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Brain or B-type natriuretic peptide (BNP) is an objective marker to diagnose the presence of heart failure (HF) and assess its severity. However, the determinants of serum BNP level in elderly patients with severe aortic valve stenosis (AS) referred for transcatheter aortic valve implantation (TAVI) have not been well investigated.We prospectively studied 106 AS patients who underwent TAVI. Cardiac catheterization, transesophageal echocardiography, and blood collection for plasma BNP level measurements were performed simultaneously just before the TAVI procedures.Ninety-nine patients (83.9±5.0 years, 33% male) were studied. The natural logarithm of BNP (lnBNP) level was 5.4±0.9 pg/mL. Significant correlations with lnBNP level were observed in: 1) the history of syncope, prior HF medication, and New York Heart Association class III or IV (R=0.255, p=0.011) (R=0.210, p=0.037) (R=0.402, p0.001), 2) albumin and hemoglobin level (R=-0.289, p=0.004) (R=0.263, p=0.009), 3) Left ventricular (LV) ejection fraction and global longitudinal strain (LVGLS) (R=-0.338, p0.001) (R=0.447, p0.001), 4) LV end-diastolic volume index (EDVI), LV mass index, and left atrial volume index (R=0.280, p=0.005) (R=0.366, p0.001) (R=0.337, p0.001), 5) the catheter-measured pressure gradient across the aortic valve (AVPG) (R=0.365, p0.001). Note that LV wall stress was not significantly correlated with lnBNP level. LVGLS, AVPG, hemoglobin level, and LVEDVI were independently correlated with ln BNP level (R=0.652, LVGLS; β=0.395, p0.006, AVPG; β=0.291, p=0.001, hemoglobin level; β=-0.216, p=0.011, and LVEDVI; β=0.203, p=0.016, respectively).In severe AS patients candidate for TAVI, multiple factors, including the severities of AS and HF conditions and subclinical LV dysfunction determined by LVGLS affects plasma BNP level.

We herein report three patients with cardiac angiosarcoma who were directly admitted to the intensive-care unit for hemodynamic instability with circulatory collapse. Using a multidisciplinary cardio-oncologic approach, we diagnosed their condition as angiosarcoma by an invasive biopsy and urgently started weekly paclitaxel administration despite their poor performance status. Their vital signs were soon stabilized, leading to the patients’ discharge from the hospital. Although no treatment guidelines for cardiac angiosarcoma have been established, chemotherapy with paclitaxel can be an option for cases presenting with hemodynamic instability.

Background Interruption in Doppler intrarenal venous flow (IRVF) has been used in assessing renal congestion and in the prediction of prognosis of cardiovascular diseases. However, there is a paucity of pathophysiological knowledge, so we aimed to clarify the determinants of IRVF interruption.Methods and Results:Intrarenal Doppler studies were performed within 24 h before right-side catheterization studies. The interruption in IRVF in 73 patients was divided into a continuous pattern, and 4 discontinuous types based on the timing of interruption. Type 1, with an interruption in early systole, was associated with a-wave elevation of right atrial pressure (RAP). Type 2, with an interruption in early diastole, was associated with v-wave elevation, tricuspid regurgitation (TR), and right ventricular dysfunction. Both Type 1 and 2 were observed even in the normal range of mean RAP. Type 3, with an interruption throughout systole, was observed in advanced right heart failure patients with markedly elevated RAP, particularly elevated x-descend and atrial fibrillation. Finally, Type 4, with limited flow at systole, was observed in 2 of the patients with pulmonary arterial hypertension. Conclusions IRVF interruption was closely related to RAP elevation at each specific point of the cardiac cycle rather than to mean RAP levels, suggesting that the characteristics of IRVF mirror right-sided heart hemodynamics, not mean RAP.

Objective Onco-cardiology services are expanding rapidly in Japan. To provide a better service, it is important to consider the needs of oncologists. However, little is known regarding specific needs for which oncologists should consult cardiologists to manage cardiovascular problems of their patients. We analysed cardiology consultations sought by oncologists to evaluate the role of cardiologists in cancer treatment. Method We retrospectively investigated consecutive 2064 cardiology consultations of cancer patients in the University of Tsukuba Hospital, Tsukuba, Japan, between January 2014 and December 2018. Results The most common timing of cardiology consultation was before the commencement of cancer treatment (n = 1355; 65.7%), followed by after the commencement of cancer treatment (n = 686; 33.2%). Among the 361 consultations before the administration of anticancer drugs, 235 (65.1%) were for anthracycline-based regimens. There were 506 (24.5%) consultations for the management of cardiovascular emergencies developing after the commencement of cancer treatment; venous thromboembolism was the most frequent (n = 125; 24.7%), followed by atrial fibrillation (n = 110; 21.7%) and heart failure (n = 74; 14.6%). There were marked differences in the types of cardiovascular emergencies depending on the type of cancer. Conclusions This survey revealed the various cardiovascular problems for which oncologists sought interventions by cardiologists. A multidisciplinary approach in an onco-cardiology service is essential to achieve optimal long-term outcomes.

The score based on the office systolic blood pressure, age, fasting blood glucose level, and estimated glomerular filtration rate (SAGE score) has been proposed as a useful marker to identify elevated values of carotid-femoral pulse wave velocity (PWV). The present cross-sectional study was conducted to examine whether the SAGE score is also a useful marker to identify subjects with elevated brachial-ankle PWV values in Japanese subjects with hypertension. We measured the brachial-ankle PWV and calculated the SAGE score in a total of 1019 employees of a Japanese company with hypertension and 817 subjects with hypertension derived from a multicenter study cohort. The analyses in this study were based on data from these two study groups as well as on a composite population of the two (n = 1836). The receiver operating characteristic curve analysis showed that the area under the curve to identify subjects with brachial-ankle PWV values of ≥1800 cm/s was over 0.70 in each of the three study groups. Even after adjustments, a SAGE score ≥7 had a significant odds ratio for identifying subjects with brachial-ankle PWV values ≥1800 cm/s in the 1836 study subjects from the composite occupational and multicenter study cohort (odds ratio = 2.1, 95% confidence interval = 1.4–3.0, P

The usefulness of brachial-ankle pulse wave velocity (baPWV), an index of arterial stiffness, is not fully known for the management of treated hypertensive patients with a history of coronary artery disease (CAD) who have blood pressure less than 130/80 mmHg, a recommended blood pressure target in the updated major hypertension guidelines. We analyzed data for 447 treated hypertensive patients with CAD enrolled in FMD-J Study A for assessment of the predictive value of baPWV for future cardiovascular events. The primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow-up period of 47.6 months, the primary outcome occurred in 64 patients. Blood pressure less than 130/80 mmHg was significantly associated with a lower risk of the composite outcome independent of other cardiovascular risk factors in treated hypertensive patients with CAD (hazard ratio, 0.59; 95% confidence interval (CI), 0.35-0.99; P = 0.04). In treated hypertensive patients with CAD who had blood pressure less than 130/80 mmHg, baPWV above the cutoff value of 1731 cm/s, derived from receiver-operator characteristic curve analysis for the composite outcome was significantly associated with a higher risk of the composite outcome independent of conventional risk factors (hazard ratio, 2.83; 95% CI, 1.02-7.91; P = 0.04). baPWV was an independent predictor of cardiovascular events in treated hypertensive patients with CAD who had blood pressure less than 130/80 mmHg, for whom measurement of baPWV is recommended for cardiovascular risk assessment.

To determine the influence of right bundle branch block (RBBB) on right ventricular (RV) size and function, we investigated the association between complete RBBB (CRBBB) and RV volume, function, and dyssynchrony by three-dimensional echocardiography. In this retrospective, cross-sectional study, 103 consecutive patients with adequate three-dimensional echocardiographic images were divided into the CRBBB, middle-range QRS, and narrow QRS group. RV volumetric and functional data were compared between the three groups. Among the 103 patients (44.8 ± 18.7 years, 50 men), the CRBBB group comprised 26 (25%) patients and the middle-range QRS group comprised 48 (47%). The CRBBB group showed a significant contraction delay in the RV inlet free wall and outflow tract; larger RV end-diastolic and systolic volume index (RV-EDVI, RV-ESVI); and lower RV systolic function. On dividing the CRBBB patients into two (with or without mechanical dyssynchrony), those with RV dyssynchrony showed larger RV-EDVI (121 ± 45 vs. 85 ± 25 mL/m2, P = 0.019) and RV-ESVI (93 ± 42 vs. 56 ± 20 mL/m2, P = 0.009) and smaller RV ejection fraction (24 ± 11 and 34 ± 11%, P = 0.026) than those without RV dyssynchrony. RV dyssynchrony in CRBBB patients might have an adverse effect on RV volume and function. Three-dimensional speckle-tracking echocardiography could provide additional and beneficial data during assessment of RV dyssynchrony.

Background Although atrial fibrillation (AF) is associated with exacerbation of heart failure with preserved ejection fraction (HFpEF), the relationships between maintenance of sinus rhythm (SR) and clinical outcomes in HFpEF is unknown. We investigated whether maintenance of SR was associated with better prognosis compared with rate control in patients with concomitant HFpEF and AF. Methods We conducted a retrospective, observational study of 283 patients with HFpEF and AF. Of these, 107 patients achieved maintenance of SR by catheter ablation and/or antiarrhythmic drugs (rhythm control) and 176 were treated with rate control. The propensity score (PS) for each patient in both treatment groups was estimated, resulting in selectively matched subgroups of 79 patients each. All-cause death and a composite of cardiovascular death or hospitalization for heart failure (HF) were analyzed. Results During a median follow-up period of 24 months, all-cause mortality was comparable between groups; however, maintenance of SR was significantly associated with a lower incidence of the composite endpoint [adjusted hazard ratio (HR), 0.30; 95% confidence interval, 0.18–0.98; p = 0.04] in the PS-matched cohort. The PS-adjusted multivariable analysis based on 283 pre-matched patients also revealed that rhythm control was associated with a lower rate of the composite endpoint (adjusted HR, 0.27; 95% CI, 0.12–0.61; p = 0.002). Subgroup analyses suggested that rhythm control was consistently related to the composite endpoint across a wide spectrum of HFpEF patients. Conclusions Maintenance of SR was associated with a lower risk of composite of cardiovascular death or hospitalization for HF in patients with HFpEF and AF. A randomized trial is necessary to confirm this result.

Background There is an ongoing debate regarding optimal management of patients with paradoxical low gradient severe aortic stenosis (PLG-SAS). We hypothesized that the presence of symptoms is closely associated with future adverse outcome. We aimed to determine the relation between symptoms and outcome in patients with PLG-SAS. Methods We prospectively enrolled 222 patients with PLG-SAS. Left ventricular (LV) volumes, mass, and strain were measured by three-dimensional echocardiography. The primary end-point was cardiac events including cardiac death, ventricular fibrillation, and heart failure leading to hospitalization. Results There were 65 cases of symptomatic PLG-SAS and 157 cases of asymptomatic PLG-SAS. Patients with symptomatic PLG-SAS received beta-blockers, angiotensin blockers, and diuretics more frequently and showed higher levels of B-type natriuretic peptide than patients with asymptomatic PLG-SAS. Although LV chamber parameters were not different, patients with symptomatic PLG-SAS had significantly higher E-wave velocity and E/A ratio than patients with asymptomatic PLG-SAS. During the median follow-up of 18 months, 20 patients reached the primary end-point. Patients with symptomatic PLG-SAS had significantly worse prognosis than patients with asymptomatic PLG-SAS. A similar trend was observed while comparing with the propensity-score-matched cohort after adjusting for age, sex, stroke volume index, and severity of AS. Conclusions Symptomatic PLG-SAS is associated with poorer prognosis even after adjusting for flow status and severity of AS. Therefore, presence of symptoms is not always related to the severity of AS itself but might be related to the underlying comorbidities. Our results suggest a possible link between PLG-SAS and heart failure with preserved ejection fraction in some symptomatic patients.

Background: Circulating triglyceride (TG) levels are a current focus as a residual risk for cardiovascular (CV) events. We evaluated the relationship between circulating TG levels and future CV events in patients with coronary artery disease (CAD) who were treated with conventional therapy. Methods and Results: We analyzed data for 652 patients who were enrolled in the FMD-J Study A. We investigated the associations between serum TG levels and first major CV events (death from CV cause, nonfatal acute coronary syndrome (ACS), nonfatal stroke, and CAD) for a 3-year follow-up period. Patients were divided into 4 groups based on serum TG level: low-normal (

Aims The objective of the study was to evaluate whether the geriatric nutritional risk index (GNRI) at discharge may be helpful in predicting the long‐term prognosis of patients hospitalized with heart failure (HF) with preserved ejection fraction (HFpEF, left ventricular ejection fraction ≥50%), a common HF phenotype in the elderly. Methods and results Overall, 110 elderly HFpEF patients (≥65 years) from the Ibaraki Cardiovascular Assessment Study‐HF (n = 838) were enrolled. The mean age was 78.5 ± 7.2 years, and male patients accounted for 53.6% (n = 59). All‐cause mortality was compared between the low GNRI (

The vasopressin type 2 receptor antagonist tolvaptan may have renoprotective effects in patients with heart failure (HF). This study aimed to reveal the renoprotective effect of tolvaptan from the viewpoint of hemodynamic combined with catheter and ultrasound examinations in a hypertensive HF model. Dahl salt-sensitive rats (n = 24) were fed an 8% high-salt diet after the age of 6 weeks and were treated with tolvaptan (n = 16) or vehicle (control group; n = 8). The tolvaptan-treated rats were divided into two groups: a low-dose group (0.01% tolvaptan diet; Low-Tol) and a high-dose group (0.05% tolvaptan diet; High-Tol). At 24 weeks, catheterizations to measure central venous pressure (CVP) and renal medullary pressure (RMP) were performed, followed by intrarenal Doppler (IRD) studies and contrast-enhanced ultrasonography (CEUS) to evaluate renal medullary perfusion. The tolvaptan diet reduced CVP (7.7 ± 1.5, 9.0 ± 1.1, and 12.2 ± 0.8 mmHg in the High-Tol, Low-Tol, and control groups, respectively; p < 0.001) and RMP (7.7 ± 0.8, 9.4 ± 1.3, and 13.7 ± 1.2 mmHg in the High-Tol, Low-Tol, and control groups, respectively; p < 0.001). Tolvaptan also reduced the venous impedance index (VII) in the IRD analysis (0.18 ± 0.03, 0.26 ± 0.04, and 0.40 ± 0.08 in the High-Tol, Low-Tol, and control groups, respectively; p < 0.001), and the time to peak intensity in CEUS (6.0 ± 0.5, 7.3 ± 1.3, 9.8 ± 1.8 s in the High-Tol, Low-Tol, and control groups, respectively; p < 0.001). Creatinine clearance (Ccr) was preserved in both the High-Tol and Low-Tol groups compared to the control group (4.80 ± 1.9, 4.24 ± 0.8, and 1.35 ± 0.3 mg/min, respectively; p = 0.001). Ccr was negatively correlated with RMP (R = -0.76, P < 0.001), the venous impedance index (R = -0.70, p < 0.001), time to peak intensity (R = -0.75, P < 0.001), and renal fibrosis (R = -0.70, p < 0.001). In contrast, Ccr had modest correlations with systolic blood pressure (R = -0.50, P = 0.02) and left ventricular ejection fraction (R = 0.48, P = 0.03). This study revealed that the renoprotective effects of tolvaptan in a hypertensive HF model depended on renal decongestion.

Objectives The endothelial dysfunction-arterial stiffness-atherosclerosis continuum plays an important pathophysiological role in hypertension. The aim of this study was to investigate the cross-sectional association between serum uric acid (SUA) and vascular markers related to this continuum, and to assess the longitudinal association between SUA and endothelial function that represents the initial step of the continuum. Methods We evaluated the baseline associations between SUA levels and vascular markers that included flow-mediated vasodilatation (FMD), brachial-ankle pulse wave velocity (baPWV), and common carotid artery intima-media thickness (CCA-IMT) in 648 subjects receiving antihypertensive treatment. The longitudinal association between baseline SUA levels and FMD measured at 1.5 and 3 yr of follow-up was also investigated. Results At baseline, modest, but significant correlations were observed between SUA and FMD in females (r = −0.171), baPWV in males with SUA >368.78 μmol/L (r = −0.122) and in females with a SUA level ≤ 362.83 μmol/L (r = 0.217), mean CCA-IMT in females with a SUA level ≤ 333.09 μmol/L (r = 0.139), and max CCA-IMT in females with SUA level ≤ 333.09 μmol/L (r = 0.138). A longitudinal association between SUA and FMD was less observed in males. In females, the baseline SUA was associated significantly with FMD values at 1.5 yr (r = −0.211), and SUA levels >237.92 μmol/L were associated significantly and independently with FMD values at 3 yr (r = −0.166). Conclusions Lower SUA levels were associated with better vascular markers of the continuum, especially in females. Furthermore, we observed a longitudinal association between SUA and endothelial function, suggesting SUA level may be a potential marker of the continuum in hypertension.

As the number of cancer survivors increases, cardiac management in anthracycline-treated patients has become more important. We planned to conduct a prospective multicenter registry study for comprehensive echocardiographic and biomarker data collection and an evaluation of the current practice in terms of diagnosis and management of anthracycline-induced cardiotoxicity (AIC registry). To examine the feasibility of this registry study, we analyzed the 1-year follow-up data of 97 patients registered during the first year of this registry. The AIC registry was launched in July 2016. Data on echocardiographic parameters (e.g., two-and three-dimensional [(2- and 3-D) left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS)) and biomarkers (e.g., troponin T and brain natriuretic peptide) were collected before anthracycline treatment, every 3 months during the first year after starting anthracycline, and every 6 months during the second year. Eighty-three patients (86%) completed a 1-year follow-up. The measurable rates of 2D LVEF, 3D LVEF, and GLS on each visit were nearly optimal (100%, 86–93%, and 84–94%, respectively). During the 1-year follow-up, 5 patients (6.0%) developed cardiotoxicity (a reduction in LVEF ≥ 10 percentage points from baseline and &lt, 55%). The AIC registry study is feasible and will be the first study to collect sizable echocardiographic and biomarker data on cardiotoxicity in Japanese patients treated with anthracycline in a real-world setting.

Background Diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging in elderly. This study investigated the diagnostic ability of the HFA-PEFF scoring system in elderly patients (>75 years of age).Methods and Results:This study enrolled 286 subjects aged >75 years (130 men; mean [± SD] age 81.5±5.1 years): 95 healthy controls, 98 with hypertension (HT), and 93 with HFpEF. The HFA-PEFF score was calculated as a sum of points in functional, morphological, and biomarker domains. In the HFpEF group, 84%, 84%, and 70% of subjects met the major functional, morphological, and biomarker criteria for HFpEF, respectively. Thus, 73 subjects with HFpEF (78%) were diagnosed as having HFpEF using the HFA-PEFF scoring system. In contrast, among the healthy controls and subjects with HT, 52% and 72%, respectively, met the major functional criteria for HFpEF, 28% and 53%, respectively, met the morphological criteria, and 0% and 24%, respectively, met the biomarker criteria. As such, 32 subjects with HT (33%) were diagnosed with HFpEF. Even in the healthy control group, 72% were classified as having an intermediate probability of HFpEF, and 3 were diagnosed with HFpEF. Conclusions In the late elderly, the HFA-PEFF scoring system diagnosed subjects with HFpEF precisely. In addition, this scoring system may be able to detect early stage HFpEF in the subclinical population.

Background Lead-induced tricuspid regurgitation (TR) after cardiac implantable electronic device (CIED) implantation is not fully understood. This study aimed to reveal the features of lead-induced TR by 3-dimensional echocardiography (3DE) in patients with heart failure (HF) events after CIED implantation.Methods and Results:In 143 patients, 3DE assessments for the tricuspid valve (TV) and right ventricular morphologies were sequentially performed within 3 days after CIED implantations, during TR exacerbations, and at ≥6 months after TR exacerbations. TR exacerbations were observed in 29 patients (median 10 months after CIED implantation, range 1-28 months), 15 of whom had lead-induced TR. In the 29 patients, the tenting height of the TV, tricuspid annular (TA) height, and TA area at baseline were independent predictors for worsening TR. In patients with lead-induced TR, tenting height of the TV and TA area were identified as the risk factors. In addition, all patients with a lead positioned on a leaflet immediately after CIED implantations developed lead-induced TR. At follow up, TR exacerbation of lead-induced TR persisted with TA remodeling, but it was improved in the lead non-related-TR group. Conclusions TA remodeling at baseline and a lead location on a leaflet immediately after CIED implantation were associated with lead-induced TR in patients with HF events after CIED implantation. Persistent TA remodeling may make lead-induced TR refractory against HF treatments.

Background Many adult patients with Fontan circulation are treated with antithrombotic agents, including direct oral anticoagulants (DOACs). However, few studies have investigated the efficacy, feasibility, and safety of DOACs in adult patients with Fontan circulation. Methods and Results In this retrospective cohort study, clinical records of 139 adult patients with Fontan circulation (70 females, 50.4%) from April 2015 to March 2018 were reviewed and classified into five groups according to the therapeutic agents used: DOAC (n = 36), vitamin K antagonist (VKA; n = 41), antiplatelet drug (n = 43), combination of an antiplatelet and anticoagulant (n = 14), and no-antithrombotic prophylaxis (n = 5). In a 1114-patient-year follow-up, 28 major events occurred, including 10 thrombotic and 18 bleeding events; 11 of 18 (61%) female patients had severe menorrhagia. The incidence (% patient-years) of major events was 0.6, 1.42, 3.74, and 5.13 in the DOAC, antiplatelet, VKA, combination, and no-antithrombotic groups, respectively. The Cox proportional hazards analysis revealed that the DOAC group had a lower rate of primary endpoints than the VKA group in males. Conclusions DOAC may be a safe antithrombotic agent for use in adult patients with Fontan circulation, particularly in males. However, these findings should be confirmed in multi-institutional prospective studies.

Background An elevated level of serum uric acid (SUA) is associated with an increased risk of cardiovascular disease. Pharmacological intervention with urate-lowering agents, such as the conventional purine analogue xanthine oxidase (XO) inhibitor, allopurinol, has been used widely for a long period of time in clinical practice to reduce SUA levels. Febuxostat, a novel non-purine selective inhibitor of XO, has higher potency for inhibition of XO activity and greater urate-lowering efficacy than conventional allopurinol. However, clinical evidence regarding the effects of febuxostat on atherosclerosis is lacking. The purpose of the study was to test whether treatment with febuxostat delays carotid intima-media thickness (IMT) progression in patients with asymptomatic hyperuricemia. Methods and findings The study was a multicenter, prospective, randomized, open-label, blinded-endpoint clinical trial undertaken at 48 sites throughout Japan between May 2014 and August 2018. Adults with both asymptomatic hyperuricemia (SUA >7.0 mg/dL) and maximum IMT of the common carotid artery (CCA) ≥1.1 mm at screening were allocated equally using a central web system to receive either dose-titrated febuxostat (10–60 mg daily) or as a control-arm, non-pharmacological lifestyle modification for hyperuricemia, such as a healthy diet and exercise therapy. Of the 514 enrolled participants, 31 were excluded from the analysis, with the remaining 483 people (mean age 69.1 years [standard deviation 10.4 years], female 19.7%) included in the primary analysis (febuxostat group, 239; control group, 244), based on a modified intention-to-treat principal. The carotid IMT images were recorded by a single sonographer at each site and read in a treatment-blinded manner by a single analyzer at a central core laboratory. The primary endpoint was the percentage change from baseline to 24 months in mean IMT of the CCA, determined by analysis of covariance using the allocation adjustment factors (age, gender, history of type 2 diabetes, baseline SUA, and baseline maximum IMT of the CCA) as the covariates. Key secondary endpoints included changes in other carotid ultrasonographic parameters and SUA and the incidence of clinical events. The mean values (± standard deviation) of CCA-IMT were 0.825 mm ± 0.173 mm in the febuxostat group and 0.832 mm ± 0.175 mm in the control group (mean between-group difference [febuxostat − control], −0.007 mm [95% confidence interval (CI) −0.039 mm to 0.024 mm; P = 0.65]) at baseline; 0.832 mm ± 0.182 mm in the febuxostat group and 0.848 mm ± 0.176 mm in the control group (mean between-group difference, −0.016 mm [95% CI −0.051 mm to 0.019 mm; P = 0.37]) at 24 months. Compared with the control group, febuxostat had no significant effect on the primary endpoint (mean percentage change 1.2% [95% CI −0.6% to 3.0%] in the febuxostat group (n = 207) versus 1.4% [95% CI −0.5% to 3.3%] in the control group (n = 193); mean between-group difference, −0.2% [95% CI −2.3% to 1.9%; P = 0.83]). Febuxostat also had no effect on the other carotid ultrasonographic parameters. The mean baseline values of SUA were comparable between the two groups (febuxostat, 7.76 mg/dL ± 0.98 mg/dL versus control, 7.73 mg/dL ± 1.04 mg/dL; mean between-group difference, 0.03 mg/dL [95% CI −0.15 mg/dL to 0.21 mg/dL; P = 0.75]). The mean value of SUA at 24 months was significantly lower in the febuxostat group than in the control group (febuxostat, 4.66 mg/dL ± 1.27 mg/dL versus control, 7.28 mg/dL ± 1.27 mg/dL; mean between-group difference, −2.62 mg/dL [95% CI −2.86 mg/dL to −2.38 mg/dL; P < 0.001]). Episodes of gout arthritis occurred only in the control group (4 patients [1.6%]). There were three deaths in the febuxostat group and seven in the control group during follow-up. A limitation of the study was the study design, as it was not a placebo-controlled trial, had a relatively small sample size and a short intervention period, and only enrolled Japanese patients with asymptomatic hyperuricemia. Conclusions In Japanese patients with asymptomatic hyperuricemia, 24 months of febuxostat treatment did not delay carotid atherosclerosis progression, compared with non-pharmacological care. These findings do not support the use of febuxostat for delaying carotid atherosclerosis in this population. Trial registration University Hospital Medical Information Network Clinical Trial Registry UMIN000012911., In a randomized, controlled trial, Atsushi Tanaka and colleagues test whether treatment with febuxostat delays carotid intima-media thickness (IMT) progression in patients with asymptomatic hyperuricemia., Author summary Why was this study done? Elevated levels of serum uric acid (SUA) increase the risk of gout and may be associated with the risk of developing cardiometabolic disorders and subsequent cardiovascular disease. Translational research suggests that urate-lowering therapy by inhibition of xanthine oxidase (XO) may attenuate experimental atherosclerosis. However, the clinical effects of XO inhibitors on atherosclerosis in patients with asymptomatic hyperuricemia remain uncertain. Carotid intima-media thickness (IMT) measurement is a simple and noninvasive method to monitor atherosclerosis. We therefore investigated whether treatment with febuxostat, a non-purine selective inhibitor of XO, delayed the progression of carotid atherosclerosis compared to non-pharmacological care for hyperuricemia in this patient population. What did the researchers do and find? The study was a multicenter, prospective, randomized, open-label, blinded-endpoint clinical trial on 483 eligible participants (mean age 69.1 [standard deviation 10.4], female 19.7%) with asymptomatic hyperuricemia (SUA >7.0 mg/dL) and maximum IMT of the common carotid artery ≥1.1 mm. The results showed that there was no significant difference between febuxostat and non-pharmacological care for hyperuricemia in the progression of carotid atherosclerosis assessed by IMT over 24 months of follow-up. Febuxostat treatment was well tolerated and did not increase the incidence of cardiovascular and all-cause mortality. What do these findings mean? Our findings do not support the use of febuxostat to delay carotid atherosclerosis in patients with asymptomatic hyperuricemia. Further research is needed to determine the effects of febuxostat on atherosclerosis and cardiovascular safety in patients with hyperuricemia irrespective of the presence of gout.

This review focused on right ventricular (RV) three-dimensional echocardiography (3DE) and discussed the following agenda. First, we summarized the clinical RV anatomy and function-related RV3DE use followed by the explanations about 3DSTE image acquisition, including pitfall. Next, we reviewed the reliability and feasibility of RV volume and RV ejection fraction measurements during the last decade. Besides, we described the techniques that might overcome the dropout images at RV anterior and out tract including the current limitations. Finally, speckle tracking echocardiography by RV3DE and novel RV shape assessment were reviewed. This review will help you get comprehensive information on the current status and future perspectives of RV3DE.

Cardiac implantable electronic devices (CIED) implantations may cause lead-induced tricuspid regurgitation (LITR). Although patients with CIED have the risk of functional non-lead induced TR (Non-LITR). This study aimed to compare of clinical outcome between LITR and Non-LITR. The mechanism of TR was determined by 3-dimensional echocardiography. The primary end point was heart failure (HF) hospitalizations after CIED implantation. In patients with HF events, subsequent clinical outcomes after HF hospitalization were compared between no TR, LITR, and Non-LITR groups. In eligible 373 patients, 67 patients had HF hospitalization, of whom worsened TR was observed in 49 patients. In the remaining 307 patients, worsened TR was observed in only 10 patients (3.3%). Of the 49 patients with worsened TR, 18 patients (37%) had LITR. In 67 patients with HF hospitalization, 25 patients (37%) met rehospitalization. All severe LITR persisted after HF events. Meanwhile, severe Non-LITR improved to moderate or mild level. Cox proportional hazard model analyses revealed LITR was the independent risk factor of rehospitalization. Both LITR and Non-LITR were common at HF events after CIED implantations. However, LITR persisted and might contribute to a worse prognosis. In patients with TR after CIED implantations, 3-dimensional echocardiography should be performed to diagnose the LITR accurately, which may contribute to improving the clinical outcome.

It remains unclear whether intrarenal venous flow (IRVF) patterns in patients with heart failure (HF) could change over the clinical course, and whether the changes could have a clinical impact. Thus, this study aimed to clarify these characteristics as well as to identify the relation between changes in the IRVF pattern and renal impairment progression.Patients with HF with repetitive IRVF evaluations were enrolled. Doppler waveforms of IRVF were classified into the following 3 flow patterns: continuous, biphasic discontinuous, and monophasic discontinuous. Primary end points included death from cardiovascular diseases and unplanned hospitalization for HF. Finally, 108 patients with adequate images were enrolled. The IRVF in 35 patients (32.4%) shifted to another pattern at the follow-up examinations. The median brain natriuretic peptide level in the continuous flow pattern at follow-up was significantly decreased (183 to 60 pg/mL, P.001), whereas that of the discontinuous flow pattern at follow-up was increased (from 339 to 366 pg/mL, P = .042) and the estimated glomerular filtration rate was decreased (from 55 to 50 mL/min/1.73 mThe IRVF pattern could be changed depending on the status of congestion. Persistent or worsened renal congestion, represented by discontinuous flow patterns, during the clinical courses indicated a poor prognosis accompanied by renal impairment in patients with HF.

Background Whether a dipeptidyl peptidase-4 (DPP-4) inhibitor can attenuate atherosclerosis is still controversial. Some clinical trials reported that DPP-4 inhibitors in diabetes patients without a previous history of cardiovascular (CV) events could reduce carotid intima-media thickness (IMT). However, in the PROLOGUE study, which enrolled diabetes patients both with and without previous CV events, sitagliptin failed to slow the progression of carotid IMT relative to conventional therapy. Aim and methods We hypothesized that the effect of DPP-4 inhibitors on carotid atherosclerosis might be different between the primary and secondary prevention groups. We performed a post hoc analysis of the PROLOGUE study and compared the effects of sitagliptin and conventional therapy on changes in carotid IMT in subgroups with or without previous CV events. Results No significant difference in the IMT changes between the treatment groups was found in the secondary prevention subgroup (sitagliptin, N = 102; conventional, 111). However, in the primary prevention subgroup (sitagliptin, 120; conventional, 109), we found significant inhibitory effects of sitagliptin on mean and max internal carotid artery IMT [estimated group difference: −0.096 mm (95% CI −0.175 to −0.018, p = 0.017) and −0.162 mm (95% CI −0.272 to −0.052, p = 0.004), respectively], although there was no significant difference in the common carotid artery IMT. Conclusions Our data suggest that there is a favorable effect of DPP-4 inhibitor treatment on carotid atherosclerosis in diabetes patients without previous CV events.

Accumulated evidence shows that some antidiabetic agents attenuate the progression of carotid atherosclerosis assessed as intima-media thickness (IMT). Although some studies have demonstrated an inhibitory effect of dipeptidyl peptidase-4 inhibitors on carotid IMT progression, in the PROLOGUE study sitagliptin failed to slow progression relative to conventional therapy for 24 months. We hypothesized that differences in the concomitant antidiabetic agents between the groups have influenced the progression of carotid IMT. We performed a post hoc analysis of the PROLOGUE study using subgroups stratified by concomitant antidiabetic agents. Although no subgroup with any combination of agents in the overall patients showed a significant difference between sitagliptin group and conventional therapy group in the changes from baseline in mean common carotid artery (CCA)-IMT at 24 months, a significant attenuation of mean CCA-IMT progression was observed in the sitagliptin group relative to conventional therapy group only in three combination subgroups aged

Age-related changes in cardiac morphology and function have not been unknown in the elderly. The Japanese eLderly data Of Normal echocardioGraphy (J-LONG) study is a prospective multicenter cohort study and aimed to investigate the echocardiographic data in the healthy Japanese elderly. Thirty domestic facilities participated in this study, and 130 healthy subjects (57 men, 73 women, 79.6 ± 4.7 years, range 75–98 years, interquartile range 76–82 years) were enrolled in this cohort. Echocardiographic and clinical data sets were obtained in each facility, and total analyses were performed in the University of Tsukuba. Almost all cardiac morphological data were significantly larger in men than those in women. However, corrected data by body surface area (BSA) were similar or closer between genders. As a gender difference, the negative correlation between BSA and age was observed in women only (r = − 0.46, p

Objectives To examine the effect of asymptomatic severe aortic stenosis (AS) on mortality late in life. Design Retrospective cohort study. Setting Large medical center. Participants Asymptomatic adults aged 80 and older (mean age 86 ± 4; N=1,060, n=569 women) with preserved left ventricular ejection fraction (LVEF; > 50%); 927 (87.5%) with no AS, 70 (6.6%) with nonsevere AS, and 63 (5.9%) with severe AS. Measurements Information was collected on demographic characteristics, comorbidities, and laboratory and echocardiographic data. Survival was assessed according to longest follow‐up available. Results During a mean follow‐up of 2.2 ± 2.3 years, there were 203 (19%) deaths, 51 of which were from cardiovascular causes. Four‐year estimates of survival were 72% for no AS, 58% for nonsevere AS, and 23% for severe AS (p

Wave intensity (WI) is a novel noninvasive index of circulatory dynamics that reflects ventriculo-arterial coupling. It is calculated as the product of the first derivative of blood pressure and that of flow velocity measured by carotid echocardiography. This study aimed to clarify the clinical implications of WI and its relation with carbon dioxide production (VE/VCO2 slope). Twenty-one healthy volunteers (control group) and 21 patients with hypertension (HT group) underwent cardiopulmonary exercise testing (CPX) and exercise stress echocardiography. WI was assessed in the right carotid artery using an ultrasound system. The first peak of WI (W1) during the early ejection phase was measured at baseline and mitral annular velocity was assessed by tissue Doppler imaging. Ventilatory kinetics during exercise was assessed using the relation of minute ventilation to VE/VCO2 slope. VE/VCO2 slope, W1, and E/E′ were greater in the HT group than in the control group. PeakVO2 and VO2 at the anaerobic threshold were lower in the HT group than in the control group. VE/VCO2 slope was significantly correlated with W1 (r = 0.58, p

Objectives To examine the longitudinal mutual association between endothelial dysfunction and arterial stiffness, and also to determine which of the two variables was more closely associated with the progression of subclinical organ damage. Methods The brachial-ankle pulse wave velocity (baPWV), carotid intima-media thickness (CIMT), estimated glomerular filtration rate, microalbuminuria and flow-mediated vasodilatation of the brachial artery (FMD) were measured three times at 1.5-year intervals in 674 Japanese patients receiving antihypertensive treatment. Results The change of the baPWV during the study period was larger in the subjects with baseline FMD values in the lowest tertile as compared to those with baseline FMD values in the highest tertile. The change of the CIMT was smaller in the subjects with baseline baPWV values in the lowest tertile than in those with baseline baPWV values in the highest tertile. After the adjustment, the FMD value at the baseline was inversely associated with the baPWV at the end of the study period (beta=−0.07, p =0.01), although, the reverse association was not significant. The baPWV, but not the FMD value, at the baseline was associated with the CIMT (beta=0.06, p =0.04) measured at the end of the study period. Conclusions In hypertension, endothelial dysfunction was associated with the progression of arterial stiffness, although the reverse association was not confirmed. The increased arterial stiffness rather than endothelial dysfunction may be more closely associated with the progression of atherosclerotic vascular damage, and the endothelial dysfunction-arterial stiffness-atherosclerosis continuum may be important in hypertension.

Controlling nutritional status (CONUT) uses 2 biochemical parameters (serum albumin and cholesterol level), and 1 immune parameter (total lymphocyte count) to assess nutritional status. This study examined if CONUT could predict the short-term prognosis of heart failure (HF) patients.A total of 482 (57.5%) HF patients from the Ibaraki Cardiovascular Assessment Study-HF (n = 838) were enrolled (298 men, 71.7 ± 13.6 years). Blood samples were collected at admission, and nutritional status was assessed using CONUT. CONUT scores were defined as follows: 0-1, normal; 2-4, light; 5-8, moderate; and 9-12, severe degree of undernutrition. Accordingly, 352 (73%) patients had light-to-severe nutritional disturbances. The logarithmically transformed plasma brain natriuretic peptide (log BNP) concentration was significantly higher in the moderate-severe nutritional disturbance group (2.92 ± 0.42) compared to the normal group (2.72 ± 0.45, P < 0.01). CONUT scores were significantly higher in the in-hospital death patients [4 (3-8), n = 14] compared with patients who were discharged following symptom alleviation [3 (1-5), n = 446, P < 0.05]. With the exception of transferred HF patients (n = 22), logistic regression analysis that incorporated the CONUT score and the log BNP, showed that a higher CONUT score (P = 0.019) and higher log BNP (P = 0.009) were predictors of in-hospital death, and the median duration of hospital stay was 20 days.Our results demonstrate the usefulness of CONUT scores as predictors of short-term prognosis in hospitalized HF patients.

Baseline brachial artery (BBA) diameter has been reported to be a potential confounding factor of flow-mediated vasodilation (FMD). The purpose of this study was to evaluate the relationships between BBA diameter and cardiovascular risk factors and compare the diagnostic accuracy of BBA diameter in subjects without cardiovascular risk factors and patients with cardiovascular disease (CVD) with that of FMD.We measured BBA diameter and FMD in 5695 male subjects. In addition, we retrospectively investigated the incidence of cardiovascular events using another population sample consisting of 440 male subjects, to compare the accuracy of BBA diameter with that of FMD in predicting cardiovascular events.BBA diameter and FMD significantly correlated with age, body mass index, systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol, and glucose as well as Framingham risk score. The prevalence of cardiovascular risk factors and CVD increased with the increase in BBA diameter and FMD. Area under the curve (AUC) value of the receiver operating characteristic (ROC) curve for BBA diameter to diagnose subjects without cardiovascular risk factors (0.59 vs. 0.62, p = 0.001) or patients with CVD (0.58 vs. 0.64, p 0.001) was significantly lower than that for FMD. In the retrospective study, the AUC value of the ROC curve for BBA diameter to predict first major cardiovascular events was significantly lower than that of FMD (0.50 vs. 0.62, p = 0.03).In men, BBA diameter was inferior to FMD for assessment of cardiovascular risk.

Renal congestion is caused by elevated central venous pressure (CVP), and decreases glomerular filtration in patients with congestive heart failure. Since real-time contrast-enhanced ultrasonography (CEUS) using microbubble-based contrast agents can visualize the perfused microvascular bed, we sought to evaluate the impairment of renal perfusion during acute renal congestion with CEUS. In Wister rats, CEUS of kidney was performed with the direct monitoring of CVP and intra-renal pressure (IRP). When CVP was elevated to 10 and 15 mmHg after the bolus injection of normal saline via the femoral vein, peak intensity (PI, dB) and time to PI (TTP) in the renal cortex and medulla were compared with control rats. There was a strong correlation between IRP and CVP (r = 0.95, p

Hypertension is associated with endothelial dysfunction. Blood pressure significantly correlates with endothelial function in antihypertensive drug-naive subjects. The purpose of this study was to determine whether treatment status affects the relationship between blood pressure and endothelial function. We measured flow-mediated vasodilation (FMD) in 2297 subjects, including 1822 antihypertensive drug-naive subjects and 475 treated hypertensive patients. FMD significantly decreased in relation to increase in systolic blood pressure (8.2±3.1% in subjects with systolic blood pressure of P P =0.77). Propensity score matching analysis revealed that the prevalence of endothelial dysfunction defined as FMD of less than the division point for the lowest tertile, and the middle tertile of FMD was significantly higher in treated hypertensive patients than in untreated subjects in all systolic blood pressure categories. Endothelial function assessed by FMD was impaired regardless of the level of blood pressure achieved by antihypertensive drug treatment in hypertensive patients.

Background Atrial tachyarrhythmias are a major morbidity in patients with adult congenital heart disease (ACHD). However, few studies have investigated risk stratification of thromboembolic events in ACHD patients with atrial tachyarrhythmias. Methods and results This retrospective cohort study reviewed the clinical records of 2314 ACHD patients from 1977 to 2014. We found 242 (10.4%) patients with atrial tachyarrhythmias and excluded 84 patients already being treated with anticoagulant therapy. The remaining 158 patients without anticoagulant therapy were retrospectively followed up from the onset of atrial tachyarrhythmia to the incidence of thromboembolic events. Fourteen thromboembolic events and 5 hemorrhagic events occurred. All patients with thromboembolic events had atrial fibrillation (AF). Thromboembolic events occurred even in the patients with low or intermediate risk as indicated by CHADS 2 or CHA 2 DS 2 -VASc score. Event rates were higher than those in data from the general adult population in previous studies. Univariate analysis revealed that age≥60years (OR 4.54, 95% CI 1.47–14.06, P =0.009), vascular disease (OR 7.83, 95% CI 1.19–51.53, P =0.032), and persistent AF (OR 5.60, 95% CI 1.73–18.11, P =0.004) were the independent risk factors of thromboembolic events. Conclusions ACHD patients with atrial tachyarrhythmias and even those with low or intermediate risk as indicated by the CHADS 2 or CHA 2 DS 2 -VASc score had a higher risk of thromboembolic events. Therefore, anticoagulation should be considered earlier than in the general population in patients with risk factors of age≥60years, vascular disease, or persistent AF.

Background Whether the optimal cut-off value of left ventricular (LV) reverse remodeling is different in patients with ischemic cardiomyopathy (ICM) vs. non-ischemic cardiomyopathy (NICM) is unclear. This study aimed to clarify this value in patients with ICM and NICM. Methods and results LV reverse remodeling was defined as a reduction in LV end-systolic volume (LVESV) at 6 months after cardiac resynchronization therapy (CRT). The clinical endpoint was the combination of cardiac death and first hospitalization for worsening heart failure. Ninety-one of 372 patients had ICM. Event-free survival rates did not differ between ICM and NICM groups (66.8% vs. 78.9%; p = 0.12). Receiver operating characteristics analysis revealed a 9% reduction in ESV as the optimal cut-off value to predict the composite endpoint in patients with ICM and a 15% reduction in patients with NICM. Multivariate analysis revealed that reductions in ESV of ≥15% and ≥9% were independent predictors of the composite endpoint, as were left bundle branch block (LBBB) and B-type natriuretic peptide (BNP) at 6 months after CRT. In combination with LBBB and BNP, reduction in ESV ≥9% had a higher, but not significant, C-statistics value than ESV ≥15% (0.854, 95% CI 0.729–0.940 vs. 0.801, 95% CI 0.702–0.908, p = 0.07). Conclusion The optimal cut-off value of a reduction in LVESV was lower in patients with ICM than in patients with NICM.

Fragmented QRS and Ventricular Arrhythmias After CRTIntroduction A fragmented QRS (fQRS) is reported to be associated with a poor prognosis or sudden cardiac death (SCD) in patients with Brugada syndrome or ischemic heart disease. However, no studies have clarified the impact of the presence of an fQRS on SCD or ventricular arrhythmic events in patients receiving cardiac resynchronization therapy (CRT). This study aimed to clarify this point in patients with nonischemic cardiomyopathy. Methods and Results This study included 137 heart failure patients with nonischemic cardiomyopathy who received CRT (NYHA functional class: II/III/IV = 25/84/28). The 12-lead ECGs before and after CRT were analyzed. The presence of an fQRS was decided in accordance with the definition in previous papers. Before the CRT, an fQRS was observed in 67 patients (fQRS-pre; 49%). However, it was masked in 35 (52% of fQRS-pre) patients after the CRT. Inversely, in 70 patients in whom an fQRS was absent before the CRT, it appeared after the CRT in 15 (21%) patients. As a result, 47 patients (34%) had an fQRS after the CRT (fQRS-post), and it was less than that before the CRT (P = 0.014). During 18 months of follow-up, SCD or ventricular arrhythmic events were observed more frequently in patients with an fQRS-post than in those without (36.2% vs. 3.3%, P < 0.001). A Cox regression analysis revealed that an fQRS-post was significantly associated with those events (hazard ratio = 9.18; 95% confidence interval = 2.45–34.48, P = 0.001). Conclusion In patients with nonischemic cardiomyopathy who received CRT, an fQRS-post was independently associated with SCD or ventricular arrhythmic events.

Background Although experimental animal studies report many pleiotropic effects of dipeptidyl peptidase-4 inhibitors (DPP-4i), their prognostic value has not been demonstrated in clinical trials.Methods and Results:Among 838 prospectively enrolled heart failure (HF) patients hospitalized for acute decompensated HF, 79 treated with DPP-4i were compared with 79 propensity score-matched non-DPP-4i diabetes mellitus (DM) patients. The primary endpoint was all-cause mortality; the secondary endpoint was a composite of cardiovascular death and hospitalization. During follow-up (423±260 days), 8 patients (10.1%) in the DPP-4i group and 13 (16.5%) in the non-DPP-4i group died (log-rank, P=0.283). The DPP-4i group did not have a significantly higher rate of all-cause mortality (log-rank, P=0.283), or cardiovascular death or hospitalization (log-rank, P=0.425). In a subgroup analysis of HF with preserved ejection fraction (HFpEF; n=75), the DPP-4i group had a significantly better prognosis than the non-DPP-4i group regarding the primary endpoint (log-rank, P=0.021) and a tendency to have better prognosis regarding the secondary endpoint (log-rank, P=0.119). In patients with HF with reduced EF (n=83), DPP-4i did not result in better prognosis. Conclusions DPP-4i did not increase the risk of adverse clinical outcomes in patients with DM and HF. DPP-4i may be beneficial in HFpEF.

Background Current prognostic implication of symptomatic patients with aortic stenosis (AS) remains undetermined. This study investigated the current prognostic implications of AS-related symptoms and the effect of aortic valve replacement (AVR) on outcome. Methods We enrolled 586 consecutive patients with severe AS (aortic valve area 2 ) with preserved left ventricular ejection fraction (≥50%). All patients were stratified into the following four groups based on the predominant symptoms: Group 1, asymptomatic ( n = 316); Group 2, chest pain ( n = 41); Group 3, heart failure ( n = 192); or Group 4, syncope ( n = 37). Results AS-related symptoms were diagnosed in 270 patients (46.1%), among whom 182 patients (32.2%) received AVR. Thirty-nine patients (6.7%) had cardiac death during the mean follow-up of 16 ± 14 months. AVR was associated with significant reduction in cardiac death in Groups 3 ( p p = 0.004) whereas no significant prognostic advantage of AVR was observed in Groups 1 or 2. Cox proportional-hazard multivariate analysis revealed that age, heart failure, and mean pressure gradient (PG) were associated with increased risk of cardiac death in all patients regardless of AVR [hazard ratio (HR): 1.079, 2.090, and 1.008 respectively, all p p Conclusion This retrospective study demonstrated the current associations between the types of AS symptoms and prognosis in Japanese patients with severe AS.

Clinical impact of changes of renal function (RF) in heart failure (HF) hospitalization is controversial. This study aimed to clarify whether clinical impact of changes of RF during HF hospitalization depends on the intrinsic RF. In 786 hospitalized HF patients, RF were classified into 3 grades based on estimated glomerular filtration rate (eGFR, mL/min/1.73 m2) at discharge; ≥ 60 (n = 243)

Aims Left ventricular diastolic dysfunction (LVDD) has prognostic significance in heart failure (HF). We aimed to assess the impact of LVDD grade stratified by the updated 2016 echocardiographic algorithm (DD2016) on post-discharge outcomes in patients admitted for acute HF and compare with the previous 2009 algorithm (DD2009). Methods and results The study included 481 patients hospitalized for acute decompensated HF. Comprehensive echocardiography and LVDD evaluation were performed just before hospital discharge. The primary endpoint was a composite of cardiovascular death and readmission for HF. The concordance between DD2016 and DD2009 was moderate (κ = 0.44, P Conclusion Despite simplification of the algorithm for LVDD evaluation, the prognostic value of DD2016 for post-discharge cardiovascular events in HF patients was maintained and not compromised in comparison with DD2009.

This study clarified the characteristics of intrarenal Doppler ultrasonography (IRD) profiles and their prognostic implications in heart failure (HF).IRD can assess intrarenal hemodynamics.Initially, 224 patients with HF were prospectively enrolled; 151 inpatients were enrolled during hospitalization for HF, and 73 were outpatients in our institution. In IRD profiles of interlobar vessels, the arterial resistance index (RI), venous impedance index (VII), and intrarenal venous flow (IRVF) pattern were assessed. Patients were followed to evaluate the associations with 1-year prognosis. Primary endpoints included death from cardiovascular disease and unplanned hospitalization for HF.Finally, 217 patients with adequate IRD images were enrolled. IRD profiles were associated with conventional risk factors for HF. In particular, IRVF was associated with mean right atrial pressure (RAP); 3 IRVF patterns were stratified by RAP (in a continuous pattern: 5.4 ± 2.5; in a biphasic pattern: 9.5 ± 3.5; and in a monophasic pattern: 14.9 ± 4.3 mm Hg; p 0.001). In addition, the monophasic IRVF pattern had a poorer prognosis than the other patterns (log rank p 0.001), and prognosis was poorer for the biphasic pattern than for the continuous flow pattern (log rank p = 0.01). Multivariate Cox proportional hazard model analysis revealed that IRVF patterns were associated with the endpoints, independent of other HF risk factors.IRVF patterns, rather than RI, depended on RAP, suggesting a correlation with renal congestion. In addition, IRVF patterns strongly correlated with clinical outcomes independent of RAP and other risk factors and might provide additional information to stratify vulnerable HF patients.

BACKGROUND Left atrial remodeling caused by persistent atrial fibrillation (AF) causes atrial functional mitral regurgitation (MR), even though left ventricular (LV) remodeling and organic changes of the mitral leaflets are lacking. The detailed mechanism of atrial functional MR has not been fully investigated. METHODS AND RESULTS Of 1,167 patients with AF who underwent 3D transesophageal echocardiography, 75 patients were retrospectively selected who developed no, mild, or moderate-to-severe atrial functional MR (n=25 in each group) despite an LV ejection fraction ≥50% and LV volumes within the normal range. Mitral valve morphology and dynamics were analyzed. Patients with moderate-to-severe MR had a larger mitral annulus (MA) area, smaller MA area fraction, and greater nonplanarity angle and tethering angle of the posterior mitral leaflet (PML) compared with other groups (all P

There are currently no therapies that can improve prognosis in cases of heart failure (HF) with preserved ejection fraction (EF). We hypothesized that there is a point of no return after which no response to treatment is noted and that for the prevention of hypertensive HF this point may be determined by left ventricle (LV) strain, in the prevention of hypertensive HF. Here an angiotensin-converting enzyme inhibitor (ACE-I) was initiated based on myocardial strain imaging and its effects were determined in an animal model.Thirty-two male Dahl salt-sensitive rats, age 6 weeks, were divided into six experimental groups and compared with low-salt (n = 8) and high-salt control groups (n = 8). In the early treatment group, ACE-I was administered from the age of 6 weeks (n = 4); in the longitudinal strain (LS) group, at 10-12 weeks when LS impairment was-21% (n = 4); in the circumferential strain (CS) group, at 16-18 weeks when CS impairment was-18% (n = 4); and in the EF group, at 20 weeks when EF was55% (n = 4). Subsequently, all rats were sacrificed at 23 weeks age, the LV and lung weight were measured, and pathologic analyses were performed.At 23 weeks of age, the lung and LV weights increased in the high-salt control, EF, and CS groups, whereas the lung and LV weights in the LS and early groups were similar to those in the low-salt control group. The percentage of area of subendocardial fibrosis was6% in the high-salt control, EF, and CS groups and3% in the LS, early, and low-salt groups. Serial echocardiography demonstrated LS improvement in the LS group; however, the CS and EF groups showed no differences.Heart failure-related lung congestion was prevented when ACE-I was administered soon after LS impairment, accompanied by suppression of cardiac hypertrophy and fibrosis, thereby suggesting that the point of no return of myocardial remodeling due to hypertension was present after LS but before CS impairment.

Background: Although 2-dimensional strain analyses based on speckle tracking echocardiography have been used to detect myocardial deformation, the prognostic impact of 2-dimensional strain is unclear in patients with acute decompensated heart failure (HF). We investigated whether left ventricular and right ventricular (RV) strain parameters assessed by speckle tracking echocardiography provide incremental prognostic information in hospitalized patients because of acute decompensated HF. Methods and Results: Six hundred eighteen patients (age, 72±13 years; 38% women; ejection fraction, 46±16%) hospitalized for acute decompensated HF underwent clinical and echocardiographic evaluation just before discharge. We performed strain analyses of left ventricular global longitudinal strain and left ventricular global circumferential strain. We also analyzed RV longitudinal strain only from the free wall (RV-fwLS) and from all segments of the RV global longitudinal strain wall by using Tomtec software. The primary composite end point was cardiovascular death and readmission for HF. There were 34.8% cardiac events during a median follow-up of 427 days. In multivariate Cox models, among echocardiographic parameters, only impaired RV-fwLS (≥−13.1%; hazard ratio, 1.51; 95% CI, 1.12–2.04; P =0.01) was independently associated with cardiac events. Adding RV-fwLS to clinical risk evaluation (age, New York Heart Association class III/IV, blood urea nitrogen, and brain natriuretic peptide) markedly improved prognostic utility and consequently increased net reclassification improvement by 0.30 ( P =0.01). Conclusions: RV-fwLS is an independent predictor of cardiac events in acute decompensated HF and provides greater prognostic power than standard echocardiographic parameters.

Adult patients with repaired coarctation of the aorta (r-CoA) show high prevalence of late hypertension, but the exact mechanisms of this phenomenon are unknown. Endothelial dysfunction has been implicated in this paradoxical hypertension. We evaluated the endothelial function of both conduit and resistance arteries by using flow-mediated dilation (FMD) and digital peripheral artery tonometry (PAT).Seventeen patients with r-CoA and one patient with repaired interrupted aortic arch (r-CoA group) aged 22.0 ± 6.9 years (5 females) underwent FMD of the right brachial artery, PAT of the right finger, blood marker tests, ambulatory blood pressure monitoring, echocardiography, carotid ultrasonography, and brachio-ankle pulse wave velocity measurement. The median age at aortic arch reconstruction was 2.0 months (interquartile range: 15 days to 7.0 years). Results were compared with 17 age-matched healthy subjects (control group).Eight (44%) patients of the r-CoA group were hypertensive (5 received antihypertensive drugs). Patients in the r-CoA group showed significantly lower FMD (3.8 ± 1.5 versus 6.6 ± 2.5%, P < 0.001), larger intima-media thickness (0.63 ± 0.17 versus 0.47 ± 0.09 mm, P = 0.001), and higher left ventricular mass index (91.4 ± 24.6 versus 73.4 ± 17.3 g/m2, P = 0.017) than those in the control group. There were no significant differences in PAT (refractory hyperemia index, 1.86 ± 0.43 versus 1.99 ± 0.59, P = 0.48) and brachio-ankle pulse wave velocity between the two groups.Vascular dysfunction in r-CoA patients, particularly endothelial dysfunction, tends to occur more significantly in conduit arteries than in resistance arteries.

Background The usefulness of vascular function tests for management of patients with a history of coronary artery disease is not fully known. Methods and Results We measured flow‐mediated vasodilation ( FMD ) and brachial–ankle pulse wave velocity (ba PWV ) in 462 patients with coronary artery disease for assessment of the predictive value of FMD and ba PWV for future cardiovascular events in a prospective multicenter observational study. The first primary outcome was coronary events, and the second primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow‐up period of 49.2 months, the first primary outcome occurred in 56 patients and the second primary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver‐operator curve analyses for the first and second primary outcomes, was significantly associated with lower risk of the first (hazard ratio, 0.27; 95% confidence interval, 0.06–0.74; P =0.008) and second (hazard ratio, 0.32; 95% confidence interval, 0.09–0.79; P =0.01) primary outcomes. ba PWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the first (hazard ratio, 1.86; 95% confidence interval, 1.01–3.44; P =0.04) and second (hazard ratio, 2.19; 95% confidence interval, 1.23–3.90; P =0.008) primary outcomes. Among 4 groups stratified according to the combination of cutoff values of FMD and ba PWV , stepwise increases in the calculated risk ratio for the first and second primary outcomes were observed. Conclusions In patients with coronary artery disease, both FMD and ba PWV were significant predictors of cardiovascular events. The combination of FMD and ba PWV provided further cardiovascular risk stratification. Clinical Trial Registration URL : www.umin.ac.jp . Unique identifier: UMIN 000012950.

Background Soluble ST2 (sST2) is a marker of inflammation and fibrosis, which is a significant predictor of prognosis of heart failure (HF), independent of brain natriuretic peptide (BNP). This study aimed to clarify how sST2 associates with clinical outcome through investigations of clinical correlates and mode of death in patients with heart failure with preserved ejection fraction (HFpEF). Methods A total 191 patients with acute decompensated HF and EF ≥50% were prospectively enrolled. Echocardiographic and laboratory data including sST2 were obtained in pre-discharge stable condition. Results Serum sST2 level showed significant positive correlations with C-reactive protein and pentraxin3 levels, and negative correlations with body mass index, albumin, and hemoglobin. Serum sST2 level was significantly higher in patients with all-cause death and non-cardiovascular (CV) death compared to those without events, whereas there was no significant difference in sST2 level between patients with and without CV death. On the other hand, BNP level was significantly higher in patients with all-cause death and CV death compared to those without events. Cox regression analyses adjusted for age and sex revealed that sST2 was a significant predictor of non-CV death, whereas BNP was a significant predictor of CV death. Conclusions Serum sST2 level was associated with non-CV death showing significant correlations with systemic factors including malnutrition and inflammation, while BNP was associated with CV death.

The pressure recovery-adjusted aortic valve area (AVA), called the energy loss coefficient (ELCo), is theoretically a more accurate parameter for evaluating aortic stenosis (AS) severity. The aim of this study was to compare the prognostic value of ELCo with that of conventional AVA.Indexed AVA (iAVA) was measured using Doppler echocardiography in 301 asymptomatic Japanese patients with AS and preserved left ventricular ejection fractions. Sinotubular junction diameter was also measured, and the indexed ELCo (iELCo) was calculated. Patients were followed for major cardiac events, including cardiac death, ventricular fibrillation, myocardial infarction, heart failure requiring admission, and aortic valve replacement.The mean sinotubular junction diameter was 2.5 ± 0.3 cm, and90% of patients had sinotubular junction diameters3 cm. There was a quadratic correlation between iAVA and iELCo (r = 0.97, P .001). During a median of 17.4 months of follow-up, 90 patients had major cardiac events. Statistical analysis failed to show any superiority of iELCo over iAVA for predicting major cardiac events. However, iELCo stratified high-risk patients for cardiac outcome in a subset of patients whose AS grades were classified as severe using iAVA and in those whose AS severity was inconsistent (iAVA 0.6 cmThe calculation of iELCo may not be always required, even in patients with asymptomatic AS with small aortic roots. However, this index should be calculated in patients whose AS grading assessed by iAVA is severe and in those in whom AS severity criteria are inconsistent.

Differences in the clinical impacts of the aldosterone receptor antagonists spironolactone and eplerenone in patients with heart failure (HF) are unclear. Among 838 prospectively enrolled patients hospitalized for HF, 90 treated with eplerenone were compared with 90 treated with spironolactone. The primary endpoint was a composite of cardiovascular death and hospitalization. A serial evaluation of the clinical parameters was performed 1 year after discharge. The mean dose of spironolactone was 27 ± 8 mg and of eplerenone was 34 ± 15 mg. During follow-up (mean 594 ± 317 days), primary endpoints occurred in 27 patients in the eplerenone group (30.0%) and 25 patients in the spironolactone group (27.8%). There were no significant intergroup differences in the primary endpoint (log-rank, p = 0.956). Serial changes in left ventricular ejection fraction, serum brain natriuretic peptide, systolic blood pressure, and estimated glomerular filtration rate did not differ significantly between groups. Although gynecomastia in men was common in the spironolactone group (p = 0.018), the discontinuation rates due to adverse events were similar in the two groups (p = 0.135). Subgroup analyses suggested that eplerenone was associated with a lower hazard rate of the primary endpoint in female patients (interaction, p = 0.076). Among patients with HF, eplerenone and spironolactone have similar impacts on cardiovascular outcomes and safety.

In the management of heart failure (HF), decongestion is critical for improving clinical outcomes in addition to patients’ symptoms. Although physicians accept this theory, there are no established markers for the achievement of optimal decongestion status. Organ congestion, in particular liver and kidney congestion, has recently attracted substantial attention. Ultrasound methods have been introduced for assessing organ congestion, although this is merely a preliminary step. Here, we review the clinical implications of the assessment of organ congestion by ultrasound.

BACKGROUND Early-diastolic mitral annular velocity (e') and the ratio of early-diastolic left ventricular (LV) inflow velocity (E) to e' (E/e') have been widely used as indexes of LV relaxation and filling pressure, respectively. However, many recent studies have demonstrated that they are not reliable in various clinical settings. We thus investigated the factors influencing these echocardiographic parameters in a multicenter study.Methods and Results:The study group comprised 69 patients, referred for cardiac catheterization, and enrolled in 5 university hospitals. Time constant (τ) and LV mean diastolic pressure (LVMDP) were measured using a micromanometer-tipped catheter. Although e' only weakly correlated with τ (r=-0.35, P

The prognosis of tetralogy of Fallot (TOF) treated only with Blalock-Taussig shunt (BTS) operation is unclear. A woman with TOF underwent classic BTS operation at 10 years of age. Despite no medication, she delivered two children and worked without apparent heart failure. At 72 years of age, she complained of dyspnea on exertion and leg edema. The cardiac angiogram revealed a well-patent BTS and severely stenotic right ventricular outflow tract. Right heart catheterization showed adequately maintained pulmonary blood flow with slight pulmonary arterial hypertension. Her unexpected yet favorable outcome reaffirms the importance of structural and functional self-adaptation even with cyanosis. If she had undergone a valve-sparing corrective surgery in adolescence, much better quality of life and outcome could have been expected.