scholarly journals Proteomic Signatures During Treatment in Different Stages of Heart Failure

2020 ◽  
Vol 13 (8) ◽  
Author(s):  
Sam A. Michelhaugh ◽  
Alexander Camacho ◽  
Nasrien E. Ibrahim ◽  
Hanna Gaggin ◽  
David D’Alessandro ◽  
...  

Background: Proteomics have already provided novel insights into the pathophysiology of heart failure (HF) with reduced ejection fraction. Previous studies have evaluated cross-sectional protein signatures of HF, but few have characterized proteomic changes following HF with reduced ejection fraction treatment with ARNI (angiotensin receptor/neprilysin inhibitor) therapy or left ventricular assist devices. Methods: In this retrospective omics study, we performed targeted proteomics (N=625) of whole blood sera from patients with American College of Cardiology/American Heart Association stage D (N=29) and stage C (N=12) HF using proximity extension assays. Samples were obtained before and after (median=82 days) left ventricular assist device implantation (stage D; primary analysis) and ARNI therapy initiation (stage C; matched reference). Oblique principal component analysis and point biserial correlations were used for feature extraction and selection; standardized mean differences were used to assess within and between-group differences; and enrichment analysis was used to generate and cluster Gene Ontology terms. Results: Core sets of proteins were identified for stage C (N=9 proteins) and stage D (N=18) HF; additionally, a core set of 5 shared HF proteins (NT-proBNP [N-terminal pro-B type natriuretic peptide], ESM [endothelial cell-specific molecule]-1, cathepsin L1, osteopontin, and MCSF-1) was also identified. For patients with stage D HF, moderate (δ, 0.40–0.60) and moderate-to-large (δ, 0.60–0.80) sized differences were observed in 8 of their 18 core proteins after left ventricular assist devices implantation. Additionally, specific protein groups reached concentration levels equivalent ( g <0.10) to stage C HF after initiation on ARNI therapy. Conclusions: HF with reduced ejection fraction severity associates with distinct proteomic signatures that reflect underlying disease attributes; these core signatures may be useful for monitoring changes in cardiac function following initiation on ARNI or left ventricular assist device implantation.

Author(s):  
David A. Ramirez ◽  
Mikayle A. Holm ◽  
Andrew Shaffer ◽  
Paul A. Iaizzo

Abstract Implanting Left ventricular assist devices (LVADs) can be life saving therapies that improve life expectancy for the patients that receive it. The target patient population suffer from end-stage heart failure and are therefore susceptible to morbidities arising from a less than ideal surgical implantation. Importantly, the graft that carries the blood from the LVAD pump to the aorta needs to be sized accordingly so as to not cause any compounding complications. The current typical surgical method, is to perform a visual estimation at the time of implantation. This present study proposes a computational tool that utilizes pre-procedural imaging to better calculate the personalized, ideal, LVAD graft length.


2019 ◽  
Vol 57 (1) ◽  
pp. 176-182
Author(s):  
Sinan Sabit Kocabeyoglu ◽  
Umit Kervan ◽  
Dogan Emre Sert ◽  
Mehmet Karahan ◽  
Emre Aygun ◽  
...  

Abstract OBJECTIVES The aim of this study was to examine the haemodynamic effects of preoperative levosimendan infusion in patients who underwent left ventricular assist device implantation and evaluate the prognoses. METHODS Between May 2013 and October 2018, 85 adult patients who underwent left ventricular assist device implantation were included; 44 and 41 patients suffered from dilated cardiomyopathy and ischaemic cardiomyopathy, respectively. Patients were divided into 2 groups: group A (58 patients) included those who received levosimendan infusion in addition to other inotropes and group B (27 patients) included those who received inotropic agents other than levosimendan. Levosimendan infusion was started at a dose of 0.1 µg⋅kg−1⋅min−1 for a maximum of 48 h without a bolus. The primary outcome was early right ventricular failure (RVF). The secondary outcomes were in-hospital mortality, need for right ventricular assist device, late RVF and recovery of end-organ functions. The safety end points of levosimendan included hypotension, atrial fibrillation, ventricular tachycardia or fibrillation and resuscitated cardiac arrest. RESULTS Patient characteristics were similar in both groups. No significant differences between groups were observed in the rates of early mortality, RVF, need for right ventricular assist device, cardiopulmonary bypass time and intensive care unit stay. Survival rates at 30 days, 1 year and 3 years and freedom from late RVF were similar between the groups. Administration of levosimendan was safe, generally well-tolerated and not interrupted because of side effects. CONCLUSIONS Levosimendan therapy was well-tolerated in patients who received permanent left ventricular assist devices. Combined preoperative therapy with inotropes and levosimendan significantly improves end-organ functions.


2018 ◽  
Vol 42 (3) ◽  
pp. 113-124 ◽  
Author(s):  
Matteo Selmi ◽  
Wei-Che Chiu ◽  
Venkat Keshav Chivukula ◽  
Giulio Melisurgo ◽  
Jennifer Ann Beckman ◽  
...  

Introduction: Despite significant technical advancements in the design and manufacture of Left Ventricular Assist Devices, post-implant thrombotic and thromboembolic complications continue to affect long-term outcomes. Previous efforts, aimed at optimizing pump design as a means of reducing supraphysiologic shear stresses generated within the pump and associated prothrombotic shear-mediated platelet injury, have only partially altered the device hemocompatibility. Methods: We examined hemodynamic mechanisms that synergize with hypershear within the pump to contribute to the thrombogenic potential of the overall Left Ventricular Assist Device system. Results: Numerical simulations of blood flow in differing regions of the Left Ventricular Assist Device system, that is the diseased native left ventricle, the pump inflow cannula, the impeller, the outflow graft and the anastomosed downstream aorta, reveal that prothrombotic hemodynamic conditions might occur at these specific sites. Furthermore, we show that beyond hypershear, additional hemodynamic abnormalities exist within the pump, which may elicit platelet activation, such as recirculation zones and stagnant platelet trajectories. We also provide evidences that particular Left Ventricular Assist Device implantation configurations and specific post-implant patient management strategies, such as those allowing aortic valve opening, are more hemodynamically favorable and reduce the thrombotic risk. Conclusion: We extend the perspective of pump thrombosis secondary to the supraphysiologic shear stress environment of the pump to one of Left Ventricular Assist Device system thrombosis, raising the importance of comprehensive characterization of the different prothrombotic risk factors of the total system as the target to achieve enhanced hemocompatibility and improved clinical outcomes.


2015 ◽  
Vol 42 (6) ◽  
pp. 572-574
Author(s):  
Heidi J. Reich ◽  
Aamir Shah ◽  
Babak Azarbal ◽  
Jon Kobashigawa ◽  
Jaime Moriguchi ◽  
...  

Evolving technology and improvements in the design of modern, continuous-flow left ventricular assist devices have substantially reduced the rate of device malfunction. As the number of implanted devices increases and as survival prospects for patients with a device continue to improve, device malfunction is an increasingly common clinical challenge. Here, we present our initial experience with an endovascular microaxial flow left ventricular assist device as a successful bridge to transplantation in a 54-year-old man who experienced left ventricular assist device malfunction.


2017 ◽  
Author(s):  
Adam C. Sieg ◽  
Jennifer A. Gass ◽  
Phillip Weeks ◽  
Indranee Rajapreyar ◽  
Igor Gregoric

The use of left ventricular assist devices (LVAD) provides a treatment strategy for advanced heart failure patients to prolong life and serve as a mediator (bridge to transplant) until an organ becomes available in patients considered suitable candidates for heart transplantation. The use of LVAD therapy is complicated by the constant risk of bleeding and thrombotic events. We reviewed and analyzed the effectiveness of our current heparin protocol with respect to overall anticoagulation and time in therapeutic range (TTR). Our analysis demonstrated that patients did not achieve therapeutic anticoagulation for at least 24 hours following initiation of heparin and that only 40% of the time patients were considered therapeutic. Even after patients achieved a therapeutic activated plasma thromboplastin time (aPTT) TTR was only approximately 50% with less than 50% of tests resulting within range. Individual centers should perform ongoing assessment of effectiveness of individual heparin protocol for LVAD patients to ensure anticoagulation is optimized in these highly complex patients.


2020 ◽  
Vol 2020 (9) ◽  
Author(s):  
Lea Timmermann ◽  
Moritz Schmelzle ◽  
Evgenij Potapov ◽  
Marcus Müller ◽  
Christian Lojewski ◽  
...  

Abstract Successful implementation of left ventricular assist devices lead to a prolonged survival in patients with chronic terminal heart failure. Thus, patients with pre-existing left ventricular assist devices with abdominal comorbidities requiring abdominal surgery, e.g. for malignancy, are upcoming issues. We carried out a major liver resection for hepatocellular carcinoma in a patient with pre-existing left ventricular assist device. The importance of this case report is that it outlines the significance of oncologic resections in patients with left ventricular assist devices as an upcoming issue and provides an interdisciplinary approach.


2019 ◽  
Vol 67 (03) ◽  
pp. 183-190 ◽  
Author(s):  
Konstantin Zhigalov ◽  
Marcin Szczechowicz ◽  
Ahmed Mashhour ◽  
Sabreen Mkalaluh ◽  
Maxim Isaev ◽  
...  

Background The main purpose of this article is to investigate the impact of previous sternotomy (PS) on the outcome of three different left ventricular assist devices (LVAD). Methods Between June 2007 and February 2018, a total of 121 patients received HeartMate II (60.3%), HeartWare (12.4%), or HeartMate III (27.3%), with or without previous sternotomy (PS and non-PS groups, respectively). Propensity matching resulted in 44 patient pairs. The primary end point was overall survival at 30 days, 1 year, 2, and 5 years, postoperatively. Secondary end points were adverse events. Results The overall cumulative survival rates for the two study groups were significantly different (77, 63, 54, and 38% for non-PS group vs 64, 39, 27, and 24% for PS group, p = 0.036). In the PS group, there was a higher need for intraoperative implantation of short-term right ventricular assist device (22.7 vs 6.8%, p = 0.034) and a higher incidence of hepatic dysfunction (20.5 vs 4.5%, p = 0.025) and acute kidney dysfunction (40.9 vs 20.5%, p = 0.032). Conclusion PS is a reliable predictor of mortality and morbidity after LVAD implantation.


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