Arrhythmogenic gene remodelling in elderly patients with type 2 diabetes with aortic stenosis and normal left ventricular ejection fraction.

NEW FINDINGS: What is the central question of this study? Type 2 diabetes is associated with a higher rate of ventricular arrhythmias compared with the non-diabetic population, but the associated myocardial gene expression changes are unknown; furthermore, it is also unknown whether any changes are attributable to chronic hyperglycaemia or are a consequence of structural changes. What is the main finding and its importance? We found downregulation of left ventricular ERG gene expression and increased NCX1 gene expression in humans with type 2 diabetes compared with control patients with comparable left ventricular hypertrophy and possible myocardial fibrosis. This was associated with QT interval prolongation. Diabetes and associated chronic hyperglycaemia may therefore promote ventricular arrhythmogenesis independently of structural changes. Type 2 diabetes is associated with a higher rate of ventricular arrhythmias, and this is hypothesized to be independent of coronary artery disease or hypertension. To investigate further, we compared changes in left ventricular myocardial gene expression in type 2 diabetes patients with patients in a control group with left ventricular hypertrophy. Nine control patients and seven patients with type 2 diabetes with aortic stenosis undergoing aortic valve replacement had standard ECGs, signal-averaged ECGs and echocardiograms before surgery. During surgery, a left ventricular biopsy was taken, and mRNA expressions for genes relevant to the cardiac action potential were estimated by RT-PCR. Mathematical modelling of the action potential and calcium transient was undertaken using the O'Hara-Rudy model using scaled changes in gene expression. Echocardiography revealed similar values for left ventricular size, filling pressures and ejection fraction between groups. No difference was seen in positive signal-averaged ECGs between groups, but the standard ECG demonstrated a prolonged QT interval in the diabetes group. Gene expression of KCNH2 and KCNJ3 were lower in the diabetes group, whereas KCNJ2, KCNJ5 and SLC8A1 expression were higher. Modelling suggested that these changes would lead to prolongation of the action potential duration with generation of early after-depolarizations secondary to a reduction in density of the rapid delayed rectifier K+ current and increased Na+ -Ca2+ exchange current. These data suggest that diabetes leads to pro-arrythmogenic changes in myocardial gene expression independently of left ventricular hypertrophy or fibrosis in an elderly population.

Intermediate and high peri-operative cardiac enzyme release following isolated coronary artery bypass surgery are independently associated with higher one-year mortality.

BACKGROUND: The relationship between cardiac enzyme (CE) release following coronary artery bypass surgery (CABG) and medium term outcome is unclear. We sought to determine the relationship between post-operative CE release and one-year survival following isolated CABG. METHODS: Over three years 3,024 consecutive patients underwent isolated CABG. Patient characteristics were prospectively recorded in a cardiac surgical database. CE release, taken as the highest single measurement recorded in the first 24 hours post-op, was abstracted from an electronic archive. All cause mortality was taken from a national registry of deaths. RESULTS: Data were complete for 2,860 (94.6%) patients. CK-MB isoenzyme (reference range 5-24 U/l) was recorded in 2,568 (89.8%), total CK in 292 (10.2%). CE release three or more times the upper limit of the reference range (ULR) were recorded in 498 (17.4%) patients, 163 (5.7%) patients had CE more than six times ULR. There were 122 deaths (4.3%). Cox proportional hazards analysis showed that CE release 3-6 times ULR (adjusted HR 2.1 [95% CI: 1.6 to 2.6], p = 0.002) and CE release six or more times the ULR (adjusted HR 5.0 [95% CI: 4.5 to 5.4], p < 0.001) were independently associated with increased one-year mortality. CONCLUSION: Cardiac enzyme release following CABG is associated with increased one-year all-cause mortality. The definition of peri-operative myocardial infarction following CABG should include elevation of CK-MB three or more times the upper limit of normal.

Does prophylactic sotalol and magnesium decrease the incidence of atrial fibrillation following coronary artery bypass surgery: a propensity-matched analysis.

BACKGROUND: Atrial fibrillation can occur in up to 40% of patients undergoing coronary surgery. METHODS: We retrospectively analysed 103 consecutive coronary surgery patients under the care of one surgeon between April 2003 and September 2003. These patients received 40 mg of sotalol orally twice daily from the first post-operative day for 6 weeks and 2 g of magnesium intravenously immediately post surgery and on the first post-operative day. We developed a propensity score for the probability of receiving sotalol and magnesium after coronary surgery. 89 patients from the sotalol and magnesium group were successfully matched with 89 unique coronary surgery patients who did not receive either sotalol or magnesium with an identical propensity score. RESULTS: Preoperative characteristics were well matched between groups. There was no significant difference with respect to in-hospital mortality between groups (sotalol and magnesium 1.1% versus control 4.5%; p = 0.17). The incidence of atrial fibrillation in the sotalol and magnesium group was 13.5% compared to 27.0% in the controls (p = 0.025). CONCLUSION: The combination of sotalol and magnesium can significantly reduce the incidence of post-operative atrial fibrillation following coronary surgery.

A survey of current myocardial protection practices during coronary artery bypass grafting.

OBJECTIVE: To identify current myocardial protection strategies for coronary artery bypass grafting (CABG) across the UK and Ireland. METHODS: A questionnaire survey of 15 questions was sent to practising cardiac surgeons between June and October 2002. The list of surgeons was obtained from the Society of Cardiothoracic Surgeons of Great Britain and Ireland database and they were contacted by postal and electronic mail. RESULTS: 118 (73.7%) out of 160 surgeons responded to the survey. 61 (51.7%) perform CABG on-pump (ONCAB) while 10 (8.5%) practice off-pump CABG (OPCAB). 47 (39.8%) perform either depending on individual cases. Of the 108 surgeons performing ONCAB, 91 (84.3%) use cardioplegia while 17 (15.7%) use cross-clamp and fibrillation techniques. Of those using cardioplegia, 76 (83.5%) use blood cardioplegia, 15 (19.7%) use warm-blood and 60 (78.9%) use cold-blood cardioplegia. 15(16.5%) use crystalloid cardioplegia. Retrograde cardioplegia is used by 23 (25.2%). We find an interesting variation of practice in relation to specifics like warm induction, graft cardioplegia, hot-shot, single cross-clamp, hypothermia and venting procedures. An overwhelming majority of surgeons performing OPCAB use the Octopus stabiliser (n=44, 77.2%) with some others preferring the Genzyme system. Supplementary stabilisation is not commonly used. While most OPCAB surgeons use intracoronary shunts (n=51), some prefer blockers (n=9) and others use coronary sloops (n=36). Ischaemic preconditioning is not commonly practised. Several surgeons have changed their practice of myocardial protection in the last 5 years (n=45). CONCLUSIONS: This survey gives us an interesting insight into current myocardial protection practices in the UK and Ireland and may be useful for future reference.

Effect of smoking status on mortality and morbidity following coronary artery bypass surgery.

BACKGROUND: We aimed to examine the effect of smoking on outcomes following coronary artery bypass grafting (CABG). METHODS: We retrospectively analysed 6 367 consecutive patients who underwent CABG between April 1997 and March 2003. Logistic regression was used to risk adjust in-hospital outcomes, while Cox proportional hazards analysis was used to risk adjust Kaplan-Meier survival curves. Outcomes were adjusted for variables suggested by the American Heart Association and American College of Cardiology. RESULTS: 947 (14.9 %) patients were current smokers (smoking within 1 month of surgery), while 3857 (60.6 %) were ex-smokers and 1 563 (24.5 %) were non-smokers. After adjusting for differences in case-mix, current smokers were more likely to develop chest infections ( p < 0.001), atelectasis ( p < 0.001), and require ventilation longer than 48 hours ( p = 0.003). Current smokers were also more likely to stay in intensive care for more than 3 days ( p < 0.001). Ex-smokers were not associated with excess mortality ( p = 0.11), while current smokers had significantly increased mortality during follow-up ( p = 0.029). CONCLUSIONS: Patients should be encouraged to stop smoking to maximise the long-term benefits of CABG.

Bullectomy for chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease is a progressive, disabling condition which leads to poor quality of life and limited survival. Over the years, a variety of surgical procedures have been used to achieve symptomatic improvement in selected patients. This article gives a historical account of these interventions and looks at current surgical options, both for primary treatment and management of complications.