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Ischemic Cardiomyopathy | Inflammation, Cardiac Sympathetic Innervation, and Arrhythmic Sudden Death

Ischemic Cardiomyopathy research study

What is the primary objective of this study?

Despite pharmacologic advances for the treatment of congestive heart failure (HF), sudden cardiac death (SCD) and pump failure remain the leading causes of mortality in patients with HF. Although, SCD is poorly understood, implantable cardiac defibrillators (ICD) have been shown to be an effective, but costly therapy in preventing SCD. At present, left ventricular systolic dysfunction is our best independent predictor of SCD, but only moderately predicts those patients who will eventually benefit from the placement of an ICD and, in most cases, left ventricular (LV) systolic dysfunction is a non-modifiable risk factor once acquired. As a result, there exists an intensive search for biomarkers that could improve the prediction of SCD and have the potential for risk factor modification. Experimental and clinical evidence has established that inflammation plays a critical role in stable coronary disease, plaque rupture, acute myocardial infarction, heart failure, and SCD. Studies at our institution have demonstrated that elevated levels of hsCRP and Interleukin-6 are predictive of arrhythmic SCD; however, the mechanism of causing this increased risk is unclear. Another well-known risk factor for SCD is abnormal sympathetic innervation. The most robust clinical test of sympathetic innervation to date is Iodine-123 Metaiodobenzylguanidine (MIBG) imaging with gamma scintigraphy. MIBG imaging has emerged as one of our strongest predictors of SCD by detecting sympathetic nervous system abnormalities in patients with HF. Preclinical and clinical evidence suggests that myocardial inflammation adversely affects myocardial innervation. Based on these findings, the investigators hypothesize that elevated levels of inflammatory biomarkers are associated with abnormal sympathetic innervation as measured by MIBG imaging. The investigators aim to establish the strength of this association. This proposal will leverage unique access to the largest, most extensively phenotyped cohort of patients who have undergone ICD implantation for primary prevention of SCD, the PRospective Observational Study of the ICD in SCD, (PROSE-ICD).

Who is eligible to participate?

Patient Population - This proposal will enroll patients from the PROSE-ICD cohort who have undergone ICD implantation for primary prevention of SCD. PROSE-ICD is a multicenter prospective observational cohort study designed to identify risk factors for SCD in high-risk patients. Inclusion Criteria The entire PROSE-ICD population with ischemic and non-ischemic cardiomyopathy will be divided into quartiles based on previously measured hsCRP levels in the PROSE-ICD database. The study sample for this study will include 50 randomly selected PROSE-ICD participants from the lowest hsCRP quartile and another 50 randomly selected participants from the highest quartile. PROSE-ICD includes patients greater than 18 years old who have a history of acute MI at least 4 weeks old (confirmed by persistent pathologic Q waves on ECG, CPK-MB > three times the upper limit of normal, or a fixed perfusion defect on nuclear imaging) or non-ischemic LV dysfunction for at least 9 months who have an EF ≤ 35% and who have undergone implantation of an FDA-approved ICD for primary prevention of SCD within 2 weeks of enrollment. Exclusion Criteria Exclusion criteria for PROSE-ICD include an indication for ICD implantation for secondary prevention; inability or unwillingness to provide informed consent; women <50 years old with anatomic child-bearing potential who are unwilling to use contraceptives; NYHA class IV HF; patients with permanent pacemakers; and unsuccessful ICD implantation Additional exclusion criteria for PROSE-ICD patients enrolled in MIBG imaging will include: 1. Positive pregnancy test in women with child bearing potential 2. Use of a medication for non-cardiac conditions that may interfere with MIBG that cannot be safely withheld for five half-lives before study procedures. 3. Renal insufficiency (GFR <30 ml/dl or creatinine >3.0 mg/dl) or dialysis. 4. Hypersensitivity to iodine.

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Ischemic Cardiomyopathy

Dilated Cardiomyopathy

Inflammation

Sudden Cardiac Death

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Primary Prevention of Sudden Cardiac DeathNo intervention will be administered. This is an observational study testing the association of inflammation and cardiac sympathetic innervation using I-123-MIBG gamma scintigraphy

Study Status

Unknown status

Start Date: March 2012

Completed Date: October 2014

Phase: N/A

Type: Observational

Design:

Primary Outcome: Determine if inflammation is associated with abnormal cardiac sympathetic innervation in patients enrolled in the PROSE-ICD study.

Secondary Outcome: Determine if inflammation, measured by IL-6, is associated with abnormal cardiac sympathetic innervation, measured by MIBG imaging

Study sponsors, principal investigator, and references

Principal Investigator: Richard T George, M.D.

Lead Sponsor: Johns Hopkins University

Collaborator: National Institutes of Health (NIH)

More information:https://clinicaltrials.gov/show/NCT01919983

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