Discovering Inflammation in Atherosclerosis: Insights from Pathogenic Pathways to Clinical Practice.

This comprehensive review explores the various scenarios of atherosclerosis, a systemic and chronic arterial disease that underlies most cardiovascular disorders. Starting from an overview of its insidious development, often asymptomatic until it reaches advanced stages, the review delves into the pathophysiological evolution of atherosclerotic lesions, highlighting the central role of inflammation. Insights into clinical manifestations, including heart attacks and strokes, highlight the disease's significant burden on global health. Emphasis is placed on carotid atherosclerosis, clarifying its epidemiology, clinical implications, and association with cognitive decline. Prevention strategies, lifestyle modifications, risk factor management, and nuanced antithrombotic treatment considerations are critical to managing cardiovascular complications, thus addressing a crucial aspect of cardiovascular health.

Strike early-strike strong lipid-lowering strategy with PCSK9i in ACS patients. Real-world evidence from AT-TARGET-IT registry.

AIMS: No data are available on early initiation of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in patients with acute coronary syndrome (ACS) in real-world. This study investigates the effects of PCSK9i started at time of ACS hospitalization on lipid control and major CV events in real-world. METHODS: The lipid control outcome was the percentage of patients reaching the LDL-C target of < 55 mg/dL at first lipid control. The clinical outcome was the incidence of composite major CV events (all cause death, non-fatal MI, non-fatal stroke, and ischemia-driven revascularization) during follow-up in relation to quartiles of LDL-C at first lipid control. RESULTS: We included 771 patients with ACS from AT-TARGET-IT registry, receiving PCSK9i prescription during hospitalization or at discharge. Median LDL-C was 137 mg/dL and decreased to 43 mg/dL at first lipid control. 527 (68.3%) patients achieved LDL-C target at the first lipid control at a median time of 37 days from hospitalization; of them, 404 (76.8%) were discharged on statin plus ezetimibe background therapy. Event curves through a median follow-up of 11 months across quartiles of LDL-C showed a stepwise lower risk of 4P-MACE, 3P-MACE, all-cause mortality, and ischemia-driven revascularization in lower quartile of LDL-C values at first lipid control (<23 mg/dL) and in patients reaching LDL-C <55 mg/dL. CONCLUSIONS: Intensive and early lipid-lowering therapy using PCSK9i in patients with ACS (strike early strike strong strategy) is safe and effective in clinical practice and associated with a reduction of residual CV risk.

This study, from AT-TARGET-IT registry, investigates the effects of PCSK9i started at time of ACS hospitalization on lipid control and major CV events in real-world. Intensive and early PCSK9i therapy reduce composite major cardiovascular (CV) events in patients in reaching LDL-C target values. A strike early-strike strong strategy is safe and effective.

Management of heart failure: similarities and discrepancies between the European Society of Cardiology and the American Heart Association guidelines.

Recommendations are the fundamental elements of guidelines and are especially significant when the amount of scientific data is expanding fast, as is the scenario of heart failure (HF). Beginning with the four pillars of treatment for HF with reduced ejection fraction, the main messages of the two most recent major HF guidelines, endorsed by the European Society of Cardiology (ESC) and the American College of Cardiology/American Heart Association/Heart Failure Society of America (ACC/AHA/HFSA), partially overlap. There are notable differences, in part due to the timing of recent publications, like the Universal Definition of HF and the EMPEROR-Preserved trial, and in part due to differing perspectives on the natural history of HF. Specific challenges, such as risk stratification and the use of implanted cardioverter-defibrillators for primary prevention in HFrEF patients with non-ischaemic aetiology, are approached from a variety of perspectives. The ACC/AHA/HFSA recommendations place increased attention on topics that are especially pertinent to the US context, such as the cost-effectiveness of medications and the impact of health inequalities on HF care. A comparison of guideline suggestions may assist readers get a better grasp of the ESC and ACC/AHA/HFSA guidelines and apply logical ways to their own practice, wherever in the world that may be. A comparison may also contribute to the harmonization of future guidelines' recommendations by highlighting the reasons why certain areas have resulted to different recommendations while seemingly analysing the same published information.

Depression in Heart Failure with Reduced Ejection Fraction, an Undervalued Comorbidity: An Up-To-Date Review.

Introduction: Depression is a common and severe comorbidity among individuals with heart failure (HF). Up to a third of all HF patients are depressed, and an even higher proportion have symptoms of depression. Aim: In this review, we evaluate the relationship between HF and depression, explain the pathophysiology and epidemiology of both diseases and their relationship, and highlight novel diagnostic and therapeutic options for HF patients with depression. Materials and Methods: This narrative review involved keyword searches of PubMed and Web of Science. Review search terms included ["Depression" OR "Depres*" OR "major depr*"] AND ["Heart Failure" OR "HF" OR "HFrEF" OR "HFmrEF" OR "HFpEF" OR "HFimpEF"] in all fields. Studies included in the review met the following criteria: (A) published in a peer-reviewed journal; (B) described the impact of depression on HF and vice versa; and (C) were opinion papers, guidelines, case studies, descriptive studies, randomized control trials, prospective studies, retrospective studies, narrative reviews, and systematic reviews. Results: Depression is an emergent HF risk factor and strongly relates with worse clinical outcomes. HF and depression share multiple pathways, including platelet dis-reactivity, neuroendocrine malfunction, inappropriate inflammation, tachi-arrhythmias, and frailty in the social and community setting. Existing HF guidelines urge evaluation of depression in all HF patients, and numerous screening tools are available. Depression is ultimately diagnosed based on DSM-5 criteria. There are both non-pharmaceutical and pharmaceutical treatments for depression. Regarding depressed symptoms, non-pharmaceutical treatments, such as cognitive-behavioral therapy and physical exercise, have shown therapeutic results, under medical supervision and with an effort level adapted to the patient's physical resources, together with optimal HF treatment. In randomized clinical studies, selective serotonin reuptake inhibitors, the backbone of antidepressant treatment, did not demonstrate advantage over the placebo in patients with HF. New antidepressant medications are currently being studied and could provide a chance to enhance management, treatment, and control of depression in patients with HF. Conclusions: Despite the substantial link between depression and HF, their combination is underdiagnosed and undertreated. Considering the hopeful yet unclear findings of antidepressant trials, further research is required to identify people who may benefit from antidepressant medication. The goal of future research should be a complete approach to the care of these patients, who are anticipated to become a significant medical burden in the future.

123I-MIBG imaging in heart failure: impact of comorbidities on cardiac sympathetic innervation.

PURPOSE: Heart failure (HF) is a primary cause of morbidity and mortality worldwide, with significant impact on life quality and extensive healthcare costs. Assessment of myocardial sympathetic innervation function plays a central role in prognosis assessment in HF patients. The aim of this review is to summarize the most recent evidence regarding the clinical applications of iodine-123 metaiodobenzylguanidine (123I-MIBG) imaging in patients with HF and related comorbidities. METHODS: A comprehensive literature search was conducted on PubMed and Web of Science databases. Articles describing the impact of 123I-MIBG imaging on HF and related comorbidities were considered eligible for the review. RESULTS: We collected several data reporting that 123I-MIBG imaging is a safe and non-invasive tool to evaluate dysfunction of cardiac sympathetic neuronal function and to assess risk stratification in HF patients. HF is frequently associated with comorbidities that may affect cardiac adrenergic innervation. Furthermore, HF is frequently associated with comorbidities and chronic conditions, such as diabetes, obesity, kidney disease and others, that may affect cardiac adrenergic innervation. CONCLUSION: Comorbidities and chronic conditions lead to more severe impairment of sympathetic nervous system in patients with HF, with a negative impact on disease progression and outcome. Cardiac imaging with 123I-MIBG can be a useful tool to reduce morbidity and prevent adverse events in HF patients.

Sacubitril/valsartan reduces cardiac decompensation in heart failure with preserved ejection fraction: a meta-analysis.

BACKGROUND: The impact of sacubitril-valsartan on heart failure (HF) patients with preserved ejection fractions (HFpEF) is uncertain. The purpose of this meta-analysis was to explore the clinical advantages and safety of sacubitril-valsartan in patients with HFpEF. METHODS: PubMed and Web of Science were searched without any restrictions from inception to 8 May 2022 to identify valuable articles. The studies that met the inclusion criteria were analyzed. RESULTS: Four trials, with a total of 7008 patients were included. Compared with valsartan, sacubitril-valsartan significantly reduced the rate of HF decompensation and of the combined end point of HF decompensation and all-cause mortality. All-cause mortality, New York Heart Association class improvement and rate of hyperkalemia were not significantly different between the two groups. Regarding safety, sacubitril-valsartan was more likely to increase the risk of hypotension. CONCLUSION: This meta-analysis suggests that sacubitril-valsartan may be an effective strategy to reduce HF decompensation events in patients with HFpEF.Systematic Review registration: CRD42022336077.

MicroRNAs: diagnostic, prognostic and therapeutic role in heart failure-a review.

Heart failure is a leading cause of morbidity and mortality, with relevant social and economic burden on global healthcare system. Although the development of novel diagnostic tools and the advance in therapies have deeply influenced the diagnosis and treatment of this disease, improving both prognosis and life expectancy of patients, hospitalization is still high, and mortality remains considerable. MicroRNAs are small endogenous RNA molecules that post-transcriptionally regulate gene expression in both physiological and pathological processes. In recent years, microRNA have arisen as attractive therapeutic targets in the treatment of a wide spectrum of pathologies, including heart failure. In cardiac pathology, deregulation of microRNAs expression and function is associated to adverse outcome and heart failure progression. Circulating levels of specific microRNAs have emerged as useful biomarkers for the diagnosis of heart failure or as prognostic indicators. In the present review, we summarize the state of current research on the role of miRNAs as biomarkers for diagnosis and prognosis in patients with heart failure and their use as potential therapeutic targets for this condition.