[Initial experience with using phosphocreatine in patients in the early (up to 6 hours) period of myocardial infarction]. Creatine supplementation improves muscle strength in patients with congestive heart failure. [Myocardial T1-201 scintigraphy in the study of the development of acute myocardial infarction. Evaluation of the effects of a drug with metabolic action: creatine phosphate]. Hemodynamic effects of creatine phosphate in patients with congestive heart failure: a double-blind comparison trial versus placebo. Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance. Reduction of ventricular arrhythmias by phosphocreatine (Neoton) in patients with acute myocardial infarction. [Use of phosphocreatinine in treatment of acute heart failure].
A randomized study of 60 patients with myocardial infarction (MI) admitted to hospital in the first 6 hours of the disease was performed in order to study the effect of phosphocreatine (PC) on the course of MI. 30 patients were treated with PC; control group consisted also of 30 patients. PC infusion in the early period of MI resulted in the decreased frequency of ventricular arrhythmias (including paroxysms of ventricular tachycardia) and lowered likelihood of cardiac failure development. No reliable influence of PC on the central hemodynamics, heart rate, heart conduction and myocardial necrosis size was determined. Both, cardiac and skeletal muscle creatine levels are depressed in patients with congestive heart failure (CHF). Oral supplementation of creatine (Cr) could increase physical performance in healthy volunteers. We therefore hypothesized that oral creatine supplementation improves skeletal muscle strength, quality of live and symptom-limited performance in patients with CHF.
                In a double-blind, placebo-controlled and crossover-designed study, 20 patients suffering from congestive heart failure more than 6 months and a peak oxygen uptake (peak VO2) below 20 ml/min/kg received 4 x 5 g Cr daily vs. placebo for 6 weeks and were crossed over for the following 6 weeks. Peak VO2, VO2 at the anaerobic threshold (VO2AT), ejection fraction (EF), distance in 6-minute-walk-test (6 min W), and muscle strength (Modified Sphygmomanometer (MS)) were determined at baseline, after 6, and after 12 weeks. Dyspnoea after 6-minute-walk-test was measured using the Borg Scale. Quality of live was assessed with the Minnesota Living with Heart Failure Questionnaire (MLHFQ).
                13 of 20 Patients finished the study. After 6 weeks of creatine supplementation there was a significant increase in body weight and muscle strength compared to baseline and placebo (p < 0.05). However, there was no significant change in peak VO2, VO2AT, walking distance, quality of life assessment and EF.
                Short-term creatine supplementation inaddition to standard medication in patients with CHF leads to an increase in body weight and an improvement of muscle strength. This effect is restricted to the time of supplementation. nan The use of metabolic drugs effective in addition to conventional therapy represents a significant challenge in patients with left ventricular dysfunction.
                The aim of this double-blind, placebo-controlled study was to investigate the hemodynamic effects of acute intravenous (i.v.) administration of creatine phosphate (CP) and of short-term treatment in patients with congestive heart failure (CHF) from ischemic heart disease (IHD) or dilated cardiomyopathy in addition to conventional therapy.
                We compared the hemodynamic effects of exogenous creatine phosphate (CP) and placebo in a double-blind, crossover design study in 13 hospitalized patients (12 men, 1 woman, mean age 52 +/- 8 years) with CHF. All patients were in New York Heart Association (NYHA) class II-III and received conventional pharmacologic therapy for CHF; this was not changed during the study period. The study design consisted of two treatment periods (CP or placebo and placebo or CP, respectively) of 4 days each, separated by a 2-day washout interval. The intravenous infusion consisted of 6 g CP or placebo (acute treatment) or 6 g CP or placebo daily for 4 days (short-term treatment) diluted in 50 ml of NaCl 0.9%; infusion duration was about 10 min. Mono-bidimensional echocardiographic examination (Hewlett Packard Sonos 1000, with a 2.5 MHz transducer) was performed at baseline, after acute infusion, and 12 h after the end of short-term treatment. Data were analyzed by ANOVA and Student's t-test for paired data; the results obtained after acute and short-term therapy were compared with the baseline values.
                After placebo therapy, no significant change was observed. The results after treatment with CP showed a significant reduction of end-systolic diameter [baseline: 4.5 +/- 0.6; acute: 4.2 +/- 0.5, (p < 0.001); short-term 4.3 +/- 0.6 cm, (p < 0.05)] and systemic vascular resistance (baseline: 1064.9 +/- 483.7; acute: 947.5 +/- 390.2 (p < 0.05); short-term: 950.7 +/- 394.3 dyne-s-cm-5 (p < 0.05); moreover, a significant increase of percent ejection fraction [baseline: 48 +/- 12%; acute 53 +/- 12% (p < 0.01); short-term 52 +/- 11% (p < 0.01)], and of percent fractional shortening [baseline: 25 +/- 7; acute 28 +/- 8 (p < 0.05); short-term 28 +/- 7% (p < 0.05)] was observed.
                CP was shown to improve cardiac function, even in the presence of a conventional CHF pharmacologic therapy. Cardiac creatine levels are depressed in chronic heart failure. Oral supplementation of creatine to healthy volunteers has been shown to increase physical performance.
                To evaluate the effects of creatine supplementation on ejection fraction, symptom-limited physical endurance and skeletal muscle strength in patients with chronic heart failure.
                With a double-blind, placebo-controlled design 17 patients (age 43-70 years, ejection fraction < 40) were supplemented with creatine 20 g daily for 10 days. Before and on the last day of supplementation ejection fraction was determined by radionuclide angiography as was symptom-limited 1-legged knee extensor and 2-legged exercise performance on the cycle ergometer. Muscle strength as unilateral concentric knee extensor performance (peak torque, Nm at 180 degrees/s) was also evaluated. Skeletal muscle biopsies were taken for the determination of energy-rich phosphagens.
                Ejection fraction at rest and at work did not change. Performance before creatine supplementation did not differ between placebo and creatine groups. While no change was seen in the placebo group compared to baseline, creatine supplementation increased skeletal muscle total creatine and creatine phosphate by 17 +/- 4% (P < 0.05) and 12 +/- 4% (P < 0.05), respectively. Increments were seen only in patients with < 140 mmol total creatine/kg d.w. (P < 0.05). One-legged performance (21%, P < 0.05), 2-legged performance (10%, P < 0.05), and peak torque, Nm (5%, P < 0.05) increased. Both peak torque and 1-legged performance increased linearly with increased skeletal muscle phosphocreatine (P < 0.05). The increments in 1-legged, 2-legged and peak torque were significant compared to the placebo group, (P < 0.05).
                One week of creatine supplementation to patients with chronic heart failure did not increase ejection fraction but increased skeletal muscle energy-rich phosphagens and performance as regards both strength and endurance. This new therapeutic approach merits further attention. On the basis of the positive results of recent experimental research, a clinical trial of phosphocreatine (Neoton) was carried out in 60 randomized patients with acute myocardial infarction (30 patients in the Neoton group and 30 patients in the control group). Neoton was given intravenously not later than 6 hours after the onset of symptoms, in a dose of 2 gm as a bolus injection, followed by a 2-hour infusion at the rate of 4 gm/hr. Holter monitoring for 24 hours showed a significant decrease in the frequency of ventricular premature beats: in the Neoton-treated group the total number of ventricular premature beats for 24 hours was 690 +/- 179 vs 2468 +/- 737 in the control group (p less than 0.02). During this period of time the number of ventricular tachycardia paroxysms was 6 +/- 2 in the treated group and 97 +/- 35 in the control group (p less than 0.01). No side effects or complications were found after administration of phosphocreatine. It is concluded that phosphocreatine may be a potentially important antiarrhythmic drug for treatment of patients with acute myocardial infarction. nan
This review found inconclusive evidence to decide on the use of creatine analogues in clinical practice. In particular, it is not clear whether there is an effect on mortality, progression of myocardial infarction and ejection fraction, while there is some evidence that dysrhythmia and dyspnoea might improve. However, it is not clear which analogue, dose, route of administration, and duration of therapy is most effective. Moreover, given the small sample size of the discussed trials and the heterogeneity of the population included in these reports, larger clinical studies are needed to confirm these observations.