Function of the right ventricle in patients with dilated cardiomyopathy]

To analyze right-ventricular size and function and their relationship to left-ventricular dimensions in patients with dilated cardiomyopathy (DCM), biplane cineventriculography was performed in 57 patients. The results were compared to 15 normals (N). In patients dilatation of the right ventricle (RVEDVI: DCM: 126.5 +/- 41.4 ml/m2, N: 90.5 +/- 9.2 ml/m2, 2 p < 0.05) was less pronounced than dilatation of the left ventricle (LVEDVI: DCM: 136.0 +/- 45.8 ml/m2, N: 76.7 +/- 7.9 ml/m2, 2 p < 0.05). Left-ventricular ejection fraction (LVEF: DCM: 36.1 +/- 10.2%, N: 64.4 +/- 3.8%, 2 p < 0.05) was more reduced than right-ventricular ejection fraction (RVEF: DCM: 39.7 +/- 11.5%, N: 58.3 +/- 3.3%, 2 p < 0.05). Concerning the individual patient, a good correlation was found between right- and left-ventricular stroke volume (r = 0.74), whereas ejection fraction (r = 0.58), enddiastolic (r = 0.52) and endsystolic volume (r = 0.55) of the left and right ventricle correlated only moderately. Twenty-three of the 57 patients showed pronounced differences between right- and left-ventricular ejection fraction. The difference RVEF-LVEF was < = -10% in six patients, i.e., right-ventricular ejection fraction was markedly more reduced than left-ventricular ejection fraction. Right-ventricular myocardial biopsy was performed in five of these six patients with histologic evidence of dilated cardiomyopathy and, also, no signs of right-ventricular dysplasia (no lipomatous tissue replacement).(ABSTRACT TRUNCATED AT 250 WORDS)     

Left ventricular regional function in patients with dilated cardiomyopathy (computerized echocardiographic data)

Computerized echography was used to assess left-ventricular dysfunction in 40 patients with dilatation cardiomyopathy (DCM). The so-called "floating" system was shown to be the most acceptable model for the correction of DCM-associated superposition. An original system was used for segment division by two- and four-chamber projections. Total left-ventricular hypokinesia and a significant reduction of the total ejection fraction (32.5 +/- 1.9%) were demonstrated.     

Combined effect of the force-frequency and length-tension mechanisms on left ventricular function in patients with dilated cardiomyopathy

BACKGROUND: The myocardial length-tension and the force-frequency relations are important mechanisms that regulate the contractile strength of the heart. AIMS: To evaluate in humans the effect on left ventricular function of the interaction between the myocardial length-tension and force-frequency relations. METHODS AND RESULTS: Eight patients with dilated cardiomyopathy (DCM) and 6 control subjects underwent radionuclide monitoring of left ventricular function during atrial pacing, saline loading and atrial pacing at the end of saline loading. In controls, atrial pacing reduced left ventricular end-diastolic (P < 0.001) and end-systolic volumes (P < 0.001) with no change in ejection fraction whereas after volume expansion end-diastolic volume (P < 0.001) and ejection fraction (P < 0.001) increased. Atrial pacing after volume expansion increased ejection fraction (P < 0.05). In patients with DCM, ejection fraction was reduced during atrial pacing (P < 0.001) and volume expansion (P < 0.05) due to an increase in left ventricular end-systolic volume (P < 0.001). Pacing tachycardia after volume expansion further increased end-systolic volume and reduced ejection fraction with a significant 'pacing by load' interaction (P < 0.001). Peak filling rate increased at each step in controls while it remained unchanged in patients with DCM. CONCLUSION: The heart rate increase during left ventricular distension improves ventricular function in normals and has detrimental effects in patients with DCM.     

Iodine-123 phenylpentadecanoic acid and single photon emission computed tomography in identifying left ventricular regional metabolic abnormalities in patients with coronary heart disease: comparison with thallium-201 myocardial tomography

Iodine-123 phenylpentadecanoic acid (IPPA) is a synthetic long chain fatty acid with myocardial kinetics similar to palmitate. Two hypotheses were tested in this study. The first hypothesis was that IPPA imaging with single photon emission computed tomography (SPECT) is useful in the identification of patients with coronary artery disease. Fourteen normal volunteers (aged 27 +/- 2 years) and 33 patients (aged 54 +/- 11 years) with stable symptomatic coronary artery disease and at least one major coronary artery with luminal diameter narrowing greater than or equal to 70% were studied with symptom-limited maximal exercise testing. The IPPA (6 to 8 mCi) was injected 1 min before the termination of exercise, and tomographic imaging was performed beginning at 9 min and repeated at 40 min after the injection of IPPA. Nine of the normal volunteers and 13 of the patients had a second examination performed at rest on another day. Using the limits of normal as 2 SD from the normal mean values, 27 of the 33 patients with coronary artery disease demonstrated abnormalities in either the initial distribution or the clearance of IPPA, or both. Nineteen of the 33 patients had a maximal variation of activity distribution of greater than or equal to 25% on the 9 min IPPA images. Twenty-two of the 33 patients had a maximal variation in IPPA washout greater than 17% and 17 had a washout rate less than or equal to 2%. There was good agreement between the location of significant coronary artery stenoses and abnormalities in the initial distribution and clearance of IPPA. The second hypothesis tested was that IPPA imaging is as or more sensitive and, therefore, complementary to thallium-201 imaging in the identification of exercise-induced ischemia in patients. Twenty-five of the 33 patients underwent both thallium-201 and IPPA tomographic imaging after symptom-limited maximal exercise testing. The amount of exercise performed by each patient during both studies was similar. Twenty-one of the 25 patients had abnormal IPPA tomographic studies, whereas 18 had abnormal thallium-201 tomographic studies (p = NS). The results of this study suggest the following conclusions: 1) iodine-123 phenylpentadecanoic acid imaging using single photon emission computed tomography and exercise provides a sensitive and relatively noninvasive method for identifying abnormalities in myocardial metabolism associated with significant coronary artery stenoses, and 2) iodine-123 phenylpentadecanoic acid is at least as sensitive as thallium-201 for this purpose using tomographic imaging and exercise testing.     

Iodine-123 phenylpentadecanoic acid myocardial scintigraphy in patients with left ventricular hypertrophy: alterations in left ventricular distribution and utilization

Regional alterations in myocardial substrate uptake and/or utilization have been demonstrated in rats with hypertension. To determine whether alterations in left ventricular fatty acid uptake and/or utilization are present in patients with left ventricular hypertrophy (LVH), we compared the results of rest and exercise iodine-123 phenylpentadecanoic acid (IPPA) myocardial scintigraphy in 10 patients with hypertension who had concentric LVH without evidence of coronary artery disease and in 15 normal subjects. Patients with LVH had more heterogeneous left ventricular activity of IPPA compared to normal subjects after exercise but not at rest (23 +/- 8% versus 13 +/- 5% difference in maximum segmental activity at 4 minutes after exercise; p = 0.005). Although IPPA clearance was similar in both patients with LVH and normal subjects, postexercise washout in segments showing decreased initial IPPA uptake was reduced compared to washout at rest in patients with LVH (11.7 +/- 7.5% versus 21.5 +/- 8.4% at 20 minutes after injection, n = 15; p = 0.005). Exercise thallium-201 (TI-201) scintigraphy was normal in all seven patients with LVH tested. Patients with LVH showed significantly greater heterogeneity in IPPA uptake compared to TI-201 uptake immediately after exercise (25 +/- 5% versus 16 +/- 6%; p = 0.013). We conclude that (1) compared to normal subjects, patients with LVH show heterogeneous myocardial IPPA activity after exercise but not at rest; (2) postexercise washout of IPPA was decreased in segments with reduced uptake after exercise in patients with LVH; and (3) the distribution of IPPA is more heterogeneous than that of TI-201 immediately after exercise in patients with concentric LVH. The postexercise heterogeneity in IPPA uptake and delayed washout in segments with reduced initial uptake is consistent with exercise-induced myocardial ischemia in patients with LVH.     

Effect of beta-blocker therapy on myocardial perfusion defects in thallium-201 scintigraphy in patients with dilated cardiomyopathy

BACKGROUND: The beneficial effects of beta-blocker therapy in patients with heart failure have been confirmed. However, the effects of beta-blockers on myocardial perfusion defects are unclear. The aim of this study was to evaluate the effect of beta-blockers on myocardial perfusion defects estimated by thallium-201 myocardial scintigraphy in patients with dilated cardiomyopathy (DCM) and to investigate the relationships between beta-blocker treatment and myocardial damage and cardiac function. METHODS:201Tl and echocardiography were performed in 37 patients before and after 6 months of beta-blocker therapy. Extent score (ES) by 201Tl was used to quantitate myocardial perfusion defects before and after treatment. RESULTS: ES was significantly decreased by beta-blocker therapy. According to the change in ES, DCM patients were classified into three groups, patients who improved, patients showing no change and patients who deteriorated. In the improvement and no-change groups, beta-blocker therapy induced a reduction in left ventricular dimensions and an associated increase in ejection fraction. However, in the deterioration group, left ventricular dimensions and ejection fraction were unchanged. There was a significant relationship between the change in left ventricular dimension at end-diastole and the change in ES. CONCLUSIONS: beta-Blocker therapy could attenuate myocardial perfusion defects in some patients with DCM. The improvement in left ventricular function associated with beta-blocker therapy may be related to the attenuation in myocardial perfusion defects.     

Global and regional diastolic filling dynamics in compensated dilated cardiomyopathy

To assess the left ventricular (LV) global and regional (anterior, apical, inferior) diastolic filling dynamics in compensated dilated cardiomyopathy (DCM), we measured left ventricular pressure and instantaneous volume from angiography in 7 normal controls (CTL) and 6 DCM patients with sinus rhythm. Global and regional peak filling rate (PER), time constant of LV pressure decline (T; Weiss's method) and LV chamber stiffness (k; Gaasch's method) were calculated. In DCM, left ventricular end-diastolic volume (ml/m2) was larger than in CTL (137 +/- 29 vs. 74 +/- 6, p less than 0.001), and stroke index (ml/m2) was not different from CTL (46 +/- 14 vs. 46 +/- 8, NS), indicating a compensated state of LV. Mitral valve opening pressure (mmHg) tended to increase in DCM compared with CTL (12 +/- 6 vs. 8 +/- 4). Global PFR (ml/sec/m2) (CTL = 216 +/- 47 vs. DCM = 201 +/- 36) and k (CTL = 0.044 +/- 0.023 vs. DCM = 0.029 +/- 0.016) were not different between 2 groups. However, T (msec) was markedly prolonged in DCM compared with CTL (61 +/- 10 vs. 35 +/- 5, p less than 0.001). In CTL, regional PFR (1/sec) showed almost the same values in each region, but in DCM, apical region showed higher PFR than in other regions. Thus, early diastolic filling might play an important role in maintaining the total transmitral flow in DCM despite severe impairment of LV relaxation. This compensation could be related mainly to accelerated regional lengthening of the LV apical region.     

Heart rate variability in idiopathic dilated cardiomyopathy: relation to disease severity and prognosis.

OBJECTIVE: To assess the clinical importance of heart rate variability (HRV) in patients with idiopathic dilated cardiomyopathy (DCM). PATIENTS AND METHODS: Time domain analysis of 24 hour HRV was performed in 64 patients with DCM, 19 of their relatives with left ventricular enlargement (possible early DCM), and 33 healthy control subjects. RESULTS: Measures of HRV were reduced in patients with DCM compared with controls (P < 0.05). HRV parameters were similar in relatives and controls. Measures of HRV were lower in DCM patients in whom progressive heart failure developed (n = 28) than in those who remained clinically stable (n = 36) during a follow up of 24 (20) months (P = 0.0001). Reduced HRV was associated with NYHA functional class, left ventricular end diastolic dimension, reduced left ventricular ejection fraction, and peak exercise oxygen consumption (P < 0.05) in all patients. DCM patients with standard deviation of normal to normal RR intervals calculated over the 24 hour period (SDNN) < 50 ms had a significantly lower survival rate free of progressive heart failure than those with SDNN > 50 ms (P = 0.0002, at 12 months; P = 0.0001, during overall follow up). Stepwise multiple regression analysis showed that SDNN < 50 ms identified, independently of other clinical variables, patients who were at increased risk of developing progressive heart failure (P = 0.0004). CONCLUSIONS: HRV is reduced in patients with DCM and related to disease severity. HRV is clinically useful as an early non-invasive marker of DCM deterioration.     

Combined thallium-201 and dynamic iodine-123 iodophenylpentadecanoic acid single-photon emission computed tomography in patients after acute myocardial infarction with effective reperfusion

BACKGROUND: Considerable derangements of energy metabolism are to be expected during ischemia and reperfusion. In ischemic myocardium, the oxidative degradation of carbohydrates is shifted toward the anaerobic production of lactate and the oxidation of fatty acids is suppressed. HYPOTHESIS: The aim of this study was to examine the uptake and metabolism of iodine-123 (123I) iodophenylpentadecanoic acid (IPPA) in stunned myocardium. METHODS: In 15 patients, SPECT with 201Tl and 123I IPPA as well as echocardiography with low-dose dobutamine stimulation were performed 12 +/- 5 days after myocardial infarction with reperfusion. Follow-up echocardiography was carried out 24 +/- 8 days later for documentation of functional improvement. Uptake of 201Tl and 123I IPPA were obtained in five left ventricular segments, and dynamic SPECT imaging was used for calculation of the fast and the slow components of the biexponential myocardial 123I IPPA clearance. RESULTS: Wall motion improved in 14 of 26 dysfunctional segments (54%). Stunned segments were characterized by a reduced 123I IPPA extraction, a shorter half-life of the fast, and a longer half-life of the slow clearance component. All parameters of the combined 201Tl/123I IPPA study predicted functional recovery with similar accuracies (area under the receiver operator characteristic curves between 0.68 and 0.76; p = NS). Analysis of 201Tl uptake alone could not predict functional recovery in this study. CONCLUSIONS: Stunned myocardium is characterized by a disturbance of fatty acid metabolism. For prediction of functional improvement, 123I IPPA imaging added significant diagnostic information.     

Left ventricular electromechanical latency period is an additional indicator to upgrade from right to biventricular DDD pacing

In DDD pacing, the left-ventricular electromechanical latency period defines the duration between premature ventricular stimulation and the prematurely ending left-atrial contribution to left-ventricular filling. It has to be considered in diastolic AV delay optimization. Individual duration of this parameter seemed to reflect the ventricular function. Therefore, we compared the left-ventricular electromechanical latency period due to right ventricular stimulus with the documented ejection fraction of two groups, 33 congestive heart failure patients carrying biventricular systems and 13 right ventricular paced bradycardia patients. A mean latency period of 168+/-26 ms was found in the heart failure patients (ejection fraction: 25+/-5%) which was significantly longer (p=0.0039) compared to the bradycardia patients (ejection fraction: 51+/-12%) with a mean latency of 119+/-13 ms. Thus, an increasing latency period during right ventricular DDD pacing therapy indicates decreasing ejection fraction. A cut-off interval of 135 ms allowed the discrimination of 93% of our patients as having an individual ejection fraction of either up to 35% or above. Thus, the left ventricular electromechanical latency period can be used as an additional parameter indicating the necessity to upgrade from right to biventricular DDD pacing.     

Effect of bypass operation and balloon angioplasty on heart function at rest]

Improvement of exercise left-ventricular ejection fraction after successful aortocoronary bypass operation and transluminal coronary angioplasty has been demonstrated. The purpose of this study was to investigate in which patients improvement of left-ventricular function at rest can be observed. Radionuclide ventriculography and exercise stress test was carried out in 34 patients before and after successful aortocoronary bypass operation (Group 1), and in 69 patients before and after successful transluminal coronary angioplasty (Group 2). After bypass surgery, mean ejection fraction at rest increased from 42 +/- 11 to 49 +/- 13% (p less than 0.001). Marked improvement (greater than or equal to 5%) was observed in 19 patients (56%) in whom severe myocardial ischemia could be documented during exercise ECG (Group 1.1: Increase of ejection fraction from 40 +/- 14 to 54 +/- 12%, p less than 0.001; ischemia score during exercise test 8.8 +/- 10). In the remaining 15 patients no significant improvement occurred (Group 1.2: 43 +/- 16 vs. 43 +/- 16%, p = n.s.; ischemia score during exercise test 3.2 +/- 2.4, p = 0.02 vs. Group 1.1). After angioplasty, resting left-ventricular ejection fraction increased, on average, from 50 +/- 11 to 52 +/- 12% (p less than 0.001). Comparable to the results observed in patients after surgery, improvement was most pronounced in patients with severe exercise-induced ST-depression (Group 2.1: Increase of ejection fraction from 49 +/- 10 to 58 +/- 10%, p less than 0.001; ischemia score during exercise 2.5 +/- 2.3).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of barucainide on left ventricular ejection fraction in patients with ventricular cardiac arrhythmias]

We studied the effect of barucainide, an investigational class lb antiarrhythmic drug, on ventricular arrhythmias and left-ventricular ejection fraction in 10 patients with frequent and complex ventricular arrhythmias (Lown grade 4a/4b). The study was conducted as a single-blind and placebo-controlled trial. With placebo, mean frequency of ventricular arrhythmias was 6238 VPB/24 h, 510 couplets/24 h, and 24 salvos/24 h. Mean left-ventricular ejection fraction was 37.6%, ranging from 18% to 58%. Therapy with barucainide (300-400 mg/day) resulted in a significant reduction of ventricular arrhythmias in 7 of 10 patients; in one patient barucainide had a clear proarrhythmic effect. Over all, left-ventricular ejection fraction (37.6% +/- 12% with placebo vs 36.1% +/- 11% with barucainide) was not significantly altered. In one patient, however, it was depressed by more than 5%; one patient complained of shortness of breath during exercise. None of the four patients with an initial ejection fraction below 35% showed a drop of ejection fraction during therapy with barucainide. The only main adverse effect was a small, but significant (p less than 0.005) rise of serum-kreatinine (1.13 +/- 0.26 vs 1.39 +/- 0.38 mg%) in all patients. We conclude that barucainide has a good antiarrhythmic effect and is usually well tolerated in patients with markedly depressed left-ventricular function. The mechanism causing the rise of serum-kreatinin, however, needs to be clarified in further studies.     

Impaired diastolic ventricular function in dilated cardiomyopathy with variously reduced systolic function. A Doppler echocardiography analysis]

Diastolic ventricular function was assessed by Doppler echocardiography in 50 patients with idiopathic dilated cardiomyopathy (DCM) and sinus rhythm. The patients were subdivided into two groups with either a moderately reduced ejection fraction (less than 32%; group 1, n = 25) or a severely reduced ejection fraction (less than 32%; group 2, n = 25), the latter having an unfavorable prognosis. The degree of heart failure according to the NYHA classification was more pronounced in group 2 (p less than 0.05). Mean pulmonary capillary wedge pressure (PCm) was also higher in group 2 (gr. 1:9.8 +/- 5.5 vs. gr. 2: 16.2 +/- 8.9; p less than 0.02), and the morphological parameters obtained by conventional M-mode echocardiography showed increased left ventricular volumes and mass in both groups with DCM, as compared with a control group (n = 16); there was a reduced volume/mass ratio in group 2. The parameters of systolic function derived from M-mode and Doppler echocardiography were reduced in patients with DCM, but were more pronounced in group 2. Doppler parameters of diastolic ventricular filling were differently affected in both groups with DCM. In group 1 there was a reduced contribution of the early diastolic phase to ventricular filling (FE/FA) (contr.: 2.29 +/- 0.99 vs gr. 1: 1.40 +/- 0.45; p less than 0.05) and a reduced early peak Doppler velocity, indicating an impaired ventricular relaxation. In group 2, as compared with controls and group 1, there was an increased ratio of early/late diastolic peak velocities (VE/VA) (contr.: 1.49 +/- 0.54 vs gr. 2: 2.32 +/- 1.37; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Heterogeneous reduction of myocardial oxidative metabolism in patients with ischemic and dilated cardiomyopathy using C-11 acetate PET.

BACKGROUND: The 11C-acetate positron emission tomography can estimate myocardial oxidative metabolism, but previous studies have only evaluated small populations and the difference between ischemic (ICM) and idiopathic dilated cardiomyopathy (DCM) has not been fully investigated. The present aims were to evaluate global and regional myocardial oxidative metabolism in a well-characterized, large population with left ventricular (LV) dysfunction in order to clarify the metabolic differences between ICM and DCM. METHODS AND RESULTS: Seventy-eight patients with ejection fraction (EF) < or =50% (33 ICM; 45 DCM) were compared with 14 healthy controls. Myocardial oxidative metabolism was estimated with a clearance rate constant (K(mono)) and the coefficient of variation (CV) of regional K(mono). Patients with LV dysfunction had reduced K(mono) and higher CV (p<0.05). In the comparison of oxidative alterations with clinical variables there was a weak correlation between K(mono) and LVEF (r=0.27). Although K(mono) was reduced in both ICM and DCM, CV was more pronouncedly increased in ICM (p=0.001). In multivariate analysis, the presence of left bundle branch block (LBBB) was an independent predictor of heterogeneous oxidative metabolism in DCM (R2=0.30, p<0.0001). CONCLUSIONS: Global reduction of myocardial oxidative metabolism occurred in both ICM and DCM. Heterogeneous oxidative metabolism was observed in these patients, especially those with ICM. Furthermore, LBBB was the independent predictor of heterogeneous oxidative metabolism in patients with DCM.     

End-systolic pressure-volume and end-systolic stress-volume relationships in patients with aortic stenosis and with normal valvular function

Summary In order to study the effect of left ventricular hypertrophy on the endsystolic pressure-volume relationship, three left ventricular angiograms were performed in ten patients with normal valvular function but with varying left ventricular function (group 1) after 0.15 mg/kg propranolol, and 1 mg atropine: at rest, after isosorbide-dinitrate at a decreased afterload and after methoxamine at an enhanced afterload. In eight patients with aortic stensis (group 2) two left ventricular angiograms were performed: at rest and after isosorbide-dinitrate. Heart rate was kept constant by atrial pacing.Left ventricular mass in group 1 was 89 g/m² and in group 2 180 g/m². In group 1 the slope k of the end-systolic pressure-volume relation was related to the ejection fraction (EF) at rest: k=0.024·e^{0.072 EF}; r=0.93. In group 2 this relation was shifted to the left (P<0.001): k=0.135·e^{0.057 EF}; r=0.81. The relations, however, between the slope k of the end-systolic stress-volume relation and the ejection fraction were close together in group 1 and in group 2 and crossed at an ejection fraction of 67%.It is concluded: 1. In patients with aortic stenosis the end-systolic pressure-volume relation is steeper than in patients without valvular dysfunction at a given ejection fraction, so the relation between the slope k and the ejection fraction is shifted to the left. 2. The end-systolic stress-volume relationship is not altered in patients with aortic stenosis and seems to be advantageous for the evaluation of left ventricles with substantial hypertrophy due to pressure load.Presented in part at the 53rd Scientific Sessions of the American Heart Association in Miami Beach, Florida, Nov. 1980These investigations were supported by a grant from the Bundesministerium für Forschung und Technologie, Grant No. DISMED 18.     

Effects of chronic nitrate therapy on left-ventricular volume in patients with heart failure secondary to coronary disease already treated with captopril: a withdrawal study.

OBJECTIVE: This randomized, double-blind, placebo-controlled study with treatment lasting 16 weeks and withdrawal lasting 6 weeks tried to determine whether stopping nitrates has an effect on left-ventricular end-systolic volume in patients with heart failure who were chronically treated with captopril and diuretics. PATIENTS AND METHODS: The study group comprised 29 patients with previous myocardial infarction, symptoms of mild-to-moderate heart failure, ejection fraction below 40%, no exercise-induced angina and no electrocardiographic signs of ischemia. After all patients had been treated with captopril (target dose: 25 mg twice daily), diuretics and the study drug (target dose: 40 mg isosorbide dinitrate twice daily or placebo) for 16 weeks, the study drug was withdrawn. The patients were then maintained on captopril and diuretics at constant doses for a 6-week withdrawal period. Radionuclide ventriculography with right-heart catheterization was performed at rest and during supine bicycle exercise after 16 weeks of double-blind treatment and at the end of the 6-week withdrawal period. RESULTS: The changes in resting parameters following the withdrawal of the study drug were not different between the groups. At comparable maximum workload (placebo group 68 +/- 15 W, nitrate group 68 +/- 20 W), nitrate withdrawal caused a decrease in ejection fraction (placebo withdrawal: +0.8 +/- 4.0%; nitrate withdrawal: -2.7 +/- 4.3%, p < 0.02) and increases in left-ventricular end-diastolic volume (-9 +/- 35 vs. 23 +/- 48 ml, p < 0.02) and end-systolic volume (-9 +/- 33 vs. +24 +/- 47 ml; p < 0.01). CONCLUSION: The addition of nitrates to a baseline therapy with captopril and diuretics might reduce exercise-induced left-ventricular dilatation in patients with heart failure from coronary disease.     

Clinical and functional determinants of coronary flow reserve in non-ischemic dilated cardiomyopathy: an echocardiographic study

Coronary flow reserve (CFR) is impaired in non-ischemic dilated cardiomyopathy (DCM). Mechanisms by which such impairment occurs are still unknown, but cofactors such as diastolic compressive force, left ventricular hypertrophy, and microvascular disease have been implied. In order to characterize the determinants of CFR in non-ischemic DCM, we evaluated 110 non-ischemic DCM patients (58 men; age=61+/-12 years) and 21 age- and gender-matched control patients (14 men; age=59+/-13 years) by transthoracic (n=88) or transesophageal (n=22) dipyridamole (0.84 mg/ kg in 10') stress echocardiography. All patients showed angiographically normal coronary arteries. Non-ischemic DCM patients had an ejection fraction <45% while control patients had normal left ventricular systolic function. CFR was assessed on LAD by pulsed Doppler as the ratio of maximal vasodilation (dipyridamole) to rest peak diastolic coronary flow velocity. Mean CFR value was 2.0+/-0.6 for DCM patients and 3.2+/-0.5 for controls (p<0.01). At individual non-ischemic DCM patient analysis, 46 patients had normal CFR> or =2 (Group 1) and 64 patients had abnormal CFR<2 (Group 2). On univariate analysis, CFR reduction correlated with NYHA functional class (r=-0.33, p=0.001), left ventricular ejection fraction ( r=0.23, p=0.02), end-systolic volume (r=-0.23, p=0.02), systolic pulmonary artery pressure (r=-0.42, p=0.0001), deceleration time (r=0.24, p=0.02). Logistic multiregression analysis showed that only NYHA functional class significantly and negatively correlated with CFR (odds ratio=0.9; 95% confidence intervals: 0.03-.35, p=0.0001). In patients with non-ischemic DCM, CFR is reduced but with substantial individual variability, only partially accounted for by level of systolic and diastolic dysfunction. The clinical functional class is the strongest predictor of CFR reduction in these patients, with lowest flow reserve found in more advanced NYHA class.     

Prognostic relevance of left ventricular diastolic function parameters in dilated cardiomyopathy

Patients with dilated cardiomyopathy (DCM) generally have an impaired functional capacity and poor long-term out-comes. A mortality of 5-15% per year has been described actually. Aim of this study was to verify the prognostic relevance of invasive and non-invasive parameters of diastolic function in patients with DCM. In 33 patients with DCM, cardiac catheterization was performed and left ventricular systolic (ejection fraction (EF; %)); left ventricular enddiastolic pressure (LVEDP; mmHg) and diastolic function (time constant of relaxation (T, ms); the constant of myocardial stiffness (b) were derived from biplane laevocardiography and simultaneous micromanometric registration of pressure-volume curves. For evaluation of clinical out-come, the follow-up period was defined as beginning on the day after cardiac catheterization and ending on the most recent date or with a cardiac event (death or cardiac transplantation). All patients were reevaluated for NYHA functional class and completed a standard questionnaire. The following hemodynamic parameters were evaluated: invasive parameters of left ventricular diastolic function (constant of relaxation: tau (ms), constant of myocardial stiffness: b)), as well as parameters of systolic function (ejection fraction (EF; %)), left ventricular pressure (LVEDP; mmHg), left ventricular muscle mass index (LVMMI; g/m2), left ventricular enddiastolic volume index (LVEDVI; ml/m2) and non-invasive parameters of morphological data, left ventricular systolic (fractional shortening (FS, %) and ejection fraction) and diastolic parameters with echocardiography. During the follow-up period of 36 months, 11 of 33 patients experienced a major cardiac event (cardiac death n = 8, heart transplantation n = 3). The major cause of death was progressive pump failure. The remaining 22 patients were further classified with respect to changes in functional status. While clinical symptoms could be improved medically in patients with moderate increase of myocardial stiffness, patients with severe increase of myocardial stiffness (b: 76.1 +/- 12.1 vs 17.9 +/- +8.1, p < 0.001) could not be improved and suffered more cardiac events. Doppler echocardiographic measurements in these patients showed a restrictive filling pattern (VE 0.91 +/- 0.21 vs 0.64 +/- 0.18 m/s; p < 0.01; VA 0.52 +/- 0.23 vs 0.57 +/- 0.24 m/s; p < 0.01, deceleration time 129 +/- 17 vs 211 +/- 14 ms; p < 0.01). The medical heart failure therapy was comparable in both groups. In patients with cardiac events, the diastolic left ventricular variables did not significantly differ between patients who underwent heart transplantation and those who died. Patients who demonstrated a sole impairment of relaxation (tau: > 50 ms) suffered no cardiac events. Impaired diastolic function contributes to the clinical picture of congestive heart failure. Parameters of left ventricular diastolic function are powerful and important predictors of major cardiac events in patients with DCM, like heart transplantation and non-sudden death, and may indicate future clinical success of medical treatment. Invasive and non-invasive parameters of diastolic function reveal comparable information for the estimation of prognosis of patients with DCM in order to initiate early therapy.     

Evaluation of cardiac sympathetic nerve activity and left ventricular remodelling in patients with dilated cardiomyopathy on the treatment containing carvedilol.

AIMS: It has been reported that carvedilol improves cardiac sympathetic nerve activity (CSNA) in patients with dilated cardiomyopathy (DCM). However, the influence of carvedilol on cardiac (123)I-meta-iodobenzylguanidine (MIBG) scintigraphic findings and left ventricular (LV) remodelling has not been determined in DCM patients. METHODS AND RESULTS: In 30 patients with DCM and 10 normal controls, the delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS), and washout rate (WR) were determined by (123)I-MIBG scintigraphy. In addition, the left ventricular end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were calculated by echocardiography. In the DCM patients, the regional defect score index (RDSI), regional washout rate index (RWRI), and wall motion score index (WMSI) were also determined to evaluate regional adrenergic dysfunction and wall motion. Examinations were repeated in all DCM patients after standard treatment containing carvedilol at a dose of 10-20 mg/day (mean dose: 16 +/- 4 mg/day) for a mean of 12 +/- 1 months. Both the (123)I-MIBG scintigraphic and echocardiographic parameters were significantly worse in the DCM patients than the normal control subjects. After treatment, all of these parameters improved significantly in the DCM patients. There was a significant correlation between the changes of (123)I-MIBG findings and changes of the LVEDV and LVESV after treatment. Moreover, there was a significant correlation between changes of the WMSI and those of the RDSI or RWRI in DCM patients. CONCLUSION: Both (123)I-MIBG scintigraphic parameters and echocardiographic parameters were improved in the DCM patients. There was a significant correlation between the changes of (123)I-MIBG scintigraphic and echocardiographic findings after treatment. These findings implicate that long-term, including carvedilol, therapy can improve both CSNA and LV remodelling in patients with DCM.