A Review of Sotagliflozin: The First Dual SGLT-1/2 Inhibitor.

Sotagliflozin (trade name INFEPA) is a novel dual sodium-glucose cotransporter-1 and -2 (SGLT-1/2) inhibitor that was developed by Lexicon Pharmaceuticals. It has emerged as a promising therapy for managing heart failure and other cardiovascular complications associated with type 2 diabetes mellitus (T2DM). Its dual inhibition of SGLT-1 and SGLT-2 receptors uniquely decreases glucose absorption in the intestine in addition to decreasing renal glucose reabsorption, leading to improved glycemic control and cardio-reno protection. Clinical trials have demonstrated its efficacy in reducing cardiovascular death, heart failure hospitalizations, and urgent visits, particularly in T2DM patients with chronic kidney disease (CKD). The drug was approved in 2023 by the Food and Drug Administration for reducing cardiovascular death and heart failure in T2DM patients with CKD and those with heart failure, irrespective of diabetic status or ejection fraction. However, despite its considerable therapeutic potential, sotagliflozin does pose notable adverse effects, including diabetic ketoacidosis, genital infections, and diarrhea. As a result, it has faced regulatory challenges in certain regions, notably the United States. The Food and Drug Administration has so far withheld approval for sotagliflozin in the treatment of type 1 diabetes due to concerns about its safety profile, specifically the risk of diabetic ketoacidosis, although Lexicon Pharmaceuticals plans to submit another new drug application for this use in 2024. Further investigation and clinical trials are warranted to fully elucidate sotagliflozin's impact on diabetes and CKD.

Atherosclerosis and HIV: Exploring Cardiovascular Risks and Management.

The advent of antiretroviral therapy has markedly improved the life expectancy of individuals with HIV, leading to a shift in clinical focus from managing opportunistic infections to addressing chronic conditions, such as atherosclerotic cardiovascular disease (ASCVD). Emerging evidence highlights an elevated risk of ASCVD among people living with HIV, characterized by a higher incidence of acute myocardial infarction, ischemic stroke, and heart failure compared with the general population. This review examines the epidemiology, pathophysiology, and management of ASCVD in the context of HIV. It explores the interplay between HIV infection, antiretroviral therapy, and traditional cardiovascular risk factors, underscoring the need for comprehensive cardiovascular risk reduction strategies tailored to people living with HIV. Through synthesizing data from clinical trials, observational studies, and basic research, the review aims to enhance understanding of HIV-associated ASCVD and inform healthcare practices to improve the longevity and quality of life for this patient population.

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.

Role of the Electrocardiogram for Identifying the Development of Atrial Fibrillation.

Atrial fibrillation (AF), a prevalent cardiac arrhythmia, is associated with increased morbidity and mortality worldwide. Stroke, the leading cause of serious disability in the United States, is among the important complications of this arrhythmia. Recent studies have demonstrated that certain clinical variables can be useful in the prediction of AF development in the future. The electrocardiogram (ECG) is a simple and cost-effective technology that is widely available in various healthcare settings. An emerging body of evidence has suggested that ECG tracings preceding the development of AF can be useful in predicting this arrhythmia in the future. Various variables on ECG especially different P wave parameters have been investigated in the prediction of new-onset AF and found to be useful. Several risk models were also introduced using these variables along with the patient's clinical data. However, current guidelines do not provide a clear consensus regarding implementing these prediction models in clinical practice for identifying patients at risk of AF. Also, the role of intensive screening via ECG or implantable devices based on this scoring system is unclear. The purpose of this review is to summarize AF and various related terminologies and explain the pathophysiology and electrocardiographic features of this tachyarrhythmia. We also discuss the predictive electrocardiographic features of AF, review some of the existing risk models and scoring system, and shed light on the role of monitoring device for screening purposes.

Managing the Intricacies of Coronary Revascularization: A Close Look at the Complete Versus Culprit-Only Approach and its Implications in Elderly Patients.

Coronary heart disease is the leading cause of mortality in the United States, and data indicates that 805,000 Americans will face a new or recurrent myocardial infarction (MI) attack every year. Frailty, a conceptual syndrome categorized by a functional decline that occurs with aging, has been linked to adverse health outcomes in cardiovascular disease and all cardiac-related procedures in general. It is therefore reasonable to deliberate that more conservative medical therapy or medical management should be considered in the frail population when managing acute coronary syndrome. This course of action has, in fact, been documented in clinical practice. However, the recent Functional Assessment in Elderly MI Patients with Multivessel Disease trial, in which all subjects were 75 years of age or above, indicated that the more invasive complete revascularization approach may be favorable over incomplete or culprit-only revascularization in patients with acute MI. In this review, we will discuss coronary heart disease and review guidelines and procedures for culprit lesion identification, including electrocardiogram procedures, coronary angiography, intravascular ultrasound, fractional flow reserve, and instantaneous fractional flow reserve. We then discuss the concept of complete vs culprit-only/incomplete coronary revascularization and staging. Following this, we will delve into recent trials discussing complete vs culprit-only revascularization, emphasizing the insights gleaned from this latest trial within this special frailty cohort which warrants special consideration.

Outpatient Continuous Intravenous Inotropy in the Modern Era.

The use of continuous inotropy in patients with advanced heart failure (HF) has been historically controversial due to the prevailing notion that it will increase mortality. In practice, clinicians have continued to revisit this idea as there remains a lack of treatment options for patients in stage D HF. Clinical trials in the past have generally not shown favorable effects of long-term chronic infusions of positive IV inotropic agents on symptoms and exercise tolerance. However, these older studies which indicated poor outcomes with palliative inotropes may not apply to current practice. Modern trials and case series have shown that milrinone and dobutamine may be safely used in patients who are bridging to device therapy or transplant or for palliation. Broad adoption of mortality-reducing modern guideline-directed medical therapy and implantable cardioverter defibrillators may have contributed to the positive results that contemporary trials have seen with inotrope use. For the stage D HF patient, modern use of outpatient inotropy (OI) can alleviate symptom burden and prolong time spent at home. Additionally, more recent studies and case series suggest that OI can be a reasonable alternative to left ventricular assist device placement for both bridging to transplant or as destination therapy. In the appropriate patient, and according to the patient's informed decision and preference, this may be a viable alternative therapeutic option. Contemporary data suggest that OI should be considered in patients who are being evaluated for advanced therapies.

Understanding Arrhythmia-Induced Cardiomyopathy: Symptoms and Treatments.

Arrhythmia-induced cardiomyopathy is a complex condition that causes a decline in heart function as a result of irregular heart rhythms. This disorder highlights the link between irregular heart rhythm and heart failure, necessitating prompt identification and intervention. It often occurs due to ongoing fast heart rhythms like atrial fibrillation or tachycardia. Understanding the mechanisms, symptoms, and available treatments is essential for enhancing patient outcomes given the complicated nature of the condition. This article delves into various aspects of arrhythmia-induced cardiomyopathy, including pathogenesis, clinical presentation, diagnostic methods, epidemiology, typical arrhythmias associated with the condition, and management options. It assesses patients' future outlook and necessary follow-up, aiming to provide healthcare providers with a comprehensive understanding of how to handle this intricate condition. The article emphasizes the important effect an integrative approach can have on both patients' lives and the clinical consequences of diagnosing and treating this condition. This extensive understanding enhances the resources at the disposal of physicians, enabling targeted treatments that enhance cardiomyopathy by targeting arrhythmia regulation. More research and development are needed in the field of cardiomyopathy and arrhythmia relationship. The presentation urges the medical field to delve deeper into the complexities of illness by emphasizing the need for continuous research and a multifaceted treatment plan. By combining these understandings, our goal is to enhance patient outcomes and create opportunities for further studies on cardiovascular wellness.

Venous Thromboembolism in Pregnancy: A Review of Diagnosis, Management, and Prevention.

Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism, is a leading cause of maternal morbidity and mortality worldwide. Physiological changes that occur in a normal pregnancy increase the risk for VTE by 4-5-fold in the antepartum period and 30-60-fold in the immediate postpartum period. Compressive ultrasonography is the diagnostic test of choice for deep vein thrombosis. Both ventilation/perfusion scanning and computed tomography pulmonary angiography can reliably diagnose pulmonary embolism. Anticoagulation for a minimum of 3 months, typically with low molecular weight heparin, is the treatment of choice for pregnancy-associated VTE (PA-VTE). Despite the significant societal burden and potentially devastating consequences, there is a paucity of data surrounding the prevention of PA-VTE, resulting in major variations between international guidelines. This review will summarize the current recommendations for diagnosis, management, and prevention of PA-VTE.

A Review of Terlipressin in Hepatorenal Syndrome: Targeting Endothelial Dysfunction and Subsequent Cardiovascular Adverse Events.

Hepatorenal syndrome (HRS) is a serious complication of decompensated liver cirrhosis that results in acute kidney injury (AKI). The mortality rate is high. Endothelial dysfunction secondary to liver cirrhosis is a key driver of the development of portal hypertension, which is eventually complicated by ascites and HRS. Ultimately, splanchnic vasodilation and excess gut lymph production result in ascites, low effective arterial blood volume, and maladaptive compensatory mechanisms that contribute to renal hypoperfusion and injury. While the only curative treatment is liver transplantation, vasoconstrictors and albumin have been the mainstay of treatment for candidates who are ineligible or waiting for transplantation. On September 14, 2022, terlipressin, a V1 vasopressin receptor agonist, was approved by the Food and Drug Administration for the treatment of HRS-AKI. In clinical trials, terlipressin plus albumin have been superior to albumin alone and equivocal to noradrenaline plus albumin in renal function improvement. Terlipressin, however, does not improve survival, is costly, and is associated with severe adverse events-including severe cardiac and vascular complications. The aim of this review is to provide an overview of terlipressin pharmacology, adverse events-with a focus on cardiovascular complications-and comparative randomized controlled trials that resulted in the Food and Drug Administration's approval of terlipressin. New literature since its approval and ongoing clinical trials will also be highlighted.

Transcatheter Intervention for Management of Tricuspid Regurgitation Using TriClip.

Severe tricuspid regurgitation (TR) is an underrated, common pathology that affects over 70 million individuals worldwide. Traditionally, TR has been managed with diuretic therapies without any significant mortality benefit. The underlying cause of TR can be primary, coming from structural issues with tricuspid valve and more commonly secondary, arising from conditions affecting the right ventricle or the pulmonary circulation. Management of TR has seen few improvements until recently. Traditionally, valve replacement and surgical repair were the therapeutic options available. Tricuspid valve is a complex cardiac structure with many technical challenges for surgical intervention. Transcatheter valve interventions have proven to be safe and effective novel therapeutic options for severe TR, which reduce the severity of TR with associated improvement in quality of life. In this review, we will provide an overview of the management of severe TR utilizing transcatheter edge-to-edge repair with the TriClip device (Abbott, Santa Clara, CA).

Zalunfiban: A Review of Current Knowledge and Future Applications of an Innovative Antiplatelet Agent.

Zalunfiban is a novel glycoprotein IIb/IIIa inhibitor currently being tested for its use in the prehospital setting for antiplatelet effect in patients with ST-elevation myocardial infarction. It has shown to be safe and effective in both phase 1 and phase 2 trials and is under investigation in phase 3 trials. In this review, we discuss zalunfiban in detail, including its mechanism of action, adverse effects, current recommendations for use, and ongoing trials.

Understanding Perioperative Acute Myocardial Ischemia Following Coronary Artery Bypass Grafting.

Surgical revascularization and coronary artery bypass grafting are often pursued as treatment for obstructive coronary artery disease. Despite trends of increased referrals for complex percutaneous coronary intervention, surgical revascularization often remains the standard of care for patients with multivessel or complex coronary artery disease. Myocardial ischemia during the perioperative and postoperative periods during coronary artery bypass grafting remains a challenge. Nuanced consideration is necessary to decide on interventions that include conservative management and percutaneous or repeat surgical revascularization.

Ninerafaxstat in the Treatment of Cardiometabolic Disease: Shifting Metabolic Paradigms.

Cardiovascular disease (CVD) refers to a wide array of conditions that damage the heart muscle and impede its ability to effectively circulate blood throughout the body. In damaged or pathological states, the heart muscle might not function as effectively as it would have had there been no insult to it. Understanding this, certain CVDs can put the heart in a "metabolic disadvantage"-a state in which it cannot synthesize energy stores, in the form of adenosine triphosphate (ATP), as efficiently as it was once able to do. While the heart typically uses fatty acids for its ATP synthesis, the metabolic processes required to do so consume more oxygen per mole than the processes required to convert glucose (or carbohydrates) to ATP. In conditions when oxygen demand outweighs supply-such as angina, heart failure, and certain inherited CVDs-the myocardium can more efficiently run via glucose oxidation. Despite this knowledge, there are no currently approved therapeutics or interventions that encourage this "metabolic shift" in the myocardial cells. Currently in phase II clinical trials, however, is a novel medication called ninerafaxstat. This novel drug is a partial inhibitor of fatty acid oxidation and thus pushes the heart to convert glucose (instead of fatty acids) to ATP-ultimately cutting down on oxygen supply. While still completing clinical trials, ninerafaxstat must undergo further safety and efficacy evaluation before it can be used as a standard of care. If, however, the drug makes it to market, it might offer a unique way to improve both the symptoms and quality of life of the millions of Americans who suffer from CVDs.

Role of Colchicine in Cardiovascular Disorders.

Inflammation has played a pivotal role in atherosclerosis and other cardiovascular disorders, prompting the exploration of anti-inflammatory therapies to improve cardiovascular outcomes. Colchicine, a well-established agent in conditions such as gout and familial Mediterranean fever, has emerged as a promising novel anti-inflammatory agent in the realm of cardiovascular diseases. Its ability to target both traditional risk factors and residual inflammatory risk marks a significant advancement in cardiovascular prevention strategies, indicating a new era in cardiovascular care. Landmark trials have supported the efficacy and safety of low-dose colchicine in reducing major adverse cardiovascular events when combined with standard therapies. In addition, its endorsement by major cardiovascular societies underscores its significance as the first targeted anti-inflammatory therapy for cardiovascular disease. However, careful monitoring for drug interactions and adverse effects, particularly on kidney and liver function, is essential for safe use. In this review, we aim to comprehensively summarize the mechanisms of action of colchicine, its molecular and biochemical targets in various cardiovascular conditions, and its pharmacokinetics, and delve deeply into the existing evidence on its safety and efficacy in the treatment of cardiovascular disorders, including coronary artery disease, pericarditis, atrial fibrillation, and heart failure.

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.

Cardiovascular Disease and Dementia: Exploring Intersections, Risks, and Therapeutic Challenges.

This review examines the complex bidirectional relationship between cardiovascular disease and various dementia subtypes, including Alzheimer's disease, vascular dementia, Lewy body dementia, and frontotemporal dementia. Traditional cardiovascular risk factors such as hypertension, coronary artery disease, arrhythmia, and diabetes mellitus are strongly linked to the development of dementia. Emerging evidence indicates that cognitive decline can exacerbate cardiovascular risks through heightened inflammatory responses and compromised autonomic regulation. Additionally, this review explores trials that investigate the impact of cardiovascular medications, such as antihypertensive and statin therapies, on cognitive outcomes, as well as studies examining how dementia treatments like anticholinesterases affect cardiovascular health. This review emphasizes the importance of early identification of at-risk individuals, integrated care approaches, and lifestyle interventions aimed at reducing both cardiovascular disease and dementia risk, ultimately aiming to enhance patient outcomes and quality of life.

Diastolic Dysfunction and Atrial Fibrillation: Recognition, Interplay, and Management.

Diastolic dysfunction occurs when the left ventricle loses its ability to relax normally, impairing ventricular filling during diastole. This most commonly occurs as a pathological sequela of left ventricular hypertrophy and remodeling due to chronic hypertension and/or age-related sclerotic changes of the aortic valve. This can subsequently deteriorate to diastolic heart failure or heart failure with preserved ejection fraction. There is a substantive interplay between atrial fibrillation and diastolic dysfunction, as atrial fibrillation can cause, exacerbate, or be a direct result of diastolic dysfunction and vice versa. In this review, we first independently define diastolic heart failure and atrial fibrillation while discussing the diagnostic guidelines, which encompass various modalities such as medical history, electrocardiography, echocardiography, and laboratory tests. We subsequently examine their interplay and pathophysiological links drawing on recent evidence in the literature. Finally, we discuss management approaches, including pharmacological interventions targeting rate and rhythm control, diuretics, and addressing comorbidities.

Exploring the Intersection of Dementia and Myocardial Infarction: Vascular Perspectives.

Emerging evidence underscores the relationship between myocardial infarction and dementia, implicating a profound influence on patient health. The bidirectional relationship between myocardial infarction and dementia is highlighted by pathophysiological changes in vasculature function, lifestyle factors, and environmental influences. Our literature review aims to explore the complex relationship between these 2 pathologies and highlight the pathways by which they mutually influence each other.

Blood Transfusions in Acute Myocardial Infarctions: A Review.

Anemia in acute myocardial infarctions has been an area of curiosity, with studies looking into clinical outcomes of blood transfusions in this patient population for decades without consistent evidence in the literature pointing in the direction of liberal or conservative transfusion use. With the recent publication of the MINT (Restrictive or Liberal Transfusion Strategy in Myocardial Infarction) trial showing that the liberal transfusion strategy did not reduce the recurrent risk of myocardial infarction but that harm in restrictive strategies cannot be excluded, we look to other literature and trials with different endpoints, which indicate that the liberal transfusion strategies may cause more harm. In this review, we will discuss new evidence as compared to the old for the conservative use of blood transfusions in the setting of myocardial infarctions.

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.