Medical Therapy for Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a challenging disease state that has long been plagued by heterogeneity in diagnostic criteria and underlying etiologies. Due in part to the complexity of defining this disease and the simplistic approach of only studying medications that have shown significant improvement in heart failure with reduced ejection fraction, there have been a multitude of negative trials in this population. In the past few years, however, there have been medications that have finally shown to benefit patients with HFpEF. In particular, the blockbuster class of medications called SGLT2 inhibitors have provided a treatment option that improves outcomes in this group of patients. There is increasing focus on HFpEF research that aims to improve the phenotyping of these patients to more successfully tailor therapy and improve patient outcomes.

Defining Vasoplegia Following Durable, Continuous Flow Left Ventricular Assist Device Implantation.

This study aimed to develop a definition of vasoplegia that reliably predicts clinical outcomes. Vasoplegia was evaluated using data from the electronic health record for each 15-minute interval for 72 hours following cardiopulmonary bypass. Standardized definitions considered clinical features (systemic vascular resistance [SVR], mean arterial pressure [MAP], cardiac index [CI], norepinephrine equivalents [NEE]), threshold strategy (criteria occurring in any versus all measurements in an interval), and duration (criteria occurring over multiple consecutive versus separated intervals). Minor vasoplegia was MAP < 60 mm Hg or SVR < 800 dynes⋅sec⋅cm-5 with CI > 2.2 L/min/m2 and NEE ≥ 0.1 µg/kg/min. Major vasoplegia was MAP < 60 mm Hg or SVR < 700 dynes⋅sec⋅cm-5 with CI > 2.5 L/min/m2 and NEE ≥ 0.2 µg/kg/min. The primary outcome was incidence of vasoplegia for eight definitions developed utilizing combinations of these criteria. Secondary outcomes were associations between vasoplegia definitions and three clinical outcomes: time to extubation, time to intensive care unit discharge, and nonfavorable discharge. Minor vasoplegia detected anytime within a 15-minute period (MINOR_ANY_15) predicted the highest incidence of vasoplegia (61%) and was associated with two of three clinical outcomes: 1 day delay to first extubation (95% CI: 0.2 to 2) and 7 day delay to first intensive care unit discharge (95% CI: 1 to 13). The MINOR_ANY_15 definition should be externally validated as an optimal definition of vasoplegia.

Direct Oral to Parenteral Anticoagulants: Strategies for Inpatient Transition.

The primary objective of this study was to describe the impact on bleeding rates of 2 different strategies for transitioning from a direct oral anticoagulant (DOAC) to a parenteral anticoagulant: a delayed, clinically driven strategy versus the standard per-package-insert strategy. This was a single-center descriptive cohort study conducted at a large academic medical center. Included patients were 18 years or older, admitted as an inpatient, and had received at least 1 dose of a DOAC prior to initiation of therapeutic parenteral anticoagulation. The primary end point was the incidence of major bleeds on the transition from a DOAC to a parenteral anticoagulant via a standard versus an intentionally delayed strategy. The secondary outcomes evaluated renal function, reason for delay, DOAC anti-factor Xa concentration, international normalized ratio values, blood product administration, and thrombotic complications. A total of 300 patients were included. The primary end point of bleeding was higher in the delayed group than the standard group, 25% and 12%, respectively (odds ratio, 0.39; P < .05). In both groups, patients who bled had a higher severity of illness, a greater incidence of acute kidney injury, and, when available, higher median DOAC anti-factor Xa concentrations. Despite a more conservative approach, patients in the delayed group experienced more bleeding, most likely attributable to a higher severity of illness, which highlights emerging challenges of inpatient anticoagulation management. Further prospective studies analyzing DOAC pharmacodynamics and pharmacokinetics in acutely ill patients are warranted.

Outcomes Associated With 4-Factor Prothrombin Complex Concentrate Administration to Reverse Oral Factor Xa Inhibitors in Bleeding Patients.

Compared with vitamin K antagonists (VKAs), oral factor Xa inhibitors are associated with at least equivalent efficacy and a lower incidence of major bleeding. Despite this benefit, bleeding remains the most common adverse event. Prior to the approval of andexanet alfa, alternative agents such as 4-factor prothrombin complex concentrate (4F-PCC) were utilized for reversal. This was a retrospective, descriptive study conducted on patients 18 years of age or older who received 4F-PCC for reversal of oral factor Xa inhibitors-associated bleeding. Patients were excluded if they received a VKA or dabigatran in the previous 48 hours. A subgroup analysis comparing 4F-PCC with andexanet alfa was conducted on patients who met the inclusion and exclusion criteria of the ANNEXA-4 trial. The primary end point of this study was to evaluate the incidence of hemostasis and associated dosing strategies in patients receiving 4F-PCC for reversal of oral factor Xa inhibitors-associated bleeding. Thirty-eight patients were included, and 28 patients (74%) achieved hemostasis. The median dose of 4F-PCC was 50 units/kg. In patients who achieved hemostasis, the median dose was 50 units/kg, and in those who failed to reach hemostasis, a median dose of 30 units/kg was seen. Within the subgroup analysis, there was no difference in overall rates of hemostasis between the 4F-PCC and andexanet alfa groups. Remaining a reasonable option to utilize for reversal of oral factor Xa inhibitors is 4F-PCC, especially when andexanet alfa is unavailable, with 50 units/kg appearing to be the most effective dose to achieve hemostasis. Further studies are needed to determine a preferential agent.

COVID-19 pandemic: Challenges and solutions from the cardiology pharmacist's perspective.

The recent coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenges pharmacists worldwide. Alongside other specialized pharmacists, we re-evaluated daily processes and therapies used to treat COVID-19 patients within our institutions from a cardiovascular perspective and share what we have learned. To develop a collaborative approach for cardiology issues and concerns in the care of confirmed or suspected COVID-19 patients by drawing on the experiences of cardiology pharmacists across the country. On March 26, 2020, a conference call was convened composed of 24 cardiology residency-trained pharmacists (23 actively practicing in cardiology and 1 in critical care) from 16 institutions across the United States to discuss cardiology issues each have encountered with COVID-19 patients. Discussion centered around providing optimal pharmaceutical care while limiting staff exposure. The collaborative of pharmacists found for the ST-elevation myocardial infarction patient, many institutions were diverting COVID-19 rule-out patients to their Emergency Department (ED). Thrombolytics are an alternative to percutaneous coronary intervention (PCI) allowing for timely treatment of patients and decreased staff exposure. An emergency response grab and go kit includes initial drugs and airway equipment so the patient can be treated and the cart can be left outside the room. Cardiology pharmacists have developed policies and procedures to address monitoring of QT prolonging medications, the use of inhaled prostacyclins, and national drug shortages. Technology has allowed us to practice social distancing, while staying in close contact with our teams, patients, and colleagues and continuing to teach. Residents are engaged in unique decision-making processes with their preceptors and assist as pharmacist extenders. Cardiology pharmacists are in a unique position to work with other pharmacists and health care professionals to implement safe and effective practice changes during the COVID-19 pandemic. Ongoing monitoring and adjustments are necessary in rapidly changing times.

Role of thromboelastography in predicting and defining pump thrombosis in left ventricular assist device patients.

INTRODUCTION: Optimal anticoagulation for left ventricular assist device recipients aims to balance thrombosis and bleeding complications. Routine plasma-based coagulation tests may not accurately reflect overall hemostasis, and surrogate markers are used to help guide clinicians in the diagnosis of pump thrombosis. Thromboelastography derived coagulation index (CI) has been shown to be a parameter that can reflect "normocoagulability" in mechanical circulatory support device patients, but there is minimal data with regard to outcomes available. Our aim was to determine the role of CI in predicting and defining suspected pump thrombosis in HeartMate II™ recipients. MATERIALS AND METHODS: We performed a single center, retrospective longitudinal cohort study with a nested case-control analysis to compare serial CI values over time in adult HeartMate II™ recipients who had confirmed or suspected pump thrombosis to those who did not. RESULTS AND CONCLUSIONS: A multivariate linear mixed model analysis of the suspected pump thrombosis versus no pump thrombosis groups found a significantly lower mean change in CI over time when recipients were followed for 24 months post-implant [0.71 (95% CI 0.1-1.32, p = .02)]; CI was first significant at six months. Within each arm, CI significantly decreased in the no pump thrombosis group, but did not significantly differ within the suspected pump thrombosis group. No significant differences were found between the two groups regarding the outcomes of death, transplant, or neurological events.

Management of Cardiogenic Shock in a Cardiac Intensive Care Unit.

Cardiogenic shock (CS) is a complex condition characterized by end-organ hypoperfusion and requiring pharmacologic and/or mechanical circulatory support. It is caused by a decline in cardiac output due to a primary cardiac disorder. CS is frequently complicated by multiorgan system dysfunction that requires a multidisciplinary approach in a critical care setting. Appropriate use of diagnostic data using tools available in a modern cardiac intensive care unit should guide optimal management incorporating both pharmacologic and nonpharmacologic therapies to minimize morbidity and mortality.

Evaluation of postoperative clinical outcomes in Jehovah's Witness patients who receive prothrombin complex concentrate during cardiac surgery.

BACKGROUND: Patients who refuse allogeneic blood transfusions (alloBT) on the basis of religious doctrine, such as Jehovah's Witnesses (JWs), can pose a challenge when undergoing surgical procedures. During cardiac surgery, special considerations regarding surgical techniques and blood loss minimization strategies can lead to improved outcomes. Limited literature exists to guide the use of four-factor prothrombin complex concentrate (4PCC) in this patient population undergoing cardiac surgery. STUDY DESIGN AND METHODS: This retrospective, single-center study evaluated the impact of 4PCC on hemoglobin (Hgb) change from baseline to postoperative nadir within a 7-day period among patients who refused alloBT during cardiac surgery. This study identified patients who refused alloBT from January 2011 to June 2017. Multivariable linear regression was used to control for confounding variables to evaluate the effectiveness of 4PCC. RESULTS: During the study timeframe, 79 patients met inclusion criteria, all of whom identified as JWs, and underwent cardiac surgery. Of these, 19 received intraoperative 4PCC. Multivariable linear regression found no difference in Hgb change in patients who received 4PCC vs those who did not. No significant differences were found in mortality, thromboembolic complications, or in-hospital postoperative events. CONCLUSIONS: In JWs undergoing cardiac surgery who refuse alloBT, intraoperative use of 4PCC was not associated with a difference in Hgb change within 7 days postoperatively when adjusting for confounding variables. In the event of excessive blood loss, the utilization of 4PCC may provide a viable option in JW patients who undergo cardiac surgery where few options exist to mitigate blood loss.

Use of Tissue Plasminogen Activator Alteplase for Suspected Impella Thrombosis.

BACKGROUND: Impella devices are being increasingly used to manage cardiogenic shock. The incidence of thrombosis and hemolysis in patients on Impella support increases with longer durations of use, and the management of Impella thrombosis remains ill-defined. METHODS: In this case series, we describe our institutional use of tissue plasminogen activator (tPA) alteplase in the Impella purge solution (0.04 or 0.08 mg/ml tPA in sterile water) for management of suspected Impella thrombosis in five patients, each with a different clinical course, treatment, and outcome. Given the limited evidence on the diagnosis of Impella thrombosis, suspicion was driven by the presence of decreased purge flow rates, increased purge pressures, and markers of hemolysis such as elevated lactate dehydrogenase and hematuria. OUTCOMES: In all cases, tPA administration resulted in resolution of low purge flow rates and high purge pressures. No major bleeding complications were directly associated with tPA. Two patients were bridged successfully to heart transplantation, two patients underwent left ventricular assist device implantation, and one patient died after withdrawal of care. CONCLUSION: Based on our experience, tPA administration appears to be a viable and safe salvage option to delay or prevent device exchange in the setting of suspected Impella thrombosis.

Gastrointestinal Bleeding in Left Ventricular Assist Device: Octreotide and Other Treatment Modalities.

Left ventricular assist devices (LVADs) offer a therapeutic strategy for patients with end-stage heart failure. Increased device utilization has also increased the incidence of device-related complications including gastrointestinal bleeding (GIB). Multiple mechanisms have been proposed in the pathophysiology of continuous-flow LVAD-associated GIB including physiologic changes associated with high shear and nonpulsatile flow such as gastrointestinal arteriovenous malformations and acquired von Willebrand syndrome. Strategies to minimize the morbidity and mortality of LVAD-associated GIB are needed. Octreotide, a somatostatin analogue, has been described as an adjunct to current therapies and interventions. Factors that contribute to LVAD-associated GIB may be targeted by the pharmacologic effects of octreotide, including improved platelet aggregation, increased vascular resistance, and decreased splanchnic circulation. Octreotide has demonstrated clinical benefit in several case series and clinical trials for the treatment of LVAD-associated GIB. The focus of this article will be to review the pathophysiology of LVAD-associated GIB, discuss pharmacologic and nonpharmacologic treatment modalities, and review available literature on the role of octreotide in the management of LVAD-associated GIB.

Effect of diltiazem on exercise capacity after heart transplantation.

BACKGROUND: Sinus tachycardia (ST) is common after heart transplantation (HTx). The aim of the study was to evaluate the effect of diltiazem treatment during the first year after HTx on heart rate (HR), cardiac allograft function, and exercise capacity. METHODS: From the total cohort, 25 HTx recipients started diltiazem treatment 4±2 weeks after HTx and continued it for at least 1 year (diltiazem group). Each study case was matched to a control. All patients underwent hemodynamic assessment and cardiopulmonary exercise test (CPET) at 1 year after HTx. RESULTS: HR decreased in the diltiazem group from 99±11 bpm to 94±7 bpm (P=.03) and did not change in the controls (98±11 bpm vs 100±13 bpm, P=.14). The difference between the groups at 1 year after HTx was significant (P=.04). In the diltiazem group left ventricular (LV), stroke volume and ejection fraction increased (48±16 vs 55±17 mL, P=.02, and 60%±10% vs 62%±12% P=.03, respectively) but did not differ from controls. E/E' decreased (10.7±2.7 vs 7.3±1.9, P=.003) while cardiac index was higher (3.5±0.8 vs 3.1±0.5; P=.05) in the diltiazem group at 1-year follow-up. The absolute peak VO2 (21±4 vs 18±6 mL/kg/min; P=.05) and normalized peak VO2 (73%±17% vs 58%±14%; P=.004) were significantly higher in the diltiazem group. CONCLUSIONS: This study showed that diltiazem treatment reduces ST, may improve cardiac allograft function and exercise tolerance during the first year after HTx.

Sinus tachycardia is associated with impaired exercise tolerance following heart transplantation.

BACKGROUND: Sinus tachycardia often presents in heart transplantation (HTx) recipients, but data on its effect on exercise performance are limited. METHODS: Based on mean heart rate (HR) value 3 months after HTx, 181 patients transplanted from 2006 to 2015 at University of Nebraska Medical Center were divided into two groups: (i) HR<95 beats/min (bpm, n=93); and (ii) HR≥95 bpm (n=88). Cardiopulmonary exercise testing (CPET) was performed 1 year after HTx. RESULTS: Mean HR at 3 months post-HTx was 94±11 bpm and did not change significantly at 1 year post-HTx (96±11 bpm, P=.13). HR≥95 bpm at 3 months was associated with younger donor age (OR 1.1; CI 1.0-1.1, P=.02), female donors (OR -2.4; CI 1.16-5.24 P=.02), and lack of donors' heavy alcohol use (OR -0.43; CI 0.17-0.61; P=.04). HR≥95 bpm at 3 months post-HTx was independently associated with decreased exercise capacity in metabolic equivalent (P=.008), reduced peak VO2 (P=.006), and percent of predicted peak VO2 (P=.002) during CPET. CONCLUSIONS: HR≥95 at 3 months following HTx is associated with reduced exercise tolerance in stable HTx recipients. Medical HR reduction after HTx could improve exercise performance after HTx and merits further investigation.

Antiplatelet Agents in Cardiology: A Report on Aspirin, Clopidogrel, Prasugrel, and Ticagrelor.

Antiplatelet drugs are the cornerstone of therapy in many cardiovascular conditions. With the current success and increased use of transcatheter aortic valve implantation (TAVI), the use of antiplatelet therapy is considered part of the medical therapy for these patients. Clinicians caring for these patients need to have a thorough understanding of the pharmacology, pharmacokinetics, pharmacodynamic, and clinical efficacy and safety of commonly used antiplatelet therapy. While aspirin therapy is widely used, dual antiplatelet therapy with clopidogrel has become part of standard of care. Despite the extensive experience with clopidogrel, there are limitations such as drug interactions, metabolism genetic polymorphisms, and variability in the antiplatelet response. More predictable and more potent antiplatelet agents, prasugrel and ticagrelor, have demonstrated superior reductions in ischemic endpoints as part of dual antiplatelet therapy compared to clopidogrel, but at the cost of more major bleeding in patients with an acute coronary syndrome. Significant research needs to be conducted in the setting of TAVI to help define the optimal antiplatelet regimen.

Assessment of adverse events and predictors of neurological recovery after therapeutic hypothermia.

BACKGROUND: Therapeutic hypothermia improves neurological recovery after witnessed cardiac arrest from ventricular fibrillation or tachycardia. Its application is expanding despite associated adverse events. OBJECTIVE: To assess the occurrence of adverse events and predictors of good versus poor neurological recovery after therapeutic hypothermia. METHODS: A single-center, retrospective review of medical records of 91 patients who received therapeutic hypothermia for ≥6 hours. Adverse events included laboratory abnormalities, shivering, acute kidney injury, or infection. Cerebral performance categories (CPC) scores delineated good (CPC of 1-3) or poor (CPC of 4 or 5) neurological outcomes. Groups were compared and parameters evaluated for effect on neurological recovery using backward logistic regression analysis. RESULTS: Therapeutic hypothermia was used for several indications, and 42 patients (46.2%) had good neurological recovery. Demographic parameters were similar between groups. Common adverse events were hypoglycemia (98.9%), shivering (84.6%), bradycardia (58.2%), electrolyte abnormalities (26.4%-91.2%), acute kidney injury (52.8%), infection (48.4%), and coagulopathy (40.7%). Characteristics independently associated with neurological recovery included faster return of spontaneous circulation (ROSC), quicker initiation of cooling, and the occurrence of infections. Pulseless electrical activity, faster achievement of goal cooling temperature, seizure, and the administration of insulin or epinephrine were inversely related to neurological recovery. CONCLUSIONS: Adverse events of therapeutic hypothermia were numerous and frequent, necessitating monitoring. Neurological recovery is primarily driven by the type of arrest, the rapidity of ROSC, the time needed to provide and achieve therapeutic hypothermia, the development of seizures or infection, and the use of insulin or epinephrine.