PULsecath mechanicaL Support Evaluation

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
PULsecath mechanicaL Support Evaluation (PULSE) - Trial

Conditions
-----------------
Coronary Artery Disease, Heart Failure, Cardiogenic Shock

Intervention / Treatment
-----------------
* Device: iVAC2L pVAD


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient is ≥ 18 years; Informed Consent must be signed by the patient, prior to HR-PCI; The multidisciplinary heart team has reached consensus for high-risk PCI. Patients may present with left ventricular systolic dysfunction (ejection fraction ≤40%); 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: No written informed consent; Left ventricular thrombus; Interventricular septal defect; Significant peripheral arterial disease or arterial lumen size < 6mm at the level of the common femoral artery; Significant aortic valve disease (more than mild aortic stenosis/regurgitation); Cardiogenic shock; Previous stroke within the last 3 months; Major bleeding event within last 3 months; Chronic kidney disease with a GFR < 25 mL/min;

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: iVAC2L pVAD<br>Clinically indicated ventricular support for high-risk PCI with Pulsecath iVAC2L. | Device: iVAC2L pVAD<br>* 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.<br>|

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. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pressure-volume loops, cardiac mechanics, high-risk PCI