Left ventricular function from end-systolic stress-shortening relations in mitral valve prolapse

Left ventricular (LV) function was studied from end-systolic stress-shortening relations in 13 patients with mitral valve prolapse (MVP). Studies were made noninvasively using M-mode echocardiography with blood pressure measurements on the right arm from a Baumanometer cuff. Fifteen age and sex-matched normal subjects formed the control group. LV end-diastolic dimension was normal in MVP, while shortening fraction (p less than 0.05) and velocity of circumferential fiber shortening (mean Vcf) in the short axis of the ventricle were increased (p less than 0.05). Ventricular afterload, as measured by meridional end-systolic stress was reduced in MVP (p less than 0.01) but the slope of the stress-shortening curve was not different form normal. The decrease in end-systolic stress was related to the severity of prolapse (r = 0.63, p less than 0.05). The study implied that mid- or basal LV contractility was normal in MVP. The increased shortening fraction of the LV minor axis was in keeping with geometrical changes and a reduced ventricular afterload.     

Left ventricular contractility and contractile reserve in humans after cardiac transplantation

Limited data are available concerning left ventricular contractility and contractile reserve in the chronically denervated, transplanted human heart. This is primarily because of the inability of traditional tests of left ventricular performance to distinguish changes in contractility from alterations in ventricular loading conditions. In this study, load-independent end-systolic indexes of left ventricular contractility were measured by echocardiography and calibrated carotid pulse tracings in 10 patients who had undergone orthotopic cardiac transplant (age 48 +/- 4 years; interval from operation to study 1.2 +/- 0.8 years) and in 10 normal control subjects (age 25 +/- 4 years) matched for donor heart age (25 +/- 6 years). None of the transplant patients had evidence of rejection as determined by endomyocardial biopsy. Baseline left ventricular contractility was assessed over a wide range of afterload generated by infusion of methoxamine. Contractile reserve was measured as the response to an infusion of dobutamine plus methoxamine. Before afterload challenge, baseline left ventricular percent fractional shortening was higher for the transplant patients than for the control subjects (36.5 +/- 5.7% vs 32.1 +/- 2.1%; p less than .05). These differences occurred at a time that end-systolic wall stress (a measure of afterload) was significantly lower for the transplant patients (38 +/- 16 vs 50 +/- 9 g/cm2; p less than .05). When the left ventricular end-systolic pressure-dimension and stress-shortening relationships were determined for the transplant and control subjects, no differences in contractility or contractile reserve were noted. Thus the chronically denervated, transplanted, nonrejecting human left ventricle demonstrates normal contractile characteristics and reserve.     

Serial effects on left ventricular load and contractility during hemodialysis in patients with concentric hypertrophy

To separate the effects of hemodialysis on loading conditions from those on contractile state, six patients with concentric left ventricular hypertrophy and normal left ventricular function were studied before, during, and after hemodialysis. Two-dimensional-directed M-mode ultrasound was used to measure left ventricular dimensions and wall thickness; a sphygmomanometer and carotid pulse recording were used to determine peak and end-systolic blood pressure. From these data, meridional stress at end systole was calculated and stress-dimension and stress-shortening relations were derived; measurements of metabolic parameters were made simultaneously. Heart rate and systolic blood pressure were stable throughout dialysis. Reductions in left ventricular dimensions and increased shortening were evident by 30 minutes of dialysis and were largely complete by mid-dialysis. These changes coincided with a decrease in potassium and an increase in ionized calcium but not in pH, which changed only in the latter half of dialysis. When stress-dimension and stress-shortening relations were examined, both individual and group data for all coordinates before, during, and after dialysis demonstrated an excellent linear fit consistent with a single contractile state. We conclude that in stable patients with left ventricular hypertrophy, the reduction in heart size and improvement in shortening are due primarily to reductions in preload and afterload.     

Left ventricular end-systolic stress-shortening and stress-length relations in humans: Normal values and sensitivity to inotropic state

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 wall stress-velocity of fiber shortening relation: a load-independent index of myocardial contractility

The velocity of circumferential fiber shortening (Vcf) is an index of myocardial performance which, although sensitive to contractile state, has limited usefulness because of its dependence on left ventricular loading conditions. This study investigated the degree and velocity of left ventricular fiber shortening as it relates to wall stress in an attempt to develop an index of contractility that is independent of preload and heart rate while incorporating afterload. Studies were performed in 78 normal subjects using M-mode echocardiography, phonocardiography and indirect carotid pulse tracings under baseline conditions. In addition, studies were performed on 25 subjects during afterload augmentation with methoxamine, 8 subjects before and during afterload challenge after increased preload with dextran and 7 subjects with enhanced left ventricular contractility with dobutamine. The relation of end-systolic stress to the velocity of fiber shortening and to the rate-corrected velocity of shortening (corrected by normalization to an RR interval of 1) was inversely linear with correlation coefficients of -0.72 and -0.84, respectively. Alterations in afterload, preload or a combination of the two did not significantly affect the end-systolic wall stress/rate-corrected velocity of shortening relation, whereas during inotropic stimulation, the values were higher, with 94% of the data points above the normal range. Age did not appear to affect the range of normal values for this index. In contrast, the end-systolic wall stress/fractional shortening relation was not independent of preload status, responding in a manner similar to that seen with a positive inotropic intervention. Thus, the velocity of circumferential fiber shortening normalized for heart rate is inversely related to end-systolic wall stress in a linear fashion. Accurate quantitation can be performed by noninvasive means and a range of normal values determined. This index is a sensitive measure of contractile state that is independent of preload, normalized for heart rate and incorporates afterload. In contrast, the end-systolic wall stress/fractional shortening relation is dependent on end-diastolic fiber length in the range of physiologically relevant changes in preload.     

Noninvasive Assessment of Regional and Global Myocardial Contractility in Normal Control Subjects and in Patients with Dilated Cardiomyopathies

The aim of the present study was to develop a new noninvasive approach for the assessment of regional and global myocardial contractility without the need for pharmacological intervention to alter load. Thirty-four healthy adults and five adults with dilated cardiomyopathy (DCM) were studied. Patients with diabetes mellitus and hyperthyroidism were eliminated from the study. The remainder underwent echocardiography, sphygmomanometric blood pressure determination, and carotid pulse tracings. Left ventricular cross section in the parasternal long-axis four- and two-chamber views was divided into 20 segments. Associated measurements of end-systolic pressure and left ventricular ejection time enabled shortening, shortening rate, and ejection fraction / afterload relationships to be determined. A discriminant analysis showed that the ejection fraction / afterload relationship in patients with DCM differed substantially from that of control subjects and was the most sensitive in this regard. Endocardial shortening, mid-wall shortening, and ejection fraction / afterload relationships demonstrated linearity or nonlinearity for control subjects. This study thus permits the assessment of contractility in individual subjects without the need for drug interventions because load alteration stems from the variation of wall stress from base to apex in the left ventricle. More importantly, the approach may be applied to patients with segmental abnormalities of contractile function.     

Left ventricular mechanical load and contractile function in patients with chronic mitral regurgitation

BACKGROUND AND AIM of the study: Left ventricular adaptation to chronic volume overload results in dramatic changes in ventricular geometry and hemodynamics. These changes are reflected in alterations in mechanical load and, eventually, contractile function. METHODS: The study included 17 patients undergoing clinically driven invasive evaluation for mitral regurgitation (MR). Simultaneous catheter-tip manometry and M-mode echocardiography allowed for derivation of meridional and circumferential wall stress at end-diastole, end-systole, peak systole, and the average over the systolic ejection period. Assessment of contractile function was performed by analysis of: the overall group relationship between baseline end-systolic stress (ESS) and end-systolic dimension (ESD); subject-specific analysis of the relationship between ESS and ESD derived from pharmacologic load alteration; and subject- specific analysis of the relationship between left ventricular minor axis shortening and ESS. The acquired data were compared to data from 10 control subjects who were undergoing invasive evaluation and were free from cardiovascular disease. RESULTS: Compared to controls, patients with chronic MR (mean regurgitant fraction 57%) were characterized by significantly increased angiographic end-diastolic and end-systolic volumes, lower cardiac indices, and similar left ventricular ejection fractions. Patients with chronic MR were also characterized by increased preload (end-diastolic stress) and afterload (mean systolic stress). ESS was not consistently increased in these patients, despite the increased chamber size. The severity of clinical symptoms was associated with the magnitude of alteration in afterload (mean systolic stress). Using different methodologies, a substantial prevalence of depressed contractile function was identified in those patients with preserved ejection fraction. CONCLUSION: When compared to an age- and gender-matched controls, symptomatic patients with MR have similar left ventricular ejection performance in the setting of increased pre-load and after-load. Symptom severity was associated with increased afterload. The prevalence of contractile dysfunction in this setting was substantial.     

Long term doxorubicin cardiotoxicity in childhood: non-invasive evaluation of the contractile state and diastolic filling.

Cardiac performance was evaluated at least two years after doxorubicin treatment in childhood in 55 patients without overt congestive cardiomyopathy. None of the patients had received mediastinal irradiation. Computer-assisted analysis of digitised echocardiograms showed impaired rapid diastolic filling and an increased change of dimension between minimal cavity dimension and mitral valve opening. This impairment of diastolic function was related to the cumulative dose of doxorubicin. In contrast when angiotensin II was infused to increase the afterload the end systolic pressure-length and stress-shortening relation indicated normal left ventricular systolic function. But during baseline conditions the end systolic wall stress was significantly increased in patients in whom the cumulative dose of doxorubicin exceeded 360 mg/m2.     

Long term doxorubicin cardiotoxicity in childhood: non-invasive evaluation of the contractile state and diastolic filling

Cardiac performance was evaluated at least two years after doxorubicin treatment in childhood in 55 patients without overt congestive cardiomyopathy. None of the patients had received mediastinal irradiation. Computer-assisted analysis of digitised echocardiograms showed impaired rapid diastolic filling and an increased change of dimension between minimal cavity dimension and mitral valve opening. This impairment of diastolic function was related to the cumulative dose of doxorubicin. In contrast when angiotensin II was infused to increase the afterload the end systolic pressure-length and stress-shortening relation indicated normal left ventricular systolic function. But during baseline conditions the end systolic wall stress was significantly increased in patients in whom the cumulative dose of doxorubicin exceeded 360 mg/m2.     

Depressed myocardial contractility in mitral stenosis--an analysis by force-length and stress-shortening relationships

To determine whether low ejection fraction (EF) in mitral stenosis (MS) is the result of depressed contractility or is mediated by other factors, left ventricular (LV) function was analyzed by force-length and stress-shortening relationships. Thirty patients without heart disease served as normal controls (Group 1). Forty-three patients with MS were divided into 2 subgroups: Group 2 (n = 19) had EF within one standard deviation of the mean of Group 1, and Group 3 (n = 24) had EF below it. Normal EF (Group 2) was associated with low preload (end-diastolic stress) and low afterload (end-systolic stress), and preload and afterload were in the normal range in patients with low EF (Group 3). A significant negative correlation was observed in the whole group of patients with MS between EF and end-systolic stress (Y = -0.14X + 72.8, r = -0.61, p less than 0.001), and a positive correlation between end-systolic stress and volume (Y = 1.39X + 65.4, r = 0.45, p less than 0.01). These observations suggest that systolic shortening and end-systolic volume of the left ventricle are in part governed by afterload in this disease. It is concluded that low EF of MS is not mediated by reduced preload or inappropriately elevated afterload, and contractility of the ventricle is mildly depressed in MS.     

Assessment of dysfunction in aortic regurgitation by stress-shortening relationship

Some patients with aortic regurgitation develop irreversible left ventricular dysfunction. The purpose of this study was to noninvasively examine left ventricular function in patients with aortic regurgitation by determining the end-systolic stress-shortening relationship using M-mode echocardiography. Ten normal volunteers and 10 patients with chronic, isolated aortic regurgitation were studied at rest and following load and inotropic alteration by cold pressor testing. The baseline ejection phase indices of ejection fraction and percent fractional shortening did not distinguish between normals and patients with aortic regurgitation (74.6% +/- 2.8% versus 67.0% +/- 4.2%, P = NS and 37.6% +/- 2.4% versus 31.6% +/- 2.7%, P = NS, respectively.) End-systolic stress was significantly greater in patients with aortic regurgitation both at rest (107.8 +/- 11.6 dynes/cm2 X 10(-3) versus 68.4 +/- 4.8 dynes/cm2 X 10(-3), P less than 0.005) and after cold pressor intervention (122.8 +/- 13.0 dynes/cm2 X 10(-3) versus 80.1 +/- 4.0 dynes/cm2 X 10(-3), P less than 0.005). Normals showed increased fractional shortening in the presence of increasing end-systolic stress. Patients with aortic regurgitation showed decreased fractional shortening during increased stress. This response suggests either left ventricular dysfunction with increasing stress or decreased myocardial contractile reserve after cold pressor inotropic stimulation. End-systolic stress-percent fractional shortening relationship may be a sensitive indicator of early left ventricular dysfunction in patients with aortic regurgitation.     

Effects of simultaneous alterations in preload and afterload on measurements of left ventricular contractility in patients with dilated cardiomyopathy: comparisons of ejection phase, isovolumetric and end-systolic force-velocity indexes.

OBJECTIVES. The study was designed to critically evaluate the clinical utility of ejection phase and nonejection phase indexes of contractile state in patients with severe left ventricular dysfunction. BACKGROUND. Ejection phase indexes of left ventricular systolic performance are unable to differentiate contractility changes from alterations in loading conditions. Isovolumetric and end-systolic force-velocity indexes have been proposed as alternative measurements of contractile state that are load independent. METHODS. Seventeen patients with nonischemic dilated cardiomyopathy were studied during cardiac catheterization. High fidelity central aortic and left ventricular pressure measurements were made with simultaneous echocardiographic recordings of chamber minor- and long-axis dimensions and wall thickness. Data were acquired under control conditions, during nitroprusside infusion and with dopamine (6 micrograms/kg per min). RESULTS. Patients were classified into those without (group 1, n = 10) and those with (group 2, n = 7) a decrease in end-diastolic circumferential wall stress in response to dopamine. There were no baseline differences between the groups in functional class, left ventricular chamber geometry or cardiovascular hemodynamics. Ejection phase indexes were variably altered by changes in preload, afterload and heart rate, thereby complicating physiologic interpretation of data. Dopamine increased the commonly used isovolumetric index, maximal rate of rise in left ventricular pressure (dP/dtmax), by 64% for group 1 but by only 16% for group 2 (p less than 0.001), resulting in an underestimation of contractile state change in 41% of patients. In contrast, the left ventricular end-systolic circumferential wall stress-rate-corrected velocity of fiber shortening relation, which incorporates afterload, ventricular wall mass and heart rate in its analysis, was a sensitive contractility measurement that was preload independent and equally augmented by dopamine for both groups. CONCLUSIONS. Of the left ventricular contractility indexes evaluated, the end-systolic circumferential wall stress-rate-corrected velocity of fiber shortening relation was the most physiologically appropriate for assessing pharmacologically induced changes in inotropic state that were accompanied by complex alterations in loading conditions in patients with dilated cardiomyopathy.     

Comparison of noninvasive measures of contractility in dilated cardiomyopathy

Left ventricular performance is usually quantified by ejection phase indices such as ejection fraction, cardiac output, and fractional shortening. The load-dependence of these measures may result in inaccurate estimation of intrinsic myocardial contractility in states of chronic pressure or volume overload. End-systolic and stress-shortening relations have been proposed as measures of contractile state insofar as they are theoretically independent of preload and incorporate afterload. This article examines the behavior of these relations in response to changes in loading conditions and contractile state and reviews their application utilizing noninvasive methodology, particularly in the setting of dilated cardiomyopathy.     

Adverse cardiac effects of acute alcohol ingestion in young adults

Previous studies of the effects of acute alcohol ingestion in normal subjects have used measures of left ventricular performance that are altered by changes in preload and afterload and in contractile state. In studies involving nine healthy, young adults, we measured sensitive load-independent end-systolic indices of left ventricular contractility over a wide range of pressures generated by methoxamine infusion before and after oral alcohol administration. Echocardiography was used in conjunction with calibrated carotid pulse tracings. Alcohol ingestion resulted in a fall (p less than 0.01) in left ventricular end-diastolic dimension (a measure of preload), end-systolic wall stress (a measure of afterload), and systemic vascular resistance, while not changing the left ventricular shortening fraction. In contrast, the end-systolic pressure-dimension slope decreased (p less than 0.001) and the rate-corrected velocity of left ventricular fiber shortening at an end-systolic wall stress of 50 g/cm2 fell (p less than 0.001). Thus, when load-independent assessment of left ventricular contractility is done, acute alcohol ingestion has a myocardial depressant effect greater than previously suspected.     

Sustained inotropic effects of a new cardiotonic agent. OPC-8212 in patients with chronic heart failure

OPC-8212, a newly synthesized noncatecholamine, nonglycosidic, orally effective inotropic agent, has been shown to exert a potent cardiotonic action in acute administration to patients with heart failure. However, its long-term effect has not yet been established. Eight patients with dilated cardiomyopathy (New York Heart Association functional class II-III) were given a single dose of 60 mg of OPC-8212 daily for 4 to 8 weeks. OPC-8212 produced symptomatic improvement in four patients. Though there were no detectable changes in arterial pressure and left ventricular end-diastolic dimension, heart rate and end-systolic dimension significantly decreased after administration of OPC-8212. Baseline fractional shortening rose significantly and depression of shortening in response to acute pressor stress (afterload mismatch) was corrected after OPC-8212. The end-systolic pressure-dimension relation was shifted to the left with a steeper slope. These findings indicate that the inotropic state was substantially enhanced by the drug. No adverse effects were observed in any patient. Thus, the drug appears to hold promise for the chronic treatment of patients with moderate congestive heart failure who are essentially asymptomatic at rest, but develop severe impairment of cardiac function in a stressed state.     

Nonlinearity of the left ventricular end-systolic wall stress-velocity of fiber shortening relation in young pigs: A potential pitfall in its use as a single-beat index of contractility

Objectives. We sought to evaluate in the young heart the primary assumptions on which the current use of the mean “velocity of fiber shortening corrected for heart rate” as a noninvasive index of contractility are based.Background. End-systolic wall stress-velocity of fiber shortening relation has been applied as a single-beat, load-independent index of contractility in children. This use is based on poorly validated assumptions of linearity, parallel shifts with changing contractile state and inotropic sensitivity of the end-systolic wall stress-velocity of fiber shortening relation.Methods. In eight anesthetized young piglets, 5F micromanometric catheters were placed in the ascending aorta and balloon occlusion catheters in the descending aorta. End-systolic wall stress and velocity of fiber shortening were calculated from aortic pressure and M-mode echocardiography under six conditions: in three contractile states 1) baseline, 2) increased contractility during dobutamine infusion (10 μg/kg per min), and 3) decreased contractility after propranolol injection (1 mg/kg), each at two afterload states (normal and increased load by partial aortic occlusion).Results. Dobutamine increased and propranolol decreased afterloadd-matched velocity of fiber shortening corrected for heart rate significantly to 140% aid 77% of baseline, respectively. However, the slope of end-systolic wall stress-velocity of fiber shortening was (251% of baseline) during dobutamine infusion, which also significantly decreased wall stress, and was much less (27% of baseline) after propranolol injection, which increased wall stress.Conclusions. The velocity of fiber shortening corrected for heart rate did change predictably with changes in contractility and as such can be ued noninvasively in the temporal evaluation of individual patients undergoing therapeutic interventions or to define the natural history of a disease process. However, the relation on which it is based is not defined by parallel straight lines across contractile states, so that abnormal single measurements may reflect only the nonlinearity of the relation rather than in contractility. Thus, we recommend that the end-systolic wall stress-velocity of fiber shortening relation should not be used as a single-beat index of contractility.     

Clinical assessment of left ventricular systolic function by force-length and stress-shortening relationships

Left ventricular (LV) systolic function was assessed in patients with hypertensive heart disease (HHD, n = 30), hypertrophic cardiomyopathy (HCM, n = 27), dilated cardiomyopathy (DCM, n = 25), volume overload heart (VOH, n = 31) and normal subjects (NS, n = 32) in the two-dimensional framework of force-length (end-systolic stress-end-systolic volume index) and stress-shortening (mid-systolic stress-ejection fraction). Quadratic discriminant analysis revealed that the ellipses of confidence of HHD and normal subjects were in the same place with regard to both force-length and stress-shortening, while all other groups were well-discriminated. Three subgroups of patients, those with DCM with mild heart failure and those with VOH (with and without heart failure), were easily distinguishable on the basis of stress-shortening, but not on the basis of force-length measurements. It is concluded that LV systolic function and afterload are maintained within the normal range under pressure and volume overload until symptoms of heart failure appear via the mechanism of compensatory hypertrophy. Stress-shortening appears to be a more useful parameter than force-length for the analysis of LV systolic function in clinical practice.     

Load dependency of end-systolic pressure-volume relations in isolated, ejecting canine hearts

If characteristic muscle properties such as myocardial viscosity and/or shortening deactivation influence left ventricular ejection in the whole heart, the slope of the left ventricular end-systolic pressure-volume relation should be a function of both the contractile state and the loading mode. Thus, the load dependence of the end-systolic pressure-volume relation was examined using isolated, perfused canine hearts ejecting saline into a hydraulic loading system. The instantaneous left ventricular volume was measured with a plethysmograph. Under constant coronary flow and heart rate, two regression lines for end-systolic pressure-volume relations in two sets of loading modes were obtained: (1) Preload (left ventricular end-diastolic pressure; 4-15 mmHg) changes under fixed afterload impedance (preload changes); (2) Afterload impedance (peripheral resistance; 1.9-9.6 x 10(3) dyn sec cm-5) changes under fixed left ventricular end-diastolic volume (afterload changes). The slope of the end-systolic pressure-volume relation with afterload changes was steeper than that with preload changes (6.3 +/- 0.7 vs 4.8 +/- 0.6 mmHg/ml, p less than 0.05). Accordingly, under constant coronary flow, the slope of the end-systolic pressure-volume relation depended on loading conditions within the physiological range of afterload impedance and preload. This finding supports our hypothesis and implies that the slope change is of limited value as a contractile index in the ejecting heart.     

Effects of enhanced afterload (methoxamine) and contractile state (dobutamine) on the left ventricular late-systolic wall stress-dimension relation

Although the left ventricular (LV) end-systolic pressure-dimension relation is a load-independent, sensitive index of contractile state, its accurate determination requires afterload manipulation. The slope value of the late-systolic stress-dimension relation determined under resting conditions has been suggested as an alternative index of contractility that can be assessed without pharmacologie intervention. To evaluate this relation, 14 normal subjects were studied by M-mode echocardiography, phonocardlography and indirect carotid pulse tracings during infusion of methoxamine to increase afterload. Seven of these subjects were also studied after infusion of dobutamine to increase contractility. Continuous systolic stress-dimension trajectories were computer generated from digitized tracings. The late-systolic portions of these curves were found to be linear and the slope and intercept were determined. The slope value was sensitive to both afterload and contractility, and the magnitude of change in slope value was relatively greater during afterload enhancement than during inotropic stimulation. A strong correlation of slope value with peak systolic stress was found. Thus, the late-systolic stress-dimension relation is linear with a slope value which is dependent on both LV contractility and afterload. Like other ejection phase indexes, the usefulness of this index is limited by its inability to distinguish changes in contractile state from alterations in loading conditions.     

Physiologic mechanisms governing hemodynamic responses to positive inotropic therapy in patients with dilated cardiomyopathy

Clinical trials in patients with dilated cardiomyopathy (DCM) have shown a wide disparity in the hemodynamic responses to positive inotropic therapy. In addition, the response of the failing left ventricle to positive inotropic agents reflects the net interaction of multiple factors, including the magnitude of contractile abnormality and compensatory mechanisms. In the current study, left ventricular geometry, loading conditions, and contractile state were assessed in 13 patients with nonischemic DCM with the use of simultaneous high-fidelity pressure measurements and echocardiographic recordings. Comparisons were made with echocardiographic and calibrated carotid pulse data acquired in nine age-matched normal subjects. The patients with DCM were divided according to the left ventricular end-diastolic wall thickness-to-dimension ratio into groups with "appropriate" hypertrophy (i.e., less than or equal to 2 SDs from mean normal; n = 5; group 1) and "inadequate" hypertrophy (i.e., greater than 2 SDs from mean normal; n = 8; group 2). Age, New York Heart Association functional class, left ventricular wall mass index, and left ventricular end-diastolic pressure and dimension were similar for the DCM groups. Baseline left ventricular afterload (defined as circumferential end-systolic wall stress, sigma es) was 168% and 203% greater than normal in groups 1 and 2, respectively. The administration of the beta-adrenoceptor agonist dobutamine decreased left ventricular afterload by 12% in the normal subjects and by 10% in group 1 patients, while augmenting afterload by 5% in group 2 patients. The latter response occurred despite a 17% fall in systemic vascular resistance. Overall left ventricular performance, as assessed by the rate-corrected mean velocity of fiber shortening (Vcfc), was related to left ventricular afterload (i.e., sigma es). The resultant sigma es -Vcfc relationship, a sensitive measure of left ventricular contractility, was determined over a wide range of afterload conditions generated by methoxamine (normal subjects) or nitroprusside (DCM). Baseline left ventricular contractile state was 61% of normal for group 1 and 44% of normal for group 2. The contractile response to dobutamine infusion was 52% of normal for group 1 and only 22% of normal for group 2. Thus, positive inotropic therapy with dobutamine in patients with DCM is limited by (1) an attenuated contractile response and (2) elevated left ventricular afterload, which may be augmented further during its administration.(ABSTRACT TRUNCATED AT 250 WORDS)