Investigation in Pregnancy Associate Cardiomyopathy

NCT ID: NCT01085955

Last Updated: 2016-01-15

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2014-08-31

Brief Summary

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.

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.

Conditions

Cardiomyopathy; Pregnancy

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Acute Peripartum

pregnant women who have recently given birth and diagnosed with peripartum cardiomyopathy

No interventions assigned to this group

Healthy Peripartum

Healthy pregnant women who have recently given birth, used as controls

No interventions assigned to this group

Healthy, non-pregnant women

Healthy non-pregnant women without cardiac disease, used as controls

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

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

• 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

• Minimum Eligible Age: 16 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

University of Pittsburgh

OTHER

Sponsor Role: lead

Responsible Party

Dennis McNamara

Prinicipal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dennis McNamara, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh Medical Center

Locations

University of Southern California

Los Angeles, California, United States

University of Miami, Miller School of Medicine

Miami, Florida, United States

Medical College of Georgia

Augusta, Georgia, United States

University of Illinois

Chicago, Illinois, United States

University of Kentucky

Lexington, Kentucky, United States

Louisiana State University Health Science Center

Louisiana, Louisiana, United States

University of Maryland

Baltimore, Maryland, United States

Johns Hopkins

Baltimore, Maryland, United States

Massachusetts General

Boston, Massachusetts, United States

Brigham and Women's

Boston, Massachusetts, United States

DMC Cardiovascular Institute / Harper University Hospital

Detroit, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University

St Louis, Missouri, United States

Gagnon Cardiovascular Institute at Morristown Memorial Hospital

Morristown, New Jersey, United States

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Columbia University

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

Stony Brook University Medical Center

Stony Brook, New York, United States

Duke University

Durham, North Carolina, United States

Wake Forest University

Winston-Salem, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

University of Texas, Southwestern

Dallas, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

Intermountain Medical Center

Salt Lake City, Utah, United States

Foothills Medical Center

Calgary, Alberta, Canada

Sir Mortimer B. Davis / Jewish General Hospital

Montreal, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 28373243 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26970832 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26293760 (View on PubMed)

Other Identifiers

IPAC

Identifier Type: -

Identifier Source: org_study_id