Hans P. Krayenbuehl

Thallium-201 scintigraphy in complete left bundle branch block.

Nineteen symptomatic patients with left bundle branch block (LBBB) were examined by thallium-201 (TI-201) exercise scintigraphy and selective coronary arteriography. All elicited significant anteroseptal perfusion defects in the exercise scintigrams, but in only 4 was coronary artery disease (CAD) involving the left anterior descending coronary artery present. To further elucidate the effect of LBBB on septal TI-201 uptake in the absence of CAD, TI-201 scintigrams combined with regional myocardial blood flow measurements using radioactive microspheres were carried out in 7 dogs during right atrial and right ventricular pacing (LBBB in the ECG) at similar heart rates. During right atrial pacing, TI-201 uptake was homogeneous in the entire left ventricle, as were tissue flows. During right ventricular pacing, TI-201 activity was reduced to 69% of maximal TI-201 activity within the septum, whereas it averaged 90% in the lateral wall (p less than 0.05) in 6 dogs. Correspondingly, regional myocardial blood flow was lower within the septum as compared with that in the lateral wall, averaging 89 and 120 ml/min/100 g, respectively (p less than 0.005). In 1 dog, normal TI-201 distribution and tissue flows were found in both studies. Thus, symptomatic patients with LBBB may elicit abnormal TI-201 exercise scintigrams, suggesting anteroseptal ischemia despite normal coronary arteries. The electrical induction of LBBB in dogs results, in most instances, in a comparable reduction in septal TI-201 uptake associated with diminished septal blood flow. Therefore, exercise-induced septal perfusion defects in the presence of LBBB do not necessarily indicate CAD even in symptomatic patients, but may reflect functional ischemia due to asynchronous septal contraction.

Effect of coronary occlusion during percutaneous transluminal angioplasty in humans on left ventricular chamber stiffness and regional diastolic pressure-radius relations

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.

Exercise-induced ischemia: the influence of altered relaxation on early diastolic pressures.

Left ventricular pressure (LVP) decay and early diastolic pressures were studied at rest and during exercise in three groups of patients. Patients in the ischemia group (n = 15) had coronary artery disease and developed new regional wall motion abnormalities documented by biplane LV cineangiography during exercise. Patients in the control group (n = 4) had a normal exercise response. Patients in the scar group (n = 5) had prior. infarction, akinetic scars and no ischemia with exercise. Isovolumic pressure data were. used to compute the time constant (T) of LVP decay (from the linear relation of LVP and negative dP/dt) and an extrapolated baseline pressure (PB) at dP/dt = 0. During exercise in the ischemia group, minimal LV diastolic pressure (PL) increased from 9 + 3 to 21 ± 5 mm Hg (p < 0.001), end-systolic volume increased from 38 7 to 55 ± 8 ml/m2 (p < 0.001) and PB rose from -10 ± 7 to 11 ± 8 mm Hg (p< 0.001); T decreased (from 55 ± 9 to 37 ± 8 msec, p < 0.001), although inadequately, compared with the decrease in the control group (from 49 ± 15 to 22 ± 2 msec, p < 0.01). Relaxation at PL during exercise was incomplete in the ischemia group (2.2 ± 0.4 T) and complete in the control group (3.8 ± 0.7 T, p < 0.05). The time course of LVP fall was extrapolated from the isovolumic period into the passive LV filling phase. The extrapolated pressure at the time PL occurred (PE) rose from 0 ± 4 to 20 ± 7 mm Hg with ischemia (p < 0.001). Thus, the characteristics of LVP decay can account for the elevated early diastolic pressures during ischemia. In contrast, the scar group maintained a low PL during exercise (11 3 to 8 ± 3 mm Hg), even though T decreased inadequately (from 66 ± 10 to 36 ± 5 msec, p < 0.01), because PB did not shift upward. Ischemia-related pressure elevations involve both delayed relaxation and a pressure baseline shift. During exercise, LVP decay is normally adjusted to maintain low diastolic pressures; with exerciseinduced ischemia, LVP decay is abnormal and early diastolic pressures are severely elevated.

Relationship between myosin isoenzyme composition, hemodynamics, and myocardial structure in various forms of human cardiac hypertrophy.

Hemodynamic and angiographic parameters, muscle fiber diameter, nonmuscle tissue content, and myosin light chain isoform composition were determined in the left ventricle of nine patients with primary (four with hypertrophic, five with dilated cardiomyopathy) and 27 patients with secondary hypertrophy (11 with aortic regurgitation, 16 with aortic stenosis), nine patients with coronary heart disease, and seven controls. In various forms of hypertrophy, a new atrial-like light chain 1 occurred in two-dimensional electrophoresis of total tissue homogenates amounting up to 29% of total light chain 1. Total light chain 1 content remained constant in all groups when related to tropomyosin. The mean content of this atrial light chain 1 was highest in dilated cardiomyopathy (12.1%), less in cases with pressure (6.4%) and volume overload (2.9%), but as low in hypertrophic cardiomyopathy (0.3%) as in controls (0.4%). In cases with coronary heart disease without prior infarction, it was lower (0.6%) than with infarction (1.9%). Its occurrence was not affected by digoxin administration. In ventricular myocardium, an atrial-like light chain 2 was never observed. Peptide patterns after limited proteolytic digestion of isolated myosin heavy chains from cases with pressure overload and hypertrophic cardiomyopathy were identical to those from controls. The content of the atrial-like light chain 1 was not correlated to either muscle fiber diameter or nonmuscle tissue content, both of which were increased in all hypertrophy groups. In individual cases, no firm correlation could be established between atrial-like light chain 1 content and various parameters of ventricular load and function. However, a significant correlation resulted when the mean values of atrial-like light chain 1 content of each disease group were related to the respective mean values of peak circumferential wall stress (r = 0.96). Thus, the shift of myosin light chain 1 isoforms in ventricle seems to characterize biochemically the hypertrophy process induced by mechanical stress.

Effect of aortic valve stenosis (pressure overload) and regurgitation (volume overload) on left ventricular systolic and diastolic function

In secondary hypertrophy from chronic pressure or volume overload, or both, systolic as well as diastolic abnormalities of left ventricular (LV) function have been described, but their relation has not been defined. In 58 patients with aortic valve disease (28 with aortic valve stenosis, and 30 with aortic regurgitation) and in 11 control subjects, LV biplane cineangiography was performed simultaneously with LV high-fidelity pressure measurements. LV ejection performance was assessed by ejection fraction, and diastolic function by the time constant of LV pressure decay, the early and late peak filling rates, and the constants of chamber (pressure-volume relation) and myocardial stiffness (stress-strain relation). In the entire cohort (n = 69), ejection fraction was inversely related to the time constant of LV relaxation (r = -0.58, p less than 0.001) and to the constant of myocardial stiffness (r = -0.62, p less than 0.001). Despite preserved systolic contractile function (as evaluated from the ejection fraction-mean systolic stress relation), abnormalities in LV diastolic function were present in 9 of 18 patients with pressure overload and 20 of 22 with volume overload. None of the 58 patients with aortic valve disease had a reduced early peak filling rate, whereas a reduction in late peak filling rate was observed in 3 with aortic stenosis, but in none with aortic regurgitation. This, it appears that abnormalities of relaxation and passive diastolic myocardial stiffness precede alterations in myocardial contractility. Assessment of peak filling rates is not helpful to detect diastolic dysfunction in patients with aortic valve disease.

Silent myocardial ischemia: Hemodynamic changes during dynamic exercise in patients with proven coronary artery disease despite absence of angina pectoris

The hemodynamic changes during exercise occurring in 36 patients with proven coronary artery disease (10 without and 26 with previous myocardial infarction) who tolerated the stress test without angina were analyzed and compared with changes observed in a control group of 36 carefully matched patients whose exercise was limited by angina. All patients were exercised to the same extent, reaching a similar rate-pressure product at the end of the stress test (19,508 +/- 4,828 [SD] versus 19,247 +/- 4,117 beats/min X mm Hg [NS] in the study and control groups without prior infarction, and 19,665 +/- 3,950 versus 17,701 +/- 4,600 beats/min X mm Hg [NS] in the respective groups with infarction). In all groups left ventricular end-diastolic pressure increased from rest to exercise (from 18 +/- 4 to 36 +/- 11 and from 13 +/- 5 to 29 +/- 9 mm Hg, respectively, in the study and control groups without prior infarction and from 17 +/- 7 to 32 +/- 13 and from 19 +/- 7 to 36 +/- 9 mm Hg in the respective groups with prior infarction). Left ventricular ejection fraction decreased (from 59 +/- 7 to 50 +/- 15 and from 60 +/- 4 to 52 +/- 9% in the study and control groups without prior infarction and from 54 +/- 9 to 47 +/- 10 and 55 +/- 9 to 50 +/- 4% in the respective groups with prior infarction). Whereas the changes from rest to exercise were highly significant within each group, no significant differences were noted between the corresponding groups. Regional de novo hypokinesia appeared in all patients without prior infarction and in 25 and 22 patients, respectively, of the groups with prior infarction. Thus, under similar physical stress conditions, comparable hemodynamic changes indicative of ischemia are observed in patients with significant coronary artery lesions with or without previous myocardial infarction irrespective of the occurrence of angina. Therefore, angina pectoris cannot be considered a prerequisite for hemodynamically significant ischemia during exertion.

High-fidelity left ventricular pressure measurements for the assessment of cardiac contractility in man

Abstract Left ventricular contractility was assessed in 110 patients by use of Vmax values derived from high-fidelity left ventricular pressure measurements. Instantaneous velocity of shortening of the contractile elements (V CE ) throughout the isovolumic phase of left ventricular systole was calculated by an analog computer using the formula: V CE in muscle lengths (ML)/ sec = ( dP / dt )/28 · P where P represents total left ventricular pressure and dP/dt its first derivative. Vmax was obtained by manual straight line extrapolation of the descending portion of the pressure-velocity curves. Group 1 (control subjects) consisted of 25 patients with no or minimal loading of the left ventricle. Vmax in Group 1 was 1.86 ML/sec. Group 2 consisted of 25 patients with atrial septal defect and Group 3 included 11 patients with slight left ventricular pressure load. In Groups 2 and 3, the Vmax value was not significantly different from that of Group 1. However, in Group 4, which consisted of 23 patients with moderate to severe left ventricular pressure load, Vmax was significantly reduced (1.53 ML/sec); in Group 5, which consisted of 14 patients with coronary artery disease and 6 patients with cardiomyopathy, Vmax was 1.21 ML/sec; and in Group 6, comprising 6 patients with mitral stenosis, Vmax was 1.26 ML/sec. In individual patients in Groups 3 to 5, assessment of contractility by comparison with resting Vmax values was not always satisfactory because of overlap with the range of the control subjects. Isometric exercise by handgrip carried out in 44 patients allowed further differentiation of individual contractile function. In Groups 1 and 2, the response to handgrip was characterized by a significant increase of Vmax with no alterations or changes not exceeding +4 mm Hg of left ventricular end-diastolic pressure. In Groups 3 to 5, we observed normal responses, as well as abnormal reaction to handgrip (increase of Vmax associated with an increase of left ventricular end-diastolic pressure that exceeded 4 mm Hg) and pathologic reaction to handgrip (decrease of Vmax accompanied by an increase of left ventricular end-diastolic pressure). Seven of 13 patients with a normal resting Vmax showed an abnormal or a pathologic reaction. A normal response to handgrip was observed in a few patients with depressed resting Vmax. It is concluded that identification of individual patients with impaired myocardial contractile function requires determination of Vmax both at rest and during an additional stress such as isometric exercise.

The contractile state of the hypertrophied left ventricular myocardium in aortic stenosis.

Abstract Left ventricular dynamics and contractility were studied in 6 patients with assumed normal myocardial function (Group 1) and in 12 patients with aortic stenosis of a different degree separated into two groups, Group 2 with a mean systolic pressure gradient of below 50 mm. Hg and Group 3 with one of above 50 mm. Hg. None of the patients showed signs of left heart failure. Routine hemodynamic parameters (cardiac index, left ventricular pressure, rate of rise of left ventricular pressure, and aortic pressure) were evaluated in all three groups. End-diastolic volume ( EDVI ), left ventricular muscle mass ( LMMI ), and mean left ventricular wall thickness (h) were determined by angiocardiography. The following values were obtained: Group 1: EDVI , 98 ± 11 (S.E.) ml./M. 2 , LMMI , 115 ± 10 Gm./M. 2 , h, 0.91 ± 0.05 cm.; Group 2: EDVI , 120 ± 22 ml./M. 2 , LMMI , 157 ± 17 Gm./M. 2 , h, 1.15 ± 0.06 cm.; Group 3: EDVI , 105 ± 8 ml./M. 2 , LMMI , 234 ± 26 Gm./M. 2 , h, 1.45 ± 0.07 cm. The left ventricular contractile state was characterized by the instantaneous tension-velocity relationship throughout the isovolumic phase of the systole. It could be shown that the tension-velocity curve of patients with a pressure load is shifted downward and to the left compared with the curve of the controls. This shift was only significant, however, between Groups 1 and 3. By grouping the patients with aortic stenosis according to their age, two pressure-loaded groups with similar mean pressure gradients could be compared with the control group. Here again the tension-velocity curve was shifted to the left and downward with increasing age. This change was only significant if one compared the older age group with the control group. The present data suggest that the intrinsic contractile state of the myocardium of the left ventricle is impaired in patients with left ventricular hypertrophy from aortic stenosis but without heart failure. It would appear that the decrease in contractility is caused both by the severity of the pressure load and by the patients age.

Diastolic simple elastic and viscoelastic properties of the left ventricle in man.

The intrapatient comparison of the simple elastic and viscoelastic stress-strain relationship showed a significantly better curve fitting (r = 0.93 vs 0.96) for the viscoelastic model. The correction by the viscoelastic model occurred mainly during the highly filling-rate dependent early diastole, whereas the correction during atrial filling was low. Early diastolic deviations from the simple elastic stress-strain relationship were especially pronounced in the patients with myocardial hypertrophy. The viscoelastic constants of myocardial stiffness, B and K, were significantly different from the corresponding simple elastic constants, b and k, indicating that the simple elastic stiffness constants include both elastic and viscous forces.

Evaluation of Left Ventricular Function from Isovolumic Pressure Measurements During Isometric Exercise

Abstract In 24 patients left ventricular (tipmanometer) and aortic pressure measurements were carried out before and during a standardized handgrip. On the basis of findings at diagnostic cardiac catheterization, the patients were divided into 2 groups. Group 1 consisted of 13 patients without or with minimal loading of the left ventricle; group 2 comprised 11 patients with a primarily pressure-loaded left ventricle or coronary heart disease. During handgrip left ventricular systolic pressure, end-diastolic pressure and heart rate increased significantly in both groups. However, the extent of the increase of left ventricular end-diastolic pressure was considerably greater in group 2 (+8.2 mm Hg) than in group 1 (+2.0 mm Hg). Both left ventricular maximal dP/dt and the maximal quotient (dP/dt)/P, which represents a measure of the velocity of shortening of the contractile elements, increased significantly in group 1; in group 2 only maximal dP/dt increased significantly, and this increase was only about half of that observed in group 1. The time intervals from the onset of contraction to the points of maximal dP/dt and maximal (dP/dt)/P, respectively, shortened significantly during handgrip in group 1 and remained unchanged in group 2. We conclude that (1) left ventricular contractile function is impaired in patients in group 2 compared with that in group 1; (2) the primary response of the normal or near normal left ventricular myocardium to an acute load produced by handgrip is enhancement of the contractile state; and (3) the compromised left ventricular myocardium is most likely to utilize the Frank-Starling mechanism to generate increased pressure.