Renal response to indomethacin in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

The impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on renal function has not been evaluated in patients with congestive heart failure. Therefore, the renal effects of indomethacin were examined in patients with chronic heart failure, and the relation between the changes in glomerular filtration rate and renal plasma flow after indomethacin administration was assessed. Twenty-five patients with congestive heart failure and an ejection fraction less than 40% were evaluated. At baseline, renal plasma flow and glomerular filtration rate were measured, using disappearance from the serum of intravenously injected 131I-orthodihippurate and urinary accumulation of intravenously injected technetium-99m diethylenetriamine pentaacetic acid, respectively. After 3 days, 75 mg of sustained release indomethacin were administered, and repeat renal function tests were performed. Mean glomerular filtration rate decreased from 40 +/- 21 to 32 +/- 16 ml/min/1.73 m2 (p less than 0.05), and mean renal plasma flow decreased from 242 +/- 122 to 222 +/- 110 ml/min/1.73 m2 (p less than 0.05). There was no correlation between the changes in glomerular filtration rate and renal plasma flow after indomethacin administration. It is concluded that 1 dose of an NSAID may cause marked and clinically important alterations in renal function in patients with heart failure. However, the decrease in glomerular filtration rate does not merely reflect a decrease in renal plasma flow, but probably the effects of NSAIDs on the intraglomerular actions of prostaglandins.     

Comparison of intravenous amrinone and dobutamine in congestive heart failure due to idiopathic dilated cardiomyopathy

A prospective randomized study was performed in 46 consecutive patients with refractory congestive heart failure (CHF) due to idiopathic dilated cardiomyopathy to compare the hemodynamic responses to 48-hour infusions of amrinone and dobutamine. Both drugs substantially reduced pulmonary arterial wedge pressure, right atrial pressure and systemic vascular resistance and increased cardiac index. Amrinone caused a greater decrease in right atrial pressure than dobutamine (p less than 0.02) and had a positive chronotropic effect not observed with dobutamine (p less than 0.01). The increase in heart rate produced by amrinone correlated inversely with the changes in right atrial and pulmonary arterial wedge pressures, suggesting a baroreceptor response to reduced preload. Dobutamine produced a larger increase in stroke volume index than amrinone (p less than 0.01). Ninety-one percent of patients receiving amrinone and only 65% receiving dobutamine had reduction of greater than or equal to 30% in pulmonary arterial wedge pressure (p less than 0.05). Cardiac index increased greater than or equal to 30% in similar numbers of patients given amrinone (74%) and dobutamine (65%). Negative fluid balance was recorded in all patients receiving amrinone and in 78% of patients receiving dobutamine (p less than 0.05). Target hemodynamic criteria were achieved in 83% of patients receiving 10 micrograms/kg/min of amrinone. The effective maintenance dose of dobutamine was extremely variable. No clinically important adverse effects were observed with either drug regimen. Both amrinone and dobutamine are effective and safe agents for short-term parenteral therapy of patients with dilated cardiomyopathy in severe CHF that is unresponsive to oral medication.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cytokine network in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

Inflammatory cytokines may play a pathogenic role in the development of congestive heart failure (CHF). Elevated circulating levels of inflammatory cytokines have been reported in CHF, but most studies have focused on only a few cytokine parameters. However, the activity of these cytokines are modulated by soluble cytokine receptors and cytokines with anti-inflammatory activities, and in the present study several of these interacting factors were examined simultaneously in 38 CHF patients with various degrees of heart failure and in 21 healthy controls. Patients with CHF had increased plasma concentrations of tumor necrosis factor (TNF)alpha, interleukin-6, soluble TNF receptors and the soluble interleukin-6 receptor, glycoprotein (gp)130. They also had elevated ratios of TNFalpha/soluble TNF receptors and interleukin-6/soluble gp130 as well as enhanced interleukin-6 bioactivity in serum, suggesting inflammatory net effects. In addition to raised circulating levels of inflammatory cytokines, CHF patients with severe heart failure also had abnormalities in the levels of anti-inflammatory cytokines, with decreased levels of transforming growth factor beta1 and inadequately raised interleukin-10 in relation to the elevated TNFalpha concentrations. This dysbalance between inflammatory and anti-inflammatory cytokines was also found in monocyte supernatants from CHF patients. The abnormalities in the cytokine network were most pronounced in patients with the most severe heart failure, and several of the immunologic parameters, in particular soluble gp130, were correlated with variables reflecting deranged hemodynamic status. The present study analyzing the complexity of the cytokine network in CHF, demonstrates profound disturbances in the levels of both inflammatory and anti-inflammatory mediators with a marked dysbalance favoring inflammatory effects.     

Oscillatory hyperventilation in severe congestive heart failure secondary to idiopathic dilated cardiomyopathy or to ischemic cardiomyopathy

Thirty-one subjects with chronic congestive heart failure (CHF) were separated into 3 groups according to ventilatory patterns during graded exercise: Group 1--oscillators (n = 6); group 2-intermediate oscillators (n = 14); and group 3--nonoscillators (n = 11). Group 1 patients showed cyclic fluctuations in minute ventilation (change of 30 to 40 liters/min) and arterial PO2 (change of 38.0 +/- 4.1 mm Hg) and PCO2 (change of 11 +/- 2.8 mm Hg). The nadir in arterial PO2 occurred at times when wasted ventilatory effort was maximal. The amplitude of ventilatory oscillations in group 1 patients increased in the transition from rest to light exercise and damped with heavy exercise. There was no evidence of alveolar hypoventilation at the nadirs of minute ventilation; arterial PCO2 was always 40 mm Hg or less. Substantial hyperventilation (ventilatory equivalent for CO2 twice normal) occurred with maximal minute ventilation in group 1 patients. Oscillatory hyperventilation correlated with severity of CHF. Maximal oxygen uptake was significantly lower in group 1 (11.7 +/- 1.1 ml/kg/min) than group 3 (17.9 +/- 1.8 ml/kg/min) (p less than 0.05). Oscillatory hyperventilation during exercise may accompany severe CHF and compounds the inadequate delivery of oxygen by the failing heart.     

Comparison of acute hemodynamic response to dobutamine and intravenous MDL 17,043 (enoximone) in severe congestive heart failure secondary to ischemic cardiomyopathy or idiopathic dilated cardiomyopathy

The acute hemodynamic response to intravenous dobutamine administration was compared with intravenous MDL 17,043 administration in 8 patients with severe, chronic congestive heart failure. Simultaneous radionuclide angiography was performed with gated equilibrium blood pool imaging to derive left ventricular volumes and ejection fraction during serial hemodynamic measurements. Six patients had an optimal dobutamine dose of 10 micrograms/kg/min; 2 others were compared at a dose of 7.5 micrograms/kg/min; comparisons with MDL 17,043 were after a 1.5-mg/kg bolus dose in all 8 patients. Dobutamine and MDL 17,043 caused significant and similar increases in cardiac index and stroke volume index. Dobutamine significantly increased heart rate and MDL 17,043 did not. MDL 17,043 significantly decreased pulmonary artery wedge, mean pulmonary artery and right atrial pressures; dobutamine did not. Dobutamine increased end-diastolic volume in 4 patients, with little concomitant decrease in wedge pressure; MDL 17,043 caused no change or a decrease in left ventricular end-diastolic volume in 5 patients, but consistently decreased wedge pressure in all. Thus, the left ventricular pressure-volume curve was displaced downward to a more favorable position after MDL 17,043 but not after dobutamine. In patients with chronic congestive heart failure, acute myocardial performance was more optimally influenced by MDL 17,043 than dobutamine administration.     

Effect of dobutamine on plasma potassium in congestive heart failure secondary to idiopathic or ischemic cardiomyopathy

Dobutamine was administered in a dose of 10 +/- 1 micrograms/kg/min to 13 patients with severe idiopathic or ischemic dilated cardiomyopathy. Acute hemodynamic improvement was noted in all patients. All patients had a significant decrease in plasma potassium (4.6 +/- 0.1 to 4.2 +/- 0.2 mEq/liter, p less than 0.0001) at peak infusion. The decrease in potassium persisted for at least 45 minutes after discontinuing the infusion. Three patients had exacerbation of baseline ventricular arrhythmias that resolved with infusion discontinuation. Changes in plasma norepinephrine could not explain the potassium decrease or arrhythmia production, which also significantly decreased in these patients (771 +/- 123 to 524 +/- 73 pg/ml, p less than 0.01). It is concluded that dobutamine causes a significant decrease in plasma potassium and that the decrease persists at least 45 minutes after the infusion is discontinued.     

Comparison of intravenous milrinone and dobutamine for congestive heart failure secondary to either ischemic or dilated cardiomyopathy

Milrinone and dobutamine are positive inotropic agents with beneficial hemodynamic effects in patients with congestive heart failure. This study was undertaken to compare the effects of intravenous milrinone and dobutamine in patients with stable New York Heart Association class III or IV congestive heart failure and to test the hypothesis that intravenous milrinone is at least as beneficial as dobutamine in this setting. Seventy-nine patients were randomized to either dobutamine therapy at incremental doses of 2.5, 5, 7.5, 10, 12.5 and 15 micrograms/kg/min, or milrinone as a bolus of 50 or 75 micrograms/kg followed by an infusion of 0.5 to 1.0 micrograms/kg/min. Both agents significantly increased heart rate, cardiac index and stroke volume index and decreased pulmonary artery wedge pressure and systemic vascular resistance compared with baseline levels (p less than 0.01). During sustained infusion for 48 hours, no difference in hemodynamic effects was observed between the 2 drugs. Ventricular tachycardia occurred in 5 patients (3 taking milrinone, 2 taking dobutamine); 1 patient taking milrinone had ventricular fibrillation. Milrinone and dobutamine elicited similar beneficial hemodynamic results with relatively few adverse effects.     

Sublingual nifedipine: acute effects in severe chronic congestive heart failure secondary to idiopathic dilated cardiomyopathy

Nine patients with chronic, severe (New York Heart Association class III to IV) congestive heart failure were studied to determine the acute effects of 10 mg of sublingual nifedipine on left ventricular (LV) function. Hemodynamic and echocardiographic data were obtained at rest and 30 minutes, 1, 2, 4 and 6 hours after nifedipine. Measurements at rest reflected LV dysfunction with elevation of end-diastolic volume index (102 +/- 46 ml/m2), pulmonary capillary wedge pressure (17 +/- 8 mm Hg), systemic vascular resistance (1,547 +/- 439 dynes s cm-5) and reduction of cardiac index (2.8 +/- 0.5 liters/min/m2). There were no adverse effects noted with administration of sublingual nifedipine. Initial changes through 1 hour reflected an unloading effect of nifedipine with reduction in pulmonary capillary wedge pressure (11 +/- 5 mm Hg) (p less than 0.05), systemic vascular resistance (1,179 +/- 289 dynes s cm-5) (p less than 0.01), end-diastolic volume index (91 +/- 37 ml/m2 [difference not significant]) and an increase in cardiac index (3.6 +/- 0.7 ml liters/min/m2) (p less than 0.01). Subsequently the cardiac index, systemic vascular resistance and end-diastolic volume index returned toward baseline. Only the pulmonary capillary wedge and pulmonary artery pressures demonstrated a sustained reduction through the 6-hour study period suggesting an effect of nifedipine on LV relaxation. Thus, sublingual nifedipine administered acutely to patients with clinical congestive heart failure is a safe and efficacious vasodilator.     

Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

This study was designed to assess the efficacy and safety of berberine for chronic congestive heart failure (CHF). One hundred fifty-six patients with CHF and >90 ventricular premature complexes (VPCs) and/or nonsustained ventricular tachycardia (VT) on 24-hour Holter monitoring were randomly divided into 2 groups. All patients were given conventional therapy for CHF, consisting of angiotensin-converting enzyme inhibitors, digoxin, diuretics, and nitrates. Patients in the treatment group (n = 79) were also given berberine 1.2 to 2.0 g/day. The remaining 77 patients were given placebo. Symptoms, a 6-minute walk test, left ventricular (LV) ejection fraction (EF), frequency and complexity of VPCs, and quality of life were assessed after 8 weeks of treatment and during a mean 24-month follow-up. After treatment with berberine, there was a significantly greater increase in LVEF, exercise capacity, improvement of the dyspnea-fatigue index, and a decrease of frequency and complexity of VPCs compared with the control group. There was a significant decrease in mortality in the berberine-treated patients during long-term follow-up (7 patients receiving treatment died vs 13 on placebo, p <0.02). Proarrhythmia was not observed, and there were no apparent side effects. Thus, berberine improved quality of life and decreased VPCs and mortality in patients with CHF.     

Factors associated with decreased cerebral blood flow in congestive heart failure secondary to idiopathic dilated cardiomyopathy

Cerebral blood flow (CBF) is decreased and cognitive dysfunction develops in the advanced stages of heart failure. However, few data are available regarding the factors associated with decreased CBF. Fifty-two patients with advanced congestive heart failure (CHF) secondary to idiopathic dilated cardiomyopathy (ejection fraction 相似文献   

Clinical determinants of mortality in chronic congestive heart failure secondary to idiopathic dilated or to ischemic cardiomyopathy

To determine which of the many clinical parameters routinely collected influence mortality in patients with congestive heart failure (CHF), 201 patients with idiopathic or ischemic dilated cardiomyopathy were prospectively followed for a 28-month study period. Mean age of the study group was 62 +/- 10 years, 60% had ischemic cardiomyopathy, and two-thirds were in New York Heart Association functional class II or III. Fifteen clinical variables were analyzed using a Cox proportional hazards model, while individual variables also were calculated for independent prognostic significance. There were 85 deaths, 26 (31%) of which were sudden cardiac deaths. Three characteristics at the study entry independently predicted an increased mortality risk: left ventricular ejection fraction, maximal oxygen uptake and ischemic cardiomyopathy. A Cox proportional hazards model showed that the combination of VO2max, S3 and the diagnosis of ischemic cardiomyopathy provided the best estimates of risk for an early death. Mortality for the low-risk group was only 5% at 6 months and 10% at 1 year. In contrast, in patients with an S3, ischemic cardiomyopathy and low maximal oxygen uptake, 6-month mortality was 24% and 36% at 1 year (p less than 0.001). Thus, these patients at high risk with left ventricular dysfunction associated with ischemic heart disease, a decreasing exercise tolerance and the development of an S3 should be strongly considered for an interventional trial with the aim of decreasing mortality.     

Effects of hydralazine on pressure-volume and stress-volume relations in congestive heart failure secondary to idiopathic dilated cardiomyopathy

The mechanism by which hydralazine improves cardiac function in patients with heart failure is not well characterized. Hydralazine may improve left ventricular (LV) function by decreasing afterloading wall stress or by increasing myocardial contractility. The effect of intravenous hydralazine was assessed in 8 patients with severe idiopathic dilated cardiomyopathy. Hydralazine increased stroke volume index (from 24 +/- 8 to 40 +/- 9 ml/m2, p less than 0.01) and decreased systemic vascular resistance from 1,603 +/- 619 to 810 +/- 317 dynes s cm-5, p less than 0.01) and peak LV wall stress (from 476 +/- 118 to 410 +/- 68 kdynes/cm2, p = 0.02). Two groups were defined by normal or high LV wall stress. Patients with high LV stress had higher LV end-diastolic pressure (38 +/- 12 vs 17 +/- 8 mm Hg, p less than 0.01), LV end-diastolic volume index (184 +/- 24 vs 149 +/- 7 ml/m2, p less than 0.01) and systemic vascular resistance (1,423 +/- 686 vs 846 +/- 293 dynes s cm-5, p = 0.01). Hydralazine decreased stress more in these patients (-101 +/- 57 vs -6 +/- 9 kdynes/cm2, p = 0.02), LV end-diastolic pressure (-12 +/- 7 vs 2 +/- 2 mm Hg, p = 0.02), systolic pressure (-15 +/- 13 vs 3 +/- 4 mm Hg, p = 0.03) and systemic vascular resistance (-1,053 +/- 247 vs -363 +/- 83 dynes s cm-5, p less than 0.01) than in patients with normal LV stress. Decreased LV stress was caused by decreased systolic and diastolic pressures and/or volumes. Late systolic pressure-volume relations in patients with normal LV stress suggested increased myocardial contractility, but this was not confirmed by LV dP/dt. Hydralazine improves LV function in patients with dilated cardiomyopathy by reducing elevated LV wall stress, with little inotropic effect.     

Hemodynamic effects of pimobendan given orally in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

Pimobendan (UD-CG 115 BS) was administered orally to 23 patients with congestive heart failure (functional class IV) caused by coronary artery disease (11 patients) or idiopathic dilated cardiomyopathy (12). All patients received maintenance doses of digoxin, furosemide and warfarin. Baseline data, collected during 15 hours, stayed within a 10% range. A 10-mg oral dose of pimobendan increased the heart rate from 95 +/- 20 to 109 +/- 24 beats/min (p less than 0.003). The pulmonary artery wedge pressure decreased from 23.0 +/- 5.9 to 10.1 +/- 5.2 mm Hg (p less than 0.0001), the cardiac index increased from 1.9 +/- 0.4 to 3.3 +/- 0.7 liters/min/m2 (p less than 0.0001) and the left ventricular stroke work index increased from 2,005 +/- 927 to 3,065 +/- 1,161 ml/mm Hg/m2 (p less than 0.0001). Statistically significant improvements in hemodynamic variables were still present 10 hours after the administration of pimobendan. Most patients felt better and reported no angina or other side effect, the incidence of ventricular arrhythmias was unchanged and no electrocardiographic changes suggesting ischemia were observed. Patients with severe congestive heart failure experienced a prolonged improvement of their cardiovascular condition after a single dose of pimobendan.     

Response of the beta-adrenergic system to maximal dynamic exercise in congestive heart failure secondary to idiopathic dilated cardiomyopathy

In congestive heart failure (CHF), prolonged exposure to high plasma catecholamine levels may reduce the responsiveness of the adrenergic system to physiologic stimuli. In healthy subjects, exercise is known to induce a rapid up-regulation of lymphocytic beta adrenoceptors. Lymphocytic beta-adrenoceptor density, lymphocytic basal and isoproterenol-stimulated cyclic adenosine monophosphate (cAMP) response, plasma catecholamine concentrations and plasma cAMP levels were studied during maximal ergometer exercise in 11 patients with CHF secondary to dilated cardiomyopathy and in 6 healthy control subjects. At rest, there was no difference in the lymphocytic beta-adrenoceptor levels between the patients and control subjects (48 +/- 3 vs 42 +/- 5 fmol/mg protein, respectively). However, the exercise-induced increase in lymphocytic beta adrenoceptors was attenuated in patients when compared with controls (26 +/- 6 fmol/mg protein [56%] vs 75 +/- 16 fmol/mg protein [204%], respectively, p less than 0.02). A subgroup of 4 patients with the lowest exercise capacity (peak oxygen uptake less than 12.5 ml/min/kg) had even more reduced up-regulation compared with the other 7 patients (13 +/- 1 fmol/mg protein [29%] vs 34 +/- 9 fmol/mg protein [71%], p less than 0.05). The lymphocytic cAMP response at rest and during exercise tended to be lower in patients compared with controls, but the differences did not reach statistical significance. The plasma levels of epinephrine and norepinephrine at rest were higher in patients compared with controls, but no difference was found in the exercise values. The plasma levels of cAMP correlated closely with plasma catecholamine levels at rest, but not during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of spironolactone on ventricular arrhythmias in congestive heart failure secondary to idiopathic dilated or to ischemic cardiomyopathy

Epidemiologic studies have shown an important increase in the high mortality of patients with congestive heart failure (CHF) despite optimal medical management. Ventricular arrhythmia was recognized as the most common cause of death in this population. Electrolyte imbalance, myocardial fibrosis, left ventricular dysfunction, and inappropriate neurohumoral activation are presumed responsible for sudden cardiac death. In this study, we focused on the deleterious effects of the overproduction of aldosterone that occurs in patients with CHF. Secondary hyperaldersteronism can be part of several factors thought to be responsible for sudden cardiac death. We randomized 35 patients (32 men, aged 48 +/- 9 years) with systolic dysfunction (ejection fraction 33 +/- 5%) and New York Heart Association class III CHF secondary to dilated or ischemic cardiomyopathy into 2 groups. The treatment group received spironolactone, an aldosterone receptor antagonist, along with standard medical management using furosemide, angiotensin-converting enzyme inhibitors, and digoxin. The control group received only the standard medical treatment. Holter monitoring was used to assess the severity of ventricular arrhythmia. After 20 weeks, patients who received spironolactone had a reduced hourly frequency of ventricular premature complexes (VPCs) (65 +/- 18 VPCs/hour at week 0 and 17 +/- 9 VPCs/hour at week 16) and episodes of nonsustained ventricular tachycardia (VT) (3.0 +/- 0.8 episodes of VT/24-hour period at week 0, and 0.6 +/- 0.3 VT/24-hour period at week 16). During monitored treadmill exercise, a significant improvement in ventricular arrhythmia was found in the group receiving spironolactone (39 +/- 10 VPCs at week 0, and 6 +/- 2 VPCs at week 16). These findings suggest that aldosterone may contribute to the incidence of ventricular arrhythmia in patients with CHF, and spironolactone helps reduce this complication.     

Prevalence and hemodynamic correlates of malnutrition in severe congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

Whereas cardiac cachexia is well recognized, the frequency and hemodynamic correlates of malnutrition in severe congestive heart failure (CHF) have not been established. Anthropometric and serum albumin assessment of nutritional status was compared with hemodynamic, echocardiographic and serum chemistry evaluation in 48 patients with severe CHF (ejection fraction 0.17 +/- 0.05). Malnutrition, as defined by decreases in percent body fat determined from skinfold thicknesses, weight/height index or serum albumin, was present in 24 of 48 (50%) patients, who did not differ from the 24 well-nourished patients in cardiac index (1.9 +/- 0.6 vs 2.1 +/- 0.6 liters/min/m2) and pulmonary artery wedge pressure (30 +/- 6 vs 27 +/- 10 mm Hg), but had higher right atrial pressure (16 +/- 5 vs 9 +/- 6 mm Hg, p less than 0.01) and more severe tricuspid regurgitation by semiquantitative Doppler grading on a 0 to 3 scale (2.0 +/- 0.9 vs 0.9 +/- 0.8, p less than 0.01). Right atrial pressure was the only independent hemodynamic predictor of malnutrition (p less than 0.0002). Malnourished patients had lower serum sodium (134 +/- 4 vs 139 +/- 4 mEq/liter, p less than 0.01) and total triiodothyronine levels (89 +/- 30 vs 115 +/- 26 ng/dl, p less than 0.01) and higher creatinine levels (1.6 +/- 0.7 vs 1.2 +/- 0.4, p less than 0.03). None of the other biochemical markers of nutritional status differed between the groups except lower serum triglyceride levels (115 +/- 73 vs 186 +/- 97 mg/dl, p less than 0.05) in malnourished patients. Malnutrition is common in patients with severe CHF and is associated with increased right atrial pressure and tricuspid regurgitation.     

Effects of milrinone on complex ventricular arrhythmias in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

To determine whether oral milrinone therapy has an effect on complex ventricular arrhythmias in patients with severe congestive heart failure and, if so, whether a change in the severity of complex ventricular arrhythmias after 1 week of milrinone therapy is associated with a change in the mode or frequency of cardiac mortality, a retrospective analysis was performed to determine the frequency of ventricular tachycardia and the density of ventricular couplets on 24-hour ambulatory electrocardiographic recordings performed before and 1 week after initiation of oral milrinone therapy in 74 consecutive patients with New York Heart Association functional class III or IV congestive heart failure. The endpoints of mortality and mode of death were assessed during a mean follow-up of 6 months. In 91% of the patients, 1 week of oral milrinone therapy was associated with no significant change (85%) or a significant decrease (6%) in the density of ventricular couplets and frequency of ventricular tachycardia. However, in 9% of patients the frequency of complex ventricular arrhythmias increased significantly at the end of 1 week of oral milrinone therapy. In this subgroup, neither total cardiac mortality nor the incidence of sudden cardiac death was significantly higher than that in patients with no change or a decrease in complex ventricular ectopic activity.     

Impaired forearm vasodilation to hyperosmolal stimuli in patients with congestive heart failure secondary to idiopathic dilated cardiomyopathy or to ischemic cardiomyopathy.

Patients with congestive heart failure (CHF) have impaired peripheral vasodilation during exercise. Hyperosmolality is one local stimulus that produces vasodilation during exercise in normal subjects. This study addressed the hypothesis that vasodilation to hyperosmolal stimuli is impaired in patients with CHF. Forearm blood flow responses to intrabrachial artery infusions of isoosmolar (280 mosm/kg) and hyperosmolal (480 and 660 mosm/kg) solutions of saline and glucose were compared in 9 patients with CHF and 13 normal subjects. Forearm blood flow was measured by strain gauge plethysmography. In the normal subjects, hyperosmolal infusions of 480 and 660 mosm/kg increased forearm blood flow by 3.12 +/- 0.40 and 6.80 +/- 0.67 ml/min/100 ml forearm volume, respectively (both p < 0.001 compared with isoosmolal infusions). In contrast, in the patients with CHF, these infusions increased forearm blood flow by 2.19 +/- 0.44 and 4.06 +/- 0.92 ml/min/100 ml forearm volume (p < 0.05 normal vs CHF). The impaired forearm blood flow responses in heart failure occurred despite significantly greater (p < 0.05, normal vs CHF) increases in venous osmolality (17.3 +/- 6.5 vs 9.6 +/- 1.3 mosm/kg for the 660 mosm/kg infusion). There were no differences between groups in forearm venous hematocrit, calcium, and sodium or potassium changes during hyperosmolal infusions. It is concluded that peripheral vasodilation to hyperosmolal stimuli is impaired in patients with CHF.     

Amrinone therapy for congestive heart failure in outpatients with idiopathic dilated cardiomyopathy

Amrinone, 100 mg orally every 8 hours, was administered to 13 patients with moderate-to-severe congestive heart failure (CHF) for 1 month on an outpatient basis to determine the beneficial and undesirable effects of this new cardioactive agent in this clinical setting. These subjects received conventional CHF medications during the course of study. Ten patients who received conventional CHF medications alone served as a control group. Changes in functional classification were not significantly different between the 2 treatment groups. Amrinone augmented exercise capacity 37% above baseline compared with a 12% improvement for the control group. Noninvasive indexes of resting left ventricular function (echocardiography and systolic time intervals) did not change significantly for either group, nor was there a significant change in the exercise ejection fraction. All patients treated with amrinone had ≥ 1 symptom-related or laboratory-detected adverse effect. An increase in the frequency of ventricular ectopic beats was noted at rest in 4 and with exercise in 6 patients (salvos of nonsustained ventricular tachycardia in 2). Six subjects treated with amrinone had gastrointestinal symptoms and 8 developed a viral-like illness. Other adverse effects noted in the amrinone-treated group included near-syncope, headaches, marked anxiety, chest pain, palpitations, maculopapular rash, hypokalemia, and elevation of serum transaminase levels. The control patients had significantly fewer adverse effects.Although individual patients with CHF may benefit from long-term amrinone therapy, the low benefitto-risk-adverse effect ratio does not warrant widespread application of this drug in the outpatient management of CHF and requires caution when prescribing.