Quantitative assessment of ventricular performance in unstable ischemic heart disease by dextran function curves.

The ability to quantitate the amount of permanent left ventricular dysfunction in patients with unstable ischemic heart disease would have important clinical value. Left ventricular function curves were constructed in sixteen patients with acute myocardial infarctions and five patients with unstable angina pectoris syndrome at an average of 56 hours (+/- 8) after the onset of symptoms. Fifty ml increments of low molecular weight dextran were rapidly infused into the right antrium during constant monitoring of the pulmonary artery end-diastolic pressure (PAEDP) via a Swan-Ganz thermodilution catheter. An average of 400 ml (range 200-800) was infused to produce a significant change in the PAEDP (range 3-13 mm Hg). The cardiac index was measured before and after the dextran infusion. The slope of the left ventricular function curve was calculated by dividing the change in the cardiac index by the change in the PAEDP. The sixteen patients with acute myocardial infarction underwent left heart catheterization and left ventricular biplane angiography an average of six months later. The five patients with unstable angina pectoris were studied within one month. The slope value of the left ventricular function curve was compared angiographic ejection fraction by linear regression analysis and the correlation coefficient was 0.80. These data demonstrate 1) the slope of the left ventricular function curve in patients with acute myocardial infarction or unstable angina correlates well with the angiographically calculated ejection fraction; 2) as early as two days post myocardial infarction, the residual impairment of left ventricular function can be estimated.

Treatment of congestive heart failure.

In treating heart failure, the physician must remain cognizant of pathophysiology as he prescribes and monitors therapy. In addition to seeking underlying and precipitating causes of the patient's heart failure, he must treat the congestive state by enhancing myocardial contractility, controlling excessive fluid retention, and reducing afterload. Figure 7 summarizes the theoretical shifts on a patient's left ventricular function curves that might occur with therapy. Left ventricular function might move from point A to point B with diuretic therapy, but overdiuresis could aggravate symptoms of low cardiac output, including postural hypotension. Digitalis would effect a shift from A to C. Isosorbide dinitrate would produce a shift from A to D in a patient not on digitalis and from C to D in a patient already receiving digitalis. Isosorbide dinitrate, in conjunction with more usual therapeutic measures, has proved clinically beneficial in the treatment of heart failure.

Reduction of hospital mortality rate of acute myocardial infarction with glucose-insulin-potassium infusion.

Free fatty acids (FFA), the predominant myocardial energy substrate, are present in increased quantities immediately following acute myocardial infarction (AMI) and may cause deleterious alterations in cardiac rhythm, oxygen consumption, and mechanical performance. In an attempt to suppress FFA and simultaneously increase the availability of carbohydrate as a myocardial substrate, 70 patients with unequivocal AMI were administered a right atrial infusion of glucose-insulin-potassium (GIK) (300 gm. of glucose, 50 U. of regular insulin, and 80 mEq. of KC1 per liter of H2O) at a constant rate of 0.5 to 2.0 ml. per kilogram per hour for 48 hours. A dramatic fall in FFA (944 +/- 57 to 289 +/- 16 muEq per liter, p less than 0.0005) occurred during GIK infusion, and FFA rebounded to 420 +/- 39 muEq per liter (p less than 0.005) when GIK was discontinued. The hospital mortality rate in the 70 GIK recipients was compared to that of 64 untreated patients (controls) from the same coronary-care unit during the previous year. GIK and control groups had similar severity of infarction as assessed by prognostic scales of Killip, Peel, and Norris, respectively. The hospital mortality rate was reduced in the GIK recipients compared to the control group (11/70 vs. 19/64, p less than 0.05). In patients without history of prior myocardial infarction, the mortality rate was reduced four-fold in GIK recipients compared to controls (6 vs. 24 per cent, p less than 0.05). Complications of GIK infusion were infrequent and included chiefly hyperglycemia and hyperkalemia, both of which dictated meticulous monitoring of serum chemistries. The data suggest that suppression of plasma FFA with GIK infusion may be associated with a significant reduction in the hospital mortality rate of acute myocardial infarction.

Isosorbide dinitrate for the relief of severe heart failure after myocardial infarction.

Severe congestive heart failure secondary to myocardial infarction remains a difficult management problem. Although intravenous vasodilators and mechanical assist devices have been reported to improve the depressed hemodynamic function, these interventions are limited to the intensive care unit and cannot be used for long-term management. This study evaluates the hemodynamic and symptomatic response to sublingual administration to isosorbide dinitrate (5 to 10 mg) in seven consecutive patients with severe congestive heart failure after anterior wall myocardial infarction. Serial measurements of mean right atrial and pulmonary arterial end-diastolic pressure, mean blood pressure, heart rate and cardiac output were obtained during the control period and during the 4 hours after administration of isosorbide dinitrate. The peak response occurred approximately 30 minutes after drug administration with an 83 percent reduction in mean right atrial pressure (from 6 to 1 mm Hg, P less than 0.02), a 36 percent reduction in pulmonary arterial end-diastolic pressure (from 25 to 16 mm Hg, P less than 0.0001) and a 6 percent reduction in mean blood pressure (from 94 to 88 mm Hg (P less than 0.05). There were small but statistically not significant increases in cardiac index (from 2.3 to 2.6 liters/min per m2 and stroke work index (from 26 to 32 gm/beat per m2). The total systemic vascular resistance was reduced by 5 percent from 1,605 to 1,518 dynes sec cm-5 (P less than 0.10). The baseline heart rate of 105 beats/min was not significantly changed. The reduction in pulmonary arterial end-diastolic pressure became statistically significant (P less than 0.05) between 15 and 30 minutes after administration of isosorbide dinitrate and remained significant for 3 to 4 hours. This reduction of pulmonary arterial end-diastolic pressure to less than 22 mm Hg was associated with relief of the patients' pulmonary symptoms. The response to nitroglycerin (0.4 mg) was similar in magnitude but of much shorter duration (approximately 15 minutes for nitroglycerin versus 4 hours for isosorbide dinitrate in patients with and without congestive heart failure. The slope (calculated by dividing the change in cardiac index or stroke work index by the change in pulmonary arterial end-diastolic pressure) was significantly (P less than 0.05) depressed in the patients with congestive heart failure. These data demonstrate that the symptomatic pulmonary venous hypertension can be effectively relieved by isosorbide dinitrate without further compromising left ventricular function.

Aortic stenosis, angina pectoris, coronary artery disease.

The data from 88 patients (pts) with aortic stenosis (AS) were reviewed to determine relationships between angina pectoris (AP) and coronary artery disease (CAD). Results of surgery performed in 81 of these pts was analyzed. All pts had coronary arteriograms, and lesions greater than or equal to 50% were considered significant. Fifty-nine pts had an aortic valve gradient measured at catheterization greater than or equal to 40 mmHg, and in 29 pts, AS was confirmed at operation. Sixty-eight pts (77%) experienced AP, and 32 had coexisting CAD (47%); 9 of 20 pts without AP had CAD (45%). There were no significant differences in the incidence of AP in pts divided into subgroups by the aortic valve gradient (40-50, 51-100, 101-200 mmHg) or age (40-59, 60-81 years). Also, no significant differences were found in the incidence or extent of CAD between the two age groups; the extent of CAD was similar regardless of the presence or absence of AP. In pts with AP (1) CAD was more likely in pts greater than or equal to 60 years of age; (2) CAD was less likely when the aortic valve gradient was greater than 100 mmHg, suggesting that AP in these pts was due to hemodynamically severe AS. All pts with 3-vessel CAD experienced AP, and the aortic valve gradient was less in these pts than in those with no CAD or less extensive CAD. In 19 pts with combined AS and CAD who had both the aortic valve replaced and a revascularization operation only 1 of pts died in the hospital, while 3 of 19 pts with combined AS and CAD who had aortic valve replacement alone died. In this study a significant number of pts with AS experienced AP, and the presence or absence of AP did not predict coexisting CAD. Coronary arteriography is recommended in the evaluation of pts greater than or equal to 40 years of age with AS. The operative mortality appears to be decreased in pts with AS and CAD who have combined surgery.

Effects of glucose-insulin-potassium on myocardial substrate availability and utilization in stable coronary artery disease. Studies on myocardial carbohydrate, lipid and oxygen arterial-coronary sinus differences in patients with coronary artery disease.

To assess the metabolic effects of myocardial substrate alteration in patients with coronary artery disease, glucose-insulin-potassium solution was administered intravenously for 30 minutes to 14 men with stable angiographically documented coronary artery disease. The glucose-insulin-potassium solution (300 g of glucose, 50 units of regular insulin and 80 mEq of potassium chloride per liter of water) was infused at a constant rate in each patient, but individual infusion rates ranged from 0.013 to 0.032 ml/kg per min (4 to 10 mg glucose/kg per min) in the 14 patients. Simultaneous arterial and coronary sinus samples were obtained at 15 minute intervals during a stable 30 minute control period and again at 15 minute intervals during the infusion; samples were assayed for glucose, lactate, free fatty acid and oxygen content. In all 14 patients, during the glucose-insulin-potassium infusion, arterial glucose and lactate increased and arterial free fatty acid levels fell; the magnitude of the changes in arterial lactate and free fatty acids was related to the rate of infusion. Arterial-coronary sinus differences (A-Cs) for glucose, lactate and free fatty acid levels correlated with the arterial concentrations of these substrates (r = 0.66, 0.87 and 0.79, respectively). Regression analyses demonstrated myocardial thresholds for the uptake of these substrates as follows: glucose 79 mg/100 ml; lactate 300 mu mole/liter; and free fatty acids 100 to 200 mu Eq/liter. Finally and most importantly, the reduction in A-Cs oxygen values after glucose-insulin-potassium infusion correlated with the reduction in A-Cs free fatty acid levels (r = 0.64, P less than 0.0001). This observation suggests that, in patients with coronary artery disease, glucose-insulin-potassium infusion may significantly diminish myocardial oxygen requirements by reduction of myocardial free fatty acid utilization and simultaneous enhancement of myocardial carbohydrate utilization. Myocardial substrate availability may be an important determinant of myocardial oxygen demand in patients with coronary artery disease. Infusion of glucose-insulin-potassium solution has the potential to alter myocardial substrate availability, thus improving the balance between myocardial oxygen demand and supply.

Relationship between echocardiography, cardiac output, and abnormally contracting segments in patients with ischemic heart disease.

Twenty-four patients with proven coronary artery disease and abnormally-contracting segments were studied by both echocardiography and biplane angiographic techniques. Comparison was made between the left ventricular biplane angiographic volumes and those obtained from echocardiographic measurements which were calculated from cubed function and regression equaltion methods. The percent abnormally contracting segment (ACS) was obtained from biplane left ventricular angiography and was calculated from the diastolic and systolic anteroposterior and lateral angiocardiograms. The angiographic end-diastolic volume correlated with that calculated from the echocardiographic dimensions with an r value of 0.865 and SEE of +/- 22.64 ml. The angiographic end-systolic volume and echo end-systolic volume did not correlate as well, with an r = 0.7063. The difference in stroke volume predicted by the diastolic and systolic echocardiographic dimensions and the actual stroke volume determined by Fick technique was related to the percent abnormally contracting segment of the left ventricle (r = 0.8967). The percent ACS could be estimated from echo and Fick stroke volume measurements by the cube function and regression equations. Echo ventricular volume determinations were analyzed for the cube function method and the regression equations of Fortuin et al. and Teichholz and coworkers, with the method of Fortuin et al. producing the most sensitive relationship: % ACS = 0.32 (SVecho - SVFick) % + 8.9%. The correlation coefficient for the estimate was 0.8967 with a SEE of +/- 4.78%. In patients with coronary artery disease and abnormally contracting segments, echocardiography can provide reliable measurements of left ventricular end-diastolic volume but estimates of end-systolic volume are less accurate. If mitral regurgitation or a ventricular aneurysm can be excluded, the difference in echocardiographic and forward stroke volume by an independent method is related to the angiographic and forward stroke volume by an independent method is related to the angiographic abnormally contracting segment, and this relationship permits estimation of the size of the abnormally, contracting segment.

Comparison of indices of muscle and pump performance in patients with coronary artery disease.

During diagnostic cardiac catheterization of 20 patients, 19 of whom had coronary artery disease (CAD), left ventricular (LV) performance was assessed by both muscle function indices and pump function indices. Muscle function indices included max dP/dt, Vpm, Vce5, and Vmax, the latter derived from both total pressure (TP) and developed pressure (DP) using catheter-tip manometry. Pump function indices included LV ejection fraction (EF) and percent abnormally contracting segment (ACS), determined from biplane LV angiography. Muscle and pump function indices were also compared to the presence of the S3 (ventricular diastolic) gallop. Correlations existed between EF and Vmax (TP), EF and Vpm, percent-ACS and Vmax(TP), and percent-ACS and Vpm, with r values of 0.760, 0.777, -0.884, and -0.841, respectively. Vmax(TP) and Vpm also correlated quantitatively with the presence of the S3 gallop (p less than 0.0005). Total pressure-derived muscle function indices appear to adquately describe mean LV performance in patients with CAD and ACS, but these muscle function indices are probably highly dependent upon the size of the myocardial scar.

Left ventricular function in patients with and without myocardial infarction and one, two or three vessel coronary artery disease.

Ninety-six patients with chest pain were studied to determine the relation between left ventricular function and severity of coronary artery disease in patients with and without a history of myocardial infarction. Coronary arteriography was performed obtaining cineangiograms (60 frames/sec) and large roll film angiograms (2 to 6 frames/sec) for precise definition of the coronary anatomy. The criteria for diagnosis of myocardial infarction were a typical history, a rise and fall in serum glutamic oxaloacetic transaminase levels and evolutionary S-T segment changes associated with Q waves of at least 0.03 second. Left ventricular function was assessed by measurement of left ventricular end-diastolic pressure and volume, and left ventricular ejection fraction, mass and compliance. Fifteen patients had normal findings; 81 were classified according to number of diseased vessels and presence or absence of myocardial infarction. There were no group differences in age or heart rate. Left ventricular end-diastolic pressure was abnormally increased in patients with three vessel disease and myocardial infarction. Left ventricular end-diastolic volume was increased and the ejection fraction was reduced in patients in each vessel disease group with myocardial infarction. Although ejection fraction was reduced in patients with three vessel disease without myocardial infarction, it was further reduced when infarction occurred. Left ventricular mass increased in patients with three vessel disease with or without myocardial infarction. Values for ventricular compliance were reduced in all patients with myocardial infarction and were lower in those with two and three vessel disease and infarction than in those with two and three vessel disease without infarction. These findings suggest that a previous history of myocardial infarction needs to be considered together with anatomic abnormalities of the coronary arteries in assessing cardiac performance in patients with ischemic heart disease, a previous myocardial infarction significantly alters left ventricular performance; the ejection fraction is a more sensitive measurement of left ventricular function than left ventricular end-diastolic pressure or volume.