Faculty Bibliography

Background: Hyperoxia produces reactive oxygen species, apoptosis, and vasoconstriction, and is associated with adverse outcomes in patients with heart failure and cardiac arrest. Our aim was to evaluate the association between hyperoxia and mortality in patients (pts) receiving positive pressure ventilation (PPV) in the cardiac intensive care unit (CICU).
Method(s): Patients admitted to our medical center CICU who received any PPV (invasive or non-invasive) from 2001 through 2012 were included. Hyperoxia was defined as time-weighted mean of PaO2 >120mmHg and non-hyperoxia as PaO2 <=120mmHg during CICU admission. Primary outcome was in-hospital mortality. Multivariable logistic regression was used to assess the association between hyperoxia and in-hospital mortality adjusted for age, female sex, Oxford Acute Severity of Illness Score, creatinine, lactate, pH, PaO2/FiO2 ratio, PCO2, PEEP, and estimated time spent on PEEP.
Result(s): Among 1493 patients, hyperoxia (median PaO2 147mmHg) during the CICU admission was observed in 702 (47.0%) pts. In-hospital mortality was 29.7% in the non-hyperoxia group and 33.9% in the hyperoxia group ((log rank test, p=0.0282, see figure). Using multivariable logistic regression, hyperoxia was independently associated with in-hospital mortality (OR 1.507, 95% CI 1.311-2.001, p=0.00508). Post-hoc analysis with PaO2 as a continuous variable was consistent with the primary analysis (OR 1.053 per 10mmHg increase in PaO2, 95% CI 1.024-1.082, p=0.0002).
Conclusion(s): In a large CICU cohort, hyperoxia was associated with increased mortality. Trials of titration of supplemental oxygen across the full spectrum of critically ill cardiac patients are warranted

Background/Purpose: Patients with systemic lupus erythematosus (SLE) are at increased risk of premature atherosclerosis and thrombosis. Hydroxychloroquine (HCQ) is widely used in the treatment of SLE and has been considered of benefit for overall vascular health albeit studies to address this benefit at the cellular level have been limited. Accordingly, this study was initiated to investigate the relationship between HCQ use and dose with platelet activity, the platelet transcriptome, and vascular functional readouts.
Method(s): Patients fulfilling ACR or SLICC criteria for SLE were consecutively recruited for platelet evaluation with the only exclusion being on nonsteroidal anti-inflammatory medications, aspirin or anticoagulants. At enrollment, blood was collected for hematology analysis using the Sysmex XN-1000 analyzer, platelet aggregation via the Helena AggRAMTM system, and platelet RNA isolation and storage. Microvascular function was assessed via sublingual sidestream darkfield imaging. Brachial artery reactivity testing was used to evaluate large vessel function. Stored platelet RNA was isolated and analyzed by RNA sequencing (Illumina HiSeq4000 Sequencing).
Result(s): Among 132 SLE subjects, 108 were on HCQ. Mean age was 39.9 +/- 13.0 and 97% were female. Lupus disease activity at the time of blood draw assessed by the SELENA-SLEDAI activity index was 3.44 (range 0-20). Demographics and SLE disease activity did not differ between those on versus off HCQ (Table 1). Platelet count and size were not different between groups (Figure 1A). Platelet aggregation in response to submaximal ADP at multiple concentrations was lower in participants on HCQ (Figure 1B). Consistently, there was an inverse relationship between HCQ dosing and platelet aggregation in response to ADP (2uM: R=-0.213, P=0.037; 1uM: R=-0.310, P=0.0025; 0.4uM: R=-0.376, P=0.00018; Figure 1C). Since no subjects were on aspirin (or any other antiplatelet therapy at enrollment), aggregation in response to arachidonic acid (AA) was robust and similar between groups. However, after incubating platelets with aspirin (3mM) in vitro, platelet aggregation in response to AA was lower in the HCQ group compared to non-HCQ group (P=0.035, Figure 1B). To investigate the potential mechanisms of HCQ induced lower platelet aggregation, we evaluated platelet RNA sequencing in 49 subjects (8 no HCQ, 41 on HCQ). Positive regulation of pathways related to platelet activation (and in particular, P-selectin expression) was inversely related to HCQ, especially with higher doses (Figure 1E). In terms of vascular function, subjects on HCQ had improved microvascular function as noted by an increased proportion of sublingual capillaries filled with RBCs (P=0.011) and smaller perfused boundary region (PBR, P=0.010). HCQ dosing correlated with PBR (R=-0.599, P=0.002, Figure 1H) and RBC Filling (R=-0.592, P=0.002, Figure 1I). BART also trended positively with HCQ dose (R=0.385, P=0.094; Figure 1J).
Conclusion(s): These findings suggest that HCQ may provide benefit for vascular health in SLE as supported by ex vivo experiments demonstrating decreased platelet aggregation and downregulation of platelet functional pathways as well as improved vascular readouts

BACKGROUND:Patients with aortic stenosis are nearly twice as likely to have a diagnosis of gout compared with individuals without aortic valve disease. METHODS:, and/or decrease in left ventricular ejection fraction due to aortic stenosis. RESULTS:/year [-0.16, -0.01], p=0.09); annualized change in peak velocity and mean gradient did not differ between groups. CONCLUSIONS:Progression to severe aortic stenosis was more frequent in patients with gout versus those without gout supporting the hypothesis that gout is a risk factor for aortic stenosis.

OBJECTIVES/OBJECTIVE:The aim of this study was to determine the prevalence of myocarditis among patients presenting with myocardial infarction with nonobstructive coronary arteries (MINOCA) in relation to the angiographic severity of nonobstructive coronary artery disease (CAD). BACKGROUND:MINOCA represents about 6% of all cases of acute myocardial infarction. Myocarditis is a diagnosis that may be identified by cardiac magnetic resonance (CMR) imaging in patients with a provisional diagnosis of MINOCA. METHODS:A systematic review was performed to identify studies reporting the results of CMR findings in MINOCA patients with nonobstructive CAD or normal coronary arteries. Study-level and individual patient data meta-analyses were performed using fixed- and random-effects methods. RESULTS:Twenty-seven papers were included, with 2,921 patients with MINOCA; CMR findings were reported in 2,866 (98.1%). Myocarditis prevalence was 34.5% (95% confidence interval [CI]: 27.2% to 42.2%) overall and was numerically higher in studies that defined MINOCA as myocardial infarction with angiographically normal coronary arteries compared with a definition that permitted nonobstructive CAD (45.9% vs. 32.3%; p = 0.16). In a meta-analysis of individual patient data from 9 of the 27 studies, the pooled prevalence of CMR-confirmed myocarditis was greater in patients with angiographically normal coronary arteries than in those with nonobstructive CAD (51% [95% CI: 47% to 56%] vs. 23% [95% CI: 18% to 27%]; p < 0.001). Men and younger patients with MINOCA were more likely to have myocarditis. Angiographically normal coronary arteries were associated with increased odds of myocarditis after adjustment for age and sex (adjusted odds ratio: 2.30; 95% CI: 1.12 to 4.71; p = 0.023). CONCLUSIONS:Patients with a provisional diagnosis of MINOCA are more likely to have CMR findings consistent with myocarditis if they have angiographically normal coronary arteries.

Pregnancy-associated myocardial infarction is a primary contributor to maternal cardiovascular morbidity and mortality. Specific attention to the cause of myocardial infarction, diagnostic evaluation, treatment strategies, and postevent care is necessary when treating women with pregnancy-associated myocardial infarction. This review summarizes the current knowledge, consensus statements, and essential nuances.

BACKGROUND:Myocardial infarction (MI) complicated by cardiogenic shock (CS) is associated with high mortality. Early coronary revascularization improves survival, but the optimal mode of revascularization remains uncertain. We sought to characterize practice patterns and outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in patients with MI complicated by CS. METHODS:Patients hospitalized for MI with CS between 2002 and 2014 were identified from the United States National Inpatient Sample. Trends in management were evaluated over time. Propensity score matching was performed to identify cohorts with similar baseline characteristics and MI presentations who underwent PCI and CABG. The primary outcome was in-hospital all-cause mortality. RESULTS:A total of 386,811 hospitalizations for MI with CS were identified; 67% were STEMI. Overall, 62.4% of patients underwent revascularization, with PCI in 44.9%, CABG in 14.1%, and a hybrid approach in 3.4%. Coronary revascularization for MI and CS increased over time, from 51.5% in 2002 to 67.4% in 2014 (P for trend < .001). Patients who underwent CABG were more likely to have diabetes mellitus (35.5% vs. 29.2%, P < .001) and less likely to present with STEMI (48.7% vs. 80.9%, P < .001) than those who underwent PCI. CABG (without PCI) was associated with lower mortality than PCI (without CABG) overall (18.9% vs. 29.0%, P < .001) and in a propensity-matched subgroup of 19,882 patients (19.0% vs. 27.0%, P < .001). CONCLUSIONS:CABG was associated with lower in-hospital mortality than PCI among patients with MI complicated by CS. Due to the likelihood of residual confounding, a randomized trial of PCI versus CABG in patients with MI, CS, and multi-vessel coronary disease is warranted.

Background: The use of positive end-expiratory pressure (PEEP) may influence cardiac output according to the patient's hemodynamics. However these effects have been only described in preclinical studies and very small patient series. Our aim was to evaluate the association between PEEP and clinical outcomes in patients undergoing mechanical ventilation (MV) who are also receiving invasive hemodynamic monitoring with a pulmonary artery catheter (PAC).
Method(s): We included patients admitted to the CICU with the diagnosis of cardiogenic shock (CS) receiving invasive MV during the first 48hrs of admission and who had a PAC in place. Patients were stratified according to their filling pressures as pulmonary artery diastolic pressure (PADP) above and below 20mmHg. Ventilatory parameters were measured and monitored every hour for the study period (48 hours). Outcomes of interest included lactate clearance, inotropic vasopressor score and survival and were compared according to the level of PEEP (above and below the median). Multivariate regression analysis was performed adjusting for age, sex, OASIS, PaO2, pH, peak lactate and presence of cardiac arrest Results: A total of 80 patients (age 65, IQR 54-79) with CS undergoing MV and PAC monitoring were included. The median PEEP in the low PADP was 7.7 (IQR 5.5-9.9, p =0.1) cmH2O and the median PEEP in the high PADP was 5.5 (IQR 5.0-6.6)cm H2O. In the low PADP group, unadjusted mortality was non statistically significantly higher in the group receiving PEEP below the median (33% vs 0%, p=0.1). In the high PADP group mortality was non-significantly higher in patients receiving PEEP above the median (57%) compared to the ones receiving PEEP below the median (33%, p =0.5). Multivariate regression demonstrated no difference in mortality according to PADP and PEEP level (OR 0.95 95% CI 0.60-1.50, p=0.83). In multivariate analysis there were no differences in lactate clearance or in the change o inotropic-vasopressor score (table).
Conclusion(s): In patients with cardiogenic shock undergoing MV and invasive hemodynamic monitoring, PEEP levels were not associated with differences in mortality, lactate clearance and inotropic/vasopressor score delta according to the left ventricular filling pressures as measured by pulmonary artery diastolic pressures. Further research in this area is need to better characterize the impact of PEEP in hemodynamics and clinical outcomes in patients with cardiogenic shock

Background: The use of positive end-expiratory pressure (PEEP) and different prescribed Tidal Volumes (TV) in patients with cardiovascular disease may affect clinical outcomes. However these effects may be dependent on the intrinsic cardiac function as well as the hemodynamic state of each patient. We aimed to analyze the interactions between PEEP and TV with survival in patients with cardiovascular disease according to their preload and afterload dependent status.
Method(s): We included patients admitted to the CICU receiving invasive MV during the first 48hrs of admission. Patients were stratified according as preload dependent (hypovolemia, right ventricular dysfunction, tamponade, hypertrophic obstructive cardiomyopathy or constriction), afterload dependent (left ventricular shock, elevated afterload) or neither preload/afterload dependence. Multivariate regression analysis was performed with PEEP, TV and covariates of survival, including age, sex, OASIS severity score, cardiac arrest, PaO2, PCO2 and plateau pressures.
Result(s): A total of 291 CICU patients (age 68, IQR 57-78) undergoing mechanical ventilation (MV) were included. There were no differences in survival according to PEEP level in patients with preload dependent status (OR 1.74 95% CI 0.85-3.55, p=0.1) or afterload dependent status (OR 1.02 95% CI 0.84-1.24, p=0.9). Similarly, TV was not associated with mortality in patients with preload dependent status (OR 0.61 95% CI 0.20-1.89, p=0.4) or afterload dependent status (OR 0.84 95% CI 0.56-1.24, p=0.3). In patients with neither preload or afterload dependent status PEEP or TV was not associated with increased mortality.
Conclusion(s): In patients with cardiovascular disease undergoing MV, there is no significant association between the level of PEEP or TV use and survival, even when stratifying patients according to their preload or afterload dependent status. Further research in this area is warranted to better understand the impact of positive pressure ventilation in patients with cardiovascular disease

Background: The use of mechanical ventilation (MV) in the cardiac intensive care unit (CICU) has become increasingly common. Low tidal volume (TV) ventilation has benefits in patients with ARDS, while positive endexpiratory pressure (PEEP) may impact hemodynamics. However the relationship between mechanical ventilation parameters and outcomes has not been systematically studied. We sought to analyze the interactions between tidal volume (TV) and PEEP with mortality.
Method(s): We included patients admitted to the CICU receiving invasive MV during the first 48hrs of admission. Patients were stratified into two groups of TV (low: <8ml/ Kg of ideal body weight), normal-high (8 ml/Kg of ideal body weight), low and high PEEP (above and below the median for the cohort). The primary outcome was all cause 30-day mortality Results: A total of 291 CICU patients (age 68, IQR 57- 78) were included. The median TV was 7.89 (IQR 7.18- 8.96) and median PEEP was 5.5 (IQR 5.00-7.71) and median plateau pressure was 19.7 (IQR 17-23) cmH2O. Mortality did not differ between low TV (30.2%) and normal-high (25.0%, p =0.8), or between PEEP (29.6% vs 254%, p=0.5, above and below the median respectively). After multivariable adjustment differences in mortality remained non-significant for TV groups (OR 0.84 95% CI 0.65-1.08) as well as for PEEP groups (OR 0.93 95% CI 0.87-1.12).
Conclusion(s): In a large cohort of patients undergoing MV in the CICU, the use of low TV ventilation is not associated with differences in mortality or MV duration. Similarly, with a median of 5cmH2O, there is no association between PEEP and mortality. Future prospective studies are required to evaluate the MV parameters in patients admitted to the CICU

Importance:Perioperative cardiovascular complications occur in 3% of hospitalizations for noncardiac surgery in the US. This review summarizes evidence regarding cardiovascular risk assessment prior to noncardiac surgery. Observations:Preoperative cardiovascular risk assessment requires a focused history and physical examination to identify signs and symptoms of ischemic heart disease, heart failure, and severe valvular disease. Risk calculators, such as the Revised Cardiac Risk Index, identify individuals with low risk (<1%) and higher risk (≥1%) for perioperative major adverse cardiovascular events during the surgical hospital admission or within 30 days of surgery. Cardiovascular testing is rarely indicated in patients at low risk for major adverse cardiovascular events. Stress testing may be considered in patients at higher risk (determined by the inability to climb ≥2 flights of stairs, which is <4 metabolic equivalent tasks) if the results from the testing would change the perioperative medical, anesthesia, or surgical approaches. Routine coronary revascularization does not reduce perioperative risk and should not be performed without specific indications independent of planned surgery. Routine perioperative use of low-dose aspirin (100 mg/d) does not decrease cardiovascular events but does increase surgical bleeding. Statins are associated with fewer postoperative cardiovascular complications and lower mortality (1.8% vs 2.3% without statin use; P < .001) in observational studies, and should be considered preoperatively in patients with atherosclerotic cardiovascular disease undergoing vascular surgery. High-dose β-blockers (eg, 100 mg of metoprolol succinate) administered 2 to 4 hours prior to surgery are associated with a higher risk of stroke (1.0% vs 0.5% without β-blocker use; P = .005) and mortality (3.1% vs 2.3% without β-blocker use; P = .03) and should not be routinely used. There is a greater risk of perioperative myocardial infarction and major adverse cardiovascular events in adults aged 75 years or older (9.5% vs 4.8% for younger adults; P < .001) and in patients with coronary stents (8.9% vs 1.5% for those without stents; P < .001) and these patients warrant careful preoperative consideration. Conclusions and Relevance:Comprehensive history, physical examination, and assessment of functional capacity during daily life should be performed prior to noncardiac surgery to assess cardiovascular risk. Cardiovascular testing is rarely indicated in patients with a low risk of major adverse cardiovascular events, but may be useful in patients with poor functional capacity (<4 metabolic equivalent tasks) undergoing high-risk surgery if test results would change therapy independent of the planned surgery. Perioperative medical therapy should be prescribed based on patient-specific risk.