4.1 cm (HR = 1.73; p = 0.011) and LVEF ≤ 45% (HR = 1.69; p = 0.027). Conclusions: Patients hospitalized for heart failure with LVEF ≥ 40% have very high mortality. Absence of hypertension, elevated BUN and lower LVEF ≤ 45% indicate increased risk of short- and long-term mortality. Lower LVEDD is an independent predictor of mortality in heart failure patients with LVEF ≥ 40%

Metabolic syndrome is associated with different clinical outcome after cardiac resynchronization therapy in patients with ischemic and non-ischemic cardiomyopathy

Background: Although association of metabolic syndrome (MS) and ischemic heart disease is strongly established, it is not known whether presence of MS may differently influence clinical responses to cardiac resynchronization therapy (CRT). The aim of this study was to evaluate the associations between obesity and metabolic features and the clinical outcome after cardiac resynchronization with defibrillator therapy (CRT-D), compared to an implantable cardioverter defibrillator (ICD). Methods: The risk of heart failure (HF) or death and death alone was evaluated in 829 non-obese patients, 156 obese patients without MS, and 277 obese patients with MS (all with left bundle branch block), who were enrolled in the Multicenter Automatic Defibrillator Implanta­tion Trial with Cardiac Resynchronization Therapy (MADIT-CRT). Results: Obese patients with MS (HR 0.50, 95% CI 0.32–0.77, p = 0.002), obese patients without MS (HR 0.57, 95% CI 0.30–1.06, p = 0.077), and non-obese patients (HR 0.48, 95% CI 0.37–0.62, p < 0.001) had a similar risk reduction of HF/death in response to CRT-D therapy when compared to ICD patients. However, among those with non-ischemic cardiomyo­pathy, obese patients with MS experienced a 90% reduction for HF/death (HR 0.11, 95% CI 0.04–0.32, p < 0.001), whereas obese patients without MS had no reduction (HR 0.98, 95% CI 0.48–1.98, p = 0.951; interaction p < 0.001). The reverse was observed in ischemic car­diomyopathy patients: obese patients with MS had no reduction in the risk of HF/death (HR 0.80, 95% CI 0.48–1.34, p = 0.402), while obese patients without MS showed a significant reduction in the risk of events (HR 0.15, 95% CI 0.04–0.65, p = 0.011; interaction p = 0.036). Similar trends were observed for the endpoint of death. Conclusions: Presence of MS differentiates the response to CRT in obese patients with is­chemic and non-ischemic etiology for HF

Effect of cardiac resynchronization therapy with implantable cardioverter defibrillator versus cardiac resynchronization therapy with pacemaker on mortality in heart failure patients: results of a high-volume, single-centre experience.

AIMS: There are limited and contradictory data on the effects of CRT with implantable cardioverter defibrillator (CRT-D) on mortality as compared with CRT with pacemaker (CRT-P). METHODS AND RESULTS: We evaluated the long-term outcome of patients implanted with a CRT-D or CRT-P device in our high-volume single-centre experience. Data on all-cause mortality were derived from clinic visits and the Hungarian National Healthcare Fund Death Registry. Kaplan-Meier survival analyses and multivariate Cox regression models were used to evaluate all-cause mortality in patients with CRT-D vs. CRT-P, stratified by the aetiology of cardiomyopathy. From 2000 to 2011, 1122 CRT devices, 693 CRT-P (LVEF 28.2 +/- 7.4%) and 429 CRT-D (LVEF 27.6 +/- 6.4%), were implanted at our centre. During the median follow-up of 28 months, 379 patients died from any cause, 250 patients (36%) with an implanted CRT-P and 129 patients (30%) with an implanted CRT-D. There was no evidence of mortality benefit in patients implanted with a CRT-D compared with a CRT-P in the total cohort [hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.73-1.32, P = 0.884]. In patients with ischaemic cardiomyopathy, CRT-D treatment was associated with a significant 30% risk reduction in all-cause mortality compared with an implanted CRT-P (HR 0.70, 95% CI 0.51-0.97, P = 0.03). In non-ischaemic patients, there was no mortality benefit of CRT-D over CRT-P (HR 0.98, 95% CI 0.73-1.32, P = 0.894, interaction P-value = 0.15). CONCLUSIONS: In heart failure patients with ischaemic cardiomyopathy, CRT-D was associated with a mortality benefit compared with CRT-P, but no benefit of CRT-D over CRT-P in mortality was observed in non-ischaemic cardiomyopathy

In-depth Analysis of Alternative Splicing Landscape in Multiple Myeloma and Potential Role of Dysregulated Splicing Factors

Splicing changes are common in cancer and are associated with dysregulated splicing factors. Here, we analyzed RNA-seq data from 323 newly diagnosed multiple myeloma (MM) patients and described the alternative splicing (AS) landscape. We observed a large number of splicing pattern changes in MM cells compared to normal plasma cells (NPC). The most common events were alterations of mutually exclusive exons and exon skipping. Most of these events were observed in the absence of overall changes in gene expression and often impacted the coding potential of the alternatively spliced genes. To understand the molecular mechanisms driving frequent aberrant AS, we investigated 115 splicing factors (SFs) and associated them with the AS events in MM. We observed that ~40% of SFs were dysregulated in MM cells compared to NPC and found a significant enrichment of SRSF1, SRSF9, and PCB1 binding motifs around AS events. Importantly, SRSF1 overexpression was linked with shorter survival in two independent MM datasets and was correlated with the number of AS events, impacting tumor cell proliferation. Together with the observation that MM cells are vulnerable to splicing inhibition, our results may lay the foundation for developing new therapeutic strategies for MM. We have developed a web portal that allows custom alternative splicing event queries by using gene symbols and visualizes AS events in MM and subgroups. Our portals can be accessed at http://rconnect.dfci.harvard.edu/mmsplicing/ and https://rconnect.dfci.harvard.edu/mmleafcutter/

Use of polyethylene glycol coatings for optical fibre humidity sensing

Humidity induced change in the refractive index and thickness of the polyethylene glycol (PEG) coatings are in situ investigated for a range from 10 to 95%, using an optical waveguide spectroscopic technique. It is experimentally demonstrated that, upon humidity change, the optical and swelling characteristics of the PEG coatings can be employed to build a plastic fibre optic humidity sensor. The sensing mechanism is based on the humidity induced change in the refractive index of the PEG film, which is directly coated onto a polished segment of a plastic optical fibre with dip-coating method. It is observed that PEG, which is a highly hydrophilic material, shows no monotonic linear response to humidity but gives different characteristics for various ranges of humidity levels both in index of refraction and in thickness. It undergoes a physical phase change from a semi-crystal line structure to a gel one at around 80% relative humidity. At this phase change point, a drastic decrease occurs in the index of refraction as well as a drastic increase in the swelling of the PEG film. In addition, PEG coatings are hydrogenated in a vacuum chamber. It is observed that the hydrogen has a preventing effect on the humidity induced phase change in PEG coatings. Finally, the possibility of using PEG coatings in construction of a real plastic fibre optic humidity sensor is discussed. (C) 2008 The Optical Society of Japan