Flemming Pedersen

Danish multicenter randomized study on fibrinolytic therapy versus acute coronary angioplasty in acute myocardial infarction: rationale and design of the danish trial in acute myocardial infarction-2 (DANAMI-2)

BACKGROUND Randomized trials have indicated that primary coronary angioplasty performed in patients admitted directly to highly-experienced angioplasty centers offers certain advantages over intravenous fibrinolytic therapy. However, the large majority of patients with acute myocardial infarction are submitted to hospitals without a catheterization laboratory. This means that additional transportation will be necessary for many patients if a strategy of acute coronary angioplasty is to be introduced as routine treatment. The delay of treatment caused by transportation might negate (part of) the benefits of primary angioplasty compared to fibrinolytic therapy given immediately at the local hospital. STUDY DESIGN The DANish trial in Acute Myocardial Infarction-2 (DANAMI-2) is the first large-scale study to clarify, in a whole community, which of the 2 treatment strategies is best. A total of 1900 patients with ST-elevation myocardial infarction are to be randomized: 800 patients will be admitted to invasive hospitals and 1100 patients will be admitted to referral hospitals. Half of the 1100 patients admitted to referral hospitals will immediately be transferred to an invasive center to be treated with primary angioplasty. IMPLICATIONS If acute transfer from a local hospital to an angioplasty center is the superior strategy, primary angioplasty should be offered to all patients as routine treatment on a community basis.

Cardiac Event Rates After Acute Myocardial Infarction in Patients Treated With Verapamil and Trandolapril Versus Trandolapril Alone

Angiotensin-converting enzyme (ACE) inhibitors improve survival in patients with congestive heart failure (CHF) after an acute myocardial infarction (AMI), but mortality may be as high as 10% to 15% after 1 year. Verapamil prevents cardiac events after an AMI in patients without CHF. We hypothesized that in postinfarct patients with CHF already prescribed diuretics and an ACE inhibitor, additional treatment with verapamil may reduce cardiac event rate. In this multicenter, double-blind study, patients with CHF receiving diuretic treatment were consecutively randomized to treatment with trandolapril 1 mg/day for 1 month and 2 mg/day the following 2 months (n = 49), or to trandolapril as mentioned plus verapamil 240 mg/day for 1 month and 360 mg/day for 2 months (n = 51). Trial medication started 3 to 10 days after AMI. All patients were followed for 3 months. End points in the trandolapril/trandolapril-verapamil groups were death 1/1, reinfarction 7/1, unstable angina 9/3, and readmission for CHF 6/2. The 3-month first cardiac event rate was 35% in trandolapril-treated patients and 14% in trandolapril-verapamil-treated patients (hazard ratio 0.35, 95% confidence interval 0.15 to 0.85, p = 0.015). These data suggest that verapamil reduces cardiac event rates in post-AMI patients with CHF when added to an ACE inhibitor and a diuretic.

Effects of acupuncture in moderate, stable angina pectoris: a controlled study

Abstract. In order to evaluate the effects of acupuncture in moderate, stable angina pectoris, 49 patients were randomized to either genuine or sham acupuncture. In sham acupuncture needles were inserted into points within the same spinal segment as in genuine acupuncture, but outside the Chinese meridian system. The effect was evaluated from exercise tests, anginal attack rate and nitroglycerin consumption. There were no significant differences between the effects of genuine and sham acupuncture either on exercise test variables or on subjective variables. In patients receiving genuine acupuncture there was a significant increase in exercise tolerance (median 9%) and in delay of onset to pain (median 10%). No significant changes were observed in patients receiving sham acupuncture. Within both groups there was a median reduction of 50% in anginal attack rate and nitroglycerin consumption, and there was no significant difference between the results achieved in the two groups. It is concluded that with the present design it was not possible to demonstrate any significant differences between the effect of genuine and sham acupuncture.

Effect of intravenous streptokinase on the relation between initial ST-predicted size and final QRS-estimated size of acute myocardial infarcts

Thrombolytic therapy has been documented to reduce acute myocardial infarct size. The previously established relation between initial ST segment elevation and final electrocardiographic (ECG) myocardial infarct size in patients without coronary reperfusion might therefore be altered by thrombolytic therapy. The effect of intravenous streptokinase on this relation was therefore studied in 73 patients with initial acute myocardial infarction who had participated in the Second International Study of Infarct Survival (ISIS-2). Patients who received streptokinase were considered as one group and patients who did not receive streptokinase as a control group. Final myocardial infarct size, which was estimated from the QRS score, was predicted from the admission standard ECG by previously developed formulas based on ST segment elevation. In the 40 control patients there was no change from ST-predicted to final QRS-estimated infarct size (median 17.7% versus 18.3%; p = NS). In the 33 patients in the streptokinase group, there was a highly significant decrease from predicted to final myocardial infarct size (median 21.9% versus 16.2%; p less than 0.0002). This decrease was found for both anterior (median 23.7% versus 19.5%; p less than 0.03) and inferior (median 21.9% versus 12.0%; p = 0.001) infarct locations. Multiple regression analysis adjusting for differences in predicted infarct size confirmed the significance of streptokinase on the difference in infarct size (p = 0.006). Based on the variability of the percent change from predicted to final infarct size in the control group, a threshold decrease greater than or equal to 20% is required for identification of salvage.(ABSTRACT TRUNCATED AT 250 WORDS)

Transcutaneous pacing: Experience with the zoll noninvasive temporary pacemaker

We investigated the effectiveness of noninvasive transcutaneous pacing in 35 patients. Pacing was achieved in 33 of 35 patients (94%). In 24 patients the indications were: acute sinoatrial block, atrioventricular block, or asystole with unconsciousness due to acute myocardial infarction in eight; sick sinus node syndrome in 12; and other indications in four patients. These patients were paced for 2 minutes to 14 hours; the median length of pacing was 15 minutes. The pacing thresholds varied from 30 to 110 mA; pacing was achieved in 22 patients without serious side effects. Nine patients needed sedation and six were unconscious; 12 later had a temporary or permanent transvenous pacemaker implanted. In 11 patients noninvasive transcutaneous pacing was performed prior to implantation of a permanent pacing catheter: in eight pacing was done just prior to catheter insertion, and in three the threshold was determined before a weekend on which the patient had to wait for implantation. Pacing thresholds were from 45 to 90 mA; the median was 55 mA. Seven of these eight patients felt chest pain. No serious side effects were seen. We conclude that transcutaneous pacing is effective and safe and can be used instead of inserting a transvenous catheter if this is impossible or until one can be inserted.

Effects of atenolol and diltiazem on exercise tolerance and ambulatory ischaemia

Twenty-five normotensive patients with stable angina, angiographically documented coronary disease and normal left ventricular function were randomized to a crossover study comparing atenolol 100 mg x 1, sustained-release diltiazem 120 mg x 2, and their combination. A maximal symptom limited bicycle exercise test and a 24-h ambulatory electrocardiographic (ECG) monitoring were performed at the end of each treatment period. Exercise duration was increased equally in the different treatment groups. Time to onset of 1-mm ST-segment depression was longer with atenolol (P < 0.02) and combination therapy (P < 0.01) than with diltiazem. The maximal ST-segment depression was decreased with atenolol (P < 0.05) and combination therapy (P < 0.02), whereas, time to onset of angina was prolonged only with combination therapy (P < 0.03). The number of ischaemic episodes during ambulatory monitoring was lower with atenolol and combination therapy than with diltiazem (P < 0.01). The difference between atenolol and diltiazem was mainly due to lower ischaemic activity with atenolol between 06:00 h and 12:00 h (P < 0.05). Anginal frequency (P < 0.01) and nitroglycerin consumption (P < 0.05) were lower with combination therapy than with monotherapy. Thus, while comparable effects were achieved on clinical variables, atenolol appeared to be more effective than diltiazem, reducing myocardial ischaemia during exercise and ambulatory monitoring. With combination therapy, both clinical and electrocardiograph signs of ischaemia were improved.

Dense Bottom Currents in Rotating Ocean

A dense bottom current is the flow created by a source of mass, momentum, and buoyancy flowing into an ambient fluid in such a way that the flow is bounded by the fixed wall and the interface. The dense bottom currents are primarily driven by buoyancy forces (reduced gravity).

Treatment with verapamil and trandolapril in patients with congestive heart failure and angina pectoris or myocardial infarction

In a double-blind, randomized trial in a consecutive group of postinfarct patients in treatment with diuretic agents for congestive heart failure, the 3 month rate of cardiac events (i.e., death, repeat infarction, unstable angina pectoris, or repeat admission because of heart failure) was 14% in patients treated with verapamil and trandolapril and 35% in patients treated with trandolapril (p = 0.01). In another study of patients with angina pectoris and left ventricular ejection fraction less than 40%, trandolapril plus verapamil improved exercise duration and left ventricular ejection fraction. These findings indicate that combined treatment with verapamil and trandolapril may be beneficial in patients with congestive heart failure.

Normal Myocardial Enzymes and Normal Echocardiographic Findings During Noninvasive Transcutaneous Pacing

Noninvasive transcutaneous pacing was performed for 30 minutes in 10 healthy volunteers. The pace rate was from 85 to 115 min, 1 and the threshold for pacing was from 38 to 70 mA, median 59 mA. Echocardiography before and during pacing showed no changes in left ventricular end‐diastolic diameter, in fractional shortening nor in contraction pattern. Also, hood pressure remained unchanged. Blood samples for determination of myoglobin, creatine phosphokinase, creatine kinase MB and lactate dehydrogenase were drawn prior to pacing and 1,2,3,4,6,8 and 24 hours after pacing. The serum concentrations were the same before and after pacing for all enzymes and myoglobin. We conclude that non‐invasive transcutaneous pacing for 30 minutes causes no muscular or myocardial injury and that the left ventricular function remains normal.

ECG and enzymatic indicators of therapeutic success after intravenous streptokinase for acute myocardial infarction

Thrombolytic therapy has been documented to result in reperfusion of jeopardized myocardium and reduction in the size of the acute myocardial infarction (AMI). The effect of intravenous streptokinase on a creatine kinase-MB (CK-MB) reperfusion index and an ECG estimate of myocardial salvage was therefore studied in 65 patients with a first AMI, randomized to treatment with streptokinase (n = 33) or placebo (control group, n = 32). Reperfusion was defined as a CK-MB appearance rate constant (k1) greater than 0.185. The final AMI size was first predicted from the admission standard ECG by previously developed formulas based on ST segment elevation. The final AMI size was estimated from the QRS score on the predischarge ECG. Myocardial salvage was defined as a greater than or equal to 20% decrease from predicted to final AMI size. The k1 value in the control group was significantly lower than that in the streptokinase group (median 0.157 versus 0.328; p = 0.0001). Accordingly the reperfusion rate was higher in the streptokinase group than in the control group (88% versus 34%; p = 0.0002). The difference in AMI size (final-predicted) was significantly greater in the streptokinase group than in the control group (median -7% versus +1%; p = 0.0001). Myocardial salvage occurred in 60% and 19%, respectively (p = 0.004). A significant correlation was found between CK-MB reperfusion and ECG salvage: 19 of 20 streptokinase-treated patients with salvage also had reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)