Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve

NCT03249272 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: Pro00082447
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to assess microvascular function as determined by a cardiovascular magnetic resonance measurement of whole-heart (global) perfusion reserve. The goal is to determine the prevalence of MVD in two common forms of non-ischemic cardiomyopathy, hypertrophic cardiomyopathy (HCM) and idiopathic dilated cardiomyopathy (IDCM). The hypothesis that an optimized technique will provide robust detection of MVD and that a multifaceted approach will provide new insights into the pathophysiology of MVD, including the influence of myocardial scarring upon the presence and severity of MVD.

Conditions

Hypertrophic Cardiomyopathy; Non-ischemic Dilated Cardiomyopathy; Microvascular Ischaemia of Myocardium

Outcome Measures

Primary Outcomes (1)

• Prevalence of Microvascular Dysfunction (MVD) by a CMR Measurement of Whole-heart (Global) Perfusion Reserve Ratio in Patients With Hypertrophic Cardiomyopathy, Non-ischemic Cardiomyopathy, and Controls.

  Prevalence of microvascular dysfunction as determined by the CMR measure of global perfusion reserve ratio (GPR) in each these patient groups. MVD was considered present when either GPR was \<2.0 or regional stress perfusion abnormalities were present. In order to calculate this ratio, coronary sinus flow was measured twice: 1. prior to the the administration of adenosine/regadenoson 2. during the administration of adenosine/regadenoson GPR is a ratio of coronary sinus flow during the administration adenosine/regadenoson divided by the baseline coronary sinus flow measured prior to the administration. Regional perfusion abnormalities will be assessed at the time of adenosine/regadenoson administration.

  The prevalence of MVD will be determined based on the findings at the time of the scan on Day 1 of the study.

Secondary Outcomes (2)

• CMR Measurement of Global Perfusion Reserve Ratio

  The global perfusion ratio will be calculated from the measurements obtained at the time of the scan on Day 1 of the study.

• The Association Between Global Perfusion Reserve (GPR) Ratio and Regional Myocardial Scarring.

  Both global perfusion ratio and the presence of regional scarring will be determined/measured from the images obtained during the scan on Day 1 of the study.

Study Arms (3)

Hypertrophic cardiomyopathy

ACTIVE COMPARATOR

Drug: Regadenoson; Drug: Adenosine

Non-ischemic dilated cardiomyopathy

ACTIVE COMPARATOR

Drug: Regadenoson; Drug: Adenosine

Control

ACTIVE COMPARATOR

Drug: Regadenoson; Drug: Adenosine

Interventions

Regadenoson DRUG

Microvascular disease will be considered present if regional perfusion defects are observed or global perfusion reserve is reduced. For the assessment of microvascular disease, the adenosine and regadenoson groups will be combined, as the medications are considered interchangeable.

Control; Hypertrophic cardiomyopathy; Non-ischemic dilated cardiomyopathy

Adenosine DRUG

Microvascular disease will be considered present if regional perfusion defects are observed or global perfusion reserve is reduced. For the assessment of microvascular disease, the adenosine and regadenoson groups will be combined, as the medications are considered interchangeable.

Control; Hypertrophic cardiomyopathy; Non-ischemic dilated cardiomyopathy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women aged 18 years or older
• Cardiomyopathy patients
• Patients presenting for CMR with the clinical diagnosis of hypertrophic cardiomyopathy based on left ventricular wall thickness of at least ≥15 mm in the absence of any other cardiac or systemic cause of hypertrophy
• Patients presenting for CMR with the clinical diagnosis of idiopathic dilated cardiomyopathy based upon left ventricular ejection fraction ≤40%, LV end-diastolic diameter ≥55 mm or left ventricular end-systolic diameter ≤45 mm, and the absence of coronary stenoses on angiography.
• Control patients
• Patients presenting for CMR without evidence of obstructive coronary artery disease either by coronary angiography or stress testing.

You may not qualify if:

• Decompensated heart failure or hemodynamic instability
• Prior coronary revascularization (PCI or CABG) or myocardial infarction (as evidenced by previously elevated CPK-MB or troponin levels)
• Accelerating angina or unstable angina
• Inability to physically tolerate MRI or implanted objects that are MRI incompatible
• Inability to provide written informed consent obtained at time of study enrollment.
• Severe claustrophobia
• Advanced heart block or sinus node dysfunction
• Hypersensitivity or allergic reaction to regadenoson or adenosine
• Hypotension
• Active bronchospasm or history of hospitalization due to bronchospasm
• History of seizures
• Recent cerebrovascular accident
• Use of dipyridamole within the last 5 days
• Contraindication to aminophylline
• Severe renal insufficiency with estimated glomerular filtration rate \<30 ml/min/ 1.73 m2

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke Cardiovascular Magnetic Resonance Center

Durham, North Carolina, 27110, United States

Location

Related Publications (5)

• Camici PG, d'Amati G, Rimoldi O. Coronary microvascular dysfunction: mechanisms and functional assessment. Nat Rev Cardiol. 2015 Jan;12(1):48-62. doi: 10.1038/nrcardio.2014.160. Epub 2014 Oct 14.

  PMID: 25311229 BACKGROUND

• Klem I, Heitner JF, Shah DJ, Sketch MH Jr, Behar V, Weinsaft J, Cawley P, Parker M, Elliott M, Judd RM, Kim RJ. Improved detection of coronary artery disease by stress perfusion cardiovascular magnetic resonance with the use of delayed enhancement infarction imaging. J Am Coll Cardiol. 2006 Apr 18;47(8):1630-8. doi: 10.1016/j.jacc.2005.10.074. Epub 2006 Mar 27.

  PMID: 16631001 BACKGROUND

• Klem I, Greulich S, Heitner JF, Kim H, Vogelsberg H, Kispert EM, Ambati SR, Bruch C, Parker M, Judd RM, Kim RJ, Sechtem U. Value of cardiovascular magnetic resonance stress perfusion testing for the detection of coronary artery disease in women. JACC Cardiovasc Imaging. 2008 Jul;1(4):436-45. doi: 10.1016/j.jcmg.2008.03.010.

  PMID: 19356464 BACKGROUND

• Camici PG, Crea F. Coronary microvascular dysfunction. N Engl J Med. 2007 Feb 22;356(8):830-40. doi: 10.1056/NEJMra061889. No abstract available.

  PMID: 17314342 BACKGROUND

• Choudhury L, Mahrholdt H, Wagner A, Choi KM, Elliott MD, Klocke FJ, Bonow RO, Judd RM, Kim RJ. Myocardial scarring in asymptomatic or mildly symptomatic patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2002 Dec 18;40(12):2156-64. doi: 10.1016/s0735-1097(02)02602-5.

  PMID: 12505229 BACKGROUND

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic

Interventions

regadenoson; Adenosine

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Intervention Hierarchy (Ancestors)

Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Limitations and Caveats

Slow recruitment led to the end of the study.

Results Point of Contact

• Title: Han Kim, MD
• Organization: Duke Cardiovascular Magnetic Resonance Center

han.kim@duke.edu

9196683539

Study Officials

• Han Kim

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The reader of the CMR scan will be blinded to the stress agent used.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants undergoing cardiovascular magnetic resonance stress testing will be recruited and randomized to receive either regadenoson or adenosine.

Study Record Dates

• First Submitted: August 8, 2017
• First Posted: August 15, 2017
• Study Start: September 5, 2017
• Primary Completion: March 31, 2019
• Study Completion: March 31, 2019
• Last Updated: September 16, 2020
• Results First Posted: September 16, 2020

Record last verified: 2020-08

Locations

US (1)