Quantification of diffuse myocardial fibrosis by cardiac magnetic resonance imaging

Background. Diffuse myocardial fibrosis plays a key role in the development and progression of non-ischemic cardiomyopathy and heart failure. Thus, a non-invasive method for the quantification of diffuse myocardial fibrosis for diagnosis and risk assessment appears highly desirable, but is currently not available in clinical routine. Recent data indicate that diffuse myocardial fibrosis can be quantified by cardiac magnetic resonance imaging (CMR) using a particular imaging sequence after contrast administration (T 1 -mapping). The amount of diffuse myocardial fibrosis by CMR T1 -mapping was highly correlated with the histological degree of fibrosis in a small group of patients. Although the method is very promising it has not been standardized and studied in larger patient numbers. Aim of the study. The aim of the study is to establish a new standard method for the quantification of diffuse myocardial fibrosis by CMR T1 -mapping. Individual T1 times by CMR will be correlated with histology of myocardial biopsies. Study design. It has been shown, that an increased collagen deposition and myocardial fibrosis is present in heart failure with normal ejection fraction (HFNEF). In this single-centre study, 110 patients with HFNEF will undergo myocardial biopsy and will be referred for CMR T1 -mapping by the study group of Doz. Bonderman (FWF protocol 009, "PREDICTORS OF OUTCOME IN HEART FAILURE WITH NORMAL EJECTION FRACTION"). For T1 - mapping ten mid-ventricular images will be acquired sequentially at increasing inversion times (50 to 1,000 ms) 15 min after contrast administration (gadolinium-DTPA). Post-contrast myocardial T1 time for each patient will be calculated and correlated with the degree of diffuse fibrosis by histology. Inclusion criteria: written informed consent, diagnosis of HFNEF Exclusion criteria: inability or unwillingness to perform any of the diagnostic tests or to participate in follow-up visits, left ventricular ejection fraction =50%, significant valvular disease, congenital heart disease, left ventricular diastolic dysfunction in the absence of symptoms or signs of heart failure, GFR < 30 ml/min, pregnancy.

In the project Quantification of diffuse myocardial fibrosis by cardiac magnetic resonance imaging we investigated a novel cardiac magnetic resonance imaging (CMR) technique for non-invasive tissue characterization, called T1-mapping, as tool for estimation of myocardial extracellular volume (CMR-ECV). Increased amounts of ECV in histological analysis have been identified as key role in a variety of cardiac diseases. We compared the ECV derived from histological analysis of endomyocardial biopsies of 36 patients with results of CMR-ECV in the same patients. We found that CMR-ECV significantly correlated with the ECV quantified in the myocardial specimens. Furthermore, we investigated the prognostic relevance of CMR-ECV in a consecutive cohort of 473 patients referred for CMR. Patients with hypertrophic cardiomyopathy, cardiac amyloidosis, or Anderson-Fabry disease were excluded from the study. We found that patients with higher CMR-ECV had a worse outcome using a combined endpoint of hospitalization for cardiovascular reasons or cardiac death. In a multivariable model, CMR-ECV was an independent predictor of outcome among imaging variables. However, it failed to show a significant influence on outcome when clinical parameters were included in the multivariable model. In conclusion we could demonstrate that T1-mapping by CMR allows accurate non-invasive quantification of ECV. CMR-ECV furthermore was independently associated with outcome among imaging parameters. However, further long-term studies are needed to identify its prognostic value on top of clinical parameters.