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

Background and Objectives: Neutrophil-to-lymphocyte ratio (NLR), a very low cost, widely available marker of systemic inflammation, has been proposed as a potential predictor of short-term outcome in patients with intracerebral hemorrhage (ICH). Methods: Patients with ICH admitted to the Neurology Department during a two-year period were screened for inclusion. Based on eligibility criteria, 201 patients were included in the present analysis. Clinical, imaging, and laboratory characteristics were collected in a prespecified manner. Logistic regression models and receiver operating characteristics (ROC) curves were used to assess the performance of NLR assessed at admission (admission NLR) and 72 h later (three-day NLR) in predicting in-hospital death. Results: The median age of the study population was 70 years (IQR: 61–79), median admission NIHSS was 16 (IQR: 6–24), and median hematoma volume was 13.7 mL (IQR: 4.6–35.2 mL). Ninety patients (44.8%) died during hospitalization, and for 35 patients (17.4%) death occurred during the first three days. Several common predictors were significantly associated with in-hospital mortality in univariate analysis, including NLR assessed at admission (OR: 1.11; 95% CI: 1.04–1.18; p = 0.002). However, in multivariate analysis admission, NLR was not an independent predictor of in-hospital mortality (OR: 1.04; 95% CI: 0.9–1.1; p = 0.3). The subgroup analysis of 112 patients who survived the first 72 h of hospitalization showed that three-day NLR (OR: 1.2; 95% CI: 1.09–1.4; p < 0.001) and age (OR: 1.05; 95% CI: 1.02–1.08; p = 0.02) were the only independent predictors of in-hospital mortality. ROC curve analysis yielded an optimal cut-off value of three-day NLR for the prediction of in-hospital mortality of ≥6.3 (AUC = 0.819; 95% CI: 0.735–0.885; p < 0.0001) and Kaplan–Meier analysis proved that ICH patients with three-day NLR ≥6.3 had significantly higher odds of in-hospital death (HR: 7.37; 95% CI: 3.62–15; log-rank test; p < 0.0001). Conclusion: NLR assessed 72 h after admission is an independent predictor of in-hospital mortality in ICH patients and could be widely used in clinical practice to identify the patients at high risk of in-hospital death. Further studies to confirm this finding are needed.

Aims None of the conventional echocardiographic parameters alone predict increased NTproBNP level and symptoms, making diagnosis of heart failure with preserved ejection fraction (HFpEF) very difficult in some cases, in resting condition. We evaluated LA functions by 2D speckle tracking echocardiography (STE) on top of conventional parameters in HFpEF and preHF patients with diastolic dysfunction (DD), in order to establish the added value of the LA deformation parameters in the diagnosis of HFpEF. Methods We prospectively enrolled 125 patients, 88 with HFpEF (68±9 yrs), and 37 asymptomatic with similar risk factors with DD (preHF) (61±8 yrs). We evaluated them by NTproBNP, conventional DD parameters, and STE. Global longitudinal strain (GS) was added. LA reservoir (R), conduit (C), and pump function (CT) were assessed both by volumetric and STE. 2 reservoir strain (S) derived indices were also measured, stiffness (SI) and distensibility index (DI). Results LA R and CT functions were significantly reduced in HFpEF compared to preHF group (all p<0.001), whereas conduit was similarly in both groups. SI was increased, whereas DI was reduced in HFpEF group (p<0.001). By adding LA strain analysis, from all echocardiographic parameters, SR_CT<-1.66/s and DI<0.57 (AUC = 0.76, p<0.001) demonstrated the highest accuracy to identify HFpEF diagnosis. However, by multivariate logistic regression, the model that best identifies HFpEF included only SR_CT, GS and sPAP (R2 = 0.506, p<0.001). Moreover, SR_CT, DI, and sPAP registered significant correlation with NTproBNP level. Conclusions By adding LA functional analysis, we might improve the HFpEF diagnosis accuracy, compared to present guidelines. LA pump function is the only one able to differentiates preHF from HFpEF patients at rest. A value of SR_CT < -1.66/s outperformed conventional parameters from the scoring system, reservoir strain, and LA overload indices in HFpEF diagnosis. We suggest that LA function by STE could be incorporated in the current protocol for HFpEF diagnosis at rest as a major functional criterion, in order to improve diagnostic algorithm, and also in the follow-up of patients with risk factors and DD, as a prognostic marker. Future studies are needed to validate our findings.