Inflammation, Cardiac Sympathetic Innervation, and Arrhythmic Sudden Death

Learn more about:
Related Clinical Trial
A 10-Minute Cardiovascular Magnetic Resonance Protocol for Cardiac Disease CorCinch-HF Repair System in Patients Who Present With Symptomatic Non-Ischemic or Ischemic Dilated Cardiomyopathy Early Administration of Ivabradine in Children With Heart Failure Metabolomics and Microbiomics in Cardiovascular Diseases Mannheim TORCH-Plus is a Registry for Patients With Cardiomyopathies and Serves as Source for Cardiovascular Research Studies Risk Stratification in Children and Adolescents With Primary Cardiomyopathy Pediatric Cardiomyopathy Mutation Analysis German Centre for Cardiovascular Research Cardiomyopathy Register Hemodynamic Evaluation of Preload Responsiveness in Children by Using PiCCO An Integrative-“Omics” Study of Cardiomyopathy Patients for Diagnosis and Prognosis in China Metabolomic Study of All-age Cardiomyopathy Coronary Artery Disease and Coronary Microvascular Disease in Cardiomyopathies Registry The Genetics of Cardiomyopathy and Heart Failure Inflammation, Cardiac Sympathetic Innervation, and Arrhythmic Sudden Death Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators in Europe Randomized Trial of Interventions to Improve Warfarin Adherence Testing Strategies to Improving Warfarin Adherence Prospective Study Looking at Quality of Life Measures in Non-ischaemic Cardiomyopathy After Mitral Valve Repair Left Cardiac Sympathetic Denervation for Cardiomyopathy Feasibility Pilot Study The Cardiovascular Genetic and Therapeutic Implications of Muscular Dystrophy A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy Role of Endothelial Function, Muscular Fitness and Metabolism in Functional Activity in Patients With Chronic Heart Failure (CHF) Echo Assessment of Intraventricular Dyssynchrony Brain Function and Perfusion in Patients With Heart Failure Molecular and Imaging Studies of Cardiovascular Health and Disease Genotype-Phenotype Associations in Pediatric Cardiomyopathy (PCM GENES) Optimizing Left Ventricular Lead To Improve Cardiac Output Using Ripple Mapping to Guide Substrate Ablation of Scar Related Ventricular Tachycardia. Long-term Evaluation of Patients Receiving Bone Marrow-derived Cell Administration for Heart Disease Study Evaluating the Safety, Tolerability and Preliminary Pharmacokinetics and Pharmacodynamics of MYK-491 Efficacy and Safety Study of Genetically Targeted Enzyme Replacement Therapy for Advanced Heart Failure Harefield Recovery Protocol Study for Patients With Refractory Chronic Heart Failure ACC – Atrial Contribution to CRT Follow-up Safety Trial in Children With Chronic Heart Failure Therapy Receiving Orodispersible Minitablets of Enalapril Non-Invasive Evaluation of Myocardial Stiffness by Elastography in Pediatric Cardiology (Elasto-Pédiatrie) Manganese-Enhanced Magnetic Resonance Imaging of the Myocardium Efficacy of Implantable Cardioverter Defibrillator in Patients With Non-ischemic Systolic Heart Failure on Mortality Cardiac Biomarkers in Pediatric Cardiomyopathy (PCM Biomarkers) Arrhythmia Prediction Trial Exome Sequencing Study in Cardiomyopathy to Identify New Risk Variants A Single Ascending Dose Study Assessing the Safety, Tolerability, PK and PD of MYK-491 Exercise Stress MRI to Evaluate Aortic Function (Compliance, Distensibility, Pulse Wave Velocity) and Left Ventricular Function : Validation in Healthy Volunteers and in Selected Patients. A Pilot Study. Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy Observational Trial of Cardiotoxicity in Patients Undergoing Chemotherapy. A Pivotal Trial to Establish the Efficacy and Safety of Algisyl in Patients With Moderate to Severe Heart Failure Effect of Rosuvastatin on Left Ventricular Remodeling Intraventricular Stasis in Non Ischemic Dilated Myocardiopathy Assessment of Right Ventricular Function in Advanced Heart Failure An Open Label Rollover Trial for Patients Randomized to the Control Group of Study LSH-10-001 Optimized Biventricular Pacing Allograft Recipients BiPAP for Cardiomyopathy With Central Sleep Apnea Relationship Between Abnormalities of Desmin Cytoskeleton, Mitochondrial Activity and Expression of Ubiquitin in Aspect of Pathogenesis of Heart Failure and Prognosis Effect of Aldosterone on Energy Starvation in Heart Failure Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside Therapy With Verapamil or Carvedilol in Chronic Heart Failure Effect of Beta-blockers on Structural Remodeling and Gene Expression in the Failing Human Heart Training Study to Evaluate the Benefit of Exercise for Patients With Chronic Heart Failure Danish ICD Study in Patients With Dilated Cardiomyopathy Cardiovascular Magnetic Resonance GUIDEd Insertion of Implantable Cardiac Defibrillator in Dilated CardioMyopathy DCM Precision Medicine Study A Randomized, Controlled Study to Evaluate Algisyl-LVR™ as a Method of Left Ventricular Augmentation for Heart Failure The Genetics of Dilated Cardiomyopathy: A Quebec-Based Study Potential Role of Water-soluble Ubiquinol in Complementary Therapy for Pediatric Dilated Cardiomyopathy A Trial of Autologous Bone Marrow Derived Stem Cells in Paediatric Heart Failure Resynchronization Therapy in Young Patients With and Without CHD Withdrawal of Medication in Recovered DCM Use of Bone Marrow Derived Stem Cell and G-CSF With Circulatory Assistance in the Treatment of DCM The Influence of Atorvastatin on the Parameters of Inflammation and the Function of Left Ventricle Safety and Feasibility of Algisyl-LVR™ as a Method of Left Ventricular Restoration in Patients With DCM Undergoing Open-heart Surgery PUFAs and Left Ventricular Function in Heart Failure 18F-deoxyglucose (FDG) PET-CMD Repetitive Intramyocardial CD34+ Cell Therapy in Dilated Cardiomyopathy (REMEDIUM) Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy Autologous Transplantation of Bone Marrow Mononuclear Stem-Cells by Mini-Thoracotomy Combination of Olmesartan Effect on Myocardial Viability of Patients With Dilated Cardiomyopathy Mesenchymal Stem Cells for Idiopathic Dilated Cardiomyopathy Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea Pathophysiology of Dilated Cardiomyopathy Multicenter Exploratory Study of Accelerometry in Dilated Cardiomyopathy Transcoronary Infusion of Cardiac Progenitor Cells in Pediatric Dilated Cardiomyopathy Autologous Transplantation of Bone Marrow Mononuclear Stem-Cells for Dilated Cardiomyopathy Clinical and Genetic Examinations of Dilated Cardiomyopathy Simvastatin Therapy in Patients With Dilated Cardiomyopathy. Bone Marrow Derived Adult Stem Cells for Dilated Cardiomyopathy Safety and Efficacy Study of Intramyocardial Stem Cell Therapy in Patients With Dilated Cardiomyopathy Respiratory Muscles Training in Patients With Dilated Cardiomyopathy Myocardial Metabolism in Patients With Dilated Cardiomyopathy Intracoronary Autologous Mesenchymal Stem Cells Implantation in Patients With Ischemic Dilated Cardiomyopathy Orodispersible Minitablets of Enalapril in Children With Heart Failure Due to Dilated Cardiomyopathy Multicenter Study of Immunoadsorption in Dilated Cardiomyopathy Cell Therapy In Dilated Cardiomyopathy Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy Intracoronary Infusion of Autologous Bone Marrow Cells for Treatment of Idiopathic Dilated Cardiomyopathy Infusion Intracoronary of Mononuclear Autologous Adult no Expanded Stem Cells of Bone Marrow on Functional Recovery in Patients With Idiopathic Dilated Cardiomyopathy and Heart Failure. Nesiritide – Dilated Cardiomyopathy A Study of Impact of Anemia on Morbidity and Mortality in Children With Dilated Cardiomyopathy Defining the Role of Insulin Resistance in ‘Idiopathic’ Dilated Cardiomyopathy Use of Ixmyelocel-T (Formerly Cardiac Repair Cell [CRC] Treatment) in Patients With Heart Failure Due to Dilated Cardiomyopathy (IMPACT-DCM) Use of Ixmyelocel-T (Formerly Catheter-based Cardiac Repair Cell [CRC]) Treatment in Patients With Heart Failure Due to Dilated Cardiomyopathy A Pilot Trial of Ranolazine to Treat Patients With Dilated Cardiomyopathy Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy Intramuscular Injection of Mesenchymal Stem Cell for Treatment of Children With Idiopathic Dilated Cardiomyopathy Honey in Idiopathic Dilated Cardiomyopathy A Clinical Study of Immunoadsorption Therapy for Dilated Cardiomyopathy

Brief Title

Inflammation, Cardiac Sympathetic Innervation, and Arrhythmic Sudden Death

Official Title

Inflammation, Cardiac Sympathetic Innervation, and Arrhythmic Sudden Death

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).
    

Detailed Description

      The primary aim is as follows:

      Primary Aim 1: Determine if inflammation is associated with abnormal cardiac sympathetic
      innervation in patients enrolled in the PROSE-ICD study.

      Rationale/Hypothesis: The investigators hypothesize that patients with increased biomarkers
      of systemic inflammation have abnormal cardiac sympathetic innervation as measured by MIBG
      imaging.

      Specifically the investigators will: Image 100 patients from the PROSE-ICD cohort, 50 each
      from the highest and lowest quartiles of hsCRP levels and determine whether patients with
      biomarker evidence of increased inflammation also have abnormal sympathetic innervation.

      In addition, the investigators will pursue the following secondary aims:

        1. Determine if inflammation, measured by IL-6, is associated with abnormal cardiac
           sympathetic innervation, measured by MIBG imaging, in patients enrolled in the PROSE-ICD
           study.

        2. Examine the association of CRP and MIBG with ICD therapies in PROSE-ICD.

        3. 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.

        4. Compare MIBG imaging to ECG metrics of sympathetic innervation.

        5. Examine the relationship between inflammation and regional myocardial innervation and
           rest myocardial perfusion using quantitative and qualitative SPECT imaging.
           Specifically, the investigators will aim to determine if inflammation is associated with
           perfusion/innervation mismatch.
    


Study Type

Observational


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

Condition

Ischemic Cardiomyopathy


Study Arms / Comparison Groups

 Primary Prevention of Sudden Cardiac Death
Description:  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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information



Estimated Enrollment

28

Start Date

March 2012

Completion Date

September 2014

Primary Completion Date

September 2014

Eligibility Criteria

        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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Richard T George, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01919983

Organization ID

1R21HL106586-1

Secondary IDs

1R21HL106586

Responsible Party

Sponsor

Study Sponsor

Johns Hopkins University

Collaborators

 National Institutes of Health (NIH)

Study Sponsor

Richard T George, M.D., Principal Investigator, Johns Hopkins University


Verification Date

December 2017