Calprotectin in patients with rheumatoid arthritis: relation to clinical and laboratory variables of disease activity.

Calprotectin (L1) is a major granulocyte and monocyte protein which is released during activation of these cells. The plasma level of L1 is thought to reflect disease activity in rheumatoid arthritis (RA). In our cross sectional study of 70 patients with RA, L1 had significant correlations with erythrocyte sedimentation rate (r = 0.50), C-reactive protein (r = 0.58), orosomucoid (r = 0.62), platelet count (r = 0.42), leukocyte count (r = 0.33) and IgM rheumatoid factor (r = 0.32); and with the following clinical variables: number of swollen joints (r = 0.24), grip strength (r = -0.22), PIP joint circumferences (r = 0.33) and a combined global assessment score (r = 0.24). L1 was higher in seropositive (median 14,861 micrograms/l) than seronegative patients (median 10,487 micrograms/l) (p less than 0.03).     

Myocardial amiodarone and desethylamiodarone concentrations in patients undergoing cardiac transplantation

Myocardial amiodarone and desethylamiodarone concentrations were measured at multiple sites in the explanted heart in four patients who underwent cardiac transplantation. Patients were taking amiodarone, 200 to 400 mg/day (mean 300 +/- 115), for 88 to 428 days (mean 229 +/- 148). The mean cumulative dose was 58 +/- 21.3 g. Plasma amiodarone concentration in three subjects was 204, 312 and 419 ng/ml and desethylamiodarone concentration was 268, 513 and 880 ng/ml, respectively. Significant interindividual variability in myocardial concentrations of amiodarone and desethylamiodarone was observed (p less than 0.05). Mean myocardial amiodarone concentration ranged from 4 +/- 1.0 to 29 +/- 17.2 micrograms/g (p less than 0.05); mean desethylamiodarone concentration ranged from 22 +/- 8.8 to 141 +/- 102.5 micrograms/g (p less than 0.05). At each site, save for fat, myocardial desethylamiodarone concentration was higher than amiodarone concentration. Greater intraindividual variability was observed in myocardial desethylamiodarone compared with amiodarone concentration particularly in septal and scar tissue (p = NS). No significant relation was found between myocardial concentration and duration of treatment. In patients with significant ventricular disease, usefulness of plasma amiodarone and desethylamiodarone concentration to estimate myocardial concentration is limited by intra- and interindividual variability.     

Myocardial ischemic conditioning: Physiological aspects and clinical applications in cardiac surgery

Ischemia–reperfusion is a major determinant of myocardial impairment in patients undergoing cardiac surgery. The main goal of research in cardioprotection is to develop effective techniques to avoid ischemia–reperfusion lesions. Myocardial ischemic conditioning is a powerful endogenous cardioprotective phenomenon. First described in animals in 1986, myocardial ischemic conditioning consists of applying increased tolerance of the myocardium to sustained ischemia by exposing it to brief episodes of ischemia–reperfusion. Several studies have sought to demonstrate its effective cardioprotective action in humans and to understand its underlying mechanisms. Myocardial ischemic conditioning has two forms: ischemic preconditioning (IPC) when the conditioning stimulus is applied before the index ischemia and ischemic postconditioning when the conditioning stimulus is applied after it. The cardioprotective action of ischemic conditioning was reproduced by applying the ischemia–reperfusion stimulus to organs remote from the heart. This non-invasive manner of applying ischemic conditioning has led to its application in clinical settings. Clinical trials for the different forms of ischemic conditioning were mainly developed in cardiac surgery. Many studies suggest that this phenomenon can represent an interesting adjuvant to classical cardioprotection during on-pump cardiac surgery. Ischemic conditioning was also tested in interventional cardiology with interesting results. Finally, advances made in the understanding of mechanisms that underlie the cardioprotective action of ischemic conditioning have paved the way to a new form of myocardial conditioning which is pharmacological conditioning.     

Tamponade in patients undergoing cardiac surgery: A clinical-echocardiographic diagnosis

The purpose of this study was to evaluate the sensitivity of current echocardiographic criteria in detecting cardiac tamponade in the patient who has undergone cardiovascular surgery. Because the current echocardiographic criteria for tamponade were initially developed and studied predominantly in patients with medical problems, relatively less information is available in patients who have undergone cardiac surgery. Of 848 consecutive patients who underwent cardiovascular surgery, patients were selected for the study if they had clinical or hemodynamic deterioration and had undergone an echocardiogram just before a successful pericardiocentesis or a surgical evacuation of pericardial blood or clot. The echocardiograms were evaluated for evidence of chamber collapse, cardiac motion, Doppler flow variations, and the location and width of pericardial separation. Fourteen patients were identified who met the inclusion criteria (clinical or hemodynamic deterioration, recent echocardiogram, and successful intervention) for cardiac tamponade. The clinical and hemodynamic findings were hypotension (13 patients), low cardiac output (7), low urine output (3), cardiopulmonary arrest (1), elevated central venous pressure (1), and shortness of breath (1). In these patients current echocardiographic criteria were seen infrequently: chamber collapse in the right atrium (6 of 14 patients) and right ventricle (4 of 14); Doppler flow variation (2 of 5); and swinging heart (0 of 15), whereas increased pericardial separation (≥10 mm) was seen in all (14 of 14) the patients. Although the sensitivity of current echocardiographic criteria for tamponade was not high (0% to 43%), the sensitivity of a combined index (unexplained clinical or hemodynamic deterioration and pericardial echo separation width ≥10 mm) was high (100%) in this group of patients who had undergone surgery. In this study standard echocardiographic criteria were found to be relatively unreliable in detecting cardiac tamponade in patients who had undergone cardiac surgery. However, the presence of ≥10 mm of pericardial separation (fluid/clot) and unexplained clinical or hemodynamic deterioration appeared to be sensitive in detecting tamponade.     

Intensity of statin therapy in relation to myocardial ischemia, troponin T release, and clinical cardiac outcome in patients undergoing major vascular surgery.

OBJECTIVES: This study sought to examine whether higher statin doses and lower low-density lipoprotein (LDL) cholesterol are associated with improved cardiac outcome in vascular surgery patients. BACKGROUND: Statins may have cardioprotective effects during major vascular surgery. METHODS: In a prospective study of 359 vascular surgery patients, statin dose and cholesterol levels were recorded preoperatively. Myocardial ischemia and heart rate variability were assessed by 72-h 12-lead electrocardiography starting 1 day before to 2 days after surgery. Troponin T was measured on postoperative day 1, 3, 7, and before discharge. Cardiac events included cardiac death or nonfatal Q-wave myocardial infarction at 30 days and follow-up (mean 2.3 years). RESULTS: Perioperative myocardial ischemia, troponin T release, 30-day events, and late cardiac events occurred in 29%, 23%, 4%, and 18%, respectively. In multivariate analysis, lower LDL cholesterol (per 10 mg/dl) correlated with lower myocardial ischemia (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.80 to 0.95), troponin T release (OR 0.89, 95% CI 0.82 to 0.96), and 30-day (OR 0.89, 95% CI 0.78 to 1.00) and late cardiac events (hazard ratio 0.91, 95% CI 0.84 to 0.96). Higher statin doses (per 10% of maximum recommended dose) correlated with lower myocardial ischemia (OR 0.85, 95% CI 0.76 to 0.93), troponin T release (OR 0.84, 95% CI 0.76 to 0.93), and 30-day (OR 0.62, 95% CI 0.40 to 0.96) and late cardiac events (hazard ratio 0.76, 95% CI 0.65 to 0.89), even after adjusting for LDL cholesterol. Significantly higher perioperative heart rate variability was observed in patients with higher statin doses. CONCLUSIONS: Higher statin doses and lower LDL cholesterol correlate with lower perioperative myocardial ischemia, perioperative troponin T release, and 30-day and late cardiac events in major vascular surgery.     

Predicting cardiac complications in patients undergoing non-cardiac surgery

The authors prospectively studied 455 consecutive patients referred to the general medical consultation service for cardiac risk assessment prior to non-cardiac surgery, in order to validate a previously derived multifactorial index in their clinical setting. They also tested a version of the index that they had modified to reflect factors they believed to be important. For patients undergoing major surgery, the original index performed less well in the validation data set than in the original derivation set (p<0.05), but still added predictive information to a statistically significant degree (p<0.05). The modified index also added predictive information for patients undergoing both major and minor surgery, demonstrating an area under the Receiver Operating Characteristic curve of 0.75 (95% confidence interval of 0.70 to 0.80). A simple nomogram is presented which will enable conversion of pretest probabilities into posttest probabilities using the likelihood ratios associated with each risk score. It is recommended that clinicians estimate local overall complication rates (pretest probabilities) for the clinically relevant populations in their settings before they apply the predictive properties (likelihood ratios) demonstrated in this study in order to calculate cardiac risks for individual patients (posttest probabilities). Received from the Departments of Health Administration and Medicine, University of Toronto, and the Division of General Internal Medicine and Clinical Epidemiology, Toronto General Hospital, Toronto, Ontario, Canada. Supported by an Ontario Ministry of Health Research Grant (DM616 and 00621) and the Toronto General Hospital Foundation. Also supported in part by the National Health and Research Development Program (Canada) through a National Health Research Scholar Award to Dr. Detsky.     

Aspirin-induced platelet inhibition in patients undergoing cardiac surgery

Platelet function and response to pharmacological inhibition are altered by cardiac surgery. For example, aggregation is increased early after aortic valve replacement (AVR) and platelet response to aspirin is often insufficient after coronary artery bypass grafting (CABG). We hypothesized that the effect of aspirin administration after cardiac surgery might be impaired due to platelet activation. Therefore, the antiplatelet effect of aspirin was compared in patients (n?=?20 per group) after CABG and AVR surgery (bileaflet prosthesis). Arachidonic acid-induced aggregation (turbidimetry) and thromboxane formation (radioimmunoassay) were determined before and 1, 5, and 10 days after surgery. In CABG-patients, antiplatelet treatment had been discontinued 10 days before surgery. Oral aspirin was started on day 1 after CABG. AVR-patients did not receive oral aspirin. Before surgery, platelet aggregation and thromboxane formation were significantly higher in patients with aortic stenosis. After CABG, thromboxane formation was not significantly changed from control values before surgery (66?±?13% on day 10) despite oral aspirin treatment, whereas thromboxane formation in patients undergoing AVR significantly increased compared to values before surgery (216?±?29% on day 10). In both groups of patients, 100?µmol/l aspirin in vitro largely inhibited platelet function before surgery, with markedly attenuated effects after surgery. In conclusion, thromboxane formation increased after AVR but not after CABG. The antiplatelet effect of aspirin, therefore, may be impaired after CABG by increased platelet activity. An additional in vitro “resistance” of platelets was seen after both CABG and AVR.     

Aspirin-induced platelet inhibition in patients undergoing cardiac surgery

Platelet function and response to pharmacological inhibition are altered by cardiac surgery. For example, aggregation is increased early after aortic valve replacement (AVR) and platelet response to aspirin is often insufficient after coronary artery bypass grafting (CABG). We hypothesized that the effect of aspirin administration after cardiac surgery might be impaired due to platelet activation. Therefore, the antiplatelet effect of aspirin was compared in patients (n = 20 per group) after CABG and AVR surgery (bileaflet prosthesis). Arachidonic acid-induced aggregation (turbidimetry) and thromboxane formation (radioimmunoassay) were determined before and 1, 5, and 10 days after surgery. In CABG-patients, antiplatelet treatment had been discontinued 10 days before surgery. Oral aspirin was started on day 1 after CABG. AVR-patients did not receive oral aspirin. Before surgery, platelet aggregation and thromboxane formation were significantly higher in patients with aortic stenosis. After CABG, thromboxane formation was not significantly changed from control values before surgery (66 +/- 13% on day 10) despite oral aspirin treatment, whereas thromboxane formation in patients undergoing AVR significantly increased compared to values before surgery (216 +/- 29% on day 10). In both groups of patients, 100 micromol/l aspirin in vitro largely inhibited platelet function before surgery, with markedly attenuated effects after surgery. In conclusion, thromboxane formation increased after AVR but not after CABG. The antiplatelet effect of aspirin, therefore, may be impaired after CABG by increased platelet activity. An additional in vitro "resistance" of platelets was seen after both CABG and AVR.     

Myocardial injury in critically ill patients: relation to increased cardiac troponin I and hospital mortality

OBJECTIVE: To examine the relationship between myocardial injury, assessed by cardiac troponin I (cTnI) levels, and outcome in selected critically ill patients without acute coronary syndromes or cardiac dysfunction. DESIGN AND SETTING: Prospective, observational study in the emergency ICU of a university teaching hospital. POPULATION: Over a 6-month period, 217 consecutive patients admitted to the ICU were studied. METHODS AND RESULTS: cTnI assays were performed in all patients on admission to the ICU. The incidence of myocardial injury, defined by cTnI level > 0.1 ng/mL, was 32% (69 of 217 patients). Overall mortality was 27% (58 of 217 patients). Patients with myocardial injury had a mortality rate of 51%, compared with only 16% mortality for those without myocardial injury (p < 0.001). The hospital mortality rate was highest among older patients (71 +/- 14% vs 58.5 +/- 20%, p < 0.0001) and patients with higher simplified acute physiology scale (SAPS) II score (62 +/- 25% vs 37 +/- 17%, p < 0.0001). Mechanical ventilation was associated with higher in-hospital death (50% vs 31%, for patients who died in the hospital vs those who were discharged alive; p = 0.03). Elevated blood levels of cTnI were found to be independently associated with hospital mortality, regardless of the presence of SAPS II score and mechanical ventilation, in the logistic regression analysis (odds ratio, 2.09; 95% confidence interval, 1.06 to 4.11; p = 0.01). CONCLUSIONS: This study demonstrates the high frequency of myocardial injury (32%) in critically ill patients without acute coronary syndromes or cardiac dysfunction on admission to ICU. Myocardial injury is an independent determinant of hospital mortality. Assessment of myocardial injury on admission to ICU would make it possible to identify patients at increased risk of death.     

Hemoglobin optimization and transfusion strategies in patients undergoing cardiac surgery

Although red blood cells (RBCs) transfusion is sometimes associated with adverse reactions, anemia could also lead to increased morbidity and mortality in high-risk patients. For these reasons, the definition of perioperative strategies that aims to detect and treat preoperative anemia, prevent excessive blood loss, and define “optimal” transfusion algorithms is crucial. Although the treatment with preoperative iron and erythropoietin has been recommended in some specific conditions, several controversies exist regarding the benefit-to-risk balance associated with these treatments. Further studies are needed to better define the indications, dosage, and route of administration for preoperative iron with or without erythropoietin supplementation. Although restrictive transfusion strategies in patients undergoing cardiac surgery have been shown to effectively reduce the incidence and the amount of RBCs transfusion without increase in side effects, some high-risk patients (e.g., symptomatic acute coronary syndrome) could benefit from higher hemoglobin concentrations. Despite all efforts made last decade, a significant amount of work remains to be done to improve hemoglobin optimization and transfusion strategies in patients undergoing cardiac surgery.     

Platelet reactivity in overweight and obese patients undergoing cardiac surgery

Body mass index (BMI) and specifically overweight and obesity have been associated with an increased platelet reactivity in different series of patients. This information is derived by different laboratory platelet function tests (PFTs) like mean platelet volume (MPV), platelet microparticles, thromboxane B2 metabolites, and others. Point-of-care PFT, which are often used in cardiac surgery, are rarely addressed. The present study aims to verify platelet reactivity using multiple-electrode aggregometry (MEA) as a function of BMI in cardiac surgery patients. One-hundred ninety-eight cardiac surgery patients free from the effects of drugs acting on the P2Y₁₂ receptor and undergoing cardiac surgery received MEA-PFT immediately before surgery. Platelet reactivity was compared between normal weight and overweight–obese subjects. There were 99 underweight/normal (BMI < 25), 60 overweight (BMI ≥ 25) and 39 obese (BMI ≥ 30) patients. Overweight–obese patients did not show higher platelet counts nor a clear platelet hyper-reactivity, when tested with MPV and MEA ADP test. At TRAPtest, the overweight/obese patients had a significantly (P = 0.011) higher platelet reactivity (median 118, interquartile range 106–136) than controls (median 112, interquartile range 101–123) and a higher rate of platelet hyper-reactivity (odds ratio 2.19, 95% confidence interval 1.15–4.16, P = 0.016) in a multivariable model. A minor association was found between the BMI and platelet reactivity at TRAPtest, with a higher degree of activity for increasing BMI. The BMI determines an increased thrombin-dependent platelet reactivity in cardiac surgery patients. Thrombin is extensively formed during cardiac surgery, and this may explain the lower postoperative bleeding observed in obese patients in previous studies.     

Cardiac resynchronization therapy in patients undergoing open-chest cardiac surgery

Purpose

Few data are available on the effects of cardiac resynchronization therapy (CRT) in candidates for cardiac surgery and affected by severe heart failure (HF). The aim of our analysis is to evaluate the percentage of patients who maintain indication for CRT after surgery and the efficacy of CRT in those patients subsequently implanted.

Methods

We enrolled 124 HF patients with indication both to heart surgery and to CRT. During surgery, an epicardial left ventricular lead was implanted, tunneled to a subclavear pocket, and capped. Afterward, patients were periodically reassessed to confirm indication for CRT.

Results

CRT indication was confirmed within 1 month from surgery in 54 patients (group A) and in 33 patients within 6 months (group B). In group A and B, 63% and 71% of patients were considered responders according to an arbitrary five-point increase of left ventricular ejection fraction (LVEF), respectively. The assessment of clinical response at 1 year, based on the definitions proposed by Packer, identified 63% and 80% of responders in group A and B, respectively.

Conclusions

Our data show that a remarkable percentage of patients maintain an indication for CRT after cardiac surgery (76%), while in the remaining 24% the lack of an indication is confirmed by a higher LVEF at last follow-up. In combination with surgery, CRT proved to be an effective therapy in those patients who were subsequently implanted. The suggested method is simple, without significant adjunctive risks, and allows easier CRT implantation with stable thresholds.     

Mid-term survival of patients undergoing major cardiac surgery

Introduction and objectives

Evaluating patient outcomes following cardiac surgery is a means of measuring the quality of that surgery. The present study analyzes survival and the risk factors associated with mid-term mortality of patients undergoing cardiac surgery in Son Dureta University Hospital (Palma, Balearic Islands, Spain).

Methods

From November 2002 thru December 2007, 1938 patients underwent interventions. Patients were stratified in 4 age groups. Of 1900 patients discharged from hospital, 1844 were followed until December 31, 2008. Following discharge, we constructed Kaplan-Meier survival curves and performed Cox regression analysis to determine which variables associated with mid-term mortality.

Results

In-hospital mortality of the 1,938 patients was 1.96% (CI 95%, 1.36%-2.6%). Survival probability at 1, 3 and 5 years follow-up was 98%, 94% and 90%, respectively. Mean follow-up was 3.2 (0.01-6.06) years. Patients aged ≥70 years showed a lower survival rate than those aged <70 (log rank test, P <.0001). At the end of follow-up, mortality was 6.5% (CI 95%, 5.4%-7.7%). Age ≥70 years, a history of severe ventricular dysfunction (ejection fraction <30%), severe pulmonary hypertension, diabetes mellitus, preoperative anemia, postoperative stroke, and hospital stay were independently associated with mid-term mortality.

Conclusions

Mid-term survival after discharge was highly satisfactory. Mid-term mortality varied with age and other pre- and postoperative factors.Full English text available from: www.revespcardiol.org     

Myocardial reperfusion: its assessment and its relation to clinical outcomes

It has become increasingly apparent that epicardial blood flow restoration is necessary, but not sufficient, to achieve optimal clinical outcomes in the setting of acute coronary syndromes. Indeed, clinical outcomes are strongly associated with myocardial perfusion. The diagnostic tools available to assess myocardial perfusion following acute myocardial infarction and their association with clinical outcomes are reviewed here. Many simple angiographic markers--the Thrombolysis in Myocardial Infarction (TIMI) count frame, TIMI myocardial perfusion grade, pulsatile flow--are all readily available measures and are strongly related to clinical outcomes. Other tools, while accurate, remain limited by their high cost, low availability, and complexity for routine use.     

Sudden deafness in patients undergoing cardiac surgery with extracorporeal circulation

Between January 1974 and December 1986, 5,975 patients underwent open heart surgery at National Institute of Cardiology "Ignacio Chávez". We reviewed all open heart cases carried out at this Center. Eleven patients (1.8/1000) presented unilateral sudden hearing loss following cardiopulmonary bypass surgery. Pure tone audiograms, speech reception threshold, discrimination testing, tympanometry and stapedius reflex testing were carried out. We then studied the relationship between the auditory deficit and the type of surgical procedure, length of time on the pump, preexisting ear disease, coexistence of diabetes, use of ototoxic drugs and occurrence of hemodynamic complications. There are 3 possible causes for hearing loss in cardiopulmonary bypass: 1) Microembolism from the cardiopulmonary bypass pump to the arteries that supply only the cochlea. 2) Decreasing cerebral flow, or 3) Microhemorrhage of the internal ear. Ototoxic drugs are used frequently, but the hallmark of these drugs is bilateral toxicity, and all the cases under discussion have been unilateral. Unilateral sudden deafness after open heart surgery constitutes another complication, fortunately rare and benign in most cases. Further studies should be undertaken to clarify the pathophysiology of this entity.