Cardiac Resynchronization and Iodine Meta-Iodobenzylguanidine (MIBG) Imaging

Cardiac Resynchronization and MIBG Imaging

Subjects were recruited if their healthcare provider decided that they needed treatment with a special Internal Cardiac Defibrillator (ICD) called a biventricular ICD. The investigators did this study to see if part of the nerve organ, called the sympathetic nervous system, may be responsible for the improvement seen in patients that receive biventricular pacing. The investigators had three ways to measure sympathetic nervous activity: 1) by using a special blood sample, 2) by monitoring heart rhythm, and 3) by performing a special heart scan.

Study Overview

• Status: Terminated
• Conditions: Congestive Heart Failure
• Intervention / Treatment: Drug: 123 iodine metaiodobenzylguanidine

Detailed Description

The Specific Aim #1 of this study is to assess, with 123iodine metaiodobenzylguanidine (123I-MIBG imaging), whether cardiac resynchronization therapy (CRT) rebalances and improves the integrity and function of sympathetic nerve terminals in the failing myocardium. The study will test the hypothesis that resynchronization of biventricular contractility attenuates excessive sympathetic drive, and improves autonomic function and cardiac performance.

The Specific Aim #2 of this study is to determine the relationship between 123I-MIBG labeling of sympathetic activity and physiological measures of cardiopulmonary and autonomic function. This aim is to test the hypothesis that impaired cardiac sympathetic activity, determined by 123I-MIBG imaging will be associated with poorer submaximal exercise gas exchange (higher ventilation - carbon dioxide (CO2) slopes, low end tidal CO2, reduced oxygen pulse and a more rapid frequency response) as well as reduced heart rate power spectral frequencies, a blunted response to positional changes and a delayed heart rate recovery.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria: Indications for Biv-ICD implantation

1. Chronic moderate to severe congestive heart failure (CHF) (NYHA class II or IV)
2. Left ventricular ejection fraction (LVEF) of 35% or less
3. Q wave, R wave and S wave (QRS complex) QRS duration of 120 ms or more
4. On optimized anti-heart failure medical regimen

5. Meet one of the following indications for ICD

   • Survivors of cardiac arrest due to ventricular fibrillation (VF) or ventricular tachycardia (VT) or spontaneous sustained VT
   • Nonsustained VT with coronary disease, prior myocardial infarction, LVEF 35% or less, and inducible VF or sustained VT at electrophysiologic study
   • LVEF of 30% or less with severe coronary artery disease

Exclusion criteria:

1. Patient condition is unstable
2. Patient is unable to give informed consent
3. Not feasible for patient to be followed at Mayo Clinic
4. Female in pregnancy and breast feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Biv-ICD; Subjects will be imaged with 123 iodine metaiodobenzylguanidine.	Drug: 123 iodine metaiodobenzylguanidine; 10 millicurie (mCi) (370 MBq); Other Names: AdreView

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 123I-MIBG parameters	changes in 123I-MIBG parameters with cardiac performance including LVEF, stroke volume (SV), left ventricle (LV) and left atrium (LA) dimension, distance of 6-minute walk, NYHA class, and ventricular arrhythmic burden	baseline, 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in submaximal exercise gas exchange	Subjects will perform simplified low intensity cardiopulmonary exercise testing in our laboratory where they breathe for 1 min at rest, perform graded step exercise, increasing from 60, 90, 120 steps per minute until achieving a perceived exertion of 12-14 on the 6-20 Borg scale. This will be followed by a 1 min recovery. Subjects will be instrumented with ECG, pulse oximeter and breathe on a mouthpiece where ventilation, oxygen and carbon dioxide are measured continuously to calculate the desired parameters of ventilatory efficiency (VE/VCO2), PetCO2 and oxygen pulse (O2Pulse) on a breath by breath basis.	baseline, 6 months
Change in Autonomic function	In addition to the simplified submaximal step test, subjects will also perform a simplified battery of tests for autonomic function. This will include supine to upright measures of heart rate and heart rate variability (HRV), paced breathing (slow to faster frequencies) as well as tracking HRV and responses to the increased metabolic demands of exercise and into recovery.	baseline, 6 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: GE Healthcare
• Investigators: Principal Investigator: Yongmei Cha, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: January 27, 2012
• First Submitted That Met QC Criteria: January 30, 2012
• First Posted (Estimate): January 31, 2012

Study Record Updates

• Last Update Posted (Actual): April 26, 2017
• Last Update Submitted That Met QC Criteria: April 24, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: cardiac resynchronization therapy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Radiopharmaceuticals; 3-Iodobenzylguanidine
• Other Study ID Numbers: 11-006296

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes