Ischemic CardiomyopathyPAREPETNCT01400334
Prediction of ARrhythmic Events With Positron Emission Tomography
An observational study of Ischemic Cardiomyopathy and Hibernating Myocardium, run by State University of New York at Buffalo at 1 site in United States.
Trial summary
The hypothesis of PAREPET is that hibernating myocardium (viable myocardium with reduced resting flow) and/or viable but denervated myocardium can predict the risk of sudden death in subjects with ischemic cardiomyopathy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemic Cardiomyopathy, Hibernating Myocardium, Nerve; Disorder, Sympathetic
- What is being tested?
- Positron Emission Tomography
- Type of treatment
- Surgery or procedure
- How many people
- 257 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2004to Dec 2012
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Residents of Western New York referred for an implantable cardiac defibrillator, transthoracic echocardiography, and/or coronary angiography
Who may be able to join
- LV EF ≤35% (by nuclear imaging, cardiac catheterization or echocardiography)
- Coronary artery disease documented by cardiac catheterization, a history of definite myocardial infarction, or reversible ischemia on nuclear imaging
- New York State Heart Association functional Class I-III heart failure
- Not a candidate for surgical or percutaneous coronary revascularization at the time of enrollment
Who cannot join
- History of resuscitated sudden cardiac death, sustained ventricular tachycardia, appropriate implantable cardiac defibrillator (ICD) discharge, or unexplained syncope
- Myocardial infarction within 30 days
- Coronary artery bypass grafting within 1 year
- Percutaneous intervention within 3 months
- Claustrophobia or physical limitation that would preclude PET scanning
- Pregnancy
Show all 9Show fewer
- Tricyclic antidepressant drug therapy
- Comorbidities that would be expected to result in noncardiac death within 2 years
- Inability to provide informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Hibernating Myocardium and Sudden Cardiac Death
The hypothesis of PAREPET is that hibernating myocardium (viable myocardium with reduced resting flow) and/or viable but denervated myocardium can predict the risk of sudden death in subjects with ischemic cardiomyopathy.
Read the detailed description
Currently available electrophysiological approaches are limited in their ability to identify the majority of patients with CAD and LV dysfunction that succumb to sudden cardiac death (SCD). Half of the patients developing SCD are not inducible at electrophysiological testing underscoring the need for new ways to identify substrates leading to arrhythmic death. Viable chronically dysfunctional with reduced resting flow, or hibernating myocardium, not amenable to revascularization appears to be a major risk factor for subsequent cardiac death and is present in up to 60% of patients with ischemic cardiomyopathy. Cause specific mortality data is limited but appears to be arrhythmic rather than from fatal myocardial infarction or progressive heart failure. Revascularization improves survival but most patients with hibernating myocardium are managed medically due to prohibitive procedural risks or technical limitations. Basic studies in swine with hibernating myocardium demonstrate SCD arising from VT/VF in the absence of myocardial scar or heart failure. The central hypothesis of this proposal is that the presence of hibernating myocardium as opposed to scar identifies a large subset of patients with ischemic cardiomyopathy that are at high risk for SCD. We further hypothesize that this risk is related to inhomogeneity in sympathetic innervation arising from chronic repetitive ischemia. PAREPET is a prospective observational study that will enroll patients with coronary disease, Class I-III heart failure and an ejection fraction ≤35%. Using positron emission tomography (PET), the frequency and amount of hibernating myocardium will be quantified in patients that are not candidates for coronary revascularization. Three Specific Aims are proposed. Aim 1 will determine whether imaging the mismatch between viability (preserved 18F-2-deoxyglucose) and reduced resting flow (13NH3) can predict an increased risk of SCD (or ICD discharge for VT/VF as a surrogate end-point) in hibernating myocardium. Aim 2 will image norepinephrine uptake using 11C-hydroxyephedrine to determine whether inhomogeneity in myocardial sympathetic innervation predicts SCD risk better than viability testing. Aim 3 will identify whether the substrate identified by PET is stable after an aborted SCD event by evaluating temporal changes in function, viability and sympathetic innervation in patients with an ICD. Our long-term objective is to develop better approaches to identify patients with CAD who are most likely to benefit from primary prevention of SCD with placement an ICD.
- Being tested
- Positron Emission Tomography
- Keywords
- Ischemic Cardiomyopathy, Sudden Cardiac Death, Positron Emission Tomography, Hibernating Myocardium, Denervated Myocardium
- Medical subject headings
- Death, Sudden, Cardiac
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Positron Emission TomographyRadiation
Quantification of cardiac function using positron emission tomography and: a)11C-meta-hydroxyephedrine [HED, 20 mCi (740 MBq)] to quantify sympathetic nerve function, b) 13N-ammonia [NH3, 20 mCi (740 MBq)] for regional perfusion, and c) 18F-2-deoxyglucose [FDG; 6.5 mCi (241 MBq)] administered during a hyperinsulinemic-euglycemic clamp to assess viability.
| Study group | Role | What they receive |
|---|---|---|
| Ischemic Cardiomyopathy | Subjects with ischemic cardiomyopathy [pre-enrollment left ventricular ejection fraction ≤0.35, with coronary artery disease documented by cardiac catheterization, a history of definite myocardial infarction, or reversible ischemia on nuclear imaging] who are considered eligible to receive an implantable cardiac defibrillator for the primary prevention of sudden cardiac death. Receives: Radiation: Positron Emission Tomography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sudden Cardiac Death
Adjudicated sudden cardiac death and implantable cardiac defibrillator therapy for fast ventricular tachycardia (>240 bpm) or ventricular fibrillation.
Measured: every 3 months
Secondary outcomes (1)
Cardiac Death
Sudden cardiac death and adjudicated non-sudden cardiac death
Measured: every 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2011 (estimated)
- Study startJul 2004
- Primary completionDec 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Ischemic CardiomyopathyStudies of the same condition, open and under way.
- More trials run by State University of New York at BuffaloThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 257 participants (actual)
Sponsor and investigators
- Lead sponsor
- State University of New York at Buffalo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, JOHN CANTY, State University of New York at Buffalo
- Investigators
- John M Canty, MD, Principal investigator, State University of New York at BuffaloJames A Fallavollita, MD, Principal investigator, State University of New York at Buffalo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01400334
- Sponsor's protocol ID
- HL76252
- Acronym
- PAREPET
- Status last verified
- Oct 2020
- First submitted
- 20 Jul 2011
- Last updated
- 12 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Fallavollita JA, Luisi AJ Jr, Michalek SM, Valverde AM, deKemp RA, Haka MS, Hutson AD, Canty JM Jr. Prediction of arrhythmic events with positron emission tomography: PAREPET study design and methods. Contemp Clin Trials. 2006 Aug;27(4):374-88. doi: 10.1016/j.cct.2006.03.005. Epub 2006 May 2.
PubMed 16647885Fallavollita 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.
PubMed 24076296Al-Zaiti SS, Fallavollita JA, Canty JM Jr, Carey MG. Electrocardiographic predictors of sudden and non-sudden cardiac death in patients with ischemic cardiomyopathy. Heart Lung. 2014 Nov-Dec;43(6):527-33. doi: 10.1016/j.hrtlng.2014.05.008. Epub 2014 Jul 2.
PubMed 24996250Al-Zaiti SS, Fallavollita JA, Wu YW, Tomita MR, Carey MG. Electrocardiogram-based predictors of clinical outcomes: a meta-analysis of the prognostic value of ventricular repolarization. Heart Lung. 2014 Nov-Dec;43(6):516-26. doi: 10.1016/j.hrtlng.2014.05.004. Epub 2014 Jun 29.
PubMed 24988910Zelt JGE, Wang JZ, Mielniczuk LM, Beanlands RSB, Fallavollita JA, Canty JM Jr, deKemp RA. Positron Emission Tomography Imaging of Regional Versus Global Myocardial Sympathetic Activity to Improve Risk Stratification in Patients With Ischemic Cardiomyopathy. Circ Cardiovasc Imaging. 2021 Jun;14(6):e012549. doi: 10.1161/CIRCIMAGING.121.012549. Epub 2021 Jun 9.
PubMed 34102857Fallavollita 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.
PubMed 28794139Cain ME. Impact of denervated myocardium on improving risk stratification for sudden cardiac death. Trans Am Clin Climatol Assoc. 2014;125:141-53; discussion 153.
PubMed 25125727
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hibernating Myocardium and Sudden Cardiac Death
- ClinicalTrials.gov ID
- NCT01400334
- Acronym / sponsor ID
- PAREPET / HL76252
- Keywords
- Ischemic Cardiomyopathy, Sudden Cardiac Death, Positron Emission Tomography, Hibernating Myocardium, Denervated Myocardium
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 257 participants (actual)
- Lead sponsor
- State University of New York at BuffaloUniversity, hospital or other
- Study start
- Jul 2004
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 22 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The hypothesis of PAREPET is that hibernating myocardium (viable myocardium with reduced resting flow) and/or viable but denervated myocardium can predict the risk of sudden death in subjects with ischemic cardiomyopathy.
Detailed description
Currently available electrophysiological approaches are limited in their ability to identify the majority of patients with CAD and LV dysfunction that succumb to sudden cardiac death (SCD). Half of the patients developing SCD are not inducible at electrophysiological testing underscoring the need for new ways to identify substrates leading to arrhythmic death. Viable chronically dysfunctional with reduced resting flow, or hibernating myocardium, not amenable to revascularization appears to be a major risk factor for subsequent cardiac death and is present in up to 60% of patients with ischemic cardiomyopathy. Cause specific mortality data is limited but appears to be arrhythmic rather than from fatal myocardial infarction or progressive heart failure. Revascularization improves survival but most patients with hibernating myocardium are managed medically due to prohibitive procedural risks or technical limitations. Basic studies in swine with hibernating myocardium demonstrate SCD arising from VT/VF in the absence of myocardial scar or heart failure. The central hypothesis of this proposal is that the presence of hibernating myocardium as opposed to scar identifies a large subset of patients with ischemic cardiomyopathy that are at high risk for SCD. We further hypothesize that this risk is related to inhomogeneity in sympathetic innervation arising from chronic repetitive ischemia. PAREPET is a prospective observational study that will enroll patients with coronary disease, Class I-III heart failure and an ejection fraction ≤35%. Using positron emission tomography (PET), the frequency and amount of hibernating myocardium will be quantified in patients that are not candidates for coronary revascularization. Three Specific Aims are proposed. Aim 1 will determine whether imaging the mismatch between viability (preserved 18F-2-deoxyglucose) and reduced resting flow (13NH3) can predict an increased risk of SCD (or ICD discharge for VT/VF as a surrogate end-point) in hibernating myocardium. Aim 2 will image norepinephrine uptake using 11C-hydroxyephedrine to determine whether inhomogeneity in myocardial sympathetic innervation predicts SCD risk better than viability testing. Aim 3 will identify whether the substrate identified by PET is stable after an aborted SCD event by evaluating temporal changes in function, viability and sympathetic innervation in patients with an ICD. Our long-term objective is to develop better approaches to identify patients with CAD who are most likely to benefit from primary prevention of SCD with placement an ICD.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ischemic Cardiomyopathy | – | Radiation: Positron Emission TomographySubjects with ischemic cardiomyopathy [pre-enrollment left ventricular ejection fraction ≤0.35, with coronary artery disease documented by cardiac catheterization, a history of definite myocardial infarction, or reversible ischemia on nuclear imaging] who are considered eligible to receive an implantable cardiac defibrillator for the primary prevention of sudden cardiac death. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Residents of Western New York referred for an implantable cardiac defibrillator, transthoracic echocardiography, and/or coronary angiography
Key inclusion criteria (4 listed)
- LV EF ≤35% (by nuclear imaging, cardiac catheterization or echocardiography)
- Coronary artery disease documented by cardiac catheterization, a history of definite myocardial infarction, or reversible ischemia on nuclear imaging
- New York State Heart Association functional Class I-III heart failure
- Not a candidate for surgical or percutaneous coronary revascularization at the time of enrollment
Key exclusion criteria (9 listed)
- History of resuscitated sudden cardiac death, sustained ventricular tachycardia, appropriate implantable cardiac defibrillator (ICD) discharge, or unexplained syncope
- Myocardial infarction within 30 days
- Coronary artery bypass grafting within 1 year
- Percutaneous intervention within 3 months
- Claustrophobia or physical limitation that would preclude PET scanning
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Positron Emission TomographyQuantification of cardiac function using positron emission tomography and: a)11C-meta-hydroxyephedrine [HED, 20 mCi (740 MBq)] to quantify sympathetic nerve function, b) 13N-ammonia [NH3, 20 mCi (740 MBq)] for regional perfusion, and c) 18F-2-deoxyglucose [FDG; 6.5 mCi (241 MBq)] administered during a hyperinsulinemic-euglycemic clamp to assess viability. | Radiation | Ischemic Cardiomyopathy |
Primary outcome
Sudden Cardiac Death
Time frame: every 3 months
Adjudicated sudden cardiac death and implantable cardiac defibrillator therapy for fast ventricular tachycardia (>240 bpm) or ventricular fibrillation.
1 secondary outcome
Cardiac Death
Time frame: every 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2020.
- Background: PubMed 16647885Fallavollita JA, Luisi AJ Jr, Michalek SM, Valverde AM, deKemp RA, Haka MS, Hutson AD, Canty JM Jr. Prediction of arrhythmic events with positron emission tomography: PAREPET study design and methods. Contemp Clin Trials. 2006 Aug;27(4):374-88. doi: 10.1016/j.cct.2006.03.005. Epub 2006 May 2.
- Results publication: PubMed 24076296Fallavollita 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.
- Results publication: PubMed 24996250Al-Zaiti SS, Fallavollita JA, Canty JM Jr, Carey MG. Electrocardiographic predictors of sudden and non-sudden cardiac death in patients with ischemic cardiomyopathy. Heart Lung. 2014 Nov-Dec;43(6):527-33. doi: 10.1016/j.hrtlng.2014.05.008. Epub 2014 Jul 2.
- Results publication: PubMed 24988910Al-Zaiti SS, Fallavollita JA, Wu YW, Tomita MR, Carey MG. Electrocardiogram-based predictors of clinical outcomes: a meta-analysis of the prognostic value of ventricular repolarization. Heart Lung. 2014 Nov-Dec;43(6):516-26. doi: 10.1016/j.hrtlng.2014.05.004. Epub 2014 Jun 29.
- Derived from this study: PubMed 34102857Zelt JGE, Wang JZ, Mielniczuk LM, Beanlands RSB, Fallavollita JA, Canty JM Jr, deKemp RA. Positron Emission Tomography Imaging of Regional Versus Global Myocardial Sympathetic Activity to Improve Risk Stratification in Patients With Ischemic Cardiomyopathy. Circ Cardiovasc Imaging. 2021 Jun;14(6):e012549. doi: 10.1161/CIRCIMAGING.121.012549. Epub 2021 Jun 9.
- Derived from this study: PubMed 28794139Fallavollita 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.
- Derived from this study: PubMed 25125727Cain ME. Impact of denervated myocardium on improving risk stratification for sudden cardiac death. Trans Am Clin Climatol Assoc. 2014;125:141-53; discussion 153.
Related trials for Ischemic Cardiomyopathy
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Recruiting
Positron Emission Tomography to Assess the Effect of Camzyos on Ischaemia in HOCM: PEACH Trial
Hypertrophic Obstructive Cardiomyopathy \(HOCM\), Left Ventricular Outflow Tract Obstruction
Recruiting
A Study Assessing Arrhythmia Mapping With a Multi-Electrode Mapping Catheter
Scar-related Atrial Tachycardia, Persistent Atrial Fibrillation
RecruitingObservational study
A 10-Minute Cardiovascular Magnetic Resonance Protocol for Cardiac Disease
Coronary Artery Disease, Myocarditis
Not yet recruitingObservational study
PAtient Similarity for Decision-Making in Prevention of Cardiovascular Toxicity (PACT): A Feasibility Study
Heart Failure, Coronary Artery Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John M Canty, MD principal investigator
State University of New York at Buffalo
James A Fallavollita, MD principal investigator
State University of New York at Buffalo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ischemic Cardiomyopathy and Hibernating Myocardium, run by State University of New York at Buffalo at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sudden Cardiac Death (time frame: every 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01400334, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2020.