Lambert P. McLaurin

Wall stress and patterns of hypertrophy in the human left ventricle.

It is generally recognized that chronic left ventricular (LV) pressure overload results primarily in wall thickening and concentric hypertrophy, while chronic LV volume overload is characterized by chamber enlargement and an eccentric pattern of hypertrophy. To assess the potential role of the hemodynamic factors which might account for these different patterns of hypertrophy, we measured LV wall stresses throughout the cardiac cycle in 30 patients studied at the time of cardiac catheterization. The study group consisted of 6 subjects with LV pressure overload, 18 with LV volume overload, and 6 with no evidence of heart disease (control). LV pressure, meridional wall stress (sigman), wall thickness (h), and radius (R) were measured in each patient throughout the cardiac cycle. For patients with pressure overload, LV peak systolic and end diastolic pressures were significantly increased (220 plus or minus 6/23 plus or minus 3 mm Hg) compared to control (117 plus or minus 7/10 plus or minus 1 mm Hg, P less than 0.01 for each). However, peak systolic and end diastolic (sigman) were normal (161 plus or minus 24/23 plus or minus 3 times 10-3 dyn/cm-2) compared to control (151 plus or minus 14/17 plus or minus 2 times 10-3 dyn/cm-2, NS), reflecting the fact that the pressure overload was exactly counterbalanced by increased wall thickness (1.5 plus or minus 0.1 cm for pressure overload vs. 0.8 plus or minus 0.1 cm for control, P less than 0.01). For patients with volume overload, peak systolic (sigman) was not significantly different from control, but end diastolic (sigmam) was consistently higher than normal (41 plus or minus 3 times 10-3 dyn/cm-2 for volume overload, 17 plus or minus 2 times 10-3 dyn/cm-2 for control, P less than 0.01). LV pressure overload was associated with concentric hypertrophy, and an increased value for the ratio of wall thickness to radius (h/R ratio). In contrast, LV volume overload was associated with eccentric hypertrophy, and a normal h/R ratio. These data suggest the hypothesis that hypertrophy develops to normalize systolic but not diastolic wall stress. We propose that increased systolic tension development by myocardial fibers results in fiber thickening just sufficient to return the systolic stress (force per unit cross-sectional area) to normal. In contrast, increased resting or diastolic tension appears to result in gradual fiber elongation or lengthening which improves efficiency of the ventricular chamber but cannot normalize the diastolic wall stress.

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.

Diastolic properties of the left ventricle.

Left ventricular pressure and volume during diastole reflect the interaction of ventricular elastic, viscous, and inertial properties, and the completeness of myocardial relazation. Myocardial relaxation may be impaired in the acutely ischemic ventricle, partly accounting for the abnormal diastolic pressure-volume relation in this condition. Altered elasticity of its wall can cause increased stiffness of the ventricular chamber, as in aortic stenosis, coronary heart disease, and infiltrative cardiomyopathies. In aortic stenosis, increased left ventricular stiffness results in an increase in pressure increment associated with left atrial contraction. Generation of such a high filling pressure is critical in maintaining adequate end diastolic sarcomere stretch in the left ventricle and probably accounts for the frequent deterioration of patients with aortic stenosis after development of atrial fibrillation or nodal rhythm. Many signs and symptoms of cardiac failure, previously attributed to impaired systolic performance, may be due to partly to altered diastolic properties of the ventricular chambers.

Impaired left ventricular relaxation during pacing-induced ischemia

Rapid atrial pacing was performed in 15 patients at the time of cardiac catheterization. The results indicate that tachycardia may produce incomplete left ventricular relaxation in patients with disorders characterized by ischemia, but not in those with a normal left ventricle. This phenomenon was characterized by (1) a decrease in the peak negative value for first derivative of left ventricular pressure (dP/dt), which was used in the study as an index of left ventricular relaxation rate, (2) an increase in left ventricular diastolic pressure, and (3) a decrease in left ventricular internal diameter. These findings suggest that ventricular relaxation is an important determinant of left ventricular diastolic pressure-volume relations and that an impairment of ventricular relaxation may be partly responsible for the apparent decrease in left ventricular diastolic compliance observed during pacing-induced angina pectoris.

Effect of angina on the left ventricular diastolic pressure-volume relationship.

The increased left ventricular end-diastolic pressure associated with myocardial ischemia was studied in 19 patients at cardiac catheterization. Single plane left ventriculograms were performed using high fidelity micromanometer tipped catheters before and immediately following rapid atrial pacing. Left ventricular diastolic properties were evaluated by constructing diastolic pressure-volume curves from the simultaneous pressure and volume data. In seven control patients, there was no significant change in left ventricular hemodynamics or the diastolic pressure-volume curve after atrial pacing. Twelve patients with significant coronary artery disease developed angina during pacing and had an increased left ventricular end-diastolic pressure (18 ± 2 mm Hg, control, vs 30 ± 2 mm Hg, angina, P < X01) in the immediate post-pacing period. In these patients, the post-pacing ejection fraction was modestly decreased (0.63 ± 0.03, control, vs 0.57 ± 0.03, angina P < 0.01), and left ventricular volumes at end systole (59 ± 8 cc, control, vs 74 ± 9 cc, angina, P < 0.01) and end diastole (158 ± 10 cc, control, vs 170 ± 11 cc, angina, P < 0.0125) were increased. The post-pacing diastolic pressure-volume curves in all 12 patients were shifted upward as compared with control so that for any given diastolic volume, pressure was higher during angina. The data indicate that the increased left ventricular diastolic pressure during myocardial ischemia is the result of both impaired left ventricular systolic performance and altered left ventricular diastolic properties.

Effects of Sodium Nitroprusside on Left Ventricular Diastolic Pressure-Volume Relations

The effect of sodium nitroprusside on the relationship between left ventricular pressure and volume during diastole was studied in 11 patients with congestive heart failure. Nitroprusside was infused to lower mean arterial pressure approximately 20-30 mm Hg. High fidelity left ventricular pressures were recorded in all patients simultaneously with left ventricular cineangiography (biplane in eight and single plane in three patients), allowing precise measurement of pressure and volume throughout the cardiac cycle. Left ventricular diastolic pressure-volume curves were constructed in each patient from data obtained before and during nitroprusside infusion. In 9 of 11 patients there was a substantial downward displacement of the diastolic pressure-volume curve during nitroprusside infusion, with left ventricular pressure being lower for any given volume with nitroprusside. Serial left ventricular cineangiograms performed 15 min apart in six additional subjects who did not receive sodium nitroprusside showed no shift in the diastolic pressure-volume relation, indicating that the shift seen with nitroprusside was not due to the angiographic procedure itself. A possible explanation for the altered diastolic pressure-volume relationships with nitroprusside might be a direct relaxant effect of nitroprusside on ventricular muscle, similar to its known relaxant effect on vascular smooth muscle. Alternatively, nitroprusside may affect the diastolic pressure-volume curve by affecting viscous properties or by altering one or more of the extrinsic constraints acting upon the left ventricle.

Assessing the Hemodynamic Severity of Acute Aortic Regurgitation Due to Infective Endocarditis

Nine patients who underwent aortic-valve replacement for acute aortic regurgitation due to infective endocarditis were studied for clinical features that may be useful in assessing the severity of this condition. The traditional physical signs of a wide pulse pressure were absent. As compared to a group of patients with chronic aortic regurgitation, the mean (plus or minus S.D.) pulse pressure (55 plus or minus 7 vs. 105 plus or minus 22 mm Hg), left ventricular end diastolic volume (146 plus or minus 28 vs. 264 plus or minus 64 ml per square meter) and stroke volume (89 plus or minus 22 vs. 163 plus or minus 57 ml per square meter) were significantly smaller in the acute group (P less than 0.01). Left ventricular pressure exceeded left atrial pressure in late diastole, causing premature closure of the mitral valve, and the degree of early closure reflected the increase in left ventricular end diastolic pressure. Premature closure of the mitral valve was demonstrated by echocardiography in all patients. Those with echocardiographic signs of very early mitral-valve closure have severely volume-overloaded ventricles and are candidates for early valve replacement.

Reduced Systemic Vascular Resistance as Therapy for Severe Mitral Regurgitation of Valvular Origin

We examined the hemodynamic response to afterload reduction by sodium nitroprusside in 7 patients with severe mitral regurgitation of purely valvular origin. Lowering of systemic vascular resistance was associated with major reductions in pulmonary capillary mean (29 +/- 2 to 13 +/- 1 mm Hg) and left ventricular end diastolic (20 +/- 3 to 9 +/- 1 mm Hg) pressures, while substantial increases were noted in cardiac index (2.2 +/- 0.5 to 3.1 +/- 0.4 litres/min per m2 body surface area) and forward stroke volume (23 +/- 4 to 34 +/- 4 ml/beat/m2 body surface area). Angiographic calculations showed significant decreases in regurgitant volume (73 +/- 19 to 55 +/- 12 ml/beat/m2 body surface area) and regurgitant fraction (0.70 +/- 0.07 to 0.57 +/- 0.06). No significant change occurred in left ventricular ejection fraction or heart rate, suggesting that the improved cardiac function was not due to a reflex increase in adrenergic stimulation. These observations support the concept that afterload reduction may be therapeutic in severe mitral regurgitation by reducing impedance to forward left ventricular output, thereby promoting greater forward and small regurgitant fractions of the total stroke volume.

Left Ventricular Stiffness Associated with Chronic Pressure and Volume Overloads in Man

The relative effects of chronic pressure overload and chronic volume overload on left ventricular diastolic chamber stiffness were examined using a combined hemodynamic and ultrasonic technique in 27 patients. The slope of the left ventricular pressure-diameter relation in late diastole was measured and found to be steep in the groups with pressure or volume overload (9.0 ± 1.8 mm Hg/mm for pressure overload, 5.6 ± 0.9 mm Hg/mm for volume overload) compared with a control group (2.2 ± 0.2 mm Hg/mm). When this slope was normalized for either pressure or diameter, chamber stiffness remained high in the pressure-overloaded ventricles but was only slightly increased in the volume-overloaded ventricles compared with control. Ventricular wall thickness was much greater in pressure-overloaded ventricles (15.6 ± 1.0 mm) than it was in normal (9.0 ± 0.4 mm) ventricles but only slightly increased in volume-overloaded ventricles (10.6 ± 0.9 mm). The large increases in both effective and normalized diastolic stiffness indexes associated with chronic pressure overload suggest an increase in intrinsic left ventricular chamber stiffness, possibly related to an increase in wall thickness. In contrast, chronic volume overload results in only slight increases in normalized diastolic stiffness indexes and wall thickness. It is suggested that differences in the pattern of hypertrophy, which result in a significant disparity in ventricular wall thickness between the two conditions, best account for the observed differences in diastolic left ventricular chamber stiffness.

Combined hemodynamic-ultrasonic method for studying left ventricular wall stress

Abstract Calculation of left ventricular wall stress in man has traditionally required angiographic and left ventricular pressure measurement, making study of interventions difficult. We have developed a combined hemodynamic-ultrasonic technique for measuring left ventricular meridional wall stress ( σ m ) throughout the cardiac cycle. Simultaneous measurements of left ventricular pressure, ultrasonically determined wall thickness (h[echo]), and minor axis (D[echo]) were made during cardiac catheterization in nine subjects, three with chronic left ventricular pressure overload, four with left ventricular volume overload and two with normal left ventricular function. Within 30 minutes, left ventricular cineangiography was performed in each subject and angiographic wall thickness (h[angio]) and minor axis (D[angio]) were measured. Comparison of values for each subject throughout the cardiac cycle (average 18 data points/cycle) yielded close correlation: For D(echo) versus D(angio), r values ranged from 0.82 to 0.98 whereas for h(echo) versus h(angio), r values ranged from 0.56 to 0.98 for the nine subjects. Meridional wall stress was calculated after the method of Sandler and Dodge as PRi2h(2Ri + h), where R i equals the inner wall radius, calculated as D/2 for both ultrasonic and angiographic methods. Agreement between ultrasonic and angiographic methods was excellent in each subject, with close superimposition of the stresstime plots constructed by the different techniques. In summary, a new method for measurement of left ventricular wall stress has been developed and validated by comparison with an angiographic reference standard. This method has potential advantages, including the ability to study meridional wall stress continuously and to assess its response to serial interventions.