Pallav Shah

Methylprednisolone in patients undergoing cardiopulmonary bypass (SIRS): a randomised, double-blind, placebo-controlled trial

BACKGROUND Cardiopulmonary bypass initiates a systemic inflammatory response syndrome that is associated with postoperative morbidity and mortality. Steroids suppress inflammatory responses and might improve outcomes in patients at high risk of morbidity and mortality undergoing cardiopulmonary bypass. We aimed to assess the effects of steroids in patients at high risk of morbidity and mortality undergoing cardiopulmonary bypass. METHODS The Steroids In caRdiac Surgery (SIRS) study is a double-blind, randomised, controlled trial. We used a central computerised phone or interactive web system to randomly assign (1:1) patients at high risk of morbidity and mortality from 80 hospital or cardiac surgery centres in 18 countries undergoing cardiac surgery with the use of cardiopulmonary bypass to receive either methylprednisolone (250 mg at anaesthetic induction and 250 mg at initiation of cardiopulmonary bypass) or placebo. Patients were assigned with block randomisation with random block sizes of 2, 4, or 6 and stratified by centre. Patients aged 18 years or older were eligible if they had a European System for Cardiac Operative Risk Evaluation of at least 6. Patients were excluded if they were taking or expected to receive systemic steroids in the immediate postoperative period or had a history of bacterial or fungal infection in the preceding 30 days. Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcomes were 30-day mortality and a composite of death and major morbidity (ie, myocardial injury, stroke, renal failure, or respiratory failure) within 30 days, both analysed by intention to treat. Safety outcomes were also analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00427388. FINDINGS Patients were recruited between June 21, 2007, and Dec 19, 2013. Complete 30-day data was available for all 7507 patients randomly assigned to methylprednisolone (n=3755) and to placebo (n=3752). Methylprednisolone, compared with placebo, did not reduce the risk of death at 30 days (154 [4%] vs 177 [5%] patients; relative risk [RR] 0·87, 95% CI 0·70-1·07, p=0·19) or the risk of death or major morbidity (909 [24%] vs 885 [24%]; RR 1·03, 95% CI 0·95-1·11, p=0·52). The most common safety outcomes in the methylprednisolone and placebo group were infection (465 [12%] vs 493 [13%]), surgical site infection (151 [4%] vs 151 [4%]), and delirium (295 [8%] vs 289 [8%]). INTERPRETATION Methylprednisolone did not have a significant effect on mortality or major morbidity after cardiac surgery with cardiopulmonary bypass. The SIRS trial does not support the routine use of methylprednisolone for patients undergoing cardiopulmonary bypass. FUNDING Canadian Institutes of Health Research.

Rationale and design of the Left Atrial Appendage Occlusion Study (LAAOS) III

BACKGROUND Occlusion of the left atrial appendage (LAA) is a promising approach to stroke prevention in atrial fibrillation (AF). However, evidence of its efficacy and safety to date is lacking. We herein describe the rationale and design of a definitive LAA occlusion trial in cardiac surgical patients with AF. METHODS We plan to randomize 4,700 patients with AF in whom on-pump cardiac surgical procedure is planned to undergo LAA occlusion or no LAA occlusion. The primary outcome is the first occurrence of stroke or systemic arterial embolism over a mean follow-up of four years. Other outcomes include total mortality, operative safety outcomes (chest tube output in the first post-operative 24 hours, rate of post-operative re-exploration for bleeding in the first 48 hours post-surgery and 30-day mortality), re-hospitalization for heart failure, major bleed, and myocardial infarction. RESULTS Left Atrial Appendage Occlusion Study (LAAOS) III is funded in a vanguard phase by the Canadian Institutes for Health Research (CIHR), the Canadian Network and Centre for Trials Internationally, and the McMaster University Surgical Associates. As of September 9, 2013, 162 patients have been recruited into the study. CONCLUSIONS LAAOS III will be the largest trial to explore the efficacy of LAA occlusion for stroke prevention. Its results will lead to a better understanding of stroke in AF and the safety and efficacy of surgical LAA occlusion.

Survival after myocardial revascularization for ischemic cardiomyopathy: a prospective ten-year follow-up study.

Abstract Objective The aim was to prospectively analyze all-cause mortality, predictors of survival, and late functional results after myocardial revascularization for ischemic cardiomyopathy over a 10-year follow-up. Methods We prospectively studied 57 patients with stable coronary artery disease and poor left ventricular ejection function ( Results Operative mortality was 1.7% (1/57). The mean left ventricular ejection fraction (0.30) at 15 months postoperatively did not change from before operation (0.28, P = .09). There were 8 deaths at 1 year and 42 deaths over the course of the study, producing a survival of 82.5% at 1 year, 55.7% at 5 years, and 23.9% at 10 years (95% confidence interval: 14.6%-39.1%). Symptom-free survival was 77.2% at 1 year and 20.3% at 10 years. The leading cause of death was heart failure in 29% (12/42). Multivariate analysis showed that large reversible defects on stress thallium were associated with improved left ventricular ejection fraction at 1 year ( P = .01) but only male sex was associated with improved long-term survival ( P = .036). Conclusions Myocardial revascularization for ischemic cardiomyopathy is associated with good functional relief from the symptoms of angina initially and, to a lesser extent, heart failure. Revascularization may have the advantage of preserving the remaining left ventricular function. However, the long-term mortality remains high.

Risk Factors and Management Approach for Deep Sternal Wound Infection After Cardiac Surgery at a Tertiary Medical Centre

BACKGROUND Deep sternal wound infection (DSWI) is a rare but severe complication following cardiac surgery. Our study investigated the risk factors and treatment options for patients who developed DSWI at our institution between May 1988 and April 2008. METHOD Data was collected prospectively in a database and information on demographics reviewed retrospectively on 5649 patients who underwent cardiac surgery during this period. RESULTS The incidence of DSWI was 34/5649 (0.6%). These patients were older (mean age 66.1 vs. 64.5), more likely to die (in hospital mortality 11.8% vs. non DSWI group 1.8%) and had longer hospital stays (DSWI group mean stay 25 days vs. non DSWI group 9 days). Using Fishers exact test the risk predictors for DSWI determined at our institution included diabetes managed with oral medications (p=0.021), previous cardiac surgery (p=0.038), BMI≥30 (p=0.041), LVEF≤30 (p=0.010), IABP usage (p=0.028) and homologous blood usage (p<0.001). Most commonly bilateral pectoralis major muscle flap (BPMMF) was used for treatment of DSWI (11/30, 36.7%). CONCLUSION Ultimately our data was comparable to published data in the literature on known risk predictors.

Early and mid-term outcomes following surgical management of infective endocarditis with associated cerebral complications: a single centre experience

BACKGROUND Surgical management of patients with infective endocarditis (IE) who have suffered preoperative cerebrovascular complications remains controversial. This study evaluates the impact of timing from stroke to valvular surgery on the early and mid-term neurological sequelae, functional status and quality of life in this high-risk group of patients with IE. METHOD Data on 13/108 (12%) patients with IE who suffered cerebrovascular complications during the period 1998-2009 was prospectively collected. Mean follow-up was 37.2 months (100% complete). RESULTS Three of 13 (23%) suffered haemorrhagic stroke, 10/13 (77%) had embolic events (nine, stroke; one, TIA). The clinical diagnosis was made by a neurologist in 6/13 (46%) and confirmed in all by CT scan. Twelve of 13 had motor deficit involving MCA territory. Thirty-day mortality was 2/13 (one, cardiac; one, neurological) with no late deaths. The mean time from embolic stroke to surgery was 2.3 weeks (range 3-60 days). The reason for operating on eight patients in less than two weeks was heart failure in five, uncontrolled sepsis, AMI and TIA (one each). 2/8 (25%) suffered additional postoperative neurological events (one, brain death, one, new MCA stroke). On follow-up of the remaining eight patients with embolic events, five had improved neurology and three had stable neurology. The mean time to surgery from haemorrhagic stroke was 5.8 weeks (range 3-60 days). Deficit improved in two patients (<1 week, 1; >8 weeks, 1). On follow-up the NYHA class was I-II in 6/11 (56%). The EQ-5D questionnaire was used to assess quality of life. Mean index for the group was 0.67 using the US preference-weighted index score (SD 0.27). CONCLUSIONS Results regarding timing for haemorrhagic stroke cannot be defined from the small numbers. Timely surgical intervention (embolic greater than two weeks and preferably four weeks in absence of heart failure) is associated with acceptable neurological outcome, functional class and quality of life.

Rationale and design of the Steroids in Cardiac Surgery trial

BACKGROUND Steroids may improve outcomes in high-risk patients undergoing cardiac surgery with the use of cardiopulmonary bypass (CBP). There is a need\ for a large randomized controlled trial to clarify the effect of steroids in such patients. METHODS We plan to randomize 7,500 patients with elevated European System for Cardiac Operative Risk Evaluation who are undergoing cardiac surgery with the use of CBP to methylprednisolone or placebo. The first coprimary outcome is 30-day all-cause mortality, and the most second coprimary outcome is a composite of death, MI, stroke, renal failure, or respiratory failure within 30 days. Other outcomes include a composite of MI or mortality at 30 days, new onset atrial fibrillation, bleeding and transfusion requirements, length of intensive care unit stay and hospital stay, infection, stroke, wound complications, gastrointestinal complications, delirium, postoperative insulin use and peak blood glucose, and all-cause mortality at 6 months. RESULTS As of October 22, 2013, 7,034 patients have been recruited into SIRS in 82 centers from 18 countries. Patients mean age is 67.3 years, and 60.4% are male. The average European System for Cardiac Operative Risk Evaluation is 7.0 with 22.1% having an isolated coronary artery bypass graft procedure, and 66.1% having a valve procedure. CONCLUSIONS SIRS will lead to a better understanding of the safety and efficacy of prophylactic steroids for cardiac surgery requiring CBP.

Contemporary results following surgical repair of acute type a aortic dissection (AAAD): a single centre experience.

OBJECTIVES The study aims to define predictors of neurological dysfunction, 30-day mortality, long-term survival and quality of life following repair of acute type A aortic dissection (AAAD). METHODS Between 2000 and 2008, 65 patients underwent repair of AAAD. Sixty-four pre-, intra- and post-operative variables were studied. Mean follow-up was 26.6 months. RESULTS The mean age was 61years; 60% were male and five had Marfans syndrome. At presentation, ischaemic ECG changes were seen in 45%, malperfusion syndrome in 59%, moderate-severe aortic regurgitation in 48% and tamponade in 16%. EF was <40% in 17%. There was a delay of >12hours between diagnosis and operation in 64%. Axillary cannulation was performed in 37%. Cerebral protection was by hypothermic arrest (HCA) alone (19%), HCA with retrograde cerebral perfusion (RCP) (11%), or HCA with antegrade cerebral perfusion (ACP) (46%). The procedure was performed on cross-clamp in 24%. Full arch replacement was performed in 14% and concomitant coronary artery grafting was performed in 11%. Post-operative neurological dysfunction was present in 33.8%. The only significant predictor of poor neurological outcome was full arch replacement (p=0.04) on univariate analysis. In-hospital OR 30 mortality was 23.53%. Significant predictors of mortality were low ejection fraction (p=0.017) and post-operative renal failure (p=0.012). Long-term survival was 70% at two years, 50% at five years and 25% at nine years. Functional outcomes and long-term quality of life were assessed in 69% of patients who were alive at last follow-up. Ninety percent of patients reported minimal limitation on functional scores. Quality of life was assessed using the EQ-5D questionnaire. Forty-eight percent of patients recorded full health with an overall mean index of 0.854 (where the best possible score is 1) using the US preference weighted index score. CONCLUSIONS Discharged patients have reasonable long-term survival and good quality of life.

Cardiac tumors in adults: surgical management and follow-up of 19 patients in an Australian tertiary hospital

The objective of this report is to share our experience with the different types of cardiac tumors, surgical management, postoperative complications and mid-term outcome of patients in an Australian tertiary hospital. Nineteen patients underwent cardiac surgery for tumors between 2001 and 2008. Their data was prospectively collected and retrospectively analyzed. The mean follow-up was 17 months. The follow-up was 100% through telephone interviews. There were multiple presenting symptoms with shortness of breath (7/19) as the most common. The tumors were atrial myxoma (14/19), fibroelastoma (2/19), angiosarcoma (1/19) and intravascular leiomyomatosis (1/19). A calcified thrombus (1/19) was misdiagnosed as a tumor. The fibroelastomas were shaved preserving valvular function. The angiosarcoma was incompletely resected with palliation intent. The leiomyomatosis and atrial myxoma were completely resected with satisfactory outcome. There was no in-hospital mortality. All patients were alive and were in New York Heart Association (NYHA) class I, except for the patient with a high-grade angiosarcoma who died eight months postoperatively. There was no evidence of recurrence in follow-up echocardiograms. Our experience and outcome is consistent with current literature. Atrial myxoma is the most common cardiac tumor and is curable with complete surgical resection. Fibroelastomas can be shaved off with low-risk of recurrence. Surgical management of angiosarcoma is palliative.

Return to work after coronary artery bypass in patients aged under 50 years

Background: This study was designed to identify factors associated with return to work and quality of life in patients undergoing primary coronary artery bypass at age <50 years. Methods: 172 patients <50-years old underwent primary coronary artery bypass between January 2000 and December 2006. Predictors of return to work were analysed from variables in a prospectively collected database and on follow-up by the SF-36 questionnaire in 129 (75%) patients. Results: 136 (79%) patients were working prior to surgery. The educational level was: primary 14.5%, secondary 47%, trade 22%, tertiary 13%, and postgraduate 3%. Type of occupation was blue collar 51%, white collar 41%, pensioner 27%, and unspecfied 8%. The mean follow-up was 86.4 ± 23.4 months. One hundred and twenty-six (69%) patients attended cardiac rehabilitation. Forty (23%) patients experienced recurrence of symptoms; 11 (6%) required reintervention. One hundred and twenty-seven (93%) patients returned to work postoperatively. Univariate predictors of return to work were male sex, blue-collar work, and working prior to surgery. Independent predictors of return to work were working prior to surgery and blue-collar work. Patients who returned to work had significantly higher scores in all 8 domains on the SF36-Questionnaire compared to those who did not return to work. Conclusions: Preoperative employment and blue collar occupation were associated with a higher rate of return to work after coronary artery bypass in patients of working age. Patients who returned to work had significantly better measured quality of life than those who did not.

Expression of fat mobilizing genes in human epicardial adipose tissue

BACKGROUND Epicardial adipose tissue (EAT) mass correlates with metabolic syndrome and coronary artery disease (CAD). However, little is known about the expression of genes involved in triglyceride (TG) storage and mobilization in EAT. We therefore analyzed the expression of genes involved in fat mobilization in EAT in comparison to subcutaneous abdominal adipose tissue (AAT) in CAD patients and in controls. METHODS EAT and AAT were obtained during coronary artery bypass graft (CABG) surgery from 16 CAD patients and from 14 non-CAD patients presenting for valve surgery. The state of atherosclerosis was assessed by angiography. RNA from tissues were extracted, reversibly transcribed and quantified by real time polymerase chain reaction (RT-PCR). The following genes were analyzed: perilipin-1 and -5 (PLIN1, PLIN5), lipoprotein lipase (LPL), hormone sensitive lipase (HSL), adipose triglyceride lipase (ATGL), comparative gene identification-58 (CIG-58), angiopoietin like protein 4 (ANGPTL4), in addition to interleukine-6 (IL-6), leptin (LEP) and adiponectin (ADPN). RESULTS A significant expression of all listed genes could be observed in EAT. The relative expression pattern of the 10 genes in EAT was comparable to the expression in AAT, yet there was a significantly higher overall expression in AAT. The expression of the listed genes was not different between CAD patients and controls. CONCLUSION It is suggested that the postulated difference in EAT volume between CAD patients and non-CAD patients is not caused by a differential mRNA expression of fat mobilizing genes. Further work on protein levels and enzyme activities will be necessary to get a complete picture.