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A beneficial effect of verapamil on left ventricular relaxation has been reported in patients with hypertrophic cardiomyopathy. The effect of 0.1 mg/kg intravenous verapamil on left ventricular relaxation and diastolic mechanics was studied in 10 patients with hypertrophic cardiomyopathy and 13 patients with aortic stenosis. M mode echocardiograms and left ventricular high-fidelity pressure measurements were obtained simultaneously in patients at rest and 10 to 15 min after verapamil. The time constant of left ventricular pressure decay (T; in msec) and the pressure intercept (PB; in mm Hg) were calculated from left ventricular pressure and negative dP/dt during isovolumetric relaxation with the use of a linear regression analysis. Left ventricular early and mean diastolic filling rates as well as diastolic pressure-diameter relationships before and after verapamil were determined from simultaneous echocardiographic and pressure measurements. After verapamil heart rate, left ventricular peak systolic pressure, and maximum and minimum dP/dt remained unchanged in both groups. Left ventricular end-diastolic pressure increased significantly from 15 to 17 mm Hg (p less than .02) in patients with aortic stenosis but did not change in those with hypertrophic cardiomyopathy. However, the time constant T decreased significantly from 79 to 60 msec (p less than .001) in patients with hypertrophic cardiomyopathy but increased significantly from 53 to 68 msec (p less than .025) in those with aortic stenosis. Parallel to the decrease in time constant, early (5.3 vs 7.3 cm/sec, p less than .05) and mean (3.0 vs 4.3 cm/sec, p less than .06) diastolic lengthening rate increased in patients with hypertrophic cardiomyopathy after verapamil. In contrast, early (7.7 vs 7.6 cm/sec, p = NS) and mean (4.3 vs 4.2 cm/sec, p = NS) diastolic lengthening rate remained unchanged in patients with aortic stenosis. The diastolic pressure-diameter relationship did not change in either group after verapamil. Cycle efficiency of the left ventricular pressure-diameter loop was significantly decreased in patients with hypertrophic cardiomyopathy when compared with that in those with aortic stenosis (71% vs 80%; p less than .01), but improved significantly from 71% to 77% (p less than .02) in patients with hypertrophic cardiomyopathy and remained unchanged in those with aortic stenosis (80% vs 80%) after verapamil. We conclude that verapamil improves left ventricular relaxation in patients with hypertrophic cardiomyopathy but delays relaxation in those with aortic stenosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Left ventricular volumes were determined by means of digital subtraction cineangiocardiography (DSA) which was performed in the right anterior oblique projection after contrast agent injection into the superior vena cava. Monoplane end-diastolic (EDV), end-systolic volumes (ESV), and ejection fraction (EF) were calculated using the 'area-length' method and were compared with the same parameters obtained by conventional left ventricular cineangiocardiography. A first group of 20 patients was studied at rest and a second group of 10 patients during bicycle exercise at a work load of 64 watts during 2 min, by DSA and conventional cineangiocardiography. Three different subtraction modes were evaluated: (1) mask mode subtraction (MMS), (2) time interval difference (TID) method and (3) a combination of MMS and TID called MMS + TID method. With the MMS method good correlations were obtained for EDV, ESV and EF at rest (r greater than 0.91) and during exercise (r greater than 0.91). The TID method showed only moderate correlations for patients at rest (r greater than 0.86) and during exercise (r greater than 0.79). Similar results as with MMS were achieved by the combined method (MMS + TID) at rest (r greater than 0.91) and during exercise (r greater than 0.91). Interobserver variability indicated a high reproducibility for all methods except for TID during exercise. It is concluded that DSA is an accurate technique for left ventricular volume determination not only at rest but also during exercise. The best results are obtained with MMS or MMS + TID methods, while left ventricular contour detection is easier and more convenient with MMS + TID.

Left ventricular contraction, relaxation and diastolic mechanics were investigated before and after intravenous administration of 15 mg of diltiazem in 15 patients with coronary artery disease. High fidelity left ventricular pressure measurements were performed in all 15 patients, with simultaneous biplane cineangiography in 13. The time constant of left ventricular isovolumic pressure decay was calculated from the linear relation of left ventricular pressure and its rate of change with time (negative dP/dt). Frame by frame volume analysis through one cardiac cycle was completed to construct volume-time and pressure-volume curves before and after the administration of diltiazem. After diltiazem, left ventricular peak systolic pressure decreased from 124 to 113 mm Hg (p less than 0.001), while left ventricular end-diastolic pressure and heart rate were not altered. Maximal positive dP/dt also remained unchanged. End-diastolic volume was not changed after diltiazem, but end-systolic volume increased from 48 to 52 ml/m2 (p less than 0.025); as a result, ejection fraction decreased slightly from 57 to 55% (p less than 0.025). The time constant of left ventricular pressure decay and maximal negative dP/dt decreased from 58 to 54 ms (p less than 0.025) and from -1,404 to -1,321 mm Hg/s (p less than 0.025), respectively. Peak early diastolic filling rate increased from 621 to 752 ml/s (p less than 0.01) in association with an increase in filling volume during the first half of diastole from 60 to 68% (p less than 0.005). No consistent displacement of the diastolic pressure-volume curve was observed after diltiazem.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulsus alternans has been observed in patients with severe aortic valve disease and hypertensive or coronary artery disease, and has been considered a sign of severe ventricular dysfunction. Between 1974 and 1982 we observed 12 patients with severe aortic valve disease (10 aortic stenosis, 1 aortic insufficiency and 1 with a combination of both valve lesions) and pulsus alternans (group 1). Twelve patients (9 aortic stenosis, 1 aortic insufficiency and 2 with a combination of both valve lesions), but without pulsus alternans, served as controls (group 2). All 24 patients underwent surgery and were followed up for 36 months (group 1) and 50 months (group 2) respectively. One patient from group 2 died after surgery from cerebral hemorrhage. Mean age was similar in both groups (56 vs. 55 years). Preoperatively, the patients in group 1 were in a higher NYHA class (2.7 vs. 2.3; p less than 0.05) and had a higher heart rate (90 vs. 71 beats/min; p less than 0.005) than patients in group 2. M-mode echocardiography showed reduced left ventricular systolic shortening (23% vs. 35%; p less than 0.001) and increased left atrial diameter (4.6 cm vs. 3.8 cm; p less than 0.05) in group 1 compared with group 2. Systolic pressure gradient, aortic regurgitation, left ventricular end-diastolic and peak systolic pressure were, however, similar in both groups. Left ventricular angiographic ejection fraction was significantly reduced in group 1 (48% vs. 60%; p less than 0.01) compared with group 2. Postoperative follow-up was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of repeated (3 to 10 second) and transient (15 to 75 second) abrupt coronary occlusion on the global and regional chamber stiffness was studied in nine patients undergoing angioplasty of a single proximal left anterior descending coronary artery stenosis. The left ventricular high fidelity pressure and volume relation was obtained before and after the procedure as well as during coronary occlusion, after 20 seconds (n = 9) and after 50 seconds (n = 5). During ischemia, there was an upward shift of the pressure-volume relation. The nonlinear simple elastic constant of chamber stiffness increased from 0.0273 +/- 0.017 before angioplasty (mean +/- SD) to 0.0621 +/- 0.026 after 20 seconds of occlusion (p less than 0.05) and 0.0605 +/- 0.015 after 50 seconds of occlusion (p less than 0.01). In five patients, the postangioplasty value remained higher than the control value, but at the group level the mean value (0.0529 +/- 0.037) was not statistically different. The regional stiffness was determined from the changes in the length of six segmental radii during diastole, from the lowest diastolic to the end-diastolic pressure. The regional constant of elastic stiffness was unaffected in the nonischemic zone. In the adjacent and ischemic zones, the regional stiffness was increased during occlusion (p less than 0.05). These regional abnormalities in diastolic function persisted at the time of postangioplasty measurements, 12 minutes after the end of the procedure. This suggests that recovery of normal diastolic function after repeated ischemic injuries is delayed after restoration of normal blood flow and systolic function.

In 33 patients with aortic stenosis (AS), 27 with combined aortic valve lesion (AS + AI) and 23 with chronic aortic insufficiency (AI) left ventricular angiographic muscle mass (LMMI) was determined before and after successful valve replacement. Preoperative age in the three groups was 51, 47 and 42 years (P less than 0.05 vs. AS) respectively; recatheterization was carried out 17, 20 and 21 months postoperatively (not significant). In all three groups angiographic mass decreased (P less than 0.001) following surgery: In AS from 167 to 117, in AS + AI from 200 to 127 and in AI from 192 to 142 g/m2. Left ventricular end-diastolic wall thickness decreased from 1.22 to 1.02 (P less than 0.001) in AS and from 1.19 to 1.03 cm (P less than 0.001) in AS + AI. No change of wall thickness occurred in the patients with AI. Left ventricular ejection fraction (EF) increased from 61 to 68% (P less than 0.01) in AS, from 58 to 68% (P less than 0.005) in AS + AI and from 52 to 59% (P less than 0.02) in AI. The postoperative EF in the patients with AI was smaller (P less than 0.05) than in AS, AS + AI and in controls (EF = 68%, n = 18). Postoperative normalization of LMMI (less than or equal to 120 g/M2) occurred in 22/33 (67%) patients with AS, in 14/27 (52%) with AS + AI and in 8/23 (35%) with AI. The age of the patients and the time interval between surgery and recatheterization had no influence on postoperative normalization or non-normalization of LMMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiologic hypertrophy occurs as the result of exercise conditioning and is characterized by normal or supranormal left ventricular (LV) contractile function and reversibility of structural alterations. Whether hypertrophy produced by chronic abnormal loading can be termed 'physiologic' is a matter of debate because in experimental pressure overload hypertrophy normal in vivo ventricular function may be associated with abnormal in vitro function of the papillary muscles. In patients with moderate LV hypertrophy from aortic valve disease (angiographic mass less than 180 g/m2) ejection fraction (EF) is preserved, but at similar levels of afterload, when mass exceeds 180 g/m2, EF is depressed. Comparison of LV function with myocardial structure (endomyocardial biopsies) has shown that in patients with compensated LV function and those with left heart failure (EF less than 57%, LVEDP greater than 20 mm Hg and/or cardiac index less than 2.5 l/min/m2) interstitial fibrosis (IF) was increased to a similar extent (16 and 18%; normal less than 5%), whereas muscle fiber diameter (MFD; normal less than or equal to 20 mu) was larger (P less than 0.05) in the patients with failure (30 mu) than in those with preserved function (27 mu). Moreover patients with depressed postoperative function had a larger (P less than 0.01) preoperative MFD (35 mu) than those with normal postoperative function (30 mu). Seventeen months after successful aortic valve replacement IF increased (P less than 0.02) and MFD decreased (P less than 0.001) but did not become normal regardless whether postoperative function was normal or depressed. Thus in secondary hypertrophy myocardial structure is pathologic even in the presence of normal LV function and depressed function appears likely to be related to excessive fiber hypertrophy rather than to IF. Massive fiber hypertrophy heralds an unfavorable postoperative LV function and fibrosis is irreversible after surgical correction of the abnormal load.

Between 1969 and 1984, 68 patients with dilated cardiomyopathy (mean age 44 years) were observed for an average period of 45 months. 46 patients (68%) died (17 sudden death, 13 congestive heart failure, 5 other causes and 11 unknown causes) during the observation period according to a cumulative 5-year survival rate of 40%. All patients underwent diagnostic cardiac catheterization. Left ventricular ejection fraction was 32%, left ventricular end-diastolic volume index 195 ml/m2, left ventricular end-diastolic pressure 17 mm Hg and cardiac index 2.7 l/min/m2. The initial hemodynamic findings in the non-survivors and the survivors were statistically not significantly different. The prognostic significance of 12 clinical and hemodynamic parameters was evaluated by multivariate regression analysis (Cox model). Only 3 hemodynamic parameters, namely left ventricular end-diastolic volume, left ventricular end-diastolic pressure and cardiac index, showed prognostic significance in regard to survival. Prognostic evaluation of medical therapy (antiarrhythmic drugs n = 14, vasodilators n = 17, anticoagulation n = 37) revealed an improved cumulative 3-year survival rate (87% versus 46%) only for vasodilators.

In the present study 12 patients with severe chronic heart failure (7 with dilated cardiomyopathy and 5 with ischaemic heart disease) underwent right heart catheterization at rest and during isometric exercise by handgrip before and 6 months after treatment with captopril (mean dose 2 X 39.6 mg/day) while concomitant digitalis and diuretics were unchanged. After 6 months resting haemodynamics changed as follows: decrease in heart rate, mean arterial pressure, pulmonary capillary pressure and total vascular resistance; increase in stroke volume index and stroke work index. During handgrip the following changes were observed after captopril: decrease in total vascular resistance; increase in stroke volume index and stroke work index. Before captopril 11 patients showed no increase or even a decrease in stroke work index during isometric exercise, whereas after captopril 5 out of the 12 patients showed an increase in stroke work index. The results demonstrate that in patients with severe chronic heart failure long-term treatment with captopril lowers preload and afterload, which is accompanied by a significant improvement in left ventricular performance at rest. Furthermore, during isometric exercise after captopril an improvement in left ventricular function was found in 5 out of 12 patients.

In the experimental animal, acute ischemia by interruption of coronary blood supply is accompanied by a steepening of the slope of the left ventricular pressure-volume and pressure-segment length relations. This increase in chamber stiffness is associated with an increase in myocardial stiffness assessed from the slope of the diastolic stress-strain relation. Supply-type ischemia in humans brought about by balloon inflation during coronary angioplasty leads to an upward shift of the pressure-length relation of the ischemic and the adjacent segment combined with a steepening of the slope. In demand ischemia produced by rapid pacing in patients with coronary artery disease, an increased radial stiffness modulus at any level of radial stress was present when compared with that during the resting state. These alterations of the stress-strain relation suggest that the physical properties of the myocardium change during both supply and demand ischemia. The increased diastolic myocardial stiffness appears to result, at least in part, from increased residual interaction between actin and myosin filaments.

Angiographic techniques have been used for the quantification of mitral or aortic and rarely tricuspid regurgitation. Mitral or aortic regurgitant volume per beat and the regurgitation fraction (fao and fm, respectively) are obtained from the angiographic determination of total left ventricular stroke volume (TSV) and forward stroke volume (FSV) estimated by a different technique. Although this procedure is generally accepted as the gold standard for quantification of left heart regurgitations, there are several limitations: In the presence of mitral and aortic regurgitation no separate quantification of fao and fm is feasible; heart rate at the time of determination of FSV (from Fick or dye dilution cardiac output) and of TSV (angio) may be different; there is a tendency to consistently overestimate stroke volume by angio techniques; repeated estimations of TSV by angio are influenced by the circulatory effects of the contrast dye. In contrast indicator dilution techniques, where upstream and downstream sampling allow the simultaneous estimation of forward and regurgitant flow, the accuracy of the determination of FSV is well established and repeated estimations of fao and fm are possible because the indicators do not have cardiovascular effects. These methods are, however, crucially dependent on thorough mixing of the regurgitant volume with the blood in the upstream chamber. In 23 patients with isolated aortic regurgitation there was a positive correlation between fao evaluated by thermodilution and fao determined by the biplane angio-Fick method (r = 0.59). fao by thermodilution averaged 0.40 and fao by angio-Fick 0.46 (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental animal investigations have shown that already after a few seconds of occlusion of a coronary artery a reduction in the systolic myocardial shortening and wall thickening takes place in the corresponding supply area. Following 1-2 minutes of ischemia systolic expansion occurs. Wall-thickness increase and myocardial shortening then take place during the isovolumetric relaxation phase. When at least 25% of the myocardium of the left ventricle becomes acutely ischemic the end-diastolic pressure and end-diastolic volume increase. As a rule an augmentation of myocardial contraction appears in the non-ischemic section of myocardium, which in part takes place through the Frank-Starling mechanism. With a gradual reduction of the coronary inflow, and a decline in the wall thickening of c. 50% of the control value, a significant reduction in blood flow took place only in the innermost quarter of the ventricular wall. With akinesia of the ischemic area, no reduction of the blood flow could be determined in the subepicardial region. Only with the occurrence of dyskinetic wall motion was a transmural reduction of blood flow effected. The ischemic contraction disturbances are fully reversible if coronary occlusion last only a few minutes. With a 15 minute occlusion the recovery time of the myocardial function can require several days (postischemic "stunned myocardium"). The first myocardial necroses occur after 20 minutes of ischemia, and after 3-6 hours of ischemia the infarction is complete.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular filling dynamics were investigated in 24 patients with aortic stenosis (AS). Biplane cineangiography was performed with simultaneous micromanometry in these 24 patients and in six control subjects. Twelve of the patients with AS had moderate hypertrophy with a left ventricular muscle mass index of less than 180 g/m2 (ASI group) and 12 had severe hypertrophy with an index of 180 g/m2 or more (AS2 group). Filling dynamics were also evaluated postoperatively in eight patients in the AS1 and six patients in the AS2 group. Preoperatively, end-diastolic and end-systolic volume indexes were larger and ejection fraction was lower in the AS2 compared with the control or AS1 group. Percent volume increase during the first half of diastole (%V1) was smaller in the AS1 than in the AS2 group. Peak filling rate in the first half of diastole (PFR 1) was higher in the AS2 than in the control or in AS1 group, while peak filling rate in the second half of diastole (PFR2) was considerably greater in the AS1 group than in the other two groups. The time constant of left ventricular pressure decline, an index of the rate of relaxation, was prolonged in the AS2 group. In contrast, mitral valve opening pressure (MVOP) was significantly higher in this group than in the other two groups. The constant of left ventricular chamber stiffness was slightly but not significantly greater in both AS groups than in the control subjects. After surgery in patients in the AS1 group, preoperatively reduced %V1 had increased and preoperatively enhanced PFR2 had decreased. In patients in the AS2 group, excluding one with a persistent low ejection fraction after surgery, preoperatively enhanced PFR1 decreased in association with a decrease in MVOP. Thus, left ventricular filling dynamics vary in patients with AS depending on the degree of left ventricular hypertrophy and systolic function. In patients with AS and moderate hypertrophy %V1 is slightly reduced but is compensated for by a forceful atrial contraction. In those with severe hypertrophy and systolic dysfunction increased driving pressure allows %V1 to remain within normal limits, despite prolonged left ventricular relaxation and decreased elastic recoil. Both changes in left ventricular filling dynamics tend to normalize after surgery in association with a reduction in left ventricular hypertrophy and/or an improvement of systolic function.

The sensitivity and specificity of three clinical signs used for the diagnosis of tricuspid regurgitation (hepato-jugular reflux, congestion of the neck veins, inspiratory dilatation of the neck veins) were evaluated in 27 patients by contrast echocardiography. Tricuspid regurgitation was diagnosed when regurgitation of microbubbles into the inferior vena cava occurred at the time of the v-wave of the atrial pressure pulse. Nine of the 27 patients had tricuspid regurgitation (group I) and 18 patients (group II) did not. The end-diastolic diameter (group I: 3.1 cm; group II: 2.4 cm; p less than 0.05) and the end-systolic diameter (group I: 2.9 cm; group II: 2.3 cm; p less than 0.05) of the vena cava inferior were larger in the patients with tricuspid regurgitation than in those without. The end-diastolic short axis of the right ventricle (group I: 3.5 cm; group II: 3.2 cm; n.s.) did not differ significantly between the groups. Within group II, the echocardiographic dimensions of the vena cava inferior and the right ventricle did not differ in patients with congestion of the neck veins from those without. A significant correlation between clinical signs and tricuspid regurgitation could only be demonstrated for the hepato-jugular reflux (p less than 0.01, chi 2-test) and for inspiratory dilatation of the neck veins (p less than 0.05, chi 2-test).(ABSTRACT TRUNCATED AT 250 WORDS)

Vasomotility of normal and stenosed coronary arteries was studied at rest and during supine bicycle exercise in 10 patients with classical exercise-induced angina pectoris receiving 1 mg intracoronary propranolol before the exercise test (propranolol group). Normal and stenotic coronary lumen areas were determined from biplane coronary arteriograms using a computer-assisted system. Measurements were performed at rest, after 1 mg intracoronary propranolol, during supine exercise (89 W for 3.4 minutes) and 5 minutes after 1.6 mg sublingual nitroglycerin administered at the end of the exercise test. The results were compared with previously obtained data on the effect of dynamic exercise on coronary lumen area in 12 patients receiving no medication (control group) and in 6 patients receiving 0.1 mg intracoronary nitroglycerin before the exercise test (nitroglycerin group). In the control group, coronary stenosis area decreased during exercise to 71% of levels at rest (p less than 0.001) whereas normal coronary lumen area increased to 123% of control (p less than 0.01). In the propranolol group both normal (113%, p less than 0.05 versus rest) and stenotic coronary lumen area (122%, p less than 0.05 versus rest) increased during exercise. A similar increase in both normal and stenotic areas was observed during exercise after pretreatment with 0.1 mg intracoronary nitroglycerin (123%, p less than 0.01 and 114%, p = NS versus rest). Sublingual administration of 1.6 mg nitroglycerin at the end of exercise increased coronary stenosis area to 145% (p less than 0.01 versus rest) in the propranolol group and to 115% in the control group (p = NS versus rest). It is concluded that intracoronary administration of propranolol does not potentiate coronary vasoconstriction of the epicardial vessels at rest and during exercise. In contrast, intracoronary propranolol prevents exercise-induced stenosis narrowing either because of reduced myocardial oxygen demand with a lower coronary blood flow resulting in a smaller transstenotic pressure gradient and, thus, a smaller flow-induced fall in stenosis distending pressure; or because of "local" beta-receptor blockade with unopposed distal arteriolar alpha-receptor tone, resulting in a higher poststenotic pressure and, thus, in a greater stenosis distending pressure; or because of a local anesthetic effect of propranolol with a decrease in calcium influx to the coronary smooth musculature.

Diastolic stiffness of the septum and the posterior wall were determined in 6 patients with hypertrophic obstructive cardiomyopathy before and 10 to 15 min after the intravenous administration of verapamil, 0,1 mg/kg. Left ventricular high-fidelity pressure measurements and M-mode echocardiography were carried out in all patients before and after verapamil. Diastolic stiffness of the septum (beta S) and of the posterior wall (beta) were assessed from the slope of a viscoelastic stress-strain relationship: sigma = alpha (e beta epsilon -1) + eta epsilon where sigma = meridional wall stress (g/cm2) alpha = intercept (g/cm2), beta = constant of myocardial stiffness, epsilon = mid-wall strain, eta = constant of myocardial viscosity (g. sec/cm2), epsilon = strain rate (sec-1). Left ventricular relaxation was evaluated from the time constant of left ventricular pressure fall (T; msec) by plotting left ventricular pressure versus dP/dt during the isovolumic relaxation period. Heart rate (71 versus 74 beats/min), left ventricular end-diastolic pressure (17 versus 17 mmHg) and peak systolic pressure (152 versus 146 mmHg) were not significantly different before and after intravenous administration of verapamil. The constant of myocardial wall stiffness of the septum (17 versus 16) and the posterior wall (15 versus 13) remained unchanged after verapamil, however, myocardial stiffness of the septum was slightly higher than myocardial stiffness of the posterior wall. The time constant of left ventricular pressure fall decreased significantly (P less than 0.05) from 53 to 43 msec following administration of verapamil. It is concluded that in patients with hypertrophic, obstructive cardiomyopathy, diastolic myocardial stiffness of the septum is slightly higher than the stiffness of the posterior wall. Verapamil does not influence the regional passive diastolic properties but has a beneficial effect on ventricular relaxation.

Dilated cardiomyopathy is a primary myocardial disease of unknown origin. The typical findings are severe systolic pump failure and dilatation of all cardiac chambers with severe cardiomegaly. Clinical symptomatology is determined by myocardial dysfunction with congestive heart failure. Cardiomegaly and arrhythmia may precede clinical symptoms of congestive heart failure by years. Medical therapy is based on classical treatment of congestive heart failure with digitalis and diuretics; recently, afterload-reducing agents, such as converting enzyme inhibitors, have become the drug of choice for patients with severe congestive heart failure. Antiarrhythmic therapy is necessary in the presence of severe arrhythmia, and anticoagulation is indicated when a low-output state or atrial fibrillation are present. Clinical course in dilated cardiomyopathy is usually poor and 5-year survival is 38% in our group.

Abnormalities of left ventricular function during ischemia have been described in animal models and in humans. Exercise, while a physiologic means of inducing ischemia, has a complex effect on left ventricular function by itself. In addition, patients with coronary artery disease have a diversity of chronic changes in myocardial structure and function. Therefore, with use of micromanometer left ventricular pressure measurements and ventricular volumes, calculated from biplane cineangiograms, left ventricular function at rest and during exercise was studied in 57 patients. Exercise-induced ischemia produced a decrease in ejection fraction, an increase in end-systolic volume, dramatic increases in diastolic pressures and an upward shift in the diastolic pressure-volume relation. Central to these changes was abnormal myocardial contraction and relaxation, with reduced regional shortening and impaired left ventricular pressure decay. However, nonischemic areas were capable of augmented shortening, and global pressure decay did accelerate slightly. These findings demonstrate that exercise-induced adjustments in contraction and relaxation are intertwined with ischemia-related abnormalities. Exercise studies in patients after bypass surgery and in patients with scars from distant myocardial infarction were useful in clarifying confounding factors. For example, asynchrony of contraction and relaxation, and chronic changes in passive chamber properties, also compromise systolic and diastolic function during exercise. In patients with coronary artery disease without ischemia during exercise, left ventricular end-diastolic pressure, but not early diastolic pressure, increased during exercise. The increase in pressure was appropriate for a slight increase in end-diastolic volume in a ventricle with a steep pressure-volume relation. Furthermore, end-systolic volume, while maintained during exercise, was not reduced, as occurs normally.(ABSTRACT TRUNCATED AT 250 WORDS)

In seven patients with aortic valve disease the time course of an auxotonic beat was compared with that of an isovolumetric beat produced by aortic cross clamping during open heart surgery. The rate of systolic stress rise (dS/dt; g.cm-2) of the isovolumetric beat at peak meridional wall stress (Sp; g.cm-2) of the auxotonic beat was determined by tipmanometry and simultaneous sonomicrometry and was found to be 87% of maximum dS/dt. In the second part of the study the stiffness index (k) was calculated in patients undergoing cardiac catheterisation according to: k = 0.87.(max.dS/dt)/Sp.Vcf, where Vcf = normalised midwall circumferential fibre shortening velocity (circ.s-1). In 22 patients, 10 controls and 12 patients with aortic stenosis before (pre) and after (post) valve replacement the systolic stiffness index k (circ-1) was determined using tipmanometry and frame by frame angiocardiography. Muscle fibre diameter and interstitial fibrosis were assessed from left ventricular endomyocardial biopsies. The systolic stiffness index k was 15 circ-1 in controls, 14 in preoperative patients with aortic stenosis and 12 (p less than 0.01 v controls) in postoperative patients. There was a significant correlation between k and muscle fibre diameter (r = 0.55; p less than 0.01) but not between k and interstitial fibrosis or ejection fraction. We conclude that systolic stiffness index k is normal despite marked left ventricular hypertrophy in preoperative patients with aortic stenosis. Following successful valve replacement systolic stiffness index decreased and was significantly lower than in controls. Series elasticity appears to be determined by structures related to the muscle cell rather than to interstitial fibrosis.

The effect of long-term medical treatment in patients with hypertrophic obstructive cardiomyopathy (HOCM) is still controversial, and it is not clear whether propranolol or verapamil should be recommended in these patients. We therefore observed 49 patients (mean age 34.8 years) with hypertrophic cardiomyopathy and mostly mild obstruction for a mean follow-up period of 7.4 years. 13 patients died (10 suddenly and 3 in congestive heart failure) during the observation period (annual mortality rate 3.6%). According to medical treatment the patients were divided into 3 groups: group I consisted of 20 patients who received no medical treatment, group II of 15 patients receiving an average daily dose of 175 mg propranolol, and group III of 14 patients receiving an average daily dose of 360 mg verapamil. The mean follow-up was 6.4 years for group I, 7.0 years for group II, and 3.7 years for group III. 8 patients in group I died during the observation period (annual mortality rate 6.3%), 4 patients died in group II (annual mortality rate 3.8%), and 1 patient died in group III (annual mortality rate 1.8%). Functional limitation was similar in all 3 groups at the beginning and at the end of the study, and mean NYHA class was 1.9 in all 49 patients at the beginning and 1.8 at the end of the follow-up period. Left ventricular peak systolic and enddiastolic pressure were similar during heart catheterization (n = 41) in all 3 groups. Systolic outflow tract gradient at rest was 44 mmHg in group I, 32 mmHg in group II, and 11 mmHg in group III (difference not significant). The actuarial survival curves showed a significant difference (p less than 0.025) between group I and groups II or III.(ABSTRACT TRUNCATED AT 250 WORDS)

A correlation was attempted in 106 patients with myocardial insufficiency between linear and volume parameters of the laevocardiogram and the corresponding parameters on plain chest films, as well as between pressure measurements and the degree of pulmonary congestion. Measurements on the plain radiograph provide only limited information on the function of the myocardium and the severity of myocardial lesion respectively. Nevertheless, they are of some value during the course of the disease.

Serum carnitine is an essential cofactor for the transport of free fatty acids into the mitochondria. We determined the free and the total serum carnitine in 99 healthy blood donors and 58 patients with different forms of heart muscle disease. Thirty patients had dilated (DCM), 10 hypertrophic (HCM) and 8 alcoholic (ACM) cardiomyopathy and 10 patients had congestive heart failure of different etiology than cardiomyopathy (CHF). Free and total serum carnitine were determined by an enzymatic-spectrophotometric assay according to Pearson. Mean values for free and total serum carnitine were as follows: 47 and 74 mumol/l in controls (C; blood donors), 74 (P less than 0.01 vs. C) and 83 mumol/l in DCM, 66 (P less than 0.01 vs. C) and 89 mumol/l in HCM, 85 (P less than 0.01 vs. C) and 104 mumol/l (P less than 0.05 vs. C) in ACM and 86 (P less than 0.01 vs. C) and 129 mumol/l (P less than 0.01 vs. C) in CHF. Ten patients died during the mean observation time of 13 months, 8 patients with DCM and 2 with CHF; 9 of these 10 patients had initially a markedly increased serum carnitine. Patients with DCM were divided into two groups with normal (n = 15; 25-68 mumol/l) and increased (n = 15; greater than 68 mumol/l) free serum carnitine. Patients with increased serum carnitine showed a significantly higher mortality rate (47%) than patients with normal serum carnitine. It is concluded that free and total serum carnitine are elevated in patients with congestive heart failure, dilated and hypertrophic cardiomyopathy. The etiology of this carnitine metabolism disturbance is unclear but it is probably due to a secondary phenomenon in patients with congestive heart failure or primary myocardial hypertrophy. An increased serum carnitine is a poor prognostic sign in patients with dilated cardiomyopathy.

A new direct method has been developed for predicting postoperative performance in patients undergoing aortic valve replacement. Employing micromanometry and cineangiography, a number of conventional hemodynamic and angiographic variables, including the peak value of the first derivative of ventricular pressure divided by ventricular pressure (dP/dt/P)max, were evaluated in 171 patients studied preoperatively and in 44 patients studied pre- and postoperatively with an additional 14 patients serving as control subjects. Normal contractile state relations (dP/dt/P)max versus end-diastolic pressure (over a range of 125 mm Hg or less to more than 15 mm Hg) were derived from patients whose preoperative ejection fraction and peak wall stress were equal to or more than control mean--2 standard deviations. Postoperative function was predicted to be abnormal (ejection fraction less than control mean--2 standard deviations) if preoperative values of (dP/dt/P)max and end-diastolic pressure fell below the 95 percent confidence bands of these contractile state relations. The method accurately predicted postoperative function in 40 of 44 patients with a sensitivity of 100 percent. This result was confirmed by a discriminant function analysis (based on preoperative ejection fraction, end-diastolic pressure and [dP/dt/P]max) that yielded correct classifications in 42 of 44 patients. These studies indicate that the preoperative contractile state of the myocardium is the major determinant of postoperative performance in aortic valve disease.

Coronary arterial spasms are thought to be responsible for acute myocardial infarction in some patients with normal coronary arteries. A report is presented on a patient with a history of Prinzmetal angina pectoris involving ST-segment elevations in the electrocardiogram and recurrent ventricular fibrillation. Selective coronary arteriography revealed normal coronary arteries. Administration of nifedipin and isosorbide dinitrate brought about prompt relief of pain. One year after cardiac catheterization the patient developed recurrent ventricular arrhythmias when administration of nifedipin was discontinued. It is concluded that coronary arterial spasms may occur in patients with normal coronaries and may cause transient myocardial ischemia with severe ventricular arrhythmias. A history of Prinzmetal angina pectoris is usually present and medical treatment consists in administration of nifedipin and isosorbide dinitrate.

Whether exercise-induced vasoconstriction of coronary artery stenoses is modified by the administration of calcium antagonists was examined in 14 patients with classic angina pectoris. In this group the effect of intracoronary diltiazem (2 to 3 mg) on luminal area was evaluated in normal and stenotic segments of epicardial coronary arteries during symptom-limited supine exercise. The luminal area of a normal and a stenotic coronary artery segment was determined by quantitative coronary arteriography with a computer-assisted system. Patients were studied at rest, 6 min after 2 to 3 mg of intracoronary diltiazem, during supine bicycle exercise (96 W) and 5 min after sublingual administration of 1.6 mg nitroglycerin. Heart rate, mean pulmonary and aortic pressure as well as the percent change of both normal and stenotic luminal area were determined. Intracoronary administration of diltiazem was associated with mild dilation of both normal (19%, p less than 0.01) and stenotic coronary luminal area (11%, p less than 0.05). During subsequent exercise, luminal area of the stenotic vessel segment increased by 23% (p less than 0.001) and that of the normal vessel segment by 24% (p less than 0.001), whereas in a previously reported control group, luminal area of the stenotic vessel segment decreased by 29% during exercise. After sublingual administration of nitroglycerin, the luminal area of both the normal and the stenotic vessel segment increased further by 19% (p less than 0.01) and 22% (p less than 0.01), respectively, compared with the values after intracoronary administration of diltiazem.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular biplane cineangiography, micromanometry, and endomyocardial biopsies were performed in 27 patients with aortic stenosis (AS) and in 17 patients with aortic insufficiency (AI). Twenty-three patients with AS and 15 with AI were restudied at an intermediate time (18 months after successful valve replacement), and nine patients with AS and six with AI were restudied late (70 and 62 months after surgery). Biopsy samples were evaluated for muscle fiber diameter, percent interstitial fibrosis, and volume fraction of myofibrils. In control biopsy samples obtained from five donor hearts at transplantation, these morphometric variables averaged 21.2 microns, 7.0%, and 57.2%, respectively. After surgery, mass determined by cineangiography decreased from 186 to 115 and 94 g/m2 in patients with AS and from 201 to 131 and 93 g/m2 in patients with AI. At the three studies, muscle fiber diameter was 30.9, 28.0, and 28.7 microns in patients with AS and was 31.4, 27.6, and 26.4 microns in patients with AI. Percent interstitial fibrosis was 18.2, 25.8, and 13.7% in patients with AS and was 20.4, 23.7, and 19.2% in patients with AI. Left ventricular fibrous content decreased from 34.2 to 29.8 and to 12.7 g/m2 in patients with AS and from 42.1 to 28.9 and to 18.9 g/m2 in patients with AI. Volume fraction of myofibrils was 57.7, 56.8, and 49.0% in patients with AS and was 56.8, 56.6 and 48.8% in patients with AI. Thus, the decrease of muscle mass determined by cineangiography at the intermediate time after valve replacement is mediated by regression of myocardial cellular hypertrophy in patients with AS and AI and in addition by a decrease of fibrous content in patients with AI. Late after surgery, left ventricular fibrous content also decreases in patients with AS. This late decrease associated with minor changes of end-diastolic volume may be important for improvement of increased diastolic myocardial stiffness. Even 6-7 years after valve replacement, incomplete regression of structural abnormalities of left ventricular hypertrophy still exists compared with the normal myocardium. The residually increased relative interstitial fibrosis and the small late postoperative decrease of volume fraction of myofibrils, associated with a prosthesis-related slight left ventricular pressure increase, are at the origin of a persistent systolic overload at the myofibrillar level.

A reduced coronary flow reserve has been reported in patients with ischemia-like symptoms and normal coronary arteries. In 13 such subjects both coronary vasomotion and flow reserve were studied. The luminal area of the proximal and distal third of the left anterior descending and left circumflex artery were determined by biplane quantitative coronary arteriography using a computer-assisted system. Subjects were studied at rest, during submaximal supine bicycle exercise (4.0 min, 116 W) and 5 min after sublingual administration of 1.6 mg nitroglycerin. Heart rate, mean pulmonary and aortic pressure as well as the percent change of both proximal and distal luminal area were determined. In 10 of the 13 subjects, coronary sinus blood flow was measured by coronary sinus thermodilution technique at rest and after dipyridamole infusion (0.5 mg/Kg in 15 min) 10 +/- 5 days after quantitative coronary arteriography. Coronary flow ratio (dipyridamole/rest) and coronary resistance ratio (rest/dipyridamole) were determined in these subjects. Subjects were divided into 2 groups according to the behaviour of the coronary vessels during exercise (vasodilation = Group 1, vasoconstriction = Group 2). Coronary vasodilation of the proximal (luminal area + 26%; p less than 0.001) and distal (+ 45%; p less than 0.001) artery was observed in 7 subjects (Group 1) during exercise and after sublingual nitroglycerin (+46%; p less than 0.001 and +99%; p less than 0.001, respectively). In Group 2 (n = 6), however, there was coronary vasoconstriction of the distal vessel segments (-24%; p less than 0.001) during exercise, whereas the proximal coronary artery showed vasodilation (+ 26%; p less than 0.001) during exercise. Following sublingual nitroglycerin, both vessel segments elicited vasodilation (distal coronary + 44%; p less than 0.001, proximal coronary artery +47%; p less than 0.001). Coronary flow ratio amounted to 2.5 in Group 1 and to 1.2 in Group 2 (p less than 0.05) and coronary resistance ratio to 2.7 in Group 1 and to 1.2 in Group 2 (p less than 0.05), respectively. Thus, among subjects with ischemia-like symptoms and normal coronary arteries there is a subgroup of patients (Group 2) with an abnormal dilator response of the distal coronary arteries to the physiologic dilator stimulus of exercise and a reduced dilator capacity of the resistance vessels after dipyridamole (= abnormal coronary vasodilator syndrome). The nature of this exercise-induced distal coronary vasoconstriction is not clear but might be due to an abnormal neurohumoral tone which may cause or contribute to the blunted vascular response during exercise.