Faculty Bibliography

Intravenous (IV) digoxin loading dose recommendations for rate control of atrial arrhythmias in critically ill patients are not well studied. When using digoxin in the setting of atrial fibrillation/atrial flutter (AF/AFL), a loading dose (LD) in either a fixed-dose regimen, weight-based dose, or pharmacokinetic-based calculation to target a serum digoxin concentration (SDC) of 0.8-1.5 ng/mL is recommended. The objective of this study was to assess the safety and effectiveness of digoxin LD used in critically ill patients for rate control of AF/AFL and to assess the SDC achieved. This single center retrospective cohort study included patients who received IV digoxin and had a SDC drawn. The primary endpoint was the median SDC achieved after a digoxin LD. Secondary outcomes included the frequency of SDCs ≥1.5 ng/mL and heart rate (HR) control. A total of 92 patients were included. The median total LD of digoxin for the entire cohort was 11mcg/kg (750 mcg). For 61% of the cohort, the LD was distributed over six-hour intervals. The median SDC after completion of the IV digoxin LD was 1.3 ng/mL (0.9, 1.7). The incidence of supratherapeutic SDC was 36% for the total cohort. A target HR < 110 beats per minute within 24 hours from digoxin LD was achieved in 60% of the cohort. In conclusion, a median total digoxin LD of 750 mcg in critically ill patients with AF/AFL, targeting a SDC < 1.5ng/mL may be considered for acute rate control, taking into account drug-drug interactions in the cardiac intensive care unit. Future studies are necessary to confirm our findings.

The clinical effect of drug-drug interactions (DDIs) between antiplatelets and antiretrovirals (ART) on bleeding, thrombosis, and other major adverse cardiovascular events (MACE) is unknown. The objective of this retrospective study was to assess the incidence of DDI at P2Y12 inhibitor (P2Y12inh) initiation and the effect of DDI on patient outcomes. Adult people living with human immunodeficiency virus (PLWH; HIV) receiving ART newly initiated on an oral P2Y12inh were included. The primary outcome was the incidence of DDI between ART and P2Y12inh at P2Y12inh initiation. Secondary outcomes included bleeding events, MACE, and switches in P2Y12inh. There were 149 PLWH included, of these, 119 (80%) were initiated on clopidogrel, 23 (15%) on ticagrelor, and 7 (5%) on prasugrel. 93 PLWH (60%) had a DDI at time of P2Y12inh initiation, with highest incidence in the clopidogrel group (n=84, 71%), followed by ticagrelor (n=9, 39%) and none with prasugrel. Within 1 year, MACE occurred in 12 PLWH, with DDI present at the time of 4 events. There were 29 bleeding events occurring within 1 year, including 17 events with DDI at time of event. However, 88% of DDI in patients with bleeding events were expected to decrease the efficacy of P2Y12inh. Though we observed high incidence of DDI between P2Y12inh and ART in PLWH, MACE and bleeding events at 1 year did not correlate with DDI. It remains unknown if DDI presence at P2Y12inh initiation with ART causes clinical outcomes of concern, or if underlying platelet reactivity in PLWH is associated with these events.

OBJECTIVE:To evaluate the impact of inflammation on anticoagulation monitoring for patients supported with extracorporeal membrane oxygenation (ECMO). DESIGN/METHODS:Prospective single-center cohort study. SETTING/METHODS:University-affiliated tertiary care academic medical center. PARTICIPANTS/METHODS:Adult venovenous and venoarterial ECMO patients anticoagulated with heparin/ MEASUREMENTS AND MAIN RESULTS: C-Reactive protein (CRP) was used as a surrogate for overall inflammation. The relationship between CRP and the partial thromboplastin time (PTT, seconds) was evaluated using a CRP-insensitive PTT assay (PTT-CRP) in addition to measurement using a routine PTT assay. Data from 30 patients anticoagulated with heparin over 371 ECMO days was included. CRP levels (mg/dL) were significantly elevated (median, 17.2; interquartile range [IQR], 9.2-26.1) and 93% of patients had a CRP of ≥5. The median PTT (median 58.9; IQR, 46.9-73.3) was prolonged by 11.3 seconds compared with simultaneously measured PTT-CRP (median, 47.6; IQR, 40.1-55.5; p < 0.001). The difference between PTT and PTT-CRP generally increased with CRP elevation from 2.7 for a CRP of <5.0 to 13.0 for a CRP between 5 and 10, 17.7 for a CRP between 10 and 15, and 15.1 for a CRP of >15 (p < 0.001). In a subgroup of patients, heparin was transitioned to argatroban, and a similar effect was observed (median PTT, 62.1 seconds [IQR, 53.0-78.5 seconds] vs median PTT-CRP, 47.6 seconds [IQR, 41.3-57.7 seconds]; p < 0.001). CONCLUSIONS:Elevations in CRP are common during ECMO and can falsely prolong PTT measured by commonly used assays. The discrepancy due to CRP-interference is important clinically given narrow PTT targets and may contribute to hematological complications.

Patients, often with underlying rheumatologic disease, may present with pericardial effusions in the setting of pulmonary hypertension (PHTN). Pericardial drainage in PHTN is associated with significant morbidity and mortality. We describe a patient with PHTN who developed cardiac tamponade that was managed safely and effectively with pulmonary artery catheter-guided pericardiocentesis.

Given the high morbidity and mortality associated with cardiopulmonary arrest, there have been multiple trials aimed at better monitoring and augmenting coronary, cerebral, and systemic perfusion. This article aims to elucidate these interventions, first by detailing the physiology of cardiopulmonary resuscitation and the available tools for managing cardiopulmonary arrest, followed by an in-depth examination of the newest advances in the monitoring and delivery of advanced cardiac life support.

Cerebral collateral circulation is a dynamic and adaptive process by which alternative vascular pathways supply perfusion to ischemic brain tissue in the event of an arterial occlusion. This complicated network of blood vessels that acts as a natural bypass plays a pivotal role in stroke pathophysiology and has become a key area of study given its significance in stroke treatment and patient outcomes. In this review, we will study the factors influencing the formation, recruitment, and endurance of collateral vessels; discuss imaging modalities for quantitative and qualitative assessment of this network; explore the role of collaterals in stroke management; and highlight several cardiovascular strategies to minimize damage to collaterals and optimize stroke outcomes.

KEY CLINICAL MESSAGE/UNASSIGNED:A robust inflammatory and febrile response from acute viral illness such as with SARS-CoV-2 in patients with Brugada syndrome may lead to triggering of ventricular arrhythmias. The use of targeted temperature management (TTM) using cooling devices may mitigate the febrile triggering of ventricular arrhythmias in patients with Brugada syndrome. ABSTRACT/UNASSIGNED:Brugada syndrome (BrS) is an autosomonal dominant genetic disorder, with a risk of ventricular tachycardia (VT). Triggers of VT in BrS include fevers. Here, we report a case of BrS secondary to SARSs-CoV-2 infection and the use of targeted temperature management (TTM) to decrease fever and prevent VT triggering.

INTRODUCTION: Thrombotic and hemorrhagic complications are a significant contributor to morbidity and mortality in patients supported with extracorporeal membrane oxygenation (ECMO). The impact of inflammation on anticoagulation monitoring in ECMO is unknown.
METHOD(S): We conducted a prospective, single-center, observational cohort study of patients supported on ECMO treated with heparin for systemic anticoagulation. C-Reactive protein (CRP) levels were measured as a surrogate for overall inflammation. The relationship between CRP and the partial thromboplastin time (PTT) was evaluated using a CRPinsensitive PTT assay (PTT-CRP) alongside standard PTT measurements.
RESULT(S): We analyzed data from 30 patients anticoagulated with heparin over 371 ECMO days. CRP levels were significantly elevated (median 17.2 mg/dL, interquartile range, 9.2 - 26.1) and 93% of patients had a CRP > 5mg/dL (10-fold upper limit of normal) during their ECMO course. The median PTT (58.9 seconds (46.9 - 73.3)) was prolonged by 11.3 seconds compared to the simultaneously measured PTT-CRP (47.6 seconds (40.1 - 55.5), p< 0.001). The median difference between PTT and PTT-CRP generally increased with CRP elevation from 2.7 seconds for CRP < 5.0 mg/dL to 13.0 seconds for CRP between 5 to 10 mg/dL, 17.7 seconds for CRP between 10 to 15 mg/dL, and 15.1 seconds for CRP > 15 mg/dL (p < 0.001). A subgroup of patients was transitioned from heparin to argatroban; in these patients a similar difference was observed (PTT: 62.1 (53.0 - 78.5) vs. PTT-CRP: 47.6 (41.3 - 57.7), p< 0.001).
CONCLUSION(S): Elevation in CRP is common in patients on ECMO and can falsely prolong PTT as measured by commonly used assays. The degree of discrepancy introduced due to CRP-interference is clinically important given narrow therapeutic PTT targets in this high-risk patient population and may contribute to the development of hematologic complications

Amiodarone-induced thyrotoxicosis (AIT) carries significant cardiovascular morbidity. There are two types of AIT with treatment including antithyroid medications and corticosteroids and treatment of ventricular arrhythmias. Therapeutic plasma exchange (TPE) also known as "PLEX" may help remove thyroid hormones and amiodarone. We report a case of PLEX in an attempt to treat cardiogenic shock secondary to AIT. This case highlights the robust rapidly deleterious demise of AIT, specifically in patients with decompensated heart failure. The decision to PLEX or not to PLEX for AIT should be individualized, prior to definitive therapy.