Dilated cardiomyopathy (DCM) represents one of the most common causes of non-ischemic heart failure, characterised by ventricular dilation alongside systolic dysfunction. Despite advances in therapy, DCM mortality rates remain high, and it is one of the leading causes of heart transplantation. It was recently recognised that many patients present minor structural cardiac abnormalities and express different arrhythmogenic phenotypes before overt heart-failure symptoms. This has raised several diagnostic and management challenges, including the differential diagnosis with other phenotypically similar conditions, the identification of patients at increased risk of malignant arrhythmias, and of those who will have a worse response to medical therapy. Recent developments in complementary diagnostic procedures, namely cardiac magnetic resonance and genetic testing, have shed new light on DCM understanding and management. The present review proposes a comprehensive and systematic approach to evaluating DCM, focusing on an improved diagnostic pathway and a structured stratification of arrhythmic risk that incorporates novel imaging modalities and genetic test results, which are critical for guiding clinical decision-making and improving outcomes.

Sacubitril/Valsartan (LCZ696) reduced sudden cardiac death in the PARADIGM-HF trial. However, the mechanism by which LCZ696 reduces ventricular arrhythmias remains unclear. The aim of this study was to compare electrocardiographic (ECG) parameters and mechanical dispersion index, assessed by left ventricular (LV) global longitudinal strain (GLS), before and after LCZ696 therapy. We prospectively evaluated chronic Heart Failure (HF) patients with LV ejection fraction ≤40%, despite optimal medical and device therapy, in which LCZ696 therapy was started, while no additional HF treatment was expected to change. ECG and transthoracic echocardiographic data were gathered in the week before starting LCZ696 and at six months of therapy. A semiautomated analysis of LV GLS was performed and mechanical dispersion index was defined as the standard deviation from 16 time intervals corresponding to each LV segment. Of the 42 patients, 35 completed the six month follow-up, since two patients died and five discontinued treatment for adverse events. QTc interval (451.9 vs. 426.0 ms, p < 0.001), QRS duration (125.1 vs. 120.8 ms, p = 0.033) and mechanical dispersion index (88.4 vs. 78.1 ms, p = 0.036) were significantly reduced at six months. LCZ696 therapy is associated with a reduction in QTc interval, QRS duration and mechanical dispersion index as assessed by LV GLS.

The mechanisms that regulate the systemic extent of atherosclerosis are not fully understood. We investigated whether the expression of circulating miRNAs is associated with the extent of stable atherosclerosis to a single territory or multiple territories (polyvascular) and with the severity of atherosclerosis in each territory. Ninety-four participants were prospectively recruited and divided into five age- and sex-matched groups: presenting no atherosclerosis, isolated coronary atherosclerosis, coronary and lower extremity atherosclerosis, coronary and carotid atherosclerosis, and atherosclerosis of the coronary, lower extremity, and carotid territories. The expression of six circulating miRNAs with distinct biological roles was assessed. The expression of miR-27b and miR-146 differed across groups (p < 0.05), showing a decrease in the presence of atherosclerosis, particularly in the three territories. miR-27b and miR-146 expression decreased in association with a higher severity of coronary, lower extremity, and carotid atherosclerosis. Polyvascular atherosclerosis involving the three territories was independently associated with a decreased miR-27b and miR-146 expression. Both miRNAs presented an area under the curve of ≥0.75 for predicting polyvascular atherosclerosis involving the three territories. To conclude, miR-27b and miR-146 were associated with the presence of severe polyvascular atherosclerosis and with the atherosclerosis severity in each territory. Both are potential biomarkers of severe systemic atherosclerosis.

Aims: Myocardial work is a new transthoracic echocardiogram (TTE) parameter that enhances the information provided through left ventricular (LV) global longitudinal strain (GLS). Nothing is known about the impact of sacubitril/valsartan (LCZ696) therapy on myocardial work parameters. The aim of this study was to evaluate the effects of LCZ696 on LV myocardial work in heart failure patients. Methods: Prospective evaluation of chronic heart failure patients with LV ejection fraction of 40% or less despite optimized standard of care therapy, in which LCZ696 therapy was started and no other heart failure treatment was expected to change. TTE study was performed before and 6 months after LCZ696 therapy. A semiautomated analysis of LV GLS was made and myocardial work estimated using custom software of the GE Vivid E95 ultrasound system. Results: Of the 42 patients, 35 (83.3%) completed the 6 months, follow-up, since 2 (4.8%) patients died and 5 (11.9%) discontinued treatment due to adverse events. Mean age was 58.6 ± 11.1 years. TTE data showed a significant reduction in LV dimensions and atrial volumes, as well as an improvement in LV ejection fraction (29.3 vs. 35.2%, P = 0.001) and GLS (−7.0 vs. −8.9%, P = 0.001). Myocardial work had a significant increase in global constructive work (720.2 vs. 900.6 mmHg%, P = 0.016) and global work efficiency (78.6 vs. 86.6%, P = 0.027), with a nonsignificant decrease in global wasted work (150.2 vs. 136.8 mmHg%, P = 0.441) at 6 months. Conclusion: LCZ696 therapy was associated with signs of reverse remodelling by usual TTE parameters and LV myocardial work at 6 months, including an increase in global constructive work and work efficiency.