Prognostic value of estimating appendicular muscle mass in heart failure using creatinine/cystatin C.

BACKGROUND AND AIMS: Heart failure with concomitant sarcopenia has a poor prognosis; therefore, simple methods for evaluating the appendicular skeletal muscle mass index (ASMI) are required. Recently, a model incorporating anthropometric data and the sarcopenia index (i.e., serum creatinine-to-cystatin C ratio [Cre/CysC]), was developed to estimate the ASMI. We hypothesized that this model was superior to the traditional model, which uses only anthropometric data to predict prognosis. This retrospective cohort study compared the prognostic value of low ASMI as defined by the biomarker and anthropometric models in patients with heart failure. METHODS AND RESULTS: Among 847 patients, we estimated ASMI using an anthropometric model (incorporating age, body weight, and height) in 791 patients and a biomarker model (incorporating age, body weight, hemoglobin, and Cre/CysC) in 562 patients. The primary outcome was all-cause mortality. Overall, 53.4% and 39.1% of patients were diagnosed with low ASMI (using the Asian Working Group for Sarcopenia cut-off) by the anthropometric and biomarker models, respectively. The two models showed a poor agreement in the diagnosis of low ASMI (kappa: 0.57, 95% confidence interval: 0.50-0.63). Kaplan-Meier curves showed that a low ASMI was significantly associated with all-cause death in both models. However, this association was retained after adjustment for other covariates in the biomarker model (hazard ratio: 2.32, p = 0.001) but not in the anthropometric model (hazard ratio: 0.79, p = 0.360). CONCLUSION: Among patients hospitalized with heart failure, a low ASMI estimated using the biomarker model, and not the anthropometric model, was significantly associated with all-cause mortality.

Clinical and prognostic implications of hyaluronic acid in hospitalized patients with heart failure.

We investigated the clinical and prognostic implications of hyaluronic acid, a liver fibrosis marker, in patients with heart failure. We measured hyaluronic acid levels on admission in 655 hospitalized patients with heart failure between January 2015 and December 2019. Patients were stratified into three groups according to hyaluronic acid level: low (< 84.3 ng/mL, n = 219), middle (84.3-188.2 ng/mL, n = 218), and high (≥ 188.2 ng/mL, n = 218). The primary endpoint was all-cause death. The high hyaluronic acid group had higher N-terminal pro-brain-type natriuretic peptide levels, larger inferior vena cava, and shorter tricuspid annular plane systolic excursion than the other two groups. During the follow-up period (median 485 days), 132 all-cause deaths were observed: 27 (12.3%) in the low, 37 (17.0%) in the middle, and 68 (31.2%) in the high hyaluronic acid (P < 0.001) groups. Cox proportional hazards analysis revealed that higher log-transformed hyaluronic acid levels were significantly associated with all-cause death (hazard ratio, 1.38; 95% confidence interval, 1.15-1.66; P < 0.001). No significant interaction was observed between hyaluronic acid level and reduced/preserved left ventricular ejection fraction on all-cause death (P = 0.409). Hyaluronic acid provided additional prognostic predictability to pre-existing prognostic factors, including the fibrosis-4 index (continuous net reclassification improvement, 0.232; 95% confidence interval, 0.022-0.441; P = 0.030). In hospitalized patients with heart failure, hyaluronic acid was associated with right ventricular dysfunction and congestion and was independently associated with prognosis regardless of left ventricular ejection fraction.

One-Year Outcome of Patients with Chest Pain in the Rule-Out Group According to the 0-Hour/1-Hour Algorithm.

The European Society of Cardiology recommends the 0/1-hour algorithm for risk stratification of patients with suspected non-ST-elevation myocardial infarction as class I, level B; however, there are few reports on the long-term prognosis, resulting in a rule-out group. We aimed to determine whether implementation of the 0-hour/1-hour algorithm is safe and effective in emergency department (ED) patients with possible acute coronary syndrome (ACS) through a 1-year follow-up period. Our study analyzed the 1-year follow-up data from a prospective pre-post study of 1106 ED patients with possible ACS from 4 hospitals in Japan and Taiwan. Patients were 18 years or older. Accrual occurred for 1 year after implementing the 0-1-hour algorithm from November 2014 to December 2018. Overall, 520 patients were stratified into the rule-out group. Major advanced cardiovascular events (all-cause death, acute myocardial infarction [AMI], stroke, unstable angina, and revascularization) at 1-year were determined using data from health records and phone calls. The 0-1-hour algorithm stratified 47.0% of patients in the rule-out group. Over the 1-year follow-up period (follow-up rate = 86.9%), cardiovascular death and subsequent AMI did not occur in the rule-out group. Among the 27 patients who underwent the procedure within 30 days post-index visit, 3 patients (0.7%) had a stroke, 6 patients (1.3%) died of non-cardiovascular cause, and 30 patients (6.7%) underwent coronary revascularization within 1 year. At the 1-year follow-up, implementation of the 0-hour/1-hour algorithm was associated with very low rates of adverse event among patients in the rule-out group.

Prevalence and Prognostic Relevance of Isolated Tubular Dysfunction in Patients With Acute Heart Failure.

BACKGROUND: Renal dysfunction includes glomerular dysfunction (GD) and tubular dysfunction (TD); however, there is limited information regarding the prevalence, coexistence, and prognostic relevance of TD and GD among patients with acute heart failure (AHF).Methods and Results:This study reviewed 489 patients with AHF who had undergone testing at the time of their admission to identify GD (estimated glomerular filtration rate <60 mL/min/1.73 m2) and TD (urinary ß-2-microglobulin ≥300 µg/gCr). Patients were grouped according to the presence/absence of GD and TD as having neither condition (n=116), isolated TD (n=101), isolated GD (n=83), or coexisting GD plus TD (n=189). During a median follow up of 466 days (interquartile range: 170-871 days), 107 deaths were observed. Kaplan-Meier curve analysis revealed that, relative to the absence of a GD and TD group, higher mortality rates were observed in the groups with isolated TD, isolated GD, and coexisting GD plus TD (log-rank P<0.001). Similarly, the adjusted Cox regression analyses revealed that significantly higher risks of mortality were associated with isolated TD, isolated GD, and coexisting GD plus TD. Moreover, isolated GD and isolated TD were both independently associated with increased risks of all-cause mortality. CONCLUSIONS: As a significant proportion of patients with AHF had isolated TD and an increased risk of mortality, patients with AHF should be screened for TD even if they do not have GD.

Sex differences in the prevalence and prognostic impact of physical frailty and sarcopenia among older patients with heart failure.

BACKGROUND AND AIMS: Frailty and sarcopenia are common and confer poor prognosis in elderly patients with heart failure; however, gender differences in its prevalence or prognostic impact remain unclear. METHODS AND RESULTS: We included 1332 patients aged ≥65 years, who were hospitalized for heart failure. Frailty and sarcopenia were defined using the Fried phenotype model and Asian Working Group for Sarcopenia criteria, respectively. Gender differences in frailty and sarcopenia, and interactions between sex and prognostic impact of frailty/sarcopenia on 1-year mortality were evaluated. Overall, 53.9% men and 61.0% women and 23.7% men and 14.0% women had frailty and sarcopenia, respectively. Although sarcopenia was more prevalent in men, no gender differences existed in frailty after adjusting for age. On Kaplan-Meier analysis, frailty and sarcopenia were significantly associated with 1-year mortality in both sexes. On Cox proportional hazard analysis, frailty was associated with 1-year mortality only in men, after adjusting for confounding factors (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.19-3.16; P = 0.008 for men; HR, 1.63; 95% CI, 0.84-3.13; P = 0.147 for women); sarcopenia was an independent prognostic factor in both sexes (HR, 1.93; 95% CI, 1.13-3.31; P = 0.017 for men; HR, 3.18; 95% CI, 1.59-5.64; P = 0.001 for women). There were no interactions between sex and prognostic impact of frailty/sarcopenia (P = 0.806 for frailty; P = 0.254 for sarcopenia). CONCLUSIONS: Frailty and sarcopenia negatively affect older patients with heart failure from both sexes. CLINICAL TRIALS: This study was registered at the University Hospital Information Network (UMIN-CTR, unique identifier: UMIN000023929) before the first patient was enrolled.

Sarcopenic obesity is associated with impaired physical function and mortality in older patients with heart failure: insight from FRAGILE-HF.

BACKGROUND: The purpose of this study was to clarify the prevalence, association with frailty and exercise capacity, and prognostic implication of sarcopenic obesity in patients with heart failure. METHODS: The present study included 779 older adults hospitalized with heart failure (median age: 81 years; 57.4% men). Sarcopenia was diagnosed based on the guidelines by the Asian Working Group for Sarcopenia. Obesity was defined as the percentage of body fat mass (FM) obtained by bioelectrical impedance analysis. The FM cut-off points for obesity were 38% for women and 27% for men. The primary endpoint was 1-year all-cause death. We assessed the associations of sarcopenic obesity occurrence with the short physical performance battery (SPPB) score and 6-minute walk distance (6MWD). RESULTS: The rates of sarcopenia and obesity were 19.3 and 26.2%, respectively. The patients were classified into the following groups: non-sarcopenia/non-obesity (58.5%), non-sarcopenia/obesity (22.2%), sarcopenia/non-obesity (15.3%), and sarcopenia/obesity (4.0%). The sarcopenia/obesity group had a lower SPPB score and shorter 6MWD, which was independent of age and sex (coefficient, - 0.120; t-value, - 3.74; P < 0.001 and coefficient, - 77.42; t-value, - 3.61; P < 0.001; respectively). Ninety-six patients died during the 1-year follow-up period. In a Cox proportional hazard analysis, sarcopenia and obesity together were an independent prognostic factor even after adjusting for a coexisting prognostic factor (non-sarcopenia/non-obesity vs. sarcopenia/obesity: hazard ratio, 2.48; 95% confidence interval, 1.22-5.04; P = 0.012). CONCLUSION: Sarcopenic obesity is a risk factor for all-cause death and low physical function in older adults with heart failure. TRIAL REGISTRATION: University Hospital Information Network (UMIN-CTR: UMIN000023929 ).

Low coenzyme Q10 levels in patients with acute cardiovascular disease are associated with long-term mortality.

Coenzyme Q10 (CoQ10) plays a potential role in the prevention and treatment of cardiovascular disease through improved cellular bioenergetics. Critical illness in the intensive care unit has been reported to be associated with decreased circulating CoQ10 levels, and we previously demonstrated the association of low CoQ10 levels with in-hospital mortality. However, the association of CoQ10 with the acute phase of cardiovascular disease and long-term mortality remains unclear. We enrolled 242 consecutive patients with cardiovascular disease admitted to the coronary care unit of Juntendo University Hospital to investigate the association between long-term mortality and serum CoQ10 levels. During a mean follow-up of 3.2 years, 58 patients died. The mean serum CoQ10 levels were significantly lower in the non-survivors than in the survivors (0.48 ± 0.27 vs. 0.58 ± 0.38 mg/L; p = 0.035). Compared with the patients with above-median CoQ10 levels (0.46 mg/L), the cumulative incidence of all-cause mortality was significantly higher in those with lower CoQ10 levels (p = 0.025). Multivariate Cox regression analysis further demonstrated that lower CoQ10 levels were associated with poor prognosis. Low serum CoQ10 levels during the acute phase of cardiovascular diseases were associated with long-term mortality in patients, suggesting the utility of low serum CoQ10 levels as a predictor and potential therapeutic target.

Elevated Heart Rate in Combination with Elevated Blood Pressure Predicts Lower Cardiovascular Mortality in Acute Decompensated Heart Failure.

Despite its clinical relevance, a subclass of acute decompensated heart failure (ADHF) with elevated blood pressure, known as hypertensive ADHF (HT-ADHF), has been less intensively evaluated. This study aimed to characterize the prognostic nature and pathophysiology of HT-ADHF. A total of 509 consecutive patients with first-time ADHF hospitalization were subjects of the study. Participants were divided into two groups: an HT-ADHF group (systolic blood pressure, SBP > 140 mmHg at presentation) and a non-HT-ADHF group (SBP ≤ 140 mmHg). Median follow-up duration measured 253 days. Unadjusted Kaplan-Meier analysis demonstrated both a lower cardiovascular mortality rate in the HT-ADHF group and similar incidences of heart failure rehospitalization in both groups. Adjusted Cox hazard analysis showed an association of elevated SBP at presentation with significantly lower cardiovascular mortality, though no such association was observed with heart failure rehospitalization. Moreover, elevated heart rate in combination with elevated SBP at presentation predicted a significantly lower risk of cardiovascular mortality (Hazard Ratio: 0.32, 95% CI: 0.14-0.77, P = 0.01). Also, significantly lower cardiovascular mortality was observed in this subtype, compared with other types of ADHF.

Prevalence of Restless Legs Syndrome and Its Effects on Sleep and Health-Related Quality of Life in Patients With Heart Failure.

BACKGROUND: Restless legs syndrome (RLS) is a neurological disorder characterized by leg restlessness and dysesthesia. Although the relationship between RLS and heart failure (HF) has been reported, the prevalence and clinical significance of RLS in patients with HF remain to be elucidated. METHODS AND RESULTS: We enrolled consecutive patients with HF who were admitted to our institutions. RLS was diagnosed using the International Restless Legs Syndrome Study Group criteria. Subjective sleepiness, sleep quality, and quality of life (QoL) were assessed using the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and 8-item Short Form (SF-8), respectively. Among the 133 patients, 18 (13.6%) had RLS and were younger than those without RLS (62.4±13.4 vs 70.0±12.2, P = .017). The RLS group had significantly disrupted sleep quality and QoL, with greater PSQI score (8.0±3.2 vs 5.9±3.3, P = .015) and lower SF-8 physical component summary (PCS) score (35.6±6.5 vs 40.7±9.5, P = .031), despite similar ESS and SF-8 mental component summary scores. In the multivariable regression analysis, RLS was associated with greater PSQI (ß=0.211; P = .014) and lower PCS score (ß=-0.177; P = .045). CONCLUSION: In the patients with HF, RLS was prevalent, and sleep quality and QoL may be disrupted by RLS.

Association between C-reactive protein levels at hospital admission and long-term mortality in patients with acute decompensated heart failure.

The C-reactive protein (CRP) levels obtained at hospital admission are associated with the prognosis of several cardiovascular diseases, including acute coronary syndrome. Although the admission CRP level is associated with in-hospital mortality in patients with acute decompensated heart failure (ADHF), there are limited data on the association between the admission CRP level and long-term mortality in patients with ADHF. This study included consecutive ADHF patients admitted to our institution from 2007 to 2011. Eligible patients were divided into four groups based on quartiles of admission CRP levels. The association between the admission CRP level and long-term mortality was assessed by multivariable Cox proportional analysis, including other independent variables with p values < 0.1 in the univariable analyses. Overall, 527 eligible patients were examined. There were 142 deaths (27%) during a median follow-up period of 2.0 years. In the multivariable analysis, the hazard ratio (HR) significantly increased with admission CRP levels in a dose-dependent manner for mortality (p for trend = 0.034). Multivariable analysis also showed a significant association between the admission CRP level, when treated as a natural logarithm-transformed continuous variable, and increased mortality (HR 1.16, p = 0.030). In patients with ADHF, the admission CRP level was associated with an increased risk of long-term mortality.

Chest X-Ray Revealed a Slowly Progressive Giant Right Coronary Artery Aneurysm in an Asymptomatic Patient.

A giant right coronary artery aneurysm (60 × 70 mm in size) was incidentally found by chest X-ray as an abnormal right atrial enlargement, and it needed surgical resection. Although the majority of giant coronary artery aneurysms present with symptoms of coronary ischemia, this case presented without any specific symptom. This study indicates that when chest X-ray shows abnormal atrial enlargement, a differential diagnosis of giant coronary artery aneurysm may need to be considered.

Relationship between blood urea nitrogen-to-creatinine ratio at hospital admission and long-term mortality in patients with acute decompensated heart failure.

Although elevated blood urea nitrogen (BUN)-to-creatinine (BUN/Cr) ratio at hospital admission has been reported to be associated with poor short-term prognosis, its association to long-term mortality in patients with acute decompensated heart failure (ADHF) remains to be elucidated. Moreover, an additive prognostic value to preexisting renal markers including creatinine and BUN has not been well described. A cohort of 557 consecutive ADHF patients admitted to the cardiac intensive care unit was studied. All cohorts were divided into high and low BUN/Cr ratios according to the median value of BUN/Cr ratio at admission. Association between admission BUN/Cr ratio and long-term all-cause mortality was assessed. There were 145 deaths (27%) observed during the follow-up period of 1.9 years in median. Patients with high BUN/Cr ratio showed with higher mortality compared to low BUN/Cr ratio (log-rank: P = 0.006). In the multivariable analysis, patients with high BUN/Cr ratio at admission were associated with high mortality independently from other covariates including BUN and creatinine (HR 1.81, 95% CI 1.16-2.80, P = 0.009). In patients with ADHF, there is a relationship between admission BUN-to-creatinine ratio and long-term mortality.

Relationship Between Serum Sodium Level Within the Low-Normal Range on Admission and Long-Term Clinical Outcomes in Patients with Acute Decompensated Heart Failure.

Although hyponatremia during hospitalization for acute decompensated heart failure (ADHF) is reportedly related with poor prognosis, the available data regarding the impact of serum sodium level within the low-normal range at admission on clinical events in patients with ADHF is limited.We studied eligible patients admitted to our institution in 2007-2011. All the patients were categorized into 3 groups according to the admission serum sodium levels of < 135 mmol/L (hyponatremia), ≥ 135 and < 140 mmol/L (low-normal range), or ≥ 140 mmol/L (normal range). The association between admission serum sodium levels and long-term clinical events, a composite of all-cause deaths and re-hospitalizations for ADHF, was assessed by multivariable Cox proportional analysis.Of the 584 eligible patients, 208 (35.6%) were in the low-normal range and 99 (16.9%) had hyponatremia on admission. On multivariable analysis, compared with those with a sodium level ≥ 140 mmol/L, patients with hyponatremia were at increased risk for clinical events (hazard ratio [HR], 1.53; P = 0.041), whereas the HR of those in the low-normal range was attenuated and insignificant (HR, 1.08; P = 0.625). However, the HR of each category increased significantly as sodium level decreased (P value for HR trend, 0.024). In addition, when serum sodium level was treated as a continuous variable, the lower the serum sodium level, the greater the risk of clinical events (P = 0.012). The cut-off value of serum sodium level to predict mortality was < 138 mmol/L.In conclusion, a low serum sodium level on admission for ADHF, even if low-normal, can increase the risk of long-term mortality and/or re-hospitalization for ADHF.

Low 1,5-anhydroglucitol levels are associated with long-term cardiac mortality in acute coronary syndrome patients with hemoglobin A1c levels less than 7.0.

BACKGROUND: Diabetes mellitus is considered an important risk factor for cardiovascular diseases. High hemoglobin A1c (HbA1c) levels, which indicate poor glycemic control, have been associated with occurrence of cardiovascular diseases. There are few parameters which can predict cardiovascular risk in patients with well-controlled diabetes. Low 1,5-anhydroglucitol (1,5-AG) levels are considered a clinical marker of postprandial hyperglycemia. We hypothesized that low 1,5-AG levels could predict long-term mortality in acute coronary syndrome (ACS) patients with relatively low HbA1c levels. METHODS: The present study followed a retrospective observational study design. We enrolled 388 consecutive patients with ACS admitted to the cardiac intensive care unit at the Juntendo University Hospital from January 2011 to December 2013. Levels of 1,5-AG were measured immediately before emergency coronary angiography. Patients with early stent thrombosis, no significant coronary artery stenosis, malignancy, liver cirrhosis, a history of gastrectomy, current steroid treatment, moderately to severely reduced kidney function (estimated glomerular filtration rate < 45 ml/min/1.73 m2; chronic kidney disease stage 3B, 4, and 5), HbA1c levels ≥ 7.0%, and those who received sodium glucose co-transporter 2 inhibitor therapy were excluded. RESULTS: During the 46.9-month mean follow-up period, nine patients (4.5%) died of cardiovascular disease. The 1,5-AG level was significantly lower in the cardiac death group compared with that in the survivor group (12.3 ± 5.3 vs. 19.2 ± 7.7 µg/ml, p < 0.01). Kaplan-Meier survival analysis showed that low 1,5-AG levels were associated with cardiac mortality (p = 0.02). Multivariable Cox regression analysis showed that 1,5-AG levels were an independent predictor of cardiac mortality (hazard ratio 0.76; 95% confidence interval 0.41-0.98; p = 0.03). CONCLUSION: Low 1,5-AG levels, which indicate postprandial hyperglycemia, predict long-term cardiac mortality even in ACS patients with HbA1c levels < 7.0%.

Impact on Clinical Outcomes of Periodic Leg Movements During Sleep in Hospitalized Patients Following Acute Decompensated Heart Failure.

BACKGROUND: Periodic leg movements during sleep (PLM) are characterized by regularly recurring movement of the legs during sleep. Although PLM is common and a predictor of death in patients with chronic heart failure, the clinical significance of PLM in hospitalized patients with a reduced left ventricular ejection fraction (LVEF) following acute decompensated heart failure (ADHF) remains unknown.Methods and Results:After initial improvement of acute signs and symptoms of ADHF, 94 consecutive patients with reduced LVEF who underwent polysomnography were enrolled. They were divided into 2 groups based on the presence or absence of severe PLM defined as PLM index ≥30. The risks for clinical events, composite of all-cause death and rehospitalization, were assessed using a stepwise multivariable Cox proportional model including variables showing P<0.10 in univariate analyses. Severe PLM was observed in 21 patients (22%). At a median follow-up of 5.2 months, 30 patients experienced clinical events (32%). In the multivariable analysis, the presence of severe PLM was significantly associated with increasing clinical events (hazard ratio, 2.16; 95% confidence interval, 1.03-4.54; P=0.042) independent of hemoglobin level and the severity of sleep-disordered breathing. CONCLUSIONS: In hospitalized patients with systolic dysfunction following ADHF, severe PLM was prevalent and significantly associated with increased risk of death and/or rehospitalization.

Low circulating coenzyme Q10 during acute phase is associated with inflammation, malnutrition, and in-hospital mortality in patients admitted to the coronary care unit.

Coenzyme Q10 (CoQ10) has a potential role in the prevention and treatment of heart failure through improved cellular bioenergetics. In addition, it has antioxidant, free radical scavenging, and vasodilatory effects that may be beneficial. Although critical illness in intensive care unit is associated with decreased circulating CoQ10 levels, the clinical significance of CoQ10 levels during acute phase in the patients of cardiovascular disease remains unclear. We enrolled 257 consecutive cardiovascular patients admitted to the coronary care unit (CCU). Serum CoQ10 levels were measured after an overnight fast within 24 h of admission. We examined the comparison of serum CoQ10 levels between survivors and in-hospital mortalities in patients with cardiovascular disease. Serum CoQ10 levels during the acute phase in patients admitted to the CCU had similar independent of the diagnosis. CoQ10 levels were significantly lower in patients with in-hospital mortalities than in survivors (0.43 ± 0.19 vs. 0.55 ± 0.35 mg/L, P = 0.04). In patients admitted to the CCU, CoQ10 levels were negatively associated with age and C-reactive protein levels, and positively associated with body mass index, total cholesterol, and high-density lipoprotein cholesterol levels. Low CoQ10 levels correlated with low diastolic blood pressure. Multivariate logistic regression analysis demonstrated that low CoQ10 levels were an independent predictor of in-hospital mortality. Low serum CoQ10 levels during acute phase are significantly associated with cardiovascular risk and in-hospital mortality in patients admitted to the CCU.

Decreased circulating dihomo-gamma-linolenic acid levels are associated with total mortality in patients with acute cardiovascular disease and acute decompensated heart failure.

BACKGROUND: Polyunsaturated fatty acids (PUFAs) have important roles in the pathogenesis of cardiovascular diseases. However, the clinical significance of omega-6 PUFAs in acute cardiovascular disease remains unknown. METHODS: We enrolled 417 consecutive patients with acute cardiovascular disease admitted to the cardiac intensive care unit at Juntendo University Hospital between April 2012 and October 2013. We investigated the association between serum PUFA levels and long-term mortality. Blood samples were collected after an overnight fast, within 24 h of admission. We excluded patients who received eicosapentaenoic acid therapy and those with malignancy, end-stage kidney disease, chronic hepatic disease, and connective tissue disease. RESULTS: Overall, 306 patients (mean age: 66.4 ± 15.0 years) were analysed. During the follow-up period of 2.4 ± 1.2 years, 50 patients (16.3%) died. The dihomo-gamma-linolenic acid (DGLA) levels, arachidonic acid (AA) levels, and DGLA/AA ratio were significantly lower in the nonsurvivor group than in the survivor group (DGLA: 23.2 ± 9.8 vs. 31.5 ± 12.0 µg/ml, AA: 151.1 ± 41.6 vs. 173.3 ± 51.6 µg/ml, and DGLA/AA: 0.16 ± 0.05 vs. 0.19 ± 0.06, all p < 0.01). Kaplan-Meier curves showed that survival rates were significantly higher in the higher DGLA, AA, and DGLA/AA groups than in their lower counterparts (DGLA and AA; p < 0.01, DGLA/AA; p = 0.01), although omega-3 PUFAs were not associated with prognosis. Furthermore, in patients with acute decompensated heart failure (ADHF), survival rates were significantly higher in the higher DGLA, AA, and DGLA/AA groups than in their lower counterparts (DGLA and AA; p < 0.01, DGLA/AA; p = 0.04). However, among patients with acute coronary syndrome, none of the PUFA levels were associated with prognosis. Among patients with ADHF, after controlling for confounding variables, DGLA and DGLA/AA were associated with long-term mortality [DGLA: hazard ratio (HR), 0.94; 95% confidence interval (CI), 0.88-0.99; p = 0.01 and DGLA/AA: HR, 0.87; 95% CI, 0.77-0.97; p < 0.01], whereas AA was not associated with prognosis. CONCLUSION: Low omega-6 PUFA levels, particularly DGLA, and a low DGLA/AA ratio predict long-term mortality in patients with acute cardiovascular disease and ADHF. TRIAL REGISTRATION: UMIN-CTR; UMIN000007555 .

Successful Treatment of Congestive Heart Failure Due to Severe Aortic Valve Stenosis With Low Dose Tolvaptan in Elderly Patients.

Medical therapy for severe aortic valve stenosis (AS) is necessary for inoperable patients due to comorbid conditions. Tolvaptan (TLV), unlike other diuretics, resulted in modest changes in filling pressures associated with an increase in urine output, suggesting that TLV improves congestive heart failure (CHF) due to severe AS without hemodynamic instability.We retrospectively investigated 14 consecutive patients ≥ 80 years of age admitted due to decompensated CHF with severe AS at Juntendo University Hospital from April 2014 to November 2015. Seven of the 14 patients were treated with TLV. We examined the safety and efficacy of TLV treatment for severe AS.Mean age was 90.0 ± 6.3 years and mean aortic valve area was 0.57 ± 0.22 cm2. Urine volume at day 1 of TLV treatment was increased and urine osmolality significantly decreased at day 1 of TLV treatment (all P < 0.05). New York Heart Association classification and brain natriuretic peptide levels significantly improved 1 week after treatment and at discharge (all P < 0.05) whereas brain natriuretic peptide levels did not improve in the patients without TLV. Severe adverse events did not occur during TLV treatment. During the first 3 days, blood pressure and heart rate were relatively stable. TLV treatment did not affect serum creatinine, blood urea nitrogen, or the estimated glomerular filtration rate.In elderly patients with severe AS, TLV treatment improved CHF without hemodynamic instability. Further prospective studies are needed to assess the safety and efficacy of TLV in decompensated heart failure due to severe AS.

Left ventricular apical aneurysm caused by takotsubo cardiomyopathy.

A 78-year-old woman with hypertension was admitted to our hospital with palpitation and chest discomfort. She had been nervous since she learned about a severe earthquake on the news. An electrocardiogram showed ST-segment elevation in leads I, aVL, and V2-6. Emergency coronary angiography demonstrated no significant coronary stenosis and left ventriculography revealed marked akinesis of apical left ventricle with hyperkinesis of the basal segments, indicating typical takotsubo cardiomyopathy. On day 24, an electrocardiogram showed diffuse T-wave inversion, but ST-segment elevation remained in V3-6. Cardiac magnetic resonance imaging revealed left ventricular apical aneurysm and epicardial late gadolinium enhancement in the apex, indicating takotsubo-inflicted myocardial injury. Although many previous reports show takotsubo cardiomyopathy is a reversible left ventricular systolic dysfunction with less significant complications, it should be reconsidered as benign disease with long-term complications. Learning objective: Although many previous reports show takotsubo cardiomyopathy (TC) is a reversible left ventricular (LV) systolic dysfunction with less significant complications, our patient is a rare case of TC which led to LV apical aneurysm. It was believed that lack of late gadolinium enhancement (LGE) was necessary to diagnose TC, however we detected epicardial LGE in the LV apical wall and this finding might indicate nonreversible change in this case.

Impact of sleep-disordered breathing on overnight changes in arterial stiffness in patients with acute heart failure.

Overnight increases in arterial stiffness associated with sleep-disordered breathing may adversely affect patients with acute heart failure. Thus, we investigated overnight changes in arterial stiffness and their association with sleep-disordered breathing in patients hospitalized for acute heart failure. Consecutive patients with acute heart failure were enrolled. All participants underwent overnight full polysomnography following the initial improvement of acute signs and symptoms of acute heart failure. The arterial stiffness parameter, cardio-ankle vascular index (CAVI), was assessed before and after polysomnography. Overall, 60 patients (86.7% men) were analyzed. CAVI significantly increased overnight (from 8.4 ± 1.6 at night to 9.1 ± 1.7 in the morning, P < 0.001) in addition to systolic and diastolic blood pressure (from 114.1 mmHg to 121.6 mmHg, P < 0.001; and from 70.1 mmHg to 78.2 mmHg, P < 0.001, respectively). Overnight increase in CAVI (ΔCAVI ≥ 0) was observed in 42 patients (70%). The ΔCAVI ≥ 0 group was likely to have moderate-to-severe sleep-disordered breathing (i.e., apnea-hypopnea index ≥15, 55.6% vs 80.9%, P = 0.047) and greater obstructive respiratory events (29.4% vs 58.5%, P = 0.041). In multivariable analysis, moderate-to-severe sleep-disordered breathing and greater obstructive respiratory events were independently correlated with an overnight increase in CAVI (P = 0.033 and P = 0.042, respectively). In patients hospitalized for acute heart failure, arterial stiffness, as assessed by CAVI, significantly increased overnight. Moderate-to-severe sleep-disordered breathing and obstructive respiratory events may play an important role in the overnight increase in cardio-ankle vascular index.