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Background Several echocardiographic parameters are currently used to evaluate left ventricular (LV) filling pressure. However, these parameters are not always consistent in the clinical setting. We aimed to determine a novel parameter by multiplying log B-type natriuretic peptide (lnBNP) and the ratio of mitral inflow early and late diastolic filling velocities (E/A) for the prediction of pulmonary capillary wedge pressure (PCWP). Methods and Results One hundred ninety-eight patients suspected of chronic heart failure were analyzed. The product of lnBNP and E/A (BNP × E/A) showed the highest correlation coefficient with mean PCWP ( R = 0.7326) compared with E/A ( R = 0.7010) and E/e′ ( R = 0.3922). Multivariate logistic regression analysis revealed that BNP × E/A was associated with elevated PCWP (odds ratio 1.640, 95% confidence interval 1.312–2.197; P .01). In the receiver operating characteristic curve analysis for detecting elevated PCWP, BNP × E/A showed the largest area under the curve (AUC) compared with E/A and E/e′ (0.880 vs 0.827 and 0.788, respectively; P .05). BNP × E/A still showed large AUC (0.842) for detection of elevated PCWP in patients with normal LV ejection fraction. Conclusion BNP × E/A is a useful parameter for detecting elevated PCWP regardless of the LV ejection fraction.

Background: Breath acetone is reported to be a noninvasive biomarker for heart failure. However, the measurement of this metabolite requires expertize and is not standardized yet. Acetone is also released from the skin; thus, measuring acetone as a skin gas may be easier than breath analysis. Methods: We analyzed skin acetone collected from 41 hospitalized patients with cardiovascular diseases. Passive samplers were used to measure skin acetone emission. Passive sampler was softly fixed on the surface of forearm skin for 10 hour at night. Results: Skin acetone emission ranged from 0.00 to 2.70 ng/cm2/h, and was significantly correlated with blood ketone bodies (r = 0.377, p = 0.017). Conclusions: This is the first study to analyze skin gas in patients with cardiovascular diseases. Skin acetone emission was found to reflect blood ketone bodies. It is feasible to measure skin acetone emission for reflecting blood ketone bodies in patients with cardiovascular diseases.

Background: Atrial septal defect is the third most common type of congenital heart disease. Surgical closure was the standard treatment for atrial septal defects before transcatheter closure was approved as minimally invasive treatment in Japan in 2006. In our hospital, this procedure has been performed since 2015. Objective: To evaluate the safety and effectiveness of transcatheter closure of atrial septal defects in our hospital. Methods: Thirty patients (mean age 57.0 ± 19.7 years, 11 males), who underwent transcatheter closure of atrial septal defect between September 2015 and February 2018 at the Fukushima Medical University Hospital, were enrolled. All procedures were performed under general anesthesia with angiographic and transesophageal echocardiographic guidance. Safety and effectiveness were evaluated by the procedural results and complications. Results: All 30 patients successfully underwent transcatheter closure of atrial septal defects and no patient developed complications. New York Heart Association functional class was improved, and the right ventricular area and right atrium area were decreased, postoperatively. Conclusion: Transcatheter closure is a safe and effective treatment for atrial septal defects, and thus could be an alternative option to open heart surgery.

Hereditary ATTR amyloid cardiomyopathy is defined as the intramyocardial deposition of amyloid fibrils derived from the mutation of transthyretin (TTR). A 51-year-old man was referred to our hospital for congestive heart failure. He and his family had no past history of heart diseases. Echocardiography showed remarkable left ventricular hypertrophy and reduced ejection fraction. Endomyocardial biopsy specimens presented positive staining of Congo-Red and transthyretin. A genetic test showed heterozygous V122I TTR gene mutation, which is very rare in Japan. We diagnosed him as with sporadic ATTR amyloidosis with mutation, and tafamidis was administered to stabilize TTR tetramer. Since the phenotype of ATTR amyloidosis varies depending on its penetration rate, it is crucial to always keep in mind the possibility of hereditary ATTR amyloidosis even in the case of amyloidosis with no clear family history.

AIM To explore changes in left ventricular (LV) function and the relationship of these changes with myocardial blood flow (MBF) evaluated by 13N-ammonia hybrid positron-emission tomography (PET)/magnetic resonance imaging (MRI) during vasodilator stress in patients with suspected coronary artery disease (CAD). MATERIALS AND METHODS Fifty-two consecutive patients with suspected CAD, who underwent 13N-ammonia PET/MRI, were enrolled. Vasodilator stress was induced by intravenous injection of adenosine. MBF and coronary flow reserve (CFR) were calculated from dynamic acquisition of 13N-ammonia PET. LV function was evaluated by MRI both at rest and during vasodilator stress. An abnormal perfusion on myocardial images was defined as a summed difference score of ≥4. RESULTS MRI showed that the LV end-diastolic volume, LV end-systolic volume, and LV ejection fraction (LVEF) remained unchanged during vasodilator stress in all patients (n=52) as well as in the patients with CFR of 5% during vasodilator stress. In these four patients, CFR was lower (1.57 ± 0.12 versus 2.18 ± 0.86, p CONCLUSION The LV volume and systolic function evaluated by cardiac MRI remained unchanged during vasodilator stress; however, LV dysfunction during vasodilator stress may occur in patients with severe CAD.

Aims Heart failure with preserved ejection fraction (HFpEF) has several pathophysiological aspects, including stiffness and/or congestion of multiple organs. Poor prognosis is expected in heart failure patients with liver stiffness, which has recently been assessed by non-alcoholic fatty liver disease fibrosis score (NFS; based on aspartate aminotransferase to alanine aminotransferase ratio, platelet counts, and albumin). We aimed to investigate the impact of NFS on prognosis of HFpEF patients, with consideration for the peripheral collagen markers such as procollagen type III peptide (PIIIP), type IV collagen 7S, and hyaluronic acid. Methods and results We performed a prospective observational study. Consecutive 492 hospitalized HFpEF patients were divided into four groups based on their NFS: first–fourth quartiles (n = 123). The fourth quartile group had the highest levels of PIIIP, type IV collagen 7S, hyaluronic acid, and B-type natriuretic peptide (P

Aims The failing heart is accompanied by disturbed energy metabolism with mitochondrial dysfunction. Carnitine transports fatty acids into mitochondria for β-oxidation. Decreased myocardial carnitine levels accompanied by increased plasma carnitine levels in heart failure (HF) have been reported. The plasma acylcarnitine to free carnitine ratio (AC/FC) is recognized as a marker of carnitine deficiency. We aimed to investigate the impact of the AC/FC on HF prognosis, taking into consideration differences between HF patients with preserved ejection fraction (HFpEF) and those with reduced ejection fraction (HFrEF). Methods and results Consecutive 168 HF patients were divided into three groups based on their AC/FC: first to third tertiles (n = 56, respectively). We followed up all patients for cardiac events including cardiac death and/or worsening HF. During the follow-up period (1004 days), there were 23 cardiac deaths and 28 worsening HF. In the Kaplan–Meier analysis, the cardiac event rate of the third group was highest among the three groups (P = 0.022). In the Cox proportional hazard analysis, AC/FC was a predictor of cardiac events (P = 0.007). When HFpEF (n = 79) and HFrEF (n = 89) were analysed separately, the cardiac event rate of the third group was highest with regard to HFpEF (P = 0.008), but not HFrEF (P = 0.321). In the Cox proportional hazard analysis, AC/FC was a predictor of cardiac events with regard to HFpEF (P = 0.031), but not HFrEF (P = 0.095). Therefore, the impact of the AC/FC on cardiac events was different between HFpEF and HFrEF (P = 0.042 for interaction). Conclusions The AC/FC can identify high risk HF patients, especially in HFpEF.

Aim To investigate the clinical features of heart failure in extremely elderly patients. Methods We analyzed 1163 consecutive hospitalized heart failure patients. The patients were divided into an extremely elderly group (≥85 years-of-age, n = 88) and a non-extremely elderly group (

Background: The intravascular compartment is known as the plasma volume, and the extravascular compartment represents fluid within the interstitial space. Plasma volume expansion is a major symptom of heart failure. The aim of the current study was to investigate the impact of plasma volume status on the prognosis of acute heart failure syndromes. Methods and results: We analyzed 1115 patients with acute heart failure syndromes who were admitted to our hospital. These patients were divided into three groups based on their plasma volume status at admission: first tertile (plasma volume status Conclusion: Increased congestion is associated with increased morbidity and mortality in heart failure patients. Plasma volume status, which represents intravascular compartment and congestion, can identify poor prognosis in patients with acute heart failure syndromes.

BackgroundIntake of n-3 polyunsaturated fatty acids (n-3 PUFAs) lowers the risk of atherosclerotic cardiovascular events, particularly ischemic heart disease. In addition, the ratio of eicosapentaenoic acid (EPA; n-3 PUFA) to arachidonic acid (AA; n-6 PUFA) has recently been recognized as a risk marker of cardiovascular disease. In contrast, the prognostic impact of the EPA/AA ratio on patients with heart failure (HF) remains unclear.Methods and ResultsA total of 577 consecutive patients admitted for HF were divided into 2 groups based on median of the EPA/AA ratio: low EPA/AA (EPA/AA

A growing body of evidence suggests that mitral regurgitation (MR) is associated with higher mortality in heart failure patients with reduced ejection fraction. However, prognostic impact of MR on heart failure patients with preserved ejection fraction (HFpEF) has not been fully examined. The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, prospective registration of consecutive Japanese hospitalized HFpEF patients with LVEF ≥ 50%. Severe valvular heart disease was excluded from this cohort. We divided the consecutive 341 patients into two groups based on the severity of MR at discharge: no or mild MR group (n = 317) and moderate MR group (n = 24). Compared with no or mild MR group, moderate MR group showed larger left ventricular end-diastolic diameter (52 [48–59] vs. 46 [42–50] mm, P

The restless legs syndrome (RLS) is a neurological disorder characterized by an irresistible urge to move the legs or arms for relief of uncomfortable or unpleasant sensations. Prevalence and prognostic impact of RLS on patients with heart failure (HF) remain unclear. We aimed to investigate the clinical characteristics and prognostic impact of RLS on HF patients.Consecutive 338 HF patients were evaluated for RLS and divided into two groups on the basis of presence of RLS: HF patients with RLS (RLS group, n = 29) and HF patients without RLS (non-RLS group, n = 309). We compared clinical characteristics, parameters of laboratory data and echocardiography, and rate of follow-up cardiac events including worsening HF and cardiac death between the two groups. Compared with the non-RLS group, the RLS group had higher prevalence of anemia (65.5% versus 40.8%, P = 0.010), higher usage of inotropic agents (31.0% versus 15.2%, P = 0.028), higher levels of B-type natriuretic peptide (570.8 versus 215.8 pg/mL, P = 0.018), and lower levels of left ventricular ejection fraction (40.4% versus 48.4%, P = 0.019). By contrast, age, gender, prevalence of other co-morbidities and medications were comparable between the groups. In the Kaplan-Meier analysis, the cardiac event rate was significantly higher in the RLS group than in the non-RLS group (log-rank P = 0.034). In the Cox proportional hazard analysis, RLS was a predictor for cardiac events in HF patients (hazard ratio: 1.783, 95% confidence interval: 1.038-3.063).RLS is associated with adverse prognosis in HF patients.

Background: Acetoacetate is used as an alternative energy source in the heart, and has the potential to improve cardiac function. However, the prognostic impact of acetoacetate has not been investigated in heart failure. Methods: This study enrolled consecutive 615 hospitalized patients with heart failure. We investigated the associations between circulating acetoacetate and clinical characteristics or prognosis in HF patients. Results: We divided the patients into two groups based on circulating acetoacetate levels (high group: acetoacetate ≥35 µmoL/L, n = 313; and low group: acetoacetate

The clinical scenario, which is based on systolic blood pressure (SBP) upon admission, is useful for classifying and determining initial treatment for acute heart failure (HF). However, the prognostic significance of SBP following the initial treatment is unclear.The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, and prospective registration of consecutive Japanese patients hospitalized with HF with preserved ejection fraction (HFpEF) and left ventricular ejection fraction ≥ 50%. We divided 525 patients into three groups based on their SBP on the day following hospitalization: high (SBP140 mmHg, n = 72, 13.7%); normal (100 ≤ SBP ≤ 140 mmHg, n = 379, 72.2%); and low (SBP100 mmHg, n = 74, 14.1%) groups. This analysis had two primary endpoints: (1) all-cause death and (2) all-cause death or rehospitalization for HF. In the Kaplan-Meier analysis, both of the endpoints were the highest in the low group (Log-Rank0.05, respectively). Compared to the normal and high groups, the low group demonstrated a higher prevalence of atrial fibrillation (67.1%, 63.9%, and 47.8%, P = 0.026) and the lowest left ventricular outflow tract velocity time integral determined by echocardiography (16.4 cm, 19.4 cm, and 23.3 cm, P = 0.001). In the multivariable Cox proportional hazard analysis, low SBP on the day following hospitalization was an independent predictor of all-cause death (hazard ratio 1.868, 95% confidence interval 1.024-3.407, P = 0.042) and the composite endpoint (hazard ratio 1.660, 95% confidence interval 1.103-2.500, P = 0.015).Classification based on SBP on the day following initial treatment predicts post-discharge prognosis in hospitalized patients with HFpEF.

BACKGROUND Heart failure (HF) and cancer (CA) are becoming increasingly prevalent as the population ages. We aimed to evaluate prior history and occurrence of CA and its prognostic impact on HF.Methods and Results:Consecutive hospitalized HF patients (n=2,103) were divided into 2 groups according to prior history of CA: non-prior-CA group (n=1,828) and prior-CA group (n=275). Compared with the non-prior-CA group, the prior-CA group were older, and had higher prevalence of chronic kidney disease, anemia, and atrial fibrillation (P

Aims Atrial fibrillation (AF) is common in patients with heart failure (HF). CHA2DS2-VASc score was originally employed as a risk assessment tool for stroke in patients with AF; however, it has recently been used to predict not only stroke but also various cardiovascular diseases beyond the original AF field. We aimed to verify the CHA2DS2-VASc score as a risk assessment tool to predict mortality in patients with HF. Methods and Results Consecutive 1011 patients admitted for treatment of HF were divided into three groups based on their CHA2DS2-VASc scores: score 1–3 group (n = 317), score 4–6 group (n = 549) and score 7–9 group (n = 145). Of the 1011 HF patients, 387 (38.3%) had AF. We compared patient characteristics among the three groups and prospectively followed for all-cause mortality. Although left ventricular ejection fraction was similar among all three groups, all-cause mortality was higher in the score 4–6 group and score 7–9 group than in the score 1–3 group (37.9 and 29.3% vs. 15.1%, log-rank P

In heart failure patients, exhaled acetone concentration, a noninvasive biomarker, is increased according to heart failure severity. Moreover, exhaled acetone concentration is also known to be affected by diabetes mellitus. However, there have been no reports on exhaled acetone concentration in heart failure patients with diabetes mellitus. A 77-year old man was admitted to our hospital with acute decompensated heart failure and atrioventricular block. He had controlled diabetes mellitus under insulin treatment with hemoglobin A1c of 6.5%. He underwent treatment of diuretics and permanent pacemaker implantation. His condition improved and he was discharged at Day 12. Due to the heart failure improvement, his levels of exhaled acetone concentration decreased from 1.623 ppm at admission to 0.664 ppm at discharge. This is the first report to reveal a change of exhaled acetone concentration in a diabetic patient with acute decompensated heart failure.

Although the use of trastuzumab has been reported to improve overall survival in patients with HER2-positive breast cancer, there is increasing concern about the adverse effects of trastuzumab-induced cardiotoxicity (TIC). The aim of the present study was to investigate the predictor of TIC and to consider appropriate management for such patients. The present study breast cancer 119 patients with breast cancer who had been treated with trastuzumab. Patients were referred to our department for cardiac function screening. The patients' baseline characteristics, echocardiographic data, presence of trastuzumab-induced cardiotoxicity (TIC) and all-cause mortality were investigated. TIC was defined as a manifestation of overt heart failure or ≥10% reduction of left ventricular ejection fraction (LVEF) from baseline to an LVEF

Background The prognostic impact of chronic obstructive pulmonary disease (COPD) on heart failure (HF) with preserved ejection fraction (HFpEF) patients and its clinical characteristics have not yet been fully examined. Methods The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, prospective registration of consecutive Japanese hospitalized HFpEF patients with left ventricular ejection fraction (LVEF) of ≥50%. Among 535 patients enrolled in the registry, 10 lacking COPD data, and seven who died during the first hospitalization, were excluded. Finally, 518 patients were enrolled in this analysis. We divided these patients into two groups: the COPD group (n = 40, 7.7%) and the non-COPD group (n = 478, 92.3%). This analysis had two primary endpoints: (1) all-cause death and (2) all-cause death or rehospitalization for HF. Results The COPD group showed a higher prevalence of male sex (70.0% vs. 48.1%, p = 0.008), history of prior hospitalization for HF (63.2% vs. 35.1%, p = 0.001), smoking history (71.8% vs. 43.3%, p = 0.001), and a higher usage of loop diuretics (70.0% vs. 50.0%, p = 0.015). In the follow-up period after discharge (median 733 days), there were 82 all-cause deaths and 127 rehospitalizations for HF. In the Kaplan–Meier analysis, the COPD group showed higher all-cause death and reached the composite endpoint more often than in the non-COPD group (all-cause death, log-rank 0.035; all-cause death or rehospitalization for HF, log-rank 0.025). In the Cox proportional hazard analysis, COPD was a predictor of all-cause death (hazard ratio 1.957, 95% confidence interval 1.037–3.694, p = 0.038) and the composite endpoint (hazard ratio 1.694, 95% confidence interval 1.064–2.697, p = 0.026). Conclusions COPD is associated with adverse prognosis in hospitalized patients with HFpEF.

Aims It has been reported that circulating soluble neprilysin (sNEP), which catalyses the degradation of several vasodilator peptides such as natriuretic peptides, predicts prognosis in heart failure patients with reduced ejection fraction. Hypoxia‐induced decrease in NEP expression in lungs has been reported. However, the associations between sNEP and haemodynamic parameters, as well as the prognostic impact of sNEP in pulmonary hypertension (PH), remain unclear. We aimed to clarify the relationships between sNEP and natriuretic peptide, haemodynamics (e.g. parameters of echocardiography and right heart catheter) or prognosis in PH patients. Methods and results First, we examined the associations between sNEP levels and natriuretic peptide, echocardiography, or right heart catheter in PH patients (mean pulmonary artery pressure ≥ 25 mmHg and pulmonary artery wedge pressure ≤ 15 mm Hg on the basis of right heart catheterization, n = 79). Next, we followed up the patients for all‐cause mortality. Laboratory data revealed no significant correlations between sNEP and B‐type natriuretic peptide (R = 0.022, P = 0.872), N‐terminal proBNP (R = −0.018, P = 0.872), and high‐sensitivity troponin I (R = 0.206, P = 0.107). Regarding the parameters of echocardiography and right heart catheter, there were no significant correlations between sNEP and left ventricular ejection fraction (R = −0.036, P = 0.764), right ventricular fractional area change (R = −0.259, P = 0.064), tricuspid valve pressure gradient (R = −0.037, P = 0.767), and any of the right heart catheter parameters. In the Kaplan–Meier analysis (mean follow‐up, 1284 days, log‐rank P = 0.531), all‐cause mortality rates were comparable between the higher NEP group (sNEP ≥ median levels of 1.45 ng/mL, n = 39) and the lower NEP group (sNEP

Background The Get With the Guidelines–Heart Failure ( GWTG ‐ HF ) risk score was developed using American Heart Association GWTG ‐ HF program data and predicts in‐hospital mortality in patients with acute heart failure (HF). We aimed to clarify the prognostic impacts of the GWTG ‐ HF risk score in patients with HF after discharge. Methods and Results We examined the GWTG ‐ HF score in 1452 patients with HF, who were admitted to our hospital and discharged after treatment, by calculating 7 predetermined variables. We divided all subjects into 3 groups according to the GWTG ‐ HF risk score (low, moderate, and high score groups). The plasma B‐type natriuretic peptide level significantly increased with increasing GWTG ‐ HF risk score severity (median values of B‐type natriuretic peptide: 167.0 in low, 260.7 in moderate, and 418.2 pg/mL in high score groups). We followed up all subjects after discharge, and there were 347 (23.9%) all‐cause deaths and 407 (28.0%) cardiac events in follow‐up periods. A Kaplan‐Meier survival curve demonstrated that event rates of all‐cause death and cardiovascular events, including worsening HF and cardiac death, significantly increased with increasing GWTG ‐ HF risk score severity in all subjects, and also in 749 patients with HF with preserved ejection fraction (ejection fraction ≥50%) and 703 patients with HF with reduced ejection fraction (ejection fraction GWTG ‐ HF risk score was one of the significant predictors of all‐cause mortality and cardiac events (all‐cause mortality: hazard ratio, 1.537, 95% confidence interval, 1.172–2.023; cardiac events: hazard ratio, 1.584, 95% confidence interval, 1.344–1.860, per 10‐point increase of GWTG ‐ HF score). Conclusions The GWTG ‐ HF risk score is a useful multivariable score model for several years after hospitalization in patients with HF in a Japanese population.

Sarcoidosis is a systemic granulomatous disease including heart (cardiac sarcoidosis, CS). It has recently been reported that isolated CS, which presenting primarily cardiac symptoms without clinical evidence of sarcoid involvement in other organs. Diagnostic and prognostic biomarkers of CS, especially in isolated CS, have not yet been established.We studied plasma levels of angiotensin-converting enzyme (ACE), soluble interleukin-2 receptor (sIL-2R), B-type natriuretic peptide (BNP) and cardiac troponin I (cTnI) in consecutive 172 patients with diagnosed sarcoidosis. We compared these markers between non-cardiac sarcoidosis (non-CS, n = 123, 71.5%) and CS patients (n = 49, 28.5%), including non-isolated CS (n = 30, 17.4%) and isolated CS (n = 19, 11.1%). ROC analysis revealed that BNP identified CS with AUC of 0.85 (P < 0.01) in sarcoidosis patients. In addition, ACE and sIL-2R levels were significantly higher in non-isolated CS than in isolated CS (P < 0.05). Furthermore, in the Cox proportional hazard analysis, cTnI, but not ACE, IL2R or BNP, was a predictor of fatal arrhythmia in sarcoidosis patients (HR 2.418, P = 0.003).Higher ACE and sIL2-R are associated with systemic lesions, whereas BNP is a useful marker for detecting cardiac involvement in sarcoidosis patients. cTnI is a predictor of fatal arrhythmia in CS patients. A multiple biomarker approach supports comprehensive management of sarcoidosis.

Exhaled acetone concentration is one of the expected compounds to be a breath biomarker in heart failure. However, it has not been clarified how exhaled acetone concentration changes in clinical course of heart failure.To investigate whether exhaled acetone concentration changes after treatment in acute decompensated heart failure (ADHF).This study included 19 patients with ADHF (ADHF group) and eight patients with stable heart failure (control group). Exhaled acetone was collected from these patients, and the concentration was measured with gas chromatography.The ADHF group had higher heart rates (P = 0.046), higher New York Heart Association class (P0.001), higher levels of brain natriuretic peptide (P = 0.026), blood total ketone bodies (P = 0.015), and exhaled acetone concentration (P0.001), compared with the control group. In ADHF group, exhaled acetone concentration significantly decreased after treatment (median: 2.40 versus 0.92 ppm, P0.001). However, in the control group, exhaled acetone concentration did not significantly change (median: 0.73 versus 0.49 ppm, P = 0.141).In these preliminary findings, exhaled acetone concentration in patients with ADHF drastically decreased by treatment. Serial exhaled acetone measurement might be useful to evaluate the course of ADHF.

The differential diagnosis of cardiomyopathy is important. It has been recently reported that urinary titin N (U-TN) is increased in patients with muscular dystrophy (MD), and is associated with muscular damage. We aimed to clarify whether U-TN is useful as a diagnostic tool for distinguishing MD from various cardiomyopathies [e.g. dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM)]. We measured and compared the U-TN/creatinine ratio (U-TN/Cr; pmol/mg/dl) in 278 control subjects and 331 patients with various cardiomyopathies (DCM, n = 199; sarcoidosis, n = 18; HCM, n = 86; amyloidosis, n = 15; Fabry disease, n = 6; MD, n = 7). The U-TN/Cr was significantly higher in MD patients than in patients with various cardiomyopathies and the control subjects (P 0.001). From the ROC analysis, the U-TN/Cr (with a cut-off value of 8.7) identified MD with 100% sensitivity, 82% specificity, and an area under the curve (AUC) of 0.92 (95% CI 0.87-0.98, P 0.001). The AUC of the U-TN/Cr that was able to predict MD was superior to those of U-TN, creatinine kinase, B-type natriuretic peptide, and troponin I. Urinary Titin-N is a novel marker to diagnose MD.

Background Atrial fibrillation (AF) is common in patients with heart failure and is associated with higher mortality. Although previous studies have reported that direct oral anticoagulants (DOACs) reduce the risk of cardiovascular events in out-patients with AF, it remains unclear whether DOACs reduce mortality in hospitalized heart failure (HHF) patients with AF. Therefore, we examined the impact of DOACs on mortality in this group of patients. Methods Consecutive 497 HHF patients with AF were retrospectively registered and divided into three groups on the basis of the presence of anticoagulant therapy: non-anticoagulant group (Non, n = 90), Vit K antagonists (VKAs) group (n = 257) and DOACs group (n = 150). We followed up all the patients for mortality. Results In the Kaplan-Meier analysis (mean follow-up of 1093 days), all-cause mortality was significantly lower in the VKAs and DOACs groups than in the Non group (31.1% and 15.3% vs. 43.3%, log-rank P

A 40-year-old man was transferred to our hospital following an isolated horse kick injury to the anterior chest wall. The case showed bi-fascicular block, severe tricuspid valve regurgitation due to ruptured chordae tendineae of the anterior leaflet, moderate mitral valve regurgitation due to prolapse of mitral anterior leaflet, and hypokinetic motion of the inferior septal wall. Both tricuspid and mitral insufficiency were completely repaired by a surgical operation. Fortunately, these injuries were not fatal in this case, but the comprehensive assessment of cardiac damage and careful observation are important for managing patients with cardiac injury.

Background Pulmonary hypertension (PH) is a common complication of chronic respiratory disease. Recent studies have reported diabetes mellitus (DM) to be a poor prognostic factor in patients with chronic respiratory disease, including chronic obstructive pulmonary disease or interstitial pneumoniae. However, the association between DM and PH in chronic respiratory disease remains unclear. In this study, we aimed to investigate whether DM is a predictor of PH in patients with chronic respiratory disease. Methods We prospectively analyzed 386 patients in our hospital with chronic respiratory disease. An echocardiographic pressure gradient between the right atrium and the right ventricle of ≥ 40 mmHg was defined as PH. We compared the clinical characteristics and impact of DM between chronic respiratory disease patients with and those without PH. Results Of the 386 patients, 42 (10.9%) were diagnosed as having PH. The PH group had higher modified medical research council (mMRC) grade and complication rate of DM, but not hypertension and hyperlipidemia, when compared to the non-PH group. Multivariable logistic regression analysis revealed that mMRC scale (odds ratio 1.702, 95% confidence interval, 1.297 to 2.232, P < 0.001) and presence of DM (odd ratio 2.935, 95% confidence interval, 1.505 to 5.725, P = 0.002) were associated with PH in chronic respiratory disease patients. Conclusion DM is potentially associated with PH and is an independent factor for prediction of PH in patients with chronic respiratory disease.

Serum uric acid is a predictor of cardiovascular mortality in heart failure with reduced ejection fraction. However, the impact of uric acid on heart failure with preserved ejection fraction (HFpEF) remains unclear. Here, we investigated the association between hyperuricemia and mortality in HFpEF patients. Consecutive 424 patients, who were admitted to our hospital for decompensated heart failure and diagnosed as having HFpEF, were divided into two groups based on presence of hyperuricemia (serum uric acid ≥7 mg/dl or taking antihyperuricemic agents). We compared patient characteristics, echocardiographic data, cardio-ankle vascular index, and cardiopulmonary exercise test findings between the two groups and prospectively followed cardiac and all-cause mortality. Compared with the non-hyperuricemia group ( n = 170), the hyperuricemia group ( n = 254) had a higher prevalence of hypertension ( P = 0.013), diabetes mellitus ( P = 0.01), dyslipidemia ( P = 0.038), atrial fibrillation ( P = 0.001), and use of diuretics ( P < 0.001). Cardio-ankle vascular index (8.7 vs. 7.5, P < 0.001) and V̇e/V̇co2 slope (34.9 vs. 31.9, P = 0.02) were also higher. In addition, peak V̇o2 (14.9 vs. 17.9 ml·kg−1·min−1, P < 0.001) was lower. In the follow-up period (mean 897 days), cardiac and all-cause mortalities were significantly higher in those with hyperuricemia ( P = 0.006 and P = 0.004, respectively). In the multivariable Cox proportional hazard analyses after adjustment for several confounding factors including chronic kidney disease and use of diuretics, hyperuricemia was an independent predictor of all-cause mortality (hazard ratio 1.98, 95% confidence interval 1.036–3.793, P = 0.039). Hyperuricemia is associated with arterial stiffness, impaired exercise capacity, and high mortality in HFpEF.

Background Right-heart dysfunction is associated with poor prognosis in heart failure with preserved left ventricular ejection fraction (HFpEF). It remains unclear whether sleep-disordered breathing (SDB) treatment using positive airway pressure (PAP) improves right-heart and pulmonary function and exercise capacity and reduces mortality rates of HFpEF patients. Hypothesis PAP may improve right-heart and pulmonary function, exercise capacity and prognosis in HFpEF patients with SDB. Methods One hundred nine consecutive patients with HFpEF (left ventricular ejection fraction >50%) and moderate to severe SDB (apnea-hypopnea index ≥15/h) treated with medications were divided into 2 groups: 31 patients with PAP (PAP group) and 78 patients without PAP (non-PAP group). Right ventricular fractional area change (RV-FAC), tricuspid valve regurgitation pressure gradient (TR-PG), tricuspid valve E/E′, forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC), percentage of vital capacity, and peak VO2 were determined before and 6 months later, and all-cause mortality was followed up for 916 days. Results All parameters improved in the PAP group (RV-FAC, 36.0% –46.5%; TR-PG, 31.1 mm Hg–22.4 mm Hg; tricuspid valve E/E′, 7.8–5.1; FEV1/FVC, 83.9%–89.8%; percentage of vital capacity, 83.5%–89.9%; and peak VO2, 16.6 mL/kg/min–19.6 mL/kg/min; P

Titin is associated with myocardial stiffness and hypertrophy, and mutations in its gene have been identified in cardiac myopathies such as dilated cardiomyopathy (DC). It has recently been reported that in damaged muscle, the N-terminal fragment of titin (Titin-N) is cleaved by calpain-3, and urinary Titin-N (U-TN) could be a marker of sarcomere damage. We aimed to investigate the impact of U-TN on prognosis of DC. We measured urinary levels of Titin-N/creatinine ratio (U-TN/Cr; pmol/mg/dl) in 102 patients with DC, and followed up all the patients (mean 1,167 days). The patients were divided into 3 groups based on the U-TN/Cr: first (U-TN/Cr

Background Breath acetone is a noninvasive biomarker of heart failure; however, its significance in heart failure patients with diabetes mellitus has yet to be clarified. The objective of this study is to investigate whether exhaled acetone concentration is a noninvasive biomarker in heart failure patients with diabetes mellitus. Methods This study prospectively included 35 diabetic patients with stage C heart failure and 20 diabetic patients with or at risk of heart failure (stage A or B). Exhaled breath was collected after an overnight fast. Results The stage C group had significantly higher brain natriuretic peptide levels, larger left ventricular diameter, lower left ventricular ejection fraction, and more frequent use of β-blocker, compared with the stage A or B group. The stage C group had higher exhaled acetone concentrations than the stage A or B group (p = 0.013). Exhaled acetone concentration was correlated with total ketone bodies (r = 0.588, p

Zinc is an essential cofactor for energy transfer and physiological heart function, has antioxidant properties, and is involved in multiple signaling pathways. We aimed to investigate the associations between serum zinc levels with prognosis, as well as underlying cardiac function and exercise capacity, in patients with heart failure (HF).We measured serum zinc levels in 968 consecutive hospitalized patients with decompensated HF, who were divided into 3 groups based on serum zinc levels (µg/dL): first (zinc ≥75, n = 323), second (62≤ zinc75, n = 322), and third (zinc62, n = 323) tertiles. We examined cardiac function and exercise capacity and followed up on all patients. Although cardiac function did not differ among the 3 groups, peak oxygen consumption was significantly lower in the third tertile than in the first and second tertiles (peak oxygen consumption, 14.2 vs 15.9 and 15.2 mL/kg/min, P = .010). In the Kaplan-Meier analysis (mean duration of follow-up 1103 days), cardiac and all-cause mortality was highest in the third tertile compared with the first and second tertiles. In the Cox proportional hazard analysis, serum zinc level was a predictor of cardiac and all-cause mortality. In the subgroup analysis, there were no interactions concerning associations between serum zinc levels with prognosis and other important variables, including age, gender, comorbidities, medications, other micronutrient levels, B-type natriuretic peptide, and left ventricular ejection fraction. The associations between zinc levels with mortality were consistent in all subgroups.Decreased serum zinc levels are associated with high mortality, accompanied by impaired exercise capacity.

It is widely recognized that overt hyper- as well as hypothyroidism are potential causes of heart failure (HF). Additionally it has been recently reported that subclinical hypothyroidism (sub-hypo) is associated with atherosclerosis, development of HF, and cardiovascular death. We aimed to clarify the effect of sub-hypo on prognosis of HF, and underlying hemodynamics and exercise capacity.We measured the serum levels of thyroid stimulating hormone (TSH) and free thyroxine (FT4) in 1100 consecutive HF patients. We divided these patients into 5 groups on the basis of plasma levels of TSH and FT4, and focused on euthyroidism (0.4 ≤ TSH ≤ 4 μIU/mL and 0.7 ≤ FT4 ≤ 1.9 ng/dL; n = 911; 82.8%) and sub-hypo groups (TSH4 μIU/mL and 0.7 ≤ FT4 ≤ 1.9 ng/dL; n = 132; 12.0%). We compared parameters of echocardiography, cardiopulmonary exercise testing, and cardiac catheterization, and followed up for cardiac event rate and all-cause mortality between the 2 groups.Although left ventricular ejection fraction did not differ between the 2 groups, the sub-hypo group had lower peak breath-by-breath oxygen consumption and higher mean pulmonary arterial pressure than the euthyroidism group (peak breath-by-breath oxygen consumption, 14.0 vs 15.9 mL/min/kg; P = 0.012; mean pulmonary arterial pressure, 26.8 vs 23.5 mm Hg, P = 0.020). In Kaplan-Meier analysis (mean 1098 days), the cardiac event rate and all-cause mortality were significantly higher in the sub-hypo group than those in the euthyroidism group (log rank, P 0.01, respectively). In Cox proportional hazard analysis, sub-hypo was a predictor of cardiac event rate and all-cause mortality in HF patients (P 0.05, respectively).Sub-hypo might be associated with adverse prognosis, accompanied by impaired exercise capacity and higher pulmonary arterial pressure, in HF patients.

Background Effective treatments in heart failure (HF) patients with ischemic etiology have not been fully established. Nicorandil, combination of nitrate component and sarcolemmal adenosine triphosphate-sensitive potassium channel opener, is a potent vasodilator of coronary and peripheral vessels and has been used as an antianginal agent. Therefore, we examined impacts of nicorandil on cardiac mortality in ischemic HF patients. Methods Consecutive 334 HF patients with ischemic etiology were retrospectively registered and divided into 2 groups based on oral administration of nicorandil: nicorandil group (n = 116) and non-nicorandil group (n = 218). We retrospectively examined cardiac mortality. Results In the Kaplan-Meier analysis (mean follow-up period 963 days), cardiac mortality was significantly lower in the nicorandil group than in the non-nicorandil group (11.2% vs. 19.7%, P = 0.032). In the Cox proportional hazard analysis, usage of nicorandil was a suppressor of cardiac mortality (hazard ratio 0.512, 95% confidence interval 0.275–0.953, P = 0.035), and this result was consistent in several subgroup analyses, such as left ventricular ejection fraction, percutaneous coronary intervention, coronary artery bypass graft, diabetes, β-blockers, and statins. Conclusion Nicorandil is potentially effective for reducing mortality in patients with ischemic heart failure. Trial registration This was a retrospective study.

Background It has been recently reported that histamine H 2 receptor antagonists (H2 RA s) are associated with impairment of ventricular remodeling and incident heart failure. In addition, favorable pleiotropic effects and adverse effects of proton pump inhibitors ( PPI s) on cardiovascular disease have also been reported. We examined the associations of acid suppressive therapy using H2 RA s or PPI s with cardiac mortality in patients with heart failure. Methods and Results In total, 1191 consecutive heart failure patients were divided into 3 groups: a non–acid suppressive therapy group (n=363), an H2 RA group (n=164), and a PPI group (n=664). In the follow‐up period (mean 995 days), 169 cardiac deaths occurred. In the Kaplan–Meier analysis, cardiac mortality was significantly lower in the PPI group than in the H2 RA and non–acid suppressive therapy groups (11.0% versus 21.3% and 16.8%, respectively; log‐rank P =0.004). In the multivariable Cox proportional hazards analysis, use of PPI s, but not H2 RA s, was found to be an independent predictor of cardiac mortality ( PPI s: hazard ratio 0.488, P =0.002; H2 RA s: hazard ratio 0.855, P =0.579). The propensity‐matched 1:1 cohort was assessed based on propensity score (H2 RA s, n=164; PPI s, n=164). Cardiac mortality was significantly lower in the PPI group than in the H2 RA group in the postmatched cohort (log‐rank P =0.025). In the Cox proportional hazards analysis, the use of PPI s was a predictor of cardiac mortality in the postmatched cohort (hazard ratio 0.528, P =0.028). Conclusions PPI s may be associated with better outcome in patients with heart failure.

Background: High mitral inflow early (E) velocity to tissue Doppler E′ ratio (E/E′) and an E to late diastolic filling velocity ratio (E/A) are used to evaluate left ventricular (LV) diastolic function and filling pressure, but the usefulness of combined assessment of E/E′ and E/A is not fully understood. Methods: We retrospectively analyzed 1,266 patients who underwent echocardiography to assess cardiac function. Patients were grouped based on the values of E/E′ (low E/E′0.8). Results: High E/E′ with both high and low E/A groups showed lower LV ejection fraction and higher LV mass index compared to low E/E′ with both high and low E/A groups. High E/E′ with both high and low E/A groups showed slower E′ velocity and larger left atrial volume index compared to low E/E′ with both high and low E/A groups, but high E/E′ with low E/A group exhibited smaller left atrial volume index and higher pulmonary venous systolic to diastolic peak velocity ratio compared to high E/E′ with high E/A group. Moreover, high E/E′ with low E/A group displayed lower tricuspid regurgitant pressure gradient than the high E/E′ with high E/A group. Conclusion: Even in the situation of high E/E′, low E/A condition indicated lower LV filling pressure and controlled fluid retention.

Aims The failing heart is accompanied by disturbed energy metabolism with mitochondrial dysfunction. Carnitine transports fatty acids into mitochondria for β‐oxidation. Decreased myocardial carnitine levels accompanied by increased plasma carnitine levels in heart failure (HF) have been reported. The plasma acylcarnitine to free carnitine ratio (AC/FC) is recognized as a marker of carnitine deficiency. We aimed to investigate the impact of the AC/FC on HF prognosis, taking into consideration differences between HF patients with preserved ejection fraction (HFpEF) and those with reduced ejection fraction (HFrEF). Methods and results Consecutive 168 HF patients were divided into three groups based on their AC/FC: first to third tertiles (n = 56, respectively). We followed up all patients for cardiac events including cardiac death and/or worsening HF. During the follow‐up period (1004 days), there were 23 cardiac deaths and 28 worsening HF. In the Kaplan–Meier analysis, the cardiac event rate of the third group was highest among the three groups (P = 0.022). In the Cox proportional hazard analysis, AC/FC was a predictor of cardiac events (P = 0.007). When HFpEF (n = 79) and HFrEF (n = 89) were analysed separately, the cardiac event rate of the third group was highest with regard to HFpEF (P = 0.008), but not HFrEF (P = 0.321). In the Cox proportional hazard analysis, AC/FC was a predictor of cardiac events with regard to HFpEF (P = 0.031), but not HFrEF (P = 0.095). Therefore, the impact of the AC/FC on cardiac events was different between HFpEF and HFrEF (P = 0.042 for interaction). Conclusions The AC/FC can identify high risk HF patients, especially in HFpEF.

Accumulating evidence suggests that there are direct interactions between β-adrenergic and angiotensin II signaling pathways, and β-blockers protect the heart against angiotensin II-induced cardiac remodeling. Phosphodiesterase 3A (PDE3A) regulates β-adrenergic receptor/protein kinase A signaling by metabolizing cAMP. Therefore, we hypothesized that overexpressed PDE3A has cardioprotective effects against angiotensin II-induced cardiac remodeling by regulating angiotensin II signaling. In the present study, we used transgenic mice with cardiac-specific overexpressed PDE3A1. We showed that continuous administration of angiotensin II caused cardiac hypertrophy in the wild-type mouse heart, but not in the transgenic mouse heart. Angiotensin II induced cardiac fibrosis in both wild-type and transgenic mice, but the extent of fibrosis was less in transgenic mice compared to wild-type mice. Moreover, basal expression levels of transforming growth factor-β were lower in transgenic mouse hearts, and it remained at lower levels after angiotensin II stimulation. These findings suggest that PDE3A protects the heart from angiotensin II-induced cardiac remodeling through its modulation of the functional connection between angiotensin II and transforming growth factor-β.

BACKGROUND Cardiac troponins are independent predictors of cardiac mortality in patients with heart failure (HF). Recently, elevation of troponins was described in non-cardiac diseases such as stroke and infection, among others, but it remains unclear whether high-sensitivity troponin T (hs-TnT) predicts non-cardiac mortality in HF patients. METHODS AND RESULTS Four-hundred and forty-four consecutive HF patients admitted to hospital for the treatment of decompensated HF were divided into 2 groups based on median hs-TnT: group L (

Background Melatonin is a multifunctional indolamine and has a cardioprotective role in a variety of cardiovascular processes via antioxidant, anti‐inflammatory, antihypertensive, antithrombotic, and antilipemic effects. It has been reported that lower levels of circulating melatonin are significantly associated with a higher risk of acute myocardial infarction (AMI) and later cardiac remodeling. However, levels of melatonin in patients with dilated cardiomyopathy (DCM) and associations between melatonin levels and cardiac function remain unclear. Methods and Results We measured and compared plasma levels of melatonin in 61 control subjects, 81 AMI patients, and 77 DCM patients. Plasma levels of melatonin were progressively decreased from 71.9 pg/mL in the control group to 52.6 pg/mL in the DCM group and 21.9 pg/mL in the AMI group. Next, we examined associations of melatonin levels with parameters of laboratory data, echocardiography, and right‐heart catheterization. In the DCM patients, circulating melatonin showed significant correlations with both high‐sensitivity troponin T (R = −0.422, P