Avraham T. Weiss

Prevention of Myocardial Damage in Acute Myocardial Ischemia by Early Treatment with Intravenous Streptokinase

We evaluated the effectiveness of early intravenous administration of 750,000 units of streptokinase in 53 patients with acute myocardial ischemia treated by a mobile-care unit at home (9 patients) or in the hospital (44 patients). Treatment was begun an average (+/- S.D.) of 1.7 +/- 0.8 hours from the onset of pain. Non-Q-wave infarctions developed subsequently in eight patients, whereas all the others had typical Q-wave infarct patterns. In 81 per cent of the patients the infarct-related artery was patent at angiography performed four to nine days after admission. Vessel patency was independent of the time of treatment, but residual left ventricular function was time dependent. Patients treated less than 1.5 hours after the onset of pain had a significantly higher ejection fraction (56 +/- 15 vs. 47 +/- 14 per cent; P less than 0.05) and infarct-related regional ejection fraction (51 +/- 19 vs. 34 +/- 20 per cent; P less than 0.01) and a lower QRS score (5.6 +/- 4.9 vs. 8.6 +/- 5.5; P less than 0.01) than patients receiving treatment between 1.5 and 4 hours after the onset of pain. Patients treated earlier by the mobile-care unit also had better-preserved left ventricular function than patients treated in the hospital. We conclude that thrombolytic therapy with streptokinase is most effective if given within the first 1.5 hours after the onset of symptoms of acute myocardial infarction.

The use of calcium with verapamil in the management of supraventricular tachyarrhythmias

Verapamil, a calcium channel blocking drug, terminates supraventricular arrhythmias but may have a negative inotropic effect and produce peripheral vasodilatation and hypotension. We studied the efficacy of intravenous calcium gluconate in reversing or preventing the hypotensive effect of verapamil in 31 patients with atrial tachyarrhythmias. In 21 instances, verapamil was given first, and in 13 calcium was used as pretreatment before the administration of verapamil. Calcium gluconate, when given as pretreatment, prevented the fall in blood pressure induced by verapamil, and when given after verapamil restored blood pressure to control values. The administration of calcium did not alter the antiarrhythmic effect of verapamil.

Exercise echocardiography in postmenopausal hormone users with mild systemic hypertension

Rest and exercise echocardiography (at dynamic and isometric exercise) were performed in 30 postmenopausal women (aged 54 +/- 4 years) with borderline to mild hypertension. They were then divided into 2 groups: 17 women who started oral hormone replacement therapy (0.625 mg/day conjugated estrogens or 2 mg/day estradiol) and a control group of 13 nonusers. After 6 to 9 months, a second echocardiography was performed in 26 women (4 withdrew). There were only a few changes in values obtained in the 12 controls at the end of follow-up compared with baseline. Primarily, these changes included a slight decrease in systolic blood pressure at rest and on exercise. Several significant morphologic and hemodynamic alterations appeared in 14 hormone users. Left ventricular cavity dimensions and mass became smaller: mean end-diastolic diameter decreased from 45.9 +/- 3 mm at baseline to 44.4 +/- 3 mm at study termination (p = 0.007). The corresponding values for end-systolic diameter were 25.8 +/- 4 mm and 23.9 +/- 4 mm (p = 0.006); for left atrium diameter, it was 34.5 +/- 4 mm and 32.5 +/- 4 mm (p = 0.001); for left ventricular wall width, it was 19.9 +/- 2 mm and 19.3 +/- 2 mm (p = 0.02); for left ventricular mass, it was 197 +/- 28 g and 179 +/- 32 g (p = 0.006). The resting aortic blood flow velocity and acceleration increased: 119 +/- 18 cm/s before therapy versus 129 +/- 23 cm/s while on hormone substitution (p = 0.04), and 13.6 +/- 3 m/s2 versus 16.5 +/- 4 m/s2 (p = 0.008), respectively. Mean rest to peak exercise systolic blood pressure difference became smaller after hormones: 39 +/- 19 mm Hg versus 28 +/- 13 mm Hg (p = 0.03) during dynamic exercise, and 43 +/- 22 mm Hg versus 25 +/- 13 mm Hg (p = 0.004) during isometric exercise. The above data probably indicate that with hormone replacement therapy, there is an improvement in cardiac function both at rest and during exercise.

Angiographic findings in the coronary arteries after thrombolysis in acute myocardial infarction.

The angiographic appearance of the coronary arteries was examined in 308 patients with acute myocardial infarction (AMI) who received high-dose intravenous thrombolytic therapy. Coronary angiography was performed on day 7 after admission to the hospital. Patients had an average of 2.4 discrete arterial narrowings or obstructions. The narrowings were proximal and related to bifurcations. Four fifths of the culprit arteries were patient; 104 (34%) had a ruptured plaque, 22 (7%) had an ulcerated plaque, and in 190 (62%) the lesions were eccentric. Patients differed from a comparable, previously studied, control series of 302 patients with chronic stable angina pectoris who had more extensive disease. They had 5.7 narrowings/patient, also located proximally and at bifurcations, but more widely distributed in the coronary tree. Patients with AMI who are suitable for thrombolysis have a unique coronary angiographic picture. The data confirm that AMI is caused by sudden rupture of a localized atheromatous plaque that initiates an obstructive thrombotic cascade.

Early intravenous thrombolysis in acute myocardial infarction: the Jerusalem experience

Myocardial damage in acute myocardial infarction is a time-dependent process. We examined the influence of very early thrombolytic therapy, comparing prehospital to hospital administration, in a consecutive group of patients with myocardial infarction on mortality, complications and the preservation of left ventricular function. Seven hundred sixty patients received early thrombolytic therapy: 114 at home (time delay to treatment 1.4 +/- 0.8 h) and 646 in hospital (2.1 +/- 1.0 h). Sixteen patients died in hospital and significant hemorrhage occurred in 15 (including three patients with hemorrhagic stroke). There was no difference between groups in hospital mortality or rate of complications. The duration of ischemia was shorter in patients with prehospital therapy (pain duration: 3.3 +/- 2.1 vs. 4.0 +/- 2.2; P < 0.05, and time to recovery of the ST segment in the electrocardiogram: 4.3 +/- 3.3 vs. 6.6 +/- 6.3; P < 0.002). Peak plasma creatine kinase was earlier in patients with prehospital therapy (11.2 +/- 5.0 vs. 13.0 +/- 5.8; P < 0.002), although there was no difference between groups in the absolute peak plasma level. Left ventricular function was assessed by contrast ventriculography 1 week after admission (616 patients). Ventricular function was better in patients with prehospital therapy: (ejection fraction of 58 +/- 13% vs. 54 +/- 15%; P < 0.05 and a left ventricular dysfunction index of 534 +/- 515 vs. 691 +/- 519 units; P < 0.05). We conclude that prehospital thrombolytic therapy is feasible and safe. Reperfusion is achieved earlier and more myocardium can be salvaged using this strategy without increasing the rate of complications.

Rates, variability, and associated factors of polypharmacy in nursing home patients

Objectives To determine the rate and variability of polypharmacy in nursing home (NH) residents and investigate its relationship to age, sex, functional status, length of stay, and comorbidities. Methods We conducted a cross sectional, multicenter study that included six nursing homes. Demographic, clinical characteristics, Charlson comorbidity index (CCI), the number and classes of chronic medications, rate of polypharmacy >5 drugs (per day) and polypharmacy >7 drugs (per day) were recorded. Results Nine hundred and ninety-three residents were included; 750 (75.5%) fully dependent residents and 243 (24.5%) mobile demented residents requiring institutional care. The mean age was 85.04±7.55 (65–108) years. The mean rates of polypharmacy >5 drugs and polypharmacy >7 drugs were 42.6% and 18.6%, respectively. Differences in polypharmacy >5 drugs and polypharmacy >7 drugs were observed in NHs 24.7%–56% and 4.9%–30.4%, respectively (P<0.001). Mean number of chronic drugs per resident was 5.14±2.60 from 3.81±2.24 to 5.95±2.73 (P<0.001). No differences in polypharmacy were found between sex and fully dependent versus mobile demented residents. The most common medications taken were for gastrointestinal, neurological, and cardiovascular disorders. Regression analysis revealed four independent variables for polypharmacy >5 drugs: groups aged 75–84 and >85 relative to 65–74, odds ratio (OR) 0.46 (95% confidence interval [CI] 0.27–0.78) P=0.004, OR 0.35 (95% confidence interval 0.19–0.53), respectively, P<0.001; length of stay >2 years, OR 0.51 (95% CI 0.36–0.73) P<0.001; CCI, OR 1.58 (95% CI 1.42–1.75) P<0.001; and feeding tube versus normal feeding, OR 0.27 (95% CI 0.12–0.60) P=0.001. Conclusion Rates of polypharmacy in NHs are high with significant variability. Variability rates of polypharmacy, distinct residents’ characteristics, and excessive use of certain drug groups may indicate that a decrease in medication is potentially feasible.

Regional and global left ventricular function during intra-aortic balloon counterpulsation in patients with acute myocardial infarction shock☆

We evaluated the improvement in hemodynamic and left ventricular (LV) function in 15 patients with acute myocardial infarction and cardiogenic shock, who were treated with intraaortic balloon counterpulsation (IABP). They were studied by flow-directed right heart catheterization and nuclear angiography. IABP decreased LV end-diastolic volume from 134 to 114 ml and LV end-systolic volume from 100 to 72 ml. LV stroke volume increased from 34 to 42 ml and cardiac output from 3.0 to 3.6 L/min. Global LV ejection fraction increased from 27.6% to 36.1%, and this was due to improvement in regional ejection fraction in ischemic areas. Pulmonary capillary wedge pressure and pulmonary blood volume decreased. Right ventricular ejection fraction also increased significantly. IABP improved LV function in acute myocardial infarction.

Feasibility of pre-hospital fibrinolytic therapy in acute myocardial infarction

Intravenous streptokinase (STK) was given in the field by a physician-staffed mobile intensive care ambulance to 13 patients. Patients waited 33 +/- 17 minutes to call the ambulance, arrival time was 5 +/- 3 minutes, and a further work-up time of 32 +/- 8 minutes elapsed. The average time from the onset of pain until administration of STK was 66.7 minutes. Patients were transferred to hospital without important side effects or complications. Eleven of 12 of the infarction-related arteries were patent on subsequent coronary angiography. Three patients had minor hematomas and two had microscopic hematuria. This pilot study shows that intravenous STK can be given with relative ease and safety at home by an experienced physician capable of treating any complications.

Left ventricular volumes and function during atrial pacing in coronary artery disease: A radionuclide angiographic study

This study set out to determine the pathophysiologic changes in the left ventricle during atrial pacing in 22 patients with coronary artery disease. Graduated right atrial pacing to a rate of 160 beats/min, or the induction of angina pectoris or significant ST depression was undertaken. Ventricular volumes were measured at rest and at rates of 100, 120, 140 and 160 beats/min using radionuclide angiography. The volumes at a pacing rate of 100 beats/min were used as a reference standard (100%). In the 22 patients with coronary artery disease, left ventricular end-diastolic volume decreased from 118 +/- 3% at rest to 80 +/- 5% at a rate of 160 beats/min; stroke volume from 121 +/- 3% to 54 +/- 5%; and ejection fraction (EF) from 49 +/- 3% to 37 +/- 5%. End-systolic volume decreased from 118 +/- 4% at rest, reached its minimal value of 94 +/- 5% at a rate of 120 beats/min and then increased slightly to 106 +/- 9% at 160 beats/min. Cardiac output and blood pressure did not change significantly. Compared to the control group of 10 normal subjects, the patients had a significantly smaller decrease in end-diastolic volume and end-systolic volume than in normal control subjects. EF in the normal subjects did not change. Blood pressure, cardiac output and stroke volume were similar in both groups. Atrial pacing tachycardia induced reversible ventricular dysfunction with a decrease in EF. Stroke volume was maintained because of relative ventricular dilatation.

Prevention of congestive heart failure by early, prehospital thrombolysis in acute myocardial infarction: a long-term follow-up study

The long term impact of pre-hospital thrombolysis in acute myocardial infarction on the subsequent development of heart failure symptoms was investigated in 362 consecutive patients. The pre hospital strategy, used in 61 patients, allowed for very early administration of streptokinase, within 1.2+/-0.6 (mean+/-S.D.) hours from pain onset. In contrast, 294 patients treated in hospital received lytic treatment within 2.0+/-0.9 hours. The pre hospital group showed faster reperfusion, as measured by the time to peak creatine kinase and to ST segment recovery, but only a slightly better ventricular function, as compared to hospital treated patients. Heart failure symptoms were significantly reduced in the pre hospital group during hospitalization and at long term follow up: there were less dyspnea, fatigue, orthopnea, nocturnal dyspnea, nocturia, peripheral edema and episodes of pulmonary edema. Angina was reduced as well. We conclude that the initial benefit of prehospital thrombolysis translates into long term reduction of heart failure symptoms, thus improving quality of life.