Author + information
- Andrea Barison, MD, PhD∗ (, )
- Giovanni Donato Aquaro, MD and
- Pier Giorgio Masci, MD
- ↵∗Fondazione “G. Monasterio” CNR–Regione Toscana, Via Moruzzi, 1–56124 Pisa, Italy.
Measuring myocardial extracellular volume (ECV) with cardiovascular magnetic resonance is achieving increasing importance because it allows quantification of diffuse fibrosis not detectable with conventional late gadolinium enhancement techniques. However, the conditio sine qua non to accurately measure myocardial ECV consists of achievement of a steady-state equilibrium of gadolinium-based contrast agent between plasma and the cardiac interstitium. Currently, this requires a rather complicated and time-consuming protocol, which hinders the large-scale clinical application of this technique. In a recent issue of iJACC, White et al. (1) wrote a seminal paper validating a bolus-only (pseudo-equilibrium) technique to estimate the ECV in a wide range of cardiac diseases, with different degrees of extracellular matrix expansion, by comparing it against both a previously validated equilibrium (infusion) technique and histology. In particular, they demonstrated that a pseudo-equilibrium protocol (15 min after a 0.1 mmol/kg gadolinium bolus) yielded ECV estimates comparable to those obtained with the equilibrium protocol (0.1 mmol/kg bolus + 0.011 mmol/kg/min gadolinium infusion), even though the former overestimated myocardial ECV in case of an important expansion of cardiac interstitium (i.e., ECV >0.4, as in the case of amyloid deposition or fibrotic scars). Moreover, both techniques showed very tight correlation with the histologically determined collagen volume fraction.
Overall, the paper by White et al. (1) paves the way for clinical studies on cardiac interstitium remodeling and for further methodological studies exploring gadolinium contrast kinetics with particular regard to diseases with extreme ECV expansion. In previous work, Flett et al. (2) provided evidence on how the equilibrium can be reached with a constant gadolinium infusion (0.1 mmol/kg + 0.0011 mmol/kg/min gadolinium) in patients with aortic stenosis or hypertrophic cardiomyopathy. They acquired T1 values every 5 min and demonstrated that the ECV remained constant over time and correlated with histology. Another group (3) validated a different pseudo-equilibrium technique (12 to 50 min after 0.2 mmol/kg gadolinium bolus) against a different equilibrium technique (0.1 mmol/kg bolus + 0.0017 mmol/kg/min gadolinium infusion) in healthy volunteers, again by acquiring T1 values every 5 min and demonstrating that ECV remained constant.
Conversely, little is known about gadolinium kinetics in cardiac amyloidosis, which is characterized by marked interstitial expansion and fast gadolinium accumulation but also very rapid gadolinium washout from both the myocardium and the blood pool (4). In the current paper (1), T1 acquisitions were performed only 15 min after bolus and during infusion, with no serial T1 acquisitions to demonstrate a blood–myocardium steady-state equilibrium. Moreover, the histological validation provided by the authors was limited to patients with aortic stenosis undergoing valve replacement or patients with hypertrophic cardiomyopathy undergoing septal myectomy (1,2). Histological validation of equilibrium or pseudo-equilibrium techniques is still lacking for cardiac disease with ECV >0.4, such as in cardiac amyloidosis, in which interstitial remodeling may be ascribed to disparate mechanisms (including myocyte necrosis, amyloid deposition, and scarring).
Finally, we agree with the authors (1) that further technical development is required before a bolus-only protocol for ECV measurement becomes clinically available. This protocol should account for all potentially relevant parameters (contrast delivery rate, dose, agent, and acquisition timing) and be validated for diverse cardiac pathologies.
- American College of Cardiology Foundation
- White S.K.,
- Sado D.M.,
- Fontana M.,
- et al.
- Flett A.S.,
- Hayward M.P.,
- Ashworth M.T.,
- et al.
- Emdin M.,
- Aquaro G.D.,
- Pugliese N.R.,
- et al.