Central and Cerebral Circulation in Early Stages After LVAD Implantation (ECOH3)

Evaluation of Central and Cerebral Circulation in Early Stages After Implantation of Left Ventricular Assist Device (LVAD)

This trial will evaluate patients with a mechanical Left Ventricular Assist Device (LVAD) in early stages after surgical implantation. Within the first 2 days of postoperative ICU care, 20 patients will firstly be exposed to 4 different LVAD pump flow settings with a stable blood pressure. A second intervention will be mean arterial blood pressure (MAP) adjustments to 4 preset levels (60-70-80 and 90 mmHg) with a constant preset LVAD flow. The two manipulations; 1) Constant MAP with variation of LVAD flow and 2) Constant LVAD flow with variation of MAP, will be monitored by Central hemodynamic parameters, echocardiographic parameters and cerebral blood flow velocity (CBFV) parameters. The purpose of the trial is to find the optimal combination of LVAD pump flow, mean arterial pressure and right heart ventricle function for each patient. And at the same time describe the effect of flow and pressure variations on CBFV.

Study Overview

• Status: Unknown
• Conditions: Heart Failure, Right-Sided; Heart Failure, Left-Sided
• Intervention / Treatment: Device: LVAD flow velocity setting-Rounds per Minute(RPM) on HeartMate III®; Drug: MAP intervention using Noradrenalin

Detailed Description

Patients with severe left ventricular heart failure and estimated short expected survival time despite optimal medical therapy can be treated with a left ventricular mechanical heart pump - described as a Left Ventricular Assist Device (LVAD). The LVAD can be used as a bridge for patient survival prior to heart transplantation, or as a destination therapy for terminal heart failure. The LVAD delivers a non-pulsatile blood flow into the patients aorta, supporting and/or taking over the left ventricular function. However the right heart ventricle (RV) is not supported by the LVAD. RV failure is a major threat to the patient, in particular during the early postoperative period. Postoperative RV failure after LVAD implantation is medically treated, but in severe cases a mechanical temporary right ventricular assist (RVAD) may be needed. Patients in need of postoperative RVAD after an LVAD implant have a significantly increased mortality. Thus it is of vital importance to balance the LVAD pump flow against the native RV function in order to avoid the need for an RVAD. If the LVAD flow rate is set too low the RV will be exposed to a high afterload and risk failure. If, on the other hand, the LVAD flow is set too high it can potentially completely empty the left ventricle with secondary geometrical distortion of the heart chambers and an increased venous return to the RV. This too increases the risk for RV failure. To find the optimal LVAD flow rate it is custom to do an extensive evaluation of central hemodynamic parameters (Cardiac Output(CO), Pulmonary Capillary Wedge Pressure (PCWP), Pulmonary Arterial Pressure (PAP), Central Venous Pressure (CVP)) and cardiac echocardiographic evaluation of RV function at different LVAD pump flow rates and MAP. The instant balance between RV filling pressure-CVP, and LV filling pressure-PCWP, is on the other hand easy to obtain. However it is not known if these measurements can be used to obtain an optimal LVAD flow rate. Furthermore all mechanically driven circulatory support devices, including LVAD, will expose the peripheral arterial circulation to a non-pulsatile blood flow.There are few previous reports on how an LVAD affects the cerebral blood flow autoregulation and microembolic load at different settings and MAP. This investigation aims to describe these cerebral effect af an LVAD using a continous Transcranial Doppler (TCD) detection of cerebral arteries.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Gothenburg, Sweden, 41345
    • Recruiting
    • Sahlgrenska University Hospital. Department of Cardiothoracic Anaesthesia & Intensive Care
    • Contact: Bjorn Reinsfelt, PhD; Phone Number: 0046313428183; Email: bjorn.reinsfelt@gu.se
    • Contact: Bengt Redfors, PhD; Phone Number: 0046313427445; Email: bengt.redfors@vgregion.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients receiving LVAD of the type HeartMate3® at Sahlgrenska University hospital

Exclusion Criteria:

• Perioperative need for an RVAD first 3 days postoperatively after an LVAD implantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Observation of hemodynamic parameters; LVAD flow velocity setting-Rounds Per Minute(RPM) intervention: Change of LVAD RPM while observing Central hemodynamic, echocardiographic and CBFV effects. MAP intervention: Stepwise Change of MAP from 60-70-80 to 90 mmHg with a fixed set of LVAD RPM. After a 5 minute steady state for each level of MAP, the observations of central hemodynamics, echocardiographic measures and CBFV measurements will be repeated.

Device: LVAD flow velocity setting-Rounds per Minute(RPM) on HeartMate III®; Increase in LVAD RPM setting induces an actual increase in LVAD outflow to the patient.This gives the patient an increased systemic Cardiac Output(CO); Other Names: RPM setting; Drug: MAP intervention using Noradrenalin; At a fixed RPM rate for the LVAD the Mean Arterial Pressure (MAP) is increased to preset levels of 60-70-80-90 mmHG using Noradrenalin; Other Names: MAP setting

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes PCWP/CVP ratio	The change in PCWP (mmHg)/CVP (mmHg) ratio at different levels of LVAD flow as a marker for the optimal balance between LVAD flow and RV function	Change from baseline at different settings of LVAD RPM within 10 minutes for each level

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CO	Cardiac Output in litres/minute	Change from baseline at different settings of LVAD RPM within 10 minutes for each level
LVAD Velocity Time Integral	LVAD Velocity Time Integral in centimeters(cm)	Change from baseline at different settings of LVAD RPM within 10 minutes for each level
Right Ventricle Outflow Tract (RVOT) Velocity Time Integral (VTI)	RVOT Velocity Time Integral in centimeters(cm)	Change from baseline at different settings of LVAD RPM within 10 minutes for each level
CBFV	CBFV in cm/second	Change from baseline at different settings of LVAD RPM within 10 minutes for each level

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes PCWP/CVP ratio at different MAP	The change in PCWP (mmHg)/CVP (mmHg) ratio at different levels of MAP as a marker for the optimal balance between LVAD flow and RV function	Change from baseline at different settings of MAP with a fixed LVAD RPM setting within 10 minutes for each level
LVAD VTI at different MAP	LVAD Velocity Time Integral in centimeters(cm)	Change from baseline at different settings of MAP with a fixed LVAD RPM setting within 10 minutes for each level
CO at different MAP	Cardiac Output in litres/minute	Change from baseline at different settings of MAP with a fixed LVAD RPM setting within 10 minutes for each level
RVOT VTI at different MAP	RVOT Velocity Time Integral in centimeters(cm)	Change from baseline at different settings of MAP with a fixed LVAD RPM setting within 10 minutes for each level
CBFV at different MAP	CBFV in cm/second	Change from baseline at different settings of MAP with a fixed LVAD RPM setting within 10 minutes for each level

Collaborators and Investigators

• Sponsor: Sahlgrenska University Hospital, Sweden
• Investigators: Study Director: Sven Erik Ricksten, MD.PhD, Sahlgrenska University Hospital, Sweden

Publications and helpful links

General Publications

• Uriel N, Adatya S, Maly J, Kruse E, Rodgers D, Heatley G, Herman A, Sood P, Berliner D, Bauersachs J, Haverich A, Zelizko M, Schmitto JD, Netuka I. Clinical hemodynamic evaluation of patients implanted with a fully magnetically levitated left ventricular assist device (HeartMate 3). J Heart Lung Transplant. 2017 Jan;36(1):28-35. doi: 10.1016/j.healun.2016.07.008. Epub 2016 Jul 17.
• Uriel N, Sayer G, Addetia K, Fedson S, Kim GH, Rodgers D, Kruse E, Collins K, Adatya S, Sarswat N, Jorde UP, Juricek C, Ota T, Jeevanandam V, Burkhoff D, Lang RM. Hemodynamic Ramp Tests in Patients With Left Ventricular Assist Devices. JACC Heart Fail. 2016 Mar;4(3):208-17. doi: 10.1016/j.jchf.2015.10.001. Epub 2015 Dec 30.
• Ono M, Joshi B, Brady K, Easley RB, Kibler K, Conte J, Shah A, Russell SD, Hogue CW. Cerebral blood flow autoregulation is preserved after continuous-flow left ventricular assist device implantation. J Cardiothorac Vasc Anesth. 2012 Dec;26(6):1022-8. doi: 10.1053/j.jvca.2012.07.014.

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2017
• Primary Completion (Anticipated): March 1, 2020
• Study Completion (Anticipated): March 1, 2020

Study Registration Dates

• First Submitted: February 28, 2017
• First Submitted That Met QC Criteria: March 21, 2017
• First Posted (Actual): March 22, 2017

Study Record Updates

• Last Update Posted (Actual): March 22, 2017
• Last Update Submitted That Met QC Criteria: March 21, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Hemodynamic monitoring; Left Ventricular Assist Device
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Norepinephrine
• Other Study ID Numbers: ECOH 3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No