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AssocIation of PULSatility and Occurrence of Complications Related to Mechanically Assisted Circulatory Support

Not Applicable
Recruiting
Conditions
End-stage Heart Failure
Interventions
Other: Blood sampling
Registration Number
NCT04951999
Lead Sponsor
Assistance Publique - Hôpitaux de Paris
Brief Summary

The primary objective of this study is to determine whether preserved pulsatility for patients supported by CF-LVAD (continuous flow Left Ventricular Assist Device) is associated with less acquired deficiency of the Von Willebrand factor, a blood glycoprotein involved in hemostasis.

Detailed Description

Implantation of LVADs (Left Ventricular Assist Device) is a medium to long-term therapeutic option for patients with end-stage heart failure and isolated left ventricular dysfunction. Nevertheless, LVADs use remain limited by the frequency of their adverse effects, most of which being unpredictable. In the literature, loss of pulsatility seems to be associated with CF-LVADs complications, including bleeding. Accordingly, the primary objective of this study is to determine whether patient's preserved pulsatility is associated with less acquired deficiency of the Von Willebrand factor (VWF), a blood glycoprotein involved in hemostasis. This deficiency, characterized by a decrease or absence of VWF High Molecular Weight Multimers (HMWMs), is present to varying degrees in almost all patients with LVADs and is a major risk factor for bleeding complications in these patients. Pulsatility is estimated by the patient's blood pressure differential, measured 1) at discharge from the operating room (=transfer to care), 2) at discharge from care (=transfer to his or her room), 3) at discharge from the hospital (=transfer to rehabilitation), and then at each follow-up visit up to 6 months post-implantation. The primary endpoint is to determine whether a preserved pulsatility is associated with less acquired deficiency of the Von Willebrand factor ratio of High Molecular Weight Multimers (HMWMs).

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
70
Inclusion Criteria
  1. Patients over 18 years of age
  2. Patients for whom a decision to implant a left-sided monoventricular assist has been retained after discussion in the RCP of heart failure, transplantation and circulatory assistance (whatever the therapeutic strategy envisaged: waiting for transplantation, recovery or destination therapy).
  3. Patients affiliated to a social security system (beneficiaries or beneficiaries entitled to benefits, excluding AME)
  4. Signature of an informed consent by the patient or by the trusted person, or a close relative, if the patient is not able to do so
Exclusion Criteria
  1. Heart transplant patients
  2. Patients who already had LVAD
  3. Chronic renal failure patients on dialysis
  4. Patients refusing to give informed consent
  5. Patients deprived of liberty or under legal protection (guardianship, curators)
  6. Pregnant or breastfeeding women
  7. Ongoing participation in another intervention research protocol except LEVOECMO project (NCT04728932) and ANCHOR project (NCT04184635)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Blood samplingBlood sampling-
Primary Outcome Measures
NameTimeMethod
Von Willebrand factor high molecular weight multimers (HMWM) ratio30 days after LVAD IMPLANTATION

Comparison of Von Willebrand factor high molecular weight multimers (HMWM) ratio at LVAD pre-implantation and at day 30.

Measure of an correlation between preserved pulsatility and the HMWM ratio evolution during the first month after implantation.

Secondary Outcome Measures
NameTimeMethod
Vascular endothelium dysfunction6 months

Vascular endothelial dysfunction defined by a significant increase in circulating levels of syndecan, thrombomodulin, TFPI and PAI-1 between pre- and post-implantation

Prolonged systemic inflammatory reaction syndrome6 months

Monthly measures of following circulating inflammatory factors : TNFα et β, NF kappab, TGF α /β1/β2,IFNγ et β, IL-1β, IL-1RA, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL12-P70, IL-17, IL17A et F,CX3CL1 (fractalkine),MCP-1(CCL2), MIP-1 (CCL3), MIP-1β(CCL4), MIP-3-beta (CCL19), 6Ckine(CCL21), MCD (CCL22) Myostatin, calveolin-1.

Aortic valve fusion6 months

Monthly echographic evaluation

Aortic valve insufficiency6 months

Monthly echographic evaluation

Severe postoperative gastrointestinal bleeding6 months

Track record of patients undergoing gastrointestinal bleeding, identified by a decreased hemoglobin level associated with chronic iron deficiency anemia of unexplained cause and melena or bleeding demonstrated by exploration of the gastrointestinal tract by esophageal endoscopy, colonoscopy, or endoscopic videoscopy and resulting in any of the following:

* Death

* Re-operation

* Hospitalization

* An erythrocyte transfusion defined as:

* Within 7 days of implantation :

* Patients weighing 50 kg or more: ≥ 4U of packed red blood cells in a 24-hour period.

* Patients weighing less than 50 kg: ≥ 20 mL/kg of packed red blood cells over a 24-hour period

* After 7 days post-implantation : any transfusion of packed red blood cells.

Post-operative right ventricular failure6 months

Track record of patients undergoing right ventricular failure, identified by:

* Elevation of central venous pressure (CVP) \>16 mmHg by direct or echocardiographic measurement (inferior vena cava diameter \>20 mm and respiratory variations \<50%) for more than 48 hours

* and at least one of the following signs of hemodynamic failure persisting for more than 48 hours:

* Increased inotropic score

* Hyperlactatemia \>3 mmol/l

* Hepatic cytolysis: increase in AST and/or ALT by a factor of 3 or more after implantation

* Degradation of renal function (AKIN grade 2: creatinine elevation \> 50% compared with before explantation and diuresis \< 0.5 ml/kg/24h for 12 hours)

* Implantation of right temporary circulatory support (ECMO)

Post-operative transient or permanent ischemic attack6 months

Track record of patients undergoing ischemic attack (between 24 hours and 6 months post-operative) as assessed per INTERMACS definition

Platelet dysfunction6 months

Platelet dysfunction defined by a significant increase in circulating levels of p-selectin and glycocalicin between pre- and post-implantation

Evolution of immune responses6 months

Monthly phenotyping of monocytes and T cells

Evaluation of cardiac recovery6 months

Monthly exercise stress test evaluation (starting 2 months post-operative)

Trial Locations

Locations (1)

Groupement Hospitalier pitié Salpêtrière

🇫🇷

Paris, France

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