Monoclonal Anti-PCSK9 Antibodies: Real-World Data.

Background: Real-world data on the use of lipid-lowering therapy (LLT) in clinical practice show that about 80% of (very) high-cardiovascular (CV)-risk patients disregard the 2019 European Society of Cardiology (ESC) Guidelines' recommendations on dyslipidemias. The availability of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9mAb) should reduce this gap. Our aim was to provide data on PCSK9mAb use in clinical practice, investigating the achievement of the ESC Guidelines' recommendations in the real world. Methods: Between April 2018 and December 2022, patients who started on PCSK9mAb therapy (140 mg of evolocumab or 75 mg or 150 mg of alirocumab, subcutaneous injection every 2 weeks) were included in a prospective registry. Our cohort consisted of 256 patients: 95 (37.1%) were women (mean age: 65.43 ± 11.12 yrs), 53 (20.7%) were at high CV risk, and 203 (79.3%) were at very high CV risk. Results: After one year of PCSK9mAb treatment, nearly 60% of patients demonstrated full adherence to the ESC Guidelines' recommendations, defined as achieving at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C) levels along with reaching LDL-C target levels (≤55 and ≤70 mg/dL for very high and high risk, respectively). Concomitant high-dose statin therapy emerged as the primary predictor of LDL-C target attainment. Heterozygous familial hypercholesterolemia (HeFH), statin intolerance, and female gender were associated with a significant lower probability of achieving LDL-C target levels. Conclusions: Our analysis confirms that PCSK9mAb treatment is safe and effective, enabling 60% of our cohort to fully achieve the LDL-C guideline recommendations. The use of high-intensity statins emerged as a significant predictor of efficacy. Conversely, familial hypercholesterolemia and female gender were identified as predictors of therapeutic failure. Hence, it is crucial to address disparities in cardiovascular disease prevention between genders and to enhance strategies for managing elevated LDL-C in HeFH patients.

Layer-specific strain in dipyridamole stress echo: A new tool for the diagnosis of microvascular angina.

BACKGROUND: Dipyridamole stress echocardiography (DSE) represents a fundamental test in patients with suspected coronary artery disease (CAD). The diagnosis of microvascular disease is still challenging. We aimed to determine the diagnostic value of left ventricular (LV) layer-specific longitudinal (LS) and circumferential strain (CS) by Speckle Tracking in detecting CAD during DSE and to study if they can help in discriminate between a negative echo and a suspected microvascular angina. METHODS AND RESULTS: We enrolled 66 patients with known or suspected CAD. All underwent standard DSE. We identified 3 groups according to the result of DSE (36 negative DSE, 19 positive DSE, 11 indicatives for microvascular disease). Wall motion score index, global LV LS and CS (global longitudinal strain [GLS] and global circumferential strain [GCS]), and layer-specific LV LS and CS were measured at rest and peak stress. The Delta between rest and peak stress values was calculated. GLS increased after injection in negative DSE and microvascular disease while reducing in positive DSE. Endocardial GCS and transmural GCS values were stable in microvascular disease while increasing significantly in negative DSE, helping in the diagnosis. The specific analysis of endocardial LS showed the most powerful difference between healthy and macrovascular CAD patients, both for LS and CS. CONCLUSIONS: Global circumferential strain can be a new valuable added tool in the echocardiographic diagnosis of microvascular disease. Endocardial GLS is the best indicator of an altered wall deformation in the presence of macrovascular ischemia.

Left heart longitudinal deformation analysis in mitral regurgitation.

In mitral regurgitation (MR), left atrium (LA) and left ventricle (LV) undergo remodeling even if the patient is asymptomatic. The aim of our study was to identify the best echo index that correlates with MR severity in asymptomatic patients affected by MR. We enrolled 150 MR patients (50: mild, 50: moderate, 50: severe), asymptomatic for exertional dyspnea and 50 healthy controls. MR was graded using Doppler quantitative method. All underwent standard and Speckle Tracking Echocardiography (STE) with analysis of global peak atrial longitudinal strain (PALS), LV longitudinal strain (LS) and global atrio-ventricular strain (GAVS). LA dimensions showed significant differences between the groups while LV end-diastolic diameter did not significantly differ, although having a slight increase. PALS was slightly higher in patients with mild MR, while decreased in moderate and, mainly, in severe MR (controls 37.4 ± 12.2%, mild MR 38.2 ± 9%, moderate MR 29.1 ± 9%, severe MR 19.8 ± 10.6%, p < 0.0001 by ANOVA); the same was found for GAVS (56.1 ± 13%, 57.6 ± 9.7%, 48.2 ± 9% 39 ± 9.4%, p < 0.0001 by ANOVA). LV LS showed a tendency for gradual reduction in the three groups. In multivariate analysis, PALS and GAVS were far superior than GLS as predictors of MR groups. PALS emerged as an added value to the LA indexed volumes as predictor of MR severity. STE-derived PALS and GAVS emerged as promising tools to investigate heart longitudinal function in patients with chronic MR and no symptoms. PALS can represent a surplus in the prediction of severity of MR, in addition to the assessment of LA volumes.