Moderate Chronic Congestive Heart Failure Research Articles

Clinical Value of Cystatin C in Elderly Patients with Mild to Moderate Chronic Congestive Heart Failure

Clinical Value of Cystatin C in Elderly Patients with Mild to Moderate Chronic Congestive Heart Failure

Digitalis therapy for patients in clinical heart failure.

The most commonly used preparation of digitalis is digoxin, which is obtained from the leaves of Digitalis lanata , a common flowering plant called “foxglove.” The words digitalis and digoxin in this article are used interchangeably. An exhaustive review published in 19961 cited a large number of references and had detailed data and descriptions of a large number of studies and all early trials. The present article summarizes those data but focuses on and emphasizes data collected since that time. These have been described in detail previously1 and are briefly summarized. ### Inotropic Effects The inotropic effects have been documented in the isolated papillary muscles and in the normal hearts of animals and humans. The inotropic action occurs in both ventricles and in both atria. In the normal heart and in those with coronary artery disease and normal left ventricular (LV) systolic function, with digitalis the LV function curve is moved upward and to the left.1 As a result, LV end-diastolic pressure and LV end-diastolic and end-systolic volumes are reduced, and there is an increase of LV ejection fraction (LVEF).1 ### Patients With Heart Failure In patients with heart failure (HF), digoxin slows the ventricular rate (1) in sinus rhythm because of an improvement in HF and withdrawal of sympathetic stimulation and (2) in atrial fibrillation by increasing parasympathetic tone. The combination of digoxin and carvedilol is superior to digoxin or carvedilol alone.2 ### Peripheral Vessels In normal subjects given intravenous ouabain, there is arterial and venous vasocontriction.3 The vasoconstriction is obviated by administering digoxin slowly over a period of 15 to 20 minutes1; moreover, the vasoconstriction lasts up to 30 minutes. The seminal study of Mason and Braunwald3 showed that in HF, the effects are different. Digitalis produces an increase of blood flow, a decrease of vascular resistance, venodilation, and a …

Effects of short-acting and long-acting loop diuretics on heart rate variability in patients with chronic compensated congestive heart failure

Background We investigated the effects of a short-acting loop diuretic (furosemide) and a long-acting loop diuretic (azosemide) on heart rate variability, fluid balance, and neurohormonal responses in patients with mild to moderate chronic congestive heart failure. Methods Nineteen patients with mild to moderate chronic congestive heart failure received furosemide (40 to 60 mg/day) or azosemide (60 to 90 mg/day) for 5 days in a crossover manner. We performed time-domain and frequency-domain analyses of 24-hour Holter electrocardiographic recordings to assess heart rate variability. Results The 24-hour urinary sodium excretion was similar during the furosemide and azosemide treatment periods but was significantly greater in the first 2 hours after drug administration during furosemide treatment. Plasma renin activity and the hematocrit level increased and high-frequency power significantly decreased 2 hours after the administration of furosemide only. The standard deviation of all normal R-R intervals and the root mean square of successive differences in the R-R interval were lower with furosemide than with azosemide ( P < .05). Conclusions Furosemide, a short-acting loop diuretic, has a greater influence on heart rate variability and fluid balance than azosemide, a long-acting loop diuretic, in patients with mild to moderate chronic congestive heart failure. (Am Heart J 1999;137:543-8.)

Successes and failures of current treatment of heart failure

Successes and failures of current treatment of heart failure

Clinical and neurohumoral differences between spirapril and captopril in mild to moderate chronic congestive heart failure

Background: This study was done to determine whether the difference in duration of action of the long-acting angiotensin-converting enzyme (ACE) inhibitor spirapril compared with the short-acting ACE inhibitor captopril affects clinical efficacy in patients with congestive heart failure. Methods and Results: The effects on exercise capacity, neurohumoral status, and quality of life were studied in 20 patients with mild to moderate congestive heart failure in a double-blind, randomized, comparative study in parallel groups with a duration of 12 weeks. All assessments during the study were performed in the morning, before intake of the study medication, to avoid the expected peak effect of the ACE inhibitors used. Mean peak oxygen consumption (peak Vo 2) was 17.4 mL/min/kg (range, 14.2–19.9 mL/min/kg) and mean left ventricular ejection fraction was 28% (range, 13–40%). Exercise duration in the captopril group showed a significant increase after 12 weeks ( P < .05) of treatment compared with the spirapril group. Peak oxygen consumption tended only to increase in the captopril-treated patients compared with the spirapril-treated patients. Serum ACE activity was significantly different between the two treatment groups during treatment ( P < .0001) and showed only a significant decrease in the spirapril group. There was no difference in improvement of quality of life between the two treatment groups. Conclusions: This study showed that the effects of the ACE inhibitors spirapril and captopril on exercise capacity are not related to the degree of inhibition of serum ACE activity.

Effects of 12 weeks of ramipril treatment on the quality of life in patients with moderate congestive heart failure: Results of a placebo-controlled trial

The assessment of quality of life (QoL) has become recognized as an important tool for evaluating heart failure therapy. The angiotensin-converting enzyme inhibitor ramipril (mean dose 8 mg) was evaluated in 223 patients with moderate chronic congestive heart failure at 24 centers in 4 Nordic countries following a randomized, double-blind, placebo-controlled, parallel group design. The follow-up period was 12 weeks. QoL was evaluated using a questionnaire with 47 items, including the disease-specific Severe Heart Failure Questionnaire, the Sleep Dysfunction Scale, and the Psychological General Well-Being Index. In both treatment groups the total score increased from baseline to 12 weeks for both the Severe Heart Failure Questionnaire and for the Psychological Well-Being Index, reflecting relief of symptoms and improved well-being. However, no significant differences between the placebo and ramipril groups could be detected. Only a trend toward improvement in sleep on ramipril compared with placebo therapy was observed. In conclusion, in this placebo-controlled trial no significant effects of 12-week ramipril treatment of QoL could be demonstrated in patients with moderate congestive heart failure.

Absence of effect on exercise capacity of 12-weeks treatment with ramipril in patients with moderate congestive heart failure

Pharmacological therapy in cases of chronic congestive heart failure (CHF) is usually evaluated by maximal exercise time. To assess the effect of an angiotensin converting enzyme inhibitor, ramipril, 223 patients with moderate CHF were studied in 24 centres in four Nordic countries in a randomized, double-blind, placebo-controlled, parallel group design. The study drug was titrated from 1.25 mg to a maximum of 10 mg once daily (o.d) over a period of 4 weeks (mean dose 8 mg). A symptom-limited bicycle exercise test, starting at 30 watts and increasing by 10 watts.min-1, was used to evaluate exercise capacity. Reproducible tests were required at baseline, and the test was repeated after 4, 8 and 12 weeks of treatment. Seven deaths were recorded in the placebo group and one death in the ramipril group. A total of 195 patients completed 12 weeks of treatment (placebo group n = 91, ramipril group n = 104). The groups had similar baseline characteristics. Maximal exercise time was increased by mean (SD) 35 s (9) and 41 s (8) in the placebo and ramipril groups, respectively. The adjusted difference between the groups at 12 weeks was 9 s (12) (ns). A significant decrease in blood pressure and rate-pressure product at rest and at end of exercise was obtained by ramipril as compared with placebo. Significantly fewer patients deteriorated in NYHA class from baseline to 12 weeks of ramipril treatment compared to placebo (P = 0.012). Concomitant medication for CHF increased significantly in the placebo group as compared with ramipril-treated patients (P = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Determinants of the initial effects of captopril on blood pressure, glomerular filtration rate, and natriuresis in mild-to-moderate chronic congestive heart failure secondary to coronary artery disease

Whereas angiotensin-eonverting enzyme inhibitors are now indicated for all grades of chronic heart failure, the 2 adverse effects that limit use of these drugs are systemic hypotension and renal dysfunction. The recognized clinical correlates such as hyponatremia and high diuretic dose, which predict occurrence of these adverse effects in severe chronic congestive heart failure (CHF), are rarely evident in patients with mild-to-moderate CHF. Accordingly, we studied 36 patients with stable, moderate CHF in a double-blind, placebo-controlled, crossover fashion to evaluate by multiple discriminate regression analysis the pathophysiologic determinants of changes in blood pressure, glomerular filtration rate, and urinary sodium excretion after initial converting enzyme inhibition with captopril 25 mg. A captopril-mediated decrease in mean arterial pressure was predicted by 3 factors (r 2 = 0.74): the decrease in serum angiotensin II (F ratio = 10.3, p <0.01), the decrease in plasma norepinephrine (F = 8, p = 0.02), and, inversely by pretreatment mean arterial pressure (F = 5.6, p = 0.04), patients with higher initial values exhibiting greater decreases in response to captopril. A captopril-mediated decline in glomerular filtration rate, determined by radioisotope elimination, was also predicted by 3 factors (r 2 = 0.67): a decrease in renal plasma flow (F = 48.6, p <0.01), low pretreatment glomerular filtration rate (F = 11.1, p <0.01), and low absolute post-treatment serum angiotensin II (F = 5, p = 0.04). Change in urinary sodium excretion was related directly to change in glomerular filtration rate (F = 30.4, p <0.01) and inversely to change in angiotensin II level (F = 4.7, p = 0.05) in response to captopril (r 2 = 0.73). Captopril-mediated effects on blood pressure did not determine changes in either glomerular filtration rate or urinary sodium excretion. These findings emphasize the central role for circulating angiotensin II in CHF as the modifiable factor that mediates a potent antinatriuretic action while simultaneously playing a part in maintaining systemic blood pressure and, independently, in maintaining glomerular filtration rate.

Double-Blind Placebo-Controlled Study of Ibopamine and Diagoxin in Patients With Mild to Moderate Heart Failure: Results of the Dutch of the Ibopamine Multicenter Trial (DIMT)

Objectives. This study was conducted to determine the efficacy and safety of long-term treatment with the orally active dopamine agonist ibopamine in patients with mild to moderate chronic congestive heart failure and to compare the results with those of treatment with digoxin and placebo.BackgroundIbopamine and digoxin are drugs that exert hemodynamic and neurohumoral effects. Because there is accumulating evidence that progression of disease in chronic heart failure is related not only to hemodynamic but also to neurohumoral factors, both drugs might be expected to have a favorable long-term effect.Methods. We studied 161 patients with mild to moderate chronic heart failure (80% in New York Heart Association functional class II and 20% in class III), who were treated with ibopamine (n = 53), digoxin (n = 55) or placebo (n = 53) for 6 months. Background therapy consisted of furosemide (0 to 80 mg); all other drugs for heart failure were excluded. Clinical assessments were made at baseline and after 1, 3 and 6 months.Results. Of the 161 patients, 128 (80%) completed the study. Compred with placebo, digoxin but not ibopamine significantly increased exercise time after 6 months (p = 0.008 by intention to treat analysis). Ibopamine was only effective in patients with relatively preserved left ventricular function, as it significantly increased exercise time in this subgroup (for patients with a left ventricular ejection fraction > 0.30; p = 0.018 vs. placebo). No patient receiving digoxin withdrew from the study because of progression of heart failure, compared with six patients receiving ibopamine and two receiving placebo. At 6 months, plasma norepinephrine was decreased with digoxin and ibopamine therapy (−106 and −13 pg/ml, respectively) but increased with placebo administration (+62 pg/ml) (both p < 0.05 vs. placebo). Plasma aldosterone was unaffected, but renin was decreased by boat agents after 6 months (p < 0.05 vs. placbo). Total mortality and ambulatory arrhythmias were not significantly affected by the two drugs.Conclusions. Ibopamine and digoxin both inhibit neurohumoral activation in patients with mild to moderate chronic heart failure. However, the clinical effects of these drugs are different and appear to be related to the degree of left ventricular dysfunction.

Randomized study assessing the effect of digoxin withdrawal in patients with mild to moderate chronic congestive heart failure: Results of the PROVED trial

Objectives. The purpose of this study was to determine whether digoxin is effective in patients with chronic, stable mild to moderate heart failure.Background. Digoxin has been a traditional therapy in heart failure, but methodologic limitations in earlier studies have prevented definitive conclusions regarding its efficacy.Methods. Withdrawal of digoxin (placebo group, n = 46) or its continuation (digoxin group, n = 42) was performed in a prospective, randomized, double-blind, placebo-controlled multicenter trial of patients with chronic, stable mild to moderate heart failure secondary to left ventricular systolic dysfunction who had normal sinus rhythm and were receiving long-term treatment with diuretic drugs and digoxin.Results. Patients withdrawn from digoxin therapy showed worsened maximal exercise capacity (median change in exercise time −96 s) compared with that of patients who continued to receive digoxin (change in exercise time +4.5 s) (p = 0.003). Patients withdrawn from digoxin therapy showed an increased incidence of treatment failures (p = 0.039) (39%, digoxin withdrawal group vs. 19%, digoxin maintenance group) and a decreased time to treatment failure (p = 0.037). In addition, patients who continued to receive digoxin had a lower body weight (p = 0.044) and heart rate (p = 0.003) and a higher left ventricular ejection fraction (p = 0.016).Conclusions. These data provide strong evidence of the clinical efficacy of digoxin in patients with normal sinus rhythm and mild to moderate chronic heart failure secondary to systolic dysfunction who are treated with diuretics.

Efficacy and acceptability of perindopril in mild to moderate chronic congestive heart failure

The aim of this 3-month double-blind, placebo-controlled, multicenter trial was to evaluate the clinical efficacy and safety of perindopril, a new long-acting angiotensin-converting enzyme inhibitor in the second-line treatment of mild to moderate chronic congestive heart failure. After a run-in period of at least 14 days, 125 patients with grade II or III New York Heart Association chronic congestive heart failure on baseline diuretic therapy were randomized to perindopril, 2 mg ( n = 61), or placebo ( n = 64), once daily. Assessment was at 2-week intervals for the first month and then monthly for the 2 following months. After 2 weeks, active treatment was increased to perindopril, 4 mg once daily, if systolic blood pressure was 100 mm Hg or greater. Apart from sex, the two groups were homogeneous before treatment. As shown by the end-point analysis, the increase in exercise time was greater with perindopril than with placebo for both the ergometric bicycle (+111 ± 21 versus +16 ± 20 seconds; p = 0.002) and the treadmill (+171 ± 39 versus +36 ± 42 seconds; p = 0.024). Compared with placebo, this increase in exercise tolerance with perindopril was accompanied by an improvement in New York Heart Association functional class ( p = 0.009), overall heart failure severity score ( p < 0.001), and cardiothoracic ratio ( p = 0.05). Of the 12 withdrawals from the study, seven were attributed to adverse events, two in the perindopril group and five, including one death, in the placebo group. Changes in blood pressure were not significantly different between the two groups except for a moderate fall in erect diastolic blood pressure with perindopril (−4 ± 2 mm Hg vs +2 ± 1 mm Hg; p = 0.007). Plasma creatinine levels remained stable in each group. In conclusion, in patients with mild to moderate chronic congestive heart failure on baseline diuretic therapy, perindopril increases functional capacity and exercise tolerance with a good safety profile, particularly in terms of blood pressure and renal function.

Neuropeptide Y, noradrenaline and invasive haemodynamic data in mild to moderate chronic congestive heart failure.

Neuropeptide Y (NPY) is a peptide released together with noradrenaline (NA) from sympathetic nerve endings. Elevated plasma levels of NA and NPY-like immunoreactivity (LI) are found in patients with congestive heart failure. In order to assess any relationship found between plasma NPY-LI and haemodynamic data 12 patients with mild to moderate chronic congestive heart failure were studied during cardiac catheterization. All patients were treated with diuretics but not ACE inhibitors and were in New York Heart Association functional class II or III. Mean left ventricular ejection fraction determined by echocardiography was 34%. Plasma NPY-LI from mixed venous blood was elevated in five patients and NA in nine. Mean plasma NPY-LI was 29 +/- 3 pmoll-1 (mean +/- standard error of the mean) and NA 2.6 +/- 0.3 nmoll-1. Heart rate was 70 +/- 3 beats min-1, systolic blood pressure (SBP) 131 +/- 7 mmHg, stroke volume index (SVI) 29 +/- 1.9 ml m-2 and cardiac index (CI) 2.0 +/- 0.13 l min-1 m-2. Elevated levels of plasma NPY-LI (> 30 pmol l-1) were associated with lower SVI, CI, and SBP and a higher pulmonary vascular resistance. Elevated plasma NA (> 2 nmol l-1) did not correlate with haemodynamic data. Log NPY-LI correlated inversely with SVI (P < 0.01) and CI (P < 0.05) but not with plasma NA. It is concluded that log NPY-LI in mixed venous blood correlates inversely with SVI and CI in patients with mild to moderate chronic congestive heart failure.

Ventricular unloading and improvement in left ventricular function after angiotensin converting enzyme inhibition with enalapril in patients with chronic congestive heart failure.

To clarify how angiotensin converting enzyme inhibition affects left ventricular function through ventricular unloading, ventricular wall stress, ventricular volumes, and other cardiac indices and exercise tolerance were evaluated in 17 patients with mild to moderate chronic congestive heart failure before and after 3 months of treatment with enalapril. Echocardiographic examination revealed that treatment with this angiotensin converting enzyme inhibitor resulted in significant reductions in end-systolic wall stress (117 +/- 25 to 89 +/- 28 g/cm2, p < 0.01) and left ventricular volume indices (end-diastolic: 163 +/- 56 to 143 +/- 60; end-systolic 99 +/- 51 to 77 +/- 57 ml/m2 p < 0.01). Ejection fraction (42 +/- 11 to 48 +/- 13%, p < 0.01) and systolic blood pressure/end-systolic volume (SBP/ESV; 1.06 +/- 0.30 to 1.33 +/- 0.48 mmHg/ml, p < 0.01) were both increased. By radionuclide ventriculography, ejection fraction and peak ejection rate (2.30 +/- 0.74 to 2.80 +/- 0.76 EDV/sec, p < 0.01) were increased, while time to peak ejection, time to peak filling, and peak filling rate were unchanged. Heart rate and double product at exercise were decreased and delta EF was significantly increased (-1.4 +/- 4.1 to 1.6 +/- 4.4%, p < 0.02). The decrease in end-systolic wall stress was consistently related to both the increase in ejection fraction and SBP/ESV, while the decrease in end-diastolic volume was related only to SBP/ESV and not to ejection fraction. Furthermore, there was a direct relationship between the decrease in systolic wall stress and the decrease in end-diastolic volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic input impedance in mild to moderate chronic congestive heart failure: lack of interrelation with neurohormonal activation.

Patients with chronic congestive heart failure (CHF) have activated neurohormonal systems, which may induce vasoconstriction. In addition, the arterial wall sodium content may increase and could have direct trophic effects on vascular smooth muscle cells. These mechanisms might elevate left ventricular (LV) pulsatile load. We measured aortic input impedance to find out the LV pulsatile load and neurohormonal activation in 20 patients with mild to moderate chronic CHF. Cardiac index (2.2 +/- 0.3 l.min-1 x m-2) and LV ejection fraction (38 +/- 4%) were reduced, pulmonary wedge pressure was elevated (21 +/- 2 mmHg). Plasma norepinephrine levels (462 +/- 62 pg.ml-1), plasma renin concentration (12 +/- 4 ng.AI.ml-1h-1), plasma levels of atrial natriuretic peptide (408 +/- 64 pg.ml-1) and, to a slight degree, plasma arginine vasopressin (1.1 +/- 0.3 pg.ml-1) were increased. Characteristic impedance, Zc, was within the normal range (80 +/- 6 dyn.s.cm-5) and showed no significant correlation with the degree of neurohormonal activation (r-values: -0.05 to -0.35). Our data demonstrate that in early stages of CHF stimulation of the neurohormonal systems does not significantly elevate LV pulsatile load; therefore there is no substantial alteration in the physical properties of the great arteries.

Comparison between New York Heart Association Classification and peak oxygen consumption in the assessment of functional status and prognosis in patients with mild to moderate chronic congestive heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy

To compare the value of the New York Heart Association (NYHA) classification and measurement of peak oxygen consumption (VO 2) in the assessment of functional status and prognosis in patients with mild to moderate chronic congestive heart failure (CHF), 94 patients with clinically stable NYHA class II and III CHF were prospectively studied. In all patients, left ventricular ejection fraction was ≤40% (mean 22 ± 9); 49 patients were in NYHA class II, and 45 were in NYHA class III. Mean peak VO 2 was 17 ± 5 ml/min/kg. During a follow-up period of 23 ± 11 months, 21 patients died. The 1-, 2- and 3-year cumulative survival rates for the 94 patients were 88, 79 and 69%, respectively. Functional status, as assessed both by peak VO 2 and NYHA classification, and left ventricular ejection fraction were significantly worse in the group of nonsurvivors. The most powerful independent predictor of mortality was peak VO 2. Although mean peak VO 2 was significantly higher in NYHA class II than in NYHA class III (20 ± 4 vs 13 ± 3 ml/min/kg, p < 0.0001), categorization into subgroups on the basis of the attained peak VO 2 revealed a marked discrepancy with the NYHA classification. Nevertheless, the survival curves of patients subdivided at a peak VO 2 of 16 ml/min/kg showed a strong resemblance with survival curves of both NYHA classes. In conclusion, both NYHA classification and peak VO 2 are significantly associated with survival time in patients with mild to moderate CHF, but peak VO 2 subdivides patients more clearly into subgroups according to the severity of functional impairment and lifetime prognosis.

Aortic input impedence and neurohormonal activation in patients with mild to moderate chronic congestive heart failure.

The aim was to investigate the interrelation between pulsatile components (assessed by determination of aortic input impedance) and neurohormonal activation in chronic congestive heart failure. Aortic input impedance, plasma noradrenaline, renin, atrial natriuretic factor, and arginine vasopressin were measured in 20 patients with mild to moderate chronic congestive heart failure (coronary artery disease n = 12, idiopathic dilated cardiomyopathy n = 8). Cardiac index [2.2(SEM 0.3) litre.min-1.m-2] and left ventricular ejection fraction [38(4)%] were reduced, and pulmonary wedge pressure was increased [21(2) mmHg]. Plasma concentrations of noradrenaline [462(62) pg.ml-1], renin [12(4) ng AI.ml.h-1], atrial natriuretic factor [408(64) pg.ml-1], and--to a slight degree--arginine vasopressin [1.1(0.3) pg.ml-1] were increased. Characteristic impedance Zc [80(6) dyne.s.cm-5) and relative oscillatory aortic input pressure power [10(1)%]--both reflecting the pulsatile components of left ventricular afterload--were within the normal range. There was no significant correlation between these variables and the degree of neurohormonal activation (r values: -0.05 to -0.35). The data show that in patients with mild to moderate chronic congestive heart failure there is no interrelationship between the degree of neurohormonal activation and pulsatile components of left ventricular afterload. This may indicate that in these stages of heart failure there are no trophic effects of stimulated neurohormonal systems on the physical properties of the great arteries.

Large artery function in patients with chronic heart failure. Studies of brachial artery diameter and hemodynamics.

Although progressive chronic congestive heart failure (CHF) is associated with elevated systemic vascular resistance and increased impedance to ventricular outflow, the contribution of changes in large artery function has not been well documented in humans. We studied 45 patients with a broad range of clinical severity of CHF and compared noninvasive measurements of brachial artery diameter, flow, and pulse wave velocity with 22 normal controls of similar age. In CHF, mean arterial pressure was lower than in controls (85 +/- 1 versus 93 +/- 2 mm Hg, p less than 0.001), as were brachial artery diameter (4.07 +/- 0.10 versus 4.53 +/- 0.09 mm, p less than 0.001), flow (40.9 +/- 4.1 versus 70.9 +/- 11.5 ml.min-1, p less than 0.02), compliance (1.29 +/- 0.12 versus 2.00 +/- 0.18 cm4.dyne-1.10(-7), p less than 0.002), and conductance (0.49 +/- 0.05 versus 0.76 +/- 0.13 units, p = 0.06). Limb vascular resistance (40.2 +/- 5.0 versus 20.5 +/- 3.1 units, p less than 0.001) and pulse wave velocity (10.6 +/- 0.5 versus 9.2 +/- 0.4 m.sec-1, p less than 0.03) were higher than in controls. Brachial artery diameter was progressively lower than in controls as severity of CHF increased (New York Heart Association class II, 4.47 +/- 0.23 mm, p = NS; class III, 4.05 +/- 0.10 mm, p less than 0.05; class IV, 3.71 +/- 0.28 mm, p less than 0.05). Similar changes were observed for arterial compliance (class II, 1.76 +/- 0.32 cm4.dyne-1.10(-7), p = NS; class III, 1.21 +/- 0.13 cm4.dyne-1.10(-7), p less than 0.05; class IV, 0.95 +/- 0.10 cm4.dyne-1.10(-7), p less than 0.05). While the lower arterial pressure and flow might be expected to passively reduce arterial diameter, this would be associated with a reduced pulse wave velocity and improved arterial compliance, yet the opposite was observed. Differences in large artery function were not likely caused by underlying atherosclerosis alone, because patients with dilated cardiomyopathy and patients with ischemic heart disease of the same sex, age, left ventricular ejection fraction, and exercise treadmill duration had similar changes in large artery function. We conclude that alterations in brachial artery function are present in patients with moderate and severe CHF. The observed reduction in arterial compliance, if present diffusely throughout the arterial tree, could increase left ventricular end-systolic stress directly and through increased velocity of reflected pressure waves from the periphery.

Effects of acetylsalicylic acid on renal function in patients with chronic heart failure

We conducted a double-blind, placebo-controlled trial to determine whether the administration of acetylsalicylic acid has adverse effects on renal function in patients with moderate chronic congestive heart failure with and without stimulation of the renin system. Forty patients were randomly assigned to one of the following four groups: Group 1, low sodium diet and placebo; Group 2, low sodium diet and acetylsalicylic acid; Group 3, normal sodium diet and placebo; or Group 4, normal sodium diet and acetylsalicylic acid. Patients were studied over 8 days. After Day 5, patients in Groups 2 and 4 received acetylsalicylic acid (500 mg three times a day). The low sodium diet consisted of 13.6 mmol of sodium per day and the normal sodium diet consisted of 136 mmol of sodium per day. The low sodium diet resulted in a highly significant increase in the plasma renin (2p = 0.0001), aldosterone (2p = 0.0006), and urinary prostaglandin E2 (2p = 0.01) concentrations and the renal potassium excretion (2p = 0.0009), whereas renal sodium excretion was significantly reduced (2p = 0.0001). Severe sodium depletion led to a reduction of the glomerular filtration rate (2p = 0.007), which was independent from cyclooxygenase inhibition. In patients on the low sodium diet, acetylsalicylic acid reduced the elevated urinary prostaglandin E2 levels to normal values without changing the renal sodium excretion rate. In patients with a normal sodium intake, acetylsalicylic acid significantly reduced the renal sodium excretion rate by 29% (2p = 0.04). We conclude that severe sodium depletion has adverse effects on kidney function in patients with heart failure due to a reduction in the glomerular filtration rate. Administration of acetylsalicylic acid in doses that reduce the synthesis of renal prostaglandin E2 significantly reduces renal sodium excretion.

Effect of maintenance digoxin therapy on aerobic performance and exercise left ventricular function in mild to moderate heart failure due to coronary artery disease: A randomized, placebo-controlled, crossover trial

Despite 200 years of use, the ability of digitalis glycosides to improve exercise capacity in patients with congestive heart failure remains controversial, partly because of imprecise end points and suboptimal study design. Therefore, this question was examined in 10 ambulatory patients (8 men and 2 women) aged 46 to 70 years (mean 57.8) in sinus rhythm with mild to moderate chronic stable congestive heart failure due to coronary artery disease and systolic left ventricular dysfunction (ejection fraction 32 +/- 12). All underwent maximal treadmill exercise with respiratory gas analysis and upright cycle ergometry with gated radionuclide angiography after 4 weeks of digoxin or placebo therapy, administered in a randomized double-blind crossover protocol. Neither treadmill exercise duration (7.7 +/- 2.3 versus 7.3 +/- 2.7 min) nor peak oxygen consumption (18.7 +/- 3.7 versus 18.4 +/- 5.4 ml/kg per min) differed between digoxin and placebo regimens. However, the change in peak oxygen consumption induced by digoxin was inversely related to the peak oxygen consumption during placebo therapy (r = -0.64, p less than 0.05). At maximal treadmill effort, heart rate (138 +/- 16 versus 141 +/- 21 beats/min), oxygen pulse (10.3 +/- 2.1 versus 9.9 +/- 2.2 ml/beat), ventilation (40.3 +/- 10.6 versus 42.0 +/- 10.8 liters/min) and ventilatory equivalent (29.4 +/- 4.8 versus 31.5 +/- 6.8) did not differ between digoxin and placebo treatment, although systolic blood pressure was higher during digoxin therapy (163.0 +/- 23.1 versus 153.2 +/- 25.3 mm Hg, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of acetylsalicylic acid on renal function in patients with chronic heart failure

purpose: We conducted a double-blind, placebo-controlled trial to determine whether the administration of acetylsalicylic acid has adverse effects on renal function in patients with moderate chronic congestive heart failure with and without stimulation of the renin system. patients and methods: Forty patients were randomly assigned to one of the following four groups: Group 1, low sodium diet and placebo; Group 2, low sodium diet and acetylsalicylic acid; Group 3, normal sodium diet and placebo; or Group 4, normal sodium diet and acetylsalicylic acid. Patients were studied over 8 days. After Day 5, patients in Groups 2 and 4 received acetylsalicylic acid (500 mg three times a day). The low sodium diet consisted of 13.6 mmol of sodium per day and the normal sodium diet consisted of 136 mmol of sodium per day. results: The low sodium diet resulted in a highly significant increase in the plasma renin (2p = 0.0001), aldosterone (2p = 0.0006), and urinary prostaglandin E 2 (2p = 0.01) concentrations and the renal potassium excretion (2p = 0.0009), whereas renal sodium excretion was significantly reduced (2p = 0.0001). Severe sodium depletion led to a reduction of the glomerular filtration rate (2p = 0.007), which was independent from cyclooxygenase inhibition. In patients on the low sodium diet, acetylsalicylic acid reduced the elevated urinary prostaglandin E 2 levels to normal values without changing the renal sodium excretion rate. In patients with a normal sodium intake, acetylsalicylic acid significantly reduced the renal sodium excretion rate by 29% (2p = 0.04). conclusion: We conclude that severe sodium depletion has adverse effects on kidney function in patients with heart failure due to a reduction in the glomerular filtration rate. Administration of acetylsalicylic acid in doses that reduce the synthesis of renal prostaglandin E 2 significantly reduces renal sodium excretion.