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.

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.

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.

Atrial Fibrillation and Cognitive Disorders.

The prevalence of atrial fibrillation among older adults is increasing. Research has indicated that atrial fibrillation is linked to cognitive impairment disorders such as Alzheimer and vascular dementia, as well as Parkinson disease. Various mechanisms are believed to be shared between atrial fibrillation and cognitive impairment disorders. The specific pathologies and mechanisms of different cognitive disorders are still being studied. Potential mechanisms include cerebral hypoperfusion, ischemic or hemorrhagic infarction, and cerebrovascular reactivity to carbon dioxide. Additionally, circulatory biomarkers and certain infectious organisms appear to be involved. This review offers an examination of the overlapping epidemiology between atrial fibrillation and cognitive disorders, explores different cognitive disorders and their connections with this arrhythmia, and discusses trials and guidelines for preventing and treating atrial fibrillation in patients with cognitive disorders. It synthesizes existing knowledge on the management of atrial fibrillation and identifies areas that require further investigation to bridge the gap in understanding the complex relationship between dementia and atrial fibrillation.

The Risk of Ventricular Septal Defects Associated With Prenatal Marijuana Exposure: A Systematic Review and Meta-Analysis.

With the recent legalization of marijuana across the United States, its usage in pregnant women has increased. The aim of this meta-analysis was to determine if prenatal marijuana use increases the likelihood of ventricular septal defects. The analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search strategy identified 4 case-control studies that were ultimately included in the analysis with a combined 381,621 infant records. Quantitative analysis demonstrated prenatal marijuana usage significantly increases the likelihood of ventricular septal defects (odds ratio = 2.39, 95% confidence interval = 1.11-5.18).

Cardiac Manifestations of Lymphoma: A Review of Primary and Secondary Cardiac Lymphoma.

Primary cardiac lymphoma (PCL) is a very unique and uncommon disease presentation, with reports in the literature limited to case reports. Most often it is B-cell in origin, predominantly diffuse large B-cell lymphoma. Symptomatic presentation of PCL depends on the location of anatomic involvement, but most often involves the right heart, with presentation consistent with heart failure, pericardial effusions, and atrioventricular nodal blockade. Endomyocardial biopsy is necessary for diagnosis, but cardiac magnetic resonance imaging has been the most useful for staging of the disease. The disease has a poor prognosis but treatment with chemotherapy has been the most successful approach. Particularly, the chemotherapy regimen of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone has been reported to be successful for diffuse large B-cell lymphoma, so it is often utilized first. In newer reports of patients with PCL, there may be a role of autologous stem cell transplant along with consolidative chemotherapy in younger patients diagnosed with PCL. Secondary cardiac lymphoma (SCL) is a more common occurrence that is often asymptomatic and recognized after the patient has passed from either the primary lymphoma or some other reason. Unlike PCL, SCL is more expansive and not often confined to the right heart. However, in patients with SCL who do have cardiac symptoms, the diagnostic approach and treatment are similar to that of PCL.

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.

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.

Semaglutide in Heart Failure With Preserved Ejection Fraction: Exploring Recent Evidence in Therapeutic Potential for the Obese Population.

Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent condition, particularly among the aging population in the United States, and is associated with significant challenges due to its complex pathophysiology and limited therapeutic options. Historically, few pharmacological therapies have successfully mitigated HFpEF, making the emergence of effective treatments particularly significant. This review evaluates recent evidence on the therapeutic potential of semaglutide for managing HFpEF, especially in the obese population. Results from the STEP-HFpEF and STEP-HFpEF DM trials demonstrate that semaglutide, a glucagon-like peptide-1 receptor agonist originally developed for type 2 diabetes but now also approved for obesity treatment, significantly improves clinical outcomes such as symptom scores, body weight, exercise capacity, and inflammation markers in the obese population suffering from HFpEF. These improvements are attributed to both the weight loss induced by semaglutide and its direct effects on the congestive pathophysiology of HFpEF. The efficacy of semaglutide offers new hope for addressing a condition that has long lacked effective pharmacological interventions.

Bloodless Cardiac Surgery in Jehovah's Witness: A Comprehensive Review.

This article explores the major challenges and specialized strategies involved in managing cardiovascular surgery patients who are Jehovah's Witnesses and refuse blood transfusions due to their religious beliefs. It delves into preoperative, intraoperative, and postoperative approaches aimed at minimizing blood loss and optimizing patient outcomes while respecting their autonomy. Preoperative measures focus on correcting anemia and coagulopathy through targeted interventions, such as iron supplementation and erythropoietin therapy, and meticulous screening for bleeding disorders. Intraoperative techniques include the use of vasoconstrictors, hemostatic agents, and innovative blood conservation methods like acute normovolemic hemodilution and cell salvage. Postoperative care emphasizes infection control, hemostasis, and judicious monitoring to prevent anemia and facilitate recovery. Through a multidisciplinary approach and adherence to evidence-based practices, healthcare providers can effectively meet the needs of Jehovah's Witness patients, ensuring safe and successful cardiovascular surgery outcomes without the use of blood transfusions.

Goflikicept and Related IL-1 Inhibitors in the Treatment of Recurrent Pericarditis.

Anticytokine biologics are a promising anti-inflammatory therapy for recurrent pericarditis. Several studies have proved the efficacy and safety of interleukin-1 (IL-1) inhibitors, such as anakinra and rilonacept in patients with recurrent pericarditis. Treatment with goflikicept in a recent phase 2 and 3 trial significantly reduced the pericarditis recurrence rate compared with both the placebo and the allowed withdrawal of standard-of-care therapy. Patients with idiopathic recurrent pericarditis (IRP) achieved remission within the first 14 days of therapy. In rilonacept inhibition of interleukin-1 alpha and beta for recurrent pericarditis (phase 3 trial of interleukin-1 trap rilonacept in recurrent pericarditis), rilonacept led to a significantly lower risk of pericarditis recurrence than placebo (hazard ratio, 0.04; P < 0.001) and a rapid resolution of recurrent pericarditis episodes. However, 74% of patients in the placebo group demonstrated recurrence, compared with 7% in the rilonacept group. The efficacy of anakinra was demonstrated by the AIRTRIP (anakinra-treatment of recurrent idiopathic pericarditis) trial, which showed a reduction in the incidence of recurrent pericarditis in anakinra versus placebo-treated patients (18.2% vs 90%). In patients with recurrences, the mean time to flare was 28.4 days in the placebo group versus 76.5 days in the anakinra group. IL-1 inhibitors require further research and have the potential to decrease the use of first-line drug regimens for recurrent pericarditis that are not tolerated in specific patient groups.

The Significance of Parametric Mapping in Advanced Cardiac Imaging.

Cardiac magnetic resonance imaging has witnessed a transformative shift with the integration of parametric mapping techniques, such as T1 and T2 mapping and extracellular volume fraction. These techniques play a crucial role in advancing our understanding of cardiac function and structure, providing unique insights into myocardial tissue properties. Native T1 mapping is particularly valuable, correlating with histopathological fibrosis and serving as a marker for various cardiac pathologies. Extracellular volume fraction, an early indicator of myocardial remodeling, predicts adverse outcomes in heart failure. Elevated T2 relaxation time in cardiac MRI indicates myocardial edema, enabling noninvasive and early detection in conditions like myocarditis. These techniques offer precise insights into myocardial properties, enhancing the accuracy of diagnosis and prognosis across a spectrum of cardiac conditions, including myocardial infarction, autoimmune diseases, myocarditis, and sarcoidosis. Emphasizing the significance of these techniques in myocardial tissue analysis, the review provides a comprehensive overview of their applications and contributions to our understanding of cardiac diseases.

Transcatheter Aortic Valve Implantation for Aortic Regurgitation: A Comprehensive Review.

Aortic regurgitation (AR), a left-sided valvular heart disease, poses challenges in both diagnosis and treatment. From rheumatic fever to trauma, the vast etiologies of AR can manifest with varying symptoms and disease progression. Nonetheless, without interventions, patients with acute and chronic symptomatic AR have a poor prognosis. This article synthesizes current knowledge on AR management, emphasizing advancements in transcatheter aortic valve implantation (TAVI). While surgical aortic valve replacement remains the gold standard, TAVI has emerged as a promising alternative, particularly for inoperable patients. It is currently used off-label for patients with bicuspid valve and valve-in-valve procedures. Clinical data from various studies underscore TAVI's efficacy in AR, demonstrating improvements in left ventricular function and mortality rates with use of the new-generation devices. However, challenges persist with conditions such as aortic aneurysms, including device positioning and selection. With ongoing technological innovations, TAVI holds potential as a viable option in selected AR patients, necessitating further research for optimized outcomes.

The Impact of the Apolipoprotein E Genotype on Cardiovascular Disease and Cognitive Disorders.

Apolipoprotein E (ApoE) plays a critical role in cholesterol transport and protection against the development of atherosclerotic cardiovascular disease (ASCVD). Humans have 3 prevalent isoforms of ApoE: apolipoprotein E2 (ApoE2), apolipoprotein E3 (ApoE3), and apolipoprotein E4 (ApoE4). The E4 allele has been associated with higher ASCVD risk. While E4 patients do have higher cholesterol levels, they do not have enough to account for the substantially elevated ASCVD risk relative to E2 and E3 patients. ASCVD risk calculators would underestimate the true effect of E4 if the difference was caused entirely by a difference in cholesterol level. This article reviews the function of ApoE in atherosclerosis, and how each isoform functions differently. We review what is known about the molecular mechanisms through which ApoE prevents endothelial dysfunction and damage, how ApoE stimulates macrophage efflux of cholesterol from atherogenic lesions, and the ways in which ApoE decreases inflammation throughout atherosclerosis. The impact of ApoE on Alzheimer's disease and a discussion of why it is possibly unrelated to ASCVD prevention are included. Clinical applications to hyperlipidemia management and ASCVD prevention in specific patient populations are discussed.

SGLT-2 Inhibitors: Focus on Dapagliflozin.

Dapagliflozin (trade name FARXIGA) is a sodium-glucose cotransporter-2 (SGLT-2) inhibitor that has transcended its initial antidiabetic application to demonstrate benefits in cardiac and renal diseases. It was first approved by the food and department administration for type 2 diabetes in 2014. Since then, it has gained food and department administration approval for chronic kidney disease in 2021, heart failure with reduced ejection fraction in 2020, and heart failure with preserved ejection fraction in 2023. Thus, dapagliflozin plays a pivotal role in improving patient outcomes. By competitive binding to renal SGLT-2 cotransporters, dapagliflozin effectively prevents glucose and sodium reabsorption, leading to glucosuria. Its pharmacokinetic profile involves minimal cytochrome P450-induced metabolism, rapid absorption with an 18-hour duration of action, and stable effects. Clinical trials have revealed dapagliflozin's efficacy in glycemic control without the risk of hypoglycemia, making it an advantageous choice for patients insufficiently managed on other antidiabetic drugs. Comparative analysis with other SGLT-2 inhibitors suggests dapagliflozin's potential superiority in preventing heart failure. Compared to empagliflozin, it has more extended effects, contributing to stable sodium diuresis, reduced blood pressure fluctuations, and potentially lower cardiovascular disease risks. However, it leads to less urinary glucose excretion compared with canagliflozin. Dapagliflozin has specific contraindications, such as type 1 diabetes and end-stage chronic kidney disease. Adverse effects include an increased risk of genital infections, urinary tract infections, and Fournier's gangrene. A nuanced understanding of dapagliflozin's benefits and limitations is imperative for informed clinical decision-making in the management of diabetes and its complications.

Intravenous Iron Therapy in Heart Failure Patients With Iron Deficiency: Benefits, Safety, and Guidelines.

Iron deficiency is a common comorbidity in heart failure (HF) patients, with up to 50% of ambulatory patients with HF affected. Intravenous (IV) iron therapy has emerged as a promising treatment approach for HF patients with concomitant iron deficiency. This review summarizes the current literature on the use of IV iron therapy in HF patients, focusing on its benefits in improving quality of life, and exercise capacity, and reducing HF hospitalizations. However, concerns about the long-term cardiotoxic effects of IV iron, including the risk of iron overload, are also addressed. The review highlights the importance of a balanced approach to iron replacement and provides an overview of the 2022 American College of Cardiology/American Heart Association guidelines, which recommend IV iron therapy for eligible patients. Additionally, the review underscores the need for further research, particularly in HF patients with preserved ejection fraction and acute HF. While IV iron therapy shows promise, questions about its safety and specific formulations remain to be fully addressed.

Percutaneous Tricuspid Valve Repair: The Triclip.

Tricuspid regurgitation is an often overlooked, but severe cardiac valvular disease associated with significant morbidity and poor quality of life. Tricuspid valve surgery is the only treatment that prevents progression of the disease but is often complicated or made impossible by perioperative risk factors. Due to the high-risk nature, tricuspid valve surgery is typically only done for severe tricuspid regurgitation at the time of left heart surgery, leaving many patients untreated. Medical therapy is limited primarily to diuretic agents, which are often unsuccessful in alleviating symptoms. Treatment of tricuspid regurgitation with transcatheter edge-to-edge repair has emerged after the success of this technique in mitral valve pathologies. This percutaneous procedure parallels surgical principles previously used for valve repair but eliminates the need for cardiac surgery, thus having the potential to serve as an alternative treatment in high-risk patients. The TriClip (Abbott Labs) device is an example of this therapy and the subject of this review.