New Advanced Imaging Parameters and Biomarkers—A Step Forward in the Diagnosis and Prognosis of TTR Cardiomyopathy

Abstract

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an infiltrative disorder characterized by extracellular myocardial deposits of amyloid fibrils, with poor outcome, leading to heart failure and death, with significant treatment expenditure. In the era of a novel therapeutic arsenal of disease-modifying agents that target a myriad of pathophysiological mechanisms, timely and accurate diagnosis of ATTR-CM is crucial. Recent advances in therapeutic strategies shown to be most beneficial in the early stages of the disease have determined a paradigm shift in the screening, diagnostic algorithm, and risk classification of patients with ATTR-CM. The aim of this review is to explore the utility of novel specific non-invasive imaging parameters and biomarkers from screening to diagnosis, prognosis, risk stratification, and monitoring of the response to therapy. We will summarize the knowledge of the most recent advances in diagnostic, prognostic, and treatment tailoring parameters for early recognition, prediction of outcome, and better selection of therapeutic candidates in ATTR-CM. Moreover, we will provide input from different potential pathways involved in the pathophysiology of ATTR-CM, on top of the amyloid deposition, such as inflammation, endothelial dysfunction, reduced nitric oxide bioavailability, oxidative stress, and myocardial fibrosis, and their diagnostic, prognostic, and therapeutic implications

A review of transthyretin cardiac amyloidosis

“…Misfolded TTR commonly occupy interstitial spaces of the myocardium, eventually leading to cardiac amyloidosis [5]. Upon protein deposition, the myocardium becomes hypertrophied with accompanying compromise in ventricular compliance, progressing to restrictive cardiomyopathy [8]. The diastolic dysfunction that arises from this pathologic aggregation causes worsening heart failure, new onset conduction disorders, and arrythmias [5].…”

“…In fact, studies have shown that cutoffs of 3000 pg/mL and 0.05 ng/mL for NT-proBNP and hsTnT, respectively, help stratify mortality risk in ATTR amyloidosis patients [9]. However, there are limitations of biomarkers given their low sensitivity and specificity in early diagnosis of ATTR cardiomyopathy [8]. Additional biomarkers, such as matrix metallosis protein ACEs and tissue inhibitors of metallic proteinase, are being investigated for their potential role in differentiating between AL and ATTR cardiomyopathy [8].…”

“…However, there are limitations of biomarkers given their low sensitivity and specificity in early diagnosis of ATTR cardiomyopathy [8]. Additional biomarkers, such as matrix metallosis protein ACEs and tissue inhibitors of metallic proteinase, are being investigated for their potential role in differentiating between AL and ATTR cardiomyopathy [8].…”

Special Issue “Multimodality Imaging in Cardiomyopathies”

“…The review by Rimbas et al [ 7 ] focused on transthyretin amyloid cardiomyopathy (ATTR-CM), a condition with widespread amyloid extracellular myocardial deposits, which can lead to heart failure, having high treatment and diagnostic costs. Early diagnosis is crucial for a better therapeutic strategy.…”

“…Several interesting findings come from these articles. The multimodality approach is always a good choice when evaluating complex cardiac diseases, such as HCM [ 8 ], ATTR-CM [ 7 ], and LVNC [ 5 ], and in a sports cardiology context [ 6 , 9 ]. The physicianshould be able to select the right imaging technique for each clinical scenario following a reasoned step-by-step approach.…”