Cees A. Swenne

Low Heart Rate Variability in a 2-Minute Rhythm Strip Predicts Risk of Coronary Heart Disease and Mortality From Several Causes The ARIC Study

BackgroundLow heart rate variability (HRV) is associated with a higher risk of death in patients with heart disease and in elderly subjects and with a higher incidence of coronary heart disease (CHD) in the general population. Methods and ResultsWe studied the predictive value of HRV for CHD and death from several causes in a population study of 14 672 men and women without CHD, aged 45 to 65, by using the case-cohort design. At baseline, in 1987 to 1989, 2-minute rhythm strips were recorded. Time-domain measures of HRV were determined in a random sample of 900 subjects, for all subjects with incident CHD (395 subjects), and for all deaths (443 subjects) that occurred through 1993. Relative rates of incident CHD and cause-specific death in tertiles of HRV were computed with Poisson regression for the case-cohort design. Subjects with low HRV had an adverse cardiovascular risk profile and an elevated risk of incident CHD and death. The increased risk of death could not be attributed to a specific cause and could not be explained by other risk factors. ConclusionsLow HRV was associated with increased risk of CHD and death from several causes. It is hypothesized that low HRV is a marker of less favorable health.

Heart rate variability and first cardiovascular event in populations without known cardiovascular disease: meta-analysis and dose–response meta-regression

AIMS Heart rate variability (HRV) is associated with cardiovascular disease (CVD) in individuals with known CVD. It is less clear whether HRV is associated with a first cardiovascular event. Therefore, we performed a meta-analysis to study the association between HRV and incident cardiovascular events in populations without known CVD. METHODS AND RESULTS We performed a meta-analysis and dose-response meta-regression of studies assessing the association between HRV and CVD. We searched Pubmed, Embase, Web of Science, Cochrane library, ScienceDirect, and CINAHL up to December 2011 for eligible studies. We selected studies that used the standard deviation of the normalized N-N interval (SDNN), low-frequency (LF) or high-frequency (HF) spectral component as a measure of HRV. Primary outcomes were (non)fatal cardiovascular events. Eight studies with a total number of 21 988 participants were included. The pooled relative risk (RR) comparing the lowest level to the highest level of SDNN was 1.35 (95% CI 1.10, 1.67). The pooled RRs for LF and HF were 1.45 (95% CI 1.12, 1.87) and 1.32 (95% CI 0.96, 1.81), respectively. In a meta-regression, the predicted RR of incident CVD of the 10th and 90th HRV (SDNN) percentiles compared with the 50th percentile were 1.50 (95% CI 1.22, 1.83) and 0.67 (95% CI 0.41, 1.09). CONCLUSION In conclusion, low HRV is associated with a 32-45% increased risk of a first cardiovascular event in populations without known CVD. An increase in SDNN of 1% results in an ∼1% lower risk of fatal or non-fatal CVD.

Cardiovascular disease, risk factors and heart rate variability in the elderly general population: Design and objectives of the CARdiovascular disease, Living and Ageing in Halle (CARLA) Study

BackgroundThe increasing burden of cardiovascular diseases (CVD) in the ageing population of industrialized nations requires an intensive search for means of reducing this epidemic. In order to improve prevention, detection, therapy and prognosis of cardiovascular diseases on the population level in Eastern Germany, it is necessary to examine reasons for the East-West gradient of CVD morbidity and mortality, potential causal mechanisms and prognostic factors in the elderly.Psychosocial and nutritional factors have previously been discussed as possible causes for the unexplained part of the East-West gradient. A reduced heart rate variability appears to be associated with cardiovascular disease as well as with psychosocial and other cardiovascular risk factors and decreases with age. Nevertheless, there is a lack of population-based data to examine the role of heart rate variability and its interaction with psychosocial and nutritional factors regarding the effect on cardiovascular disease in the ageing population. There also is a paucity of epidemiological data describing the health situation in Eastern Germany. Therefore, we conduct a population-based study to examine the distribution of CVD, heart rate variability and CVD risk factors and their associations in an elderly East German population. This paper describes the design and objectives of the CARLA Study.Methods/designFor this study, a random sample of 45–80 year-old inhabitants of the city of Halle (Saale) in Eastern Germany was drawn from the population registry. By the end of the baseline examination (2002–2005), 1750 study participants will have been examined. A multi-step recruitment strategy aims at achieving a 70 % response rate.Detailed information is collected on own and family medical history, socioeconomic, psychosocial, behavioural and biomedical factors. Medical examinations include anthropometric measures, blood pressure of arm and ankle, a 10-second and a 20-minute electrocardiogram, a general physical examination, an echocardiogram, and laboratory analyses of venous blood samples. On 200 participants, a 24-hour electrocardiogram is recorded. A detailed system of quality control ensures high data quality. A follow-up examination is planned.DiscussionThis study will help to elucidate pathways to CVD involving autonomic dysfunction and lifestyle factors which might be responsible for the CVD epidemic in some populations.

Predicting Ventricular Arrhythmias in Patients with Ischemic Heart Disease: Clinical Application of the ECG derived QRS-T Angle

Background—In patients with primary prevention implantable cardioverter-defibrillators (ICDs), the incidence of life-threatening ventricular arrhythmias resulting in ICD therapy is relatively low, prompting for better risk stratification. The aim of this study was to assess the value of the QRS-T angle for prediction of ICD therapy and mortality in primary prevention patients with ischemic heart disease. Methods and Results—ICD patients (n=412, 361 men; age, 63±11 years) with ischemic heart disease and a left ventricular ejection fraction ≤40% were included. After device implantation, the occurrence of appropriate ICD therapy and mortality was noted. A survival analysis was performed comparing patients with a planar QRS-T angle ≤90° (n=124, 30%) with patients with a planar QRS-T angle >90° before device implantation. Furthermore, patients with a spatial QRS-T angle ≤100° (n=56, 14%) were compared with patients with a spatial QRS-T angle >100°, before implantation. For patients with a planar QRS-T angle >90° as compared with ≤90°, the adjusted hazard ratio for the occurrence of appropriate device therapy was 2.4 (95% CI, 1.1 to 5.2); a spatial QRS-T angle >100° was associated with an adjusted hazard ratio of 7.3 (95% CI, 1.0 to 53.8). Furthermore, a spatial QRS-T angle ≤100° exhibited a positive predictive value of 98% (95% CI, 95 to 100) for the prediction of an appropriate therapy-free follow-up. Conclusions—A wide QRS-T angle is a strong predictor of appropriate device therapy in primary prevention ICD recipients with ischemic heart disease. Furthermore, a spatial QRS-T angle ≤100° might be of value in the identification of patients in whom, although currently indicated, ICD treatment should be reconsidered.

Tryptophan Depletion Affects Heart Rate Variability and Impulsivity in Remitted Depressed Patients with a History of Suicidal Ideation

BACKGROUND Depression is a major risk factor for cardiovascular disease. An important risk factor for cardiovascular disease, low heart rate variability, often has been found in depressed patients and has been associated with impulsivity. The present study investigated whether experimental lowering of serotonin would decrease heart rate variability and increase impulsivity in remitted depressed patients, in particular in those patients with disturbed impulse control. METHODS Nineteen patients in remission from depression received high-dose and low-dose acute tryptophan depletion in a randomized, counterbalanced, double-blind crossover design. Heart rate variability and impulsivity were assessed during each acute tryptophan depletion session and during a baseline session. Suicidal ideation during past depression was used as an index for individual differences in impulse control. RESULTS High-dose acute tryptophan depletion led to a larger increase in depressive symptoms than did low-dose acute tryptophan depletion. High-dose acute tryptophan depletion decreased heart rate variability and increased impulsivity and anxiety, but only in patients with a history of suicidal ideation. Symptom effects of high-dose acute tryptophan depletion correlated with low heart rate variability at baseline. CONCLUSIONS Depressed patients who have problems with controlling impulsivity might be more at risk for developing cardiovascular disease, possibly related to increased vulnerability to impaired 5-hydroxytryptamine function.

Normal limits of the spatial QRS-T angle and ventricular gradient in 12-lead electrocardiograms of young adults: dependence on sex and heart rate

BACKGROUND AND PURPOSE Normal limits of the spatial QRS-T angle and spatial ventricular gradient (SVG) are only available from Frank vectorcardiograms (VCGs) of male subjects. We determined normal limits for these variables derived from standard 12-lead electrocardiograms (ECGs) of 660 male and female students aged 18 to 29 years. METHODS A computer algorithm was used that constructed approximated VCG leads by inverse Dower matrix transformation of the 12-lead ECG and subsequently calculated the spatial QRS-T angle, SVG magnitude, and orientation. RESULTS In female subjects, the QRS-T angle was more acute (females, 66 degrees +/- 23 degrees; normal, 20 degrees-116 degrees; males, 80 degrees +/- 24 degrees; normal, 30 degrees-130 degrees; P < .001), and the SVG magnitude was smaller (females, 81 +/- 23 mV x ms; normal, 39-143 mV x ms; males, 110 +/- 29 mV x ms; normal, 59-187 mV x ms; P < .001) than in male subjects. The male SVG magnitude in our study was larger than that computed in Frank VCGs (79 +/- 28 mV.ms; P < .001). CONCLUSIONS The spatial QRS-T angle and SVG depend strongly on sex. Furthermore, normal limits of SVG derived from Frank VCGs differ markedly from those derived from VCGs synthesized from the standard ECG. As nowadays, VCGs are usually synthesized from the 12-lead ECG; normal limits derived from the standard ECG should preferably be used.

The importance of high-frequency paced breathing in spectral baroreflex sensitivity assessment

Objective Computation of the low-frequency (LF) blood pressure variability (BPV) to heart rate variability (HRV) transfer-index is a common method to assess baroreflex sensitivity (BRS), tacitly assuming that all LF-HRV is caused by baroreflex feedback of LF-BPV. However, respiration may also cause HRV by mechanisms not involving the baroreflex. Application of narrow-band (controlled) high-frequency breathing would keep such non-baroreflex-mediated HRV best out of the LF band. Spontaneous breathing, because of its broad-band character, might cause extra, non-baroreflex-mediated, HRV in the LF band, while paced LF breathing would even concentrate most non-baroreflex-mediated HRV in the LF band. Our study addresses the likely resulting BRS overestimation. Design We recorded HRV and BPV in 20 healthy young subjects in the sitting position. We varied the sympathovagal balance by gradual leg-lowering from horizontal till 60°. At each angle the subjects performed controlled 0.10 Hz, spontaneous, and controlled 0.25 Hz respiration. Results Resting BRS values were 15.5(7.2), 13.1(3.7), and 11.6(6.2) ms/mmHg, respectively. Both the 15/min and the free breathing values differed significantly, P < 0.01 and P = 0.04, from the 6/min breathing value. With lowered legs, the BRS values were 8.2(3.4), 8.3(2.9), and 8.3(3.4) ms/mmHg, respectively. Conclusion Controlled 6/min breathing caused significant BRS overestimation under resting conditions. For the group, spontaneous respiration yielded acceptable BRS values, but individual BRS values deviated sometimes considerably. Conversely, with gravitational load, the respiratory pattern had only minor impact on BRS. Our results demonstrate that the risk of an overestimated BRS value is realistic as long as respiration is not controlled and of high-frequency.

LEADS: an interactive research oriented ECG/VCG analysis system

We recently developed a MATLAB program, LEADS (Leiden ECG analysis and decomposition software), for research oriented ECG/VCG analysis. Any eight-channel recording in comma-separated values format (CSV) can be input. After detection of QRST complexes in the spatial velocity signal and baseline correction, LEADS generates a default selection of beats for subsequent averaging. The analyst may then adjust this selection, after which the selected beats are averaged to generate a representative and low-noise averaged beat (ECG and VCG). In this beat, LEADS computes default onset-QRS, end-QRS and end-T instants, which may be subsequently reviewed/edited. Finally, several conventional and advanced ECG and VCG parameters are automatically computed, and the results are output in the form of a CSV file. By virtue of the combination of adjustable configuration settings and interactive procedures, LEADS has provided us with the ability to reliably analyze ECGs ranging from normal to highly pathological

Changes in frequency of premature complexes and heart rate variability related to shift work.

OBJECTIVES To investigate whether an increased risk of cardiovascular disease might be caused by increased arrhythmogeneity and by unfavourable changes in autonomic cardiac control the changes in the occurrence of premature complexes (PVCs) and in heart rate variability (HRV) were studied in subjects who started to work in shifts. METHODS 1 Year changes in frequency of PVCs and HRV were measured in 49 shift workers and 22 control subjects working in daytime. All respondents were starting in a new job in integrated circuit or waste incinerator plants. RESULTS The incidence of PVC increased significantly in shift workers over the 1 year follow up, compared with daytime workers. The frequency of ventricular extrasystoles increased in 48.9% of the shift workers, and in 27.3% of the daytime workers. The Spearman correlation coefficient between the number of nights worked and the change in PVCs was 0.33 (p=0.004). A small non-significant unfavourable change in HRV was found in both the shift and daytime workers. CONCLUSIONS A change in arrhythmogeneity, but not in cardiac autonomic control, might explain the increased risk of cardiovascular disease in shift workers.

Validation of ECG Indices of Ventricular Repolarization Heterogeneity: A Computer Simulation Study

Introduction: Repolarization heterogeneity (RH) is functionally linked to dispersion in refractoriness and to arrhythmogenicity. In the current study, we validate several proposed electrocardiogram (ECG) indices for RH: T‐wave amplitude, ‐area, ‐complexity, and ‐symmetry ratio, QT dispersion, and the Tapex‐end interval (the latter being an index of transmural dispersion of the repolarization (TDR)).