Cardiovascular tolerance and autonomic nervous responses in unsedated upper gastrointestinal small-caliber endoscopy: a comparison between transnasal and peroral procedures with newly developed mouthpiece.

BACKGROUND: Transnasal esophagogastroduodenoscopy (EGD) with small-caliber endoscopy appears to be less stressful to the cardiovascular system and has good patient tolerance. ENDO LEADER, a newly developed mouthpiece for peroral EGD with small-caliber endoscopy, is expected to reduce patient stress. We compared the patient acceptance, cardiovascular tolerance and autonomic nervous responses between transnasal EGD and peroral EGD with ENDO LEADER. PATIENTS AND METHODS: A total of 130 patients (transnasal group, 77; peroral group, 53) were enrolled. Pulse rate (P), blood pressure (BP), and peripheral blood oxygen saturation (SpO(2) ) were monitored. Acceptance of EGD was also assessed. Autonomic nervous responses were evaluated through analysis of heart rate variability using amplitude of the high-frequency component (HF) and low-frequency-to-high-frequency power ratio (LF/HF) as indices of cardiac vagal activity and sympathetic activity, respectively. RESULTS: Analysis of patient acceptance showed no differences between the two groups, except with regard to nasal pain. Increases in BP and P between before and during EGD examination were significantly higher in the peroral group. Although throat pain and overall tolerance scores were significantly correlated with ΔBP and ΔP, no correlations with nasal pain score were noted. Heart rate variability analysis revealed that heart rate increased significantly in the peroral group, but there were no differences in ΔHF or ΔLF/HF between the two groups. CONCLUSIONS: Patient acceptance was not significantly different between the transnasal and peroral with ENDO LEADER groups; however, transnasal EGD appears to be less stressful to the sympathetic nervous system, leading to smaller elevations in BP, P and heart rate.

Reduced renal function is associated with combined increases in ventricular-systolic stiffness and arterial load in patients undergoing cardiac catheterization for coronary artery disease.

Although mildly reduced renal function is associated with increased risk for heart failure in patients with coronary artery disease (CAD), mechanisms underlying the association remain unclear. We tested the hypothesis that abnormal ventricular-arterial interaction may occur in mildly reduced renal function. We examined the relationships of the estimated glomerular filtration rate (eGFR) with various indices reflecting ventricular-arterial coupling [effective arterial elastance (the ratio of left ventricular (LV) end-systolic pressure to stroke volume, E (a)], LV end-systolic elastance (the ratio of LV end-systolic pressure to end-systolic volume, E (es)), and the total arterial compliance (the ratio of stroke volume to aortic pulse pressure)] and those of LV systolic and diastolic function [peak systolic and diastolic mitral annular velocities (S' and E') and the ratio of peak early diastolic mitral inflow to annular velocity (E/E')] in 320 consecutive patients who underwent cardiac catheterization for CAD and had normal (≥ 0.50) ejection fractions (EF). As eGFR decreased, E (a) and E (es) increased and total arterial compliance and E' decreased. eGFR did not correlate with E (a)/E (es), S', or E/E'. After adjusting for potential confounders, the findings were generally similar, but the correlation of eGFR with E' did not remain significant. In conclusion, reduced renal function may be associated with combined increases in ventricular-systolic stiffness and arterial load in known or suspected CAD patients with normal EF.

Impact of arterial load on left ventricular diastolic function in patients undergoing cardiac catheterization for coronary artery disease.

BACKGROUND: Although left ventricular (LV) diastolic dysfunction is associated with increased risk for incident heart failure in patients with coronary artery disease (CAD), no specific treatment for diastolic abnormalities has been established. Animal and small human studies have shown that an acute increase in LV afterload adversely impacts on LV early diastolic relaxation, but little is known about its chronic effect on diastolic function. METHODS AND RESULTS: The relationships of various components of arterial load (arterial compliance, total vascular resistance index, and augmentation index [AI] in the ascending aorta) with LV diastolic function indices determined on cardiac catheterization (relaxation time constant [Tau] and end-diastolic pressure [EDP]) and those on tissue Doppler echocardiography (early diastolic mitral annular velocity [E'] and the ratio of early diastolic mitral inflow to annular velocities [E/E']) were investigated in 303 consecutive patients undergoing cardiac catheterization for CAD. All components of arterial load correlated with diastolic function indices, with AI, an index reflecting late-systolic load, having the strongest correlations with diastolic function indices. After adjustment for potential confounders, AI correlated with Tau (standardized beta=0.25, P<0.001), EDP (beta=0.25, P<0.001), E' (beta=-0.21, P<0.001), and E/E' (beta=0.23, P<0.001). CONCLUSIONS: Increased AI is independently associated with LV diastolic function in patients with known or suspected CAD. Late-systolic load may be a therapeutic target to improve LV diastolic abnormalities in this population.

Usefulness of plasma brain natriuretic peptide measurement and tissue Doppler imaging in identifying isolated left ventricular diastolic dysfunction without heart failure.

Left ventricular (LV) diastolic dysfunction carries a substantial risk for the subsequent development of heart failure and reduced survival, even when it is asymptomatic. Plasma brain natriuretic peptide (BNP) level and tissue Doppler imaging indexes provide powerful incremental assessment of LV diastolic function. Accordingly, the aim of this study was to clarify whether these methodologies could identify LV diastolic dysfunction without heart failure in 280 patients with preserved LV ejection fractions (> or =50%) who underwent echocardiography and cardiac catheterization for the evaluation of coronary artery disease. Patients were classified into 2 groups, those with diastolic dysfunction (tau > or =48 ms; n = 91) and those with normal diastolic function (tau <48 ms; n = 189). Plasma BNP > or =22.4 pg/ml, an unexpectedly low value, had sensitivity of 74.7% and specificity of 60.8% for identifying isolated LV diastolic dysfunction; the combined use of BNP > or =22.4 pg/mL and mitral annular velocity during early diastole <7.4 cm/s had relatively low sensitivity of 44.0% but high specificity of 86.8%. In conclusion, using plasma BNP level and with the combination of BNP level and mitral annular velocity during early diastole, invasively proved isolated LV diastolic dysfunction without heart failure could be identified in patients with coronary artery disease.

Relationship between renal function, aortic stiffness and left ventricular function in patients with coronary artery disease.

BACKGROUND: There are plausible reasons to hypothesize that increased aortic stiffness and left ventricular (LV) dysfunction may occur in early renal insufficiency. METHODS AND RESULTS: The correlation of glomerular filtration rate (GFR) with the augmentation index (AI) of ascending aortic pressure and indices of LV systolic and diastolic function (ejection fraction, LV pressure relaxation time constant, LV end-diastolic pressure and mitral inflow (E/A) and annular velocities (S' and E')) was examined in 359 consecutive patients undergoing cardiac catheterization for coronary artery disease (CAD). When patients were stratified according to GFR of 60, 75 and 90 ml x min(-1) x 1.73 m(-2), there was a progressive increase in AI and decreases in E/A and E' with decreasing GFR. There were no linear trends in other indices of systolic or diastolic function across GFR groups. After adjustment for potential confounders, reduced GFR was associated with increased AI, but not with decreased E/A or E'. CONCLUSIONS: Early renal impairment may be partly associated with increased aortic stiffness, but not with LV systolic or diastolic function in CAD patients.

Correlation between left ventricular end-diastolic pressure and peak left atrial wall strain during left ventricular systole.

OBJECTIVE: Left atrial (LA) reservoir function is determined by integration of LA relaxation and left ventricular (LV) systolic function, and LV diastolic dysfunction increases LA volume at end systole. This study investigates the effect of LV end-diastolic pressure on LA wall tension during LV systole. METHODS: A total of 101 stable patients with sinus rhythm undergoing cardiac catheterization were studied. LA wall extension during LV systole was evaluated as LA wall strain in the longitudinal direction obtained using two-dimensional ultrasound speckle tracking imaging. LV end-diastolic pressure and LV end-systolic and end-diastolic volumes were obtained in cardiac catheterization, and LV ejection fraction was determined. RESULTS: Peak LA wall strain during LV systole had a significant inverse correlation with LV end-diastolic pressure (r = - 0.76, P < .0001). This correlation was also significant in patients with preserved LV systolic function (LV ejection fraction > or =50%) (r = - 0.64, P < .0001). In patients with peak LA wall strain during LV systole of less than 30%, 89% had elevated LV end-diastolic pressure (> or =16 mm Hg). CONCLUSION: Elevated LV end-diastolic pressure is associated with a decrease of peak LA wall strain in the longitudinal direction during LV systole. In patients with peak LA wall strain during LV systole of less than 30%, the majority had elevated LV end-diastolic pressure, while most patients with peak LA wall strain during LV systole 45% or higher had normal LV end-diastolic pressures. In patients whose LV ejection fraction is 50% or more, when peak LA wall strain during LV systole is between 30% and 44%, it is not possible to predict LV end-diastolic pressure from peak LA wall strain measures.

Elevated plasma levels of B-type natriuretic Peptide but not C-reactive protein are associated with higher red cell distribution width in patients with coronary artery disease.

Although higher red cell distribution width (RDW) has recently been reported to be associated with increased mortality independent of anemia in patients with heart failure and those with coronary artery disease (CAD), the mechanism underlying this association is unknown. We hypothesized that higher RDW may reflect neurohumoral activation and a chronic inflammatory state that each contribute to adverse clinical outcomes in these populations. We measured RDW and plasma levels of B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hs-CRP) in 226 consecutive patients undergoing cardiac catheterization for CAD (age, 67 +/- 8 years; males, 77%; RDW, 45.8 +/- 3.3 fL; hemoglobin, 13.2 +/- 1.4 g/dL; BNP, median [interquartile range], 26.0 [9.0-58.4] pg/mL; hs-CRP, 679 [345-1920] ng/mL). Plasma BNP (r = 0.21, P < 0.01) but not hs-CRP (r = 0.04, P > 0.1) levels correlated with RDW. After adjustment for potential confounders including age, gender, body mass index, glomerular filtration rate, hemoglobin, and known hemodynamic determinants of BNP, including elevated left ventricular end-diastolic pressure and volume and slow left ventricular relaxation, RDW was independently predicted by BNP (r(2) = 0.058, P < 0.001). In conclusion, elevated BNP levels are independently associated with higher RDW in patients with CAD. Neurohumoral activation may be a mechanistic link between increased RDW and adverse clinical outcomes in this population.

Loss of fractal heart rate dynamics in depressive hemodialysis patients.

OBJECTIVE: To assess the relationship between depression, reduced heart rate (HR) variability, and altered HR dynamics among patients with end-stage renal disease who are receiving hemodialysis (HD) therapy. METHODS: We analyzed the 24-hour electrocardiograms of 119 outpatients receiving chronic HD. HR variability was quantified with the standard deviation of normal-to-normal R-R intervals, the triangular index, and the powers of the high- (HF), low- (LF), very-low (VLF), and ultra-low frequency (ULF) components. Nonlinear HR dynamics was assessed with the short-term (alpha(1)) and long-term (alpha(2)) scaling exponents of the detrended fluctuation analysis and approximate entropy. The depression level was assessed using the Beck Depression Inventory, Second Edition (BDI-II). HR variability and dynamics measurements were compared by gender, diabetes, and depression with adjustment for age and serum albumin concentration. RESULTS: Most indices of HR variability and dynamics were negatively correlated with age, serum albumin concentration, depression score, and were lower in women and patients with diabetes. The alpha(2) was inversely associated with these variables. Depressed men had significantly lower HF, LF, VLF, and marginally lower ULF than nondepressed persons after adjustment for diabetes and other covariates; no difference in depression was observed in women. The alpha(2) showed marginally significant difference in depression independent from gender and diabetes. CONCLUSIONS: Among the patients who received HD, depression is associated with reduced HR variability and loss of fractal HR dynamics. However, the influence of depression on HR variability may vary by gender and physiological backgrounds. Further prospective studies are necessary to confirm their association with poor prognosis.

Anemia is an independent predictor for elevated plasma levels of natriuretic peptides in patients undergoing cardiac catheterization for coronary artery disease.

BACKGROUND: It is unknown whether the association of anemia with elevated plasma levels of B-type and atrial natriuretic peptides (BNP and ANP) is mediated by the hemodynamic effects of anemia. METHODS AND RESULTS: The study group comprised 237 consecutive patients (BNP, median [interquartile range], 28.3 [9.5-77.1] pg/ml; ANP, 17.8 [8.5-39.0] pg/ml) undergoing determination of hemoglobin (Hb) and natriuretic peptide levels and cardiac catheterization for evaluation of coronary artery disease (CAD). Hb correlated with BNP (r=-0.36, p<0.001) and ANP (r=-0.35, p<0.001). Patients with anemia (Hb <12 g/dl for females; <13 g/dl for males, n=63) were more likely to be older with reduced body mass index and renal function, greater severity of CAD and to have higher heart rate, mean pulmonary capillary wedge pressure, and cardiac output. Anemia was a significant predictor for elevated (>third quartile value) natriuretic peptide levels and the predictive value remained significant after adjustment for other predictors, including increased left ventricular end-diastolic pressure and differences in clinical and hemodynamic variables between patients with and without anemia (adjusted odds ratio [95% confidence interval] for elevated BNP and ANP levels, 7.39 [2.76-19.8] and 2.56 [1.08-6.07], respectively). CONCLUSION: Anemia is an independent predictor for elevated natriuretic peptide levels in patients with known or suspected CAD.

Relationship between blood pressure obtained from the upper arm with a cuff-type sphygmomanometer and central blood pressure measured with a catheter-tipped micromanometer.

Recently, the importance of central blood pressure for cardiovascular risk stratification has been emphasized. Accordingly, the differences in peak systolic and bottom diastolic pressures between the ascending aorta and the brachial artery should be clarified. Study subjects consisted of 82 consecutive patients with suspected coronary artery disease who underwent cardiac catheterization, and in whom ascending aortic pressure waveform was obtained using a catheter-tipped micromanometer, and at the same time systolic and diastolic pressures were measured (single measurement) from the right upper arm with a cuff-type sphygmomanometer based on the oscillometric technique. No significant systematic difference (bias) was found between the peak pressure obtained in the ascending aorta and the systolic pressure from the right upper arm (133.6 +/- 25.1 vs 131.8 +/- 21.5 mmHg, not significant). Bland-Altman analysis showed only a small bias of +1.8 mmHg, and the limits of agreement were 25.4 mmHg and -21.8 mmHg. In contrast, the bottom pressure in the ascending aorta was significantly lower compared with the diastolic pressure from the upper arm (68.5 +/- 10.7 vs 73.0 +/- 12.4 mmHg, P < 0.0001). Bland-Altman analysis showed a small but significant bias of -4.5 mmHg, and the limits of agreement were 14.1 mmHg and -23.1 mmHg. The observed biases seemed to remain within practical range. However, random variation in the two measurements was rather large. This is considered to be caused by the random error in the single measurement with the cuff-type sphygmomanometer.

Both HDL3 and HDL2 exert a powerful anti-oxidative and protective effect against acceleration of oxidative modification of LDL by ascorbic acid.

The objective of the present study was to establish whether high-density lipoprotein 3 (HDL3) or high-density lipoprotein 2 (HDL2) might show an anti-oxidative effect on the acceleration of the oxidative modification of low-density lipoprotein (LDL) by ascorbic acid from measurement of the agarose gel electrophoretic mobility of LDL. LDL was incubated without adding transitional-metal ions for 48 or 96 h in phosphate-buffered saline (PBS) alone, with ascorbic acid (20 microg/mL), or with both ascorbic acid (20 microg/mL) and HDL3 (200 microg protein/mL). The LDL autoxidation occurred in PBS alone. Although ascorbic acid significantly suppressed oxidative modification of LDL after incubation for 48 h, the opposite was true after 96 h. However, since the anti-oxidative ability of HDL2 shows a weaker tendency than that of HDL3, both HDL3 and HDL2 significantly inhibited this acceleration of oxidative modification of LDL by ascorbic acid as assessed by electrophoretic mobility. If there is an augmented oxidative modification of LDL due to ascorbic acid in vivo, HDL3 or HDL2 may thus have an important role in inhibiting this ascorbic acid-accelerated oxidation of LDL.

Usefulness of plasma brain-type natriuretic peptide level to differentiate left ventricular diastolic dysfunction from preserved diastolic function in patients with systolic dysfunction.

The extent of left ventricular (LV) diastolic dysfunction is related to the finding that some patients with cardiomegaly due to LV systolic dysfunction have good exercise tolerance, although others have limited tolerance. A brain-type natriuretic peptide level of >/=104 pg/ml reliably enables the detection of relatively worse LV diastolic function in patients with systolic dysfunction, and this value may provide clinically useful information for the management of patients with cardiomegaly.

Tl-201 washout rate in remote normal regions in patients with prior myocardial infarction and left ventricular remodeling.

BACKGROUND: Myocardial characteristics of remote normal regions in patients with myocardial infarction (MI) and left ventricular (LV) remodeling have not been fully elucidated. Thus, we investigated this issue from the viewpoint of myocardial Tl-201 dynamics. METHODS AND RESULTS: In 14 patients with prior anterior MI, 10 with inferior MI, and 14 age-matched patients with atypical chest pain served as controls; exercise stress Tl-201 SPECT and cardiac catheterization were performed. Tl-201 washout rate was calculated for 8 myocardial segments, and LV end-diastolic volume index was obtained as a parameter of LV remodeling. LV end-diastolic volume index was greater in anterior MI patients than in control patients; in contrast, no significant difference was observed between inferior MI patients and control patients. The washout rate in remote normal regions was significantly less in anterior MI patients than in the corresponding segments in control patients (39.8% +/- 8.7% vs 48.4% +/- 4.4%, P < .01). There was no significant difference between inferior MI patients and control patients (43.6% +/- 6.9% vs 47.8% +/- 4.5%). CONCLUSIONS: Reduced Tl-201 washout rates in remote normal regions are found in patients with anterior MI and LV remodeling. Subclinical myocardial ischemia during exercise in remote normal regions exists and may be related to the pathologic condition of such LV walls.

Paradoxical brain embolism caused by pulmonary arteriovenous fistula and coincident pulmonary embolism--a case report.

The authors encountered a very rare case of paradoxical brain embolism resulting from pulmonary arteriovenous fistula and coincident pulmonary embolism. Enhanced computed tomography was useful for diagnosing this infrequent condition.

Two cases with renal infarction diagnosed in the early course using contrast-enhanced CT.

We experienced two cases of renal infarction with atrial fibrillation who presented with acute abdominal pain. On initial urinalysis, both patients showed no hematuria, but the plasma lactate dehydrogenase level was markedly elevated with little or no rise in plasma transaminases. Their diagnosis was confirmed by contrast-enhanced CT of the abdomen on the second and third days of the crisis. We immediately initiated anticoagulant therapy, resulting in successful prevention of new embolism. Contrast-enhanced CT should be considered if abdominal symptoms develop in patients with atrial fibrillation. Renal infarction could be diagnosed in the early course, even in cases with incomplete occlusion of the renal arteries and normal renal function.

Spectral indices of human cerebral blood flow control: responses to augmented blood pressure oscillations.

We set out to fully examine the frequency domain relationship between arterial pressure and cerebral blood flow. Oscillatory lower body negative pressure (OLBNP) was used to create consistent blood pressure oscillations of varying frequency and amplitude to rigorously test for a frequency- and/or amplitude-dependent relationship between arterial pressure and cerebral flow. We also examined the predictions from OLBNP data for the cerebral flow response to the stepwise drop in pressure subsequent to deflation of ischaemic thigh cuffs. We measured spectral powers, cross-spectral coherence, and transfer function gains and phases in arterial pressure and cerebral flow during three amplitudes (0, 20, and 40 mmHg) and three frequencies (0.10, 0.05, and 0.03 Hz) of OLBNP in nine healthy young volunteers. Pressure fluctuations were directly related to OLBNP amplitude and inversely to OLBNP frequency. Although cerebral flow oscillations were increased, they did not demonstrate the same frequency dependence seen in pressure oscillations. The overall pattern of the pressure-flow relation was of decreasing coherence and gain and increasing phase with decreasing frequency, characteristic of a high-pass filter. Coherence between pressure and flow was increased at all frequencies by OLBNP, but was still significantly lower at frequencies below 0.07 Hz despite the augmented pressure input. In addition, predictions of thigh cuff data from spectral estimates were extremely inconsistent and highly variable, suggesting that cerebral autoregulation is a frequency-dependent mechanism that may not be fully characterized by linear methods.

The role of apically directed intraventricular isovolumic relaxation flow in speeding early diastolic left ventricular filling.

Left ventricular (LV) systolic performance has been acknowledged to have a close relation to LV early diastolic filling and LV relaxation. However, the mechanism showing how good LV systolic function enhances the LV early diastolic filling has not been fully elucidated from the viewpoint of intraventricular flow dynamics. Thus, we investigated this issue in 82 patients with suggested coronary artery disease who underwent cardiac catheterization. Apically directed intraventricular isovolumic relaxation flow (IRF) and the propagation velocity of early diastolic filling flow were measured using pulsed and color Doppler echocardiography. LV ejection fraction and LV relaxation time constant tau were obtained in cardiac catheterization. As we were not able to measure the IRF velocity less than 14 cm/s that was limited by a Doppler low-cut filter, we analyzed the data collected from 78 patients with measurable IRF velocity. The IRF velocity significantly correlated with LV ejection fraction (r = 0.74, P <.001) and with LV relaxation time constant tau (r = -0.31, P <.01). The propagation velocity of early diastolic filling flow significantly correlated with the IRF velocity (r = 0.73, P <.001) and also significantly correlated with LV ejection fraction (r = 0.70, P <.001). Good LV systolic performance augments LV early diastolic filling directly, mediated by IRF. A faster IRF velocity may play a role in delivering good LV systolic performance to LV early diastolic filling.

Effect of systolic blood pressure and carotid stiffness on baroreflex gain in elderly subjects.

BACKGROUND: Aging is associated with diminished baroreflex sensitivity (gain), which predisposes elderly people to orthostatic hypotension, syncope, and cardiovascular morbidity. Aging is also associated with systolic blood pressure (SBP) elevation and carotid artery stiffness, which may both affect baroreflex gain. METHODS: We examined the relation between SBP, carotid artery stiffness, and baroreflex gain in 34 healthy elderly (71 +/- 4 years) and 10 healthy young (31 +/- 3 years) subjects. SBP (Finapres) and carotid artery stiffness (ultrasound measures of relative carotid artery diameter changes during each blood pressure pulse) were measured. The gain of the transfer function relating the R-R interval to SBP fluctuations at a frequency of 0.05-0.15 Hz was used to assess cardiovagal baroreflex gain. RESULTS: Elderly subjects had higher carotid artery stiffness (14.2 +/- 5.1 vs 6.6 +/- 1.8, p <.05), higher SBP (146 +/- 24 vs 125 +/- 8 mmHg, p =.012), and lower baroreflex gain (8.2 +/- 6.4 vs 16.3 +/- 7.4, p <.05) than young subjects. Among all subjects, SBP and carotid artery stiffness both correlated with baroreflex gain (r = -.39, p =.02 for both). Although SBP was related to stiffness across all subjects, this relation was not present among the elderly subjects. Within the elderly group, only SBP was independently related to baroreflex gain (R(2) =.51, p =.009). CONCLUSIONS: SBP elevation in elderly people may affect the neural or cardiac response to blood pressure fluctuations, independent of the mechanical properties of barosensory regions in the carotid artery. Future studies should examine the effect of pharmacologic treatment of hypertension on baroreflex gain in elderly people.

Prognostic value of heart rate variability in patients with end-stage renal disease on chronic haemodialysis.

BACKGROUND: Although decreased heart rate variability (HRV) is an independent predictor of death in various populations, its prognostic value in patients with end-stage renal disease on chronic haemodialysis is unknown. METHODS: We prospectively studied 120 chronic haemodialysis patients (age 61+/-11 years; males 51%; diabetics 38%; duration of haemodialysis therapy 50+/-114 months) who underwent 24 h electrocardiography at baseline for analysis of time- and frequency-domain HRV. RESULTS: All HRV measures in the patients were significantly reduced compared with those obtained from 62 age-matched healthy subjects. During a follow-up period of 26+/-10 months, 21 patients died (17.5%); 10 from cardiac causes and 11 from non-cardiac causes (seven fatal strokes and four other causes). A Cox proportional hazards model revealed that, of the HRV measures, decreases in the triangular index (TI), very-low-frequency (0.0033-0.04 Hz) power, ultra-low-frequency (<0.0033 Hz) power (ULF) and the ratio of low-frequency (0.04-0.15 Hz) power to high-frequency (0.15-0.4 Hz) power had significant predictive value for cardiac death. None of the HRV measures, however, had predictive value for non-cardiac death, including stroke death. Even after adjustment for other univariate predictors including age, diabetes, serum albumin and coronary artery disease, the predictive value of decreased TI and ULF remained significant-adjusted relative risk (95% confidence interval) per 1 SD decrement of TI and ULF, 3.28 (1.08-9.95) and 1.92 (1.01-3.67), respectively. CONCLUSIONS: Decreases in some HRV measures, particularly those reflecting long-term variability, are independent predictors of cardiac death in chronic haemodialysis patients.