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

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.

New Myocardial Deformation by 2D Multi-layer Speckle-Tracking Analysis in Healthy Patients: Normal Reference Values and Their Physiologic Determinants.

There are limited data regarding intrinsic changes of the left (LV) and right ventricular (RV) deformation assessed layer-by-layer. We designed a prospective multi-centric study, using a new multi-layer 2D-speckle-tracking-echo (MSTE). We investigated the impact of different physiologic parameters on layer-specific LV/RV myocardial deformation and synchrony, in a large group of healty subjects. 151 subjects were feasible for MSTE, divided in 4 groups: <40 yrs, 41 to 50 yrs, 51 to 60, and >61 yrs. We found a significant higher LV dyssynchrony index with age. In all groups, an endo-epicardial gradient was present in longitudinal LV/RV and circumferential deformation, with higher values in endocardial layer (p<0.001). There were no differences in deformation with age in all layers. We provided normal reference values for a new index of LV dyssynchrony, and also for RV longitudinal, LV circumferential and longitudinal layer-specific deformation, which can be further used when assessing subclinical dysfunction in myocardial diseases.

New Definition Criteria of Myocardial Dysfunction in Patients with Liver Cirrhosis: A Speckle Tracking and Tissue Doppler Imaging Study.

There are no clear recommendations regarding cirrhotic cardiomyopathy (CC) evaluation in patients with pre-transplant liver cirrhosis. The roles of new methods, tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) in the diagnosis and prognosis of cirrhotic cardiomyopathy remain controversial. We investigated the utility of TDI/STE parameters in cirrhotic cardiomyopathy diagnosis and also in predicting mortality in patients with liver cirrhosis. Left/right ventricular function was studied using conventional TDI (velocities) and STE (strain/strain rate). We assessed left ventricular diastolic dysfunction, graded into four new classes (I/Ia/II/III). Serum NTproBNP (N-terminal prohormone of brain natriuretic peptide), troponin I, ß-crosslaps, QTc interval, arterial compliance and endothelial function were measured. Liver-specific scores (Child-Pugh, MELD, MELDNa) were computed. There was a 1-y follow-up visit to determine mortality. We observed resting biventricular diastolic myocardial dysfunction, not presently included in the definition of cirrhotic cardiomyopathy. We provided an improved characterization of cardiac dysfunction in patients with liver cirrhosis. This might change the current definition. However, the utility of STE/TDI parameters in predicting long-term mortality in patients with liver cirrhosis remains controversial.