Comparison of Soluble ST2, Pentraxin-3, Galectin-3, and High-Sensitivity Troponin T of Cardiovascular Outcomes in Patients With Acute Decompensated Heart Failure.

BACKGROUND: Data regarding a direct comparison of soluble suppression of tumorigenesis-2 (sST2), pentraxin 3 (PTX3), galectin-3 (Gal-3), and high-sensitivity troponin T of cardiovascular outcome in patients with heart failure (HF) are lacking. METHODS AND RESULTS: A total of 616 hospitalized patients with HF were evaluated prospectively. Biomarker data were obtained in the stable predischarge condition. sST2 levels were associated with age, sex, body mass index, inferior vena cava diameter, B-type natriuretic peptide (BNP), PTX3, C-reactive protein, and Gal-3 levels. During follow-up, 174 (28.4%) primary composite end points occurred, including 58 cardiovascular deaths and 116 HF rehospitalizations. sST2 predicted the end point after adjustment for 13 clinical variables (hazard ratio 1.422; 95% confidence interval [CI] 1.064 to 1.895, P = .018). The association between sST2 and the end point was no longer statistically significant after adjustment for BNP (P = .227), except in the subgroup of patients with preserved ejection fraction (hazard ratio 1.925, 95% CI 1.102-3.378, P = .021). Gal-3 and high-sensitivity troponin T predicted the risk for the end point after adjustment for age and sex, but were not significant after adjustment for clinical variables. The prognostic value of PTX3 was not observed (age and sex adjusted, P = .066). CONCLUSIONS: This study did not show significant additional value of biomarkers to BNP for risk stratification, except sST2 in patients with preserved ejection fraction.

Clinical significance of the presence of puff-chandelier ruptures detected by nonobstructive aortic angioscopy.

OBJECTIVE: This study aimed to investigate the prevalence and prognostic significance of atherosclerotic aortic plaques (AAPs) or specific AAP types detected by nonobstructive angioscopy (NOA) in patients who underwent percutaneous coronary intervention (PCI). BACKGROUND: Although recent studies have reported the presence of various patterns of AAPs, identified by NOA, the clinical significance of the presence of AAPs remains elusive. METHODS: In this retrospective, multicenter cohort study, a total of 167 patients who underwent PCI and intra-aortic scans with NOA were studied. The association between AAPs and the incidence of major adverse cardiac events (MACEs), including cardiac death, myocardial infarction, stroke, and clinically driven unplanned revascularizations, was assessed. RESULTS: AAPs were detected in 126 patients (75%) who underwent NOA. MACEs occurred in 28 (17%) patients during the follow-up (median 2.9 years [range 2.1-3.8]). Among all types of AAPs, only puff-chandelier rupture (PCR) showed a significant difference in frequency between patients with and those without MACEs: 21 (75%) and 49 (35%), respectively (p < .001). Multivariable Cox proportional hazard analysis revealed that PCR (hazard ratio [HR] 3.73, 95% confidence interval [CI] 1.57-8.87, p = .004) and chronic kidney disease (HR 2.97, 95% CI 1.37-6.44, p = .010) were independent predictors of MACEs. Kaplan-Meier analysis revealed that PCR was significantly associated with more frequent MACEs. CONCLUSION: The detection of PCR in the aorta using NOA was significantly associated with an increased risk of subsequent adverse events after PCI.

Clinical impacts of changes of renal function during hospitalization depend on grades of renal dysfunction in acute decompensated heart failure.

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), < 60 and ≥ 30 (n = 400), and < 30 (n = 143). Increase and decrease of serum creatinine over 0.3 mg/dL during HF hospitalization were defined as worsening renal function (WRF) and improved renal function (IRF), respectively, and remaining subjects were defined as stable RF. The primary endpoint was a composite of cardiovascular death and rehospitalization for HF. In all patients, WRF was not associated with clinical outcomes, although eGFR has a significant association with prognosis. Clinical outcomes did not differ between changes of RF patterns in both preserved and severely impaired RF groups. In contrast, IRF, not WRF, was an independent predictor of clinical outcomes in the moderately impaired RF group (HR 1.965, 95% CI 1.09-3.18, p = 0.01). Only in patients with moderately impaired RF, changes of RF were associated with clinical outcome, and IRF was an independent predictor of clinical outcomes.

The Usefulness and Limitations of Impedance Cardiography for Cardiac Resynchronization Therapy Device Optimization.

Identifying the optimal atrioventricular (AV) or interventricular (VV) delay is beneficial for patients using cardiac resynchronization therapy (CRT) devices. Ultrasonic echocardiography (UCG) has been the most commonly used method; however, it requires high technical knowledge. Impedance cardiography (ICG) can calculate stroke volume by measuring changes in transthoracic electric impedance. This study sought to assess the clinical utility of ICG in comparison with that of UCG for the optimization of CRT devices.Patients who underwent CRT device implantation were retrospectively analyzed. One week after implantation, optimization of AV delay (AVD) was performed in every patient with ICG (AVD-ICG) and UCG (AVD-UCG). VV delay (VVD) was then determined according to the optimal AVD using these two methods.Forty-two patients were enrolled. Average AVD-ICG was significantly shorter than AVD-UCG (128 ± 49 versus 146 ± 41 milliseconds, P = 0.018). Five patients (12%) had the same optimized AVD with two methods, and the difference between AVD-ICG and AVD-UCG was ≤ 20 milliseconds in 19 patients (45%). In the multivariate analysis, the presence of postoperative mitral regurgitation (MR) was an independent predictor of AVD-ICG/AVD-UCG mismatch, defined as a difference over 20 milliseconds (odds ratio = 10.71; 95% confidence interval = 1.72 to 66.72; P = 0.018). The results of optimized VVD were similar using both methods.ICG might be a promising tool for the rapid optimization of CRT devices. However, in patients with moderate-to-severe MR, ICG may not be able to optimize AVD.

Different Impact of Changes in Left Ventricular Ejection Fraction Between Heart Failure Classifications in Patients With Acute Decompensated Heart Failure.

BACKGROUND: Left ventricular ejection fraction (LVEF) can dramatically change when the patient has acute decompensated heart failure (ADHF). We investigated the impact of LVEF and subsequent changes on prognosis in patients with ADHF through a prospective study.Methods and Results: A total of 516 hospitalized patients with ADHF were evaluated. Echocardiography was performed on admission, prior to discharge, and 1 year after discharge. The primary endpoint was a composite of cardiovascular death and hospitalization. In heart failure with reduced EF (HFrEF; LVEF <40%), LVEF did not significantly improve during hospitalization (P=0.348); however, it improved after discharge (P<0.001). In contrast, LVEF improved during hospitalization (P<0.001) in HF with preserved EF (HFpEF; LVEF ≥50%). In HF with mid-range EF (HFmrEF; LVEF 40-49%), LVEF consistently improved throughout the observation period (P<0.001). A multivariable Cox model showed that improved LVEF after discharge was associated with a better outcome in HFrEF (hazard ratio [HR]: 0.951; 95% confidence interval [CI]: 0.928-0.974; P<0.001), while improved LVEF during hospitalization was associated with a better outcome in HFpEF (HR: 0.969; 95% CI: 0.940-0.998; P=0.038). CONCLUSIONS: Improved LVEF after discharge in HFrEF and during hospitalization in HFpEF was associated with a better prognosis in patients with ADHF. Longitudinal improvements in LVEF had different prognostic impact, depending on the HF type by LVEF measurement.

Prognostic Value of Phase-Contrast Cine-Magnetic Resonance Imaging-Derived Global Coronary Flow Reserve in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome Treated With Urgent Percutaneous Coronary Intervention.

BACKGROUND: Phase-contrast cine-magnetic resonance imaging (PC-CMR) of the coronary sinus (CS) is a promising approach for quantifying coronary sinus flow (CSF) and global coronary flow reserve (G-CFR). We evaluated the prognostic value of G-CFR using PC-CMR in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS).Methods and Results:The study prospectively enrolled 116 NSTE-ACS patients who underwent uncomplicated urgent PCI within 48 h of symptom onset. Post-PCI (median, 20 days) PC-CMR images of the CS were acquired to assess absolute CSF at rest and during maximum hyperemia. The association of G-CFR with major adverse cardiac events (cardiac death, nonfatal myocardial infarction, late revascularization, or hospitalization for congestive heart failure) was investigated. Rest and maximal hyperemic CSF and corrected G-CFR were 1.27 [interquartile range, 0.79-1.73] mL/min/g, 2.95 [2.02-3.84] mL/min/g, and 2.42 [1.69-3.34], respectively. At a median follow-up of 17 months, cardiac event-free survival was significantly worse in patients with a corrected G-CFR <2.33 (log-rank χ2=19.5, P<0.001). Cox proportional-hazards analysis showed that corrected G-CFR (hazard ratio, 0.434, 95% CI, 0.270-0.699, P<0.001) and NT-pro BNP at admission (hazard ratio, 1.0001, 95% CI, 1.0000-1.0001, P=0.007) were independent predictors of adverse cardiac events during follow-up. CONCLUSIONS: In NSTE-ACS patients successfully revascularized within 48 h of onset, post-PCI PC-CMR-derived G-CFR provided significant prognostic information independent of infarct size and conventional risk scores.

Comparison of effects of aldosterone receptor antagonists spironolactone and eplerenone on cardiovascular outcomes and safety in patients with acute decompensated heart failure.

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.

High-sensitivity cardiac troponin decrease after percutaneous coronary intervention in patients with stable coronary artery disease.

Baseline cardiac troponin is a strong predictor of major adverse cardiac events (MACE), and the high sensitive assay can provide risk stratification under the 99th percentile values. Currently, prognostic benefit of PCI has not been established in patients with stable coronary artery disease (CAD), and the influence on baseline troponin levels is unknown. This study aimed to investigate the impact of PCI on baseline high-sensitivity cardiac troponin-I (hs-cTnI) levels and the association with MACE incidence. For 401 patients with stable CAD who were indicated for PCI, baseline hs-cTnI levels were measured before PCI for two times (the average: pre-PCI hs-cTnI) and 10 months after PCI (post-PCI remote hs-cTnI). Hs-cTnI day-to-day variability was assessed based on the pre-PCI values and patients were divided into three groups (Increase/No change/Decrease group) according to the extent of hs-cTnI change (post-PCI remote hs-cTnI minus pre-PCI hs-cTnI) considering the day-to-day variability. A total of 77 patients were categorized into Decrease group. Although Decrease group had significantly higher pre-PCI hs-cTnI levels compared to the other groups, this group had lowest incidence of MACE (p < 0.001). Hs-cTnI changes were independently associated with MACE incidence after adjustment (HR 2.069, 95% CI 1.032-4.006, p = 0.041 for Increase group vs. No change group; HR 0.143, 95% CI 0.008-0.680, p = 0.009 for Decrease group vs. No change group). Hs-cTnI change following PCI was significantly predicted by pre-PCI hs-cTnI, hs-cTnI variability, the presence of dyslipidemia, multivessel disease, and lesions with chronic total occlusion or low quantitative flow ratio. In conclusion, PCI could lower hs-cTnI levels in a certain subset of patients, in whom prognostic benefit might be expected by the intervention.

Absolute Myocardial Blood Flow After Elective Percutaneous Coronary Intervention Evaluated on Phase-Contrast Cine Cardiovascular Magnetic Resonance Imaging.

BACKGROUND: Few studies have documented changes in myocardial blood flow (MBF) after percutaneous coronary intervention (PCI). Phase-contrast cine cardiovascular MRI (PC-CCMR) of the coronary sinus (CS) is a promising approach to quantify MBF. The aim of this study was to quantify CS flow (CSF) on PC-CCMR as a measure of volumetric MBF before and after elective PCI.Methods and Results:We prospectively studied 34 patients with stable angina undergoing elective PCI for a single de novo lesion. Breath-hold PC-CCMR of CS was acquired to assess CSF and coronary flow reserve (CFR) at rest and during maximum hyperemia both before and after PCI (median, 3 days before PCI and 10 days after PCI, respectively). In total, hyperemic CSF increased significantly after PCI (before PCI, median, 2.3 mL/min/g [IQR, 1.5-3.2 mL/min/g] after PCI, 3.0 [1.8-3.7] mL/min/g), although 13 patients (38.2%) had a decrease despite successful PCI and fractional flow reserve (FFR) improvement. Global CFR also significantly increased from a median of 2.5 (IQR, 1.5-3.5) to 3.4 (IQR, 2.1-4.2), whereas 12 patients had decreased CFR after PCI. Pre-PCI hyperemic CSF was the only independent factor of change in CSF following PCI. CONCLUSIONS: Serial PC-CCMR of CS as a measure of change in absolute MBF is feasible. Uncomplicated PCI does not necessarily increase hyperemic global MBF, despite regional FFR improvement.

Utility of Nutritional Screening in Predicting Short-Term Prognosis of Heart Failure Patients.

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.

Value of 3-Dimensional Speckle Tracking Echocardiography in the Prediction of Microvascular Obstruction and Left Ventricular Remodeling in Patients With ST-Elevation Myocardial Infarction.

BACKGROUND: In patients with myocardial infarction (MI), microvascular obstruction (MVO) determined by cardiac magnetic resonance imaging (CMR) is associated with left ventricular (LV) remodeling and worse prognosis.Methods and Results:In 71 patients with ST-segment elevation MI (STEMI) treated by primary percutaneous coronary intervention (PCI), speckle tracking echocardiography (STE) and CMR were performed early after PCI. All patients underwent CMR at 6 months after hospital discharge to assess the occurrence of LV remodeling. The values of 3-dimensional (3D)-circumferential strain (CS), area change ratio (ACR), and 2-dimensional (2D)-CS were significantly different for the transmural extent of infarct, whereas the values of 3D- and 2D- longitudinal strain (LS) were not significantly different. In transmural infarct segments, the values of 3D-CS and ACR were significantly lower in segments with MVO than in those without MVO. At 6-month follow-up, LV remodeling was observed in 22 patients. In multivariable logistic regression models, global 3D-CS and ACR were significant determinants of LV remodeling rather than the number of MVO segments. CONCLUSIONS: Regional 3D-CS and ACR reflected the transmural extent of infarct and were significantly associated with the presence of MVO. In addition, global 3D-CS and ACR were preferable to the extent of MVO in the prediction of LV remodeling.

Effect of Dipeptidyl Peptidase-4 Inhibitors on Cardiovascular Outcome and Cardiac Function in Patients With Diabetes and Heart Failure　- Insights From the Ibaraki Cardiac Assessment Study-Heart Failure (ICAS-HF) Registry.

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.

Nutritional screening based on the controlling nutritional status (CONUT) score at the time of admission is useful for long-term prognostic prediction in patients with heart failure requiring hospitalization.

The objective of the study was to clarify whether controlling nutritional status (CONUT) is useful for predicting the long-term prognosis of patients hospitalized with heart failure (HF). 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). At admission, blood samples were collected and nutritional status assessed using CONUT. CONUT scores were defined as follows: 0-1, normal; 2-4, light; 5-8, moderate; and 9-12, severe undernutrition. Accordingly, 352 (73%) patients had light-to-severe nutritional disturbances. In the follow-up period [median 541.5 (range 354-786) days], 109 deaths were observed. A Kaplan-Meier analysis revealed that all-cause deaths occurred more frequently in HF patients with nutritional disturbances [n = 93 (26.4%)] than in those with normal nutrition [n = 16 (12.3%); log-rank p < 0.001]. The Cox proportional hazard analyses revealed that a per point increase in the CONUT score was associated with an increased risk of all-cause death (hazard ratio 1.142; 95% confidence interval, 1.044-1.249) after controlling simultaneously for age, sex, previous history of HF hospitalization, log brain natriuretic peptide, and use of therapeutic agents at admission (tolvaptan and aldosterone antagonists). This study suggests that nutritional screening using CONUT scores is helpful in predicting the long-term prognosis of patients hospitalized with HF in a multicenter registry setting.

Enhancement patterns detected by multidetector computed tomography are associated with microvascular obstruction and left ventricular remodelling in patients with acute myocardial infarction.

AIMS: This study evaluated the clinical value of myocardial contrast-delayed enhancement (DE) with multidetector computed tomography (MDCT) for detecting microvascular obstruction (MVO) and left ventricular (LV) remodelling revealed by DE magnetic resonance imaging after acute myocardial infarction (AMI). METHODS AND RESULTS: In 92 patients with first AMI, MDCT without iodine reinjection was performed immediately following successful percutaneous coronary intervention (PCI). Delayed-enhancement magnetic resonance imaging performed in the acute and chronic phases was used to detect MVO and LV remodelling (any increase in LV end-systolic volume at 6 months after infarction compared with baseline). Patients were divided into two groups according to the presence (n = 33) or absence (n = 59) of heterogeneous enhancement (HE). Heterogeneous enhancement was defined as concomitant presence of hyper- and hypoenhancement within the infarcted myocardium on MDCT. Microvascular obstruction and LV remodelling were detected in 49 (53%) and 29 (32%) patients, respectively. In a multivariable analysis, HE and a relative CT density >2.20 were significant independent predictors for MVO [odds ratio (OR) 13.5; 95% confidence interval (CI), 2.15-84.9; P = 0.005 and OR 12.0; 95% CI, 2.94-49.2; P < 0.001, respectively). The presence of HE and relative CT density >2.20 showed a high positive predictive value of 93%, and the absence of these two findings yielded a high negative predictive value of 90% for the predictive value of MVO. Heterogeneous enhancement was significantly associated with LV remodelling (OR 6.75; 95% CI, 1.56-29.29; P = 0.011). CONCLUSION: Heterogeneous enhancement detected by MDCT immediately after primary PCI may provide promising information for predicting MVO and LV remodelling in patients with AMI.

Novel Mechanistic Insights Into Atrial Functional Mitral Regurgitation　- 3-Dimensional Echocardiographic Study.

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<0.001). In the multiple regression analysis, the MA area, MA area fraction, nonplanarity angle, and PML angle were independent determinants of the effective regurgitant orifice area of MR after adjusting for LV parameters (adjusted R(2)=0.725, P<0.001). The PML angle and MA area had a higher standardized regression coefficient (ß=0.403, P<0.001, ß=0.404, P<0.001, respectively) than the other variables. CONCLUSIONS: Functional atrial MR in persistent AF is caused by not only MA dilatation, but also by multiple factors including the MA contractile dysfunction, disruption of the annular saddle shape, and atriogenic PML tethering. (Circ J 2016; 80: 2240-2248).

Pathophysiological role of right ventricular function and interventricular functional mismatch in the development of pulmonary edema in acute heart failure.

BACKGROUND: Parameters of cardiac function related to the development of pulmonary edema (PE) in acute heart failure (AHF), including right ventricular (RV) function and a mismatch of interventricular function, are not fully elucidated. The aim of this study was to verify the hypothesis that a relatively preserved RV function compared with left ventricular function may be associated with the development of PE by using two-dimensional speckle tracking echocardiography (2DSTE). METHODS: Hospitalized patients with AHF at 11 institutions were enrolled. PE was defined as lung congestion on chest X-ray with hypoxemia. Patients with systolic blood pressure ≥140 mmHg on admission were defined to have hypertensive AHF. Echocardiographic analyses, including 2DSTE, were performed prior to discharge. The index of mismatch between RV and left ventricular systolic function was assessed by interventricular longitudinal strain difference (IVLSD) which was defined as RV free wall longitudinal strain and left ventricular global longitudinal strain. RESULTS: Of 610 patients with AHF, 422 (69.2%) had PE. In patients with PE, IVLSD (p = 0.007) and RV fractional area change ratio (p<0.001) was significantly higher than those in patients without PE. In patients with non-hypertensive AHF, RV fractional area change ratio, age, ischemic etiology, and serum brain natriuretic peptide (BNP) levels were independent predictors of PE. In patients with hypertensive AHF, IVLSD, age, and serum BNP levels were independent predictors of PE. CONCLUSIONS: Preserved RV function might be one of the underlying mechanisms of the development of PE in AHF. Furthermore, interventricular functional mismatch might be related to the development of PE in hypertensive AHF.

Impact of regional functional ischemia on global coronary flow reserve in patients with stable coronary artery disease.

BACKGROUND: Global coronary flow reserve (g-CFR) provides powerful prognostic information. The relationship between g-CFR and the regional physiological indices of fractional flow reserve (FFR), coronary flow reserve (r-CFR), and the index of microcirculatory resistance remains undetermined. This study aimed to assess the relationship between regional and global physiological indices and determinants of cardiovascular magnetic resonance imaging (CMR)-derived g-CFR. METHODS: A total of 151 patients with single de novo intermediate to stenotic epicardial lesions referred for diagnostic invasive coronary angiography who underwent phase-contrast cine CMR of the coronary sinus (CS) were included. g-CFR was calculated as the ratio of hyperemic and resting CS flow (CSF). Regional and global physiological parameters were compared, and determinants of g-CFR were assessed. RESULTS: There was a weak linear relationship between FFR and g-CFR (R2=0.04, p=0.013), while r-CFR and g-CFR, or combinations of the other regional-global indices were not significantly correlated. When patients were divided into two groups by FFR of 0.80, there were also no significant differences in global physiological indices between the groups (FFR≤0.80 vs. FFR>0.80; g-CFR: 2.73 vs. 2.61, p=0.48; hyperemic CSF: 3.32 vs. 3.52ml/min/g, p=0.84). Higher high-sensitivity cardiac troponin-I (hs-cTnI) and higher resting CS flow were independently associated with impaired g-CFR, and the combination could efficiently identify patients with g-CFR<2.0. CONCLUSIONS: Given weak relationship among global and regional physiological indices, these indices may provide complementary efficacy for prognostication in patients with single-vessel stable coronary artery disease. Combination of hs-cTnI and resting CS flow could estimate g-CFR without pharmacological hyperemic induction.

Prognostic value of post-intervention fractional flow reserve after intravascular ultrasound-guided second-generation drug-eluting coronary stenting.

AIMS: The aim of this study was to investigate the prognostic value of fractional flow reserve (FFR) and a novel index (the D-index) of residual diffuse disease after intravascular ultrasound (IVUS)-guided second-generation drug-eluting stent (DES) implantation. METHODS AND RESULTS: We evaluated 201 patients (201 lesions) who underwent IVUS-guided second-generation DES implantation in the left anterior descending artery with pre- and post-intervention physiological evaluations. Post-intervention hyperaemic pullback pressure recording was used to quantify residual diffuse disease using the novel D-index, defined as the difference between the distal stent and the far distal FFR values divided by distance. Clinical outcomes were assessed by vessel-oriented composite endpoints (VOCE) and major adverse cardiac events (MACE). The incremental discriminant and reclassification abilities of far distal FFR or D-index for VOCE and MACE were compared. Post intervention, far distal FFR and D-indices were significantly lower in vessels with VOCE. The optimal far distal FFR and D-index cut-off values for VOCE and MACE were 0.86 and 0.017 cm, respectively. Although both indices remained significant predictors of VOCE, only the D-index proved to be a significant predictor of MACE and significantly improved the incremental reclassification ability for MACE. CONCLUSIONS: Residual diffuse disease assessed by the D-index after IVUS-guided second-generation DES implantation can help to predict both VOCE and MACE, while far distal FFR can help to predict VOCE specifically.

Geriatric nutritional risk index predicts all-cause deaths in heart failure with preserved ejection fraction.

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 (<92) with moderate or severe nutritional risk group and the high GNRI (≥92) with no or low nutritional risk group. Cox proportional hazard regression models were constructed to evaluate the influence of the GNRI on all-cause death with the following covariates using forward stepwise selection: age, sex, nutritional status based on the GNRI as a categorical variable, history of HF hospitalization, haemoglobin level, estimated glomerular filtration rate, log brain natriuretic peptide levels (logBNP), history of hypertension, log C-reactive protein levels, left ventricular ejection fraction, left ventricular mass index, and the New York Heart Association functional classification (I/II or III class). The prognostic value of the GNRI was compared with that of serum albumin using C-statistics. The GNRI was added to the logBNP, serum albumin or the body mass index was added to the logBNP, and the C-statistic was compared using DeLong's test. Cox regression analysis revealed that age and a low GNRI were independent predictors of all-cause death (P < 0.05, n = 103; hazard ratio = 1.095, 95% confidence interval = 1.031-1.163, for age, and hazard ratio = 3.075, 95% confidence interval = 1.244-7.600, for the GNRI). DeLong's test for the two correlated receiver operating characteristic curves [area under the receiver operating characteristic curve (AUROC) of serum albumin, 0.71; AUROC of the GNRI, 0.75] demonstrated significant differences between the groups (P = 0.038). Adding the GNRI to the logBNP increased the AUROC for all-cause death significantly (0.71 and 0.80, respectively; P = 0.040, n = 105). The addition of serum albumin or the body mass index to the logBNP did not significantly increase the AUROC for all-cause death (P = 0.082 and P = 0.29, respectively). CONCLUSIONS: Nutritional screening using the GNRI at discharge is helpful to predict the long-term prognosis of elderly HFpEF patients.

Soluble ST2 and brain natriuretic peptide predict different mode of death in patients with heart failure and preserved ejection fraction.

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.