Rationale and design of ACTIVE: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events.

BACKGROUND: Atrial fibrillation (AF) is the most frequently occurring cardiac arrhythmia with often serious clinical consequences. Many patients have contraindications to anticoagulation, and it is often underused in clinical practice. The addition of clopidogrel to aspirin (ASA) has been shown to reduce vascular events in a number of high-risk populations. Irbesartan is an angiotensin receptor-blocking agent that reduces blood pressure and has other vascular protective effects. METHODS AND RESULTS: ACTIVE W is a noninferiority trial of clopidogrel plus ASA versus oral anticoagulation in patients with AF and at least 1 risk factor for stroke. ACTIVE A is a double-blind, placebo-controlled trial of clopidogrel in patients with AF and with at least 1 risk factor for stroke who receive ASA because they have a contraindication for oral anticoagulation or because they are unwilling to take an oral anticoagulant. ACTIVE I is a partial factorial, double-blind, placebo-controlled trial of irbesartan in patients participating in ACTIVE A or ACTIVE W. The primary outcomes of these studies are composites of vascular events. A total of 14000 patients will be enrolled in these trials. CONCLUSIONS: ACTIVE is the largest trial yet conducted in AF. Its results will lead to a new understanding of the role of combined antiplatelet therapy and the role of blood pressure lowering with an angiotensin II receptor blocker in patients with AF.

Effect of amiodarone on mortality after myocardial infarction: a double-blind, placebo-controlled, pilot study.

OBJECTIVES: The goal of this study was to evaluate the effect of amiodarone on mortality, ventricular arrhythmias and clinical complications in high risk postinfarction patients. BACKGROUND: No therapy has been shown to reduce sudden death in patients ineligible to receive beta-adrenergic blocking agents after myocardial infarction. METHODS: Patients who were not eligible to receive beta-blockers were randomized to receive amiodarone (n = 305) or placebo (n = 308) for 1 year. RESULTS: There were 21 deaths in the amiodarone group compared with 33 in the placebo group (odds ratio 0.62, 95% confidence interval [CI] 0.35 to 1.08, p = 0.095). There were two noncardiac deaths in the amiodarone group and none in the placebo group; thus, the difference in cardiac mortality (19 vs. 33, respectively) was statistically significant (odds ratio 0.55, 95% CI 0.32 to 0.99, p = 0.048). There was a significant decrease in Lown class 4 ventricular arrhythmias (7.5% vs. 19.7%, respectively, p < 0.001). Adverse effects developed in 30% of amiodarone-treated patients and 10% of placebo-treated patients. Pulmonary toxicity, which was mild and reversible, occurred in only one patient in the amiodarone group but in no patient in the placebo group. CONCLUSIONS: This trial demonstrated a significant reduction in cardiac mortality and ventricular arrhythmias with amiodarone treatment. However, given the wide confidence intervals and borderline statistical significance of our trial, larger trials are needed to confirm or refute this view.

Evidence for the detrimental effect of adrenaline infused to healthy dogs in doses imitating spontaneous secretion after coronary occlusion.

We have previously shown that acute coronary occlusion in the dog is often accompanied by increased adrenaline release into the blood. In the present study the consequences of this humoral reaction were studied in anaesthetised healthy mongrel dogs subjected to adrenaline infusion administered at a rate relevant to spontaneous release of this amine in coronary occlusion. Adrenaline was infused in a dose of 1.2 microgram.kg-1.min-1 for 4 h. Dogs receiving saline served as the control. Adrenaline administration led to the decrease in insulin/glucose ratio, to a significant fall in serum triiodothyronine and in blood pH. Free fatty acid levels doubled. Histochemically, a diminution in succinic dehydrogenase and ATPase activity in adrenaline-treated hearts was found. A significant fall in the activity of mitochondrial hexokinase in these hearts was detected spectrophotometrically. Electron microscopic study revealed alterations in the mitochondrial structure. These findings indicate that an excess of adrenaline in ammounts similar to that seen in experimental infarction leads to profound metabolic and hormonal disturbances and exerts a detrimental effect upon myocardium.

Secondary prevention after myocardial infarction with class III antiarrhythmic drugs.

First-year mortality after myocardial infarction (MI) is high, amounting to 15%. It has been well documented that ventricular arrhythmias late after MI constitute a risk factor for sudden cardiac death. Consequently, several authors undertook attempts to decrease post-MI mortality with antiarrhythmic drugs. Unfortunately, the class I drugs most widely used in clinical practice proved to be ineffective or they even increased the risk of death, as occurred in the Cardiac Arrhythmia Suppression Trial (CAST). So far, only beta blockers, although not particularly effective in controlling ventricular ectopic beats, have been found to decrease first-year mortality after MI by 26-36%. Class III drugs appear to be promising in this clinical setting. Early study with sotalol showed a positive, although statistically nonsignificant, trend toward decreasing mortality. In a more recent trial with amiodarone (Basel Antiarrhythmic Study of Infarct Survival [BASIS]) done in Switzerland, total mortality was reduced (p < 0.05). It should be stressed that the drug was administered at a low dosage level (200 mg/day) to 98 patients and did not cause serious side effects. Similarly encouraging results have been provided by the Polish Amiodarone Study. Amiodarone given to 305 patients at a low dose (200-400 mg/day) reduced first-year cardiac mortality by 42% (p < 0.05). No serious side effects were noticed. Several ongoing trials should further substantiate the impact of this regimen on mortality after MI.

Effect of supplemental oral L-arginine on exercise capacity in patients with stable angina pectoris.

A randomized, double-blind, placebo-controlled study in patients with clinical symptoms of stable angina pectoris and healed myocardial infarction (n = 22) has shown that oral supplementation with L-arginine (6 g/day for 3 days) increases exercise capacity (tested on a Marquette case 12 treadmill according to the modified Bruce protocol). Results suggest that the inefficient L-arginine/nitric oxide system contributes to limitation of myocardial perfusion and/or peripheral vasodilation during maximum exercise in patients with stable angina pectoris.

Effects of antioxidant vitamins C and E on signal-averaged electrocardiogram in acute myocardial infarction.

Experimental studies indicate that oxygen-free radicals contribute to ischemic myocardial damage and affect electric properties of cellular membranes. We hypothesize that an association exists between an oxygen-free radical-induced component of myocardial ischemic injury and altered electric function that underlies the genesis of ventricular late potentials in the course of myocardial infarction. If so, antioxidant vitamins C and E may prevent alterations in the signal-averaged electrocardiogram (SAECG). To test this hypothesis, we investigated the effect of supplementation with vitamins C and E on the indices of the SAECG in patients with acute myocardial infarction (AMI). Sixty-one patients with AMI were randomized to receive conventional treatment and vitamins C and E, each 600 mg/day, orally for 14 days (supplemented group, n = 33) or conventional treatment only (control group, n = 28). SAECG was recorded on days 1 or 2 and between days 9 and 13 (mean 10). Serum ascorbic acid, tocopherol, plasma lipid peroxides, and oxygen-free radical production by isolated leukocytes were measured on days 1 or 2 and between days 12 and 14. In the control group, SAECG showed an increase in mean QRS and low-amplitude ( < 40 microV) signal durations, from 99 +/- 10 to 111 +/- 13 ms (p < 0.001) and from 31 +/- 8 to 38 +/- 10 ms (p < 0.001), respectively, and a decrease in the root-mean-square voltage of the last 40 ms of the QRS complex, from 36 +/- 25 to 21 +/- 11 microV (p < 0.002). In vitamin-supplemented patients, all these indices remained unchanged. Oxygen-free radical production by isolated leukocytes was decreased compared with that in controls (p < 0.02). Supplementation was confirmed by elevation of serum ascorbic acid and tocopherol. Results support the hypothesis that in patients with AMI, oxygen-free radical-induced cellular damage contributes to alterations in electric function of the heart as seen on the SAECG.

Effect of early captopril treatment on blood adrenaline levels in acute myocardial infarction (the substudy of ISIS-4). International Study of Infarct Survival-4.

Of patients with acute myocardial infarction eligible for the International Study of Infarct Survival-4, randomized to captopril (n = 30) or placebo (n = 33), the captopril group had a significant decrease in blood adrenaline on day 3 compared with baseline values. Results suggest that suppression of sympathetic activity contributes to the beneficial effects of treatment with angiotensin-converting enzyme inhibitors in the early phase of acute myocardial infarction.

Clinical symptoms of mitral valve prolapse are related to hypomagnesemia and attenuated by magnesium supplementation.

Mitral valve prolapse syndrome (MVP) is a frequent disorder characterized by a number of complaints which lessen the quality of life. The pathogenesis of MVP symptoms has not been fully elucidated. Hyperadrenergic activity and magnesium deficiency have been suggested. This study was designed to verify the concept that heavily symptomatic MVP is accompanied by hypomagnesemia and to elucidate whether magnesium supplementation alleviates the symptoms and influences adrenergic activity. We assessed serum magnesium in 141 subjects with heavily symptomatic primary MVP and in 40 healthy controls. Decreased serum magnesium was found in 60% of patients and in 5% of controls (p <0.0001). Patients with low serum magnesium were subjected to magnesium or placebo supplementation in a double-blind, crossover fashion. Typical symptoms of MVP (n = 13), intensity of anxiety, and daily excretion of catecholamines were determined. After 5 weeks, the mean number of symptoms per patient decreased from 10.4 +/- 2.1 to 5.6 +/- 2.5 (p <0.0001), and a significant reduction in weakness, chest pain, dyspnea, palpitations, and anxiety was observed. Increased noradrenaline excretion before and after magnesium was seen in 63% and 17% of patients, respectively (p <0.01). Mean daily excretion of noradrenaline and adrenaline was significantly diminished after magnesium. It is concluded that many patients with heavily symptomatic MVP have low serum magnesium, and supplementation of this ion leads to improvement in most symptoms along with a decrease in catecholamine excretion.

The Organization to Assess Strategies for Ischemic Syndromes (OASIS) registry in patients with unstable angina.

Clinical approaches to the prevention of the potentially catastrophic consequences of coronary ischemic phenomena such as unstable angina and suspected non-Q-wave myocardial infarction (MI) differ across the world. In addition to prevailing physician beliefs in different societies, the level of access to catheterization laboratories largely determines whether an interventionist or conservative strategy is adopted. The Organization to Assess Strategies for Ischemic Syndromes (OASIS)--a prospective registry of approximately 8,000 patients with acute myocardial ischemia with no ST elevation, treated in 95 hospitals across 6 countries--furnished a unique window into regional differences in clinical management and the frequency and timing of invasive procedures (i.e., angiography, percutaneous transluminal coronary angioplasty [PTCA], and coronary artery bypass graft [CABG] surgery), as well as the outcomes of these trends. At 6 months after symptom onset, patients in the United States and Brazil, where the catheterization laboratory facilities are more accessible, underwent significantly (p <0.001) more angiography (69.4%), PTCA (23.6%), and CABG (25.2%) than in Canada and Australia, where the corresponding rates were 48.4%, 17.0%, and 16.8% (p <0.001), respectively; and in Hungary and Poland, where the respective rates were 23.5%, 5.8%, and 10.9% (p <0.001). This relatively aggressive approach led at 6 months to a more substantial decrease in refractory angina in the United States and Brazil than in Canada and Australia (20.4% vs 13.9%; p <0.001), but no improvement in rates of cardiovascular mortality and MI (10.5% versus 10.5%; p = 0.36). There was a significant (p < or = 0.012) increase in stroke, (1.9% vs 1.3%; p = 0.010) and major bleeding (1.9% vs 1.1%; p = 0.009) events. Furthermore, an inverse correlation emerged between baseline cardiovascular risk status and frequency of angiography and PTCA interventions preferentially for low-risk compared with high-risk patients. In concert with findings from other recent randomized trials, the OASIS Registry data suggest that although there are fewer hospital readmissions for unstable angina, there is a trend toward increased rates of death, MI, and stroke. These data urge a cautious approach to the use of invasive procedures in patients with unstable angina unless future trials demonstrate a clear benefit with an aggressive approach.

Nifedipine and captopril exert divergent effects on heart rate variability in patients with acute episodes of hypertension.

Acute changes of heart rate variability (HRV) depict alterations in autonomic influences on cardiovascular system and often precede ventricular arrhythmias. The aim of the study was to assess effects of sublingual 10 mg nifedipine (n = 15) or 25 mg captopril (n = 13) on HRV in consecutive patients admitted to hospital due to severe hypertension. HRV was calculated on-line from 300 cardiac cycles before and 60-90 min after drug administration. At baseline systolic blood pressure (SBP) was > 190 mm Hg and/or diastolic blood pressure (DBP) > 110 mm Hg. Both agents caused similar reduction of blood pressure (BP). Nifedipine reduced variance (-63 +/- 6%; P < 0.0001) and high-frequency (HF) component (-72 +/- 8%; P < 0.0001), and increased both LF/HF ratio (+870 +/- 336%; P < 0.02) and heart rate (+14 +/- 3%; P < 0.0001). Captopril exerted different effects: variance and HF component increased by +176 +/- 55%; (P < 0.007) and +126 +/- 44% (P < 0.015), respectively. LF/HF (low/high frequency) ratio decreased (-44 +/- 19%; P < 0.04) together with heart rate (-4 +/- 1%; < 0.009). It is concluded that captopril, in contrast to nifedipine, increases HRV and decreases LF/HF ratio and therefore is a better choice in hypertensive patients who might be prone to dangerous arrhythmias.

Lack of effect of amiodarone on survival after extensive infarction. Polish Amiodarone Trial.

BACKGROUND: The purpose of this study was to elucidate whether the reduction of mortality with amiodarone after myocardial infarction depended on ejection fraction. METHODS: The data from the Polish Amiodarone Trial were analysed retrospectively. Patients with acute myocardial infarction and contraindications to beta-blockers were randomized on days 5-7 after admission to receive amiodarone (n = 305) or placebo (n = 308). Short and long-term (46 months) mortality were analysed comparing the groups with impaired (ejection fraction < 40%) and preserved (ejection fraction > or = 40%) left ventricular function. A subset of patients (n = 523) with available echocardiograms were subjected to this analysis. RESULTS: Long-term and sudden cardiac mortality were significantly reduced with amiodarone in the group of patients with ejection fraction > or = 40% (amiodarone versus placebo, respectively: 9.1 versus 16.5%, P < 0.05; 3.4 versus 8.2, P < 0.05). No beneficial effect of amiodarone was observed in the group with low ejection fraction (cardiac and sudden cardiac mortality: amiodarone versus placebo, 20.8 versus 19.3% and 7.8 versus 5.7% respectively). One-year mortality also revealed a favourable trend only in amiodarone-allocated patients with ejection fraction > or = 40%. CONCLUSION: Amiodarone decreased long-term and sudden cardiac mortality after myocardial infarction only in patients with preserved left ventricular function. No benefit was observed in patients with decreased ejection fraction.

Platelet aggregation and arrhythmias after myocardial infarction.

We investigated the relationship between platelet aggregability and occurrence of complex arrhythmias in 72 males in the third or fourth week after the onset of myocardial infarction. The patients who displayed complex arrhythmias (n = 31), as opposed to those with stable rhythm (n = 41) showed higher platelet aggregability (48 +/- 27% vs 37 +/- 22%, mean +/- standard deviation, respectively, P less than 0.01). No differences were found with respect to plasma free fatty acids and excretion of catecholamines. It is suggested that, after myocardial infarction, increased platelet aggregability may contribute to the development of complex arrhythmias.

Platelet adhesion is related to heart rhythm disturbances in the acute phase of myocardial infarction.

This study examines the relationship between platelet adhesion, aggregation and the occurrence of heart rhythm disturbances in 43 consecutive patients (mean age 58) admitted to a coronary care unit with acute myocardial infarction. Blood for platelet studies was taken prior to institution of any medication and heart rhythm was monitored (Holter) for 24 h after admission. The control group consisted of 22 healthy subjects (mean age 55 yr). Platelet adhesion to collagen was measured in EDTA-platelet rich plasma by recording the changes in light transmission in an optical aggregometer. Platelet aggregation was measured by the Born method. Platelet adhesion was increased in the group of patients with acute myocardial infarction as compared to controls and was significantly higher in the patients with complex ventricular arrhythmias (Lown 3-4b, n = 18) than in the patients with stable rhythm. Platelet aggregation in the patients with acute myocardial infarction did not differ significantly from the controls and was not related to heart rhythm disturbances. The causal relationship of increased platelet adhesiveness to collagen and heart rhythm disturbances in acute myocardial infarction remains to be established.

Increased activity of circulating polymorphonuclear leukocytes in acute myocardial infarction.

Acute myocardial infarction results in an increased sensitivity of circulating polymorphonuclear leukocytes to ex vivo aggregation. This increase was prevented by pretreatment of leukocytes with BW755, but not with aspirin, suggesting that the activation of blood leukocytes in infarction is due to a stimulation of cellular lipoxygenase.

Increase of R-wave in pre-discharge ergometric test after myocardial infarction indicates advanced left ventricular injury, latent serious arrhythmias and worse prognosis.

Changes in R-wave amplitude during exercise tests performed soon after myocardial infarction (15-31 days, mean 22) were analyzed in 78 men in relation to left ventricular injury (determined by 2-D echocardiography), ventricular arrhythmias (24-h Holter monitoring) and survival after myocardial infarction. It has been found that in patients with mild left ventricular injury (n = 51, Heger index < or = 3) the sum of the R-wave amplitude in 15 precordial leads recorded immediately after exercise decreased by 3.7 +/- 10% in comparison with resting values. In the patients with major left ventricular injury (n = 26, Heger Index > 3) the sum of R-wave amplitude after exercise increased by 12.9 +/- 17.5% (P < 0.001). Positive linear correlation (r = 0.35, P < 0.01) was observed between the level of left ventricular wall motion disturbances and R-wave amplitude changes. In patients with normal or slightly disturbed cardiac rhythm (n = 42, Lown scale 0-2) the sum of the R-wave amplitude after exercise decreased by 5 +/- 18% as compared to resting values, whereas in the patients with complex arrhythmias (n = 23, Lown scale 3-5) the sum of R-wave amplitude increased amounting to 9.9 +/- 17% (P < 0.001). Out of 17 patients who died during 5-year follow up, 16 displayed an increase or no change of the sum of R-wave amplitude. The same kind of relations between R-wave amplitude changes and left ventricular injury or cardiac arrhythmias were noted in patients with anterior and inferior myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

The incidence of asymptomatic paroxysmal atrial fibrillation in patients treated with propranolol or propafenone.

Anti-arrhythmic therapy for paroxysmal atrial fibrillation leads to complete symptomatic relief in a number of patients. The elimination of symptoms may be associated either with a complete elimination of arrhythmia or with a conversion of symptomatic atrial fibrillation into asymptomatic episodes of arrhythmia. The aim of the study was to evaluate the occurrence of asymptomatic paroxysmal atrial fibrillation in 52 patients treated with propafenone (35 drug trials) or propranolol (34 drug trials) by means of ambulatory ECG Holter monitoring. Propafenone was clinically effective (complete relief of symptoms) in 26 (74%) patients. However, in 7 cases (27%) asymptomatic episodes of arrhythmia were still recorded when awake. In patients treated with propranolol clinical symptoms were absent in 18 (53%). However, in 4 (22%) patients attacks of paroxysmal atrial fibrillation were present. The mechanism of drug-induced conversion of symptomatic episodes of atrial fibrillation into asymptomatic spells of arrhythmia was a marked shortening in duration of episodes in 7 patients (from 2215 +/- 3843 s to 16 +/- 10 s, N.S.) or by a significant slowing of ventricular response during atrial fibrillation in 4 patients (from 125 +/- 27 to 84 +/- 8 beats/min, P = 0.05). In conclusion, in a significant proportion of patients with symptomatic paroxysmal atrial fibrillation asymptomatic episodes of arrhythmia may occur while on anti-arrhythmic drug therapy. Some of these patients, particularly those with other risk factors for stroke such as advanced age or the presence of organic heart disease, may require anti-coagulant therapy or change in anti-arrhythmic treatment, and can be selected on the basis of ambulatory ECG monitoring.

Effects of oral L-arginine supplementation on exercise-induced QT dispersion and exercise tolerance in stable angina pectoris.

We assessed the effects of L-arginine (an endogenous precursor of nitric oxide) on the magnitude of exercise-induced QT dispersion in patients with coronary artery disease. The study had a randomized double-blind cross-over design. Twenty-five patients with stable coronary artery disease underwent two separate exercise tests: after oral administration of L-arginine (6 g/24 h for 3 days) or placebo. Indications for cessation of exercise included: pulse limit, exhaustion, chest pain, ST segment depression >2 mm. We found that arginine significantly increased exercise duration from 604+/-146 to 647+/-159 s (P<0.03). However, it had no effect on the sum of exercise-induced ST segment depressions (1.9+/-2.3 and 2.4+/-3.3 on and off arginine, respectively, NS). Exercise shortened QT interval to a similar extent in patients treated with placebo or arginine. QT dispersion changed during exercise from 55+/-21 to 60+/-19 ms (NS) and from 60+/-21 to 53+/-17 ms (NS), respectively. We conclude that, in patients with coronary artery disease, oral supplementation of L-arginine does not affect exercise-induced changes in QT interval duration, QT dispersion or the magnitude of ST segment depression. However, it significantly increases exercise tolerance, most likely due to improved peripheral vasomotion. These results may be of clinical and therapeutic importance.

Isosorbide dinitrate inhibits platelet adhesion and aggregation in nonthrombolyzed patients with acute myocardial infarction.

BACKGROUND: Apart from their vasodilatatory properties, nitrates have been shown to inhibit platelet aggregation. The effects of nitrates on platelet adhesion have not been studied. Nonselected patients with acute myocardial infarction (AMI) have been suggested to gain no benefit from administration of nitrates. However, the importance of nitrates may be greater in a subgroup of nonthrombolyzed patients with AMI. HYPOTHESIS: Isosorbide dinitrate (ISDN) decreases platelet adhesion and aggregation in nonthrombolyzed patients with AMI. METHODS: Consecutive 48 men with AMI, not eligible for thrombolytic therapy because of late presentation (> 12 h), were prospectively randomized 2:1 to double-blind ISDN (mean dose 2.4 +/- 0.9 mg/h) (n = 33) or placebo (0.9% sodium chloride) (n = 15) infusion. All patients received aspirin. Blood samples were taken at baseline (no study medication) and 3 h into ISDN or placebo infusion. Platelet adhesion to collagen was measured in the ethylene diamine tetraacetic acid (EDTA)-platelet rich plasma by recording changes in light transmission with an optical aggregometer. Platelet aggregation was measured using the Born's method. RESULTS: Isosorbide dinitrate significantly decreased both platelet adhesion and aggregation. No effect was seen in the placebo group. CONCLUSIONS: In patients with AMI who do not receive thrombolytic therapy, ISDN effectively inhibits platelet adhesion and aggregation. These effects of nitrates may be of therapeutic and prognostic significance in this group of patients.

Ventricular arrhythmias late after myocardial infarction are related to hypomagnesemia and magnesium loss: preliminary trial of corrective therapy.

It has been well established that in acute myocardial infarction (MI) many patients display low serum magnesium (Mg). This is associated with complex ventricular arrhythmias. The question arises whether predischarge arrhythmias occurring late after MI might also be related to Mg imbalance. In 118 patients subjected to heart rhythm 24 h Holter monitoring in the second or third week after MI, we investigated (1) the relationship between serum Mg, urinary Mg loss, and ventricular arrhythmias, and (2) the effect of Mg supplementation on heart rhythm disturbances. In patients with undisturbed rhythm or monomorphic ventricular ectopic beats (VEB) (Lown 0-2; n = 84), mean serum Mg level (mg% +/- SD) was 1.83 +/- 0.21, whereas in patients with multifocal VEB, pairs, or nonsustained ventricular tachycardia (VT) (Lown 3-4; n = 34) serum Mg was decreased to 1.68 +/- 0.27 (p < 0.01). Serum Mg normal range in our laboratory is 1.7-2.6 mg%. The lowest serum Mg reaching 1.55 +/- 0.27 was found in nonsustained VT (Lown 4 b) subgroup (n = 14). Urinary Mg loss measured in 81 patients was more pronounced in those with Lown 3-4 arrhythmias (n = 26) than with Lown 0-2 (n = 55). The daily values were 73 +/- 22 and 54.4 +/- 26 mg, respectively (p < 0.001). Thirteen patients with complex arrhythmias and low serum Mg received Mg supplementation (MgSO4, 8 g in 500 ml 5% glucose intravenously during 24 h). This resulted in restoration of almost undisturbed rhythm in 10 subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical characteristics of patients with increased urinary excretion of adrenaline in mild to moderate heart failure.

BACKGROUND: We have previously demonstrated that adrenaline (AD) is released into the circulation during acute myocardial infarction and is associated with a more severe clinical course. The role of elevated AD levels in congestive heart failure is not known. HYPOTHESIS: The study aimed to determine whether increased daily AD excretion is associated with more severe clinical symptoms and a more complicated clinical course in patients with exacerbation of congestive heart failure (CHF). METHODS: Urinary excretion of AD, noradrenaline, magnesium (Mg), and potassium (K), serum levels of aldosterone, K, and Mg, as well as the incidence of arrhythmias (24-h Holter) were assessed in 49 patients with CHF New York Heart Association (NYHA) class II-III. The patients were allocated to two groups, with normal (Group 1) and increased (Group 2) excretion of AD. RESULTS: Groups 1 and 2 did not differ in respect of age, etiology of CHF, or the medication used. Also, left ventricular ejection fraction was similar in the two groups. However, left ventricular end-diastolic dimension was greater in Group 2 (61+/-9 vs. 55+/-11 mm, p<0.05), as was the proportion of patients in NYHA class III (74 vs. 40%). Group 2 was also characterized by increased urinary excretion of Mg (60+/-24 vs. 43+/-16 mg/24 h, p < 0.007) and the presence of more complex and numerous ventricular arrhythmias (74 vs. 37% and 68 vs. 33% of patients, respectively). CONCLUSIONS: Urinary excretion of AD is increased only in a subgroup of patients with CHF. These patients are characterized by a more advanced NYHA class, increased end-diastolic left ventricular diameter, and increased urinary excretion of magnesium. It is likely that all these factors contribute to the presence of more complex and numerous ventricular arrhythmias in this subgroup of patients.