PULsecath mechanicaL Support Evaluation (PULSE)

PULsecath mechanicaL Support Evaluation (PULSE) - Trial

The objective of this study is to determine ventricular loading conditions during and after PulseCath® iVAC2L support, and assess its impact on specific load dependent humoral factors and cardiac enzymes. These specific patterns are so far unknown and will be evaluated invasively.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Heart Failure; Cardiogenic Shock
• Intervention / Treatment: Device: iVAC2L pVAD

Detailed Description

This is a mechanistic exploratory study. The objective is to determine the effects of the new PFLVAD PulseCath® iVAC2L on ventricular loading using left ventricular pressure-volume loops, in association with systemic and pulmonary hemodynamic parameters obtained from right and left catheterization. Additionally, assessments of specific load and flow-dependent humoral factors and cardiac enzymes will be made during and after the use of mechanical circulatory support. These specific patterns are so far unknown. Knowledge of optimal patterns may help in determining the ideal circulatory device platform.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Toulouse, France
    • Clinic Pasteur
• Netherlands
  • South Holland
    • Rotterdam, South Holland, Netherlands, 3015CE
      • Erasmus Medical Center
• United Kingdom
  • London, United Kingdom
    • Kings College London, St. Thomas' Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient is ≥ 18 years;
2. Informed Consent must be signed by the patient, prior to HR-PCI;
3. The multidisciplinary heart team has reached consensus for high-risk PCI. Patients may present with left ventricular systolic dysfunction (ejection fraction ≤40%);
4. Anatomical criteria: Intervention to an unprotected left main coronary artery, left main equivalent or single remaining vessel; multivessel disease; intervention in a distal left main bifurcation.

Exclusion Criteria:

1. No written informed consent;
2. Left ventricular thrombus;
3. Interventricular septal defect;
4. Significant peripheral arterial disease or arterial lumen size < 6mm at the level of the common femoral artery;
5. Significant aortic valve disease (more than mild aortic stenosis/regurgitation);
6. Cardiogenic shock;
7. Previous stroke within the last 3 months;
8. Major bleeding event within last 3 months;
9. Chronic kidney disease with a GFR < 25 mL/min;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: iVAC2L pVAD; Clinically indicated ventricular support for high-risk PCI with Pulsecath iVAC2L.

Device: iVAC2L pVAD; To determine the effects of the new PFLVAD PulseCath® iVAC2L on ventricular loading using left ventricular pressure-volume loops, in association with systemic and pulmonary hemodynamic parameters obtained from right and left catheterization. Additionally, assessments of specific load and flow-dependent humoral factors, and cardiac enzymes, will be made during and after the use of mechanical circulatory support.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pressure-volume Area (PVA)	Numerical continuous variable representing the change in Myocardial Oxygen Consumption (MVO2) following ventricular unloading. The PULSE trial will measure in real-time how discrepant this measurement can be when resulting from continuous or pulsatile flow ventricular assist devices. This is not a time-to-event outcome: the change in PVA will be obtained from real-time data collected during the intervention. The time frame will be the time of the Intervention. Unit: mmHg.mL	From the beginning of the PCI until its conclusion. This period can be variable and is estimated in 40 to 270 minutes.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cardiac Output	Numerical continuous variable representing the change in Cardiac Output (CO), following ventricular unloading. The PULSE trial will measure in real-time how discrepant this measurement can be when resulting from continuous or pulsatile flow ventricular assist devices. This is not a time-to-event outcome: the change in CO will be obtained from real-time data collected during the intervention. The time frame will be the time of the Intervention. Unit: L/min	From the beginning of the PCI until its conclusion. This period can be variable and is estimated in 40 to 270 minutes.
Change on the Mean Pulmonary Capillary Wedge Pressure	Numerical continuous variable representing the change in Mean Pulmonary Capillary Wedge Pressure (mPCWP), following ventricular unloading. The PULSE trial will measure in real-time how discrepant this measurement can be when resulting from continuous or pulsatile flow ventricular assist devices. This is not a time-to-event outcome: the change in mPCWP will be obtained from real-time data collected during the intervention. The time frame will be the time of the Intervention. Unit: mmHg.	From the beginning of the PCI until its conclusion. This period can be variable and is estimated in 40 to 270 minutes.
Change in the PCWP v-wave	Numerical continuous variable representing the change in PCWP v-wave (vPCWP), following ventricular unloading. The PULSE trial will measure in real-time how discrepant this measurement can be when resulting from continuous or pulsatile flow ventricular assist devices. This is not a time-to-event outcome: the change in vPCWP will be obtained from real-time data collected during the intervention. The time frame will be the time of the Intervention. Unit: mmHg.	From the beginning of the PCI until its conclusion. This period can be variable and is estimated in 40 to 270 minutes.
Change in Mean Pulmonary Artery Pressure	Numerical continuous variable representing the change in Mean Pulmonary Artery Pressure (mPAP), following ventricular unloading. The PULSE trial will measure in real-time how discrepant this measurement can be when resulting from continuous or pulsatile flow ventricular assist devices. This is not a time-to-event outcome: the change in mPAP will be obtained from real-time data collected during the intervention. The time frame will be the time of the Intervention. Unit: mmHg.	From the beginning of the PCI until its conclusion. This period can be variable and is estimated in 40 to 270 minutes.
Change in Pulmonary Artery Oxygen Saturation	Numerical continuous variable representing the change in Pulmonary Artery Oxygen Saturation, also known as Mixed Oxygen Saturation (SVO2), following ventricular unloading. The PULSE trial will measure in real-time how discrepant this measurement can be when resulting from continuous or pulsatile flow ventricular assist devices. This is not a time-to-event outcome: the change in SVO2 will be obtained from real-time data collected during the intervention. The time frame will be the time of the Intervention. Unit: %	From the beginning of the PCI until its conclusion. This period can be variable and is estimated in 40 to 270 minutes.
Change in Right Atrial Pressure	Numerical continuous variable representing the change in Right Atrial Pressure (RAP), following ventricular unloading. The PULSE trial will measure in real-time how discrepant this measurement can be when resulting from continuous or pulsatile flow ventricular assist devices. This is not a time-to-event outcome: the change in RAP will be obtained from real-time data collected during the intervention. The time frame will be the time of the Intervention. Unit: mmHg.	From the beginning of the PCI until its conclusion. This period can be variable and is estimated in 40 to 270 minutes.
Change in Preload-recruitable Stroke Work	Numerical continuous variable representing the change in Preload-recruitable Stroke Work (PRSW), following ventricular unloading. The PULSE trial will measure in real-time how discrepant this measurement can be when resulting from continuous or pulsatile flow ventricular assist devices. This is not a time-to-event outcome: the change in PRSW will be obtained from real-time data collected during the intervention. The time frame will be the time of the Intervention. Unit: mmHg	From the beginning of the PCI until its conclusion. This period can be variable and is estimated in 40 to 270 minutes.
Change in the Starling Contractile Index	Numerical continuous variable representing the change in the Starling Contractile Index (SCI), following ventricular unloading. The PULSE trial will measure in real-time how discrepant this measurement can be when resulting from continuous or pulsatile flow ventricular assist devices. This is not a time-to-event outcome: the change in SCI will be obtained from real-time data collected during the intervention. The time frame will be the time of the Intervention. Unit: mmHg/ml⋅s	From the beginning of the PCI until its conclusion. This period can be variable and is estimated in 40 to 270 minutes.
Change in End-systolic Wall Stress	Numerical continuous variable representing the change in the End-systolic Wall Stress (WSes), following ventricular unloading. The PULSE trial will measure in real-time how discrepant this measurement can be when resulting from continuous or pulsatile flow ventricular assist devices. This is not a time-to-event outcome: the change in WSes will be obtained from real-time data collected during the intervention. The time frame will be the time of the Intervention. Unit: mmHg.	From the beginning of the PCI until its conclusion. This period can be variable and is estimated in 40 to 270 minutes.
Change in the first derivative of pressure over time	Numerical continuous variable representing the change in the first derivative of pressure over time (+dP/dtmax), following ventricular unloading. The PULSE trial will measure in real-time how discrepant this measurement can be when resulting from continuous or pulsatile flow ventricular assist devices. This is not a time-to-event outcome: the change in +dP/dtmax will be obtained from real-time data collected during the intervention. The time frame will be the time of the Intervention. Unit: mmHg/s	From the beginning of the PCI until its conclusion. This period can be variable and is estimated in 40 to 270 minutes.
Change in Systemic Vascular Resistance	Numerical continuous variable representing the change in the Systemic Vascular Resistance (SVR), following ventricular unloading. The PULSE trial will measure in real-time how discrepant this measurement can be when resulting from continuous or pulsatile flow ventricular assist devices. This is not a time-to-event outcome: the change in SVR will be obtained from real-time data collected during the intervention. The time frame will be the time of the Intervention. Unit: (dyn∙s)/(cm^(-5))	From the beginning of the PCI until its conclusion. This period can be variable and is estimated in 40 to 270 minutes.
Change in Pulmonary Vascular Resistance	Numerical continuous variable representing the change in the Pulmonary Vascular Resistance (PVR), following ventricular unloading. The PULSE trial will measure in real-time how discrepant this measurement can be when resulting from continuous or pulsatile flow ventricular assist devices. This is not a time-to-event outcome: the change in PVR will be obtained from real-time data collected during the intervention. The time frame will be the time of the Intervention. Unit: (dyn∙s)/(cm^(-5))	From the beginning of the PCI until its conclusion. This period can be variable and is estimated in 40 to 270 minutes.
Change in Cardiac Power Output	Numerical continuous variable representing the change in the Cardiac Power Output (CPO), following ventricular unloading. The PULSE trial will measure in real-time how discrepant this measurement can be when resulting from continuous or pulsatile flow ventricular assist devices. This is not a time-to-event outcome: the change in CPO will be obtained from real-time data collected during the intervention. The time frame will be the time of the Intervention. Unit: Watts	From the beginning of the PCI until its conclusion. This period can be variable and is estimated in 40 to 270 minutes.
Change in Hematocrit	Numerical continuous variable. Change in Hematocrit (Ht) as an indicative of bleeding or hemolysis. Unit: %	From baseline (beginning of PCI) to immediately after the procedure and 12 hours after PCI.
Change in Hemoglobin	Numerical continuous variable. Change in Hemoglobin (Hb) as an indicative of bleeding or hemolysis. Unit: mmol/L	From baseline (beginning of PCI) to immediately after the procedure and 12 hours after PCI.
Change in Platelet Count	Numerical continuous variable. Change in Platelet Count as an indicative of bleeding events. Unit: 10^9/L	From baseline (beginning of PCI) to immediately after the procedure and 12 hours after PCI.
Change in haptoglobin	Numerical continuous variable. Change in haptoglobin as an indicative of hemolytic events. Unit: g/L	From baseline (beginning of PCI) to immediately after the procedure and 12 hours after PCI.
Change in total and conjugated bilirubin	Numerical continuous variable. Change in total and conjugated bilirubin as an indicative of hemolytic events. Unit: umol/L	From baseline (beginning of PCI) to immediately after the procedure and 12 hours after PCI.
Change in lactate dehydrogenase	Numerical continuous variable. Change in lactate dehydrogenase as an indicative of hemolytic events. Unit: U/L.	From baseline (beginning of PCI) to immediately after the procedure and 12 hours after PCI.
Change in hs-troponin	Numerical continuous variable. Change in hs-troponin as an indicative of myocardial necrosis. Unit: ng/L	From baseline (beginning of PCI) to immediately after the procedure and 12 hours after PCI.
Change in creatinephosphokinase	Numerical continuous variable. Change in creatinephosphokinase (CK) as an indicative of myocardial necrosis. Unit: U/L	From baseline (beginning of PCI) to immediately after the procedure and 12 hours after PCI.
Change in creatinophosphokinase MB mass assay	Numerical continuous variable. Change in creatinophosphokinase MB mass assay (CKMB-mass) as an indicative of myocardial necrosis. Unit: ug/L	From baseline (beginning of PCI) to immediately after the procedure and 12 hours after PCI.
Change in N-terminal pro b-type natriuretic peptide	Numerical continuous variable. Change in N-terminal pro b-type natriuretic peptide (NT-proBNP) as an indicative of chamber overload. Unit: pmol/L	From baseline (beginning of PCI) to immediately after the procedure and 12 hours after PCI.
Change in serum lactate	Numerical continuous variable. Change in serum lactate as an indicative of hypoperfusion states. Unit: mmol/L.	From baseline (beginning of PCI) to immediately after the procedure and 12 hours after PCI.
Change in serum creatinine	Numerical continuous variable. Change in serum creatinine as an indicative of acute kidney injury. Unit: umol/L	From baseline (beginning of PCI) to immediately after the procedure and 12 hours after PCI.
All-cause mortality	Constitutes one of the components of the MACCE composite endpoint: all-cause mortality, acute myocardial infarction, stroke or transient ischemic attack (TIA), and repeat revascularization (PCI or CABG). Time-to-event variable, measured in days.	30 days follow up
Acute myocardial infarction	According to the "Fourth Universal Definition of Acute Myocardial Infarction". Constitutes one of the components of the MACCE composite endpoint: all-cause mortality, acute myocardial infarction, stroke or transient ischemic attack (TIA), and repeat revascularization (PCI or CABG). Time-to-event variable, measured in days.	30 days follow up
Stroke or transient ischemic attack	As per VARC 2 definitions 2013 J Thorac Cardiovasc Surg 2013;145:6-23. Constitutes one of the components of the MACCE composite endpoint: all-cause mortality, acute myocardial infarction, stroke or transient ischemic attack (TIA), and repeat revascularization (PCI or CABG). Time-to-event variable, measured in days.	30 days follow up
Repeat revascularization	As per ARC definition - Circulation. 2007;115:2344-2351. Constitutes one of the components of the MACCE composite endpoint: all-cause mortality, acute myocardial infarction, stroke or transient ischemic attack (TIA), and repeat revascularization (PCI or CABG). Time-to-event variable, measured in days.	30 days follow up
Major Bleeding	Major bleeding (BARC 3 to 5), according to the BARC Bleeding Classification (BARC definitions 2011. Circulation. 2011; 123(23): 2736-47. Time-to-event variable, measured in days.	30 days follow up
Major vascular complications	Major vascular complications (e.g.: arteriovenous fistula, limb ischemia), as per VARC-2 definitions (VARC 2 definitions 2013, J Thorac Cardiovasc Surg 2013;145:6-23) . Time-to-event variable, measured in days.	30 days follow up
Acute renal dysfunction	Acute renal dysfunction (AKIN 1 or above), using the AKIN Classification as described in the VARC-2 definitions (VARC 2 definitions 2013 J Thorac Cardiovasc Surg 2013;145:6-23).	30 days follow up
Increase in Aortic regurgitation	Increase in aortic regurgitation by more than one grade (TTE). Binary outcome obtained at the second echocardiogram, performed at discharge.	30 days follow up
Severe hypotension	Severe hypotension (MAP < 60mmHg for more than 10 minutes despite fluid resuscitation or use of vasoactive amines to maintain MAP ≥ 60 mm Hg), or shock, defined based on the definition from the SHOCK trial (1) SBP ≤ 90mmHg for at least 30 minutes, (2) Need for vasopressors to maintain SBP > 90mmHg; (3) evidence of end-organ hypoperfusion; (4) Evidence of elevated filling pressures. A similar concept has been applied in the BCIS-1 study to measure procedural instability (JAMA. 2010;304(8):867-874).	First 48 hours after the start of PCI.
Ventricular arrhythmias	VT requiring cardioversion and / or need for CPR. Binary outcome, VF at anytime during follow up. Time-to-event analysis, measured in days.	30 days follow up
Angiographic failure	Angiographic failure/ procedural failure, as defined in the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention Circulation. 2011;124:e574-e651): post PCI TIMI flow < III, residual stenosis (>50% post-balloon or > 10% post stenting), or presence of thrombus, side branch loss or flow limiting dissection. It is a binary outcome (yes/no answer). No time-to-event analysis will be applied.	Assessed at the end of the PCI. This time point (end of PCI) can be variable and is estimated in 40 to 270 minutes after the beginning of the procedure.
Time of hospitalization	Time to hospital discharge (in days).	30 days follow up
Change in Left ventricular ejection fraction	Numerical continuous variable. Change in LVEF measured by trans-thoracic echocardiography at baseline and discharge. Not a time-to-event variable. Unit: %	From baseline (beginning of PCI) to the moment of discharge, assessed up to 30 days.

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Investigators: Principal Investigator: Nicolas v. Mieghem, MD, PhD, Erasmus Medical Center

Publications and helpful links

General Publications

• Bastos MB, McConkey H, Malkin O, den Uil C, Daemen J, Patterson T, Wolff Q, Kardys I, Schreuder J, Lenzen M, Zijlstra F, Redwood S, Van Mieghem NM. Effect of Next Generation Pulsatile Mechanical Circulatory Support on Cardiac Mechanics: The PULSE Trial. Cardiovasc Revasc Med. 2022 Sep;42:133-142. doi: 10.1016/j.carrev.2022.03.013. Epub 2022 Mar 14.
• Dedic A, Bastos MB, Van Mieghem NM. Pressure-Volume Loop Analysis in Percutaneous Coronary Intervention-Induced Shock. JACC Case Rep. 2020 Sep 23;2(12):1882-1883. doi: 10.1016/j.jaccas.2020.07.026. eCollection 2020 Oct.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2016
• Primary Completion (ACTUAL): December 31, 2019
• Study Completion (ACTUAL): December 31, 2019

Study Registration Dates

• First Submitted: June 8, 2017
• First Submitted That Met QC Criteria: June 23, 2017
• First Posted (ACTUAL): June 28, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 29, 2021
• Last Update Submitted That Met QC Criteria: March 24, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: pressure-volume loops; cardiac mechanics; high-risk PCI
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Shock; Coronary Disease; Myocardial Infarction; Infarction; Coronary Artery Disease; Shock, Cardiogenic
• Other Study ID Numbers: Pulse version 2.9

Plan for Individual participant data (IPD)

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