Abstract 218: Nuclear Remodeling Following Mechanical Circulatory Support

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Jun Luo ◽  
Stephen Farris ◽  
Deri Helterline ◽  
April Stempien-Otero
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Dna Content ◽  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Circulatory Support ◽  
Ventricular Assist ◽  
Imaging Flow Cytometry ◽  
Nuclear Number ◽  
Nuclear Remodeling

Rationale: Cardiomyocytes increase DNA content in normal growth and in response to stress in humans by both increases in nuclear number and ploidy. This observation complicates the analysis of human cardiomyocyte proliferation as DNA content can increase in the absence of cytokinesis. Proliferation has been reported in cardiomyocytes following LVAD unloading which may represent a reversal of this process. However, cardiac recovery from LVAD is rare. Thus, we sought to analyze changes in cardiomyocyte nuclear characteristics for clues to this paradox. Objective: We used a novel technique-imaging flow cytometry-to determine changes in nuclear content to test the hypothesis that adult cardiomyocytes can complete cell cycle progression by mitosis after long-term hemodynamic unloading of the failing heart. Methods and Results: Cardiomyocytes were isolated from 8 subjects undergoing primary heart transplantation and 15 subjects following unloading with left ventricular assist device (LVAD, mean unloading time 13.7 ± 9.1 months). Myocyte size, nuclear number and size, DNA content (per cell and per nucleus) and the frequency of cell cycling markers were evaluated by imaging flow cytometry. Myocyte size and nuclear morphology was not significantly different between the groups. However, DNA content per nucleus was significantly decreased (P < 0.01) and the correlation between nuclear size and DNA content lost. The frequency of the cell cycle markers, Ki67 and phospho-histone3 (H3P) were not increased after hemodynamic unloading. Conclusions: Our data demonstrate that unloading of failing hearts with mechanical ventricular assist devices does not alter nucleation state of cardiomyocytes. However, unloading is associated with decreased DNA content of nuclei independent of nucleation state within the cell. As these changes were associated with a trend to decreased cell size but not increased cell cycle markers, they may represent a regression of hypertrophic nuclear remodeling.

Abstract 401: Nuclear Remodeling After Mechanical Circulatory Support

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Jun Luo ◽  
Stephen Farris ◽  
Deri Helterline ◽  
April Stempien-Otero
Keyword(s):  
Cell Cycle ◽  
Dna Content ◽  
Normal Growth ◽  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Circulatory Support ◽  
Cardiomyocyte Proliferation ◽  
Ventricular Assist ◽  
Nuclear Number ◽  
Nuclear Remodeling

Rationale: Cardiomyocytes increase DNA content in normal growth and in response to stress in humans by both increases in nuclear number and ploidy. This observation complicates analysis of human cardiomyocyte proliferation as DNA content can increase in the absence of cytokinesis. Proliferation has been reported in cardiomyocytes following LVAD unloading which may represent a reversal of this process. However, cardiac recovery from LVAD is rare. Thus, we sought to analyze changes in cardiomyocyte nuclear characteristics for clues to this paradox. Objective: We used a novel technique to determine changes in nuclear content to test the hypothesis that adult cardiomyocytes can complete cell cycle progression by mitosis after long-term hemodynamic unloading of the failing heart. Methods and Results: The makeup of myocyte nuclear number, ploidy (per cell and per nucleus) and the frequency of cell cycling markers were evaluated by imaging flow cytometry. Hypertrophic hearts from 15 subjects with left ventricular assist device (LVAD) were compared with 8 non-LVAD unloaded hearts. After hemodynamic unloading for 13.7 ± 9.1 months, myocyte nuclear makeup, specifically the average sizes of both cell and individual nuclei, did not significantly change. DNA content per nucleus was significantly decreased (P < 0.01). The frequency of cell cycle markers, i.e. Ki67 and phospho-histon3 (H3P) were not increased after hemodynamic unloading. Conclusions: Our data demonstrate that unloading of failing hearts with mechanical ventricular assist devices does not alter nucleation state of cardiomyocytes. However, unloading is associated with decreased DNA content of nuclei independent of nucleation state within the cell. As these changes were associated with a trend to decreased cell size but not increased cell cycle markers, they may represent a regression of hypertrophic nuclear remodeling.

scholarly journals Mechanical Unloading is Associated with Decreased DNA Content in Cardiomyocytes Independent of Nucleation State

2020 ◽  
Author(s):  
Jun Luo ◽  
Stephen D. Farris ◽  
Deri Helterline ◽  
April Stempien-Otero
Keyword(s):  
Cell Cycle ◽  
Cell Size ◽  
Dna Content ◽  
Human Subjects ◽  
Imaging Flow Cytometry ◽  
Mechanical Unloading ◽  
Phosphohistone H3 ◽  
Response To Stress ◽  
Nuclear Number ◽  
Nuclear Remodeling

ABSTRACTBackgroundCardiomyocytes increase DNA content in response to stress in humans. Proliferation has been reported in cardiomyocytes in failing hearts and following LVAD unloading which may represent a resolution of this process through cell division. However, cardiac recovery from LVAD is rare.MethodsWe quantified cardiomyocyte nuclear number, cell size, DNA content and the frequency of cell cycling markers by imaging flow cytometry from human subjects undergoing LVAD implantation or primary transplantation.ResultsCardiomyocyte size was 15 percent smaller in unloaded versus loaded samples without differences in the percentage of mono-, bi, or multi-nuclear cells. DNA content per nucleus was significantly decreased in unloaded hearts versus loaded controls. Cell cycle markers, Ki67 and phosphohistone H3 (H3P) were not increased in unloaded versus failing samples.ConclusionsUnloading of failing hearts is associated with decreased DNA content of nuclei independent of nucleation state within the cell. As these changes were associated with a trend to decreased cell size but not increased cell cycle markers, they may represent a regression of hypertrophic nuclear remodeling and not proliferation.

scholarly journals Endocrine Challenges in Patients with Continuous-Flow Left Ventricular Assist Devices

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 861
Author(s):  
Gennaro Martucci ◽  
Federico Pappalardo ◽  
Harikesh Subramanian ◽  
Giulia Ingoglia ◽  
Elena Conoscenti ◽  
...  
Keyword(s):  
Continuous Flow ◽  
Left Ventricular ◽  
Endocrine Function ◽  
Ventricular Assist Devices ◽  
Circulatory Support ◽  
Endocrine Dysfunction ◽  
Left Ventricular Assist Devices ◽  
Ventricular Assist ◽  
Assist Devices ◽  
Left Ventricular Assist

Heart failure (HF) remains a leading cause of morbidity, hospitalization, and mortality worldwide. Advancement of mechanical circulatory support technology has led to the use of continuous-flow left ventricular assist devices (LVADs), reducing hospitalizations, and improving quality of life and outcomes in advanced HF. Recent studies have highlighted how metabolic and endocrine dysfunction may be a consequence of, or associated with, HF, and may represent a novel (still neglected) therapeutic target in the treatment of HF. On the other hand, it is not clear whether LVAD support, may impact the outcome by also improving organ perfusion as well as improving the neuro-hormonal state of the patients, reducing the endocrine dysfunction. Moreover, endocrine function is likely a major determinant of human homeostasis, and is a key issue in the recovery from critical illness. Care of the endocrine function may contribute to improving cardiac contractility, immune function, as well as infection control, and rehabilitation during and after a LVAD placement. In this review, data on endocrine challenges in patients carrying an LVAD are gathered to highlight pathophysiological states relevant to this setting of patients, and to summarize the current therapeutic suggestions in the treatment of thyroid dysfunction, and vitamin D, erythropoietin and testosterone administration.

Development of Mechanical Circulatory Support Devices: 55 Years and Counting

2021 ◽  
Vol 32 (4) ◽  
pp. 424-433
Author(s):  
Emalie Petersen
Keyword(s):  
Mechanical Circulatory Support ◽  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Circulatory Support ◽  
Left Ventricular Assist Devices ◽  
Ventricular Assist ◽  
Assist Devices ◽  
Left Ventricular Assist ◽  
Mechanical Circulatory Support Devices ◽  
Support Devices

Heart failure is a leading cause of morbidity and mortality in the United States. Treatment of this condition increasingly involves mechanical circulatory support devices. Even with optimal medical therapy and use of simple cardiac devices, heart failure often leads to reduced quality of life and a shortened life span, prompting exploration of more advanced treatment approaches. Left ventricular assist devices constitute an effective alternative to cardiac transplantation. These devices are not without complications, however, and their use requires careful cooperative management by the patient’s cardiology team and primary care provider. Left ventricular assist devices have undergone many technological advancements since they were first introduced, and they will continue to evolve. This article reviews the history of different types of left ventricular assist devices, appropriate patient selection, and common complications in order to increase health professionals’ familiarity with these treatment options.

Cerebrovascular Events in Patients with Centrifugal-Flow Left Ventricular Assist Devices: A Propensity Score Matched Analysis from the Intermacs Registry

Circulation ◽  
2021 ◽  
Author(s):  
Sung-Min Cho ◽  
J. Hunter Mehaffey ◽  
Susan L. Myers ◽  
Ryan S. Cantor ◽  
Randall C. Starling ◽  
...  
Keyword(s):  
Risk Factors ◽  
Propensity Score ◽  
Secondary Analysis ◽  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Circulatory Support ◽  
Left Ventricular Assist Devices ◽  
Ventricular Assist ◽  
Assist Devices ◽  
Left Ventricular Assist

Background: Ischemic and hemorrhagic cerebrovascular accidents (ICVA and HCVA, respectively) remain common among patients with centrifugal-flow left ventricular assist devices (CF-LVADs), despite improvements in survival and device longevity. Therefore, the incidence of neurological adverse events (NAEs) associated with two contemporary CF-LVADs, the Abbott HeartMate3 ® (HM3) and the Medtronic HeartWare ™ HVAD ® (HVAD), were compared. Methods: Using the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs), we collected data on adult patients who received a CF-LVAD as a primary isolated implant between 1/1/2017 and 9/30/2019. Major NAEs were defined as transient ischemic attack (TIA), ICVA, and HCVA. The association of HVAD with risk of NAE in the first year post implant was evaluated using propensity score matching to balance for pre-implant risk factors. After matching, freedom from first major NAE in the HM3 and HVAD cohorts was compared with Kaplan-Meier curves. A secondary analysis using multivariable multiphase hazard models was used to identify predictors of NAE, which uses a data driven parametric fit of the early declining and constant phase hazards and the associations of risk factor with either phase. Results: Of 6,205 included patients, 3,076 (49.6%) received the HM3 and 3,129 (50.4%) received the HVAD. Median follow-up was 9 and 12 months (HM3 and HVAD). HVAD patients had more major NAEs (16.4% vs. 6.4%, p <0.001), as well as each subtype (TIA: 3.3% vs. 1.0%, p <0.001; ICVA: 7.7% vs. 3.4%, p <0.001; and HCVA: 7.2% vs. 2.0%, p <0.001), than did HM3 patients. A propensity-matched cohort balanced for pre-implant risk factors showed that HVAD was associated with higher probabilities of major NAEs (% freedom from NAE: 82% vs. 92%, p <0.001). Device type was not significantly associated with NAEs in the early hazard phase, but HVAD was associated with higher incidence of major NAEs during the constant hazard phase (hazard ratio: 5.71, confidence interval: 3.90-8.36). Conclusions: HM3 is associated with lower hazard of major NAEs than is HVAD beyond the early post-implantation period and during the constant hazard phase. Defining the explanation for this observation will inform device selection for individual patients.

Hemodynamic Support by Left Ventricular Assist Devices Reduces Cardiomyocyte DNA Content in the Failing Human Heart

Circulation ◽  
2010 ◽  
Vol 121 (8) ◽  
pp. 989-996 ◽  
Author(s):  
Jeremias Wohlschlaeger ◽  
Bodo Levkau ◽  
Gero Brockhoff ◽  
Klaus Jürgen Schmitz ◽  
Moritz von Winterfeld ◽  
...  
Keyword(s):  
Dna Content ◽  
Human Heart ◽  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Left Ventricular Assist Devices ◽  
Ventricular Assist ◽  
Assist Devices ◽  
Hemodynamic Support ◽  
Left Ventricular Assist

Outpatient use of left ventricular assist devices: nursing, technical, and educational considerations

1997 ◽  
Vol 6 (5) ◽  
pp. 355-362 ◽  
Author(s):  
DA Moroney ◽  
K Powers
Keyword(s):  
Clinical Training ◽  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Circulatory Support ◽  
Left Ventricular Assist Devices ◽  
Hospital Data ◽  
Ventricular Assist ◽  
Assist Devices ◽  
Left Ventricular Assist ◽  
Permanent Implants

Improvements in technology and in the selection, care, and treatment of patients have led to wider clinical use of mechanical circulatory support. Considerable progress has been made with the use of left ventricular assist devices. Patients are currently maintained in outpatient facilities until a donor heart becomes available; recently, left ventricular assist devices have started to be used as permanent implants. This article outlines the steps that are taken to prepare the patient, the patient's family, and the medical staff for discharge from the hospital of a patient supported with a left ventricular assist device. Extensive technical and clinical training of the primary caregiver and the patient is required to prepare for discharge from the hospital. Data are rapidly accumulating that show that left ventricular assist devices are safe and efficacious for outpatient use. Similar success is expected in clinical trials of permanent left ventricular assist devices, suggesting that many more patients will benefit from this technology in the future.

scholarly journals Analysis of Operating Modes for Left Ventricle Assist Devices via Integrated Models of Blood Circulation

Mathematics ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 1331 ◽  
Author(s):  
Sergey Simakov ◽  
Alexander Timofeev ◽  
Timur Gamilov ◽  
Philip Kopylov ◽  
Dmitry Telyshev ◽  
...  
Keyword(s):  
Left Ventricular ◽  
Operating Conditions ◽  
Ventricular Assist Devices ◽  
Circulatory Support ◽  
Left Ventricular Assist Devices ◽  
Ventricular Assist ◽  
Lumped Model ◽  
Assist Devices ◽  
Operating Modes ◽  
Mock Circulation

Left ventricular assist devices provide circulatory support to patients with end-stage heart failure. The standard operating conditions of the pump imply limitations on the rotation speed of the rotor. In this work we validate a model for three pumps (Sputnik 1, Sputnik 2, Sputnik D) using a mock circulation facility and known data for the pump HeartMate II. We combine this model with a 1D model of haemodynamics in the aorta and a lumped model of the left heart with valves dynamics. The model without pump is validated with known data in normal conditions. Simulations of left ventricular dilated cardiomyopathy show that none of the pumps are capable of reproducing the normal stroke volume in their operating ranges while complying with all criteria of physiologically feasible operation. We also observe that the paediatric pump Sputnik D can operate in the conditions of adult circulation with the same efficiency as the adult LVADs.

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