Identification of low circulatory transforming growth factor beta-1 in patients with degenerative heart valve disease.

Transforming growth factor ß-1 (TGF-ß1) is an immunosuppressive cytokine. It exerts cardioprotection during acute myocardial ischaemia, promoting healing of the injured myocytes. Lower plasma concentrations of TGF-ß1 have been identified in patients with coronary artery disease (CAD) compared to those with normal coronary arteries. We measured plasma TGF-ß1 concentrations in patients with CAD compared to those with degenerative heart valves (DHVs) and normal coronary arteries. The mean concentration of TGF-ß1 in patients with valvular heart disease was significantly lower (18.67 µg/l) than the mean in the coronary artery bypass graft (CABG) group (26.46 µg/l). There was no correlation between the patient characteristics and preoperative concentration of TGF-ß1. It is possible that the lower plasma concentration of TGF-ß1 in patients with valvular heart disease and the lack of its regulatory effect results in the increased inflammation and calcification seen in DHVs.

Transcatheter aortic valve implantation for severe aortic stenosis-a new paradigm for multidisciplinary intervention: a prospective cohort study.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an alternative treatment option for patients with aortic stenosis deemed high risk or unsuitable for aortic valve replacement. The aim of this study was to assess the feasibility of TAVI in elderly patients, the delivery of this technology with a multidisciplinary approach, and the use of traditional surgical scoring systems. METHODS: One hundred fifty-one consecutive patients (mean age 82.6 +/- 7.3 years) with severe aortic stenosis underwent TAVI with the Edwards Lifesciences (Irvine, CA) Sapien bioprosthesis using the transapical (n = 84; 56%) or transfemoral (n = 67; 44%) approach from August 2007 to September 2009 at King's Health Partners, London, United Kingdom. We analyzed procedural outcome, complications, functional status, and midterm outcome of patients. RESULTS: The multidisciplinary team comprised interventional cardiologists, cardiothoracic surgeons, imaging specialists, cardiac anesthetists, and specialist nurses. Seventy percent of patients were in New York Heart Association class III/IV, and logistic EuroSCORE was 21.6 +/- 11.9. Procedural success was achieved in 98%. Postoperative complications included stroke (6%), complete atrioventricular block (5.3%), renal failure requiring hemofiltration (9.3%), and vascular injury (8.6%). Overall 30-day mortality was 9.9% (n = 15). The logistic EuroSCORE was a predictor of short-term mortality (logistic regression model, P < .05). Thirty-day mortality post-TAVI for patients with logistic EuroSCORE <20, 20 to 40, and >40 was 5.4%, 13.2%, and 22.2%, respectively. CONCLUSIONS: Transcatheter aortic valve implantation is a feasible treatment option in this patient group with promising short/medium-term results. Renal failure is the commonest short-term complication, and the incidence of vascular complications remains high. Risk prediction/case selection remains challenging, and a multidisciplinary team approach appears to be helpful in appropriate patient selection.

Brain natriuretic peptide a predictive marker in cardiac surgery.

BACKGROUND: BNP which stands for B-type natriuretic peptide is a cardiac neurohormone and is secreted in response to myocardial stress and causes natriuresis and vasodilatation. Studies have reported close correlation between a high concentration of BNP in blood and worse short-term and long-term prognosis following myocardial infarction and heart failure. In this study, we have tested its usefulness and predictive value in the outcome post cardiac surgery. METHODS: Between March 2006 and June 2007, 141 patients, undergoing cardiac surgery, were enrolled in this study. Their BNP concentration was measured prior to the operation and their comorbidities were examined against their BNP levels. Postoperatively their outcome was closely monitored. Main clinical endpoints were atrial fibrillation (AF), inotrope use, renal impairment, early deaths and hospital stay. RESULTS: Some preoperative comorbidities, such as renal impairment, peripheral vascular disease (PVD) and low ejection fraction (EF) were associated with higher BNP level. Statistically, EuroSCORE and Parsonnet score showed significant correlation with preoperative BNP concentration (P<0.0001). Postoperatively, high-BNP concentration predicted inotropic use, higher than baseline creatinine level, longer ventilation time, longer hospital stay and early mortality (P<0.05) but our study did not reveal any predictive value for BNP in identifying those developing AF or infection postoperatively. CONCLUSIONS: BNP is a valuable biochemical marker, which is easy to measure and can be beneficial in predicting the operative outcome.

Does stopping amiodarone after successfully treating atrial fibrillation occurring after cardiac surgery increase the risk of recurrence?

OBJECTIVES: Atrial fibrillation (AF) following cardiac surgery is common and can complicate postoperative recovery. Amiodarone is a drug frequently used for cardioversion. Some clinicians advocate only in-hospital use of amiodarone until cardioversion, whereas others continue its use for several weeks following cardiac surgery. Inadvertent long-term administration of the drug could be harmful. This study assessed the risk of AF recurrence under 2 different regimens of amiodarone treatment. METHODS: From January 2005 to July 2007, we reviewed 296 patients who developed postoperative AF. Group A consisted of 198 patients who were discharged on amiodarone treatment, and group B consisted of 98 patients who were discharged without amiodarone treatment. The patients were followed for 8 weeks after cardiac surgery and were observed for the development of symptoms such as palpitations, transient ischemic attack (TIA), stroke, and recurrence of or readmission for AF. In addition, we evaluated a control group of 145 patients with similar characteristics and no postoperative AF for the incidence of stroke and AF and compared the results with their rates in the study groups. RESULTS: Patients discharged on amiodarone therapy were more likely to experience episodes of palpitations than those not on amiodarone (13% versus 10%); however, the rates of AF recurrence were almost the same for the 2 groups (8% and 9%, respectively). The 2 groups also showed no difference in the incidence of TIA and stroke (5% versus 4%). A low incidence of stroke and AF (1%-2%) was observed in patients with no perioperative AF. CONCLUSIONS: Long-term treatment of patients with amiodarone should be reconsidered, because it may not be as effective as previously thought in preventing symptoms and AF recurrence. The surprising incidence of neurologic events requires further investigation.

Reduced nicotinamide adenine dinucleotide phosphate oxidase-derived superoxide and vascular endothelial dysfunction in human heart failure.

OBJECTIVES: We investigated the role of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in endothelial dysfunction in human heart failure. BACKGROUND: Vascular endothelial dysfunction in human heart failure contributes to increased tone, exercise limitation, and dysregulation of venous capacitance and vascular volume. The NADPH oxidases (Nox) are an important source of oxidative stress, but their role in the endothelial dysfunction of human heart failure remains unknown. METHODS: Endothelium-dependent and -independent vasorelaxation were assessed in saphenous vein segments obtained from consecutive patients with heart failure (n = 19) or normal left ventricular function (control; n = 35) undergoing coronary artery bypass graft. Saphenous vein superoxide production was measured by lucigenin-enhanced chemiluminescence and messenger ribonucleic acid expression of relevant transcripts quantified by real-time polymerase chain reaction. RESULTS: Heart failure patients had significantly worse endothelial function than control subjects (15.2 +/- 3% vs. 40.5 +/- 8.4% relative relaxation; p < 0.05), elevated C-reactive protein (CRP) levels (8.6 +/- 2.7 mg/l vs. 2.6 +/- 0.4 mg/l; p < 0.05), over 2-fold higher NADPH-dependent superoxide generation (p < 0.05), and significantly higher expression of the Nox4 isoform and regulatory subunit p67phox. Superoxide levels were positively correlated with New York Heart Association functional class (r = 0.684; p < 0.05) and CRP (r = 0.501; p < 0.005; n = 32). CONCLUSIONS: Venous endothelial dysfunction in human heart failure is associated with increased Nox-derived superoxide generation. Inflammatory mechanisms may be involved in the increased reactive oxygen species generation.

Clinical and potential use of pharmacological agents to reduce radial artery spasm in coronary artery surgery.

The radial artery has increased in popularity as a conduit for use in coronary artery bypass surgery. However, concerns remain regarding the risk of radial artery spasm. Although the use of different pharmacological agents to prevent and treat this has been described, there is currently no clear agreement as to the optimal agent. To clarify which agents are most suitable for clinical use, all pertinent studies to date (January 2007) that have reported the efficacy of pharmacological agents in the prevention and treatment of radial artery spasm have been reviewed. It can be argued that verapamil-glycerine tri-nitrate solution represents the optimum agent when used in the perioperative period.

Leptin is an endothelial-independent vasodilator in humans with coronary artery disease: Evidence for tissue specificity of leptin resistance.

AIMS: We sought to define the mechanisms and correlates of leptin's vascular actions in humans with coronary artery disease. METHODS AND RESULTS: In 131 patients (age 65.7+/-0.7 years mean+/-SEM), ex vivo vascular reactivity to leptin (10(-13)-10(-7) M) was assessed in saphenous vein (SV) rings. Leptin led to SV relaxation (maximal relaxation 24.5+/-1.6%). In separate experiments, relaxation to leptin was unaffected by L-NMMA (17.4+/-3.4 vs.17.8+/-3.3%, P = 0.9) or endothelial denudation (17.4+/-4.4 vs. 22.5+/-3.0%, P = 0.4). We explored the possibility that leptin's vascular effects are mediated via smooth muscle hyperpolarization. In the presence of KCl (30 mmol/L) to inhibit hyperpolarization, the vasodilator effect of leptin was completely blocked (0.08+/-4.1%, P < 0.001 vs. control). Similar results were demonstrated in internal mammary artery rings. The only independent correlate of leptin-mediated vasodilatation was plasma TNF-alpha (r = 0.25, P < 0.05). Neither body mass index nor waist circumference correlated with leptin-mediated vasorelaxation. This lack of a correlation with markers of total body fat/fat distribution suggests that leptin resistance may not extend to the vasculature. CONCLUSION: Leptin is a vasoactive peptide in human SV and internal mammary artery. Its action is not nitric oxide or endothelial-dependent. Markers of body fat did not correlate with leptin-mediated vasodilatation, raising the intriguing possibility of selective resistance to leptin's actions.

Incidence of sternal infection in diabetic patients undergoing bilateral internal thoracic artery grafting.

BACKGROUND: Bilateral internal thoracic artery (BITA) bypass grafts have advantages over single internal thoracic artery (SITA) bypass grafts in the medium term, particularly in diabetics. However, the perceived higher sternal complication rates seen in diabetics have led many surgeons to avoid the use of BITA surgery. The aim of our study was to assess the validity of this approach by assessing the incidence of sternal infections over a 10-year period in one institution. METHODS: A retrospective analysis was made of our coronary artery bypass graft (CABG) patients over a 10-year period (7,581 patients). Nine hundred and twenty-two of the patients were diabetics (261 insulin-dependent diabetes mellitus [IDDM]). Of the insulin-dependent diabetics, 166 had SITA, and 95 had BITA grafts. RESULTS: There was no significant difference in this subgroup in terms of gender, preoperative angina, dyspnea class, left ventricular function, and number of distal anastomoses. Comparing the rates of sternal wound complications of SITA and BITA in IDDM are the following: (1) superficial sternal infection, 6.6% in SITA, 1.1% in BITA (p = 0.04); (2) deep sternal infection, 1.2% in SITA, 3.2% in BITA (p = 0.27); (3) sternal dehiscence, 1.2% in SITA, 3.2% in BITA (p = 0.27). CONCLUSIONS: Our data do not support the perception that BITA grafting increases the risk of sternal complications in insulin-dependent diabetic patients.

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. CONCLUSIONS: 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.

Dopamine therapy for patients at risk of renal dysfunction following cardiac surgery: science or fiction?

OBJECTIVES: We aimed to evaluate the renoprotective role of renal-dose dopamine on cardiac surgical patients at high risk of postoperative renal dysfunction. The latter included older patients or those with pre-existing renal disease, elevated preoperative serum creatinine (Cr), poor ventricular function, hypertension, diabetes mellitus and unstable angina requiring intravenous therapy. METHODS: Fifty patients undergoing cardiopulmonary bypass (CPB) who fulfilled the entry criteria were prospectively randomized into two groups: Group 1 received a 'renal-dose' (3 microg kg(-1) min(-1)) dopamine infusion starting at anaesthetic induction for 48 h whilst saline infusion acted as placebo in Group 2. The anaesthetic and CPB regimes were standardized. Urinary excretion of retinol binding protein (RBP) indexed to Cr, an accurate and sensitive marker of early renal tubular damage, was assessed daily for 6 days. Additional outcome measures included daily fluid balance, blood urea and serum Cr. Statistical comparisons were made using ANOVA and Mann-Whitney U-test. RESULTS: No significant difference was found between the groups in their age, gender, preoperative NYHA class, ejection fraction, baseline serum Cr and duration of CPB and aortic cross-clamping. Renal replacement therapy was not required in any instance. Both groups demonstrated a similar and significant rise in urinary RBP throughout the study period. Dopamine-treated patients achieved more negative average fluid balance than those on placebo (5 vs. 229 ml, P<0.05). CONCLUSIONS: Renal-dose dopamine therapy failed to offer additional renoprotection to patients considered at increased risk of renal dysfunction after CPB.

Pulmonary vein gas analysis for assessing donor lung function.

BACKGROUND: Radial artery oxygenation (PaO2) is the standard method for assessing potential lung donors. This study was proposed to assess the use of pulmonary vein gases (PvO2) in selection of donor lung for transplantation. METHODS: We studied 170 lungs from 85 consecutive donors. Lungs were classified into group A, PaO2 and PvO2 > 300 mm Hg; group B, PaO2 < 300 mm Hg, and PvO2 > 300 mm Hg; and group C, PvO2 < 300 mm Hg. RESULTS: Lungs retrieved from group A and group B were used for transplantation. Allograft function, assessed by the arterial and alveolar oxygen tension ratio, was similar at 12 hours and at 24 hours after operation (0.69, 0.73, vs 0.70, 0.71, for groups A and B, respectively (p = 0.8, 0.7, respectively). Similar radiologic appearance was seen in both groups (p = 0.2). Median duration of intubation was also similar (p = 0.6). The 30-day mortality rate was 12% versus 11.3% (p = 0.8), and 1-year survival rate was 80% versus 82% (p = 0.8) for recipient received lungs from group A and B donors, respectively. CONCLUSIONS: Selective pulmonary veins analysis gives an accurate assessment of individual gas exchange in comparison with arterial PaO2, identifying more potential donor lungs for transplantation.