Heart rate variability as a predictor of sudden cardiac death.ABSTRACT Different noninvasive approaches have been developed for risk stratification risk stratification Medical decision-making The constellation of activities–eg, lab and clinical testing used to determine a person's risk for suffering a particular condition and need–or lack thereof–for preventive intervention of patients with myocardial infarction and heart failure with aim to select patients at high risk of sudden cardiac death Sudden Cardiac Death Definition Sudden cardiac death (SCD) is an unexpected death due to heart problems, which occurs within one hour from the start of any cardiac-related symptoms. SCD is sometimes called cardiac arrest. who might mostly benefit from preventive therapy. Reduced heart rate variability Heart rate variability (HRV) is a measure of variations in the heart rate. It is usually calculated by analysing the time series of beat-to-beat intervals from ECG or arterial pressure tracings. (HRV HRV Croatia (ISO Country code) HRV Heart Rate Variability HRV Human Rhinovirus HRV Heat Recovery Ventilator HRV High Resolution Visible HRV Haute Resolution Visible HRV Hypersonic Research Vehicle HRV Hercules Recovery Vehicle ) was a strong predictor of mortality in myocardial infarction and heart failure in early studies. However, in the era of modern treatment strategies the prognostic significance of HRV indices has been challenged. We thought to review the role of conventional, nonlinear and novel spectral indices of HRV in prediction of sudden cardiac death in patients with myocardial myocardial /myo·car·di·al/ (-kahr´de-al) pertaining to the muscular tissue of the heart. myocardial pertaining to the muscular tissue of the heart (the myocardium). infraction Violation or infringement; breach of a statute, contract, or obligation. The term infraction is frequently used in reference to the violation of a particular statute for which the penalty is minor, such as a parking infraction. INFRACTION. and heart failure. Keywords: myocardial infarction, heart failure, sudden cardiac death, heart rate variability Introduction Epidemiological and population based studies reported that annually about 1-2 of 1000 people die suddenly, though there has been a significant decline in mortality due to coronary artery disease coronary artery disease, condition that results when the coronary arteries are narrowed or occluded, most commonly by atherosclerotic deposits of fibrous and fatty tissue. in past 20 years (1-3). Early risk stratification of patients with heart disease carrying the risk of sudden cardiac death (SCD ScD [L.] Scien´tiae Doc´tor (Doctor of Science). SCD 1 Sickle cell disease, see there 2 Subacute combined degeneration, see there 3 Sudden cardiac death, see there ) is important since the preventive therapy with implantable cardioverter defibrillator defibrillator, device that delivers an electrical shock to the heart in order to stop certain forms of rapid heart rhythm disturbances (arrhythmias). The shock changes a fibrillation to an organized rhythm or changes a very rapid and ineffective cardiac rhythm to a (ICD ICD International Classification of Diseases (of the World Health Organization); intrauterine contraceptive device. ICD abbr. ) is effective in reducing mortality (4, 5). Different noninvasive approaches have been developed for risk stratification of patients with myocardial infarction (MI) and heart failure (HF) with aim to select patients who might mostly benefit from preventive therapy (5-10). Heart rate variability (HRV), the indicator of the cardiac autonomic modulation was low in survivors of cardiac arrest (11-13) and abnormal HRV patterns preceded the episodes of life-threatening arrhythmias on Holter monitoring and ICD storing electrograms (14, 15). Reduced HRV was a strong predictor of mortality in patients with MI (7, 16-18). However, in the era of modern treatment strategies that have modifying role in prognosis of patients with MI like treatment with beta-blockers and revascularization (19, 20, 21, 22), the prognostic significance of conventional HRV indices has been challenged. Time-domain, frequency-domain and geometric indices of HRV and SCD Time-domain indices of HRV were strong predictors of total mortality after MI in early studies (16-18), however there was no association of SDNN SDNN Standard Deviation of Normal-to-Normal Intervals (standard deviation of normal-to-normal RR intervals) with SCD in 700 patients with acute MI, 97% of whom were treated with beta-blockers (19). Bigger et al. (17, 23) described the relationship of HRV spectral indices with arrhythmic ar·rhyth·mic adj. Lacking rhythm or regularity of rhythm. death and SCD in patients with MI. In the MPIP MPIP Melanoma Patients' Information Page MPIP Maintenance Posture Improvement Program study (17, 23), which included 715 patients with acute MI, long-term 24-hour and short-term frequency-domain indices of HRV predicted development of arrhythmic death and SCD during 31 months of follow-up. The prognostic significance of HRV index, a geometric measure of RR variability, was studied in patients with low left ventricular ejection fraction (LVEF LVEF Left ventricular ejection fraction. See Ejection fraction. ) soon after MI (24, 25), however HRV index did not predict arrhythmic death, though it was a significant multivariate predictor of mortality in patients with MI (25). In heart failure, the data on prognostic significance of time-domain HRV indices in prediction of SCD are somewhat controversial (26-29). In UK-Heart prospective study, SDNN was found to be a significant multivariate predictor of total mortality, however it could not predict development of SCD in 18 of 433 patients with HF, NYHA NYHA New York Heart Association class I-III and LVEF [less than or equal to] 45% during mean 482 [+ or -] 161 days of follow-up (26). While Bilchik et al. (28) showed that SDNN [less than or equal to] 65.3 ms was the significant predictor of SCD and worse survival in patients with HF presented with NYHA class II-IV, LVEF [less than or equal to] 40% and ventricular ectopic beats Ventricular Ectopic Beats Definition A ventricular ectopic beat (VEB) is an extra heart-beat originating in the lower chamber of the heart. This beat, also called a premature ventricular contraction (PVC), occurs before the beat triggered by the heart's on Holter monitoring during 50 months of follow-up period. Spectral indices of HRV, specially low frequency power (LF) estimated from 24-hour Holter monitoring during day (30), during night (31) or extracted from short-term recording during controlled breathing (32) have been shown to have high prognostic value in prediction of SCD in patients with HF. The day-time LF [less than or equal to] 3.3 In (30) was a significant multivariate predictor of SCD (RR=2.8, 95%CI 1.2-8.6, p<0.05) during 3 years of follow-up period in 190 patients with HF, NYHA class II-IV, and mean LVEF [less than or equal to] 45%. Guzetti et al. (31) have demonstrated that night-time LF [less than or equal to] 20 [m.sup.2] is significantly associated with SCD in a larger population of patients with HF and LVEF [less than or equal to] 30%. The night-time LF below cut-off value carried a 2.6 fold higher risk (95%CI 1.2-5.5, p=0.012) of SCD during 3 years of follow-up (9% of patients died suddenly). The LF, extracted from short-term recordings during controlled breathing had even stronger association with SCD (32). La Rovere et al. (32), in a derivation sample of 202 patients with HF, have shown that LF [less than or equal to] 13 [ms.sup.2] (RR=3.7 95% Cl 1.5-9.3, p=0.005) and LV end-diastolic dimension [greater than or equal to] 77 mm (p=0.04) were the only independent multivariate predictors of SCD, while in validation model (242 patients) the patients with LF [less than or equal to] 11 [ms.sup.2] were 3 times more likely to die suddenly during follow-up period (95% Cl 1.2-7.5, p=0.01). Combination of ventricular premature complexes and low LF had negative predictive value The negative predictive value is the proportion of patients with negative test results who are correctly diagnosed. Worked example
Condition (as determined by "Gold standard") True False of 97% and positive predictive value Positive predictive value (PPV) The probability that a person with a positive test result has, or will get, the disease. Mentioned in: Genetic Testing positive predictive value of 18% in prediction of SCD. Nonlinear indices of HRV and SCD The analysis of MPIP data (33) has demonstrated that power law regression parameters of HRV in patients after MI have significant multivariate association with arrhythmic death (RR- 3.21, p<0.001), which was stronger than predictive power of 24-hour Holter spectral indices, after adjustment for clinical variables. The nonlinear short-term fractal scaling exponent [alpha] (DFA DFA - Deterministic Finite-state Automaton. See Finite State Machine. [alpha]1) was the only parameter independently associated with increased risk of SCD in 446 patients with MI and LVEF [less than or equal to] 35% (39-45% were treated with beta-blockers), 75 of whom died due to arrhythmia arrhythmia (ārĭth`mēə), disturbance in the rate or rhythm of the heartbeat. Various arrhythmias can be symptoms of serious heart disorders; however, they are usually of no medical significance except in the presence of during mean follow-up of 685 +360 days (35). In multivariate analysis DFA [alpha]1 after adjustment for clinical variables like age, NYHA class, wall motion index, medications, ventricular arrhythmias on 24-hour Holter monitoring and randomization randomization (ranˈ·d  ·m for dofetilide and placebo
predicted arrhythmic death with RR of 1.4 ( 95% Cl 1.1-1.7, p<0.05).
The DFA [alpha]1 <0.75 was the most powerful predictor of worse
cumulative (arrhythmic and nonarrhythmic cardiac deaths) survival during
1200 day of follow up as compared with SDNN and very low frequency
spectral component (p<0.001).
In the study by Makikallio et al (36), which included 2130 patients with acute MI, undergoing contemporary treatment, DFA [alpha]1 along with turbulence slope and NSVT NSVT Non-Sustained Ventricular Tachycardia NSVT Network Security Vulnerability Technician NSVT Navy Secure Voice Terminal NSVT Network Services Virtual Terminal were significant predictors of SCD in multivariate analysis after adjustment for age, diabetes and LVEF. Patients with MI and DFA [alpha]1 <0.75 were 1.9 times (HR 1.9 95% Cl 1.0-3.6, p=0.04) more likely to die suddenly during 1600 days of follow-up. Interestingly, the predictive significance of HRV was different in subgroups of patients dichotomized by LVEF: none of the HRV indices were predictive for SCD in patients with LVEF [less than or equal to] 35% (226 patients), while in patients with LVEF [greater than or equal to] 35% (1094 patients) the DFA [alpha]1 <0.75 predicted SCD with HR of 2.7 (95% Cl 1.3-5.7, p=0.0088) In patients with HF, among nonlinear indices the abnormal Poincare plot was a significant, multivariate and independent of LVEF, norepinephrine norepinephrine (nôr'ĕpīnĕf`rən), a neurotransmitter in the catecholamine family that mediates chemical communication in the sympathetic nervous system, a branch of the autonomic nervous system. levels, ventricular tachycardia and ventricular premature complexes predictor of SCD (HR 5.3, 95% Cl 1.0-27.5, p<0.05) in 95 patients with HF, of whom 11 died suddenly during 4-year follow-up period (37, 38). Novel spectral indices of HRV and SCD Two novel spectral indices have been recently introduced (39-41). The prognostic significance of prevalent LF oscillation (PLF Noun 1. PLF - a terrorist group formed in 1977 as the result of a split with the Popular Front for the Liberation of Palestine; became a satellite of al-Fatah; made terrorist attacks on Israel across the Lebanese border ) of HRV was investigated in ATRAMI ATRAMI Autonomic Tone and Reflexes After Myocardial Infarction study population (39), which included 1139 patients after MI and mean LVEF-49.0 [+ or -] 1.8%. In this study, only presence of PLF along with reduced LVEF [less than or equal to] 35% could predict the combined end-point during mean 674 [+ or -] 234 days of follow-up. The patients with frequency of PLF [greater than or equal to] 0.1 Hz have 3.61 fold (95% Cl 1.25-10.5, p<0.02) higher risk of death, including cardiac arrest and ventricular fibrillation. However, PLF was present only in 80% of patients, which may limit its use as a risk marker in patients after MI. Further it has been shown that the combination of PLF with heart rate turbulence Heart Rate Turbulence (HRT) is the return to equilibrium of heart rate after a premature ventricular contraction (PVC). It consists of a brief speed-up in heart rate, followed by a slow decrease back to the baseline rate. slope improved prediction of arrhythmic death with RR of 5.1 (95% Cl 2.8-9.3, [p=9.8.sup.*] [10.sup.-8) in patients of placebo group in EMIAT study population (40). Kiviniemi et al. (41) have recently demonstrated that new HRV spectral parameter--Vi, derivative of high frequency (HF) spectral component and RRi intervals, had a strong prognostic power in prediction of SCD in 700 patients with MI, among them 17 patients (2.9%) died suddenly during mean 39 [+ or -] 14 months of follow-up period. In univariate analysis SDNN, LF, HF and new index Vi were significant predictors of SCD, however, after adjustment for clinical variables and LVEF, the Vi was a sole multivariate predictor of SCD; the patients with Vi <4.45[ms.sup.2] had 4.2-fold (95% Cl 1.2-15.2, p=0.02) higher risk of SCD during follow-up period. It worth mentioning, that Vi parameter was a significant predictor of worse survival in patients with low LVEF (p=0.03). The merit of conventional HRV predictors of mortality and SCD has changed during the past decade, with gaining in value of spectral, nonlinear and novel HRV indices as the potential risk markers in patients with MI and HF. However, the positive predictive value of HRV in prediction of SCD remains low. Further prospective investigations including combination of HRV indices with other noninvasive risk markers (4) in prediction of SCD should be addressed. References (1.) Smith TW, Cain ME. 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Fractal analysis and time- and frequency-domain measures of heart rate variability as predictors of mortality in patients with heartfailure. Am J Cardiol 2001; 87: 178-82. (38.) Brouwer J, van Veldhuisen DJ, Man in't Veld veld or veldt (both: vĕlt, Du. fĕlt) [Du.,=field], term applied to the grassy undulating plateaus of the Republic of South Africa and of Zimbabwe. AJ, Haaksma J, Dijk WA, Visser KR, et al. Prognostic value of heart rate variability during long-term follow-up in patients with mild to moderate heart failure. The Dutch Ibopamine Multicenter Trial Study Group. J Am Coll Cardiol 1996; 28:1183-9. (39.) Wichterle D, Simek J, La Rovere MT, Schwartz PJ, Camm AJ, Malik M. Prevalent low-frequency oscillation of heart rate: novel predictor of mortality after myocardial infarction. Circulation 2004;110:1183-90. (40.) Wichterle D, Simek J, Camm J, Malik M. Predictive characteristics of Holter-based postinfarction risk stratifiers appear superior to electrophysiological testing. Pacing Clin Electrophysiol 2005; 28: S182-6. (41.) Kiviniemi AM, Tulppo MP, Wichterle D, Hautala AJ, Tiinanen S, Seppanen T, et al. Novel spectral indexes of heart rate variability as predictors of sudden and non-sudden cardiac death after an acute myocardial infarction. Ann Med 2007; 39: 54-62. Gulmira Kudaiberdieva, Bulent Gorenek*, Bilgin Timuralp * National Center of Cardiology and Therapy, Bishkek, Kyrgyzstan, Adana, Turkey * Department of Cardiology, Medical Faculty, Osmangazi University, Eskisehir, Turkey Address for Correspondence: Gulmira Kudaiberdieva, MD, Beyazevler Mah. 26. Sokak, Irem Apt. 1/2, Adana, Turkey Email: gkudaiberdieva@@gmail.com |
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