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      Differential Index: A Simple Time Domain Heart Rate Variability Analysis with Prognostic Implications in Stable Angina Pectoris

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          Objectives: To examine the usefulness of time domain heart rate variability (HRV) measurements by a simple graphical method, the differential index (DI), in prognostic assessments of patients with chronic stable angina pectoris. Methods: HRV measurements in the time domain by DI were compared to conventional measurements of standard deviation of all normal-to-normal intervals (SDNN), percent of differences between adjacent normal RR intervals >50 ms (PNN50) and square root of the mean of the sum of squares of differences between adjacent normal RR intervals (RMSSD) from 24-hour ambulatory electrocardiographic recordings in 678 patients in the Angina Prognosis Study in Stockholm. The patients received double-blind treatment with metoprolol or verapamil. Main outcome measures were cardiovascular death or non-fatal myocardial infarction during follow-up (median 40 months). Results: Patients suffering cardiovascular death (n = 30) had lower DI, SDNN and PNN50 (all p < 0.001). In a multivariate Cox model, DI below median independently predicted cardiovascular death (p = 0.002), as did SDNN (p = 0.016) and PNN50 (p = 0.030), but not RMSSD (p = 0.10). The separation of survival curves was most pronounced and specificity was slightly better with DI. DI and PNN50 increased with metoprolol but not verapamil treatment. Short-term treatment effects were not related to prognosis. Conclusions: Low time domain HRV carries independent prognostic information regarding cardiovascular death in stable angina pectoris. The simple DI method provided equally good or better prognostic information than conventional, more laborious HRV methods.

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          Most cited references 17

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          Accuracy of assessment of cardiac vagal tone by heart rate variability in normal subjects.

          The correlations of 11 indexes of heart rate variability were examined with pharmacologically determined cardiac vagal tone in 15 normal subjects at supine rest. After sympathetic influences by intravenous propranolol were eliminated, RR interval variability was measured for 10 minutes under controlled respiration (0.25 Hz), and cardiac vagal tone was determined as the decrease in mean RR interval following complete vagal blockade with atropine. Time domain indexes (standard deviation, coefficient of variance and mean successive difference) correlated strongly with vagal tone (r = 0.87, 0.81 and 0.92, respectively; p less than 0.001 for all). The same was true for frequency domain indexes for the high-frequency (0.25 Hz) component calculated both by autoregressive spectrum analysis (square root of power and coefficient of component variance) and by fast Fourier transform (mean amplitude) (r = 0.91, 0.85 and 0.86, respectively; p less than 0.0001 for all). However, frequency domain indexes for the low-frequency spectral component (0.03 to 0.15 Hz) correlated less strongly (r = 0.69, 0.55 and 0.70, respectively), and the fraction of power [power/(total power greater than 0.03 Hz)] of both components showed no correlation. Principal component analysis showed that the first 6 indexes with strong correlations contained solely the first principal component closely related to vagal tone, whereas the remaining 5 indexes also contained the second component unrelated to vagal tone. These results indicate that most of the time and frequency domain analyses in use provides an accurate and common measure of cardiac vagal tone at rest.
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            Lower heart rate variability is associated with the development of coronary heart disease in individuals with diabetes: the atherosclerosis risk in communities (ARIC) study.

            The objective of this study was to test prospectively in a population sample whether individuals with impaired heart rate variability (HRV) are at increased risk of developing coronary heart disease (CHD) and of non-CHD mortality and to test whether this relationship is more pronounced among individuals with diabetes. We examined the association between HRV and incident CHD and non-CHD mortality in a cohort of 11,654 men and women aged 45-64 years at intake, from the biracial, population-based Atherosclerosis Risk in Communities Study. Supine, resting, 2-min beat-to-beat heart rate data were collected at the baseline examination. High frequency (HF; 0.15-0.40 Hz) and low frequency (LF; 0.04-0.15 Hz) spectral powers, LF/HF ratio, normalized HF and LF, the standard deviation of all normal R-R intervals (SDNN), and the mean of the sum of the squared differences between adjacent normal R-R intervals (MSSD) were used as the conventional indexes of HRV to measure cardiac autonomic control. From this cohort, 635 cases of incident CHD (including 346 cases of incident myocardial infarction [MI] and 82 cases of fatal CHD), and 623 non-CHD deaths were identified and validated after an average of 8 years of follow-up. Among individuals with diabetes, the multivariable adjusted proportional hazards ratios (95% CI) were 2.03 (1.28-3.23), 1.60 (1.12-2.27), 1.50 (0.65-3.42), and 1.27 (0.84-1.91) for incident MI, incident CHD, fatal CHD, and non-CHD deaths, respectively, comparing the lowest quartile to the upper most three quartiles of HF. A similar pattern of associations was found for LF, SDNN, and MSSD. By contrast, there was no consistent pattern of associations among individuals without diabetes. At the population level, a lower HRV (reflective of impaired cardiac autonomic control) is statistically significantly related to the development of CHD among individuals with diabetes, independent of markers of the duration/severity of the glucose metabolism impairment. These data suggest a contribution of an impaired cardiac autonomic control to the risk of CHD among individuals with diabetes.
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              Percutaneous coronary intervention versus conservative therapy in nonacute coronary artery disease: a meta-analysis.

              Percutaneous coronary intervention (PCI) has been shown to improve symptoms compared with conservative medical treatment in patients with stable coronary artery disease (CAD); however, there is limited evidence on the effect of PCI on the risk of death, myocardial infarction, and subsequent revascularization. Therefore, we performed a meta-analysis of 11 randomized trials comparing PCI to conservative treatment in patients with stable CAD. A total of 2950 patients were included in the meta-analysis (1476 received PCI, and 1474 received conservative treatment). There was no significant difference between the 2 treatment strategies with regard to mortality, cardiac death or myocardial infarction, nonfatal myocardial infarction, CABG, or PCI during follow-up. By random effects, the risk ratios (95% CIs) for the PCI versus conservative treatment arms were 0.94 (0.72 to 1.24), 1.17 (0.88 to 1.57), 1.28 (0.94 to 1.75), 1.03 (0.80 to 1.33), and 1.23 (0.80 to 1.90) for these 5 outcomes, respectively. A possible survival benefit was seen for PCI only in trials of patients who had a relatively recent myocardial infarction (risk ratio 0.40, 95% CI 0.17 to 0.95). Except for PCI during follow-up, there was no significant between-study heterogeneity for any outcome. In patients with chronic stable CAD, in the absence of a recent myocardial infarction, PCI does not offer any benefit in terms of death, myocardial infarction, or the need for subsequent revascularization compared with conservative medical treatment.

                Author and article information

                S. Karger AG
                August 2008
                31 March 2008
                : 111
                : 2
                : 126-133
                aMedical Products Agency, and bUppsala Clinical Research Center, Uppsala University Hospital, Uppsala, cDepartment of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Karolinska Institutet, dStockholm University College of Physical Education and Sports, eCardiology Unit and fClinical Pharmacology Unit, Department of Medicine, Karolinska University Hospital (Solna), and gSwedish Council on Technology Assessment in Health Care (SBU), Stockholm, Sweden
                119700 Cardiology 2008;111:126–133
                © 2008 S. Karger AG, Basel

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                Page count
                Figures: 3, Tables: 3, References: 28, Pages: 8
                Original Research


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