ISCHAEMIC HEART DISEASE

How long to wait before a plane journey after AMI ▸Aircrafts are pressurised to achieve cabin pressures equivalent to 5000–8000 feet altitude. At this cabin pressure, PIo₂ falls from 150 to 107 mm Hg and Pao₂ falls from 98 to 55 mm Hg. Although in healthy individuals this results in only a small drop in Sao₂, if Sao₂ is low to start with, the fall may be clinically significant. Short distance helicopter transport of patients with acute myocardial infarction (AMI) for emergency medical care has been assessed in a number of small studies and appears safe, with the most frequent side effects being hypotension (~10%), bradycardia (~10%), and tachycardia (atrial fibrillation/flutter or ventricular tachycardia ~5%). There is some discordance in current guidelines for unescorted patients travelling after AMI. After an uncomplicated AMI, travel should be deferred for at least two weeks (American College of Cardiology/American Heart Association, two weeks; Aerospace Medical Association, three weeks; and American Medical Association, four weeks).

Atorvastatin induced neuropathy ▸ A case report of a 57 year old man in good health, excluding hyperlipidaemia, with progressive numbness and burning in both feet, particularly the dorsal aspect, for six months is described. His medications included atorvastatin, 5 mg, and one aspirin daily. The patient did not report muscle tenderness, weakness, or paralysis, and had no difficulty walking. Punch biopsy of the proximal thigh, distal thigh, and distal leg revealed a neuropathic process affecting small calibre sensory nerve fibres. Three months after treatment with atorvastatin was discontinued, the burning resolved. There is a four- to 14-fold increased risk for idiopathic polyneuropathy, the mechanism for which is unclear.

When to start statins ▸ Should statins be started predischarge after acute coronary syndrome (ACS)? There are no conclusive data to suggest mortality advantage over later initiation, but in a busy world, “later” may mean “never”. Using data from patients in the EPILOG (evaluation in PTCA to improve long-term outcome with abciximab GP IIb/IIIa blockade) trial, 175 were discharged taking lipid lowering treatment and 1951 were not. After six months, 77% of patients who started taking lipid lowering agents before hospital discharge continued taking treatment, compared with only 25% of those discharged without these agents (adjusted relative risk 3.17, 95% confidence interval (CI) 2.88 to 3.41; p < 0.001).

There is a point to stopping smoking even after you have developed IHD ▸ A study population of 3122 patients with a previous myocardial infarction or stable angina participated in the bezafibrate infarction prevention trial. Patients were prospectively followed up for a mean of 8.2 years. Among the 370 patients who were current smokers, 30 (8.1%) experienced sudden cardiac death (SCD); 83 (4.6%) of the 1821 patients who had quit smoking and 43 (4.6%) of the 931 patients who had never smoked experienced SCD (p  =  0.01). In multivariate analyses, current smoking was associated with a significant increase in the risk of SCD (hazard ratio 2.47, 95% CI 1.46 to 4.19). Patients who had stopped smoking had no significant increase in the risk of SCD compared with patients who had never smoked (hazard ratio 1.06, 95% CI 0.70 to 1.62).

What is the risk of AMI from combination antiretroviral therapy? ▸ In this prospective observational study, 23 468 patients from 11 previously established cohorts were enrolled. Data were collected on infection with the human immunodeficiency virus and on risk factors for and the incidence of myocardial infarction. In total, 126 patients had a myocardial infarction. The incidence of myocardial infarction increased with longer exposure to combination antiretroviral therapy (adjusted relative rate per year of exposure 1.26, 95% CI 1.12 to 1.41; p < 0.001). Other factors significantly associated with myocardial infarction were older age, current or former smoking, previous cardiovascular disease, and male sex, but not a family history of coronary heart disease. A higher total serum cholesterol concentration, a higher triglyceride concentration, and the presence of diabetes were also associated with an increased incidence of myocardial infarction.

No advantage to adding valsartan to captopril post-AMI ▸ In a double blind trial, the effect of the angiotensin receptor blocker valsartan, the angiotensin converting enzyme (ACE) inhibitor captopril, and combination of the two, on mortality was compared in a post-AMI population with heart failure. Patients receiving conventional treatment were randomly assigned, 0.5 to 10 days after AMI, to additional treatment with valsartan (4909 patients), valsartan + captopril (4885 patients), or captopril (4909 patients). The primary end point was death from any cause. During the 24 month follow up, 979 patients in the valsartan group died, as did 941 patients in the valsartan + captopril group and 958 patients in the captopril group (hazard ratio in the valsartan group as compared with the captopril group 1.00, 97.5% CI 0.90 to 1.11, p  =  0.98; hazard ratio in the valsartan + captopril group as compared with the captopril group 0.98, 97.5% CI 0.89 to 1.09, p  =  0.73). The valsartan + captopril group had the most drug related adverse events. With monotherapy, hypotension and renal dysfunction were more common in the valsartan group, and cough, rash, and taste disturbance were more common in the captopril group.

HYPERTENSION

Which antihypertensive drug to use? ▸ The benefits of reducing blood pressure on the risks of major cardiovascular disease are well established, but uncertainty remains about the comparative effects of different blood pressure lowering regimens. Data from 29 randomised trials (n  =  162 341) suggested that the relative risks of total major cardiovascular events were reduced by regimens based on ACE inhibitors (22%, 95% CI 17% to 27%) or calcium antagonists (18%, 95% CI 5% to 29%). Greater risk reductions were produced by regimens that targeted lower blood pressure goals (15%, 95% CI 5% to 24%). Angiotensin receptor blocker (ARB) based regimens reduced the risks of total major cardiovascular events (10%, 95% CI 4% to 17%) compared with control regimens. There were no significant differences in total major cardiovascular events between regimens based on ACE inhibitors, calcium antagonists, or diuretics or β blockers, although ACE inhibitor based regimens reduced blood pressure less. Treatment with any commonly used regimen reduces the risk of total major cardiovascular events, and larger reductions in blood pressure produce larger reductions in risk.

GENERAL CARDIOLOGY

How to detect insulin resistance ▸ Although obese individuals tend to be insulin resistant, hyperinsulinaemic, glucose intolerant, and dyslipidaemic, not all overweight or obese individuals are insulin resistant. The adult treatment panel III (ATP III) criteria are three or more of the following: waist circumference > 102 cm in men and > 88 cm in women; triglyceride (TG) concentration > 1.69 mmol/l; high density lipoprotein (HDL) cholesterol concentration < 1.03 mmol/l in men and < 1.29 mmol/l in women; blood pressure > 130/85 mm Hg or treatment with antihypertensive medication; and fasting plasma glucose concentration > 6.11 mmol/l (sensitivity 52%, specificity 85%). In 285 non-diabetic individuals, the optimal cut points were TG > 1.47 mmol/l, 1.8 for the TG/HDL ratio, and 109 pmol/l for insulin. These gave similar sensitivity and specificity in obese patients to ATP III criteria. It may be worth targeting risk reduction treatment at these individuals.

PFO closure for paradoxical emboli ▸ Ten studies of transcatheter closure (1355 patients) and six studies of medical treatment (895 patients) for patent foramen ovale (PFO) were included. Overall, the one year rate of recurrent neurologic thromboembolism with transcatheter intervention was 0–4.9%, and the incidence of major and minor complications was 1.5% and 7.9%, respectively. Medical management was associated with a one year recurrence rate of 3.8–12.0%. General differences in study samples included older age, greater proportion of men, and higher prevalence of diabetes and smoking among medically treated patients. Patients undergoing treatment with a transcatheter device were more likely to have had multiple thromboembolic events at baseline. Conclusion—randomised controlled trials are needed to prove if PFO closure is worthwhile.

Treating high INR ▸ Treatment of patients with excessive anticoagulation is routinely done by intravenous phytonadione (vitamin K₁). Oral administration of phytonadione has been shown to be an effective alternative to the intravenous route, but these methods have never been compared directly. Patients with a baseline international normalised ratio (INR) of 6–10 (n  =  44, 47 episodes) received either intravenous or oral phytonadione (0.5 mg or 2.5 mg, respectively), and patients with an INR > 10 (n  =  17, 19 episodes) received 1 mg or 5 mg, respectively. Efficacy and safety end points were sequential INR changes and the proportion of patients achieving therapeutic range (INR 2–4), overcorrection (INR < 2.0), or undercorrection (INR > 4.0) INR values. Sixty six episodes of excessive anticoagulation were studied. In patients with baseline INR 6–10 the response to intravenous phytonadione was more rapid than in the oral group, and the proportion of patients reaching therapeutic range INR at six hours (11/24 v 0/23) and at 12 hours (16/24 v 8/23) was significantly higher. However, mean (SD) INR values were similar for both groups at 24 hours (2.9 (0.8) v 2.6 (0.8)). Patients in the intravenous group tended to be more often (7/24 v 2/23) overcorrected (INR < 2). In patients with baseline INR values > 10 efficacy and safety were comparable for both routes of administration.

Progressive carotid stenosis is a risk factor for CVA ▸ The progression of carotid stenosis may be a better predictor of adverse neurological outcomes than a single measurement of stenosis in asymptomatic patients. A total of 1701 carotid arteries from 1004 asymptomatic patients were prospectively followed by duplex ultrasonographic scanning. The baseline degree of carotid stenosis was less than 50% of artery diameter in 75% of patients. The annual rates of ipsilateral transient ischaemic attacks (TIA) and cerebrovascular accidents (CVA) were 2.0% and 2.1%, respectively. Univariable Cox proportional hazards modelling showed that both baseline carotid stenosis and progression of stenosis were significant predictors of the composite outcome TIA and CVA, as well as the outcome CVA alone. In multivariable modelling, the progression of carotid stenosis was a highly significant predictor of the composite outcome TIA and CVA (risk ratio 1.68, p < 0.001) and of CVA alone (risk ratio 1.78, p < 0.001).

Risks of spironolactone ▸ In 125 patients with poor left ventricular function started on spironolactone, the level of side effects was assessed. Taking spironolactone is associated with considerably more frequent side effects than previously thought. Serum potassium > 6 mmmol/l occurred in 10% and a doubling of creatinine occurred in 24%. In this analysis the New York Heart Association (NYHA) class (3.36, 95% CI 1.17 to 9.69, for each class) and lower left ventricular ejection fraction (0.37, 95% CI 0.15 to 0.95, for each 10% increase) were predictive factors for these two complications. Potassium supplements should be curtailed, and other diuretic treatment may need to be reduced.

Preventing contrast nephropathy ▸ N-acetyl cysteine given orally or intravenously before contrast may reduce contrast nephropathy. Prehydration is also important. Fenoldopam has also been suggested. Between March 2001 and July 2002, 315 patients with creatinine clearance < 60 ml/min (1.00 ml/s) at 28 centres in the USA were randomised to receive fenoldopam mesylate (n  =  157) or placebo (n  =  158). The primary end point of contrast induced nephropathy occurred in 33.6% of patients assigned to receive fenoldopam versus 30.1% assigned to receive placebo (relative risk 1.11, 95% CI 0.79 to 1.57; p  =  0.61). There were no significant differences in the 30 day rates of death (2.0% v 3.8%, p  =  0.50), dialysis (2.6% v 1.9%, p  =  0.72), or rehospitalisation (17.6% v 19.9%, p  =  0.66) in fenoldopam versus placebo randomised patients, respectively.

Ximelagatran for atrial fibrillation ▸ In 3410 patients with non-valvar atrial fibrillation, ximelagatran 36 mg twice daily in an open label design proved not to be inferior to warfarin (INR maintained at 2–3) in the prevention of strokes. There were a similar number of individuals with major bleeding episodes, but fewer with minor bleeding in the ximelagatran group. As in previous trials, liver enzymes were transiently raised—in 6% of patients on ximelagatran in this study, compared with 3% of patients treated with 24 mg twice daily and 7% with 36 mg twice daily in ESTEEM, a trial of the drug in coronary disease.

Journals scanned

American Journal of Medicine; American Journal of Physiology: Heart and Circulatory Physiology; Annals of Emergency Medicine; Annals of Thoracic Surgery; Archives of Internal Medicine; BMJ; Chest; European Journal of Cardiothoracic Surgery; Lancet; JAMA; Journal of Clinical Investigation; Journal of Diabetes and its Complications; Journal of Immunology; Journal of Thoracic and Cardiovascular Surgery; Nature Medicine; New England Journal of Medicine; Pharmacoeconomics; Thorax

Reviewers

Dr Diana Gorog, Dr Akhil Kapur, Dr Masood Khan, Dr Pipin Ko, Dr Vias Markides, Dr Oliver Segal, Dr Andrew Sharp, Dr Tom Wong