Diastolic function in hypertrophic cardiomyopathy: effects of propranolol and verapamil on diastolic stiffness

In patients with hypertrophic cardiomyopathy (HCM), impaired left ventricular (LV) relaxation and diastolic filling have been reported. Therefore, we determined LV diastolic stiffness in nine patients with HCM before and 10 to 15 min after 0·15 mg/kg propranolol i.v. (group 1) and in six patients with HCM before and 10 to 15 min after 0·1 mg/kg verapamil i.v. (group 2). Simultaneous LV cineangiography and high-fidelity pressure measurements were performed in group 1 and simultaneous M-mode echocardiography and high-fidelity pressure measurements in group 2. Passive LV chamber stiffness was determined in group 1 from the diastolic pressure-volume data using an exponential three-parameter model: P =αeβV + C, where P = pressure, α = intercept, β = constant of chamber stiffness, V = volume and C = baseline pressure. Passive LV myocardial stiffness was estimated in group 2 from the diastolic stress-strain data using a viscoelastic model. ο = α′ (eβ′ε - 1) + ηέ, where ο = meridional wall stress, α = intercept, β′ = constant of myocardial stiffness, ε = midwall strain, η = constant of myocardial viscosity and έ = strain rate. LV relaxation was assessed from the time constant of LV pressure decay (T) by plotting LV pressure versus negative dP/dt. LV diastolic filling was evaluated from peak and mean LV filling rate in group I and from peak and mean midwall lengthening rate in group 2. LV chamber and myocardial stiffness, respectively, remained unchanged before and after administration of propranolol (β=0·054 and 0·047) and verapamil (β = 14·8 and 12·6); however, the time constant of LV pressure decay T increased significantly in group I from 45 to 66 ms (P<0·05) and decreased significantly in group 2 from 53 to 43 ms (P<0·05). Parallel to the changes in LV isovolumic relaxation, mean LV diastolic filling rate decreased significantly in group 1 from 257 to 196 ml m−2 s−1 (P<0·025) and mean LV midwall lengthening rate increased significantly in group 2 from 2·37 to 4·31 cm/sec (P<0<05). It is concluded that LV diastolic stiffness remains unchanged in patients with HCM after propranolol and verapamil. LV relaxation and mean diastolic filling, however, are impaired in patients with HCM following propranolol but are improved after verapamil. Thus, the beneficial effect of verapamil on diastolic mechanics is related to improved relaxation and diastolic filling rather than to changes in LV diastolic stiffnes

Spontaneous course of aortic valve disease

The fate of patients with aortic valve disease of varying degrees of severity and the relationship between symptoms and haemodynamic status have been studied in 190 adults undergoing cardiac catheterization during the last two decades. During the follow-up period, 41 patients died and 86 underwent aortic valve replacement; these two events were the endpointsfor the calculation of ‘event-free' cumulative survival. First-year survival in haemodynamically severe disease was 60% in aortic stenosis and 96% in aortic regurgitation; in moderate and mild disease (in the absence of coronary artery disease) first-year survival was 100% in both groups. After 10 years, 9% of those with haemodynamically severe aortic stenosis and 17% of those with severe regurgitation were event-free, in contrast to 35% and 22%, respectively, of those with moderate changes and 85% and 75%, respectively, of those with mild abnormalities. In the presence of haemodynamically severe disease, 66% of the patients with stenosis and 14% of those with regurgitation were severely symptomatic (history of hear (failure, syncope or New York Heart Association class HI and IV); 23% of patients with moderate stenosis and 14% with moderate regurgitation were also severely symptomatic. Only 40% of those with disease that was severe both haemodynamically and symptomatically with either stenosis or regurgitation survived the first two years; only 12% in the stenosis group and none in the regurgitation group were event-free at 5 years. Patients with haemodynamically severe aortic stenosis who had few or no symptoms had a 100% survival at 2 years; the comparable figure for the aortic regurgitation group was 94%; 75% of the patients in the stenosis group and 65% in the regurgitation group were event-free at 5 years. In the moderate or mild stenosis and regurgitation groups there was no mortality within the first 2 years in the absence of coronary artery disease, regardless of symptomatic status. Haemodynamically and symptomatically severe aortic stenosis and regurgitation have a very poor prognosis and require immediate valve surgery. Asymptomatic and mildly symptomatic patients with haemodynamically severe aortic stenosis are at low risk and surgical treatment can be postponed until marked symptoms appear without a significant risk of sudden death. In severe aortic regurgitation, the decision for surgery should depend not only on symptoms but should be considered in patients with few or no symptoms because of risk of sudden death. In the absence of coronary artery disease, moderate aortic valve disease does not require valve operation for prognostic reason

Myocardial function and structure in aortic valve disease before and after surgery

Left ventricular (LV) micromanometry, cine-angiography and endomyocardial biopsies were performed in 13 patients with aortic valve disease {AVD) before and 12 to 28 months after successful valve replacement. (AVR). Patients with coronary artery disease were excluded. In nine patients (Group I: five AS, four AI) postoperative LV ejection fraction (EF) and total pressure Vmax were normal(EF ≥ 0.61; Vmax ≥ 1.50 ML/s). In four patients (Group II: three AS, one AT) postoperative EF (0.41) and Vmax (1.21 ML/s) were depressed. Pre-operative muscle fiber diameter (MFD; normal < 20 n) was 31 μ in Group I and 38 μ in Group II (P < 0.01). After AVR MFD decreased to 27 μ in Group I (P < 0.005) and to 28 μ in Group II (P < 0.02). Prior to surgery EF and Vmax showed no significant correlation with the LV fibrous content (FC in g/m2; FC = interstitial fibrosis in percent × LV angiographic muscle mass/100) in the 13 patients with AVD. After AVR, however, FC was related inversely to EF (P < 0.01, r = −0.69) and to Vmax (P < 0.025, r = −0.63). It is concluded that: (1) in AVD massive pre-operative fiber hypertrophy heralds impaired postoperative LV function; (2) fiber hypertrophy regresses following AVR regardless of the-LV functional state, and (3) the content of fibrous tissue appears to be a determinant of postoperative LV functio

Echocardiographic findings late after myectomy in hypertrophic obstructive cardiomyopathy

Postoperative echocardiograms of 50 patients undergoing myectomy for hypertrophic obstructive cardiomyopathy between 1965 and 1982 have been evaluated. In 21 patients a comparison with preoperative echocardiograms showed that postoperatively there was a significant reduction of septal and free wall thickness, an increase of left ventricular end-diastolic as well as outflow tract dimensions and a reduction or disappearance of systolic anterior motion of the mitral leaflet. Postoperative examination at intervals > 3 years revealed a significant increase of left ventricular and left atrial cavity size with unchanged contractile parameters and little reduction of left ventricular hypertrophy. In 4of 12 patients evaluated > 8 years after myectomy, left ventricular dilatation was observed and 3 of these 4 patients developed congestive heart failure. Development of leftventricular dilatation was independent of whether a transventricular and/or transaortic approach was used for myectomy. These data indicate that the late course after myectomy in hypertrophic obstructive cardiomyopathy may be complicated by dilatation of the left ventricular cavit

Physiologic or pathologic hypertrophy

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 20 mm Hg and/or cardiac index 2·5 l/mm/m2)interstitial fibrosis (IF) was increased to a similar extent (16 and 18%: normal <5%), whereas muscle fiber diameter (MFD normal ≤ 20 μ) was larger (P <0·05) in the patients with failure (30 μ) than in those with preserved function (27 μ). Moreover patients with depressed postoperative function had a larger (P < 001) preoperative MFD (35 μ) than those with normal postoperative function (30 μ). Seventeen months after successful aortic valve replacement IF increased (P < 0·02) and MFD decreased (P < 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 loa

Diltiazem alone and combined with nitroglycerin: effect on normal and diseased human coronary arteries

The vasodilatory effect of diltiazem and nitroglycerin on the large epicardial coronary arteries was evaluated in 26 patients with coronary artery disease. The luminal area of a normal and a stenotic coronary artery was determined at rest, after intracoronary administration of diltiazem, during submaximal exercise as well as 5 min after 1·6 mg sublingual nitroglycerin using biplane quantitative coronary arteriography. Twelve patients with no pretreatment prior to the exercise test served as group 1 (controls) and 14 patients with intracoronary administration of 2 to 3 mg diltiazem prior to the exercise test as group 2. Normal vessel: In the control group luminal area increased significantly during exercise (+23%, P<0·01) and after sublingual administration of nitroglycerin (+40%, P<0·001). In group 2 luminal area increased after intracoronary administration of diltiazem (+19%, P<0·01), during bicycle exercise (+23%, P<0·001) and after sublingual administration of nitroglycerin (+39%, P<0·001). Stenotic vessel: In the control group luminal area decreased significantly (−29%, P<0·001) during bicycle exercise but increased after sublingual administration of nitroglycerin at the end of the exercise test (+12%, NS vs. rest). In group 2 intracoronary administration of diltiazem was associated with a mild increase in stenosis area (+11%, P<0·05). There was a further increase in stenosis area during bicycle exercise (+23%, P<0·001 vs. rest) and after sublingual nitroglycerin (+32%, P<0·001). Coronary vasodilation of the stenotic segment was, however, significantly more pronounced after sublingual nitroglycerin in group 2 than 1 (+32% versus 12%, P<0·05). Thus, it is concluded that diltiazem prevents exercise-induced coronary vasoconstriction of the stenotic vessel segment probably due to its direct vasorelaxing action on the smooth vasculature. Diltiazem combined with nitroglycerin elicits an additive effect on coronary vasodilation of the stenotic vessel segments but not on the normal coronary arteries. The exact mechanism of this additive effect is not clear but might be due to the combined action of the two vasoactive drugs with different mode of actio

Determination of left ventricular systolic wall thickness by digital subtraction angiography

The accuracy of digital subtraction angiography (DSA) for determination of left ventricular (LV) systolic wall thickness and muscle mass was evaluated in 20 patients (mean age 50±11 years). Conventional LV angiograms were digitized and subtracted using a combined subtraction mode (‘mask mode' and ‘time interval difference' subtraction). Wall thickness and muscle mass were determined at end-diastole, after the first- and second-third of systole and at end-systole. M-mode echo- cardiography (Echo), which was obtainedfrom beam selection of the two-dimensional echocardiogram and conventional angiography (LVA), served as reference techniques. Angiographic LV wall thickness and muscle mass were determined according to the technique of Rackley in both, right (RAO) and left (LAO) anterior oblique projections, whereas echocardiographic wall thickness was measured just below the mitral valve orthogonal to the posterior wall (= LAO equivalent). Percent wall thickening was calculated in all patients. LV end-diastolic wall thickness and muscle mass correlated well between DSA and LVA (LV end-diastolic wall thickness in LAO projection r=0·72, biplane LV end-diastolic muscle mass r=0·83 LV end-systolic wall thickness (1·44 vs 1·33 cm, P<0·05) and percent wall thickening (52 vs 42%, P<0 comparedfavourably between echocardiography and DSA but was sign larger when echocardiographically measured than with DSA (LAO projection). DSA and echocardiography showed a good correlation in regard to LV end-diastolic and end-systolic wall thickness (correlation coefficient r=0·89, standard error of estimate SEE =0·15 cm or 13% of the mean value). There were only minimal changes in LV biplane muscle mass (DSA)from end-diastole to end-systole (+ 4%). It is concluded that both LV end-diastolic and end-systolic wall thickness and muscle mass can be determined accurately by DSA. Systolic wall thickening is systematically overestimated by M-mode echocardiography compared to DSA due to the overestimation of end-systolic wall thicknes

Determination of left ventricular wall thickness and muscle mass by intravenous digital subtractionangiocardiography: validation of the method

Left ventricular (LV) wall thickness and muscle mass are important measures of LV hypertrophy. In 24 patients LV end-diastolic wall thickness and muscle mass were determined (two observers) by digital subtraction angiocardiography (DSA) and conventional LV angiocardiography (LVA). Wall thickness was determined over the anterolateral wall of the left ventricle according to the technique of Rackley (method 1) or by planimetry (method 2). Seventeen patients were studied at rest and seven during dynamic exercise. Wall thickness correlated well between LVA and DSA; the best correlations were obtained by a combined subtraction mode using either method 1 or 2 (method 1, r≥0-80; method2, r≥0. 75). The standard error of estimate of the mean (SEE) was slightly lower for method 2 (≤ 10%) than for method 1 (≤ 13%). DSA significantly overestimated wall thickness by 5-7% with method 1 and underestimated by 12-14% with method 2. Muscle mass correlated well between LVA and DSA; the SEE was ≤ 15% for method 1 and≤ 12% for method 2. Overestimation of muscle mass by DSA was 7-11% with method 1 and underestimation was 13-15% with method 2.It is concluded that LV wall thickness can be determined accurately by DSA with an SEE ranging between 10 and 13%. Determination of LV muscle mass is slightly less accurate and the SEE is slightly larger ranging between 13 to 17%. With method 1, wall thickness and muscle mass were over estimated and with method 2 underestimate

Coronary vasomotor tone during static and dynamic exercise

Coronary vasomotion is an important determinant of myocardial perfusion in patients with angina pectoris, and it influences not only normal but also stenotic coronary arteries. The ability of a stenotic coronary artery to change its size is dependent on the presence of a normal musculo-elastic wall segment within the stenosis (i.e., eccentric stenosis). Coronary vasoconstriction of normal and stenotic coronary arteries has been reported by Brown and coworkers (Circulation 1984; 70: 18-24) during isometric exercise. The effect of dynamic exericse on coronary vasomotion was evaluated in one group of 13 patients with ischaemia-like symptoms and normal coronary arteries (group 1) and in a second group of 12 patients with coronary artery disease with exercise-induced angina pectoris (group 2). Luminal area of a normal and a stenotic vessel segment was determined by biplane quantitative coronary arteriography at rest, during supine bicycle exercise and 5 min after administration of 1·6 mg sublingual nitroglycerin. Coronary sinus blood flow was measured in group 1 at rest and after 0·5 mg kg−1 intravenous dipyridamole using coronary sinus thermodilution. Coronary flow reserve was calculated from coronary sinus flow after dipyridamole divided by coronary sinus flow at rest. In group 1, coronary vasodilation of the large (i.e., proximal) and the small (i.e., distal) coronary arteries was observed during exercise in seven patients (subgroup A). However, in the remaining six patients (subgroup B) coronary vasoconstriction of the small arteries (−24%, P<0·001) was found during exercise, whereas the large vessels showed coronary vasodilation (+26%, P<0·001). Coronary flow reserve was significantly (P<0·05) larger in subgroup A (mean 2·5) than in subgroup B (mean 1·2) with exercise-induced vasoconstriction of the small epicardial arteries. In group 2 vasodilation of the normal (+23%, P<0·001) and vasoconstriction of the stenotic coronary arteries (−29, P<0·001) was found during supine bicycle exercise. Administration of sublingual nitroglycerin at the end of the exercise test was accompanied by coronary vasodilation of both normal (+40%, P<0·001 vs rest) and stenotic (+12%, NS vs rest) vessel segments. It is concluded that isometric exercise is associated with reflex coronary vasoconstriction of the normal and stenotic vessel segments due to enhanced sympathetic stimulation. Dynamic exercise in patients with ischaemia-like symptoms and normal coronary arteries is accompanied by an abnormal dilatory response of the small coronary arteries in a subgroup of patients with reduced coronary flow reserve. Dynamic exercise in patients with coronary artery disease is, however, associated with coronary vasodilation of the normal and coronary vasoconstriction of the stenotic vessel segments. The nature of this exercise-induced vasoconstriction of stenotic coronary arteries is not clear, but might be related to endothelial dysfunction with an insufficient production of the endothelium-derived relaxing factor during exercis