Inflammation, Cardiac Sympathetic Innervation, and Arrhythmic Sudden Death

NCT01919983 | Completed DMC

• 2 other identifiers: 1R21HL106586-11R21HL106586
• Study Type: observational
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Ischemic Cardiomyopathy; Dilated Cardiomyopathy; Inflammation; Sudden Cardiac Death

Keywords

cardiac; innervation; inflammation; sudden; death

Outcome Measures

Primary Outcomes (1)

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

  The investigators will determine if inflammation, measured by high sensitivity C-reactive protein is associated with abnormal cardaic sympathetic innervation defined as a heart to mediastinum ratio \< 1.60.

  within 3 years

Secondary Outcomes (3)

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

  within 3 years

• Examine the combination of CRP and MIBG

  within 3 years

• Compare several MIBG imaging metrics of sympathetic innervation, in addition to the late H/M ratio, including the early H/M ratio and the MIBG washout rate, in regards to their association with biomarkers of inflammation (CRP and IL-6).

  within 3 years

Study Arms (1)

Primary Prevention of Sudden Cardiac Death

No intervention will be administered. This is an observational study testing the association of inflammation and cardiac sympathetic innervation using I-123-MIBG gamma scintigraphy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with a cardiomyopathy with an LVEF ≤35% who have undergone placement of an implantable cardioverter-defibrillator for primary prevention of sudden cardiac death

You may not qualify if:

• Positive pregnancy test in women with child bearing potential
• 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.
• Renal insufficiency (GFR \<30 ml/dl or creatinine \>3.0 mg/dl) or dialysis.
• Hypersensitivity to iodine.

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institutes of Health (NIH): collaborator
• General Electric: collaborator

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood Sample

MeSH Terms

Conditions

Cardiomyopathy, Dilated; Inflammation; Death, Sudden, Cardiac; Death

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Heart Arrest; Death, Sudden

Study Officials

• Richard T George, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2013
• First Posted: August 9, 2013
• Study Start: March 1, 2012
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: December 8, 2017

Record last verified: 2017-12

Locations

US (1)