Investigation in Pregnancy Associate Cardiomyopathy (IPAC)

Immune Activation and Myocardial Recovery in Peripartum Cardiomyopathy

Peri-partum cardiomyopathy is a heart muscle weakness that occurs during or following pregnancy. Research suggests that many initial heart injuries including viruses, pregnancy and other unknown causes, can lead to a process of inflammation of the heart muscle which can weaken the heart and cause cardiomyopathy. Why this process occurs in women during pregnancy is not well understood and if it differs from those women who develop cardiomyopathy from a virus is unknown. This study has been proposed to look at genetic information (DNA) as well as the immune system (the body's response to fight off infections and/or viruses) to find possible causes for the heart muscle damage that occurs in peripartum cardiomyopathy.

Study Overview

• Status: Completed
• Conditions: Pregnancy; Cardiomyopathy

Detailed Description

Specific Aim 1: Evaluate systemic immune activation as the etiology of PPCM. We will determine a) the degree of immune activation in PPCM and b) the relationship of autoimmunity to left ventricular dysfunction and time course of myocardial recovery, in 100 women enrolled at 30 centers. Subjects will have blood drawn for assessment of autoantibodies, and cellular immune activation at presentation, 2 month and 6 month postpartum, and will have assessment of LVEF by transthoracic echo at presentation, 2 months, 6 months and 12 months post partum. This aim will explore the hypothesis that more prolonged activation of the cellular and/or humoral immune system is associated with greater likelihood of persistent chronic cardiomyopathy.

In addition this aim will determine genetic and clinical predictors of LV recovery, and evaluate racial differences in presentation, remodeling and recovery. This study will evaluate the echo parameters of dysynchrony, diastolic function, LV size and volumes to determine echo predictors of subsequent recovery. In addition racial differences in presentation, remodeling and recovery will be investigated.

Specific Aim 2: Investigate frequency of myocardial injury or inflammation on cardiac MRI and the ability of tissue characteristics to predict subsequent recovery of LVEF. Cardiac MRI with gadolinium enhancement will be performed in 50 subjects with PPCM from Aim 1 at presentation and repeated at 6 months post partum. We will test the hypothesis is that subjects with more extensive injury (defined as % myocardium with late gadolinium enhancement) will have less recovery at 6 months.

Specific Aim 3: Establish DNA and serum to facilitate future investigations of the pathogenesis of peripartum cardiomyopathy. All subjects enrolled will have DNA, RNA from peripheral blood and serum banked at entry. Serum will be repeated at 2 and 6 months post partum.

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Center
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Sir Mortimer B. Davis / Jewish General Hospital
• United States
  • California
    • Los Angeles, California, United States, 90033-1026
      • University of Southern California
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami, Miller School of Medicine
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Medical College of Georgia
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Louisiana
    • Louisiana, Louisiana, United States, 71130
      • Louisiana State University Health Science Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's
    • Boston, Massachusetts, United States, 02114-2696
      • Massachusetts General
  • Michigan
    • Detroit, Michigan, United States, 48201
      • DMC Cardiovascular Institute / Harper University Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Gagnon Cardiovascular Institute at Morristown Memorial Hospital
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
  • New York
    • New York City, New York, United States, 10032
      • Columbia University
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • Stony Brook, New York, United States, 11794-8167
      • Stony Brook University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University
    • Winston-Salem, North Carolina, United States, 27157-1045
      • Wake Forest University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15237
      • University of Pittsburgh Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas, Southwestern
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Intermountain Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

100 women diagnosed with peripartum cardiomyopathy

Description

Inclusion Criteria:

• Patient of 16 years of age or older
• Diagnosis of peripartum cardiomyopathy
• Presentation for enrollment no earlier than one month pre-term and no later than two months post partum.
• LVEF less than OR equal to 0.45 by echocardiogram

Additional inclusion criteria for MRI substudy:

• Must be post partum
• Participant is not breast feeding or is willing to forego breast feeding for 24 hours post gadolinium.

Exclusion Criteria:

• Previous diagnosis of cardiomyopathy, valvular disease or complex congenital heart disease
• Evidence of CAD (>50% stenosis of major epicardial vessel or positive non-invasive stress test)
• Previous cardiac transplant
• Chemotherapy or chest radiation within 5 years of enrollment
• Evidence of ongoing bacterial septicemia (positive blood cultures)
• Medical, social, or psychiatric condition which limit the ability to comply with follow-up (Example: alcohol or drug abuse)

Additional Exclusion for MRI Substudy

• GFR < 30mL/1.7 m2 by MDRD equation (http://www.kidney.org/professionals/kdogi/gfr_calculator.cfm)
• Currently breast feeding or unwilling to forego for 24 hour period post gadolinium
• Implanted devices (cochlear implants, pacemakers, defibrillators, infusion pumps, nerve stimulators, etc)
• Cerebral aneurysm clips
• Swan Ganz catheter or intra aortic balloon pump
• Ocular metal or metallic splinters in the eye
• Pregnant women
• Metal shrapnel or bullet
• Allergy to Gadolinium

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Acute Peripartum; pregnant women who have recently given birth and diagnosed with peripartum cardiomyopathy
Healthy Peripartum; Healthy pregnant women who have recently given birth, used as controls
Healthy, non-pregnant women; Healthy non-pregnant women without cardiac disease, used as controls
New Non-ischemic CMP; Women 18-60 years old who have been diagnosed with non-ishemic cardiomyopathy within the last 6 months and have an ejection fraction less than OR equal to 45% by echocardiogram.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate systemic immune activation as the etiology of PPCM	determine the degree of immune activation in PPCM and the relationship of autoimmunity to left ventricular dysfunction and time course of myocardial recovery, in 100 women enrolled at multiple centers.	6-12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigate frequency of myocardial injury or inflammation on cardiac MRI and the ability of tissue characteristics to predict subsequent recovery of LVEF	Cardiac MRI with gadolinium enhancement will be performed in 50 subjects with PPCM from Aim 1 at presentation and repeated at 6 months post partum. We will test the hypothes that subjects with more extensive injury (defined as % myocardium with late gadolinium enhancement) will have less recovery at 6 months	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long Term Survival Data	We are asking women to extend thier consent for 5 additional years from thier delivery date to collect survival data (alive, transplanted, VAD implanted; medications; NYAH Class; subsequent pregnancies)	up to 5 years

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: National Institutes of Health (NIH)

Publications and helpful links

General Publications

• Schelbert EB, Elkayam U, Cooper LT, Givertz MM, Alexis JD, Briller J, Felker GM, Chaparro S, Kealey A, Pisarcik J, Fett JD, McNamara DM; Investigations of Pregnancy Associated Cardiomyopathy (IPAC) Investigators. Myocardial Damage Detected by Late Gadolinium Enhancement Cardiac Magnetic Resonance Is Uncommon in Peripartum Cardiomyopathy. J Am Heart Assoc. 2017 Apr 3;6(4):e005472. doi: 10.1161/JAHA.117.005472.
• Damp J, Givertz MM, Semigran M, Alharethi R, Ewald G, Felker GM, Bozkurt B, Boehmer J, Haythe J, Skopicki H, Hanley-Yanez K, Pisarcik J, Halder I, Gorcsan J 3rd, Rana S, Arany Z, Fett JD, McNamara DM; IPAC Investigators. Relaxin-2 and Soluble Flt1 Levels in Peripartum Cardiomyopathy: Results of the Multicenter IPAC Study. JACC Heart Fail. 2016 May;4(5):380-8. doi: 10.1016/j.jchf.2016.01.004. Epub 2016 Mar 9.
• McNamara DM, Elkayam U, Alharethi R, Damp J, Hsich E, Ewald G, Modi K, Alexis JD, Ramani GV, Semigran MJ, Haythe J, Markham DW, Marek J, Gorcsan J 3rd, Wu WC, Lin Y, Halder I, Pisarcik J, Cooper LT, Fett JD; IPAC Investigators. Clinical Outcomes for Peripartum Cardiomyopathy in North America: Results of the IPAC Study (Investigations of Pregnancy-Associated Cardiomyopathy). J Am Coll Cardiol. 2015 Aug 25;66(8):905-14. doi: 10.1016/j.jacc.2015.06.1309.

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: March 10, 2010
• First Submitted That Met QC Criteria: March 10, 2010
• First Posted (Estimate): March 12, 2010

Study Record Updates

• Last Update Posted (Estimate): January 15, 2016
• Last Update Submitted That Met QC Criteria: January 14, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: cardiomyopathy; peripartum; post pregnancy; myocardial recovery; pregnant women with peripartum cardiomyopathy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Cardiomyopathies
• Other Study ID Numbers: IPAC