Prognostic significance of left atrial strain combined with left ventricular strain using cardiac magnetic resonance feature tracking in patients with heart failure with preserved ejection fraction.

We aimed to evaluate the prognostic value of left ventricular global longitudinal strain (LVGLS) and left atrial strain (LAS) obtained from magnetic resonance imaging (MRI) feature tracking in patients with heart failure with preserved ejection fraction (HFpEF). We retrospectively enrolled consecutive patients with HFpEF admitted to our hospital who underwent cardiac MRI. LVGLS and LAS were obtained from cine MRI by feature tracking. The end point was defined as a composite of all-cause death, myocardial infarction, and hospitalization due to decompensated HF. One-hundred patients with HFpEF were enrolled. Mean LVGLS and LAS were - 13.7 ± 3.7% and 22.5 ± 11.6%, respectively. During follow-up of 4.4 ± 1.9 years, 24 events occurred. Multivariate Cox proportional hazards model analysis demonstrated LAS was independently associated with adverse cardiac events. Kaplan-Meier curve analysis revealed that the patients with both LVGLS and LAS worse than the median (LVGLS ≥ - 12.2% and LAS ≤ 13.8%) had a significantly lower event-free rate compared to those with preserved strain (Log-rank P < 0.001). Simultaneous assessment of LVGLS and LAS using MRI was useful for risk stratification in the patients with HFpEF.

Calcium-Phosphorus Product Is Associated with Adverse Prognosis in Hospitalized Patients with Heart Failure and Chronic Kidney Disease.

It has been reported that high levels of calcium-phosphorus (Ca-P) product are an indicator of coronary calcification and mortality risk in patients undergoing chronic hemodialysis. In the present study, we aimed to evaluate the significance of Ca-P product to predict the prognosis of patients with heart failure (HF) and chronic kidney disease (CKD). We conducted a prospective observational study of 793 patients with decompensated HF and CKD, and measured the value of Ca-P product. The cut-off value was obtained from the survival classification and regression tree (CART) analysis to predict post-discharge all-cause mortality and/or worsening HF, and the patients were divided into 2 groups: a high group (Ca-P product > 28, n = 594) and a low group (Ca-P product ≤ 28, n = 199). We compared the patient baseline characteristics and post-discharge prognosis between the 2 groups. The age as well as the prevalence of male sex, ischemic etiology, and anemia were significantly higher in the low group than in the high group. In contrast, there was no difference in echocardiographic parameters between the 2 groups. In the Kaplan-Meier analysis (mean follow-up 1089 days), all-cause mortality and/or worsening HF event rates were higher in the low group than in the high group (log-rank P = 0.001). In the multivariable Cox proportional hazard analysis, lower Ca-P product was found to be an independent predictor of all-cause mortality and/or worsening HF (hazard ratio 0.981, P = 0.031). Lower Ca-P product predicts adverse prognosis in patients with HF and CKD.

Predictive Value of Aortic Valve Calcium Volume Measured by Computed Tomography for Paravalvular Leakage After Transcatheter Aortic Valve Implantation.

Paravalvular leakage (PVL) is a complication of transcatheter aortic valve implantation (TAVI) for aortic stenosis, leading to an adverse prognosis. We investigated whether aortic valve calcium volume (Ca-Vol) measured by preoperative cardiac computed tomography had a predictive value for PVL after TAVI using a third-generation self-expandable valve.We retrospectively analyzed 59 consecutive patients who underwent TAVI using a third-generation self-expandable valve. We measured Ca-Vol in the aortic valve and each cusp (non-coronary cusp [NCC], right-coronary cusp [RCC], and left-coronary cusp [LCC]). We divided the patients into 2 groups: a PVL group (32.2%) and a non-PVL group (67.8%). Total Ca-Vol was significantly higher in the PVL group than in the non-PVL group (P < 0.001). Ca-Vol in each cusp was also significantly higher in the PVL group ([NCC] P < 0.001, [RCC] P = 0.001, [LCC] P < 0.001). Univariate logistic regression analysis for PVL indicated that the total and per-cusp Ca-Vols were predictors for PVL (total, odds ratio [OR] 4.0, P < 0.001; NCC, OR 12.5, P = 0.002; RCC, OR 16.0, P = 0.008; LCC, OR 44.5, P < 0.001).Receiver operating characteristic curve analysis of Ca-Vol for predicting PVL revealed the optimal cut-off values of Ca-Vol were 2.4 cm3 for the total, 0.74 cm3 for NCC, 0.73 cm3 for RCC, and 0.56 cm3 for LCC (area under the curve, 0.85, 0.79, 0.76, and 0.83, respectively).Preoperative total, NCC, RCC, and LCC calcium volumes were significant predictors for PVL after TAVI using third-generation self-expandable valves.

Left atrial epicardial adipose tissue exacerbates electrical conduction disturbance in normal-weight patients undergoing pulmonary vein isolation for atrial fibrillation.

INTRODUCTION: Epicardial adipose tissue (EAT) exacerbates both electrical and structural remodeling in obese atrial fibrillation (AF) patients, but the impacts of EAT on atrial arrhythmogenicity remain unclear in normal-weight AF patients. Therefore, we sought to investigate this issue using electroanatomic mapping. METHODS AND RESULTS: We enrolled drug-refractory 105 paroxysmal AF patients in the normal body mass index range (18.5-24.9 kg/m2 ), who had undergone electroanatomic mapping after pulmonary vein isolation (PVI). One day before PVI, we assessed P-wave duration in a 12-lead electrocardiogram and left atrial (LA)-EAT volumes using contrast-enhanced computed tomography. The patients were divided into two groups based on the median LA-EAT volume (16.0 ml); the high LA-EAT group (≥16.0 ml, n = 53) and low LA-EAT group (<16.0 ml, n = 52). We compared P-wave duration, LA conduction velocity and bipolar voltage, the presence of low-voltage zone (<0.5 mV), and LA volume index on echocardiography between the two groups. The LA bipolar voltage, low-voltage zone, and LA volume index were not different between the high and low LA-EAT groups. However, P-wave duration was significantly longer in the high group than in the low group (p < .001). Additionally, the LA conduction velocity was significantly more depressed in the high group than in the low group (p < .001). Multivariate linear regression analysis revealed that LA-EAT volume was correlated with P-wave duration (ß = .367, p < .001) and conduction velocity (ß = -.566, p < .001), respectively. CONCLUSIONS: Increased LA-EAT volumes were associated with electrical conduction disturbance after PVI in normal-weight patients with AF. P-wave duration may be a clinically useful predictor of LA-EAT.

Utility of short-time electrocardiogram to assess risk for atrial arrhythmia recurrence: Impact of atrial premature beat occurrence 1 day after pulmonary vein isolation for atrial fibrillation.

INTRODUCTION: Atrial premature beats (APBs) are the trigger for atrial fibrillation (AF). We sought to investigate the clinical significance of APB occurrence 1 day after pulmonary vein isolation (PVI) for AF using a short-time electrocardiogram. METHODS: A total of 206 patients undergoing PVI for paroxysmal AF were included. Electrocardiogram recording for 100 consecutive beats was performed 1 day after PVI. The patients were divided into two groups: those with reproducible APBs (≥1 beat) during reassessment (APB group, n = 49) or those without (non-APB group, n = 157). Late recurrence was defined as atrial tachyarrhythmia recurrence 3-12 months after PVI. The impact of APB occurrence on outcomes was investigated. RESULTS: Late recurrence occurred in 19 patients (9.2%). The presence of low-voltage areas, left atrial volume, and recurrence rate were higher in the APB group than in the non-APB group. In the APB group, the patients with recurrence had lower prematurity index (PI, coupling interval of APB/previous cycle length) compared to those without. Receiver-operating characteristic analysis revealed PI (<59.3) to be a predictive factor of recurrence (area under the curve: 0.733). The study subjects were then reclassified into three groups according to the absence of APB occurrence (n = 157), presence thereof with PI ≥ 59.3 (n = 33), and presence with PI < 59.3 (n = 16). The multivariate Cox models revealed that APB with PI < 59.3 was an independent predictor for recurrence (hazard ratio, 8.735; p < 0.001). CONCLUSION: A short-time electrocardiogram enables risk assessment for arrhythmia recurrence, and APB with low PI 1 day after PVI is a powerful predictor.

Simultaneous assessment of left ventricular mechanical dyssynchrony using integrated 13N-ammonia PETMR system: direct comparison of PET phase analysis and MR feature tracking.

BACKGROUND: To compare phase analysis with positron emission tomography (PA) and magnetic resonance feature tracking derived myocardial strain (FT) for left ventricular (LV) mechanical dyssynchrony using PETMR system in patients with ischemic heart disease. METHODS AND RESULTS: Patients who underwent rest-pharmacological stress 13N ammonia PETMR were enrolled. Histogram bandwidth (BW) and phase standard deviation (PSD) were compared to global longitudinal, long axis radial, short axis circumferential, and radial strain (GLS, GRS, SA Circ, and SA Rad) obtained from FT. LV dyssynchrony index (SDI) derived from PA and FT were compared. BW and PSD showed significant correlations with FT (a Pearson's coefficient r = 0.64, P < .0001, and r = 0.51, P < .0001 for SA Circ; r = 0.67, P < .0001, and r = 0.74, P < .0001 for GLS; r = - 0.60, P < .0001, r = - 0.61, P < .0001 for SA Rad; r = - 0.62, P < .0001, and r = - 0.68, P < .0001 for GRS, respectively). Bland-Altman plots for SDI showed a preferable agreement (95% limit of agreement - 0.12 to 0.075, - 0.20 to 0.098, - 0.38 to 0.077, and - 0.37 to 0.032; bias 0.0068 ± 0.056, 0.026 ± 0.068, 0.11 ± 0.088, and 0.13 ± 0.079 for SA Circ, SA Rad, GLS, and GRS, respectively). CONCLUSION: In simultaneous acquisition using PETMR, comparison of PET phase analysis and MR strain showed a good correlation.

Regional Variation in the Clinical Practice and Prognosis in Patients With Heart Failure With Reduced Ejection Fraction in Japan　- A Report From the Japanese Registry of Acute Decompensated Heart Failure (JROADHF).

BACKGROUND: The present study aimed to clarify the regional variations in clinical practice and the prognosis of patients with heart failure with reduced ejection fraction (HFrEF) in Japan using the Japanese Registry of Acute Decompensated Heart Failure (JROADHF).Methods and Results: We recruited data of hospitalized patients with HFrEF (n=4,329) from the JROADHF. The patients were divided into 6 groups based on the region of Japan where they were hospitalized: Hokkaido-Tohoku (n=504), Kanto (n=958), Chubu (n=779), Kinki (n=902), Chugoku-Shikoku (n=446), and Kyushu (n=740). We compared the patients' characteristics, including etiology of HF and prognosis after discharge. The age of the patients was lowest in the Kanto and Kinki regions. In contrast, there were no differences in the prevalence of comorbidities, levels of B-type natriuretic peptide, or left ventricular EF among the 6 groups. Post-discharge cardiospecific prognosis, specifically, the composite of cardiac death or HF hospitalization, cardiac death, and HF hospitalization, was comparable among the 6 regions. CONCLUSIONS: There were no differences in cardiospecific prognosis in patients with HFrEF among the 6 regions in Japan.

The Prognostic Implications of Living Alone on Long-Term Mortality in Patients with Chronic Coronary Syndrome after Percutaneous Coronary Intervention.

Living alone is associated with increased cardiac events and mortality in patients with acute myocardial infarction. However, the prognostic impact of living alone with chronic coronary syndrome (CCS) still remains unclear. In the present study, we examined the relationship between living alone and long-term mortality in patients with CCS who underwent percutaneous coronary intervention (PCI).Consecutive 830 patients with CCS who underwent PCI were enrolled and divided into 2 groups according to whether or not they were living alone at the time of admission (living alone group and non-living alone group). We compared the clinical characteristics between the 2 groups and followed up cardiac mortality. The living alone group was younger compared with the non-living alone group (67.5 versus 70.7 years old, P = 0.017). The prevalence of comorbidities, including coronary risk factors, atrial fibrillation, heart failure, stroke, peripheral artery disease, coronary lesion characteristics, laboratory data, and left ventricular ejection fraction, were comparable between the 2 groups. During the follow-up period (median 1,622 days), 52 cardiac deaths occurred. In the Kaplan-Meier analysis, cardiac mortality was significantly higher in the living alone group than in the non-living alone group (24% versus 11%, P = 0.008). In the multivariable Cox proportional hazard analyses after adjusting for possible confounding factors, living alone was an independent predictor of cardiac mortality (hazard ratio, 2.426, 95% confidence interval 1.225-4.804, P = 0.011).Among CCS patients who underwent PCI, living alone was associated with high long-term cardiac mortality.

Acute myocardial infarction caused by Kawasaki disease requires more intensive therapy: Insights from the Japanese registry of All Cardiac and Vascular Diseases-Diagnosis Procedure combination.

BACKGROUND: Kawasaki disease (KD) induces coronary arteritis, which causes subsequent coronary aneurysms, and contributes to acute myocardial infarction (AMI). However, the differences regarding real-world treatment selection and mortality between AMI-complicated KD and AMI due to typical atherosclerosis (AMI-non KD) are unknown. AIM: The aim of the present study was to examine the current treatment strategy and prognosis of AMI-complicated KD compared with AMI due to typical atherosclerosis. METHOD: We used data from 2012 to 2019 from a nationwide claim database, the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination. RESULTS: Compared to the AMI-non KD patients (n = 70,227), the AMI-complicated KD patients (n = 73): (1) underwent percutaneous coronary intervention (PCI) less often and more coronary artery bypass grafting, intracoronary thrombolysis or intravenous coronary thrombolysis more often; (2) underwent stentless PCI using old balloon angioplasty or rotablator, when they underwent PCI; and (3) needed in-hospital cardiopulmonary resuscitation and intensive mechanical therapy such as intra-aortic balloon pump, percutaneous cardiopulmonary support or a respirator. Both the AMI-non KD and AMI-complicated KD patients had similar in-hospital mortality rates. CONCLUSIONS: Compared with AMI-non KD patients, AMI-complicated KD patients underwent non-PCI strategies such as bypass surgery or thrombolysis, and required intensive therapy with mechanical supports more often, but presented similar in-hospital mortality. When the AMI-complicated KD patients underwent PCI, stentless PCI using balloon angioplasty or rotablator was performed more often compared with the AMI-non KD patients.

Temporal Trends in the Practice Pattern for Sleep-Disordered Breathing in Patients With Cardiovascular Diseases in Japan　- Insights From the Japanese Registry of All Cardiac and Vascular Diseases - Diagnosis Procedure Combination.

BACKGROUND: After the publication of the Japanese Circulation Society guideline of sleep-disordered breathing (SDB) in 2010, with new evidence and changes to the health insurance system, trends in the practice pattern for SDB in patients with cardiovascular disease (CVD) might have changed.Methods and Results: This study evaluated the temporal changes in the practice pattern for SDB by using a nationwide claim database, the Japanese Registry of All Cardiac and Vascular Diseases - Diagnosis Procedure Combination (JROAD-DPC), from 2012 to 2019. The main findings were: (1) the number of CVD patients diagnosed with SDB increased (especially those with atrial fibrillation [AF] and heart failure [HF]); (2) the number of diagnostic tests for SDB performed during hospitalization increased for AF patients (from 1.3% in 2012 to 1.8% in 2019), whereas it decreased for other CVD patients; (3) the number of patients diagnosed with SDB increased in each type of CVD, except for patients with acute myocardial infarction (AMI); (4) continuous positive airway pressure (CPAP) treatment increased for AF patients (from 15.2% to 17.5%); (5) CPAP treatment decreased for patients with angina pectoris (AP) and AMI, and any treatment decreased for HF patients (from 46.1% to 39.7%); and (6) SDB was treated more often in HF patients than in AF, AP, and AMI patients (41.7% vs. 17.2%, 19.1% and 20.4%, respectively). CONCLUSIONS: The practice pattern for SDB in CVD patients has changed from 2012 to 2019.

Prognostic Effects of Changes in Right Ventricular Fractional Area Change in Patients With Heart Failure.

BACKGROUND: It is still unclear whether changes in right ventricular function are associated with prognosis in heart failure (HF) patients. This study aimed to examine the prognostic effect of changes in right ventricular fractional area change (RVFAC).Methods and Results: This study enrolled 480 hospitalized patients with decompensated HF, and measured RVFAC with echocardiography at discharge (first examination) and post-discharge in the outpatient setting (second examination). RVFAC was divided into 3 categories: >35% in 314 patients, 25-35% in 108 patients, and <25% in 58 patients. Next, based on changes in RVFAC from the first to the second examination, the patients were further classed into 4 groups: (1) Preserved/Unchanged (preserved and unchanged RVFAC, n=235); (2) Reduced/Improved (improved RVFAC in at least 1 category, n=106); (3) Reduced/Unchanged (reduced and unchanged RVFAC, n=47); and (4) Preserved or Reduced/Worsened (deteriorated RVAFC in at least 1 category, n=92). Multivariate logistic regression analysis revealed that chronic kidney disease and anemia were the predictors of the preserved or reduced/worsened RVFAC. In the Kaplan-Meier analysis, changes in RVFAC were associated with the cardiac event rate and all-cause mortality. In the multivariable Cox proportional hazard analysis, the preserved or reduced/worsened RVFAC was an independent predictor of cardiac events and all-cause mortality. CONCLUSIONS: Changes in RVFAC were associated with post-discharge prognosis in hospitalized heart failure patients.

Procedural characteristics of pulmonary vein isolation with high-power short-duration setting compared to conventional setting.

PURPOSE: The purpose of this study was to investigate the safety and efficacy of high-power short-duration (HP-SD) ablation compared to conventional ablation in patients with atrial fibrillation (AF). METHODS: We enrolled consecutive 158 drug-refractory symptomatic AF patients (119 males, mean age 63 ± 10 years) who had undergone first radiofrequency pulmonary vein isolation (PVI). PVI was performed using the conventional setting (20-35 W) in 73 patients (Conventional group) and using the HP-SD setting (45-50 W) in 85 patients (HP-SD group). The rate of first pass isolation, remaining gaps after circumferential ablation, dormant conduction, and the radiofrequency application time in each pulmonary vein (PV) were compared between the groups. RESULTS: The first pass isolation ratio was significantly higher in the HP-SD group than in the Conventional group (81% vs. 65%, P = 0.027) in the right PV, but did not differ in the left PV. The remaining gaps were fewer in the right superior PV (4% vs. 21%, P = 0.001) and left inferior PV (1% vs. 8%, P = 0.032) areas, and the radiofrequency application time in each PV was shorter (right PV, 12.0 ± 8.9 min vs. 34.0 ± 31.7 min, P < 0.001; left PV, 10.6 ± 3.6 min vs. 25.7 ± 22.3 min, P < 0.001) in the HP-SD group than in the Conventional group. CONCLUSION: The use of the HP-SD setting might contribute to improve the first pass isolation rate and to shorten the radiofrequency application time in each PV.

Predictive impacts of chronic kidney disease and cardiac sympathetic nervous activity on lethal arrhythmic events in chronic heart failure.

BACKGROUND: The clinical implications of chronic kidney disease (CKD) and cardiac sympathetic nervous activity (CSNA) regarding lethal arrhythmic events have not yet been fully elucidated in patients with chronic heart failure (CHF). We hypothesized that the combination of CKD and abnormal CSNA, assessed by 123 I-metaiodobenzylguanidine (123 I-MIBG) scintigraphy, may provide useful prognostic information for lethal arrhythmic events. METHODS: We studied 165 consecutive hospitalized CHF patients without dialysis. Cardiac 123 I-MIBG scintigraphy was performed in a clinically stable condition, and abnormal CSNA was defined as a late heart-to-mediastinum ratio of <1.6. CKD was defined as an estimated glomerular filtration rate of <60 ml/min/1.73 m2 . We then investigated the incidence of lethal arrhythmic events (sustained ventricular tachyarrhythmia, appropriate implantable cardioverter-defibrillator therapy, or sudden cardiac death). RESULTS: During a median follow-up of 5.3 years, lethal arrhythmic events were observed in 40 patients (24.2%). The patients were divided into four groups according to the presence of CKD and CSNA abnormality: non-CKD/normal CSNA (n = 52), CKD/normal CSNA (n = 39), non-CKD/abnormal CSNA (n = 33), and CKD/abnormal CSNA (n = 41). Kaplan-Meier analysis showed that CKD/abnormal CSNA had the highest event rate (log-rank p = .004). Additionally, the Cox proportional hazard analysis revealed that CKD/abnormal CSNA was a predictor for lethal arrhythmic events compared with non-CKD/normal CSNA (hazard ratio, 5.368, p = .001). However, the other two groups did not show significant differences compared with the non-CKD/normal CSNA group. CONCLUSIONS: The combination of CKD and abnormal CSNA, assessed by 123 I-MIBG scintigraphy, had a high predictive value for lethal arrhythmic events in patients with CHF.

Prognostic Value of Simultaneous Analysis with Myocardial Flow Reserve and Right Ventricular Strain by Hybrid 13N-Ammonia Positron Emission Tomography/Magnetic Resonance Imaging in Coronary Artery Disease.

Myocardial flow reserve (MFR) derived from 13N-ammonia positron emission tomography (PET) is used to predict adverse cardiac events in patients with coronary artery disease (CAD). Right ventricular global longitudinal strain (RVGLS) measured by magnetic resonance imaging (MRI) is used to evaluate RV function and predict cardiac events. This study aimed to evaluate the prognostic value of MFR and RVGLS measured by hybrid 13N-ammonia PET/MRI in patients with CAD.Sixty-one patients who underwent 13N-ammonia PET/MRI were analyzed. The end points were defined as a composite of all-cause death, myocardial infarction, sustained ventricular arrhythmia, hospitalization due to decompensated heart failure, and revascularization. At a follow-up of 2.8 ± 1.9 years, 21 events had occurred. Kaplan-Meier analysis showed that the event-free rate was significantly lower in the group with MFR < 1.80 than in that with MFR ≥ 1.80 (P < 0.001). Additionally, the event-free rate was significantly lower in the group with RVGLS > -18.22% than in that with RVGLS ≤ -18.22% (P = 0.025). After dividing the patients into 4 groups by the median MFR and the median RVGLS, the event-free rate was lowest in the combined group of MFR < 1.80 and RVGLS > -18.22% than any other groups (P < 0.001). In a Cox proportional hazard analysis, MFR and RVGLS were independent predictors of cardiac adverse events in the patients with CAD.The simultaneous assessment of MFR and RVGLS by 13N-ammonia PET/MRI revealed the feasibility of precise risk stratification for cardiac events in patients with CAD.

DNA Damage Induced by Radiation Exposure from Cardiac Catheterization.

Almost 40% of medical radiation exposure is related to cardiac imaging or intervention. However, the biological effects of low-dose radiation from medical imaging remain largely unknown. This study aimed to evaluate the effects of ionized radiation from cardiac catheterization on genomic DNA integrity and inflammatory cytokines in patients and operators.Peripheral mononuclear cells (MNCs) were isolated from patients (n = 51) and operators (n = 35) before and after coronary angiography and/or percutaneous coronary intervention. The expression of γH2AX, a marker for DNA double-strand breaks, was measured by immunofluorescence. Dicentric chromosomes (DICs), a form of chromosome aberrations, were assayed using a fluorescent in situ hybridization technique.In the patient MNCs, the numbers of γH2AX foci and DICs increased after cardiac catheterization by 4.5 ± 9.4-fold and 71 ± 122%, respectively (P < 0.05 for both). The mRNA expressions of interleukin (IL)-1α, IL-1ß, leukemia inhibitory factor, and caspase-1 were significantly increased by radiation exposure from cardiac catheterization. The increase in IL-1ß was significantly correlated with that of γH2AX, but not with the dose area product. In the operators, neither γH2AX foci nor the DIC level was changed, but IL-1ß mRNA was significantly increased. The protein expression of IκBα was significantly decreased in both groups.DNA damage was increased in the MNCs of patients, but not of operators, who underwent cardiac catheterization. Inflammatory cytokines were increased in both the patients and operators, presumably through NF-κB activation. Further efforts to reduce radiation exposure from cardiac catheterization are necessary for both patients and operators.

Prognostic Value of the Pattern of Non-Adherence to Anti-Platelet Regimen in Stented Patients (PARIS) Bleeding Risk Score for Long-Term Mortality After Percutaneous Coronary Intervention.

The Patterns of non-Adherence to Anti-Platelet Regimen in Stented Patients (PARIS) bleeding risk score has been proposed to predict the risk of bleeding events after percutaneous coronary intervention (PCI). However, the prognostic value of the PARIS bleeding risk score for long term all-cause mortality, cardiac mortality and hospitalization due to heart failure has not yet been evaluated. Therefore, the aim of the present study was to evaluate the prognostic value of the PARIS bleeding risk score for all-cause and cardiac mortalities and hospitalization due to heart failure after PCI. Consecutive 1061 patients who had undergone PCI were divided into 3 groups based on the PARIS bleeding risk score; low (n = 112), intermediate (n = 419) and high-risk groups (n = 530). We prospectively followed up the 3 groups for all-cause and cardiac mortalities and hospitalization due to heart failure. Kaplan-Meier analysis revealed that all of the outcomes were highest in the high-risk group among the 3 groups (P < 0.001, P < 0.001 and P < 0.001 respectively). Multivariable Cox proportional hazard analysis, adjusted for confounding factors, revealed that all-cause mortality of the intermediate or high-risk groups was higher than those of the low-risk group (adjusted hazard ratio 6.06 and 12.50, P = 0.013 and P < 0.001, respectively). The PARIS bleeding risk score is a significant indicator of prognosis for all-cause mortality in patients after PCI.

The Prognostic Impact of D-Dimer on Long-Term Mortality in Patients with Coronary Artery Disease after Percutaneous Coronary Intervention.

D-dimer is a common measurable coagulation marker that is associated with the risk of thrombotic events in vascular diseases. However, the impact of D-dimer on long-term mortality in coronary artery disease (CAD) patients remains unclear. This study investigated the association between D-dimer and long-term all-cause, cardiac and cancer mortality in CAD patients. Continuous 1,440 patients with CAD who underwent percutaneous coronary intervention (PCI) and survived to discharge were enrolled. These patients were divided into 3 groups based on plasma D-dimer levels at admission. Baseline D-dimer levels were grouped by tertiles: first (D-dimer < 0.7 µg/mL, n = 455), second (0.7 ≤ D-dimer < 1.2, n = 453), and third (1.2 ≤ D-dimer, n = 532). In a Kaplan-Meier analysis (mean follow-up periods 1,572 days), all-cause, cardiac and cancer mortalities were significantly higher in the third tertile than others (P < 0.001, P < 0.001 and P < 0.001, respectively). In multivariable Cox proportional hazard analyses after adjusting for confounding factors, a high D-dimer level was an independent predictor of all-cause, cardiac, non-cardiac and cancer mortalities (HR 3.23, P < 0.001; HR 3.06, P = 0.008; HR 3.11, P = 0.026). In a subgroup analysis, there were no interactions except for the gender subgroup in cancer mortality. In patients with CAD after PCI, high D-dimer levels were associated with long-term all-cause, cardiac and cancer mortality.

Amyloid precursor protein 770 is specifically expressed and released from platelets.

Platelets not only play an essential role in hemostasis after vascular injury but are also involved in the development of coronary artery disease (CAD) and cerebrovascular lesions. Patients with CAD and cerebral ischemia are recommended to undergo antiplatelet therapy, but they have an increased incidence of major bleeding complications. Both assessment of the platelet activation status and response to antiplatelet therapy in each patient are highly desired. ß-Amyloid precursor protein (APP) 770 is expressed in vascular endothelial cells, and its extracellular region, a soluble form of APP770 (sAPP770, also called nexin-2), is proteolytically cleaved for shedding. Abundant sAPP770 is also released from activated platelets. In this study, we used peripheral blood samples from patients with CAD and control subjects and evaluated sAPP770 as a specific biomarker for platelet activation. First, the plasma levels of sAPP770 correlated well with those of the soluble form CD40 ligand (CD40L), an established biomarker for platelet activation. Additionally, flow cytometry analysis using peripheral blood cells showed that CD40L expression is up-regulated in activated T cells, whereas APP770 expression is negligible in all blood cell types except platelets. Following stimulation with collagen or ADP, aggregating platelets immediately released sAPP770. Finally, patients with dual antiplatelet therapy showed significantly lower levels of plasma sAPP770 than those with no therapy. Taken together, our data show that plasma sAPP770 could be a promising biomarker for platelet activation.

Effects of canagliflozin on NT-proBNP stratified by left ventricular diastolic function in patients with type 2 diabetes and chronic heart failure: a sub analysis of the CANDLE trial.

BACKGROUND: Identification of the effective subtypes of treatment for heart failure (HF) is an essential topic for optimizing treatment of the disorder. We hypothesized that the beneficial effect of SGLT2 inhibitors (SGLT2i) on the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) might depend on baseline diastolic function. To elucidate the effects of SGLT2i in type 2 diabetes mellitus (T2DM) and chronic HF we investigated, as a post-hoc sub-study of the CANDLE trial, the effects of canagliflozin on NT-proBNP levels from baseline to 24 weeks, with the data stratified by left ventricular (LV) diastolic function at baseline. METHODS: Patients (n = 233) in the CANDLE trial were assigned randomly to either an add-on canagliflozin (n = 113) or glimepiride treatment groups (n = 120). The primary endpoint was a comparison between the two groups of the changes from baseline to 24 weeks in NT-pro BNP levels, stratified according to baseline ventricular diastolic function. RESULTS: The change in the geometric mean of NT-proBNP level from baseline to 24 weeks was 0.98 (95% CI 0.89-1.08) in the canagliflozin group and 1.07 (95% CI 0.97-1.18) in the glimepiride group. The ratio of change with canagliflozin/glimepiride was 0.93 (95% CI 0.82-1.05). Responder analyses were used to investigate the response of an improvement in NT-proBNP levels. Although the subgroup analyses for septal annular velocity (SEP-e') showed no marked heterogeneity in treatment effect, the subgroup with an SEP-e' < 4.7 cm/s indicated there was an association with lower NT-proBNP levels in the canagliflozin group compared with that in the glimepiride group (ratio of change with canagliflozin/glimepiride (0.83, 95% CI 0.66-1.04). CONCLUSIONS: In the subgroup with a lower LV diastolic function, canagliflozin showed a trend of reduced NT-pro BNP levels compared to that observed with glimepiride. This study suggests that the beneficial effects of canagliflozin treatment may be different in subgroups classified by the severity of LV diastolic dysfunction.

Crucial role of hematopoietic JAK2 V617F in the development of aortic aneurysms.

JAK2V617F is the most frequent driver mutation in myeloproliferative neoplasms (MPNs) and is associated with vascular complications. However, the impact of hematopoietic JAK2V617F on the aortic aneurysms (AAs) remains unknown. Our cross-sectional study indicated that 9 (23%) out of 39 MPN patients with JAK2V617F exhibited the presence of AAs. Next, to clarify whether the hematopoietic JAK2V617F contributes to the AAs, we applied a bone marrow transplantation (BMT) with the donor cells from Jak2V617F transgenic (JAK2V617F) mice or control wild-type (WT) mice into lethally irradiated apolipoprotein E-deficient mice. Five weeks after BMT, the JAK2V617F-BMT mice and WT-BMT mice were subjected to continuous angiotensin II infusion to induce AA formation. Four weeks after angiotensin II infusion, the abdominal aorta diameter in JAK2V617F-BMT mice was significantly enlarged compared to that in the WT-BMT mice. Additionally, the abdominal AA-free survival rate was significantly lower in the JAK2V617F-BMT mice. Hematopoietic JAK2V617F accelerated aortic elastic lamina degradation as well as activation of matrix metalloproteinase (MMP)-2 and MMP-9 in the abdominal aorta. The numbers of infiltrated macrophages were significantly upregulated in the abdominal aorta of the JAK2V617F-BMT mice accompanied by STAT3 phosphorylation. The accumulation of BM-derived hematopoietic cells carrying JAK2V617F in the abdominal aorta was confirmed by use of reporter GFP-transgene. BM-derived macrophages carrying JAK2V617F showed increases in mRNA expression levels of Mmp2, Mmp9, and Mmp13. Ruxolitinib decreased the abdominal aorta diameter and the incidence of abdominal AA in the JAK2V617F-BMT mice. Our findings provide a novel feature of vascular complications of AAs in MPNs with JAK2V617F.