Altered myocardial oxygenation and impaired energy efficiency: a pilot study in patients with light chain cardiac amyloidosis

Presenting Author(s)

• 

  Jie Zheng, PhD, FSCMR

  Professor
  Washington University in St. Louis
  Saint Louis, Missouri, United States

Primary Author(s)

• LD

  Liya Dai, MD

  associate chief physician
  The Fifth Affiliated Hospital of Wenzhou Medical University
  Lishui, China (People's Republic)

Co-Author(s)

• KW

  Keyan Wang, MD

  physician
  the first affiliated hospital of zhengzhou university, China (People's Republic)
• RL

  Ran Li, MSc

  PhD student
  Washington University in St. Louis
  St. Louis, Missouri, United States
• JQ

  Jinghan Qiao, MD

  physician
  the first affiliated hospital of zhengzhou university, China (People's Republic)
• CB

  Caleb Berberet, BSc

  research assistant
  Washington University in St. Louis
  St. Louis, Missouri, United States
• QH

  Qi Huang, PhD

  Postdoc
  Washington University in St. Louis, Missouri, United States
• jj

  jiansong ji, MD, PhD

  Chief physician
  The Fifth Affiliated Hospital of Wenzhou Medical University, China (People's Republic)
• SB

  Scott Bugenhagen, MD, PhD

  Cardiothoracic Radiologist
  Washington University School of Medicine
  St. Louis, Missouri, United States
• TS

  Thomas Schindler, MD

  Professor
  Washington University School of Medicine, United States
• LP

  Linda Peterson, MD

  Professor
  Washington University School of Medicine, United States
• PW

  Pamela Woodard, MD

  Professor
  Washington University School of Medicine, Missouri, United States

Background: Light chain cardiac amyloidosis (AL-CA) is an infiltrative cardiomyopathy characterized by the deposition of misfolded immunoglobulin light chains in the myocardium. By utilizing ¹¹C-Acetate positron emission tomography, patients with CA had increased total myocardial oxygen consumption (MOV₂) and reduced myocardial external efficiency (MEE), compared to healthy controls. The purpose of this study was to leverage newly developed CMR oxygenation techniques for the evaluation of altered myocardial oxygen metabolism secondary to the toxic protein in patients with AL-CA.

Methods: This prospective study included 10 AL-CA patients and 10 healthy controls (HCs). All subjects underwent cine imaging for the quantification of left ventricular global longitudinal strain (LVGLS), pre- and post-contrast T1 mapping imaging for the calculation of myocardial extracellular volume (ECV) maps, and first-pass perfusion imaging after a bolus injection of MR gadolinium contrast agents. In addition, a new CMR technique was applied to quantify myocardial oxygen extraction fraction (mOEF) maps. Segmented (AHA style) analysis was performed in all maps. Myocardial blood flow (MBF) via the slope of the first-pass perfusion curves, myocardial oxygen consumption (MVO₂), and myocardial external efficiency (MEE) were all quantified for statistical analysis.

Results: In patients with AL-CA (Fig. 1), mOEF, native T1, and ECV values were all significantly elevated compared to HCs (all p ≤ 0.001), whereas MBF (p = 0.013), MVO₂ (p = 0.041) and LVGLS (p = 0.006) were significantly reduced. MEE in AL-CA patients was lower (63.2 versus 77.2 in HCs) whereas total MVO₂ was higher (6.25 versus 4.6), although neither difference was statistically significant (both p > 0.05). The mOEF showed strong correlation with LV mass (r = 0.72), moderate correlation with ECV (r = 0.60, p = 0.006), native T1 (r = 0.64, p = 0.018), LVGLS (r = -0.52, p = 0.019) and MBF (r = -0.65, p = 0.015). The MVO₂ exhibited moderately negative correlation with ECV (r = -0.57, p = 0.022), native T1 (r = -0.56, p = 0.026), and LV mass (r = -0.60, p = 0.015). The MEE demonstrated a strong positive correlation with LVEF (r = 0.78, p < 0.001) and a moderate correlation with LVGLS (r = 0.59, p = 0.015).

Conclusion: Our pilot CMR study demonstrated the feasibility of quantification of myocardial oxygenation and associated mechanical efficiency in AL-CA, without involving any irradiation. Elevated mOEF and reduced MBF may reflect microvascular dysfunction from amyloid infiltration while impaired MEE and increased total MVO₂ may underscore metabolic-mechanical uncoupling.

Representative ECV (top row) and mOEF (bottom row) images from HC (A) and AL-CA patients (B and C). Both mOEF and ECV increase progressively from HC to AL-CA. AL-CA, immunoglobulin light chain cardiac amyloidosis; HC, healthy control; ECV, extracellular volume fraction; mOEF, myocardial oxygen extraction fraction.
Differences in multiple parameters (mOEF, MBF, MVO2, total MVO2, MEE and EW) between HC and AL-CA groups. Statistically significant differences were observed for mOEF, MBF and MVO2 (* p<0.05, *** p<0.001). mOEF, myocardial oxygen extraction fraction; MBF, myocardial blood flow; MVO2, myocardial oxygen consumption; EW, external work; MEE, myocardial external efficiency.