Intraoperative blood loss may be associated with myocardial injury after non-cardiac surgery.

BACKGROUND: This study aimed to evaluate the association between intraoperative blood loss and myocardial injury after non-cardiac surgery (MINS), which is a severe and common postoperative complication. METHODS: We compared the incidence of MINS based on significant intraoperative bleeding, defined as an absolute hemoglobin level < 7 g/dL, a relative hemoglobin level less than 50% of the preoperative measurement, or need for packed red cell transfusion. We also estimated a threshold for intraoperative hemoglobin level associated with MINS. RESULTS: We stratified a total of 15,926 non-cardiac surgical patients with intraoperative hemoglobin and postoperative cardiac troponin (cTn) measurements according to the occurrence of significant intraoperative bleeding; 13,416 (84.2%) had no significant bleeding while 2,510 (15.8%) did have significant bleeding. After an adjustment with inverse probability weighting, the incidence of MINS was higher in the significant bleeding group (35.2% vs. 16.4%; odds ratio, 1.58; 95% confidence interval, 1.43-1.75; p < 0.001). The threshold of intraoperative hemoglobin associated with MINS was estimated to be 9.9 g/dL with an area under the curve of 0.643. CONCLUSION: Intraoperative blood loss appeared to be associated with MINS. Further studies are needed to confirm these findings. CLINICAL REGISTRATION: The cohort was registered before patient enrollment at https://cris.nih.go.kr (KCT0004244).

Elevated high-sensitivity C-reactive protein concentrations may be associated with increased postdischarge mortality in patients with myocardial injury after noncardiac surgery: A retrospective observational study.

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is one of the most common cardiovascular complications associated with mortality and morbidity during the first 2 years after surgery. However, the relevant variables associated with mortality after discharge in patients with MINS have not been fully investigated. OBJECTIVES: This study aimed to evaluate the association between persistent inflammation detected by high-sensitivity C-reactive protein (hsCRP) at discharge and postdischarge mortality after MINS. DESIGN: Retrospective observational analysis of acquired data from Samsung Medical Center Troponin in Noncardiac Operation (SMC-TINCO) registry. SETTING: A tertiary hospital from January 2010 to June 2019. PATIENTS: Patients who were discharged alive after a diagnosis of MINS. MAIN OUTCOME MEASURES: The primary endpoint was postdischarge 1-year mortality, and 30-day mortality and the mortality from 30 days to 1 year was also compared. RESULTS: Data from a total of 4545 adult patients were divided into two groups according to hsCRP concentration at discharge. There were 757 (16.7%) patients in the normal hsCRP group and 3788 (83.3%) patients in the elevated hsCRP group. After inverse probability weighting, 1-year mortality was significantly higher in the elevated group than the normal group (hazard ratio 1.93, 95% CI 1.45 to 2.57, P  < 0.001). Thirty-day mortality and the mortality from 30 days to 1 year were also increased in the elevated group. CONCLUSION: In patients with MINS, an elevated hsCRP concentration at discharge appeared to be associated with increased mortality. Further research is needed to determine whether controlling inflammation can be helpful in reducing mortality.

Pre-operative anaemia and myocardial injury after noncardiac surgery: A retrospective study.

BACKGROUND: Pre-operative anaemia is associated with adverse outcomes of noncardiac surgery, but its association with myocardial injury after noncardiac surgery (MINS) has not been fully investigated. OBJECTIVE: The association between pre-operative anaemia and MINS. DESIGN: A single-centre retrospective cohort study. SETTING: Tertiary care referral centre. PATIENTS: Patients with measured cardiac troponin (cTn) I levels after noncardiac surgery. INTERVENTIONS: Patients were separated according to pre-operative anaemia (haemoglobin <13 g dl-1 in men and <12 g dl-1 in women). Anaemia was further stratified into mild and moderate-to-severe at a haemoglobin level threshold of 11 g dl-1. MAIN OUTCOME MEASURES: The primary outcome was MINS, defined as a peak cTn I level more than 99th percentile of the upper reference limit within 30 postoperative days. RESULTS: Data from a total of 35 170 patients were collected, including 22 062 (62.7%) patients in the normal group and 13 108 (37.3%) in the anaemia group. After propensity score matching, 11919 sets of patients were generated, and the incidence of MINS was significantly associated with anaemia [14.5 vs. 21.0%, odds ratio (OR) 1.57, 95% confidence interval (CI) 1.47 to 1.68, P < 0.001]. For the entire population, multivariable analysis showed a graded association between anaemia severity and MINS (OR 1.32, 95% CI 1.22 to 1.43, P < 0.001 for mild anaemia and OR 1.80, 95% CI 1.66 to 1.94, P < 0.001 for moderate-to-severe anaemia compared with the normal group) and a significantly higher incidence of MINS for moderate-to-severe anaemia than mild anaemia (18.6 vs. 28.6%, OR 1.37, 95% CI 1.25 to 1.50, P < 0.001). The estimated threshold for pre-operative haemoglobin associated with MINS was 12.2 g dl-1, with an area under the curve of 0.622. CONCLUSIONS: Pre-operative anaemia was independently associated with MINS, suggesting that MINS may be related to the association between anaemia and postoperative mortality. TRIAL REGISTRATION: SMC 2019-08-048.

Association Between High Body Mass Index and Mortality Following Myocardial Injury After Noncardiac Surgery.

BACKGROUND: Despite an association between obesity and increased risks for various diseases, obesity has been paradoxically reported to correlate with improved mortality in patients with established cardiovascular disease. However, its effect has not been evaluated to date in patients with myocardial injury after noncardiac surgery (MINS). METHODS: From January 2010 to June 2019, of a total of 35,269 adult patients with postoperative cardiac troponin level data, 5633 (16.0%) patients had MINS as diagnosed by postoperative cardiac troponin I above the 99th-percentile upper reference of 40 ng·L-1 using the TnI-Ultra immunoassay. Patients with MINS were divided into 3 groups according to body mass index (BMI), with 3246 (57.6%) were in the normal (18.5-25 kg·m-2), 425 (7.5%) in the low BMI (<18.5 kg·m-2), and 1962 (34.8%) in the high BMI (≥25 kg·m-2) groups, respectively. The primary outcome was mortality during the first year after surgery, and the mortality during 30 days was also compared. RESULTS: Following adjustment for confounding with inverse probability of treatment weighting, mortality within the first year appeared to be significantly lower in the high BMI group compared with the normal (14.8% vs 20.9%; hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.66-0.85; P < .001) and the low BMI (14.8% vs 25.6%; HR: 0.56; 95% CI, 0.48-0.66; P < .001) groups. CONCLUSIONS: High BMI may be associated with decreased mortality following MINS. Further investigations are needed to support this finding.

The role of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography in the differential diagnosis of pericardial disease.

This study aimed to assess the role of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT) in the differential diagnosis of pericardial disease. The diagnosis is often troublesome because pericardial fluid analysis or biopsy does not always provide answers. 18FDG-PET/CT can visualize both inflammation and malignancy and offers a whole-body assessment. Patients who visited the Pericardial Disease Clinic of Samsung Medical Center with an 18FDG-PET/CT order code were extracted. Exclusion criteria were as follows: (1) the purpose of the differential diagnosis was not pericardial disease; (2) the patient had a known advanced-stage malignancy; (3) the patient already have confirmative diagnosis using a serology, pericardial effusion analysis or biopsy. The analysis included 107 patients. The most common final diagnosis was idiopathic (n = 46, 43.0%), followed by tuberculosis (n = 30, 28.0%) and neoplastic (n = 11, 10.3%). A maximum standardized uptake value (SUVmax) ≥ 5 typically indicates tuberculosis or neoplastic pericarditis except in just one case of autoimmune pericarditis); especially all of the SUVmax scores ≥ 10 had tuberculosis. The diagnostic yield of pericardial biopsy was very low (10.2%). Interestingly, all of the pericardium with an SUVmax < 4.4 had nondiagnostic results. In contrast, targeted biopsies based on 18FDG uptake demonstrated a higher diagnostic yield (38.7%) than pericardium. The sensitivity of 18FDG-PET/CT was 63.6%. The specificity was 71.9%. The positive predictive value was 20.6%. The negative predictive value 94.5%, and the accuracy was 71.0% for excluding malignancy based upon the FDG uptake patterns. It is possible to explore the differential diagnosis in some patients with difficult pericardiocentesis or pericardial biopsy in a noninvasive manner using on the SUVmax or uptake patterns. In addition, the biopsy strategy depending on 18FDG uptake is helpful to achieve biopsy more safely and with a higher yield. 18FDG-PET may enhance the diagnostic efficacy in patients with pericardial disease.

Preoperative cardiac troponin below the 99th-percentile upper reference limit and 30-day mortality after noncardiac surgery.

Preoperative high-sensitivity cardiac troponin (hs-cTn) above the 99th-percentile upper reference limit (URL) is associated with mortality after noncardiac surgery. This study aimed to evaluate whether preoperative hs-cTn concentrations above the lowest limit of detection (LOD) but below the 99th-percentile URL can predict mortality after noncardiac surgery.From January 2010 to April 2019, a total of 12,415 noncardiac surgical patients with preoperative hs-cTn I below the 99th-percentile URL were enrolled. The patients were divided into two groups according to preoperative hs-cTn I concentration: (1) [hs-cTn] below the LOD (6 ng/L), and (2) mildly elevated [hs-cTn] but below the 99th-percentile URL (40 ng/L). The primary outcome was 30-day mortality. Of the 12,415 patients enrolled, 7958 (64.1%) were in the LOD group whereas 4457 (35.9%) were in the mild elevation group. The incidence of 30-day mortality was significantly greater in the mild elevation group (2.1% vs. 4.0% hazard ratio [HR] 1.73; 95% confidence interval [CI] 1.39-2.16; p < 0.001) in the multivariate analyses. The propensity score matched analyses also produced a similar result (2.6% vs. 4.2% HR 1.61; 95% CI 1.26-2.07; p < 0.001). The threshold at which the risk of mortality increased corresponded to a preoperative hs-cTn I ≥ 12 ng/L. Patients with preoperative hs-cTn I above the LOD and below the 99th-percentile URL had greater 30-day mortality after noncardiac surgery.

Mildly Elevated Cardiac Troponin below the 99th-Percentile Upper Reference Limit after Noncardiac Surgery.

BACKGROUND AND OBJECTIVES: In patients with perioperative cardiac troponin (cTn) I below the 99th-percentile upper range of limit (URL), mortality according to cTn I level has not been fully evaluated. This study evaluated the association between postoperative cTn I level above the lowest limit of detection but within the 99th-percentile URL and 30-day mortality after noncardiac surgery. METHODS: Patients with cTn I values below the 99th-percentile URL during the perioperative period were divided into a no-elevation group with cTn I at the lowest limit of detection (6 ng/L) and a minor elevation group with cTn I elevation below the 99th percentile URL (6 ng/L < cTn I < 40 ng/L). The primary outcome was 30-day mortality. RESULTS: Of the 5,312 study participants, 2,582 (48.6%) were included in the no-elevation group and 2,730 (51.4%) were included in the minor elevation group. After propensity score-matching, the minor elevation group showed significantly increased 30-day mortality (0.5% vs. 2.3%; hazard ratio, 4.30; 95% confidence interval, 2.23-8.29; p<0.001). The estimated cutoff value of cTn I to predict 30-day mortality was 6 ng/L with the area under the receiver operating characteristic curve 0.657. CONCLUSIONS: A mild elevation of cTn I within the 99th-percentile URL after noncardiac surgery was significantly associated with increased 30-day mortality as compared with the lowest limit of detection. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0004244.

Postoperative statin treatment may be associated with improved mortality in patients with myocardial injury after noncardiac surgery.

Myocardial injury after noncardiac surgery (MINS) is recently accepted as a strong predictor of mortality, regardless of symptoms. However, anticoagulation is the only established treatment. This study aimed to evaluate the association between statin treatment and mortality after MINS. From January 2010 to June 2019, a total of 5,267 adult patients who were discharged after the occurrence of MINS were enrolled. The patients were divided into two groups according to statin prescription at discharge. The outcomes were 1-year and overall mortalities. Of the total 5,109 patients, 1,331 (26.1%) patients were in the statin group and 3,778 (73.9%) patients were in the no statin group. The 1-year and overall mortalities were significantly lower in the statin group compared with the no statin group (6.1% vs. 13.3%; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.41-0.74; p < 0.001 for 1-year mortality and 15.0% vs. 25.0%; HR, 0.62; 95% CI, 0.51-0.76; p < 0.001 for overall mortality). Analyses after inverse probability treatment weighting showed similar results (HR, 0.61; 95% CI, 0.50-0.74; p < 0.001 for 1-year mortality and HR, 0.70; 95% CI, 0.54-0.90; p = 0.006 for overall mortality), and the mortalities did not differ according to the dose of statin. Our results suggest that statin treatment may be associated with improved survival after MINS. A trial is needed to confirm this finding and establish causality.

Prevention of medical malpractice and disputes through analysis of lawsuits related to coronary angiography and intervention.

BACKGROUND/AIMS: Possible fatal complications arising from coronary angiography (CAG), percutaneous coronary intervention (PCI), and coronary artery disease itself, are likely to cause medical disputes. Presenting the current status and reasons for judgments given in lawsuits related to CAG/PCI, this study aimed to identify ways to prevent unnecessary disputes and medical malpractice suits related to CAG/PCI through lawsuit analysis. METHODS: A total of 13 cases (20 judgments) found in the Supreme Court of Korea's Written Judgment Management System from 1998 to 2017 were analyzed. RESULTS: Coronary artery injury was the most common causative complication that led to lawsuits (n = 6, 46%). Six cases (46%) were ruled in favor of the plaintiff for violation of duty of care (n = 4) and duty of explanation (n = 2), respectively. Cases that violated duty of care included two errors in intra-procedure device manipulation, one in pre-procedure diagnosis, and one in management of post-procedure complication. Lack of explanation regarding the risk of complications was pointed out in both cases that violated duty of explanation. The average awarded amount for the damages was 114,436,064 Korean won. CONCLUSION: Physicians need not fear unfair judgments so long as they follow standard of care because the Court consistently looked at the probability, the foreseeability, and the evidence. Therefore, maintaining standard of care is important. Besides, specific, detailed, and comprehensible explanations, including the risk of complications in addition to the necessity of procedures, are important to ensure the patient clearly understands the possible risk of adverse outcomes.

Medical malpractice related to drug-induced anaphylaxis: An analysis of lawsuit judgments in South Korea.

Drug-induced anaphylaxis (DIA) is a highly paradoxical disorder involving a fatal response to medicines prescribed for therapeutic purposes. This study aimed to improve the awareness on DIA and to prevent errors through an analysis of lawsuit judgments.Sentenced judgments involving DIA from 1998 to 2017 using the database of the Korean Supreme Court Judgment System were collected. General characteristics, results, and recognized negligence of DIA litigation cases were analyzed.Of 27 lawsuit cases included, antibiotics (n = 6, 22.2%), radiocontrast media (n = 6, 22.2%), and non-steroidal anti-inflammatory drugs (n = 5, 18.5%) were the most common drugs that had caused DIA. Cardiac arrest was reported in 23 cases (85.2%). The median time interval from drug administration to diagnosis and from diagnosis to cardiac arrest were 7 (interquartile range, IQR = 0-35) and 5 minutes (IQR = 0-33), respectively, suggesting insufficient time to cope with anaphylaxis. Consequently, either death (n = 18, 66.7%) or ischemic brain injury (n = 9, 33.3%) occurred in all cases. Violation of duty of care was recognized in 19 cases (70.4%) with median awarded amount of $106,060 (IQR = $70,296-$168,363). The recognized negligence included inadequate observation after drug administration (n = 6), delayed or missed epinephrine administration (n = 6), ignoring a history of allergy or drug hypersensitivity (n = 6), and prescription error (n = 5).It is necessary to improve the awareness on DIA, because making a trivial error in any process of history taking, drug prescription and administration, observation, and/or emergency treatment may have fatal consequences that can lead to indemnity.

Influence of previous statin therapy on cholesterol-lowering effect of ezetimibe.

BACKGROUND AND OBJECTIVES: The inhibition of cholesterol absorption by ezetimibe increases cholesterol synthesis. The effect of inhibition of cholesterol synthesis on cholesterol absorption is controversial. The influence of these interactions on cholesterol levels is unknown. We investigated on the extent to which cholesterol levels were affected by the reaction of one pathway to the inhibition of the other pathway. SUBJECTS AND METHODS: This case-controlled study enrolled 198 patients who needed cholesterol-lowering drugs. Ezetimibe (10 mg) was administered to the patients with (n=58) and without on-going statin therapy (n=58). Simvastatin (20 mg) was administered to the patients treated with (n=41) and without ezetimibe (n=41). RESULTS: Ezetimibe without statin lowered the total cholesterol by 13.3±8.8% (p<0.001) and the low density lipoprotein-cholesterol (LDL-C) by 18.7±15.3% (p<0.001). Ezetimibe added to statin decreased the total cholesterol by 21.1±7.7% (p<0.001) and the LDL-C by 29.9±12.6% (p<0.001). The total cholesterol and LDL-C were reduced more by ezetimibe in patients with statin therapy than in those without statin therapy (p<0.001 and p<0.001, respectively). The differences in the effect of simvastatin on total cholesterol and LDL-C between the patients with and without ezetimibe showed borderline significance (p=0.10 and p=0.055, respectively). CONCLUSION: A prior inhibition of cholesterol synthesis by statin enhanced the effect of ezetimibe on total cholesterol and LDL-C by 7.8% and 11.2%, respectively. This finding suggests that ezetimibe increased cholesterol synthesis, resulting in a significant elevation of cholesterol levels.

Fenofibrate reduces C-reactive protein levels in hypertriglyceridemic patients with high risks for cardiovascular diseases.

BACKGROUND AND OBJECTIVES: The effects of fenofibrate on C-reactive protein (CRP) are under debate. We investigated the effect of fenofibrate on CRP levels and the variables determining changes. SUBJECTS AND METHODS: This case-control study enrolled 280 hypertriglyceridemic patients who were managed either with 200 mg of fenofibrate (Fenofibrate group, n=140) or with standard treatment (comparison group, n=140). CRP levels were measured before and after management for 2 months. RESULTS: CRP levels decreased in both the fenofibrate (p=0.003) and comparison (p=0.048) groups. Changes in CRP levels were not significantly different between the two groups (p=0.27) and were negatively associated with baseline CRP levels (r=-0.47, p<0.001). In patients with a baseline CRP level ≥1 mg/L, CRP levels also decreased in both groups (p=0.000 and p=0.001 respectively), however, more in the fenofibrate group than in the comparison group (p=0.025). The reduction of CRP was associated with higher baseline CRP levels (r=-0.29, p=0.001), lower body mass index (BMI, r=0.23, p=0.007), and fenofibrate therapy (r=0.19, p=0.025). CRP levels decreased more in the fenofibrate group than in the comparison group in patients with a BMI ≤26 kg/m(2) with borderline significance (-1.21±1.82 mg/L vs. -0.89±1.92 mg/L, p=0.097). In patients with a high density lipoprotein-cholesterol level <40 mg/dL, CRP levels were reduced only in the fenofibrate group (p=0.006). CONCLUSION: Fenofibrate reduced CRP levels in hypertriglyceridemic patients with high CRP and/or low high density lipoprotein-cholesterol levels and without severe overweight. This finding suggests that fenofibrate may have an anti-inflammatory effect in selected patients.

Relation Between RR Intervals and Early Diastolic Mitral Annular Velocities in Atrial Fibrillation.

BACKGROUND AND OBJECTIVES: Irregular RR intervals in atrial fibrillation (AF) make beat-to-beat changes in left ventricular (LV) systolic performance. Early diastolic mitral annular velocity (E') is one of the well-established parameters for evaluating LV diastolic function. The relation between RR intervals and E's is unknown. The aim of this study was to observe the influence of continuous changes in RR interval on the parameter for diastolic function in AF. SUBJECTS AND METHODS: Echocardiography was performed in 117 patients with AF. E' was adjusted for the effect of pre-preceding RR interval (RR-2) using the logarithmic equation between RR-2 and E'. The logarithmic equation between adjusted E' and preceding RR interval (RR-1) was calculated. RESULTS: The slope in the relation between RR-1 and E' varied from -2.5 to 2.6. The slope was lower (more likely negative) in patients with higher ratio of early diastolic mitral flow velocity (E) to E' (r=-0.21, p=0.023), ischemic heart disease (IHD, r=0.21, p=0.026), and higher systolic blood pressure (r=-0.19, p=0.046). When patients were divided into these 3 groups on the basis of slope, the lowest slope group (<-0.55, n=39) was associated with higher E'/E (p=0.004) and IHD (p=0.018) compared with the highest slope group (>0.57, n=39). The slope with regards to the relationship between RR-2 and E' also varied from -3.4 to 3.1. CONCLUSION: Changes in RR intervals had variable effects on E's according to clinical variables in AF.