Ultra High Resolution CT to Assess Role of Intramyocardial Fat and Delayed Enhancement in Ventricular Arrhythmogenesis

This research is being done to determine how well cardiac computed tomography (CT) scanning measures of fat within the heart can predict abnormal heart rhythms and how well cardiac CT can measure scar within the heart versus cardiac magnetic resonance imaging (MRI).

• People who have been enrolled in PROSe-ICD (NA_00045142) and Reynolds (NA_00037404) studies may join
• The procedures, tests, drugs or devices that are part of this research and will be paid for by the study

Study Overview

• Status: Active, not recruiting
• Conditions: Ventricular Arrhythmias

Detailed Description

The investigators aim to investigate the role of intramyocardial fat on ventricular arrhythmogenesis. Intramyocardial fat deposition has been frequently observed in patients with ischemic heart disease and is readily detectable by multi-detector computed tomography (MDCT) with high sensitivity and specificity, unlike other modalities. Like intramyocardial fat, reentrant ventricular tachycardia (VT) tends to occur late after the onset of myocardial infarction and the investigators hypothesize that lipomatous metaplasia within the infarct may precipitate later onset ventricular arrhythmias (VA). Prior studies have shown that intramyocardial fat correlates with slow myocardial conduction velocity and with critical circuits for VA but the investigators do not know the causal relationship between intramyocardial fat and future risk of VA.

Intramyocardial fat deposition or lipomatous metaplasia has been frequently observed in patients with ischemic heart disease and is readily detectable by multi-detector computed tomography (MDCT) with high sensitivity and specificity. Like intramyocardial fat, reentrant ventricular tachycardia (VT) tends to occur late after the onset of myocardial infarction and the investigators hypothesize that there may be a causal relationship. Prior studies have shown that intramyocardial fat correlates with slow myocardial conduction velocity and with critical circuits for VT in patients referred for VT ablation who already manifest VA.

However, the correlation of intramyocardial fat on CT with late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) in a general population of patients with ischemic cardiomyopathy with no prior history of VA has not been reported. Specifically, it is unknown whether the presence, distribution and/or volume of fat is an independent predictor of VA. Further CMR is less widely available in medical centers, and is more expensive with longer scanning times compared to CT. CT provides higher spatial resolution, is widely available and is not as susceptible to magnetic interference from internal cardiac defibrillator (ICD) generators and thus makes it an attractive imaging modality for risk stratification, particularly longitudinally over time.

Hypothesis: The investigators' objective is to define the prevalence and distribution of intramyocardial fat in patients with ischemic heart disease scheduled for or with in-situ implantable defibrillators. Further, the investigators aim to assess the independent association of intramyocardial fat with VA and determine whether it adds any utility above LGE measured by CMR. Finally, the investigators will assess how well delayed enhanced CT correlates with LGE on MRI and test its association with ventricular arrhythmias.

Importance: The significance of the investigators' research is that the investigators will: 1) test whether intramyocardial fat on CT can be used as a non-invasive tool for sudden cardiac death risk stratification in patients who have or are scheduled to undergo ICDs, and 2) define whether delayed enhancement CT is comparable to the current non-invasive gold standard of CMR for identifying myocardial scar.

• Study Type: Observational
• Enrollment (Estimated): 110

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Medical Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The investigators will recruit patients with a history of an ischemic cardiomyopathy from the current PROSe-ICD to undergo a cardiac CT performed using an ultra-high-resolution (UHR) CT scanner (Canon, Precision) using iodinated contrast for (a) identification of myocardial fat, and (b) myocardial scar visualization (areas of delayed contrast enhancement).

Description

Inclusion Criteria:

• Patients aged 18 or older with history of ischemic cardiomyopathy enrolled in the current Reynolds study or PROSe-ICD study will be asked to participate
• Women of child bearing potential must demonstrate a negative pregnancy test within 24 hours of the study CT
• Ability to understand and willingness to sign the Informed Consent Form

Exclusion Criteria:

• Known allergy to iodinated contrast media
• Patients with glomerular filtration rate (GFR) ≤ 30 mL/min will not be enrolled in the study due to the use of intravenous iodinated contrast agents
• Atrial fibrillation or uncontrolled tachyarrhythmia
• Evidence of severe symptomatic heart failure (NYHA Class III or IV)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
PROSe-ICD; PROSe-ICD [NCT00733590/ Institutional Review Board (IRB) NA_00045142], a large prospective cohort study of patients who received an ICD for primary prevention.
Reynolds study; Functional Energetics (Reynolds study, NA_00037404), a study with conventional contrast-enhanced 1H MRI to determine ventricular geometry, global and regional function, as well as infarct size characteristics following delayed contrast enhancement.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of intramyocardial fat in patients with ischemic heart disease	The primary aim is to test whether intramyocardial fat on MDCT is as effective or adds additional utility to risk stratification for VA above that of CMR-LGE characteristics in ischemic cardiomyopathy patients who are candidates for ICD therapy or have in situ ICDs. Our objective is to define the prevalence and distribution of intramyocardial fat in patients with ischemic heart disease scheduled for or with in-situ implantable defibrillators. Further, we aim to assess the independent association of intramyocardial fat with VA and determine whether it adds any utility above LGE measured by CMR.	2 years
Prevalence of delayed enhanced CT detected scar	Comparison of the scar distribution on delayed enhanced CT with LGE on cardiac MRI. The significance of our research is that we will test whether delayed enhanced CT can be used as a non-invasive tool for sudden cardiac death risk stratification in patients with ischemic heart disease and whether delayed enhancement CT is comparable to the current non-invasive gold standard of CMR for identifying myocardial scar.	2 years
Quantification of delayed enhanced CT detected scar	Comparison of the scar distribution on delayed enhanced CT with LGE on cardiac MRI. The significance of our research is that we will test whether delayed enhanced CT can be used as a non-invasive tool for sudden cardiac death risk stratification in patients with ischemic heart disease and whether delayed enhancement CT is comparable to the current non-invasive gold standard of CMR for identifying myocardial scar.	2 years

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Canon Medical Systems, USA
• Investigators: Principal Investigator: Jonathan Chrispin, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2021
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: May 14, 2020
• First Submitted That Met QC Criteria: May 14, 2020
• First Posted (Actual): May 19, 2020

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Ischemic Cardiomyopathy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac
• Other Study ID Numbers: IRB00236647

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No