Study Looking at the Recovery of New Onset Cardiomyopathy



Status:Completed
Conditions:Cardiology
Therapuetic Areas:Cardiology / Vascular Diseases
Healthy:No
Age Range:18 - Any
Updated:4/21/2016
Start Date:January 2004
End Date:March 2011

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Genetic Modulation of Left Ventricular Recovery in Recent Onset Cardiomyopathy

This is a multi-center, prospective evaluation of left ventricular recovery on conventional
therapy in patients with the recent onset of dilated cardiomyopathy. In some subjects with
this disorder, the heart will recover significantly over the first year, while others will
be left with a chronically weak heart. The proteins that help the heart recover are encoded
by genes, which can differ markedly between individuals. The goal of the current study is to
determine whether variation in these genes involved affect the probability that the heart
will recover. We will also look at which genes are involved in inflammation and which ones
are "turned on" (producing proteins) in circulating white blood cells.{These statements will
only be added if the site has chosen to participate in RNA analysis}. In addition, this
study will look at how levels of proteins in the blood, proteins called "cytokines' which
control inflammation and proteins called "neurohormones" which are released when the heart
weakens, affect the likelihood of recovery.

Enrollment will take place at 15 centers. The goal is to enroll approximately 500 adult
subjects (age 18 years or older, both men and women) over the course of approximately 48
months.

After presenting with new onset idiopathic dilated cardiomyopathy, one third of patients
experience dramatic recovery of left ventricular function, while for the majority chronic
heart failure and left ventricular dysfunction persist. This marked variation in clinical
outcomes is determined in part by genetic heterogeneity of the systemic response to
myocardial injury. This population has been excluded from most clinical trials and few
studies have examined the role of cytokine and neurohormonal mediators in modulating the
balance between left ventricular recovery and remodeling in early cardiomyopathy. This
proposal will investigate whether genetic polymorphisms of inflammatory and neurohormonal
mediators influence subsequent clinical outcomes for patients with recent onset primary
(idiopathic) dilated cardiomyopathy. The study will enroll 500 patients with recent onset
left ventricular dysfunction (LVEF < 0.40) due to non-ischemic primary cardiomyopathy at
eleven centers and follow these patients prospectively to evaluate subsequent left
ventricular recovery and freedom from clinical events.

Specific aim 1 will be to determine the correlation of echocardiographic parameters of
systolic and diastolic functional entry with circulating inflammatory mediators: TNF, IL-6
and TNF receptors 1 and 2. Specific aim 2 will be to determine the predictive value of early
plasma TNFα levels and of left ventricular size by transthoracic echo at baseline in
predicting improvements in left ventricular ejection function (LVEF) at 6 months. Specific
aim 3 will evaluate the effects of the TNFA 1/2 promoter polymorphism on circulating plasma
TNF levels and its influence on subsequent improvement in LVEF. Specific aim 4 will look at
the impact of the deletion allele of the angiotensin-converting enzyme and the genetic
variation of beta 1 and beta 2 adrenergic receptors on left ventricular recovery.

Inclusion Criteria:

1. Patients must be 18 years or over, and may be of either gender and of any race.

2. Patients must have significantly systolic dysfunction, defined as a left ventricular
ejection fraction of less than or equal to 40% by transthoracic echocardiography.

3. The patients must have a recent onset of dilated cardiomyopathy. Specifically, the
initial signs or symptoms of cardiomyopathy should not pre-date the time of
evaluation for the study by more than six months.

4. Subjects diagnosed during with peripartum cardiomyopathy (PPCM) are allowed as long
as they are enrolled within six months of cardiac symptoms.

5. Subjects presenting with acute heart failure with a positive familial history of
cardiomyopathy are included. Subjects who are asymptomatic, but are diagnosed with a
cardiomyopathy of unknown duration during screening for known familial disease are
excluded

6. Patients must be competent to give informed consent.

Exclusion Criteria:

1. Coronary artery disease as defined as a single coronary artery stenosis of a major
epicardial vessel greater than 50% or a previous history of myocardial infarction.

2. Patients with a history of familial cardiomyopathy, or a primary relative defined as
parents, siblings or children with a dilated cardiomyopathy are excluded.

3. Past or present history of alcoholism, or in whose current alcohol consumption
exceeds an average of three drinks per day. A past history of cocaine or IV drug
abuse as a possible explanation for their cardiomyopathy as well as substance abuse
of prescription pain relievers or any illicit drug that may hinder the participant's
ability to complete study follow-up.

4. Patients who are post cardiac transplant.

5. Patients whose heart failure is felt to be secondary to primary valvular disease,
uncorrected thyroid disease, uncontrolled hypertension despite medical therapy,
obstructive or hypertrophic cardiomyopathy, pericardial disease, or a systemic
illness such as sarcoidosis.

6. Patients whose history of cardiac symptoms or signs of cardiac disease predate the
time of evaluation by more than six months are excluded.

7. Evidence of ongoing bacteremia or sepsis. Patient with a febrile illness felt to be
secondary to myocarditis can be included (even with a non-diagnostic biopsy) if a
bacteriologic cause of the illness is excluded.

8. Patients with other life threatening diseases such as malignancy which would likely
decrease their life expectancy over the next three years. Any history of malignancy
treated with either chest radiation or chemotherapy.

9. The following patients are excluded for medical reasons: Patients with evidence of
chronic liver disease (total bilirubin >3.0mg%) or chronic renal disease (creatinine
> or equal to 2.5mg%) are excluded from the study. Subjects who present with an acute
worsening of renal function or liver function tests in the setting of potentially
fulminant myocarditis can be enrolled. Patients whose hepatic abnormalities are
secondary to hypoperfusion can also be considered.

10. Patients with previous history of diabetes and with evidence of multisystem end organ
damage (i.e. end stage renal disease and cardiomyopathy) or with evidence of any
coronary disease. Patient with diabetes without significant end organ damage is
allowed.

11. Patients enrolled in other placebo controlled experimental trials.

12. Patients who have had a myocardial biopsy, which reveals evidence of hemochromatosis,
amyloid, sarcoidosis, or giant cell myocarditis, are excluded.
We found this trial at
15
sites
3400 N Charles St
Baltimore, Maryland 21205
410-516-8000
Johns Hopkins University The Johns Hopkins University opened in 1876, with the inauguration of its...
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185 Cambridge Street
Boston, Massachusetts 02114
617-724-5200
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Boston, MA
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Gainesville, Florida 32610
(352) 392-3261
University of Florida The University of Florida (UF) is a major, public, comprehensive, land-grant, research...
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Gainesville, FL
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601 Elmwood Avenue
Rochester, New York 14642
(585) 275-2100
Univ of Rochester Medical Center One of the nation's top academic medical centers, the University...
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Rochester, NY
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2049 E 100th St
Cleveland, Ohio 44106
(216) 444-2200
Cleveland Clinic Foundation The Cleveland Clinic (formally known as The Cleveland Clinic Foundation) is a...
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Dalls, TX
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Hershey, Pennsylvania 17033
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Houston, Texas 77030
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201 Lyons Ave
Newark, New Jersey 07112
(973) 926-7000
Newark Beth Israel Medical Center Newark Beth Israel Medical Center, a regional care, teaching hospital...
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Newark, NJ
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Orange, California 92868
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1020 Walnut St
Philadelphia, Pennsylvania 19107
(215) 955-6000
Thomas Jefferson University We are dedicated to the health sciences and committed to educating professionals,...
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Philadelphia, PA
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200 Lothrop St
Pittsburgh, Pennsylvania 15213
University of Pittsburgh Medical Center UPMC is one of the leading nonprofit health systems in...
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Rochester, Minnesota 55905
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Toronto, Ontario
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Winston-Salem, North Carolina 27157
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