Deaths from opioid abuse have increased markedly among an otherwise young and healthy population. 1 Approximately a million people used heroin in the United States in 2016, 2 times more than the number who used heroin in the entire period between 2002 and 2013. 2 Because people who inject drugs (PWID) are at risk for bacteremia, we hypothesized that their mortality from infective endocarditis has increased.
The molecular differences between ischemic (IF) and non-ischemic (NIF) heart failure are poorly defined. A better understanding of the molecular differences between these two heart failure etiologies may lead to the development of more effective heart failure therapeutics. In this study extensive proteomic and phosphoproteomic profiles of myocardial tissue from patients diagnosed with IF or NIF were assembled and compared.Proteins extracted from left ventricular sections were proteolyzed and phosphopeptides were enriched using titanium dioxide resin. Gel- and label-free nanoscale capillary liquid chromatography coupled to high resolution accuracy mass tandem mass spectrometry allowed for the quantification of 4,436 peptides (corresponding to 450 proteins) and 823 phosphopeptides (corresponding to 400 proteins) from the unenriched and phospho-enriched fractions, respectively.Protein abundance did not distinguish NIF from IF. In contrast, 37 peptides (corresponding to 26 proteins) exhibited a ≥2-fold alteration in phosphorylation state (p<0.05) when comparing IF and NIF. The degree of protein phosphorylation at these 37 sites was specifically dependent upon the heart failure etiology examined. Proteins exhibiting phosphorylation alterations were grouped into functional categories: transcriptional activation/RNA processing; cytoskeleton structure/function; molecular chaperones; cell adhesion/signaling; apoptosis; and energetic/metabolism.Phosphoproteomic analysis demonstrated profound post-translational differences in proteins that are involved in multiple cellular processes between different heart failure phenotypes. Understanding the roles these phosphorylation alterations play in the development of NIF and IF has the potential to generate etiology-specific heart failure therapeutics, which could be more effective than current therapeutics in addressing the growing concern of heart failure.
Since its introduction in the late 19 th century, the Langendorff isolated heart perfusion apparatus, and the subsequent development of the working heart model, have been invaluable tools for studying cardiovascular function and disease [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] . Although the Langendorff heart preparation can be used for any mammalian heart, most studies involving this apparatus use small animal models (e.g., mouse, rat, and rabbit) due to the increased complexity of systems for larger mammals 1,3,11 . One major difficulty is ensuring a constant coronary perfusion pressure over a range of different heart sizes -a key component of any experiment utilizing this device 1,11 . By replacing the classic hydrostatic afterload column with a centrifugal pump, the Langendorff working heart apparatus described below allows for easy adjustment and tight regulation of perfusion pressures, meaning the same set-up can be used for various species or heart sizes. Furthermore, this configuration can also seamlessly switch between constant pressure or constant flow during reperfusion, depending on the user's preferences. The open nature of this setup, despite making temperature regulation more difficult than other designs, allows for easy collection of effluent and ventricular pressure-volume data.
Background: Kidney and liver dysfunction are common in patients with advanced heart failure undergoing left ventricular assistant device (LVAD) implantation. We have previously shown that Model of End-Stage Liver Disease excluding INR (MELD-XI) scores can predict poor outcomes after heart transplantation. Whether MELD-XI predicts outcomes after LVAD implantation is not well understood. Methods: All patients who underwent LVAD implantation at a tertiary referral center (2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017) were included and preoperative MELD-XI was calculated. Cox proportional hazard models and Kaplan Meier method were used to describe association with overall post-implant mortality. Penalized smoothed splines were used to visualize the association between continuous MELDXI and mortality. Results: A total of 94 patients were included. Mean age was 60 §13 years, 78% males, 64% Caucasian, 76% had the HeartMate II. Median MELD-XI was 12.4(9.9-15.9). At a median follow-up of 2.8 years, 31 patients died. There was no difference between patients with MELD-XI >12.4 and MELD-XI 12.4 in overall mortality (P=0.14), figure (panel A). There was no association between continuous MELD-XI and mortality (HR 1.04; 95% CI: 0.96-1.13, P=0.32), figure (panel B). Conclusion: Our findings showed that MELD-XI is not associated with mortality after LVAD implantation. These findings need to be validated in a larger group registry to identify best bridging strategy in patients with advanced heart failure and combined kidney-liver dysfunction.Introduction: As the number of persons living with advanced heart failure (HF) continues to increase, so does the implantation of mechanical circulatory support devices. Over half of the left ventricular assist devices (LVADs) currently implanted are indicated for destination therapy (DT) but there is a gap in the current evidence regarding the end-of-life experiences (EOL) of this group. Purpose: To investigate the EOL experiences of LVAD-DT recipients and their family caregivers throughout the LVAD-DT trajectory including: 1) pre-implantation experiences, 2) conversations about device deactivation, 3) use of EOL services including palliative care and hospice, and 4) device deactivation prior to death. Methods: Thirty five individuals and their family caregivers (n=70) from 2 longitudinal prospective studies participated in qualitative interviews that occurred approximately every month for up to 24 months or until the death of the LVAD-DT recipient. After the death of LVAD-DT recipient, the caregiver was interviewed about LVAD deactivation and use of EOL services. Qualitative content analysis was utilized to explore the experiences of participants through the EOL. EOL service utilization determined via EMR review. Results: During study enrollment LVAD-DT recipients had on average 6 readmissions. The main reasons for readmission included: infection/ sepsis, GI bleed, RHF, and anemia. Sixty percent of the dyads (21/35) received a palliative care consult prior to implantation...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.