Inclisiran: A New Pharmacological Approach for Hypercholesterolemia.

Therapeutic approaches based on gene silencing technologies represent a new opportunity to manage hypercholesterolemia. Inclisiran is a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA. Clinical studies have demonstrated that inclisiran is effective, safe, and well-tolerated in reducing low-density lipoprotein cholesterol (LDL-C) in patients with familial hypercholesterolemia, atherosclerotic cardiovascular disease, and atherosclerotic cardiovascular disease risk equivalents. A meta-analysis of phase 3 trials demonstrated a 51% reduction in LDL-C levels at 18 months as compared with placebo. Adverse event incidence was found to be comparable in individuals treated with inclisiran and those receiving placebo, though the reactions at the site of injection were more common in patients receiving inclisiran as compared with those receiving placebo. The recommended inclisiran dose is 284 mg administered as a subcutaneous injection to be repeated after three months with a subsequent 6-month maintenance regimen. Overall, since the pharmacological efficacy of inclisiran in LDL-C reduction is comparable to that of monoclonal antibodies against PCSK9, the longer effect duration and the favorable safety profile may favor this newer approach for hypercholesterolemia management.

The peer-review process in Europe's leading case report journal for cardiovascular diseases: a survey for improving transparency and quality.

Graphical abstract summarizing main study results.

Artificial intelligence-powered insights into high-risk, non-obstructive coronary atherosclerosis: a case report.

Background: Advanced coronary plaque analysis by cardiac computed tomography (CT) has recently emerged as a promising technique for better prognostic stratification. However, this evaluation application in clinical practice is still uncertain. Case summary: In the present case, we described the clinical picture of a 44-year-old tennis player with ectopic ventricular beats in which cardiac CT enabled the identification of a non-obstructive but high-risk plaque on proximal left anterior descendent artery. The application of artificial intelligence (AI)-enhanced software enabled to better stratify the patients' risk. The present case describes how early identification of non-obstructive but high-risk coronary plaque evaluated by cardiac CT using AI-enhanced software enabled accurate and personalized risk assessment. Discussion: The main clinical message of this case report is that advanced plaque analysis by cardiac CT, especially when performed with AI-based software, may provide important prognostic information leading to a personalized preventive approach. Moreover, AI-based software may contribute to promote a routine evaluation of these important data already included in traditional cardiac CT.

Clinical and cardiac CT characteristics of congenital coronary abnormalities occasionally detected in a middle-aged population: A long-term follow-up study.

INTRODUCTION: Congenital coronary artery anomalies (CCAA) represent one of the most challenging conditions as their clinical presentation may range from sudden cardiac death to a complete subclinical form. The aim of the present study was to evaluate the diagnostic and prognostic role of cardiac CT (CCT) evaluation in patients with CCAA, focusing on anomalies of origin. MATERIAL AND METHODS: The present is a retrospective analysis of a prospective clinical registry including a consecutive cohort of patients who underwent clinically indicated CCT from January 2007 to October 2015 for suspected but unknown coronary artery disease (CAD) and were diagnosed for having a congenital coronary abnormality compared to a control group matched for age, sex and segment stenosis score (SSS). Dedicated analysis of all CCT was performed for the present study and only coronary anomalies of origin were considered and included in the study. Two different composite end-points were identified for the present analysis: major cardiovascular events (MACE) and all-cause of death. RESULTS: Among the 81 patients with CCAAs enrolled the most frequent anomaly was left main artery absence, which was identified in 41 individuals (50.6%). Forty-five subjects (55.5%) have an anomalous origin of the coronary artery from a different sinus of Valsalva and 45 subjects had also an anomalous course with the retro-aortic being the most common (32%). Eleven participants (13.6%) displayed also an intramural segment, while 10 (10.3%) had a slit-like ostial morphology. At multivariate analysis CT identification of ARCA, anomalous inter-arterial course and abnormal ostial morphology were significantly associated with MACE even when adjusted for age and SSS, without any differences in all-cause mortality between the two groups (6.2% vs 2.4% p â€‹= â€‹0.2478). CONCLUSION: The result of the present study is that CCT can be successfully used to define the anatomy and features of CAA. It suggested that in middle-aged patients, the identification of high risk characteristics at CT may have a prognostic value in term of cardiovascular events occurrence at follow-up even if the rate of events strictly linked to CCAA is low.

Preprocedural imaging with cardiac computed tomography for endo-epicardial ventricular tachycardia ablation.

BACKGROUND: Studies evaluating the systematic use of cardiac computed tomography (CCT) for the preprocedural assessment of myocardial fibrosis are limited. Their implementation in the electrophysiology workflow has not been extensively described. OBJECTIVE: This study aimed to explore the degree of concordance between CCT and electroanatomic mapping (EAM) for the evaluation of cardiac fibrosis in patients undergoing endo-epicardial ventricular tachycardia (VT) ablation. METHODS: From November 2017 to December 2021, patients undergoing endo-epicardial VT catheter ablation with CCT as the only source of preprocedural scar assessment were prospectively enrolled. After image integration, myocardial fibrosis detected with CCT was compared with low-voltage areas identified by endo-epicardial EAM. Postprocedural VT recurrences of this approach were evaluated after at least 1 year of follow-up. RESULTS: The study enrolled 35 patients (mean age, 60.7 ± 13.2 years; 94.2% male). The most common underlying arrhythmic substrate was dilated cardiomyopathy (48.6%). CCT was employed for contraindications to cardiac magnetic resonance, such as unstable VTs (31.4%) or nonconditional implantable cardioverter-defibrillators (28.6%), but also for patients' and operators' preferences (14.3%-25.7%). Myocardial fibrosis was correctly identified by CCT and EAM, with strong agreement between these techniques both overall (Cohen κ for agreement, 0.933) and in per-segment analysis (κ ranging from 0.796 to 1.0). Ischemic patients showed the best correlation (κ = 1.000), whereas myocarditis showed the worst (κ = 0.750). After a median follow-up of 14 (12-24) months, 1-year freedom from recurrences was achieved in 74.3% patients; overall freedom from recurrences was 60.0%. CONCLUSION: A CCT-based preprocedural assessment before VT ablation is feasible, showing high diagnostic concordance with EAM in detecting myocardial fibrosis.

Post-cardiac injury syndrome and pericardial effusion recurrence after pericardial effusion drainage in chronic idiopathic pericardial effusion.

INTRODUCTION: The management of even large pericardial effusions in asymptomatic patients is still a matter of debate. Aim of the present study is to explore, in a multicenter setting, the rate of post-cardiac injury syndromes (PCIS) and pericardial effusion recurrence after pericardial effusion drainage procedure. MATERIAL AND METHODS: This is a multicenter international retrospective study including a consecutive cohort of patients diagnosed with large, chronic and idiopathic pericardial effusions, prospectively evaluated from January 2003 to December 2021 who underwent a clinically indicated pericardial drainage procedure. Two separate end-points were recorded: 1) recurrence of pericardial effusion after drainage without any sign of pericardial inflammation 2) occurrence of PCIS, defined as the new onset of pericarditis 1 to 6 weeks after pericardial intervention. RESULTS: 124 patients were enrolled (50 % female, mean age 64 years old). A mean follow-up of 29.6 ± 25.6 months was obtained in 110 patients (88 %). 110 patients were treated with pericardiocentesis (89 %), 25 with pleuro-pericardial windows (20 %), and 1 with pericardiectomy (1 %). PCIS occurred in 21 out of 124 patients followed for at least 6 weeks (16.9%). Recurrence of pericardial effusion after drainage without any sign of pericardial inflammation occurred in 68 out of 110 patients at a longer follow-up (61.8 %). At multivariate analysis only inflammatory cells in pericardial fluid was associated with PCIS and pericardiocentesis with pericardial effusion recurrency. CONCLUSION: Our data support the need of caution with the use of pericardiocentesis in asymptomatic patients with large pericardial effusion as it is often associated with pericardial effusion recurrence. Of interest the presence of inflammatory cells in the pericardial fluid is associated with PCIS after pericardial drainage procedures.

D-Dimer and procalcitonin in patients with recurrent pericarditis: a prospective study.

Recurrent pericarditis, an inflammatory syndrome with a pathogenesis not fully elucidated, often presents diagnostic challenges. This study aims to assess the correlation of D-Dimer (D-D) and procalcitonin (PCT) levels with clinical, laboratory and imaging features in recurrent idiopathic pericarditis. We analyzed 412 patients with idiopathic recurrent pericarditis from 2019 to 2023 in our referral center. D-D and PCT values were obtained from emergency room in other Italian facilities. Among the cohort, PCT levels were assessed in 50 of 412 patients (12.1%), with only 4 showing marginal elevation. D-D levels were measured in 48 of 412 patients (11.6%), with 33 of them exhibiting elevated values. None of these patients had venous thromboembolism, and elevated D-D levels were significantly associated with pleural effusion, fever, higher CRP, increased white blood cell counts, higher neutrophil counts, reduced relative lymphocyte counts. Multivariate analysis revealed fever as the sole correlate of elevated D-D. PCT elevation was infrequent and unrelated to any variables. In idiopathic recurrent pericarditis unrelated to specific conditions, we observed a close association between elevated D-D levels and non-specific inflammation markers, including fever, increased CRP, and neutrophil leukocytosis. PCT levels were typically normal or mildly elevated.

Predictors of adverse cardiac events of coronary myocardial bridging diagnosed with computed tomography angiography.

AIMS: Myocardial bridging (MB) is a frequent congenital anomaly of the epicardial coronary arteries commonly considered a benign condition. However, in some cases a complex interplay between anatomical, clinical and physiology factors may lead to adverse events, including sudden cardiac death. Coronary CT angiography (CCTA) emerged as the gold standard noninvasive imaging technique for the evaluation of MB. Aim of the study was to evaluate MB prevalence and anatomical features in a large population of patients who underwent CCTA for suspected CAD and to identify potential anatomical and clinical predictors of adverse cardiac events at long-term follow-up. METHODS AND RESULTS: Two-hundred and six patients (mean age 60.3 ± 11.8 years, 128 male) with MB diagnosed at CCTA were considered. A long MB was defined as ≥25 mm of overlying myocardium, whereas a deep MB as ≥2 mm of overlying myocardium. The study endpoint was the sum of the following adverse events: cardiac death, bridge-related acute coronary syndrome, hospitalization for angina or bridge-related ventricular arrhythmias and MB surgical treatment. Of the 206 patients enrolled in the study, 9 were lost to follow-up, whereas 197 (95.6%) had complete follow-up (mean 7.01 ± 3.0 years) and formed the analytic population. Nineteen bridge-related events occurred in 18 patients (acute coronary syndrome in 7, MB surgical treatment in 2 and hospitalization for bridge-related events in 10). Typical angina at the time of diagnosis and long MB resulted as significant independent predictors of adverse outcome. CONCLUSIONS: Typical angina and MB length ≥ 25 mm were independent predictors of cardiac events.

The Role of Multimodality Imaging (CT & MR) as a Guide to the Management of Chronic Coronary Syndromes.

Chronic coronary syndrome (CCS) is one of the leading cardiovascular causes of morbidity, mortality, and use of medical resources. After the introduction by international guidelines of the same level of recommendation to non-invasive imaging techniques in CCS evaluation, a large debate arose about the dilemma of choosing anatomical (with coronary computed tomography angiography (CCTA)) or functional imaging (with stress echocardiography (SE), cardiovascular magnetic resonance (CMR), or nuclear imaging techniques) as a first diagnostic evaluation. The determinant role of the atherosclerotic burden in defining cardiovascular risk and prognosis more than myocardial inducible ischemia has progressively increased the use of a first anatomical evaluation with CCTA in a wide range of pre-test probability in CCS patients. Functional testing holds importance, both because the role of revascularization in symptomatic patients with proven ischemia is well defined and because functional imaging, particularly with stress cardiac magnetic resonance (s-CMR), gives further prognostic information regarding LV function, detection of myocardial viability, and tissue characterization. Emerging techniques such as stress computed tomography perfusion (s-CTP) and fractional flow reserve derived from CT (FFRCT), combining anatomical and functional evaluation, appear capable of addressing the need for a single non-invasive examination, especially in patients with high risk or previous revascularization. Furthermore, CCTA in peri-procedural planning is promising to acquire greater importance in the non-invasive planning and guiding of complex coronary revascularization procedures, both by defining the correct strategy of interventional procedure and by improving patient selection. This review explores the different roles of non-invasive imaging techniques in managing CCS patients, also providing insights into preoperative planning for percutaneous or surgical myocardial revascularization.

Cardiac Magnetic Resonance to Predict Cardiac Mass Malignancy: The CMR Mass Score.

BACKGROUND: Multimodality imaging is currently suggested for the noninvasive diagnosis of cardiac masses. The identification of cardiac masses' malignant nature is essential to guide proper treatment. We aimed to develop a cardiac magnetic resonance (CMR)-derived model including mass localization, morphology, and tissue characterization to predict malignancy (with histology as gold standard), to compare its accuracy versus the diagnostic echocardiographic mass score, and to evaluate its prognostic ability. METHODS: Observational cohort study of 167 consecutive patients undergoing comprehensive echocardiogram and CMR within 1-month time interval for suspected cardiac mass. A definitive diagnosis was achieved by histological examination or, in the case of cardiac thrombi, by histology or radiological resolution after adequate anticoagulation treatment. Logistic regression was performed to assess CMR-derived independent predictors of malignancy, which were included in a predictive model to derive the CMR mass score. Kaplan-Meier curves and Cox regression were used to investigate the prognostic ability of predictors. RESULTS: In CMR, mass morphological features (non-left localization, sessile, polylobate, inhomogeneity, infiltration, and pericardial effusion) and mass tissue characterization features (first-pass perfusion and heterogeneity enhancement) were independent predictors of malignancy. The CMR mass score (range, 0-8 and cutoff, ≥5), including sessile appearance, polylobate shape, infiltration, pericardial effusion, first-pass contrast perfusion, and heterogeneity enhancement, showed excellent accuracy in predicting malignancy (areas under the curve, 0.976 [95% CI, 0.96-0.99]), significantly higher than diagnostic echocardiographic mass score (areas under the curve, 0.932; P=0.040). The agreement between the diagnostic echocardiographic mass and CMR mass scores was good (κ=0.66). A CMR mass score of ≥5 predicted a higher risk of all-cause death (P<0.001; hazard ratio, 5.70) at follow-up. CONCLUSIONS: A CMR-derived model, including mass morphology and tissue characterization, showed excellent accuracy, superior to echocardiography, in predicting cardiac masses malignancy, with prognostic implications.

Prediction of the development of new coronary atherosclerotic plaques with radiomics.

BACKGROUND: Radiomics is expected to identify imaging features beyond the human eye. We investigated whether radiomics can identify coronary segments that will develop new atherosclerotic plaques on coronary computed tomography angiography (CCTA). METHODS: From a prospective multinational registry of patients with serial CCTA studies at ≥ 2-year intervals, segments without identifiable coronary plaque at baseline were selected and radiomic features were extracted. Cox models using clinical risk factors (Model 1), radiomic features (Model 2) and both clinical risk factors and radiomic features (Model 3) were constructed to predict the development of a coronary plaque, defined as total PV â€‹≥ â€‹1 â€‹mm3, at follow-up CCTA in each segment. RESULTS: In total, 9583 normal coronary segments were identified from 1162 patients (60.3 â€‹± â€‹9.2 years, 55.7% male) and divided 8:2 into training and test sets. At follow-up CCTA, 9.8% of the segments developed new coronary plaque. The predictive power of Models 1 and 2 was not different in both the training and test sets (C-index [95% confidence interval (CI)] of Model 1 vs. Model 2: 0.701 [0.690-0.712] vs. 0.699 [0.0.688-0.710] and 0.696 [0.671-0.725] vs. 0.0.691 [0.667-0.715], respectively, all p â€‹> â€‹0.05). The addition of radiomic features to clinical risk factors improved the predictive power of the Cox model in both the training and test sets (C-index [95% CI] of Model 3: 0.772 [0.762-0.781] and 0.767 [0.751-0.787], respectively, all p â€‹< â€‹00.0001 compared to Models 1 and 2). CONCLUSION: Radiomic features can improve the identification of segments that would develop new coronary atherosclerotic plaque. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT0280341.

Rapid Plaque Progression Is Independently Associated With Hyperglycemia and Low HDL Cholesterol in Patients With Stable Coronary Artery Disease: A PARADIGM Study.

BACKGROUND: We assessed whether combinations of cardiometabolic risk factors independently predict coronary plaque progression (PP) and major adverse cardiovascular events in patients with stable coronary artery disease. METHODS: Patients with known or suspected stable coronary artery disease (60.9±9.3 years, 55.4% male) undergoing serial coronary computed tomography angiographies (≥2 years apart), with clinical characterization and follow-up (N=1200), were analyzed from the PARADIGM study (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging). Plaque volumes measured in coronary segments (≥2 mm in diameter) were summed to provide whole heart plaque volume (mm3) and percent atheroma volume (plaque volume/vessel volume×100; %) per patient at baseline and follow-up. Rapid PP was defined as a percent atheroma volume increase of ≥1.0%/y. Major adverse cardiovascular events included nonfatal myocardial infarction, death, and unplanned coronary revascularization. RESULTS: In an interscan period of 3.2 years (interquartile range, 1.9), rapid PP occurred in 341 patients (28%). At multivariable analysis, the combination of cardiometabolic risk factors defined as metabolic syndrome predicted rapid PP (odds ratio, 1.51 [95% CI, 1.12-2.03]; P=0.007) together with older age, smoking habits, and baseline percent atheroma volume. Among single cardiometabolic variables, high fasting plasma glucose (diabetes or fasting plasma glucose >100 mg/dL) and low HDL-C (high-density lipoprotein cholesterol; <40 mg/dL in males and <50 mg/dL in females) were independently associated with rapid PP, in particular when combined (odds ratio, 2.37 [95% CI, 1.56-3.61]; P<0.001). In a follow-up of 8.23 years (interquartile range, 5.92-9.53), major adverse cardiovascular events occurred in 201 patients (17%). At multivariable Cox analysis, the combination of high fasting plasma glucose with high systemic blood pressure (treated hypertension or systemic blood pressure >130/85 mm Hg) was an independent predictor of events (hazard ratio, 1.79 [95% CI, 1.10-2.90]; P=0.018) together with family history, baseline percent atheroma volume, and rapid PP. CONCLUSIONS: In patients with stable coronary artery disease, the combination of hyperglycemia with low HDL-C is associated with rapid PP independently of other risk factors, baseline plaque burden, and treatment. The combination of hyperglycemia with high systemic blood pressure independently predicts the worse outcome beyond PP. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02803411.