D J Coltart

Coronary artery ectasia--a variant of occlusive coronary arteriosclerosis.

In a study of 1000 consecutive coronary arteriograms, 12 patients (all men) had coronary artery ectasia. Ectasia was found most frequently in the circumflex or right coronary artery. Only 1 patient had ectasia in the left anterior descending coronary artery. In 11 patients, ectasia of one artery was associated with severe stenosis or occlusion of other vessels, typical of arteriosclerosis. Histology from an ectatic segment in one of this group showed changes of severe arteriosclerosis with extensive intimal fibrosis and destruction of the media. One patient had a mixed collagen vascular disease. Measurement of coronary sinus flow in 2 patients with coronary artery ectasia showed flows in the range of patients with non-ectatic coronary artery disease. At cardiac surgery flows down the graft to ectatic arteries were in the same range as in grafts to non-ectatic vessels. Patients with coronary artery ectasia should be anticoagulated.

Enzymic analysis of endomyocardial biopsy specimens from patients with cardiomyopathies.

Myocardial biopsies have been obtained from patients with hypertrophic or congestive cardiomyopathies. Marker enzymes for the principal subcellular organelles of the myocardium were estimated using highly sensitive assay procedures. The results were compared with those obtained in tissue from patients with valvular heart disease with good or poor left ventricular function. Left ventricular myocardial tissue from patients with hypertrophic cardiomyopathy showed essentially normal levels of enzymic activities. In congestive cardiomyopathy, right ventricular tissue showed reduced levels of mitochondrial enzymes with increased levels of lactate dehydrogenase. Left ventricular tissue from patients with congestive cardiomyopathy showed reduced levels of mitochondrial and myofibril enzymes but high levels of lactate dehydrogenase. The reduced levels of myofibril Ca++-activated ATP in congestive cardiomyopathy is similar to that found in patients with impaired left ventricular function secondary to valvular disease. It is suggested that defective mitochondrial function is a characteristic feature of congestive cardiomyopathy and that the increased levels of lactate dehydrogenase reflect a compensatory response.

Haemodynamic effects of intravenous amrinone in patients with impaired left ventricular function.

The effects of intravenous amrinone on resting haemodynamic function were investigated in 15 patients with impaired left ventricular function. All patients received 1 X 5 mg/kg and 10 received a further 2 mg/kg. We observed dose related increases in heart rate and cardiac index, and reductions in mean arterial pressure, left ventricular end-diastolic pressure, and systemic vascular resistance. A small reduction in left ventricular end-diastolic volume and a 36% increase in ejection fraction occurred. No significant change in max dp/dt, min dp/dt, (Max dp/dt/P), max (dp/dt/P), KVmax or the ratio of left ventricular end-systolic pressure to left ventricular end-systolic volume was detected. It is concluded that the beneficial effects of intravenous amrinone on the resting haemodynamics in our patients were attributable to vasodilatation, with the drug having no demonstrable positive inotropic effect.

Effects of propranolol on myocardial oxygen consumption, substrate extraction, and haemodynamics in hypertrophic obstructive cardiomyopathy.

Myocardial substrate extraction, coronary sinus flow, cardiac output, and left ventricular pressure were measured at increasing pacing rates before and after propranolol (0.2 mg/kg) in 13 patients with hypertrophic obstructive cardiomyopathy (HOCM) during diagnostic cardiac catheterisation. At the lowest pacing rate myocardial oxygen consumption varied considerably between patients and very high values were found in several individuals (range 10.1 to 57.5 ml/min). These large differences between patients were not explicable by differences in cardiac work; consequently, cardiac efficiency, estimated from the oxygen cost of external work, varied between patients and was lower than normal in all but two. The pattern of substrate extraction at the lowest pacing rate was similar to results reported for the normal heart, and measured oxygen consumption could be accounted for by complete oxidation of the substrates extracted; thus there was no evidence of a gross abnormality of oxidative metabolism, suggesting that low efficiency lay in the utilisation rather than in the production of energy. Each of the four patients with the highest myocardial oxygen consumption and lowest values of efficiency sustained progressive reductions in lactate and pyruvate extraction as heart rate increased, and at the highest pacing rate had low (< 3%) or negative lactate extraction ratios. In three of these four, coronary sinus flow did not increase progressively with each increment in heart rate. One patient with low oxygen consumption and normal efficiency also failed to increase coronary flow with the final increment in heart rate, and produced lactate at the highest pacing rate. Thus the five patients in whom pacing provoked biochemical evidence of ischaemia all had excessive myocardial oxygen demand and/or limited capacity to increase coronary flow. Propranolol did not change lactate extraction significantly at any pacing rate in either the ischaemic or non-ischaemic groups. In only one patient was ischaemia at the highest pacing rate abolished after propranolol, and this was associated with a 30 per cent reduction in oxygen consumption. These results do not demonstrate a direct effect of propranolol upon myocardial metabolism in patients with HOCM, but emphasise the potential value of beta-blockade in protecting these patients from excessive increases in heart rate.

Comparison of the effects of amrinone and sodium nitroprusside on haemodynamics, contractility, and myocardial metabolism in patients with cardiac failure due to coronary artery disease and dilated cardiomyopathy.

The effects of intravenous amrinone and sodium nitroprusside on haemodynamic indices, left ventricular contractility, and myocardial metabolism were compared in patients with cardiac failure. All patients received one dose of each drug and some received serial doses. Eight patients had dilated cardiomyopathy and six coronary artery disease, but the responses to the two drugs were independent of the aetiology of cardiac failure. Both drugs lowered left ventricular end diastolic pressure and aortocoronary sinus oxygen difference and increased cardiac index and left ventricular efficiency; these effects were dose related. Although the effects of the drugs on peripheral blood substrate concentrations were different, those on myocardial substrate metabolism were identical. Pressure derived indices of contractility in each group of patients were unaltered by either drug. After amrinone administration increases in cardiac index were related to plasma amrinone concentration, but alterations in contractility were not. In four individual patients increases in contractility were associated with alterations in plasma metabolite concentrations, which suggested that catecholamine release had occurred. For the groups of patients as a whole, however, amrinone had effects which did not differ significantly from those of the pure vasodilator, nitroprusside. There was no evidence that amrinone had a direct positive inotropic effect since no dose related changes in indices of contractile function could be established.

Estimation of time constant of left ventricular relaxation.

When the fall in left ventricular pressure during isovolumic relaxation is treated as a monoexponential the rate of relaxation can be measured by a time constant. Though an empirical measurement, the time constant has been used extensively to study relaxation. It can be accepted, however, as a valid measurement only if isovolumic pressure fall approximates very closely to a monoexponential in a wide range of circumstances. We analysed 60 beats recorded at different heart rates in 20 patients with a variety of left ventricular disease. In the first part of the study a powerful non-linear regression program was used off-line to test three exponential models: (1) a monoexponential, the asymptote of which is zero, (2) a monoexponential with a variable asymptote, and (3) a biexponential. The pressures predicted by models 2 and 3 were in very close agreement with measured pressure, whereas the predictions of model 1 were consistently less accurate. Model 3 had no advantage over model 2. Thus, in all the beats tested isovolumic pressure fall approximated very closely to a monoexponential of which both the time constant and asymptote are variable. A second exponential term does not increase precision, and is an unnecessary complication. In the second part of the study the same 60 beats were analysed by a small program on the catheter laboratory computer. The time constant was estimated by two methods, corresponding to models 1 and 2 described above: (1) from the slope of In (pressure) against time, and (2) by a method of exponential analysis. The first method underestimated the time constant of model 1, particularly in beats where pressure fell to low levels. The second method accurately estimated the time constant of model 2. It is concluded that isovolumic pressure fall approximates closely to a monoexponential in a wide variety of circumstances, and it is legitimate, therefore, to describe the rate of relaxation by a time constant. But the time constant must be estimated by a method based upon an exponential model of which both the time constant and asymptote are variable. We have shown that such a time constant can be estimated reliably by a small program suitable for use on-line. The usual method of estimating the time constant, from the slope of In (pressure) against time, provides an unreliable estimate of the time constant of an unsatisfactory model.

Inaccuracies in using aortic valve gradients alone to grade severity of aortic stenosis.

The severity of aortic stenosis is an important determinant of prognosis in patients with symptoms who do not undergo valve replacement. To assess the pitfalls of using valve gradients alone 636 patients with aortic stenosis in whom the aortic valve area had been calculated by the Gorlin formula were studied. The correlation between valve area and aortic gradients was poor. No gradient was found that was both sensitive and specific for aortic stenosis. The maximum predictive accuracy was 81% for a mean gradient of 30 mm Hg and 80% for a peak gradient of 30 mm Hg. A mean gradient of 50 mm Hg or a peak gradient of 60 mm Hg were specific with a 90% or more positive predictive value. It proved difficult, however, to find a lower limit with a 90% negative predictive value. Patients with severe aortic stenosis and low gradients (peak or mean gradient of less than 30 mm Hg) had small ventricles (on both angiographic and echocardiographic data) with good ejection fractions and so were unlikely to be detected subjectively. In comparison patients with mild aortic stenosis and low gradients tended to have more aortic regurgitation but have similar degrees of left ventricular hypertrophy on echocardiographic or electrocardiographic criteria. The aortic valve area should be measured in all patients with the suspicion of severe aortic stenosis with a mean gradient of less than 50 mm Hg (50% of patients in this study) or a peak gradient of less than 60 mm Hg (47% of patients in this study).

Correlations of fibrosis in endomyocardial biopsies from patients with aortic valve disease.

The amount of fibrosis in endomyocardial biopsies from 55 patients with aortic stenosis and 42 patients with aortic regurgitaion was measured. Sixty per cent of the patients with aortic stenosis had some degree of fibrosis; the degree of fibrosis correlated strongly with ejection fraction, peak systolic gradient, symptoms of cardiac failure, and mortality. In patients with aortic regurgitation, fibrosis was found in 40 per cent and was never severe. A correlation was found with symptoms of cardiac failure and mortality at follow-up, but not with ejection fraction or degree of regurgitation.

Measurement of the circulatory effects of dobutamine, a new inotropic agent, in patients following cardiac surgery

The use of an extractable aortic electromagnetic flow probe to provide a continuous on-line display of ascending aortic flow and cardiac output following open heart surgery is described. Utilizing this equipment, the hemodynamic actions of dobutamine and isoprenaline are compared in 14 patients immediately following cardiac surgery. The study confirmed an inotropic action produced by dobutamine at a heart rate 10 to 15 per cent lower than isoprenaline, with less peripheral vascular action. Arterial and coronary sinus blood analyses revealed little difference in the myocardial metabolic actions of either drug. Because inotropic drugs produce only relatively small increases in stroke volume in this group of patients, the rise in cardiac output caused by these agents is more dependent on the effects upon heart rate rather than improved myocardial contractile state and consequently dobutamine has little advantage over isoprenaline in this situation.

Effects of intracoronary and intravenous amrinone infusions in patients with cardiac failure and patients with near normal cardiac function.

The effects of intracoronary and intravenous infusions of amrinone were studied to distinguish the drugs direct cardiac actions from its peripheral vascular and neuroendocrine properties. Intracoronary infusions of amrinone were found to have no haemodynamic effect other than producing a slight reduction in the left ventricular ejection fraction and some suggestion of coronary vasodilatation in patients with impaired left ventricular function. They did not improve contractility, cardiac output, or filling pressures and had no significant effect on myocardial metabolism, although therapeutic concentrations of the drug were detected in coronary sinus blood. Intravenously administered amrinone reduced filling pressures and improved the cardiac index in all patients, but haemodynamic improvements were most pronounced in the patients with the worst cardiac function. These changes were accompanied by improvements in the indices of contractility only in patients in whom alterations in concentrations of free fatty acid, glycerol, and glucose suggested peripheral catecholamine release. In the patients with the best basal cardiac function intravenously administered amrinone produced a reduction in myocardial work and evidence of myocardial ischaemia, as a result of excessive reduction of coronary perfusion pressure and increased heart rate, without any appreciable increase in cardiac index. It is concluded that, at the concentrations of the drug that can be achieved in man without adverse effects, amrinone has no direct positive inotropic effect. Haemodynamic changes are predominantly the result of vasodilatation, although catecholamines may be released in some patients.