Background A systemic inflammatory response is observed in coronavirus disease 2019 (COVID-19). Elevated serum levels of C-reactive protein (CRP), a marker of systemic inflammation, are associated with severe disease in bacterial or viral infections. We aimed to explore associations between CRP concentration at initial hospital presentation and clinical outcomes in patients with COVID-19. Methods and results Consecutive adults aged ≥18 years with COVID-19 admitted to a large New York healthcare system between 1 March and 8 April 2020 were identified. Patients with measurement of CRP were included. Venous thrombo-embolism (VTE), acute kidney injury (AKI), critical illness, and in-hospital mortality were determined for all patients. Among 2782 patients hospitalized with COVID-19, 2601 (93.5%) had a CRP measurement [median 108 mg/L, interquartile range (IQR) 53–169]. CRP concentrations above the median value were associated with VTE [8.3% vs. 3.4%; adjusted odds ratio (aOR) 2.33, 95% confidence interval (CI) 1.61–3.36], AKI (43.0% vs. 28.4%; aOR 2.11, 95% CI 1.76–2.52), critical illness (47.6% vs. 25.9%; aOR 2.83, 95% CI 2.37–3.37), and mortality (32.2% vs. 17.8%; aOR 2.59, 95% CI 2.11–3.18), compared with CRP below the median. A dose response was observed between CRP concentration and adverse outcomes. While the associations between CRP and adverse outcomes were consistent among patients with low and high D-dimer levels, patients with high D-dimer and high CRP have the greatest risk of adverse outcomes. Conclusions Systemic inflammation, as measured by CRP, is strongly associated with VTE, AKI, critical illness, and mortality in COVID-19. CRP-based approaches to risk stratification and treatment should be tested.

Importance Major adverse cardiovascular and cerebrovascular events (MACCE) are a significant source of perioperative morbidity and mortality following non-cardiac surgery. Objective To evaluate national trends in perioperative cardiovascular outcomes and mortality after major non-cardiac surgery and identify surgical subtypes associated with cardiovascular events using a large administrative database of United States hospital admissions. Design, Setting, Participants Patients who underwent major non-cardiac surgery from 2004 to 2013 were identified using the National Inpatient Sample. Main Outcomes Perioperative MACCE (primary outcome), defined as in-hospital, all-cause death, acute myocardial infarction (AMI), or acute ischemic stroke, were evaluated over time. Results Among 10,581,621 hospitalizations for major non-cardiac surgery, perioperative MACCE occurred in 317,479 (3.0%), corresponding to an annual incidence of ≈150,000 after applying sample weights. Major adverse cardiovascular and cerebrovascular events occurred most frequently in patients undergoing vascular (7.7%), thoracic (6.5%), and transplant surgery (6.3%). Between 2004 and 2013, the frequency of MACCE declined from 3.1% to 2.6% (p for trend <0.0001; adjusted OR 0.95, 95% CI 0.94–0.97) driven by a decline in frequency of perioperative death (adjusted OR 0.79, 95% CI 0.77–0.81) and AMI (adjusted OR 0.87, 95% CI 0.84–0.89) but with an increase in perioperative ischemic stroke from 0.52% in 2004 to 0.77% in 2013 (p for trend <0.0001; adjusted OR 1.79; CI 1.73–1.86). Conclusions & Relevance Perioperative MACCE occurs in 1 of every 33 hospitalizations for non-cardiac surgery. Despite reductions in the rate of death and AMI among patients undergoing major non-cardiac surgery in the United States, perioperative ischemic stroke increased over time. Additional efforts are necessary to improve cardiovascular care in the perioperative period of patients undergoing non-cardiac surgery.

Background— Sex differences in early mortality after myocardial infarction (MI) vary by age. MI with nonobstructive coronary arteries (MINOCA [<50% stenosis]) is more common among younger patients and women, and MINOCA has a better prognosis than MI with obstructive coronary artery disease (MI-CAD). The relationship between age, sex, and obstructive CAD status and outcomes post-MI has not been established. Methods and Results— Adults who underwent coronary angiography for acute ST-segment–elevation and non–ST-segment–elevation MI in the National Cardiovascular Data Registry ACTION Registry-GWTG (Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines) from 2007 to 2014 were identified. Patients with cardiac arrest, thrombolytic therapy, prior revascularization, or missing demographic or angiographic data were excluded. The primary outcome was all-cause, in-hospital mortality. Secondary outcomes included major adverse cardiovascular events. Demographics, clinical history, presentation, and in-hospital treatments were compared by sex and CAD status (MI-CAD or MINOCA). Mortality and major adverse cardiovascular outcomes were analyzed by age, sex, and CAD status. Among 322 523 patients with MI, MINOCA occurred in 18 918 (5.9%). MINOCA was more common in women than men (10.5% versus 3.4%; P <0.0001), and women had higher mortality than men overall (3.6% versus 2.4%; P <0.0001). In-hospital mortality was lower after MINOCA than MI-CAD (1.1% versus 2.9%; P <0.0001). Among patients with MI-CAD, women had higher mortality than men (3.9% versus 2.4%; P <0.0001) while no sex difference in mortality was observed with MINOCA (1.1% versus 1.0%; P =0.84). The higher risk of post-MI death among women with MI-CAD was most pronounced at younger ages. Conclusions— MINOCA was associated with lower mortality than MI-CAD. Higher risk of post-MI death among women in comparison to men was restricted to patients with MI-CAD.

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: Vascular injury and inflammation during percutaneous coronary intervention (PCI) are associated with increased risk of post-PCI adverse outcomes. Colchicine decreases neutrophil recruitment to sites of vascular injury. The anti-inflammatory effects of acute colchicine administration before PCI on subsequent myocardial injury are unknown. Methods: In a prospective, single-site trial, subjects referred for possible PCI (n=714) were randomized to acute preprocedural oral administration of colchicine 1.8 mg or placebo. Results: Among the 400 subjects who underwent PCI, the primary outcome of PCI-related myocardial injury did not differ between colchicine (n=206) and placebo (n=194) groups (57.3% versus 64.2%, P =0.19). The composite outcome of death, nonfatal myocardial infarction, and target vessel revascularization at 30 days (11.7% versus 12.9%, P =0.82), and the outcome of PCI-related myocardial infarction defined by the Society for Cardiovascular Angiography and Interventions (2.9% versus 4.7%, P =0.49) did not differ between colchicine and placebo groups. Among 280 PCI subjects in a nested inflammatory biomarker substudy, the primary biomarker end point, change in interleukin-6 concentrations did not differ between groups 1-hour post-PCI but increased less 24 hours post-PCI in the colchicine (n=141) versus placebo group (n=139; 76% [−6 to 898] versus 338% [27 to 1264], P =0.02). High-sensitivity C-reactive protein concentration also increased less after 24 hours in the colchicine versus placebo groups (11% [−14 to 80] versus 66% [1 to 172], P =0.001). Conclusions: Acute preprocedural administration of colchicine attenuated the increase in interleukin-6 and high-sensitivity C-reactive protein concentrations after PCI when compared with placebo but did not lower the risk of PCI-related myocardial injury. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifiers: NCT02594111, NCT01709981.

IMPORTANCEPerioperative 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 (Ն1%) 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 Ն2 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.

Myocardial injury after noncardiac surgery (MINS) is a common postoperative complication associated with adverse cardiovascular outcomes. The purpose of this systematic review was to determine the incidence, clinical features, pathogenesis, management, and outcomes of MINS. We searched PubMed, Embase, Central and Web of Science databases for studies reporting the incidence, clinical features, and prognosis of MINS. Data analysis was performed with a mixed-methods approach, with quantitative analysis of meta-analytic methods for incidence, management, and outcomes, and a qualitative synthesis of the literature to determine associated preoperative factors and MINS pathogenesis. A total of 195 studies met study inclusion criteria. Among 169 studies reporting outcomes of 530,867 surgeries, the pooled incidence of MINS was 17.9% [95% confidence interval (CI), 16.2–19.6%]. Patients with MINS were older, more frequently men, and more likely to have cardiovascular risk factors and known coronary artery disease. Postoperative mortality was higher among patients with MINS than those without MINS, both in-hospital (8.1%, 95% CI, 4.4–12.7% vs 0.4%, 95% CI, 0.2–0.7%; relative risk 8.3, 95% CI, 4.2–16.6, P < 0.001) and at 1-year after surgery (20.6%, 95% CI, 15.9–25.7% vs 5.1%, 95% CI, 3.2–7.4%; relative risk 4.1, 95% CI, 3.0–5.6, P < 0.001). Few studies reported mechanisms of MINS or the medical treatment provided. In conclusion, MINS occurs frequently in clinical practice, is most common in patients with cardiovascular disease and its risk factors, and is associated with increased short- and long-term mortality. Additional investigation is needed to define strategies to prevent MINS and treat patients with this diagnosis.

Myocardial injury after noncardiac surgery is defined by elevated postoperative cardiac troponin concentrations that exceed the 99th percentile of the upper reference limit of the assay and are attributable to a presumed ischemic mechanism, with or without concomitant symptoms or signs. Myocardial injury after noncardiac surgery occurs in ≈20% of patients who have major inpatient surgery, and most are asymptomatic. Myocardial injury after noncardiac surgery is independently and strongly associated with both short-term and long-term mortality, even in the absence of clinical symptoms, electrocardiographic changes, or imaging evidence of myocardial ischemia consistent with myocardial infarction. Consequently, surveillance of myocardial injury after noncardiac surgery is warranted in patients at high risk for perioperative cardiovascular complications. This scientific statement provides diagnostic criteria and reviews the epidemiology, pathophysiology, and prognosis of myocardial injury after noncardiac surgery. This scientific statement also presents surveillance strategies and treatment approaches.