Detecting Ongoing Acute Ischemia Prior to Troponin Elevation with Hyper-Acute Native T1 Mapping: From Ultrastructural Tissue Changes to Early Diagnosis of Non-ST-Elevation Myocardial Infarction (RF_SA_494)

Saturday, February 1, 2025

11:00 AM – 11:10 AM East Coast USA Time

Location: Blue Room PreFunction

Presenting Author(s)

SC

Shing Fai Chan, PhD

Research Assistant Professor
Department of Radiology and Imaging Sciences, Indiana University School of Medicine

Primary Author(s)

SC

Shing Fai Chan, PhD

Research Assistant Professor
Department of Radiology and Imaging Sciences, Indiana University School of Medicine

Co-Author(s)

TL

Ting Liu, PhD

professor
The First Hospital of China Medical University, China (People's Republic)
DS

Dhirendra Singh, PhD

Assistant Professor
Indiana University
YH

Yuheng Huang, MS

Visiting Graduate Researcher
Radiology and Imaging Sciences, Indiana University School of Medicine
Hsin-Jung Yang, PhD

Assistant Professor
Cedars-Sinai Medical Center
GY

Ghazal Yoosefian

Student
Indiana University School of Medicine
RT

Richard LQ. Tang, MD

Faculty
Indiana University School of Medicine
BT

Balaji Tamarappoo, MD

Cardiac Imaging Specialist
Banner University Medical Center Phoenix
AH

Andrew G. Howarth, MD, PhD

Associate Professor
Libin Cardiovascular Institute; University of Calgary, Canada
Keyur P. Vora, MD, MS, FACC

Cardiologist, Assistant Professor of Medicine
Indiana University School of Medicine
AK

Andreas Kumar, MD

doctor
Northern Ontario School of Medicine, Sudbury,Ontario, Canada, Canada
Rohan Dharmakumar, PhD

Executive Director
Indiana University School of Medicine

Background: Timely detection of acute ischemia in patients with non-ST-elevation MI (NSTEMI+) is crucial for the prompt initiation of treatment. Conventional biomarkers, such as high-sensitivity cardiac troponin-I (hs-cTnI), may require several hours from onset of myocardial injury to exhibit a detectable rise, potentially leading to delays in diagnosis and therapeutic intervention. We hypothesized that hyper-acute native T1 mapping using CMR could facilitate the rapid identification of active ischemia. This hypothesis was initially studied in canine models of ischemia and subsequently evaluated in patients with suspected NSTEMI+.

Methods:

We ligated the left anterior descending (LAD) coronary artery inside a CMR system to induce no-flow ischemia in a canine model (n=18) and performed serial T1 and T2 mapping every five minutes from onset of ischemia to 90 mins. We obtained myocardial tissue biopsies at baseline, and at defined time points from both ischemic and non-ischemic (remote) regions, and then analyzed the cardiac ultrastructure using transmission electron microscopy (TEM). In addition, we performed native cine imaging, along with T1 and T2 mapping, on patients with suspected of NSTEMI+ (n=16) and NSTEMI- (n=9) using a 3T CMR system.

Results:

T1 values increased significantly from 1182±51ms (baseline) to 1265±56ms (5 to 10 mins after onset of ischemia), p< 0.05; and continued to rise through 90 min (1327±56ms), while T2 values showed no significant changes over the first 90 min in canine models of ischemia. TEM showed that the mitochondrial cristae density in ischemic zones was significantly decreased: 100±9.8%(baseline) vs 54±4.4% (5-min of ischemia), p< 0.01, and further declined to 40.6±9.8% by 90 mins. After 5-min of ischemia, both mitochondrial width and circuity index showed no difference compared to baseline, but both paraments increased significantly: (a) mitochondrial width: 990.4±118.6nm (15 min of ischemia) vs 577±61nm (baseline), p< 0.01; (b) circuity index: 0.87±0.04 (15 min of ischemia) vs 0.8± 0.04 (baseline), p< 0.01, and continued to rise and persist at high levels 90 min: 1091±148 nm (mitochondrial width) and 0.94±0.01 (circuity index), respectively. Cristae number was significantly reduced 13.8±2.7 (baseline) vs 24.4±2.9 (5 min of ischemia), p< 0.01, and remained low and reduced to 7.6±1.8 by 90 min. DT1 value in patients were significantly higher in patients positive for NSTEMI than in negative for MI (NSTEMI-): 11.51±3.7% vs 2.06±1.7%, p< 0.0001. [hs-cTnI] levels from NSTEMI+ gradually increased over time and were only significantly higher than NSTEMI-, several hours after CMR exam and peaked at 24 hrs (12.6±7.3ng/ml vs 0.03±0.02ng/ml, p< 0.05).

Conclusion:

Our findings support the notion that hyper-acute native T1 mapping shows promise for early detection of myocardial ischemia before hs-cTnI elevation, especially in NSTEMI patients. This could enable earlier diagnosis and timely intervention in patients requiring immediate care.