Prognostic value of leucine/phenylalanine ratio as an amino acid profile of heart failure.

Heart failure (HF) causes a hypercatabolic state that enhances the catabolic activity of branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in the heart and skeletal muscles and reduces protein synthesis in the liver. Consequently, free plasma aromatic amino acids (AAA, tyrosine and phenylalanine) are increased. To date, we have reported the prognostic value of the BCAA/AAA ratio (Fischer's ratio) in patients with HF. However, the leucine/phenylalanine ratio, which is a simpler index than the Fischer's ratio, has not been examined. Therefore, the prognostic value of the leucine/phenylalanine ratio in patients with HF was investigated. Overall 157 consecutive patients hospitalized for worsening HF (81 men, median age 78 years) were enrolled in the study. Plasma amino acid levels were measured when the patients were stabilized at discharge. Cardiac events were defined as a composite of cardiac death and hospitalization for worsening HF. A total of 46 cardiac events occurred during the median follow-up period of 238 (interquartile range 93-365) days. The median leucine/phenylalanine ratio was significantly lower in patients with cardiac events than in those without cardiac events (1.4 vs. 1.8, P < 0.001). The best cutoff value of the leucine/phenylalanine ratio was determined as 1.7 in the receiver operating characteristic (ROC) curve for cardiac events. Following a Kaplan-Meier survival analysis, the low group (leucine/phenylalanine ratio < 1.7, n = 72) had more cardiac events than the high group (leucine/phenylalanine ratio ≥ 1.7, n = 85) (log-rank, P < 0.001). Multivariate Cox proportional hazards regression analysis showed that the leucine/phenylalanine ratio was an independent predictor of cardiac events. Furthermore, on comparing the prognostic values for cardiac events based on ROC curves of leucine levels, BCAA levels, Fischer's ratio, and leucine/phenylalanine ratio, the leucine/phenylalanine ratio was the most accurate in predicting future cardiac events (area under the curve 0.763,; sensitivity 0.783,; specificity 0.676,; P < 0.001). The leucine/phenylalanine ratio could be a useful predictor of future cardiac events in patients with HF, reflecting an imbalance in amino acid metabolism.

Usefulness of the plasma branched-chain amino acid/aromatic amino acid ratio for predicting future cardiac events in patients with heart failure.

BACKGROUND: Heart failure (HF) is a hypercatabolic state that promotes branched-chain amino acid (BCAA) catabolic activity in the heart and skeletal muscle and reduces protein synthesis in the liver. Consequently, plasma free aromatic amino acids (AAAs) are increased. We investigated the prognostic value of the BCAA/AAA ratio (Fischer's ratio, FR) in patients with HF. METHODS: We enrolled 157 consecutive patients hospitalized for worsening HF (81 men, 76 women; mean ± SD age 75 ± 14 years). Plasma BCAA levels (i.e. total leucine, isoleucine, valine) and AAA levels (i.e. total tyrosine, phenylalanine) were measured at a time when the patients were stabilized (at discharge). FR was calculated as the combined plasma BCAA levels divided by the AAA level. Cardiac events were defined as a composite of cardiac death and hospitalization for worsening HF. RESULTS: The patients were divided into two groups based on the median FR (high-FR group: FR ≥ 3.1, n = 78; low-FR group: FR < 3.1, n = 79). Compared with the high-FR group, low-FR patients were older, had more prior hospitalizations for HF, lower albumin and cholinesterase levels, and lower geriatric nutritional risk index (GNRI). Altogether, 46 cardiac events occurred during the follow-up period (221 ± 135 days), including 14 cardiac deaths and 32 hospitalizations for worsening HF. In a Kaplan-Meier survival analysis, the low-FR group had more cardiac events than the high-FR group (log-rank, p < 0.001). The best cut-off value of FR was determined as 2.9 in the receiver operating characteristic curve for cardiac events. A multivariate Cox proportional hazards regression analysis showed that being in the low-FR group was an independent determinant of cardiac events from parameters of liver function tests and GNRI. CONCLUSIONS: FR might be useful for predicting future cardiac events in patients with HF, reflecting nutritional status which cannot be assessed by liver function tests and GNRI.

Prognostic impact of mitral L-wave in patients with hypertrophic cardiomyopathy without risk factors for sudden cardiac death.

Hypertrophic cardiomyopathy (HCM) with severe diastolic dysfunction is a major cause of heart failure and sudden cardiac death (SCD) associated with lethal arrhythmia. Although various risk factors for cardiac events have been reported in HCM patients, previous studies have reported that some HCM patients exhibit either no risk or a low risk of SCD experienced cardiac events. The mid-diastolic transmitral flow velocity curve (mitral L-wave) is an echocardiographic index of left ventricular compliance, and it has been reported as one of the parameters of advanced diastolic dysfunction assessed noninvasively. However, little is known about the association between the mitral L-wave and long-term clinical outcomes in HCM patients without SCD risk factors. Between July 2005 and February 2016, 112 patients were diagnosed with HCM and 96 patients without risk factors were enrolled. After excluding 3 patients whom we could not detect L-wave more than once, 93 patients (mean age 57.7 ± 13.1 years, 33 females) were divided into the following two groups, according to the presence or absence of the mitral L-wave: Group L (+) (with the mitral L-wave) and Group L (-) (without the mitral L-wave). The correlations between the mitral L-wave and rates of cardiac events were investigated. The mitral L-wave was present in 14 (15.1%) patients [Group L]. During the follow-up period [4.7 (2.9-7.5) years], patients experienced 7 cardiac events. Kaplan-Meier survival analysis showed that the event-free rate was significantly lower in Group L (+) than in Group L (-) (log-rank P = 0.002). Additionally, in multivariate analysis, L-wave positivity was identified as independent predictors of cardiac events. Existence of the mitral L-wave can predict cardiac events, even in HCM patients without SCD risk factors.

The Selvester QRS score as a predictor of cardiac events in nonischemic dilated cardiomyopathy.

BACKGROUND: Myocardial fibrosis is associated with poor prognosis in nonischemic dilated cardiomyopathy (NIDCM) patients. The Selvester QRS score on 12-lead electrocardiogram is associated with both the amount of myocardial scar and poor prognosis in myocardial infarction patients. However, its use in NIDCM patients is limited. We investigated the prognostic value of the QRS score and its association with collagen volume fraction (CVF) in NIDCM patients. METHODS: We enrolled 91 consecutive NIDCM patients (66 men, 53±13 years) without permanent pacemakers or cardiac resynchronization therapy devices. The Selvester QRS score was calculated by two expert cardiologists at NIDCM diagnosis. All patients were followed up over 4.5±3.2 years. Cardiac events were defined as a composite of cardiac death, hospitalization for worsening heart failure, and lethal arrhythmia. We also evaluated CVF using endomyocardial biopsy samples. RESULTS: At baseline, the left ventricular ejection fraction was 32±9%, plasma brain natriuretic peptide level was 80 [43-237] pg/mL, and mean Selvester QRS score was 4.1 points. Twenty cardiac events were observed (cardiac death, n=1; hospitalization for worsening heart failure, n=16; lethal arrhythmia, n=3). Cox proportional hazard regression analysis revealed that the Selvester QRS score was an independent determinant of cardiac events (hazard ratio, 1.32; 95% confidence interval, 1.05-1.67; p=0.02). The best cut-off value was determined as 3 points, with 85% sensitivity and 47% specificity (area under the curve, 0.688, p=0.011). In Kaplan-Meier survival analysis, the QRS score ≥3 group had more cardiac events than the QRS score <3 group (log-rank, p=0.007). Further, there was a significant positive correlation of Selvester QRS score with CVF (r=0.46, p<0.001). CONCLUSIONS: The Selvester QRS score can predict future cardiac events in NIDCM, reflecting myocardial fibrosis assessed by CVF.

Sokolow-Lyon voltage is suitable for monitoring improvement in cardiac function and prognosis of patients with idiopathic dilated cardiomyopathy.

BACKGROUND: The clinical significance of electrocardiogram in the assessment of patients with idiopathic dilated cardiomyopathy (IDCM) is currently unknown. The aim of this study was to determine the feasibility of recording serial changes in Sokolow-Lyon voltage (∆%QRS-voltage) in one year to estimate left ventricular reverse remodeling (LVRR) and predict a prognosis of IDCM patients under tailored medical therapy. METHODS: Sixty-eight consecutive patients with mild symptoms (52.1 ± 13 years old; 69% men; NYHA I/II/III/IV; 33/29/6/0) underwent electrocardiography and echocardiography at baseline and 12 month follow-up (follow-up period: 3.9 years). RESULTS: LVRR was observed in 30 patients (44.1%). The ∆%QRS-voltage was significantly lower in the LVRR group (LVRR; -26.9%, non-LVRR: -9.2%, p < .001). Univariate analysis showed that ∆%QRS-voltage correlated with ∆%LV end-diastolic diameter (r = .634, p < .001), and with ∆%LV ejection fraction and ∆%LV mass index (r = -.412, p < .001; r = .429, p < .001 respectively). Using receiver operating characteristic curve analysis for the estimation of LVRR, ∆%QRS of -14.7% showed optimal sensitivity (63.2%) and specificity (83.3%) (AUC = 0.775, p < .001). The composite endpoints of cardiac death (n = 0), hospitalization for advanced heart failure (n = 11) and fatal arrhythmia (n = 2) were observed in 13 patients during the follow-up period. Kaplan-Meier analysis showed significantly higher event-free rate in patients of the low ∆%QRS-voltage group (<-14.7%) (83%) than those of the high group (66%, p = .022). CONCLUSIONS: The present study showed that decrease in Sokolow-Lyon voltage is associated with improvement in cardiac function and favorable prognosis in IDCM patients on medical therapy, suggesting that this index is a feasible marker for response to treatment of IDCM.

Usefulness of the Combination of In-Hospital Poor Diuretic Response and Systemic Congestion to Predict Future Cardiac Events in Patients With Acute Decompensated Heart Failure.

We aimed to (1) investigate the relation between diuretic response (DR) with or without systemic congestion and prognosis and (2) explore the potential predictors of poor DR for risk stratification in patients with acute decompensated heart failure (ADHF). We enrolled 186 consecutive patients hospitalized for ADHF. The DR was defined as (body weight at discharge - body weight at admission)/40 mg furosemide or equivalent loop diuretic dose. Systemic congestion on admission was simply evaluated by the presence of leg edema or jugular venous distention. All patients were divided into 4 groups based on the median of DR (-0.50 kg/40 mg) and the status of systemic congestion; GR/C (good DR with systemic congestion, n = 66), GR/N (good DR without systemic congestion, n = 27), PR/C (poor DR with systemic congestion, n = 48); and PR/N (poor DR without systemic congestion, n = 45). The composite outcome was defined as cardiac death and rehospitalization for worsening heart failure. In survival analysis, the cardiac event-free rate in PR/C was significantly lower than that in any other groups (log-rank, p <0.001), and PR/C was an independent predictor of cardiac events (hazard ratio 2.17, p = 0.016). In conclusion, the combination of in-hospital poor DR, characterized by previous ischemic heart disease, and prehospital dose of daily loop diuretics, and systemic congestion provides a risk stratification for future cardiac events in patients with ADHF.

Impact of Renal Functional/Morphological Dynamics on the Calcification of Coronary and Abdominal Arteries in Patients with Chronic Kidney Disease.

AIM: Fast-progressing vascular calcification (VC) is accompanied by renal atrophy and functional deterioration along with atherosclerosis in patients with chronic kidney disease (CKD). However, the relationship between VC progression and renal functional and/or morphological changes remains unclear. METHODS: We included 70 asymptomatic patients with CKD without hemodialysis in our study. To identify temporal variations, the coronary artery calcification score (CACS), abdominal aortic calcification index (ACI), and renal parenchymal volume index (RPVI) were determined via spiral computed tomography scans taken during the study. We investigated significant factors related to annualized variations of CACS (ΔCACS/y) and ACI (ΔACI/y). RESULTS: During the follow-up period (4.6 years), median values of CACS [in Agatston units (AU)] and ACI increased from 40.2 to 113.3 AU (p=0.053) and from 13.2 to 21.7% (p=0.036), respectively. Multivariate analysis revealed that CACS at baseline (p＜0.001) and diabetes mellitus (DM) status (p=0.037) for ΔCACS/y and ACI at baseline (p=0.017) and hypertension (HT) status (p= 0.046) for ΔACI/y were significant independent predictors. Furthermore, annualized RPVI variation was significantly related to both ΔCACS/y and ΔACI/y (R=-0.565, p＜0.001, and R=-0.289, p=0.015, respectively). On the other hand, independent contributions of the estimated glomerular filtration rate (eGFR) and annualized eGFR variation to VC progression were not confirmed. CONCLUSION: The degree of VC at baseline, DM, HT, and changes in renal volume, but not eGFR, had a strong impact on VC progression in patients with CKD.

Myocardial contractile reserve predicts left ventricular reverse remodeling and cardiac events in dilated cardiomyopathy.

BACKGROUND: Catecholamine sensitivity estimated using a dobutamine stress test (DST) is recognized as a measure of the beta-adrenergic myocardial contractile reserve, which is involved with left ventricular reverse remodeling (LV-RR). We investigated whether the prognostic ability of the DST for LV-RR could predict cardiac events. METHODS: There was a total of 192 enrolled patients with dilated cardiomyopathy (DCM). DCM was defined as a LV ejection fraction (LV-EF) ≤45% and LV end-diastolic dimension (LVDd) ≥55mm. One hundred patients were subjected to micromanometer-based measurement of the maximal first derivative of LV pressure (LVdP/dtmax), an index of LV contractility, at baseline and following the infusion of dobutamine (10µg/kg/min) via a pigtail catheter. Percentage changes in LVdP/dtmax from the baseline to peak values under dobutamine stress (ΔLVdP/dtmax) were also calculated. After excluding 17 patients who received cardiac resynchronization therapy within 3 months of undergoing DST (n=15) and who did not receive follow-up echocardiography (n=2), 83 patients were enrolled (52.5±12.3 years). RESULTS: During the follow-up period (4.7±2.6 years), LV-RR was recognized in 49 of 83 patients (59.0%). A multivariate logistic regression analysis revealed that ΔLVdP/dtmax (hazard ratio: 1.024, p=0.007) and the symptom duration (hazard ratio: 0.977, p=0.003) were independent predictors of LV-RR. A receiver operating characteristic curve analysis revealed a ΔLVdP/dtmax cut-off value of 75.1% for LV-RR and a significantly lower cardiac event rate in the ΔLVdP/dtmax≥75.1% group (p=0.045). CONCLUSIONS: ΔLVdP/dtmax estimated using DST was a useful predictor of LV-RR and cardiac events in patients with DCM.

Cholesterol metabolism as a prognostic marker in patients with mildly symptomatic nonischemic dilated cardiomyopathy.

BACKGROUND: Little is known about whether the alteration of cholesterol metabolism reflects abdominal organ impairments due to heart failure. Therefore, we investigated the prognostic value of cholesterol metabolism by evaluating serum campesterol and lathosterol levels in patients with early-stage nonischemic dilated cardiomyopathy (NIDCM). METHODS: We enrolled 64 patients with NIDCM (median age 57.5 years, 31% female) with New York Heart Association functional class I/II. Serum campesterol and lathosterol levels were measured in all patients. The patients were then divided into four subsets based on the median non-cholesterol sterol levels (campesterol 3.6µg/mL, lathosterol 1.4µg/mL): reference (R-subset), high-campesterol/high-lathosterol; absorption-reduced (A-subset), low-campesterol/high-lathosterol; synthesis-reduced (S-subset), high-campesterol/low-lathosterol; double-reduced (D-subset), low-campesterol/low-lathosterol. Endpoint was a composite of cardiac events, including cardiac-related death, hospitalization for worsening heart failure, and lethal arrhythmia. RESULTS: Median brain natriuretic peptide (BNP) level was 114pg/mL. Mean left ventricular ejection fraction was 31.4%. D-subset had the lowest total cholesterol level and cardiac index and the highest BNP level and pulmonary capillary wedge pressure. D-subset also had the highest cardiac event rate during the mean 3.8 years of follow-up (log-rank p=0.001). Multivariate regression analysis showed that D-subset was an independent determinant of cardiac events. The receiver operating characteristic curve analysis revealed that total cholesterol <153mg/dL was a best cut-off value for discrimination of the D-subset. CONCLUSIONS: The combined reduction of campesterol and lathosterol that indicated intestinal cholesterol absorption and liver synthesis predicts future cardiac events in patients with mildly symptomatic NIDCM.

Meningitis-retention Syndrome; A Case Report.

We report a case of meningitis-retention syndrome followed by urodynamic tests. A 48-year-old man was admitted to the hospital for an undiagnosed fever with headache and urinary retention. Aseptic meningitis was suspected according to cerebrospinal fluid analyses, and urodynamic test showed an underactive detrusor, leading to inadequate contraction of the bladder on voiding in spite of a normal sensation during bladder filling. Clean intermittent self-catheterization was required temporarily, but normal urinary voiding without the need for medication was restored in 2 weeks after discharge from the hospital, when urodynamic tests showed normal contractility of the bladder during voiding.

A novel objective sour taste evaluation method based on near-infrared spectroscopy.

One of the most important themes in the development of foods and drinks is the accurate evaluation of taste properties. In general, a sensory evaluation system is frequently used for evaluating food and drink. This method, which is dependent on human senses, is highly sensitive but is influenced by the eating experience and food palatability of individuals, leading to subjective results. Therefore, a more effective method for objectively estimating taste properties is required. Here we show that salivary hemodynamic signals, as measured by near-infrared spectroscopy, are a useful objective indicator for evaluating sour taste stimulus. In addition, the hemodynamic responses of the parotid gland are closely correlated to the salivary secretion volume of the parotid gland in response to basic taste stimuli and respond to stimuli independently of the hedonic aspect. Moreover, we examined the hemodynamic responses to complex taste stimuli in food-based solutions and demonstrated for the first time that the complicated phenomenon of the "masking effect," which decreases taste intensity despite the additional taste components, can be successfully detected by near-infrared spectroscopy. In summary, this study is the first to demonstrate near-infrared spectroscopy as a novel tool for objectively evaluating complex sour taste properties in foods and drinks.