not-yet-known not-yet-known not-yet-known unknown Background and aims: The assessment of left ventricular (LV) outflow velocity time integral (LVOT-VTI) has gained favor in the stratification of patients with heart failure (HF). We evaluated the prognostic significance of LVOT-VTI compared with the commonly used indices of LV outflow: cardiac index (CI) and stroke volume index (SVI), their reproducibility and cut-off values. Methods and results: 424 outpatients diagnosed with HF and LV systolic dysfunction (LV ejection fraction <50%) underwent a Doppler echocardiographic examination, including the assessment of CI, SVI and LVOT-VTI. The Bland-Altman analysis showed LVOT-VTI the most reproducible outflow index. The study follow-up duration was 3.5 years (interquartile range 1.6 to 6.5), at the end of which there were 94 cardiovascular deaths (29%). Cox regression univariate analysis showed that LVOT-VTI was the most predictive of the study end-point. The ratio of tricuspid annular displacement-to-pulmonary artery systolic pressure (TAPSE/PASP) (p<0.0001), LVOT-VTI (p=0.0001) and end-systolic volume index (p=0.0006) independently predicted the study end-point. At Receiver-operating characteristic (ROC) analysis, LVOT-VTI <12.0 cm had the best sensitivity and specificity for predicting cardiovascular mortality. Reduced LV EF (p=0.0011), raised BNP levels (p=0.0053) and high LV filling pressure (p=0.044) were associated with low LVOT-VTI in multivariate logistic regression analysis. Patients with low LVOT-VTI and TAPSE/PASP<0.32 mm/mmHg exhibited the worst prognosis on Kaplan-Meier survival curves (p<0.0001). Conclusions. A LVOT-VTI < 12.0 cm represents the best predictor of the cardiovascular outcome and proved the most reproducible index of LV forward flow in patients with chronic HF and systolic dysfunction.

Background: The aim of this meta-analysis was to compare the efficacy of PCSK9 and ANGPTL3 inhibitors in patients with Homozygous familial hypercholesterolemia (HoFH) Methods: We systematically searched selected electronic databases until 30th November 2024. Main endpoint was the effect of lipid lowering therapy on lipid profile: total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and lipoproteins levels. The secondary endpoint was adverse clinical effects. Results: 12 trials involving a total of 392 patients with HoFH, were included in the meta-analysis. At a median follow-up of 12 months, the ANGPTL3i group demonstrated a greater reduction in mean TC [–4.27 mmol/L (165.1 mg/dL) vs. –1.37 mmol/L (52.9 mg/dL); p for subgroup <0.001], LDL-C [–3.51 mmol/L (135.7 mg/dL) vs. –1.81 mmol/L (69.9 mg/dL); p for subgroup <0.001], and TG [–0.61 mmol/L (54.1 mg/dL) vs. –0.21 mmol/L (18.6 mg/dL); p for subgroup <0.001], but a smaller impact on HDL-C compared to those treated with PCSK9i. Lipids were reduced more in adults compared to children in the PCSK9i group (p<0.01) but not in the ANGPTL3i group (p=0.23). Likewise, Apo-B reduced more with ANGPTL3i compared to PCSK9i but Apo-A and Lipoprotein (a) remained comparable between the two groups. The treatment-related adverse events and discontinuation rates were not different between groups. Conclusions: PCSK9 inhibitors have lower efficacy in reducing lipid levels in HoFH patients compared to ANGPTL3 inhibitors, particularly in children. Their effectiveness in different functional variations of LDL-C receptors in HoFH patients needs to be established.