© 2006 European Society of Cardiology
Heart rate turbulence and death due to cardiac decompensation in patients with chronic heart failure
a The Cardiothoracic Center Liverpool United Kingdom
b University of Liverpool School of Medicine United Kingdom
c National Refractory Angina Centre, Cardiothoracic Centre Liverpool, United Kingdom
d University of Edinburgh Medical School United Kingdom
e Cardiothoracic Centre, North Staffordshire Hospital Stoke on Trent, United Kingdom
f Cardiovascular Division, King's College Bessemer Road, London, SE59PJ, United Kingdom
* Corresponding author. Tel.: +44 2073464025; fax: +44 2073464771. E-mail address: mark.kearney{at}kcl.ac.uk (M.T. Kearney).
 |
Abstract |
|---|
 Top Abstract 1. Introduction2. Methods3. 12-Lead electrocardiographs,...4. Measurement of heart...5. Statistical analysis6. Results7. Discussion8. Study limitations9. ConclusionReferences |
|---|
Background: As treatment strategies for patients with chronic heart failure (HF) become more sophisticated, identifying patients at high risk of death and predicting mode of death is important. The aim of this study was to explore the potential utility of heart rate turbulence (HRT) to identify patients with HF at high risk of death.
Methods and results: In a prospective study, 553 ambulant outpatients age 63 ± 10 with symptoms of HF and evidence of cardiac dysfunction were recruited. All patients underwent 24-h Holter ECG recordings, which were analysed for arrhythmias, heart rate variability and HRT a measurement that is thought to quantify cardiac autonomic regulatory mechanisms. Baseline chest radiograph, biochemistry and 12-lead electrocardiograms were also obtained. In patients with HRT measurements at 5 years follow up, 146 patients had died, 59 due to decompensated HF. Independent predictors of death from decompensated HF at 5-year follow up (Cox proportional hazard model) were HRT slope (HR for 10% increment 0.84, 95% CI 0.77–0.91), serum sodium (HR for 10% increment 0.75, 95% CI 0.62–0.91) and serum creatinine (for 10% increment HR 1.14, 95% CI 1.08–1.19) all P < 0.01. These 3 variables combined had excellent discrimination between patients dying of decompensated HF and other patients, C-statistic = 0.82.
Conclusions: In patients with mild-to-moderate HF, HRT slope is an independent predictor of death due to decompensated HF. HRT may have the potential to help tailor therapy in this patient group.
Key Words: Heart failure • Heart rate • Mortality
Received May 4, 2005; Revised September 22, 2005; Accepted November 10, 2005
|
1. Introduction |
|---|
|
TopAbstract1. Introduction2. Methods3. 12-Lead electrocardiographs,...4. Measurement of heart...5. Statistical analysis6. Results7. Discussion8. Study limitations9. ConclusionReferences |
|---|
Chronic heart failure (HF) has emerged as a major healthcare problem [1]. Symptomatic HF has a poor prognosis [2,3], which is worse than many soft tissue tumours [4]. Despite this, unlike many cancers, accurate methods of predicting prognosis and mode of death in patients with HF are incompletely explored and poorly developed. It is now well established that the most frequent modes of death in patients with HF is a progressive decline in left ventricular systolic function ending in cardiac decompensation, or sudden unexpected fatal cardiac arrhythmia [5]. Identifying HF patients at high risk of different modes of death is important as treatment strategies for these patients become increasingly more sophisticated, complex, and targeted at different modes of death [6,7].
The prospective United Kingdom Evaluation and Assessment of risk Trial (UK-HEART) was specifically designed to explore the utility of a-priori selected non-invasive measurements of cardiac size/function, electrical stability, autonomic function, renal function and abnormalities of electrolyte homeostasis to predict mortality in ambulant outpatients with HF. UK-HEART is the largest study of its kind, with complete 5-years follow up and detailed characterisation of an outpatient population of HF patients [8-10]. As such the UK-HEART database provides a unique and powerful tool to explore the potential role of different measurements to predict prognosis and mode of death in HF patients.
Heart rate turbulence (HRT) is the term used to describe the short-term fluctuation in sinus cycle that follows a ventricular premature complex (PVC) and is thought to reflect the autonomic response to the perturbation of arterial blood pressure occurring after a PVC [11,12]. HRT has emerged as a promising measurement that can identify patients who have had a myocardial infarction at high risk of premature death [12]. Despite having substantial abnormalities of autonomic function [13,14], the potential role of HRT in predicting mortality in patients with HF is less clear. The present report establishes HRT as a measurement, which allied to measurement of renal function and serum sodium has the potential to identify with a high level of discrimination, patients with mild-to-moderate HF at risk of death specifically due to decompensated HF.
|
2. Methods |
|---|
|
TopAbstract1. Introduction2. Methods3. 12-Lead electrocardiographs,...4. Measurement of heart...5. Statistical analysis6. Results7. Discussion8. Study limitations9. ConclusionReferences |
|---|
2.1. Patient enrollment
The UK Heart Study is a multicentre prospective study of HF patients. The details of which have been described previously [8,9]. Patient recruitment and data collection was carried out in 8 centres within the United Kingdom between December 1993 and April 1995. The ethical committee at each of the recruiting institutions approved the research protocol. Patients of either gender aged 18-80 years were eligible for the trial if they had symptoms of HF present for at least 3 months. In addition, they had to be classified as NYHA functional class II or III in association with objective evidence of cardiac dysfunction at rest (pulmonary venous congestion, pulmonary oedema, a cardiothoracic ratio of >0.55 on chest radiogram or radionuclide/echocardiographic left ventricular ejection fractions of less than 45%). Patients were excluded in the presence of concomitant disease known to influence autonomic function, constrictive or hypertrophic cardiomyopathy and noncardiac disease likely to affect survival. All patients had detailed 12-lead electrocardiographic analysis performed, 24-h Holter analysis of time domain heart rate variability, renal function and biochemistry and echocardiographic measurement of left ventricular internal dimensions.
Study patients were registered with the UK national death-reporting scheme (Office of Population Censuses and Surveys) that notified the steering committee of all deaths. All reported events were reviewed by at least two senior physicians. Death certificates, post-mortem findings, and hospital and general practitioners' records were examined. Mode of death was classified using predefined criteria as (1) sudden cardiac death if it occurred within 1 h of change of symptoms or if it occurred whilst the subject was asleep or unobserved if circumstantial evidence suggested death from cardiovascular causes in the absence of clinical or post-mortem evidence of acute myocardial infarction or progressive heart failure, (2) progressive/decompensated heart failure if death occurred after a documented period of symptomatic or haemodynamic deterioration, (3) other cardiovascular death if it did not occur suddenly and was not associated with progressive heart failure, (4) noncardiovascular death.
|
3. 12-Lead electrocardiographs, ambulatory electrocardiographs: arrhythmia and heart rate variability analysis |
|---|
|
TopAbstract1. Introduction2. Methods3. 12-Lead electrocardiographs,...4. Measurement of heart...5. Statistical analysis6. Results7. Discussion8. Study limitations9. ConclusionReferences |
|---|
All subjects were investigated with 12-lead electrocardiographs, which were analysed as previously reported [10]. Ambulatory ECG recordings during a 24-h period of unrestricted out of hospital activity using a miniature tape recorder (Tracker, Reynolds Medical Ltd.) with a crystal generated time reference track that allows correction for recording and replay speed errors to within 0.5%. The ECG recordings were analysed using a Pathfinder arrhythmia analyser (Reynolds Medical Ltd.) to document the presence of ventricular arrhythmia (>10 ventricular ectopic beats per hour or the occurrence of couplets or runs of nonsustained ventricular tachycardia, defined as three or more consecutive ventricular ectopic beats at a rate of >120 bpm). Ambulatory ECGs of less than 16 h in duration or with less than 90% of the recording suitable for analysis were excluded to avoid confounding effects due to circadian rhythms in HRV. After initial arrhythmia analysis and editing, the remaining normal-to-normal RR intervals were measured and time domain analysis of HRV carried out according to published guidelines as previously reported [10].
|
4. Measurement of heart rate turbulence |
|---|
|
TopAbstract1. Introduction2. Methods3. 12-Lead electrocardiographs,...4. Measurement of heart...5. Statistical analysis6. Results7. Discussion8. Study limitations9. ConclusionReferences |
|---|
The 24-h ECG data was initially analysed and edited by a single experienced operator using the Delmar Reynolds Pathfinder TM. The correctly categorised RR interval sequences for the 24-h ECG recordings were then exported to a QuantecTM data analysis workstation for turbulence analysis. The Turbulence analysis followed the method described by Grimm [11] and Schmidt [12] with the mean HRT slope and mean HRT onset calculated from all valid PVCs. The HRT onset was defined as the difference between the mean of the first two sinus RR intervals preceding the PVC and the mean of the subsequent two sinus RR intervals, expressed as a percentage. The HRT slope is defined as the maximum positive value of the slope of a regression line assessed over any sequence of five subsequent sinus-rhythm RR intervals within the first 20 sinus-rhythm intervals after PVC. If more than one positive slope occurred in this period the first positive slope was accepted. The value of HRT slope is expressed in milliseconds per RR interval. PVC were excluded if they failed to satisfy the following criteria: (1) The PVC should occur in isolation with normal sinus beat occurring for at least 12 beats before the PVC and for at least 20 beats after the PVC. (2) The PVC RR maximum and minimum RR intervals should be greater than 20% and less than 20%, respectively, of the mean of the five preceding normal sinus RR intervals. (3) All RR intervals for the 12 beats before the PVC and 20 beats after the PVC should be greater than 300 ms and less than 2000 ms in duration. (4) All normal sinus RR intervals 12 beats before the PVC and 20 beats after the PVC should be within 20% of the mean RR interval of all beats in the 24-h ECG recording. (5) Any change in adjacent normal sinus RR intervals, 12 beats before the PVC and 20 beats after the PVC, should not be greater than 200 ms.
|
5. Statistical analysis |
|---|
|
TopAbstract1. Introduction2. Methods3. 12-Lead electrocardiographs,...4. Measurement of heart...5. Statistical analysis6. Results7. Discussion8. Study limitations9. ConclusionReferences |
|---|
Descriptive data are presented as mean±S.D. unless otherwise stated and correlations between baseline characteristics were described using Spearman's Rank method. Receiver operator characteristic (ROC) analysis was used to generate C-statistics [15]. A C-statistic of 0.5 indicates that the test results are no better than those obtained by chance whereas an area of 1.0 denotes a perfectly sensitive and specific test. Variables entered into the all cause and cardiac decompensation model were; age, heart rate, left ventricular end systolic diameter, left ventricular end diastolic diameter, left ventricular ejection fraction, non-sustained ventricular tachycardia, left ventricular hypertrophy, cardiothoracic ratio, SDNN, sodium, creatinine, average HRT slope, average HRT onset, maximum QRS duration and maximum QT interval corrected for rate. The Cox proportional hazards regression model was used to determine which parameters were significantly related to mortality during the follow up period a multivariable model with a forward stepwise approach was used to adjust for the effect of covariates. Non-normally distributed data were log transformed prior to analysis. Deaths occurring as a function of time were described using the product limit methodology of Kaplan and Meier with TS dichotomised at >2.5 m/s in line with earlier studies [11,12].
|
6. Results |
|---|
|
TopAbstract1. Introduction2. Methods3. 12-Lead electrocardiographs,...4. Measurement of heart...5. Statistical analysis6. Results7. Discussion8. Study limitations9. ConclusionReferences |
|---|
Five hundred and fifty-three patients were recruited into the study, of these, 433 24-h tapes were suitable for HRV and 414 for HRT analysis. 56 patients did not have a VPB, which matched the exclusion criteria and were therefore excluded from the analysis. The minimum number of PVCs/patient/24 h used for analysis was 2. The present report describes the analysis of the 358 patients in whom HRT measurements were made, the characteristics of which are detailed in Table 1. In this study population 27 (8%), subjects were prescribed beta-blocker medication and 64 (18%) were taking Digoxin.
|
6.1. Correlation of heart rate turbulence measurements with clinical features of HF
HRT onset and turbulence slope were significantly correlated with measurements of left ventricular size, as shown in Table 2. Both HRT indices were also significantly correlated with New York Heart Association class, serum urea, serum creatinine and heart rate. The time domain heart rate variability measurement SDNN was significantly correlated with both HRT onset (R=–0.352, p<0.001) and HRT slope (R=0.459, p<0.001).
|
6.2. Mode of death and its relationship to HRT and other covariates
At 5 years follow up, 146 deaths had occurred within the patients in whom HRT was measured, giving an annual mortality rate of 7.1%. Of these 146 deaths, 50 were attributable to sudden cardiac death (34%), 59 to cardiac decompensation (39%), 17 (12%) to other cardiovascular events and a further 20 (15%) deaths were classed as non-cardiac.
6.3. All cause mortality
In multivariable analysis, the independent predictors of all cause mortality given as HR (95% CI) were: standard deviation of all normal RR intervals over 24 h (SDNN) for every 10% increment HR 0.91 (95% CI 0.86-0.96), P=0.001, left ventricular end systolic diameter, for every 1 cm increment HR 1.24 (95% CI 1.09-1.42) P=0.01, cardiothoracic ratio, for every 10% increment HR 1.24 (95% CI 1.09-1.42) P=0.001, serum sodium, for every 2 mmol/L increment HR 0.79 (95% CI 0.70-0.88) P=0.001 and plasma creatinine, for every 10 µmol/L increment HR 1.10 (95% CI 1.06-1.14) P=0.001.
6.4. Death due to cardiac decompensation
The predictors of death due to decompensated heart failure given as HR (95% CI) were: HRT slope, for every 10% increment HR 0.84 (95% CI 0.77-0.91) P<0.001, serum sodium, for every 2 mmol/L increment HR 0.75 (95% CI 0.62-0.91), P=0.002, and plasma creatinine for every 10 µmol/L increment HR 1.14 (95% CI 1.08-1.14) P=0.001.
The mean HRT slope in patients who died from decompensated heart failure was 6.42±3.0 ms compared to a mean of 10.16±5.8 ms for the rest of the cohort (P=0.001). The Kaplan-Meier survival curves for the dichotomised HRT slope are shown in Fig. 1. ROC analysis demonstrated a C-statistic for the progressive heart failure model (Sodium, Creatinine, HRT slope) of 0.818, P<0.001. It is possible that TO and HRT slope may provide complimentary information, to explore this possibility we added TO to the progressive heart failure model, this only marginally increased the C-statistic to 0.821 (P<0.001).
|
2.5 or >2.5 ms).HRT slope was also predictive of death due to cardiac decompensation in patients with relatively preserved systolic function ejection fraction (n=189) >40% (HR 0.77 95% CI 0.67-0.89, P=0.001) and in patients with ejection fractions (n=225) <40% (HR 0.86 95% CI 0.77-0.95, P=0.005). In patients with ejection fractions >40% 11% died of progressive heart failure and 13% sudden death, whereas in patients with ejection fractions <40% 16% died of progressive heart failure and 11% sudden death.
6.5. Sudden cardiac death
There was no significant association between HRT and sudden death (OR for HR slope 0.98 95% CI (0.88-1.1) P=0.7). HRT measurement were significantly lower in patients dying of progressive heart failure compared to those dying suddenly (Table 3).
|
|
7. Discussion |
|---|
|
TopAbstract1. Introduction2. Methods3. 12-Lead electrocardiographs,...4. Measurement of heart...5. Statistical analysis6. Results7. Discussion8. Study limitations9. ConclusionReferences |
|---|
The principal finding of the present report is that HRT slope is a powerful and specific predictor of death due to cardiac decompensation in patients with HF. In an earlier report, we demonstrated that SDNN one marker of cardiac autonomic traffic was a predictor of death due to progressive heart failure [9]. HRT slope in the present analysis was a more important and powerful predictor than SDNN.
7.1. Heart rate turbulence
HRT is a recently described [11,12] measurement of the short-term oscillation of sinus cycle following a PVC, PVCs are thought to lead to a deviation from the pressure set point of the baroreceptor reflex for at least one beat. The ejection of a lower stroke volume by the extra-systolic beat into the aorta induces a lower extra-systolic pulse wave amplitude leading to reduced filling of the arterial vascular compartment. PVC response analysis has been applied successfully to risk stratification after acute myocardial infarction [12] two novel risk predictors; turbulence onset and turbulence slope were introduced. Turbulence onset measures the degree of early overshoot deceleration that occurs after a single PVC-induced pause, turbulence slope indicates how fast the RR interval changes after the pause. The two limbs of the autonomic nervous system are thought to contribute to heart rate turbulence. In healthy humans, the unloading of baroreceptors is thought to lead to a transient withdrawal of cardiac vagal efferent traffic and sympathoactivation, which in turn leads to cardioacceleration. Sympathetically mediated overshoot of blood pressure then leads to deceleration of sinus rate via increased vagal traffic. As such HRT measurements seem to evaluate both parasympathetic and sympathetic autonomic regulatory mechanisms in response to a defined stimulus.
7.2. Heart rate turbulence slope and progression of heart failure to cardiac decompensation
Consistent with the present data set, a small study by Koyama et al. [16] demonstrated that HRT slope was lower in patients with HF subsequently dying or being admitted to hospital with worsening HF. The present study demonstrates for the first time that HRT slope is an important independent predictor of death due to decompensated HF in ambulant HF patients across a wide range of ejection fractions. Moreover, when combined with sodium and creatinine (variables we have previously shown to predict death due to cardiac decompensation [9]) these measurements have excellent ability (C-statistic >0.80) to discriminate between patients dying of decompensated HF and survivors/patients dying of other modes of death.
7.3. Heart rate turbulence slope: a measurement that integrates measurements of cardiac autonomic function and left ventricular performance?
The potential mechanisms by which HRT slope predicts death due to cardiac decompensation warrant further discussion. Our data provide potential insights into this question, in our data set HRT slope had a close positive correlation with SDNN and a significant negative correlation with heart rate both of which are dependant on sympathovagal balance. Withdrawal of parasympathetic activity coupled with activation of the sympathetic nervous system would appear to play a part in blunting of HRT slope in patients with HF.
HRT slope may also be influenced by postextrasystolic potentiation, in which beats immediately following PVCs display augmented contractility a phenomenon exaggerated in patients with dilated cardiomyopathy and left ventricular dilatation [17]. In this study, HRT slope and onset were closely related to left ventricular size suggesting that myocardial geometry and function also play a role in determining HRT slope. HRT slope would therefore appear to be a consequence of the interrelationship between autonomic function, left ventricular size and contractility and baroreflex sensitivity making HRT slope a measurement that integrates information regarding a number of the multiple abnormalities predisposing to progressive cardiac dysfunction.
7.4. Comparison with post myocardial infarction studies
Heart rate turbulence has been investigated as a predictor of mortality in several large post-infarction cohorts [12,18] with both HRT onset and slope identified as independent predictors of all cause mortality. Other investigators [19] have also demonstrated the ability of both parameters to identify patients at risk of sudden cardiac death (SCD) following myocardial infarction. In this study, the failure of turbulence parameters to predict SCD may reflect differing mechanisms underlying autonomic disturbance. It has been shown that patients have evidence of prolonged sympathetic activation following myocardial infarction independent from abnormalities in left ventricular function. In addition, SCD in the setting of CHF will be precipitated by different mechanisms to the general post-infarction population with a lower prevalence of ischaemia and greater risk of sudden cardiac decompensation. It might be expected that the prevalence of sudden cardiac death in this mild moderate heart failure group should be higher with respect to the prevalence of progressive cardiac death. This observation may in part reflect the increasing importance of progressive cardiac failure as a cause of death over longer follow up periods.
|
8. Study limitations |
|---|
|
TopAbstract1. Introduction2. Methods3. 12-Lead electrocardiographs,...4. Measurement of heart...5. Statistical analysis6. Results7. Discussion8. Study limitations9. ConclusionReferences |
|---|
The UK-Heart Study was enrolled prior to the publication of landmark trials demonstrating the benefit of beta-adrenergic blocker antagonists in patients with CHF and therefore the number of patients prescribed these medications was low. Current data in patients with low ejection fractions post-myocardial infarction suggests that HRT is still a predictor of mortality in patients on beta-blockade [12]. This study in keeping with all other HRT studies relied on identification of PVCs from Holter ECG recordings. This method is not capable of differentiating between actual PVCs and aberrant atrial premature complexes, which have different HRT characteristics. The present study was a retrospective exploratory analysis and this should be borne in mind when considering the use of HRT slope as a predictor in patients with HF. In particular, it is a possibility that our study did not have sufficient statistical power to detect a small relationship between HRT and sudden death this warrants further attention in prospective studies.
|
9. Conclusion |
|---|
|
TopAbstract1. Introduction2. Methods3. 12-Lead electrocardiographs,...4. Measurement of heart...5. Statistical analysis6. Results7. Discussion8. Study limitations9. ConclusionReferences |
|---|
HRT slope is an independent predictor of death due to cardiac decompensation in patients with mild to moderate HF across a wide range of ejection fractions. The potential utility of HRT slope to predict outcome and guide therapy warrants future studies.
|
Acknowledgement |
|---|
Dr. Kearney, Fox and Shah are supported by the British Heart Foundation.
|
References |
|---|
|
TopAbstract1. Introduction2. Methods3. 12-Lead electrocardiographs,...4. Measurement of heart...5. Statistical analysis6. Results7. Discussion8. Study limitations9. ConclusionReferences |
|---|
- Ghali J.K., Cooper R., Ford E. Trends in hospitalisation for heart failure in the United States, 1973-1986: evidence for increasing population prevalence. Arch Intern Med (1990) 150:769–773.
[Abstract/Free Full Text] - MERIT-HF Study Group. Effect of Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet (1999) 353:2001–2007.[CrossRef][Web of Science][Medline]
- The Captopril-Digoxin Multicentre Research Group. Comparative effects of therapy with Captopril and Digoxin in mild to moderate heart failure. JAMA (1988) 259:539–544.
[Abstract/Free Full Text] - Stewart S., MacIntyre K., Hole D.J., Capewell S., McMurray J.J. More malignant than cancer? Five-year survival following a first admission for heart failure. Eur J Heart Fail (2001) 3:315–322.
[Abstract/Free Full Text] - Schaufelberger M., Swedberg K., Koster M., Rosen M., Rosengren A. Decreasing one-year mortality and hospitalization rates for heart failure in Sweden; data from the Swedish Hospital Discharge Registry 1988 to 2000. Eur Heart J (2004) 25:300–307.
[Abstract/Free Full Text] - The SOLVD Investigators. Effects of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive cardiac failure. N Engl J Med (1992) 327:685–691.[Abstract]
- Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med (2005) 352:225–237.
[Abstract/Free Full Text] - Nolan J., Batin P.D., Andrews R., et al. Prospective study of heart rate variability and mortality in chronic heart failure. Results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-Heart). Circulation (1998) 98:1510–1516.
[Abstract/Free Full Text] - Kearney M.T., Fox K.A., Lee A.J., et al. Predicting death due to progressive heart failure in patients with mild to moderate chronic heart failure. J Am Coll Cardiol (2002) 40:1801–1808.
[Abstract/Free Full Text] - Kearney M.T., Zaman A., Eckberg D.L., et al. Cardiac size, autonomic function, and 5-year follow-up of chronic heart failure patients with severe prolongation of ventricular activation. J Card Fail (2003) 9:93–99.[CrossRef][Web of Science][Medline]
- Grimm W., Sharkova J., Christ M., Schneider R., Schmidt G., Maisch B. Heart rate turbulence following premature beats in healthy controls. Ann Noninvasive Electrocardiol (2003) 8:127–131.[CrossRef][Web of Science][Medline]
- Schmidt G., Malik M., Barthel P., et al. Heart rate variability after premature beats as a predictor of mortality after acute myocardial infarction. Lancet (1999) 353:1390–1396.[CrossRef][Web of Science][Medline]
- Porter T.R., Eckberg D.L., Fritsch J.M., et al. Autonomic pathophysiology in heart failure patients: sympathetic-cholinergic interrelations. J Clin Invest (1990) 85:1362–1371.[Web of Science][Medline]
- Rundqvist B., Elam M., Bergmann-Sverrisdottir Y., Eisenhofer G., Friberg P. Increased cardiac adrenergic drive precedes generalized sympathetic activation in human heart failure. Circulation (1997) 95:169–175.
[Abstract/Free Full Text] - Kearney M.T., Nolan J., Lee A.J., et al. A prognostic index to predict long-term mortality in patients with mild to moderate chronic heart failure stabilised on angiotensin converting enzyme inhibitors. Eur J Heart Fail (2003) 5:489–497.
[Abstract/Free Full Text] - Koyama J., Watanabe J., Yamada A., et al. Evaluation of heart rate turbulence as a new prognostic marker in patients with chronic heart failure. Circ J (2002) 66:902–907.[CrossRef][Web of Science][Medline]
- Voss A., Baier V., Schumann A., et al. Postextrasystolic regulation patterns of blood pressure and heart rate in patients with idiopathic dilated cardiomyopathy. J Physiol (2002) 538:271–278.
[Abstract/Free Full Text] - Barthel P., Schneider R., Bauer A., et al. Risk stratification after acute myocardial infarction by heart rate turbulence. Circulation (2003) 108:1221–1226.
[Abstract/Free Full Text] - Ghuran A., Reid F., La Rovere M.T., et al. Heart rate turbulence-based predictors of fatal and nonfatal cardiac arrest (The Autonomic Tone and Reflexes after Myocardial Infarction substudy). Am J Cardiol (2002) 89(2):184–190. [Jan 15].[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Arya, M. Block, J. Kautzner, T. Lewalter, H. Mortel, S. Sack, B. Schumacher, P. Sogaard, M. Taborsky, D. Husser, et al. Influence of Home Monitoring on the clinical status of heart failure patients: Design and rationale of the IN-TIME study Eur J Heart Fail, November 1, 2008; 10(11): 1143 - 1148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bauer, M. Malik, G. Schmidt, P. Barthel, H. Bonnemeier, I. Cygankiewicz, P. Guzik, F. Lombardi, A. Muller, A. Oto, et al. Heart Rate Turbulence: Standards of Measurement, Physiological Interpretation, and Clinical Use: International Society for Holter and Noninvasive Electrophysiology Consensus J. Am. Coll. Cardiol., October 21, 2008; 52(17): 1353 - 1365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. de Sousa, C. A. Morillo, F. T. Rabelo, A. M. N. Filho, and A. L.P. Ribeiro Non-sustained ventricular tachycardia as a predictor of sudden cardiac death in patients with left ventricular dysfunction: A meta-analysis Eur J Heart Fail, October 1, 2008; 10(10): 1007 - 1014. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||