Assessing Cardiomyocyte DNA Damage Using Cardiovascular Magnetic Resonance T1 Mapping: Insights From Comparative
Mizuki Ichikawa1, Shiro Nakamori1, Masaki Ishida2
1Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Insights
Cardiovascular magnetic resonance T1 mapping can detect cardiomyocyte DNA damage and fibrosis in dilated cardiomyopathy (DCM) patients. Higher DNA damage correlates with better myocardial recovery after treatment, independent of fibrosis.
Area of Science:
- Cardiology
- Biomedical Imaging
- Molecular Cardiology
Background:
- DNA damage in cardiomyocytes is a critical factor in heart failure progression, preceding apoptosis and fibrosis.
- Cardiovascular magnetic resonance (CMR) T1 mapping's role in assessing this DNA damage remains unclear.
Purpose of the Study:
- To investigate the relationship between CMR T1 mapping parameters and cardiomyocyte DNA damage in patients with dilated cardiomyopathy (DCM).
Main Methods:
- 36 DCM patients underwent endomyocardial biopsy and serial 3T CMR scans before and after therapy.
- Native and postcontrast T1 mapping were used to quantify extracellular volume (ECV).
- DNA damage (poly(ADP-ribose)) and collagen volume fraction (CVF) were assessed in biopsy specimens.
Main Results:
- Native T1 and ECV strongly correlated with CVF. Native T1 moderately correlated with DNA damage severity, while ECV did not.
- Higher native T1 relative to ECV indicated significant DNA damage.
- Baseline DNA damage, not CVF, predicted myocardial tissue recovery and improved ejection fraction after therapy.
Conclusions:
- Native T1 mapping is effective for detecting both DNA damage and fibrosis in DCM.
- An elevated native T1/ECV ratio suggests early myocardial injury preceding fibrosis.
- DNA damage assessment may have implications for predicting treatment response and myocardial recovery.
Background:
DNA damage in cardiomyocytes is a key pathological pathway in heart failure progression. It is a reversible process that precedes apoptosis and fibrosis. However, the utility of cardiovascular magnetic resonance T1 mapping for assessing DNA damage is uncertain.
Objectives:
This study aimed to evaluate the relationship between T1 mapping and cardiomyocyte DNA damage in patients with dilated cardiomyopathy (DCM).
Methods:
We identified 36 recent-onset DCM patients undergoing endomyocardial biopsy and serial 3T cardiovascular magnetic resonance before and after guideline-directed therapy. Extracellular volume (ECV) was quantified from native and postcontrast T1 mapping. DNA damage was assessed via poly(ADP-ribose) quantification in biopsy specimens, alongside collagen volume fraction (CVF) measurement.
Results:
Native T1 and ECV showed a strong correlation with histological CVF (r = 0.62 and r = 0.67, respectively; P < 0.001), while native T1 moderately correlated with the severity of cardiomyocyte DNA damage (r = 0.41, P = 0.01), but ECV did not. This association remained significant after controlling for CVF. Patients with substantial DNA damage have significantly higher native T1 for an equivalent ECV (P = 0.004). In the absence of severe fibrosis, myocardial tissue recovery following guideline-directed therapy, along with improvements in left ventricular ejection fraction and reductions in left ventricular cavities, was associated with baseline DNA damage (r = -0.49, P = 0.004) but not with CVF (r = -0.17, P = 0.38).
Conclusions:
Native T1 mapping effectively detects DNA damage and fibrosis, revealing different pathophysiological mechanisms behind the increased native T1 and ECV. A disproportionate increase in native T1 relative to ECV suggests early myocardial injury preceding fibrosis in DCM, with potential implications for myocardial tissue recovery after guideline-directed therapy.
