Gen Shimizu

Left ventricular midwall mechanics in systemic arterial hypertension. Myocardial function is depressed in pressure-overload hypertrophy.

BackgroundLeft ventricular (LV) midwall geometry has been described conventionally as the sum of the chamber radius and half of the wall thickness; this convention is based on the assumption of uniform transmural thickening during systole. However, theoretical considerations and experimental data indicate that the inner half (inner shell) of the LV wall thickens more than the outer half (outer shell). Thus, an end-diastolic circumferential midwall fiber exhibits a relative migration toward the epicardium during systole. As a result, the conventional method provides an overestimate of the extent of the midwall fiber shortening. Methods and ResultsWe developed an ellipsoidal model with a concentric two-shell geometry (nonuniform thickening) to assess midwall fiber length transients throughout the cardiac cycle. This modified midwall method was used in the analysis of LV cineangiograms from 15 patients with systemic arterial hypertension and 14 normal subjects. Study groups were classified according to LV mass index (LVMI): 14 normal subjects (group I), eight hypertensive patients with a normal LVMI (group II), and seven hypertensive patients with an increased LVMI (group III). There were no significant differences in LV end-diastolic pressure or volume among the three groups; the ejection fraction was slightly greater in group 11 (70 + 5%) than in groups I (65±8%) and III (664±4%), but this trend did not achieve statistical significance. Values for endocardial and conventional midwall fractional shortening (FS) were also similar in the three groups. By contrast, FS by the concentric two-shell geometry (modified midwall method) in group III (16±2%) was significantly less than that seen in groups I and II (21±4% and 21 + 5%, respectively; both p < 0.05). This difference achieves greater importance when it is recognized that mean systolic circumferential stress was lower in group III (151±22 g/cm2) than in groups I and 11 (244±37 g/cm2 and 213+38 g/cm2, respectively; both p<0.01). The midwall stressshortening coordinates in six of the seven group III patients were outside the 95% confidence limits for the normal (group I) subjects. Thus, despite a normal ejection fraction, systolic function is subnormal in hypertensive patients with LV hypertrophy. ConclusionsChamber dynamics provide an overestimate of myocardial function, especially when LV wall thickness is increased. This is due to a relatively greater contribution of inner shell thickening in pressure-overload hypertrophy.

Right ventricular pacing reduces the rate of left ventricular relaxation and filling

Right ventricular pacing alters left ventricular synchrony and loading conditions, each of which may independently influence left ventricular relaxation. Addition of a properly timed atrial contraction by using sequential atrioventricular (AV) pacing minimizes changes in left ventricular loading conditions, but ventricular asynchrony persists. To separate the effects of altered loading from those of asynchrony, the effects of right ventricular pacing and sequential AV pacing on the rate of isovolumic pressure decline (relaxation time constant), myocardial (segment) lengthening rate and chamber (minor axis dimension) filling rate were examined. In 12 open chest anesthetized dogs, left ventricular pressure (micromanometer) and either left ventricular free wall segment length transients (n = 6) or minor axis dimension transients (n = 6) were measured during right atrial, right ventricular and sequential AV pacing; length and dimension were measured using ultrasonic crystals. Compared with right atrial pacing, right ventricular pacing produced a decrease in systolic pressure, a reduction in fractional shortening, a prolongation of the relaxation time constant (23.5 +/- 0.7 to 29.8 +/- 0.8 ms, p less than 0.05), slower peak segment lengthening rate (6.2 +/- 0.6 to 4.6 +/- 0.8 s-1, p less than 0.05) and a slower rate of increase in chamber dimension (3.5 +/- 0.1 to 2.7 +/- 0.1 s-1, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular chamber filling and midwall fiber lengthening in patients with left ventricular hypertrophy: overestimation of fiber velocities by conventional midwall measurements.

Observations that the inner (subendocardial) half of the left ventricular wall contributes more to total left ventricular wall thickening than the outer (subepicardial) half may have important implications in the analysis of myocardial fiber length transients. Accordingly, we measured endocardial and midwall shortening and lengthening rates in normal and hypertrophic heart and compared the results obtained with conventional methods of measurement with those obtained with a modified model that does not depend on use of conventional assumptions about the midwall. This modified (two-shell) cylindrical model) method considers the substantial contribution of inner wall thickening and thus does not require the assumption of a theoretical midwall fiber that remains at the midwall throughout the cardiac cycle. Echocardiographic data from six normal subjects and six patients with concentric left ventricular hypertrophy (LVH) were examined; left ventricular wall thickness ranged from 8 to 10 mm in normal subjects and from 11 to 16 mm in the patients with LVH. By design, the standard measurements of left ventricular size (diastolic and systolic dimensions) and systolic function (fractional shortening and endocardial fiber shortening velocities) were equal in the two groups. Endocardial, conventional midwall, and modified midwall methods all indicate reduced fiber lengthening rates in patients with LVH; peak fiber lengthening rates for normal and LVH groups were 4.5 +/- 0.7 vs 3.1 +/- 0.8 sec-1 (p less than .02) at the endocardium, 2.3 +/- 0.4 vs 1.6 +/- 0.4 sec-1 (p less than .02) at the midwall (conventional method), and 2.1 +/- 0.3 vs 1.4 +/- 0.3 sec-1 (p less than .01) at the midwall (modified method).(ABSTRACT TRUNCATED AT 250 WORDS)

Functional and histopathologic correlation in patients with dilated cardiomyopathy: An integrated evaluation by multivariate analysis

To correlate left ventricular function and histologic features in patients with dilated cardiomyopathy, precise indexes of hemodynamics and semiquantitative histologic data were combined for multivariate analysis. Right endomyocardial biopsy was performed at the time of cardiac catheterization. Five hemodynamic indexes were used for functional assessment: ejection fraction, ratio of end-systolic stress to volume index, end-diastolic stress, time constant (T) of left ventricular pressure fall, and end-systolic stress. Six histologic findings (disarray of myofibers, hypertrophy of myofibers, scarcity of myofibrils, nuclear changes of myofibers, vacuolization of myofibers and proliferation of collagen fibers) were graded from (-) to (4+). Each finding was assigned to category (-) or (+) according to the absence or presence of significant abnormality. Ordinary statistical analysis revealed that, although ejection fraction was lower in category (+) for proliferation of collagen fibers, ratio of end-systolic to volume index was reduced for category (+) of hypertrophy of myofibers. A significant correlation was present between hypertrophy of myofibers and proliferation of collagen fibers by Spearman rank correlation. When principal component analysis was applied to the hemodynamic data, two principal components could be extracted. Fishers discriminant analysis could clearly differentiate two categories (-) and (+) in the semiquantitative histologic finding of proliferation of collagen fibers. The analysis indicated that contractility was reduced with elevated afterload in that category (+). Thus, proliferation of collagen fibers may play a pivotal role in deteriorating contractility in patients with dilated cardiomyopathy.

Hypertrophic nonobstructive cardiomyopathy: A precise assessment of hemodynamic characteristics and clinical implications

A precise assessment of left ventricular function was performed in 20 patients with hypertrophic nonobstructive cardiomyopathy to elucidate the basic pathophysiology, and the data were compared with those in 22 normal subjects. Whereas end-diastolic pressure was high in those with cardiomyopathy, a more accurate index of preload, end-diastolic stress, did not differ from normal value. Afterload was about half the normal value. Both isovolumic indexes [peak positive dP/dt and (dP/dt)/DP40] and ejection phase indexes of contractility (ejection fraction) were in the normal range; however, the end-systolic stress volume ratio was significantly reduced (43% of the normal value). Although the left ventricular minute work index was in the normal range, the unit muscle performance (minute work/mass) was very low (49%). An abnormality of left ventricular relaxation was demonstrated by low peak negative dP/dt (56%) and prolonged time constant T (191%), and a stiff left ventricle was demonstrated by a high diastolic elastic stiffness constant (129%). These observations suggest that the contraction of a unit muscle is inappropriate to produce an adequate contraction of the whole ventricle, and that hypertrophy might be an adaptive process to maintain normal systolic function by increasing mass and reducing afterload.

Spectrum of restrictive cardiomyopathy: Report of the national survey in Japan

This report describes clinical profiles and echocardiographic, hemodynamic, and histologic findings in 26 cases of idiopathic RCM based on the diagnostic criteria of (1) heart failure resulting from a stiff left ventricle, (2) normal LV size and systolic function, (3) absence of LV hypertrophy, and (4) cause or association unknown. There were 14 male and 12 female patients ranging in age from 5 to 63 years. Ten patients died during the mean follow-up period of 145 months, and five died of heart failure after 10 years. Three had a family history of HCM. Thromboembolism was observed in eight. Echocardiograms showed normal LV wall thickness and contraction. Hemodynamic characteristics included elevated biventricular filling pressures and a pulmonary wedge pressure that was usually higher than the right atrial pressure. Equalization of biventricular filling pressures was seen, however, in almost all patients with severe tricuspid regurgitation (seven of eight). The square root sign was seen in 50% in RV diastolic pressure tracings and 28% in LV tracings. This sign was observed in patients with elevated filling pressures. Interstitial fibrosis (22 of 23), endocardial thickening (13 of 23), and myofibrillar hypertrophy (10 of 23) were common histologic findings. Severe myocardial fiber disarray consistent with HCM was seen in four patients.

Mechanisms of compensation and decompensation in dilated cardiomyopathy

Left ventricular (LV) function was evaluated in 32 patients with dilated cardiomyopathy (DC) who underwent cardiac catheterization during the past 6 years (group 4), and the results were compared with the data of 30 normal subjects (group 1). The patients were divided into mildly (group 2, 12 patients) and severely symptomatic subgroups (group 3, 20 patients). DC was characterized by dilated and poorly contracting left ventricle with increased muscle mass, reduced cardiac output and elevated systemic vascular resistance. LV volume was larger, ejection fraction was lower, and end-diastolic and end-systolic stresses were higher in group 3 than in groups 1 and 2. No significant differences were seen in LV muscle mass and wall thickness between groups 2 and 3. A significant inverse correlation was seen between ejection fraction and end-systolic stress in patients with DC (Y = -0.05x + 48.7, r = 0.57, p less than 0.01). The slope of the correlation line between end-systolic stress and volume in DC (Y = 1.20x + 135, r = 0.52, p less than 0.02) was less steep than that of normal subjects (Y = 3.68x + 40, r = 0.64, p less than 0.001). These observations indicate that the primary problem of DC is depressed contractility.(ABSTRACT TRUNCATED AT 250 WORDS)

Empiric determination of the transition from concentric hypertrophy to congestive heart failure in essential hypertension

OBJECTIVES Our aim was to determine whether there is a final transition from left ventricular hypertrophy to congestive heart failure in the late stage of essential hypertension. BACKGROUND A theoretic model using the concept of systolic transmural nonuniform wall thickening was applied to develop a concentric two-shell geometry allowing evaluation of the mechanics of circumferential midwall fibers. METHODS We evaluated pressure-volume data from 46 normal control subjects (control group) and 70 patients with hypertension: 33 without hypertrophy (hypertension only group), 14 with hypertrophy (hypertrophy group) and 23 with heart failure in addition to hypertrophy (heart failure group). RESULTS End-diastolic volume index was higher in the heart failure group than in the control group (p < 0.01). Although left ventricular wall thickness and mass index were increased in both the hypertrophy and the heart failure group, concentricity indexes as assessed by ratios of left ventricular wall thickness to dimension and mass index to end-diastolic volume index were maximal in the former. Although endocardial and standard midwall fractional shortening did not differ among the control, hypertension only and heart failure groups, that of the modified midwall by concentric two-shell geometry was decreased in the hypertrophy and the heart failure groups (p < 0.05). The Hotelling T2 test and Mahalanobis distance clearly discriminated the latter two groups with end-systolic stress and modified midwall fractional shortening relation. CONCLUSIONS A fitting segmented regression model predicted a progression to hypertrophy and identified a transition from hypertrophy to heart failure by a combination of modified midwall fractional shortening and concentricity indexes.

Force patterns of hypoxic myocardium applied to oxygenated muscle preparations: comparison with effects of regional ischemia on the contraction of non-ischemic myocardium

OBJECTIVE To examine the basis for local wall motion abnormalities commonly seen in patients with ischemic heart disease, computer-controlled isolated muscle studies were carried out. METHODS Force patterns of physiologically sequenced contractions (PSCs) from rat left ventricular muscle preparations under well-oxygenated conditions and during periods of hypoxia and reoxygenation were recorded and stored in a computer. Force patterns of hypoxic-reoxygenating and oxygenated myocardium were applied to oxygenated and hypoxic-reoxygenating myocardium, respectively. RESULTS Observed patterns of shortening and lengthening closely resemble those obtained from ischemic and non-ischemic myocardial segments using ultrasonic crystals in intact dog hearts during coronary occlusion and reperfusion, and are similar to findings reported in angiographic studies of humans with coronary artery disease. CONCLUSION The current study, demonstrating motions of oxygenated isolated muscle preparations which are similar to those in perfused segments of intact hearts with regional ischemia, supports the concept that the multiple motions of both ischemic and non-ischemic segments seen in regional myocardial disease can be explained by interactions of strongly and weakly contracting muscle during the physiologic cardiac cycle.

Assessment of Cardiac Function in Diseased Heart by Catheterization Study

The assessment of cardiac function by catheterization began with the application of Frank-Starling’s mechanism in clinical practice. Although numerous indexes of contractility have been proposed in the past 20 years, the most reliable methods currently used are: (1) Emax (the slope of end-systolic pressure volume line obtained by changing afterload) by means of pressure and volume recordings, (2) the force-length (end-systolic stress-end-systolic volume) relationship either in the two-dimensional framework or these ratio, and (3) the stress-shortening (afterload-shortening) relationship in the two-dimensional framework for the analysis of systolic function.