Clinical trial NCT01085955: Investigation in Pregnancy Associate Cardiomyopathy
Official title: Immune Activation and Myocardial Recovery in Peripartum Cardiomyopathy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cardiomyopathy
Pregnancy
Keywords: peripartum
cardiomyopathy
post pregnancy
myocardial recovery
pregnant women with peripartum cardiomyopathy
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2010-03-12
Enrollment: 100
Sex: FEMALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 100 women diagnosed with peripartum cardiomyopathy

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.

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

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

Primary outcomes:
measure: Evaluate systemic immune activation as the etiology of PPCM
timeFrame: 6-12 months
Secondary outcomes:
measure: Investigate frequency of myocardial injury or inflammation on cardiac MRI and the ability of tissue characteristics to predict subsequent recovery of LVEF
timeFrame: 6 months
Other outcomes:
measure: Long Term Survival Data
timeFrame: up to 5 years
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Miami
country: United States
facility: University of Miami, Miller School of Medicine
state: Florida
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Louisiana
country: United States
facility: Louisiana State University Health Science Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Massachusetts General
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's
state: Massachusetts
city: Detroit
country: United States
facility: DMC Cardiovascular Institute / Harper University Hospital
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Morristown
country: United States
facility: Gagnon Cardiovascular Institute at Morristown Memorial Hospital
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: New York City
country: United States
facility: Columbia University
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas, Southwestern
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: Intermountain Medical Center
state: Utah
city: Calgary
country: Canada
facility: Foothills Medical Center
state: Alberta
city: Montreal
country: Canada
facility: Sir Mortimer B. Davis / Jewish General Hospital
state: Quebec
Study officials:
affiliation: University of Pittsburgh Medical Center
name: Dennis McNamara, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.