J Brouwer

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.

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.

ANALYSIS OF THE MORPHOLOGY OF THE UNIPOLAR ENDOCARDIAL PACED EVOKED-RESPONSE

In a retrospective study we analyzed the unipolar endocardial evoked response signal (ERS) of 103 patients prior to pacemaker implantation. The objective of this study was to give a complete description of the ERS morphology and to evaluate influences on this morphology of both various electrode characteristics and pacing rate. In addition, spontaneous endocardial signals were studied. The results demonstrate that acute leads had both higher R wave and T wave amplitudes and a faster downslope of the T wave. In the acute leads those with porous titanium carbon coated tips showed a more pronounced T wave. Pacing rate influences the R wave amplitude and the stimulus to T wave interval. Both stimulus to maximum and stimulus to minimum T wave interval show an exponential correlation with the stimulus interval. The interval between maximum and minimum of the T wave and the absolute amplitude of the T wave are not influenced by rate. Although there were significant correlations of the spontaneous endocardial signal with the ERS, the predictive value of the spontaneous signal for the ERS morpology is low. Prospective studies will be necessary to confirm the findings in this study.

Diagnostic performance of various QTc interval formulas in a large family with long QT syndrome type 3 : Bazett's formula not so bad after all

Background: Recently, we identified a novel mutation of SCN5A (1795insD) in a large family with LQTS3. The aim of this study was to assess whether the various proposed corrections of the QT interval to heart rate help to improve the identification of carriers of the mutant gene.

EFFECT OF EXERCISE ON CYCLE LENGTH IN ATRIAL-FLUTTER

OBJECTIVE--To examine the effect of exercise on cycle length in atrial flutter. PATIENTS--15 patients with chronic atrial flutter. Seven patients were taking digoxin and six verapamil; two were not taking medication. METHODS--All patients underwent bicycle ergometry. Flutter cycle length was measured at rest and at peak exercise. RESULTS--Mean flutter cycle length increased from 245 ms to 256 ms (P = 0.002). Six patients developed 1:1 atrioventricular conduction. Significant increases in flutter cycle length were observed irrespective of development of 1:1 atrioventricular conduction and use of digoxin and verapamil. CONCLUSION--Exercise prolongs flutter cycle length. This effect would promote development of 1:1 atrioventricular conduction during exercise, causing inordinately high ventricular rates.

Exploratory study of the effects of single doses of isomazole on hemodynamics and heart rate variability parameters in chronic heart failure

Ventricular arrhythmias and disturbed auto-nomic control, as reflected by abnormal heart rate variability (HRV), are related to hemodynamic impairment in chronic heart failure (CHF). We investigated the effects of orally (p.o.) administered isomazole, a new phosphodiesterase (PDE) inhibitor with calcium-sensitizing properties, on hemodynamics, ventricular arrhythmias, and HRV and examined a possible interaction between these parameters. Hemodynamic measurements and ambulatory ECG monitoring were performed in 12 patients with stable CHF class III–IV after single doses of isomazole 5–30 mg. Pulmonary wedge pressure decreased after 5, 10, 20, and 30 mg, but cardiac output, (CO) increased only after the higher doses [20 mg, +20%(p = 0.031)] of isomazole. HR did not change. Mean arterial and pulmonary artery pressure, (MAP, PAP) decreased significantly in the 10-and 20-mg groups [10 mg, −6%(p = 0.035) and — 14%(p < 0.001) respectively; 20 mg, — 13%(p = 0.047) and — 31%(p = 0.006), respectively]. Isomazole did not exert a significant effect on ventricular arrhythmias in the subsequent 24 h after acute dosing. Analysis of HRV showed that rMSSD and pNN50 (parameters of vagal tone) tended to increase after isomazole administration. Normalized high-frequency power during the day increased from 17.4 to 22.3 nu (p < 0.05), whereas low frequency tended to decrease from 52.7 to 48.2 nu (p = 0.06). Acute isomazole administration improves hemodynamics but has no effect on ventricular arrhythmias. The HRV variability data suggest development of an increase in vagal control of HR, parallel to the acute hemodynamic improvement after isomazole. Withdrawal of vagal control of HR in CHF may be a reversible process.

The influence of recording length on time and frequency domain analysis of heart rate variability

Analysis of Heart Rate Variability (HRV) is used to assess autonomic control of the heart. Many technical aspects may influence the outcome of HRV analysis. One of these aspects is recording length. Ambulatory monitoring recordings are frequently used as a data source. Because of their mathematical properties, some HRV variables are influenced by recording length. Further more, recording length may play a role, since, in clinical practice, hook-up times of ambulatory monitoring are not randomly distributed over time. In order to test recording-length related changes of HRV the authors tested three groups: 1. healthy subjects (n=24); 2. congestive heart failure patients (n=24); and 3. patients with coronary artery disease (n=21). Results revealed that although the average normal to normal interval already changed after 1 hour reduction, most time domain variables differed statistically significantly after 4 hours reduction in length. Frequency domain variables proved to be less sensitive to recording-length changes. The extent of length related changes of HRV was shown to vary in different patient categories. It is concluded that ambulatory monitoring recordings less than 20 hours long should not be used for HRV analysis.

CLINICAL AND ELECTROCARDIOGRAPHIC CORRELATES OF EXERCISE-INDUCED ATRIAL-FIBRILLATION - A CASE-CONTROL STUDY

Clinical and electrocardiographic correlates of atrial fibrillation (AF) induced during routine exercise testing were examined in a case-control study. With the use of a prospective data base 11,730 consecutive exercise tests in 7,273 patients were reviewed. AF developed in 14 patients during exercise and in 9 patients during recovery (total incidence 0.3%). The mean age was 62 (range 36-76) years, and most patients were male (87%). AF was sustained (> 30 s) in 17 patients. The median duration of AF was 233 s. Atrial premature activity, including atrial tachycardia, often (13 patients) preceded AF. In 6 patients (26%) no structural heart disease was apparent. Compared with controls, matched for age, sex, and test indication, AF patients used less beta blockers (9 vs. 43%; p <0.05) and had a higher maximal heart rate (144 vs. 127 beats/min; p <0.05). Also, ischemic responses to exercise were observed more often in these patients (26 vs. 6%; p <0.05). These findings indicate that most patients with exercise-induced AF have associated cardiac disorders, foremost ischemic heart disease. In a subset of patients, however, symphathetic activation per se appears to play an important role.

Effects of metronome breathing on the assessment of autonomic control using heart rate variability

Analysis of Heart Rate Variability is a non-invasive quantitative tool to study the influence of the autonomic nervous system on the heart. Rapid variations in heart rate, related to breathing are primarily mediated by the vagal limb of the autonomic nervous system. The resulting variations in heart rate are usually referred to as respiratory sinus arrhythmia. Metronome breathing (MB) is often advocated to assess more accurately vagal control. However, the additional value of MB over SB has never been established. The authors studied the effect of MB (0.25 Hz) on HRV variables in 12 healthy male subjects under stable conditions using pharmacological autonomic blockade. During MB several variables showed a lower absolute value, however a strong correlation existed between variables computed during spontaneous breathing (SB) and MB. MB offers some, but no important advantages over spontaneous breathing.