Outcome of exercise training on the long-term burden of hospitalisation in patients with chronic heart failure. A retrospective study.

AIMS: Heart failure is a major cause of hospitalisation, particularly in patients more than 65 years of age in the western world. A common endpoint in studies designed to evaluate treatment effects in heart failure is mortality and morbidity, often reported as an event of hospitalisation. It has recently been reported that this endpoint is misleading with respect to the burden of the disease with regard to the patient, the health service and costs. Furthermore, it can be hypothesized that different treatment effects are better evaluated using more sensitive parameters than those traditionally used in clinical studies. Short-term beneficial effects of exercise training in heart failure patients have previously been showed. Therefore, the aim of this study was to evaluate the long-term effects of exercise training in heart failure patients with regard to different outcome parameters. METHOD AND STUDY GROUP: Patients with chronic heart failure, stabilised on pharmacological treatment, who had participated in a physical training program for 8 weeks, were analysed retrospectively after 5 years. The study group was compared to a matched control group which received conventional treatment and was diagnosed during the same period but not participating in a training program. RESULTS: Exercise training in heart failure patients resulted in significantly less hospitalisation events (2+/-3 vs. 3+/-3, p<0.05) and hospitalisation days (10+/-17 vs. 20+/-27, p<0.05) due to cardiac problems at 5 years after follow-up. Exercise training did not effect mortality. CONCLUSION: Long-term effects of exercise training on burden of disease in chronic heart failure patients is associated with significantly less events and days of hospitalisation due to worsening of cardiac disease.

Oscillation of pain intensity during adenosine infusion. Relationship to beta-endorphin and sympathetic tone.

Adenosine is a neuromodulator with both excitatory and inhibitory effects dependent in part upon preconditions; it can act as an algesic or an analgesic agent. Previously we found variations of pain intensity during constant infusion of adenosine. We therefore quantified pain intensity during constant infusion of adenosine at a rate of 140 microg/kg/min intravenously in healthy volunteers, placebo controlled, double blind, and the relation to hemodynamic, vasomotor and sudomotor responses of the sympathetic nervous system and to the role of peripheral beta-endorphin response. The perceived chest pain during adenosine infusion showed an oscillatory pattern. Painful periods of about 30s were interrupted by painfree periods, and pain was always preceded by an increase in vasomotor sympathetic activity and by increased sudomotor activity. Plasma beta-endorphin values were heterogenous but exhibited an increase during infusion.

The effects of metoprolol and captopril on heart rate variability in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: The effects of treatment with captopril or metoprolol on heart rate variability (HRV) were investigated in 38 patients (29 men and 9 women) with mild to moderate symptoms of heart failure due to idiopathic dilated cardiomyopathy (DCM). HYPOTHESIS: The aim of the study was to investigate and compare the effects of the angiotensin-converting enzyme inhibitor captopril with those of the selective beta-adrenergic receptor blocker metoprolol on HRV in patients with idiopathic DCM. METHODS: Heart rate variability was analyzed in the time and frequency domains from 18th of Holter monitoring before randomized treatment was started, after 6 months of therapy, and 1 month after therapy was stopped. RESULTS: Captopril treatment increased HRV expressed as total power and low-frequency power in the frequency domain. There was no change in the time domain. In the metoprolol group, there was a pronounced increase in both time- and frequency-domain indices of HRV. The increase in total power was partly maintained 1 month after therapy was stopped in both treatment groups. CONCLUSION: Treatment with captopril and metoprolol increases HRV in patients with DCM. This effect seems to be maintained for at least 1 month after therapy is stopped. The increase in HRV seems to be more pronounced with metoprolol, and the two different pharmacologic approaches may have additive effects that are of prognostic importance in patients with heart failure.

Beat-to-beat QRS amplitude variability after acute myocardial infarction and coronary artery bypass grafting.

Ischemic myocardial injury has been demonstrated to be associated with increased beat-to-beat electrical variability of the depolarization phase. This can be quantified by electrocardiographic (ECG) signal variance analysis, a technique that has proven its diagnostic value in the detection of coronary artery disease (CAD). This study evaluates QRS amplitude variability during a 6-month follow-up period in 73 patients with acute myocardial infarction (AMI) and in 56 patients subjected to coronary artery bypass grafting (CABG). The beat-to-beat QRS amplitude variability was quantified with variance electrocardiography. The equipment allows computerized time domain analysis of high-fidelity ECG signals from 24 leads, and the detected electrical heterogeneity is then expressed as a nondimensional index ranging from 0 to 150, with values >90 being indicative of ischemic myocardial involvement. One week after AMI 55% of the patients presented with an abnormal QRS variability index >90. A significant (p <0.01) increase in the index values occurred during the follow-up period, but only in the patients with an initial index <70. In the CABG group 44% of the patients had a preoperative QRS variability index >90. The values increased (p <0.05) in all patients after surgery; the increase was transient in patients with an initial index <70 (p <0.01). The results demonstrate that the myocardial injury in patients with CAD is often associated with increased electrical variability of myocardial depolarization. The QRS amplitude variability index can be used as a marker of such an injury, and analysis of its changes in the course of ischemic cardiac events may provide new insights into the dynamics of ischemic heart disease and the myocardial healing process.

Chaos-related deterministic regulation of heart rate variability in time- and frequency domains: effects of autonomic blockade and exercise.

OBJECTIVES: To study non-linear complexity or chaotic behaviour of heart rate in short time series and its dependence on autonomic tone. METHODS: Ten healthy individuals (5 men, mean age 44 years) were investigated at rest, after intravenous injections of propranolol (0.15 mg/kg), followed by atropine (0.03 mg/kg). On another occasion, investigation was made during exercise on a bicycle ergometer at 40% and at 70% of maximal working capacity. Heart rate variability was assessed by: local sensitive dependence on initial conditions as quantitated by the dominant Lyapunov exponent, coefficient of variation of heart rate, power spectral analysis of high- and low-frequency bands and the 1/f-slope of the very-low-frequency band and time domain analysis. RESULTS: The approximate dominant Lyapunov exponent was positive at rest and remained positive during autonomic blockade and during exercise. The exponent decreased significantly with propranolol+atropine and even more so during exercise but did not attain zero. At baseline approximate predictability was lost after about 30 s whereas after autonomic blockade or exercise it was lost after about 60 s. The 1/f-slope remained unaltered around -1. As expected, power in high- and low-frequency bands as well as time domain index decreased significantly with autonomic blockade. The low-frequency band and time domain index were affected by exercise. CONCLUSIONS: Heart rate variability of sinus rhythm in healthy individuals has characteristics suggestive of low-dimensional chaos-like determinism which is modulated but not eliminated by inhibition of autonomic tone or by exercise. The dominant Lyapunov exponent characterises heart rate variability independent or the other investigated measures.

Beat-to-beat QRS amplitude variability during dobutamine infusion in patients with coronary artery disease.

The aim of this study was to investigate if provoked myocardial ischemia induces increased beat-to-beat QRS amplitude variability in patients with angiographically verified coronary artery disease. 15 patients (median age 62 years, range 46-73 years) and 10 healthy controls (median age 25 years, range 22-42 years) were studied. Dobutamine was infused intravenously at a low and at a high dose. The mean low dose of the drug was 10.0 micrograms/kg/min for both patients and controls, whereas the mean maximum dose was 31 +/- 2 for patients and 38 +/- 1 microgram/kg/min for controls. The total QRS amplitude beat-to-beat variance from 12 leads as well as individual variance scores in each single lead were evaluated. Before infusion, the total QRS variance did not differ between patients and controls, nor did the individual variance in 9 of the 12 ECG leads. Dobutamine elicited an increase (p < 0.01) in the total QRS variance, with significantly higher (p < 0.001) total variance in patients than in controls. At the high dose of the drug, the patients displayed significantly higher individual variance values in each ECG lead as well. During dobutamine infusion, 7 of 15 patients developed ST depressions (> or = 0.1 mV in > or = 2 leads) in 12-lead ECG readings. Eleven of 15 patients developed chest pain (grade > or = 3 at the Borg's CR-10 scale). In conclusion, in patients with ischemic heart disease, dobutamine-provoked stress gives rise to increased QRS amplitude beat-to-beat variability, as a sign of electrical instability of the myocardium.

Platelet and leukocyte activation after myocardial infarction. Influence of enalapril.

In this double-blind placebo-controlled study with enalapril, 74 patients with acute myocardial infarction were followed at 0, 7, 30, 60 and 180 days after the event. Platelets and leukocytes were activated during the first 7 days. During the 6-month period fibrinogen, leukocytes, elastase, and B beta 30-43 remained elevated in 50, 15, 30 and 80% of the patients, respectively, but there was no detectable angiotensin converting enzyme activity in platelets. Enalapril did not modulate fibrinogen, leukocyte count or elastase, while B beta 30-43 peptide showed decreased levels, although the proportion of patients with values above the reference limit did not differ from placebo. In conclusion, in the 6-month post acute myocardial infarction period, while platelet function is activated only during the first week after acute myocardial infarction, fibrinogen and leukocyte function continue to be activated throughout the 6 months in a considerable proportion of patients. These signs may indicate an ongoing atherosclerotic process. Enalapril has no major influence on these reactivities.

Variance ECG detection of coronary artery disease--a comparison with exercise stress test and myocardial scintigraphy.

Variance electrocardiogram (ECG) is a newly developed method by which resting ECG is registered with 24 leads during 220 beats. The temporal beat-to-beat QRS microamplitude variability is computed and a nondimensional diagnostic variance ECG coronary artery disease (CAD) index is derived from it. Consecutive outpatients (n = 160) were referred to myocardial scintigraphy (SPECT) investigation for the evaluation of angina pectoris. The variance ECG CAD index was compared with a symptom-limited exercise stress test and SPECT during and after the exercise test and with coronary angiography (n = 67). Discriminant accuracy was tested with receiver-operating characteristics (ROC). Relative to angiographic coronary pathology (prevalence 0.85), diagnostic information for the variance ECG CAD index and for SPECT were both p < 0.001, while the outcome of the exercise stress test was non-contributory. Prevalence of persistent or transient perfusion defects at SPECT was 0.59. The exercise stress test had a diagnostic capacity of p < 0.01 for transient perfusion defects and variance ECG CAD index showed a high diagnostic performance (p < 0.001) for persistent perfusion defects. Overall pathology at SPECT was better (p < 0.05) identified by variance ECG CAD index than by symptom-limited exercise stress test. It was concluded that in this high prevalence population the variance ECG CAD index has a diagnostic capacity at least as good as that of SPECT and better than that of the exercise stress test. The variance ECG CAD index was strongly diagnostic for persistent perfusion defects while exercise stress test was slightly diagnostic for transient perfusion defects. Therefore, the two tests provide complementary diagnostic information.

Streptokinase, but not tissue plasminogen activator, attenuates platelet aggregation in patients with acute myocardial infarction.

OBJECTIVES: To investigate if tissue plasminogen activator (tPA) and streptokinase given during acute myocardial infarction (AMI) have different effects on platelet aggregation which could contribute to the higher reocclusion rate observed after tPA. DESIGN: Open labelled on consecutive patients. SETTING: Coronary care unit. SUBJECTS: Twenty patients with chest pain and ST elevations on an electrocardiogram suggestive of AMI. INTERVENTIONS: Ten patients were treated with tPA (100 mg 3 h-1), 10 patients with streptokinase (1.5 x 10(6) IU 1 h-1). MAIN OUTCOME MEASURES: Before, immediately after and 24 h after fibrinolytic therapy, platelet aggregation was estimated with filtragometry and whole blood aggregometry. Fibrinogen, beta-thromboglobulin, elastase and the fibrinogen-derived peptide B beta 30-43 were also measured. RESULTS: The groups were comparable at baseline. Directly after treatment, streptokinase prolonged aggregation time in filtragometry with 112 +/- 140 s (P < 0.03) and reduced conductance in whole blood aggregometry by 6.2 +/- 6.1 omega (P < 0.03), both tests indicating inhibited platelet function. Fibrinogen decreased 2.5 +/- 1.0 g l-1 (P < 0.02). In the tPA-treated group corresponding changes were 68 +/- 225 s (NS) and 2.5 +/- 7 omega (NS) with no significant reduction in fibrinogen. After 24 h, at which time every patient was on acetylsalicylic acid, aggregation was inhibited in both groups as measured by aggregometry. Directly after fibrinolytic treatment, neutrophils were similarly activated in both groups with increments of elastase and B beta 30-43 by 26 +/- 46 micrograms l-1 (P < 0.03) and 280 +/- 381 pmol l-1 (P < 0.03) respectively (streptokinase) and by 12 +/- 6 micrograms l-1 (P < 0.02) and 919 +/- 856 pmol l-1 (P < 0.02) respectively (tPA). CONCLUSIONS: Despite similar degrees of platelet and leucocyte activation, streptokinase but not tPA treatment appears to inhibit platelet aggregation. One possible reason could be a streptokinase-induced pronounced decrease of fibrinogen and increase of fibrinogen split products. Therefore, further development of adjuvant antiplatelet therapy could be of clinical importance.

Electrocardiogram signal variance analysis in the diagnosis of coronary artery disease--a comparison with exercise stress test in an angiographically documented high prevalence population.

Variance electrocardiography (variance ECG) is a new resting procedure for detection of coronary artery disease (CAD). The method measures variability in the electrical expression of the depolarization phase induced by this disease. The time-domain analysis is performed on 220 cardiac cycles using high-fidelity ECG signals from 24 leads, and the phase-locked temporal electrical heterogeneity is expressed as a nondimensional CAD index (CAD-I) with the values of 0-150. This study compares the diagnostic efficiency of variance ECG and exercise stress test in a high prevalence population. A total of 199 symptomatic patients evaluated with coronary angiography was subjected to variance ECG and exercise test on a bicycle ergometer as a continuous ramp. The discriminant accuracy of the two methods was assessed employing the receiver operating characteristic curves constructed by successive consideration of several CAD-I cutpoint values and various threshold criteria based on ST-segment depression exclusively or in combination with exertional chest pain. Of these patients, 175 with CAD (> or = 50% luminal stenosis in 1 + major epicardial arteries) presented a mean CAD-I of 88 +/- 22, compared with 70 +/- 21 in 24 nonaffected patients (p < 0.01). Variance ECG provided a stochastically significant discrimination (p < 0.01) which was matched by exercise test only when chest pain variable was added to ST-segment depression as a discriminating criterion. Even then, the exercise test diagnosed single-vessel disease with a significantly lower sensitivity. At a cutpoint of CAD-I > or = 70, compared with ST-segment depression > or = 1 mm combined with exertional chest pain, the overall sensitivity of variance ECG was significantly higher (p < 0.01) than that of exercise test (79 vs. 48%). When combined, the two methods identified 93% of coronary angiography positive cases. Variance ECG is an efficient diagnostic method which compares favorably with exercise test for detection of CAD in high prevalence population.

[Diagnostic innovations in electrophysiology. Variance ECG]. / Diagnostiskt nytänkande inom elektrofysiologin. Varians-EKG.

Variance ECG constitutes an important technological and methodological advance in electrocardiography (ECG). The variance index has been found to diagnose ischaemic heart disease at least as well as myocardial scintigraphy, and considerably better than exercise testing. Exercise testing detects acute myocardial ischaemia provoked by physical exertion, whereas resting variance ECG findings presumably reflect any deficiency in the regulation of electrical impulse distribution due to structural changes and chronic low-grade ischaemia that may occur in patients with coronary artery disease.

Enhanced platelet function in acute myocardial infarction is attenuated by streptokinase treatment.

The aim of this study was to determine whether platelets are activated and aggregation is increased in myocardial infarction treated with streptokinase. Twelve consecutive patients were studied. Before streptokinase infusion (1.5 x 10(6) IU i.v. over a period of 1 h), 7 +/- 4 h after the onset of symptoms, fibrinogen, leucocyte and platelet functions were enhanced compared to reference values. Plasma fibrinogen was 3.1 +/- 0.6 g 1-1 (P less than 0.03), leucocyte count was 14.3 +/- 3.3 x 10(3) l-1 (P less than 0.0005), elastase was 39 +/- 8 micrograms l-1 (P less than 0.0002), beta-thromboglobulin was 68 +/- 71 micrograms 1-1 (P less than 0.0001) and filtragometer platelet aggregation time was 137 +/- 40 s (P less than 0.0001). After streptokinase the leucocyte count, elastase and beta-thromboglobulin levels increased further, by about 40% (P less than 0.02), 130% (P less than 0.02) and 140% (P less than 0.005), respectively. Fibrinogen was almost eliminated. Despite signs of increased activation, platelet aggregation was decreased as indicated by both filtragometer aggregation time, which increased by about 480% (P less than 0.003), and whole-blood aggregometry, in which electrical impedance decreased by about 65% (P less than 0.01).