Cardiac surgery in acute heparin-induced thrombocytopenia managed with therapeutic plasma exchange and intravenous immunoglobulin.

Background: Urgent surgery requiring heparin exposure during cardiopulmonary bypass can be challenging in patients with acute heparin-induced thrombocytopenia (HIT). The use of treatments such as therapeutic plasma exchange (TPE) to remove HIT antibodies and intravenous immunoglobulin (IVIg) to antagonize HIT antibody-mediated platelet activation are increasingly reported in patients who undergo cardiac surgery. The optimal treatment approach to mitigate the risks of heparin administration in this situation is not known. Key Clinical Question: Can TPE coupled to IVIg allow for safe heparin exposure in patients with HIT? Clinical Approach: TPE and IVIg were used to enable heparin exposure for surgical placement of a left ventricular assist device in a patient with HIT. Serial patient samples were tested in antigen-based and functional HIT assays. Conclusion: Dissociation between antigen-based (enzyme-linked immunosorbent assay) and functional (serotonin release assay) testing was noted, and TPE coupled to IVIg was associated with an excellent clinical response.

Impact of high MELD scores on CMV viremia following liver transplantation.

INTRODUCTION: Advanced liver disease or cirrhosis is associated with an increased risk of infections; however, the impact of high pretransplant model for end-stage liver disease (MELD) score on cytomegalovirus (CMV) viremia after liver transplantation is unknown. METHODS: This single-center, retrospective, cohort study evaluated CMV high-risk (CMV immunoglobulin G D+/R-) liver transplant recipients who received valganciclovir prophylaxis for 3 months between 2009 and 2019. Patients were stratified by pretransplant MELD score of <35 (low MELD) and ≥35 (high MELD). The primary outcome was 12-month CMV viremia, and secondary outcomes included CMV resistance and tissue invasive disease, mortality, biopsy-proven acute rejection (BPAR), leukopenia, and thrombocytopenia. Multivariable Cox proportional-hazards modeling was used to assess the association of MELD score with the time to CMV viremia. RESULTS: There were 162 and 79 patients in the low and high MELD groups, respectively. Pretransplant MELD score ≥35 was associated with an increased risk of CMV viremia (hazard ratio [HR] 1.73; confidence interval 1.06-2.82, p = .03). CMV viremia occurred at 162 ± 61 days in the low MELD group and 139 ± 62 days in the high MELD group. Although BPAR occurred early at 30 days (13-59) in the low-MELD group and at 18 days (11-66) in the high-MELD group (p = .56), BPAR was not associated with an increased risk of CMV viremia (HR 1.55 [0.93-2.60], p = .1). DISCUSSION: MELD scores ≥35 were associated with an increased hazards of CMV viremia. In liver transplant recipients with MELD scores ≥35 who are CMV high-risk, additional CMV intervention may be warranted.

New-Onset Atrial Arrhythmias Are Independently Associated With In-Hospital Mortality in Veno-Venous Extracorporeal Membrane Oxygenation.

OBJECTIVE: To explore if atrial arrhythmias are associated with in-hospital mortality in veno-venous extracorporeal membrane oxygenation (VV-ECMO) patients. DESIGN: Retrospective observational cohort study. SETTING: Quaternary care academic medical center. PARTICIPANTS: Patients with respiratory failure requiring VV-ECMO for >24 hours between January 1, 2016, and January 1, 2019. INTERVENTIONS: None, observational study. MEASUREMENTS AND MAIN RESULTS: Two hundred nineteen VV-ECMO patients were included. Patients were stratified by absence or presence of clinically significant atrial arrhythmias during the VV-ECMO run. Atrial arrhythmias were defined as either atrial fibrillation or atrial flutter that occurred during VV-ECMO and required pharmacologic or electrical intervention. The primary outcome was in-hospital mortality. Secondary outcomes included a composite of thrombotic events, which included ischemic stroke and on-pump arterial thrombosis. Other objectives of this analysis included characterization of atrial arrhythmia incidence, risk factors, and management. A total of 67 patients (30.5%) experienced new-onset atrial arrhythmias post-ECMO cannulation. Age, male sex, and norepinephrine use were independently associated with atrial arrhythmia development. In-hospital mortality was significantly higher in the atrial arrhythmia group (38.8% v 19.1%; p = 0.003). In the multivariate logistic regression analysis, atrial arrhythmias during VV-ECMO were independently associated with increased odds of in-hospital mortality (odds ratio, 2.21; 95% confidence interval, 1.08-4.55; p = 0.03), after controlling for Respiratory Extracorporeal Membrane Oxygenation Survival Prediction score, acute renal failure, total norepinephrine dose, and total cannulation time. CONCLUSIONS: New-onset atrial arrhythmias are a frequent complication during VV-ECMO and are independently associated with excessive in-hospital mortality. Thus, their presence may serve as an important prognostic tool in this patient population.

Comparison of two individualized antithrombotic protocols in HeartWare HVAD recipients.

We previously reported low rates of pump thrombosis and hemorrhagic stroke, but increased bleeding, under our original antithrombosis protocol (P1) in HeartWare recipients. We designed and implemented a revised protocol (P2) to reduce complexity and bleeding. Thrombelastography and PFA-100 guide antiplatelet titration. Goals for P2 were altered to decrease antiplatelet use and anticoagulation intensity. We compared the incidence and rates of gastrointestinal bleeding (GIB), embolic (eCVA) and hemorrhagic (hCVA) stroke, pump thrombosis (PT), and total bleeding (GIB+hCVA), total thrombosis (eCVA+PT), and total events between P1 and P2. Laboratory and medication data were assessed. Patients with and without hemocompatibility-related adverse events (HRAEs) were compared. The study included 123 patients (P1: 65; P2: 58). GIB rate decreased (P1: 0.66; P2 0.30 EPPY, P = .003). CVA rates and incidence were statistically similar, although hCVA incidence increased (P1: 3%; P2: 12%, P = .06). Incidence (P1: 3%; P2: 16%, P = .02) and rate (P1: 0.03; P2: 0.12 EPPY, P = .08) of PT increased. Incidence and rate of overall HRAEs and thrombotic events were similar, while bleeding rate decreased (P1: 0.69; P2: 0.40 EPPY, P = .02). Twelve-month medication burden decreased. Compared to non-HRAE patients, patients with bleeding HRAEs had more antiplatelet and pentoxifylline use, but less statin use; and lower PFAs. Patients with thrombotic HRAEs had less dual antiplatelet use, lower INRs, R-times, and PFA-ADP values. A revised antithrombotic protocol decreased GIB and overall hemorrhagic HRAE rate and medication burden. Unfortunately, PT increased. Non-HRAE and HRAE patients differed in anticoagulation and antiplatelet intensity. These differences will guide the revision of P2.

Precannulation International Normalized Ratio is Independently Associated With Mortality in Veno-Arterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: To explore whether precannulation international normalized ratio (INR) is associated with in-hospital mortality in venoarterial extracorporeal membrane oxygenation (VA-ECMO) patients. DESIGN: A retrospective, observational cohort study. SETTING: A quaternary care academic medical center. PARTICIPANTS: Patients with cardiogenic shock on VA-ECMO for >24 hours. INTERVENTIONS: None, observational study. MEASUREMENTS AND MAIN RESULTS: A total of 188 patients who were on VA-ECMO were included over three years. Patients were stratified into three groups based on their pre-ECMO INR: INR <1.5, INR 1.5 to 1.8, and INR >1.8. For all patients, demographics, comorbidities, and ECMO details were recorded. The study's primary outcome was in-hospital mortality and secondary outcomes included major bleeding, minor bleeding, allogeneic transfusion, ischemic stroke, intracranial hemorrhage, acute renal failure, acute liver failure, gastrointestinal bleeding, intensive care unit and hospital lengths of stay. A multivariate logistic regression was used to determine whether precannulation INR was associated independently with in-hospital mortality. In-hospital mortality differed significantly by INR group (51.6% INR >1.8 v 42.3% INR 1.5-1.8 v 24.3% INR <1.5; p = 0.004). In a multivariate logistic regression model, precannulation INR >1.8 was associated independently with an increased odds of mortality (odds ratio, 2.48; 95% confidence interval, 1.05-6.04) after controlling for sex, Survival after VA- ECMO score, and ECMO indication. An INR within 1.5 to 1.8 did not confer an increased mortality risk. CONCLUSIONS: An INR >1.8 before VA-ECMO cannulation is associated independently with in-hospital mortality. Precannulation INR should be considered by clinicians so that ECMO resources can be better allocated and risks of organ failure and intracranial hemorrhage can be better understood.

Management of noncardiovascular comorbidities in patients with heart failure with reduced ejection fraction.

Patients with heart failure with reduced ejection fraction often have one or more noncardiovascular comorbidities. The presence of concomitant disease states is associated with worse outcomes, including increased risk of mortality, decreased quality of life, and increased healthcare resource utilization. Additionally, the presence of heart failure with reduced ejection fraction complicates the management of these comorbidities, including varying safety and efficacy of therapies compared to those without heart failure. This article will review the literature on the pharmacologic management of common noncardiovascular comorbidities-including chronic obstructive pulmonary disease, depression, diabetes mellitus, gout, chronic kidney disease, and iron deficiency-in patients with heart failure with reduced ejection fraction, as well as provide recommendations for appropriate treatment selection in this population.

Clinical Outcomes of Perioperative Desensitization in Heart Transplant Recipients.

BACKGROUND: Sensitization remains a barrier to heart transplantation (HT). Perioperative desensitization strategies have been described; however, a paucity of evidence exists to demonstrate efficacy and safety in HT. METHODS: This single-center, retrospective study consisted of adults who received an HT. Perioperative desensitization was initiated if virtual crossmatch or flow-cytometry crossmatch was positive. Therapy consisted of plasmapheresis, intravenous immunoglobulin, and rabbit antithymocyte globulin. Historical controls received standard immunosuppression or induction. The primary endpoint was survival at 12 mo. Secondary endpoints included freedom from acute rejection, cardiac allograft vasculopathy (CAV), and infectious complications. RESULTS: Of the 104 patients included, 48 received no induction, 46 received induction, and 10 underwent perioperative desensitization. No differences were observed in the primary endpoint at 12 mo (90.0% versus 97.9%, P = 0.25 for desensitization versus no-induction; 90.0% versus 100%, P = 0.72 for desensitization versus induction). Rates of acute rejection were lower with induction and desensitization compared with no-induction. There were no significant differences in CAV between the groups. Infectious complications were also similar among the groups (10.0% versus 16.7%, P = 0.62 for desensitization versus no-induction; 10.0% versus 30.4%, P = 0.34 for desensitization versus induction). CONCLUSIONS: This study suggests that a perioperative desensitization strategy triggered by positive virtual crossmatch or flow-cytometry crossmatch allows for successful transplantation of sensitized HT recipients and results in acceptable rates of survival, rejection, CAV, and infection at 12 mo.

Novel Use of Tamoxifen to Reduce Recurrent Gastrointestinal Bleeding in Patients with Left Ventricular Assist Devices.

Gastrointestinal bleeding (GIB) is a frequent complication in patients with continuous-flow left ventricular assist devices (LVAD). We retrospectively evaluated eight patients implanted with a HeartWare LVAD between July 2017 and June 2020 who experienced at least one episode of GIB and were started on tamoxifen 20 mg once daily for secondary prevention. Tamoxifen was associated with a significant decrease in major GIB from a median of 3 (IQR 1.4-7) events/patient-year pre-tamoxifen initiation to 0 (IQR 0-0.9) events/patient-year post-tamoxifen initiation (p = 0.02). Transfusion of packed red blood cells also decreased from 16.8 (IQR 9.9-30.6) units/patient-year pre-tamoxifen initiation to 1.5 (IQR 0-7.5) units/patient-year post-tamoxifen (p = 0.04). Tamoxifen was well tolerated and no thromboembolic complications were observed. This small cohort study suggests that tamoxifen is associated with reduced GIB and transfusion requirements, with no apparent increase in thrombotic risk. A larger, randomized study is warranted to confirm the results of this exploratory analysis. Graphical abstract.

Pharmacologic Management of Gout in Patients with Cardiovascular Disease and Heart Failure.

Gout is the most common inflammatory arthritis and is often comorbid with cardiovascular disease (CVD). Hyperuricemia and gout are also independent risk factors for cardiovascular events, worsening heart failure (HF), and death. The recommended treatment modalities for gout have important implications for patients with CVD because of varying degrees of cardiovascular and HF benefit and risk. Therefore, it is critical to both manage hyperuricemia with urate-lowering therapy (ULT) and treat acute gout flares while minimizing the risk of adverse cardiovascular events. In this review, the evidence for the safety of pharmacologic treatment of acute and chronic gout in patients with CVD and/or HF is reviewed. In patients with CVD or HF who present with an acute gout flare, colchicine is considered safe and potentially reduces the risk of myocardial infarction. If patients cannot tolerate colchicine, short durations of low-dose glucocorticoids are efficacious and may be safe. Nonsteroidal anti-inflammatory drugs should be avoided in patients with CVD or HF. The use of canakinumab and anakinra for acute gout flares is limited by the high cost, risk of serious infection, and relatively modest clinical benefit. For long-term ULT, allopurinol, and alternatively probenecid, should be considered first-line treatments in patients with CVD or HF given their safety and potential for reducing cardiovascular outcomes. An increased risk of cardiovascular death and HF hospitalization limit the use of febuxostat and pegloticase as ULT in this population. Ultimately, the selection of agents used for acute gout management and long-term ULT should be individualized according to patient and agent cardiovascular risk factors.

An aspirin a day? Clinical utility of aspirin therapy for the primary prevention of cardiovascular disease.

Introduction: Cardiovascular disease remains a leading cause of morbidity and mortality. Since the description of its therapeutic potential, aspirin has been a cornerstone of therapy following vascular events. However, aspirin in the primary prevention setting is controversial and major guideline groups provide inconsistent recommendations. Thus, there is variability in practice as providers are faced with a balance of therapeutic benefit and drug-induced harm. Areas covered: This article provides a critical appraisal of both past and present data for aspirin in the primary prevention setting. PubMed and Cochrane Central Register databases were searched from inception to May 1st, 2019. Expert opinion: The decision to initiate or withdraw aspirin for primary prevention requires an understanding of the equilibrium between efficacy and safety. In adults greater than 70 years of age, low to moderate cardiovascular risk, controlled diabetes, or at high risk of bleeding, initiation of aspirin for primary prevention should generally be avoided. Instead, risk factor modification should be prioritized. The net benefit of aspirin in those at high risk for cardiovascular disease and in those with uncontrolled diabetes is largely unknown. Ultimately, initiation or withdrawal of aspirin therapy must involve discussion of the patient's wishes and treatment expectations.

The antibiotic arms race: current and emerging therapy for Klebsiella pneumoniae carbapenemase (KPC) - producing bacteria.

Introduction: The rapid spread of Klebsiella pneumoniae Carbapenemase (KPC)-producing bacteria comprises one of the greatest challenges to global health. Historically, clinicians were limited to therapies with suboptimal efficacy and intolerable toxicity until the FDA approved ceftazidime-avibactam and meropenem-vaborbactam, adding two essential pharmacotherapies to our antibiotic armamentarium. These agents display superior efficacy and safety compared to historical treatment options; however, resistance has already been reported. Several antimicrobials currently in the drug pipeline exhibit early promise and may fill needed gaps in therapy. Areas covered: This article encompasses both the past and present treatment options for the management of KPC-producing bacterial infections via an extensive review and critical appraisal of the current literature. Expert opinion: Traditional treatment options can no longer be recommended as first-line options for the management of KPC-producing bloodstream infections. Ceftazidime-avibactam or meropenem-vaborbactam plus or minus an aminoglycoside or polymyxin should be utilized as backbone therapies given their superior efficacy and safety profiles when compared to traditional treatment options. For susceptible KPC-producing urinary tract infections, it is reasonable to consider treatment with an aminoglycoside or with fosfomycin as a monotherapy. All of these decisions should be based on patient-specific characteristics, severity of infection and source control, susceptibility patterns, and input from infectious diseases experts.