Fiber Shortening Rate Research Articles

Preload dependence of fiber shortening rate in conscious dogs with left verntricular hypertrophy

Employing the new concept of systolic myocardial stiffness, this study addresses the questions of linearity of the end-systolic stress-strain relations in left ventricular hypertrophy and the preload dependence of fiber shortening rate. Pressure overload hypertrophy was induced in six puppies by banding the ascending aorta. Ultrasonic crystals were implanted for measurement of short axis and wall thickness in the six dogs with hypertrophy and in five control dogs. A pressure catheter was inserted through the apex for left ventricular pressure measurement. Load was altered by graded infusions of phenylephrine in the setting of betaadrenergic blockade.Linearity of the end-systolic stress-strain relations was observed in all cases, and preload-corrected shortening rate-afterload relations were derived from these stress-strain relations. Without preload correction, mid wall and endocardial shortening rate were depressed (p < 0.05 and p < 0.005, respectively) in the hypertrophy group. However, with preload correction at 35 g/cm2, there was no significant difference in shortening rate between the control and hypertrophy groups at afterloads of 150, 200 and 250 g/cm2. Endocardial shortening rate at a preload of 25 versus 35 g/cm2demonstrated a preload dependence in both the control (p < 0.04) and the hypertrophy group (p < 0.01). Mid wall shortening rate displayed a preload dependence only in the hypertrophy group (p < 0.05).It is concluded that end-systolic stress-strain relations are linear in control conditions and in hypertrophy, fiber shortening rate is preload-dependent and, thus, shortening rate-afterload relations currently used to assess myocardial contractility need to be modified to account for these preload effects.

Increased sympathoadrenomedullary activity and left ventricular hypertrophy in young patients with borderline hypertension

Echocardiographic dimensions and endocrinological examination were performed in 71 young patients with borderline hypertension (BHT) and 31 age-matched normotensive subjects (NT). Patients with BHT had significantly higher relative wall thickness (RWT) and left ventricular mass index than NT, although all BHT patients showed no asymmetric increase in the ratio of septal to posterior wall thickness. Moreover, these BHT patients demonstrated an increased cardiac output and an augmented mean circumferential fiber shortening rate (mean Vcf), suggesting left ventricular hyperfunction. Overall, there was a positive correlation between RWT and mean Vcf in BHT patients (r = 0.700, P less than 0.001), although there was no significant relationship between RWT and blood pressure. Furthermore, these BHT patients had higher plasma epinephrine (PE) and plasma renin activity compared to NT, suggesting the increased sympathoadrenomedullary activity in BHT. These BHT patients were divided into two groups with regards to PE levels; namely a high PE group (PE greater than or equal to 46 pg/ml) and a normal PE group (PE less than 46 pg/ml). The high PE group had a significantly higher mean Vcf and RWT than the normal PE group. These findings suggest that in young BHT patients left ventricular hypertrophy could be related to abnormalities of the sympathoadrenomedullary systems.

Systemic and regional hemodynamic and humoral effects of nitrendipine in essential hypertension.

The hemodynamic effects of 3 months of nitrendipine therapy were evaluated in 14 patients with mild to moderate essential hypertension. Nitrendipine reduced systolic and diastolic pressures from 145 +/- 4/95 +/- 3 to 119 +/- 3/78 +/- 2 mm Hg, respectively, (p less than 0.001) through a fall in total peripheral resistance index (46 +/- 4 to 34 +/- 3 units/m2, p less than 0.001) without associated reflex cardiac stimulation. This antihypertensive effect was related directly to the height of pretreatment arterial pressure (r = -0.67, p = 0.006) but not to age or pretreatment plasma renin activity. Renal and forearm blood flow increased, vascular resistance decreased, and glomerular filtration rate remained stable. In addition, nitrendipine reduced left ventricular mass index (133 +/- 7 to 116 +/- 5 g/m2, p = 0.003) and wall thickness, changes that were accompanied by improvement in diastolic as well as systolic (ejection fraction and fractional fiber shortening rate) left ventricular functions. Intravascular volume did not expand with reduction in pressure. This study provides new information concerning the long-term hemodynamic effects and associated echocardiographic changes with nitrendipine. It also provides the first regional hemodynamic data in essential hypertensive patients detailing forearm and splanchnic changes and renal blood flow increase during prolonged treatment.

Immediate and short-term cardiovascular effects of a new converting enzyme inhibitor (lisinopril) in essential hypertension

The immediate and short-term effects of lisinopril, a new converting enzyme inhibitor, on systemic and regional hemodynamics, cardiac structure and function and humoral indexes were evaluated in 10 patients with mild to moderate essential hypertension. A single oral dose of 5 mg lisinopril reduced mean arterial pressure from 118 to 104 mm Hg (p < 0.01) and significantly increased (p < 0.05) all load-dependent indexes of ventricular function (i.e., ejection fraction, velocity of circumferential fiber shortening and fractional fiber shortening rate). After 10 to 12 weeks of once-daily administration of lisinopril, mean arterial pressure remained reduced over a full 24-hour period (p < 0.01), and was mediated through arteriolar dilation as expressed by the dose correlation (r = 0.93, p < 0.01) between changes in mean arterial pressure and changes in total peripheral resistance. Cardiac index decreased from 3.06 to 2.68 liters/min/m 2 (p < 0.01) without correlation to the decrease in arterial pressure (r = 0.06). Despite this reduction in cardiac index, renal blood flow increased from 861 to 1,053 ml/min (p < 0.05) and renal vascular resistance decreased from 14 to 9 units (p < 0.01). Left ventricular mass index decreased from 124 to 109 g/m 2 (p < 0.05), and left ventricular function remained unchanged. Thus, the decrease in arterial pressure produced by lisinopril was associated with improved renal hemodynamics and reduced left ventricular mass.

Effects of acute changes in load and inotropic state on the exponential rate of fiber shortening and other indices of myocardial contractility in the anesthetized intact dog.

The effects of an acute increase in preload, afterload, and inotropic state on several indices of left ventricular contractility were studied in 20 anesthetized intact dogs. The behaviour of the exponential rate of fiber shortening (ERFS), a newly described index, which is based on the instantaneous fiber length--time relationship through ejection, was compared with other classical ejection and isovolumic indices of left ventricular contractility. Acute volume overload by dextran 40 infusion produced a significant increase in preload as reflected by a 103% (p less than 0.01) increase in left ventricular end-diastolic pressure and a 121% (p less than 0.001) increase in end-diastolic circumferential wall stress. There was also a smaller but significant increase (p less than 0.05) of heart rate (30%) and of peak systolic circumferential wall stress (24%). None of the left ventricular contractility indices showed any significant change. Acute pressure overload, produced mechanically by an aortic balloon, increased the afterload significantly as reflected by a 33% (p less than 0.05) rise of end-systolic circumferential wall stress and a 43% (p less than 0.001) increase in systemic resistance. Stroke volume decreased significantly by 23% (p less than 0.05). All ejection indices, including ERFS, were significantly diminished by 30-37%; all isovolumic indices showed no significant changes. Positive inotropic intervention was induced by dopamine infusion, which caused a significant 28% (p less than 0.05) increase in cardiac output. End-diastolic and end-systolic circumferential wall stress were significantly diminished. All indices of left ventricular contractility increased significantly and ERFS showed the quantitatively greatest change.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanical and inotropic reserve in conscious dogs with left ventricular hypertrophy.

We studied the left ventricular (LV) responses to infusions of norepinephrine and prenalterol, a specific beta 1-adrenergic receptor agonist, in conscious, chronically instrumented adult dogs with severe LV hypertrophy. The goal of this study was to determine the extent of compensation induced by LV hypertrophy in an animal model in which the pressure overload was gradually increased, as occurs in human pathological states. One to 2 yr after banding the ascending aorta of puppies, six dogs with severe LV hypertrophy (LV free-wall weight-to-body weight ratio 7.0 +/- 0.4 g/kg), and nine sham-operated littermates (LV free-wall weight-to-body weight ratio 4.0 +/- 0.2 g/kg) were studied. The dogs were instrumented with ultrasonic dimension crystals (to measure LV short-axis diameter and wall thickness), miniature LV pressure transducers, and LV and aortic catheters. In the control dogs norepinephrine (0.4 micrograms X kg-1 X min-1) increased LV systolic/diastolic pressure from 121 +/- 2/9 +/- 1 to 177 +/- 9/20 +/- 2 mmHg, mean arterial pressure from 97 +/- 2 to 143 +/- 9 mmHg, LV dP/dt from 3,363 +/- 123 to 5,174 +/- 343 mmHg/s, and mean systolic wall stress from 194 +/- 14 to 299 +/- 22 g/cm2, while mean velocity of circumferential fiber shortening (Vcf), (dD/dt/D)max, and heart rate did not change from base line. In dogs with LV hypertrophy norepinephrine increased LV pressure from 224 +/- 16/11 +/- 1 to 305 +/- 22/19 +/- 1 mmHg, mean arterial pressure from 90 +/- 2 to 132 +/- 4 mmHg, LV dP/dt from 3,246 +/- 156 to 5,619 +/- 345 mmHg/s, and mean systolic wall stress from 224 +/- 11 to 307 +/- 24 g/cm2.(ABSTRACT TRUNCATED AT 250 WORDS)

Nuclear medical determination of the left ventricular normalized velocity of contraction.

The normalized velocity of contraction (vn) and its maximal value (vnmax) are related to the normalized flow acceleration within the ventricle, to the subendocardial fiber shortening rate, strain rate, and stress. This paper presents the method of the nuclear medical determination of vn and analyzes a typical volume-velocity-time curve. In 60 patients with different stages of coronary artery disease, global vnmax showed good correlation with the minimal ventricular transit time (y = 6.18-1.36 x, P less than 0.001) and global ejection fraction (y = -(2.5 + 356/(x - 104], P less than 0.001). The segmental vnmax showed a highly significant correlation with the regional ejection fraction (y = -(2.5 + 371/(x - 104], P less than 0.001). The mathematical relationships of vn with the mechanical properties of the ventricular wall are described in the appendix.

Relationship between ejection phase indices of performance and myocardial functions during the development of pressure overload hypertrophy

The present study examines the temporal relationship between performance of the hypertrophied nonfailing rabbit heart and the contractility of muscles isolated from these same hearts. Ejection phase indices of ventricular function were determined cineradiographically during the development of hypertrophy. Isolated papillary muscle function was examined an average of 8.6 (early), 40.1 (middle), and 97.5 (late) days after banding of the pulmonary artery. Active tension development at L max (F) was depressed by 65% in the muscles examined early and by 43% in the middle group. By the late group, F was comparable to control levels. Early depression and a return to normal function were also observed for peak dF dt and velocity of shortening at L max. Time to peak tension was unchanged at 8.6 days and increased at the middle and late time points. Both percentage of shortening and mean normalized velocity of shortening, determined cineradiographically in the intact heart, were depressed immediately following surgery, gradually returned toward “normal function” by the third week, and plateaued at a stable level of performance, which was maintained thereafter. The similarity of in vivo function of the hypertrophied and control hearts, despite the profound differences observed in the myograph, indicate that “ejection phase indices,” such as fiber shortening rate, are poor indicators of intrinsic function during the development of hypertrophy. Moreover, these results demonstrate the extent to which intrinsic functional deficits may be overcome in the whole heart and suggest the presence of mechanisms such as enhanced sympathetic nervous activity, which contribute to the maintenance of this normal basal ventricular function.

Left ventricular performance in patients with coexistent mitral stenosis and aortic insufficiency

Isolated mitral stenosis and isolated aortic insufficiency impose unique and opposite loading conditions on the left ventricle. To assess these combined effects, hemodynamic and angiographic factors were compared among normal subjects and patients with isolated mitral stenosis, isolated aortic insufficiency or combined mitral stenosis and aortic insufficiency. Left ventricular end-diastolic volume index was lower in patients with combined lesions and severe or moderate aortic insufficiency than in patients with isolated severe or moderate aortic insufficiency (138 +/- 19 versus 206 +/- 20 cc/m2 and 87 +/- 5 versus 145 +/- 22 cc/m2, respectively) (p less than 0.05 for both). Left ventricular end-diastolic and end-systolic volume indexes were normal in two-thirds of patients with combined lesions and moderate or severe aortic insufficiency, whereas these indexes were high in all but one patient with isolated moderate or severe aortic insufficiency. Among patients with moderate or severe aortic insufficiency, 8 of 14 with isolated insufficiency had a reduced ejection fraction or circumferential fiber shortening rate compared with 5 of the 9 patients with combined lesions. Among patients with isolated aortic insufficiency, left ventricular end-systolic wall stress and end-diastolic and end-systolic volume indexes were higher (p less than 0.05) in those with reduced ejection performance than in those with normal ejection performance. These variables did not differ between patients with reduced or normal ejection performance in the group with combined lesions. The contractile index (ratio of end-systolic wall stress to end-systolic volume index) was significantly depressed in patients with severe aortic insufficiency in the groups with isolated aortic insufficiency or combined lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Intra-aortic Balloon Counterpulsation in an Experimental Model of Myocardial Infarction

The efficacy of intra-aortic balloon counterpulsation for heart failure during acute myocardial infarction has been controversial, and early intervention has been suggested as crucial. We have examined this type of therapy in the intact anesthetized dog during complete occlusion of the proximal left anterior descending coronary artery with a balloon-tipped catheter. Group 1 (n = 8) represented untreated animals undergoing four hours of ischemia. Group 2 (n = 7) consisted of animals undergoing counterpulsation with an intra-aortic balloon after 15 minutes of ischemia. Initially, stroke volume and the mean rate of left ventricular fiber shortening were similarly diminished in both groups, while filling pressure rose proportionately. After four hours, the mean rate of fiber shortening, stroke volume, and left ventricular filling pressure rose to a greater extent in untreated compared to treated animals (p less than 0.01). The degree of swelling in ischemic tissue and the number of sites with ST-segment elevation and their sums were comparable in the two groups. Thus, intra-aortic counterpulsation applied early in the course of ischemia can improve global left ventricular dysfunction without affecting the extent of myocardial injury.

Acute effects of hemodialysis on echographic-determined cardiac performance: Improved contractility resulting from serum increased calcium with reduced potassium despite hypovolemic-reduced cardiac output

The hemodialysis session leads to reduction in circulating blood volume (TBV) and arterial pressure (BP) plus correction of electrolyte imbalance. The effect of these alterations on cardiac performance was evaluated in 18 patients with end-stage renal disease. Hemodialysis for 5 hours led to significant reduction ( p < 0.001) in weight, TBV, and BP. Neither ejection fraction nor percentage fiber shortening was altered, whereas mean velocity of circumferential fiber shortening (mean V CF) and mean systolic ejection rate (MSER) were both significantly increased (1.17 ± 0.20 to 1.38 ± 0.28 circ/sec and 2.38 ± 0.27 to 2.80 ± 0.40 EDV/sec, respectively; p < 0.001 for each). Since both venous return and systolic BP were decreased, increase in velocity of ventricular contraction implies enhancement of cardiac performance beyond what would be expected from alterations in ventricular filling and resistance to ejection. This enhancement is possibly related to concomitant reduction in serum potassium ( p < 0.001) and increase in serum calcium ( p < 0.005) achieved by hemodialysis.

A method for measuring mean circumferential fiber shortening rate from gated blood pool scans.

Ejection fraction and ejection rate are easily obtained from gated cardiac images, but no method is available for calculating mean circumferential fiber shortening rate. We assumed that the cube root of left ventricular end-diastolic volume or counts is proportional to the minor axis of the left ventricle at end-diastole or end-systole. Mean circumferential fiber shortening rate is then equal to the [cube root of the end-diastolic volume (count) minus cube root of end-systolic volume (count)] divided by [cube root of end-diastolic volume (count) multiplied by the ejection time]. In 250 contrast ventriculograms, the standard mean circumferential fiber shortening rate (MCFSR) and that derived by the cube root method correlated well (r = 0.94). The mean value of MCFSR (0.85 +/- 0.35) was greater than the cube root value (0.75 +/- 0.35) (P less than 0.001). The regression equation was y = 0.86x + 0.02. Similar correlations were obtained from gated radionuclide images using a semiautomated program (r = 0.93) in 24 subjects or completely automated program (r = 0.85) in 28 patients. The regression equation between MCFSR and that derived from the cube root of counts for the semiautomated program was y = 0.82x + 0.04 and for the automated program was y = 0.84x + 0.004. Similar correlations, slopes, and intercepts were seen using circumferential fractional shortening for angiographic data when correlated with both the semiautomated and automated gated blood pool scan programs. These data indicate that MCFSR and circumferential fractional shortening may be obtained from gated blood pool images using cube root estimates of end-diastolic and end-systolic radii with a high degree of correlation with the standard contrast ventriculographic technique.

Patterns of Left Ventricular Adaptation in Borderline and Mild Essential Hypertension: Echocardiographic Findings

To assess patterns of left ventricular adaptation, 38 patients with borderline and 38 with sustained mild essential hypertension, all lacking electrocardiographic and roentgenographic criteria for left ventricular hypertrophy, were compared using systemic hemodynamic values and M-mode echocardiograms. All patients had normal left ventricular function and measurements of wall thickness. Those with borderline hypertension showed no asymmetric increase in the ratio of septal to posterior wall thickness. The ratio of the left ventricular radius to wall thickness remained normal in both groups, indicating no disproportionate hypertrophy or dilatation of chambers during the phase of normal left ventricular function. Neither finding substantiates asymmetric septal hypertrophy in early hypertension. Those with mild essential hypertension demonstrated an augmented mean circumferential fiber shortening rate compared to those with borderline hypertension (P < 0.005), suggesting an early stage of left ventricular hyperfunction in the development and elaboration of hypertensive heart disease.

Exercise response of the denervated heart in long-term cardiac transplant recipients

The left ventricular response to volume loading and graded supine bicycle exercise (3 minutes at 15, 45 and 90 watts) was assessed in nine long-term (more than 1 year) cardiac transplant recipients. Computer-aided fluoroscopy of radiopaque myocardial markers implanted in the left ventricle at the time of surgery was used to measure left ventricular dynamics. Pulmonary arterial and left ventricular pressures were monitored. Plasma norepinephrine was measured by radio-enzymatic assay at each level of exercise. Early in exercise mean end-diastolic volume (six patients) increased from a resting value of 125 to 138 ml (p < 0.02) at the 45 watt level, then decreased to 121 ml at the 90 watt level. End-systolic volume decreased from 68 to 63 ml and then to 49 ml (p < 0.01) at corresponding exercise levels. Stroke volume increased from 57 to 76 ml (p < 0.01) then declined slightly to 71 ml (p < 0.02 for increase relative to resting value). Heart rate increased gradually from 102 to 116 beats/min (p < 0.05) and then rapidly to 140 beats/min (p < 0.01). Thus cardiac output increased significantly at all levels of exercise from 5.7 liters/min at rest, to 6.5 at 15 watts (p < 0.02), to 8.7 at 45 watts (p < 0.01) and to 10.0 liters/min at 90 watts (p < 0.01). Plasma norepinephrine increased slowly from 233 pcg/ml at rest to 460 at 45 watts, then rapidly to 1,970 pcg/ml at 90 watts. Increases in velocity of circumferential fiber shortening (Vcf) and heart rate were correlated with increasing norepinephrine concentrations (r = 0.92 for Vcf; r = 0.79 for heart rate). A functioning Frank-Starling mechanism was demonstrated in seven patients with volume loading by leg elevation resulting in significant increases in end-diastolic volume, stroke volume and cardiac output in the absence of any increase in heart rate. Thus, cardiac output increases in the transplanted heart were brought about early in exercise by augmented preload and the Frank-Starling mechanism, and later in exercise by chronotropic and inotropic influences of increased circulating catecholamines.

Modification of left ventricular diastolic behavior by isometric handgrip exercise.

SUMMARY To clarify the basis of increased left ventricular (LV) end-diastolic pressure associated with isometric exercise, LV diastolic and systolic function were examined in 25 patients during sustained handgrip. During handgrip, average systemic arterial mean pressure increased by 20 mm Hg, and LV systolic pressure rose by 31 mm Hg, though in five patients, no increase in mean arterial or LV systolic pressure occurred. LV end-diastolic pressure rose by 10 mm Hg, right ventricular systolic and end-diastolic pressures increased by 10 and 5 mm Hg, respectively (p < 0.01 for all pressures). LV end-systolic volume rose by 23%, but end-diastolic volume was unchanged. Reduction of ejection fraction by 13% and mean circumferential fiber shortening rate by 7% indicated further impairment of LV function, though ejection fraction was unchanged or augmented in 14 patients. In all patients, diastolic pressure-volume curves were displaced upward and to the right, without change in the rate constant of the exponentially fit pressure-volume or normalized pressure-volume elasticity relations, operational end-diastolic stiffness or the rate of isovolumic relaxation. Thus, upward transposition of diastolic pressure-volume relations during handgrip does not depend on changes in LV chamber elastic properties or relaxation, LV systolic function or coronary perfusion pressure, but appears, by inference, to be caused by the concomitantly increased right ventricular pressures, perhaps mediated in part by pericardial constraint in association with right ventricular distension.

Quantitative ultrastructure of the myocardium in chronic aortic valve disease.

Light and electron microscopic morphometry was carried out in tissue samples which were obtained from the left ventricular free wall in 29 patients with chronic aortic valve disease during open-heart surgery. 6 patients had aortic stenosis, 9 had aortic insufficiency and 14 had a mixed aortic valve lesion. Hemodynamics were studied before operation. Patients with mixed aortic valve disease had a higher left ventricular mass, a lower ejection fraction and mean circumferential fiber shortening rate than patients with aortic stenosis. Peak systolic wall stress was comparable between groups. The intracellular content of contractile material was lower and the sarcoplasmic volume was higher in mixed aortic valve disease than in aortic stenosis. Mitochondrial volume and interstitial fibrosis were not different between groups. Patients with aortic insufficiency showed no significant difference of parameters as compared to both other groups. We conclude that an intracellular deficiency of myofibrils causes lack of contractility in advanced hypertrophy due to mixed aortic valve disease.

Left Ventricular Function and Compliance in Swine during Halothane Anesthesia

Halothane (0.05--1.7 vol per cent end-tidal) in nitrous oxide (N2O), 60 per cent: oxygen (O2), 40 per cent was administered to nonmedicated, closed-chest pigs. Ventricular function was analyzed from cardiac output (thermodilution) and left ventricular (LV) pressure indices. Ventricular volumes and compliance were estimated from single and biplane LV angiography. In separate experiments, the effects of N2O, time, and the angiographic dye injections were shown to be minimal. Halothane caused dose-dependent decreases in aortic blood pressure, cardiac output, peak first derivative of left ventricular pressure (LV dP/dt), the in-vivo maximum velocity of fiber shortening (Vmax), and ejection fraction; non-dose-dependent decreases in heart rate and circumferential fiber shortening rate. Although a pronounced dose-related negative inotropic effect of halothane in the pig heart was demonstrated, there was no definite effect on ventricular pressure-volume relationships (compliance). If there was any such effect of halothane, it was obscured by the cardiac depression produced.

Recovery from myocardial failure after aortic valve replacement

Left ventricular hypertrophy and function were studied in 27 consecutive patients with chronic aortic valve disease before and 6.4 +/- 2.2 (S.D.) months after aortic valve replacement with Björk-Shiley prostheses. Four patients were excluded because of postoperative paravalvular regurgitation. Five patients had aortic stenosis (AS), seven patients AS plus insufficiency (AS-AI), and 11 patients aortic insufficiency (AI). Left ventricular muscle mass (LVMI), ejection fraction (EF), mean circumferential fiber shortening rate (VCF), mean normalized systolic ejection rate (MNSER), and peak systolic wall stress (PSWS) were determined angiographically. LVMI fell significantly after corrective surgery, whereas EF, VCF, and MNSER increased. PSWS decreased after the operation. Comparison of stress ventriculograms before and after surgery in six patients with predominant AS (isoproterenol infusion, 0.3 microgram per kilogram of body weight per minute) showed an increase of EF, VCF, and MNSER and a decrease of PSWS. We conclude that hypertrophy in chronic aortic valve disease regresses after aortic valve replacement, and thereby depressed cardiac function and reserve recover.

Cardiac reserve during isoproterenol stress in patients with aortic valve disease before and after corrective surgery

The relations between left ventricular (LV) hypertrophy as estimated by LV mass and LV function and between LV hypertrophy and cardiac reserve were evaluated in 26 patients with aortic valve disease and in nine normal patients who served as controls. Ejection fraction (EF) and mean circumferential fiber shortening rate (VCF) served as indices of LV function. Reserve force of the left ventricle was tested by ventriculography during infusion of 0.3 μg/Kg. body weight/min. isoproterenol. EF and VCF were not significantly different (p > 0.05) either at rest or during isoproterenol infusion if patients with aortic stenosis were compared to patients with aortic regurgitation having comparable LV masses. Therefore we correlated the EF and VCF to the LV mass of all patients irrespective of the type of aortic valve lesion. Poor but significant inverse correlations were found at rest between LV mass and EF (r = 0.62) and between LV mass and VCF (r = 0.57). These correlations improved considerably during isoproterenol: r = 0.84 for EF and r = 0.74 for VCF. LV function was evaluated in another six patients with aortic valve disease before and nine months after successful aortic valve replacement by Björk-Shiley prostheses. LV mass before surgery was 3.6 times control and decreased after surgery to 1.7 times control (p < 0.01) which is still significantly elevated (p < 0.05). EF and VCF which were depressed before surgery (p < 0.05, p < 0.001) normalized after surgery (p . 0.05) but were reduced during isoproterenol infusion if compared to controls (p < 0.05). Thus, stress ventriculography in aortic valve disease could demonstrate a linear decrease of cardiac reserve with increasing severity of hypertrophy when resting function was normal or depressed only slightly. Regression of hypertrophy was incomplete 9 months after correction of overload and LV function, which was depressed before surgery, normalized at rest but was impaired during stress suggesting that cardiac reserve was not fully restored.

Evidence for cardiomyopathy in familial diabetes mellitus.

Recent epidemiologic studies have suggested that cardiac disease in common in diabetics and may often have a noncoronary basis. To examine the status of the left ventricle, 17 adult-onset diabetics of familial type without hypertension or obesity underwent hemodynamic study and were compared to 9 controls of similar age. Of the 17, 12 subjects had no significant occlusive lesions by coronary angiography. From this group eight without heart failure had a modest, but significant, elevation of left ventricular end-diastolic pressure. End-diastolic and stroke volumes were reduced, but ejection fraction and mean rate of fiber shortening were within normal limits. The left ventricular end-diastolic pressure/volume ratio was significantly higher than controls. Afterload increments effected a significant increase of filling pressure compared to normals without a stroke volume response, consistent with a preclinical cardiomyopathy. Four patients with prior heart failure had similar but more extensive abnormalities. None had local dyskinesia by angiography, and lactate production was not observed during pacing-induced tachycardia. Left ventricular biopsy in two patients without ventricular decompensation showed interstitial collagen deposition with relatively normal muscle cells. These findings suggest a myopathic process without ischemia. Postmortem studies were performed in 11 uncomplicated diabetics. Nine were without significant obstructive disease of the proximal coronary arteries, and the majority succumbed with cardiac failure. On left ventricular sections, none had evident luminal narrowing of the intramural vessels. All nine exhibited periodic acid-Schiff-positive material in the interstitium. Collagen accumulation was present in perivascular loci, between myofibers, or as replacement fibrosis. Multiple samples of left ventricle and septum revealed enhanced triglyceride and cholesterol concentrations, as compared to controls. Thus, a diffuse extravascular abnormality may be a basis for cardiomyopathic features in diabetes.