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: Recruiting
• Conditions: Heart Failure; Cardiogenic Shock
• Intervention / Treatment: Drug: 1:1 Randomization to receive 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

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • The University of Chicago
      • Contact: Carlisa Dixon; Phone Number: 773-834-4337; Email: cdixon520@bsd.uchicago.edu
      • Contact: Leila Yazdanbakhsh; Phone Number: 773-834-5087; Email: leila.yazdanbakhsh@bsd.uchicago.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. LVEF ≤ 40%

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; Milrinone will be given as a bolus dose of 50 mcg/kg. If a maintenance milrinone infusion is felt to be necessary, it will be maintained at 0.125-0.375 mcg/kg/min.	Drug: 1:1 Randomization to receive milrinone; Randomized to receive either inotropic agent: milrinone or no agent; Other Names: Milrinone
No Intervention: 1:1 No Intervention; Subjects without evidence of cardiogenic shock will not receive Milrinone.

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

• 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.
• Hsu S, Thiruvengadam SK, 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.
• Zhang X, Wang Z, Zhang L, Zhao X, Han Y. Comparative Effectiveness and Safety of Intermittent, Repeated, or Continuous Use of Levosimendan, Milrinone, or Dobutamine in Patients With Advanced Heart Failure: A Network and Single-Arm Meta-analysis. J Cardiovasc Pharmacol. 2024 Jul 1;84(1):92-100. doi: 10.1097/FJC.0000000000001561.
• Gayatri D, Tongers J, Efremov L, Mikolajczyk R, Sedding D, Schumann J. Prophylactic use of inotropic agents for the prevention of low cardiac output syndrome and mortality in adults undergoing cardiac surgery. Cochrane Database Syst Rev. 2024 Nov 27;11(11):CD013781. doi: 10.1002/14651858.CD013781.pub2.

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

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 (Actual): August 6, 2026
• Last Update Submitted That Met QC Criteria: August 4, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infarction; Necrosis; Myocardial Ischemia; Myocardial Infarction; Ischemia; Shock; Pathological Conditions, Signs and Symptoms; Heart Failure; Shock, Cardiogenic; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Amines; Aminopyridines; Amrinone; Milrinone
• 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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes