The role of phosphodiesterase 9A inhibitors in heart failure.

INTRODUCTION: There are currently limited effective treatments available to improve lusitropy in patients suffering from heart failure with preserved ejection fraction. The role of PDE9A in diastolic dysfunction has been well-studied over recent years, with a special focus on its association with myocardial hypertrophy. Recent insights into PDE9A inhibition have brought to light the potential for reversal of cardiac remodeling, with multiple studies showing promising results in preclinical data. AREAS COVERED: This expert opinion provides an overview of the role of PDE9A in diastolic heart dysfunction along with the efficacy of PDE9A inhibitors in laboratory models of heart failure with preserved ejection fraction. EXPERT OPINION: The available data on PDE9A inhibition in preclinical studies suggest that there is potential for reversal of diastolic dysfunction and myocardial hypertrophy, however, conflicting data suggests that further studies are required before progressing to clinical trials.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

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.

Pregnancy-Associated Venous Thromboembolism.

One of the leading causes of maternal death in the United States is venous thromboembolism (VTE), which is influenced by acquired, genetic, and environmental factors. Pregnancy-associated physiological changes that exhibit the characteristics of Virchow's triad: reduced fibrinolysis, increased coagulation factors, trauma, and venous stasis all raise the risk of VTE. Furthermore, multiple gestations, advanced maternal age, cesarean delivery, and obesity are all pregnancy-associated risk factors that also increase the risk of VTE. Management of VTE during pregnancy can be challenging due to the risks and benefits of anticoagulant therapy and potential hazard for both the fetus and the mother. In this review, we discuss the prevalence, pathogenesis, predisposing factors, and therapeutic options such as systemic thrombolysis, mechanical thrombectomy, and catheter-directed thrombolysis.

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.

Shorter Dual Antiplatelet Therapy for Older Adults After Percutaneous Coronary Intervention: A Systematic Review and Network Meta-Analysis.

Importance: The optimal duration of dual antiplatelet therapy (DAPT) for older adults after percutaneous coronary intervention (PCI) is uncertain because they are simultaneously at higher risk for both ischemic and bleeding events. Objective: To investigate the association of abbreviated DAPT with adverse clinical events among older adults after PCI. Data Sources: The Cochrane Library, Google Scholar, Embase, MEDLINE, PubMed, Scopus, and Web of Science were searched from inception to August 9, 2023. Study Selection: Randomized clinical trials comparing any 2 of 1, 3, 6, and 12 months of DAPT were included if they reported results for adults aged 65 years or older or 75 years or older. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was used to abstract data and assess data quality. Risk ratios for each duration of DAPT were calculated with alternation of the reference group. Main Outcomes and Measures: The primary outcome of interest was net adverse clinical events (NACE). Secondary outcomes were major adverse cardiovascular events (MACE) and bleeding. Results: In 14 randomized clinical trials comprising 19 102 older adults, no differences were observed in the risks of NACE or MACE for 1, 3, 6, and 12 months of DAPT. However, 3 months of DAPT was associated with a lower risk of bleeding compared with 6 months of DAPT (relative risk [RR], 0.50 [95% CI, 0.29-0.84]) and 12 months of DAPT (RR, 0.57 [95% CI, 0.45-0.71]) among older adults. One month of DAPT was also associated with a lower risk of bleeding compared with 6 months of DAPT (RR, 0.68 [95% CI, 0.54-0.86]). Conclusions and Relevance: In this systematic review and meta-analysis of different durations of DAPT for older adults after PCI, an abbreviated DAPT duration was associated with a lower risk of bleeding without any concomitant increase in the risk of MACE or NACE despite the concern for higher-risk coronary anatomy and comorbidities among older adults. This study, which represents the first network meta-analysis of this shortened treatment for older adults, suggests that clinicians may consider abbreviating DAPT for older adults.

Subcutaneous Furosemide: A Novel to Euvolemia.

Furoscix, a subcutaneous pH-neutral formulation of furosemide, obtained US Food and Drug Administration approval in October 2022 for adult patients with New York Heart Association class II and class III chronic heart failure. This approval marks an anticipated potential shift in the traditional management of decongestive therapy in chronic heart failure patients from the confines of the hospital to more accessible outpatient or home-based care. In this review, we will summarize existing evidence regarding the use of subcutaneous furosemide in comparison to both oral and intravenous formulations, highlighting the demonstrable benefits of its application in both outpatient and inpatient settings, and also discuss several factors that may limit its use.

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.