ABSTRACT
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.
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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.
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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.
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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.
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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.
Subject(s)
Angina Pectoris , Ergonovine , Humans , Heart , Coronary Angiography , Coronary Vessels/diagnostic imagingABSTRACT
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.
Subject(s)
Coronary Stenosis , Fractional Flow Reserve, Myocardial , Humans , Coronary Angiography/methods , Fractional Flow Reserve, Myocardial/physiology , Coronary Stenosis/diagnostic imaging , Coronary Vessels/diagnostic imaging , Predictive Value of Tests , Severity of Illness Index , Cardiac Catheterization/methodsABSTRACT
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.
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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.
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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.).
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Percutaneous coronary intervention (PCI) is increasingly performed for symptom relief and survival benefit, particularly in patients presenting with acute coronary syndromes. It remains controversial whether prior PCI, and specifically when index PCI is performed on previously treated lesion(s), affects peri-procedural and in-hospital mortality. We queried an institutional PCI registry for all unique patients undergoing PCI during a 4-year period and classified them as having had or not prior PCI. If prior PCI had occurred, we further defined index PCI as a target lesion (TLR) PCI or non-TLR PCI, according to lesion(s) treated during the prior PCI. Multivariable analysis was performed to identify predictors of in-hospital mortality. Prior PCI was an independent predictor of in-hospital survival or lower mortality (HR 0.41 [0.22-0.76], P = 0.004), together with lower age (per 5 years, HR 0.73 [0.66-0.82], P < 0.001) and elective PCI (HR 0.63 [0.58-0.70], P < 0.0001). Among prior PCI patients, TLR PCI was associated with higher mortality (HR 3.03 [1.05-8.33]. P = 0.045), while elective PCI status was associated with lower mortality (HR 0.10 [0.01-0.80], P = 0.03). This excess mortality was only present in non-elective PCI cases (PINT = 0.02). We conclude that PCI mortality risk is decreased in patients with prior PCI, particularly when index PCI is performed electively on a lesion not previously treated.
Subject(s)
Acute Coronary Syndrome , Coronary Artery Disease , Percutaneous Coronary Intervention , Humans , Child, Preschool , Percutaneous Coronary Intervention/adverse effects , Hospital Mortality , Acute Coronary Syndrome/etiology , Treatment Outcome , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Coronary Artery Disease/etiology , Risk Factors , RegistriesABSTRACT
Fractional flow reserve (FFR) has become the gold standard for invasively assessing the functional significance of coronary artery disease (CAD) to guide revascularization. The amount of evidence supporting the role of FFR in the cardiac catheterization laboratory is large and still growing. However, FFR uptake in the daily practice is limited by a variety of factors such as invasive instrumentation of the coronary artery that requires extra time and need for vasodilator medications for hyperemia. In this review, we describe the details of wire-based alternatives to FFR, providing insights as to their development, clinical evidence, and limitations.
Subject(s)
Coronary Stenosis , Fractional Flow Reserve, Myocardial , Humans , Coronary Stenosis/diagnosis , Coronary Stenosis/surgery , Coronary Angiography , Cardiac Catheterization , Predictive Value of Tests , Severity of Illness IndexABSTRACT
BACKGROUND: Heterogeneity in diagnostic criteria and provocation protocols has posed challenges in understanding the safety of coronary provocation testing with intracoronary acetylcholine (ACh) for the contemporary diagnosis of epicardial and microvascular spasm. OBJECTIVES: We examined the safety of testing and subgroup differences in procedural risks based on ethnicity, diagnostic criteria, and provocation protocols. METHODS: PubMed and Embase were searched in November 2021 to identify original articles reporting procedural complications associated with intracoronary ACh administration. The primary outcome was the pooled estimate of the incidence of major complications including death, myocardial infarction, ventricular tachycardia/fibrillation, and shock. RESULTS: A total of 16 studies with 12,585 patients were included in the meta-analysis. The overall pooled estimate of the incidence of major complications was 0.5% (95% CI: 0.0%-1.3%) without any reports of death. Exploratory subgroup analyses revealed that the pooled incidence of major complications was significantly higher in the studies that followed the contemporary diagnosis criteria for epicardial spasm defined as ≥90% diameter reduction (1.0%; 95% CI: 0.3%-2.0%) but significantly lower in Western populations (0.0%; 95% CI: 0.0%-0.45%). The rate of positive epicardial spasm and the incidence of major complications were similar between provocation protocols using the maximum ACh doses of 100 µg and 200 µg. CONCLUSIONS: Intracoronary ACh administration for the contemporary diagnosis of epicardial and microvascular spasm is a safe procedure. Moreover, excellent safety records are observed in Western populations primarily presenting with myocardial ischemia and/or infarction with nonobstructive coronary arteries. This study will help standardize ACh testing to improve clinical diagnosis and ensure procedural safety.
Subject(s)
Acetylcholine , Coronary Vasospasm , Acetylcholine/adverse effects , Coronary Angiography/methods , Coronary Vasospasm/chemically induced , Coronary Vasospasm/diagnosis , Coronary Vessels/diagnostic imaging , Humans , Meta-Analysis as Topic , Spasm , Ventricular FibrillationABSTRACT
INTRODUCTION: The prevalence and long-term consequences of differences in baseline cardiac geometry (as a result of hypertension) in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) are ill-defined. The primary purpose of this study was to clarify whether there were differences among sexual and racial groups in echocardiographic findings reflecting cardiac geometry and adaptation in patients undergoing PCI for ACS and whether this could explain the differences in outcomes seen between these groups. MATERIAL AND METHODS: We analyzed 1-year follow-up data from a single institution, a retrospective, observational study that enrolled 1,153 patients who presented with ACS and were treated with PCI, for whom echocardiographic data were available. RESULTS: Normal, concentric hypertrophy, and eccentric hypertrophy in males vs. females were observed as follows: 29% vs. 19% (p = 0.001), 25% vs. 31% (p = 0.02), and 8% vs. 14% (p = 0.004), respectively. The primary endpoint of all-cause death (n = 89, 7.7%) occurred in 48 (10.5%) females and in 41 (8.2%) males, p = 0.03. Major adverse cardiac events and bleeding (MACE-B - all-cause death, non-fatal myocardial infarction, stroke or hospitalization for bleeding) was higher among women than men (21.6% vs. 13.5%, p = 0.0002). Males with eccentric hypertrophy (EH) had similar MACE-B outcomes as females with EH 1-year post-PCI (29% vs. 32%, respectively, p = 0.77). CONCLUSIONS: Females undergoing PCI for ACS are at higher risk for worse outcomes because they are more likely to express the eccentric hypertrophy phenotype; however, it did not account for the difference in adverse outcomes observed between sexes.
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Iatrogenic complications may manifest in a variety of ways. We present the case of an 86-year-old woman who underwent a percutaneous coronary intervention with a drug-eluting stent for non-ST-segment elevation myocardial infarction followed by leadless pacemaker placement through a femoral approach. Her post-procedure course was complicated by new onset high-output heart failure secondary to iatrogenic arteriovenous fistula formation, requiring covered stent placement. (Level of Difficulty: Advanced.).
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OBJECTIVES: We sought to assess in-hospital and long-term outcomes of retrograde compared with antegrade-only percutaneous coronary intervention for chronic total occlusion (CTO PCI). BACKGROUND: Procedural and clinical outcomes following retrograde compared with antegrade-only CTO PCI remain unknown. METHODS: Using the core-lab adjudicated OPEN-CTO registry, we compared the outcomes of retrograde to antegrade-only CTO PCI. Primary endpoints included were in-hospital major adverse cardiac and cerebrovascular events (MACCE) (all-cause death, stroke, myocardial infarction [MI], emergency cardiac surgery, or clinically significant perforation) and MACCE at 1-year (all-cause death, MI, stroke, target lesion revascularization, or target vessel reocclusion). RESULTS: Among 885 single CTO procedures from the OPEN-CTO registry, 454 were retrograde and 431 were antegrade-only. Lesion complexity was higher (J-CTO score: 2.7 vs. 1.9; p < .001) and technical success lower (82.4 vs. 94.2%; p < .001) in retrograde compared with antegrade-only procedures. All-cause death was higher in the retrograde group in-hospital (2 vs. 0%; p = .003), but not at 1-year (4.9 vs. 3.3%; p = .29). Compared with antegrade-only procedures, in-hospital MACCE rates (composite of all-cause death, stroke, MI, emergency cardiac surgery, and clinically significant perforation) were higher in the retrograde group (10.8 vs. 3.3%; p < .001) and at 1-year (19.5 vs. 13.9%; p = .03). In sensitivity analyses landmarked at discharge, there was no difference in MACCE rates at 1 year following retrograde versus antegrade-only CTO PCI. Improvements in Seattle Angina Questionnaire Quality of Life scores at 1-year were similar between the retrograde and antegrade-only groups (29.9 vs 30.4; p = .58). CONCLUSIONS: In the OPEN-CTO registry, retrograde CTO procedures were associated with higher rates of in-hospital MACCE compared with antegrade-only; however, post-discharge outcomes, including quality of life improvements, were similar between technical modalities.
Subject(s)
Coronary Occlusion , Percutaneous Coronary Intervention , Aftercare , Coronary Occlusion/diagnostic imaging , Coronary Occlusion/surgery , Humans , Patient Discharge , Percutaneous Coronary Intervention/adverse effects , Quality of Life , Registries , Treatment OutcomeABSTRACT
Background For patients with ST-segment-elevation myocardial infarction (STEMI) and multivessel coronary artery disease, the optimal treatment of the non-infarct-related artery has been controversial. This up-to-date meta-analysis focusing on individual clinical end points was performed to further evaluate the benefit of complete revascularization with percutaneous coronary intervention for patients with STEMI and multivessel coronary artery disease. Methods and Results We systematically identified all randomized trials comparing complete revascularization with percutaneous coronary intervention to culprit-only revascularization for multivessel disease in STEMI and performed a random-effects meta-analysis. The primary efficacy end point was cardiovascular death analyzed on an intention-to-treat basis. Secondary end points included all-cause mortality, myocardial infarction, and unplanned revascularization. Ten studies (7542 patients) were included: 3664 patients were randomized to complete revascularization and 3878 to culprit-only revascularization. Across all patients, complete revascularization was superior to culprit-only revascularization for reduction in the risk of cardiovascular death (relative risk [RR], 0.68; 95% CI, 0.47-0.98; P=0.037; I2=21.8%) and reduction in the risk of myocardial infarction (RR, 0.65; 95% CI, 0.54-0.79; P<0.0001; I2=0.0%). Complete revascularization also significantly reduced the risk of unplanned revascularization (RR, 0.37; 95% CI, 0.28-0.51; P<0.0001; I2=64.7%). The difference in all-cause mortality with percutaneous coronary intervention was not statistically significant (RR, 0.85; 95% CI, 0.69-1.04; P=0.108; I2=0.0%). Conclusions For patients with STEMI and multivessel disease, complete revascularization with percutaneous coronary intervention significantly improves hard clinical outcomes including cardiovascular death and myocardial infarction. These data have implications for clinical practice guidelines regarding recommendations for complete revascularization following STEMI.