Cardiac Complications of Multiple Myeloma Treatments.

Multiple myeloma (MM) arises in plasma cells, a type of white blood cell. The cancerous plasma cells produce monoclonal immunoglobulins in the bone marrow. The extent of proliferation in the malignant state can manifest in many complications including osteopenia, osteolytic lesions, pathologic fractures, hypercalcemia, anemia, and kidney dysfunction. As is the case with the treatment of other malignancies, the research relating to the management of MM is dynamic and evolving. In this review, we aim to succinctly summarize and categorize the major treatment options of MM, including both new treatments and also older treatments that are now less frequently utilized, with a specific focus on the cardiotoxicity of these agents.

Acute Limb Ischemia Management and Complications: From Catheter-Directed Thrombolysis to Long-Term Follow-up.

Acute limb ischemia (ALI) is a vascular emergency that needs to be diagnosed and treated quickly to prevent permanent tissue damage and amputation. Catheter-directed thrombolysis is a possible treatment option for mild to moderate ALI, with improved results from endovascular procedures and thrombolytic drugs. However, patients receiving thrombolysis may experience higher rates of distal embolization, serious bleeding events, and stroke than those undergoing surgery. The review article emphasizes the need for postoperative and extended management of ALI patients, including monitoring for compartment syndrome, managing reperfusion damage, and reducing changeable cardiovascular risk factors such as lipid-lowering therapy, diabetes management, and smoking cessation. Complications that can arise from thrombolytic therapy are also discussed, including hemorrhagic complications, minor bleeding, and reperfusion damage, with recommendations to monitor patients closely during treatment and discontinue therapy immediately if any abnormalities are detected. Follow-up evaluations for patients, including Doppler ultrasound, ankle brachial index, pulse volume recordings, and laboratory tests, are recommended to ensure the best possible outcome for patients with ALI.

Ninerafaxstat in the Treatment of Diabetic Cardiomyopathy and Nonobstructive Hypertrophic Cardiomyopathy.

Ninerafaxstat is a novel mitotrope under investigation in 2 large clinical trials: IMPROVE-DiCE (a phase IIa trial investigating ninerafaxstat) and IMPROVE-hypertrophic cardiomyopathy (HCM). IMPROVE-DiCE is a single-center, open-label, phase 2a trial investigating the effectiveness of ninerafaxstat in diabetic cardiomyopathy. Ninerafaxstat significantly improved phosphocreatine/adenosine triphosphate median by 32% (P < 0.01) and reduced myocardial triglyceride content by 34% (P = 0.026). Magnetic resonance imaging (MRI) analysis showed improved left ventricular peak circumferential diastolic strain rate by 15% (P < 0.047) and peak left ventricular filling rate by 11% (P < 0.05). Pyruvate dehydrogenase flux was increased in 7 of 9 patients (P = 0.08), consistent with improved glucose utilization. IMPROVE-HCM (ninerafaxstat safe, effective for nonobstructive hypertrophic cardiomyopathy patients) is a phase 2, multicenter, randomized controlled and double-blinded study. From baseline to 12 weeks, ninerafaxstat was associated with a significantly improved ventilatory efficiency slope compared with placebo (P = 0.006). In a post hoc analysis with 35 patients with baseline Kansas City Cardiomyopathy Questionnaire score ≤80, changes in ventilatory efficiency slope favored ninerafaxstat versus placebo (P = 0.02). Left atrial size, a surrogate marker of diastolic dysfunction, was significantly decreased in patients on ninerafaxstat versus placebo (P = 0.01). These findings support a larger phase 3 study in symptomatic nonobstructive HCM patients to further investigate ninerafaxstat. Several drugs that also improve glucose utilization including fatty acid oxidation inhibitors, carnitine palmitoyltransferase I inhibitors, and glucagon-like peptide-1 receptor agonists are presently under investigation in clinical trials.

Cardiovascular Implications of Gynecological Disorders: Bridging the Gap Between Gynecology and Cardiology.

Gynecological disorders such as endometriosis, polycystic ovary syndrome, and gynecological cancers are increasingly recognized as potential risk factors for cardiovascular disease (CVD). Endometriosis, a chronic inflammatory condition, exhibits shared pathogenic mechanisms with CVD, including endothelial dysfunction and an atherogenic lipid profile. Emerging evidence suggests a link between endometriosis and an elevated risk of cardiovascular events such as myocardial infarction, ischemic heart disease, and hypertension. Polycystic ovary syndrome, characterized by hormonal imbalances and metabolic derangements, is associated with an increased risk of hypertension, myocardial infarction, and structural cardiac abnormalities, even after controlling for obesity. Gynecological cancers, such as ovarian, endometrial, and cervical cancers, are also associated with an increased burden of cardiovascular comorbidities and mortality. Cancer treatments, including chemotherapy and radiation therapy, can further contribute to cardiovascular toxicity. Understanding the interplay between gynecological disorders and CVD is crucial for identifying high-risk individuals, implementing preventive strategies, and providing comprehensive care. A multidisciplinary approach involving gynecologists, cardiologists, and other specialists is essential for optimizing the management of these complex conditions and improving overall patient outcomes.

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.

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.

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.