Lipid-lowering approaches to manage statin-intolerant patients.

Statins have improved the potential to prevent cardiovascular disease events and to prolong the lives of patients. Statins, among the most widely used drugs worldwide, reduce the levels of low-density lipoprotein cholesterol (LDL-C) by an average of 30-50%. However, non-adherence to statin therapy, due to statin intolerance, might be as high as 60% after 24 months of treatment and is associated with a 70% increase in the risk of cardiovascular disease events. Statin intolerance can be classified as a complete inability to tolerate any dose of a statin or a partial intolerance with the inability to tolerate the dose necessary to achieve the patient-specific therapeutic objective. Reasons for discontinuation are many, with statin-associated muscle symptoms being cited as the most frequent reason for stopping therapy and the incidence of muscle symptoms increasing with treatment intensity. Considering the causal effect of LDL-C in the atherosclerotic process, clinicians should consider that regardless of the lipid-lowering drugs patients are willing to take, any reduction in LDL-C they achieve will afford them some benefit in reducing cardiovascular risk. Besides statins, the current therapeutic armamentarium offers different strategies to reach LDL-C targets in statin-intolerant patients (i.e. a fixed combination between a lower dose of statin plus ezetimibe, bempedoic acid, or proprotein convertase subtilisin/kexin type 9 inhibition).

OPTImal PHARMacological therapy for patients with heart failure: Rationale and design of the OPTIPHARM-HF registry.

AIMS: Patients with heart failure (HF) remain often undertreated for multiple reasons, including treatment inertia, contraindications, and intolerance. The OPTIimal PHARMacological therapy for patients with Heart Failure (OPTIPHARM-HF) registry is designed to evaluate the prevalence of evidence-based medical treatment prescription and titration, as well as the causes of its underuse, in a broad real-world population of consecutive patients with HF across the whole ejection fraction spectrum and among different clinical phenotypes. METHODS: The OPTIPHARM-HF registry (NCT06192524) is a prospective, multicenter, observational, national study of adult patients with symptomatic HF, as defined by current international guidelines, regardless of ejection fraction. Both outpatients and inpatients with chronic and acute decompensated HF will be recruited. The study will enroll up to 2500 patients with chronic HF at approximately 35 Italian HF centres. Patients will be followed for a maximum duration of 24 months. The primary objective of the OPTIPHARM-HF registry is to assess prescription and adherence to evidence-based guideline-directed medical therapy (GDMT) in patients with HF. The primary outcome is to describe the prevalence of GDMT use according to target guideline recommendation. Secondary objectives include implementation of comorbidity treatment, evaluation of sequence of treatment introduction and up-titration, description of GDMT implementation in the specific HF population, main causes of GDMT underuse, and assessment of cumulative rate of cardiovascular events. CONCLUSION: The OPTIPHARM-HF registry will provide important implications for improving patient care and adoption of recommended medical therapy into clinical practice among HF patients.

Unraveling the Enigma of Moderate Aortic Stenosis: Challenges and Future Prospects.

According to current guidelines, only clinical surveillance is recommended for patients with moderate aortic valve stenosis (AS), while aortic valve replacement may be considered in patients undergoing surgery for other indications. Recent studies have shown that moderate AS is associated with a high risk of adverse cardiovascular events, including death, especially in patients with left ventricular dysfunction. In this context, multimodality imaging can help to improve the accuracy of moderate AS diagnosis and to assess left ventricular remodeling response. This review discusses the natural history of this valve disease and the role of multimodality imaging in the diagnostic process, summarizes current evidence on the medical and non-medical management, and highlights ongoing trials on valve replacement.

Exercise response in post-acute coronary syndrome patients survived to COVID-19 infection.

AIMS: Many studies evaluated the functional response in post-Covid-19 patients; however, they systematically excluded patients with concomitant acute coronary syndrome (ACS). We evaluated the long-term functional capacity assessed by cardiopulmonary exercise test (CPET) in patients hospitalized for ACS and concomitant SARS-CoV2 infection. The secondary aim was to investigate the functional response in patients with symptoms related to "long COVID-19 syndrome" (LCS). METHODS: This cross-sectional case-control study compared 20 patients with ACS and concomitant SARS-COV2 infection with 20 patients without COVID-19. At the follow-up visit (between 6 and 12 months after revascularization procedure) all patients underwent a CPET. RESULTS: Patients with previous ACS and concomitant COVID-19 showed a reduced O2 consumption than controls (predicted peak V̇O2 74.00% vs 86.70%; p = 0.01) with a high degree of ventilatory inefficiency (VE/ V̇CO2 slope 38.04 vs 30.31; p = 0.002). 50% of subjects with previous COVID-19 disease showed symptoms related to "LCS"; this subgroup demarcates the characteristic reduced exercise capacity found in the entire COVID + group. CONCLUSIONS: This study is the first in literature having analyzed the long-term functional capacity phenotype in a population of ACS patients and concomitant SARS-CoV2 infection. Severe ventilatory inefficiency emerged as the functional signature of these patients. Moreover, the subset of patients with symptoms related to LCS has the most compromised long term reduced exercise capacity and an altered ventilation control.

Left ventricular systolic dysfunction in obesity: a meta-analysis of speckle tracking echocardiographic studies.

BACKGROUND: Obesity is a risk factor for left ventricular hypertrophy (LVH) and diastolic dysfunction. Available evidence on impaired myocardial deformation in obese patients without apparent systolic dysfunction assessed by LV ejection fraction (LVEF) is based on single studies. The aim of the present meta-analysis was to provide a comprehensive and updated information on this issue. METHODS: The PubMed, OVID-MEDLINE, and Cochrane library databases were analysed to search English-language articles published from the inception up to 31 December 2023. Studies were identified by using MeSH terms and crossing the following search items: ' myocardial strain', 'left ventricular mechanics', 'longitudinal global strain', 'speckle tracking echocardiography', 'systolic dysfunction', 'left ventricular ejection fraction', and 'obesity'. RESULTS: Twenty-four studies including 5792 obese and 5518 nonobese individuals from different clinical settings were considered for the analysis. LV global longitudinal strain (GLS) was significantly impaired in the obese group [standard means difference (SMD): -0.86 ±â€Š0.08; confidence interval (CI) -1.02 to -0.69, P  < 0.0001] and this was paralleled by a significant difference in pooled LVEF between obese and controls (SMD -0.27 ±â€Š0.06; CI -0.40 to -0.15, P  < 0.0001). Unlike GLS, however, the majority of the selected studies failed to show statistically significant differences in LVEF. Furthermore, in patients with advanced obesity (BMI > 35 kg/m 2 , data from six studies), LV systolic dysfunction was more significantly detected by GLS (SMD -1.24 ±â€Š0.19, CI -1.61/-0.87, P  < 0.0001) than by LVEF (SMD -0.54 ±â€Š0.27, CI -1.07 to -0.01, P  = 0.046). CONCLUSION: The present meta-analysis suggests that GLS may unmask systolic dysfunction often undetected by conventional LVEF in the obese setting; thus, this parameter should be incorporated into routine work-up aimed to identify obesity-mediated subclinical cardiac damage.

Targeting subclinical ventricular dysfunction in atrial fibrillation: What can myocardial work add?

Atrial fibrillation (AF) could impact on left ventricular function leading to a sublinical myocardial dysfunction, as identified by myocardial work parameters in a population-based cohort of AF patients compared with healthy individuals; factors associated with these parameters are also shown. SBP: systolic blood pressure; LAVI: left atrial volume index.

Tri-ponderal mass index and left ventricular hypertrophy in a cohort of caucasian children and adolescents with obesity.

BACKGROUND: Pediatric obesity is a global emerging burden for society; among its health-related consequences there are hypertension (HTN) and left ventricular hypertrophy (LVH). Several anthropometric indices have been investigated for the early identification of cardiovascular risk in children. The aim of the present study was to assess whether tri-ponderal mass index (TMI) was associated with LVH in a cohort of Caucasian children and adolescents with obesity. METHODS: In this observational study, 63 children and adolescents with obesity aged 7-to-16 years were enrolled. During outpatient visits, adiposity, and cardio-metabolic indices (BMI z-score, WHR, TMI, ABSI) were collected. All subjects underwent a 24-hour ambulatory blood pressure monitoring (ABPM) and transthoracic echocardiography. RESULTS: Children and adolescents with obesity with LVH had significantly higher BMI z-score (p = 0.009), WHR (p = 0.006) and TMI (p = 0.026) compared to children without LVH. WC and WHR were the only indices significantly associated with left ventricular mass index (LVMI). CONCLUSION: Left ventricular remodeling is associated with the cardio-metabolic risk markers WC and WHR, but not with the adiposity index TMI among children with obesity.

[Optimizing the care management pathway of patients with ischemia and non-obstructive coronary arteries]. / Ottimizzazione del percorso clinico-gestionale del paziente con ischemia in assenza di malattia coronarica ostruttiva.

Ischemia with non-obstructive coronary arteries (INOCA) is defined by the coexistence of anginal symptoms and demonstrable ischemia, with no evidence of obstructive coronary arteries. The underlying mechanism of INOCA is coronary microvascular dysfunction with or without associated vasospasm. INOCA patients have recurrent symptoms, functional limitations, repeated access to the emergency department, impaired quality of life and a higher incidence of cardiovascular events than the general population. Although well described in chronic coronary syndrome guidelines, INOCA remains underdiagnosed in clinical practice because of insufficient awareness, lack of accurate diagnostic tools, and poorly standardized and consistent definitions to diagnose, both invasively and non-invasively, coronary microvascular dysfunction.To disseminate current scientific evidence on INOCA as a distinct clinical entity, during 2022 we conducted at 30 cardiology units all over the country a clinical practice improvement initiative, with the aim of developing uniform and shared management pathways for INOCA patients across different operational settings. The present document highlights the outcomes of this multidisciplinary initiative.

Exploring the role of epicardial adipose-tissue-derived extracellular vesicles in cardiovascular diseases.

Epicardial adipose tissue (EAT) is a fat depot located between the myocardium and the visceral layer of the epicardium, which, owing to its location, can influence surrounding tissues and can act as a local transducer of systemic inflammation. The mechanisms upon which such influence depends on are however unclear. Given the role EAT undoubtedly has in the scheme of cardiovascular diseases (CVDs), understanding the impact of its cellular components is of upmost importance. Extracellular vesicles (EVs) constitute promising candidates to fill the gap in the knowledge concerning the unexplored mechanisms through which EAT promotes onset and progression of CVDs. Owing to their ability of transporting active biomolecules, EAT-derived EVs have been reported to be actively involved in the pathogenesis of ischemia/reperfusion injury, coronary atherosclerosis, heart failure, and atrial fibrillation. Exploring the precise functions EVs exert in this context may aid in connecting the dots between EAT and CVDs.

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.

A study protocol for evaluating aortic stiffness modifications in patients treated with endovascular aortic repair.

BACKGROUND: Arterial stiffness, particularly aortic stiffness (AoS), is associated with an increased risk of cardiovascular disease. Endovascular repair for abdominal (EVAR) and thoracic (TEVAR) aortic disease may increase AoS. This study protocol aims to assess changes in AoS before and after interventions for aortic disease. METHODS: Patients scheduled for EVAR or TEVAR during a three-year period will be enrolled. An indirect AoS indicator, carotid-to-femoral pulse wave velocity (cf-PWV) will be measured non-invasively using applanation tonometry and reported with others perioperative data before and after the endovascular treatment. Moreover, cardiological data will be collected through echocardiography. RESULTS: Fifty EVAR and 50 TEVAR will be enrolled. We will primarily analyze changes in cf-PWV. To ensure the reliability of our findings, we will also include supplementary data such as clinical information, morphological data, and functional echocardiographic data. CONCLUSIONS: By examining AoS modifications before and after endovascular aortic repair, this study aims to enhance our understanding of how arterial stiffness changes following endoprosthesis deployment. The findings from the applied protocol are expected to be informative for innovative graft designs with minimized mechanical mismatch with the aortic wall and with improved vascular hemodynamic, aligning with the current trend in improving patient outcomes. Moreover, understanding these modifications is important for predicting and improving long-term cardiovascular outcomes in patients undergoing such interventions.

Effect of lipid-lowering therapies on C-reactive protein levels: a comprehensive meta-analysis of randomized controlled trials.

Chronic low-degree inflammation is a hallmark of atherosclerotic cardiovascular (CV) disease. To assess the effect of lipid-lowering therapies on C-reactive protein (CRP), a biomarker of inflammation, we conducted a meta-analysis according to the PRISMA guidelines. Databases were searched from inception to July 2023. Inclusion criteria were: (i) randomized controlled trials (RCTs) in human, Phase II, III, or IV; (ii) English language; (iii) comparing the effect of lipid-lowering drugs vs. placebo; (iv) reporting the effects on CRP levels; (v) with intervention duration of more than 3 weeks; (vi) and sample size (for both intervention and control group) over than 100 subjects. The between-group (treatment-placebo) CRP absolute mean differences and 95% confidence intervals were calculated for each drug class separately. A total of 171 668 subjects from 53 RCTs were included. CRP levels (mg/L) were significantly decreased by statins [-0.65 (-0.87 to -0.43), bempedoic acid; -0.43 (-0.67 to -0.20), ezetimibe; -0.28 (-0.48 to -0.08)], and omega-3 fatty acids [omega3FAs, -0.27 (-0.52 to -0.01)]. CRP was reduced by -0.40 (-1.17 to 0.38) with fibrates, although not statistically significant. A slight increase of CRP concentration was observed for proprotein convertase subtilisin/kexin type 9 inhibitors [0.11 (0.07-0.14)] and cholesteryl-ester transfer protein inhibitors [0.10 (0.00-0.21)], the latter being not statistically significant. Meta-regression analysis did not show a significant correlation between changes in CRP and LDL cholesterol (LDL-C) or triglycerides. Statins, bempedoic acid, ezetimibe, and omega3FAs significantly reduce serum CRP concentration, independently of LDL-C reductions. The impact of this anti-inflammatory effect in terms of CV prevention needs further investigation.

Myocardial strain of the left ventricle by speckle tracking echocardiography: From physics to clinical practice.

Speckle tracking echocardiography (STE) is a reliable imaging technique of recognized clinical value in several settings. This method uses the motion of ultrasound backscatter speckles within echocardiographic images to derive myocardial velocities and deformation parameters, providing crucial insights on several cardiac pathological and physiological processes. Its feasibility, reproducibility, and accuracy have been widely demonstrated, being myocardial strain of the various chambers inserted in diagnostic algorithms and guidelines for various pathologies. The most important parameters are Global longitudinal strain (GLS), Left atrium (LA) reservoir strain, and Global Work Index (GWI): based on large studies the average of the lower limit of normality are -16%, 23%, and 1442 mmHg%, respectively. For GWI, it should be pointed out that myocardial work relies primarily on non-invasive measurements of blood pressure and segmental strain, both of which exhibit high variability, and thus, this variability constitutes a significant limitation of this parameter. In this review, we describe the principal aspects of the theory behind the use of myocardial strain, from cardiac mechanics to image acquisition techniques, outlining its limitation, and its principal clinical applications: in particular, GLS have a role in determine subclinical myocardial dysfunction (in cardiomyopathies, cardiotoxicity, target organ damage in ambulatory patients with arterial hypertension) and LA strain in determine the risk of AF, specifically in ambulatory patients with arterial hypertension.

Prognostic Role of Early Cardiac Magnetic Resonance in Myocardial Infarction With Nonobstructive Coronary Arteries.

BACKGROUND: Cardiac magnetic resonance (CMR) plays a pivotal diagnostic role in myocardial infarction with nonobstructive coronary arteries (MINOCA). To date, a prognostic stratification of these patients is still lacking. OBJECTIVES: This study aims to assess the prognostic role of CMR in MINOCA. METHODS: The authors assessed 437 MINOCA from January 2017 to October 2021. They excluded acute myocarditis, takotsubo syndromes, cardiomyopathies, and other nonischemic etiologies. Patients were classified into 3 subgroups according to the CMR phenotype: 1) presence of late gadolinium enhancement (LGE) and abnormal mapping (M) values (LGE+/M+); 2) regional ischemic injury with abnormal mapping and no LGE (LGE-/M+); and 3) nonpathological CMRs (LGE-/M-). The primary outcome was the presence of major adverse cardiovascular events (MACE). The mean follow-up was 33.7 ± 12.0 months and CMR was performed on average at 4.8 ± 1.5 days from the acute presentation. RESULTS: The final cohort included 198 MINOCA; 116 (58.6%) comprised the LGE+/M+ group. During follow-up, MACE occurred significantly more frequently in MINOCA LGE+/M+ than in the LGE+/M- and normal-CMR (LGE-/M-) subgroups (20.7% vs 6.7% and 2.7%; P = 0.006). The extension of myocardial damage at CMR was significantly greater in patients who developed MACE. In multivariable Cox regression, %LGE was an independent predictor of MACE (HR: 1.123 [95% CI: 1.064-1.185]; P < 0.001) together with T2 mapping values (HR: 1.190 [95% CI: 1.145-1.237]; P = 0.001). CONCLUSIONS: In MINOCA with early CMR execution, the %LGE and abnormal T2 mapping values were identified as independent predictors of adverse cardiac events at ∼3.0 years of follow-up. These parameters can be considered as high-risk markers in MINOCA.