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Biomedical subjects

Phyllis K Stein

Publications and source records attributed to Phyllis K Stein.

At least 19 recordsLinked to original sources

Heart rate turbulence, depression, and survival after acute myocardial infarction.

OBJECTIVE: Depression is a risk factor for mortality after acute myocardial infarction (AMI), possibly as a result of altered autonomic nervous system (ANS) modulation of heart rate (HR) and rhythm. The purposes of this study were to determine: a) whether depressed patients are more likely to have an abnormal HR response (i.e., abnormal turbulence) to premature ventricular contractions (VPCs), and b) whether abnormal HR turbulence accounts for the effect of depression on increased mortality after AMI. METHODS: Ambulatory electrocardiographic data were obtained from 666 (316 depressed, 350 nondepressed) patients with a recent AMI; 498 had VPCs with measurable HR turbulence. Of these, 260 had normal, 152 had equivocal, and 86 had abnormal HR turbulence. Patients were followed for up to 30 (median = 24) months. RESULTS: Depressed patients were more likely to have abnormal HR turbulence (risk factor adjusted odds ratio = 1.8; 95% confidence interval [CI] = 1.0-3.0; p = .03) and have worse survival (odds ratio = 2.4; 95% CI = 1.2-4.6; p = .02) than nondepressed patients. When HR turbulence was added to the model, the adjusted hazard ratio for depression decreased to 1.9 (95% CI = 0.9-3.8; p = .08), and to 1.6 (95% CI = 0.8-3.4; p = .18) when a measure of HR variability (LnVLF) was added. The hazard was found to differ over time with depression posing little risk for mortality in year 1 but greater risk in years 2 and 3 of the follow up. CONCLUSION: ANS dysregulation may partially mediate the increased risk for mortality in depressed patients with frequent VPCs after an AMI.

Aged↗

Diastolic dysfunction and autonomic abnormalities in patients with systolic heart failure.

BACKGROUND: Patients with systolic heart failure (SHF) often have concomitant diastolic dysfunction (DD). SHF is associated with decreased heart rate variability (HRV), but the impact of degree of DD on HRV in SHF is unclear. METHODS AND RESULTS: HRV was measured in 139 patients, aged 64+/-12 years, 74% male, LVEF 30+/-8%. Patients had stable NYHA class II-III CHF on ACE inhibitors or ATII receptor blockers, with LVEF or=200 pg/ml. Subjects underwent 2-D echocardiography with Doppler assessment and 24-h Holters. Patients were categorized as having impaired relaxation (E-deceleration time>2 SD above age-adjusted normal values (AANV), E/A or=1; N=30), pseudonormal (E-deceleration time within 2 SD of AANV, E/A=1-2, systolic/diastolic pulmonary vein flow<1; N=25) or restrictive filling patterns (E-deceleration time>2 SD below AANV or/and E/A ratio>or=2; N=84) Differences were adjusted for clinical covariates using UNIANOVA, p<0.05. HRV was reduced and BNP higher in pseudonormal patients compared to impaired relaxation, but this difference was only significant for restrictive vs. impaired filling. Differences remained significant after adjustment for covariates. CONCLUSION: Significantly more abnormal HRV, reflecting greater cardiac autonomic dysfunction, is associated with restrictive DD compared to impaired relaxation.

Adult↗

Vagal modulation and aging.

Cardiovascular disease accounts for approximately 30% of all deaths worldwide, and will only worsen as the world's population ages. It is well-established that age, per se, is a major risk factor and contributor to all cardiovascular morbidities and mortalities. However, environmental factors, including a lack of exercise, appear to play a critical role in the onset and progression of cardiovascular disease. This paper reviews the literature on cardiac variability and aging and addresses risk factors associated with aging that can be modified and possibly attenuate the decline of heart rate variability with aging, including exercise training to increase vagal modulation. Thus, results of the studies described in this review support a potential benefit of increasing or maintaining fitness in order to slow the decline of parasympathetic control of HR with normal aging.

Adaptation, Physiological↗

Cerebrospinal fluid corticotropin-releasing factor concentration is associated with pain but not fatigue symptoms in patients with fibromyalgia.

Previous studies have identified stress system dysregulation in fibromyalgia (FM) patients; such dysregulation may be involved in the generation and/or maintenance of pain and other symptoms. Corticotropin-releasing factor (CRF) is the principal known central nervous system mediator of the stress response; however, to date no studies have examined cerebrospinal fluid (CSF) CRF levels in patients with FM. The relationship between CSF CRF level, heart rate variability (HRV), and pain, fatigue, and depressive symptoms was examined in patients with FM. Among participants (n=26), CSF CRF levels were associated with sensory pain symptoms (r=0.574, p=0.003) and affective pain symptoms (r=0.497, p=0.011), but not fatigue symptoms. Increased HRV was also strongly associated with increased CSF CRF and FM pain. In multivariate analyses adjusting for age, sex, and depressive symptoms, the association between CSF CRF and sensory pain symptoms (t=2.54, p=0.027) persisted. Women with FM who reported a history of physical or sexual abuse had lower CSF CRF levels than women who did not report such a history. CSF CRF levels are associated with both pain symptoms and variation in autonomic function in FM. Differences in CSF CRF levels among women with and without a self-reported history of physical or sexual abuse suggest that subgroups of FM patients may exist with different neurobiological characteristics. Further studies are needed to better understand the nature of the association between CSF CRF and pain symptoms in FM.

Adrenal Cortex Hormones↗

Dietary fish and n-3 fatty acid intake and cardiac electrocardiographic parameters in humans.

OBJECTIVES: We evaluated the association between dietary fish intake and several cardiac electrocardiographic parameters in humans relevant to arrhythmic risk. BACKGROUND: Fish consumption may reduce the incidence of sudden death and atrial fibrillation, possibly related to anti-arrhythmic effects. METHODS: In a population-based study of 5,096 men and women, we evaluated cross-sectional associations between usual dietary fish intake and electrocardiographic measures of heart rate, atrioventricular conduction (PR interval), ventricular repolarization (QT interval), and ventricular conduction (QRS interval). Multivariate models were adjusted for age, gender, race, education, smoking, body mass index, diabetes, coronary heart disease, physical activity, and intakes of beef or pork, fried fish, fruits, vegetables, alcohol, and total calories. RESULTS: Consumption of tuna or other broiled or baked fish (comparing the highest to the lowest category of intake) was associated with lower heart rate (-3.2 beats/min, 95% confidence interval [CI] = 1.3 to 5.1; p trend <0.001), slower atrioventricular conduction (PR interval +7.2 ms, 95% CI = 1.4 to 12.9; p trend = 0.03), and substantially lower likelihood of prolonged QT (relative risk = 0.50, 95% CI = 0.27 to 0.95; p trend = 0.03). Tuna/other fish intake was not associated with ventricular conduction (p = 0.60). Findings were similar for estimated intake of marine n-3 fatty acids: a 1 g/day higher intake was associated with 2.3 beats/min lower heart rate (95% CI = 0.9 to 3.7), 7.6 ms longer PR interval (95% CI = 3.3 to 11.9), and 46% lower likelihood of prolonged QT (relative risk = 0.54, 95% CI = 0.33 to 0.88). CONCLUSIONS: These findings in this large, population-based study suggest that dietary fish intake is associated with cardiac electrophysiology in humans, including heart rate, atrioventricular conduction, and ventricular repolarization, with potential implications for arrhythmic risk.

Aged↗

Circadian and ultradian rhythms in heart rate variability.

AIM: Heart rate variability (HRV) patterns reflect the changing effect of sympathetic and parasympathetic modulation of the autonomic nervous system. While overall and circadian heart rate (HR) and HRV are well characterized by traditional measures, there is currently no method to measure ultradian cycles of HR and HRV. MATERIALS AND METHODS: HR/HRV for each 2-min interval was calculated using normal-to-normal interbeat intervals from overnight polysomnographic ECGs in 113 subjects, aged 58+/-10 years (65 male, 48 female). HR, SDNN2, high-frequency power (HF) and the LF (low-frequency power)/HF ratio were plotted. A curve-fitting algorithm, developed in MatLab, identified cyclic patterns of HR/HRV and extracted parameters to characterize them. Results were compared for older vs. younger patients, males vs. females, with vs. without severe sleep apnea, and for the upper and lower half of sleep efficiency. RESULTS: Ultradian patterns for different HR/HRV indices had variable correspondences with each other and none could be considered surrogates. Differences were seen for all comparison groups, but no one marker was consistently different across comparisons. CONCLUSION: Each HR/HRV parameter has its own rhythm, and the correspondence between these rhythms varies greatly across subjects. Quantification of ultradian patterns of HRV is feasible and could provide new insights into autonomic physiology.

Age Factors↗

Complex autonomic dysfunction in cardiovascular, intensive care, and schizophrenic patients assessed by autonomic information flow.

BACKGROUND: The cardiovascular control system is mediated by mechanisms acting at different time scales, such as heart period, vagal, sympathetic, and other slower controllers. Since these elements are interrelated in a complex manner, classical control theory fails and information-based description, based on autonomic information flow (AIF) functions, is appropriate. We investigated the hypothesis that AIF functions of typical time scales specifically characterize autonomic dysfunction and prognosis. MATERIALS AND METHODS: Holter recordings of patients with multiple organ dysfunction syndrome (MODS) (26 survivors, 10 non-survivors), heart failure (13 low risk, 13 high risk of cardiac arrest), idiopathic dilated cardiomyopathy (IDC) (26 low risk, 11 high risk), after abdominal aorta surgery (AAS) [32 with length of stay in hospital (LOS) >7 days; 62 with LOS < or =7 days] or with schizophrenia (n=20) were assessed and compared to 20 control subjects. RESULTS: We found different AIF time scales discriminating risk. AIF measures of heart beat period had predominant prognostic value in heart failure patients, those of vagal communication in MODS and IDC, and those of long-term communication after AAS. Schizophrenic patients were discriminated from controls by vagally mediated communication. CONCLUSION: Different time scales of AIF represent specific pathophysiological aspects of altered complex autonomic control (communication) and consequently have predictive implications.

Autonomic Nervous System↗

Low heart rate variability and the effect of depression on post-myocardial infarction mortality.

BACKGROUND: Depression is associated with an increased risk for mortality after acute myocardial infarction (MI). The purpose of this study was to determine whether low heart rate variability (HRV) mediates the effect of depression on mortality. METHODS: Twenty-four-hour ambulatory electrocardiograms were obtained from 311 depressed patients with a recent acute MI who were enrolled in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial and from 367 nondepressed patients who met the ENRICHD medical inclusion criteria. Standard HRV indexes were extracted from the recordings. RESULTS: The log of very low-frequency (LnVLF) power, an index of HRV derived from power spectral analysis of the electrocardiogram signal (0.0033-0.04 Hz [in milliseconds squared]), was lower in the depressed than in the nondepressed patients (P<.001). There were 47 deaths (6.1%) during a 30-month follow-up. After adjusting for potential confounders, the depressed patients remained at higher risk for all-cause mortality compared with the nondepressed patients (hazard ratio, 2.8; 95% confidence interval [CI], 1.4-5.4; P<.003). When LnVLF power was entered into the model, the hazard ratio for depression dropped to 2.1 (95% CI, 1.1-4.2; P = .03). The proportion of the risk for depression attributable to LnVLF power was 0.27 (95% CI, 0.23-0.31; P<.001). CONCLUSIONS: Low HRV partially mediates the effect of depression on survival after acute MI. This finding helps to clarify the physiological mechanisms underlying depression's role as a risk factor for mortality in patients with coronary heart disease. It also raises the possibility that treatments that improve both depression and HRV might also improve survival in these patients.

Circadian Rhythm↗

Non-linear heart rate variability and risk stratification in cardiovascular disease.

Traditional time and frequency domain heart rate variability (HRV) have cardiac patients at risk of mortality post-myocardial infarction. More recently, non linear HRV has been applied to risk stratification of cardiac patients. In this review we describe studies of non linear HRV and outcome in cardiac patients. We have included studies that used the three most common non-linear indices: power law slope, the short term fractal scaling exponent and measures based on Poincare plots. We suggest that a combination of traditional and non-linear HRV may be optimal for risk stratification. Considerations in using non linear HRV in a clinical setting are described.

Journal Article↗

Characteristics of heart beat intervals and prediction of death.

OBJECTIVE: To assess the value for improving risk stratification of measures, unadjusted and adjusted for heart rate, of heart rate variability (HRV) and heart rate turbulence (HRT) based on 2- to 24-h ambulatory electrocardiographic recordings; and to relate this to the decision to use an implantable cardiac defibrillator (ICD) and the attendant consequences on effectiveness and cost-effectiveness. BACKGROUND: Risk stratification for high risk or low risk of lethal ventricular arrhythmic events, and hence for a decision about defibrillator implant, most commonly utilizes the left ventricular ejection fraction (LVEF). Electrocardiographic (ECG) approaches include 24-h ambulatory ECG recordings, with counts of ventricular premature contractions (VPCs), measures of heart rate variability (HRV), and heart rate turbulence (HRT). HRT has two components: turbulence onset (TO) and turbulence slope (TS). METHODS AND RESULTS: We evaluated the qualifying ambulatory ECG recordings from 744 patients in the active treatment arms of the Cardiac Arrhythmia Suppression Trial (CAST). Beat characteristics, VPC counts, normal-to-normal beat intervals, and time-domain measures of HRV and HRT were calculated. Tachograms were rescaled to a heart rate of 75 and the resulting "normalized" measures evaluated as risk predictors for death, compared to unnormalized measures. Measures based on 2-h ECGs were also evaluated as risk predictors. The most powerful univariate predictor of survival was the normalized turbulence slope. The best multivariate prediction model had six components: history of angina, hypertension, diabetes, and absence of post-myocardial infarction revascularization, the log of LVEF, normalized TS, HR, and an interaction term of HR and normalized TS. Gains in effectiveness from use of this model cost between $0 and $4000 per year of life saved. CONCLUSIONS: Turbulence slope substantially exceeded other ECG-based measures in improving prediction of subsequent death in models which included LVEF, and other clinical parameters. Use of this model would improve the effectiveness and cost-effectiveness of the ICD.

Arrhythmias, Cardiac↗

QT dynamicity: a prognostic factor for sudden cardiac death in chronic heart failure.

INTRODUCTION: The aim of this study was to determine whether impaired adaptation of the QT interval to changes in heart rate predicts sudden death in patients with chronic heart failure (CHF). METHODS: We prospectively included 175 CHF patients in sinus rhythm. QT dynamicity was evaluated by analyzing 24-h Holter recordings. The linear regression slope of QT interval measured to the apex and to the end of T wave plotted against RR intervals was calculated using a dedicated Holter algorithm. RESULTS: Mean follow-up was 29.9+/-17.9 months. There were 48 deaths, of which 21 were sudden. The actuarial 3-year mortality rates were 38.4% for overall mortality and 14.1% for sudden death. Of all the parameters, an increased QTe/RR slope (>0.28) was the strongest independent predictor of sudden death (relative risk 3.47, 95% confidence interval 1.43-8.40, p=0.006). CONCLUSION: Increased 24-h QTe dynamicity is independently predictive of sudden death among patients with heart failure. This simple parameter may help to stratify risk and select patients who may benefit from antiarrhythmic prophylaxis.

Adult↗

Traditional and nonlinear heart rate variability are each independently associated with mortality after myocardial infarction.

INTRODUCTION: Decreased heart rate variability (HRV) and abnormal nonlinear HRV shortly after myocardial infarction (MI) are risk factors for mortality. Traditional HRV predicts mortality in patients with a range of times post-MI, but the association of nonlinear HRV and outcome in this population is unknown. METHODS AND RESULTS: HRV was determined from 740 tapes recorded before antiarrhythmic therapy in Cardiac Arrhythmia Suppression Trial patients with ventricular premature contractions (VPCs) suppressed on the first randomized treatment. Patients were 70 +/- 121 days post-MI. Follow up was 362 +/- 241 days (70 deaths). The association between traditional time and frequency-domain HRV and mortality and nonlinear HRV and mortality were compared for the entire population (ALL), those without coronary artery bypass graft post-MI (no CABG), and those without CABG or diabetes (no CABG, no DIAB) using univariate and multivariate Cox regression analysis. Strength of association was compared by P values and Wald Chi-square values. Nonlinear HRV included short-term fractal scaling exponent, power law slope, and SD12 (Poincare dimension). For ALL and for no CABG, increased daytime SD12 had the strongest association with mortality (P=0.002 ALL and P <0.001 no CABG). For no CABG, no DIAB increased 24-hour SD12 hours had the strongest association (P <0.001) with mortality. Upon multivariate analysis, increased SD12, decreased ln ULF (ultra low frequency), and history of prior MI and history of congestive heart failure each remained in the model. CONCLUSION: Nonlinear HRV is associated with mortality post-MI. However, as with traditional HRV, this is diluted by CABG surgery post-MI and by diabetes. Results suggest that decreased long-term HRV and increased randomness of heart rate are each independent risk factors for mortality post-MI.

Algorithms↗

Sometimes higher heart rate variability is not better heart rate variability: results of graphical and nonlinear analyses.

OBJECTIVE: To determine the prevalence and effect on traditional heart rate variability (HRV) indices of abnormal HRV patterns in the elderly. METHODS: Hourly Poincaré plots and plots of spectral HRV from normal-to-normal interbeat intervals and hourly nonlinear HRV values were examined in a subset of 290 consecutive participants in the Cardiovascular Health Study. Only subjects in normal sinus rhythm with > or = 18 hours of usable data were included. Eligible subjects were 71 +/- 5 years. During 7 years of follow-up, 21.7% had died. Hours were scored as normal (0), borderline (0.5), or abnormal (1) from a combination of plot appearance and HRV. Summed scores were normalized to 100% to create an abnormality score (ABN). Short-term HRV versus each 5th percentile of ABN was plotted and a cutpoint for markedly increased HRV identified. The t-tests compared HRV for subjects above and below this cutpoint. Cox regression evaluated the association of ABN and mortality. RESULTS: Of 5,815 eligible hourly plots, 64.4% were normal, 14.5% borderline, and 21.1% abnormal. HR, SDNN, SDNNIDX, ln VLF and LF power, and power law slope did not differ by the cutpoint for increased short-term HRV, while SDANN and ln ULF power were significantly lower for those above the cutpoint. However, many HRV indices including LF/HF ratio and normalized LF and HF power were significantly different between groups (P < 0.001). Increased ABN was significantly associated with mortality (P = 0.019). Despite similar values for many HRV indices, being in the group above the cutpoint was significantly associated with mortality (P = 0.04). CONCLUSIONS: Abnormal HR patterns that elevate many HRV indices are prevalent among the elderly and associated with higher risk of mortality. Consideration of abnormal HRV may improve HRV-based risk stratification.

Aged↗

Heart rate variability: measurement and clinical utility.

Electrocardiographic RR intervals fluctuate cyclically, modulated by ventilation, baroreflexes, and other genetic and environmental factors that are mediated through the autonomic nervous system. Short term electrocardiographic recordings (5 to 15 minutes), made under controlled conditions, e.g., lying supine or standing or tilted upright can elucidate physiologic, pharmacologic, or pathologic changes in autonomic nervous system function. Long-term, usually 24-hour recordings, can be used to assess autonomic nervous responses during normal daily activities in health, disease, and in response to therapeutic interventions, e.g., exercise or drugs. RR interval variability is useful for assessing risk of cardiovascular death or arrhythmic events, especially when combined with other tests, e.g., left ventricular ejection fraction or ventricular arrhythmias.

Autonomic Nervous System↗

Sex effects on heart rate variability in fibromyalgia and Gulf War illness.

OBJECTIVE: To investigate autonomic abnormalities in male and female fibromyalgia (FM) and Gulf War illness (GWI) patients by comparing heart rate variability (HRV) with that of age- and sex-matched healthy controls. METHODS: Subjects included 26 (19 women, 7 men) with FM, 11 (6 men, 5 women) with GWI, and 36 (18 men,18 women) healthy controls. HRV was determined from Holter recordings obtained in the Clinical Research Center. Analysis of variance compared 24-hour, daytime, and nighttime HRV by sex within groups and by group within sex. RESULTS: In women with FM or GWI, HRV was significantly lower than in men with FM or GWI. HRV was similar in male and female controls. When HRV was compared by group within sex, HRV was significantly decreased in women with FM or GWI and no significant differences were seen for men with these conditions. CONCLUSION: Decreased HRV in FM and GWI appears to be sex dependent. Results suggest that different mechanisms may be operative in symptom expression in men and women with this spectrum of illness.

Adult↗