Impact of vessel morphology on CT-derived fractional-flow-reserve in non-obstructive coronary artery disease in right coronary artery.

OBJECTIVES: Computed tomography (CT)-derived fractional flow reserve (FFRCT) decreases continuously from proximal to distal segments of the vessel due to the influence of various factors even in non-obstructive coronary artery disease (NOCAD). It is known that FFRCT is dependent on vessel-length, but the relationship with other vessel morphologies remains to be explained. PURPOSE: To investigate morphological aspects of the vessels that influence FFRCT in NOCAD in the right coronary artery (RCA). METHODS: A total of 443 patients who underwent both FFRCT and invasive coronary angiography, with < 50% RCA stenosis, were evaluated. Enrolled RCA vessels were classified into two groups according to distal FFRCT: FFRCT ≤ 0.80 (n = 60) and FFRCT > 0.80 (n = 383). Vessel morphology (vessel length, lumen diameter, lumen volume, and plaque volume) and left-ventricular mass were assessed. The ratio of lumen volume and vessel length was defined as V/L ratio. RESULTS: Whereas vessel-length was almost the same between FFRCT ≤ 0.80 and > 0.80, lumen volume and V/L ratio were significantly lower in FFRCT ≤ 0.80. Distal FFRCT correlated with plaque-related parameters (low-attenuation plaque, intermediate-attenuation plaque, and calcified plaque) and vessel-related parameters (proximal and distal vessel diameter, vessel length, lumen volume, and V/L ratio). Among all vessel-related parameters, V/L ratio showed the highest correlation with distal FFRCT (r = 0.61, p < 0.0001). Multivariable analysis showed that calcified plaque volume was the strongest predictor of distal FFRCT, followed by V/L ratio (ß-coefficient = 0.48, p = 0.03). V/L ratio was the strongest predictor of a distal FFRCT ≤ 0.80 (cut-off 8.1 mm3/mm, AUC 0.88, sensitivity 90.0%, specificity 76.7%, 95% CI 0.84-0.93, p < 0.0001). CONCLUSIONS: Our study suggests that V/L ratio can be a measure to predict subclinical coronary perfusion disturbance. CLINICAL RELEVANCE STATEMENT: A novel marker of the ratio of lumen volume to vessel length (V/L ratio) is the strongest predictor of a distal CT-derived fractional flow reserve (FFRCT) and may have the potential to improve the diagnostic accuracy of FFRCT. KEY POINTS: • Physiological FFRCT decline depends not only on vessel length but also on the lumen volume in non-obstructive coronary artery disease in the right coronary artery. • FFRCT correlates with plaque-related parameters (low-attenuation plaque, intermediate-attenuation plaque, and calcified plaque) and vessel-related parameters (proximal and distal vessel diameter, vessel length, lumen volume, and V/L ratio). • Of vessel-related parameters, V/L ratio is the strongest predictor of a distal FFRCT and an optimal cut-off value of 8.1 mm3/mm.

Impact of coronary bifurcation angle on computed tomography derived fractional flow reserve in coronary vessels with no apparent coronary artery disease.

OBJECTIVES: Computed tomography (CT) derived fractional flow reserve (FFRCT) decreases from the proximal to the distal part due to a variety of factors. The energy loss due to the bifurcation angle may potentially contribute to a progressive decline in FFRCT. However, the association of the bifurcation angle with FFRCT is still not entirely understood. This study aimed to investigate the impact of various bifurcation angles on FFRCT decline below the clinically crucial relevance of 0.80 in vessels with no apparent coronary artery disease (CAD). METHODS: A total of 83 patients who underwent both CT angiography including FFRCT and invasive coronary angiography, exhibiting no apparent CAD were evaluated. ΔFFRCT was defined as the change in FFRCT from the proximal to the distal in the left anterior descending artery (LAD) and left circumflex artery (LCX). The bifurcation angle was calculated from three-dimensional volume rendered images. Vessel morphology and plaque characteristics were also assessed. RESULTS: ΔFFRCT significantly correlated with the bifurcation angle (LAD angle, r = 0.35, p = 0.001; LCX angle, r = 0.26, p = 0.02) and vessel length (LAD angle, r = 0.30, p = 0.005; LCX angle, r = 0.49, p < 0.0001). In LAD, vessel length was the strongest predictor for distal FFRCT of ≤ 0.80 (ß-coefficient = 0.55, p = 0.0003), immediately followed by the bifurcation angle (ß-coefficient = 0.24, p = 0.02). The bifurcation angle was a good predictor for a distal FFRCT ≤ 0.80 (LAD angle, cut-off 31.0°, AUC 0.70, sensitivity 74%, specificity 68%; LCX angle, cut-off 52.6°, AUC 0.86, sensitivity 88%, specificity 85%). CONCLUSIONS: In vessels with no apparent CAD, vessel length was the most influential factor on FFRCT, directly followed by the bifurcation angle. KEY POINTS: • Both LAD and LCX bifurcation angles are factors influencing FFR CT. • Bifurcation angle is one of the predictors of a distal FFRCT of ≤ 0.80 and an optimal cut-off value of 31.0° for the LAD and 52.6° for the LCX. • Bifurcation angle should be taken into consideration when interpreting numerical values of FFRCT.

Initiation and Up-Titration of Guideline-Based Medications in Hospitalized Acute Heart Failure Patients　- A Report From the West Tokyo Heart Failure Registry.

BACKGROUND: Despite recommendations from clinical practice guidelines to initiate and titrate guideline-directed medical therapy (GDMT) during their hospitalization, patients with acute heart failure (AHF) are frequently undertreated. In this study we aimed to clarify GDMT implementation and titration rates, as well as the long-term outcomes, in hospitalized AHF patients.Methods and Results: Among 3,164 consecutive hospitalized AHF patients included in a Japanese multicenter registry, 1,400 (44.2%) with ejection fraction ≤40% were analyzed. We assessed GDMT dosage (ß-blockers, renin-angiotensin inhibitors, and mineralocorticoid-receptor antagonists) at admission and discharge, examined the contributing factors for up-titration, and evaluated associations between drug initiation/up-titration and 1-year post-discharge all-cause death and rehospitalization for HF via propensity score matching. The mean age of the patients was 71.5 years and 30.7% were female. Overall, 1,051 patients (75.0%) were deemed eligible for GDMT, based on their baseline vital signs, renal function, and electrolyte values. At discharge, only 180 patients (17.1%) received GDMT agents up-titrated to >50% of the maximum titrated dose. Up-titration was associated with a lower risk of 1-year clinical outcomes (adjusted hazard ratio: 0.58, 95% confidence interval: 0.35-0.96). Younger age and higher body mass index were significant predictors of drug up-titration. CONCLUSIONS: Significant evidence-practice gaps in the use and dose of GDMT remain. Considering the associated favorable outcomes, further efforts to improve its implementation seem crucial.

Impact of ramus coronary artery on computed tomography derived fractional flow reserve (FFRCT ) in no apparent coronary artery disease.

BACKGROUND: The ramus artery contributes to the development of turbulence, which may influence computed tomography (CT) derived fractional flow reserve (FFRCT ) even without coronary artery disease (CAD). The relationship between ramus-induced turbulence and FFRCT is unclear. METHOD AND RESULTS: A total of 120 patients with <20% coronary stenosis assessed by both FFRCT and invasive coronary angiography were evaluated. The patients were divided into three groups: absent-ramus (n = 72), small-ramus that could not be analyzed by FFRCT (n = 18), and large-ramus that could be analyzed by FFRCT (n = 30). FFRCT measurements were performed at the proximal and distal segments of the left anterior descending (LAD), left circumflex (LCX), and ramus artery. With absent-ramus and small-absent ramus groups, FFRCT was measured at the distal end of the left main trunk at the same level for the proximal segments of the LAD and LCX. In absent-ramus group, proximal FFRCT showed no significant differences between three vessels (LAD = .96 ± .02; MID = .97 ± .02; LCX = .97 ± .02). However, in small and large-ramus groups, proximal FFRCT was significantly higher in the ramus artery than LAD and LCX (small-ramus, LAD = .95 ± .03, Ramus = .97 ± .02, LCX = .95 ± .03; large-ramus: LAD = .95 ± .03, Ramus = .98 ± .01; LCX = .96 ± .03; p < .05). A large ramus was associated with a higher prevalence of a distal FFRCT ≤.80 (odds ratio 7.0, 95% CI 1.2-40.1, p = .03). A proximal ramus diameter predicted distal FFRCT ≤.80 (cut-off 2.1 mm, AUC .76, sensitivity 100%, specificity 52%, 95% CI .61-.90). CONCLUSIONS: The presence of a large-ramus artery may cause an FFRCT decline in no apparent CAD.

Reactive Oxygen Species in the Aorta and Perivascular Adipose Tissue Precedes Endothelial Dysfunction in the Aorta of Mice with a High-Fat High-Sucrose Diet and Additional Factors.

Metabolic syndrome (Mets) is the major contributor to the onset of metabolic complications, such as hypertension, type 2 diabetes mellitus (DM), dyslipidemia, and non-alcoholic fatty liver disease, resulting in cardiovascular diseases. C57BL/6 mice on a high-fat and high-sucrose diet (HFHSD) are a well-established model of Mets but have minor endothelial dysfunction in isolated aortas without perivascular adipose tissue (PVAT). The purpose of this study was to evaluate the effects of additional factors such as DM, dyslipidemia, and steatohepatitis on endothelial dysfunction in aortas without PVAT. Here, we employed eight-week-old male C57BL/6 mice fed with a normal diet (ND), HFHSD, steatohepatitis choline-deficient HFHSD (HFHSD-SH), and HFHSD containing 1% cholesterol and 0.1% deoxycholic acid (HFHSD-Chol) for 16 weeks. At week 20, some HFHSD-fed mice were treated with streptozocin to develop diabetes (HFHSD-DM). In PVAT-free aortas, the endothelial-dependent relaxation (EDR) did not differ between ND and HFHSD (p = 0.25), but in aortas with PVAT, the EDR of HFHSD-fed mice was impaired compared with ND-fed mice (p = 0.005). HFHSD-DM, HFHSD-SH, and HFHSD-Chol impaired the EDR in aortas without PVAT (p < 0.001, p = 0.019, and p = 0.009 vs. ND, respectively). Furthermore, tempol rescued the EDR in those models. In the Mets model, the EDR is compromised by PVAT, but with the addition of DM, dyslipidemia, and SH, the vessels themselves may result in impaired EDR.

Artificially Created Reentry Circuit by Laser Irradiation Causes Atrial Tachycardia to Persist in Murine Atria.

BACKGROUND: There is a gradual progression from paroxysmal to persistent atrial fibrillation (AF) in humans. To elucidate the mechanism involved, the creation of an artificial atrial substrate to persist AF in mice was attempted.Methods and Results:This study used wild type (WT) mice, but it is difficult to induce AF in them. A novel antegrade perfusion method from the left ventricle (LV) to enlarge both atria for artificial atrial modification was proposed in this study. Short duration AF was induced by burst pacing under this method. Optical mapping analysis revealed non-sustained focal type and meandering spiral reentrants after short duration AF. A tiny artificial substrate (~1.2 mm in diameter) was added in by laser irradiation to create a critical atrial arrhythmogenic substrate. Burst pacing was performed in a non-laser group (n=8), a circular-shape laser group (n=8), and a wedge-shaped dent laser group (n=8). We defined AF and atrial tachycardia (AT) as atrial arrhythmia (AA). Long-lasting AA was defined as lasting for ≥30 min. Long-lasting AA was observed in 0/8, 0/8, and 6/8 (75%) mice in each group. Optical mapping analysis revealed that the mechanism was AT with a stationary rotor around the irradiated margin. CONCLUSIONS: Regrettably, this study failed to reproduce persistent AF, but succeeded in creating an arrhythmic substrate that causes sustained AT in WT mice.

Paradoxical changes of coronary computed tomography derived fractional flow reserve.

A total of 1335 outpatients with suspected coronary artery disease and who underwent computed tomography derived fractional flow reserve (FFRCT ) analysis were examined. Only four patients showed reverse increase of FFRCT from the proximal to the distal vessel and all of them had a large ramus artery (RAM). Of all parameters (vessel length, lumen volume, plaque volume, and left ventricular mass), only the bifurcation angle was significantly higher in reverse increase of FFRCT with RAM group (106.0 ± 15.8°) than normal FFRCT with RAM group (82.6 ± 21.7°) and normal FFRCT without RAM group (66.9 ± 21.1°).

Impact of Left Ventricular Chamber Size on Outcome in Heart Failure with Preserved Ejection Fraction.

Although heart failure with preserved ejection fraction (HFpEF) has a highly variable phenotype, heterogeneity in left ventricular chamber size (LVCS) and its association with long-term outcome have not been thoroughly investigated. The present study sought to determine the impact of LVCS on clinical outcome in HFpEF.A total of 1505 consecutive HFpEF patients admitted to hospitals in the multicenter WET-HF Registry for acute decompensated HF (ADHF) between 2006 and 2017 were analyzed. The patients (age: 80 [73-86], male: 48%) were divided into larger (L) or smaller (S) LV end-diastolic diameter (LVEDD) groups by the median value 45 mm.Younger age, male sex, higher body mass index, more favorable nutritional status, valvular etiology, and lower LVEF were associated with larger LVEDD. After propensity matching (399 pairs), the L group showed a larger left atrial diameter, E/e', and tricuspid regurgitation pressure gradient and greater severity of mitral regurgitation. The L group had a higher rate of composite endpoint of all-cause death and ADHF re-admission (P = 0.021) and was an independent predictor. On the other hand, in the pre-matched cohort, the S group rather showed higher in-hospital (4% versus 2%. P = 0.004) and post-discharge mortality (P = 0.009).In HFpEF, LVCS was affected by demographic and cardiac parameters. After adjustment for demographic parameters, larger LVCS was associated with worse clinical outcome. Higher mortality in the S group in the pre-matched cohort might be related to the demographic factors suggesting frailty and/or sarcopenia.

Layer-specific longitudinal strain predicts left ventricular maximum wall thickness in patients with hypertrophic cardiomyopathy.

AIMS: The aim of this study was (a) to clarify the detailed mechanisms of structural and functional abnormalities of myocardial tissue in hypertrophic cardiomyopathy (HCM) using layer-specific strain (LSS) and compare it with healthy subjects (b) to investigate the diagnostic accuracy of LSS for HCM. METHODS AND RESULTS: Forty-one patients with HCM and preserved left ventricular ejection fraction (LVEF; 66% male, 52 ± 18 years, LVEF 62.9% ± 3.7%) and 41 controls matched for age and sex (66% male, 52 ± 20 years, LVEF 63.5% ± 8.2%) underwent 2D-speckle tracking echocardiography. Absolute values of LSS were globally lower and the ratio of endocardial/epicardial layer (End/Epi ratio) was higher in HCM. LSS gradually increased from the epicardial toward the endocardial layer at all chamber views and at all levels of the LV. LSS and End/Epi ratio at the apex were higher than those at the middle or basal level of the LV. End/Epi ratio was correlated with LV maximal wall thickness both controls (r = .35, P = .03) and HCM (r = .81, P < .001). End/Epi ratio was an independent factor associated with LV maximal wall thickness (ß = 0.96, P < .001). A higher End/Epi ratio (≥1.31) was associated with diagnostic criteria for HCM (sensitivity 98%, specificity 95%, area under the curve 0.99, P < .001). CONCLUSION: LSS has the potential for unraveling the mechanism of impaired LV wall motion in HCM and to accurately detect HCM.

In-Hospital Serum Uric Acid Change Predicts Adverse Outcome in Patients With Heart Failure.

BACKGROUND: Elevated serum uric acid (UA) is associated with an increased risk of adverse outcome in patients with heart failure (HF), but it remains unknown whether the change of serum UA level during the treatment of acute decompensated HF (ADHF) predicts adverse events. METHODS AND RESULTS: We retrospectively analyzed consecutive 1562 patients who were hospitalized for ADHF. Serum UA levels both at admission and discharge were available in 1246 patients (78 years of age, range 69-84 years, 40% female). UA values increased or unchanged (group I) in 766 patients and it decreased in the remaining patients (group D). Group I was characterized by older age, higher proportion of females, preserved left ventricular ejection fraction, and the features of less severity of HF such as lower plasma N-terminal pro B-type natriuretic peptide level and lower percentage of catecholamine use. Nevertheless, group I was associated with higher incidence of the primary end point defined as the composite of all-cause death and ADHF rehospitalization (P = .013, log-rank test). UA change, but not UA at discharge, was an independent predictor of the primary end point (hazard ratio 1.30, interquartile range 1.04-1.64, P = .022). Age, estimated glomerular filtration rate, left ventricular ejection fraction, dose of loop diuretics, and thiazide prescription at discharge were independently associated with the UA change. CONCLUSIONS: In patients with HF, UA change through the treatment of ADHF might predict future adverse outcome.

Prediction of sudden cardiac death in Japanese heart failure patients: international validation of the Seattle Proportional Risk Model.

AIMS: Heart failure (HF) is associated with an increased risk of sudden cardiac death (SCD). This study sought to demonstrate the incidence of SCD within a multicentre Japanese registry of HF patients hospitalized for acute decompensation, and externally validate the Seattle Proportional Risk Model (SPRM). METHODS AND RESULTS: We consecutively registered 2240 acute HF patients from academic institutions in Tokyo, Japan. The discrimination and calibration of the SPRM were assessed by the c-statistic, Hosmer-Lemeshow statistic, and visual plotting among non-survivors. Patient-level SPRM predictions and implantable cardioverter-defibrillator (ICD) benefit [ICD estimated hazard ratio (HR), derived from the Cox proportional hazards model in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)] was calculated. During the 2-year follow-up, 356 deaths (15.9%) occurred, which included 76 adjudicated SCDs (3.4%) and 280 non-SCDs (12.5%). The SPRM showed acceptable discrimination [c-index = 0.63; 95% confidence interval (CI) 0.56-0.70], similar to that of original SPRM-derivation cohort. The calibration plot showed reasonable conformance. Among HF patients with reduced ejection fraction (EF; < 40%), SPRM showed improved discrimination compared with the ICD eligibility criteria (e.g. New York Heart Association functional Class II-III with EF ≤ 35%): c-index = 0.53 (95% CI 0.42-0.63) vs. 0.65 (95% CI 0.55-0.75) for SPRM. Finally, in the subgroup of 246 patients with both EF ≤ 35% and SPRM-predicted risk of ≥ 42.0% (SCD-HeFT defined ICD benefit threshold), mean ICD estimated HR was 0.70 (30% reduction of all-cause mortality by ICD). CONCLUSION: The cumulative incidence of SCD was 3.4% in Japanese HF registry. The SPRM performed reasonably well in Japanese patients and may aid in improving SCD prediction.

Impact of Pulmonary Artery-to-Aorta Ratio by CT on the Clinical Outcome in Heart Failure.

INTRODUCTION: Previous studies have indicated that the ratio of pulmonary artery (PA) to ascending aorta (Ao) diameter as measured by computed tomography (PA/Ao) is strongly associated with pulmonary artery pressure. However, the clinical significance of PA/Ao in heart failure (HF) has not been fully characterized. We sought to investigate the prognostic impact of PA/Ao in HF. METHODS: Based on the prospective registry of patients admitted to our institution due to acute decompensated HF (ADHF), the records of the consecutive 761 patients admitted between 2011 and 2016 were reviewed. Thoracic computed tomography data during the hospital stays were obtained from 447 patients (median 78 (70-84) years of age; male, 62.2%). The diameters of PA and Ao were measured at the level of PA bifurcation. The subjects were divided into the H group (PA/Ao ≥ 1.0) and the L group (PA/Ao < 1.0) according to the PA/Ao values. The cutoff value was derived from receiver operating curve analysis. RESULTS: There were no significant differences in age, sex or body mass index between the H and L groups. The H group was associated with significantly larger left atrial dimension (LAD), higher tricuspid regurgitation peak gradient (TRPG) and E/e' (LAD, H, 48 (42-55) mm vs L, 45 (39-50) mm, P < 0.001; TRPG, H, 34 (26-48) mm Hg vs L, 28 (22-38) mm Hg, P < 0.001; E/e', H, 23.3 (42-55) vs L, 18.4 (13.9-25), P < 0.001). Length of hospital stay was significantly longer in the H group than in the L group (H, 19 (14-32) days vs L, 16 (12-23) days, P < 0.001). In-hospital mortality was significantly higher in the H group compared with the L group (H, 5.4% vs L, 1.2%, P = 0.02). Age, sex, LAD and TRPG were independently associated with PA/Ao. The primary endpoint, defined as the composite of all-cause death and ADHF rehospitalization during a median of 479 days after discharge, was significantly more common in the H group (P < 0.001, log-rank test). PA/Ao was independently associated with the primary endpoint, even after adjusting for the other confounding factors (P = 0.002). CONCLUSIONS: PA/Ao is a reliable marker for the prediction of the outcome of patients with ADHF.

Heart Failure With Midrange Ejection Fraction in Patients Admitted for Acute Decompensation: A Report from the Japanese Multicenter Registry.

BACKGROUND: Patients having heart failure with midrange ejection fraction (HFmrEF: 40% ≤ EF < 50%) are increasingly being considered a new subset of the population with heart failure. Despite recent advances in heart-failure treatment strategies, the prognosis of these patients has not improved substantially over time. In addition, the significance of this new phenotype in hospitalized patients with acute decompensated heart failure (ADHF), another population whose prognosis has not improved, also remains poorly understood. This study aimed to describe the clinical characteristics, prognosis and treatment responses of patients with HFmrEF hospitalized for ADHF. METHODS: On the basis of consecutive inpatient data from a multicenter ADHF registry, 651 of 3572 patients (17.1%) were classified as having HFmrEF. Prognostic factors predicting composite outcomes, defined as all-cause death and heart failure readmission, as well as all-cause death alone, were analyzed. RESULTS: In the median follow-up duration of 724 days, both composite endpoints and all-cause death alone were comparable in those with heart failure with preserved ejection fraction, HFmrEF and heart failure with reduced ejection fraction. Age, anemia, hyponatremia, elevated blood urea nitrogen, chronic kidney disease, and elevated plasma brain natriuretic peptide levels were significant predictors of composite outcomes in HFmrEF. CONCLUSIONS: Roughly one-sixth of the patients with ADHF had HFmrEF. The long-term prognosis of patients with HFmrEF was not significantly different from that of patients with heart failure with preserved ejection fraction and heart failure with reduced ejection fraction in the population with ADHF. Risk factors for adverse outcomes in HFmrEF were also similar to those for heart failure with preserved ejection fraction and HFmrEF in the hospitalized population with ADHF.

Validation and Recalibration of Seattle Heart Failure Model in Japanese Acute Heart Failure Patients.

BACKGROUND: Precise risk stratification in heart failure (HF) patients enables clinicians to tailor the intensity of their management. The Seattle Heart Failure Model (SHFM), which uses conventional clinical variables for its prediction, is widely used. We aimed to externally validate SHFM in Japanese HF patients with a recent episode of acute decompensation requiring hospital admission. METHODS AND RESULTS: SHFM was applied to 2470 HF patients registered in the West Tokyo Heart Failure and National Cerebral And Cardiovascular Center Acute Decompensated Heart Failure databases from 2006 to 2016. Discrimination and calibration were assessed with the use of the c-statistic and calibration plots, respectively, in HF patients with reduced ejection fraction (HFrEF; <40%) and preserved ejection fraction (HFpEF; ≥40%). In a perfectly calibrated model, the slope and intercept would be 1.0 and 0.0, respectively. The method of intercept recalibration was used to update the model. The registered patients (mean age 74 ± 13 y) were predominantly men (62%). Overall, 572 patients (23.2%) died during a mean follow-up of 2.1 years. Among HFrEF patients, SHFM showed good discrimination (c-statistic = 0.75) but miscalibration, tending to overestimate 1-year survival (slope = 0.78; intercept = -0.22). Among HFpEF patients, SHFM showed modest discrimination (c-statistic = 0.69) and calibration, tending to underestimate 1-year survival (slope = 1.18; intercept = 0.16). Intercept recalibration (replacing the baseline survival function) successfully updated the model for HFrEF (slope = 1.03; intercept = -0.04) but not for HFpEF patients. CONCLUSIONS: In Japanese acute HF patients, SHFM showed adequate performance after recalibration among HFrEF patients. Using prediction models to tailor the care for HF patients may improve the allocation of medical resources.

Prognostic Impact of Previous Hospitalization in Acute Heart Failure Patients.

BACKGROUND: The natural course of heart failure (HF) is typically associated with repeated hospitalizations, and subsequently, patient prognosis deteriorates. However, the precise relationship between repeated admissions for HF and long-term prognosis remains unknown. Methods and Results: We analyzed data from 1,730 consecutive acute HF patients registered in the West Tokyo Heart Failure (WET-HF) registry between June 2005 and April 2014 (median age, 76 years). Patients were divided into 3 groups according to the number of previous HF admissions at the time of the index admission (0, n=876 [55.4%]; 1, n=425 [26.9%]; ≥2, n=279 [17.7%] previous admissions). A history of multiple previous admissions was an independent predictor for all-cause death and HF readmission in reference to a history of a single previous admission (hazard ratio (HR), 1.53; 95% confidence interval (CI) 1.10-2.13; HR, 1.90 95% CI, 1.47-2.44, respectively) or no previous admissions (HR, 1.37, 95% CI, 1.01-1.85; HR, 2.83, 95% CI, 2.19-3.65, respectively). On the other hand, a history of a single previous admission was an independent predictor for HF readmission in reference to a history of no previous admissions (HR, 1.51, 95% CI, 1.18-1.92), but not for all-cause death (HR, 0.89, 95% CI, 0.66-1.20). CONCLUSIONS: Based on a contemporary multicenter HF registry, a history of multiple previous HF admissions was revealed as an independent, strong risk factor of adverse events following the index admission. The number of hospitalizations could be a simple and important surrogate indicating subsequent adverse events in patients with HF.

Length of hospital stay and its impact on subsequent early readmission in patients with acute heart failure: a report from the WET-HF Registry.

Heart failure (HF) is characterized by frequent rehospitalization and prolonged hospital stay. Although length of stay has been used as a surrogate marker for hospital performance, its association with early rehospitalization remains unknown. We investigated their precise association using contemporary Japanese HF registry. We analyzed the 2785 acute HF patients who were registered in the West Tokyo Heart Failure registry and discharged or transferred to the recuperation facilities (mean age, 73.8 ± 13.5 years; 60.8% were men). Median length of stay was 15 days (interquartile range, 10-23 days). One-hundred and fourteen patients (4.1%) were readmitted for worsening HF within 30 days after discharge. Thirty-day risk-adjusted HF readmission after a shorter length of stay (1-12 days; the lower tertile within the cohort) was higher than those after intermediate (13-19 days; the middle tertile) [HR 1.71, 95% confidence interval (CI) 1.05-2.77]. Even after a longer length of stay, there tended to be a higher risk of 30-day HF readmission (HR 1.59, 95% CI 0.96-2.65). In conclusion, the Japanese acute HF patients had low rates of early-HF readmission after quite a long length of stay at urban tertiary care centers. Shorter length of stay was associated with increased rates of 30-day HF readmission, while longer length of stay also the same trended.Clinical Trial Registration: https://www.umin.ac.jp/icdr/index-j.html . Unique identifier: UMIN000001171.

Multiple papillary fibroelastomas attached to left ventricular side and aortic side of the aortic valve: A report of new case and literature review.

The aortic valve (AV) is the most commonly affected site in multiple papillary fibroelastomas, but the frequency of embolism caused by the attachment side of the AV has not been elucidated. According to the review of the previous literature, 16 cases have been found attached to the AV. Of these, 6 of these have been found to be attached on the aortic side and 4 on the left ventricular side, 1 was bilateral, and 5 cases were unknown. Of the cases found on the aortic side, embolism occurred in 3 of them, and of the left ventricular side cases, embolism occurred in 2 of them. The frequency of embolism is equivalent even if papillary fibroelastoma attached to either side of the AV.

Anemia Is Associated With Blunted Response to ß-Blocker Therapy Using Carvedilol　- Insights From Japanese Chronic Heart Failure (J-CHF) Study.

BACKGROUND: Anemia portends a poor clinical outcome in patients with chronic heart failure (CHF). However, its mechanism remains unknown. We sought to elucidate the effect of anemia on patients with HF with reduced ejection fraction (HFrEF) who receive carvedilol therapy.Methods and Results:J-CHF study was a prospective, randomized, multicenter trial that assigned 360 HFrEF patients to 2.5 mg/5 mg/20 mg carvedilol groups according to the target dose. At baseline 70 patients (19%) had anemia ([A]) defined as hemoglobin level (Hb) <13 g/dL (male) or <12 g/dL (female) and the remaining 290 did not ([N]). Allocated and achieved doses of carvedilol were similar. Left ventricular ejection fraction (LVEF) and plasma B-type natriuretic peptide (BNP) level significantly improved in both groups over 56 weeks, but they were smaller in [A] than in [N] (LVEF, P=0.046; BNP, P<0.0001 by ANOVA). Baseline Hb was an independent predictor of absolute change in LVEF (ß=0.13, P=0.047) and BNP (ß=-0.10, P=0.01). Presence of chronic kidney disease defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2at baseline was not associated with differential response to carvedilol therapy. During 3.8±1.4 years follow-up, group [A] had a higher incidence of the composite endpoint of death, hospitalization for cardiovascular causes including HF compared with [N] (P=0.006). Baseline Hb was an independent predictor of the composite endpoint (hazard ratio 0.86, P=0.04), whereas baseline eGFR was not. CONCLUSIONS: Our data suggested that anemia was associated with a blunted response to carvedilol in HFrEF patients.

Effects of glycemic control on in-hospital mortality among acute heart failure patients with reduced, mid-range, and preserved ejection fraction.

The relationship between glycemic control and outcome in patients with heart failure (HF) remains contentious. A recent study showed that patients with HF with mid-range ejection fraction (HFmrEF) more frequently had comorbid diabetes relative to other patients. Herein, we examined the association between glycosylated hemoglobin (HbA1c) and in-hospital mortality in acute HF patients with reduced, mid-range, and preserved EF. A multicenter retrospective study was conducted on 5205 consecutive patients with acute HF. Potential risk factors for in-hospital mortality were selected by univariate analyses; then, multivariate Cox regression analysis with backward stepwise selection was performed to identify significant factors. Kaplan-Meier survival curves and log-rank testing were used to compare in-hospital mortality between groups. Across the study cohort, 44% (2288 patients) had reduced EF, 20% had mid-range EF, and 36% had preserved EF. The overall in-hospital mortality rate was 4.6%, with no significant differences among the HF patients with reduced, mid-range, and preserved EF groups. For patients with HFmrEF, higher HbA1c level was a significant risk factor for in-hospital mortality (hazard ratio 1.387; 95% confidence interval 1.014-1.899; P = 0.041). In contrast, HbA1c was not an independent risk factor for in-hospital mortality in HF patients with preserved or reduced EF. In conclusion, HbA1c is an independent risk factor for in-hospital mortality in acute HF patients with mid-range EF, but not in those with preserved or reduced EF. Elucidation of the pathophysiological mechanisms behind these findings could facilitate the development of more effective individualized therapies for acute HF.

Effect of Obesity on the Prognostic Impact of Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Although obesity is associated with left ventricular hypertrophy, diastolic dysfunction, and occurrence of atrial fibrillation (AF), obese heart failure (HF) patients have a more favorable clinical outcome (obesity paradox). The clinical impact of AF on obese or lean HF patients has not been fully elucidated.Methods and Results:We analyzed 1,681 patients who were enrolled in the West Tokyo Heart Failure Registry (WET-HF Registry), a multicenter, prospective cohort registry from 2005 through 2014. We assigned them to 3 categories based on body mass index (BMI): low, BMI <18.5; medium, BMI ≥18.5 and <25; and high, BMI ≥25 (n=182/915/400). The clinical endpoint was all-cause death or readmission for acute decompensated HF. During 406 days of follow-up (IQR, 116-739 days), AF was associated with a higher risk of the endpoint in the HF with preserved ejection fraction (HFpEF) group (P<0.001, log-rank test), but not in the HF with reduced EF (HFrEF) group. AF was associated with a higher risk of the endpoint in low and medium BMI patients with HFpEF (P=0.016 and 0.009, respectively). On Multivariate Cox proportional hazards analysis, AF was an independent predictor of the endpoint in patients with BMI <25 from the HFpEF group (hazard ratio, 1.74; 95% CI: 1.21-2.54, P=0.003), but not in the other subgroups. CONCLUSIONS: AF had a negative impact on clinical outcome in non-obese patients with HFpEF.