Jaap Haaksma

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.

Prognostic value of heart rate variability during long-term follow-up in patients with mild to moderate heart failure

OBJECTIVES We sought to assess the prognostic value of heart rate variability measures, including Poincaré plots, in patients with mild to moderate chronic heart failure. BACKGROUND Mortality is high in patients with heart failure, and many of them die suddenly. However, identification of high risk patients, particularly those with an increased risk for sudden death, has remained difficult. METHODS We studied 95 patients with heart failure (mean [+/- SD] age 60 +/- 8 years, left ventricular ejection fraction 0.29 +/- 0.09, New York Heart Association functional class II [81%] and III [19%]) during up to 4 years of follow-up. Heart rate variability measures and Poincaré plots were obtained from 24-h Holter recordings. RESULTS During follow-up, 17 (18%) of the 95 patients died. In 15 patients, death was cardiac related (11 patients experienced sudden death). None of the conventional time and frequency domain measures of heart rate variability were related to survival. In contrast, abnormal Poincaré plots identified a significantly higher risk for all-cause cardiac death (Cox proportional hazards ratio 5.7, 95% confidence interval [CI] 1.6 to 20.6, univariate analysis) and for sudden cardiac death (hazards ratio 6.8, 95% CI 1.5 to 31.4) compared with those with normal Poincaré plots. Patients with abnormal Poincaré plots were shown to have a lower left ventricular ejection fraction (0.26 +/- 0.10 vs. 0.31 +/- 0.08, p < 0.05) and higher plasma norepinephrine concentrations (506 +/- 207 pg/ml vs. 411 +/- 175 pg/ml, p < 0.05). In multivariate analysis, abnormal Poincaré plots still had independent prognostic value, both for all-cause cardiac mortality and for sudden cardiac death (hazards ratio 5.3, 95% CI 1.2 to 17.1, hazards ratio 4.5, 95% CI 1.0 to 27.5, respectively. CONCLUSIONS Heart rate variability analysis, as assessed by Poincaré plots, has independent prognostic value in patients with mild to moderate chronic heart failure and identifies an increased risk for all-cause and sudden cardiac death in these patients.

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

Pacemaker Treatment in LQT3 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.

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.

Heart rate variability in left ventricular dysfunction and heart failure: effects and implications of drug treatment.

OBJECTIVE--To review the importance of heart rate variability analysis in left ventricular dysfunction and heart failure and to assess the effects of drug treatment. In patients with left ventricular dysfunction or heart failure, a low heart rate variability is a strong predictor of a low probability of survival. Because drug treatment in these patients has rapidly changed over the past two decades, the effect of these drugs on heart rate variability needs special attention. DESIGN--A study of published reports to give an overview of heart rate variability in patients with left ventricular dysfunction or heart failure and how it is affected by drug treatment. RESULTS--Analysis of heart rate variability provides an easily obtained early marker for progression of disease. It seems to be more closely related to the degree of neurohumoral activation than to haemodynamic variables. Cardiovascular drugs may either stimulate or inhibit the degree of neurohumoral activation, and the effects of pharmacological intervention can be closely monitored with this method. CONCLUSIONS--The analysis of heart rate variability, including spectral analysis, is a novel non-invasive way to obtain potentially useful clinical information in patients with reduced left ventricular function. The effects of drug treatment on heart rate variability are in general consistent with their long-term effects in left ventricular dysfunction and heart failure.

Heart rate variability in patients with mild to moderate heart failure: Effects of neurohormonal modulation by digoxin and ibopamine

OBJECTIVES: This study assessed the effects of digoxin and ibopamine on variables of heart rate variability in relation to neurohormonal activation. BACKGROUND: Analysis of heart rate variability can be used to study the autonomic dysfunction that characterizes chronic heart failure. In the Dutch Ibopamine Multicenter Trial, patients with heart failure were found to have increased neurohormonal activation with placebo therapy but not with digoxin and ibopamine therapy. METHODS: We studied 59 patients with mild to moderate heart failure (mean [+/- SEM] age 60 +/- 1 years, mean ejection fraction 0.30 +/- 0.01). Patients were randomized to double-blind treatment with digoxin (0.25 mg [n = 22]), ibopamine (100 mg three times a day [n = 19]) or placebo (n = 18); background therapy consisted of furosemide (up to 80 mg). RESULTS: After 3 months, plasma norepinephrine levels had increased with placebo, whereas they decreased with digoxin (+31 vs. -60 pg/ml, respectively, p 50 ms (pNN50) increased (+ 1.7 +/- 0.9%, p < 0.01), along with absolute and normalized high frequency power (+ 40 +/- 33 ms2, p < 0.05 and + 2.4 +/- 1.7%, p < 0.01, respectively). These changes were observed during daytime hours only and were most pronounced in patients with the most impaired baseline heart rate variability. With ibopamine, nonsignificant trends similar to the changes with digoxin were observed. CONCLUSIONS: In patients with early stages of heart failure, digoxin may prevent a progressive deterioration in heart rate variability, whereas ibopamine does not show statistically significant effects. The changes in heart rate variability with digoxin parallel an observed decrease in neurohormonal activation. Digoxin apparently enhances cardiac vagal tone in the setting of neuroendocrine activation.

Relation between severity of disease and impairment of heart rate variability parameters in patients with chronic congestive heart failure secondary to coronary artery disease

The present data show that HR variability has a statistically significant, but moderate, correlation with clinical variables of severity of CHF. Therefore, HR variability analysis may be a new, important tool in the clinical assessment of CHF patients.

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 AERP430 ms 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 (ΔAERP) (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 ΔAERP (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 ΔAERP increased. A high vagal tone during recovery from ERA was associated with a short AERP and an attenuated recovery of ERA.

Clustering of RR intervals predicts effective electrical cardioversion for atrial fibrillation

Introduction: Atrial fibrillation (AF) is characterized by an irregularly irregular (“random”) heart beat. However, controversy exists whether the ventricular rhythm in AF is truly random. We investigated randomness by constructing three‐dimensional RR interval plots (3D plots), allowing identification of “clustering” of RR intervals. It was hypothesized that electrical cardioversion (ECV) would be more effective in AF patients with clustering, because clustering might reflect a higher degree of organization of atrial fibrillatory activity.

Usefulness of heart rate variability in predicting drug efficacy (metoprolol vs diltiazem) in patients with stable angina pectoris.

We investigated whether analysis of heart rate (HR) variability may be used to predict the efficacy of drug treatment of myocardial ischemia. In a double-blind, crossover study, 28 patients with stable angina pectoris, proven coronary artery disease, and myocardial ischemia during Holter monitoring received metoprolol controlled-release 200 mg once daily and diltiazem 60 mg 4 times daily. After a placebo run-in phase and after each treatment period, 72-hour Holter recordings were obtained for HR variability and ST-segment analysis. At baseline, the total duration of myocardial ischemia was 11.4 +/- 13.9 minutes (mean +/- SD per 24 hours), and the total number of episodes was 2.2 +/- 2.3. Metoprolol significantly reduced the total duration of ischemia by -8.7 minutes (95% CI -14.5 to -2.8) and the total number of episodes by -1.9 (-2.9 to -0.8) in patients with a low SD of normal-to-normal intervals at baseline (SDNN), using the median value of 50 ms as a cut-off value. In contrast, significant treatment effects were not observed in patients with a high SDNN at baseline. Similar results were obtained using baseline total power or low-frequency power, but not when using baseline heart rate. Diltiazem reduced the total duration of ischemia by -4.9 minutes (-9.7 to -0.1), but not the number of episodes. Moreover, in contrast to metoprolol, efficacy of diltiazem was not related to baseline HR variability. In conclusion, patients with reduced HR variability at baseline responded to treatment with metoprolol.(ABSTRACT TRUNCATED AT 250 WORDS)