Israel Mirsky

Increased regional myocardial stiffness of the left ventricle during pacing-induced angina in man.

The left ventricular diastolic pressure-volume. relationship shifts upward during angina, but why this happens is not known. To assess regional myocardial stiffness, we studied 12 patients who. had coronary artery disease using simultaneous left ventricular micromanometer pressure recording and Mmode echocardiography before and during angina induced. by pacing tachycardia. All patients had two- or three-vessel coronary artery disease that involved the posterior left ventricular wall circulation and had positive pacing stress tests, i.e., development of angina and a postpacing rise in left ventricular end-diastolic pressure (15±3 to 31±6 mm Hg, p < 0.001). A marked upward shift in the relationship between the diastolic left ventricular pressure and the posterior wall thickness (h) occurred after pacing tachycardia, but the change in left ventricular posterior wall end-diastolic thickness was minimal (8.9±2.1 to 9.2±2.1 mm, NS). After pacing, the peak rate of left ventricular posterior wall thinning decreased (82±37 to 48±27 mm/sec, p < 0.005) and the time constant of relaxation derived from the best exponential fit to the isovolumic left ventricular pressure decay increased (49±5 to 58±7 msec,. p < 0.001). Diastolic active left ventricular pressure decay, extrapolated from the exponential fit, was subtracted from the measured left ventricular pressure (which is equal in magnitude but opposite in sign to the radial stress at the endocardium) to calculate residual left ventricular pressure (PR) and hence residual stress (6R = -PR). A radial stifiness modulus (ER) was determined by the slope of the PR VS log h plots before and after pacing. Over the same range of residual radial stress (aR), ER was always higher during pacing-induced angina, indicating increased residual myocardial stiffness. Increased myocardial stiffness in addition to a decreased rate of wall thinning and slow active pressure decay contribute to the upward shift in left ventricular pressure-wall thickness and pressure-volume relationships during pacing-induced angina.

Assessment of Left Ventricular Stiffness in Primary Myocardial Disease and Coronary Artery Disease

Stress-strain relations (&sgr;-&egr;) were obtained in the form d&sgr;/d&egr; = k&sgr; + c, where k is a stiffness constant. Utilizing the pressure-volume relation dP/dV = &agr;P, the elastic stiffness (d&sgr;/d&egr;) and k were evaluated at end diastole in ten patients with normal ventricles (N), in 34 patients with coronary artery disease (CAD), and in 22 patients with primary myocardial disease. This latter group was classified into Type I (normal contraction patterns and elevated end-diastolic pressure), Type II (hypertrophy without obstruction), and Type III (hypokinetic and/or asynergic).The mean values and standard error of the means (SEM) of k and elastic stiffness were 14.8 ± 0.7, 329 ± 54 gm/cm2 (N); 17.8 ± 0.3, 684 ± 80 gm/cm2 (CAD); 18.2 ± 0.5, 1133 ± 127 gm/cm2 (Type I); 22.4 ± 1.2, 833 ± 150 gm/cm2 (Type II); 18.7 ± 0.6, 1623 ± 348 gm/cm2 (Type III).These studies indicate that 1) dP/dV, wall stress, and volume-mass ratio are the important determinants of stiffness, 2) normal stiffness levels can be recorded from hypertrophied ventricles, 3) CAD patients with end-diastolic pressure ≦ 12 mm Hg have normal stiffness levels, 4) normal contraction patterns and normal stiffness levels are not necessarily related.

Myocardial Force-Velocity Relationships in Clinical Heart Disease

Myocardial force-velocity relationships were studied in 33 children and young people with varying heart lesions. From analysis of left ventricular pressures and consideration of left ventricular geometry, measured from biplane angiocardiograms, maximal contractile element velocity (Vmax) was determined by extrapolation of a stress-velocity plot to zero stress. The value of Vmax in each patient was compared with the assessment of cardiac function by usual hemodynamic criteria (left ventricular end-diastolic pressure [LVEDP], volume [LVEDV], and ejection fraction [EF]).In general, patients with normal LVEDP, LVEDV, and EF had values for Vmax above 3 circumferences/sec. Patients with elevated LVEDP or LVEDV or with EF below 0.5 had lower values for Vmax. Three patients whose usual catheterization data suggested normal ventricular function were found to have low Vmax. In all three, other evidence for myocardial abnormality was found. Several patients with excessive afterloads had impaired function by conventional criteria, yet had normal Vmax.Evaluation of myocardial mechanics in man with measurement of Vmax appears to aid significantly in evaluating patients with heart disease by giving an index to the state of the myocardium not available from routine catheterization data.

General index for the assessment of cardiac function

Abstract The concept of a “normalized velocity” was employed to provide a uniform approach for the assessment of cardiac function. In particular, the quantities [(dp/dt/)/p]max, [(dV/dt/)/V]max and [t(dl/dt/)/l]max were applied to data taken from 89 studies in 71 infants, children and young adult patients. Here p represented the total left ventricular pressure, V the instantaneous ventricular volume and I the instantaneous outward displacement as recorded from an apex cardiogram at time t from the onset of displacement. Results were as follows: (1) The contractility index [(dp/dt)/p]max appeared to relate to myocardial function assessed clinically and to be more consistent with the clinical findings in the clear-cut situations than Vmax based on total pressure, Vmax based on developed pressure and [(dP/dt)/P] at P = 40 mm Hg developed pressure where P = total pressure minus end-diastolic pressure. (2) The ejection velocity [(dV/dt)/V]max was found to reflect hemodynamic function and correlated with the ejection fraction ( r = 0.80). (3) The index [t(dl/dt)/l]max as obtained from the apex cardiogram related well to [(dp/dt)/p]max ( r = 0.72). These studies suggest that values for “normalized velocity” obtained from direct or indirect methods, give reliable guides to myocardial function and allow for meaningful comparisons among patients.

Assessment of myocardial contractility in children and young adults from ventricular pressure recordings

Abstract The index V pm (the actual or physiologic maximal shortening velocity of the contractile element) has been obtained from the analysis of left ventricular pressure recordings and then applied to the assessment of myocardial contractility in man. Pressures during the isovolumic period of ventricular systole were recorded during routine catheterization of 46 patients with a variety of cardiac lesions. The quantity V pm , that is (dp/dt/kp) max , was compared with the hemodynamic evaluation of each patient based on the left ventricular end-diastolic pressure, ejection fraction and left ventricular end-diastolic volume. V pm was selected for this study since it appeared to be largely independent of load and does not require biplane angiocardiography and extrapolation analyses. Preliminary results suggest that a value of V pm greater than 1.6 sec −1 indicates normal myocardial function; lower values indicate abnormal function. In several instances this index was not in agreement with the hemodynamic measures, but in most cases the clinical assessment supported the conclusion drawn from V pm . This study suggests that reliable guides to myocardial contractility can readily be obtained from high fidelity pressure recordings alone.

In vivo stresses in the human left ventricular wall: Analysis accounting for the irregular 3-dimensional geometry and comparison with idealised geometry analyses

Abstract The in vivo stresses in the left ventricular wall are of interest to a cardiologist in evaluating the state of response or adjustment of the left ventricle to a heart disease. To determine the instantaneous in vivo stresses, we employ data consisting cineangiocardiographic determination (in single plane antero-posterior projection) of the instantaneous dimensions of the left ventricle and the left ventricular and chamber pressure. At each frame, an irregular planor outline of the LV is obtained from the X-ray film; each half of the frame is revolved into an irregular shell chamber of revolution, which is analysed for the wall stresses (due to the chamber pressure loading) by finite element procedure. The characteristic features of the finite element procedure are: (i) the left ventricular shell is divided into shell ring elements; the meridian of each element is represented by a 4th order polynomial passed through closely spaced points on the cineangiographically obtained single plane contour of the left ventricle, (ii) the geometrical properties of the shell are found from the derivatives of the equation of the meridional curve, (iii) the governing equilibrium equations of a shell ring element include effects of bending and transverse shear deformation, (iv) Displacement method of solution is employed; this is essentially an application of Ritz method utilizing the principle of minimum total potential energy, (v) the high order displacement polynomials that are employed in the analysis, provide good approximations for the displacements as well as for the stresses. The wall stress results obtained from finite element analysis are compared with the ventricular wall stresses obtained by Mirsky and Ghista (thick shell and exact elasticity, respectively) idealised geometry (ellipsoidal shaped) models of the left ventricle. The peak stress states obtained from the two models are nearly the same, with the idealised geometry models underestimating the peak circumferential stress at the apex. So the finite element analysis of the left ventricle is effectively able to incorporate the effect of variations in the curvature of the left ventricular wall boundary on the stress distribution across the wall thickness and on, the level of stress concentrations.

Correction for preload in assessment of myocardial contractility in aortic and mitral valve disease. Application of the concept of systolic myocardial stiffness.

With single-beat analysis, the new concept of systolic myocardial stiffness is applied to provide a new approach for the assessment of myocardial contractility in aortic and mitral valve disease. Seventy patients underwent diagnostic right and left heart catheterization. Twenty-six patients had aortic stenosis, 18 had aortic insufficiency, and 26 had mitral regurgitation. Patients with aortic stenosis were divided into two groups on the basis of left ventricular mass index less than 172 g/m2 (AS1) and mass index greater than or equal to 172 g/m2 (AS2). The mitral regurgitation patients were divided into those in normal sinus rhythm (MR1) and those in atrial fibrillation (MR2). Nine patients without significant coronary or cardiovascular disease served as controls. Thirteen patients with aortic stenosis and eight with aortic insufficiency were evaluated (average, approximately 18 months) after successful aortic valve replacement. With simultaneous left ventricular pressure and cineangiographic methods, myocardial contractility was assessed by the conventional ejection fraction-afterload relation (uncorrected for preload) and by two new methods that permit the correction of the ejection fraction for preload. Assessments of the contractile state by these two new methods differed from those by the conventional method in 20-40% of the cases studied. Contractile state improved postoperatively in aortic stenosis and aortic insufficiency even in patients with preoperative depressed contractile states. In patients with mitral regurgitation, there was considerable heterogeneity of contractile function preoperatively. Severe left ventricular hypertrophy in aortic stenosis was not a marker for postoperative outcome since contractility was normal postoperatively in AS1 and AS2 in equal numbers. This study demonstrates that preload correction is important in a preoperative assessment of contractility in aortic and mitral valve disease but that it is less important postoperatively, presumably because of reductions in the preload.

Effects of anisotropy and nonhomogeneity on left ventricular stresses in the intact heart

The qualitative effects of anisotropy and nonhomogeneity are considered in the evaluation of left ventricular stresses in the intact heart. Maximum stresses and their location are significantly dependent on the nonhomogeneity factors and to a lesser degree on anisotropy of the ventricular wall material. If the circumferential elastic modulus is assumed to vary in a parabolic manner through the wall thickness, maximum stresses occur within the endocardial layers, a result in qualitative agreement with experimental studies.

Comparison of echocardiography and radionuclide angiography as predictors of mortality in patients with left ventricular dysfunction (studies of left ventricular dysfunction)

Left ventricular (LV) systolic dysfunction, as indicated by a reduced LV ejection fraction (EF) is a potent predictor of cardiovascular mortality. Radionuclide angiography accurately and reproducibly assesses LVEF; however, echocardiography is used more frequently in clinical practice. Whether these methods predict similar mortality has not been fully investigated. We performed a retrospective analysis of patients with baseline radionuclide angiographic (RNA; n = 4,330) and echocardiographic (echo; n = 1,376) based EFs < or =0.35 who were enrolled in the Studies Of Left Ventricular Dysfunction (SOLVD) to address this hypothesis. After adjusting for important prognostic variables, the risk of death (RR 1.15; 95% confidence interval 1.01 to 1.30; p = 0.03) and of cardiovascular death (RR 1.15; 95% confidence interval 1.01 to 1.32; p = 0.04) was higher for patients with ECG-based EFs. To compare the 2 techniques across a range of EF values, we divided the cohort into tertiles of EF. The adjusted risk estimates for all-cause and cardiovascular mortality were similar within each tertile. Of note, the mortality difference in patients with echo- versus RNA-based EFs was most prominent in women. Further, patients with echo-based EFs had significantly higher mortality at sites where this technique was less frequently used to assess the EF. Thus, for a given EF < or =0.35, an echo-based value was associated with a higher risk of death compared with the RNA-based method of measurement. These data suggest that EF values determined by echocardiography and radionuclide angiography predict different mortality and this may, in part, be related to technical proficiency as well as patient characteristics.

Effects of Cardiac Denervation on Development of Heart Failure and Catecholamine Desensitization

BACKGROUND Two signatures of heart failure are activation of the sympathetic nervous system and catecholamine desensitization. However, whether or not the elimination of cardiac nerves affects either the progression of heart failure or catecholamine desensitization is not clear. METHODS AND RESULTS We studied 8 dogs with selective ventricular denervation (VD) (surgical technique) and 10 intact dogs, chronically instrumented for measurement of left ventricular (LV) and arterial pressures, LV dP/dt, LV internal diameter, and wall thickness before and after heart failure was induced by rapid pacing (240 bpm) for 3 to 4 weeks. VD was confirmed by the absence of reflex effects induced by intracardiac veratrine and depletion of tissue norepinephrine and by supersensitive responses to norepinephrine. During the development of heart failure, LV end-systolic and end-diastolic stresses and heart rate increased, while myocardial contractility, as reflected by LV dP/dt and mean velocity of circumferential fiber shortening corrected for heart rate (Vcf(c)), decreased in both intact and VD dogs. However, the increases in LV end-diastolic stress and decreases in LV dP/dt as well as the relationship between LV systolic stress and Vcf(c) in heart failure were less (P<.05) in VD dogs. The responses of LV dP/dt and heart rate to both isoproterenol and norepinephrine in intact dogs were reduced in heart failure. The physiological desensitization to the inotropic effects of isoproterenol and norepinephrine was less in dogs with VD (P<.05), but chronotropic responses were similar because atrial innervation remained intact. Plasma norepinephrine levels were not different in VD dogs (592+/-79 pg/mL) compared with intact dogs (576+/-81 pg/mL) in heart failure. CONCLUSIONS Dogs with selective VD tolerated the development of heart failure better than intact dogs and demonstrated significantly less catecholamine desensitization. The latter indicates that intact ventricular innervation is required for physiological expression of catecholamine desensitization despite comparable elevation of plasma catecholamines during the development of heart failure.