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.

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.

New Oral PCSK9 Inhibitor: "MK-0616".

MK-0616, a novel oral macrocyclic peptide inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9), represents a significant advancement in the treatment of hypercholesterolemia. Unlike current PCSK9 inhibitors, which are injectable monoclonal antibodies and siRNA molecules, MK-0616 offers a patient-friendly alternative. The development of MK-0616 involved innovative synthetic chemistry and in vitro mRNA display technology. This cutting-edge approach led to the creation of an orally administered peptide with the ability to cover a larger portion of PCSK9 compared to smaller, linear peptides. Phase 1 and 2b clinical trials have demonstrated MK-0616's safety, efficacy, and pharmacokinetics. These trials indicate the drug's dose-dependent systemic absorption and long half-life. Notably, MK-0616 has exhibited comparable low-density lipoprotein cholesterol-lowering effects to currently available PCSK9 inhibitors, all while maintaining good tolerability in diverse patient populations, including those concurrently on statin therapy. As MK-0616 advances to Phase 3 trials, its lipid-lowering potential for heterozygous familial hypercholesterolemia and its impact on reducing the time to adverse cardiac events will be evaluated in a broad and diverse population, including underrepresented groups. The results achieved so far are promising for individuals with hypercholesterolemia, as they offer a potential solution for effectively lowering low-density lipoprotein cholesterol in patients on statin therapy and mitigating the risk of cardiovascular events. Ongoing research and monitoring will be critical to establish its long-term safety and efficacy, but MK-0616 may emerge as a valuable addition to the array of lipid-lowering therapies available to patients.

Health Literacy Analytics of Accessible Patient Resources in Cardiovascular Medicine: What are Patients Wanting to Know?

Introduction: There remains an increasing utilization of internet-based resources as a first line of medical knowledge. Among patients with cardiovascular disease, these resources often are relied upon for numerous diagnostic and therapeutic modalities. However, the reliability of this information is not fully understood. The aim of this study was to provide a descriptive profile on the literacy quality, readability, and transparency of publicly available educational resources in cardiology. Methods: The frequently asked questions and associated online educational articles on common cardiovascular diagnostic and therapeutic interventions were investigated using publicly available data from the Google RankBrain machine learning algorithm after applying inclusion and exclusion criteria. Independent raters evaluated questions for Rothwell's Classification and readability calculations. Results: Collectively, 520 questions and articles were evaluated across 13 cardiac interventions, resulting in 3,120 readability scores. The sources of articles were most frequently from academic institutions followed by commercial sources. Most questions were classified as "Fact" at 76.0% (n = 395), and questions regarding "Technical Details" of each intervention were the most common subclassification at 56.3% (n = 293). Conclusions: Our data show that patients most often are using online search query programs to seek information regarding specific knowledge of each cardiovascular intervention rather than form an evaluation of the intervention. Additionally, these online patient educational resources continue to not meet grade-level reading recommendations.

Primary Central Nervous System T-cell Lymphoma Associated With Hepatitis B and D Virus Coinfection.

Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin's lymphoma. It is defined as lymphoma of the central nervous system without any systemic disease elsewhere at the time of diagnosis. Based on the phenotypical features, it is divided into two categories, B-cell and T-cell, with the latter being less common. Viruses, such as human immunodeficiency virus (HIV) and human T-lymphotropic virus type 1 (HTLV-1), are linked to the T-cell variant; however, there is a lack of evidence suggesting associating hepatitis B and D virus coinfection with it. We report a case of a 34-year-old male who presented with T-cell PCNSL and was later diagnosed with a hepatitis B and D virus coinfection.