Prognostic impact of a reduction in the fibrosis-4 index among patients hospitalized with acute heart failure.

Although the fibrosis-4 index (FIB-4) is associated with right atrial pressure or prognosis in acute heart failure (AHF), the prognostic impact of its reduction during hospitalization remains uncertain. We included 877 patients (age, 74.9 ± 12.0 years; 58% male) hospitalized with AHF. The reduction in FIB-4 was defined as: (FIB-4 on admission-FIB-4 at discharge)/FIB-4 on admission × 100. Patients were divided into low (< 1.0%, n = 293), middle (1.0-27.4%, n = 292), and high (> 27.4%, n = 292) FIB-4 reduction groups. The primary outcome was a composite of all-cause death or heart failure rehospitalization within 180 days. The median FIB-4 reduction was 14.7% (interquartile range - 7.8-34.9%). The primary outcome was observed in 79 (27.0%), 63 (21.6%), and 41 (14.0%) patients in the low, middle, and high FIB-4 reduction groups, respectively (P = 0.001). Adjusted Cox proportional-hazards analysis revealed that the middle and low FIB-4 reduction groups were associated with the primary outcome, independent of the pre-existing risk model including baseline FIB-4 ([high vs. middle] hazard ratio [HR]: 1.70, 95% confidence interval [CI]: 1.10-2,63, P = 0.017; [high vs. low] HR: 2.16, 95% CI 1.41-3.32, P < 0.001). FIB-4 reduction provided additional prognostic value to the baseline model, including well-known prognostic factors ([continuous net reclassification improvement] 0.304; 95% CI 0.139-0.464; P < 0.001; [integrated discrimination improvement] 0.011; 95% CI 0.004-0.017; P = 0.001). Additionally, the combination of the reduction in FIB-4 and brain natriuretic peptide was useful for risk stratification. In conclusion, among patients hospitalized with AHF, a greater FIB-4 reduction during hospitalization was associated with better prognoses.

Prognostic Impact of Multiple Drug Use at Discharge in Patients Hospitalized with Heart Failure.

The association between polypharmacy/multiple drug use (MDU) and prognosis in patients hospitalized with heart failure (HF) is unclear. It is also unknown whether the prognostic values of MDU vary depending on the presence/absence of a previous history of HF and preserved/reduced left ventricular ejection fraction (LVEF). We analyzed consecutive 1,034 patients hospitalized with HF (age, 74.9 ± 11.5 years; 58.7% male). MDU was defined as ≥5 drugs at discharge. The primary endpoint was a composite of all-cause death and HF readmission. MDU was observed in 695 patients (67.2%). Patients with MDU use had higher prevalences of a previous history of HF, reduced LVEF, and comorbidities than those without MDU. Cox proportional hazard analysis showed that MDU was significantly associated with the primary endpoint after adjustment for possible confounders (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.03-1.79; P = 0.030). There was significant interaction between the presence/absence of a history of HF and the prognostic impact of MDU (HF history [-]: HR, 0.86; 95% CI, 0.54-1.40; P = 0.553; HF history [+]: HR, 1.72; 95% CI, 1.16-2.55; P = 0.007; P for interaction = 0.005). However, there was no significant interaction between preserved/reduced LVEF and the prognostic impact of MDU (P for interaction = 0.274). In conclusion, MDU at discharge is an independent risk factor for the composite of death or HF readmission in patients hospitalized with HF. We observed a significant interaction between the presence of de novo versus recurrent HF and the prognostic value of MDU.

Prevalence and Risk Factors of Silent Cerebral Microbleeds in Patients with Coronary Artery Disease.

OBJECTIVES: Cerebral microbleeds (CMBs), which can be detected by gradient-echo T2*-weighted magnetic resonance imaging (MRI), represent small chronic brain hemorrhages caused by structural abnormalities in cerebral small vessels. CMBs are known to be a potential predictor of future stroke, and are associated with age, various cardiovascular risk factors, cognitive impairment, and the use of antithrombotic drugs. Patients with coronary artery disease (CAD) are at potentially high risk of CMBs due to the presence of coexistent conditions. However, little is known about CMBs in patients with CAD. We aimed to identify the factors associated with the presence of CMBs among patients with CAD. METHODS: We evaluated 356 consecutive patients [mean age, 72 ± 10 years; men = 276 (78%)] with angiographically proven CAD who underwent T2*-weighted brain MRI. The brain MRI was assessed by researchers blinded to the patients' clinical details. RESULTS: CMBs were found in 128 (36%) patients. Among 356 patients, 119 (33%) had previously undergone percutaneous coronary intervention (PCI), and 26 (7%) coronary artery bypass grafting (CABG). There was no significant relationship between CMBs and sex, hypertension, dyslipidemia, diabetes mellitus, anticoagulation therapy, antiplatelet therapy, or prior PCI. CMBs were significantly associated with advanced age, previous CABG, eGFR, non-HDL cholesterol, carotid artery disease, long-term antiplatelet therapy, and long-term dual antiplatelet therapy (DAPT) using univariate logistic regression analysis. The multivariate logistic regression analysis showed that long-term antiplatelet therapy (odds ratio, 1.73; 95% CI, 1.06 - 2.84; P = 0.03) or long-term DAPT (odds ratio, 2.92; 95% CI, 1.39 - 6.17; P = 0.004) was significantly associated with CMBs after adjustment for confounding variables. CONCLUSIONS: CMBs were frequently observed in patients with CAD and were significantly associated with long-term antiplatelet therapy, especially long-term DAPT.

Prognostic Value of the FAN Score, a Combination of the Fibrosis-4 Index, Albumin-Bilirubin Score and Neutrophil-Lymphocyte Ratio, in Patients Hospitalized with Heart Failure.

The fibrosis-4 index, albumin-bilirubin score and neutrophil-lymphocyte ratio are all prognostic markers in patients with heart failure. Recently, the FAN score, which includes all 3 of these markers, was developed as a useful risk stratification tool in patients with cancer. However, its cut-off values have not been validated for heart failure. We aimed to investigate the optimal cut-off and prognostic values of the FAN score in patients with heart failure. We analyzed 669 consecutive patients hospitalized with heart failure (age, 75.8 ± 11.3 years). Their median values of the fibrosis-4 index, albumin-bilirubin score, and neutrophil-lymphocyte ratio at discharge were 2.12, -2.25, and 2.41, respectively. The FAN score for heart failure (HF-FAN score) was calculated using these median values. The primary outcome was a composite of all-cause death and heart failure rehospitalization. Patients were divided into 4 groups according to HF-FAN scores of 0 (n = 112), 1 (n = 231), 2 (n = 242) and 3 (n = 84). Patients with HF-FAN scores of 3 were older, had higher brain natriuretic peptide levels, and larger inferior vena cava diameters. Kaplan-Meier analysis showed a direct correlation between higher HF-FAN scores and occurrence of the primary endpoint (log-rank P < 0.001). Cox proportional hazard analysis revealed a higher HF-FAN score was significantly associated with a worse prognosis even after adjustment for possible prognostic factors. Changing from the FAN score to HF-FAN score provided significant continuous net reclassification improvement. In conclusion, the HF-FAN score at discharge was useful for risk stratification in patients hospitalized with heart failure. The HF-FAN score might be more suitable for patients with heart failure than the FAN score.

Effect of canagliflozin on N-terminal pro-brain natriuretic peptide in patients with type 2 diabetes and chronic heart failure according to baseline use of glucose-lowering agents.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of a deterioration in heart failure (HF) and mortality in patients with a broad range of cardiovascular risks. Recent guidelines recommend considering the use of SGLT2 inhibitors in patients with type 2 diabetes (T2D) and HF, irrespective of their glycemic control status and background use of other glucose-lowering agents including metformin. However, only a small number of studies have investigated whether the effects of SGLT2 inhibitor in these patients differ by the concomitant use of other glucose-lowering agents. METHODS: This was a post-hoc analysis of the CANDLE trial (UMIN000017669), an investigator-initiated, multicenter, open-label, randomized, controlled trial. The primary aim of the analysis was to assess the effect of 24 weeks of treatment with canagliflozin, relative to glimepiride, on N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration in patients with T2D and clinically stable chronic HF. In the present analysis, the effect of canagliflozin on NT-proBNP concentration was assessed in the patients according to their baseline use of other glucose-lowering agents. RESULTS: Almost all patients in the CANDLE trial presented as clinically stable (New York Heart Association class I to II), with about 70% of participants having HF with a preserved ejection fraction phenotype (defined as a left ventricular ejection fraction ≥ 50%) at baseline. Of the 233 patients randomized to either canagliflozin (100 mg daily) or glimepiride (starting dose 0.5 mg daily), 85 (36.5%) had not been taking any glucose-lowering agents at baseline (naïve). Of the 148 patients who had been taking at least one glucose-lowering agent at baseline (non-naïve), 44 (29.7%) and 127 (85.8%) had received metformin or a dipeptidyl dipeptidase-4 (DPP-4) inhibitor, respectively. The group ratio (canagliflozin vs. glimepiride) of proportional changes in the geometric means of NT-proBNP concentration was 0.95 (95% confidence interval [CI] 0.76 to 1.18, p = 0.618) for the naïve subgroup, 0.92 (95% CI 0.79 to1.07, p = 0.288) for the non-naïve subgroup, 0.90 (95% CI 0.68 to 1.20, p = 0.473) for the metformin-user subgroup, and 0.91 (95% CI 0.77 to 1.08, p = 0.271) for the DPP-4 inhibitor-user subgroup. No heterogeneity in the effect of canagliflozin, relative to glimepiride, on NT-proBNP concentration was observed in the non-naïve subgroups compared to that in the naïve subgroup. CONCLUSION: The impact of canagliflozin treatment on NT-proBNP concentration appears to be independent of the background use of diabetes therapy in the patient population examined. Trial registration University Medical Information Network Clinical Trial Registry, number 000017669. Registered on May 25, 2015.

Splenic Volume Index Determined Using Computed Tomography upon Admission Is Associated with Readmission for Heart Failure Among Patients with Acute Decompensated Heart Failure.

The spleen is associated with inflammation, and the size of the spleen is affected by hemodynamic congestion and sympathetic stimulation. However, the association between splenic size and prognosis in patients with heart failure remains unknown. Between January 2015 and March 2017, we analyzed 125 patients with acute decompensated heart failure who were assessed by computed tomography (CT) on the day of admission. The spleen was measured by 3-dimensional CT and then the patients were assigned to groups according to their median splenic volume indexes (SpVi; splenic volume/body surface area). We then compared their baseline characteristics and rates of readmission for heart failure after one year. The median SpVi was 63.7 (interquartile range: 44.7-95.3) cm3/m2. Age did not significantly differ between the groups. Patients with a high SpVi had more significantly enlarged left atria and left ventricles. Multiple regression analysis identified significant positive correlations between SpVi and posterior wall thickness as well as left ventricular mass index. Kaplan-Meier analysis revealed lower event-free rates in the patients with a high, than a low SpVi (P = 0.041, log-rank test). After adjustment for potential cofounding factors, SpVi was independently associated with readmission for heart failure (Hazard ratio, 2.25; 95% confidence interval, 1.01-5.02; P = 0.047). In conclusion, increased splenic volume is independently associated with readmission for heart failure among patients with acute decompensated heart failure.

Febuxostat does not delay progression of carotid atherosclerosis in patients with asymptomatic hyperuricemia: A randomized, controlled trial.

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.

Prognostic impact of a novel index of nutrition and inflammation for patients with acute decompensated heart failure.

Malnutrition and systemic inflammation are associated with poor outcomes in patients with heart failure. Recent studies have reported that the advanced lung cancer inflammation index (ALI), derived from the body mass index (BMI), serum albumin level, and neutrophil-to-lymphocyte ratio (NLR), is associated with poor prognosis in several types of cancers. Each marker is also known to prognostic factor of heart failure. Therefore, we hypothesized that ALI may be useful for determining the prognosis of patients with acute decompensated heart failure (ADHF). We reviewed survival in 381 consecutive patients (age, 73.1 ± 11.4 years, 59% men) who were hospitalized for ADHF and discharged. ALI at discharge, calculated as BMI × albumin level/NLR, was used to divide the patients into tertiles (ALI < 23.88, 23.88 ≤ ALI < 42.43, and ALI ≥ 42.43). The patients were also stratified into six groups according to the ALI tertiles and median concentration (177 pg/mL) of brain natriuretic peptide (BNP). The primary endpoint comprised all-cause mortality and readmission because of heart failure. The median follow-up duration was 363 days (interquartile range: 147-721 days), and 166 patients (44%) experienced the primary endpoint. Kaplan-Meier analysis showed that the event rate decreased progressively from the first to the third ALI tertile (52%, 48%, and 31%, respectively; p = 0.0013). In a multivariate Cox proportional hazards model, the first tertile was an independent prognostic factor for the primary endpoint (third vs. first tertile: hazard ratio, 0.57; 95% confidence interval, 0.34-0.95; p = 0.031). The hazard ratio for the primary endpoint for the patients with high BNP and first tertile ALI relative to the patients with low BNP and third tertile ALI was 5.3 (95% confidence interval, 2.9-9.5; p < 0.001). ALI at discharge, a novel and simple index of nutrition and inflammation, may be useful for risk stratification and predicting the prognosis of patients with ADHF.

Fibrosis-4 index reflects right-sided filling pressure in patients with heart failure.

The fibrosis-4 index (FIB-4 index) is a marker of liver fibrosis. It has been reported that the FIB-4 index in compensated phase is associated with estimated right-sided filling pressure and poor prognosis in patients with heart failure. However, the relationship with invasively obtained right-sided cardiac pressures has been unclear. Hemodynamic status was evaluated by right heart catheterization in 189 heart failure patients who were in a clinically compensated phase between January 2015 and September 2017. Patients were assigned to two groups based on a median FIB-4 index of 2.15, then hemodynamic parameters and event rates were compared. Endpoint was defined as a composite of all-cause death, readmission for heart failure, or left ventricular-assist device implantation. Then, we also investigated correlations between the FIB-4 index and clinical factors, including hemodynamic parameters. Patients with a high FIB-4 index were significantly older (76 [IQR, 63-80] vs. 65 [IQR, 56-74] years, P < 0.001) and had higher right atrial pressure (RAP; 7 [IQR, 5-11] vs. 4 [IQR, 1-6] mmHg, P < 0.001) and pulmonary capillary wedge pressure (16 [IQR, 12-22] vs. 12 [IQR, 8-19] mmHg, P = 0.011) than those with a low FIB-4 index. The FIB-4 index correlated more strongly with parameters of right-sided than left-sided HF (RAP, R = 0.41, P < 0.001; inferior vena cava diameter, R = 0.44, P < 0.001; pulmonary capillary wedge pressure, R = 0.15, P = 0.038; brain natriuretic peptide, R = 0.14, P = 0.29). Multiple regression analysis showed that the FIB-4 index independently correlated with RAP. In conclusion, the FIB-4 index can non-invasively reflect right-sided filling pressure, which might explain why it is associated with a poor prognosis, among patients with heart failure.

Correction to: Increased prevalence of cerebral microbleeds in patients with low left ventricular systolic function.

In the original publication of the article, under the results section, the following sentence.

Increased prevalence of cerebral microbleeds in patients with low left ventricular systolic function.

Gradient-echo T2-star (T2*)-weighted magnetic resonance imaging (MRI) is a sensitive method to detect cerebral microbleeds (CMBs). The presence of CMBs was reported to be a marker of future cardiovascular mortality and is associated with various cardiovascular risk factors, use of antithrombotic drugs, and cognitive dysfunction. However, the relationship between cardiac function and CMBs remains unclear. We investigated the association between cardiac function and presence of CMBs in patients with cardiovascular diseases. This single-center retrospective study included a total of 424 participants (mean age 70 ± 12 years; men 286 (67%); mean left ventricular ejection fraction (LVEF) 61% ± 12%] who underwent echocardiography and brain T2*-weighted MRI within 1 month without neurologic abnormality. CMBs were found in 118 (28%) patients. There was no significant relationship between CMBs and anticoagulant or antiplatelet therapy. LVEF was significantly lower in patients with CMBs than in those without CMBs (59% ± 13% vs. 62% ± 11%, P < 0.05). On multivariate logistic analysis, lower LVEF [odds ratio (OR) 0.98, 95% confidence interval (CI) 0.96-1.00; P < 0.05] and age (OR 1.02, 95% CI 1.00-1.05; P < 0.05) were significantly associated with CMBs. The presence of CMBs was frequently observed in the patients with cardiovascular disease and was significantly associated with age and LVEF.

Usefulness of tissue Doppler-derived atrial electromechanical delay for identifying patients with paroxysmal atrial fibrillation.

BACKGROUND: Tissue Doppler imaging (TDI)-derived atrial electromechanical delay (AEMD) has been reported to be useful for detecting paroxysmal atrial fibrillation (PAF). However, its usefulness remains unknown when analyzed along with patients seemingly at high-risk for AF as controls. From this standpoint, we investigated whether AEMD would be of use for identifying patients with PAF. METHODS: We retrospectively analyzed TDI recordings to obtain AEMD in 63 PAF patients. Thirty-three patients with multiple cardiovascular risk factors (MRFs) but without history of AF and 50 healthy individuals served as disease and healthy controls, respectively. AEMD was defined as the time-interval between the electrocardiogram P-wave and the beginning of the spectral TDI-derived A' for the septal (septal EMD) and lateral (lateral EMD) sides of the mitral annulus. RESULTS: There was no significant difference in the left atrial volume index between PAF patients and disease controls (28 ± 9 mL/m2 vs. 27 ± 5 mL/m2). PAF patients had longer AEMD, particularly for the lateral EMD (75 ± 23 ms), compared with disease (62 ± 22 ms, P = 0.009) and healthy (54 ± 24 ms, P < 0.001) controls. Multivariate logistic regression analysis revealed that the lateral EMD (OR 1.25, 95%CI 1.03-1.52, P = 0.023), along with the left atrial volume index (OR 2.25, 95%CI 1.44-3.51, P < 0.001), was one of the significant independent associates of identifying PAF patients. CONCLUSIONS: This cross-sectional study indicates that even analyzed together with MRFs patients, AEMD remains useful for identifying patients at risk for AF. Our results need to be confirmed by a large-scale prospective study.

Improved diagnosis of the number of stenosed coronary artery vessels by segmentation with scatter and photo-peak window data for attenuation correction in myocardial perfusion SPECT.

BACKGROUND: Attenuation correction using segmentation of scatter and photo-peak window data (SSPAC) enables an evaluation of the attenuation map in a patient-specific manner without additional radiation exposure. We compared the accuracy of SSPAC and non-corrected myocardial perfusion scintigraphy methods for diagnosing the number of stenosed coronary artery vessels. METHODS AND RESULTS: We retrospectively reviewed the data from 183 consecutive patients who underwent 99mTc-tetrofosmin stress/rest SPECT examination and a coronary angiography within 3 months. The MPS images were reconstructed with and without SSPAC attenuation correction. We examined the accuracy of the quantitative interpretation using summed differential score in the detection of coronary artery disease (CAD). The attenuation maps were successfully determined in 179 of 183 patients (98%). In terms of the vessel-based diagnostic ability, sensitivity, specificity, positive predictive and negative predictive values of the SSPAC and non-correction methods for diagnosing CAD in individual coronary territories were 77%*, 89%, 74%*, and 90%* vs 51%, 87%, 62%, and 82%, respectively (*P < .05). In 35 patients with multi-vessel CAD, those values were 78%*, 81%, 93%, and 55%* vs 49%, 81%, 89%, and 34%, respectively (*P < .05; AUC: 0.82 vs 0.62, P < .05). CONCLUSION: SSPAC-corrected SPECT myocardial perfusion images exhibit improved accuracy in the detection of the number of stenosed coronary artery vessels, even in patients with multi-vessel CAD.

Spontaneous Reduction in Abnormal Myocardial Uptake of Fluorine-18 Fluorodeoxygluose in a Patient with Cardiac Sarcoidosis.

Fluorine-18 fluorodeoxygluose (18F-FDG) positron emission tomography (PET) is a useful tool for evaluating disease activity in sarcoidosis including cardiac involvement. A 67-year-old patient who developed atrioventricular block requiring permanent pacemaker implantation was diagnosed with cardiac sarcoidosis. The patient did not undergo steroid or immunosuppressive therapy but underwent serial 18F-FDG PET examination, which showed spontaneous reduction in the myocardial FDG uptake, indicating the remission of immune-inflammatory activity. Although the global systolic function remained preserved, thinning of the septal wall emerged during the clinical course of follow-up, which is characteristic for cardiac sarcoidosis.

Basal wall hypercontraction of Takotsubo cardiomyopathy in a patient who had been diagnosed with dilated cardiomyopathy: a case report.

BACKGROUND: Takotsubo cardiomyopathy is characterized by the basal hypercontractility and apical ballooning of the left ventriculum and T-wave inversion in the electrocardiogram. It has been suggested that Takotsubo cardiomyopathy might underlie the pathogenesis of persistent cardiac dysfunction; however, few reports are present demonstrating the advent of Takotsubo cardiomyopathy in patients with idiopathic cardiomyopathy. CASE PRESENTATION: A 64-year-old women was admitted due to dyspnea on effort and lower extremity edema. She had been diagnosed with idiopathic dilated cardiomyopathy 2.5 years before owing to the reduced left ventricular ejection fraction (24%), normal coronary artery, and interstitial fibrosis of the myocardial samples. On admission, her electrocardiogram showed giant negative T wave in II, III, aVF, and precordial leads. Echocardiography showed dyskinesis of the left ventricular apex and hypercontraction of the basal wall, which had not been observed in the previous examinations. Coronary angiography showed normal coronary arteries, and apical ballooning and basal hypercontractility was confirmed by left ventriculography. On day 15 of admission, contraction of apical wall was recovered, and basal hypercontraction was disappeared. CONCLUSION: The present case is the first report demonstrating appearance the transient basal wall hypercontraction along with the advent of Takotsubo cardiomyopathy in a patient diagnosed with dilated cardiomyopathy. Whether such findings are indicative of fair prognosis and have the utility of understanding the pathogenesis of dilated cardiomyopathy needs further investigation.

Rationale and design of a multicenter randomized study for evaluating vascular function under uric acid control using the xanthine oxidase inhibitor, febuxostat: the PRIZE study.

BACKGROUND: Xanthine oxidase inhibitors are anti-hyperuricemic drugs that decrease serum uric acid levels by inhibiting its synthesis. Xanthine oxidase is also recognized as a pivotal enzyme in the production of oxidative stress. Excess oxidative stress induces endothelial dysfunction and inflammatory reactions in vascular systems, leading to atherosclerosis. Many experimental studies have suggested that xanthine oxidase inhibitors have anti-atherosclerotic effects by decreasing in vitro and in vivo oxidative stress. However, there is only limited evidence on the clinical implications of xanthine oxidase inhibitors on atherosclerotic cardiovascular disease in patients with hyperuricemia. We designed the PRIZE study to evaluate the effects of febuxostat on a surrogate marker of cardiovascular disease risk, ultrasonography-based intima-media thickness of the carotid artery in patients with hyperuricemia. METHODS: The study is a multicenter, prospective, randomized, open-label and blinded-endpoint evaluation (PROBE) design. A total of 500 patients with asymptomatic hyperuricemia (uric acid >7.0 mg/dL) and carotid intima-media thickness ≥1.1 mm will be randomized centrally to receive either febuxostat (10-60 mg/day) or non-pharmacological treatment. Randomization is carried out using the dynamic allocation method stratified according to age (<65, ≥65 year), gender, presence or absence of diabetes mellitus, serum uric acid (<8.0, ≥8.0 mg/dL), and carotid intima-media thickness (<1.3, ≥1.3 mm). In addition to administering the study drug, we will also direct lifestyle modification in all participants, including advice on control of body weight, sleep, exercise and healthy diet. Carotid intima-media thickness will be evaluated using ultrasonography performed by skilled technicians at a central laboratory. Follow-up will be continued for 24 months. The primary endpoint is percentage change in mean intima-media thickness of the common carotid artery 24 months after baseline, measured by carotid ultrasound imaging. CONCLUSIONS: PRIZE will be the first study to provide important data on the effects of febuxostat on atherosclerosis in patients with asymptomatic hyperuricemia. Trial Registration Unique trial Number, UMIN000012911 ( https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000015081&language=E ).

Is cardiac and hepatic iron status assessed by MRI T2* associated with left ventricular function in patients with idiopathic cardiomyopathy?

Excess accumulation of iron in the heart is known to aggravate cardiac function in some cases of genetic and acquired iron overload. We investigated the possible association between cardiac function and iron content in the heart and liver, estimated non-invasively by T2 star (T2*)-weighted magnetic resonance (MR) imaging among patients with cardiomyopathy. MR images were acquired on a 3.0 T MR imaging system using an 8-channel phased-array cardiac coil. Average T2* values of the heart were estimated at regions of interest that were located on short axis mid-ventricular slices positioned at the cardiac septum. In total, 82 patients were enrolled: 48 patients with dilated cardiomyopathy (DCM), 16 patients with hypertrophic cardiomyopathy (HCM), and 18 patients without apparent cardiovascular abnormalities. Cardiac T2* values were lower in the DCM group (median 18.6 ms) than in the HCM (22.0 ms) and control (21.4 ms) groups, although hepatic T2* values did not differ significantly across the groups. Among the whole population, the highest cardiac T2* tertile (≥21.2 ms) was significantly negatively associated with a low left ventricular ejection fraction (LVEF) of <50 %, and this association retained statistical significance after adjustment for sex, age, renal function, hemoglobin and hepatic T2*. Among DCM patients, both hemoglobin and cardiac T2* were selected as parameters that were, respectively, negatively and positively, associated with LVEF (P < 0.05). DCM patients with lower cardiac T2*, and thus higher iron content, were found to have lower LVEF. The possibility that cardiac iron overload may have a role in reducing the systolic cardiac function in DCM patients who do not have systemic iron overload requires further investigation in the future.