Hypothermia resulting in characteristic ECG changes mimicking an acute myocardial infarction: Osborn waves and atrial fibrillation.

Hypothermia can cause several ECG changes which can be mistaken for other cardiac diseases, most importantly acute transmural ischaemia. These ECG changes correlate strongly with the degree of hypothermia and the prognosis of the patient. This brief report presents a 32-year-old male who was seen after a drowning accident. After resuscitation a 12-lead electrocardiogram showed changes typical for hypothermia: atrial fibrillation and Osborn waves. The ECG of the patient normalised after rewarming.

Successful aortic valve replacement in a patient with AIDS.

In trying to assess the benefit of cardiac surgery in AIDS patients, the question arises whether a patient with a deficient immune system can tolerate open heart surgery well enough to make the operation worthwhile. Surgical procedures and cardiopulmonary bypass have been noted to alter immune function (Diettrich et al., Ide et al.). Therefore, the presence of clinical AIDS is often still regarded as a contraindication to cardiac surgery. In this report we describe an AIDS patient who developed endocarditis of the native aortic valve. The endocarditis was successfully treated with antibiotic drugs, but the patient was left with damaged valves. Over the months he developed a massive aortic insufficiency and underwent aortic valve replacement. The patient did well after surgery, and is alive and well 18 months after the operation, suggesting that cardiac surgery might be a good and valuable treatment option in AIDS patients.

Pharmacodynamics and safety of lefradafiban, an oral platelet glycoprotein IIb/IIIa receptor antagonist, in patients with stable coronary artery disease undergoing elective angioplasty.

OBJECTIVE: Lefradafiban is the orally active prodrug of fradafiban, a glycoprotein IIb/IIIa receptor antagonist. The present phase II study aimed to determine the dose of lefradafiban that provides 80% blockade of the glycoprotein IIb/IIIa receptors by fradafiban, and to study the pharmacodynamics and safety of different doses in patients with stable angina undergoing angioplasty. DESIGN: A double blind, placebo controlled, dose finding study. SETTING: Four academic and community hospitals in the Netherlands. PATIENTS: 64 patients with stable coronary artery disease undergoing elective percutaneous transluminal coronary angioplasty. INTERVENTIONS: 30 mg, 45 mg, and 60 mg of lefradafiban three times daily or placebo was given for 48 hours. MAIN OUTCOME MEASURES: The primary safety end point was the occurrence of bleeding, classified as major, minor, or insignificant according to the thrombolysis in myocardial infarction (TIMI) criteria. Efficacy indices included per cent fibrinogen receptor occupancy (FRO), ex vivo platelet aggregation, and plasma concentrations of fradafiban. RESULTS: Administration of lefradafiban 30, 45, and 60 mg three times daily resulted in a dose dependent increase in median FRO levels of 71%, 85%, and 88%, respectively. Inhibition of platelet aggregation was closely related to FRO. There were no major bleeding events. The 60 mg lefradafiban group had a high (71%) incidence of minor and insignificant bleeding. The incidence of bleeding was 44% in the 30 mg and 45 mg groups, compared with 9% in placebo patients. Puncture site bleeding was the most common event. The odds of bleeding increased by 3% for every 1% increase in FRO. CONCLUSIONS: Lefradafiban is an effective oral glycoprotein IIb/IIIa receptor blocker. The clinical effectiveness of doses up to 45 mg three times daily should be investigated.

Safety and efficacy of eptifibatide vs placebo in patients receiving thrombolytic therapy with streptokinase for acute myocardial infarction; a phase II dose escalation, randomized, double-blind study.

AIMS: Thrombolytic therapy restores coronary patency in patients with acute myocardial infarction, although normal perfusion (TIMI 3 flow) is not achieved in all patients. In an attempt to improve TIMI 3 flow, a combination of full-dose streptokinase, aspirin and escalating dosages of a platelet glycoprotein IIb/IIIa receptor blocker, eptifibatide, vs placebo were tested. METHODS AND RESULTS: A bolus of 180 microg. kg(-1)of eptifibatide was administered in each group, followed by a 72 h continuous infusion of 0.75 (44 patients), 1.33 (n=45) and 2.00 microg. kg(-1). min(-1)(n = 30); 62 patients received placebo. Normal perfusion (TIMI 3 flow) at 90 min was observed in 31% of placebo patients compared to 46, 42 and 45% in the ascending eptifibatide groups (44% for combined eptifibatide groups, P = 0.07). Patency (TIMI 2 and 3 flow combined) increased from 61% (placebo) to 78% for the combined eptifibatide groups (P = 0.02). Reocclusion was infrequent. No differences were observed in TIMI flow grades among eptifibatide groups. Major and minor bleeding was increased and occurred mainly at the arterial puncture site. CONCLUSION: A combination of full dose streptokinase with different eptifibatide regimens enhanced coronary perfusion, but bleeding risk was excessive. Additional trials are needed with different dosage regimens to determine the optimal combination of fibrinolytic agents and platelet glycoprotein IIb/IIIa receptor blockers.

Stents and IIb/IIIa receptor blockers combined: usefulness in various types of coronary artery disease.

Both the implantation of intracoronary stents and the use of glycoprotein IIb/IIIa receptor blocking agents have been proven to be of value in the invasive management of coronary artery disease. Stenting is shown to decrease restenosis rate considerably, and is of great use in countering complications of balloon angioplasty, e.g. dissection and abrupt closure. The use of glycoprotein IIb/IIIa receptor blocking agents has been demonstrated to be beneficial as an adjunctive to intracoronary interventions; it has a profound effect on the rate of acute intervention related complications, but not on the occurrence of chronic restenosis. The scope of this article is to evaluate the usefulness of the combination of stents and glycoprotein IIb/IIIa blocking agents in various manifestations of coronary artery disease. It is concluded that a glycoprotein IIb/IIIa receptor antagonist as an adjunctive to the application of a stent is especially useful when thrombus can be assumed to be present in a clinically relevant quantity.

Reduction in the need for unplanned stenting with the use of platelet glycoprotein IIb/IIIa blockade in percutaneous coronary intervention.

Data from the 5 large randomized, double-blind, placebo-controlled trials that used glycoprotein IIb/IIIa inhibitors during percutaneous transluminal coronary angioplasty were pooled for a total of 10,691 patients. We found that the use of glycoprotein IIb/IIIa inhibitors in percutaneous coronary interventions significantly decreases the need for unplanned stenting for abrupt closure.

Antiplatelet therapy in therapy-resistant unstable angina. A pilot study with REO PRO (c7E3).

Patients with unstable angina, refractory to intensive medical therapy, are at high risk of developing thrombotic complications, such as myocardial infarction and coronary occlusion during coronary angioplasty. As platelet aggregation and thrombus formation play an important role in this ongoing ischaemic process, a monoclonal platelet GPIIb/IIIa receptor antibody (c7E3) has been designed to modify the clinical course and underlying coronary lesion morphology. To evaluate whether c7E3 could influence the incidence of complications, we randomized 60 patients to c7E3 or placebo after initial angiography had demonstrated a culprit lesion amenable for angioplasty. All patients exhibited dynamic ECG changes and recurrent pain attacks, despite intensive medical therapy. After study drug bolus and infusion, angiography was repeated and angioplasty performed. Recurrent ischaemia during study drug infusion occurred in nine and 16 patients from the c7E3 and placebo groups, respectively (P = 0.06). Major events defined as death, myocardial infarction or urgent intervention occurred in one and seven patients, respectively (P = 0.03). One patient from the placebo group died as a result of recurrent infarction. Resolution of clots was only observed in the c7E3 group, combined with improvement in TIMI flow grade in 20% of patients. Quantitative angiography showed an improvement in percentage diameter stenosis in the c7E3 group, which was not observed in the placebo group, although the difference between the two treatment groups was not significant. No excess bleeding was observed in the treatment group. Thus, c7E3 bolus and infusion, combined with heparin and aspirin improved the clinical course, the coronary lesion morphology and rheology in patients with unstable angina, refractory to medical treatment.

Ridogrel as an adjunct to thrombolysis in acute myocardial infarction.

An open pilot study was performed to assess the safety and preliminary efficacy of ridogrel, a selective thromboxane-A2 synthetase inhibitor and thromboxane-A2/prostaglandin endoperoxide receptor blocker, as adjunct to thrombolysis, with alteplase and heparin. In 50 patients with acute myocardial infarction, 300 mg ridogrel was injected intravenously in addition to alteplase and heparin. Ridogrel was continued orally (300 mg) twice daily for 5 days. Patency rate at initial (90 min) angiography, defined as thrombolysis in myocardial infarction perfusion grades 2 or 3, was 86%. Rescue percutaneous transluminal coronary angioplasty was performed in 10 patients; immediate results were good in nine, while a large dissection occurred in one patient. New ischemia occurred in 10 patients within 24 h, and after the second angiogram in seven cases. Three underwent coronary artery bypass grafting and seven percutaneous transluminal coronary angioplasty without further complication. Patency rate at second angiography (between 6 and 24 h) was 94%. New Q-waves appeared in 56% of the patients; 36% had a non-Q-wave infarction and 8% had no enzyme rise. Enzymatic infarct size, estimated by the cumulative quantity of alpha-hydroxybutyrate dehydrogenase released in 72 h, was substantially smaller than in comparable studies with rt-PA and heparin. One patient died due to a cerebrovascular hemorrhage. No other deaths occurred. Bleeding complications were seen in 18 patients (36%), necessitating blood transfusion in three. Reinfarction did not occur. Eventually 49 patients were discharged in good condition. Safety with regard to bleeding complications of ridogrel in conjunction with alteplase is about the same as that of aspirin. Immediate and late patency rates were high. Rescue percutaneous transluminal coronary angioplasty could be performed with relative safety and early reocclusion could be successfully dealt with by repeat percutaneous transluminal coronary angioplasty. Further studies with this or similar compounds seem warranted.

Correlation between clinical course and quantitative analysis of the ischemia related artery in patients with unstable angina pectoris, refractory to medical treatment. Results of two randomized trials. The European Cooperative Study Group.

Patients with unstable angina, refractory to intensive medical therapy, are at high risk for developing thrombotic complications, such as recurrent ischemia, myocardial infarction and coronary occlusion during coronary angioplasty. As both platelet aggregation and/or thrombus formation play an important role in this ongoing ischemic process, a monoclonal platelet GPIIb/IIIa receptor antibody (c7E3) or thrombolytic therapy (alteplase) might be able to modify the clinical course and underlying coronary lesion morphology. To evaluate whether alteplase or c7E3 could influence the incidence of complications, we randomized 36 and 60 patients, respectively to alteplase or placebo, or c7E3 or placebo. All patients exhibited dynamic ECG changes and recurrent pain attacks, despite maximal tolerated medical therapy. Patients were randomized in both studies after initial angiography had demonstrated a culprit lesion amenable for angioplasty. After study drug infusion quantitative angiography was repeated and angioplasty performed. Recurrent ischemia during study drug infusion occurred in 5, 6, 9 and 16 patients from the alteplase, placebo, c7E3 and placebo group, respectively. Major events defined as death, myocardial infarction or urgent intervention occurred in 7, 3, 1 and 7 patients, respectively. Two patients died: one in the alteplase group and one in the placebo group from the c7E3 study. The first patient due to retroperitoneal hemorrhage, the second as a result of recurrent infarction. Qualitative angiography showed resolution of clots in the c7E3 group only, while the same group of patients showed in 20% an improvement in TIMI flow grade, without deterioration in any patient from this group.(ABSTRACT TRUNCATED AT 250 WORDS)

A pilot study of coronary angioplasty in outpatients.

BACKGROUND: Is it safe to discharge patients from hospital on the same day as percutaneous transluminal coronary angioplasty (PTCA)? The hypothesis tested was that careful pre and post angioplasty selection of patients can identify a group that is at very low risk of postprocedural complications and that these patients may be discharged on the day of the procedure. METHODS: 63 patients undergoing limited risk coronary angioplasty of 72 lesions were studied. So that patients would be able to walk soon after PTCA miniature equipment (6 French catheters and balloon-on-a-wire devices) was passed percutaneously through the right brachial artery. After coronary angioplasty patients with angiographic evidence of dissection and/or thrombus and with complications were assigned to an inpatient group and those in whom PTCA had achieved a good angiographic result were assigned to an outpatient group. RESULTS: Two patients were excluded because the brachial approach failed, leaving 61 patients (70 lesions). After PTCA 50 patients (82%) with 57 lesions (81%) attempted were assigned to the outpatient group. No cardiac complication occurred in this subset (0%; 95% confidence interval 0 to 7%). Eleven patients (18%), in whom 13 lesions (19%) were attempted, were assigned to the inpatient group. Three of these patients (27%; 95% confidence interval 6 to 61%) had cardiac complications. Two patients needed local surgical repair after catheterisation of the brachial artery; one had a haematoma and one had a false aneurysm. CONCLUSIONS: Coronary angioplasty with miniature equipment passed through the brachial artery was a safe procedure with a high initial success rate. The results of this pilot trial suggest that with careful selection of patients before and after angioplasty PTCA can be performed safely in outpatients.

Randomized trial of a GPIIb/IIIa platelet receptor blocker in refractory unstable angina. European Cooperative Study Group.

BACKGROUND: Patients with unstable angina despite intensive medical therapy, ie, refractory angina, are at high risk for developing thrombotic complications: myocardial infarction or coronary occlusion during percutaneous transluminal coronary angioplasty (PTCA). Chimeric 7E3 (c7E3) Fab is an antibody fragment that blocks the platelet glycoprotein (GP) IIb/IIIa receptor and potently inhibits platelet aggregation. METHODS AND RESULTS: To evaluate whether potent platelet inhibition could reduce these complications, 60 patients with dynamic ST-T changes and recurrent pain despite intensive medical therapy were randomized to c7E3 Fab or placebo. After initial angiography had demonstrated a culprit lesion suitable for PTCA, placebo or c7E3 Fab was administered as 0.25 mg/kg bolus injection followed by 10 micrograms/min for 18 to 24 hours until 1 hour after completion of second angiography and PTCA. During study drug infusion, ischemia occurred in 9 c7E3 Fab and 16 placebo patients (P = .06). During hospital stay, 12 major events occurred in 7 placebo patients (23%), including 1 death, 4 infarcts, and 7 urgent interventions. In the c7E3 Fab group, only 1 event (an infarct) occurred (3%, P = .03). Angiography showed improved TIMI flow in 4 placebo and 6 c7E3 Fab patients and worsening of flow in 3 placebo patients but in none of the c7E3 Fab patients. Quantitative analysis showed significant improvement of the lesion in the patients treated with c7E3 Fab, which was not observed in the placebo group, although the difference between the two treatment groups was not significant. Measurement of platelet function and bleeding time demonstrated > 90% blockade of GPIIb/IIIa receptors, > 90% reduction of ex vivo platelet aggregation to ADP, and a significantly prolonged bleeding time during c7E3 Fab infusion, without excess bleeding. CONCLUSIONS: Combined therapy with c7E3 Fab, heparin, and aspirin appears safe. These pilot study results support the concept that effective blockade of the platelet GPIIb/IIIa receptors can reduce myocardial infarction and facilitate PTCA in patients with refractory unstable angina.

Acquired aorto-pulmonary fistula in acute dissection.

We describe a 41-year-old man with an acute dissection of the ascending aorta with fistulation into the pulmonary artery. The diagnosis was made pre-operatively by 2-D and Doppler echocardiography. Surgery was successfully performed.

Dextrocardia, situs inversus and severe mitral stenosis in a pregnant woman: successful closed commissurotomy.

A 16-weeks' pregnant woman with situs inversus and dextrocardia underwent successful closed commissurotomy for severe mitral stenosis. The electrocardiogram revealed sinus rhythm with right axis deviation and progressive diminishing of QRS amplitude towards the left precordial leads. The chest X-ray showed dextrocardia with situs inversus. Doppler echocardiography depicted severe mitral stenosis; the mitral valve area increased from 0.9 cm2 pre-operatively to 1.8 cm2 post-operatively with mild increase of mitral regurgitation from grade I to II post-valvotomy. She also had associated mild functional tricuspid insufficiency and moderate pulmonary hypertension. No thrombo-embolic complications occurred intra- or post-operatively. There was no evidence of either clinical or Doppler restenosis. The course of pregnancy was uneventful. At 39 weeks a healthy baby was vaginally delivered. The patient is still free of cardiac symptoms.

Long-term efficacy of diltiazem controlled release versus metoprolol in patients with stable angina pectoris.

In a randomized, double-blind, multicenter study, the efficacy of diltiazem controlled-release (CR) 120 mg b.i.d. was compared with metoprolol 100 mg b.i.d. in 56 patients with stable exertional angina pectoris. Fifty-one patients (28 receiving diltiazem CR, 23 receiving metoprolol), completed a follow-up period of 8 weeks. Thirty-nine patients (20 receiving diltiazem CR, 19 receiving metoprolol), completed a follow-up period of 32 weeks. Maximal exercise testing was performed at baseline and after 8, 20, and 32 weeks of treatment. Most exercise parameters were not significantly different between the patients on diltiazem CR and those on metoprolol. However, exercise duration was longer and maximal work load was higher in patients on diltiazem CR than in patients on metoprolol, and significant differences were observed at 20 weeks of treatment (p = 0.006 and p = 0.008, respectively). At all times during treatment, heart rate at maximal exercise and rate-pressure product at maximal exercise were significantly lower in the patients treated with metoprolol. In conclusion, monotherapy with diltiazem CR is at least as effective as monotherapy with metoprolol in patients with stable angina pectoris. As compared to metoprolol, diltiazem CR has a minor depressing effect on rate-pressure product, resulting in a favorable effect on exercise duration.

[Myocardial infarct following use of amphetamine derivatives]. / Myocardinfarct na gebruik van amfetaminederivaten.

Development of an acute myocardial infarction is described in two previously healthy men of 25 and 40 years respectively, shortly after taking oral amphetamine derivatives. Coronary angiography disclosed in both men a normal coronary system without stenoses or irregularities. Ventriculography revealed in both a segmental dysfunction of the left ventricle. A relationship is postulated between use of amphetamine and occurrence of acute myocardial infarction in the absence of coronary artery disease.

Probe exchange catheter used for angioplasty of total coronary artery occlusions.

Percutaneous transluminal coronary angioplasty (PTCA) for total occlusions frequently fails, because the guidewire fails to pass the occlusion. With the use of the Probe exchange catheter (PEC), however, stiffness of the guidewire is increased and a higher pushability is obtained in order to manipulate the guidewire beyond the lesion. Once the guidewire has passed, the PEC is advanced and a non-over-the-wire dilatation catheter can be introduced through the PEC. This paper describes the technique in a representative case. The results of this technique in 19 consecutive patients with class III-IV/IV(NYHA) angina due to an occluded coronary artery are presented. In 16 patients the PEC reached the lesion (84%) and in all these patients the guidewire could pass the occlusion. A successful PTCA was performed in 14 patients (74%).