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Background: Endothelial dysfunction and increased left ventricular (LV) stiffness are associated with the incidence of heart failure with preserved ejection fraction (HFpEF). This study evaluated the association between endothelial dysfunction and LV diastolic stiffness., Methods and results: Endothelial dysfunction evaluated by flow-medicated vasodilation (FMD) and the reactive hyperemia index (RHI), which reflects endothelial dysfunction in the microvasculature, was measured in 112 subjects with hypertension in the Flow-Mediated Dilation Japan (FMD-J) study. Using transthoracic echocardiography, LV diastolic stiffness was evaluated by measuring diastolic wall strain (DWS) in the LV posterior wall. In this cross-sectional study, associations among FMD, RHI, and DWS were investigated using multiple regression analyses. The mean (±SD) age of the subjects 65±9 years, and 63% were men. DWS was significantly associated with RHI, but not FMD, on multivariate linear regression analysis (β=0.39; P<0.0001). This association was preserved in subjects without LV hypertrophy (β=0.46; P<0.0001). A DWS ≤median, suggesting increased LV diastolic stiffness, was significantly associated with RHI on multivariate logistic regression analysis (odds ratio 20.58; 95% confidence interval 4.83-87.63; P<0.0001). The receiver operating characteristic curve presented a cut-off value of 2.21 for RHI, with a sensitivity of 77% and a specificity of 71%, for DWS ≤median., Conclusions: RHI, rather than FMD, was associated with DWS. Endothelial dysfunction in the microvasculature may be associated with increased LV diastolic stiffness.

Background: In the EARLIER (Efficacy and Safety of Early Initiation of Eplerenone Treatment in Patients with Acute Heart Failure) trial, eplerenone did not reduce heart failure (HF) hospitalizations or all-cause mortality in 300 patients admitted for acute HF (AHF). However, the trial might have been underpowered for these endpoints, and a comprehensive overview of the effect of eplerenone on diuretic doses and patients' clinical stability is warranted., Methods: The EARLIER trial included Japanese patients hospitalized for AHF randomly assigned to eplerenone or placebo over 6 months. Cox proportional hazards and mixed-effects models were used for analyses., Results: Three hundred patients were included (mean age, 67 ± 13 years; 73% males). The median furosemide equivalent dose was 40 (20-62) mg at randomization. Patients with higher furosemide-equivalent doses had more severe signs and symptoms of congestion and a higher risk of all-cause mortality or HF hospitalization during 6-month follow-up (adjusted-hazard ratio per 10 mg/day increase = 1.25, 95% confidence interval: 1.05-1.49). Eplerenone significantly decreased furosemide-equivalent diuretic doses and b-type natriuretic levels throughout the follow-up (overall-joint-p < 0.05 for both) and reduced E/e' and inferior vena cava diameter at 4 weeks (both p < 0.05). Additionally, eplerenone significantly reduced left ventricular (LV) end-diastolic diameter at 24 weeks (p < 0.05)., Conclusions: Eplerenone treatment improved the clinical stability particularly during short period following hospitalization for AHF, translated by lower diuretic doses, natriuretic peptide levels, indirect markers of filling pressure and venous congestion, and a smaller LV volume., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aims: A mineralocorticoid receptor antagonist (MRA) is effective in patients with chronic heart failure; however, the effects of the early initiation of an MRA in patients with acute heart failure (AHF) have not been elucidated., Methods and Results: In this multicentre, randomized, double-blind, placebo-controlled, parallel-group study, we focused on the safety and effectiveness of the treatment with eplerenone, a selective MRA in 300 patients with AHF, that is, 149 in the eplerenone group and 151 in the placebo group in 27 Japanese institutions. The key inclusion criteria were (i) patients aged 20 years or older and (ii) those with left ventricular ejection fraction of ≤40%. The primary outcome was a composite of cardiac death or first re-hospitalization due to cardiovascular disease within 6 months. The mean age of the participants was 66.8 years, 27.3% were women, and the median levels of brain natriuretic peptide were 376.0 pg/mL. The incidences of the primary outcome were 19.5% in the eplerenone group and 17.2% in the placebo group [hazard ratio (HR): 1.09, 95% confidence interval (CI): 0.642-1.855]. In prespecified secondary outcomes, HR for the composite endpoint, cardiovascular death, or first re-hospitalization due to heart failure within 6 months was 0.55 (95% CI: 0.213-1.434). The safety profile for eplerenone was as expected., Conclusion: The early initiation of eplerenone in patients with AHF could safely be utilized. The reduction of the incidence of a composite of cardiovascular death or first re-hospitalization for cardiovascular diseases by eplerenone is inconclusive because of inadequate power., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Increased heart rate (HR) is an independent risk factor for cardiovascular outcomes in chronic heart failure (HF). Ivabradine, anI f inhibitor, improved outcomes in patients with HF and reduced ejection fraction (HFrEF) in the SHIFT study. We evaluated its efficacy and safety in Japanese HFrEF patients in a randomized, double-blind, placebo-controlled phase III study: the J-SHIFT study. The main objective was to confirm a hazard ratio of <1 in the primary composite endpoint of cardiovascular death or hospital admission for worsening HF.Methods and Results:Patients with NYHA functional class II-IV, left ventricular EF ≤35%, and resting HR ≥75 beats/min in sinus rhythm under optimal medical therapy received ivabradine (n=127) or placebo (n=127). Mean reduction in resting HR was significantly greater in the ivabradine group (15.2 vs. 6.1 beats/min, P<0.0001). However, symptomatic bradycardia did not occur. A total of 26 (20.5%) patients in the ivabradine group and 37 (29.1%) patients in the placebo group had the primary endpoint event (hazard ratio 0.67, 95% CI 0.40-1.11, P=0.1179) during median follow-up of 589 days. Mild phosphenes were reported in 8 (6.3%) patients in the ivabradine group and 4 (3.1%) patients in the placebo group (P=0.3760)., Conclusions: The J-SHIFT study supported the efficacy and safety of ivabradine for Japanese HFrEF patients, in accord with the SHIFT study.

Aims: Pulmonary congestion is associated with poor prognosis following hospitalization for worsening heart failure (HF), although its quantification and optimal timing during HF hospitalization remains challenging. The aim of this study was to assess the prognostic value of radiographic pulmonary congestion at admission and discharge in patients with worsening HF., Methods and Results: Clinical, echocardiographic, laboratory and chest X-ray data of 292 acute decompensated HF patients were retrospectively studied (follow-up 1 year). Lung congestion was blindly scored on chest X-ray performed at admission and discharge using a systematic 6-zone approach. Primary clinical outcome was a composite outcome of re-hospitalization for worsening HF or all cause death. Patients were stratified according to the median of congestion score index (CSI) at both admission (median CSI(A) = 1.33) and discharge (median CSI(D) = 0.33). BNP levels, LVEF and eGFR did not differ between CSI categories. In multivariable Cox regression analysis, discharge CSI (HR for 1-point increase = 1.83 [1.02 to 3.27] p = 0.04) and discharge BNP were significantly associated with the composite outcome whereas NYHA class, physical signs, admission CSI and echocardiographic data were not. Furthermore, discharge CSI significantly increased reclassification on top of clinical covariates (continuous NRI = 19.6% [4.0 to 30.0] p = 0.03 and IDI = 2.2% [0.0 to 7.6] p = 0.046) while discharge BNP did not significantly improve risk reclassification., Conclusions: Residual pulmonary congestion assessed by radiographic scoring predicts poor prognosis beyond physical assessment, echocardiographic parameters and BNP. These findings further support the capital prognostic value of radiographic pulmonary congestion in patients hospitalized for worsening HF., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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 (baPWV) in 462 patients with coronary artery disease for assessment of the predictive value of FMD and baPWV 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. baPWV 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 baPWV, 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 baPWV were significant predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification., Clinical Trial Registration: URL: www.umin.ac.jp. Unique identifier: UMIN000012950., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Because type 2 diabetes mellitus is associated strongly with an increased risk of cardiovascular diseases, the number of patients with diabetes with chronic heart failure is increasing steadily. However, clinical evidence of therapeutic strategies in such patients is still lacking. A recent randomized, placebo-controlled trial in patients with type 2 diabetes with high cardiovascular risk demonstrated that the SGLT2 inhibitor, empagliflozin, reduced the incidence of hospitalization for heart failure. Because SGLT2 inhibitors cause a reduction in body weight and blood pressure in addition to improving glycemic control, they have the potential to exert beneficial effects on the clinical pathophysiology of heart failure. The aim of the ongoing CANDLE trial is to test the safety and non-inferiority of canagliflozin, another SGLT2 inhibitor, compared with glimepiride, a sulfonylurea agent, in patients with type 2 diabetes mellitus and chronic heart failure., Methods: A total of 250 patients with type 2 diabetes who are drug-naïve or taking any anti-diabetic agents and suffering from chronic heart failure with a New York Heart Association classification I to III will be randomized centrally into either canagliflozin or glimepiride groups (1: 1) using the dynamic allocation method stratified by age (<65, ≥65 year), HbA1c level (<6.5, ≥6.5 %), and left ventricular ejection fraction (<40, ≥40 %). After randomization, all the participants will be given the add-on study drug for 24 weeks in addition to their background therapy. The primary endpoint is the percentage change from baseline in NT-proBNP after 24 weeks of treatment. The key secondary endpoints after 24 weeks of treatment are the change from baseline in glycemic control, blood pressure, body weight, lipid profile, quality of life score related to heart failure, and cardiac and renal function., Discussion: The CANDLE trial is the first to assess the safety and non-inferiority of canagliflozin in comparison with glimepiride in patients with type 2 diabetes with chronic heart failure. This trial has the potential to evaluate the clinical safety and efficacy of canagliflozin on heart failure. Trial registration Unique trial Number, UMIN000017669.

Background: Elevated heart rate (HR) is an independent risk factor for cardiovascular outcomes in various cardiac diseases, including heart failure (HF)., Methods and results: Randomized placebo-controlled study was conducted to evaluate the effects of ivabradine, an Ifinhibitor, on the resting HR in 126 Japanese symptomatic HF patients with left ventricular ejection fraction ≤35%, resting HR ≥75 beats/min in sinus rhythm, and stable, optimal background treatment. Patients were randomly allocated into 3 groups: placebo; starting dose of ivabradine 2.5 mg twice daily (BID; 2.5 mg group); 5 mg BID group. The dose was increased up to 7.5 mg BID according to dose-adjustment criteria. After the 6-week treatment, the reductions in resting HR were significant in both the 2.5-mg (16.6±8.1 beats/min) and 5-mg (16.4±9.6 beats/min) groups (P<0.0001 for both groups) compared with placebo (1.7±8.7 beats/min). The most frequent side effect of ivabradine was phosphenes, but all were mild. Treatment was discontinued in 1 patient due to HF in the 5 mg group., Conclusions: Ivabradine starting at 2.5 or 5 mg BID effectively reduced resting HR in Japanese HF patients. Ivabradine at the starting dose of 2.5 mg BID could be safer than 5 mg BID. (Circ J 2016; 80: 668-676).

Background and Aims: Aldosterone is one of the major factors to cause organ damage during an acute phase of heart failure (HF), and many reports have demonstrated that patients with acute decompensated HF (ADHF) have high blood aldosterone concentrations, and the high aldosterone concentrations predict poor prognosis in patients with HF. These findings suggest that eplerenone, an antagonist of aldosterone receptors may provide a new concept and strategy for the treatment of ADHF, protecting the heart and other organs during chronic phases, depending on the restoration of hemodynamic abnormalities., Methods: EARLIER is an event-driven clinical trial with an estimated enrolment of 300 patients hospitalized with ADHF with reduced left ventricular ejection fraction. ADHF includes ischemic or non-ischemic HF, and patients can be enrolled within 72 h after the visit to the hospital. We randomize the patients taking standard therapies for ADHF to the eplerenone and placebo groups. Eplerenone, either 25 or 50 mg, is administered for 6 months in the eplerenone group, and the corresponding placebo is administered in the placebo group on top of the standard care. We set the primary endpoint as the incidence of the composite endpoint (cardiac death or first re-hospitalization due to cardiac disease) 6 months after the enrollment, and also check the quality of life, i.e., exercise capacity and safety features of eplerenone., Conclusion and Perspectives: EARLIER is a clinical trial of eplerenone targeting ADHF and also the first multicenter investigator-initiated phase III trial in the cardiovascular field in Japan, funded by the Japanese government.

Background: The detection of significant coronary artery disease (CAD) in patients with heart failure (HF) from left ventricular (LV) systolic dysfunction is crucial. We evaluated the usefulness of LV mechanical dyssynchrony as assessed by phase analysis compared with conventional gated single-photon emission computed tomography to identify ischemic etiology in patients with HF., Methods and Results: Forty-one consecutive patients who were initially admitted to hospital due to HF resulting from systolic dysfunction were evaluated. All patients underwent cardiac catheterization. LV mechanical dyssynchrony was evaluated using SyncTool™ to obtain the phase SD and histogram bandwidth. The changes in phase SD and histogram bandwidth with stress were calculated. The summed stress score, summed difference score, and changes in phase SD and histogram bandwidth with stress were greater in 26 patients with CAD than in 15 patients without CAD (P=0.001 and P=0.01). On multivariate analysis a phase SD of >14° (odds ratio [OR], 16.7) and a summed stress score of >17 (OR, 8.0) best differentiated LV dysfunction of ischemic and non-ischemic etiologies, with a sensitivity of 89% and a specificity of 87% (χ(2)=20), compared with summed stress score only (sensitivity, 46%; specificity, 87%; χ(2)=4.5)., Conclusions: The addition of phase analysis to conventional perfusion analysis enables better differentiation of the etiology of HF in patients with systolic dysfunction.

Background: In patients with chronic heart failure (CHF), the presence of sleep-disordered breathing, including either obstructive sleep apnea or Cheyne-Stokes respiration-central sleep apnea, is associated with a poor prognosis. A large-scale clinical trial showed that continuous positive airway pressure (CPAP) did not improve the prognosis of such patients with CHF, probably because of insufficient sleep-disordered breathing suppression. Recently, it was reported that adaptive servo-ventilation (ASV) can effectively treat sleep-disordered breathing. However, there are no specific data about the efficacy of flow-triggered ASV for cardiac function in patients with CHF with sleep-disordered breathing. The aim of this study was to compare the efficacy of flow-triggered ASV to CPAP in patients with CHF with coexisting obstructive sleep apnea and Cheyne-Stokes respiration-central sleep apnea., Methods and Results: Thirty-one patients with CHF, defined as left ventricular ejection fraction <50% and New York Heart Association class >or=II, with coexisting obstructive sleep apnea and Cheyne-Stokes respiration-central sleep apnea, were randomly assigned to either CPAP or flow-triggered ASV. The suppression of respiratory events, changes in cardiac function, and compliance with the devices during the 3-month study period were compared. Although both devices decreased respiratory events, ASV more effectively suppressed respiratory events (DeltaAHI [apnea-hypopnea index], -35.4+/-19.5 with ASV; -23.2+/-12.0 with CPAP, P<0.05). Compliance was significantly greater with ASV than with CPAP (5.2+/-0.9 versus 4.4+/-1.1 h/night, P<0.05). The improvements in quality-of-life and left ventricular ejection fraction were greater in the ASV group (DeltaLVEF [left ventricular ejection fraction], +9.1+/-4.7% versus +1.9+/-10.9%)., Conclusions: These results suggest that patients with coexisting obstructive sleep apnea and Cheyne-Stokes respiration-central sleep apnea may receive greater benefit from treatment with ASV than with CPAP.

Background: Although a very simple method of measuring brachial -- ankle pulse wave velocity (baPWV) has become available in a clinical setting, whether baPWV can predict future cardiovascular events remains uncertain. We examined whether baPWV is a predictor of cardiovascular events in patients with acute coronary syndrome (ACS)., Methods and Results: baPWV measurement was performed in 215 consecutive patients with ACS. During the follow-up period (26+/-10 months), 46 patients experienced post-hospitalization cardiovascular events (18 patients experienced a major event (eg, stroke, re-admission for heart failure or cardiac death), and 28 patients experienced coronary re-intervention). A receiver operating characteristic curve demonstrated that the best cut-off point of a baPWV for predicting a post-hospitalization cardiovascular event was 17.00 m/s and that for predicting a major cardiovascular event was 18.00 m/s. After the adjustment for the conventional risk factors influencing the prognosis, a multivariate Cox proportional hazards model demonstrated that both cut-off points of baPWV had a significant hazard ratio for a post-hospitalization event: 5.47 (2.69-11.09) and for a major cardiovascular event: 9.22 (2.78-30.56)., Conclusions: baPWV is a simple predictor of the prognosis of patients with ACS that is independent of conventional risk factors for ACS.

While arterial stiffness is known to be related to atherosclerosis, the association between arterial stiffness and cardiac systolic and diastolic function in hypertension has not been fully evaluated. The present study was conducted to simultaneously evaluate the relationship of brachial-ankle pulse wave velocity (PWV) to parameters reflecting atherosclerosis and to those reflecting the risk of congestive heart failure in patients with hypertension. In 147 patients with hypertension, the left ventricular ejection fraction, the ratio of the peak velocity of early rapid filling and the peak velocity of atrial filling (E/A ratio), and left ventricular mass index were obtained from echocardiographs, the intima-media thickness of the common carotid artery was obtained by ultrasonography, the plasma B-type natriuretic peptide (BNP) level was measured by radioimmunoassay, and the brachial-ankle PWV was measured by the volume rendering method. Brachial-ankle PWV correlated positively with the intima-media thickness of the carotid artery, E/A ratio and BNP. Multiple linear regression analysis demonstrated that the relationship between the brachial-ankle PWV and the E/A ratio was significantly independent from other clinical variables. The receiver operator characteristic curve demonstrated that a brachial-ankle PWV of 1,600 cm/s was useful to discriminate mild cardiac diastolic dysfunction (E/A ratio of < or =0.75) (sensitivity=78% and specificity=58%). The present study demonstrated that increased brachial-ankle PWV relates not only to the parameters reflecting atherosclerosis but also to those reflecting cardiac diastolic dysfunction. Therefore, increased arterial stiffness is a possible simultaneous risk for atherosclerotic cardiovascular disease and diastolic heart failure in patients with hypertension.

Background: The significance of antioxidant therapy in heart failure has not been fully examined. This study evaluated whether vitamin C has beneficial effects on renal function or augments the renal effects of furosemide in patients with heart failure., Methods: There were 2 protocols. In protocol 1, plasma level of thiobarbituric acid-reactive substances (TBARS) and renal function were assessed before and after intravenous infusion of vitamin C or placebo in 8 patients with moderate congestive heart failure (CHF) treated with enalapril. In protocol 2, a randomized crossover study was performed in patients with moderate CHF treated with either an ACE inhibitor (enalapril) (n = 10) or an angiotensin II receptor antagonist (losartan) (n = 9) and in asymptomatic patients with impaired left ventricular function treated with enalapril (n = 8). TBARS and renal function were assessed before and after intravenous infusion of furosemide alone, coinfusion of furosemide with placebo and vitamin C, or coinfusion of furosemide with vitamin C and a kallikrein inhibitor (nafamostat mesilate)., Results: In protocol 1, although vitamin C reduced TBARS, it did not affect renal function. In protocol 2, TBARS was higher in patients with moderate CHF than in asymptomatic patients. Vitamin C augmented natriuretic effect of furosemide (from 179 +/- 98 to 192 +/- 104 micromol/min, P <.01) only in patients with moderate CHF treated with enalapril but not in the other 2 groups. Nafamostat mesilate prevented this augmentation., Conclusions: In patients with CHF treated with enalapril, counteraction of the increased oxidative stress by vitamin C may contribute to the augmented natriuretic effect of furosemide through the renal kinin-nitric oxide pathway.

Summary: Background: The presence and severity of coronary artery disease may be underestimated in patients who do not reach significant end-points of stress testing during myocardial perfusion imaging. We examined how the effect of the level of exercise may affect the ability of the quantitative gated single-photon emission computed tomography (SPECT) imaging to predict the future cardiac events (cardiac death, non-fatal myocardial infarction and severe heart failure). Method: Of the 4629 consecutively registered patients for J-ACCESS (Japanese-assessment of cardiac event and survival study by quantitative gated SPECT), 2821 patients who underwent the exercise test were selected, and divided into two groups, which reached a target heart rate (group; n =925) or not (n =1896). Leg fatigue was the most common reason for stopping the exercise test in non-reaching groups, we conducted a study comparing group with leg fatigue group (group II). Results: During a 3-year follow-up period, total of 25 cardiac events (2.7%) occurred in group I and total of 73 events (3.9%) occurred in group II. The incidence of cardiac death was slightly but significantly higher in group II (P.04). A summed stress score (SSS) was able to separate the high-risk from low-risk patients in group II. The maximal heart rate was not an independent predictor for cardiac events. In Cox multivariate regression analysis, higher age (70 years), history of DM, EDV at rest and LVEF at rest were predictor of cardiac major events (cardiac death, myocardial infarction, heart failure), and higher age (70 years), ESV at rest were independent predictor of cardiac hard events (cardiac death, myocardial infarction) in group II. Conclusion: Exercise SPECT imaging provides the useful prognostic information in patients who do not reach a significant end-point due to the leg fatigue. In such patients, those with normal SSS score and normal resting ESV have also a most favorable prognosis. [ABSTRACT FROM AUTHOR]

Cardiotoxicity is a limiting factor in the treatment of cancer with adriamycin. We administered adriamycin by a method which minimizes the risk of peritonitis in an adriamycin-induced cardiomyopathy rat model. Sixty male Wistar rats were given 1 mg/kg of adriamycin intraperitoneally 15 times over a 3-week period (total dose, 15 mg/kg) to induce the cardiomyopathy model. Fifteen control rats received 10 ml/kg body wt. saline 15 times over 3 weeks. The animals were observed for 12 weeks and assessed for mortality, and cardiac volume and function was analyzed by echocardiography at 4, 8, and 12 weeks. In rats treated with adriamycin, the cumulative mortality was 35.8% while in the controls, none of the rats died. Left ventricular diameter of the systole (LVDs) was significantly increased at 4 weeks (4.5 vs. 3.3 mm; P<0.001). Left ventricular diameter of the diastole (LVDd) was significantly increased at 12 weeks (7.9 vs. 7.0 mm; P<0.01) and the % fractional shortening (FS) was significantly decreased at 8 weeks (33.4% vs. 50.0%; P<0.01) in the adriamycin-treated rats. This administration method appears to be useful for investigating the cardiac effect of adriamycin while avoiding the influence of peritonitis typically caused by an intraperitoneal injection of higher single doses of adriamycin. [ABSTRACT FROM AUTHOR]

Aim Whether myocardial ischemia identified using myocardial perfusion imaging (MPI) can be an alternative target of coronary revascularization to reduce the incidence of cardiac events remains unclear. Methods and results This multicenter, prospective cohort study aimed to clarify the prognostic impact of reducing myocardial ischemia. Among 494 registered patients with possible or definite coronary artery disease (CAD), 298 underwent initial pharmacological stress 99m Tc-tetrofosmin MPI before, and eight months after revascularization or medical therapy, and were followed up for at least one year. Among these, 114 with at least 5% ischemia at initial MPI were investigated. The primary endpoints were cardiac death, non-fatal myocardial infarction and hospitalization for heart failure. Ischemia was reduced ≥5% in 92 patients. Coronary revascularization reduced ischemia ( n  = 89) more effectively than medical therapy ( n  = 25). Post-stress cardiac function also improved after coronary revascularization. Ejection fraction significantly improved at stress (61.0% ± 10.7% vs. 65.4% ± 11.3%; p  < 0.001) but not at rest (67.1% ± 11.3% vs. 68.3% ± 11.6%; p  = 0.144), among patients who underwent revascularization. Rates of coronary revascularization and cardiac events among the 114 patients were significantly higher (13.6%, p  = 0.035) and lower (1.1% p  = 0.0053), respectively, in patients with, than without ≥5% ischemia reduction. Moreover, patients with complete resolution of ischemia at the time of the second MPI had a significantly better prognosis. Conclusions Reducing ischemia by ≥5% and the complete resolution of ischemia could improve the prognosis of patients with stable CAD. [ABSTRACT FROM AUTHOR]

Fibrotic lesions in the myocardium exhibit delayed contrast enhancement (DCE) on MR images. On the other hand, plexiform fibrosis is observed in hypertrophic cardiomyopathy (HCM), indicating an association of this condition with the pathogenesis of heart failure and arrhythmia. To examine the occurrence and extent of DCE and its relation to cardiac function and arrhythmia in HCM, we studied 59 patients with HCM who had undergone MRI. The relationship of DCE to cardiac function and arrhythmia was further investigated. DCE occurred in 45 (76.3%) of the 59 patients with HCM, with a high frequency of localization in regions, where the right ventricle is attached. As for the relationship of DCE to cardiac function, a significant decrease (P = 0.007) in cardiac function was observed in the group in which 4 or more segments exhibited DCE, compared with the group in which DCE was observed in 3 or less segments. Regarding the relationship of DCE to arrhythmia, both the occurrence of DCE and the extent of DCE were significantly larger (p < 0.05, p = 0.026, respectively) in the group with VT. These results indicate that DCE may save to identify severe cases of HCM on the basis of cardiac function, arrhythmia, and pathophysiological aspects. [Copyright &y& Elsevier]

Introduction: The usefulness of vascular function tests for management of patients with a history of coronary artery disease (CAD) is not fully known. Methods: We measured flow-mediated vasodilation (FMD) and brachial-ankle pulse wave velocity (baPWV) in 462 patients with CAD for assessment of the predictive value of vascular function tests for future cardiovascular events in a prospective multicenter observational study. The primary outcome was coronary events, and the secondary outcome was a composite of coronary events, stroke, heart failure, and sudden death. Results: During a median follow-up period of 49.2 months, the primary outcome occurred in 56 patients and the secondary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver-operator curve analyses for the primary and secondary outcomes, was significantly associated with lower risk of the primary (hazard ratio, 0.27; 95% confidence interval [CI], 0.06-0.74; P=0.008) and secondary (hazard ratio, 0.32; 95% CI, 0.09-0.79; P=0.01) outcomes. baPWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the primary (hazard ratio, 1.86; 95% CI, 1.01-3.44; P=0.04) and secondary (hazard ratio, 2.19; 95% CI, 1.23-3.90; P=0.008) outcomes. Among four groups stratified according to the combination of cutoff values of FMD and baPWV, stepwise increases in the calculated risk ratio for the primary and secondary outcomes were observed. Conclusions: In patients with CAD, both FMD and baPWV were independent predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification. [ABSTRACT FROM AUTHOR]