Laurence H. Green

Contractile state of the left ventricle in man as evaluated from end-systolic pressure-volume relations.

End-systolic pressure (PE8), volume (VES), wall tension (TE8) and circumference (CES) of the human left ventricle were studied at cardiac catheterization in 24 subjects with varying degrees of left ventricular dysfunction. Acute alterations in systolic load consistently resulted in changes in VEs and CEs, with a smaller volume and circumference characterizing the lower systolic load in each subject. End systolic pressure-volume lines were constructed by plotting PEs against VEs at the higher and lower systolic load in each subject. The slope of the resultant lines was considerably steeper for normal than for poorly contractile left ventricles. V., the volume axis in- tercept of the line (i.e., the theoretical VES at PES = 0) was significantly smaller for normal than for poorly contractile ventricles. Similar findings were noted for C., the theoretic end-systolic circumference at zero end-systolic ventricular wall tension. Postextrasystolic potentiation resulted in decreased VES and Cg8 with no change in PES and only a slight fall in TE8. In conclusion, end-systolic pressure-volume and tension-circumference relations reflect the contractile state of left ventricular myocardium. Quantitation of these relationships may provide a useful new approach to the assessment of myocardial function in man.

Hemodynamic determinants of prognosis of aortic valve replacement in critical aortic stenosis and advanced congestive heart failure.

SUMMARYFourteen patients with critical aortic stenosis (valve area ⩽ 0.4 cm2/m2), a history of advanced congestive heart failure, left ventricular ejection fraction less than 0.45 (mean 0.28 ± 0.03) and no other valvular lesions or obstructive coronary artery disease were studied to assess prognosis with aortic valve replacement. Eleven of 14 (79%) survived surgery; 10 of these 11 showed major clinical improvement postoperatively and form group 1. The three patients who died and the patient who did not improve form group 2. Although group 2 had higher preoperative values for aortic valve area and left ventricular end-diastolic volume and lower ejection fraction and cardiac output than group 1, none of these factors alone reliably predicted outcome. The mean systolic gradient was an important predictor of outcome: No patient with a mean systolic gradient ± 30 mm Hg had a good outcome, irrespective of valve area or other hemodynamic variables. Ejection fraction was plotted against left ventricular wall stress for both groups. For group 1, there was a close linear relation that could be extrapolated back to normal wall stress and normal ejection fraction. This suggested afterload mismatch as a major cause for this groups depressed ejection fraction. In group 2 ejectionf raction was lower for any given wall stress, suggesting depressed contractility, rather than afterload mismatch, as the cause of the left ventricular dysfunction. Thus, either afterload mismatch or depressed contractility may result in depressed ejection fraction in patients with aortic stenosis; which one predominates may have major prognostic importance.

End-systolic volume as a predictor of postoperative left ventricular performance in volume overload from valvular regurgitation.

Abstract Although over-all cardiac performance may remain normal in patients with left ventricular volume overload from valvular regurgitation, impairment of myocardial function may occur and remain undetected by currently accepted methods of assessing ventricular performance. Since end-systolic volume reflects myocardial contractile function yet is independent of preload, we assessed preoperative end-systolic volume as a measure of myocardial function in 41 patients with aortic regurgitation, mitral regurgitation or both. Preoperative end-systolic volume was compared to postoperative left ventricular performance as measured by postoperative echocardiographic per cent dimension change (% ΔD) and New York Heart Association class. Preoperative end-systolic volume correlated well with postoperative left ventricular performance in patients with aortic regurgitation (r = 0.77) or mitral regurgitation (r = 0.73). Much poorer correlations existed for preoperative ejection fraction, enddiastolic volume or left ventricular end-diastolic pressure. Preoperative end-systolic volume also predicted patients at high risk for perioperative cardiac death, with all such cardiac deaths occurring in patients with an end-systolic volume >60 cc/m 2 . Again, both preoperative ejection fraction and end-diastolic volume were less precise predictors of surgical outcome. Patients with aortic regurgitation appeared to tolerate a larger end-systolic volume better than those with mitral regurgitation. End-systolic volume is an easily determinable parameter of left ventricular function which is independent of the abnormal preload that occurs in mitral regurgitation and aortic regurgitation and appears to provide a measure for the onset of myocardial dysfunction in patients with these lesions. Whether this myocardial dysfunction is due to a depressed inotropic state of individual sarcomeres, a stress-shortening imbalance or to other factors is unknown, but its presence has major prognostic importance.

Estimation of left ventricular volumes in man from biplane cineangiograms filmed in oblique projections

Abstract In patients with coronary artery disease, right and left anterior oblique views of the left ventricle are considered optimal for assessment of regional wall motion, but the accuracy of ventricular volumes determined from these projections has not been validated. Eleven postmortem left ventricular casts were filmed with the 35 mm cine technique in the 30 ° right anterior oblique and 60 ° left anterior oblique positions, and volumes were calculated using the area-length method. True volume, assessed from volume displacement, ranged from 15 to 185 cc. Calculated volume (V oblique ) slightly but consistently overestimated true volume (V T ), with close correlation and a small standard error of the estimate (SEE):V T = 0.989 V oblique − 8.1 cc, r = 0.99, SEE = 8 cc. With use of this regression equation, values for left ventricular volumes and ejection fraction were calculated from biplane oblique (30 ° right anterior oblique/60 ° left anterior oblique) cineanglograms In 17 normal adults. Values for end-diastolic volume index (72 ± 15 cc/m 2 [mean ± standard deviation]), end-systolic volume index (20 ± 8 cc/m 2 ), stroke volume Index (51 ± 10 cc/m 2 ) and ejection fraction (0.72 ± 0.08) were similar to those reported by others. Examination of the effects of variable obliquity suggests that strict standardization of the degree of obliquity is necessary to offset variation In the long axis in the left anterior oblique projection caused by foreshortening.

Left ventricular end-systolic stress-shortening and stress-length relations in humans

Abstract Experimental studies suggest that the extent of left ventricular (LV) fiber shortening is determined by both the wall stress at end-systole and the contractile state. To evaluate the relation between these variables assessed noninvasively, 26 normal subjects were studied by M-mode echocardiography, phonocardiography, and indirect carotid pulse tracings during infusion of methoxamine to alter load (in all 26 subjects) and infusion of dobutamine (in 10 subjects) to increase contractility. End-systolic pressure was estimated from the incisura of a calibrated carotid pulse tracing. LV end-systolic dimension and wall thickness, and percent internal dimension shortening were determined by echocardiography, and end-systolic meridional wall stress was calculated. The relation between end-systolic stress and shortening was inversely linear (r = −0.83) for 130 control points. Dobutamine infusion resulted in a higher percent fractional shortening for any end-systolic stress; all 43 stress-shortening points were more than 2 standard deviations above the mean for the regression line. The relation between stress and dimension for the control points showed wider scatter than between stress and shortening (r = 0.56). However, in individual patients dobutamine always shifted the stress-dimension lines to the right, as compared with the baseline position resulting in a smaller end-systolic dimension for any end-systolic wall stress. Thus, LV end-systolic wall stress and percent fractional shortening are inversely and linearly related and their relation can be accurately assessed by noninvasive methods. The end-systolic stress-shortening relation is highly sensitive, while the end-systolic stress-dimension relation is less sensitive to alterations in LV inotropic state.

Left Ventricular End-Systolic Pressure-Dimension and Stress-Length Relations in Normal Human Subjects

Abstract To determine whether the left ventricular end systolic pressure-dimension and end-systolic stress-dimension relations in human beings are linear and sensitive to altered contractility, we studied 13 normal subjects during methoxamine infusion and with postextrasystolic potentiation induced by an external mechanical cardiac stimulator. End-systolic diameter was obtained with echocardiography and end-systolic pressure was estimated in six subjects from the dicrotic notch of a simultaneously recorded carotid pulse tracing, standardized by cuff pressure, whereas in seven subjects intraarterial pressure was recorded. For each subject, the end-systolic pressure-dimension relation was linear ( r = 0.83–0.99) over a range of 76 mm Hg (84 to 160) for end-systolic pressure. The mean slope of the end-systolic pressure-dimension line was 62 ± 22 mm Hg/cm. Peak systolic pressure was also linearly related to end-systolic diameter ( r = 0.82–0.99) over a range of 100 mm Hg (104 to 204). End-systolic stress was a linear function of end-systolic dimension as well ( r = 0.93–0.99) over an end-systolic stress range of 181 g/cm 2 . With postextrasystolic potentiation the potentiated beat had a smaller end-systolic dimension for any given end-systolic pressure and thus shifted the end-systolic pressure-dimension relation to the left. Thus, end-systolic pressure-dimension and stress-dimension relations in human subjects appear to be linear and are sensitive to the inotropic state.

Left ventricular function after repair of tetralogy of fallot and its relationship to age at surgery.

Left ventricular (LV) work-function curves were used to assess LV performance in eight postoperative tetralogy of Fallot (TOF) patients who underwent repair before 2 years of age (group 1) and 12 patients who underwent repair after 2 years of age (group 2). All patients were without significant residual shunts or pulmonary stenosis. Results were compared with those in seven control patients. Left- and right-heart hemodynamics were measured at various levels of afterload induced by methoxamine while heart rate was maintained constant. Cardiac output was serially measured. The slope (m) for each patients LV end-diastolic pressure (EDP) vs LV minute-work index (MWI) relationship was determined. There were no significant differences in resting cardiac index, LV systolic pressure, LVEDP, aortic oxygen saturation or MWI among the groups. However, with afterload stress, group 2 patients had abnormal work-function curves with depressed slopes (m = 0.21 0.04) compared with the values for group 1 patients (m = 0.89 ± 0.13, p < 0.001) or the control group (m = 1.13 ± 0.12, p < 0.001). Thus, LV dysfunction unmasked by an afterload stress was present in the older TOF patients but not in the patients repaired during infancy. These findings raise the possibility that early, definitive repair of TOF may help preserve postoperative LV function.

Prevention of nifedipine of abnormal coronary vasoconstriction in patients with coronary artery disease.

The hemodynamic and myocardial metabolic responses to the cold pressor test were studied in 15 patients with coronary artery disease and stable exertional angina. Every patient had abnormal coronary vasoconstriction during a control cold pressor test, even though 14 were receiving propranolol and 12 were receiving long-acting nitrates. Mean coronary vascular resistance for the group increased 18 ± 6% (SD) (from 0.80 ± 0.12 to 0.94 ± 0.20 mm Hg/ml/min, p < 0.05); coronary sinus blood flow was unchanged, and the arterial-coronary sinus oxygen difference widened significantly (from 11.5 ± 1.2 to 12.3 ± 1.2 ml/100 ml, p < 0.05), Four patients developed angina, accompanied in each instance by a negative arterial-coronary sinus lactate difference. After the administration of nifedipine (10 mg buccally) in 10 patients, the coronary vascular responses to a repeat cold pressor test were normal in each patient. Mean coronary sinus blood flow increased 27 ± 12% (from 122 ± 32 to 153 ± 35 ml/min, p < 0.05), coronary vascular resistance decreased 10 ± 6% (from 0.85 ± 0.16 to 0.76 ± 0.16 mm Hg/m1/min, p < 0.05), and the arterial–coronary sinus oxygen difference was unchanged. No patient experienced angina. The hemodynamic and coronary vascular responses to a repeat cold pressor test in five patients given placebo were unaltered from control responses.The protective effects of nifedipine were unaccompanied by any change in mean arterial pressure, left ventricular filling pressure or myocardial oxygen consumption either at test or in response to the cold pressor test. Nifedipine appears to exert a selective antivasoconstrictor effect on the coronary vasculature.

Blood oxygen measurements in the assessment of intracardiac left to right shunts: A critical appraisal of methodology

Abstract The proper use of sequential diagnostic blood oxygen determinations for assessing left to right shunts requires a thorough understanding of the normal variability of blood oxygen measurements among the various right heart chambers and the influence of alterations in circulating hemoglobin levels and systemic blood flow. Oximetric measurements were obtained in 23 patients without a left to right shunt and compared with measurements obtained in 42 patients with a proved left to right shunt to examine the normal range of oxygen variability in blood samples from right heart chambers. The effect of fluctuations in hemoglobin levels was evaluated by comparing increases in percent oxygen saturation and oxygen content. Differences in percent saturation were found to be more useful than differences in oxygen content for detection of cardiac shunts. A mean difference of at least 7 percent oxygen saturation was found to be required for a firm diagnosis of a shunt at the atrial level, and 5 percent oxygen saturation for a shunt at the ventricular or great vessel level. The curvilinear relation between systemic blood flow and oxygen step-up in determining the pulmonary to systemic flow ( Q P Q S ) ratio was expressed in a series of equations and depicted by a three dimensional surface. Interventions such as exercise augment both systemic blood flow and oxygen step-up, resulting in a shift to a more steeply rising portion of the surface and a dramatic increase in shunt flow. The minimal left to right shunt detectable with oxlmetry is largely dependent on the level of systemic blood flow.

Coronary hemodynamic and myocardial metabolic alterations accompanying coronary spasm

Arterial pressure, coronary sinus blood flow with the thermodilution technique and calculated coronary vascular resistance were measured and coronary arteriography performed at rest and after the administration of ergonovine in 14 patients with atypical chest pain (group 1) and 6 patients with variant angina (group II). Mild diffuse narrowing of the left coronary bed in group I was not accompanied by S-T segment shifts, and coronary vascular resistance did not change significantly. In contrast, severe focal spasm (greater than 90 percent narrowing) of the left anterior descending coronary artery in group II patients was accompanied by S-T elevation and a marked overall increase in coronary vascular resistance (from 0.65 +/- 0.07 to 1.14 +/- 0.10 mm Hg/ml per min) (P less than 0.005). In addition, the myocardial arteriovenous oxygen difference increased and net lactate extraction changed to lactate production in the two patients in group II in whom these measurements were made. Thus, thermodilution coronary sinus blood flow measurement may be a sensitive method for detecting primary increases in coronary vascular resistance due to a high grade focal spasm in the left anterior descending coronary artery.