Diagnosis and Management of Cardiac Sarcoidosis: A Scientific Statement From the American Heart Association.

Cardiac sarcoidosis is an infiltrative cardiomyopathy that results from granulomatous inflammation of the myocardium and may present with high-grade conduction disease, ventricular arrhythmias, and right or left ventricular dysfunction. Over the past several decades, the prevalence of cardiac sarcoidosis has increased. Definitive histological confirmation is often not possible, so clinicians frequently face uncertainty about the accuracy of diagnosis. Hence, the likelihood of cardiac sarcoidosis should be thought of as a continuum (definite, highly probable, probable, possible, low probability, unlikely) rather than in a binary fashion. Treatment should be initiated in individuals with clinical manifestations and active inflammation in a tiered approach, with corticosteroids as first-line treatment. The lack of randomized clinical trials in cardiac sarcoidosis has led to treatment decisions based on cohort studies and consensus opinions, with substantial variation observed across centers. This scientific statement is intended to guide clinical practice and to facilitate management conformity by providing a framework for the diagnosis and management of cardiac sarcoidosis.

Differences in quality of anticoagulation care delivery according to ethnoracial group in the United States: A scoping review.

Anticoagulation therapy is standard for conditions like atrial fibrillation, venous thromboembolism, and valvular heart disease, yet it is unclear if there are ethnoracial disparities in its quality and delivery in the United States. For this scoping review, electronic databases were searched for publications between January 1, 2011 - March 30, 2022. Eligible studies included all study designs, any setting within the United States, patients prescribed anticoagulation for any indication, outcomes reported for ≥ 2 distinct ethnoracial groups. The following four research questions were explored: Do ethnoracial differences exist in 1) access to guideline-based anticoagulation therapy, 2) quality of anticoagulation therapy management, 3) clinical outcomes related to anticoagulation care, 4) humanistic/educational outcomes related to anticoagulation therapy. A total of 5374 studies were screened, 570 studies received full-text review, and 96 studies were analyzed. The largest mapped focus was patients' access to guideline-based anticoagulation therapy (88/96 articles, 91.7%). Seventy-eight articles made statistical outcomes comparisons among ethnoracial groups. Across all four research questions, 79 articles demonstrated favorable outcomes for White patients compared to non-White patients, 38 articles showed no difference between White and non-White groups, and 8 favored non-White groups (the total exceeds the 78 articles with statistical outcomes as many articles reported multiple outcomes). Disparities disadvantaging non-White patients were most pronounced in access to guideline-based anticoagulation therapy (43/66 articles analyzed) and quality of anticoagulation management (19/21 articles analyzed). Although treatment guidelines do not differentiate anticoagulant therapy by ethnoracial group, this scoping review found consistently favorable outcomes for White patients over non-White patients in the domains of access to anticoagulation therapy for guideline-based indications and quality of anticoagulation therapy management. No differences among groups were noted in clinical outcomes, and very few studies assessed humanistic or educational outcomes.

Cardio-Oncology Drug Interactions: A Scientific Statement From the American Heart Association.

In the cardio-oncology population, drug interactions are of particular importance given the complex pharmacological profile, narrow therapeutic index, and inherent risk of therapies used to manage cardiovascular disease and cancer. Drug interactions may be beneficial or detrimental to the desired therapeutic effect. Clinicians in both cardiology and oncology should be cognizant of these potential drug-drug interactions that may reduce the efficacy or safety of either cardiovascular or cancer therapies. These risks can be mitigated through increased recognition of potential drug-drug interaction, use of alternative medications when possible, and careful monitoring. This scientific statement provides clinicians with an overview of pharmacodynamic and pharmacokinetic drug-drug interactions in patients with cancer exposed to common cardiovascular and cancer medications.

Iron Deficiency in Heart Failure: A Scientific Statement from the Heart Failure Society of America.

Iron deficiency is present in approximately 50% of patients with symptomatic heart failure and is independently associated with worse functional capacity, lower quality of, life and increased mortality. The purpose of this document is to summarize current knowledge of how iron deficiency is defined in heart failure and its epidemiology and pathophysiology, as well as pharmacological considerations for repletion strategies. This document also summarizes the rapidly expanding array of clinical trial evidence informing when, how, and in whom to consider iron repletion.

Polypharmacy and Cardiovascular Diseases: Consideration for Older Adults and Women.

PURPOSE OF REVIEW: The intent of this review is to provide an update in polypharmacy in older adults and women with a focus on common determinants and strategies to mitigate polypharmacy. RECENT FINDINGS: Polypharmacy is becoming a critical focus in the management of cardiovascular diseases. It may emerge unintentionally while managing multimorbidity in older adults or in the vulnerable subgroup of patients, such as pregnant and lactating females. Clinicians should utilize several approaches such as deprescribing, sex-specific risk assessment, and encouraging healthy lifestyle to minimize inappropriate and unnecessary use of medications. A shared decision-making model along with coordination and collaboration among healthcare providers should be utilized in the selection and management of pharmacotherapies.

Selatogrel: A Novel Subcutaneous P2Y12 Inhibitor.

ABSTRACT: The use of a P2Y12 inhibitor as a component of dual antiplatelet therapy in patients with an acute coronary syndrome (ACS) is well established. However, the P2Y12 inhibitors currently available have pharmacokinetic limitations due to delayed absorption, lack of enteral access for administration with oral formulations, need for intravenous access with cangrelor, or need for metabolization to be ideal in the critical 3-hour window during an ACS. Selatogrel is a novel, potent, reversible, and selective 2-phenylprimdine-4-carboxamide administered subcutaneously under development. Results from preclinical, phase 1, and phase 2 trials have confirmed that the agent provides sustained and reversible P2Y12 platelet inhibition with an acceptable safety profile. The most commonly reported adverse effects include minor bleeding and dyspnea. Phase 3 trials are being designed to understand the critical role this agent can play in upstream management of patients with ACS including a more defined understanding of the adverse effect profile, how to transition from this agent to an oral agent, who will be administering, and does this agent allow for a safe and quick transition to coronary artery bypass graft surgery if needed. Should it obtain approval, selatogrel has the potential to provide a unique and advantageous mechanism for P2Y12 inhibition.

The Role of the Non-Steroidal Mineralocorticoid Antagonist Finerenone in Cardiorenal Management.

PURPOSE OF REVIEW: Finerenone is a novel, non-steroidal mineralocorticoid receptor antagonist (MRAs) that has been investigated for the management of cardiorenal conditions. This article provides an overview of recent evidence of benefits on cardiovascular (CV) outcomes. RECENT FINDINGS: The recently published phase III FIDELIO-DKD and FIGARO-DKD, alone and pooled, in patients with CKD and diabetes demonstrate that finerenone reduces the composite of CV death, non-fatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure (HF) with hospitalization for HF being the primary driver of this composite. Finerenone is indicated to reduce renal and CV outcomes in patients with CKD and diabetes. Future investigations of this agent include patients with non-diabetic CKD, HF with preserved ejection fraction, and with the use of sodium-glucose transporter type 2 inhibitors.

Osocimab: A Novel Agent in Preventing Venous Thromboembolism.

The nature of orthopedic surgery, and specifically total knee arthroplasty, lends itself to the development of venous thromboembolism given endothelial injury from the surgical procedure, promotion of an acute hypercoagulable state, and the prolonged period of immobilization after surgery promoting stasis; all factors of Virchow's triad. Current guidelines recommend the direct acting oral anticoagulants, enoxaparin, fondaparinux, and warfarin as options for venous thromboembolism prevention. However, these agents may still be prone to unacceptable bleeding risk, given they mostly target the extrinsic pathway of the clotting cascade, and have other characteristics which can be problematic for use. Investigators have determined patients with factor XI deficiency seem to be protected for thrombotic risk and seem to be devoid of bleeding sequelae. This has led to the development of osocimab, a fully humanized monoclonal G1 antibody designed specifically to functionally neutralize factor XIa. Phase 1 clinical trials have demonstrated an agent with a long half-life (∼30 days) with minimal requirement of renal elimination and hepatic metabolism. Phase 2 trials have identified that an optimal dose range, 0.6-1.2 mg/kg, as a 1-time dose preoperatively or postoperatively is effective in preventing thrombotic complications with minimal bleeding risk compared with standard of care for elective total knee arthroplasty patients. Future clinical development will be able to clearly outline the role this agent will play in the future.

Role of Bempedoic Acid in Dyslipidemia Management.

Statins remain the preferred agent to reduce low-density lipoprotein cholesterol (LDL-C) and lower atherosclerotic cardiovascular disease (ASCVD) risk. Additional nonstatin agents are recommended to further lower LDL-C among patients at high-risk of ASCVD or those with heterozygous familial hypercholesterolemia, despite statin therapy. Patients unable to tolerate recommended doses of statin therapy due to adverse effects, including statin-associated muscle symptoms, may also require additional nonstatin agents to lower LDL-C and ASCVD risk. Bempedoic acid is a first-in-class, once-daily oral agent, recently approved as monotherapy and in combination with ezetimibe, as an adjunct to maximally tolerated statin therapy in patients with ASCVD or heterozygous familial hypercholesterolemia who require additional LDL-C lowering. Its novel mechanism is reported to avoid adverse muscle symptoms associated with statins. The effectiveness and safety of bempedoic acid and bempedoic acid/ezetimibe combination have been reported in multiple phase 2 and 3 trials. In this review, we report the lipid-lowering effects associated with bempedoic acid, and the safety profile from multiple clinical trials. Based on available data, bempedoic acid significantly lowers LDL-C and other atherogenic lipoprotein measures, and high-sensitivity C-reactive protein when added to background lipid-lowering therapy in patients with and without statin intolerance. Overall safety of bempedoic acid seems to be comparable to placebo, except for increased serum uric acid and tendon rupture. Ongoing clinical trials assessing the long-term safety and cardiovascular outcomes will provide additional insight into the role of bempedoic acid as an adjunct lipid-lowering medication.

Reduced dose thrombolysis with ultrasound-facilitated catheter-directed administration for acute pulmonary embolism reduces length of stay.

The optimal dose and duration of tissue plasminogen activator (tPA) administered with ultrasound-facilitated catheter-directed thrombolysis (USCDT) to patients with acute PE remains to be determined. Our institution recently adopted a shorter duration (4 h) of USCDT and lower dosing strategy (tPA 1 mg/h) based on data from the OPTALYSE PE Trial. The purpose was to evaluate the implementation at our institution of shorter duration (4 h) of USCDT and lower dosing strategy (tPA 1 mg/h) as outlined by OPTALYSE PE Trial. This was a retrospective, single-center, observational study included patients from 01/01/2017 to 12/31/2018 in a large, academic medical center. Group 1 represented patients who underwent USCDT prior to 01/18/18. Group 2 represented patients who underwent USCDT after 01/18/18 and received 4 h of USCDT and tPA 1 mg/h/catheter. The primary outcome was intensive care unit (ICU) length of stay (LOS). Secondary outcomes were the proportion of patients experiencing a composite of major adverse events (death, recurrent PE, major bleeding, or stroke), change in right ventricle size/function and pulmonary artery pressures, need for mechanical respiratory or hemodynamic support, hospital LOS and drug cost. A total of 31 patients were included in the study: twenty patients in Group 1 and eleven patients in Group 2. Median ICU LOS was 3.5 days in Group 1 and 1 day in Group 2. Group 2 had reduced MACE, requirement for mechanical respiratory or hemodynamic support, hospital LOS, drug costs and adverse events. Implementation of a shorter duration of USCDT and lower dosing strategy for tPA in patients with acute PE may be one strategy to reduce the total ICU LOS and costs associated with care.

Still sour about lactic acidosis years later: role of metformin in heart failure.

Metformin remains a widely-used, first-line pharmacotherapy agent for patients with type 2 diabetes mellitus because of its efficacy, mild side effects, and affordability.However, use of this medication has traditionally been shunned by clinicians in patient populations that are considered at risk of lactic acidosis, such as those with heart failure. The underutilization of metformin can largely be attributed to the historical stigma of its biguanide predecessor, phenformin, and its association with lactic acidosis. Despite various studies finding low rates of lactic acidosis and the United States Federal Drug Administration's subsequent removal of heart failure from metformin's contraindication labeling in 2006, this oral hypoglycemic remains underutilized in this patient population. In addition to reports of the safe use of metformin in the heart failure population, a multitude of studies have also additionally suggested a modest reduction in mortality and morbidity. Metformin's role should be strongly reconsidered in the armamentarium of diabetes management in heart failure patients.

Leveraging the Cardiovascular Team in Peripheral Artery Disease Diagnosis: A Call to Action.

Lower extremity peripheral artery disease (PAD) is a common atherosclerotic cardiovascular disease (ASCVD) involving the aortoiliac, femoropopliteal, and infrapopliteal arterial segments. PAD remains a largely underdiagnosed and undertreated condition. The ankle-brachial index (ABI) is a simple and widely available test that is key detection tool in the diagnosis of PAD and is prognostic for mortality and morbidity. The cardiovascular (CV) team is a diverse array of health care clinicians (eg, nurses, nurse practitioners, physician assistants/associates, pharmacists, podiatrists) who have the qualifications and skills to be able to recognize when patients are at risk for PAD and perform an ABI. It is critical that the healthcare community recognize the critical role the CV team could play in improving outcomes and reducing disparities for patients with PAD.

Management of Iron Deficiency in Heart Failure: Practical Considerations and Implementation of Evidence-Based Iron Supplementation.

Iron deficiency (ID) is present in approximately 50% of patients with heart failure (HF) and even higher prevalence rate up to 80% in post-acute HF setting. The current guidelines for HF recommend intravenous (IV) iron replacement in HF with reduced or mildly reduced ejection fraction and ID based on clinical trials showing improvements in quality of life and exercise capacity, and an overall treatment benefit for recurrent HF hospitalization. However, several barriers cause challenges in implementing IV iron supplementation in practice due, in part, to clinician knowledge gaps and limited resource availability to protocolize routine utilization in appropriate patients. Thus, the current review will discuss practical considerations in ID treatment, implementation of evidence-based ID treatment to improve regional health disparities with toolkits, inclusion/exclusion criteria of IV iron supplementation, and clinical controversies in ID treatment, as well as gaps in evidence and questions to be answered.

Use of Glycoprotein IIb/IIIa Inhibitors in the Modern Era of Acute Coronary Syndrome Management: A Survey of Cardiovascular Clinical Pharmacists.

Evidence for the use of glycoprotein IIb/IIIa inhibitors (GPIs) in the management of acute coronary syndrome (ACS) is from the era of either limited utilization of P2Y12 inhibitors or prior the introduction of more potent P2Y12 inhibitors. This leads to divergent opinions regarding the role of these agents in contemporary practice. This study sought the opinion of cardiovascular clinical pharmacists regarding the role of GPIs in the modern of ACS management. A 13-question survey was created and distributed from June 2018 to July 2018 via the American College of Clinical Pharmacy's Cardiology Practice and Research Network e-mail listserv. The survey consisted of questions regarding the ideal use of GPIs in ACS management, preferred agent selection, and rational for selection. All results were analyzed with descriptive statistics. There were a total 69 responses of 1175 (response rate 5.9%). The majority felt there was still a role for GPI in accordance to the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for ST-segment elevation myocardial infarction (65.2%), with eptifibatide being preferred (55.1%). For non-ST-segment myocardial infraction (NSTEMI), only 49.3% felt role of GPI was in line with the ACC/AHA guidelines, but a notable number of respondents felt GPIs were only indicated in NSTEMI patients for bailout or thrombotic complications (18.8%). A majority (56.5%) felt GPIs could be used as an alternative for cangrelor when bridging. The decision to use one agent over another were efficacy data, cost, and pharmacokinetic profile.

Optimizing anticoagulation for patients receiving Impella support.

Anticoagulation of patients treated with the Impella percutaneous mechanical circulatory support (MCS) devices is complex and lacks consistency across centers, potentially increasing the risk of complications. In order to optimize safety and efficacy, an expert committee synthesized all available evidence evaluating anticoagulation for patients receiving Impella support in order to provide consensus recommendations for the management of anticoagulation with these devices. The evidence synthesis led to the creation of 42 recommendations to improve anticoagulation management related to the use of the Impella devices. Recommendations address purge solution management, intravenous anticoagulation, monitoring, evaluation and management of heparin-induced thrombocytopenia (HIT), and management during combination MCS support. The use of a heparinized, dextrose-containing purge solution is critical for optimal device function, and a bicarbonate-based purge solution may be an alternative in certain situations. Likewise, intravenous (ie, systemic) anticoagulation with heparin is often necessary, although evidence supporting the optimal assay and target range for monitoring the level of anticoagulation is generally lacking. Patients treated with an Impella MCS device may develop HIT, which is more difficult to evaluate and treat in this setting. Lastly, the use of Impella with extracorporeal membrane oxygenation or for biventricular support creates additional anticoagulation challenges.

Use of Alternative Antiplatelet Agents for Clopidogrel Hypersensitivity.

Clopidogrel is a widely used agent for secondary prevention of vascular events and is a cornerstone of dual antiplatelet therapy in patients with acute coronary syndrome (ACS) post coronary stent implantation. Hypersensitivity reactions to clopidogrel are well documented and may range from localized to systemic in presentation. This can lead to discontinuation of therapy, thus increasing the risk of vascular events. The authors have developed recommendations for potential alternative agents for the management of clopidogrel hypersensitivity reactions. Proposed strategies include treatment with an alternative P2Y12 inhibitor, cilostazol or warfarin.