Association between sodium-to-potassium ratio in spot urine and hospitalization due to heart failure in high-risk Japanese patients.

Background: In Japanese cardiovascular (CV) high-risk patients, the ESPRIT (Evaluation of Sodium Intake for the Prediction of Cardiovascular Events in Japanese High-risk Patients) study showed that high sodium excretion (≥4.0 g/day) was associated with a composite CV events of heart failure (HF) hospitalization, acute coronary syndrome, cerebrovascular events, and CV deaths. In this context, the sodium-to-creatinine (Na/Cr) ratio in spot urine was found to be significantly associated with HF hospitalizations. Since a stable potassium balance plays a particularly relevant role for CV patients, this post-hoc study was designed to investigate the extent to which consideration of the sodium-to-potassium (Na/K) ratio represents a better predictor of HF hospitalizations in the ESPRIT study population. Methods: This is a post-hoc analysis of a previously reported ESPRIT study (n = 520, 60 HF hospitalizations). Results: Receiver operating curve analysis yielded optimal Na/K ratio cut-off value of 2.9 for detecting HF hospitalization. Kaplan-Meier curve showed that high Na/K ratio in spot urine was associated with increased HF hospitalization (p < 0.001). Cox proportional hazards model analysis revealed that high Na/K ratio was associated with HF hospitalization with a hazard ratio of 2.97 (confidence interval: 1.67-5.61). An association between high Na/K ratio and HF hospitalization remained after adjustments for Na/Cr ratio in spot urine or the use of diuretics. Conclusion: The Na/K ratio in spot urine is associated with HF hospitalization in high-risk Japanese patients.

The electrophysiological index can effectively predict subsequent coronary artery aneurysm in children with Kawasaki disease.

Objectives: The Gunma score is used to predict the severity of Kawasaki disease (KD), including coronary artery aneurysm (CAA) as a cardiac complication, in Japan. Additionally, the characteristic ratio of ventricular repolarization (T-peak to T-end interval to QT interval [Tp-e/QT]) on a surface electrocardiogram reflects myocardial inflammation. This study aimed to determine whether the Tp-e/QT can be used to predict CAA in children with KD. Methods: We analyzed chest surface electrocardiograms of 112 children with KD before receiving intravenous immunoglobulin therapy using available software (QTD; Fukuda Denshi, Tokyo, Japan). Results: The Tp-e/QT (lead V5) was positively correlated with the Gunma score (r=0.352, p<0.001). The Tp-e/QT was larger in patients with CAA (residual CAA at 1 month after onset) than in those without CAA (0.314±0.026 versus 0.253±0.044, p=0.003). A receiver operating characteristic curve analysis was performed to assess whether the Gunma score and Tp-e/QT could predict subsequent CAA. The area under the curve of the Gunma score was 0.719 with the cutoff set at 5 points. The area under the curve of the Tp-e/QT was 0.892 with a cutoff value of 0.299. The fit of the prediction models to the observed probability was tested by the Hosmer-Lemeshow test with calibration plots using Locally weighted scatterplot smoothing (LOESS) fit. The Gunma score (p=0.95) and Tp-e/QT (p=0.95) showed a good fit. Conclusions: The Tp-e/QT is a useful biomarker in predicting coronary aneurysm complications in KD.

Effect of Hypothermia on Myocardial Depolarization and Repolarization in Neonates with Hypoxic-Ischemic Encephalopathy Due to Asphyxia.

Therapeutic hypothermia (TH) is effective for neonatal hypoxic-ischemic encephalopathy (HIE). The combination of abnormal myocardial repolarization and fatal arrhythmia in patients with accidental hypothermia has prompted clinical validation of the proarrhythmic potential of TH. However, to our knowledge, there have been few clinical studies on myocardial depolarization and repolarization abnormalities caused by TH in neonates. Therefore, we investigated the effects of TH on neonatal myocardial depolarization and repolarization by capturing the waveform changes in electrocardiograms (ECGs) associated with body temperature (BT) before and after TH. We included three neonates with HIE diagnosed at birth who were treated with TH in our hospital. The heart rate, RR interval, P wave duration, PR interval, QRS duration, QT interval, corrected QT (QTc) interval by Fridericia's formula, J point-T end (JT) interval, corrected JT (JTc) interval by Fridericia's formula, T peak-T end (Tpe) interval, Tpe/QT, and QRS/QTc were calculated retrospectively using an ECG. The correlations of ECG parameters recorded concurrently with 33 samples in which BT measurements were confirmed were performed. BT and heart rate were positively correlated (R: 0.589, p = 0.0003). BT was negatively correlated with Tpe/QT (R: - 0.470, p = 0.0058), the QTc interval (R: - 0.680, p < 0.0001), and the corrected JT interval (R: - 0.697, p < 0.0001). TH does not affect atrial or ventricular depolarization but prolongs the ventricular repolarization process in a temperature-dependent manner.

Sodium to creatinine ratio in spot urine is associated with heart failure hospitalization in Japanese high-risk patients.

Our previous study [Evaluation of sodium intake for the prediction of cardiovascular events in Japanese high-risk patients (ESPRIT study)] reported that increased sodium excretion ≥4.0 g/day was associated with composite cardiovascular events in hospitalization for heart failure (HF), acute coronary syndrome, cerebrovascular events and documented cardiovascular-related mortality in Japanese high-risk patients with either stable and compensated HF, coronary artery disease, cerebrovascular disease, chronic kidney disease or atrial fibrillation. However, the method of estimating sodium excretion levels using spot urine is complex, requiring age, body weight, height and multiplier factors for calculation. The aim of the present study was to elucidate whether the sodium to creatinine ratio in spot urine, a key component in estimating daily sodium excretion, was associated with hospitalization for HF. The present study performed a post-hoc analysis of the ESPRIT study (n=520; 60 hospitalizations for HF). Receiver operating curve analysis yielded an optimal sodium to creatinine ratio cut-off value of 24.8 for detecting hospitalization for HF. Kaplan-Meier curve analysis revealed that a high sodium to creatinine ratio in spot urine was associated with an increased hospitalization for HF (P<0.001). Cox regression analysis revealed that a high sodium to creatinine ratio was associated with hospitalization for HF with a hazard ratio (HR) of 2.49 [95% confidence interval (95% CI), 1.47-4.16]. Following adjustment for age, sex and body weight, the HR was as high as 2.74 (95% CI, 1.51-4.71). This association remained following further adjustment for brain natriuretic peptide, estimated glomerular filtration rate, diabetes mellitus or the use of diuretics. Overall, the present study demonstrated that the sodium to creatinine ratio in spot urine is associated with hospitalization for HF in Japanese high-risk patients.

Myocardial repolarization time, J-point to T-peak and T-peak to T-end intervals, have different heart rate dependency and autonomic nerve interference in healthy prepubertal children.

OBJECTIVE: The JT interval of the myocardial repolarization time can be divided into Jpoint to T-peak interval (JTp) and T-peak to T-end interval (Tpe). It is well known that the JT interval is dependent on the heart rate, but little is known regarding heart rate dependence for JTp and Tpe. The aim of the present study was to clarify the heart rate dependence of JTp and Tpe and to elucidate the interference of autonomic nervous activity with these parameters. METHODS: We evaluated 50 prepubertal children (mean age: 6.4 ± 0.5 years; male:female, 22:28) without heart disease. JTp, Tpe, and the preceding RR intervals were measured using 120 consecutive beats (lead CM5). First, the relationships between the RR interval and JTp and Tpe were evaluated by Pearson's correlation coefficient. Second, to evaluate autonomic interference with JTp and Tpe, the degree of coherence between RR interval variability and JTp or Tpe variability was calculated using spectral analysis. RESULTS: Significant positive correlations were observed between the RR interval and JTp (y = 0.116x + 105.5; r = 0.594, p < 0.001) and between the RR interval and Tpe (y = 0.037x + 44.7; r = 0.432, p < 0.001). Tpe variability had a lower degree of coherence with RR interval variability (range: 0.039-0.5 Hz) than with JTp variability (0.401 [interquartile range, 0.352-0.460] vs. 0.593 [0.503-0.664], respectively; p < 0.001). CONCLUSIONS: Tpe had lower heart rate dependence and a lower degree of autonomic nervous interference than did JTp.

Factors associated with heart failure hospitalization in patients with high sodium excretion: subanalysis of the ESPRIT, evaluation of sodium intake for the prediction of cardiovascular events in Japanese high-risk patients, cohort study.

We have reported that high sodium excretion ≥ 4.0 g/day, assessed by repeated measurements of spot urine, is associated with composite cardiovascular (CV) events of heart failure (HF) hospitalization, acute coronary syndrome, cerebrovascular events, and documented CV deaths in Japanese high-risk patients with either stable and compensated congestive HF, high brain natriuretic peptide, coronary artery disease, cerebrovascular disease, chronic kidney disease, or atrial fibrillation. A total of 520 patients were enrolled. During the median follow-up period of 5.2 years, 105 (20%) experienced composite CV events, which were predominantly driven by 60 (12%) HF hospitalizations. The aim of the present study was to elucidate which subgroups of patients with high sodium excretion were associated with HF hospitalization. We divided the enrolled patients into three groups according to the amount of sodium excretion (< 3.0 g/day, 3.0-3.99 g/day (reference), and ≥ 4.0 g/day) based on a median of 14 measurements during follow-up. We assessed the hazard ratio for HF hospitalization according to age, bodyweight, and gender, using the Cox hazard model. In the total population, high sodium excretion ≥ 4.0 g/day was associated with HF hospitalization [hazard ratio (HR) 1.75, confidence interval (CI) 1.05-2.83] after adjustment for gender, age, and bodyweight, but was not associated with other CV events. In older patients (≥ 75 years old), high sodium excretion ≥ 4.0 g/day was associated with HF hospitalization after adjustment for gender and bodyweight (HR 3.25, CI 1.55-6.55), which was not observed in younger (< 75 years old) patients. In patients with lower bodyweight (< 60 kg), high sodium excretion ≥ 4.0 g/day was associated with HF hospitalization after adjustment for age and gender (HR 3.05, CI 1.34-6.61), which was not observed in heavier (≥ 60 kg) patients. High sodium excretion is associated with HF hospitalization in patients with older age and lower bodyweight in Japanese high-risk patients.

QT Variability Index is Correlated with Autonomic Nerve Activity in Healthy Children.

The QT variability index (QTVI), which measures the instability of myocardial repolarization, is usually calculated from a single electrocardiogram (ECG) recording and can be easily applied in children. It is well known that frequency analysis of heart rate variability (HRV) can detect autonomic balance, but it is not clear whether QTVI is correlated with autonomic tone. Therefore, we evaluated the association between QTVI and HRV to elucidate whether QTVI is correlated with autonomic nerve activity. Apparently, healthy 320 children aged 0-7 years who visited Fujita Health University Hospital for heart checkup examinations were included. The RR and QT intervals of 60 continuous heart beats were measured, and the QTVI was calculated using the formula of Berger et al. Frequency analysis of HRV, including the QTVI analysis region, was conducted for 2 min and the ratio of low-frequency (LF) components to high-frequency (HF) components (LF/HF) and HF/(LF + HF) ratio was calculated as indicators of autonomic nerve activity. Then, the correlations between QTVI and these parameters were assessed. QTVI showed a significant positive correlation with LF/HF ratio (r = 0.45, p < 0.001) and negative correlation with HF/(LF + HF) ratio (r = -0.429, p < 0.001). These correlations remained after adjustment for sex and age. QTVI, which is calculated from non-invasive ECG and can detect abnormal myocardial repolarization, is significantly correlated with frequency analysis of HRV parameters. QTVI reflects autonomic nerve balance in children.

Evaluation of perinatal autonomic development in infants using the QT/RR variability ratio.

OBJECTIVES: Development of the autonomic nervous system may play a role in myocardial repolarization lability in infants, but its relationship to repolarization abnormalities remains unclear. Thus, the aim of the present study was to evaluate the relationship between gestational age and ventricular repolarization lability using the variability ratio (VR). METHODS: Infants who underwent electrocardiography at a 1-month check-up were included (n=209; 125 males). Gestational age and the following four VR parameters at 1 month of age were compared: VR-I, SDQT/SDRR; VR-II, SDQT/rMSSD; VR-III, SDQTc/SDRR; and VR-IV, SDQTc/rMSSD; where SD, QTc, and rMSSD are standard deviation, QT interval corrected using Fridericia's formula, and root mean square difference of successive RR intervals, respectively. Twenty-eight preterm infants born at <37 weeks of gestation and 181 full-term infants were included. RESULTS: Significant correlations were observed between gestational age and VR-I, -III, and -IV (all p<0.05). All VR values were significantly higher in preterm infants compared with full-term infants (I: 0.54 vs 0.48, II: 1.15 vs 0.96, III: 0.88 vs 0.68, IV: 1.59 vs 1.39; median, all p<0.05). CONCLUSION: VR assessed at 1 month after birth was impaired in preterm infants, suggesting immaturity of their cardiac autonomic nervous system and ventricular myocardial repolarization.

Evaluation of sodium intake for the prediction of cardiovascular events in Japanese high-risk patients: the ESPRIT Study.

The optimal level of sodium intake remains controversial, and the effects on a broad range of cardiovascular (CV) conditions remain unknown. The Evaluation of sodium intake for the prediction of cardiovascular events in Japanese high-risk patients (ESPRIT) is a prospective observational study designed to investigate whether sodium intake assessed by spot urine testing is associated with adverse CV events. A total of 520 patients who visited our cardiology clinic with various cardiovascular risk profiles were included. Sodium intake was estimated by spot urine testing at the time of entry, and the measurement was repeated at least every 6 months during follow-up. The primary endpoint was composed of (1) hospitalization due to heart failure, (2) acute coronary syndrome, (3) cerebrovascular events, and (4) documented CV deaths. The secondary endpoint was all-cause mortality. During the median follow-up period of 5.2 years, there were 105 composite CV events (3.9%/year), including 60 hospitalizations due to heart failure, 9 acute coronary syndromes, 21 cerebrovascular events, 15 CV deaths, and 26 cases of all-cause mortality. The average sodium excretion (from a median of 14 measurements) during the follow-up period was 3.52 ± 0.67 g/day. After adjustment for age, sex, and body weight, higher sodium excretion ( ≥ 4.0 g/day) was associated with composite CV events (hazard ratio 1.79, confidence interval 1.01-3.15 compared with the reference value of 3.0-3.49 g/day) but not all-cause mortality. The ESPRIT study showed that high sodium excretion (≥ 4.0 g/day) was associated with the predefined composite CV events (UMIN ID: UMIN000005419).

Maturation of the QT Variability Index is Impaired in Preterm Infants.

Reduced heart rate (HR) variability in preterm infants compared with full-term infants suggests that autonomic cardiac control is developmentally delayed. However, the association between developmental changes in myocardial repolarization and gestational age remains unknown. This study investigated the association between the myocardial repolarization lability index, namely the QT variability index (QTVI) = log10 [(QTv/QTm2)/(HRv/HRm2)], and the perinatal profile of healthy 1-month-old infants. We included 209 infants (143 boys and 87 girls; mean gestational weeks at birth, 38.6 ± 1.7) who were born in university hospitals between 2014 and 2015 without apparent cardiac disease. We compared the ECG variability indices in 28 infants born before 37 gestational weeks (mean gestational weeks at birth, 35.6 ± 1.1 as preterm) and 181 infants born at the average number of gestational weeks (mean gestational weeks at birth, 38.8 ± 1.1 as controls). There was a negative correlation between the QTVI and gestational weeks (r = - 0.460, p = 0.035). QTVI values in preterm infants were larger than those in the controls (0.01 ± 0.50 vs. -0.26 ± 0.48, p = 0.023). In conclusion, the QTVI is negatively correlated with gestational age. The QTVI can serve as an index of the maturity of the cardiac autonomic nervous system and myocardial depolarization.

Effects of single-session dietary counseling by dieticians on salt reduction in cardiology outpatients who consumed large amounts of salt.

The purpose of the present study was to assess the effects of single-session dietary counseling on salt restriction in Japanese cardiology outpatients as assessed using spot urine measurements. A total of 72 patients (73±11 years old, including 30 females) who visited a cardiology outpatient clinic and had a salt intake of >8 g/day were included in this study. The patients received dietary counseling for salt restriction by expert dieticians at the time of enrollment. The daily dietary salt intake was estimated using the spot urine test at baseline prior to dietary counseling, at 3-9 weeks (next office visit), and at 24-52 weeks during follow-up evaluations. The baseline level of estimated salt excretion was 11.3±1.5 g/day, which was reduced to 9.6±2.3 g/day (P<0.01) at 3-9 weeks, but increased again at 24-52 weeks to 10.4±2.1 g/day, which was less than the baseline value (P=0.034 vs. 3-9 weeks; P=0.025 vs. baseline). The numbers of patients who achieved salt excretion levels of <6.0 and <8.0 g/day at 3-9 weeks were 4 (5.6%) and 19 (26%) patients, respectively, and were further reduced to no patients (0%; P=0.043 vs. 3-9 weeks) and 9 (13%; P=0.035 vs. 3-9 weeks) patients at 24-52 weeks of follow-up evaluation, respectively. In conclusion, the efficacy of dietary counseling by expert dieticians in restricting the salt intake of patients who consumed large amounts of salt was modest and temporary. Multiple nutritional- and behavioral-oriented approaches should be considered to achieve further reductions in salt intake.

Long-term compliance with salt restriction assessed using the spot urine method in Japanese cardiology outpatients.

The purpose of this study was to evaluate long-term compliance with salt restriction in Japanese cardiology outpatients assessed by spot urine measurements. A total of 466 patients (72 ± 10 years old, 216 females) who visited a cardiology outpatient clinic and were followed for at least 1 year were included in this study. Daily dietary salt intake was estimated based on the sodium and creatinine concentrations determined by spot urine at the time of enrollment, during an 8-26 week follow-up and at a long-term follow-up (>1 year). The average follow-up duration was 2.2 ± 0.6 (1.0-3.4) years after enrollment, and spot urines were collected 5.2 ± 2.8 times after 1 year. The baseline estimated salt excretion was 9.6 ± 2.7 g per day, which was reduced to 8.7 ± 2.3 g per day (P<0.01) at 8-26 weeks and remained unchanged at the long-term follow-up (8.9 ± 2.0 g per day, P = 0.36 vs. 8-26 weeks, P < 0.01 vs. baseline). The percent of patients who achieved an average salt excretion<6.0 g per day was unchanged from baseline (6.9% vs. 7.7%, P = 0.61). Among several variables (gender, age, body weight, salt excretion at enrollment) that might affect the incidence of salt excretion <6.0 g per day, salt excretion at baseline was the only determinant of successful salt restriction (P<0.01). In conclusion, compliance with salt restriction, assessed using a spot urine method, was maintained over the long term; however, achieving salt reduction to the level recommended by the guidelines remains a challenge.

Spot urine-guided salt reduction is effective in Japanese cardiology outpatients.

Dietary salt restriction is recommended for the prevention of cardiovascular disease in patients with hypertension and heart failure as well as in the general population. However, salt reduction is very difficult without knowing the daily salt intake of individual patients. A total of 524 subjects (72 ± 10 year old, 246 female) who visited an outpatient cardiology clinic were included in this study. Daily dietary salt intake was estimated based on the sodium and creatinine concentrations of spot urine at the time of enrollment and during follow-up for 8-26 weeks. The attending physicians explained the individual data to the patients and encouraged them to reduce their salt intake through simple counseling. The baseline estimated salt excretion was 9.6 ± 2.7 (range: 3.5-22.1) g per day, which decreased to 8.7 ± 2.3 (3.7-18.0) g per day during follow-up. The systolic blood pressure decreased from 127.0 ± 15.4 (range: 80-170) to 125.6 ± 14.5 (80-172) mm Hg (P=0.026), and the diastolic blood pressure decreased from 73.4 ± 11.0 (range: 40-106) to 71.5 ± 10.8 (50-102) mm Hg (P<0.001). In conclusion, the estimation of salt intake by spot urine was a useful method for motivating patients to reduce their salt intake; however, achieving salt reduction to the level recommended by the guideline could be a challenge.

Steady-state B-type natriuretic peptide levels in patients with atrial fibrillation of various clinical backgrounds.

B-type natriuretic peptide level is increased in patients with atrial fibrillation. The aim of the present study was to present the distribution of steady-state B-type natriuretic peptide levels of various clinical backgrounds and to elucidate the usefulness of measuring them in patients with atrial fibrillation. B-type natriuretic peptide was measured in stable conditions in patients with atrial fibrillation (74 ± 10 y/o, n = 473). The average B-type natriuretic peptide level was 161 ± 202 (median 101) pg/ml. Multiple regression analysis showed that age, left ventricular ejection fraction, left atrial diameter, structural heart disease, chronic atrial fibrillation, and heart failure symptoms were independently associated with elevated B-type natriuretic peptide levels. However, in chronic atrial fibrillation patients without structural heart disease, B-type natriuretic peptide levels did not differ between those with and without heart failure symptoms. Notably, B-type natriuretic peptide levels were high (≥ 150 pg/ml) in 41% of asymptomatic chronic atrial fibrillation without structural heart disease. Steady-state B-type natriuretic peptide levels of various clinical backgrounds were presented. Contributions of BNP elevation by clinical variables were somewhat different in different population. B-type natriuretic peptide was elevated in substantial percentage of asymptomatic chronic atrial fibrillation even without structural heart disease.