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.

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.

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.

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.

Fontan-Associated Liver Disease: A Review.

Fontan-associated liver disease (FALD) is a chronic complication of the Fontan procedure, a palliative surgery for patients with congenital heart disease that results in a single-ventricle circulation. The success of the Fontan procedure has led to a growing population of post-Fontan patients living well into adulthood. For this population, FALD is a major cause of morbidity and mortality. It encompasses a spectrum of hepatic abnormalities, ranging from mild fibrosis to cirrhosis and hepatocellular carcinoma. The pathophysiology of FALD is multifactorial, involving hemodynamic and inflammatory factors. The diagnosis and monitoring of FALD present many challenges. Conventional noninvasive tests that use liver stiffness as a surrogate marker of fibrosis are unreliable in FALD, where liver stiffness is also a result of congestion due to the Fontan circulation. Even invasive tissue sampling is inconsistent due to the patchy distribution of fibrosis. FALD is also associated with both benign and malignant liver lesions, which may exhibit similar imaging features. There is therefore a need for validated diagnostic and surveillance protocols to address these challenges. The definitive treatment of end-stage FALD is also a subject of controversy. Both isolated heart transplantation and combined heart-liver transplantation have been employed, with the latter becoming increasingly preferred in the US. This article reviews the current literature on the epidemiology, pathophysiology, diagnosis, and management of FALD, and highlights knowledge gaps that require further research.

Landiolol for Treating Arrhythmias: A State-of-The-Art Review.

This article provides a state-of-the-art review on landiolol, a medication that was recently submitted for 7 approvals. Focusing on its pharmacology, pharmacokinetics, and pharmacodynamics, the analysis underscores landiolol's unique attributes compared to conventional beta-blockers, particularly esmolol. As a sympatholytic agent, landiolol exhibits a short half-life, high cardioselectivity, and minimal impact on blood pressure, setting it apart in the realm of arrhythmia treatment. The review explores landiolol's potential applications, emphasizing scenarios where other beta-blockers may be limited. A detailed examination of its efficacy in preventing postoperative atrial fibrillation reveals promising results from clinical trials, suggesting its utility in diverse surgical settings. Additionally, the article delves into landiolol's role in rate control for atrial fibrillation/flutter, treatment of ventricular tachycardia/fibrillation, and its use in managing sepsis-related tachyarrhythmias. The evolving landscape of landiolol's applications extends beyond cardiac care, including potential anti-inflammatory, antioxidative, analgesic, and anticancer effects. While the outcomes from various studies are promising, challenges persist, requiring further research to optimize dosing strategies, identify optimal patient populations, and elucidate mechanisms underlying its diverse effects. The potential expansion of landiolol's applications highlights the importance of ongoing clinical investigation, offering a promising avenue for enhancing arrhythmia management and addressing broader medical needs.

Endocardial Fibroelastosis: A Comprehensive Review.

Endocardial fibroelastosis emerged as a challenging clinical phenomenon in the 1940s. It is characterized by an atypical proliferation of fibrous and elastic tissue within the heart and is primarily observed in childhood, occasionally displaying familial inheritance. While the precise cause remains elusive, various factors, including genetic, infectious, metabolic, autoimmune, oncologic, and medication-related influences, appear to play a role in its pathogenesis. The coexistence of endocardial fibroelastosis with multiple cardiac structural abnormalities manifests in symptoms of congestive heart failure and rhythm abnormalities. Despite its challenging diagnosis, various findings from ECG and imaging have proven beneficial in further evaluation of this condition. Finally, the treatment approach to endocardial fibroelastosis became complex due to addressing its concurrent cardiac abnormalities. Strategies for managing and preventing this condition are still under investigation. In this review, we intend to highlight the existing knowledge and illuminate future considerations regarding the etiology, diagnosis, and management of this disease.

Multisystem Inflammatory Syndrome in Children during the COVID-19 Pandemic: A Review of Clinical Manifestations, Cardiac Complications and Medical Management.

The SARS-CoV-2 pandemic has led to widespread research on associated clinical syndromes. While pediatric patients were initially deemed as a low-risk population for severe COVID-related disease, an increasing number of case reports have revealed a rare but potentially life-threatening syndrome, multisystem inflammatory syndrome in children (MIS-C). MIS-C is hypothesized to be due to hyperactivation of the immune system via a cytokine storm which leads to end-organ damage via endothelial dysfunction and changes in vascular permeability. Laboratory studies have displayed increased inflammatory markers such as C-reactive protein, erythrocyte sedimentation rate, D-dimer, tumor necrosis factor-alpha, and various interleukins. Studies have reported a wide range of clinical manifestations, including but not limited to fever, hypotension, shock, rash, coagulopathy, and gastrointestinal distress. Cardiac imaging and screening tests have revealed several complications, such as left ventricular failure, arrhythmias, and pericardial effusions. Medical management of MIS-C and cardiac sequelae have included supportive care, intravenous immunoglobulins, and corticosteroids, as well as immunomodulators, monoclonal antibodies, aspirin, and therapeutic anticoagulation, which have prevented serious outcomes in the majority of pediatric patients. Future multicenter and large-scale research is required for precise risk-stratification of MIS-C as well as long-term monitoring of sequelae. In this review, we aim to (1) outline the laboratory findings and clinical manifestations of MIS-C, and (2) describe cardiac complications and medical management of MIS-C.

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.

Cardiotoxicity of breast cancer chemotherapy.

Breast cancer is one of the leading causes of malignancy affecting women in the United States. Although many effective treatments are available, most come with notable side effects that providers and patients must take into consideration. Various classes of chemotherapeutic agents, including anthracyclines and human epidermal growth factor receptor-2 antagonists, are known to be toxic to myocardial tissue. In this review article, we discuss what is reported in the literature regarding the cardiotoxicity of these agents as well as how to monitor and prevent cardiac injury and dysfunction.

Baxdrostat: An Aldosterone Synthase Inhibitor for the Treatment of Systemic Hypertension.

Systemic hypertension remains one of the leading cause of morbidity and mortality in the United States and throughout the world. Baxdrostat (CIN-107), a new drug developed by Roche is a selective aldosterone synthase inhibitor that is being evaluated as one of the potential treatments for hypertension, especially in patients with drug treatment-resistant hypertension. An increased level of aldosterone is associated with inflammation, systemic hypertension, and organ fibrosis, contributing to adverse cardiovascular events. A phase 2 trial, BrigHTN, showed promising results in demonstrating the efficacy of baxdrostat, where The HALO (efficacy and safety of baxdrostat in patients with uncontrolled hypertension) trial did not demonstrate any blood pressure-lowering benefit of baxdrostat when compared with the placebo. Several additional studies are now underway to evaluate the effectiveness of baxdrostat as an anti-hypertensive agent.

Examining the Use of a Polypill in Cardiovascular Disease Prevention.

Cardiovascular disease (CVD) is a significant cause of death worldwide. To address the global burden of CVD and its risk factors, the polypill, an all-in-one therapy that combines multiple existing medications for preventing CVD and reducing CVD events (such as angiotensin-converting enzyme inhibitor, beta-blocker, statin, or aspirin) into a single combination pill, has emerged as a potential strategy to improve CVD prevention. Clinical trials on the polypill have found that polypill use is associated with significant reductions in CVD events and risk factors in both patients with established CVD and at risk of developing CVD, suggesting a potential benefit in primary and secondary CVD prevention. The polypill has also been demonstrated to be a cost-effective therapy that may potentially increase treatment accessibility, affordability, and availability particularly in low- and middle-income countries. Further, patients on polypill therapy have shown high rates of treatment compliance, with significant improvements in medication adherence for patients with low baseline compliance. Given its potential advantages and benefits, the polypill may become a promising therapy for the prevention of CVD.

Incidental Breast Arterial Calcifications and Assessment of Coronary Artery Disease Risk: A Review and Recommendation.

Coronary artery disease (CAD) continues to be the leading cause of morbidity and mortality in women, contributing to about 20%, or nearly 400,000, of female deaths annually in the United States. Despite their significant burden from CAD, women have been traditionally underrepresented in trials, and therefore, there is still much to be studied regarding the sex-based variations that have been reported regarding the pathophysiology, clinical presentation, efficacy of diagnostic workup, and response to therapy in CAD. Previous studies have reported that breast arterial calcifications, commonly found incidentally on screening mammography, may be associated with risk of CAD; however, there are currently no specific guidelines concerning reporting and quantification practices, as well as further workup recommendations for patients who are found to have vascular calcifications. Thus, the question remains whether breast arterial calcifications can serve as a sex-specific marker for CAD, and whether there is enough evidence to support the use of mammography as a screening tool for CAD in women. In this review, we will summarize the current understanding of cardiovascular disease in women, the existing literature regarding breast arterial calcifications and current reporting practices, and the association of vascular calcifications with CAD risk; based on the collected evidence, we will make a recommendation whether screening mammography and breast arterial calcifications should be used to assess CAD risk, and if so, what additional workup, if any, we recommend in women found to have breast arterial calcifications on imaging.

Back Up at the Pump? I Have a Gut Feeling About This: A Review of the Gastrointestinal Manifestations From Congestive Heart Failure.

Heart failure, which is a clinical syndrome characterized by the heart's inability to maintain adequate cardiac output, is known to affect various organ systems in the body due to its ischemic nature and activation of the systemic immune response, but the resultant complications specifically on the gastrointestinal tract and the liver are not well discussed and poorly understood. Gastrointestinal-related phenomena are common symptoms experienced in patients with heart failure and frequently found to increase morbidity and mortality in these populations. The relationship between the gastrointestinal tract and heart failure are strongly linked and influence each other much so that the bidirectional association of the two is oftentimes referred to as cardiointestinal syndrome. Manifestations include gastrointestinal prodrome, bacterial translocation and protein-losing gastroenteropathy by gut wall edema, cardiac cachexia, hepatic insult and injury, and ischemic colitis. More attention is needed from a cardiology perspective to recognize these common presenting gastrointestinal phenomena that affect much of our patient population with heart failure. In this overview, we describe the association between heart failure and the gastrointestinal tract, the pathophysiology, lab findings, clinical manifestations and complications, and the management involved.

The Critical Role of the Adipocytokine NOV in Obstructive Sleep Apnea Induced Cardiometabolic Dysfunction: A Review.

Obstructive sleep apnea (OSA) is highly prevalent and associated with oxidative stress, chronic inflammation, and adverse cardiovascular consequences. The comorbid condition of obesity remains epidemic. Both obesity and OSA are highly comorbid in patients with cardiovascular disease including atrial fibrillation, resistant hypertension, congestive heart failure, and coronary artery disease. Patients with these preexisting cardiovascular conditions should be screened for OSA with a low threshold to treat, even if OSA severity is mild. Nephroblastoma overexpressed (NOV/CCN3) protein has been identified in multiple chronic inflammatory states, most notably in obesity and more recently in OSA, even in the absence of obesity. As such, NOV may represent an important biomarker for oxidative stress in OSA and may lead to a deeper understanding of the relationship between OSA and its clinical sequelae.

Landiolol: An Ultra-Short-Acting ß-Blocker.

Landiolol is an ultra-short-acting, highly cardio-selective, ß-blocker, that is currently approved for clinical use in Japan and the European Union, for the treatment of tachyarrhythmias. Landiolol is highly cardio-selective with high ß1 selectivity and receptor affinity, resulting in a more potent chronotropic effect and less potent hypotensive effect compared with other ß-blockers such as esmolol and propranolol. Based on the recent randomized controlled trials, low-dose landiolol may have a beneficial role in the prevention and management of postoperative atrial fibrillation following noncardiac and cardiac surgeries, including on-pump and off-pump coronary artery bypass grafting and valve surgery. Additionally, landiolol may have potential utility for myocardial salvage and prevention of postpercutaneous coronary intervention myocardial infarction. Furthermore, the use of landiolol may also have a therapeutic effect for rate control of sepsis-related tachyarrhythmias. Positive results of recent randomized controlled trials should continue to inspire clinicians to conduct further, larger studies, to find new potential clinical applications for this novel drug.

Emerging Modalities for Temporary Mechanical Circulatory Support in Cardiogenic Shock.

Cardiogenic shock (CS) is a life-threatening medical condition that requires prompt recognition and treatment. The use of standardized CS criteria, such as the Society for Cardiovascular Angiography and Interventions criteria, can categorize patients and guide therapeutic strategies. Temporary mechanical circulatory support (MCS) devices have become valuable tools in the treatment of CS, as they can provide cardiovascular support as a bridge to recovery, cardiac surgery, or advanced therapies such as cardiac transplant or durable ventricular assist devices. The use of MCS should be tailored to each individual patient, focused on a stepwise escalation of circulatory support to support both end-organ perfusion and myocardial recovery. As newer MCS devices reduce myocardial oxygen demand without increasing ischemia, the possibility of recovery is optimized. In this review, we discuss the different modalities of MCS focusing on the mechanism of support and the advantages and disadvantages of each device.

Hydroxychloroquine and Cardiotoxicity.

Hydroxychloroquine (HCQ) has been used for rheumatological diseases such as systemic lupus erythematous and rheumatoid arthritis and demonstrated to improve clinical symptoms and reduce long-term sequelae. The drug is metabolized in the liver, is primarily excreted through the kidney, and works by modulating major histocompatibility complex (MHC) and various cytokines, suppressing the immune system in the process. Prolonged administration and high dosages of HCQ have been associate with cardiotoxic effects such as bradycardia, tachycardia, QT prolongation, atrioventricular block, and cardiomyopathy. Common cardiac biopsy findings of HCQ-induced toxicity are enlarged and vacuolated cells on light microscopy along with the presence of myelinoid and curvilinear bodies on transmission electron microscopy. HCQ cardiotoxicity is not very well recognized, and there are no current guidelines for routine cardiac function monitoring from either rheumatology or cardiology societies.

Nonalcoholic Fatty Liver Disease and Cardiovascular Disease: Causation or Association.

Nonalcoholic fatty liver disease (NAFLD) is a disease process that is gaining increasing recognition. The global prevalence of NAFLD is increasing in parallel with growing rates of risk factors for NAFLD such as hypertension, obesity, diabetes, and metabolic syndrome. NAFLD has been referred to as a risk factor for cardiovascular disease (CVD). As CVD is the leading cause of morbidity and mortality worldwide, there are constant efforts to describe and alleviate its risk factors. Although there is conflicting data supporting NAFLD as a causative or associative factor for CVD, NAFLD has been shown to be associated with structural, electrical, and atherosclerotic disease processes of the heart. Shared risk factors and pathophysiologic mechanisms between NAFLD and CVD warrant further explication. Pathologic mechanisms such as endothelial dysfunction, oxidative stress, insulin resistance, genetic underpinnings, and gut microbiota dysregulation have been described in both CVD and NAFLD. The mainstay of treatment for NAFLD is lifestyle intervention including physical exercise and hypocaloric intake in addition to bariatric surgery. Investigations into various therapeutic targets to alleviate hepatic steatosis and fibrosis by way of maintaining the balance between lipid synthesis and breakdown. A major obstacle preventing the success of many pharmacologic approaches has been the effects of these medications on CVD risk. The future of pharmacologic treatment of NAFLD is promising as effective medications with limited CVD harm are being investigated.