Predictors of ventricular tachyarrhythmia in high-risk myocardial infarction patients treated with primary coronary intervention.

Background. We investigated the association between clinical characteristics, angiographic data and ventricular arrhythmia in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI)Methods. In patients with STEMI (n=225), a Holter analysis was performed the first 12 hours after primary PCI.Results. A total of 151 (66%) patients had >/=1 episode of ventricular tachycardia (VT). Age <70 years (RR 4.9, 95% CI 1.8 to 12.7), TIMI 0-1 pre-PCI (RR 2.6, 95% CI 1.1 to 6.1) and peak CK (RR 3.5, 95% CI 1.9 to 5.8) were independent predictors of VT. One-year mortality was 7%, no association between mortality and presence of early VT was found.Conclusion. Ventricular tachycardia is common in the first 12 hours after primary PCI for STEMI. Independent predictors of VT are younger age, TIMI 0-1 flow prior to PCI and larger infarct size. The presence of early VT was not significantly associated with one-year mortality. (Neth Heart J 2010;18:122-8.).

Low-dose anthracyclines in childhood Acute Lymphoblastic Leukemia (ALL): no cardiac deterioration more than 20 years post-treatment.

INTRODUCTION: In children with cancer a well-known risk factor for cardiotoxicity is a high cumulative dose of anthracyclines, but little is known about cardiac function in low-dose anthracycline-treated survivors. Also, it is unclear if a safe anthracycline-dose exists at all. PATIENTS AND METHODS: Cardiac function was assessed in 23 long-term ALL-survivors with a median follow-up of 22 years (range 19.5-24.5) post-treatment. Age at diagnosis and current age were 5.0 (2.0-14.0) and 29.0 (24.0-39.0) years. All 23 survivors were treated according to DCLSG protocol ALL-5, including 18-25 Gy cranial irradiation. Thirteen of them received 4 x 25 mg/m(2) daunorubicin by randomization. Cardiac evaluation included blood pressure measurement, echocardiography, and (24 h-) electrocardiogram. Results were compared with an earlier assessment at median 12 years post-treatment. RESULTS: None of the survivors had cardiac abnormalities. Cardiac status of daunorubicin-treated survivors showed no deterioration compared with the previous assessment in 1995. CONCLUSION AND IMPLICATION FOR CANCER SURVIVORS: After prolonged follow-up (more than 20 years post-treatment), ALL-survivors treated with low dose daunorubicin had no clinical relevant deterioration of cardiac function.

Long-term cardiac follow-up in survivors of a malignant bone tumour.

BACKGROUND: Longitudinal studies of cardiac function in long-term childhood cancer survivors are scarce and frequently concern a median follow-up shorter than 13 years. PATIENTS AND METHODS: Cardiac assessment was performed in 22 doxorubicin-treated long-term survivors of a malignant bone tumour at median 22 years (range 15-27.5) post-treatment. Age at follow-up was 39 years (range 27-59) and cumulative dose of doxorubicin was 360 mg/m(2) (range 225-550). Cardiac function was assessed by echocardiography and (24-h) ECG. The results were compared with those of earlier assessments at 9 years (1992) and 14 years (1997) post-treatment. RESULTS: Systolic dysfunction was found in 27% (9% in 1997; P = 0.02) and diastolic dysfunction in 45% (18% in 1997; P = 0.02). Heart rate variability showed further deterioration compared with earlier results. CONCLUSIONS: Twenty-two years after doxorubicin-treatment, bone tumour survivors showed progressive cardiac dysfunction.

Macronutrient digestibility, nitrogen balance, plasma indicators of protein metabolism and mineral absorption in horses fed a ration rich in sugar beet pulp.

In a cross-over study with six mature horses, the effect of iso-energetic replacement of dietary glucose by beet pulp on macronutrient digestibility, nitrogen metabolism and mineral absorption was studied. The test ration contained 25% beet pulp in the total dietary dry matter. Beet pulp feeding significantly lowered crude fat and non-structural carbohydrate digestibility, but had no significant effect on digestibility of other macronutrients, faecal and urinary nitrogen excretion and the faecal to urinary nitrogen excretion quotient. However, on the beet pulp diet, plasma ammonia and creatinin concentrations were significantly lower than on the glucose diet. No diet effect on magnesium absorption was observed. It is suggested that dietary beet pulp stimulates the conversion of ammonia into urea.

Effects of dietary fermentable carbohydrates on behavior and heat production in group-housed sows.

The effects of dietary nonstarch polysaccharides (NSP) on behavior and heat production in group-housed sows were studied. Twelve groups of six nonpregnant sows were fed one of four experimental diets that were similar in composition except for starch and NSP contents. Exchanging sugar beet pulp silage (SBPS) for tapioca created the difference in dietary starch and NSP ratio. On a dry matter (DM) basis, diets contained 0, 10, 20, or 30% SBPS. Sows were group-housed. Intake of fermentable NSP (fNSP) for diets containing 0, 10, 20, or 30% SBPS averaged 7.06, 9.18, 11.61, and 13.73 g x kg(-0.75) d(-1), respectively. Sows were fed, once a day at 0800. Dry matter intake for diets containing 0, 10, 20, or 30% SBPS, averaged 38.05, 38.38, 38.53, and 38.35 g x kg(-075) x d(-1), respectively, and ME intake averaged 523, 518, 514, and 493 kJ x kg(-0.75) x d(-1), respectively. On average, sows spent 177 min/d on physical activity, of which 8.8% was spent on eating. Time spent in physical activity was affected by diet (P = 0.005). Sows fed 0 or 10% SBPS spent more time on physical activity than sows fed 20 or 30% SBPS (P = 0.002). Energy cost of physical activity averaged 464 kJ x kg(-0.75) x d(-1) (standard estimated mean of 31) and was similar for diets (P = 0.679). Total heat production (HP) and activity-related heat production (AHP) were affected by diet (P < 0.05). Sows tended to be quieter when fNSP intake increased (P = 0.063). The effect of fNSP intake on HP and AHP was not constant during the day. During the night period, fNSP intake did not affect HP and AHP (P > 0.10). During the day period, increased fNSP intake decreased HP (P = 0.006) and tended to decrease AHP (P = 0.062). During eating, increased fNSP intake increased HP (P = 0.012) and tended to increase AHP (P = 0.074). Despite similar DMI, sows fed 0 or 10% SBPS spent less time eating than sows fed 20 or 30% SBPS (P = 0.009). Feed consumption rate was higher (P = 0.003) in groups fed 0 or 10% SBPS than in groups fed 20 or 30% SBPS. Feed consumption rate decreased by 0.19 g DM x kg(-0.75). min(-1) (P = 0.003) for each gram of fNSP intake. The energy saving effect of physical activity on the NE value of fNSP from SBPS ranged between 2.3 and 3.7 kJ/g of fNSP intake. In conclusion, intake of fNSP from SBPS affected energy expenditure for physical activity (P = 0.063); however, this effect was not constant during the day.

Cardiac status in bone tumor survivors up to nearly 19 years after treatment with doxorubicin: a longitudinal study.

BACKGROUND: Longitudinal assessment of cardiac toxicity in anthracycline-treated long-term bone tumor survivors. PROCEDURES: Cardiac status was assessed in 29 patients 14.1 (range 7-18.7) years after treatment with doxorubicin (DOXO) 360 mg/m(2) (median 225-550). The median age of the patients at the time of the study was 32.5 years (range 19.7-52). The evaluation consisted of an electrocardiogram (ECG), 24-hr ambulatory ECG with analysis of heart rate variability (HRV) and echocardiography. The results were compared to those of a study of the same patients that was performed 5 years earlier 8.9 years (range 2.3-14.1) after treatment. [Postma et al.: Med Pediatr Oncol 26:230-237, 1996] RESULTS: We found no progression of ECG abnormalities, arrhythmias, or echocardiographic abnormalities. Females were at risk for reduced contractility (P = 0.006). HRV was significantly reduced compared to age- and sex-matched controls and compared to the previous results. CONCLUSIONS: Anthracycline-related late echocardiographic abnormalities and arrhythmias detected 8.9 years after treatment, showed no further deterioration with ongoing follow-up. However, there was a significant reduction of HRV. This suggests that HRV might be a sensitive test for detection of anthracycline-induced cardiac toxicity.

A large family characterised by nocturnal sudden death.

BACKGROUND: We recently identified a novel mutation in large family characterised by premature nocturnal sudden death. In the present paper we provide an overview of the findings in this family. METHODS: From 1958 onwards, when the first patient presented, we collected clinical data on as many family members as possible. After identification in 1998 of the underlying genetic disorder (SCN5A, 1795insD), genotyping was performed diagnostically. RESULTS: Since 1905 unexplained sudden death occurred in 26 family members, 17 of whom died during the night. Besides sudden death, symptomatology was rather limited; only six patients reported syncopal attacks. In one of them, a 13-year-old boy, asystolic episodes up to nine seconds were documented. Until now, the mutation has been found in 114 family members (57 males, 57 females). Carriers of the mutant gene exhibited bradycardia-dependent QT-prolongation, intrinsic sinus node dysfunction, generalised conduction abnormalities, a paucity of ventricular ectopy, and the Brugada sign. Cardiomyopathy or other structural abnormalities were not found in any of the carriers. Electrophysiological studies showed that mutant channels were characterised by markedly reduced INa amplitude, a positive shift of voltage-dependence of activation and a substantial negative shift of voltage-dependence of inactivation of INa. From 1978 onwards, a pacemaker for anti-brady pacing was implanted for prevention of sudden death. In patients in whom a prophylactic pacemaker was implanted no unexplained sudden death occurred, whereas 5 sudden deaths occurred in the group of patients who did not receive a pacemaker. CONCLUSION: We have described a large family with a SCN5A-linked disorder (1795insD) with features of LQT3, Brugada syndrome and familial conduction system disease. Anti-brady pacing was successful in preventing sudden death. The mode of death is possibly bradycardic.

Autonomic and hemodynamic effects of a new selective dopamine agonist, CHF1035, in patients with chronic heart failure.

Dopamine agonists have been studied in chronic heart failure, but earlier reports with non-selective compounds demonstrated unfavourable long-term effects. CHF 1035 is an orally active, new selective dopamine agonist, primarily activating DA2- and alpha2 receptors, thereby inhibiting norepinephrine release, which may be beneficial in heart failure. We conducted a double-blind, placebo-controlled comparison of CHF 1035 (10 mg/day, n = 20) and placebo (n = 9) in patients with mild to moderate chronic heart failure (left ventricular ejection fraction <0.45). Patients were clinically stable on diuretics and angiotensin converting enzyme inhibitors. Both acute and chronic assessments were made, including plasma neurohormones and 24-hr Holter monitoring for heart rate variability analysis. CHF1035 was generally well tolerated during the study. After 10 days, there were no significant changes between the groups regarding heart rate and blood pressure. Compared to placebo, plasma norepinephrine levels decreased on CHF1035, both in the first 4 hours and after 10 days (p<0.05 between groups). Other neurohormones (natriuretic peptides, renin, aldosteron and endothelin) were not significantly affected. Heart rate variability parameters generally increased on CHF1035, but were unaffected by placebo (p < 0.05 between groups). Short-term treatment with the selective dopaminergic agonist CHF1035 is well tolerated, reduces plasma norepinephrine concentrations and increases heart rate variability in mild chronic heart failure.

Possible bradycardic mode of death and successful pacemaker treatment in a large family with features of long QT syndrome type 3 and Brugada syndrome.

INTRODUCTION: We recently identified a novel mutation of SCN5A (1795insD) in a large family with features of both long QT syndrome type 3 and the Brugada syndrome. The purpose of this study was to detail the clinical features and efficacy of pacemaker therapy in preventing sudden death in this family. METHODS AND RESULTS: The study group consisted of 116 adult family members: 60 carriers (29 males) and 56 noncarriers (28 males) of the mutant gene. Investigations included 24-hour Holter monitoring, ergometry, and electrophysiologic studies. Mean, lowest, and highest heart rate were lower in the carriers, but heart rate variability was comparable. In carriers, disproportional QT prolongation was present during bradycardia. No complex ventricular ectopy was recorded, and there were fewer isolated premature beats (both ventricular and atrial) in carriers. All patients were asymptomatic, except for two individuals who experienced syncope; in one of these patients, asystolic episodes (up to 9 sec) were repeatedly recorded. Prolonged HV intervals were present in 5 of 6 patients. Thirty carriers received a prophylactic backup pacemaker. During median follow-up of 4.5 years (range 0.0 to 22.6), their survival rate was 100%. There were five sudden deaths among the remaining 30 carriers without a pacemaker (P = 0.019). CONCLUSION: This family with a high incidence of nocturnal sudden death is characterized by bradycardia-dependent QT prolongation, intrinsic sinus node dysfunction, and generalized conduction abnormalities. There is a striking absence of complex ventricular ectopy, and pacemaker implantation was effective in preventing sudden death. These findings raise the possibility of a bradycardic rather than tachycardic mode of death.

Prospective evaluation of early cardiac damage induced by epirubicin-containing adjuvant chemotherapy and locoregional radiotherapy in breast cancer patients.

PURPOSE: To evaluate prospectively the cardiotoxic effects of epirubicin-containing adjuvant chemotherapy in breast cancer patients. PATIENTS AND METHODS: Patients (median age, 46 years; range, 28 to 55 years) were treated with five cycles of fluorouracil, epirubicin (90 mg/m2), and cyclophosphamide (FEC) (group I, n = 21) or with four cycles of FEC followed by high-dose chemotherapy consisting of cyclophosphamide, thiotepa, and carboplatin (group II, n = 19). Locoregional radiotherapy was applied subsequently. Cardiac evaluation was performed before chemotherapy (T0), 1 month after chemotherapy, 1 month after radiotherapy (T2), and 1 year after start of chemotherapy (T3). Left ventricular ejection fraction (LVEF) was determined by radionuclide ventriculography and diastolic function by echocardiography. Autonomic function was assessed by 24-hour ECG registration for heart rate variability (HRV) analysis. Time-corrected QT (QTc) was assessed and N-terminal atrial natriuretic peptide (NT-ANP) and brain natriuretic peptide (BNP) were measured as biochemical markers of cardiac dysfunction. RESULTS: No patient developed overt congestive heart failure (CHF) and the mean LVEF declined from 0.61 at T0 to 0.54 at T3 (P =.001), resulting in an LVEF below 0.50 (range, 0.42 to 0.49) in 17% of the patients, whereas 28% had a decline of more than 0.10. Plasma NT-ANP levels increased gradually from 237 pmol/L at T0 to 347 pmol/L at T3 (P <.01), whereas plasma BNP levels increased from 2.9 pmol/L to 5.1 pmol/L (P =.04). Mean QTc increased from 406 msec at T0 to 423 msec at T3 (P <.01). No persistent alterations were found in diastolic function and HRV. CONCLUSION: Relatively low doses of epirubicin in adjuvant chemotherapy for breast cancer results in mild subclinical myocardial damage demonstrated by a decline in LVEF, an increase in natriuretic peptide levels, and an increase in QTc, which may indicate a long-term risk of CHF.

Effects of dietary fermentable carbohydrates on energy metabolism in group-housed sows.

The effect of dietary nonstarch polysaccharide (NSP) content on the metabolic rate in group-housed sows was studied. Twelve groups of six nonpregnant sows were each fed one of four experimental diets similar in composition except for the starch and NSP content. Exchanging sugar beet pulp silage (SBPS) for tapioca created the difference in starch and NSP ratio in the diet. On a DM basis, diets contained 0, 10, 20, or 30% SBPS. Sows were group-housed and fed at 1.30 times the assumed maintenance energy requirements. Nitrogen and energy balances were measured per group during a 7-d experimental period, which was preceded by a 33-d adaptation period. Both digestibility and metabolizability of energy decreased with increasing dietary SBPS content (P < 0.05). Heat production and energy retention were unaffected by the exchange of starch for NSP (P > 0.1). Based on energy retention data and apparent fecal digestibilities of crude protein, crude fat, starch, and NSP, the estimated net energy value of fermented NSP was 13.4 kJ/g. The present study shows that group-housed sows are capable of using energy from fermented NSP (i.e., NSP from SBPS) as efficiently as energy from digested starch (i.e., starch from tapioca).

Effect of mibefradil on heart rate variability in patients with chronic heart failure.

BACKGROUND: Mibefradil was recently withdrawn from the market because of an unfavorable clinical profile in patients with chronic heart failure. Although drug interactions appear to play a role, other mechanisms such as proarrhythmia and autonomic deterioration could also be relevant. Chronic heart failure is accompanied by autonomic impairment and analysis of heart rate variability can be used to examine autonomic modulation of heart rate. METHODS: We studied 18 heart failure patients (age 63.2+/-10.1 years (mean+/-S.D. ), ejection fraction 0.21+/-0.07) treated with mibefradil or placebo, who participated in the MACH-I (Mortality Assessment in Chronic Heart failure) trial in our center, and compared them with 18 healthy matched controls. Heart rate variability analysis was performed at baseline and after 7 months of treatment. RESULTS: At baseline, heart rate variability parameters were impaired in patients with heart failure compared to healthy controls (P<0.05). After 7 months of treatment a reduction in (24-h) heart rate was observed (P=0.02, versus placebo). Apart from the effect on mean NN, no significant differences were observed for the remaining heart rate variability parameters. CONCLUSIONS: Mibefradil does not impair autonomic balance and in fact reduces heart rate in patients with heart failure. These findings suggest that autonomic activation did not contribute to the adverse effects of mibefradil.

Tachycardia induced electrical remodeling of the atria and the autonomic nervous system in goats.

Atrial fibrillation (AF) shortens the atrial effective refractory period (AERP). To investigate the role of the autonomic nervous system during this so-called electrical remodeling of the atria (ERA) and during recovery from ERA we analyzed heart rate variability (HRV). In 12 goats atrioventricular (300:150 beats/min) pacing was performed for 24 hours, interrupted at 4, 8, 16, and 24 hours for recording of 500 atrial (AA) intervals during sinus rhythm and measurement of the AERP(430ms) at 7.4 +/- 0.6 sites. After 24 hours, pacing was stopped and the electrophysiological study and recording of the AA intervals was repeated at 4, 8, 16, and 24 hours after cessation of pacing. Time- and frequency-domain parameters were computed from each 500 AA interval recording. After 24 hours of rapid pacing the AERP had shortened significantly (147 +/- 5.6 to 102+/- 6.4 ms, P < 0.0001). No significant changes in HRV and dispersion of refractoriness (AAERP) (47 +/- 7.1 to 44 +/- 4.2 ms) were observed. After cessation of pacing, the AERP prolonged again (102 +/-6.4 to 135+/-8.8 ms, P < 0.0001) and was paralleled by a significant increase in AAERP (44 +/- 4.2 to 63+/- 7.1 ms, P = 0.01). Furthermore, HRV increased significantly. At each time point an inverse relation between the logarithmically transformed vagal parameter HF (InHF) and AERP was observed. We calculated the mean InHF for each goat using all time points and used the median value to divide the 12 goats into high and low vagal tone groups. We compared the degree of ERA and recovery from ERA for both groups. The AERP shortened 47.4 +/- 6.5 versus 43.0+/-5.0 ms (NS) for goats with high and low vagal tone, respectively. During recovery from ERA the AERP lengthened 23.6 +/- 4.0 versus 42.5 +/- 1.7 ms (P = 0.001) for goats with high and low vagal tone, respectively. Multivariate regression analysis indicated a short AERP as the single independent determinant of the inducibility of AF during ERA and recovery from ERA (P < 0.0001). During recovery from ERA, the AERP prolonged and vagal tone and AAERP increased. A high vagal tone during recovery from ERA was associated with a short AERP and an attenuated recovery of ERA.

Different effects of bisoprolol on heart rate in patients with ischemic or idiopathic dilated cardiomyopathy (a 24-hour Holter substudy of the Cardiac Insufficiency Bisoprolol Study [CIBIS]).

The effect of beta blockade on heart rate in patients with either idiopathic or ischemic cardiomyopathy was studied. It was found that beta blockade reduced the early morning increase in heart rate to a greater extent in patients with idiopathic dilated cardiomyopathy than in those with ischemic dilated cardiomyopathy.

Depressed heart rate variability is associated with events in patients with stable coronary artery disease and preserved left ventricular function. REGRESS Study Group.

BACKGROUND: Little is known about the value of heart rate variability in patients with symptomatic coronary artery disease with a preserved left ventricular function. We hypothesized that in these patients heart rate variability might be a helpful adjunct to conventional parameters to predict clinical events. METHODS: In a prospective 2-year follow-up study ambulatory electrocardiographic recordings were performed in 263 consecutive male patients (mean age 56+/-8 years) with stable angina pectoris and a mean left ventricular ejection fraction of 71%+/-12%. Clinical events consisted mainly of coronary events such as percutaneous transluminal angioplasty or coronary artery bypass graft operation. RESULTS: Low measures of standard deviation of normal R-R intervals, standard deviation of the mean R-R intervals of 5 minutes, and two spectral components of heart rate variability were found in patients who had had an event compared with patients with no event. Adjusted for severity of angina, the presence of a previous myocardial infarction, and the use of beta-blockers in a logistic regression model this relation remained statistically significant for SDNN. Healthy volunteers appeared to have the highest measures of heart rate variability. CONCLUSION: In patients with ischemic heart disease and normal or near normal ventricular function decreased heart rate variability is associated with adverse clinical events.

Early recurrences of atrial fibrillation after electrical cardioversion: a result of fibrillation-induced electrical remodeling of the atria?

OBJECTIVES: We sought to investigate whether, in humans, the timing and incidence of a relapse of atrial fibrillation (AF) during the first month after cardioversion indicates the presence of electrical remodeling and whether this could be influenced by prevention of intracellular calcium overload during AF. BACKGROUND: Animal experiments have shown that AF induces shortening of the atrial refractory period, resulting in an increased vulnerability for reinduction of AF. This electrical remodeling was completely reversible within 1 week after cardioversion of AF and was presumably related to intracellular calcium overload. METHODS: Using transtelephonic monitoring in 61 patients cardioverted for chronic AF, we evaluated the daily incidence of recurrence of AF and determined, by Cox regression analysis, the influence of patient characteristics and medication on relapse of AF. RESULTS: During 1 month of follow-up, 35 patients (57%) had a relapse of AF, with a peak incidence during the first 5 days after cardioversion. Furthermore, in patients with a recurrence of AF, there was a positive correlation between the duration of the shortest coupling interval of the premature atrial beats after cardioversion and the timing of the recurrence of AF (p = 0.0013). Multivariate analysis revealed that the use of intracellular calcium-lowering drugs during AF was the only significant variable related to maintenance of sinus rhythm after cardioversion (p = 0.03). CONCLUSIONS: The daily distribution of recurrences of AF suggests a temporary vulnerable electrophysiologic state of the atria. Use of intracellular calcium-lowering medications during AF appeared to reduce recurrences, possibly due to a reduction of electrical remodeling during AF.

The energetic value of nonstarch polysaccharides in relation to physical activity in group-housed, growing pigs.

The dose response effect of dietary nonstarch polysaccharide (NSP) content on physical activity in relation to metabolic rate in pigs was studied. Twelve clusters of 14 pigs (50-kg castrated males) were fed one of four diets, similar in composition, except for the starch and NSP content. The difference in starch and NSP ratio was created by exchanging sugar beet pulp silage (SBPS) for tapioca. On a DM basis, diets contained 0, 5, 10, or 15% SBPS. Pigs were housed in groups and fed at 2.5 times the maintenance energy requirements. Nitrogen and energy balances were measured per cluster during a 7-d experimental period, which was preceded by a 2-wk adaptation period. Dietary composition did not affect ADG. Metabolizability decreased with increasing dietary SBPS content (P < .01). Heat production as well as energy retention were unaffected by the exchange of starch for NSP (P > .1). However, dietary composition affected energy expenditure on physical activity (P < .10). Pigs were more quiet when dietary NSP content increased. Based on heat production data and on apparent digestibility of crude protein, crude fat, and NSP, the estimated net energy value of fermented NSP was 14.8 kJ/g. This relatively high energy value of fermented NSP was mainly related to the lowered energy expenditure for physical activity, 3.9 kJ/g of fermented NSP. The present study demonstrated that the lower energetic utilization of fermented NSP compared with that of starch can be fully compensated in pigs by reducing their physical activity. Thus, energy evaluation systems should account for systematic dietary influences on physical activity.

Heart rate variability in patients with atrial fibrillation is related to vagal tone.

BACKGROUND: Analysis of heart rate variability (HRV) has thus far not been applied in patients with atrial fibrillation, probably because of the presumed absence of any form of patterning of the ventricular rhythm, particularly vagally mediated respiratory arrhythmia. However, such patterning is theoretically conceivable given the function of the atrioventricular node in atrial fibrillation and its susceptibility to autonomic influences. METHODS AND RESULTS: Sixteen patients (mean age, 56+/-4 years) with long-term atrial fibrillation on fixed doses of digoxin or verapamil were studied; 12 healthy men in sinus rhythm were used as control subjects. HRV (standard deviation of RR intervals [SD], coefficient of variance [CV], the root-mean-square of successive difference [RMSSD], and low-frequency [LF] and high-frequency power [HF]) was analyzed during 500 RR intervals at baseline, after administration of propranolol (0.2 mg/kg I.V.), and after subsequent administration of methylatropine (0.02 mg/kg I.V.). HRV at baseline and changes in HRV after methylatropine were then related to vagal tone (vagal cardiac control), quantified as the decrease in mean RR after methylatropine. Baseline HRV was higher in the atrial fibrillation group than in the control group; after propranolol, HRV increased in both groups; after methylatropine, HRV neared zero in the control group, whereas it returned to baseline values in the atrial fibrillation group. SD, RMSSD, LF, and HF at baseline were significantly (P<.05) correlated with vagal tone in the control group but also in the atrial fibrillation group (correlation coefficients of .60, .61, .57, and .64, respectively). Even stronger correlations were observed between changes in these parameters after methylatropine and vagal tone, particularly in the atrial fibrillation group (correlation coefficients of .89, .87, .72, and .90, respectively). CONCLUSIONS: This study shows that HRV in patients with atrial fibrillation is related to vagal tone.