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Highlighted articles from non-cardiological journals relevant to cardiology. This page features a preview of the next issue's JournalScan.
Series Editor: Alistair Lindsay
The latest JournalScan with abstract and full text: August 2008 issue JournalScan
(available only to subscribers or on a pay per view basis - $12)
[Journals Scanned] [Reviewers]
General cardiology
Smoking cessation provides rapid vascular benefit
A causal relationship between smoking and cardiovascular death is well established. But, for those patients who successfully stop smoking, are the detrimental effects fully reversible? And if so, how quickly do the benefits become apparent?
A total of 104 519 patients from the Nurses’ Health Study were followed up between 1980 and 2004, during which 12 483 deaths occurred. Of these, 4485 (35.9%) were people who had never smoked, 3602 (28.9%) were current smokers and 4396 (35.2%) were past smokers. As expected, a relationship was found between the risk of death and the number of cigarettes a day; however, this trend was found to be less pronounced for vascular disease, suggesting that even a few cigarettes may account for most of the associated increase in vascular risk. Similarly, the age at which a participant started smoking seemed to have less of an influence on the risk of death from vascular causes than it did for other diseases such as lung disease.
In examining cessation, the authors looked at outcomes at 5-year intervals. Sixty-one per cent of the full benefit of quitting for reduced death from coronary heart disease and 42% of the benefit for reduced cerebrovascular death was seen within 5 years of stopping smoking. In contrast, the excess mortality risk associated with respiratory disease took 30 years to decline to that of someone who had never smoked.
Although the study was performed exclusively in women, the authors feel their results are also applicable to men who have a similar smoking profile. The message remains that it is never too early to stop smoking, but as an added incentive cardiologists might mention that vascular benefits are among the earliest to become apparent.
Kenfield SA, Stampfer MJ, Rosner BA, et al. Smoking and smoking cessation in relation to mortality in women. JAMA 2008;299:2037–47.
B6 and ischaemia–reperfusion injury
MC-1 (pyridoxal 5-phosphate, a naturally occurring metabolite of vitamin B6) is a purinergic P2-receptor antagonist that blocks intracellular calcium influx and has the potential to reduce cell damage and death in patients undergoing coronary artery bypass grafting (CABG). In the first MC-1 to Eliminate Necrosis and Damage in CABG (MEND-CABG I) trial, the drug had shown some promise in reducing perioperative myocardial infarction (MI) (as defined by a creatine kinase level >100 ng/ml).
MEND-CABG II was a phase III, multicentre, randomised, double-blind, placebo-controlled trial, with 3023 intermediate- to high-risk patients undergoing CABG surgery on cardiopulmonary bypass at 130 centres. Patients were randomised to receive either 250 mg/day MC-1 (n=1519) or matching placebo (n=1504) immediately before and for 30 days after surgery. The primary efficacy end point was cardiovascular death or non-fatal MI, defined as a CK-MB fraction of at least 100 ng/ml or new Q waves up to postoperative day 30.
Overall, the primary outcome occurred in 140/1510 patients (9.3%) in the MC-1 group and 133/1486 patients (9.0%) in the placebo group (p=0.76). All-cause mortality was higher in those patients given MC-1 than in those receiving placebo after 4 days (1.0% vs 0.3%, p=0.03), but was similar at 30 days (1.9% vs 1.5%, p=0.44). There was no difference in the 8–24-h CK-MB area under the curve between the MC-1 and placebo groups (p=0.11).
Therefore in this high risk of group of patients undergoing CABG surgery, MC-1 failed to reduce the composite end point of cardiovascular death or non-fatal MI, and there are as yet no clear reasons as to why the results of this trial differ from MEND-CABG I. A number of other drugs have failed to show any benefit in reducing ischaemia–reperfusion injury at the time of bypass surgery, including pexelizumab and cariporide, however the adenosine-regulating drug acadesine has shown some promise in phase II testing and is currently in phase III trials.
MEND-CABG II Investigators. Alexander JH, Emery RW, Carrier M, et al. Efficacy and safety of pyridoxal 5-phosphate (MC-1) in high-risk patients undergoing coronary artery bypass graft surgery: The MEND-CABG II randomized clinical trial. JAMA 2008;299:1777–87.
Perioperative β blockade: the need for POISE
Over 1 million patients a year are estimated to have complications during non-cardiac surgery. The PeriOPerative Ischemic Evaluation (POISE) trial was a randomised controlled trial comparing the effect of extended-release metoprolol succinate with that of placebo on 30-day risk of major cardiovascular events in patients undergoing cardiac surgery.
A total of 8351 patients with, or at risk, of atherosclerotic disease who were undergoing non-cardiac surgery were randomised to receive metoprolol succinate (n=4174) or placebo (n=4177); patients, healthcare providers, data collectors and outcome adjudicators were masked to treatment allocation. Metoprolol (100 mg) was given orally 2–4 h before surgery and continued for 30 days. The primary end point was a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal cardiac arrest.
Twenty patients did not complete the 30-day follow-up. Fewer patients in the metoprolol group than in the placebo group reached the primary end point (244 (5.8%) vs 290 (6.9%), p=0.0399) and fewer patients in the metoprolol group had a myocardial infarction (176 (4.2%) vs 239 (5.7%), p=0.0017). However, there were more deaths in the metoprolol group than in the placebo group (129 (3.1%) vs 97 (2.3%), p=0.0317) and more patients in the metoprolol group had a stroke (41 (1.0%) vs 19 (0.5%) patients; p=0.0053). Stroke was associated with perioperative hypotension, bleeding, atrial fibrillation and a history of stroke or transient ischaemic attack in patients receiving metoprolol.
The results of this study call into question several current guidelines that recommend the use of perioperative blockade—POISE suggests that for every 1000 patients treated, metoprolol would prevent 15 cases of myocardial infarction, but there would be an excess of eight deaths and five severe disabling strokes. Why? For one thing, the dose of blocker used in the trial was high and may have been disadvantageous to those who developed hypotension. In an accompanying editorial, Dr Lee Fleisher and Dr Don Poldermans instead advocate a low-dose, long-acting agent titrated to effect at least 7 days advance—this regimen showed some benefit in one of the DECREASE (Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echo) studies run by Dr Poldermans. Indeed, as a result of POISE it is likely that current guidelines will be changed, but for now it should be remembered that patients who have been receiving long-term -blocker treatment should continue to receive the treatment throughout surgery.
POISE Study Group. Devereaux PJ, Yang H, Yusuf S, et al. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet 2008;371:1839–47.
Fleisher LA, Poldermans D. Perioperative beta blockade: where do we go from here? Lancet 2008;371:1813–4.
AEDs: an essential home accessory?
The use of automated external defibrillators (AEDs) in community-based public health programmes has led to an increase in survival after sudden cardiac arrest. About 75% of sudden cardiac arrests occur in the home, yet successful resuscitation only occurs in about 2% of cases. Technological advances with ease of use, low cost and minimal maintenance suggest that home AED treatment may improve survival. This was evaluated in the Home Automated External Defibrillator Trial (HAT), an international multicentre clinical trial.
A total of 7001 patients, with a stable medical condition who had had a previous anterior wall Q-wave or non-Q-wave myocardial infarction (a population that is known to be at increased risk for a sudden cardiac arrest) were selected and randomised to receive an AED for home use or no AED. Patients were excluded if they were candidates for implantable cardiac defibrillator therapy. Current evidence-based drug treatment after myocardial infarction was encouraged for all participants. Patients were required to have a relative or companion who was able to call emergency services, perform cardiopulmonary resuscitation and use an AED.
Education on performing cardiopulmonary resuscitation and AED use was performed by a video educational aid with refresher training every 3 months. The AED was to be kept in a prominent position in the home to facilitate access. The primary outcome was death from any cause. Secondary outcomes included death from sudden cardiac arrest, survival from witnessed sudden cardiac arrest in the home and outcome after the use of an AED.
The median age of enrolled patients was 62 years and 17% were female. Follow-up was for a median of 37.3 months. Overall, 450 patients died: 228/3506 (6.5%) in the control arm and 222/3495 (6.4%) in the AED arm (hazard ratio = 0.97, 95% CI 0.81 to 1.17, p=0.77). One hundred and sixty deaths (35.6%) were due to sudden cardiac arrest caused by tachyarrhythmia. Of these, 117 occurred at home, of which 58 were witnessed. AEDs were used in 32 patients, 14 received an appropriate shock and 4 survived to hospital discharge. No inappropriate shocks were given.
The HAT trial demonstrated that a home AED device in patients with a previous anterior myocardial infarction without an indication for an implantable cardioverter-defibrillator did not reduce mortality as compared with standard response training for cardiac arrest. However, the overall mortality rate and incidence of sudden cardiac arrest were much lower than had been predicted from historical data. This reflected the effectiveness of modern medical treatment and the high rate of previous revascularisation (72.2%) in trial participants. This led to the trial having significantly less power than initially thought—even a doubling of the trial population would have been insufficient to demonstrate a mortality benefit. Furthermore, the intensive resuscitation therapy and frequent “refresher training” is not indicative of current “real-world” practice. It is interesting to note that of those events witnessed, not all had an AED applied despite the training. The reason for this failure is unclear: a more aggressive reminder and retraining programme might have been beneficial but would have been extremely difficult to implement both from a financial and a practical perspective. The successful delivery of a shock in 14 patients and in four neighbours demonstrates that it is possible to train lay users without an additional risk of inappropriate usage. However, a strategy of home AED usage in this intermediate-risk group cannot currently be justified as an efficient public health strategy.
Bardy GH, Lee KL, Mark DB, et al. Home use of automated external defibrillators for sudden cardiac arrest. N Engl J Med 2008;358:1793–804.
In: Callans DJ, ed. Can home AEDs improve survival? N Engl J Med 2008;358:1853–5.
Interventional cardiology
Stenting versus surgery in left main stem disease
The MAIN-COMPARE registry (Revascularisation for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous Coronary Angioplasty versus Surgical Revascularisation) compared the long-term outcomes of coronary stent implantation (percutaneous coronary intervention (PCI), n=1102) and coronary artery bypass grafting (CABG, n=1138) in patients with unprotected left main stem disease in Korea. Patients from 12 major cardiac centres were enrolled between January 2000 and June 2006. Patients underwent PCI instead of CABG either because of patient or doctor preference or where CABG was felt to be high risk. From January 2000 to May 2003 stenting was performed exclusively with bare metal stents (BMS; wave 1) and from May 2003 to June 2006 with drug-eluting stents (DES; wave 2). Patients were followed up at 1 month, 6 months and 1 year and then annually. Routine angiographic follow-up was recommended for all patients who underwent PCI, 6–10 months after the index procedure. However, patients deemed at high risk for angiographic complications and who had no symptoms or signs of ischaemia (and those who declined) did not undergo this. In the CABG arm, angiographic follow-up was only recommended if the patients were symptomatic. The end points of the study were death; the composite of death, myocardial infarction or stroke; and target vessel revascularisation. The two arms were propensity score matched as well as the subgroups for type of stent.
In the overall cohort there was no significant difference between the stenting and CABG groups in the risk of death (hazard ratio (HR) for the stenting group = 1.18, 95% CI 0.77 to 1.80) or the risk of composite outcome (HR=1.10, 95% CI 0.75 to 1.62). The rates of target vessel revascularisation were significantly higher in the group who received stents than in the group who underwent CABG (HR=4.76, 95% CI 2.80 to 8.11). A comparison of the BMS subgroup with the CABG group and the DES subgroup with CABG showed similar results, although there was a trend towards higher rates of death and the composite end point in the group who received DES.
This was an observational study and therefore treatment strategy was not randomised but left to the discretion of the individual doctor or the patient. The findings are subject to selection bias and confounding, which will have been minimised but not eliminated by propensity score matching. Although the rate of repeat revascularisation was lower with DES than BMS, CABG was still more effective at reducing this. However, since there was a significantly higher rate of follow-up angiography in the PCI arm (73% vs 14.6%, p<0.001), the rate of asymptomatic graft stenosis or occlusion may have been underestimated. The study was underpowered to detect significant differences in mortality, especially in the comparison between DES and CABG. There remains a compelling case for a randomised trial to assess the efficacy of these two treatments, although this should be designed to inform management decisions for individual patients and not become a competition with the aim of identifying a “superior” technology.
Seung KB, Park DW, Kim YH, et al. Stents versus coronary artery bypass grafting for left main coronary artery disease. N Engl J Med 2008;358:1781–92.
In: Jones RH, ed. Percutaneous intervention vs coronary artery bypass grafting in left main coronary disease. N Engl J Med 2008;358:1851–3.
Electrophysiology
Early repolarisation: not a benign phenomenon
Early repolarisation is a common ECG finding, affecting 1–5% of the general population. Although emerging evidence from experimental studies suggests that it may signify an underlying predisposition to arrhythmia, the condition has generally been considered benign as supporting clinical evidence is lacking.
This international multicentre case–control study involved 206 patients with idiopathic ventricular fibrillation (VF). It assessed the prevalence of early repolarisation and the relationship with documented arrhythmias as monitored by implantable cardiac defibrillators. Patients aged >60 years were excluded to minimise the risk of subclinical structural heart disease. Baseline ECGs were reviewed for the presence of an early repolarisation (defined as an elevation of the QRS–ST junction, J point, in at least two leads) at the time of defibrillator implantation. The anterior praecordial leads (V1–3) were excluded from the analysis to avoid the enrolment of patients with either right ventricular dysplasia or Brugada syndrome. Patients were classed as having idiopathic VF if they had structurally normal hearts on echocardiography with normal ventricular function, no detectable coronary artery disease on either stress testing or coronary angiography and no known repolarisation abnormalities. The prevalence and amplitude of early repolarisation was assessed in a control group of 412 healthcare professionals with normal echocardiograms. Global frequency matching was used for the distribution of known confounding factors (age, sex, race and physical activity). In all patients, electrophysiological testing was performed with the use of multielectrode catheters. VF was considered to be inducible if it lasted for >30 s or required electrical cardioversion. In cases with recurrent VF despite the use of antiarrhythmic agents, catheter ablation targeting the initial ventricular ectopy was performed. All case subjects received implantable cardiac defibrillators and were reviewed every 6–12 months or as necessary. When antiarrhythmic drugs were deemed necessary, these were chosen by the individual doctor.
Early repolarisation was significantly more often seen in case subjects with idiopathic VF than in controls (31% vs 5%, p<0.001). Of the case subjects, early repolarisation was more often seen in men, those with a history of sudden cardiac arrest during sleep or syncope. In eight subjects the origin of ectopy that precipitated ventricular arrhythmias was mapped to sites concordant with the localisation of repolarisation abnormalities. During a mean (SD) follow-up of 61 (50) months, defibrillator monitoring demonstrated a higher incidence of recurrent VF in case subjects with a repolarisation abnormality than in those without (hazard ratio = 2.1, 95% CI 1.2 to 3.5, p=0.008).
The results of this study suggest a relationship between sudden cardiac arrest and early repolarisation. The definition of early repolarisation in this study included abnormalities in the inferior lateral leads, whereas the traditional definition involves the right praecordial leads. Few of the participants in this study belonged to subgroups with a high prevalence of early repolarisation (blacks and athletes), which suggests that cofactors influence the association with sudden cardiac arrhythmia. Arrhythmias associated with early repolarisation may be responsible for a proportion of unexplained deaths in young men as has previously been reported. They may also be responsible for some undiagnosed cause of syncope. Further studies including patients with structural heart disease, athletes and blacks will be necessary to clarify these findings and identify factors that modulate arrhythmogenicity and hence allow the identification of patients at risk.
Haissaguerre M, Derval N, Sacher F, et al. Sudden cardiac arrest associated with early repolarisation. N Engl J Med 2008;358:2016–23.
In: Wellens HJ, ed. Early repolarisation revisited. N Engl J Med 2008;358:2063–5.
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; JAMA; Journal of Clinical Investigation; Journal of Diabetes and its Complications; Journal of Immunology; Journal of Thoracic and Cardiovascular Surgery; Lancet; Nature Medicine; New England Journal of Medicine; Pharmacoeconomics; Thorax
Reviewers
Dr Alistair C Lindsay, Dr Katie Qureshi
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