Remote preconditioning and major clinical complications following adult cardiovascular surgery: systematic review and meta-analysis.

BACKGROUND: A number of 'proof-of-concept' trials suggest that remote ischaemic preconditioning (RIPC) reduces surrogate markers of end-organ injury in patients undergoing major cardiovascular surgery. To date, few studies have involved hard clinical outcomes as primary end-points. METHODS: Randomised clinical trials of RIPC in major adult cardiovascular surgery were identified by a systematic review of electronic abstract databases, conference proceedings and article reference lists. Clinical end-points were extracted from trial reports. In addition, trial principal investigators provided unpublished clinical outcome data. RESULTS: In total, 23 trials of RIPC in 2200 patients undergoing major adult cardiovascular surgery were identified. RIPC did not have a significant effect on clinical end-points (death, peri-operative myocardial infarction (MI), renal failure, stroke, mesenteric ischaemia, hospital or critical care length of stay). CONCLUSION: Pooled data from pilot trials cannot confirm that RIPC has any significant effect on clinically relevant end-points. Heterogeneity in study inclusion and exclusion criteria and in the type of preconditioning stimulus limits the potential for extrapolation at present. An effort must be made to clarify the optimal preconditioning stimulus. Following this, large-scale trials in a range of patient populations are required to ascertain the role of this simple, cost-effective intervention in routine practice.

Acute aortic dissection type A.

BACKGROUND: Acute aortic dissection type A (AADA) is a life-threatening vascular emergency. Clinical presentation ranges from pain related to the acute event, collapse due to aortic rupture or pericardial tamponade, or manifestations of organ or limb ischaemia. The purpose of this review was to clarify important clinical issues of AADA management, with a focus on diagnostic and therapeutic challenges. METHODS: Based on a MEDLINE search the latest literature on this topic was reviewed. Results from the German Registry for Acute Aortic Dissection Type A (GERAADA) are also described. RESULTS: Currently, the perioperative mortality rate of AADA is below 20 per cent, the rate of definitive postoperative neurological impairment approaches 12 per cent and the long-term prognosis after surviving the acute phase of the disease is good. Many pathology- and therapy-associated factors influence the outcome of AADA, including prompt diagnosis with computed tomography and better cerebral protection strategies during aortic arch reconstruction. Endovascular technologies are emerging that may lead to less invasive treatment options. CONCLUSION: AADA is an emergency that can present with a wide variety of clinical scenarios. Advances in the surgical management of this complex disease are improving outcomes.

Management of the heartbeating brain-dead organ donor.

The main factor limiting organ donation is the availability of suitable donors and organs. Currently, most transplants follow multiple organ retrieval from heartbeating brain-dead organ donors. However, brain death is often associated with marked physiological instability, which, if not managed, can lead to deterioration in organ function before retrieval. In some cases, this prevents successful donation. There is increasing evidence that moderation of these pathophysiological changes by active management in Intensive Care maintains organ function, thereby increasing the number and functional quality of organs available for transplantation. This strategy of active donor management requires an alteration of philosophy and therapy on the part of the intensive care unit clinicians and has significant resource implications if it is to be delivered reliably and safely. Despite increasing consensus over donor management protocols, many of their components have not yet been subjected to controlled evaluation. Hence the optimal combinations of treatment goals, monitoring, and specific therapies have not yet been fully defined. More research into the component techniques is needed.

Disease-specific survival benefit of lung transplantation in adults: a national cohort study.

The lung transplantation candidate population is heterogeneous and survival benefit has not been established for all patient groups. UK data from a cohort of 1997 adult (aged > or = 16), first lung transplant candidates (listed July 1995 to July 2006, follow-up to December 2007) were analyzed by diagnosis, to assess mortality relative to continued listing. Donor lungs were primarily allocated according to local criteria. Diagnosis groups studied were cystic fibrosis (430), bronchiectasis (123), pulmonary hypertension (74), diffuse parenchymal lung disease (564), chronic obstructive pulmonary disease (COPD, 647) and other (159). The proportion of patients in each group who died while listed varied significantly (respectively 37%, 48%, 41%, 49%, 19%, 38%). All groups had an increased risk of death at transplant, which fell below waiting list risk of death within 4.3 months. Thereafter, the hazard ratio for death relative to listing ranged from 0.34 for cystic fibrosis to 0.64 for COPD (p < 0.05 all groups except pulmonary hypertension). Mortality reduction was greater after bilateral lung transplantation in pulmonary fibrosis patients (p = 0.049), but not in COPD patients. Transplantation appeared to improve survival for all groups. Differential waiting list and posttransplant mortality by diagnosis suggest further use and development of algorithms to inform lung allocation.

Epicardial adipose tissue as a source of nuclear factor-kappaB and c-Jun N-terminal kinase mediated inflammation in patients with coronary artery disease.

CONTEXT: Visceral adipose tissue (AT) is known to confer a significantly higher risk of type 2 diabetes and cardiovascular disease. Epicardial AT has been shown to be related to cardiovascular disease and myocardial function through unidentified mechanisms. Epicardial AT expresses an inflammatory profile of proteins; however, the mechanisms responsible are yet to be elucidated. OBJECTIVES: The objectives of the study were to: 1) examine key mediators of the nuclear factor-kappaB (NFkappaB) and c-Jun N-terminal kinase (JNK) pathways in paired epicardial and gluteofemoral (thigh) AT from coronary artery disease (CAD) and control patients and 2) investigate circulating endotoxin levels in CAD and control subjects. DESIGN: Serums and AT biopsies (epicardial and thigh) were obtained from CAD (n = 16) and non-CAD (n = 18) patients. Inflammation was assessed in tissue and serum samples through Western blot, real-time PCR, ELISAs, and activity studies. RESULTS: Western blotting showed epicardial AT had significantly higher NFkappaB, inhibitory-kappaB kinase (IKK)-gamma, IKKbeta, and JNK-1 and -2 compared with thigh AT. Epicardial mRNA data showed strong correlations between CD-68 and toll-like receptor-2, toll-like receptor-4, and TNF-alpha. Circulating endotoxin was elevated in patients with CAD compared with matched controls [CAD: 6.80 +/- 0.28 endotoxin unit(EU)/ml vs. controls: 5.52 +/- 0.57 EU/ml; P<0.05]. CONCLUSION: Epicardial AT from patients with CAD shows increased NFkappaB, IKKbeta, and JNK expression compared with both CAD thigh AT and non-CAD epicardial AT, suggesting a depot-specific as well as a disease-linked response to inflammation. These studies implicate both NFkappaB and JNK pathways in the inflammatory profile of epicardial AT and highlight the role of the macrophage in the inflammation within this tissue.

Thoraco-abdominal aneurysm repair in a Jehovah's Witness: maximising blood conservation.

Thoraco-abdominal aneurysm repair usually necessitates blood or blood product transfusion which is prohibited in Jehovah's Witnesses. We report the blood conservation strategy used during thoraco-abdominal aneurysm repair in a Jehovah's Witness. This included pre-operative recombinant erythropoietin, per-operative acute normovolaemic haemodilution, cell salvage, aprotinin, restricted heparinisation, left atrial-distal bypass and recombinant factor VIIa. Post-operative haemoglobin levels were maintained, but a left haemothorax necessitated re-thoracotomy on post-operative day 4. Following re-thoracotomy, Hb was 12.0 g.dL(-1) and platelet count 49 x 10(9).L(-1). Recombinant erythropoietin was recommenced. At discharge (day 12), Hb was 10.1 g.d(L-1). The patient remains well at one year. A thoroughly, pre-planned multi-disciplinary blood conservation strategy can be used to undertake high-risk procedures.

Rapid serodiagnosis of Staphylococcus aureus surgical site infection following median sternotomy.

OBJECTIVES: To determine the sensitivity and specificity of a novel ELISA for the serodiagnosis of surgical site infection (SSI) due to staphylococci following median sternotomy. METHODS: Twelve patients with a superficial sternal SSI and 19 with a deep sternal SSI due to Staphylococcus aureus were compared with 37 control patients who also underwent median sternotomy for cardiac surgery but exhibited no microbiological or clinical symptoms of infection. A further five patients with sternal SSI due to coagulase-negative (CoNS) staphylococci were studied. An ELISA incorporating a recently recognised exocellular short chain form of lipoteichoic acid (lipid S) recovered from CoNS, was used to determine serum levels of anti-lipid S IgG in all patient groups. RESULTS: Serum anti-lipid S IgG titres of patients with sternal SSI due to S. aureus were significantly higher than the control patients (P<0.0001). In addition, patients with deep sternal SSI had significantly higher serum anti-lipid S IgG titres than patients with superficial sternal SSI (P = 0.03). Serum anti-lipid S IgG titres of patients with sternal SSI due to CoNS were significantly higher than the control patients (P = 0.001). CONCLUSION: The lipid S ELISA may facilitate the diagnosis of sternal SSI due to S. aureus and could also be of value with infection due to CoNS.

Outcome of heart-lung and bilateral sequential lung transplantation for cystic fibrosis: a UK national study.

Cystic fibrosis (CF) patients requiring transplantation for respiratory failure may undergo either heart-lung (HLT) or bilateral sequential lung (BSLT) transplantation. The choice of operation varies between surgeons, centres and countries. The current authors investigated whether operation type influenced outcome in adult CF patients transplanted in the UK between July 1995 and June 2002. Propensity scores for receipt of BSLT versus HLT were derived using logistic regression. Cox regression was used to compare survival. In total, 88 BSLTs and 93 HLTs were identified. Patient characteristics were similar overall, but HLT recipients were more likely to be on long-term oxygen therapy and to have had prior resuscitation. There were 72 deaths (29 BSLT and 43 HLT) within 4 yrs. There was a trend towards higher unadjusted survival following BSLT, but, after adjustment, no difference was found (hazard ratio = 0.77; 95% confidence interval 0.29-2.06). Time to the first rejection episode and infection rates were also similar. A total of 82% of hearts from HLT recipients were used as domino heart transplants. In conclusion, after adjusting for comorbidity, donor factors and ischaemia time, it was found that heart-lung and bilateral sequential lung transplantation achieved a similar outcome. The use of domino heart transplantation ameliorated the impact of heart-lung transplantation on total organ availability.

Changing practice of cardiac surgery in adult patients with congenital heart disease.

OBJECTIVES: To review 13 years' data from a unit for grown ups with congenital heart disease (GUCH) to understand the change in surgical practice. METHODS: Records were reviewed of patients over 16 years of age undergoing surgery between 1 January 1990 and 31 December 2002 in a dedicated GUCH unit. Patients with atrial septal defects were included but not those with Marfan's syndrome or undergoing a first procedure for bicuspid aortic valves. Three equal time periods of 52 months were analysed. RESULTS: Of 474 operations performed, 162 (34.2%) were repeat operations. The percentage of repeat operations increased from 24.8% (41 of 165) in January 1990-April 1994 to 49.7% (74 of 149) in September 1998-December 2002. Mortality was 6.3% (n = 30). The median age decreased from 25.4 years (interquartile range 18.7) in January 1990-April 1994 to 23.9 (interquartile range 17.3) in September 1998-December 2002 (p = 0.04). The proportion of patients with a "simple" diagnosis decreased from 45.4% (74 or 165) in January 1990-April 1994 to 27.5% (41 of 149) in September 1998-December 2002 (p = 0.013). Pulmonary valve replacements in operated tetralogy of Fallot increased from one case in January 1990-April 1994 to 23 cases in September 1998-December 2002 and conduit replacement increased from five cases to 17. However, secundum atrial septal defect closures decreased from 35 cases to 14 (p < 0.0001). The estimated cost (not including salaries and prosthetics) incurred by an adult patient with congenital heart disease was pound2290 compared with pound2641 for a patient undergoing coronary artery bypass grafting. CONCLUSION: Despite the impact of interventional cardiology, the total number of surgical procedures remained unchanged. The complexity of the cases increased particularly with repeat surgery. Nevertheless, the patients do well with low mortality and the inpatient costs remain comparable with costs of surgery for acquired disease.

Selective antegrade cerebral perfusion attenuates brain metabolic deficit in aortic arch surgery: a prospective randomized trial.

BACKGROUND: Aortic arch surgery has a high incidence of brain injury. This may in part be caused by a cerebral metabolic deficit observed after hypothermic circulatory arrest (HCA). We hypothesized that selective antegrade cerebral perfusion (SACP) would attenuate this phenomenon. METHODS AND RESULTS: In a prospective randomized trial, 42 adult patients were allocated to either HCA (22) or SACP. HCA occurred at a nasopharyngeal temperature of 15 degrees C and SACP at a corporeal temperature of 25 degrees C with cerebral perfusion at 15 degrees C. Paired arterial and jugular venous samples were taken before and after arrest. Continuous transcranial Doppler monitoring of middle cerebral artery velocity (MCAV) was performed. Neuropsychometric testing was performed preoperatively and at 6 and 12 weeks postoperatively. There were 3 hospital deaths (7.1%), 2 strokes (4.8%), and 6 episodes of transient neurological deficit (14.3%). From before to after arrest, jugular bulb pO2 changed by -21.67 mm Hg (26.4) in the HCA group versus +2.27 mm Hg (18.8) in the SACP group (P=0.007). Oxygen extraction changed by +1.7 mL/dL (1.3) in the HCA group versus -1 mL/dL (2.4) in the SACP group (P<0.001). MCAV increased by 6.25 cm/s (9.1) in the HCA group and 19.2 cm/s (10.1) in the SACP group (P=0.001). Incidence of neuropsychometric deficit at 6 weeks was 6/12 (50%) in HCA patients and 8/10 (80%) in SACP patients (P=0.2), and at 12 weeks was 6/16 (38%) in HCA patients and 4/11 (36%) in SACP patients (P=1). CONCLUSIONS: SACP attenuates the metabolic changes seen after HCA. Further studies are required to assess optimal perfusion conditions and clinical outcome.

Evaluation of PCR in the molecular diagnosis of endocarditis.

OBJECTIVE: Infective endocarditis (IE) is diagnosed by the Duke criteria, which can be inconclusive particularly when blood cultures are negative. This study investigated the application of polymerase chain reaction (PCR) to identify bacterial DNA in excised valvular tissue, and its role in establishing the diagnosis of IE. METHODS: Ninety-eight patients undergoing valve replacement surgery were studied. Twenty-eight patients were confirmed as definite for endocarditis by the Duke criteria; nine were considered as possible and 61 had no known or previous microbial infection of the endocardium. A broad-range PCR technique was used to amplify prokaryotic 16S rRNA genes present within homogenised heart valve tissue. Subsequent DNA sequencing of the PCR amplicon allowed identification of the infecting microorganism. RESULTS: PCR results demonstrated the presence of bacterial DNA in the heart valves obtained from 14 out of 20 (70%) definite IE patients with positive blood cultures preoperatively. The causative microorganism for one patient with definite culture negative endocarditis was identified by PCR. Two out of nine (22%) of the valves from possible endocarditis patients also had bacterial DNA present converting them into the definite criteria whereas in the valves of seven out of nine (78%) of these patients no bacterial DNA was detected. CONCLUSION: The application of PCR to the explanted valves in patients with possible or confirmed diagnosis can augment the Duke criteria thereby improving post-surgical antimicrobial therapeutic options.

Neuropsychometric outcome following aortic arch surgery: a prospective randomized trial of retrograde cerebral perfusion.

BACKGROUND: Aortic surgery requiring hypothermic circulatory arrest is associated with a high incidence of brain injury. However, knowledge of neuropsychometric outcome is limited. Retrograde cerebral perfusion has become a popular adjunctive technique to hypothermic circulatory arrest. The aim of this study was to assess neuropsychometric outcome and compare the 2 techniques. METHODS: In a prospective randomized trial, 38 patients requiring elective aortic arch surgery were allocated to either hypothermic circulatory arrest plus retrograde cerebral perfusion or hypothermic circulatory arrest alone. Neuropsychometric testing was performed preoperatively, and at 6 weeks and 12 to 24 weeks postoperatively. Deficit was defined as a 20% decline in 2 tests or more. Standardized Z scores were calculated for each patient and test. Eighteen patients underwent hypothermic circulatory arrest and 20 patients underwent hypothermic circulatory arrest plus retrograde cerebral perfusion. The mean cardiopulmonary bypass, hypothermic circulatory arrest, and retrograde cerebral perfusion durations were 169, 30, and 25 minutes, respectively. RESULTS: There were 2 deaths and 2 neurological deficits. At 6 weeks postoperatively, 77% of the hypothermic circulatory arrest group and 93% of the hypothermic circulatory arrest plus retrograde cerebral perfusion group had a deficit (P =.22). At 12 weeks this was reduced to 55% and 56%, respectively (P =.93). There was a worse total Z test score in the hypothermic circulatory arrest plus retrograde cerebral perfusion group at 12 weeks (P =.05). Neuropsychometric change did not correlate with hypothermic circulatory arrest duration, presence of aortic atheroma, cannulation technique, or procedure. CONCLUSIONS: Hypothermic circulatory arrest plus/minus retrograde cerebral perfusion is associated with a high incidence of neuropsychometric change despite ostensibly normal clinical outcomes and apparently safe arrest duration. Retrograde cerebral perfusion did not improve outcome in this small study.

The heart failure revascularisation trial (HEART): rationale, design and methodology.

BACKGROUND: Most patients with heart failure due to left ventricular systolic dysfunction (LVSD) secondary to coronary artery disease (CAD) have evidence of myocardium in jeopardy (reversible ischaemia and/or stunning hibernation). It is not known whether revascularisation in such cases is safe or beneficial. AIMS: To determine whether revascularisation will improve the survival of patients with LVSD and heart failure secondary to CAD and myocardium in jeopardy. METHODS: This is a randomised controlled trial comparing revascularisation or not, in addition to optimal medical therapy with ACE inhibitors, beta-blockers, aldosterone antagonists and an anti-thrombotic agent. Patients must have heart failure requiring treatment with diuretics, a left ventricular ejection fraction <35% and evidence of coronary disease. Myocardial viability and ischaemia are assessed by a broad range of techniques including stress echocardiography and nuclear imaging. All imaging tests are reviewed in core laboratories to ensure uniform reporting. Any conventional revascularisation technique is permitted. The primary outcome measure is all cause mortality. Symptoms, quality of life and health economic issues will also be explored. Assuming an annual mortality of 10% in the control group and allowing for substantial cross-over rates, a study of 800 patients followed for 5 years has 80% power with an alpha of 0.05 (two-sided) to show a 25% reduction in mortality with revascularisation. RESULTS: At the time of writing 180 patients have been screened for inclusion, 111 have consented to participate and 70 have been randomised. The results of viability testing are awaited in 22 patients. Twenty-six patients had been investigated for myocardial viability and/or by angiography prior to consent, as part of the routine practice in that cardiology department. Of 68 patients who have completed assessment only after consent, 47 (69%) were included. The principal reason for drop-out between consent and randomisation was lack of evidence of myocardial ischaemia or hibernation. CONCLUSION: The HEART trial will help to determine whether investigation of myocardial ischaemia and/or viability with a view to revascularisation should become part of the routine care of patients with heart failure due to LVSD and CAD.

Management of aortobronchial fistula following coarctation repair.

Aortobronchial fistula is a rare complication following thoracic aortic operations and is invariably fatal if not promptly diagnosed and repaired. Direct prosthetic repair carries a risk of graft repair sepsis and fistula recurrence. We describe two cases presenting with aortobronchial fistula following coarctation repair which were successfully treated by different surgical approaches.

Chronotropic effects of nitric oxide in the denervated human heart.

Nitric oxide synthase is expressed in the sino-atrial node and animal data suggests a direct role for nitric oxide on pacemaker activity. Study of this mechanism in intact humans is complicated by both reflex and direct effects of nitric oxide on cardiac autonomic control. Thus, we have studied the direct effects of nitric oxide on heart rate in human cardiac transplant recipients who possess a denervated donor heart. In nine patients, the chronotropic effects of systemic injection of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) (3 mg kg(-1)) or increasing bolus doses of the nitric oxide donor, sodium nitroprusside (SNP), were studied. Injection of L-NMMA increased mean arterial pressure by 17 +/- 2 mmHg (mean +/- S.E.M.; P < 0.001) and also had a significant negative chronotropic effect, lengthening the R-R interval by 54 +/- 8 ms (P < 0.001). This bradycardia was not reflex in origin since injection of the non-NO-dependent vasoconstrictor, phenylephrine (100 microg) achieved a similar rise in mean arterial pressure (18 +/- 3 mmHg; P < 0.001) but failed to change R-R interval duration (Delta R-R = -3 +/- 4 ms). Furthermore, no change in levels of circulating adrenaline was observed with L-NMMA. Conversely, injection of sodium nitroprusside resulted in a positive chronotropic effect with a dose-dependent shortening of R-R interval duration, peak Delta R-R = -25 +/- 8 ms with 130 microg (P < 0.01). These findings indicate that nitric oxide exerts a tonic, direct, positive chronotropic influence on the denervated human heart. This is consistent with the results of animal experiments showing that nitric oxide exerts a facilitatory influence on pacemaking currents in the sino-atrial node.

Failure of retrograde cerebral perfusion to attenuate metabolic changes associated with hypothermic circulatory arrest.

OBJECTIVES: Although retrograde cerebral perfusion has become a popular adjunctive technique and may improve cerebral ischemic tolerance during hypothermic circulatory arrest, direct cerebral metabolic benefit has yet to be demonstrated in human subjects. We investigated the post-arrest metabolic phenomena with and without retrograde cerebral perfusion in patients. METHODS: In a prospective randomized trial, 42 patients undergoing aortic surgery requiring hypothermic circulatory arrest were allocated to receive hypothermic circulatory arrest alone (n = 21) or hypothermic circulatory arrest with additional retrograde cerebral perfusion (n = 21). Circulatory arrest was commenced at 15 degrees C, and retrograde perfusion was instituted through the superior vena cava at a maximum jugular bulb pressure of 25 mm Hg. Transcranial, paired, repeated samples of the arterial and jugular bulb blood were analyzed for oxygen and glucose. Velocity in the right middle cerebral artery was also measured simultaneously. RESULTS: There were 3 (7.1%) deaths and 3 (7.1%) episodes of neurologic deficit. Mean bypass and circulatory arrest duration (in minutes) were similar between groups (P =.4 and.14). The mean retrograde perfusion duration was 23 minutes. Post-arrest nasopharyngeal temperature was similar (15.3 degrees C vs. 15.3 degrees C). Retrograde perfusion did not affect post-arrest oxygen extraction, glucose extraction, or jugular bulb Po(2). There was no immediate lactate release immediately after hypothermic circulatory arrest. CONCLUSIONS: Retrograde cerebral perfusion did not influence immediate post-arrest nasopharyngeal temperature or cerebral metabolic recovery. The low jugular bulb Po(2) suggests equivalent ischemia. These findings cast doubt on the effectiveness of retrograde cerebral perfusion as a metabolic adjunct to hypothermic circulatory arrest.

Surgical repair of ruptured thoracic and thoracoabdominal aortic aneurysms.

BACKGROUND: Rupture is the single most common cause of death in patients with thoracic aortic and thoracoabdominal aneurysm (TAA/TAAA) and is almost uniformly fatal. METHODS: This was a retrospective review of patients admitted to a single practice with rupture of a TAA/TAAA between 1993 and 2000. RESULTS: Twenty-two consecutive patients with a leaking TAA/TAAA were identified. The aetiology of rupture was either secondary to a degenerative TAAA or a type B dissection. Seventeen patients underwent surgery; one had a Crawford extent I, seven an extent II, one an extent III and two an extent IV TAAA. Six patients had an acute type B dissection with rupture in the upper descending thoracic aorta. The 30-day survival rate was 88 per cent (15 of 17 patients). Actuarial survival at 1 year in patients who had surgery was 65 per cent. Survival at 1 year for all presenting patients who consented to surgery was 40 per cent. Median survival was greater than 36 months. CONCLUSION: As a result of improving medical care, more patients with a contained rupture of a TAA/TAAA may present for treatment. Surgery is complex and requires specialist teams for optimal care.