Left atrial volume index as a predictor for left atrial appendage thrombus in patients with non-valvular atrial fibrillation receiving appropriate oral anticoagulation therapy: A prospective multi-center study.

OBJECTIVES: We previously reported a higher left atrial volume index (LAVI) was independently associated with left atrial (LA) appendage (LAA) thrombus formation in 737 patients with non-valvular atrial fibrillation (NVAF) receiving appropriate oral anticoagulation therapy. Since our previous study was a retrospective single-center study, we designed and conducted a prospective multi-center study to verify our findings for LAVI as a predictor of LAA thrombus in patients with NVAF receiving appropriate oral anticoagulation therapy. METHODS: This prospective multi-center study comprised 746 consecutive patients with NVAF recruited between December 2021 and March 2023 from eight institutions in Japan, who were receiving appropriate oral anticoagulation therapy, had undergone transthoracic echocardiography and transesophageal echocardiography (TEE). RESULTS: LAA thrombi were observed in 21 patients (2.8%). The prevalence of LAA thrombus formation in patients with paroxysmal AF (PAF) was significantly lower than that in patients with non-PAF (0.7% vs. 4.1%, p = .006). LAA thrombus formation was detected in none (0/171) of the patients with normal size LA (LAVI ≤ 34 mL/m2 ). The prevalence of LAA thrombus formation in patients with mildly dilated LA (LAVI: 34-49.9 mL/m2 ) was 2.1% (6/283), but that in PAF patients was low at 1.0% (1/104). Furthermore, this prevalence in patients with severely dilated LA (LAVI ≥ 50 mL/m2 ) was high at 5.1% (15/292). CONCLUSIONS: The findings of this prospective multi-center study are consistent with those of our previous study. Thus, the need for TEE prior to catheter ablation or electrical cardioversion can be determined by the level of LAVI.

Association Between Serum 3-Hydroxyisobutyric Acid and Prognosis in Patients With Chronic Heart Failure　- An Analysis of the KUNIUMI Registry Chronic Cohort.

BACKGROUND: Diabetes increases the risk of heart failure (HF). 3-Hydroxyisobutyric acid (3-HIB) is a muscle-derived metabolite reflecting systemic insulin resistance. In this study, we investigated the prognostic impact of 3-HIB in patients with chronic HF.Methods and Results: The KUNIUMI Registry chronic cohort is a community-based cohort study of chronic HF in Awaji Island, Japan. We analyzed the association between serum 3-HIB concentrations and adverse cardiovascular (CV) events in 784 patients from this cohort. Serum 3-HIB concentrations were significantly higher in patients with than without diabetes (P=0.0229) and were positively correlated with several metabolic parameters. According to Kaplan-Meier analysis, rates of CV death and HF hospitalization at 2 years were significantly higher among HF patients without diabetes in the high 3-HIB group (3-HIB concentrations above the median; i.e., >11.30 µmol/L) than in the low 3-HIB group (log-rank P=0.0151 and P=0.0344, respectively). Multivariable Cox proportional hazard models adjusted for established risk factors for HF revealed high 3-HIB as an independent predictor of CV death (hazard ratio [HR] 1.82; 95% confidence interval [CI] 1.16-2.85; P=0.009) and HF hospitalization (HR 1.72; 95% CI 1.17-2.53, P=0.006) in HF patients without diabetes, whereas no such trend was seen in subjects with diabetes. CONCLUSIONS: In a community cohort, circulating 3-HIB concentrations were associated with prognosis in chronic HF patients without diabetes.

Estimating Incidence of Acute Heart Failure Syndromes in Japan　- An Analysis From the KUNIUMI Registry.

BACKGROUND: Few registries have provided precise information concerning incidence rates for acute heart failure syndrome (AHFS) in Japan.Methods and Results:All hospitals with acute care beds in Awaji Island participated in the Kobe University heart failure registry in Awaji Medical Center (KUNIUMI Registry), a retrospective, population-based AHFS registration study, enabling almost every patient with AHFS in Awaji Island to be registered. From 1 January 2015 to 31 December 2017, 743 patients with de novo AHFS had been registered. Mean age was 82.1±11.5 years. Using the general population of Japan as of 2015 as a standard, age- and sex-adjusted incidence rates for AHFS were 133.8 per 100,000 person-years for male and 120.0 for female. In 2015, there were an estimated 159,702 new-onset patients with AHFS, which was predicted to increase to 252,153 by 2040, and reach a plateau. The proportion of patients aged >85 years accounted for 42.6% in 2015, which was predicted to increase up to 62.5% in 2040. The proportion of patients with heart failure with preserved ejection fraction was estimated at 52.0% in 2015, which was predicted to increase gradually to 57.3% in 2055. CONCLUSIONS: The present analysis suggested that the number of patients with de novo AHFS keeps increasing with progressive aging in Japan. Establishment of countermeasures against the expanding burden of HF is urgently required.

Association of Apical Longitudinal Rotation with Right Ventricular Performance in Patients with Pulmonary Hypertension: Insights into Overestimation of Tricuspid Annular Plane Systolic Excursion.

BACKGROUND: Current guidelines recommend the routine use of tricuspid annular plane systolic excursion (TAPSE) as a simple method for estimating right ventricular (RV) function. However, when ventricular apical longitudinal rotation (apical-LR) occurs in pulmonary hypertension (PH) patients, it may result in overestimated TAPSE. METHODS: We studied 105 patients with PH defined as mean pulmonary artery pressure >25 mmHg at rest measured by right heart cardiac catheterization. TAPSE was defined as the maximum displacement during systole in the RV-focused apical four-chamber view. RV free-wall longitudinal speckle tracking strain (RV-free) was calculated by averaging 3 regional peak systolic strains. The apical-LR was measured at the peak rotation in the apical region including both left and right ventricle. The eccentricity index (EI) was defined as the ratio of the length of 2 perpendicular minor-axis diameters, one of which bisected and was perpendicular to the interventricular septum, and was obtained at end-systole (EI-sys) and end-diastole (EI-dia). Twenty age-, gender-, and left ventricular ejection fraction-matched normal controls were studied for comparison. RESULTS: The apical-LR in PH patients was significantly lower than that in normal controls (-3.4 ± 2.7° vs. -1.3 ± 1.9°, P = 0.001). Simple linear regression analysis showed that gender, TAPSE, EI-sys, and EI-dia/EI-sys were associated with apical-LR, but RV-free was not. Multiple regression analysis demonstrated that gender, EI-dia/EI-sys, and TAPSE were independent determinants of apical-LR. CONCLUSIONS: TAPSE may be overestimated in PH patients with clockwise rotation resulting from left ventricular compression. TAPSE should thus be evaluated carefully in PH patients with marked apical rotation.

Association of left atrial booster-pump function with heart failure symptoms in patients with severe aortic stenosis and preserved left ventricular ejection fraction.

BACKGROUND: Identification of heart failure (HF) symptoms in patients with severe aortic stenosis (AS) and preserved left ventricular (LV) ejection fraction (EF) is clinically important, but assessment of HF symptoms is challenging. It was recently reported that resting left atrium (LA) functions are related to exercise performance and are also important prognostic markers for patients with HF. The aim of this study was to assess the association of the HF symptoms with LA function in patients with severe AS and preserved LVEF. METHODS: We retrospectively studied 40 patients with severe AS and preserved LVEF (all ≥50%) who were referred for aortic valve replacement (AVR). LA reservoir (SR-LAs), conduit (SR-LAe), and booster-pump (SR-LAa) functions were determined as the averaged global LA speckle tracking longitudinal strain rate from apical four- and two-chamber views. Twenty patients were symptomatic and 20 asymptomatic. RESULTS: Aortic stenosis severity was similar for the 2 groups. Symptomatic status was associated with age, LV mass index, hemoglobin, B-type natriuretic peptide, LV end-systolic volume index, LVEF, LA volume index, SR-LAs, SR-LAe, and SR-LAa. Importantly, multivariate logistic regression analysis revealed that SR-LAa was the only independent determinant of symptomatic status (OR = 0.242, P = 0.002). Furthermore, significant improvement of SR-LAa was observed along with the reduction in LA volume index and LV mass index after AVR. CONCLUSIONS: SR-LAa was found to be associated with the HF symptoms. Characterization of LA booster-pump function may be useful for the assessment of the symptomatic status in patients with severe AS patients and limited physical activity.

Impact of Right Ventricular Geometry on Mitral Regurgitation After Transcatheter Closure of Atrial Septal Defect.

Worsening of mitral regurgitation (MR) is sometimes observed after closure of an atrial septal defect (ASD). However, since the mechanism of this deterioration remains unclear, the aim of our study was to investigate the effect of left (LV) and right ventricular (RV) geometry on MR after transcatheter closure of ASD.We studied 27 patients with ASD who underwent transcatheter closure. Echocardiography was performed before and 6 ± 2 months after the procedure. In addition to conventional echocardiographic parameters, full volume data of the whole LV and RV heart was obtained with 3-dimensional echocardiography. MR was quantified by measuring the width of the vena contracta, and was graded as mild (< 3.0 mm), moderate (3.0 to 6.9 mm), or severe (≥ 7.0 mm).Ten patients (37%) were classified as having worsening MR and the remaining 17 (63%) as not having worsening MR. The two groups showed similar baseline characteristics, except for patients with worsening MR being more likely to be older (P = 0.009) and having a larger left-to-right shunt of pulmonary and systemic blood flow ratio (P = 0.02). It is noteworthy that the horizontal-to-vertical ratio of basal-RV at end-systole for patients with worsening MR was significantly smaller than that for patients without worsening MR (1.0 ± 0.2 versus 1.4 ± 0.2, P < 0.0001). Furthermore, multivariate analysis showed that the horizontal-to-vertical ratio of basal-RV at end-systole was the independent predictor of worsening MR during follow-up (P < 0.001).RV geometry may affect MR after closure of ASD. The pre-operative horizontal-to-vertical ratio of basal-RV is considered useful for predicting worsening of MR after closure of ASD.

Easy-to-use comprehensive speckle-tracking approach for cardiac resynchronization therapy.

BACKGROUND: Left ventricular (LV) dyssynchrony has emerged as an important mechanism contributing to the patient's response to cardiac resynchronization therapy (CRT), but other potential factors, especially LV myocardial viability, are also influential. METHODS AND RESULTS: We studied 132 patients undergoing CRT. LV dyssynchrony was determined by anteroseptal-to-posterior wall delay on the mid-LV short-axis view using 2-dimensional speckle-tracking radial strain (≥130 ms as significant). Global circumferential strain (GCS), considered as a parameter of LV intrinsic myocardial function, was also determined as the peak GCS from the same view. Long-term follow-up was tracked over 40 months. Kaplan-Meier analysis indicated that patients with GCS >3.9% experienced fewer cardiovascular events overall (log-rank P=0.034). Similarly, patients with GCS >3.9% and ≥6.6% experienced fewer cardiovascular events than those with GCS ≤3.9% and <6.6% among patients with and without LV dyssynchrony (log-rank P=0.025 and P=0.029, respectively). An important finding from multivariate Cox proportional hazards analysis was that LV dyssynchrony and GCS were independently associated with cardiovascular events. Of note, only 2±1 min per patient were needed to analyze both LV dyssynchrony and GCS from the same routine mid-LV short-axis view. CONCLUSIONS: This easy-to-use combined assessment of LV dyssynchrony and myocardial function using speckle-tracking strain from the same mid-LV short-axis view may well have clinical implications for CRT.

Severe tricuspid regurgitation with biannular disjunction requiring surgical treatment: a case report.

Background: Tricuspid annular disjunction (TAD) is an annular disjunction of the right-sided heart. Although TAD is often concomitant with mitral annular disjunction (MAD), it often presents as mitral regurgitation (MR), rather than tricuspid regurgitation (TR). While the clinical significance of MAD has been well-established, there is still little data on TAD. This is a rare case of severe TR due to TAD that appears to be isolated from MAD. Case summary: A 63-year-old female complaining of pre-syncope and dyspnoea on exertion was referred to our department. Initial transthoracic echocardiography showed MR and TR due to tricuspid valve prolapse (TVP). On transoesophageal echocardiography, the TVP consisted of an excessively redundant anterior leaflet, where the annular disjunction and severe regurgitation were formed. She recently underwent mitral and tricuspid valve plasties for symptomatic primary severe TR. Discussion: This case report emphasizes the clinical significance of TAD as a potential cause of severe TR, even without significant MR. Tricuspid annular disjunction progresses more gradually compared with MAD. This case suggests that remodelling of the right atrium, particularly in chronic atrial fibrillation, may contribute to the development of TR. Despite diagnostic challenges due to the flexible and dynamic nature of the tricuspid annulus, this is the first report of TAD-induced severe TR necessitating surgical intervention. Accurately diagnosing TAD remains challenging with current imaging modalities, emphasizing the need for improved diagnostic tools to optimize treatment strategies.

Accuracy of lung ultrasound examinations of residual congestion performed by novice residents in patients with acute heart failure.

AIMS: The popularity of B-line-guided congestion assessment by lung ultrasound (LUS) has been increasing. However, the ability of novice residents to detect residual congestion with B-line-guided assessment by LUS after decongestion treatment is poorly understood. In this study, we investigated whether novice residents (no prior echocardiography experience) can acquire the skills for B-line-guided residual congestion assessment and whether the range of variation in assessment is acceptable in actual clinical use. METHODS AND RESULTS: The study included 30 postgraduate first-year novice residents and an expert. The residents underwent training for LUS. At the end of the training session, a set of 15 LUS videos was provided to the residents, and they were asked to estimate the number of B-lines in each video. When the residents' answers greatly differed from the correct answer, we provided feedback to raise awareness of the discrepancies. After the training session, the residents performed residual congestion assessment by LUS after decongestion treatment in patients hospitalized with acute heart failure. The residents identified residual congestion in 57% of the patients. The sensitivity and specificity to identify residual congestion by the residents were 90% and 100%, respectively. The inter-operator agreement between the residents and the expert was substantial (κ = 0.86). The Spearman rank correlation coefficient for the B-lines between the expert and each resident was very high at 0.916 (P < 0.0001). CONCLUSIONS: After a brief lecture, novice residents can achieve proficiency in quantifying B-lines on LUS and can reliably identify residual congestion on LUS.

Recurrent cardiac arrests caused by Kounis syndrome without typical allergic symptoms.

Kounis syndrome is a rare disease in which coronary spasm or acute coronary syndrome is induced by type I allergy. Concurrence of allergic reaction and chest pain are important clues to establish diagnosis. We report a rare case of Kounis syndrome without obvious signs of allergy.A 52-year-old woman experienced abdominal pain followed by ventricular fibrillation (VF) storm. Ten months earlier, the patient underwent subcutaneous implantable cardioverter-defibrillator implantation based on the previous diagnosis of idiopathic VF. In both episodes, the patient was given dental treatment and administered loxoprofen before VF onset. After we performed loxoprofen provocation test, electrocardiogram revealed ST-segment elevation in leads II, III, and aVF. Moreover, the patient developed VF again. An emergency coronary angiography after recovery showed no significant findings. However, myocardial scintigraphy presented a perfusion-metabolism mismatch in the inferior wall. Furthermore, laboratory test results after provocation revealed increased histamine level. Based on these findings, we diagnosed the patient with Kounis syndrome.Kounis syndrome without typical allergic symptoms is challenging to diagnose. Therefore, suspecting the possibility of allergic reactions and detailed history taking are important, particularly when confronted with recurrent coronary spasm, acute coronary syndrome, and inexplicable cardiac arrest. Learning objective: Kounis syndrome is a rare coronary disease with vasospasm or plaque rupture, induced by type I allergy. Since Kounis syndrome without typical allergic symptoms is challenging to diagnose, a high index of suspicion is necessary. Detailed history taking can provide important clues to establish diagnosis, particularly when confronted with recurrent coronary spasm, acute coronary syndrome, and inexplicable cardiac arrest.

Association between B-lines on lung ultrasound, invasive haemodynamics, and prognosis in acute heart failure patients.

AIMS: Increased left atrial pressure leads to pulmonary congestion. Although the B-lines in lung ultrasound (LUS) are useful in detecting pulmonary congestion, data regarding the association between B-lines and invasive haemodynamics are inconsistent. This study aimed to explore the correlation of the B-line count by LUS with pulmonary capillary wedge pressure (PCWP) stratified for preserved and reduced ejection fraction (EF) in acute heart failure patients. METHODS AND RESULTS: We performed a prospective observational study on 116 hospitalized patients with acute heart failure (mean age, 75.2 ± 10.3 years), who underwent right heart catheterization before discharge. LUS was performed in eight zones within 4 h of right heart catheterization and compared with PCWP separately in each EF group. Cardiac events were recorded 1 year after discharge. PCWP revealed a clear pivot point at which the B-lines began to increase in the overall cohort and each EF. Specific thresholds of the increase in B-lines were identified at 19 and 25 mmHg for preserved and reduced EF, respectively. Residual congestion at discharge was defined as the presence of ≥6 B-lines. Patients with residual congestion had a higher risk for cardiac events than those without residual congestion (hazard ratio, 12.6; 95% confidence interval, 4.71-33.7; log-rank, P < 0.0001). CONCLUSION: A clear pivot point was associated with increased B-lines count in PCWP at 19 and 25 mmHg for preserved and reduced EF, respectively. Moreover, the increased B-line count above the defined cut-off used to quantify residual congestion was associated with significantly worse outcomes.

Clinical impact of portal vein pulsatility on the prognosis of hospitalized patients with acute heart failure.

BACKGROUND: Heart failure (HF) causes extracardiac organ congestion, including in the hepatic portal system. Reducing venous congestion is essential for HF treatment, but evaluating venous congestion is sometimes difficult in patients with chronic HF. The portal vein (PV) flow pattern can be influenced by right atrial pressure. Ultrasound images of the PV are quite easy to obtain and are reproducible among sonographers. However, the association between PV pulsatility and the condition of HF remains unclear. We hypothesize that PV pulsatility at discharge reflects the condition of HF. AIM: To evaluate the usefulness of PV pulsatility as a prognostic marker for hospitalized patients with acute HF. METHODS: This observational study was conducted from April 2016 to January 2017 and April 2018 to April 2019 at Shinko Hospital. We enrolled 56 patients with acute HF, and 17 patients without HF served as controls. PV flow velocity was measured by ultrasonography on admission and at discharge. We calculated the PV pulsatility ratio (PVPR) as the ratio of the difference between the peak and minimum velocity to the peak velocity. The primary endpoint was cardiac death and HF re-hospitalization. The observation period was 1 year from the first hospitalization. The Kaplan-Meier method was used to determine the stratified composite event-free rates, and the log-rank test was used for comparisons between groups. RESULTS: On admission, the PVPR was significantly higher in patients with acute HF than controls (HF: 0.29 ± 0.20 vs controls: 0.08 ± 0.07, P < 0.01). However, the PVPR was significantly decreased after the improvement in HF (admission: 0.29 ± 0.20 vs discharge: 0.18 ± 0.15, P < 0.01) due to the increase in minimum velocity (admission: 12.6 ± 4.5 vs discharge: 14.6 ± 4.6 cm/s, P = 0.03). To elucidate the association between the PVPR and cardiovascular outcomes, the patients were divided into three groups according to the PVPR tertile at discharge (PVPR-T1: 0 ≤ PVPR ≤ 0.08, PVPR-T2: 0.08 < PVPR ≤ 0.21, PVPR-T3: PVPR > 0.21). The Kaplan-Meier analysis showed that patients with a higher PVPR at discharge had the worst prognosis among the groups. CONCLUSION: PVPR at discharge reflects the condition of HF. It is also a novel prognostic marker for hospitalized patients with acute HF.

Aetiology of chronic heart failure in patients from a super-aged society: the KUNIUMI registry chronic cohort.

AIMS: With the rapidly increasing ageing population, heart failure is an urgent challenge, particularly in developed countries. The study aimed to investigate the main aetiologies of chronic heart failure in a super-aged society. METHODS AND RESULTS: The KUNIUMI registry chronic cohort is a community-based, prospective, observational study of chronic heart failure in Awaji Island, Japan. Inhabitants of this island aged ≥65 years accounted for 36.3% of the population. In the present study, data from patients with symptomatic heart failure were extracted from the registry. A total of 1646 patients were enrolled from March 2019 to March 2021, accounting for ~1.3% of the inhabitants of Awaji Island. We analysed 852 patients with symptomatic heart failure. The mean age was high (78.7 ± 11.1 years), with 357 patients (41.9%) being female. The proportion of women increased significantly with advancing age and constituted more than half of the patients aged 85 years and older (P < 0.01). The prevalence of atrial fibrillation, and in particular long-standing persistent atrial fibrillation, increased at 70 years of age (P < 0.01). The proportion of patients with heart failure with preserved ejection fraction increased to ~60% when age was over 75 years. Although ischaemic heart disease accounted for 35.0% of chronic heart failure aetiologies, valvular heart disease was the most common cause of chronic heart failure (49.8%). The major types of valvular heart disease were mitral regurgitation and tricuspid regurgitation (27.2% and 21.7%, respectively), both of which increased significantly with age (P < 0.01). The incidence of aortic valve stenosis increased markedly over the age of 85 years (P < 0.01). Atrial functional mitral regurgitation increased with age and was the major cause of mitral regurgitation in patients aged >75 years. Patients with atrial functional mitral regurgitation had a higher prevalence of atrial fibrillation (especially long-standing persistent atrial fibrillation) and a larger left atrial volume index when compared with patients with other types of mitral regurgitation (P < 0.001, respectively). CONCLUSIONS: The KUNIUMI registry chronic cohort showed a change in heart failure aetiology to valvular heart disease in a super-aged society. Effective and comprehensive countermeasures are required to prepare for the rapid rise in heart failure incidence in a super-aged society.

Effect of Ivabradine on Left Ventricular Diastolic Function of Patients With Preserved Ejection Fraction　- Results of the IVA-PEF Study.

Background: The association between heart rate (HR) reductions caused by ivabradine and left ventricular (LV) diastolic function in heart failure with preserved ejection fraction (HFpEF) remains uncertain because of off-label use. Thus, the present study investigated the effect of HR reductions by ivabradine on LV diastolic function in HFpEF patients. Methods and Results: This study enrolled 16 HFpEF patients with HR ≥75 beats/min. After 3 months administration of ivabradine, no significant changes were observed in mitral inflow E and mitral e' annular velocities, B-type natriuretic peptide, or left atrial volume index, but there were significant improvements in global longitudinal strain. Conclusions: Ivabradine did not improve LV diastolic function for HFpEF patients with HR ≥75 beats/min. Because this may be due to some study limitations, further studies should be conducted.

Differences in Prognostic Factors among Patients Hospitalized for Heart Failure According to the Age Category: From the KUNIUMI Registry Acute Cohort.

Objective Previous studies have described several prognostic factors for heart failure (HF); however, these results were derived from registries consisting of conventional age groups, which might not represent the increasingly aging society. The present study explored the prognostic factors for all-cause death in hospitalized patients with HF across different age categories using an acute HF registry that included relatively old patients. Methods From a total of 1,971 consecutive patients with HF, 1,136 patients were enrolled. We divided the patients into 4 groups (≤65, 66-75, 76-85, and >85 years old) to evaluate all-cause death and prognostic factors of all-cause death. Results During the mean follow-up period of 1,038 days, 445 patients (39.2%) had all-cause death. A Kaplan-Meier analysis demonstrated significantly higher incidence of all-cause death in the elderly groups than in the younger groups (log-rank p<0.001). A Cox proportional-hazard regression analysis revealed that the presence of atrial fibrillation [hazard ratio (HR): 23.3, 95% confidence interval (CI): 2.36-231.1, p=0.007] was a notable predictive factor for all-cause death in the ≤65 years old group, whereas the Clinical Frailty Scale score (HR: 1.33, 95% CI: 1.16-1.52, p<0.001) and hypoalbuminemia (HR: 0.49, 95% CI: 0.31-0.78, p=0.003) were predictors in the >85 years old group. Conclusions Atrial fibrillation was a notable predictor of HF in young patients, whereas frailty and low-grade albuminemia were essential predictive factors of HF in elderly patients. With the increasing number of elderly patients with HF, comprehensive multidisciplinary treatment will be necessary.

Efficacy of Renin-angiotensin-aldosterone-system inhibitors for heart failure with preserved ejection fraction and left ventricular hypertrophy -from the KUNIUMI Registry Acute Cohort.

BACKGROUND: Heterogeneity of heart failure (HF) with preserved ejection fraction (HFpEF) would contribute to the difficulty in identifying effective treatments, and interest in the phenogrouping of HFpEF as a potential means for predicting patients who respond to cardioprotective drugs has been increasing. METHODS: We studied 468 first-hospitalized HFpEF patients among 1971 acute-hospitalized HF patients from KUNIUMI Registry Acute Cohort. The primary endpoint was defined as HF-rehospitalization and cardiovascular death over a median follow-up period of 508 days. RESULTS: In HFpEF patients with left ventricular hypertrophy (LVH), patients prescribed renin-angiotensin-aldosterone-system (RAAS) inhibitors had similar outcomes compared to those without (HR, 0.77; 95% CI 0.51-1.16; p = 0.21), and the outcome was also similar between patients with and without RAAS inhibitors' prescription in HFpEF patients without LVH. Moreover, in HFpEF patients with LVH and mild-moderate chronic kidney disease (CKD), which was determined as an estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m2, patients prescribed RAAS inhibitors had significantly favorable outcomes compared to those without (HR 0.39; 95% CI 0.19-0.80; p = 0.01). In HFpEF patients with LVH and severe CKD, which was defined as eGFR <30 mL/min/1.73 m2, the outcome was similar between patients with and without RAAS inhibitor prescription. Multivariable Cox regression analysis showed that the prescription of RAAS inhibitors was the only independent predictor of outcome in HFpEF patients with LVH and mild-moderate CKD (HR 0.49; 95% CI 0.25-0.94; p = 0.03). CONCLUSIONS: Our findings showed the importance of HFpEF phenogrouping for identifying effective pharmacological treatments.

Association of congestion with worsening renal function in acute decompensated heart failure according to age.

AIMS: Acute decompensated heart failure (ADHF) is a frequent cause of hospitalization for patients with heart disease, and ADHF patients are at high risk of heart failure (HF) re-hospitalization. Residual congestion at discharge is also a strong predictor of poor outcomes and re-hospitalization for ADHF patients. However, the impact of residual congestion at discharge on worsening renal function (WRF) in both high-aged and older patients remains uncertain because previous studies of WRF in ADHF patients were conducted for older patients. We therefore designed and conducted a retrospective, population-based study using the Kobe University Heart Failure Registry in Awaji Medical Center (KUNIUMI) Registry to investigate the association of residual congestion at discharge with WRF in ADHF patients according to age. METHODS AND RESULTS: We studied 966 hospitalized ADHF patients with a mean age of 80.2 ± 11.4 years from among 1971 listed in the KUNIUMI Registry. WRF was defined as an increase of ≥0.3 mg/dL in the serum creatinine level during the hospital stay compared with the value on admission. The primary endpoint was defined as cardiovascular death or HF re-hospitalization after discharge over a mean follow-up period of 2.0 ± 0.1 years. The primary endpoint was recorded for 369 patients (38.2%). As expected, patients with both WRF and residual congestion at discharge had significantly less favourable outcomes compared with those without one of them, and patients without either of these two characteristics had the most favourable outcomes, whereas those with residual congestion and with WRF had the least favourable outcomes. Moreover, WRF was significantly associated with worse outcomes for high-aged patients ≥80 years old, but not for those <80 years old if decongested. Multivariable Cox regression analysis showed that both residual congestion at discharge and WRF were the independent predictors of outcomes for high-aged patients, but residual congestion at discharge, not WRF, was the independent predictor of outcomes for older patients. CONCLUSIONS: Association of residual congestion at discharge with WRF for hospitalized ADHF patients can differ according to age. Our findings showed the importance of WRF and residual congestion at discharge for high-aged ADHF patients and of aggressive diuresis to alleviate congestion for older ADHF patients for better management of such patients in a rapidly ageing society.

Development of microsatellite markers for Euryale ferox (Nymphaeaceae), an endangered aquatic plant species in Japan.

PREMISE OF THE STUDY: Microsatellite markers were developed to investigate genetic diversity and genetic structure of Euryale ferox, a vulnerable aquatic plant. METHODS AND RESULTS: Ten microsatellite loci were isolated and characterized for this species. Eight loci showed polymorphisms with two or three alleles per locus. As for the polymorphic markers, the expected and observed heterozygosities ranged from 0.00 to 0.08 and 0.17 to 0.64, respectively. CONCLUSIONS: The 10 microsatellite markers described here will be useful for investigating genetic diversity, genetic structure, and gene flow between populations of E. ferox.

Effect of ivabradine on left ventricular diastolic function of patients with heart failure with preserved ejection fraction -IVA-PEF study.

BACKGROUND: High resting heart rate (HR) is a known marker of cardiovascular outcomes for heart failure (HF) patients. Ivabradine is a new class of HR lowering drug and a specific inhibitor of the If current in the sinoatrial node. Ivabradine substantially and significantly reduces major risks associated with HF when added to guideline-based treatment for left ventricular (LV) ejection fraction ≤35% and HR ≥70 bpm in sinus rhythm. On the other hand, HF with preserved ejection fraction (HFpEF) currently accounts for roughly half of all HF cases and usually presents as LV diastolic dysfunction. However, the association between HR reduction and LV diastolic function for HFpEF patients remains uncertain. METHODS/DESIGN: This investigation into the effect of IVAbradine on left ventricular diastolic function of patients with heart failure with Preserved Ejection Fraction (IVA-PEF) is a multicenter, prospective, uncontrolled, open-label, single assignment, and an interventional single-arm study to investigate the effect of ivabradine on LV diastolic function of HFpEF patients. The key inclusion criterion is HFpEF with resting HR ≥75bpm in sinus rhythm. After completed informed consent forms are obtained, patients will be given 5 mg/day of ivabradine during the study. LV diastolic function is assessed in terms of mitral inflow E and mitral e' annular velocities (E/e'). The primary endpoint will be defined as a change in E/e' between baseline and 3 months after the start of administration of ivabradine. CONCLUSION: The findings of our trial may provide a new perspective on ivabradine for the treatment of HFpEF.

Precipitating factors and clinical impact of early rehospitalization for heart failure in patients with heart failure in Awaji Island, Japan.

BACKGROUND: Recent reports have revealed that patients who experienced early rehospitalization for heart failure (HF) had worse prognoses in terms of all-cause and cardiovascular deaths as compared to those who did not. However, precipitating factors for early rehospitalization for HF remain unknown. In this study, we assessed the precipitating factors for early rehospitalization and their impact in patients with HF. METHODS AND RESULTS: We consecutively included 242 patients (mean age: 80.4 years, females: 46.3%) with a history of rehospitalization for HF. They were divided into 2 groups: the early rehospitalization group (71 patients who were readmitted within 3 months of discharge) and the late rehospitalization group (171 patients who were readmitted after more than 3 months following discharge). During the mean follow-up period of 1,144 days (range: 857-1,417 days), 121 patients (50.0%) died. Kaplan-Meier analysis revealed that patients in the early rehospitalization group had worse prognosis (all-cause death and cardiovascular death) than those in the late rehospitalization group (log-rank p<0.001). As the major precipitating factor for rehospitalization, poor compliance with the doctor's instructions on fluid and physical activity restrictions (determined by the patients or their families admittance of non-compliance with the instructions given at the time of discharge) was higher in the early rehospitalization group than in the late rehospitalization group [poor compliance with fluid restriction: 19.7% vs. 7.6% (p = 0.006), poor compliance with physical activity restriction: 21.1% vs. 9.4% (p = 0.013)]. CONCLUSIONS: We concluded that early hospital readmission in patients with HF was associated with higher mortality rates. Compared to late rehospitalization, precipitating factors for early rehospitalization were more strongly dependent on the self-care behaviors of the patients. A more effective approach, such as multidisciplinary intervention, is essential to prevent early hospital readmission and subsequent poor prognosis.