Clinical trial NCT03493516: Prediction of ARrhythmic Events With Positron Emission Tomography II
Official title: Prediction of ARrhythmic Events With Positron Emission Tomography II
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Sudden Cardiac Arrest
Ischemic Cardiomyopathy
Congestive Heart Failure
Keywords: Positron Emission Tomography
Sympathetic Innervation
Sudden Death
Ventricular Fibrillation
LMI-1195
Ischemic Cardiomyopathy
Risk Prediction
Lead sponsor: State University of New York at Buffalo
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Lantheus Medical Imaging
First posted: 2018-04-10
Enrollment: 302
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population comprises adult patients of either sex with ischemic cardiomyopathy who have an ejection fraction ≤ 35% and New York Heart Association Class II or III CHF or an ejection fraction ≤ 30% and Class I CHF who are candidates to place an ICD for the primary prevention of SCA. Subjects already having a primary prevention ICD are eligible if they have not yet received an appropriate ICD shock for ventricular arrhythmias.

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Sudden Cardiac Arrest Events
timeFrame: Through study completion, an average of 3 years
Secondary outcomes:
Other outcomes:
measure: All cause cardiac mortality
timeFrame: Through study completion, an average of 3 years
measure: All appropriate ICD therapies
timeFrame: Through study completion, an average of 3 years
measure: Hospitalization for heart failure and myocardial infarction.
timeFrame: Through study completion, an average of 3 years
Locations:
city: Buffalo
country: United States
facility: University at Buffalo Clinical and Translational Research Center
state: New York
Study officials:
affiliation: University at Buffalo
name: John M Canty, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.
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.