The effect of coenzyme Q10 in patients with congestive heart failure.

BACKGROUND: Coenzyme Q10 is commonly used to treat congestive heart failure on the basis of data from several unblinded, subjective studies. Few randomized, blinded, controlled studies have evaluated objective measures of cardiac performance. OBJECTIVE: To determine the effect of coenzyme Q10 on peak oxygen consumption, exercise duration, and ejection fraction. DESIGN: Randomized, double-blind, controlled trial. SETTING: University and Veterans Affairs hospitals. PATIENTS: 55 patients who had congestive heart failure with New York Heart Association class III and IV symptoms, ejection fraction less than 40%, and peak oxygen consumption less than 17.0 mL/kg per minute (or <50% of predicted) during standard therapy were randomly assigned. Forty-six patients completed the study. INTERVENTION: Coenzyme Q10, 200 mg/d, or placebo. MEASUREMENTS: Left ventricular ejection fraction (measured by radionuclide ventriculography) and peak oxygen consumption and exercise duration (measured by a graded exercise evaluation using the Naughton protocol) with continuous metabolic monitoring. RESULTS: Although the mean (+/-SD) serum concentration of coenzyme Q10 increased from 0.95+/-0.62 microg/mL to 2.2+/-1.2 microg/mL in patients who received active treatment, ejection fraction, peak oxygen consumption, and exercise duration remained unchanged in both the coenzyme Q10 and placebo groups. CONCLUSION: Coenzyme Q10 does not affect ejection fraction, peak oxygen consumption, or exercise duration in patients with congestive heart failure receiving standard medical therapy.

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.

Elevated concentrations of endogenous ouabain in patients with congestive heart failure.

BACKGROUND: An endogenous digitalis-like compound in mammals has long been postulated, but only recently has a substance indistinguishable from ouabain been identified in human plasma. Because of the potential significance of such a substance in patients with congestive heart failure, we sought to evaluate the pathophysiology of endogenous ouabain in these individuals. METHODS AND RESULTS: Using an immunoassay, we determined plasma ouabain concentrations in 51 patients with heart failure and in 19 control subjects. Plasma ouabain concentrations in control subjects ranged from 0.16 to 0.77 nM (mean, 0.44 +/- 0.20 nM). In 19 matched heart failure patients receiving digoxin, the mean ouabain was significantly elevated at 1.59 +/- 2.2 nM (range, 0.17-8.76 nM, p less than 0.05 versus control subjects). The ouabain concentration correlated inversely with both cardiac index (r = -0.62, p less than 0.005) and mean arterial pressure (r = -0.51, p less than 0.05). However, there was no correlation between ouabain and left ventricular filling (r = 0.19, NS) or right atrial pressures (r = 0.20, NS). In 16 heart failure patients not receiving digoxin, the mean ouabain was 1.52 +/- 2.58 nM. No relation between renal function and ouabain was detected. CONCLUSIONS: The unanticipated lack of correlation of ouabain with atrial pressures indicates that volume is not the chief determinant of ouabain concentration in patients with congestive heart failure. However, the significant relations of plasma ouabain concentration with cardiac index and mean arterial pressure imply that endogenous ouabain may be an important homeostatic factor in humans.

Determinants of the renal response to ACE inhibition in patients with congestive heart failure.

The objective of the present study was to determine whether pretreatment neurohormonal and renal hemodynamic parameters predict the change in renal function with the administration of quinapril, a new angiotensin-converting enzyme (ACE) inhibitor. Twenty patients with New York Heart Association (NYHA) class III and IV heart failure were evaluated. Following pretreatment determination of renal function and plasma neurohormones, patients were treated daily with 10 mg of quinapril. Measurements of glomerular filtration rate (GFR) and renal plasma flow (RPF) were repeated after 7 weeks to assess changes in function (delta GFR and delta RPF). Mean GFR increased from 49 +/- 6 to 56 +/- 7 ml/min/1.73 m2 (p = 0.10), but decreased in five patients. Mean RPF increased from 235 +/- 23 to 252 +/- 23 ml/min/1.73 m2 (p = 0.08), but decreased in five patients. There was no relation between delta GFR and baseline determinations of GFR, RPF, plasma renin activity, plasma angiotensin II, or serum Na. Only a high filtration fraction (GFR/RPF) predicted a decreased GFR (r = 0.61, p less than 0.005). In contrast, no baseline renal hemodynamic parameter correlated with delta RPF. We conclude that poor renal function does not increase the risk of renal deterioration with quinapril. However, dependence of renal function upon the renin-angiotensin system may be predicted by a high filtration fraction.