Escalating and De-escalating Temporary Mechanical Circulatory Support in Cardiogenic Shock: A Scientific Statement From the American Heart Association.

The use of temporary mechanical circulatory support in cardiogenic shock has increased dramatically despite a lack of randomized controlled trials or evidence guiding clinical decision-making. Recommendations from professional societies on temporary mechanical circulatory support escalation and de-escalation are limited. This scientific statement provides pragmatic suggestions on temporary mechanical circulatory support device selection, escalation, and weaning strategies in patients with common cardiogenic shock causes such as acute decompensated heart failure and acute myocardial infarction. The goal of this scientific statement is to serve as a resource for clinicians making temporary mechanical circulatory support management decisions and to propose standardized approaches for their use until more robust randomized clinical data are available.

Building an Extracorporeal Cardiopulmonary Resuscitation Program at a High-volume Extracorporeal Membrane Oxygenation Center.

Extracorporeal Cardiopulmonary Resuscitation (ECPR) is an emerging approach to cardiac arrest. We present two contrasting cases from a high-volume extracorporeal membrane oxygenation (ECMO) center (defined as greater than 30 ECMO cases per year) without a 24/7 ECPR program to highlight how to establish an ECPR program with a focus on patient selection and outcome optimization. In one case, a patient presented with cardiac arrest during initial triage for chest pain within the emergency department, and in the other case, a patient experienced an out-of-hospital cardiac arrest with prolonged no-flow and low-flow time. Despite the lack of a 24/7 ECPR program at the presenting center, both patients received an ECPR evaluation, as both patients presented while all services necessary for ECMO cannulation were available. The in-hospital cardiac arrest patient was successfully cannulated for ECMO during cardiopulmonary resuscitation and survived with few complications. The out-of-hospital cardiac arrest patient was deemed a poor candidate for ECPR and expired soon after presentation. These two cases highlight the complex decision-making in ECPR and further illustrate how to create ECPR protocols at a high-volume ECMO center before resources are available for a 24/7 ECPR program.

Prevention of Complications in the Cardiac Intensive Care Unit: A Scientific Statement From the American Heart Association.

Contemporary cardiac intensive care units (CICUs) have an increasing prevalence of noncardiovascular comorbidities and multisystem organ dysfunction. However, little guidance exists to support the development of best-practice principles specific to the CICU. This scientific statement evaluates strategies to avoid the potentially preventable complications encountered within contemporary CICUs, focusing on those that are most applicable to the CICU environment. This scientific statement reviews evidence-based practices derived in non-CICU populations, assesses their relevance to CICU practice, and highlights key knowledge gaps warranting further investigation to attenuate patient risk.

Outcomes of catheter-directed versus systemic thrombolysis for the treatment of pulmonary embolism: A real-world analysis of national administrative claims.

Catheter-directed thrombolysis (CDT) and systemic thrombolysis (ST) are used to treat intermediate/high-risk pulmonary embolism (PE) in the absence of comparative safety and effectiveness data. We utilized a large administrative database to perform a comparative safety and effectiveness analysis of catheter-directed versus systemic thrombolysis. From the Optum® Clinformatics® Data Mart private-payer insurance claims database, we identified 100,744 patients hospitalized with PE between 2004 and 2014. We extracted demographic characteristics, high-risk PE features, components of the Elixhauser Comorbidity Index, and outcomes including intracranial hemorrhage (ICH), all-cause bleeding, and mortality among all patients receiving CDT and ST. We used propensity score methods to compare outcomes between matched cohorts adjusted for observed confounders. A total of 1915 patients (1.9%) received either CDT (n = 632) or ST (n = 1283). Patients in the CDT group had fewer high-risk features including less shock (5.4 vs 11.1%; p < 0.001) and cardiac arrest (6.8 vs 11.0%; p = 0.004). In 1:1 propensity-matched groups, ICH rates were 1.9% in both the CDT and ST groups (p = 1.0). All-cause bleeding was higher in the CDT group (15.9 vs 8.7%; p < 0.001), while in-hospital mortality was lower (6.5 vs 10.0%; p = 0.02). Among a nationally representative cohort of patients with PE at higher risk for mortality, CDT was associated with similar ICH rates, increased all-cause bleeding, and lower short and intermediate-term mortality when compared with ST. The competing risks and benefits of CDT in real-world practice suggest the need for large-scale randomized clinical trials with appropriate comparator arms.

Systemic, noncerebral, arterial embolism in 21,105 patients with atrial fibrillation randomized to edoxaban or warfarin: results from the Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction Study 48 trial.

BACKGROUND: Atrial fibrillation (AF) is a major risk factor for stroke and systemic embolism. Trials comparing warfarin with non-vitamin K oral anticoagulants (NOACs) have demonstrated that, when compared with warfarin, the NOACs are at least as effective in preventing stroke, although detailed analyses characterizing systemic embolic events (SEEs) are lacking. METHODS AND RESULTS: We performed a prespecified analysis in 21,105 patients with AF enrolled in the ENGAGE AF-TIMI 48 trial, which compared 2 once-daily regimens of edoxaban with warfarin for the prevention of stroke and SEE. Of 1,016 patients who met the primary end point, 67 (6.6%) experienced an SEE of which 13% were fatal. Of 73 total SEEs (including recurrent events), 85% involved the extremities, and 41% required a surgical or percutaneous intervention. There were 23 (0.12%/year) SEEs with warfarin versus 15 with higher dose edoxaban (0.08%/year; hazard ratio vs warfarin 0.65; 95% CI 0.34-1.24; P = .19) and 29 with lower dose edoxaban (0.15%/year; hazard ratio vs warfarin 1.24; 95% CI 0.72-2.15; P = .43). In a meta-analysis of 4 warfarin-controlled phase 3 AF trials, NOACs significantly reduced the risk of SEE by 37% (relative risk 0.63; 95% CI 0.43-0.91; P = .01). CONCLUSION: Although considerably less frequent than stroke, systemic embolism is associated with significant morbidity and mortality in patients with AF. Although the overall number of events was too small to show a significant difference in the risk of SEE between edoxaban and warfarin, a meta-analysis of all the NOAC trials demonstrates that NOACs significantly reduce the risk of SEE compared with warfarin.

Autoantibodies to phosphorylcholine and cardiovascular outcomes in patients with acute coronary syndromes in the ATLAS ACS-TIMI 46 trial.

Atherogenesis is a complex inflammatory process stemming from the accumulation and oxidation of low density lipoproteins (LDL). IgM autoantibodies against phosphorylcholine (anti-PC) bind to the PC epitope on oxidized LDL (OxLDL), inhibiting the uptake of oxLDL by macrophages in atherosclerotic lesions. Anti-PC autoantibodies have been reported to be protective against atherothrombosis. We investigated the relationship of anti-PC concentrations with cardiovascular outcomes in patients with acute coronary syndromes (ACS). We measured anti-PC levels within 7 days of an ACS in 3,356 patients enrolled in the ATLAS ACS-TIMI 46 trial, a randomized dose ranging study of rivaroxaban versus placebo. The primary endpoint was death, myocardial infarction (MI), stroke, or severe recurrent ischemia (SRI) requiring revascularization during 6 months. The median baseline anti-PC concentration was 40.9 U/mL (25th, 75th percentiles: 25.4, 67.4). There was no significant association between anti-PC levels and the primary endpoint (Q1: 6.8 %, Q2: 4.2 %, Q3: 7.8 %, Q4: 5.4 %, p-trend = 0.87), all-cause mortality (Q1: 1.4 %, Q2: 0.7 %, Q3: 2.4 %, Q4: 0.9 %, p-trend = 0. 96), or any of the other individual endpoint components (MI: p-trend = 0.87, Stroke: p-trend = 0.43, SRI: p-trend = 0.66). Using the previously reported anti-PC cutpoint of 17 U/mL did not reveal a significant relationship between anti-PC concentrations and cardiovascular outcomes (<17 U/mL: 8.1 % vs. ≥17 U/mL: 5.8 %; p = 0.11). Similarly, evaluation of anti-PC as a continuous variable did not reveal a significant association (p = 0.30). In this study of patients early after ACS undergoing intensive secondary preventive therapy, IgM anti-PC titers did not exhibit a significant relationship with cardiovascular outcomes.

Arterial hyperoxia and mortality in the cardiac intensive care unit.

BACKGROUND: Arterial hyperoxia (hyperoxemia), defined as a high arterial partial pressure of oxygen (PaO2), has been associated with adverse outcomes in critically ill populations, but has not been examined in the cardiac intensive care unit (CICU). We evaluated the association between exposure to hyperoxia on admission with in-hospital mortality in a mixed CICU cohort. METHODS: We included unique Mayo Clinic CICU patients admitted from 2007 to 2018 with admission PaO2 data (defined as the PaO2 value closest to CICU admission) and no hypoxia (PaO2 < 60mmHg). The admission PaO2 was evaluated as a continuous variable and categorized (60-100 mmHg, 101-150 mmHg, 151-200 mmHg, 201-300 mmHg, >300 mmHg). Logistic regression was used to evaluate predictors of in-hospital mortality before and after multivariable adjustment. RESULTS: We included 3,368 patients with a median age of 70.3 years; 70.3% received positive-pressure ventilation. The median PaO2 was 99 mmHg, with a distribution as follows: 60-100 mmHg, 51.9%; 101-150 mmHg, 28.6%; 151-200 mmHg, 10.6%; 201-300 mmHg, 6.4%; >300 mmHg, 2.5%. A J-shaped association between admission PaO2 and in-hospital mortality was observed, with a nadir around 100 mmHg. A higher PaO2 was associated with increased in-hospital mortality (adjusted OR 1.17 per 100 mmHg higher, 95% CI 1.01-1.34, p = 0.03). Patients with PaO2 >300 mmHg had higher in-hospital mortality versus PaO2 60-100 mmHg (adjusted OR 2.37, 95% CI 1.41-3.94, p < 0.001). CONCLUSIONS: Hyperoxia at the time of CICU admission is associated with higher in-hospital mortality, primarily in those with severely elevated PaO2 >300 mmHg.

Training Paradigms in Critical Care Cardiology: A Scoping Review of Current Literature.

Background: Over the past decade there has been increasing interest in critical care medicine (CCM) training for cardiovascular medicine (CV) physicians either in isolation (separate programs in either order [CV/CCM], integrated critical care cardiology [CCC] training) or hybrid training with interventional cardiology (IC)/heart failure/transplant (HF) with targeted CCC training. Objective: To review the contemporary landscape of CV/CCM, CCC, and hybrid training. Methods: We reviewed the literature from 2000-2022 for publications discussing training in any combination of internal medicine CV/CCM, CCC, and hybrid training. Information regarding training paradigms, scope of practice and training, duration, sequence, and milestones was collected. Results: Of the 2,236 unique citations, 20 articles were included. A majority were opinion/editorial articles whereas two were surveys. The training pathways were classified into - (i) specialty training in both CV (3 years) and CCM (1-2 years) leading to dual American Board of Internal Medicine (ABIM) board certification, or (ii) base specialty training in CV with competencies in IC, HF or CCC leading to a non-ABIM certificate. Total fellowship duration varied between 4-7 years after a three-year internal medicine residency. While multiple articles commented on the ability to integrate the fellowship training pathways into a holistic and seamless training curriculum, few have highlighted how this may be achieved to meet competencies and standards. Conclusions: In 20 articles describing CV/CCM, CCC, and hybrid training, there remains significant heterogeneity on the standardized training paradigms to meet training competencies and board certifications, highlighting an unmet need to define CCC competencies.

Sedation and shivering management after cardiac arrest.

Management of sedation and shivering during targeted temperature management (TTM) after cardiac arrest is limited by a dearth of high-quality evidence to guide clinicians. Data from general intensive care unit (ICU) populations can likely be extrapolated to post-cardiac arrest patients, but clinicians should be mindful of key differences that exist between these populations. Most importantly, the goals of sedation after cardiac arrest are distinct from other ICU patients and may also involve suppression of shivering during TTM. Drug metabolism and clearance are altered considerably during TTM when a low goal temperature is used, which can delay accurate neuroprognostication. When neuromuscular blockade is used to prevent shivering, sedation should be deep enough to prevent awareness and providers should be aware that this can mask clinical manifestations of seizures. However, excessively deep or prolonged sedation is associated with complications including delirium, infections, increased duration of ventilatory support, prolonged ICU length of stay, and delays in neuroprognostication. In this manuscript, we review sedation and shivering management best practices in the post-cardiac arrest patient population.

COVID-19 and Disruptive Modifications to Cardiac Critical Care Delivery: JACC Review Topic of the Week.

The COVID-19 pandemic has presented a major unanticipated stress on the workforce, organizational structure, systems of care, and critical resource supplies. To ensure provider safety, to maximize efficiency, and to optimize patient outcomes, health systems need to be agile. Critical care cardiologists may be uniquely positioned to treat the numerous respiratory and cardiovascular complications of the SARS-CoV-2 and support clinicians without critical care training who may be suddenly asked to care for critically ill patients. This review draws upon the experiences of colleagues from heavily impacted regions of the United States and Europe, as well as lessons learned from military mass casualty medicine. This review offers pragmatic suggestions on how to implement scalable models for critical care delivery, cultivate educational tools for team training, and embrace technologies (e.g., telemedicine) to enable effective collaboration despite social distancing imperatives.

Evolving Strategies in Cardiac Arrest Management.

Cardiac arrest is a leading cause of death in the United States, with a hospital discharge rate of approximately 10%. International resuscitation guidelines offer standardized cardiac arrest management approaches, but beyond the guidelines, are promising innovations to improve resuscitative care. Although clinical data do not yet support the routine use of mechanical chest compressions, corticosteroids, thrombolytics, and adjunctive ventilation devices during arrest, these therapies may have an important role in select patients. Extracorporeal membrane oxygenation during cardiopulmonary resuscitation is a promising advancement and may have survival benefit in select patients. The evidence for standard therapies and these innovations is discussed.

Oxacalixarenes and oxacyclophanes containing 1,8-naphthyridines: a new class of molecular tweezers with concave-surface functionality.

The first examples of oxacalix[4]arenes and [1(4)]oxacyclophanes bearing 1,8-naphthyridine units are reported, and these systems function as molecular tweezers containing inner-cavity hydrogen bond acceptors.

Synthesis of oxacalixarenes incorporating nitrogen heterocycles: evidence for thermodynamic control.

[structure: see text] Oxacalix[2]arene[2]hetarenes are formed in a single step by cyclooligomerization of meta-diphenols with meta-dichlorinated azaheterocycles. The high selectivity for cyclic tetramer formation results from thermodynamic product control. Macrocycles as large as oxacalix[5]arene[5]hetarenes have been isolated under nonequilibrating conditions.