Prediction of ARrhythmic Events With Positron Emission Tomography II

Congestive Heart Failure Clinical Trial

— PAREPET II  

Official title:

Prediction of ARrhythmic Events With Positron Emission Tomography II

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03493516
• Other study ID #: HL-130266
• Secondary ID: R01HL130266-01
• Status: Active, not recruiting
• Start date: April 8, 2018
• Est. completion date: December 31, 2025

Study information

• Verified date: January 2024
• Source: State University of New York at Buffalo
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Sudden cardiac death continues to be a major contributor to mortality in patients with ischemic cardiomyopathy. While implantable defibrillators can prevent death from ventricular arrhythmias, our current approach to identify patients at highest risk primarily rests on demonstrating a reduction in left ventricular ejection fraction less than 35%. The purpose of this observational cohort study is to prospectively test whether this can be enhanced by quantifying the amount of sympathetic denervation, left ventricular end-diastolic volume or brain natriuretic peptide levels.

Description:

Using current guidelines based primarily on ejection fraction (EF), only one-quarter of patients receiving an implantable cardiac defibrillator (ICD) for the primary prevention of sudden cardiac arrest (SCA) require appropriate ICD therapy within 5 years. The NIH-sponsored PAREPET study (Prediction of ARrhythmic Events with Positron Emission Tomography, ClinicalTrials.gov, NCT01400334) identified four independent risk factors that predict SCA or ICD equivalent in patients with ischemic cardiomyopathy. Using retrospectively defined cut-points, the absence of these risk factors identified 38% of the cohort with a very low risk of SCA (<1% per year). This rate is actually lower than the 1.5-2% annual rate of SCA among patients with coronary artery disease and mild left ventricular (LV) dysfunction, who are not considered candidates for a primary prevention ICD. This proposal will prospectively determine whether these risk factors can form the basis of a clinically applicable approach to identify a subgroup of patients who are candidates for an ICD, but are at low enough risk of SCA to have an ICD safely withheld. Our long-term goal is to develop better approaches to identify patients with coronary artery disease who are most likely to benefit from prevention of SCA with placement of an implantable defibrillator.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 302
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Coronary artery disease (by cardiac catheterization or definite myocardial infarction)
• ICD implantation for the primary prevention of SCA
• Primary prevention patients with a Biventricular ICD
• Eligible immediately when this is placed to prevent dysynchrony related to intermittent RV pacing and the native QRS duration is = 130 msec in the absence of pacing.
• Eligible 6 months after implantation when the native QRS duration prior to implant is >130 msec or there is persistent RV pacing.
• Optimal medical therapy for heart failure.

Exclusion Criteria:

• Plans for coronary revascularization (due to the independent impact on SCA)
• Contraindication for PET (i.e. claustrophobia, pregnancy, physical limitation)
• Tricyclic antidepressant use (inhibits norepinephrine and LMI1195 uptake)
• Comorbidities limiting life expectancy <2yr.
• Age <18 years or inability to provide informed consent
• Primary prevention ICD/BiV recipients who have received an appropriate ICD shock prior to enrollment

Related Conditions & MeSH terms

• Cardiomyopathies
• Congestive Heart Failure
• Death, Sudden, Cardiac
• Heart Failure
• Ischemic Cardiomyopathy
• Sudden Cardiac Arrest

Intervention

Diagnostic Test:
• PET scan quantifying sympathetic denervation using [18F]-LMI1195
A cardiac PET scan will be obtained to quantify the percentage of the left ventricle that is denervated and has reduced uptake of the sympathetic nerve tracer [18F]-LMI1195

Locations

Country	Name	City	State
United States	University at Buffalo Clinical and Translational Research Center	Buffalo	New York

Sponsors (3)

Lead Sponsor	Collaborator
State University of New York at Buffalo	Lantheus Medical Imaging, National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Fallavollita JA, Dare JD, Carter RL, Baldwa S, Canty JM Jr. Denervated Myocardium Is Preferentially Associated With Sudden Cardiac Arrest in Ischemic Cardiomyopathy: A Pilot Competing Risks Analysis of Cause-Specific Mortality. Circ Cardiovasc Imaging. 2017 Aug;10(8):e006446. doi: 10.1161/CIRCIMAGING.117.006446. — View Citation

Fallavollita JA, Heavey BM, Luisi AJ Jr, Michalek SM, Baldwa S, Mashtare TL Jr, Hutson AD, Dekemp RA, Haka MS, Sajjad M, Cimato TR, Curtis AB, Cain ME, Canty JM Jr. Regional myocardial sympathetic denervation predicts the risk of sudden cardiac arrest in ischemic cardiomyopathy. J Am Coll Cardiol. 2014 Jan 21;63(2):141-9. doi: 10.1016/j.jacc.2013.07.096. Epub 2013 Sep 25. — View Citation

Goldberger JJ, Basu A, Boineau R, Buxton AE, Cain ME, Canty JM Jr, Chen PS, Chugh SS, Costantini O, Exner DV, Kadish AH, Lee B, Lloyd-Jones D, Moss AJ, Myerburg RJ, Olgin JE, Passman R, Stevenson WG, Tomaselli GF, Zareba W, Zipes DP, Zoloth L. Risk stratification for sudden cardiac death: a plan for the future. Circulation. 2014 Jan 28;129(4):516-26. doi: 10.1161/CIRCULATIONAHA.113.007149. No abstract available. — View Citation

Malhotra S, Canty JM Jr. Life-Threatening Ventricular Arrhythmias: Current Role of Imaging in Diagnosis and Risk Assessment. J Nucl Cardiol. 2016 Dec;23(6):1322-1334. doi: 10.1007/s12350-015-0392-0. Epub 2016 Jan 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	All cause cardiac mortality	Adjudicated total cardiac mortality (SCA + non-sudden cardiac death).	Through study completion, an average of 3 years
Other	All appropriate ICD therapies	Adjudicated appropriate ICD therapies (ICD shock and anti-tachycardia pacing) for ventricular arrhythmias. Appropriate ICD therapies will be determined from ICD device interrogation.	Through study completion, an average of 3 years
Other	Hospitalization for heart failure and myocardial infarction.	Interval hospitalizations for heart failure or myocardial infarction will be assessed via phone follow-up at 3 month intervals. Subjects having either will be invited to return for a repeat PET scan, echocardiogram and serum sampling to assess whether the underlying substrate for arrhythmogenesis has changed.	Through study completion, an average of 3 years
Primary	Sudden Cardiac Arrest Events	The primary end-point will be SCA or ICD equivalent as used in PAREPET. This will consist of ICD therapies for ventricular fibrillation or ventricular tachycardia >240 bpm, and adjudicated arrhythmic death using the modified Hinkle-Thaler criteria.	Through study completion, an average of 3 years