Cardiac Power Output in Cardiogenic Shock Patients

Myocardial Reserve in Advanced Heart Failure Patients

The main purpose of this study is to determine whether differences in myocardial reserve predict clinical outcomes for heart failure patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure; Cardiogenic Shock
• Intervention / Treatment: Drug: 1:1 Randomization to receive milrinone or dobutamine; Drug: 1:1 Randomization to receive dobutamine or milrinone

Detailed Description

This study is designed as a prospective, observational, crossover study to assess the feasibility of using differences in invasive hemodynamics of cardiac function, representing myocardial reserve, to predict clinical outcomes for heart failure patients. Patients with heart failure referred for right heart catheterization (RHC) by the advanced heart failure team as part of 1) evaluation for advanced heart failure therapies, including left ventricular assist device (LVAD), orthotopic heart transplant (OHT), temporary or long-term inotrope therapy, or counter-pulsation (temporary intra-aortic balloon pump (IABP) or long-term with NuPulse device), 2) for accurate assessment of invasive hemodynamics due to worsening clinical status, 3) assessment of myocardial recovery for consideration of LVAD or NuPulse decommissioning or removal or mechanical circulatory support removal, or 4) accurate assessment of cardiac function in patients with reduced LVEF prior to valve replacement for aortic insufficiency (AI) or mitral regurgitation (MR).

• Study Type: Interventional
• Enrollment (Estimated): 5
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: David Onsager, MD; Phone Number: 7737021000; Email: donsager1@uchgicagomedicine.org
• Study Contact Backup: Name: Daniel Rodgers; Email: drodgers3@uchgicagomedicine.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. LVEF ≤ 35%

2. Referred for RHC for:

   1. Evaluation for advanced heart failure therapies, including LVAD, OHT, temporary or long-term inotrope therapy, or counter-pulsation (temporary or long-term with NuPulse device OR
   2. Accurate assessment of invasive hemodynamics due to worsening clinical status, OR
   3. Assessment of myocardial recovery for consideration of LVAD or counter-pulsation (temporary IABP or long-term with NuPulse device) decommissioning or removal OR
   4. Assessment of cardiac function and valvular abnormalities prior to planned valvular surgery for MR or AI
3. Estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m2
4. Age ≥ 18 years-old
5. Intent for admission based on RHC data

Exclusion Criteria:

1. eGFR < 30 ml/min/1.73 m2
2. Severe, non-revascularized coronary artery disease
3. Concurrent acute coronary syndrome
4. Age < 18 years-old
5. History of significant ventricular arrhythmia without an ICD

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1:1 Randomization to Milrinone or Dobutamine; Patients will be randomized 1:1 to either Milrinone or Dobutamine. Milrinone will be given as a bolus at a dose of 5 mcg/kg/min over 15 minutes, for a total of 75 mcg/kg. For patients randomized to the arm for maintenance milrinone, they will be maintained at 0.125-0.375 mcg/kg/min. Patients may be randomized to dobutamine will be infused at 10-40 mcg/kg/min during the infusion phase and for those randomized to dobutamine for maintenance, they will be kept at 5-10 mcg/kg/min.	Drug: 1:1 Randomization to receive milrinone or dobutamine; Randomized to receive either inotropic agent: milrinone or dobutamine; Other Names: Milrinone
Active Comparator: 1:1 Randomization to Dobutamine or Milrinone; Patients will be randomized 1:1 to either Milrinone or Dobutamine. Dobutamine will be infused at 10-40 mcg/kg/min during the infusion phase, and for those randomized to dobutamine for maintenance, they will be kept at 5-10 mcg/kg/min. Milrinone will be given as a bolus at a dose of 5 mcg/kg/min over 15 minutes, for a total of 75 mcg/kg. For patients randomized to the arm for maintenance milrinone, they will be maintained at 0.125-0.375 mcg/kg/min.	Drug: 1:1 Randomization to receive dobutamine or milrinone; Randomized to receive either inotropic agent: milrinone or dobutamine; Other Names: Dobutamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in invasive hemodynamics using a pulmonary artery (PA) catheter measuring mmHg	Changes invasive hemodynamics representing myocardial reserve will be measured in 5 patients using a pulmonary artery (PA) catheter: Pulmonary capillary wedge pressure (PCWP mmHg); Right Atrial pressure (RA mmHg); Pulmonary Atrial pressures (PA mmHg);	Baseline and 6,12,24,36,72 Hours post-inotrope challenge.
Changes in invasive hemodynamics using a pulmonary artery (PA) catheter measuring L/min/m2	Changes invasive hemodynamics representing myocardial reserve will be measured in 5 patients using a pulmonary artery (PA) catheter: Cardiac output by Fick (CO L/min/m2); Cardiac index by Fick (CI L/min/m2).	Baseline and 6,12,24,36,72 Hours post-inotrope challenge.
Advanced heart failure therapy	Duration of time without need for definitive advanced heart failure therapy (LVAD, OHT) or death.	2 years
Inotropes	Duration of time on inotropes during hospitalization	2 years
Death	Cardiovascular death and/or all-cause mortality	2 years
Cardiac output measurement using a pulmonary artery (PA) catheter measuring mmHg at 2 years	Efficacy of increasing cardiac output with milrinone compared to dobutamine using changes invasive hemodynamics in 5 patients using a pulmonary artery (PA) catheter: Pulmonary capillary wedge pressure (PCWP mmHg), Right Atrial pressure (RA mmHg), Pulmonary Atrial pressures (PA mmHg),	2 years
Cardiac output measurement using a pulmonary artery (PA) catheter measuring CO L/min/m2 at 2 years	Efficacy of increasing cardiac output with milrinone compared to dobutamine using changes invasive hemodynamics in 5 patients using a pulmonary artery (PA) catheter: Cardiac output by Fick (CO L/min/m2), Cardiac index by Fick (CI L/min/m2.)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Durable support	Duration of time successfully off of counterpulsation, LVAD, or ECMO support	6 hours
Durable support	Duration of time successfully off of counterpulsation, LVAD, or ECMO support	12 hours
Durable support	Duration of time successfully off of counterpulsation, LVAD, or ECMO support	24 hours
Durable support	Duration of time successfully off of counterpulsation, LVAD, or ECMO support	36 hours
Durable support	Duration of time successfully off of counterpulsation, LVAD, or ECMO support	48 hours
Durable support	Duration of time successfully off of counterpulsation, LVAD, or ECMO support	72 hours
Hospital discharge	Hospital discharge without LVAD, OHT, home-inotropes, long-term counter-pulsation device (i.e NuPulse), or death. Patients will be monitored at the the following timepoints while admitted in the Cardiac Intensive Care Unit (CICU) 12 Hours 24 Hours 36 Hours 48 Hours 72 Hours	Up to 12 weeks
Home inotropic	Duration of time on home inotropic agents	2 years
LVAD decommissioning measuring mmHg	If a patient is enrolled in the study that has an left ventricular assist device (LVAD) decommissioning or removal (not due to open heart transplant, pump malfunction, or death) the following will be assessed: A. Changes in invasive hemodynamics using a pulmonary artery (PA) catheter: Pulmonary capillary wedge pressure (PCWP mmHg) Right Atrial pressure (RA mmHg) Pulmonary Atrial pressures (PA mmHg)	2 years
LVAD decommissioning measuring L/min/m2	If a patient is enrolled in the study that has an left ventricular assist device (LVAD) decommissioning or removal (not due to open heart transplant, pump malfunction, or death) the following will be assessed: A. Changes in invasive hemodynamics using a pulmonary artery (PA) catheter: Cardiac output by Fick (CO L/min/m2); Cardiac index by Fick (CI L/min/m2) B. Myocardial reserve (i.e. cardiac power output, aortic pulsatility index, Cardiac output by Fick (CO L/min/m2) Cardiac index by Fick (CI L/min/m2)) after inotrope challenge. C. Association of myocardial reserve with other known variables of cardiovascular and all-cause mortality.	2 years

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Valluvan Jeevanandam, MD, University of Chicago

Publications and helpful links

General Publications

• Hsu S, Kambhampati S, Sciortino CM, Russell SD, Schulman SP. Predictors of intra-aortic balloon pump hemodynamic failure in non-acute myocardial infarction cardiogenic shock. Am Heart J. 2018 May;199:181-191. doi: 10.1016/j.ahj.2017.11.016. Epub 2017 Dec 13.
• Fincke R, Hochman JS, Lowe AM, Menon V, Slater JN, Webb JG, LeJemtel TH, Cotter G; SHOCK Investigators. Cardiac power is the strongest hemodynamic correlate of mortality in cardiogenic shock: a report from the SHOCK trial registry. J Am Coll Cardiol. 2004 Jul 21;44(2):340-8. doi: 10.1016/j.jacc.2004.03.060.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2023
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: November 1, 2022
• First Submitted That Met QC Criteria: January 17, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Estimated): June 2, 2023
• Last Update Submitted That Met QC Criteria: June 1, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Shock; Myocardial Infarction; Infarction; Heart Failure; Shock, Cardiogenic; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Adrenergic Agonists; Cardiotonic Agents; Phosphodiesterase Inhibitors; Adrenergic beta-Agonists; Sympathomimetics; Adrenergic beta-1 Receptor Agonists; Phosphodiesterase 3 Inhibitors; Milrinone; Dobutamine
• Other Study ID Numbers: IRB22-0817

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
• product manufactured in and exported from the U.S.: No