Faculty Bibliography

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.

AIMS/OBJECTIVE:Contemporary cardiac intensive care unit (CICU) outcomes remain highly heterogeneous. As such, a risk-stratification tool using readily available lab data at time of CICU admission may help inform clinical decision-making. METHODS AND RESULTS/RESULTS:The primary derivation cohort included 4352 consecutive CICU admissions across 25 tertiary care CICUs included in the Critical Care Cardiology Trials Network (CCCTN) Registry. Candidate lab indicators were assessed using multivariable logistic regression. An integer risk score incorporating the top independent lab indicators associated with in-hospital mortality was developed. External validation was performed in a separate CICU cohort of 9716 patients from the Mayo Clinic (Rochester, MN, USA). On multivariable analysis, lower pH [odds ratio (OR) 1.96, 95% confidence interval (CI) 1.72-2.24], higher lactate (OR 1.40, 95% CI 1.22-1.62), lower estimated glomerular filtration rate (OR 1.26, 95% CI 1.10-1.45), and lower platelets (OR 1.18, 95% CI 1.05-1.32) were the top four independent lab indicators associated with higher in-hospital mortality. Incorporated into the CCCTN Lab-Based Risk Score, these four lab indicators identified a 20-fold gradient in mortality risk with very good discrimination (C-index 0.82, 95% CI 0.80-0.84) in the derivation cohort. Validation of the risk score in a separate cohort of 3888 patients from the Registry demonstrated good performance (C-index of 0.82; 95% CI 0.80-0.84). Performance remained consistent in the external validation cohort (C-index 0.79, 95% CI 0.77-0.80). Calibration was very good in both validation cohorts (r = 0.99). CONCLUSION/CONCLUSIONS:A simple integer risk score utilizing readily available lab indicators at time of CICU admission may accurately stratify in-hospital mortality risk.

Purpose/UNASSIGNED:Previous studies have shown longer delays from symptom onset to hospital presentation (S2P time) in women than men with acute myocardial infarction. The aim of this study is to understand the reasons for delays in seeking care among women and men presenting with an ST-Segment Elevation Myocardial Infarction (STEMI) through a detailed assessment of the thoughts, perceptions and patterns of behavior. Patients/Methods and Results/UNASSIGNED:A total of 218 patients with STEMI treated with primary angioplasty at four New York City Hospitals were interviewed (24% female; Women: 68.7 ± 13.1 years and men: 60.7 ± 13.8 years) between January 2009 and August 2012. A significantly larger percentage of women than men had no chest pain (62% vs 36%, p<0.01). Compared to men, a smaller proportion of women thought they were having a myocardial infarction (15% vs 34%, p=0.01). A larger proportion of women than men had S2P time >90 minutes (72% of women vs 54% of men, p= 0.03). Women were more likely than men to hesitate before seeking help, and more women than men hesitated because they did not think they were having an AMI (91% vs 83%, p=0.04). Multivariate regression analysis showed that female sex (Odds Ratio: 2.46, 95% CI 1.10-5.60 P=0.03), subjective opinion it was not an AMI (Odds Ratio 2.44, 95% CI 1.20-5.0, P=0.01) and level of education less than high school (Odds ratio 7.21 95% CI 1.59-32.75 P=0.01) were independent predictors for S2P >90 minutes. Conclusion/UNASSIGNED:Women with STEMI have longer pre-hospital delays than men, which are associated with a higher prevalence of atypical symptoms and a lack of belief in women that they are having an AMI. Greater focus should be made on educating women (and men) regarding the symptoms of STEMI, and the importance of a timely response to these symptoms.

BACKGROUND:With the high prevalence of COVID-19 infections worldwide, the multisystem inflammatory syndrome in adults (MIS-A) is becoming an increasingly recognized entity. This syndrome presents in patients several weeks after infection with COVID-19 and is associated with thrombosis, elevated inflammatory markers, hemodynamic compromise and cardiac dysfunction. Treatment is often with steroids and intravenous immunoglobulin (IVIg). The pathologic basis of myocardial injury in MIS-A, however, is not well characterized. In our case report, we obtained endomyocardial biopsy that revealed a pattern of myocardial injury similar to that found in COVID-19 cardiac specimens. CASE PRESENTATION:A 26-year-old male presented with fevers, chills, headache, nausea, vomiting, and diarrhea 5 weeks after his COVID-19 infection. His SARS-CoV-2 PCR was negative and IgG was positive, consistent with prior infection. He was found to be in cardiogenic shock with biventricular failure, requiring inotropes and diuretics. Given concern for acute fulminant myocarditis, an endomyocardial biopsy (EMB) was performed, showing an inflammatory infiltrate consisting predominantly of interstitial macrophages with scant T lymphocytes. The histologic pattern was similar to that of cardiac specimens from COVID-19 patients, helping rule out myocarditis as the prevailing diagnosis. His case was complicated by persistent hypoxemia, and a computed tomography scan revealed pulmonary emboli. He received IVIg, steroids, and anticoagulation with rapid recovery of biventricular function. CONCLUSIONS:MIS-A should be considered as the diagnosis in patients presenting several weeks after COVID-19 infection with severe inflammation and multi-organ involvement. In our case, EMB facilitated identification of MIS-A and guided therapy. The patient's biventricular function recovered with IVIg and steroids.

AIMS/OBJECTIVE:The incidence of respiratory failure and use of invasive or non-invasive mechanical ventilation (MV) in the cardiac intensive care units (CICUs) is increasing. While institutional MV volumes are associated with reduced mortality in medical and surgical ICUs, this volume-mortality relationship has not been characterized in the CICU. METHODS AND RESULTS/RESULTS:National population-based data were used to identify patients admitted to CICUs (2005-2015) requiring MV in Canada. CICUs were categorized into low (≤100), intermediate (101-300), and high (>300) volume centres based on spline knots identified in the association between annual MV volume and mortality. Outcomes of interest included all-cause in-hospital mortality, the proportion of patients requiring prolonged MV (>96 h) and CICU length of stay (LOS). Among 47 173 CICU admissions requiring MV, 89.5% (42 200) required invasive MV. The median annual CICU MV volume was 43 (inter-hospital range 1-490). Compared to low-volume centres (35.9%), in-hospital mortality was lower in intermediate [29.2%, adjusted odds ratio (aOR) 0.84, 95% confidence interval (CI) 0.72-0.97, P = 0.019] and high-volume (18.2%; aOR 0.82, 95% CI 0.66-1.02, P = 0.076) centres. Prolonged MV was higher in low-volume (29.2%) compared to high-volume (14.8%, aOR 0.70, 95% CI 0.55-0.89, P = 0.003) and intermediate-volume (23.0%, aOR 0.85, 95% CI 0.68-1.06, P = 0.14] centres. Mortality and prolonged MV were lower in percutaneous coronary intervention (PCI)-capable and academic centres, but a shorter CICU LOS was observed only in subgroup of PCI-capable intermediate- and high-volume hospitals. CONCLUSIONS:In a national dataset, we observed that higher CICU MV volumes were associated with lower incidence of in-hospital mortality, prolonged MV, and CICU LOS. Our data highlight the need for minimum MV volume benchmarks for CICUs caring for patients with respiratory failure.