Contractile and relaxation reserve of the left ventricle. IV. Patients with coronary heart disease (author's transl)

51 patients with coronary heart disease had exercise tests on a bicycle ergometer (86 +/- 32 watts). Compared to a normal control group, only 13 patients had normal contractile reserve (group 4.1). In 32 patients the increase in contractility during exercise was reduced (max dP/dt below 3200 mm Hg/s, group 4.2). Patients with reduced contractile reserve were graded according to the height of left ventricular enddiastolic pressure during exercise: In patients with grade 1, enddiastolic pressure was normal. In patients with grade 2, enddiastolic pressure increased between + 4 and + 15 mm Hg and in the patients with grade 3a a above + 15 mm Hg. Contractile and relaxation reserve decreased along with a rise in enddiastolic pressure and an increase in the complaints of the patients. Severe chest pain led to termination of exercise in patients of grade 3b. Enddiastolic pressure increased above + 15 mm Hg. During ischemia, peak-measured velocity of contractile elements (dP/dt/P) and the maximal rate of left ventricular pressure fall (min dP/dt) decreased. In conclusion, with increasing chest pain a decrease of contractile reserve was observed. Left ventricular enddiastolic pressure rose excessively. This has to be taken as a sign of myocardial failure due to ischemic dyskinesia and impeded relaxation.     

Contractile and relaxation reserve of the left ventricle. II. Patients with rheumatic valvular disease (author's transl)

The function of the left ventricle is important for the success of surgery. To differentiate between normal and abnormal ventricular function, the contractile and relaxation reserve was measured. In 19 patients, 10 with mitral and 9 with aortic valve disease, max dP/dt and min dP/dt were measured at rest and during exercise (ergometer). Max dP/dt increased in 7 patients above 3200 mm Hg/s and dP/dt/P above 60 s-1 (normal contractile reserve). Only 3 of these patients reached a normal increment of relaxation velocity (min dP/dt above 2400 mm Hg/s). In 12 patients the contractile and relaxation reserve was decreased. All patients with mitral stenosis had abnormal relaxation reserve despite normal contractile function in 4 cases. Left ventricular enddiastolic pressure did not correlate well with myocardial dysfunction. Isovolumic contractility during exercise was decreased in patients with aortic valve disease. Enddiastolic pressure increased from 18 +- 8 to 22 +- 14 mm Hg during exercise.     

Left ventricular relaxation in myocardial diseases. Hemodynamic study

Left ventricular relaxation as opposed to contraction, was studied by recordings of left ventricular pressure and its first derivation in primary hypertrophic cardiomyopathy without obstruction (25 cases, Group II) in primary dilated cardiomyopathy (33 cases, Group III) and in normal subjects (22 cases, Group I). Simultaneous recording of the pressure, the first derivation and intraventricular and intraaortic phonocardiogrammes showed the significance of certain features of the tracings and allowed a simplified protocol: ventricular relaxation was then defined from the pressure tracing (high fidelity recording) and its first derivation. The onset of isovolumic relaxation corresponded to the point of inflection on the descending part of the first derivation tracing, preceding its negative peak by an average of 0.02 s. The end of isovolumic relaxation corresponded to the crossing point of the atrial and ventricular pressure curves. In the absence of atrial pressure tracings the initial part of the rapid filling phase was included as far as the return of the first derivation tracing to its baseline (early diastole on the ventricular pressure tracing) as the duration of this period seemed remarkably constant (0.07 s). The parameters studied were: duration of isovolumic relaxation or the period defined above including the rapid filling phase; the average rate of fall of left ventricular pressure during this part of diastole; the value of the negative peak of the first derivation (dp/dt min); the rate of lengthening of the contractile elements at minimum dp/dt (dp/dt min/28P). Changes in relaxation were obvious in the pathological groups. The duration was increased and its average speed, dp/dt min, and dp/dt min/28 P were reduced. In the hypertrophic group, however, these changes seemed to be primary and contractility was usually unaffected. In dilated cardiomyopathy these changes could be considered secondary to decreased contractility. The hypothesis that changes in relaxation are specific for hypertrophic forms, and that changes in contractility are specific for dilated forms of primary cardiomyopathy may therefore be proposed.     

An analysis of pulsus alternans in aortic stenosis.

Pulsus alternans was studied hemodynamically in 5 patients with calcific aortic stenosis. Left ventricular function was assessed by angiographic volume analysis and by force-velocity analysis. All cases showed alternation of max and min dP/dt and kVmax. Inconsistent factors were an alternating left ventricular enddiastolic pressure, alternating left ventricular enddiastolic volume, alternating left ventricular endsystolic volume, ejection fraction, enddiastolic wall stress and wall stiffness. All cases had a high ventricular mass, but the critical value of ventricular mass or the ratio of mass to left ventricular enddiastolic volume were also inconsistent. Pulses alternans is primarily due to alternating contractility.     

Left-ventricular relaxation in patients with ischemic heart disease, congestive cardiomyopathy and mitral and aortic valve defects

Left ventricular relaxation was studied in 105 patients with coronary heart disease (CHD), 42 with mitral and aortic valvular diseases, and 14 with congestive cardiomyopathy. To assess the left ventricular relaxation, the values of dP/dt and T time constants for isovolumic exponential fall in intraventricular pressure were defined in the patients. Depressed left ventricular relaxation was found in the majority of the patients with CHD whatever the status of global and segmental pumping function of the left ventricle. Abnormal left ventricular relaxation turned out to be a characteristic feature in patients with congestive cardiomyopathy and valvular diseases that contributed to the generation of left ventricular overload by its pressure and volume. In CHD patients, depressed relaxation was accompanied by lower volume and slower early diastolic filling of the left ventricle.     

Effects of verapamil and nifedipine on rate of left ventricular relaxation in coronary arterial disease patients

We have evaluated the effects of nifedipine and verapamil on rate of left ventricular relaxation in 26 patients having coronary arterial disease with normal ejection fraction and normal left ventricular contractility. None of the patients had myocardial infarction. All patients showed normal contractile indices and abnormally high values of T constant, neg, dP/dt and left ventricular protodiastolic pressure, suggesting an impairment of left ventricular relaxation. Nifedipine, injected intravenously (15 micrograms/kg) in 14 patients induced a significant reduction of afterload parameters and an increase of contractility. Nifedipine also improved left ventricular relaxation, as it induced a reduction of the T constant from 42 +/- 2 msec to 33 +/- 2 msec (P less than 0.01). It induced a tendency to a reduction of negative dP/dt and protodiastolic pressure without reaching statistical significance. Verapamil, injected intravenously in the remaining 12 patients (0.1 mg/kg as a bolus followed by chronic infusion of 0.005 mg/kg/min for 3 min) induced a reduction of the T constant from 43 +/- 10 to 37 +/- 6 msec (P less than 0.01). It reduced the negativity of dP/dt from 2302 +/- 273 to 2021 +/- 252 mm Hg/sec (P less than 0.05) and of left ventricular protodiastolic pressure from 3.2 +/- 1.4 to 1.5 +/- 1.1 mm Hg (P less than 0.01). Verapamil, like nifedipine, reduced the afterload parameters although to a lesser extent. It did not substantially affect the left ventricular contractility. These data suggest that abnormalities of left ventricular relaxation may precede changes in systolic function and that nifedipine and verapamil favourably modify the indices of left ventricular diastolic function in patients with coronary arterial disease.     

Pressure-derived indices of left ventricular isovolumic relaxation in patients with hypertrophic cardiomyopathy.

High fidelity measurements of left ventricular pressure were made at increasing pacing rates in 21 patients with hypertrophic cardiomyopathy and a control group of 11 patients investigated for chest pain who proved to have normal hearts. In both groups the fall in pressure during isovolumic relaxation from the point of min dp/dt approximated closely to a monoexponential, and could be described by a time constant and asymptote. The time constant shortened and the asymptote increased as heart rate rose in both groups. The time constant was longer and min dp/dt less in the cardiomyopathy group than controls at all heart rates. In the cardiomyopathy patients min dp/dt, but not the time constant, was related to systolic pressure. During pacing, eight cardiomyopathy patients developed metabolic evidence of myocardial ischaemia, but indices of relaxation did not differ between these eight and the other 13 either at basal heart rate or the highest pacing rate. In 10 cardiomyopathy patients measurements were repeated at comparable pacing rates after propranolol (0.2 mg/kg). Left ventricular end-diastolic pressure and indices of contractility decreased after the drug, but the time constant did not change. Eight patients received verapamil (20 mg) after which there were substantial reductions in systolic pressure and contractility. Min dp/dt decreased in proportion to systolic pressure, but the time constant was unchanged. At the highest pacing rate before drug administration three patients had abnormal lactate extraction which was corrected by either propranolol (one patient) or verapamil (two patients). Despite abolition of metabolic evidence of ischaemia, relaxation did not improve. It is concluded that abnormal isovolumic relaxation is common in patients with hypertrophic cardiomyopathy, but its severity correlates poorly with other features of the disease. Abnormal relaxation is not the result of ischaemia, and pressure derived indices of relaxation do not improve after the administration of propranolol or verapamil.     

Correlation between left ventricular contractility and relaxation in patients with idiopathic dilated cardiomyopathy

Background and hypothesis: It is not fully understood whether alterations in left ventricular (LV) relaxation in patients with idiopathic dilated cardiomyopathy (DCM) precede or follow alterations in LV systolic function. Accordingly, we investigated the relationship between LV systole and diastolic relaxation in patients with DCM using LV pressure-volume analysis. Methods: Hemodynamic data were collected for 38 consecutive patients with DCM in normal sinus rhythm and in the resting steady state (New York Heart Association functional class II to III). Continuous simultaneous pressure-volume relationships were obtained by conductance catheter. Left ventricular end-systolic elastance (Ees) was determined during transient occlusion of the inferior vena cava. Results: Left ventricular ejection fraction, peak negative dP/dt, and peak positive dP/dt were depressed (31 ± 11%, - 1242 ± 351 mmHg/s, and 1118 ±253 mmHg/s, respectively ). The LV end-diastolic volume index, the time constants of isovolumic LV pressure decay Tl and Td were increased (141 ±38 ml/m², 54+14 ms, and 69 ± 17 ms, respectively). Ees was markedly depressed (0.9 ± 0.5 mmHg/ml) and was not correlated with established systolic or diastolic indices except for peak positive dP/dt. Our results showed that abnormalities of relaxation were not correlated with contractile dysfunction in patients with DCM in the resting steady state however, most patients (79%) had both prolonged relaxation and extremely depressed contractility. Abnormal relaxation may have been transient or compensated in some patients (21%) with DCM who had preserved relaxation despite severely depressed contractility.     

Left atrial and left ventricular diastolic function during acute myocardial ischaemia.

OBJECTIVE--To study indices of diastolic left ventricular function during the first few seconds of myocardial ischaemia. DESIGN--Isovolumic and total relaxation times and left atrial and left ventricular dP/dt were identified from high fidelity (micromanometer) pressure recordings in the left ventricle and left atrium during percutaneous transluminal angioplasty of the left anterior descending coronary artery. PATIENTS--20 patients with isolated disease of the left anterior descending artery and normal left ventricular function. RESULTS--The isovolumic relaxation time lengthened during the first seven to nine seconds of ischaemia; then it shortened by an average of 15% up to the twentieth second, initially as a result of increased left atrial contractility and subsequently because of impaired ventricular relaxation. Ventricular ischaemia resulted in impaired left ventricular diastolic compliance, as shown by an increase in the total relaxation time, before there was evidence of systolic impairment. Minimum dP/dt decreased progressively (by -37% at the twentieth second of ischaemia), whereas maximum dP/dt fell only after 20 seconds of ischaemia (by -11%). CONCLUSIONS--Relaxation and filling of the left ventricle (indices of diastolic function) are more sensitive to myocardial ischaemia than myocardial contractility and systolic function. Left atrial contractility increases during left ventricular ischaemia.     

Cardiovascular effect of [3,4-dihydro-8-(2-hydroxy-3-isopropylaminopropoxy)-3-nitrato-2H-1-benzopyran] (K 351)

Cardiovascular effect of a new compound, K 351, was examined in anesthetized dogs. Intravenous injections of 100 micrograms/Kg or over of K 351 caused a fall in systemic blood pressure, reduced peripheral vascular resistance, left ventricular enddiastolic pressure, max dP/dt and Vmax, and increased time constant T and PQ interval. Heart rate was reduced with 1 microgram/Kg K 351. The magnitudes of the changes in heart rate, T and PQ interval were not different between K 351 and propranolol groups, while those in max dP/dt and Vmax caused by K 351 were larger than those induced by the same doses of propranolol. It is suggested that K 351 suppressed left ventricular contractility, sinus node activity and atrioventricular conduction through its beta-receptor blocking action and reduced peripheral vascular resistance and left ventricular enddiastolic pressure through its vasodilating action.     

Acute haemodynamic and metabolic effects of felodipine in congestive heart failure.

Felodipine is a new calcium antagonist with a high degree of vascular selectivity. To examine its potential value as an afterload reducing agent in congestive heart failure 11 patients were studied. Substantial increments in cardiac index were associated with a fall in systemic vascular resistance. Left ventricular end diastolic pressure was also significantly reduced. Although left ventricular maximum dP/dt remained unchanged, maximum dP/dt/P increased. Left ventricular unloading was reflected by a reduction in cavity dimensions and a shift in the relation between end systolic pressure and dimension downwards and to the left. The myocardial oxygen supply to demand ratio was also improved: coronary sinus flow increased significantly despite a decline in myocardial oxygen consumption. These beneficial haemodynamic and metabolic effects suggest that felodipine may extend the clinical application of calcium antagonists to include the treatment of congestive heart failure.     

Beta-adrenergic stimulation with isoproterenol enhances left ventricular diastolic performance in hypertrophic cardiomyopathy despite potentiation of myocardial ischemia. Comparison to rapid atrial pacing

Impaired left ventricular relaxation and filling is an important pathophysiologic mechanism in hypertrophic cardiomyopathy. To determine whether isoproterenol, known to improve relaxation in isolated cardiac muscle, could favorably modify this effect, we assessed simultaneous left ventricular volume and regional systolic asynchrony (by radionuclide angiography), left ventricular pressure (by micromanometer catheters), and lactate metabolism in 12 patients with hypertrophic cardiomyopathy. Pressure-volume relations were studied during atrial pacing stress to induce myocardial ischemia and during isoproterenol infusion to similar heart rates. Angina occurred in 10 patients with pacing and in 11 patients during isoproterenol infusion; lactate consumption was reduced in nine patients during isoproterenol compared with pacing, including five patients who produced lactate with isoproterenol. During isoproterenol compared with pacing, peak left ventricular pressure was higher (205 +/- 33 vs. 142 +/- 21 mm Hg, p less than 0.001), ejection fraction was higher (77 +/- 10% vs. 71 +/- 12%, p less than 0.02), and regional systolic nonuniformity was diminished. Despite ischemia, these changes in load and nonuniformity during isoproterenol were associated with enhanced diastolic function compared with pacing tachycardia: isoproterenol reduced T 1/2, the half-time of pressure decline after peak negative dP/dt (from 46 +/- 10 to 33 +/- 6 msec, p less than 0.001), shifted the diastolic pressure-volume curve downward and rightward in 10 of 12 patients, and increased end-diastolic volume (from 77 +/- 18% to 100 +/- 11% of control values, p less than 0.001) with no change in end-diastolic pressure (19 +/- 7 to 19 +/- 5 mm Hg, p = NS). Thus, despite ischemia, isoproterenol improved left ventricular relaxation and filling compared with tachycardia in the absence of beta-adrenergic stimulation. Although isoproterenol is detrimental in hypertrophic cardiomyopathy by provoking ischemia, these data suggest that the adverse effects of ischemia on ventricular relaxation and distensibility may be alleviated by beta-adrenergic stimulation, possibly as a result of enhanced inactivation and restored load sensitivity.     

Usefulness of exercise-induced changes in plasma levels of brain natriuretic peptide in predicting right ventricular contractile reserve after repair of tetralogy of Fallot

Elevated levels of brain natriuretic peptide (BNP) have been associated with ventricular dysfunction, and exercise tests have been used for assessing cardiac contractile reserve. We examined the relation between BNP and right ventricular (RV) contractile reserve during exercise in patients after repair of tetralogy of Fallot (TOF). A total of 45 patients, 26 of whom underwent repair of TOF at 2 to 3 years of age and 19 age-matched healthy children, were studied. Plasma levels of BNP were measured at baseline and at maximal exercise. Echocardiography combined with tissue Doppler imaging (TDI) was performed at rest and during supine bicycle submaximal exercise. The peak value of the first derivation of RV pressure (peak dP/dt) was measured by the continuous-wave Doppler method. The severity of pulmonary regurgitation (PR) (mild, moderate, or severe) was based on color Doppler findings. Plasma BNP levels were significantly higher in patients with TOF than in controls (44 +/- 34 vs 6 +/- 4 pg/ml, p <0.01). Exercise was associated with increased plasma BNP levels in both groups. A larger increment in BNP was noted in patients with TOF than in normal subjects (15 +/- 12 vs 2 +/- 2 pg/ml, p <0.01). The peak systolic myocardial velocity (Sa) and peak dP/dt values increased significantly in both groups during exercise; however, the magnitude of increase in both of these values was significantly less in patients with TOF than in controls (36 +/- 19% vs 70 +/- 19% and 42 +/- 11% vs 81 +/- 12%, respectively; p <0.01). There were significant correlations between the increment in BNP and changes in Sa and peak dP/dt values (r = -0.67 and -0.53, p <0.01, respectively), and the severity of PR (r = 0.74, p <0.01). Thus, exercise increases plasma levels of BNP, and greater increases are associated with impaired RV contractile reserve in patients with TOF with various degrees of PR.     

Hypertrophic nonobstructive cardiomyopathy: A precise assessment of hemodynamic characteristics and clinical implications

A precise assessment of left ventricular function was performed in 20 patients with hypertrophic nonobstructive cardiomyopathy to elucidate the basic pathophysiology and the data were compared with those In 22 normal subjects. Whereas end-diastolic pressure was high in those with cardiomyopathy, a more accurate Index of preload, end-diastolic stress, did not differ from normal value. Afterload was about half the normal value. Both isovolumic indexes [peak positive dP/dt and (dP/dt)/DP₄₀] and ejection phase indexes of contractility (ejection fraction) were in the normal range; however, the end-systolic stress volume ratio was significantly reduced (43% of the normal value). Although the left ventricular minute work index was in the normal range, the unit muscle performance (minute work/mass) was very low (49%). An abnormality of left ventricular relaxation was demonstrated by low peak negative dP/dt (56 %) and prolonged time constant T (191 %) and a stiff left ventricle was demonstrated by a high diastolic elastic stiffness constant (129%).These observations suggest that the contraction of a unit muscle is inappropriate to produce an adequate contraction of the whole ventricle and that hypertrophy might be an adaptive process to maintain normal systolic function by increasing mass and reducing afterload.     

Coronary disease. II. Analysis of diastolic pressure-volume correlations and left ventricular elasticity in 110 patients]

Left ventricular pressure-volume relationships as well as diastolic compliance were determined in 110 patients with coronary heart disease during routine right and left heart catheterization, coronary angiography and ventriculography. 1. Enddiastolic and endystolic volume of the left ventricle were increased in severe coronary heart disease dependent on the degree of coronary stenosis; left ventricular ejection fraction was consecutively reduced. 2. Left ventricular enddiastolic pressure, diastolic pressure difference and diastolic rate of pressure rise were increased in corrleation with coronary artery stenosis. In contrast, last diastolic volume inflow into the left ventricle was nearly the same in all groups. Left ventricular stiffness, expressed as dP/dV, was significantly increased dependent on the severity degree of coronary artery disease. 3. Diastolic pressure-volume relationships revealed greater steepness in coronary artery disease, significantly dependent, on the corresponding severity degree. 4. Hemodynamic measures (stroke volume, cardiac index, ejection fraction) were decreased parallel to the increased left ventricular wall stiffness. The results demonstrated decreased left ventricular compliance in coronary heart disease. There was a striking correlation between the severity degree of coronary heart disease and the decrease of left ventricular compliance. Validity and limitations of the techniques of estimating left ventricular compliance from diastolic pressures and volumes as well as the effects of a decrease of left ventricular compliance on cardiac mechanics are discussed.     

Ventricular and myocardial function in aortic regurgitation (author's transl)]

The influence of chronic volume load on ventricular function and myocardial load and shortening was investigated in 10 patients with chronic aortic regurgitation by means of biplane ventriculography and simultaneous pressure measurements. The regurgitant fraction was 63 +/- 15 per cent. Enddiastolic volume (EDVI 227 +/- 37 ml/m2), systolic (161 +/- 18 mm Hg) and enddiastolic ventricular pressure (30 +/- 12 mm Hg) were elevated, ejection fraction was reduced (54 +/- 7 per cent). Myocardial mass related to EDV was normal (1.2 +/- 0.2 g/ml). Contractility as measured from dp/dt max (1736 +/- 492 mm Hg s-1) and dp/dtmax/PI (22.2 +/- 4.3 s-1) was slightly reduced. Mean velocity of equatorial midwall fiber shortening VMW 0.45 +/- 0.13 cir X s-1) was significantly diminished, equatorial midwall fiber stress during ejection (sigma tej 267 +/- 44.5 X 10(3) dyn X cm-2) was elevated. In spite of a very high enddiastolic stress (sigma ED 96 +/- 36 X 10(3) dyn X cm-2) mean systolic power (sigma tej X VMX 123 +/- 43.2 X 10(3) dyn X cm-2 X s-1) was normal. Compensation of chronic volume load in aortic regurgitation is not compensated by an increased contractility but by ventricular enlargement and a pronouned increase in preload. Myocardial load and shortening in chronic aortic regurgitation are altered in the same way (increased stress and reduced shortening) as in chronic pressure overload.     

Left ventricular relaxation in lone atrial fibrillation and atrial fibrillation with heart disease]

Atrial fibrillation with organic heart disease shows a steady value for the time constant of left ventricular isovolumetric relaxation (TC), whereas left ventricular contractility varies from beat to beat. However, there is no report on left ventricular relaxation in lone atrial fibrillation. This study assessed left ventricular relaxation in 5 patients with lone atrial fibrillation, 3 with ischemic heart disease and one with hypertrophic cardiomyopathy. Left ventricular pressure was recorded at 3 msec intervals, with a high fidelity micromanometer-tipped catheter. Maximal positive dP/dt (dP/dtmax) and TC of isovolumetric left ventricular relaxation period [P(t) = (P0-P infinity) exp (-t/TC) + P infinity] were measured as indices of left ventricular contractility and left ventricular relaxation, respectively. Correlation coefficients of dP/dtmax and TC versus the ratio of the preceding to the pre-preceding RR-interval (RR2/RR1) were calculated. A good correlation was found between dP/dtmax and RR2/RR1 in all patients (r = 0.71-0.84, p < 0.0001). No correlation between TC and RR2/RR1 was found in patients with atrial fibrillation with organic heart disease, but a good correlation was found between TC and RR2/RR1 in patients with lone atrial fibrillation (r = 0.74-0.95, p < 0.0001). The correlation between TC and RR2/RR1 is well preserved in lone atrial fibrillation. The mechanism of the variation of TC with the RR2/RR1 interval in lone atrial fibrillation may be similar to the change of TC in postextrasystolic potentiation, which is attributed to the change of intracellular Ca2+ concentration. Absence of correlation between TC and RR2/RR1 interval may indicate that left ventricular relaxation is disturbed in patients with atrial fibrillation with organic heart disease.     

Left ventricular regional relaxation and its nonuniformity in hypertrophic nonobstructive cardiomyopathy

BACKGROUND. Regional nonuniformity has been suggested to be closely related to left ventricular (LV) relaxation in diseased heart. The purpose of the present study was to assess LV global and regional relaxation in patients with nonobstructive hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS. Left ventriculography was conducted simultaneously with pressure micromanometry in 10 normal control subjects and 11 patients with nonobstructive HCM. LV silhouettes in the right anterior oblique projection were divided into eight regions, and regional wall stress during isovolumic relaxation was computed for six regions from the midventricle to the apex. In HCM patients, isovolumic relaxation time (IRT) and the time constant of LV pressure decrease (Tp) were greater than in control subjects (IRT, 84 +/- 13 versus 66 +/- 6 msec; Tp, 51 +/- 8 versus 36 +/- 5 msec, respectively; p less than 0.01). In HCM patients, the (-)dP/dt upstroke pattern was convex-downward, and dP/dt(20/60), the ratio of dP/dt values 20 and 60 msec after peak (-)dP/dt, was less than in control subjects (1.46 +/- 0.16 versus 2.15 +/- 0.14, p less than 0.01). These findings suggest that there is impaired LV relaxation in HCM patients. End-systolic regional wall stress was lower, and the time constant of regional stress decrease (Tst) was prolonged for each region in HCM patients compared with control subjects. In the HCM group, Tst tended to be more prolonged in regions with increased wall thickness than in regions with normal wall thickness (60 +/- 15 versus 50 +/- 11 msec, p less than 0.01). The coefficient of variation for Tst values in six areas of the left ventricle was calculated in each subject and was greater in HCM patients than in control subjects (13 +/- 7% versus 7 +/- 3%, p less than 0.05), indicating regional nonuniformity in Tst during isovolumic relaxation in HCM patients. CONCLUSIONS. Significant correlations existed between the coefficients of variation for Tst and Tp (r = 0.80, p less than 0.01), IRT (r = 0.79, p less than 0.01), and dP/dt(20/60) (r = -0.67, p less than 0.05) in the HCM group. Thus, regional nonuniformity is closely related to the impairment of LV relaxation in HCM.     

Cardiac nitric oxide production due to angiotensin-converting enzyme inhibition decreases beta-adrenergic myocardial contractility in patients with dilated cardiomyopathy

OBJECTIVES: This study tested the hypothesis that angiotensin-converting enzyme (ACE) inhibitors attenuate beta-adrenergic contractility in patients with idiopathic dilated cardiomyopathy (DCM) through nitric oxide (NO) myocardial signaling. BACKGROUND: The ACE inhibitors increase bradykinin, an agonist of NO synthase (NOS). Nitric oxide inhibits beta-adrenergic myocardial contractility in patients with heart failure. METHODS: The study patients were given the angiotensin-1 (AT-1) receptor antagonist losartan for one week. The hemodynamic responses to intravenous dobutamine were determined before and during intracoronary infusion of enalaprilat (0.2 mg/min) with and without the NOS inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 5 mg/min). RESULTS: In patients with DCM (n = 8), dobutamine increased the peak rate of rise of left ventricular pressure (+dP/dt) by 49 +/- 8% (p < 0.001) and ventricular elastance (Ecs) by 53 +/- 16% (p < 0.03). Co-infusion with enalaprilat decreased +dP/dt to 26 +/- 12% and Ecs to -2 +/- 17% above baseline (p < 0.05), and this anti-adrenergic effect was reversed by L-NMMA co-infusion (p < 0.05 vs. enalaprilat). In addition, intracoronary enalaprilat reduced left ventricular end-diastolic pressure (LVEDP), but not left ventricular end-diastolic volume, consistent with increased left ventricular distensibility. Infusion with L-NMMA before enalaprilat in patients with DCM (n = 5) prevented the reduction in +dP/dt, Ecs and LVEDP. In patients with normal left ventricular function (n = 5), enalaprilat did not inhibit contractility or reduce LVEDP during dobutamine infusion. CONCLUSIONS: Enalaprilat attenuates beta-adrenergic contractility and enhances left ventricular distensibility in patients with DCM, but not in subjects with normal left ventricular function. This response is NO modulated and occurs in the presence of angiotensin receptor blockade. These findings may have important clinical and pharmacologic implications for the use of ACE inhibitors, AT-1 receptor antagonists and their combination in the treatment of heart failure.