Mohamed Amrani

Does off-pump coronary artery bypass (OPCAB) surgery improve the outcome in high-risk patients?: a comparative study of 1398 high-risk patients

OBJECTIVE Although there has been some evidence supporting the theoretical and practical advantages of off-pump coronary artery bypass (OPCAB) over the conventional coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB), it has not yet been determined which group of patients would benefit most from it. It has been advocated recently that high-risk patients could benefit most from avoidance of CPB. The aim of this retrospective study is to assess the efficacy of the OPCAB technique in multi-vessel myocardial revascularization in a large series of high-risk patients. METHODS The records of 1398 consecutive high-risk patients who underwent primary isolated CABG at Harefield Hospital between August 1996 and December 2001 were reviewed retrospectively. Patients were considered as high-risk and included in the study if they had a preoperative EuroSCORE of > or =5. Two hundred and eighty-six patients were operated on using the OPCAB technique while 1112 patients were operated on using the conventional CABG technique with CPB. The OPCAB patients were significantly older than the CPB patients (68.1+/-8.3 vs. 63.7+/-9.9 years, respectively, P<0.001). The OPCAB group included significantly more patients with poor left ventricular (LV) function (ejection fraction (EF) < or =30%) (P<0.001) and more patients with renal problems (P<0.001). RESULTS There was no significant difference in the number of grafts between the groups. The CPB patients received 2.8+/-1.2 grafts per patient while OPCAB patients received 2.8+/-0.5 grafts per patient (P=1). Twenty-one (7.3%) OPCAB patients had one or more major complications, while 158 (14.2%) CPB patients (P=0.008) developed major complications. Thirty-eight (3.4%) CPB patients developed peri-operative myocardial infarction (MI) while only two (0.7%) OPCAB patients developed peri-operative MI (P=0.024). The intensive therapy unit (ITU) stay for OPCAB patients was 29.3+/-15.4 h while for CPB patients it was 63.6+/-167.1 h (P<0.001). There were ten (3.5%) deaths in the OPCAB patients compared to 78 (7%) deaths in the CPB patients (P=0.041) within 30 days postoperatively. CONCLUSIONS This retrospective study shows that using the OPCAB technique for multi-vessel myocardial revascularization in high-risk patients significantly reduces the incidence of peri-operative MI and other major complications, ITU stay and mortality. Even though the OPCAB group included a significantly higher proportion of older patients with poor LV function (EF < or =30%) and renal problems, the beneficial effect of OPCAB was evident.

Role of Human Valve Interstitial Cells in Valve Calcification and Their Response to Atorvastatin

Background— Calcific aortic valve stenosis is a common disease in the elderly and is characterized by progressive calcification and fibrous thickening of the valve, but the cellular and molecular mechanisms are not fully understood. We hypothesized that human valve interstitial cells (ICs) are able to differentiate into osteoblast-like cells through the influence of defined mediators and that this process can be modulated pharmacologically. Methods and Results— To test this hypothesis, we treated primary cultures of human aortic valve ICs with osteogenic media, bone morphogenic proteins ([BMPs] BMP-2, BMP-4, and BMP-7), and tissue growth factor-β ([TGF-β] TGF-β1 and TGF-β3) for 21 days. These mediators induced osteoblast differentiation of valve ICs by significantly increasing the activity and expression of alkaline phosphatase ([ALP] P<0.001). A cytokine protein array revealed that atorvastatin treatment (100 &mgr;mol/L) of human valve ICs caused a downregulation in levels of expression of BMP-2, BMP-6, TGF-β1, and TGF-β3 after 24 hours. In addition, human valve ICs treated with atorvastatin in the presence of osteogenic media showed a significant reduction in ALP activity in comparison to cells treated with osteogenic media only (P=<0.001). This was further confirmed with immunocytochemical staining of valve ICs, whereby atorvastatin markedly reduced the expression of ALP and osteocalcin induced by osteogenic media in comparison to untreated cells. Conclusions— These findings suggest that human valve ICs are capable of osteoblastic differentiation, by potential mediators which can be pharmacologically targeted by atorvastatin.

Effect of off-pump coronary artery bypass surgery on clinical, angiographic, neurocognitive, and quality of life outcomes: randomised controlled trial

Abstract Objective To compare the clinical, angiographic, neurocognitive, and quality of life outcomes of off-pump coronary artery bypass surgery with conventional coronary artery bypass grafting surgery using cardiopulmonary bypass. Design Randomised controlled clinical trial. Setting Tertiary cardiothoracic centre in Middlesex, England. Participants 168 patients (27 women) requiring primary isolated coronary artery bypass grafting surgery. Interventions Patients were randomised to conventional coronary artery bypass grafting surgery using cardiopulmonary bypass (n = 84) or off-pump coronary artery bypass surgery (n = 84), carried out by one surgeon. Angiographic examination was carried out at three months postoperatively. Neurocognitive tests were carried out at baseline and at six weeks and six months postoperatively. Main outcome measures Clinical outcome, graft patency at three months, neurocognitive function at six weeks and six months, and health related quality of life. Results Graft patency was evaluated by angiography in 151 (89.9%) patients and was similar between the cardiopulmonary bypass and off-pump groups (risk difference − 1%, 95% confidence interval − 5% to 4%), with the off-pump group considered the treatment group. Patients in the off-pump group required fewer blood transfusions (1.7 units v 1.0 unit, P = 0.02), shorter duration of mechanical ventilation (7.7 hours v 3.9 hours, P = 0.03), and shorter hospital stay (10.8 days v 8.9 days). Scores for neurocognitive function showed a significant difference in three memory subtests at six weeks and two memory subtests at six months in favour of the off-pump group. Conclusions Patients who underwent off-pump coronary artery bypass surgery showed similar patency of grafts, better clinical outcome, shorter hospital stay, and better neurocognitive function than patients who underwent conventional coronary artery bypass grafting surgery using cardiopulmonary bypass.

Off-pump Coronary Artery Bypass (OPCAB) surgery reduces risk-stratified morbidity and mortality: A United Kingdom multi-center comparative analysis of early clinical outcome

Objective—Off-Pump Coronary Artery Bypass (OPCAB) surgery is gaining more popularity worldwide. The aim of this United Kingdom (UK) multi-center study was to assess the early clinical outcome of the OPCAB technique and perform a risk-stratified comparison with the conventional Coronary Artery Bypass Grafting (CABG) using the Cardio-Pulmonary Bypass (CPB) technique. Methods—Data were collected on 5,163 CPB patients from the database of the National Heart and Lung institute, Imperial College, University of London, and on 2,223 OPCAB patients from eight UK cardiac surgical centers, which run established OPCAB surgery programs. All patients had undergone primary isolated CABG for multi-vessel disease through a midline sternotomy approach, between January 1997 and April 2001. Postoperative morbidity and mortality were compared between the CPB and OPCAB patients after adjusting for case-mix. The mortality of the OPCAB patients was also compared, using risk stratification, to the mortality figures reported by the Society of Cardiothoracic Surgeons of Great Britain and Ireland (SCTS) based on 28,018 patients in the national database who were operated on between January 1996 and December 1999. Results—Morbidity and mortality were significantly lower in the OPCAB patients compared with the CPB patients and the UK national database of CABG patients, over the same period of time, after adjusting for case-mix. Conclusion—This study demonstrates that risk stratified morbidity and mortality are significantly lower in OPCAB patients than CPB patients and patients in the UK national database.

Early outcomes of bilateral sequential single lung transplantation after ex-vivo lung evaluation and reconditioning

BACKGROUND Ex vivo lung perfusion (EVLP) is a novel approach for extended evaluation and/or reconditioning of donor lungs not meeting standard International Society for Heart and Lung Transplantation criteria for transplantation. METHODS We retrospectively evaluated 13 consecutive EVLP runs between January 2009 and December 2010. Lungs rejected for routine transplantation were implanted to the EVLP circuit and reperfused using acellular supplemented Steen Solution (Vitrolife, Göteborg, Sweden) up to a target flow rate of 40% of the donors calculated flow at a cardiac index of 3.0 liters/min/m(2); target left atrial pressure < 5 mm Hg; and pulmonary artery pressure < 15 mm Hg. Mechanical ventilation was introduced after rewarming to 32°C: tidal volume, 6 to 8 ml/kg; respiratory rate, 7 to 8 breaths/min; duration of inspiration/expiration (I/E) ratio, 1:2; and positive end-expiratory pressure, 5 to 10 cm H(2)O. Hemodynamic and respiratory data monitoring with hourly clinical assessment were performed. Donor data, conversion rate to transplantation, and recipient outcome were analyzed. RESULTS Donor data (n = 13) were: age, 44.23 ± 8.33 years; female/male, 8:5; cause of death: intracranial hemorrhage, 11 (85%), stroke, 1 (7.5%), hypoxic brain injury, 1 (7.5%); smoking history, 9 (69%), 17.44 ± 8.92 pack-years; mechanical ventilation, 102.6 ± 91.92 hours; chest x-ray imaging: abnormal, 12 (92.5%); normal, 1 (7.5%). EVLP: mean 141 ± 28.83 minutes. Arterial partial pressure of oxygen/fraction of inspired oxygen 100% before termination of the circuit vs pre-retrieval value: 57.32 ± 9.1 vs 42.36 ± 14.13 kPa (p < 0.05). Six (46%) pairs of donor lungs were transplanted. Median follow-up was 297.5 days (range, 100-390 days), with 100% survival at 3 months. CONCLUSIONS EVLP may facilitate assessment and/or reconditioning of borderline lungs, with a conversion rate of 46 % and good short-term survival.

Predictors of poor mid-term health related quality of life after primary isolated coronary artery bypass grafting surgery

Objective: To assess the determinants of poor mid-term health related quality of life (HRQoL) at one year after primary isolated coronary artery bypass grafting (CABG). Methods: 463 patients who underwent primary isolated CABG for multivessel disease and came for their annual follow up at the outpatient clinic during one year at Harefield Hospital, Middlesex, were approached to participate in the present study. Prospective clinical data were collected as part of the clinical care of the patients and were retrospectively analysed when the patients consented to participate in the study at their outpatient visit. After their consent they were given three HRQoL assessment questionnaires. Scores, together with clinical data, were analysed by both univariate and multivariate analyses with regard to poor HRQoL outcome. Results: 437 (94.4%) patients consented to participate in the study and filled in the HRQoL questionnaires. Ten variables were identified in the univariate analysis as potential predictors of poor scores of the physical element of HRQoL; however, only three variables—gastrointestinal problems, congestive heart failure, and type D personality trait—predicted poor physical scores independently. Eleven variables were identified in the univariate analysis as potential predictors of poor scores of the mental element of HRQoL; however, only three variables—peripheral vascular disease, infective complications, and type D personality trait—predicted poor physical scores independently. Conclusion: Preoperative gastrointestinal problems, preoperative congestive heart failure, and type D personality trait were independent predictors of the poor physical component of HRQoL. Peripheral vascular disease, infective complications, and type D personality trait were independent predictors of the poor mental component of HRQoL. Interestingly, patients with type D personality were more than twice as likely to have poor physical HRQoL and more than five times as likely to have poor mental HRQoL.

Heat stress proteins and myocardial protection: experimental model or potential clinical tool?

Heat stress proteins (hsp) are induced by a variety of stimuli including elevated temperature, ischaemia, hypoxia, pressure overload and some chemicals. They help to maintain the metabolic and structural integrity of the cell, as a protective response to external stresses. They are known to protect the myocardium from the damaging effects of ischaemia and reperfusion. The heat stress response results in accumulation of heat stress proteins. The beneficial effects associated with their expression include improved endothelial and mechanical recovery of the ischaemic heart. In addition, preservation of high energy phosphates and reduction in infarct size. It has also been shown that critical amounts of hsp70 are necessary to ensure protection of the myocardium. However, questions remain regarding the biochemical mechanisms underlying this protective effect. Alterations in the cell metabolism and chaperone function of cells expressing heat shock proteins, are thought to be responsible. Despite the obvious clinical benefits related to the heat stress response in a clinical setting, the application of this phenomena remains limited. Heat, both quantitatively and qualitatively is one of the best inducers of heat stress proteins. However, the effects of heat stress are nonspecific and intracellular damage is a common occurrence. The search for alternative stimuli, particularly within the fields of pharmacotherapy or genetic manipulation may offer more viable options, if the heat stress response is take its place as an established strategy for myocardial protection.

Role of basal release of nitric oxide on coronary flow and mechanical performance of the isolated rat heart.

1. The role of nitric oxide (NO) in the regulation of coronary flow and mechanical function was studied in isolated working rat hearts. 2. The inhibition of basal release of NO by L‐Ng‐monomethylarginine (L‐NMMA; 500 microM), a specific inhibitor of its synthesis, induced a reduction of coronary flow to 39.1% (+/‐ 3.4) of its basal level. 3. Associated with this was a drop of cardiac output to 58.10% (+/‐ 5.42) of control values. 4. This mechanical dysfunction, which was more pronounced in hypertrophied hearts, appears to be related to ischaemia, as it was prevented by simultaneously administered glyceryl trinitrate. Furthermore, L‐NMMA did not alter the contractile activity of isolated cardiac myocytes, thereby excluding a direct toxic effect. 5. These findings provide evidence that NO plays a crucial role in the maintenance of basal coronary flow and appears to be essential for sustaining mechanical activity.

Clinical Experience With HeartWare Left Ventricular Assist Device in Patients With End-Stage Heart Failure

BACKGROUND The gold standard treatment for end-stage heart failure is cardiac transplantation. Because of the increasing number of heart failure patients and the limited supply of donor hearts, a ventricular assist device (VAD) is used as a bridge to transplantation, recovery, or decision. Newer generation VADs have lower risk of fatal adverse events and are also smaller in size. We present our experience with the intrapericardial HeartWare VAD (HeartWare, Framingham, MA) and its clinical outcome. METHODS The clinical outcome of HeartWare VAD implantations for end-stage heart failure patients performed at Harefield Hospital from March 2007 to June 2011 was studied. The study design was a retrospective review of the prospectively collected data. RESULTS Thirty-four patients with a mean age of 51±10 years were included in this study. Twenty-nine patients were male (85%). The mean duration of mechanical support was 261±64 days. Five patients (15%) were successfully bridged to heart transplantation. The overall mortality was 24% (8 patients). There were 1 case of mechanical device failure (2%) and 3 cases of device failure due to thrombus formation (8%). Postoperative complications included 5 reoperations for bleeding (15%), 12 acute renal failures (36%), 7 respiratory failures (21%), 2 hepatic dysfunctions (6%), 3 neurologic dysfunctions (9%), 7 right-side heart failures (21%), and 5 driveline infections (15%). CONCLUSIONS Although cardiac transplantation remains the gold standard for treatment of end-stage heart failure patients, the HeartWare VAD can be used as a safe alternative with a satisfactory clinical outcome.

l-Arginine reverses low coronary reflow and enhances postischaemic recovery of cardiac mechanical function

OBJECTIVE To evaluate the effect of L-arginine, the physiological substrate of nitric oxide (NO), upon coronary flow (CF) and mechanical function during reperfusion following cardioplegic arrest. METHODS Two groups of isolated rat hearts were subjected to cardioplegic arrest for 4 h at 4 degrees C. In group 1 (n = 10) cardioplegic arrest was followed by 4 consecutive periods of reperfusion with Krebs buffer (control), Krebs plus L-lysine (1 mmol/1), Krebs plus L-arginine (1 mmol/1) and Krebs plus L-NGmonomethylarginine (L-NMMA), a specific inhibitor of NO synthesis, (0.5 mmol/1). In group 2, hearts (n = 8) were perfused by Krebs, then L-NMMA, during both pre- and postischaemic periods. In group 3, hearts (n = 8) were perfused by Krebs, then L-arginine (1, 2 and 4 mmol/1). In group 4 (n = 5), NO released into the perfusate was measured before ischaemia and during reperfusion. RESULTS In group 1, L-arginine enhanced the postischaemic CF (ml/min +/- s.e.m.) from 15.0 +/- 0.4 to 17.2 +/-0.4. This was reduced by L-NMMA to 11.3 +/- 0.3. Postischaemic cardiac output (% of preischaemic value +/- s.e.m.) was increased from 55.8 +/- 2.4 to 80.1 +/- 2.5 by L-arginine and dropped to 54.3 +/- 2.3 with L-NMMA. In group 2, the pre- and postischaemic loss of coronary flow (CF) by L-NMMA was 51% and 31% respectively. In group 3, L-arginine did not modify CF. In group 4 the preischaemic level of NO (in nmol/ml/min) in the coronary effluent, measured by chemiluminescence, was 14.84 +/- 0.83 and dropped significantly (P < 0.05) to levels ranging from 3.80 +/- 0.56 to 4.75 +/- 0.51 during the postischaemic period. CONCLUSION Exogenous administration of L-arginine improves low coronary reflow and postischaemic mechanical function.