The Bittersweet Reality: The Cardiovascular Risk of Artificial Sweeteners.

Artificial sweeteners are increasingly popular as alternatives to sugar. Approximately 41% of the American adult population reports regular consumption of low-calorie sweeteners. People are not even aware they are ingesting artificial sweeteners as they are now in chewing gum, toothpaste, various food products, baked goods, and even pharmaceutical products. Some of these sweeteners are sweeter than sugar, some less sweet than sugar, and some are natural sweeteners. With the goal of increasing palatability, many products have multiple additives to create the perfect taste. Despite their widespread use and perceived benefits, there is increasing concern in the academic community about the long-term safety of these artificial sweeteners and their role in increasing the burden of cardiovascular diseases, including coronary heart disease, stroke, and heart failure. There is general agreement about the cardiovascular risk of added sugars to a diet. Public health authorities have recommended limiting added sugar consumption. Replacing sugar with these artificial sweeteners has become increasingly popular, but safety remains a question. While multiple well-designed randomized clinical trials are needed for the conclusion, review of the current literature gives us pause about the cardiovascular risk and long-term safety of these additives.

Changes in widespread pain after surgical weight loss in racialized adults: A secondary analysis from a two-year longitudinal study.

Widespread pain is associated with reduced function and disability. Importantly, three-fourths of the approximately 42% of U.S. adults with obesity have widespread pain. Moreover, rates of adult obesity are higher and widespread outcomes are worse in racialized non-Hispanic Black and Hispanic/Latino/a/X groups, potentially exacerbating existing pain disparities. Bariatric surgery significantly reduces weight and improves pain. However, recurrent or unresolved pain after bariatric surgery can hinder weight loss or facilitate weight regain. The current study conducted a secondary analysis of a longitudinal study of predictors and mechanisms of weight loss after bariatric surgery to examine the point prevalence of widespread pain and pain trajectories 24 months post-surgery. Our secondary aim was to examine the association between weight loss and pain characteristics. Our exploratory aim was to longitudinally examine racial differences in pain trajectories after bariatric surgery. Our results showed that point prevalence decreased after bariatric surgery. Additionally, significant improvements in pain trajectories occurred within the first 3 months post-surgery with a pattern of pain reemergence beginning at 12 months post-surgery. Hispanic/Latino/a/X participants reported a higher number of painful anatomical sites before bariatric surgery, and the rate of change in this domain for this group was faster compared to the racialized non-Hispanic Black participants. These findings suggest that pain improvements are most evident during the early stages of surgical weight loss in racialized populations of adults with widespread pain. Thus, clinicians should routinely monitor patients' weight changes after bariatric surgery as they are likely to correspond to changes in their pain experiences. PERSPECTIVE: This article presents the prevalence and pain trajectories of racialized adults with widespread pain (WP) after surgical weight loss. Clinicians should evaluate changes in the magnitude and spatial distribution of pain after significant weight change in these populations so pain interventions can be prescribed with greater precision.

GPR75: A Newly Identified Receptor for Targeted Intervention in the Treatment of Obesity and Metabolic Syndrome.

Metabolic syndrome increases the risk of stroke, cardiovascular disease, and diabetes. The morbidity and mortality associated with this constellation of risk factors are equally alarming when considering the economic and global significance that this epidemic has on an institutional and patient level. Despite several current treatments available, there needs to be a continuous effort to explore more specific and effective druggable entities for preventative and therapeutic interventions. Within this context, the G-protein coupled receptor, GPR75, is an attractive pharmacological target. GPR75 and its association with its ligand, 20-hydroxyeicosatetraenoic acid, have been shown to promote hypertension, inflammation, obesity, and insulin resistance. This review will help shed light on this novel signaling pathway and offer a perspective on a promising new direction of targeting different aspects of the metabolic syndrome involving GPR75. Gene targeting of GPR75 is more effective than current pharmacologic therapies without the known side effects.

Nanotechnology: The Future for Diagnostic and Therapeutic Intervention in Cardiovascular Diseases is Here.

With advances in technology and medicine over the last 3 decades, cardiovascular medicine has evolved tremendously. Nanotechnology provides a promising future in personalized precision medicine. In this review, we delve into the current and prospective applications of nanotechnology and nanoparticles in cardiology. Nanotechnology has allowed for point-of-care testing such as high-sensitivity troponins, as well as more precise cardiac imaging. This review is focused on 3 diseases within cardiology: coronary artery disease, heart failure, and valvular heart disease. The use of nanoparticles in coronary stents has shown success in preventing in-stent thrombosis, as well as using nanosized drug delivery medications to prevent neointimal proliferation in a way that spares systemic toxicity. In addition, by using nanoparticles as drug delivery systems, nanotechnology can be utilized in the delivery of goal-directed medical therapy in heart failure patients. It has also been shown to improve cell therapy in this patient population by helping in cell retention of grafts. Finally, the use of nanoparticles in the manufacturing of bioprosthetic valves provides a promising future for the longevity and success of cardiac valve repair and replacement.

The Interplay of Microbiome Dysbiosis and Cardiovascular Disease.

The intricate ecosystem of the mammalian gut, which hosts a diverse microbiome, plays a vital role in various physiological functions. Trillions of bacteria within the gut contribute to host metabolism, immune modulation, energy homeostasis, and more. Emerging research highlights the gut microbiota's significant impact on cardiovascular diseases (CVDs), with intestinal dysbiosis identified as a risk factor for conditions such as obesity and diabetes, both linked to atherosclerosis. Chronic inflammation, pivotal in atherosclerosis, is influenced by the gut microbiome, where microbial signals, such as lipopolysaccharides, can translocate from the gut to trigger inflammatory responses. Diet has major effects on the gut microbiota, with the Western diet, rich in saturated fats, contributing to dysbiosis and elevated cardiovascular risks. Probiotics and prebiotics offer therapeutic potential in CVD management. Probiotics, or live microorganisms, exhibit antioxidant, anti-inflammatory, and cholesterol-lowering effects. Probiotics are most effective when given with prebiotics, with the former acting on the latter as substrate. Understanding the dynamic interplay between diet, gut microbiota, and CVD provides insights into preventive and therapeutic strategies.

Titin: The Missing Link in Cardiac Physiology.

Titin, an extraordinary protein known for its colossal size and multifaceted roles, is a cornerstone in the structural and functional dynamics of striated muscle tissues, including the heart and skeletal muscles. Its sheer enormity, with a molecular weight exceeding 3000 kDa, is paralleled only by the immense influence it exerts on muscle physiology. This review will delve into the remarkable structural organization of Titin and the genetics of this molecule, including the common mutations resulting in various cardiomyopathies. We will delve deeper into its role in dilated cardiomyopathy, familial restrictive cardiomyopathy, hypertrophic cardiomyopathy, and left ventricular noncompaction cardiomyopathy. This review culminates by discussing the prospects of therapeutic strategies targeting Titin. While these interventions remain primarily theoretical, the possibilities are intriguing. Patients with Titin truncation mutations present unique challenges, but innovative approaches like gene therapy or preemptive treatments with drugs such as angiotensin-converting enzyme inhibitors or beta-blockers offer hope. This multi-pronged approach highlights the significance of understanding Titin's multifaceted role and its potential as a target for future therapeutic interventions.

Dynamic Coronary Roadmap versus standard angiography for percutaneous coronary intervention: the randomised, multicentre DCR4Contrast trial.

BACKGROUND: Decreasing the amount of iodinated contrast is an important safety aspect of percutaneous coronary interventions (PCI), particularly in patients with a high risk of contrast-induced acute kidney injury (CI-AKI). Dynamic Coronary Roadmap (DCR) is a PCI navigation support tool projecting a motion-compensated virtual coronary roadmap overlay on fluoroscopy, potentially limiting the need for contrast during PCI. AIMS: This study investigates the contrast-sparing potential of DCR in PCI, compared to standard angiographic guidance. METHODS: The Dynamic Coronary Roadmap for Contrast Reduction (DCR4Contrast) trial is a multicentre, international, prospective, unblinded, stratified 1:1 randomised controlled trial. Patients were randomised to either DCR-guided PCI or to conventional angiography-guided PCI. The primary endpoint was the total volume of iodinated contrast administered, and the secondary endpoint was the number of cineangiography runs during PCI. RESULTS: The study population included 356 randomised patients (179 in DCR and 177 in control groups, respectively). There were no differences in patient demographics, angiographic characteristics or estimated glomerular filtration rate (eGFR) between the two groups. The total contrast volume used during PCI was significantly lower with DCR guidance compared with conventional angiographic guidance (64.6±44.4 ml vs 90.8±55.4 ml, respectively; p<0.001). The total number of cineangiography runs was also significantly reduced in the DCR group (8.7±4.7 vs 11.7±7.6 in the control group; p<0.001). CONCLUSIONS: Compared to conventional angiography-guided PCI, DCR guidance was associated with a significant reduction in both contrast volume and the number of cineangiography runs during PCI. (ClinicalTrials.gov: NCT04085614).

Routine extended (30 days) chemoprophylaxis for patients undergoing laparoscopic sleeve gastrectomy may reduce Portomesenteric vein thrombosis rates.

BACKGROUND: Venous thromboembolism (VTE), including Portomesenteric vein thrombosis (PMVT), is a major complication of sleeve gastrectomy (SG). We changed our practice in July 2021 to routinely discharge all SG patients postoperatively with extended chemoprophylaxis for 30 days. OBJECTIVES: Evaluate the efficacy and safety of routine extended chemoprophylaxis compared to 2 prior timeframes using selective extended chemoprophylaxis. SETTING: University Hospital. METHODS: Between 2012-2018, SG patients were discharged on extended chemoprophylaxis for patients deemed "high-risk" for VTE, including patients with body mass index (BMI) >50, and previous VTE. Between 2018-2021, extended chemoprophylaxis was broadened to include patients with positive preoperative thrombophilia panels (including Factor VIII). After 2021, all SG were routinely discharged on extended chemoprophylaxis. The typical regimen was 30 days Lovenox BID (40-mg twice daily for BMI> 40, 60-mg twice daily for BMI >60). Outcomes evaluated were rate of VTE/PMVT and postoperative bleed, including delayed bleed. RESULTS: A total of 8864 patients underwent SG. Average age and BMI were 37.5 years and 43.0 kg/m2, respectively. The overall incidence of PMVT was 33/8864 (.37%). Converting from selective extended chemoprophylaxis (Group 1) to routine extended chemoprophylaxis (Group 3) decreased the rate of PMVT from .55% to .21% (P = .13). There was a significantly higher overall bleeding rate (.85%), including delayed bleeds (.34%) in the routine extended chemoprophylaxis patients (P < .05). These bleeds were mainly managed nonoperatively. CONCLUSIONS: Routine extended (30 day) chemoprophylaxis for all SG may reduce PMVT rate but lead to a higher bleeding rate post-operatively. The vast majority of the increased bleeds are delayed and can be managed non-operatively.

Neutrophil-to-lymphocyte ratio and prognosis in patients undergoing percutaneous coronary intervention for acute coronary syndrome.

OBJECTIVE: The purpose of this study was to characterize Acute Coronary Syndrome (ACS)-associated inflammation by investigating correlates of the neutrophil-to-lymphocyte ratio (NLR), a surrogate marker of inflammation, and its relation to 1-year mortality in a cohort of patients undergoing percutaneous coronary intervention (PCI) for ACS at a single institution. METHODS: We performed a single-institution, retrospective, observational study of all-comer ACS patients who underwent PCI and were discharged home before the COVID-19 pandemic between September 23, 2011 and July 31, 2017 for who outcomes data were available. RESULTS: NLRhigh group tended to be older, white patients, less likely to smoke, more likely to have a history of heart failure and cardiac arrest, higher creatinine values, lower LVEF, and higher CK-MB (a surrogate for infarct size). Linear regression model demonstrated a strong correlation between increasing NLR and white race (B = 1.103, p = 0.001, hemoglobin (B = -0.30, p < 0.001), peak CK-MB (B = 0.004, p = 0.02), LVEF (B = -0.048, p < 0.001), and serum creatinine (B = 0.47, p = 0.03). There were a total of 87 deaths at one year. NLR > 3.4 was associated with worse one-year survival post-PCI (91.4 % vs. 95.4 %, log-rank p < 0.004), which was confirmed on multivariate analysis. CONCLUSION: Our data confirm the independent prognostic significance of inflammation to mortality after ACS and may provide some insight into the putative benefits of inflammation modulation.

Diagnostic performances of Nonhyperemic Pressure Ratios and Coronary Angiography-Based Fractional Flow Reserve against conventional Wire-Based Fractional Flow Reserve.

BACKGROUND: Nonhyperemic pressure ratios (NHPRs) have been proposed as alternatives to fractional flow reserve (FFR) without induction of hyperemia. More recently, imaging based-FFR estimation, especially coronary angiography-derived FFR (Angio-FFR) measurement, is proposed to estimate wire-based FFR. However, little is known about the diagnostic performance of these indices against conventional FFR. AIMS: We aimed to assess and compare the diagnostic performance of both NHPRs and coronary Angio-FFR against wire-based conventional FFR. METHODS: PubMed and Embase databases were systematically searched for peer-reviewed original articles up to 08/2022. The primary outcomes were the pooled sensitivity and specificity as well as the area under the curve (AUC) of the summary receiver-operating characteristic curve of those indices. RESULTS: A total of 6693 records were identified after a literature search, including 37 reports for NHPRs and 34 for Angio-FFR. Overall, NHPRs have a lower diagnostic performance in estimating wire-based FFR with an AUC of 0.85 (0.81, 0.88) when compared with Angio-FFR of 0.95 (0.93, 0.97). When all four modalities of NHPRs (iFR, Pd/Pa, DPR, RFR) were compared, those had overlapping AUCs without major differences among each other. Similarly, when the two most commonly used Angio-FFR (QFR, FFR angio ) were compared, those had overlapping AUCs without major differences among each other. CONCLUSION: Angio-FFR may offer a better estimation of wire-based FFR than NHPRs. Our results support a wider use of Angio-FFR in the cardiac catheterization laboratory to streamline our workflow for coronary physiologic assessment. CLASSIFICATIONS: FFR,, stable ischemic disease and non-ST elevation acute coronary syndrome.

Pegozafermin Is a Potential Master Therapeutic Regulator in Metabolic Disorders: A Review.

Pegozafermin (PGZ), a novel glycopegylated version of human fibroblast growth factor 21 (FGF21), has demonstrated potential for addressing metabolic comorbidities, including severe hypertriglyceridemia, insulin resistance, nonalcoholic fatty liver disease, and obesity. FGF21 is a naturally occurring peptide hormone primarily produced by the liver, with a half-life of 0.5 to 2 hours. It can influence metabolic processes through endocrine cellular effects. FGF21 receptors are found in the liver, adipose, skeletal muscles, and pancreatic tissues. Those receptors rely on the beta klotho (KLB) coreceptors, a transmembrane protein, to activate the FGF21 signaling pathway and FGF21's associated transcription factors. PGZ, through its extended half-life of 55 to 100 hours, has evidenced significant improvements in metabolic functions. Its mechanism of action includes promoting adiponectin levels, enhancing insulin sensitivity, increasing triglyceride uptake, and reducing de novo lipogenesis. This emerging pharmaceutical compound has shown promise in treating liver fibrosis and inflammation linked to nonalcoholic steatohepatitis. The ENTRIGUE trial, a phase 2 clinical trial of PGZ, has demonstrated a 57% reduction in triglyceride level compared to placebo; a 45% reduction in liver hepatic steatosis; improved insulin sensitivity; reductions in nonhigh-density lipoprotein-cholesterol; and reductions in apolipoprotein B-100.

Cardiovascular Manifestations of Hemochromatosis: A Review of Pathophysiology, Mechanisms, and Treatment Options.

Hemochromatosis is a genetic disorder characterized by excessive absorption and accumulation of iron in the body. It is one of the most common inherited disorders. The excess iron deposition can cause damage to various organs, including the liver, heart, pancreas, and joints. If left untreated, hemochromatosis can lead to serious complications such as cirrhosis, diabetes, heart failure, and increased risk of certain cancers. Iron overload in hemochromatosis significantly affects the cardiovascular system, leading to morbidity and mortality. This article reviews the current literature describing the pathogenesis and various cardiovascular manifestations of hemochromatosis, including dilated cardiomyopathy, conduction abnormalities, heart failure, cardiac fibrosis, myocardial infarction, and valvular heart disease. This article aims to provide a detailed understanding of the cardiovascular manifestations associated with hemochromatosis and their underlying mechanisms through a review of current literature in publicly available databases.

The Relationship of Duffy Gene Polymorphism, High Sensitivity C-Reactive Protein, and Long-term Outcomes.

Background: Black adults have higher incidence of all-cause death and worse cardiovascular outcomes when compared to other populations. The Duffy chemokine receptor is not expressed in a large majority of Black adults and the clinical implications of this are unclear. Methods: Here, we investigated the relationship of Duffy receptor status, high-sensitivity C-reactive protein (hs-CRP), and long-term cardiovascular outcomes in Black members of two contemporary, longitudinal cohort studies (the Jackson Heart Study and Multi-Ethnic Study of Atherosclerosis). Data on 4,307 Black participants (2,942 Duffy null and 1,365 Duffy receptor positive, as defined using Single Nucleotide Polymorphism (SNP) rs2814778) were included in this analysis. Results: Duffy null was not independently associated with elevated levels of serum hs-CRP levels once conditioning for known CRP locus alleles in linkage disequilibrium with the Duffy gene. Duffy null status was not found to be independently associated with higher incidence of all-cause mortality or secondary outcomes after adjusting for possible confounders in Black participants. Conclusions: These findings suggest that increased levels of hs-CRP found in Duffy null individuals is due to co-inheritance of CRP alleles known to influence circulating levels hs-CRP and that Duffy null status was not associated with worse adverse outcomes over the follow-up period in this cohort of well-balanced Black participants.

Challenge in Diagnosis and Management of a Patient With Myocardial Bridge and Coronary Artery Spasm.

Positive ischemia by noninvasive imaging studies often results in nonobstructive disease in cardiac catheterization. In this case, we observed ischemia by nuclear stress test in only the anteroseptal area, and the apex is free of ischemia. Coronary angiogram findings were unremarkable, but intravascular ultrasound confirmed the long length of the myocardial bridge. Further testing with spasm provocation and microvascular testing showed diffuse epicardial spasm in this area of myocardial bridge without microvascular dysfunction. We observed the myocardial bridge but no microvascular dysfunction. This case illustrates the coexistence of spasm in the area of a myocardial bridge and the challenges in the medical management of these patients. (Level of Difficulty: Advanced.).

Percutaneous approach for reducing outflow tract obstruction in hypertrophic obstructive cardiomyopathy.

Hypertrophic obstructive cardiomyopathy (HOCM) affects approximately 1 in 500 people globally. The condition results in hypertrophy of the interventricular septum and thickening of the left ventricular wall. Surgical management to resect the thickened myocardium or septal alcohol ablation are currently considered the mainstay treatment option for HOCM refractory to pharmacological therapy. In this special report we aim to highlight the current landscape of septal mass reduction in HOCM. Next, we describe the evolving discipline of minimally invasive techniques for reducing outflow tract obstruction in patients with HOCM. We further consider future options and outline a possible percutaneous approach for septal myectomy with a novel device.

Accuracy of Ultrasound Imaging for Etiology of New-Onset Painless Jaundice.

PURPOSE: Ultrasound (US) is considered a first-line study for painless jaundice. However, in our hospital system, patients with new-onset painless jaundice often have a contrast-enhanced computed tomography (CECT) or magnetic resonance cholangiopancreatography (MRCP) regardless of the sonographic findings. Thus, we investigated the accuracy of US for detection of biliary dilatation in patients with new-onset painless jaundice. METHODS: Our electronic medical record was searched from January 1, 2012, to January 1, 2020, for adult patients with new-onset painless jaundice. Presenting complaint/setting, laboratory values, imaging studies/findings, and final diagnoses were recorded. Patients with pain or known liver disease were excluded. A gastrointestinal physician reviewed the laboratory values/chart to classify the type of suspected obstruction. Two radiologists blindly re-reviewed the US scans, and κ between the radiologists was calculated. Fisher exact test and the 2-sample t test were used for statistical analysis. RESULTS: Three hundred sixty patients presented with jaundice (>3 mg/dL), of whom 68 met the inclusion criteria (no pain and no known liver disease). Laboratory values had an overall accuracy of 54%, but were accurate in 87.5% and 85% for obstructing stones/pancreaticobiliary cancer. Ultrasound demonstrated overall accuracy of 78%, but only 69% for pancreaticobiliary cancer and 12.5% for common bile duct stone. Seventy-five percent of the patients underwent follow-up CECT or MRCP regardless of presenting setting. In the emergency department or inpatient setting, 92% of the patients underwent CECT or MRCP regardless of US, and 81% had follow-up CECT or MRCP within 24 hours. CONCLUSION: A US-first strategy in the setting of new-onset painless jaundice is accurate only 78% of the time. In practice, US was almost never a stand-alone imaging examination in patients presenting to the emergency department or inpatient setting with new-onset painless jaundice, no matter the suspected diagnosis based on clinical and laboratory grounds or on the US findings themselves. However, for milder elevations of unconjugated bilirubin (suspicious for Gilbert disease) in the outpatient setting, a US demonstrating lack of biliary dilatation was often a definitive study for exclusion of pathology.