IPAC: Investigation in Pregnancy Associate Cardiomyopathy

Sponsor

University of Pittsburgh (Other)

Overall Status

Completed

CT.gov ID

NCT01085955

Collaborator

National Institutes of Health (NIH) (NIH)

100

Enrollment

Locations

Duration (Months)

3.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiomyopathy Pregnancy

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 Design

Study Type:

Observational

Actual Enrollment :

100 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Immune Activation and Myocardial Recovery in Peripartum Cardiomyopathy

Study Start Date :

Oct 1, 2009

Actual Primary Completion Date :

Aug 1, 2014

Actual Study Completion Date :

Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

Evaluate systemic immune activation as the etiology of PPCM [6-12 months]
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.

Secondary Outcome Measures

Investigate frequency of myocardial injury or inflammation on cardiac MRI and the ability of tissue characteristics to predict subsequent recovery of LVEF [6 months]
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

Other Outcome Measures

Long Term Survival Data [up to 5 years]
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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