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[Tolerability and clinical effects of carvedilol in patients over 70 years of age with chronic heart failure due to left ventricular dysfunction].

BACKGROUND: A number of studies showed the improvement in left ventricular (LV) function and clinical outcome that carvedilol produces in patients with severe congestive heart failure (CHF). However, no data are available regarding beta-blocker treatment in older patients with CHF. The purpose of this study was to assess the tolerability and efficacy of carvedilol in patients > 70 years with CHF associated with LV systolic dysfunction. METHODS: Thirty-seven patients in NYHA functional class III-IV with LV ejection fraction < 45% and a mean age of 76 +/- 6 years were prospectively studied. They received carvedilol which was associated with conventional therapy for CHF (ACE-inhibitors + diuretics + digitalis). The changes over time in clinical and echocardiographic variables (evaluated at baseline and every 6 months) were compared with those of 23 patients treated with the sole conventional therapy. RESULTS: During a follow-up of 13 +/- 8 months, 5 patients interrupted carvedilol due to side effects (tolerability 87%). Among the 32 remaining patients, 8 died. NYHA functional class improved in the 56% of survivors, LV ejection fraction increased (30 to 42%, p = 0.0002), mitral regurgitation and pulmonary capillary wedge pressure markedly decreased (2.0 to 1.0, p = 0.0001, and 19 to 13 mmHg, p = 0.0004, respectively). None of these variables was changed at the end of follow-up in the control group. Mortality was similar between the carvedilol (25%) and control group (22%). CONCLUSIONS: In the very elderly patients with LV systolic dysfunction and CHF carvedilol is well tolerated and safe. The addition of this drug to conventional therapy for CHF provides an important improvement in functional class, LV function and hemodynamics.

Age Factors↗

Automated impedance cardiography for detecting ischemic left ventricular dysfunction during exercise testing.

UNLABELLED: Automated impedance cardiography (ICG) is an attractive method for noninvasive hemodynamic evaluation. The objective of our study was to evaluate the feasibility and diagnostic value automated ICG in patients with suspected coronary artery disease (CAD). We measured stroke index (SI) and cardiac index (CI) in 65 patients with suspected CAD at rest and during bicycle exercise testing. All patients underwent subsequent cardiac catheterization including coronary angiography (CA). Depending on the results of CA, patients were divided into three groups, patients without significant CAD (group 0), single vessel disease (group 1) or multivessel disease (group 2-3). In a subset of 20 patients, automated ICG was compared to measurements of CI by the thermodilution (TD) method. RESULTS: There were no significant differences in SI and CI at baseline between the three groups. At 75- and 100-watt exercise, patients in group 2-3 showed significantly lower mean values of SI and CI as compared to patients of group 0 and group 1 (all p < 0.05), indicating exercise-induced ischaemic left ventricular (LV) dysfunction. Three patients had to be excluded because of inappropriate quality of the ICG signals during exercise. Comparison of automated ICG with TD measurements of CI showed good correlations between both methods at rest (r = 0.73) and during exercise (r = 0.89-0.91). CONCLUSIONS: We conclude that hemodynamic monitoring by automated ICG is both feasible and practical during exercise testing. Automated ICG can provide reliable and valuable additional diagnostic information on LV function during exercise which is helpful for selecting those patients for angiography who are likely to benefit from coronary interventions.

Adult↗

Left ventricular dysfunction in hypertensive patients with Type 2 diabetes mellitus.

AIMS: To characterize left ventricular function in hypertensive patients with Type 2 diabetes and normal ejection fraction, and to relate these findings to pathogenic factors and clinical risk markers. METHODS: We examined 70 hypertensive patients with Type 2 diabetes mellitus with ejection fraction > 0.55 and fractional shortening > 0.25, all without any cardiac symptoms. Thirty-five non-diabetic subjects served as control subjects. Left ventricular longitudinal function was examined by tissue Doppler derived myocardial strain rate and peak systolic velocities. RESULTS: Hypertensive patients with diabetes had a significantly higher systolic strain rate (-1.1 +/- 0.3 s(-1) vs. -1.6 +/- 0.3 s(-1), P < 0.001) and lower systolic peak velocities (3.3 +/- 1.0 vs. 5.6 +/- 1.0 cm/s, P < 0.001) compared with control subjects. Myocardial systolic strain rate correlated significantly to left ventricular mass (r = 0.40, P < 0.01) and to both HbA1c (r = 0.43, P < 0.01), and fructosamine (r = 0.40, P < 0.01), but was not related to serum levels of carboxymethyllysine, albuminuria, blood pressure (dipping/non-dipping), or oral hypoglycaemic therapy. Patients with diastolic dysfunction had significantly higher levels of urine albumin [21.0 (5-2500) mg/l, vs. 9.5 (1-360), P < 0.01], heart rate (78 +/- 13 vs. 67 +/- 10 b.p.m., P < 0.005), and seated diastolic blood pressure (85 +/- 6 vs. 81 +/- 7 mmHg, P < 0.05) and non-dipping diastolic blood pressure was more frequent. CONCLUSIONS: Long axis left ventricular systolic function was significantly decreased in hypertensive patients with Type 2 diabetes mellitus, and is associated with hyperglycaemia and left ventricular hypertrophy. Diastolic dysfunction was closely related to increased diastolic blood pressure, non-dipping and increased urinary albumin excretion.

Blood Flow Velocity↗

Tachycardia-induced cardiomyopathy: a reversible form of left ventricular dysfunction.

Eight patients, aged 5 to 57 years, with uncontrolled symptomatic tachycardia for 2.5 to 41 years (mean 15) and significant left ventricular (LV) dysfunction in the absence of any other apparent underlying cardiac disease underwent evaluation. Incessant tachycardia was present for 0.5 to 6.0 years (mean 2.1) in 7 patients. One patient had an ectopic atrial tachycardia and 7 patients had an accessory atrioventricular pathway that participated in reciprocating tachycardia. Six patients underwent surgery; the ectopic focus was ablated in 1 patient and an accessory pathway was divided in 5 patients. One patient underwent open ablation of the His bundle and 1 patient underwent closed-chest ablation of the atrioventricular conduction system. Myocardial biopsy specimens were obtained from 5 patients, none of which yielded a specific diagnosis. Pretreatment radionuclide angiography demonstrated a mean ejection fraction (EF) of 19 +/- 9% (range 10 to 35%). Following tachycardia control a marked improvement in LV function was noted in 6 of 8 patients at rest and in 1 additional patient during exercise. The EF increased to 33 +/- 17% (range 16 to 56%) an average of 8 days after treatment and to 45 +/- 15% (range 22 to 67%) at late follow-up 3.5 +/- 40 months (mean 17) later (p less than 0.005). Seven patients remain asymptomatic 11 to 40 months (mean 22) after the corrective procedure and have resumed normal activities. These findings suggest that chronic uncontrolled tachycardia may result in significant LV dysfunction, which is reversible in some cases after control of the arrhythmia.

Adolescent↗

Myocardial perfusion defects and associated systemic ventricular dysfunction in congenitally corrected transposition of the great arteries.

BACKGROUND: Patients with systemic ventricles of right ventricular morphology are at high risk of contractile dysfunction, the cause of which has not been fully elucidated. OBJECTIVE: To assess whether ischaemia or infarction contributes to ventricular impairment in unoperated patients with uncomplicated congenitally corrected transposition of the great arteries (TGA) by studying myocardial perfusion and function. SETTING: Paediatric and adult congenital cardiac clinics of a tertiary referral centre. PATIENTS: Five patients with congenitally corrected TGA but without associated structural cardiac defects (aged 3.5 to 34 years). INTERVENTIONS: Maximal exercise stress testing using standard or modified Bruce protocols. Sestamibi (technetium-99m methoxy isobutyl isonitrile) scanning after isotope injection at maximal exercise and rest. MAIN OUTCOME MEASURES: Maximum exercise capacity; right ventricular myocardial perfusion, regional wall motion, and thickening; right ventricular ejection fraction. RESULTS: The two youngest patients (3.5 and 11 years) had normal exercise capacity for age, while the others had reduced exercise performance. Sestamibi scanning showed reversible myocardial ischaemia in four patients and fixed defects indicating infarction in five. Irreversible defects were mostly associated with impaired wall motion and thickening. The ejection fraction was normal (65%) in the youngest patient but < 55% in the others (mean (SD) 47(11)%). CONCLUSIONS: Patients with unoperated congenitally corrected TGA have a high prevalence of myocardial perfusion defects, with consequent abnormalities of regional wall motion and thickening, and impaired ventricular contractility. These data suggest that ischaemia and infarction are important in the pathogenesis of ventricular failure in this condition.

Adolescent↗

Effects of antiarrhythmic agents on left ventricular function during exercise in patients with chronic left ventricular dysfunction.

This study was designed to determine the effects of antiarrhythmic agents on global left ventricular (LV) function during exercise in patients with chronic LV dysfunction. Thirty-five patients with LV dysfunction [LV ejection fraction (LVEF) < 45%] and ventricular arrhythmias were studied. They were randomly classified into 3 groups: patients who received a single oral dose of 6 mg/kg disopyramide phosphate (n = 12), those who received a single oral dose of 4 mg/kg mexiletine hydrochloride (n = 12), and those who received a single oral dose of 4 mg/kg pilsicainide hydrochloride (n = 11). First, all patients were subjected to baseline rest and peak exercise, equilibrium-gated cardiac-pool scintigraphy with 99mTc-human serous albumin of 740 MBq (baseline data). Second, on a separate day, they were given drugs once, and were subsequently subjected to rest and peak exercise equilibrium-gated cardiac-pool scintigraphy. Exercise LVEF and peak ejection rate (PER) after administration were significantly lower in the disopyramide and pilsicainide groups than in the mexiletine group (p < 0.05, respectively). The changes in LVEF and PER from rest to peak exercise after administration were significantly less than the baseline changes in those in the disopyramide and pilsicainide groups (p < 0.05, respectively). However, no significant changes in functional parameters were recognized in the mexiletine group. Due care should be taken when disopyramide and pilsicainide are administered to patients with chronic LV dysfunction since they reduce systolic LV function during exercise.

Aged↗

Usefulness of echocardiography in detecting left ventricular dysfunction in population-based studies (The Rotterdam Study).

In a population-based study, the routine 12-lead electrocardiogram was found to have a high negative predictive value for detecting left ventricular (LV) systolic dysfunction. Withholding echocardiography in persons without major electrocardiographic abnormalities, however, would result in a considerable underestimation of LV systolic dysfunction (sensitivity only 54%); thus, echocardiography remains an essential tool for detecting LV systolic dysfunction in population-based studies.

Echocardiography, Doppler↗

Effects of a new angiotensin-converting enzyme inhibitor (idrapril) in rats with left ventricular dysfunction after myocardial infarction.

We evaluated the effects of a new angiotensin-converting enzyme (ACE) inhibitor (idrapril) in terms of hemodynamics and ventricular remodeling after myocardial infarction in rats. The animals were randomly assigned to four experimental groups. Myocardial infarction was induced by left coronary artery ligation in the first two groups treated with either idrapril (300 mg kg-1 day-1) or vehicle for 4 weeks after myocardial infarction. Two groups of sham-operated rats were treated accordingly. Hemodynamics were measured, and the diastole-arrested hearts were analyzed morphometrically to quantify left ventricular (LV) remodeling and infarct size. In infarcted rats, idrapril reduced the arterial systolic blood pressure (SBP) from 128 +/- 10 to 97 +/- 6 mm Hg (p < 0.05) and LV end-diastolic pressure (LVEDP) from 19 +/- 3 to 13 +/- 3 mm Hg (p < 0.01). The decrease in diastolic wall stress conferred by idrapril to infarcted rats (from 499 +/- 99 to 269 +/- 68 dynes mm-2, p < 0.05) was mainly due to a reduction in LVEDP and, to a lesser extent, in LV volume. Idrapril also reduced body and heart weights as compared with those of vehicle-treated animals. Four-week treatment with idrapril initiated immediately after myocardial infarction reduced LVEDP and limited LV wall stress, a major prognostic factor for the progression toward chronic ventricular failure.

Angiotensin-Converting Enzyme Inhibitors↗

Validation of echocardiographic methods for assessing left ventricular dysfunction in rats with myocardial infarction.

The rat infarct model is widely used in heart failure research, but few echocardiographic indexes of left ventricular (LV) function are validated in this model. Accordingly, the objective of this study was to validate a 13-segment LV wall motion score index (WMSI) and the myocardial performance index (MPI) in infarcted rats. Twenty-nine male Wistar rats underwent left coronary artery ligation or sham operation and were evaluated with two-dimensional and Doppler flow echocardiography 8 wk later. After echocardiography, invasive indexes were obtained using a high-fidelity catheter. WMSI and MPI were correlated with the invasive and noninvasive measurements of LV function. WMSI and MPI significantly correlated directly with end-diastolic pressure (r=0.72 and 0.42 for WMSI and MPI, respectively) and the time constant of isovolumic relaxation (r=0.68 and 0.48) and inversely with peak rate of rise of LV pressure (+dP/dt; r=-0.68 and -0.50), peak rate of decline in LV pressure (r=-0.57 and -0.44), LV developed pressure (r=-0.58 and -0.42), area fractional shortening (r=-0.85 and -0.53), and cardiac index (r=-0.74 and -0.74). Stepwise linear regression analyses revealed that LV end-diastolic pressure, +dP/dt, area fractional shortening, and cardiac index were independent determinants of WMSI (r=0.994) and that cardiac index and +dP/dt were independent determinants of MPI (r=0.781). We conclude that the 13-segment WMSI and MPI are reproducible and correlate strongly with established echocardiographic and invasive indexes of systolic and diastolic function. These findings support the use of WMSI and MPI as indexes of global LV function in the rat infarction model of heart failure.

Animals↗

Influence of age on the prognostic importance of left ventricular dysfunction and congestive heart failure on long-term survival after acute myocardial infarction. TRACE Study Group.

The aim of this study was to assess the importance of congestive heart failure and left ventricular (LV) systolic dysfunction after an acute myocardial infarction (AIM) on long-term mortality in different age groups. A total of 7,001 consecutive enzyme-confirmed AMIs (6,676 patients) were screened for entry into the TRAndolapril Cardiac Evaluation (TRACE) study. Medical history, echocardiographic estimation of LV systolic function determined as wall motion index, infarct complications, and survival were documented for all patients. To study the importance of congestive heart failure and wall motion index independent of age, we performed Cox proportional-hazard models in 4 different age strata (< or = 55 years, 56 to 65 years, 66 to 75 years, and > 75 years). Patients in these strata had 1-year mortality rates of 5%, 11%, 21%, and 32%, respectively. Three-year mortality rates were 11%, 20%, 34%, and 55%, respectively. The risk ratios (and 95% confidence limits) associated with congestive heart failure in the same 4 age strata were 1.9 (1.3 to 2.9), 2.8 (2.1 to 3.7), 1.8 (1.5 to 2.2) and 1.8 (1.5 to 2.2), respectively. The risk ratios associated with decreasing wall motion index were 6.5 (3.6 to 11.4), 3.3 (2.3 to 4.6), 2.7 (2.2 to 3.4), and 2.1 (1.7 to 2.6), respectively. In absolute percentages, there was an excess 3-year mortality associated with congestive heart failure in the 4 age strata of 14%, 24%, 25%, and 28% respectively. The absolute excess in 3-year mortality associated with LV systolic dysfunction in the 4 age strata was 15%, 19%, 25%, and 21%, respectively. Thus, the relative importance of LV systolic dysfunction and congestive heart failure diminished with increasing age. However, the absolute excess mortality associated with congestive heart failure and LV systolic dysfunction was more pronounced in the elderly than in the young.

Age Factors↗

Blood cardioplegia enhanced with nitric oxide donor SPM-5185 counteracts postischemic endothelial and ventricular dysfunction.

This study tested the hypothesis that enhancement of blood cardioplegia with the nitric oxide donor agent SPM-5185 inhibits postischemic left ventricular and coronary endothelial dysfunction. Eighteen anesthetized dogs supported by total vented bypass were subjected to 30 minutes of normothermic ischemia followed by 4 degrees C multidose blood cardioplegia. Hearts received either standard blood cardioplegia (vehicle group; n = 6), blood cardioplegia with 1 mumol/L SPM-5185 (low-dose group; n = 6), or 10 mumol/L SPM-5185 (high-dose group; n = 6). After 60 minutes of cardioplegic arrest, the heart was reperfused for a total of 60 minutes, first in the beating empty state for 30 minutes and then after discontinuation of bypass for 30 minutes. Baseline and postischemic left ventricular function was assessed by the slope of the end-systolic pressure-volume (impedance catheter) relation. Postischemic end-systolic pressure-volume relation was depressed by 53.7% of preischemic values in the vehicle group (from 8.2 +/- 1.0 to 3.8 +/- 0.3 mm Hg/ml) and by 33.7% (from 9.2 +/- 1.1 to 6.1 +/- 0.5 mm Hg/ml) in the low-dose group. In contrast, there was complete postischemic functional recovery in the high-dose group (from 7.6 +/- 1.1 to 7.2 +/- 1.2 mm Hg/ml). In coronary arteries isolated from these hearts, endothelium-dependent maximal relaxation to acetylcholine was impaired by 27% in the vehicle group and by 18% in the low-dose group, whereas the high-dose group showed complete endothelium-dependent relaxation. Myeloperoxidase activity, an index of neutrophil accumulation in postischemic myocardium, was elevated in the vehicle and low-dose groups (3.36 +/- 0.58 and 2.56 +/- 0.68 U/100 mg tissue) but was significantly reduced in the high-dose group to 1.27 +/- 0.45 U/100 mg tissue. We conclude that inclusion of 10 mumol/L nitric oxide donor SPM-5185 in blood cardioplegia improves postischemic ventricular performance and endothelial function in ischemically injured hearts, possibly via inhibition of neutrophil-mediated damage.

Animals↗