Emerging molecular imaging targets and tools for myocardial fibrosis detection

Abstract

Myocardial fibrosis is the heart’s common healing response to injury. While initially seeking to optimize the strength of diseased tissue, fibrosis can become maladaptive, producing stiff poorly functioning and pro-arrhythmic myocardium. Different patterns of fibrosis are associated with different myocardial disease states, but the presence and quantity of fibrosis largely confer adverse prognosis. Current imaging techniques can assess the extent and pattern of myocardial scarring, but lack specificity and detect the presence of established fibrosis when the window to modify this process may have ended. For the first time, novel molecular imaging methods, including gallium-68 (68Ga)-fibroblast activation protein inhibitor positron emission tomography (68Ga-FAPI PET), may permit highly specific imaging of fibrosis activity. These approaches may facilitate earlier fibrosis detection, differentiation of active vs. end-stage disease, and assessment of both disease progression and treatment–response thereby improving patient care and clinical outcomes.

Noninvasive Monitoring of Early Cardiac Fibrosis in Diabetic Mice by [68Ga]Ga-DOTA-FAPI-04 PET/CT Imaging

“…A minority of evidence has suggested that FAPI-PET imaging possesses the potential for early identification of cardiovascular fibrosis, risk stratification, and prediction of the progression of left ventricular function. 13 As expected, our finding substantiated the capability of detecting mild cardiac fibrosis through [ 68 Ga]Ga-DOTA-FAPI-04 molecular imaging. In this study, we found that both FAP protein and mRNA expression were significantly upregulated in the diabetic heart in early-and late-stage diabetes, thereby further affirming the high specificity of the [ 68 Ga]Ga-DOTA-FAPI-04 molecular probe.…”

“…Currently, the prospective utility of FAPI-PET in evaluating nononcologic pathological processes remains under active investigation. A minority of evidence has suggested that FAPI-PET imaging possesses the potential for early identification of cardiovascular fibrosis, risk stratification, and prediction of the progression of left ventricular function …”

“…In our study, we focused on the classical transforming growth factor (TGF-β1), type III procollagen N-terminal peptide (PIIINP), and soluble ST2 (sST2), which are all related to the progression of cardiac fibrosis and the prognosis of diabetic heart failure. − The concentration of these fibrosis biomarkers was evaluated by the ELISA kits (Jiangsu Enzymatic immunity, China) according to the manufacturer’s instructions. The optical density of each sample was measured by using a microplate reader (Thermo Scientific, USA).…”

The Clinical Evolution of Diffuse Myocardial Fibrosis in Patients With Arterial Hypertension and Heart Failure With Mildly Reduced Ejection Fraction Treated by Olmesartan or Sacubitril / Valsartan

“…Нормальный миокард состоит из кардиомиоцитов и окружающего внеклеточного матрикса в соотношении 3:1 [1,2]. Диффузный фиброз миокарда (ФМ) встречается при различных хронических заболеваниях сердца, он возникает в результате избыточного отложения коллагеновых волокон по всему миокарду [3]. Физико-химические свойства волокон, состав коллагена и количество фиброзных отложений имеют ключевое значение во влиянии диффузного ФМ на функцию сердца и клинические исходы у пациентов с хронической сердечной недостаточностью (ХСН) [4].…”

“…ФМ является распространенной патологической реакцией на повреждение сердечной мышцы [2,3]. Первоначальное повреждение миокарда может возникнуть в результате широкого спектра стимулов, приводящих к различным формам фиброза.…”