Focal scar and diffuse myocardial fibrosis are independent imaging markers in repaired tetralogy of Fallot

Abstract

Aims To identify the correlates of focal scar and diffuse fibrosis in patients with history of tetralogy of Fallot (TOF) repair. Methods and results Consecutive patients with prior TOF repair underwent electrocardiogram, 24-h Holter, transthoracic echocardiography, exercise testing, and cardiac magnetic resonance (CMR) including cine imaging to assess ventricular volumes and ejection fraction, T1 mapping to assess left ventricular (LV) and right ventricular (RV) diffuse fibrosis, and free-breathing late gadolinium-enhanced imaging to quantify scar area at high spatial resolution. Structural imaging data were related to clinical characteristics and functional imaging markers. Cine and T1 mapping results were compared with 40 age- and sex-matched controls. One hundred and three patients were enrolled (age 28 ± 15 years, 36% women), including 36 with prior pulmonary valve replacement (PVR). Compared with controls, TOF showed lower LV ejection fraction (LVEF) and RV ejection fraction (RVEF), and higher RV volume, RV wall thickness, and native T1 and extracellular volume values on both ventricles. In TOF, scar area related to LVEF and RVEF, while LV and RV native T1 related to RV dilatation. On multivariable analysis, scar area and LV native T1 were independent correlates of ventricular arrhythmia, while RVEF was not. Patients with history of PVR showed larger scars on RV outflow tract but shorter LV and RV native T1. Conclusion Focal scar and biventricular diffuse fibrosis can be characterized on CMR after TOF repair. Scar size relates to systolic dysfunction, and diffuse fibrosis to RV dilatation. Both independently relate to ventricular arrhythmias. The finding of shorter T1 after PVR suggests that diffuse fibrosis may reverse with therapy.

The relationship between extracellular volume fraction in symptomatic adults with tetralogy of Fallot and adverse cardiac events

“…Our 8 patients with severe cardiac events developed HF, indicating that diffuse myocardial damage was an important predictor of HF. If many patients developed VT, surgical scars and/or focal fibrosis, suggesting arrhythmogenic areas [15,16], detected by LGE may also be an effective predictor of adverse events [17].…”

Quantitative collagen assessment in right ventricular myectomies from patients with tetralogy of Fallot

“…In RV myocardium of TOF patients, different types of fibrosis have been described, 11 including compact/focal, perivascular, and diffuse interstitial fibrosis. Importantly, all types of fibrosis are thought to contribute to ventricular arrhythmogenesis in repaired TOF patients, 12 making accurate fibrosis assessment an important diagnostic and therapeutic target. Previous studies have employed traditional, mostly single two-dimensional (2D) section-based, histopathological evaluation of TOF myocardium to assess fibrosis in unrepaired and repaired TOF patients.…”

Volume Load-Induced Right Ventricular Failure in Rats Is Not Associated With Myocardial Fibrosis

“…The absence of myocardial fibrosis in the present animal model of isolated volume load-induced RV failure, and the consequential lack of a relation with ventricular function, may have relevant consequences for the interpretation of imagingbased studies, reported earlier. These studies demonstrate indirect markers of increased fibrosis in the RV of human subjects with rTOF, who are often subjected to chronic RV volume load due to pulmonary valve incompetence (Haggerty et al, 2017;Hanneman et al, 2017;Yim et al, 2017;Cochet et al, 2019). Now experimental studies increasingly disconnect RV fibrosis from function (Crnkovic et al, 2018), it seems more likely that the observed markers in humans depict processes that are secondary to remodeling or adverse loading conditions prior to surgical repair, rather than primary processes that are detrimental and are caused by volume loading.…”

“…In the volumeloaded RV, the role of myocardial fibrosis and its relation with ventricular failure is even more unclear (Bossers et al, 2018). In patients with rTOF, often exposed to RV volume loading, indirect imaging markers have suggested both focal and interstitial fibrosis, correlated to function, dilatation and the degree of volume load (Haggerty et al, 2017;Hanneman et al, 2017;Yim et al, 2017;Cochet et al, 2019). However, since these studies only report associations, it remains unclear whether this process plays either a causal and detrimental, or secondary and reactive role in RV remodeling to volume loading.…”