Fredarick L. Gobel

The rate-pressure product as an index of myocardial oxygen consumption during exercise in patients with angina pectoris.

SUMMARYIn order to evaluate hemodynamic predictors of myocardial oxygen consumption (MVO,), 27 normotensive men with angina pectoris were studied at rest and during a steady state at symptom-tolerated maximal exercise (STME). Myocardial blood flow (MBF) was measured by the nitrous oxide method using gas chromatography. MBF increased by 71% from a resting value of 57.4 ± 10.2 to 98.3 ± 15.6 ml/100 g LV/min (P < 0.001) during STME while MVO, increased by 81% from a resting value of 6.7 ± 1.3 to 12.1 ± 2.8 ml O,/100 g LV/min (P < 0.001). MVO2 correlated well with heart rate (HR) (r = 0.79), with HR X blood pressure (BP) (r = 0.83), and, adding end-diastolic pressure and peak LV dp/dt as independent variables, slightly improved this correlation (r = 0.86). Including the ejection period (tension-time index) did not improve the correlation (r = 0.80). Thus, HR and HR X BP, both easily measured hemodynamic variables, are good predictors of MVO, during exercise in normotensive patients with ischemic heart disease. Including variables reflecting the contractile state of the heart and ventricular volume may further improve the predictability.

Hemodynamic Predictors of Myocardial Oxygen Consumption During Static and Dynamic Exercise

Hemodynamic predictors of myocardial oxygen consumption (MVO2) during static and dynamic exercise were examined in ten normal subjects. Studies were done under the following circumstances: 1) during upright bicycle exercise at an average heart rate of 147 beats/min, 2) during static exercise with an isometric load in the left hand equal to 17% of the maximal voluntary contraction (MVC), and 3) during combined dynamic exercise (average heart rate 147 beats/min) and static exercise using 17% MVC of the left hand. Mean myocardial blood flow (MBF) was 181 ml/100 gm LV/min during dynamic exercise, 98 ml/100 gm LV/min during static exercise, and 201 ml/100 gm LV/min during combined static and dynamic exercise. Addition of a static load to the dynamic load resulted in a higher blood pressure (average 12 mm Hg), MVO2 and MBF than during dynamic exercise alone. MVO2 correlated best with products of heart rate and blood pressure regardless of whether the blood pressure was obtained by a central aortic catheter (r = 0.88) or by a blood pressure cuff (r = 0.85).When the current data were combined with previous data, 82 determinations of MVO2 and MBF in 29 normal subjects during several levels of upright exercise were available for analysis. Forty-four determinations were done during dynamic upright exercise, 18 during exercise after propranolol, ten during combined static and dynamic work, and ten during static work alone. MVO2 correlated best with the product of heart rate and blood pressure (r = 0.86). Heart rate alone correlated better with MVO2 (r = 0.82) than did the tension time index (r = 0.65) or the product of systolic blood pressure, heart rate, and ejection time (r = 0.68). The readily measured variables of heart rate and of heart rate × blood pressure correlated well with MVO2 in normal young men during exercise under a wide variety of circumstances.

Adherence to National Guidelines for Drug Treatment of Suspected Acute Myocardial Infarction: Evidence for Undertreatment in Women and the Elderly

BACKGROUND Evidence-based guidelines for the treatment of patients with acute myocardial infarction (AMI) have been published and disseminated by the American College of Cardiology and the American Heart Association. Few studies have examined the rates of adherence to these guidelines in eligible populations and the influence of age and gender on highly effective AMI treatments in community hospital settings. METHODS Medical records of 2409 individuals admitted to 37 Minnesota hospitals between October 1992 and July 1993 for AMI, suspected AMI, or rule-out AMI, and meeting electrocardiographic, laboratory, and clinical criteria suggestive of AMI were reviewed to determine the proportion of eligible patients who received thrombolytic, beta-blocker, aspirin, and lidocaine hydrochloride therapy. The effects of patient age, gender, and hospital teaching status on the use of these treatments were estimated using logistic regression models. RESULTS Eligibility for treatment ranged from 68% (n=1627) for aspirin therapy, 38% (n=906) for lidocaine therapy, and 30% (n=734) for thrombolytic therapy to 19% (n=447) for beta-blocker therapy. Seventy-two percent of patients eligible to receive a thrombolytic agent received this therapy; 53% received beta-blockers; 81% received aspirin; and 88% received lidocaine. Among patients ineligible for lidocaine therapy (n=1503), 20% received this agent. Use of study drugs was lower among eligible elderly patients, especially those older than 74 years (thrombolytic agent: odds ratio, 0.2; 95% confidence interval, 0.1 to 0.4; aspirin: odds ratio, 0.4, 95% confidence interval, 0.3 to 0.6; beta-blocker: odds ratio, 0.4; 95% confidence interval, 0.2 to 0.8). Female gender was associated with lower levels of aspirin use among eligible patients (odds ratio, 0.7; 95% confidence interval, 0.6 to 0.9); and there was a trend toward lower levels of beta-blocker and thrombolytic use among eligible women. CONCLUSIONS Use of lifesaving therapies for eligible patients with AMI is higher than previously reported, particularly for aspirin and thrombolytic use in nonelderly patients. Lidocaine is still used inappropriately in a substantial proportion of patients with AMI. Increased adherence to AMI treatment guidelines is required for elderly patients and women.

Long-Term Effects on Clinical Outcomes of Aggressive Lowering of Low-Density Lipoprotein Cholesterol Levels and Low-Dose Anticoagulation in the Post Coronary Artery Bypass Graft Trial

Background —The Post Coronary Artery Bypass Graft Trial, designed to compare the effects of 2 lipid-lowering regimens and low-dose anticoagulation versus placebo on progression of atherosclerosis in saphenous vein grafts of patients who had had CABG surgery, demonstrated that aggressive lowering of LDL cholesterol (LDL-C) levels to <100 mg/dL compared with a moderate reduction to 132 to 136 mg/dL decreased the progression of atherosclerosis in grafts. Low-dose anticoagulation did not significantly affect progression. Methods and Results —Approximately 3 years after the last trial visit, Clinical Center Coordinators contacted each patient by telephone to ascertain the occurrence of cardiovascular events and procedures. The National Death Index was used to ascertain vital status for patients who could not be contacted. Vital status was established for all but 3 of 1351 patients. Information on nonfatal events was available for 95% of surviving patients. A 30% reduction in revascularization procedures and 24% reduction in a composite clinical end point were observed in patients assigned to aggressive strategy compared with patients assigned to moderate strategy during 7.5 years of follow-up, P =0. 0006 and 0.001, respectively. Reductions of 35% in deaths and 31% in deaths or myocardial infarctions with low-dose anticoagulation compared with placebo were also observed, P =0.008 and 0.003, respectively. Conclusions —The long-term clinical benefit observed during extended follow-up in patients assigned to the aggressive strategy is consistent with the angiographic findings of delayed atherosclerosis progression in grafts observed during the trial. The apparent long-term benefit of low-dose warfarin remains unexplained.

Effect of Propranolol on Myocardial Oxygen Consumption and Its Hemodynamic Correlates during Upright Exercise

Measurements were made of heart rate, aortic blood pressure, systolic ejection period/beat, myocardial blood flow, and myocardial oxygen consumption in nine normal young men during three bouts of upright bicycle exercise: 1) at the workload which produced a heart rate of 120 beats/minute, 2) at the higher workload necessary to produce a heart rate of 120 beats/minute after administration of intravenous propranolol 0.25 mg/kg, and 3) with infusion of propranolol, at the same workload as the first exercise bout. Comparing exercises 1 and 2, we found a much higher workload was required to produce the same heart rate after propranolol. The blood pressure, heart rate-blood pressure product, and myocardial oxygen consumption were the same despite the much greater level of exertion. Comparing exercises 1 and 3, the heart rate, blood pressure, heart rate-blood pressure product, and myocardial oxygen consumption were all significantly lower during exercise 3 after propranolol despite the fact that the same degree of exercise was being done. As in previous studies, the heart rate-blood pressure product was an excellent correlate of myocardial oxygen consumption despite the change in contractility induced by propranolol. The systolic ejection period was prolonged significantly altering the tension-time index (TTI), which became an inadequate index of myocardial oxygen consumption. It is concluded that the heart rate-blood pressure product is a good index of myocardial metabolic needs during exercise and the relationship is undistorted by marked changes in contractility, but the tension-time index is a poor correlate. This data emphasizes the fact that the relative metabolic loads for the whole body and for the heart are determined separately and may not change in parallel with a given intervention.

Aggressive Cholesterol Lowering Delays Saphenous Vein Graft Atherosclerosis in Women, the Elderly, and Patients With Associated Risk Factors NHLBI Post Coronary Artery Bypass Graft Clinical Trial

BACKGROUND The NHLBI Post Coronary Artery Bypass Graft trial (Post CABG) showed that aggressive compared with moderate lowering of low-density lipoprotein-cholesterol (LDL-C) decreased obstructive changes in saphenous vein grafts (SVGs) by 31%.1 Using lovastatin and cholestyramine when necessary, the annually determined mean LDL-C level ranged from 93 to 97 mg/dL in aggressively treated patients and from 132 to 136 mg/dL in the others (P<0.001). METHODS AND RESULTS The present study evaluated the treatment effect in subgroups defined by age, gender, and selected coronary heart disease (CHD) risk factors, ie, smoking, hypertension, diabetes mellitus, high-density lipoprotein cholesterol (HDL-C) <35 mg/dL, and triglyceride serum levels >/=200 mg/dL at baseline. As evidenced by similar odds ratio estimates of progression (lumen diameter decrease >/=0.6 mm) and lack of interactions with treatment, a similar beneficial effect of aggressive lowering was observed in elderly and young patients, in women and men, in patients with and without smoking, hypertension, or diabetes mellitus, and those with and without borderline high-risk triglyceride serum levels. The change in minimum lumen diameter was in the same direction for all subgroup categories, without significant interactions with treatment. CONCLUSIONS Aggressive LDL-C lowering delays progression of atherosclerosis in SVGs irrespective of gender, age, and certain risk factors for CHD.

Complete Heart Block Complicating Bacterial Endocarditis

Among 142 cases of bacterial endocarditis (BE), complete heart block (CHB) was found in six cases (4%) and first-degree (1°) or second-degree (2°) A-V block in 14 cases (10%).The aortic valve was involved in 18 of 20 cases with atrioventricular (A-V) conduction disturbance, including all six cases of CHB.Anatomic observations (four autopsy, one operative) were made in five of the six cases of CHB. In these cases, a common finding, in addition to involvement of the aortic valve, was extension of the infection to adjacent structures resulting in cardioaortic fistulae. CHB likely resulted from extension of infection to the major conduction tissues.Five of the six patients with CHB died suddenly while in the hospital. One patient was treated with electric pacing while the infection was being controlled and, 38 days later, underwent successful replacement of the aortic valve. Conduction abnormalities are important possible complications of aortic valvular BE. Prompt pacing may be a lifesaving procedure, allowing eradication of infection as a prelude to surgical therapy.

Effects of sulfinpyrazone on early graft closure after myocardial revascularization

The effect of sulfinpyrazone on the incidence of early postoperative closure of saphenous vein bypass grafts was compared with placebo in a prospective randomized study of 255 eligible patients. Treatment with sulfinpyrazone (800 mg/day) was started 24 hours after operation in 130 patients; 125 patients received placebo. Graft blood flow was measured at operation in 96 percent of all patients. Graft angiography was performed between the 7th and 14th postoperative days. There was no significant difference between the two groups in graft blood flow, number and diameter of the grafted arteries, left ventricular filling pressure or ejection fraction. During the study 73 patients (41 on sulfinpyrazone, 32 on placebo therapy) were excluded because graft angiography was contraindicated or because of concomitant use of anticoagulant or antiplatelet drugs. The incidence rate of early graft closure in the remaining 182 patients (43.1 grafts) was 3.8 percent (8 or 212) in the sulfinpyrazone group and 9.1 percent (20 of 219) in the placebo group (p less than 0.025). The incidence of graft closure for the sulfinpyrazone and placebo groups classified according to the recipient coronary arteries was: (1) left anterior descending artery; 3 of 98 versus 11 of 111; p less than 0.05; (2) left circumflex coronary artery: 3 of 50 versus 5 of 43; difference not significant; (3) right coronary artery: 2 of 64 versus 4 of 65; difference not significant. The incidence of closure in grafts with a flow of less than 30 ml/min did not differ significantly in the sulfinpyrazone and placebo groups (4 of 26 versus 6 of 22). These results suggest that sulfinpyrazone reduces the incidence of early graft closure in grafts with a flow rate greater than 30 ml/min.

Intravenous amiodarone for the rapid treatment of life-threatening ventricular arrhythmias in critically ill patients with coronary artery disease

This study examined the effectiveness of intravenous amiodarone for rapid control and prevention of recurrent life-threatening ventricular tachyarrhythmias associated with cardiovascular collapse. In 22 critically ill patients with coronary artery disease (mean ejection fraction 27 +/- 13%), recurrent ventricular tachyarrhythmias proved refractory to 3.7 +/- 1.1 (mean +/- standard deviation) conventional antiarrhythmic drugs. In the 24-hour period before intravenous amiodarone treatment, patients experienced 2.4 +/- 2.3 (range 1 to 9) episodes of life-threatening ventricular tachycardia, ventricular fibrillation or both, requiring 4.0 +/- 3.9 direct current cardioversions. Within the 24 hours after initiation of intravenous amiodarone therapy (900 to 1,600 mg/day), 20 of 22 patients remained alive and had 1.1 +/- 1.6 episodes of life-threatening ventricular arrhythmias, requiring 1.9 +/- 3.1 direct current cardioversions. In the second 24-hour period, there were 19 survivors and life-threatening arrhythmias were reduced to 0.4 +/- 0.7 episode/patient requiring 0.4 +/- 0.9 direct current cardioversion. Overall, arrhythmias were controlled in 11 of 22 (50%) patients within the first 24 hours, and in 14 of 22 (64%) in the second 24 hours. Intravenous amiodarone therapy was well tolerated. Twelve patients were discharged from the hospital and 8 remained alive at a mean follow-up of 22 +/- 14 months. Thus, in critically ill patients, intravenous amiodarone may be useful for rapid control of spontaneous, refractory, life-threatening ventricular tachyarrhythmias.

Shunts between the coronary and pulmonary arteries with normal origin of the coronary arteries

Abstract Seven patients with shunts between the coronary and the pulmonary arteries with normal origin of both coronary arteries are described. Symptoms, when present, may be related to critical diversion of local blood flow or to the size of the shunt relative to total coronary blood flow. Maximal exercise testing may aid in finding those patients in whom the shunt leads to myocardial ischemia and may be a convenient way to follow up asymptomatic patients. These small shunts are frequently difficult to detect by sensitive methods; selective coronary arteriography proved to be the most helpful diagnostic procedure. Indications for surgery are not well established, but would include (1) relief of symptoms, (2) prophylaxis against complications of coronary artery disease and (3) the prevention of bacterial endarteritis.