Hypercholesterolemia and inflammation-Cooperative cardiovascular risk factors.

BACKGROUND: Maintaining low concentrations of plasma low-density lipoprotein cholesterol (LDLc) over time decreases the number of LDL particles trapped within the artery wall, slows the progression of atherosclerosis and delays the age at which mature atherosclerotic plaques develop. This substantially reduces the lifetime risk of atherosclerotic cardiovascular disease (ASCVD) events. In this context, plaque development and vulnerability result not only from lipid accumulation but also from inflammation. RESULTS: Changes in the composition of immune cells, including macrophages, dendritic cells, T cells, B cells, mast cells and neutrophils, along with altered cytokine and chemokine release, disrupt the equilibrium between inflammation and anti-inflammatory mechanisms at plaque sites. Considering that it is not a competition between LDLc and inflammation, but instead that they are partners in crime, the present narrative review aims to give an overview of the main inflammatory molecular pathways linked to raised LDLc concentrations and to describe the impact of lipid-lowering approaches on the inflammatory and lipid burden. Although remarkable changes in LDLc are driven by the most recent lipid lowering combinations, the relative reduction in plasma C-reactive protein appears to be independent of the magnitude of LDLc lowering. CONCLUSION: Identifying clinical biomarkers of inflammation (e.g. interleukin-6) and possible targets for therapy holds promise for monitoring and reducing the ASCVD burden in suitable patients.

LDL-cholesterol goal achievement and self-reported medication adherence: insights from the JET-LDL registry.

In patients with recent acute coronary syndromes (ACS), current guidelines recommend a low-density lipoprotein cholesterol (LDL-C) level <55 mg/dl. Despite the widespread use of different potent lipid-lowering therapies (LLT), this goal is not always achieved, often due to poor medication adherence. In this prespecified subanalysis of the JET-LDL registry, we sought to evaluate the relationship between LDL-C targets achievement and LLT adherence in a cohort of patients hospitalized for ACS. Patients self-reported medication adherence was assessed using the Morisky Medication Adherence Scale (MMAS) at 3-months follow-up. Depending on the score obtained, the population was divided into two groups: high adherence (HA, MMAS≥6) vs low adherence (LA, MMAS<6). The occurrence of the primary-endpoint (LDL-C reduction >50% from baseline or level <55 mg/dl at 1-month) was compared between the two groups. 963 patients were included in the present analysis; in 277 cases (28.7%) a MMAS score <6 was reported (LA-group), while in the other 686 (71.3%) the score obtained was ≥6 (HA-group). No difference between the two groups was observed regarding LDL-C levels at admission and LLT prescribed at discharge. At 1-month, primary-endpoint occurred in 62.5% of cases, with a statistically significant difference between the two groups (LA 60% vs HA 65%, p-value 0.034). At multivariate logistic regression analysis, LA was identified as an independent predictor of not achieving the primary-endpoint (OR 0.48 [0.39-0.85], p-value 0.006). In conclusion, in a real-world cohort of patients with ACS, low medication adherence to LLT was a common event (28.7%), having a negative impact on LDL-C goal achievement.

Myocardial Mechanics in Acromegaly: A Meta-Analysis of Echocardiographic Studies.

INTRODUCTION: Evidence on myocardial deformation, detected by speckle tracking echocardiography (STE), in patients with acromegaly is scanty. AIM: The aim of the present meta-analysis was to provide an updated information on left ventricular (LV) systolic function assessed by global longitudinal strain (GLS) in patients with acromegaly and preserved LVEF. METHODS: Following the PRISMA guidelines, systematic searches were conducted across bibliographic databases (Pub-Med, OVID, EMBASE and Cochrane library) to identify eligible studies from inception up to June 30-2024. Clinical studies published in English reporting data on LV mechanics in patients with acromegaly and controls were included. The statistical difference of the echocardiographic variables of interest between groups such as LVEF and global longitudinal strain (GLS) was calculated by standardized mean difference (SMD) with 95% confidence interval (CI) by using random-effects models. RESULTS: Seven studies including 288 patients with acromegaly and 294 healthy individuals were considered for the analysis. Pooled average LVEF values were 64.6 ± 1.5% in the healthy control group and 64.0 ± 1.3% in the acromegaly group (SMD: - 0.21 ± 0.22, CI -0.62/0.22, p = 0.34); the corresponding values of GLS were - 19.1.1 ± 1.2% and - 17.5 ± 1.2% (SMD: -0.52 ± 0.27, CI - 1.05/0.01, p = 0.05). No difference was found between the two groups for both global circumferential strain (GCS) and global radial strain (GRS). CONCLUSIONS: Our findings suggest that patients with acromegaly in which LVEF is completely comparable to healthy controls show an impairment in GLS of borderline statistical significance. Whether GLS assessment can actually unmask early alterations of systolic function in patients with acromegaly better than LVEF will need to be investigated by future studies.

Concordance between Coronary Artery Computed Tomography and Invasive Coronary Angiography in a Real-World Population with Suspected Chronic Coronary Syndrome.

BACKGROUND: Coronary computed tomographic angiography (CCTA) is a non-invasive imaging technique that possesses the ability to provide detailed anatomical information about coronary arteries, avoiding unnecessary invasive procedures. Our aim was to assess the ability of CCTA to identify coronary artery disease compared to invasive coronary angiography (ICA) in a real-life setting. METHODS: We examined 137 consecutive patients who underwent ICA after CCTA. The latter was conducted in various non-selected centers, and data regarding stenosis were taken from individual reports without further analysis. RESULTS: A total of 60.5% of patients who underwent CCTA were found to have at least one critical stenosis, while the remaining 39.5% underwent ICA due to concurrent clinical or instrumental indications. Among these, 29.5% had angiographically critical pathology, 20.3% underwent a percutaneous coronary intervention (PCI), and 1.8% had coronary artery bypass grafting. Among the 83 patients with positive CCTA results, 34.9% had negative ICA findings. CCTA demonstrated low sensitivity (57.8%) and a positive predictive value of 42.6%. However, it retained high specificity (83.6%) and a negative predictive value of 90.4% for identifying critical stenosis. Among the 18.2% of patients who underwent CCTA without a specific indication, 60% had critical coronary lesions on their ICA and 86.6% of these subsequently underwent a PCI. CONCLUSIONS: CCTA performed in non-selective centers has a low concordance with ICA.

Doxorubicin-related cardiotoxicity: review of fundamental pathways of cardiovascular system injury.

Over the years, advancements in the field of oncology have made remarkable strides in enhancing the efficacy of medical care for patients with cancer. These modernizations have resulted in prolonged survival and improved the quality of life for these patients. However, this progress has also been accompanied by escalation in mortality rates associated with anthracycline chemotherapy. Anthracyclines, which are known for their potent antitumor properties, are notorious for their substantial cardiotoxic potential. Remarkably, even after 6 decades of research, a conclusive solution to protect the cardiovascular system against doxorubicin-induced damage has not yet been established. A comprehensive understanding of the pathophysiological processes driving cardiotoxicity combined with targeted research is crucial for developing innovative cardioprotective strategies. This review seeks to explain the mechanisms responsible for structural and functional alterations in doxorubicin-induced cardiomyopathy.

Myocardial mechanics in anorexia nervosa: a systematic review and meta-analysis of speckle tracking echocardiographic studies.

BACKGROUND: Clinical complications of anorexia nervosa (AN) include cardiac structural and functional alterations. Available evidence on impaired myocardial deformation in AN patients without overt systolic dysfunction as assessed by left ventricular ejection fraction (LVEF) is scanty and based on a few studies. The aim of the present meta-analysis was to provide comprehensive and updated information on this issue. METHODS: Following the PRISMA guidelines, systematic searches were conducted across bibliographic databases (Pub-Med, OVID, EMBASE and Cochrane library) to identify eligible studies from inception up to 31 January 2024. Searches were limited to clinical investigations published in English reporting data on left ventricular (LV) mechanics (i.e. global longitudinal strain) in patients with anorexia and controls. The statistical difference of the echocardiographic variables of interest between groups such as LVEF and global longitudinal strain (GLS) was calculated by standardized mean difference (SMD) with 95% confidence interval (CI) by using random-effects models. RESULTS: Five studies including 171 AN and 147 healthy normal-weight individuals were considered for the analysis. Pooled average LVEF values were 63.2 ±â€Š0.4% in the healthy control group and 64.6 ±â€Š1.0% in the AN group (SMD -0.08 ±â€Š0.11, CI: -0.15/0.30, P  = 0.51); the corresponding values of GLS were -20.1 ±â€Š0.9% and -20.2 ±â€Š0.9% (SMD 0.07 ±â€Š0.3, CI: -0.46/0.60, P  = 0.80). Unlike GLS, apical strain (data from three studies) was higher in AN than in controls (-23.1 ±â€Š1.8 vs. -21.3 ±â€Š1.8; SMD: -0.42 ±â€Š0.17, CI: -0.08/-0.76, P  = 0.01). CONCLUSIONS: The results of the present meta-analysis do not support the view that myocardial deformation as assessed by GLS is impaired in patients with AN and preserved LVEF. The role of STE in detecting subclinical cardiac damage in this clinical condition deserves to be evaluated in future studies including regional LV strain.

Extensive myocardial calcifications: a systematic literature review of a rare pathological phenomenon.

Introduction: Myocardial calcifications (MC) represent a relatively rare pathological process, which may accompany different cardiovascular conditions and can be broadly categorized as dystrophic or metastatic. Myocardial infarction (MI) has been traditionally regarded as the main cause of MC overall; however, no updated comprehensive data on the relative incidence of different forms of MC is available. The purpose of this systematic review of the literature is to analyze the currently available evidence on MC in terms of pathophysiology, diagnosis, and clinical presentation. Methods and results: A total of 241 studies including a total of 368 patients affected by extensive MC were included in the final review. The majority of patients (69.8%) presented with dystrophic MC. Endomyocardial fibrosis (EMF) represents the single most common etiology of MC (24.2%), while sepsis/acute systemic inflammatory syndrome (SIRS) and chronic kidney disease were identified as the second and third most common causes respectively. The relative incidence of etiologies also varies across the years, with MI being more represented before 1990, and sepsis/SIRS becoming the single most common cause of MC after 1990. Multimodality imaging was used in the work-up of MC in 42.7% of cases. The most commonly employed imaging modality overall was echocardiography (51.9%), while after 1990 computed tomography scan became the most widely used tool (70.1%). Conclusion: The present systematic review provides new insights into the pathophysiology of MC. Previously thought to be mainly a consequence of ischemic heart disease, our data indicate that other diseases, namely EMF and sepsis/SIRS, are indeed the main conditions associated with MC. The importance of multimodality imaging in the work-up of MC is also highlighted.

Biallelic NEXN variants and fetal onset dilated cardiomyopathy: two independent case reports and revision of literature.

BACKGROUND: Dilated cardiomyopathy (DCM) is an etiologically heterogeneous group of diseases of the myocardium. With the rapid evolution in laboratory investigations, genetic background is increasingly determined including many genes with variable penetrance and expressivity. Biallelic NEXN variants are rare in humans and associated with poor prognosis: fetal and perinatal death or severe DCMs in infants. CASE PRESENTATION: We describe two male infants with prenatal diagnosis of dilated cardiomyopathy with impaired ventricular contractility. One of the patients showed hydrops and polyhydramnios. Postnatally, a DCM with severely reduced systolic function was confirmed and required medical treatment. In patient 1, Whole Exome Sequencing (WES) revealed a homozygous NEXN variant: c.1156dup (p.Met386fs) while in patient 2 a custom Next Generation Sequencing (NGS) panel revealed the homozygous NEXN variant c.1579_1584delp. (Glu527_Glu528del). These NEXN variants have not been previously described. Unlike the unfavorable prognosis described for biallelic NEXN variants, we observed in both our patients a favorable clinical course over time. CONCLUSION: This report might help to broaden the present knowledge regarding NEXN biallelic variants and their clinical expression. It might be worthy to consider the inclusion of the NEXN gene sequencing in the investigation of pediatric patients with DCM.

Indoor air pollution impacts cardiovascular autonomic control during sleep and the inflammatory profile.

The present study explores the modifications of cardiovascular autonomic control (CAC) during wake and sleep time and the systemic inflammatory profile associated with exposure to indoor air pollution (IAP) in a cohort of healthy subjects. Twenty healthy volunteers were enrolled. Indoor levels of fine particulate matter (PM2.5), nitrogen dioxide (NO2) and volatile organic compounds (VOCs) were monitored using a portable detector for 7 days. Together, a 7-day monitoring was performed through a wireless patch that continuously recorded electrocardiogram, respiratory activity and actigraphy. Indexes of CAC during wake and sleep time were derived from the biosignals: heart rate and low-frequency to high-frequency ratio (LF/HF), index of sympathovagal balance with higher values corresponding to a predominance of the sympathetic branch. Cyclic variation of heart rate index (CVHRI events/hour) during sleep, a proxy for the evaluation of sleep apnea, was assessed for each night. After the monitoring, blood samples were collected to assess the inflammatory profile. Regression and correlation analyses were performed. A positive association between VOC exposure and the CVHRI (Δ% = +0.2% for 1 µg/m3 VOCs, p = 0.008) was found. The CVHRI was also positively associated with LF/HF during sleep, thus higher CVHRI values corresponded to a shift of the sympathovagal balance towards a sympathetic predominance (r = 0.52; p = 0.018). NO2 exposure was positively associated with both the pro-inflammatory biomarker TREM-1 and the anti-inflammatory biomarker IL-10 (Δ% = +1.2% and Δ% = +2.4%, for 1 µg/m3 NO2; p = 0.005 and p = 0.022, respectively). The study highlights a possible causal relationship between IAP exposure and higher risk of sleep apnea events, associated with impaired CAC during sleep, and a pro-inflammatory state counterbalanced by an increased anti-inflammatory response in healthy subjects. This process may be disrupted in vulnerable populations, leading to a harmful chronic pro-inflammatory profile. Thus, IAP may emerge as a critical and often neglected risk factor for the public health that can be addressed through targeted preventive interventions.

PCSK9 and Coronary Artery Plaque-New Opportunity or Red Herring?

PURPOSE OF REVIEW: Although the clinical benefit of reducing low-density lipoprotein cholesterol (LDLc) in patients with coronary artery disease (CAD) is well-established, the impact on plaque composition and stability is less clear. Our narrative review aimed to assess the clinical effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on coronary plaque characteristics specifically focusing from atheroma progression to regression and stabilization. RECENT FINDINGS: The combination of statin therapy and PCSK9 inhibitors (evolocumab and alirocumab) promotes plaque stability in patients following an acute coronary syndrome. The GLAGOV study highlighted the relationship between achieved LDLc levels and changes in percentage atheroma volume. Similarly, the PACMAN-AMI study concluded that the qualitative and quantitative changes in coronary plaque were associated with the levels of LDLc. Assessing the severity of coronary artery stenosis and the extent of atherosclerotic burden by means of imaging techniques (e.g., IVUS, OCT and near-infrared spectroscopic) have significantly advanced our understanding of the benefits from promoting plaque regression and achieving to features of plaque stabilization through increasingly intensive lipid-lowering strategies.

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).

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.

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.

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.

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.

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.