Cardiovascular Medicine
Assessment of Lifetime Risk for Cardiovascular Disease: Time to Move Forward
Over the past decades there has been a notable increase in the risk of Cardiovascular Disease (CVD) even among younger individuals. Policymakers and the health community have revised CVD prevention programs to include younger people in order to take these new circumstances into account. A variety of CVD risk assessment tools have been developed in the past years with the aim of identifying potential CVD candidates at the population level; however they can hardly discriminate against younger individuals at high risk of CVD.Therefore in addition to the traditional 10-year CVD risk assessment lifetime CVD risk assessment has recently been recommended by the American Heart Association/American College of Cardiology and the European Society of Cardiology prevention guidelines particularly for young individuals. Methodologically the benefits of these lifetime prediction models are the incorporation of left truncation observed in survival curves and the risk of competing events which are not considered equivalent in the common survival analysis. Thus lifetime risk data are easily understandable and can be utilized as a risk communication tool for Public Health surveillance. However given the peculiarities behind these estimates structural harmonization should be conducted in order to create a sex- race-specific tool that is sensitive to accurately identifying individuals who are at high risk of CVD. In this review manuscript we present the most commonly used lifetime CVD risk tools elucidate several methodological and critical points their limitations and the rationale behind their integration into everyday clinical practice.
CT-derived Fractional Flow Reserve: How, When, and Where to use this Novel Cardiac Imaging Tool
Fractional flow reserve computed tomography (FFRCT) is a novel imaging modality. It utilizes computational fluid dynamics analysis of coronary blood flow obtained from CCTA images to estimate the decrease in pressure across coronary stenosis during the maximum hyperemia.
The FFRCT can serve as a valuable tool in the assessment of coronary artery disease (CAD). This non-invasive option can be used as an alternative to the invasive fractional Flow Reserve (FFR) evaluation which is presently considered the gold standard for evaluating the physiological significance of coronary stenoses. It can help in several clinical situations including Assessment of Acute and stable chest pain virtual planning for coronary stenting and treatment decision-making.
Although FFRCT has demonstrated potential clinical applications as a non-invasive imaging technique it is also crucial to acknowledge its limitations in clinical practice. As a result it is imperative to meticulously evaluate the advantages and drawbacks of FFRCT individually and contemplate its application in combination with other diagnostic examinations and clinical data.
Volatilome: A Novel Tool for Risk Scoring in Ischemic Heart Disease
Developing a novel risk score for accurate assessment of cardiovascular disease (CVD) morbidity and mortality is an urgent need in terms of early prevention and diagnosis and thereafter management particularly of ischemic heart disease. The currently used scores for the evaluation of cardiovascular disease based on the classical risk factors suffer from severe limitations including inaccurate predictive values. Therefore we suggest adding a novel non-classical risk factor including the level of specific exhaled volatile organic compounds that are associated with ischemic heart disease to the SCORE2 and SCORE2-OP algorithms. Adding these non-classical risk factors can be used together with the classical risk factors (gender smoking total cholesterol low-density lipoprotein cholesterol high-density lipoprotein cholesterol diabetes mellitus arterial hypertension ethnicity etc.) to develop a new algorithm and further program to be used widely.
A Systematic Review of Economic Evidence of Cardiovascular Interventions in India
Cardiovascular diseases (CVDs) continue to be the primary cause of mortality globally and invariably in India as well. The rapid upsurge in the prevalence of CVDs in India has created a pressing need to promote contemporary sustainable and cost-effective interventions to tackle the CVD burden. This systematic review integrates the research-based evidence of the cost-effectiveness of various interventions that can be adapted to control CVDs in India.
Databases namely PubMed Cochrane Library Embase and Google Scholar were searched for data on the economic evaluation of interventions targeting CVD based on the Indian population for a period of 30 years (1991-2021). Two reviewers assessed the articles for eligibility and data were extracted from the shortlisted articles as per a predefined template including the quantification of methodological aspects.
In total 1249 studies were examined out of which 23 completely met the inclusion criteria for full-text review. A total of 16 studies were based solely on the Indian population while the rest (7) included South Asia/Asia for the intervention of which India was a participant nation. Most of the economic evaluations targeted treatment-based or pharmacological interventions (14) for CVDs. The evaluations were based on Decision-based models (10) Randomized controlled Trials (RCTs) (9) and Observational studies (4). The cost-effectiveness ratio for the included studies exhibited a diverse range due to variations in methodological approaches such as differences in study settings populations and inconsistencies in study design. The mean ICER (Incremental Cost-effectiveness ratio) for primordial and primary preventions was found to be 3073.8 (US $2022) and 17489.9 (US $2022) respectively. Moreover the combined mean value for secondary and tertiary prevention was 2029.6 (US$2022).
The economic evidence of public health interventions are expanding but their focus is restricted towards pharmacological interventions. There is an urgency to emphasize primordial and primary prevention for better outcomes in health economics decision-making. Technology-based avenues for intervention need more exploration in order to cater to a large population like India.
Volatilome is Inflammasome- and Lipidome-dependent in Ischemic Heart Disease
Ischemic heart disease (IHD) is a pathology of global interest because it is widespread and has high morbidity and mortality. IHD pathophysiology involves local and systemic changes including lipidomic proteomic and inflammasome changes in serum plasma. The modulation in these metabolites is viable in the pre-IHD during the IHD period and after management of IHD in all forms including lifestyle changes and pharmacological and surgical interventions. Therefore these biochemical markers (metabolite changes; lipidome inflammasome proteome) can be used for early prevention treatment strategy assessment of the patient's response to the treatment diagnosis and determination of prognosis. Lipidomic changes are associated with the severity of inflammation and disorder in the lipidome component and correlation is related to disturbance of inflammasome components. Main inflammasome biomarkers that are associated with coronary artery disease progression include IL‐1β Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) and caspase‐1. Meanwhile the main lipidome biomarkers related to coronary artery disease development involve plasmalogen lipids lysophosphatidylethanolamine (LPE) and phosphatidylethanolamine (PE). The hypothesis of this paper is that the changes in the volatile organic compounds associated with inflammasome and lipidome changes in patients with coronary artery disease are various and depend on the severity and risk factor for death from cardiovascular disease in the time span of 10 years. In this paper we explore the potential origin and pathway in which the lipidome and or inflammasome molecules could be excreted in the exhaled air in the form of volatile organic compounds (VOCs).
Heart Disease in Mothers of Children with Duchenne Muscular Dystrophy
Female carriers of Duchenne Muscular Dystrophy (DMD) carry a heterozygous pathogenic variant in the dystrophin gene and can transmit pathogenic variants to their offspring. DMD is an X-linked recessive disease that affects up to 19.8 in every 100000 male births. Those carriers with symptoms can be referred to as women with dystrophinopathy. Even among asymptomatic carriers cardiac involvement can be verified in between 2.5% and 75% through echocardiography. The most commonly affected wall of the left ventricle is the inferolateral with myocardial fibrosis detected by cardiac nuclear resonance. Therefore screening is recommended for these women carriers due to the risk of cardiomyopathy. There is a lack of longitudinal studies on the evolution of these carriers. In this article data on clinical presentation cardiac assessment for female patients with dystrophinopathy and DMD carriers and approaches for these patients are discussed.
Invasive Treatment of Left Main Coronary Artery Disease: From Anatomical Features to Mechanistic Differences
There is debate on the best treatment for significant stenoses of the left main (LM) coronary artery. The available evidence is based on four randomized trials which were either performed specifically to assess patients with LM disease (EXCEL NOBLE PRECOMBAT) or had a significant fraction of patients with this disease pattern (SYNTAX). A meta-analysis revealed no difference in periprocedural and 5-year mortality but demonstrated a significant reduction of spontaneous myocardial infarction (MI) with CABG. Furthermore the recently published SWEDEHEART registry data have shown survival advantage and fewer MACCE with CABG for LM disease after adjustment. In general patients with more severe coronary artery disease (CAD) appear to have a survival advantage with CABG both over PCI and medical therapy (independent of the presence or absence of LM stenosis) which is always associated with a reduction of spontaneous MI in the CABG arm. Since the nomenclature of LM disease does not automatically reflect the complexity of CAD we review the nature of LM disease in this article. We mechanistically assess the treatment effects of PCI and CABG for patients with LM disease which is rarely isolated often distal and mostly associated with varying degrees of single and multi-vessel disease. We conclude that in patients with isolated LM shaft lesions and associated diseases of low complexity the risk of spontaneous MI is lower and PCI may achieve similar long-term outcomes compared to CABG. Thus heart teams are essential for selecting the best treatment option and should focus on assessing infarction risk in chronic CAD.
The Association between Serum Follistatin-like Proteins and Cardiovascular Diseases: A Systematic Review and Meta-analysis
Follistatin-like proteins (FSTLs) are adipomyokines secreted by adipocytes and myocytes. Previous studies have reported an increase in circulating FSTL1 levels in response to cardiovascular injuries. In this study we conducted a systematic review and meta-analysis to assess the association between circulating FSTLs and Cardiovascular Diseases (CVDs).
We performed a comprehensive literature search using PubMed Web of Science Scopus and Embase databases. After screening the articles we selected eligible studies extracted relevant data and calculated the pooled Standardized Mean Difference (SMD). We also conducted a sensitivity analysis to identify sources of heterogeneity and assessed publication bias.
Among the 577 articles initially retrieved we included 5 studies comprising a total of 941 cases with CVDs and 446 controls. All included studies measured FSTL1 levels. The pooled SMD analysis revealed a significant difference in circulating FSTL1 levels between subjects with CVDs and control groups (SMD = 0.853 95% CI = 0.158-1.548 P = 0.016). Heterogeneity was primarily attributed to a single study that measured FSTL1 levels in heart failure patients with preserved ejection fraction. No publication bias was observed.
Our findings demonstrate significantly higher levels of FSTL1 in patients with CVD compared to control subjects. This suggests that FSTL1 may have potential as a diagnostic and prognostic biomarker in CVDs. However further well-designed studies are needed to validate its clinical utility.
Cardiac Amyloidosis in Venezuela: A Pending Issue
Cardiac amyloidosis (CA) is an infiltrative disease characterized by the deposition of misfolded proteins in cardiac interstitial tissue. Interest towards studying this pathology has been growing in the last decade as new epidemiological insights have revealed that it is not as uncommon as previously believed. Likewise advances in non-invasive diagnostic approaches and the identification of molecules that modify its long-term progression even in terms of mortality have also bolstered interest in CA. Despite this global panorama in Venezuela limitations remain regarding the diagnosis of CA partly associated with a lack of knowledge of the disease. Therefore additional efforts are necessary for clinical cardiologists to hone their diagnostic skills regarding this disease as opportune identification is an essential step for its effective management.
Metabolic Dysfunction-Associated Steatohepatitis and Cardiovascular Disease Prevention: Is Resmetirom Useful?
Antiplatelet Effect of Low-Dose Prasugrel in Elderly Patients Undergoing Percutaneous Coronary Interventions
Background: Low-dose prasugrel (5 mg) has been proposed for patients with Acute Coronary Syndrome (ACS) and advanced age or low body weight. However the routine use of dose-adjusted prasugrel in this high-risk subset of patients is still debated. Aim: This study aimed to assess the prevalence and predictors of HRPR among elderly patients treated with low-dose (5 mg) prasugrel to evaluate the routine use of dose-adjusted prasugrel in this high-risk subset of patients. Methods: We included 59 elderly patients (≥75 years) treated with Dual Antiplatelet Therapy (DAPT: acetylsalicylic acid (ASA) 100-160 mg + prasugrel 5 mg) after Percutaneous Coronary Interventions (PCI) and undergoing platelet function assessment (by whole blood impedance aggregometry) 30-90 days post-discharge. Results: At a median follow-up of 43 days (interquartile range-IQR: 32-54) high-on treatment residual platelet reactivity (HRPR) occurred in 25 patients (42.4%) who displayed a greater body mass index (BMI) (p=0.02) lower levels of vitamin D (p=0.05) and were more frequently treated with nitrates (p=0.03). After multivariate analysis BMI was the only independent predictor of prasugrel HRPR and a BMI >26 was the best cut-off for predicting HRPR (adjusted Odds Ratio - OR=8.6 95%CI: 2.2-33.9 p=0.002). Conclusion: Among elderly patients receiving DAPT after PCI HRPR is common with low-dose prasugrel. A greater BMI especially for values ≥26 is the only independent predictor of HRPR with prasugrel 5 mg.
Chronic Administration of Red Yeast Rice Mitigates Endothelial Dysfunction in Spontaneously Hypertensive Rats by Inhibiting Oxidative Stress and Endothelial Nitric Oxide Synthase Uncoupling
Background: Hypertension is associated with endothelial dysfunction. An imbalance in the production of Nitric Oxide (NO) and Reactive Oxygen Species (ROS) leading to impaired NO-cyclic Guanosine Monophosphate (cGMP) pathway contributes to this disorder. Red Yeast Rice (RYR) produced from the fermentation of rice with Monascus purpureus is a traditional functional food originating from China. Although recognized for its anti-dyslipidemia properties there has been growing evidence regarding the anti-hypertensive effects of RYR. However these studies only focused on its direct and short-term effects. Aim: This study aims to investigate the vasoprotective effects of chronic oral RYR administration using Spontaneously Hypertensive Rats (SHR). Materials and Methods: SHR were randomly divided into 3 groups: SHR - Control; SHR - RYR extract (100 mg/kg/day); SHR - lovastatin (10 mg/kg/day). Wistar-Kyoto Rats (WKY) were used as normotensive controls. All animals were treated for 12 weeks by oral gavage. Systolic Blood Pressure (SBP) was measured weekly (tail-cuff method). Vascular reactivity was determined using isolated rat aortic rings in an organ bath. Aortic ROS NO tetrahydrobiopterin (BH4) and cGMP levels were evaluated. Results: Administration of RYR attenuated SBP elevation and enhanced endothelium-dependent vasodilation in aortic rings. In addition RYR decreased ROS production and significantly improved the level of vascular NO BH4 and cGMP. Conclusion: In an SHR model treatment with RYR for 12 weeks exerts an SBP lowering effect that can be attributed to improved vascular function via reduction of oxidative stress decreased endothelial NO Synthase (eNOS) uncoupling and enhanced NO-cGMP pathway.
MiR-199a-5p Deficiency Promotes Artery Restenosis in Peripheral Artery Disease by Regulating ASMCs Function via Targeting HIF-1α and E2F3
Background: Restenosis (RS) poses a significant concern leading to recurrent ischemia and the potential for amputation following intraluminal angioplasty in the treatment of Peripheral Artery Disease (PAD). Through microRNA microarray analysis the study detected a significant downregulation of miR-199a-5p within arterial smooth muscle cells (ASMCs) associated with RS. Objective: This research aims to explore the possible function and the underlying mechanisms of miR-199a-5p in the context of RS. Methods: Primary ASMCs were extracted from the femoral arteries of both healthy individuals and patients with PAD or RS. The expression levels of miR-199a-5p were assessed using both qRT-PCR and in situ hybridization techniques. To examine the impacts of miR-199a-5p a series of experiments were performed including flow cytometry TUNEL assay EdU assay CCK8 assay Transwell assay and wound closure assay. A rat carotid balloon injury model was employed to elucidate the mechanism through which miR-199a-5p mitigated neointimal hyperplasia. Results: MiR-199a-5p exhibited downregulation in RS patients and was predominantly expressed within ASMCs. Elevated the expression of miR-199a-5p resulted in an inhibitory effect of proliferation and migration in ASMCs. Immunohistochemistry and a dual-luciferase reporter assay uncovered that RS exhibited elevated expression levels of both HIF-1α and E2F3 and they were identified as target genes regulated by miR-199a-5p. The co-transfection of lentiviruses carrying HIF-1α and E2F3 alongside miR-199a-5p further elucidated their role in the cellular responses mediated by miR-199a-5p. In vivo the delivery of miR-199a-5p via lentivirus led to the mitigation of neointimal formation following angioplasty achieved by targeting HIF-1α and E2F3. Conclusion: MiR-199a-5p exhibits promise as a prospective therapeutic target for RS since it alleviates the condition by inhibiting the proliferation and migration of ASMCs via its regulation of HIF-1α and E2F3.
Cardioprotective Effects of Exercise: The Role of Irisin and Exosome
Exercise is an effective measure for preventing and treating cardiovascular diseases although the exact molecular mechanism remains unknown. Previous studies have shown that both irisin and exosomes can improve the course of cardiovascular disease independently. Therefore it is speculated that the cardiovascular protective effect of exercise is also related to its ability to regulate the concentrations of irisin and exosomes in the circulatory system. In this review the potential synergistic interactions between irisin and exosomes are examined as well as the underlying mechanisms including the AMPK/PI3K/AKT pathway the TGFβ1/Smad2/3 pathway the PI3K/AKT/VEGF pathway and the PTEN/PINK1/Parkin pathway are examined. This paper provides evidence to propose that exercise promotes the release of exosomes enriched with irisin miR-486-5p and miR-342-5p from skeletal muscles which results in the activation protective networks in the cardiovascular system. Moreover the potential synergistic effect in exosomal cargo can provide new ideas for clinical research of exercise mimics.
Pro- and Anti-inflammatory Biomarkers Responses after Aerobic Training in Heart Transplant Recipients: A Systematic Review and Meta-analysis
Background: Physical exercise (PE) may improve plasma concentration of interleukin- 6 (IL-6) tumor necrosis factor-alpha (TNF-alpha) and adiponectin (adpN) in heart transplant (HT) patients. However no consistent data is available on this population. Aim: Thus we aimed to conduct a systematic review and meta-analysis on the effects of PE over these pro- and anti-inflammatory biomarkers in HT patients. Methods: Following the guidelines established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement we conducted a systematic literature search in the PubMed Cochrane and Scopus databases. Outcomes included IL-6 TNF-alpha and adpN. Effect size (ES) was calculated using the standardized mean difference with a 95% confidence interval (CI). Results: The PE group (aerobic modality) was associated with reduced IL-6 compared to the control group (ES: −0.53; 95% CI: −0.99 to −0.06 pg/mL; P = 0.026). However the PE group did not show a significant effect on TNF-alpha and adpN levels (ES: −0.33; 95% CI: −0.79 to 0.13; P = 0.16 and ES: −0.20; 95% CI: −0.70 to 0.30 pg/mL; P = 0.444 respectively). Conclusion: PE is associated with IL-6 reductions although TNF alpha and adpN did not change after this intervention in HT patients. Therefore PE is an effective intervention to downregulate IL-6 in post-HT patients.
Cardiology and Neurophysiological Stimulation of Internet Gaming Disorders: A Systematic Review
Background: Internet Gaming Disorder (IGD) is recognized as a mental health condition associated with excessive video gaming leading to functional impairments. The inclusion of IGD in the DSM-5 has underscored the importance of comprehensively understanding its physiological and psychological effects. Objective: This systematic review aims to analyze and synthesize existing literature on the cardiophysiological and neurophysiological activities of individuals diagnosed with IGD with a focus on identifying patterns trends and implications for clinical practice and future research. Methods: A systematic search was conducted in PubMed and Scopus databases to identify relevant studies published up to 2023. The search strategy included terms related to IGD cardiophysiology neurophysiology and relevant measurement techniques. Inclusion criteria encompassed peer-reviewed research articles and clinical trials examining cardiophysiological (e.g. heart rate variability blood pressure) and neurophysiological (e.g. brain imaging electroencephalography) parameters in individuals with IGD. Exclusion criteria were applied to ensure methodological rigor and relevance to the research question. Results: The initial search yielded 1320 papers related to IGD of which twenty studies met the eligibility criteria and were included in the review. Data extraction and synthesis focused on key cardiophysiological and neurophysiological outcomes observed in individuals with IGD compared to healthy controls. Findings revealed decreased Heart Rate Variability (HRV) increased sympathetic activity and executive control deficits in IGD individuals based on Electrocardiogram (ECG) recordings and cognitive assessments. Neuroimaging studies demonstrated heightened brain activation in the lateral and prefrontal cortex altered reward processing and impulse control mechanisms among IGD subjects. Gender-specific differences were noted with males exhibiting distinct thalamic activation striatum and decreased Regional Homogeneity (ReHo) in the right Posterior Cingulate (rPCC) compared to females. Discussion: The synthesized evidence indicates a complex interplay between excessive gaming and cardiophysiological/neurophysiological changes highlighting the need for multidimensional assessments in diagnosing and managing IGD. Implications for clinical practice include early detection using ECG EEG and advanced neuroimaging techniques as well as personalized interventions tailored to individual characteristics and gender-specific differences. Conclusion: This systematic review provides a comprehensive overview of the cardiophysiological and neurophysiological activities associated with Internet Gaming Disorder. The findings underscore the need for further research to elucidate underlying mechanisms develop standardized diagnostic protocols and optimize targeted interventions for individuals with IGD.
Atrial Thrombus or Atrial Myxoma? Preliminary Analysis of Echocardiographic Findings of a Case Series
Background: Echocardiography has been proven to be a useful tool for detecting atrial-occupying lesions ranging from primary or secondary tumors to thrombi. Although the precise diagnosis is important as clinical treatment modalities differ sometimes differentiating a thrombus from a myxoma is very difficult. Case Report: From January 2019 to December 2022 we retrospectively analyzed the echocardiographic findings of 8 patients who were found to have an interatrial mass. Of the 8 patients 4 had a right atrial mass and 4 had a left atrial mass. Based on ultrasonic examination the initial diagnosis was a thrombus and the second diagnosis was a myxoma for all 8 patients. All masses were finally confirmed to be thrombi. Although an echocardiogram can provide significant information on the nature of atrial masses in many patients qualitative diagnosis of a small percentage of atrial masses remains difficult. Conclusion: An atrial thrombus is occasionally difficult to differentiate from an atrial myxoma in patients without atrial fibrillation especially when it is not attached to the left atrial appendage. Upon review of the echocardiographic findings of the 8 patients described in our study it is essential to highlight the fact that a thrombus can mimic a myxoma and thereby create a diagnostic conundrum.
Cellular and Molecular Mechanisms of Neuronal Degeneration in Early-Stage Diabetic Retinopathy
Background: Studies on the early retinal changes in Diabetic Retinopathy (DR) have demonstrated that neurodegeneration precedes vascular abnormalities like microaneurysms or intraretinal hemorrhages. Therefore there is a growing field of study to analyze the cellular and molecular pathways involved to allow for the development of novel therapeutics to prevent the onset or delay the progression of DR. Molecular Mechanisms: Oxidative stress and mitochondrial dysfunction contribute to neurodegeneration through pathways involving polyol hexosamine advanced glycation end products and protein kinase C. Potential interventions targeting these pathways include aldose reductase inhibitors and protein kinase C inhibitors. Neurotrophic factor imbalances notably brain-derived neurotrophic factor and nerve growth factor also play a role in early neurodegeneration and supplementation of these neurotrophic factors show promise in mitigating neurodegeneration. Cellular Mechanisms: Major cellular mechanisms of neurodegeneration include caspase-mediated apoptosis glial cell reactivity and glutamate excitotoxicity. Therefore inhibitors of these pathways are potential therapeutic avenues. Vascular Component: The nitric oxide pathway critical for neurovascular coupling is disrupted in DR due to increased reactive oxygen species. Vascular Endothelial Growth Factor (VEGF) a long-known angiogenic factor has demonstrated both damaging and neuroprotective effects prompting a careful consideration of long-term anti-VEGF therapy. Conclusion: Current DR treatments primarily address vascular symptoms but fall short of preventing or halting the disease. Insights into the mechanisms of retinal neurodegeneration in the setting of diabetes mellitus not only enhance our understanding of DR but also pave the way for future therapeutic interventions aimed at preventing disease progression and preserving vision.