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ISCHAEMIC HEART DISEASE
Bored with PTCA? What about carotid stenting? The more adventurous interventionalist is always on the lookout for a new procedure. TheLancet offers what looks like equivalence at three years for carotid endarterectomy and angioplasty (with a 30% stent rate). However, the combined major stroke/death rate was 10% in both groups at 30 days, higher than 6.5% in the NASCET trial and 7.0% in the ECST trial. In addition, there was no medically treated control group. One could reason that the reason for equivalence (with wide confidence intervals) was that surgery did not produce the benefits expected. The rule has to be that the surgeon has to have a low rate of stroke/death at 30 days to consider surgery a good option over medical treatment, and that angioplasty at present should only be part of a randomised trial.
1 CAVATAS Investigators. Endovascular versus surgical treatment in patients with carotid stenosis in the carotid and vertebral artery transluminal angioplasty study (CAVATAS): a randomised trial.
Thrombolysis is not contraindicated after prolonged CPR: No one doubts the benefits of thrombolysis in myocardial infarction (MI) (or in major pulmonary embolism), but patients with such conditions are prone to cardiac arrest. Standard teaching is that prolonged cardiopulmonary resuscitation (CPR) is a contraindication to thrombolytic treatment because of the risk of bleeding. This prospective study comparing consecutive patients with cardiac arrest (including asystole) showed that there is no specific bleeding risk. Of 40 patients with > 15 minutes of CPR treated with heparin and tissue plasminogen activator (tPA), two had bleeds, and both these were from gastric ulcers > 48 hours after the resuscitation. As a bonus, resuscitation was more likely to be successful in the thrombolysis group (44% with thrombolysis versus 30% in the placebo group survived to intensive therapy unit, p = 0.009).
2 Böttiger BW, Bode C, Kern S, Gries A, Gust R, Glätzer R, Bauer H, Motsch J, Martin E. Efficacy and safety of thrombolytic therapy after initially unsuccessful cardiopulmonary resuscitation: a prospective clinical trial.
The right radial for the cardiologist and the left for the surgeon? Surgeons are increasingly using the radial artery as a conduit for total arterial revascularisation of the heart. Should the cardiologist take another look at the radial artery as well? This single centre study randomised 210 patients to left radial, right radial or femoral approaches for coronary angiography. No patients had serious complications but two in the femoral group had a vascular complication that delayed discharge. Otherwise the procedures produced similar results, with a quicker mobilisation and use of fewer catheters in the radial groups, although this route required one minute more fluoroscopy time than the femoral approach. Over 40% of patients in each group underwent coronary angioplasty (PTCA) following angiography with immediate sheath withdrawal. This centre has a large experience with radial catheterisation, and acknowledges that there is a steep learning curve.
3 Louvard Y, Lefevre T, Allain A, Morice M. Coronary angiography through the radial or the femoral approach: the CARAFE study.
Patients with pacemakers seem to miss out on appropriate therapy after MI: About 2% of patients presenting with MI in a large US database had a paced rhythm. These patients were more likely to be older, male, and have previous diabetes mellitus. Unsurprisingly, they had higher 30 day mortality (26% v 21%, p = 0.001), and were treated with reperfusion, aspirin, and β blockers less often. Perhaps recognising the fact that acute MI can be diagnosed despite LBBB or a paced rhythm would allow treatment to be improved.
4 Rathore SS, Weinfurt KP, Gersh BJ, Oetgen WJ, Schulman KA, Solomon AJ. Treatment of patients with myocardial infarction who present with a paced rhythm.
Social deprivation increases pre-hospital and in-hospital mortality from first MI:Assessed by postcode, social deprivation in Scotland is associated with a worse outcome after first MI. Younger patients are twice as likely to die of their MI before reaching hospital if they are from the most deprived areas compared to the least. Even when they gained access to health care, they were 20% more likely to die in hospital. The reasons for this are complex and the solution is probably equally complicated.
5 Macintyre K, Stewart S, Chalmers J, Pell J, Finlayson A, Boyd J, Redpath A, McMurray J, Capewell S. Relation between socioeconomic deprivation and death from a first myocardial infarction in Scotland: population based analysis.
Eptifibatide benefit continues at six months: Stenting during PTCA is commonplace and the use of glycoprotein IIb/IIIa inhibitors such as abciximab, tirofiban, and eptifibatide is recommended in national UK guidelines. However, these agents are not used in all cases. This trial shows that the significant reduction in death and MI seen at 48 hours is maintained at six months (7.5% v 11.5% in the placebo group, p = 0.002). There was no significant overall mortality advantage, but the study was not powered to show this. The reduction in MI rates, even those diagnosed by creatine kinase leak alone, would be expected to have a long term advantage. Eptifibatide did not, however, reduce restenosis as assessed by rates of target vessel revascularisation. 6 O'Shea JC, Hafley GE, Greenberg S, Hasselblad V, Lorenz TJ, Kitt MM, Strony J, Tcheng JE, for the ESPRIT Investigators. Platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention. The ESPRIT trial: a randomized controlled trial
A new pill for intermittent claudication: In a double blind randomised placebo controlled trial, 155 patients with intermittent claudication received either placebo or propionyl-L-carnitine for six months. After six months treatment there was a 54% (165 seconds) increase in peak walking time with active treatment compared to 25% (75 seconds) in the placebo group (p < 0.001). These effects seem to be independent of any change in ankle:brachial index and may be mediated through increased availability of L-carnitine for muscle metabolism or effects on endothelial function. Since cilostazol is contraindicated in heart failure and pentoxyfylline trials have produced conflicting results, this new treatment has an important potential role. The study did not, however, mention how many patients in each group stopped smoking. Patients need to heed the instruction to “stop smoking and keep walking” before drug treatment is tried.
7 Hiatt WR, Regensteiner JG, Creager MA, Hirsch AT, Cooke JP, Olin JW, Gorbunov GN, Isner J, Lukjanov YV, Tsitsiashvili MS, Zabelskaya TF, Amato A. Propionyl-L-carnitine improves exercise performance and functional status in patients with claudication.
Older, male smokers are particularly helped by bupropion for smoking cessation: In 600 patients given 100, 200 or 300 mg of bupropion for seven weeks and then followed for almost one year, the highest dose produced a 44% abstinence rate overall. If you are male, older, did not smoke heavily, and were not surrounded by other smokers, you were most likely to give up smoking successfully.
8 Dale LC, Glover ED, Sachs DPL, Schroeder DR, Offord KP, Croghan IT, Hurt RD. Bupropion for smoking cessation: predictors of successful outcome.
Having babies is risky, especially if the heart suffered the first time: Little is known about the outcomes of subsequent pregnancies in women who have had peripartum cardiomyopathy, a rare but sometimes fatal form of heart failure. To investigate this, a survey of members of the American College of Cardiology identified 44 women who had previously had peripartum cardiomyopathy and then had a total of 60 subsequent pregnancies. Subsequent pregnancy was associated with a significant decrease in left ventricular function and could result in clinical deterioration or even death.
1 Elkayam U, Tummala PP, Rao K, Akhter MW, Karaalp IS, Wani OR, Hameed A, Gviazda I, Shotan A. Maternal and fetal outcomes of subsequent pregnancies in women with peripartum cardiomyopathy.
Carvedilol works just as well in black patients with mild to moderate heart failure as it does in whites: In the US carvedilol heart failure trials programme, 217 black and 877 non-black patients with a left ventricular ejection fraction of no more than 0.35 were randomly assigned to receive placebo or carvedilol for up to 15 months. The effects of carvedilol on ejection fraction, clinical status, and major clinical events were retrospectively compared between black and non-black patients and found to be similar. [Last month's JournalScan reviewed a paper suggesting the same is not true for angiotensin converting enzyme (ACE) inhibitors.]
2 Yancy CW, Fowler MB, Colucci WS, Gilbert EM, Bristow MR, Cohn JN, Lukas MA, Young ST, Packer M, for the US Carvedilol Heart Failure Study Group. Race and the response to adrenergic blockade with carvedilol in patients with chronic heart failure.
Carvedilol is also safe in severe heart failure: Carvedilol is beneficial in patients with mild to moderate heart failure, but is it safe in those worst affected? This trial looked at patients with ejection fractions less than 25% and New York Heart Association (NYHA) functional class III or IV symptoms, but without significant oedema. These patients again tolerated the drug well and gained the same benefits as previously shown in other patient groups. It is interesting then that bucindolol, a similar agent, given to a similar group of patients failed to achieve the same mortality advantage in the BEST study. The accompanying editorial suggests the confidence intervals encompass the possibility that a true benefit was missed by chance in this study.
3 Packer M, Coats AJS, Fowler MB, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Castaigne A, Roecker EB, Schultz MK, Staiger C, Curtin EL, DeMets DL, for the Carvedilol Prospective Randomized Cumulative Survival Study Group. Effect of carvedilol on survival in severe chronic heart failure.
4 The Beta-Blocker Evaluation of Survival Trial Investigators. A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure.
And give carvedilol post-MI also: In a trial of 2000 patients with an ejection fraction of < 40% 3–20 days post-MI, carvedilol titrated to 25 mg twice daily by 4–6 weeks reduced mortality from 15% to 12% (p = 0.03). There was a reduction in other cardiovascular events also. The 2.3% absolute reduction in mortality at one year is similar to that expected with ACE inhibitors in this population, but is in addition to that benefit, since most patients were already on ACE inhibitors. So, β blockers are good news post-MI, especially if the left ventricle is not good.
5 The CAPRICORN Investigators. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial.
Atrial fibrillation (AF) is common and set to become even more so: The ATRIA study estimated the prevalence of AF as 0.1% under the age of 55 years, and 9% over the age of 80. Using the study population of 1.89 million Americans, it estimated that the total AF burden in the US was 2.3 million adults, half of whom would be over 75. This is set to nearly double in 50 years as the population ages. New treatments for AF, such dofetolide, radiofrequency ablation, and bi-atrial pacing can not come soon enough.
6 Go AS, Hylek EM, Phillips KA, Chang Y-C, Henault LE, Selby JV, Singer DE. Prevalence of diagnosed atrial fibrillation in adults. National implications for rhythm management and stroke prevention: the anticoagulation and risk factors in atrial fibrillation (ATRIA) study.
Systolic BP is better than diastolic BP or pulse pressure: In the cardiovascular health study, 5888 adults > 65 years were followed for an average of 6.7 years. There were 572 MIs, 385 had a stroke, and 896 died. After adjustment for potential confounders, systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure were directly associated with the risk of incident myocardial infarction and stroke. Only SBP was associated with total mortality. Importantly, SBP was a better predictor of cardiovascular events than DBP or pulse pressure. The association between blood pressure level and cardiovascular disease risk was linear; there was no evidence of a J shaped relationship.
1 Psaty BM, Furberg CD, Kuller LH, Cushman M, Savage PJ, Levine D, O'Leary DH, Bryan RN, Anderson M, Lumley T. Association between blood pressure level and the risk of myocardial infarction, stroke, and total mortality: the cardiovascular health study.
The many actions of statins: Statins not only lower cholesterol, they also have potent effects on nitric oxide production, have immunomodulatory properties, and inhibit smooth muscle proliferation. Most of these actions occur via HMG-CoA reductase inhibition, suggesting that this enzyme is involved in much more than cholesterol synthesis. This report suggests a novel mechanism of action, whereby statins reduce the expression of lymphocyte function associated antigen-1 (LFA-1) on leucocytes, so reducing their binding to the adhesion molecule ICAM-1. This would have the effect of reducing leucocyte rolling on endothelium, the first stage of their migration and infiltration into tissues, and may in part explain how statin treatment stabilises atherosclerotic plaques.
1 Weitz-Schmidt G, Welzenbach K, Brinkmann V, Kamata T, Kallen J, Bruns C, Cottens S, Takada Y, Hommel U. Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site.
An inhibitor of smooth muscle proliferation and vasoconstriction: Heme oxygenase-1 (HO-1), an enzyme expressed during injury, reduces vasoconstriction and inhibits formation of free radicals. In a pig model, smooth muscle proliferation was directly reduced. In the search for the ideal solution to restenosis after angioplasty, local HO-1 treatment might be a possibility.
2 Duckers HJ, Boehm M, True AL, Yet S-F, San H, Park JL, Clinton Webb R, Lee M-E, Nabel GJ, Nabel EG. Heme oxygenase-1 protects against vascular constriction and proliferation.
Sonic hedgehog protein (Shh) may help to grow new blood vessels: “Hedgehog proteins” act as morphogens in many tissues during embryonic development. Sonic hedgehog (Shh) is the most widely expressed. Recent observations have suggested that Hh proteins have a role in vascularising certain embryonic tissues. In this study the investigators show that Shh receptors are still present in adult cardiac and vascular tissues in mice. They also show that Shh is a potent angiogenic factor, and when administered to aged mice it is able to induce neovascularisation of ischaemic hind limbs characterised by the formation of new large diameter vessels. Shh induced upregulation of two families of angiogenic growth factors, including vascular endothelial growth factor and the angiopoietins Ang-1 and Ang-2. Another possibility in the quest to improve revascularisation?
2 Pola R, Ling LE, Silver M, Corbley MJ, Kearney M, Blake Pepinsky R, Shapiro R, Taylor FR, Baker DP, Asahara T, Isner JM. The morphogen Sonic hedgehog is an indirect angiogenic agent upregulating two families of angiogenic growth factors.
Journals scanned—American Journal of Medicine; American Journal of Physiology: Heart and Circulatory Physiology; Annals of Thoracic Surgery; Annals of Internal Medicine; 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—C Baker, E Barnes, V Bhatia, R Desilva, M Earley, K Fox, D Gorog, G Jenkins, R Kaprilian, A Kapur, M Khan, P Lambiese, V Markides, M Poullis, P Ramrakha, J Strange, B Wasan, H Walker.
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