Faculty Bibliography

Targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA) has been a focus of debate in an attempt to improve post-arrest outcomes. Contemporary trials examining the role of TTM after cardiac arrest suggest that targeting normothermia should be the standard of care for initially comatose survivors of cardiac arrest. Differences in patient populations have been demonstrated across trials, and important subgroups may be under-represented in clinical trials compared with real-world registries. In this review, we aimed to describe the populations represented in international OHCA registries and to propose a pathway to integrate clinical trial evidence into practice. The patient case mix among registries including survivors to hospital admission was similar to the pivotal trials (shockable rhythm, witnessed arrest), suggesting reasonable external validity. Therefore, for the majority of OHCA, targeted normothermia should be the strategy of choice. There remains conflicting evidence for patients with a nonshockable rhythm, with no clear evidence-based justification for mild hypothermia over targeted normothermia.

The increase of intravenous drug use has led to an increase in right-sided infective endocarditis and its complications including septic pulmonary embolism. The objective of this study was to compare the outcomes of tricuspid valve (TV) operations in patients with drug-use infective endocarditis (DU-IE) complicated by septic pulmonary emboli (PE). Hospitalizations for DU-IE complicated by septic PE were identified from the National Inpatient Sample from 2002 to 2019. Outcomes of patients who underwent TV operations were compared with medical management. The primary outcome was the incidence of major adverse cardiovascular events (MACEs), defined as in-hospital mortality, myocardial infarction, stroke, cardiogenic shock, or cardiac arrest. An inverse probability of treatment weighted analysis was utilized to adjust for the differences between the cohorts. A total of 9,029 cases of DU-IE with septic PE were identified (mean age 33.6 years), of which 818 patients (9.1%) underwent TV operation. Surgery was associated with a higher rate of MACE (14.5% vs 10.8%, p <0.01), driven by a higher rate of cardiogenic shock (6.1% vs 1.2%, p <0.01) but a lower rate of mortality (2.7% vs 5.7%, p <0.01). Moreover, TV operation was associated with an increased need for permanent pacemakers, blood transfusions, and a higher risk of acute kidney injury. In the inverse probability treatment weighting analysis, TV operation was associated with an increased risk for MACE driven by a higher rate of cardiogenic shock and cardiac arrest, but a lower rate of mortality when compared with medical therapy alone. In conclusion, TV operations in patients with DU-IE complicated by septic PE are associated with an increased risk for MACE but a decreased risk of mortality. Although surgical management may be beneficial in some patients, alternative options such as percutaneous debulking should be considered given the higher risk.

BACKGROUND:Cardiac arrest (CA) is a common reason for admission to the cardiac intensive care unit (CICU), though the relative burden of morbidity, mortality, and resource use between admissions with in-hospital (IH) and out-of-hospital (OH) CA is unknown. We compared characteristics, care patterns, and outcomes of admissions to contemporary CICUs after IHCA or OHCA. METHODS:The Critical Care Cardiology Trials Network is a multicenter network of tertiary CICUs in the US and Canada. Participating centers contributed data from consecutive admissions during 2-month annual snapshots from 2017 to 2021. We analyzed characteristics and outcomes of admissions by IHCA vs OHCA. RESULTS:We analyzed 2,075 admissions across 29 centers (50.3% IHCA, 49.7% OHCA). Admissions with IHCA were older (median 66 vs 62 years), more commonly had coronary disease (38.3% vs 29.7%), atrial fibrillation (26.7% vs 15.6%), and heart failure (36.3% vs 22.1%), and were less commonly comatose on CICU arrival (34.2% vs 71.7%), p<0.001 for all. IHCA admissions had lower lactate (median 4.3 vs 5.9) but greater utilization of invasive hemodynamics (34.3% vs 23.6%), mechanical circulatory support (28.4% vs 16.8%), and renal replacement therapy (15.5% vs 9.4%); p<0.001 for all. Comatose IHCA patients underwent targeted temperature management less frequently than OHCA patients (63.3% vs 84.9%, p<0.001). IHCA admissions had lower unadjusted CICU (30.8% vs 39.0%, p<0.001) and in-hospital mortality (36.1% vs 44.1%, p<0.001). CONCLUSION:Despite a greater burden of comorbidities, CICU admissions after IHCA have lower lactate, greater invasive therapy utilization, and lower crude mortality than admissions after OHCA.

OBJECTIVE:To compare rates of clopidogrel response among patients receiving medication produced by 2 different manufacturers after acute coronary syndrome (ACS) and/or percutaneous coronary intervention. METHODS:This quality-improvement project included 515 adult patients receiving clopidogrel for ACS or ischemic heart disease and referred for coronary angiography/ percutaneous coronary intervention. The project was divided into 2 phases: (1) retrospective collection of baseline data (April 2019-October 2020); and (2) two 12-week, prospective phases in which all clopidogrel in the hospital was restricted to a single manufacturer at a time (November 2020-May 2021). The primary outcome was clopidogrel response measured by platelet function testing, defined as adenosine diphosphate (ADP) response <40% on light transmission aggregometry. RESULTS:Of 515 total patients included in both phases (mean age, 64.5 ± 11.4 years; 351 men [68.2%]; 450 with ACS [87.4%]), 52% were found to be clopidogrel responders based on results of platelet function testing. Among 135 patients in the prospective phase, there was a significantly lower proportion of patients who were clopidogrel responders in the Manufacturer 1 group compared with the Manufacturer 2 group (34.8% vs 55.1%, respectively; P=.03). After adjustment for age, sex, body mass index, aspirin response, therapeutic hypothermia, left heart catheterization indication, clopidogrel loading dose, time between loading dose and lab measurement, and manufacturer, aspirin response (odds ratio 0.96; 95% confidence interval, 0.95-0.97; P<.001) and manufacturer (odds ratio, 2.45; 95% confidence interval, 1.18-5.22; P=.02) were associated with clopidogrel response. CONCLUSIONS:In a large public hospital, we observed that pharmacodynamic response to clopidogrel varied by drug manufacturer. Further investigation and/or regulation is needed to minimize inter-manufacturer variability.

BACKGROUND:Targeted temperature management (TTM) has been recommended after cardiac arrest (CA), however the specific temperature targets and cooling methods (intravascular cooling (IVC) versus surface cooling (SC)) remain uncertain. METHODS:PUBMED and EMBASE were searched until October 8, 2022 for randomized clinical trials (RCTs) investigating the efficacy of TTM after CA. The randomized treatment arms were categorized into the following 6 groups: 31..C to 33..C IVC, 31..C to 33..C SC, 34..C to 36..C IVC, 34..C to 36..C SC, strict normothermia or fever prevention (Strict NT or FP), and standard of care without TTM (No-TTM). The primary outcome was neurological recovery. P-score was used to rank the treatments, where a larger value indicates better performance. RESULTS:We identified 15 RCTs, involving 5,218 patients with CA. Compared to No-TTM as the reference, the other therapeutic options significantly improved neurological outcomes (vs No-TTM; 31..C to 33.. C IVC/UNASSIGNED:RR = 0.67, 95% CI 0.54 to 0.83; 31..C to 33..C SC RR = 0.73, 95% CI 0.61 to 0.87; 34..C to 36.. C IVC/UNASSIGNED:RR = 0.66, 95% CI 0.51 to 0.86; 34..C to 36..C SC: RR = 0.73, 0.59 to 0.90; Strict NT or FP: RR = 0.75, 95% CI 0.62 to 0.90). Overall, 31-33..C IVC had the highest probability to be the best therapeutic option to improve outcomes (the ranking P-score of 0.836). As a subgroup analysis, the ranking P-score showed that IVC might be a better cooling method compared to SC (IVC vs SC P-score: 0.960 vs 0.670). CONCLUSIONS:Hypothermia (31..C to 36..C IVC and SC) and active normothermia (Strict-NT and Strict-FP) were associated with better neurological outcomes compared to No-TTM, with IVC having a greater probability of being the better cooling method than SC.

AIMS/OBJECTIVE:The aims of the Critical Care Cardiology Trials Network (CCCTN) are to develop a registry to investigate the epidemiology of cardiac critical illness and to establish a multicenter research network to conduct randomized clinical trials (RCTs) in patients with cardiac critical illness. METHODS AND RESULTS/RESULTS:The CCCTN was founded in 2017 with 16 centers and has grown to a research network of over 40 academic and clinical centers in the United States and Canada. Each center enters data for consecutive cardiac intensive care unit (CICU) admissions for at least two months of each calendar year. More than 20 000 unique CICU admissions are now included in the CCCTN Registry. To date, scientific observations from the CCCTN Registry include description of variations in care, the epidemiology and outcomes of all CICU patients, as well as subsets of patients with specific disease states, such as shock, heart failure, renal dysfunction, and respiratory failure. The CCCTN has also characterized utilization patterns, including use of mechanical circulatory support in response to changes in the heart transplantation allocation system, and the use and impact of multidisciplinary shock teams. Over years of multicenter collaboration, the CCCTN has established a robust research network to facilitate multicenter registry-based randomized trials in patients with cardiac critical illness. CONCLUSIONS:The CCCTN is a large, prospective registry dedicated to describing processes-of-care and expanding clinical knowledge in cardiac critical illness. The CCCTN will serve as an investigational platform from which to conduct randomized controlled trials in this important patient population.

Patients with ischemic heart disease (IHD) are often excluded from acute respiratory distress syndrome (ARDS) clinical trials. As a result, little is known about the impact of IHD in this population. We sought to assess the association between IHD and clinical outcomes in patients with ARDS. Participants from 4 ARDS randomized controlled trials with shared study criteria, definitions, and end points were included. Using multivariable logistic regression, we assessed for the association between IHD and a primary outcome of 60-day mortality. Secondary outcomes included 90-day mortality, 28-day ventilator-free days, and 28-day organ failure. Among 1,909 patients, 102 had a history of IHD (5.4%). Patients with IHD were more likely to be older and male (p <0.05). Noncardiac co-morbidities, severity of illness, and other markers of ARDS severity were not statistically different (all, p >0.05). Patients with IHD had a higher 60-day (39.2% vs 23.3%, p <0.001) and 90-day (40.2% vs 24.0%, p <0.001) mortality, and experienced more frequent renal (45.1% vs 32.0%, p = 0.006) and hepatic (35.3% vs 25.2%, p = 0.023) failure. After multivariable adjustment, 60-day (odds ratio [OR] 1.76; 95% confidence interval [CI]: 1.07 to 2.89, p = 0.025) and 90-day (OR 1.74; 95% CI: 1.06 to 2.85, p = 0.028) mortality remained higher. IHD was associated with 10% fewer ventilator-free days (incidence rate ratio 0.90; 95% CI: 0.85 to 0.96, p = 0.001). In conclusion, co-morbid IHD was associated with higher mortality and fewer ventilator-free days in patients with ARDS. Future studies are needed to identify predictors of mortality and improve treatment paradigms in this critically ill subgroup of patients.

Oxygen supplementation has been a mainstay in the management of patients with acute cardiac disease. While hypoxia is known to be detrimental, the adverse effects of artificially high oxygen levels (hyperoxia) have only recently been recognized. Hyperoxia may induce harmful hemodynamic effects, including peripheral and coronary vasoconstriction, and direct cellular toxicity through the production of reactive oxygen species. In addition, emerging evidence has shown that hyperoxia is associated with adverse clinical outcomes. Thus, it is essential for the cardiac intensive care unit (CICU) clinician to understand the available evidence and titrate oxygen therapies to specific goals. This review summarizes the pathophysiology of oxygen within the cardiovascular system and the association between supplemental oxygen and hyperoxia in patients with common CICU diagnoses, including acute myocardial infarction, heart failure, shock, cardiac arrest, pulmonary hypertension, and respiratory failure. Finally, we highlight lessons learned from available trials, gaps in knowledge, and future directions.

BACKGROUND:Acute heart failure (HF) is an important complication of coronavirus disease 2019 (COVID-19) and has been hypothesized to relate to inflammatory activation. METHODS:We evaluated consecutive intensive care unit (ICU) admissions for COVID-19 across 6 centers in the Critical Care Cardiology Trials Network, identifying patients with vs. without acute HF. Acute HF was sub-classified as "de novo" vs. "acute-on-chronic" based on the absence or presence of prior HF. Clinical features, biomarker profiles, and outcomes were compared. RESULTS:Among 901 COVID-19 ICU admissions, 80 (8.9%) had acute HF, including 18 (2.0%) with classic cardiogenic shock (CS) and 37 (4.1%) with vasodilatory CS. The majority (n=45) were de novo HF presentations. Compared to patients without acute HF, those with acute HF had higher cardiac troponin (cTn) and natriuretic peptides, and similar inflammatory biomarkers; patients with de novo HF had the highest cTn. Notably, among critically ill patients with COVID-19, illness severity (median SOFA, 8 [IQR, 5-10] vs. 6 [4-9]; p=0.025) and mortality (43.8% vs. 32.4%; p=0.040) were modestly higher in patients with vs. without acute HF. CONCLUSIONS:Among critically ill COVID-19 patients, acute HF is distinguished more by biomarkers of myocardial injury and hemodynamic stress than by biomarkers of inflammation.