Factors Affecting Diurnal Variability of Ventricular Tachyarrhythmias Detected by Multiprogrammable Implantable Cardioverter-Defibrillators

Factors Affecting Diurnal Variability of Ventricular Tachyarrhythmias Detected by Multiprogrammable Implantable Cardioverter-Defibrillators

ORIGINAL ARTICLE Original Article Factors Affecting Diurnal Variability of Ventricular Tachyarrhythmias Detected by Multiprogrammable Implantable Ca...

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ORIGINAL ARTICLE

Original Article

Factors Affecting Diurnal Variability of Ventricular Tachyarrhythmias Detected by Multiprogrammable Implantable Cardioverter-Defibrillators Astin K.Y. Lee, MBBS (Hons), MRCP (UK), FRACP, Mahidi Mardini, MBBS, Ph.D, FRACP, David L. Ross, MBBS, FRACP and Robert Denniss, MD, FRACP∗ Department of Cardiology, Westmead Hospital, Westmead, New South Wales 2145, Australia Available online 26 August 2004

Many cardiovascular events, including ventricular arrhythmias, display diurnal variability with a morning peak, and a less pronounced afternoon peak. Since the advent of multiprogrammable implantable cardioverter-defibrillators (ICDs), it has been possible to analyse ventricular tachyarrhythmic events. This study aims to evaluate the circadian pattern of ventricular tachycardias in patients treated with ICDs and examines whether antiarrhythmic medications affect this pattern. Data recorded from 83 patients’ ICDs were manually analysed and events other than ventricular arrhythmias were excluded. There was a morning peak of ventricular arrhythmias at around 9.00 a.m. This peak was maintained in patients with ejection fractions of less than 40% and those whose arrhythmias had cycle lengths of less than 230 ms. Beta blockers appeared to have no effect on this morning peak but the peak appeared later with amiodarone. (Heart Lung and Circulation 2004;13:256–260) © 2004 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Published by Elsevier Inc. All rights reserved. Keywords. Implantable cardioverter-defibrillators; Tachycardia; Ventricular

Introduction

Methods

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Data were reviewed from 83 consecutive patients who received a third-generation ICD at Westmead Hospital. All devices were multiprogrammable, and could deliver treatment ranging from antitachycardia pacing to low- and high-energy cardioversion. All patients receiving the ICD had documented ventricular fibrillation (VF) or monomorphic sustained ventricular tachycardia (VT) either at electrophysiological testing (EPS) or spontaneously (including sudden cardiac death). The devices had retrievable datalogging capabilities, including recording of the date, time, cycle length, and device therapy for each tachyarrhythmic episode. The devices were also capable of storing electrograms. Patients were followed at intervals of every 1–3 months after implantation of the device up to a period of at least one year. The arrhythmias recorded were manually analysed for type, rate, and appropriateness of detection by a single author (MM). The type of therapies delivered were categorised and appropriateness determined. These allowed sinus tachycardia, atrial fibrillation (AF) and inappropriate activations to be excluded from analysis. The age, sex, ejection fraction (measured by gated heart pool scan), medications, extent of coronary artery disease, and the type of revascularisation procedure, were recorded on all patients.

iurnal variability is displayed in many cardiovascular events, such as acute myocardial infarction, sudden cardiac death, supraventricular and ventricular arrhythmias.1–5 The 3 h after waking is known to be the time when there is an excess of cardiovascular events.6 Ventricular arrhythmias are known to occur in a typical circadian pattern with a predominant morning peak, and then a less pronounced afternoon peak. This pattern does not differ in patients with a history of ischaemic heart disease compared to patients without a history of ischaemic heart disease.7 Previous studies have also shown that there is a Monday peak of acute myocardial infarctions and tachyarrhythmias.8 Continuous analysis of arrhythmic events is now possible with multiprogrammable implantable cardioverter-defibrillators (ICDs). This study evaluates the diurnal pattern of ventricular tachyarrhythmic events in a population of patients treated with ICDs and examines whether antiarrhythmic medications affect the diurnal variability.



Corresponding author. Tel.: +61 9633 5658; fax: +61 9893 9616. E-mail address: [email protected] (R. Denniss).

© 2004 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Published by Elsevier Inc. All rights reserved.

1443-9506/04/$30.00 doi:10.1016/j.hlc.2004.06.011

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Table 1. Clinical Characteristics of the Study Population Number of patients Age (years) Male sex (%) Smokers (%) Hypercholesterolaemia (%) Hypertension (%) Family history of ischaemic heart disease (%) Diabetes (%) Ischaemic heart disease (%) Previous coronary artery grafting (%) Left ventricular ejection fraction (%) Clinical VT (%) Cycle length of clinical VT (ms) VT at EPS (%) Cycle length of VT at EPS (ms)

83 62 ± 9 66 (80) 66 (80) 33 (40) 33 (40) 33 (40) 8 (10) 66 (80) 41 (50) 36 ± 15 50 (60) 299 ± 60 58 (70) 281 ± 56

Values are expressed as mean ± S.D. or number (%).

Data Analysis To demonstrate the diurnal pattern of distributions, the data were grouped according to the time of the day therapy was delivered, and plotted as histograms. Each day started at midnight and extended for 24 h. Deviation from a uniform distribution and differences between hourly distributions were tested for significance using the Kolmogorov–Smirnov Goodness of Fit Test.9 The Mann–Whitney test was used to compare the distribution of the number of events per patient between the groups for each of the three variables of ejection fraction, use of beta blockers, and use of amiodarone.

Results Patient Characteristics Table 1 shows the characteristics of the study population. Hypercholesterolaemia was defined as a total cholesterol level greater than 5.0 mmol/L or receiving anti-

Figure 1. Hourly distribution of episodes.

Figure 2. Hourly distribution of episodes based on cycle lengths of arrhythmias.

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cholesterol medication, while hypertension was defined as a blood pressure greater than 140/90 or receiving antihypertensive medication. All patients had ejection fraction measured by gated heart pool scan. There was a statistically significant difference between the ejection fraction of those with clinical VT (mean 32 ± 12%) and those without clinical VT (mean 42 ± 17%), P = 0.005. However, there was no relationship between the cycle length of VT detected at EPS and those who had clinical VT and those without clinical VT (287 ± 57 ms and 268 ± 66 ms, respectively, P = 0.3).

Diurnal Variability of Tachyarrhythmias A total of 1421 tachyarrhythmic events were recorded in the 83 patients. Fig. 1 shows the hourly distribution of episodes. The episodes peaked between 9.00 a.m. and 11.00 a.m., with a second peak from 2.00 p.m. to 6.00 p.m. The fewest detections occurred from 2.00 a.m. to 3.00 a.m. Figs. 2–4 show that this morning peak was maintained

Figure 4. Hourly distribution of episodes for patients with or without beta blocker treatment.

Figure 3. Hourly distribution of episodes based on patients’ ejection fractions.

in those whose arrhythmias had cycle lengths of less than 230 ms (P < 0.02), those whose ejection fractions were less than 40% (P < 0.0001), and those who were treated with beta blockers (P < 0.0001). There was a statistically significant difference in the hourly distribution of episodes of cycle lengths less than 230 ms versus those with cycle lengths greater than 230 ms (P < 0.001). Fig. 5 shows that amiodarone treatment shifts the peak of tachyarrhythmic events significantly (P = 0.04). This was tested with a general linear model9 using the patient identifier as a random effect and amiodarone use as a fixed effect. There was no significant difference between the median number of events per patient with an ejection fraction less than 40% and those with an ejection fraction greater than 40% (6.5 versus 6.0, P = 0.97), and between those treated with amiodarone and those without amiodarone (6.5 versus 6.0, P = 0.85). However, there was a significant difference between the median number of events in those treated with beta blockers and those without beta blockers (12 versus 5, P = 0.048).

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ventricular premature beats, and ischaemic events,2,11,12 and the Monday peak of tachyarrhythmias.8 There has also been evidence that beta blockers blunt the morning peak of VT or VF among patients with ischaemic heart disease.13 This could be due to the enhancement of heart rate variability by beta blockers, as heart rate variability has been observed to be reduced before the onset of ventricular tachyarrhythmias.14 Yet other studies have shown no such attenuation of the morning peak with beta blockers.15,16 In our study, they did not affect the morning peak of VT. Amiodarone treatment, on the other hand, appeared to shift the morning peak of VT. The failure of cardio-selective beta blocker therapy to modify the morning peak of VT, and the apparent ability of amiodarone to shift the peak, imply that mechanisms other than sympathetic tone are important in the genesis of the morning increase in VT frequency. This may also reflect inadequacy of beta blockade in the usual clinical setting.15 Amiodarone, while incorporating some non-cardio-selective beta blocking action does have a much broader spectrum of antiarrhythmic activity.

Conclusion There is a clear circadian pattern to ventricular arrhythmias with a predominant morning peak. This peak was not affected by the use of beta blockers. However, the morning peak was shifted by amiodarone treatment.

References

Figure 5. Hourly distribution of episodes for patients with or without amiodarone treatment.

Discussion This study adds to the body of evidence that there is diurnal variability in ventricular tachyarrhythmias. Possible mechanisms include a morning surge in sympathetic nerve activity, a shortening of refractory periods on awakening, and diurnal variation in endothelial function and thrombogenicity.7,10 The ICDs allow accurate timing and recording of events, thereby eliminating the imprecision in recall of patients or witnesses and their estimates of timing of the events. The data in this study was not clouded by inappropriate inclusion of arrhythmias due to AF or sinus tachycardia, or noise detection, as these episodes were excluded by manual analysis. In this study, the morning peak was most prominent in patients who had faster arrhythmias (CL < 230 ms), who were on beta blockers, and who had lower ejection fractions (<40%). Data regarding the efficacy of beta blockers in modifying the morning peak of VT is controversial. They have been shown in some studies to attenuate the morning peak of supraventricular arrhythmias,

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