Beta-blocking effect of propafenone based on spectral analysis of heart rate variability

doi:10.1016/0002-9149(92)90355-3

The American Journal of Cardiology

Volume 70, Issue 11, 15 October 1992, Pages 1028-1034

https://doi.org/10.1016/0002-9149(92)90355-3 Get rights and content

Abstract

RR variability was analyzed in 15 patients with ventricular arrhythmias to evaluate whether the antiarrhythmic action of propafenone is associated with alteration of neural control mechanisms. Before drug administration, spectral analysis of RR variability was characterized by 2 major components at low and high frequency, which are considered to reflect sympathetic and parasympathetic modulation of the heart period. After propafenone (600 to 900 mg/day), there was a marked reduction in RR variance (826 ± 184 to 412 ± 77 ms²; p < 0.05), although the mean RR interval was unchanged. The drug significantly reduced the low-frequency component (52 ± 6 to 28 ± 4 nu) and augmented the high-frequency component (39 ± 6 to 55 ± 5 nu). As a result, the low-/high-frequency ratio (an index of sympathovagal balance) decreased from 2.0 ± 0.4 to 0.6 ± 0.1. A positive correlation between serum levels and drug-induced changes in the low-frequency component was also observed. Furthermore, the increase in the low-frequency component induced by tilt (53 ±5 to 79 ± 3 nu) was markedly attenuated after drug administration (27 ± 5 to 54 ± 7 nu). Thus, propafenone administration is associated with changes in spectral components that are consistent with a β-blocking effect of the drug.

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Cited by (41)

Effect of antiarrhythmic agents on heart rate variability indices after myocardial infarction: Comparative experimental study of aprindine and procainamide
2005, Biomedicine and Pharmacotherapy
The cardiac arrhythmic suppression trial (CAST) reported that antiarrhythmic treatments in post-myocardial infarction (MI) patients resulted in poor outcome and decreased in heart rate variability indices (HRV). The goal of the present study was to determine whether aprindine and procainamide, antiarrhythmic agents that increase HRV, result in beneficial effects in post-MI rabbits. Four weeks before experiment, MI was induced in four rabbits by ligating the major branch of left coronary artery. A total of eight rabbits (four post-MI and four normal rabbits) were randomly assigned to treatment with either intravenous aprindine (1 mg/kg) or intravenous procainamide (15 mg/kg). Frequency domain HRV (low frequency spectra, LF, 0.04–0.15 Hz; high frequency spectra, HF, 0.15–0.40 Hz) were assessed by MemCalc software. Aprindine significantly increased HF and LF in both MI and normal rabbits, whereas procainamide tended to decrease HF and LF in MI and normal rabbits (in total rabbits; aprindine, LF, from 6.3 ± 7.9 to 16.5 ± 15.0 ms²/Hz, P < 0.05; HF, from 8.0 ± 11.7 to 17.5 ± 15.0 ms²/Hz, P < 0.05; procainamide, LF, from 4.9 ± 7.4 to 4.8 ± 8.5 ms²/Hz, NS; HF, from 11.1 ± 23.0 to 5.1 ± 10.6 ms²/Hz, NS). Under pharmacological denervation with propranolol (0.1 mg/kg) and atropine (0.04 mg/kg), aprindine increased LF and HF (LF, from 0.2 ± 0.2 to 0.8 ± 0.7 ms²/Hz, P < 0.05; HF, from 0.1 ± 0.0 to 0.2 ± 0.0 ms²/Hz, P < 0.05). These data suggest that aprindine can increase HRV in post-MI rabbits. Further experiments in human subjects would be of benefit.
Heart rate variability and early recurrence of atrial fibrillation after electrical cardioversion
2001, Journal of the American College of Cardiology
Citation Excerpt :
Thus, the time course of electrical and mechanical changes seems to parallel the observed changes in autonomic modulation and to be inversely correlated with vulnerability for AF recurrence. As to the possibility that amiodarone might have influenced HRV parameters and recurrence rate, it must be recalled that this drug, at variance with other anti-arrhythmic drugs and beta-blockers, is known to have small effects on short-term HRV parameters during resting controlled conditions (27,28), and it was given to all patients with and without arrhythmia recurrence. Most of the data concerning the effects of autonomic nervous system and AF are related to the clinical environment in which this arrhythmia may occur (6).
OBJECTIVES
The study evaluated the role of the autonomic nervous system in atrial fibrillation (AF) recurrence.
BACKGROUND
Early recurrence of AF after cardioversion (CV) is attributed to electrical remodeling. The possibility that an abnormal autonomic modulation might contribute to this phenomenon has not yet been adequately tested.
METHODS
We analyzed short-term heart rate variability (HRV) in 93 patients with persistent AF and on chronic amiodarone treatment, after restoration of sinus rhythm by electrical CV.
RESULTS
Two weeks later, 25 patients presented with AF. Spectral analysis of HRV revealed that patients with AF recurrence were characterized by significantly greater low/high (LF/HF) frequency ratio in comparison to those in sinus rhythm (5.8 ± 6.86 vs. 1.1 ± 1.7). At univariable analysis, no clinical parameter differentiated the two groups. Using logistic regression analysis, LF/HF ratio was significantly associated with AF recurrence, with an odds ratio of 1.97 (95% confidence interval [CI] 1.33–2.94). By using a cutoff value of ≥2, LF/HF ratio presented a sensitivity and a specificity of, respectively, 76% and 90%. AF recurred in 9% of the patients with LF/HF ratio <2 compared with 73% of those with an LF/HF ratio >2. No correlation was observed between LF/HF ratio and late AF recurrences.
CONCLUSIONS
These data indicate that signs of increased sympathetic and reduced vagal modulation of sinus node characterized patients with an early AF recurrence and suggest that an abnormal autonomic control may contribute to electrical remodeling by facilitating intracellular calcium overload.
Guidelines of the Spanish Society of Cardiology on dynamic electrocardiography and ambulatory blood pressure monitoring
2000, Revista Espanola de Cardiologia
En este artículo se hace una revisión histórica y una puesta al día, tanto desde un punto de vista tecnológico como clínico, de dos procedimientos de exploración dinámica del aparato cardiovascular de tanto interés médico como son el electrocardiograma de Holter y la monitorización ambulatoria de la presión arterial. En cada uno de los procedimientos se detallan las características técnicas y metodológicas de los equipos actuales, haciéndose énfasis en la normativa que debe regular dicha tecnología para que su fiabilidad diagnóstica sea máxima.
Basándose en los documentos científicos internacionales, así como en la experiencia de los propios autores, se detallan las indicaciones, aplicaciones y limitaciones de cada una de las técnicas adaptándolas a las capacidades operativas del sistema sanitario español. Nuevos desarrollos en electrocardiografía de Holter, como el QT dinámico o la variabilidad RR o la velocidad de la onda de pulso en monitorización ambulatoria de la presión arterial, son abordados con suficiente extensión, indicándose igualmente algunas directrices futuras que mejoren el rendimiento y su aplicación clínica.
In the present paper, a historical review and a clinical up-date are done on two procedures of great medical interesest: Holter electrocardiography and ambulatory blood pressure monitoring. Technical and methodological characteristics of each procedure are carefully exposed, emphasizing each the lack of an international agreement in order to establish regulations that make all the equipment homogeneous and reliable in order to increase both accuracy and reliability in diagnosis.
Based on published international scientific documents and the personal experience of the authors, guidelines for clinical applications, indications and limitations of each technique are analyzed in relation to capacities of the Spanish political and social public health system profile. New concepts and dynamics of developments such as; dynamic QT, RR variability or pulse wave velocity are exposed, in the frame of the present time and future for improving efficiency and clinical application.
Power spectral analysis of heart period variability of preceding sinus rhythm before initiation of paroxysmal atrial fibrillation
1998, American Journal of Cardiology
Time domain analysis of heart period variability in patients without structural heart disease demonstrated increased parasympathetic modulation before paroxysmal atrial fibrillation (AF) occurring predominantly at night. However, diurnal differences in autonomic activity preceding AF episodes in a diverse patient population have not been assessed. Accordingly, we performed spectral analysis of heart period variability on Holter recordings during sinus rhythm preceding AF in 29 patients, 17 with night and 12 with day episodes. Samples taken 5, 10, and 20 minutes before AF onset were compared. Normalized high-frequency (HF) spectral power change was greater when comparing the interval 10 to 5 minutes with 20 to 10 minutes preceding AF in 26 of 29 patients (0.09 ± 0.07 vs 0.03 ± 0.02; p <0.0001). HF spectral power increased before 3 of 12 AF episodes during the day compared with 15 of 17 AF episodes during the night (p = 0.001). Nocturnal AF episodes were preceded by increased HF spectral power in the 5- versus the 20-minute sample expressed as natural logarithm–transformed values (5.6 ± 4.8 vs 4.2 ± 4.0; p <0.005) and normalized values (0.19 ± 0.09 vs 0.10 ± 0.07; p <0.02), a decrease in low-frequency/HF ratio (1.05 ± 0.61 vs 2.21 ± 1.75; p <0.05) and heart rate (60 ± 13 vs 71 ± 13 beats/min; p = 0.06). Structural heart disease was more common with daytime than nocturnal AF episodes (58% vs 18%, p <0.05). In conclusion, HF spectral power change was increased preceding most AF episodes. However, diurnal differences were demonstrated. Contrary to daytime AF, increased parasympathetic activity preceded predominantly nocturnal AF, mostly in younger patients with structurally normal hearts.
Intravenous propafenone for converting recent onset atrial fibrillation in emergency departments: A randomized placebo-controlled multicenter trial
1998, Journal of Emergency Medicine
Atrial fibrillation (AF) is one of the most frequent dysrhythmias in patients coming to emergency departments (EDs), and pharmacological treatment is frequently performed. The aim of this randomized placebo-controlled multicenter trial was to compare propafenone (a class 1C antidysrhythmic agent), administered i.v. in the ED, with placebo in the treatment of recent-onset AF (<72 h). We randomly allocated 156 patients (88 males; 68 females) from 18 to 80 years old, with recent-onset AF, to receive i.v. propafenone (2 mg/kg for 10 min) or the matching placebo. The patients were followed for 2 h. Exclusion criteria were the presence of one of the following: lack of informed consent, clinical evidence of heart failure, clinical hyperthyroidism, recent acute myocardial infarction, atrioventricular block, cardiac valve dysfunction, a history of bronchial asthma, and current treatment with antidysrhythmic agents including digitalis. The two groups did not differ significantly in terms of sex, age, body weight, or estimated time elapsed since the beginning of atrial fibrillation. Conversion to sinus rhythm occurred in 13 of the 75 patients who received the placebo (17.3%) and in 57 of the 81 patients who were given propafenone (70.3%). In conclusion, intravenous propafenone administration in the ED can be considered a safe and effective approach for converting AF to sinus rhythm.
Appraisal of the state of the autonomic nervous system in hypertrophic cardiomyophathy analyzing heart rate variability
1998, Revista Espanola de Cardiologia
El análisis de la variabilidad de la frecuencia cardíaca ha sido aceptado como método no invasivo para valorar la influencia del sistema nervioso autónomo sobre el corazón. Aunque la variabilidad de la frecuencia cardíaca se ha venido utilizando en la última década en diversas patologías, los estudios en la miocardiopatía hipertrófica son escasos.
Investigar mediante el análisis de la variabilidad de la frecuencia cardíaca la actividad del sistema nervioso autónomo en pacientes con miocardiopatía hipertrófica.
La variabilidad de la frecuencia cardíaca se ha evaluado mediante el análisis del registro electrocardiográfico de 24 h (Holter) en 20 pacientes con miocardiopatía hipertrófica y en 15 controles normales. Se utilizó como medida de la variabilidad de la frecuencia cardíaca el análisis espectral de las frecuencias que fueron calculadas mediante el análisis de la transformada de Fourier. Se analizan los componentes de alta frecuencia (0,15 a 0,40 Hz), los de baja frecuencia (0,04 y 0,15 Hz) y el componente global (0,01 y 1,0 Hz). También se valora la relación entre el componente de baja/alta frecuencia como índice del balance simpaticovagal del corazón. Los datos se presentan con valores medios ± DE. Se utiliza el test de la t de Student para datos no apareados. Se consideran significativos valores de p < 0,05.
No hubo diferencias en la frecuencia cardíaca media entre los pacientes con miocardiopatía hipertrófica y los controles (media ± DE: 71 ± 9 frente a 74 ± 11 lat/min; p = NS), mientras que hubo un descenso significativo tanto en el componente global (media ± DE: 7,14 ± 1,1 frente a 7,57 ± 0,6 ln [ms²]; p = 0,02), como en los componentes de altas (media ± DE: 5,22 ± 0,8 frente a 5,63 ± 1,3 ln [ms²]; p = 0,04) y bajas frecuencias (media ± DE: 6,14 ± 1,2 frente a 6,72 ± 0,7 ln [ms²]; p = 0,03). No hubo diferencias significativas entre el cociente de bajas/altas frecuencias (media ± DE: 1,1 ± 0,1 frente a 1,2 ± 0,1 ln [ms²]; p = NS).
Estos datos sugieren que los pacientes con miocardiopatía hipertrófica tienen una alteración en el estado del sistema nervioso autónomo tanto en la actividad simpática (componente de baja frecuencia) como en la actividad vagal (componente de alta frecuencia), si bien no se traduce en un desequilibrio entre actividad simpáticaparasimpática (relación bajas/altas frecuencias).
The analysis of heart rate variability has been accepted as a non-invasive method to evaluate the influence of the autonomic nervous system over the heart. Although heart rate variability has been used during the last decade in several illnesses the studies in hypertrophic cardiomyophathy are scarce.
We report the activity of the autonomic nervous system in patients with hypertrophic cardiomyophathy using the analysis of heart rate variability.
Heart rate variability was evaluate by the analyzing 24-h ambulatory electrocardiograms (Holter) in 20 patients with hypertrophic cardiomyopathy and in 15 controls. This method has been used to measure heart rate variability. Spectral analysis of the frequencies were calculated using fast Fourier transformation. Spectral heart rate variability was computed as high (0.15 to 0.40 Hz) low (0.04 to 0.15 Hz) and total (0.01 to 1.0 Hz). We compared the relation between low/high frequency as an index of the sympathic/parasympathic balance. All data are expressed as mean value ± SD. The unpaired Student t-test was used. A two tailed p valued < 0.05 was considered statistically significant.
There were no differences in the mean heart rates among the patients with hypertrophic cardiomyophathy and normal subjects (mean ± SD: 71 ± 9 versus 74 ± 11 beats/minute; p = NS) while there was a significant decline in total spectral (mean ± SD: 7.14 ± 1.1 versus 7.57 ± 0.6 ln [ms²]; p = 0.02) and high (mean ± SD: 5,22 ± 0.8 versus 5.63 ± 1.3 ln [ms²]; p = 0.04) as well as in low spectral frequency of heart rate variability (mean ± SD: 22 ± 0.8 versus 5.63 ± 1.3 ln [ms²]; p = 0.04) in patients with hypertrophic cardiomyopathy. There were no differences in the low/high frequency component ratio in these patients (mean ± SD: 1.1 ± 0.1 versus 1.2 ± 0.1 ln [ms²]; p = NS).
These facts suggest that the patients with hypertrophic cardiomyopathy have an alteration in the autonomic nervous system: sympathic (low spectral frequencies) and parasympathic activity (high spectral frequencies), although this does not reflect an imbalance between sympathic and parasympathic activities (relation of low to high spectral frequencies).

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Beta-blocking effect of propafenone based on spectral analysis of heart rate variability

Abstract

Am Heart J

Am Heart J

Am J Cardiol

J Chromatogr

Am J Cardiol

Am Heart J

J Am Coll Cardiol

Am J Cardiol

Am J Cardiol

Am Heart J

J Am Coll Cardiol

Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction

N Engl J Med

A new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms

Circulation

Risk stratification and survival after myocardial infarction

N Engl J Med

The relationships among ventricular arrhythmias, left ventricular dysfunction and mortality in the 2 years after myocardial infarction

Circulation

Neural activity and ventricular fibrillation

N Engl J Med