David R. Ramsdale

Acute coronary syndrome: unstable angina and non-ST segment elevation myocardial infarction

The term acute coronary syndrome refers to a range of acute myocardial ischaemic states. It encompasses unstable angina, non-ST segment elevation myocardial infarction (ST segment elevation generally absent), and ST segment elevation infarction (persistent ST segment elevation usually present). This article will focus on the role of percutaneous coronary intervention in the management of unstable angina and non-ST segment elevation myocardial infarction; the next article will address the role of percutaneous intervention in ST segment elevation infarction. Although there is no universally accepted definition of unstable angina, it has been described as a clinical syndrome between stable angina and acute myocardial infarction. This broad definition encompasses many patients presenting with varying histories and reflects the complex pathophysiological mechanisms operating at different times and with different outcomes. Three main presentations have been described—angina at rest, new onset angina, and increasing angina.​angina. Figure 1 Spectrum of acute coronary syndromes according to electrocardiographic and biochemical markers of myocardial necrosis (troponin T, troponin I, and creatine kinase MB), in patients presenting with acute cardiac chest pain

Early intravenous atenolol treatment in suspected acute myocardial infarction. Preliminary report of a randomised trial.

214 patients were studied in a randomised trial to determine whether administraiton of intravenous atenolol within 12 hours of chest pain reduced eventual infarct size, as estimated by cumulative enzyme release and by ECG changes. 135 patients already had ECG evidence of infarction at entry; 72 received atenolol which significantly decreased subsequent enzyme release (atenolol and control means = 121 IU, SE +/- 10 and 177 IU, SE +/- 17; 2p < 0.005) and enhanced R-wave preservation (atenolol and control means = 46% +/- 3 and 36% +/- 3; 2p < 0.02). 79 patients had no evidence of infarction at entry; 44 did not receive atenolol and 27 of these subsequently developed infarction, whereas only 11 of 35 treated patients infarcted during their hospital stay (2p < 0.01). In hospital, fewer atenolol patients died (4 vs 9), had non-fatal cardiac arrests (2 vs 6), or required therapy for heart-failure (36 vs 47). Unlike many previous trials which had negative results, in this trial we gave the drug intravenously and promptly (median of 4 hours from onset of pain to injecton), thereby achieving early beta-blockade.

Evidence for Free Radical Generation After Primary Percutaneous Transluminal Coronary Angioplasty Recanalization in Acute Myocardial Infarction

In animal models, oxygen-derived free radicals have been found to be important mediators of reperfusion injury to ischemic but viable myocardium. However, in humans, there is no direct evidence of free radical production after the restoration of coronary artery patency in acute myocardial infarction. The purpose of this study was to quantitate and assess the time course of free radical production in coronary venous outflow in patients with acute myocardial infarction undergoing successful recanalization of the infarct-related artery by primary percutaneous transluminal coronary angioplasty (PTCA). Primary PTCA was performed in 17 patients with acute myocardial infarction of < 6 hours duration. Direct free radical production was assessed by coronary venous effluent blood sampling before PTCA and at timed intervals up to 24 hours (or 48 hours in 6 patients) after recanalization. All samples were added to the spin trapping agent alpha-phenyl N-tert butyl nitrone and analyzed by electron paramagnetic resonance spectroscopy. Vessel patency resulted in a sharp increase in free radical signal. Relative to the level before PTCA, the changes reached statistical significance after only 15 minutes (p < 0.05). Peak signals were observed between 1 1/2 and 3 1/2 hours (p < 0.001), then declined up to 5 hours. A second increase in signal level was detected between 18 and 24 hours despite no angiographic evidence of reocclusion. A gradual decline was observed after 24 hours. These findings provide the first direct and quantitative evidence of free radical production in the immediate postrecanalization phase after thrombotic occlusion of a major coronary artery in humans.

Reduction of ventricular arrhythmias by early intravenous atenolol in suspected acute myocardial infarction.

The effect of intravenous atenolol on ventricular arrhythmias in acute myocardial infarction was assessed in 182 patients admitted within 12 hours of the onset of chest pain. Ninety-five patients were randomised to receive 5 mg intravenous atenolol followed immediately by 50 mg by mouth and 50 mg 12 hours later, then 100 mg daily for 10 days; 87 patients served as controls. The treated patients had significantly fewer ventricular extrasystoles; 58 control patients (67%) had R-on-T extrasystoles compared with only 25 treated patients (26%) (2p less than 0.0001); repetitive ventricular arrhythmias were detected in 64 control patients (74%) and 55 treated patients (58%) (2p less than 0.05). Heart rate was significantly reduced from 77 +/- 1 beats/min at entry to 65 +/- 1 beats/min (2p less than 0.001) in the first hour after intravenous atenolol, and in addition the rate was significantly different from that in the control group. There was no difference in the incidence of heart failure, but fewer patients in the treated group received other antiarrhythmic agents or digoxin. These results show that early intravenous atenolol prevents ventricular arrhythmias in suspected acute myocardial infarction.

Free-radical generation during angioplasty reperfusion for acute myocardial infarction

We describe direct and quantitative evidence of free-radical production in the early stage after recanalisation in a patient undergoing primary coronary angioplasty for acute myocardial infarction. After successful initial dilation, the procedure was complicated by re-occlusion of the artery at the same site, with subsequent fall in free-radical generation. After repeat angioplasty, recanalisation was again accompanied by increased free-radical production.

Smoking and coronary artery disease assessed by routine coronary arteriography.

The association between extent and duration of smoking habit and severity of coronary atheroma was examined in 387 patients undergoing routine coronary ateriography before valve replacement surgery. Total number of cigarettes smoked in life correlated significantly with severity of coronary artery disease (p less than 0.001) and number of coronary arteries with stenoses of 50% or more (p less than 0.001). Severity of coronary artery disease in current smokers was similar to that in former smokers. Multiple regression analysis showed diastolic blood pressure, cigarette consumption, age, ratio of total cholesterol to high density lipoprotein cholesterol, and history of angina to be the important predictors of severity of coronary artery disease. An estimate of the number of cigarettes smoked in life can be useful in identifying patients with coronary artery disease if used in conjunction with data on other important risk factors.

Antibiotic Prophylaxis for Pacemaker Implantation: A Prospective Randomized Trial

Prophylactic antibiotics are frequently prescribed for patients undergoing permanent pacemaker implantation even though data confirming their effectiveness are limited. Five hundred patients requiring elective permanent pacemaker implantation or generator replacement were prospectively randomized either to receive or not receive prophylactic antibiotic treatment at the time of implantation. The implantation site was treated with 10% povidone‐iodine solution and 0.5% alcoholic chlorhexidine preoperatively. The wounds were inspected for evidence of infection at 3 days and 1, 3, 6 and 12 months postimplantation. Three patients (two receiving prophylactic antibiotics and one no antibiotics) developed pacemaker pocket infection; Staphylococcus aureus was the pathogenic organism in each case (P = 0.56). Eighteen patients developed clinical evidence of superficial wound inflammation requiring antibiotic treatment but not pacemaker removal. Six had received prophylactic antibiotics and 12 had not (P = 0.27). We conclude that pacemaker pocket infection is unusual with careful preoperative skin preparation and close postoperative follow‐up. Under these circumstances prophylactic antibiotic treatment is of no practical value.

Ischemic pain relief in patients with acute myocardial infarction by intravenous atenolol

Pain relief in acute myocardial infarction (AMI) by the beta-adrenoceptor antagonist, atenolol, was demonstrated by three separate studies. First, 18 patients were randomized to double-blind intravenous atenolol (5 mg) or saline immediately after admission, followed by oral atenolol (50 mg) or placebo 10 minutes later. In patients receiving atenolol, pain relief coincided with reduction in heart rate (HR), systolic blood pressure (SBP), and HR X SBP product (p less than 0.05); however, pain and these parameters were unchanged by placebo. The degree of pain relief was related to the reduction in cardiac work achieved (r = 0.725; p less than 0.001). A second open study involving 22 patients receiving intravenous atenolol (5 to 15 mg) early after AMI showed ischemic pain relief in 17 patients. They achieved a more significant reduction in HR X SBP product than those whose pain remained unchanged (p = 0.004). Finally, a retrospective study of 163 patients randomized to either atenolol or no beta blockade early after AMI revealed that patients receiving atenolol needed less opiate analgesia after admission (p less than 0.001). The safety of this therapy was illustrated by a decreased incidence of left heart failure and atrial fibrillation and no tendency to second- and third-degree heart block.

Reduction in Infarct Size, Arrhythmias, Chest Pain and Morbidity by Early Intravenous β-Blockade in Suspected Acute Myocardial Infarction

Summary477 patients suspected of acute myocardial infarction, with onset of less than 12 hours, were randomised to a control group or a group receiving intravenous atenolol followed by oral treatment for 10 days. In patients with electrocardiographic (ECG) changes of infarction at entry, intravenous atenolol significantly reduced enzyme release by one- third and enhanced R wave preservation. In patients without ECG changes of infarction at entry, treatment significantly prevented the development of infarction in a proportion of patients.There was also a significant reduction in R- on- T ectopics, repetitive ventricular arrhythmias and supraventricular arrhythmias. Treated patients had greater pain relief and required less opiate analgesics. Fewer atenolol- treated patients died at 1 week, had non- fatal cardiac arrests, developed heart failure, or suffered reinfarction.

Reperfusion injury after acute myocardial infarction.

The restoration of oxygenated blood to ischaemic myocardium—reperfusion—halts the process leading to infarction. Early reperfusion is the only way to prevent progression to myocardial necrosis and thus to limit the size of the infarct. It may also, however, injure the heart. This paradox has become clinically important with the advent of thrombolytic treatment and primary coronary angioplasty for acute myocardial infarction. Several studies have shown that there are three main components of reperfusion injury: reperfusion arrhythmias, myocardial stunning, and lethal myocyte injury. Sixty years ago Tennant and Wiggers recognised that the reintroduction of blood flow could cause arrhythmias.1 In animal experiments arrhythmias may occur within seconds of the onset of reflow.2 In humans reperfusion arrhythmias are commonly associated with intracoronary thrombolytic treatment3 and primary coronary angioplasty.4 5 They may be less common after intravenous thrombolytic treatment,6 and in these circumstances it has been proposed that they pose no additional threat to life.7 The disparity may, however, be related to the rate of recanalisation. Yamazaki et al showed that in dogs sudden reperfusion was more likely to be associated with a high frequency of arrhythmias than was staged reperfusion.8 In a randomised clinical study comparing intravenous thrombolytic treatment with primary coronary angioplasty, ventricular fibrillation was significantly more common in the angioplasty group (6.7% v 2.0%).4 These studies provided angiographic …