Cardiac Resynchronization and Iodine Meta-Iodobenzylguanidine (MIBG) Imaging
Congestive heart failure (CHF) affects nearly 5 million Americans and claims more than 300,000 lives annually. A primary pathophysiologic mechanism in this deadly syndrome is an abnormally enhanced sympathetic nervous system that results in profound peripheral vasoconstriction, attenuated cardiovascular reflexes, higher susceptibility to ventricular arrhythmias, and sudden cardiac death. The reduction in mortality and morbidity in CHF by pharmacologic neurohumoral antagonists such as beta-receptor inhibitor and angiotensin II-converting enzyme (ACE) inhibitor has taught us that regulation of the impaired neurohumoral axis is important for improving clinical outcome. In addition, an emerging nonpharmacologic approach, cardiac resynchronization therapy (CRT), has shown promise for improving symptoms and quality of life in patients with New York Heart Association (NYHA) functional class III or IV and intraventricular conduction delay. However, despite significant advances in CHF treatment in the past two decades, a gap remains between clinical outcome and the mechanisms of the protective effects of these modern therapies.
CHF is associated with increased concentrations of circulating norepinephrine (NE), down-regulation of adrenergic nerve terminals, and abnormal NE reuptake. The suppression of cardiac sympathetic nerve endings could be reversed by CRT, a novel anti-heart failure therapy, by rebalance cardiac sympathetic activity, and improve cardiac function in patients with heart failure.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Cardiac Resynchronization and MIBG Imaging|
- Changes in 123I-MIBG parameters [ Time Frame: baseline & 6 months ] [ Designated as safety issue: No ]changes in 123I-MIBG parameters with cardiac performance including LVEF, SV, LV and LA dimension, distance of 6-minute walk, NYHA class, and ventricular arrhythmic burden
- submaximal exercise gas exchange [ Time Frame: baseline & 6 months ] [ Designated as safety issue: No ]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 VE/VCO2, PetCO2 and O2Pulse on a breath by breath basis.
- Autonomic function [ Time Frame: baseline & 6 months ] [ Designated as safety issue: No ]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.
|Study Start Date:||February 2012|
|Estimated Study Completion Date:||September 2016|
|Estimated Primary Completion Date:||September 2016 (Final data collection date for primary outcome measure)|
Drug: 123 iodine metaiodobenzylguanidine
The Specific Aim #1 of this study is to assess, with 123iodine metaiodobenzylguanidine (123I-MIBG imaging), whether 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 - 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01522378
|Contact: Celeste Koestler, RNemail@example.com|
|Contact: Peggy Weivodafirstname.lastname@example.org|
|United States, Minnesota|
|Mayo Clinic in Rochester||Recruiting|
|Rochester, Minnesota, United States, 55905|
|Contact: Celeste M Koestler, RN 507-255-2200 email@example.com|
|Principal Investigator: Yong-Mei Cha, MD|
|Principal Investigator:||Yongmei Cha, MD||Mayo Clinic|