Nobuyuki Ohte

Decreased magnitude of heart rate spectral components in coronary artery disease. Its relation to angiographic severity.

We analyzed the spectral components of RR interval variability under controlled respiration (15 breaths/min) in 56 patients (age range, 35-73 years) referred for coronary angiography; 14 patients had multivessel disease (group M), 21 had one-vessel disease (group S), and 21 had nonsignificant disease or normal coronary artery (group N). There were 43 healthy controls (age range, 36-71 years) (group C). The patients had no clinical evidence of heart failure, hypertension, diabetes mellitus, or acute stage of infarction and had taken no medication for 3 days. The autoregressive power spectral density of RR interval variability contains two major components, respiratory sinus arrhythmia (RSA) (0.25 Hz) and Mayer wave-like sinus arrhythmia (MWSA) (0.04-0.15 Hz), which have magnitudes that are quantitative markers of cardiac vagal activity and sympathetic activity with vagal modulation, respectively. We represented the magnitudes by the coefficient of component variance (CCV), which provided the amplitude relative to the mean RR interval. The age- and sex-adjusted mean of CCVRSA significantly decreased with advancing angiographic severity (1.64 +/- 0.09%, 1.66 +/- 0.12%, 1.22 +/- 0.13%, and 0.81 +/- 0.16% for groups C, N, S, and M, respectively) (p = 0.0001). The CCVRSA was unrelated to left ventricular function, previous myocardial infarction, or stenosis of any specific artery including the sinoatrial and atrioventricular node arteries. The CCVMWSA decreased only in group M (p = 0.0462). These results indicate that coronary artery disease is associated with vagal dominant impairment in autonomic cardiac function and that reduction in the vagal cardiac function correlates with the angiographic severity.

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.

Severity of coronary atherosclerosis correlates with the respiratory component of heart rate variability

Decreased vagal activity is frequently observed in coronary artery disease, but the mechanism of this association is unknown. We investigated cardiac autonomic function by relating heart rate spectral components to clinical and angiographic findings in 80 patients who were undergoing coronary angiography. The age- and sex-adjusted magnitude of the respiratory spectral component, which is an index of cardiac vagal tone, showed a significant negative correlation with the extent of coronary atheromatosis (r = -0.43, p less than 0.0001) and a less significant negative correlation with the severity of coronary stenosis (r = -0.30, p = 0.0070). These relationships were independent of previous myocardial infarction and of left ventricular function. Stepwise regression analysis showed that the respiratory spectral component contributed to atheromatosis independently of established coronary risk factors (partial R2 = 9.4%, p = 0.002), but not to stenosis. Our results support the hypothesis that decreased cardiac vagal activity is associated with an increased risk of coronary atherosclerosis.

Clinical usefulness of carotid arterial wave intensity in assessing left ventricular systolic and early diastolic performance

Wave intensity (WI) is a novel hemodynamic index, which is defined as (dP/dt)·(dU/dt) at any site of the circulation, where dP/dt and dU/dt are the derivatives of blood pressure and velocity with respect to time, respectively. However, the pathophysiological meanings of this index have not been fully elucidated in the clinical setting. Accordingly, we investigated this issue in 64 patients who underwent invasive evaluation of left ventricular (LV) function. WI was obtained at the right carotid artery using a color Doppler system for blood velocity measurement combined with an echo-tracking method for detecting vessel diameter changes. The vessel diameter changes were automatically converted to pressure waveforms by calibrating its peak and minimum values by systolic and diastolic brachial blood pressures. The WI of the patients showed two sharp positive peaks. The first peak was found at the very early phase of LV ejection, while the second peak was observed near end-ejection. The magnitude of the first peak of WI significantly correlated with the maximum rate of LV pressure rise (LV max. dP/dt) (r = 0.74, P ≪ 0.001). The amplitude of the second peak of WI significantly correlated with the time constant of LV relaxation (r = −0.77, P ≪ 0.001). The amplitude of the second peak was significantly greater in patients with the inertia force of late systolic aortic flow than in those without the inertia force (3 080 ± 1 741 vs 1 890 ± 1 291 mmHg m s−3, P ≪ 0.01). These findings demonstrate that the magnitude of the first peak of WI reflects LV contractile performance, and the amplitude of the second peak of WI is determined by LV behavior during the period from late systole to isovolumic relaxation. WI is a noninvasively obtained, clinically useful parameter for the evaluation of LV systolic and early diastolic performance at the same time.

Evaluation of left ventricular early diastolic performance by color tissue Doppler imaging of the mitral annulus

A noninvasive assessment of left ventricular (LV) diastolic performance by tissue Doppler imaging was performed in 56 patients (8 patients with atypical chest pain, 42 with coronary artery disease with a previous myocardial infarction, and 6 without a previous myocardial infarction) who underwent cardiac catheterization. Mitral annular velocity (MAV) during early ventricular diastole was obtained by M-mode color tissue Doppler imaging at the posterior corner of the mitral annulus. In each patient, the negative peak of the first derivative of LV pressure decay (peak -dP/dt) and a time constant of LV relaxation (tau) were calculated from the LV pressure waves obtained by a catheter-tip micromanometer. LV end-systolic volume index was measured from contrast left ventriculography. MAV during early diastole was significantly correlated with tau (r = -0.73, p <0.001), peak -dP/dt (r = 0.58, p <0.001), and LV end-systolic volume index (r = -0.63, p <0.001). On multivariate regression analysis with MAV during early diastole, tau and LV end-systolic volume index were selected as prime determinants (r = 0.80, p <0.001). These findings suggest that MAV during early diastole has a direct relation to LV elastic recoil as well as to LV relaxation. MAV during early diastole gives important information regarding LV behavior in late systole to early diastole where LV early diastolic performance is determined.

Reduced Ventricular Response Irregularity Is Associated With Increased Mortality in Patients With Chronic Atrial Fibrillation

BACKGROUND-Variations in the ventricular response interval (VRI) during atrial fibrillation (AF) may be reduced in patients with adverse clinical outcomes. The properties of VRI dynamics associated with prognosis remain undetermined. METHODS AND RESULTS-In 107 patients with chronic AF (age, 64+/-9 years), we analyzed a 24-hour ambulatory ECG for VRI variability (SD, SD of successive differences, and SD of 5-minute averages) and VRI irregularity (Shannon entropy of histogram, symbolic dynamics, and approximate entropy of beat-to-beat and minute-to-minute fluctuations [ApEn(b-b) and ApEn(m-m)]). During a follow-up period of 33+/-16 months, 18 patients died (17%), 9 from cardiac causes, 7 from fatal strokes, and 2 from malignancies. Reductions in all VRI variability and irregularity measures were associated with an increased risk for cardiac death but not for fatal stroke. A significant association with cardiac death was also found for ejection fraction (relative risk, 1.10; 95% confidence interval [CI], 1.04 to 1.17, per 1% decrement) and ischemic AF (relative risk, 6.52; 95% CI, 1.62 to 26. 3). After adjustment for these clinical variables, all irregularity measures except symbolic dynamics had predictive value (relative risks [95% CIs] per 1SD decrement: Shannon entropy of histogram, 2. 03 [1.14 to 3.61]; ApEn(b-b), 1.72 [1.14 to 2.60]; and ApEn(m-m), 1. 90 [1.03 to 3.52]); however, the predictive power of variability measures was no longer significant. When the patients were stratified with the 33rd and 67th percentile values of ApEn(b-b) (1. 83 and 1.94, respectively), the 5-year cardiac mortality rates for the upper, middle, and lower tertiles were 0%, 13%, and 43%, respectively (log-rank test, P=0.04). CONCLUSIONS-Reduced VRI irregularity in a 24-hour ambulatory ECG has an independent prognostic value for cardiac mortality during long-term follow-up in patients with chronic AF.

Normal values and clinical relevance of left atrial myocardial function analysed by speckle-tracking echocardiography: multicentre study

AIMS The aim of this multicentre study was to determine the normal range and the clinical relevance of the myocardial function of the left atrium (LA) analysed by 2D speckle-tracking echocardiography (2DSTE). METHODS AND RESULTS We analysed 329 healthy adult subjects prospectively included in 10 centres and a validation group of 377 patients with left ventricular diastolic dysfunction (LVDD). LA myocardial function was analysed by LA strain rate peak during LA contraction (LA-SRa) and LA strain peak during LA relaxation (LA-Strain). The range of values of LA myocardial function in healthy subjects was LA-SRa -2.11 ± 0.61 s(-1) and LA-Strain 45.5 ± 11.4%, and the lowest expected values of these LA analyses (calculated as -1.96 SD from the mean of healthy subjects) were LA-SRa -0.91 s(-1) and LA-Strain 23.1%. Concerning the clinical relevance of these LA myocardial analyses, LA-SRa and LA-Strain detected subtle LA dysfunction in patients with LVDD, even though LA volumetric measurements were normal. In addition, in these patients we found that the functional class (dyspnoea-NYHA classification) was inversely related to both LA-Strain and LA-SRa. CONCLUSION In the present multicentre study analysing a large cohort of healthy subjects and patients with LVDD, the normal range and the clinical relevance of the myocardial function of the LA using 2DSTE have been determined.

Assessment of pulse rate variability by the method of pulse frequency demodulation

BackgroundDue to its easy applicability, pulse wave has been proposed as a surrogate of electrocardiogram (ECG) for the analysis of heart rate variability (HRV). However, its smoother waveform precludes accurate measurement of pulse-to-pulse interval by fiducial-point algorithms. Here we report a pulse frequency demodulation (PFDM) technique as a method for extracting instantaneous pulse rate function directly from pulse wave signal and its usefulness for assessing pulse rate variability (PRV).MethodsSimulated pulse wave signals with known pulse interval functions and actual pulse wave signals obtained from 30 subjects with a trans-dermal pulse wave device were analyzed by PFDM. The results were compared with heart rate and HRV assessed from simultaneously recorded ECG.ResultsAnalysis of simulated data revealed that the PFDM faithfully demodulates source interval function with preserving the frequency characteristics of the function, even when the intervals fluctuate rapidly over a wide range and when the signals include fluctuations in pulse height and baseline. Analysis of actual data revealed that individual means of low and high frequency components of PRV showed good agreement with those of HRV (intraclass correlation coefficient, 0.997 and 0.981, respectively).ConclusionThe PFDM of pulse wave signal provides a reliable assessment of PRV. Given the popularity of pulse wave equipments, PFDM may open new ways to the studies of long-term assessment of cardiovascular variability and dynamics.

Randomized Controlled Trial of the Effect of Short-term Coadministration of Methylcobalamin and Folate on Serum ADMA Concentration in Patients Receiving Long-term Hemodialysis

BACKGROUND Serum asymmetric dimethylarginine (ADMA) levels are increased in maintenance hemodialysis patients, and this abnormality may increase cardiovascular risk. We investigated whether combined administration of oral folate and intravenous methylcobalamin in such patients is more beneficial than oral folate alone at decreasing circulating ADMA levels. STUDY DESIGN Randomized controlled trial. SETTING & PARTICIPANTS Patients undergoing hemodialysis. INTERVENTION 40 patients were randomly assigned to 1 of 2 groups. For 3 weeks, they received supplementation with either folate alone (15 mg/d; n = 20; folate group) or coadministered folate (15 mg/d) and methylcobalamin (500 mug after each hemodialysis treatment 3 times weekly; n = 20; methylcobalamin group). OUTCOMES PRIMARY OUTCOMES normalization of plasma homocysteine levels (<15 mumol/L), decrease in serum ADMA levels. SECONDARY OUTCOMES change in augmentation index in the carotid artery and ratios of S-adenosylmethionine to S-adenosylhomocysteine (as a transmethylation indicator) and dimethylamine to ADMA (as an indicator of ADMA hydrolysis). MEASUREMENTS Blood samples were collected under fasting conditions during the prehemodialysis procedure. RESULTS The proportion showing normalization of plasma homocysteine levels was much greater in the methylcobalamin group (18 of 20 patients; 90%) than in the folate group (6 of 20; 30%; P < 0.001). The percentage of decrease in ADMA levels was greater in the methylcobalamin than folate group (25.4% +/- 10.2% vs 13.2% +/- 11.2%; P < 0.001). The increase in ratio of S-adenosylmethionine to S-adenosylhomocysteine was not different between the 2 groups; however, the ratio of dimethylamine to ADMA was increased in only the methylcobalamin group (P = 0.04). Augmentation index was decreased in only the methylcobalamin group (P = 0.03). LIMITATIONS This study had an open-label nature and did not examine long-term effects of homocysteine-normalizing therapy (no clinical end points). CONCLUSION Coadministration of intravenous methylcobalamin and oral folate in hemodialysis patients normalized hyperhomocysteinemia and decreased ADMA levels and arterial stiffness. We suggest that this regimen may have greater potential than folate alone to decrease cardiovascular risk in such patients.

Effects of drug and exercise intervention on functional capacity and quality of life in heart failure with preserved ejection fraction: A meta-analysis of randomized controlled trials:

Background Patients with heart failure with preserved ejection fraction (HFpEF) are often elderly and their primary chronic symptom is severe exercise intolerance that results in a reduced quality of life (QOL).Thus, improvement of exercise capacity and QOL presents an important clinical outcome in HFpEF patients. Although the effects of interventions such as cardiovascular drugs and exercise training on exercise capacity and QOL in HFpEF patients have been examined in a number of clinical trials, the results are inconsistent due in part to limited power with small sample sizes. We aimed to conduct a meta-analysis of the randomized controlled trial (RCT)s on the effect of drug or exercise intervention on exercise capacity and QOL in HFpEF patients. Method and results The search of electronic databases identified five RCTs on exercise (245 patients) and eight RCTs on cardiovascular drugs (1080 patients). The pooled analysis showed that exercise training improved peak exercise oxygen uptake (VO2) (weighted mean difference (WMD) 2.283, 95% confidence interval (CI)) (1.318–3.248) ml/min/kg), six-minute walk distance (6MWD) (30.275 m (4.315–56.234)), and Minnesota Living with Heart Failure Questionnaire (MLHFQ) total score (8.974 points (3.321–14.627)) compared with usual care. In contrast, drug intervention did not improve peak VO2 (WMD (95% CI), –0.393 (−1.005–0.220) ml/min/kg), 6MWD (−9.463 (−21.455–2.530) m), or MLHFQ total score (1.042 (−0.982–3.066) point) compared with placebo or no treatment. Conclusion Our meta-analysis indicates that exercise training may be a therapeutic option to improve functional capacity and QOL in HFpEF patients.