Faculty Bibliography

OBJECTIVE:Hydroxychloroquine (HCQ) is a mainstay of therapy in the treatment of SLE. The effect of HCQ on platelets and vascular health is uncertain. We investigated the relationship between HCQ use and dose with platelet activity, platelet transcriptomics and vascular health in patients with SLE. METHODS:Platelet aggregation, platelet mRNA expression and vascular health (sublingual capillary perfused boundary region (PBR), red blood cell filling (RBCF) and brachial artery reactivity testing) were analysed by HCQ use and dose. RESULTS:Among 132 subjects with SLE (age: 39.7±12.9 years, 97% female), 108 were on HCQ. SLE disease activity was similar between subjects on and off HCQ. Platelet aggregation in response to multiple agonists was significantly lower in patients on HCQ. There were inverse relationships between HCQ dose and gene expression pathways of platelet activity. Gene expression of P-selectin (SELP) was inversely correlated with HCQ dose (r=-0.41, p=0.003), which was validated at the protein level. Subjects on HCQ had improved vascular function correlating with HCQ dose as measured by lower PBR (r=-0.52, p=0.007), higher RBCF (r=0.55, p=0.004) and greater brachial artery reactivity (r=0.43, p=0.056). CONCLUSION/CONCLUSIONS:HCQ use was associated with decreased platelet activation and activation-related transcripts and improved vascular health in SLE.

Thrombosis is a major concern in respiratory infections. Our aim was to investigate the magnitude and duration of risk for arterial and venous thrombosis following discharge after respiratory infection. Patients with respiratory infections were identified using the United States Nationwide Readmission Database from 2012 to 2014. Patients admitted with asthma or cellulitis served as comparators. Readmissions for acute myocardial infarction (MI) and venous thromboembolism (VTE) were evaluated at 30 to 180 days. The likelihood of a first thrombotic event after discharge was compared with a 30-day period prior to hospitalization. Among 5,271,068 patients discharged after a respiratory infection, 0.56% and 0.78% were readmitted within 30-days with MI and VTE, respectively. Relative to asthma and cellulitis, respiratory infection was associated with a greater age and sex-adjusted hazard of 30-day readmission for MI (adjusted HR [aHR] 1.48 [95% CI 1.42-1.54] vs. asthma; aHR 1.36 [95% CI 1.31-1.41] vs. cellulitis) and VTE (aHR 1.28 [95% CI 1.24-1.33] vs. asthma; aHR 1.26, [95% CI 1.22-1.30] vs. cellulitis). Risks of MI and VTE attenuated over time. In a crossover-cohort analysis, the odds of MI (OR 1.68 [95% CI 1.62-1.73]) and VTE (OR 3.30 [95% 3.19-3.41]) were higher in the 30 days following discharge after respiratory infection than during the 30-day baseline period. Hospitalization for respiratory infection was associated with increased risks of thrombosis that were highest in the first 30-days after discharge and declined over time.

Background: Myocardial infarction with non-obstructive coronary arteries (MINOCA) occurs in 6-15% of MI and disproportionately affects women. Scientific statements recommend multi-modality imaging in MINOCA to define the underlying cause. We performed coronary optical coherence tomography (OCT) and cardiac magnetic resonance imaging (CMR) to assess mechanisms of MINOCA. Methods: In this prospective, multicenter, international, observational study, we enrolled women with a clinical diagnosis of MI. If invasive coronary angiography revealed <50% stenosis in all major arteries, multi-vessel OCT was performed, followed by CMR (cine imaging, late gadolinium enhancement, and T2-weighted imaging and/or T1 mapping). Angiography, OCT, and CMR were evaluated at blinded, independent core laboratories. Culprit lesions identified by OCT were classified as definite or possible. The CMR core laboratory identified ischemia-related and non-ischemic myocardial injury. Imaging results were combined to determine the mechanism of MINOCA, when possible. Results: Among 301 women enrolled at 16 sites, 170 were diagnosed with MINOCA, of whom 145 had adequate OCT image quality for analysis; 116 of these underwent CMR. A definite or possible culprit lesion was identified by OCT in 46.2% (67/145) of participants, most commonly plaque rupture, intra-plaque cavity or layered plaque. CMR was abnormal in 74.1% (86/116) of participants. An ischemic pattern of CMR abnormalities (infarction or myocardial edema in a coronary territory) was present in 53.4% of participants undergoing CMR (62/116). A non-ischemic pattern of CMR abnormalities (myocarditis, takotsubo syndrome or non-ischemic cardiomyopathy) was present in 20.7% (24/116). A cause of MINOCA was identified in 84.5% of the women with multi-modality imaging (98/116), higher than with OCT alone (p<0.001) or CMR alone (p=0.001). An ischemic etiology was identified in 63.8% of women with MINOCA (74/116), a non-ischemic etiology was identified in 20.7% (24/116), and no mechanism was identified in 15.5% (18/116). Conclusions: Multi-modality imaging with coronary OCT and CMR identified potential mechanisms in 84.5% of women with a diagnosis of MINOCA, three-quarters of which were ischemic and one-quarter of which were non-ischemic, alternate diagnoses to MI. Identification of the etiology of MINOCA is feasible and has the potential to guide medical therapy for secondary prevention. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02905357.

BACKGROUND:Perioperative cardiovascular events are a leading cause of morbidity and mortality after non-cardiac surgery. We propose a simplified method for perioperative risk stratification. METHODS:A retrospective cohort study identified patients undergoing non-cardiac surgery between 2009-2015 in the United States National Surgical Quality Improvement Program. Multivariable logistic regression models adjusted for age, sex, race and surgery type were generated to estimate the impact of traditional cardiovascular risk factors (hypertension, diabetes mellitus, current smoking) on odds of perioperative myocardial infarction (MI). Time to event analysis was conducted using competing risk analysis, with MI as the outcome event and death as the competing risk. RESULTS:A total of 3,848,501 non-cardiac surgeries were identified. Post-operative MI occurred in 0.37% of patients and 1.04% of patients died. The 30-day event rate of perioperative MI increased in a stepwise fashion with additional risk factors (0.41% for one, 0.81% for two, and 1.07% for three; P-for-trend < 0.001) after accounting for the competing risk of death. In comparison to those with no risk factors, patients with one, two and three risk factors had increased odds of MI (aOR 2.07; 95% CI 1.96-2.19; aOR 3.63 95% CI 3.43-3.85; aOR 5.54 95% CI 5.09-6.04). Perioperative MI was rare (0.10%) in patients without risk factors. CONCLUSIONS:Patients with cardiovascular risk factors are at increased risk of perioperative MI, those without risk factors are at low risk. Further evaluation is needed to determine the impact of a simplified risk score in the perioperative setting.

BACKGROUND:Heart failure (HF) affects ∼5.7 million United States adults and many of these patients develop non-cardiac disease that requires surgery. The aim of this study was to determine perioperative outcomes associated with HF in a large cohort of patients undergoing in-hospital non-cardiac surgery. METHODS:Adults ≥18 years old undergoing non-cardiac surgery between 2012-2014 were identified using the HCUP National Inpatient Sample. Patients with HF were identified by ICD-9 diagnosis codes. The primary outcome was all-cause in-hospital mortality. Multivariable logistic regression models were used to estimate associations between HF and outcomes. RESULTS:A total of 21,560,996 surgical hospitalizations were identified, of which 1,063,405 (4.9%) had a diagnosis of HF. Among hospitalizations with HF, 4.7% had acute HF, 11.3% had acute on chronic HF, 27.8% had chronic HF, and 56.2% had an indeterminate diagnosis code that did not specify temporality. In-hospital perioperative mortality was more common with a diagnosis of any HF compared to without HF (4.8% vs. 0.78%, p < 0.001; adjusted OR [aOR] 2.15 [95% CI 2.09-2.22]), and the association between HF and mortality was greatest at small and non-teaching hospitals. Acute HF without chronic HF was associated with 8.0% mortality. Among patients with a chronic HF diagnosis, perioperative mortality was greater in those with acute on chronic HF compared to chronic HF alone (7.8% vs. 3.9%, p < 0.001; aOR 1.78, 95% CI 1.67-1.90). CONCLUSION/CONCLUSIONS:In patients hospitalized for non-cardiac surgery, HF was common and was associated with increased risk of perioperative mortality. The greatest risks were in patients with acute HF.

Contemporary approaches to cardiovascular risk stratification before noncardiac surgery focus on macrovascular atherosclerotic disease and risk factors. We sought to determine the prevalence of microvascular disease (MVD) and its associated perioperative outcomes. Adults ≥18 years old undergoing noncardiac surgery between 2004 and 2014 were identified using the Nationwide Inpatient Sample (NIS). Prevalent MVD (retinopathy, neuropathy, and nephropathy) was identified by ICD-9 diagnosis codes. The primary outcomes were all-cause in-hospital mortality and the composite of major adverse cardiac events (MACE; death, myocardial infarction, and ischemic stroke). Multivariable logistic regression models were used to estimate associations between MVD and outcomes after adjusting for demographics and clinical covariates. Among 81,297,003 hospitalizations for noncardiac surgery, 4,236,932 (5.0%) had a diagnosis of MVD. Patients with MVD were older and more likely to have traditional cardiovascular risk factors. In-hospital perioperative MACE (4.1% vs. 1.9%; adjusted odds ratio [aOR] 1.15, 95% confidence interval [CI] 1.13 to 1.17) and mortality (2.0% vs. 1.1%; aOR 1.15, 95% CI 1.12 to 1.17) were greater in hospitalizations with MVD compared with those without. Microvascular disease was associated with postoperative outcomes in when stratified by age, sex, and coronary artery disease (CAD). Compared with surgical hospitalizations without CAD or MVD, MVD alone (aOR 1.12; 95% CI 1.11 to 1.14), CAD alone (aOR 1.44; 95% CI 1.42 to 1.46), and MVD with CAD (aOR 2.01; 95% CI 1.96 to 2.06) were associated with perioperative MACE. In conclusion, microvascular disease was present in 1 in 20 hospitalizations for noncardiac surgery, and was associated with perioperative mortality and MACE independent of macrovascular disease and traditional risk factors.

BACKGROUND:Optimal medical therapy after myocardial infarction with nonobstructive coronary arteries (MINOCA; <50% stenosis) is uncertain. We evaluated variability in discharge prescription of angiotensin-converting enzyme inhibitors / angiotensin receptor blockers (ACEI/ARB) and beta-blockers (BB) to MINOCA patients between hospitals to assess physician equipoise about secondary prevention. METHODS:Patients with MINOCA between 2007-2014 were identified in the NCDR Chest Pain-MI Registry. Those with prior revascularization or missing demographic, angiographic, or medication data were excluded. Analysis was limited to high-volume hospitals with ≥20 MINOCA total discharges. Discharge prescriptions for ACEI/ARB and BB after MINOCA were analyzed for each hospital. Clinical data on left ventricular ejection fraction (LVEF), glomerular filtration rate (GFR), and diabetes mellitus status were extracted to identify other indications for ACEI/ARB or BB. RESULTS:Clinical data were available for 17,849 MINOCA patients, of whom 8,752 (49%) had LVEF <40%, GFR ≤60 mL/min, and/or diabetes. 5,913 patients without one of these indications for ACEI/ARB or BB were discharged from 156 high-volume hospitals. At discharge, ACEI/ARB was prescribed to between 16.0% and 88.8% of MINOCA patients (median 45.6%, IQR 38.0%-56.5%) and BB to between 28.0% and 97.5% (median 74.1%, IQR 64.7%-80.0%). CONCLUSION/CONCLUSIONS:There is marked variability between hospitals in the proportions of patients receiving ACEI/ARB and BB after hospitalization for MINOCA, suggesting clinical equipoise about the routine use of these agents. Randomized clinical trials are necessary to establish the benefit of ACEI/ARB and BB to improve outcomes after MINOCA.