Evaluation of the Hemocompatibility of the Direct Oral Anticoagulant Apixaban in Left Ventricular Assist Devices: The DOAC LVAD Study.

BACKGROUND: Patients receiving left ventricular assist device (LVAD) support require long-term anticoagulation to reduce the risk of thromboembolic complications. Apixaban is a direct oral anticoagulant that has become first-line therapy; however, its safety in LVAD recipients has not been well described. OBJECTIVES: This study sought to investigate whether, in patients with a fully magnetically levitated LVAD, treatment with apixaban would be feasible and comparable with respect to safety and freedom from the primary composite outcome of death or major hemocompatibility-related adverse events (HRAEs) (stroke, device thrombosis, major bleeding, aortic root thrombus, and arterial non-central nervous system thromboembolism) as compared with treatment with warfarin. METHODS: The DOAC LVAD (Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices) trial was a phase 2, open label trial of LVAD recipients randomized 1:1 to either apixaban 5 mg twice daily or warfarin therapy. All patients were required to take low-dose aspirin. Patients were followed up for 24 weeks to evaluate the primary composite outcome. RESULTS: A total of 30 patients were randomized: 14 patients to warfarin and 16 patients to apixaban. The median patient age was 60 years (Q1-Q3: 52-71 years), and 47% were Black patients. The median time from LVAD implantation to randomization was 115 days (Q1-Q3: 56-859 days). At 24 weeks, the primary composite outcome occurred in no patients receiving apixaban and in 2 patients (14%) receiving warfarin (P = 0.12); these 2 patients experienced major bleeding from gastrointestinal sources. CONCLUSIONS: Anticoagulation with apixaban was feasible in patients with an LVAD without an excess of HRAEs or deaths. This study informs future pivotal clinical trials evaluating the safety and efficacy of apixaban in LVAD recipients. (Evaluation of the Hemocompatibility of the Direct Oral Anti-Coagulant Apixaban in Left Ventricular Assist Devices [DOAC LVAD]; NCT04865978).

Design and Rationale for the Direct Oral Anticoagulant Apixaban in Left Ventricular Assist Devices (DOAC LVAD) Study.

Implantable left ventricular assist device (LVAD) therapy is used to improve quality of life, alleviate symptoms and extend survival rates in patients with advanced heart failure. Patients with LVADs require chronic anticoagulation to reduce the risk of thromboembolic complications, and they commonly experience bleeding events. Apixaban is a direct oral anticoagulant that has become first-line therapy for patients with nonvalvular atrial fibrillation and venous thromboembolism; however, its safety in patients with LVADs has not been well characterized. The evaluation of the hemocompatibility in the DOAC LVAD (Direct Oral Anti-Coagulant apixaban in Left Ventricular Assist Devices) trial is a phase 2, open-label trial of patients with LVADs who were randomized to either apixaban or warfarin therapy. Patients randomized to apixaban will be started on a dosage of 5 mg twice daily, whereas those randomized to warfarin will be managed at an International Normalized Ratio goal of 2.0-2.5. All patients will be treated with aspirin at 81 mg daily. We plan to randomize and follow as many as 40 patients for 24 weeks to evaluate the primary outcomes of freedom from death or hemocompatibility-related adverse events (stroke, device thrombosis, bleeding, aortic root thrombus, and arterial non-CNS thromboembolism). The DOAC LVAD trial will establish the feasibility of apixaban anticoagulant therapy in patients with LVADs. Clinicaltrials.gov: NCT04865978.

Training Pathways in Critical Care Cardiology: Competencies and Considerations for Cardiologists.

PURPOSE OF REVIEW: Critical care cardiology (CCC) is a rapidly developing field undergoing a renaissance of interest and growth to meet the well-documented population shift in the cardiac intensive care unit (CICU). With this has come the emergence of novel training paradigms that seek to combine specialties with meaningful overlap. RECENT FINDINGS: The benefit of having critical care expertise in the CICU has been clearly established; however, there is no formal or uniform CCC training pathway. Contemporary approaches seek to provide appropriate clinical and procedural experience while minimizing opportunity cost. The combination of additional cardiology subspecialties, specifically advanced heart failure or interventional cardiology, has been demonstrated. Educational tracks that integrate critical care training have generated interest but have not yet manifested. CCC training strives to meet the needs of an increasingly sick and diverse patient population while preparing trainees for fulfilling and meaningful careers. The hope is for ongoing development of novel training pathways to satisfy evolving needs.

Mechanical Circulatory Support and Critical Care Management of High-Risk Acute Pulmonary Embolism.

Hemodynamically significant pulmonary embolism (PE) remains a widely prevalent, underdiagnosed condition associated with mortality rates as high as 30%. The main driver of poor outcomes is acute right ventricular failure that remains clinically challenging to diagnose and requires critical care management. Treatment of high-risk (or massive) acute PE has traditionally included systemic anticoagulation and thrombolysis. Mechanical circulatory support, including both percutaneous and surgical approaches, are emerging as treatment options for refractory shock due to acute right ventricular failure in the setting of high-risk acute pulmonary embolism.

Considerations for Inotrope and Vasopressor Use in Critically Ill Patients With Pulmonary Arterial Hypertension.

ABSTRACT: Pulmonary arterial hypertension (PAH) is a rare and progressive cardiopulmonary disease, characterized by pulmonary vasculopathy. The disease can lead to increase pulmonary arterial pressures and eventual right ventricle failure due to elevated afterload. The prevalence of PAH in patients admitted to the intensive care unit (ICU) is unknown, and pulmonary hypertension (PH) in the ICU is more commonly the result of left heart disease or hypoxic lung injury (PH due to left heart disease and PH due to lung diseases and/or hypoxia, respectively), as opposed to PAH. Management of patients with PAH in the ICU is complex as it requires a careful balance to maintain perfusion while optimizing right-sided heart function. A comprehensive understanding of the underlying physiology and underlying hemodynamics is crucial for the management of this population. In this review, we summarized the evidence for use of vasopressors and inotropes in the management of PH and extrapolated the data to patients with PAH. We strongly believe that the understanding of the hemodynamic consequences of inotropes and vasopressors, especially from data in the PH population, can lead to better management of this complex patient population.

Atypical Antipsychotic Safety in the CICU.

Atypical antipsychotics are used in cardiac intensive care units (CICU) to treat delirium despite limited data on safety in patients with acute cardiovascular conditions. Patients treated with these agents may be at higher risk for adverse events such as QTc prolongation and arrhythmias. We performed a retrospective cohort study of 144 adult patients who were not receiving antipsychotics before admission and received olanzapine (n = 50) or quetiapine (n = 94) in the Michigan Medicine CICU. Data on baseline characteristics, antipsychotic dose and duration, length of stay, and adverse events were collected. Adverse events included ventricular tachycardia (sustained ventricular tachycardia attributed to the medication), hypotension (systolic blood pressure <90 mm Hg attributed to the medication), and QTc prolongation (QTc increase by ≥60 ms or to an interval ≥500 ms). Twenty-six patients (18%) experienced an adverse event. Of those adverse events, 20 patients (14%) experienced QTc prolongation, 3 patients (2%) had ventricular tachycardia, and 3 patients (2%) had hypotension. Patients who received quetiapine had a higher rate of adverse events (25% vs 6%, p = 0.01) including QTc prolongation (18% vs 6%, p = 0.046). Intensive care unit length of stay was shorter in patients who received olanzapine (6.5 vs 9.5 days, p = 0.047). Eighteen patients (13%) had their antipsychotic continued at discharge from the hospital. In conclusion, QTc prolongation was more common in patients treated with quetiapine versus olanzapine although the number of events was relatively low with both agents in a CICU cohort.

Characteristics of Heart Failure Patients With or Without Hypotension When Transitioning From Nitroprusside to Sacubitril-Valsartan.

BACKGROUND: Sacubitril-valsartan is an angiotensin receptor-neprilysin inhibitor indicated for the treatment of patients with symptomatic heart failure with reduced ejection fraction (HFrEF). Little is known about outcomes of HFrEF patients transitioned from sodium nitroprusside (SNP) to sacubitril-valsartan during an admission for acute decompensated heart failure. We sought to describe characteristics of patients initiated on sacubitril-valsartan while receiving SNP and, in particular, those patients who did and did not experience hypotension requiring interruption or discontinuation of sacubitril-valsartan. METHODS: We performed a retrospective case series of adult patients (>18 years) with HFrEF (left ventricular ejection fraction ≤40%) admitted to the University of Michigan cardiac intensive care unit between July 2018 to September 2020 who received sacubitril-valsartan while on SNP. RESULTS: A total of 15 patients with acute decompensated heart failure were initiated on sacubitril-valsartan while on SNP. The mean age was 57 ± 15.9 years. Seven (46.7%) patients experienced hypotension. The patients in the cohort who experienced hypotension were numerically older (60 ± 17 vs. 55 ± 15.5), and the majority were white (86%). Patients with hypotension had a numerically lower left ventricular ejection fraction (13 ± 4.2 vs. 18 ± 8.2) and higher serum creatinine (1.4 ± 0.54 vs. 0.88 ± 0.25). Seven (100%) patients received a diuretic on the day of sacubitril-valsartan initiation in those who experienced hypotension compared with 2 (25%) in those who did not experience hypotension. CONCLUSIONS: In almost half of patients admitted to the cardiac intensive care unit with acutely decompensated HFrEF, significant hypotension was seen when initiating sacubitril-valsartan while on SNP. Future studies should evaluate appropriate patients for this transition and delineate appropriate titration parameters.

Safety of dexmedetomidine in the cardiac intensive care unit.

AIMS: Dexmedetomidine is one of the sedative agents recommended by the Society of Critical Care Medicine as a preferred option over benzodiazepines in critically ill, mechanically ventilated patients. Little data exists describing sedation in the cardiac intensive care unit (CICU). The purpose of this study was to determine the prevalence of adverse events in CICU patients treated with dexmedetomidine. METHODS AND RESULTS: This was a retrospective cohort analysis of patients >18 years old admitted to the University of Michigan CICU from June 2014 to October 2019 who received dexmedetomidine therapy. The primary outcome was the composite of adverse events including bradycardia, hypotension, increasing vasopressor/inotrope requirements, and asystole. Secondary outcomes included individual components of the primary outcome. Patients that experienced adverse events were compared to those that did not experience adverse events to identify risk factors for adverse events. A total of 197 patients were included. There were 116 adverse events in 106 patients. Hypotension was the most common adverse event, making up 60.3% of adverse events reported. Increased vasopressor requirement and bradycardia both occurred in 22 patients (18.9%). Asystole occurred in two patients. B-type natriuretic peptide (BNP) levels were significantly higher in those experiencing an adverse event (848 pg/mL vs. 431 pg/mL; P = 0.03). CONCLUSIONS: Patients admitted to the CICU experienced a high rate of adverse events with dexmedetomidine use. Those experiencing adverse events were more likely to have a higher BNP. Future studies should explore the safety of alternative sedative agents to ascertain safe pharmacological options for patients admitted to the CICU.

Coronavirus Disease-2019 in Heart Transplant Recipients in Southeastern Michigan: A Case Series.

BACKGROUND: Since coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China, in December 2019, the number of cases has risen exponentially. Clinical characteristics and outcomes among patients with orthotopic heart transplant (OHT) with COVID-19 remain poorly described. METHODS: We performed a retrospective case series of patients with OHT with COVID-19 admitted to 1 of 2 hospitals in Southeastern Michigan between March 21 and April 22, 2020. Clinical data were obtained through review of the electronic medical record. Final date of follow-up was May 7, 2020. Demographic, clinical, laboratory, radiologic, treatment, and mortality data were collected and analyzed. RESULTS: We identified 13 patients with OHT admitted with COVID-19. The mean age of patients was 61 ± 12 years, 100% were black males, and symptoms began 6 ± 4 days before admission. The most common symptoms included subjective fever (92%), shortness of breath (85%), and cough (77%). Six patients (46%) required admission to the intensive care unit. Two patients (15%) died during hospitalization. CONCLUSIONS: Black men may be at increased risk for COVID-19 among patients with OHT. Presenting signs and symptoms in this cohort are similar to those in the general population. Elevated inflammatory markers on presentation appear to be associated with more severe illness.

Lifestyle Therapy for the Management of Atrial Fibrillation.

Atrial fibrillation (AF) is a common arrhythmia associated with increased risk of morbidity and mortality. There is evidence that lifestyle interventions may serve as complementary treatments to reduce AF burden. The objective of this review was to summarize the efficacy of lifestyle interventions for the management of AF. Studies which included patients with systolic heart failure (ejection fraction ≤40%), and those limited to an examination of vigorous physical activity were excluded from our search. Studies were identified through a search of the following databases: MEDLINE, EMBASE, CINAHIL, and PubMed, run from inception through August 2016. All studies were graded for quality using the Oxford Centre for Evidence-based Medicine recommendations. Meta-analyses of the studies were not performed due to the heterogeneity of the studies. From a total of 1,811 publications, 10 articles were identified and included. Selected publications included 1 study on yoga, 2 studies on acupuncture, 3 studies that examined weight loss programs, and 4 studies that evaluated the impact of moderate physical activity. Yoga was associated with less symptomatic AF episodes and improved quality of life. Acupuncture was associated with reduced AF occurrence in patients with persistent and paroxysmal AF. Weight loss was associated with a significant reduction AF burden and symptoms. Moderate exercise resulted in greater arrhythmia free survival and a mean reduction in AF burden. In conclusion, evidence exists to suggest that yoga, weight loss, and moderate exercise are associated with reductions in AF burden and symptoms. Evidence is greatest for weight loss and moderate exercise.

Association Between Medicare Hospital Readmission Penalties and 30-Day Combined Excess Readmission and Mortality.

Importance: US hospitals receive financial penalties for excess risk-standardized 30-day readmissions and mortality in Medicare patients. Under current policy, readmission prevention is incentivized over 10-fold more than mortality reduction. Objective: To determine how penalties for US hospitals would change if policy equally weighted 30-day readmissions and mortality. Design, Setting, and Participants: Publicly available hospital-level data for fiscal year 2014 was obtained, including excess readmission ratio (ERR; risk-standardized predicted over expected 30-day readmissions) and 30-day mortality rates for heart failure, pneumonia, and acute myocardial infarction, as well as readmission penalties (as percent of Medicare Diagnosis Group payments). An excess mortality ratio (EMR) was calculated by dividing the risk-standardized predicted mortality by the national average mortality. Case-weighted aggregate ERR (ERRAGG) and EMR (EMRAGG) were calculated, and an excess combined outcome ratio (ECORAGG) was created by averaging ERRAGG and EMRAGG. We examined associations between readmission penalties, ERRAGG, EMRAGG, and ECORAGG. Analysis of variance was used to compare readmission penalties in hospitals with concordant (both ratios >1 or <1) and discordant performance by ERRAGG and ECORAGG. Main Outcomes and Measures: The primary outcome investigated was the association between readmission penalties and the calculated excess combined outcome ratio (ECORAGG). Results: In 1963 US hospitals with complete data, readmission penalties closely tracked excess readmissions (r = 0.81; P < .001), but were minimally and inversely related with excess mortality (r = -0.12; P < .001) and only modestly correlated with excess combined readmission and mortality (r = 0.36; P < .001). Using hospitals with concordant ERRAGG and ECORAGG as the reference group, 17% of hospitals had an ECORAGG ratio less than 1 (ie, superior combined mortality/readmission outcome) with an ERRAGG ratio greater than 1, and received higher mean (SD) readmission penalties (0.41% [0.28%] vs 0.29% [0.37%]; P < .001); 16% of US hospitals had an ECORAGG ratio of greater than 1 (ie, inferior combined mortality/readmission outcome) with an ERRAGG ratio less than 1, and received minimal mean (SD) readmission penalties (0.08% [0.12%]; P < .001 for comparison with reference). Conclusions and Relevance: In fiscal year 2014, financial penalties for one-third of US hospitals would have been substantially altered if 30-day readmission and mortality were considered equally important. Under most circumstances, patients would rather avoid death than rehospitalization. Current Medicare financial penalties do not meet the goals of aligning incentives and fairly reimbursing hospitals for patient-centered outcomes.