Balloon pulmonary angioplasty for chronic thromboembolic pulmonary disease without pulmonary hypertension.

Balloon pulmonary angioplasty (BPA) is beneficial for patients with chronic thromboembolic pulmonary disease (CTEPD) with pulmonary hypertension (PH). However, the clinical benefit of BPA for the patients with CTEPD without PH remains unknown. In this study, we aimed to evaluate the efficacy, safety, and long-term outcomes of BPA in patients with CTEPD without PH. We retrospectively analyzed the data from 84 CTEPD patients with mean pulmonary artery pressure (mPAP) < 25 mmHg and 39 CTEPD patients with mPAP ≤ 20 mmHg (without PH). Among the 39 patients with CTEPD without PH, 14 underwent BPA (BPA-treated group), and the remaining 25 received no treatment (untreated group). In the patients with CTEPD without PH, BPA led to improvements in symptoms, pulmonary vascular resistance (3.6 ± 1.6 to 2.6 ± 1.1 Wood units, p < 0.001), peak oxygen consumption (16.1 ± 4.0 to 18.8 ± 4.3 mL/kg/min, p = 0.033), minute ventilation versus carbon dioxide production slope (41.4 ± 12.2 to 35.1 ± 6.7, p = 0.026), and mPAP/cardiac output slope (7.0 ± 2.6 to 4.4 ± 2.0 mmHg/L/min, p = 0.004) and facilitated the discontinuation of home oxygenation therapy, with no serious complications. Kaplan-Meier analysis showed no significant difference in all-cause mortality between the untreated and BPA-treated groups. BPA may be a safe treatment option for the patients with CTEPD without PH that can alleviate symptoms, improve exercise capacity, and facilitate weaning from home oxygen therapy. Further prospective randomized trials are needed to confirm these findings.

Clinical outcomes of upfront combination therapy for portopulmonary hypertension.

Background: Limited data exists on upfront combination therapy for portopulmonary hypertension. We evaluated the clinical efficacy, long-term outcomes, and safety of upfront combination therapy in patients with portopulmonary hypertension. Methods: We performed a retrospective, single-center cohort study involving a final analysis of 33 consecutive patients diagnosed with portopulmonary hypertension who were taking pulmonary arterial hypertension-specific medication. We compared hemodynamic parameters, risk profiles, composite clinical worsening events, and safety between monotherapy (n = 23) and upfront combination therapy (n = 10). Results: Twenty-seven patients (82 %) were classified into the Child-Pugh A stage. The change ratios of pulmonary vascular resistance (-32 % vs. -57 %, P = 0.006) were significantly better with upfront combination therapy. Upfront combination therapy also showed significant improvement in risk profiles. Kaplan-Meier analysis showed that the composite event-free rate was significantly lower in patients who received upfront combination therapy than in those who received monotherapy (P = 0.016), although no statistical differences were observed in all-cause death. In the univariate Cox proportional hazards analysis, upfront combination therapy was a factor for decreasing composite clinical worsening outcomes (hazard ratio 0.190, 95 % confidence interval 0.042-0.854; P = 0.030). No significant hepatic impairments were observed over 2 years of follow-up in the upfront combination group. Conclusions: In patients with portopulmonary hypertension, upfront combination therapy significantly improved symptoms and short-term hemodynamics, and reduced long-term clinical worsening events without serious adverse effects. This study's findings suggest that patients with portopulmonary hypertension presenting with mild hepatic impairment benefit from upfront combination therapy.

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.

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.

Prognostic Implications of Sarcoidosis Granulomas　- Insights From the Multicenter Registry, the Japanese Cardiac Sarcoidosis Prognostic Study.

Background: Definitions of cardiac sarcoidosis (CS) differ among guidelines. Any systemic histological finding of CS is essential for the diagnosis of CS in the 2014 Heart Rhythm Society statement, but not necessary in the Japanese Circulation Society 2016 guidelines. This study aimed to reveal the differences in outcomes by comparing 2 groups, namely CS patients with or without systemic histologically proven granuloma. Methods and Results: This study retrospectively included 231 consecutive patients with CS. CS with granulomas in ≥1 organs was diagnosed in 131 patients (Group G), whereas CS without any granulomas was diagnosed in the remaining 100 patients (Group NG). Left ventricular ejection fraction (LVEF) was significantly reduced in Group NG compared with Group G (44±13% vs. 50±16%, respectively; P=0.001). However, Kaplan-Meier curves showed that major adverse cardiovascular events (MACE)-free survival outcomes were comparable between the 2 groups (log-rank P=0.167). Univariable analyses showed that significant predictors of MACE were Groups G/NG, histological CS, LVEF, and high B-type natriuretic peptide (BNP) or N-terminal pro BNP concentrations, but none of these was significant in multivariable analyses. Conclusions: Overall risks of MACE were similar between the 2 groups despite different manifestations in cardiac dysfunction. The data not only validate the prognostic value of non-invasive diagnosis of CS, but also show the need for careful observation and therapeutic strategy in patients with CS without any granuloma.

Impact of bleeding event for new cancer diagnosis in patients with antiplatelet therapy after percutaneous coronary intervention.

BACKGROUND: Bleeding is a frequent event in coronary artery disease (CAD) patients treated with antiplatelet therapy after percutaneous coronary intervention (PCI). The impact of bleeding in CAD patients with antiplatelet therapy for cancer diagnosis remains unclear. METHODS AND RESULTS: Consecutive 1565 CAD patients treated with antiplatelet therapy after PCI, without anticoagulation therapy, were enrolled. We aimed to investigate the relationships between bleeding events and the incidence of new cancer diagnosis. Among 1565 patients, 178 (11.3 %) experienced any bleeding events defined as Bleeding Academic Research Consortium (BARC) type 1, 2, 3, or 5 bleeding and 75 (4.7 %) experienced minor bleeding events defined as BARC 1 or 2 bleeding, and 116 (7.4 %) were diagnosed with new cancer during a mean follow-up period of 1528 days. Among 178 patients with any bleeding and 75 patients with minor bleeding events, 20 (11.2 %) and 13 (17.3 %) were subsequently diagnosed with new cancer, respectively. The proportion of new cancer diagnosis was higher in patients with any bleeding and minor bleeding events than in those without bleeding events (3.3 versus 1.6 per 100 person-years, p < 0.001 and 6.2 versus 1.6 per 100 person-years, p < 0.001, respectively). Multivariate Cox proportional hazard analysis revealed that any bleeding and minor bleeding events were associated with higher rate of new cancer diagnosis [hazard ratio (HR) 2.27, p = 0.003 and HR 3.93, p < 0.001, respectively]. Additionally, any gastrointestinal bleeding and minor gastrointestinal bleeding events were associated with higher rate of new gastrointestinal cancer diagnosis (HR 8.67, p < 0.001 and HR 12.74, p < 0.001, respectively). CONCLUSIONS: In CAD patients with antiplatelet therapy after PCI, any bleeding and minor bleeding events were associated with subsequent new cancer diagnosis. Even minor bleeding events may be the first manifestation of underlying cancer during antiplatelet therapy after PCI.

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.

Multicenter Registry in the Japanese Cardiac Sarcoidosis Prognostic (J-CASP) Study: Baseline Characteristics and Validation of the Non-invasive Approach Using 18F-FDG PET.

Background: Recent advances in cardiac modalities contribute to the guidelines on the diagnosis of cardiac sarcoidosis (CS) updated by the Japanese Circulation Society. The multicenter registry, Japanese Cardiac Sarcoidosis Prognostic (J-CASP) study tried to reveal recent trends of diagnosis and outcomes in CS patients and to validate the non-invasive diagnostic approach, including cardiac 18F-fluorodeoxyglucose (FDG) study. Methods/results: Databases from 12 hospitals consisting of 231 CS patients (mean age, 64 years; female, 65%; LV ejection fraction, 47%) diagnosed by the guidelines with FDG positron emission tomography (PET) study were integrated to compile clinical information on the diagnostic criteria and outcomes. Cardiac 18F-FDG uptake and magnetic resonance imaging (CMR) was positive identically in the histology-proven and clinically-diagnosed groups. The histology-proven group more frequently had reduce LV ejection fraction, myocardial perfusion abnormality and low-grade electrocardiogram (ECG) abnormality (P=0.003 to 0.016) than did the clinical group. During a 45-month period, the histology-proven group more frequently underwent appropriate implantable cardioverter-defibrillator (ICD) treatment (14% versus 4%, P=0.013) and new electronic device implantation (30% versus 12%, P=0.007) than did clinical group, respectively. There, however, was no difference in all-cause or cardiac mortality or in new hospitalization due to heart failure progression between them. Conclusion: The J-CASP registry demonstrated the rationale and clinical efficacies of non-invasive approach using advanced cardiac imaging modalities in the diagnosis of CS even when histological data were available.

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.

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.

Clinical usefulness of the pattern of non-adherence to anti-platelet regimen in stented patients (PARIS) thrombotic risk score to predict long-term all-cause mortality and heart failure hospitalization after percutaneous coronary intervention.

BACKGROUND: The Patterns of non-Adherence to Anti-Platelet Regimen in Stented Patients (PARIS) thrombotic risk score has been proposed to estimate the risk of stent thrombotic events after percutaneous coronary intervention (PCI). However, the prognostic value of the PARIS thrombotic risk score for long term all-cause and cardiac mortalities, as well as 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 thrombotic risk score for all-cause and cardiac mortalities and hospitalization due to heart failure following PCI. METHODS AND RESULTS: Consecutive 1,061 patients who underwent PCI were divided into three groups based on PARIS thrombotic risk score; low- (n = 320), intermediate- (n = 469) and high-risk (n = 272) groups. We followed up on all three groups for all-cause mortality, cardiac mortality and hospitalization due to heart failure. Kaplan-Meier analysis showed that all outcomes were highest in the high-risk group (P < 0.001, P = 0.022 and P < 0.001, respectively). Multivariate Cox proportional hazard analysis, adjusted for confounding factors, showed that the risk of all-cause mortality and hospitalization due to heart failure of the high-risk group were higher than those of the low-risk group (hazard ratios 1.76 and 2.14, P = 0.005 and P = 0.017, respectively). CONCLUSION: The PARIS thrombotic risk score is a significant prognostic indicator for all-cause mortality and hospitalization due to heart failure in patients after PCI.

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.

Myocardial viability with chronic total occlusion assessed by hybrid positron emission tomography/magnetic resonance imaging.

BACKGROUND: The present study was performed to compare the relationship of 18F-fluorodeoxyglucose (FDG) uptake and late gadolinium enhancement (LGE) transmurality with the improvement of left ventricular function in patients with coronary chronic total occlusion (CTO) assessed by hybrid FDG positron emission tomography (PET)/magnetic resonance imaging (MRI). METHODS: Thirty-eight consecutive patients with CTO underwent FDG PET/MRI. Twenty-three patients then underwent percutaneous coronary intervention (PCI), and the final study population comprised 15 patients who underwent both initial and follow-up MRI. The degree of wall motion abnormality in each of the 17 myocardial segments was evaluated based on the extent of wall thickening on cine MRI using a 5-point scale. RESULTS: Among all 646 myocardial segments at baseline, FDG uptake significantly decreased as the transmurality of LGE is advanced. Of the 15 patients who underwent PCI, 152 segments showed wall motion abnormalities at baseline. The functional recovery of the wall motion abnormality of the PET-viable/MRI-viable segments was highest, and that of the PET-nonviable/MRI-nonviable segments was lowest. There were no differences in functional recovery between the PET-viable/MRI-nonviable and PET-nonviable/MRI-viable segments. CONCLUSION: Simultaneous assessment of FDG and LGE using a hybrid PET/MRI system can help to predict functional recovery after PCI in patients with CTO.

Glasgow-Blatchford Score Predicts Post-Discharge Gastrointestinal Bleeding in Hospitalized Patients with Heart Failure.

BACKGROUND: The Glasgow-Blatchford Score (GBS) is one of the most widely used scoring systems for predicting clinical outcomes for gastrointestinal bleeding (GIB). However, the clinical significance of the GBS in predicting GIB in patients with heart failure (HF) remains unclear. METHODS AND RESULTS: We conducted a prospective observational study in which we collected the clinical data of a total of 2236 patients (1130 men, median 70 years old) who were admitted to Fukushima Medical University Hospital for acute decompensated HF. During the post-discharge follow-up period of a median of 1235 days, seventy-eight (3.5%) patients experienced GIB. The GBS was calculated based on blood urea nitrogen, hemoglobin, systolic blood pressure, heart rate, and history of hepatic disease. The survival classification and regression tree analysis revealed that the accurate cut-off point of the GBS in predicting post-discharge GIB was six points. The patients were divided into two groups: the high GBS group (GBS > 6, n = 702, 31.4%) and the low GBS group (GBS ≤ 6, n = 1534, 68.6%). The Kaplan-Meier analysis showed that GIB rates were higher in the high GBS group than in the low GBS group. Multivariate Cox proportional hazards analysis adjusted for age, malignant tumor, and albumin indicated that a high GBS was an independent predictor of GIB (hazards ratio 2.258, 95% confidence interval 1.326-3.845, p = 0.003). CONCLUSIONS: A high GBS is an independent predictor and useful risk stratification score of post-discharge GIB in patients with HF.

The clinical value of the PRECISE-DAPT score in predicting long-term prognosis in patients with acute myocardial infarction.

BACKGROUND: The predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score predicts the risk of bleeding in patients treated with dual antiplatelet therapy after percutaneous coronary intervention. Although the PRECISE-DAPT score is expected to be useful beyond its original field, long-term prognostic value of this score in patients with acute myocardial infarction (AMI) remains unclear. In the current study, we aimed to investigate the performance of the PRECISE-DAPT score in predicting the long-term prognosis in patients with AMI. METHODS AND RESULTS: Consecutive 552 patients with AMI, who had been discharged from our institution, were enrolled. We divided the patients into three groups, based on their PRECISE-DAPT scores: the low (PRECISE-DAPT < 17), intermediate (17-24) and high (≥25) score groups. Kaplan-Meier analysis (mean follow-up 1424 days) revealed that all-cause mortality increased most steeply in the high score group followed by the intermediate and low score groups (P < 0.001). After adjusting for possible confounding factors, mortality of the intermediate or high score groups were higher than those of low score group (HR 2.945, 95% CI 1.182-7.237, P = 0.020, and HR 5.567, 95% CI 2.644-11.721, P < 0.001, respectively). CONCLUSIONS: In patients with AMI, a high PRECISE-DAPT score was associated with higher long-term all-cause mortality. PRECISE-DAPT score is useful for predicting all-cause mortality, as well as risk stratification of bleeding.

B-type natriuretic peptide is associated with post-discharge stroke in hospitalized patients with heart failure.

AIMS: Recently, B-type natriuretic peptide (BNP) has been attracting attention as a predictor of stroke in patients with atrial fibrillation or those with prior stroke experience. However, the association between BNP and stroke has not been examined in patients with chronic heart failure (CHF). In the current study, we assessed whether BNP is associated with future occurrence of stroke in patients with CHF. METHODS AND RESULTS: We prospectively studied 1803 consecutive patients who were admitted for decompensated HF and assessed the predictive value of circulating BNP levels for occurrence of post-discharge stroke. A total of 69 (3.8%) patients experienced a stroke (the stroke group) during the post-discharge follow-up period of a median of 1150 days. The stroke group showed a higher CHADS2 score. With respect to past medical history, the stroke group had a higher prevalence of arterial hypertension, atrial fibrillation, prior stroke, and chronic kidney disease. Echocardiographic parameters showed no significant differences between the two groups. In contrast, BNP levels were significantly higher in the stroke group than in the non-stroke group (452.1 vs. 222.7 pg/mL, P < 0.001). Multivariate Cox proportional hazard analysis indicated that BNP levels were independently associated with post-discharge stroke (hazard ratio 2.636, 95% confidence interval 1.595-4.357, P < 0.001). The survival classification and regression tree analysis revealed that the accurate cut-off point of BNP in predicting post-discharge stroke was 187.7 pg/mL. We added high BNP level (BNP ≥ 180 pg/mL) as one point to CHADS2 score. The BNP-added CHADS2 score was compared with CHADS2 score alone by using c-statistics. The areas under the curve of CHADS2 score, BNP, and BNP-added CHADS2 score were 0.698, 0.616, and 0.723, respectively. The predictive value of BNP-added CHADS2 score was higher compared with those of CHADS2 score (P = 0.026). CONCLUSIONS: The assessment of BNP may predict the occurrence of stroke in CHF patients used alone or in combination with established CHADS2 score.

Associations of Benzodiazepine With Adverse Prognosis in Heart Failure Patients With Insomnia.

Background The prognostic impact of benzodiazepines has been unclear in patients with heart failure (HF). Methods and Results This was a historical observational cohort study. A total of 826 patients who had been hospitalized for HF and were being treated for insomnia with either benzodiazepines or Z-drugs (zolpidem, zopiclone, or eszopiclone), were enrolled and divided on the basis of their hypnotics: benzodiazepine group (n=488 [59.1%]) and Z group (n=338 [40.9%]). We compared the patient characteristics and postdischarge prognosis between the groups. The primary end points were rehospitalization for HF and cardiac death. The benzodiazepine group was older (age, 72.0 versus 69.0 years; P=0.010), had a higher prevalence of depression (17.4% versus 8.9%; P<0.001), and showed a higher use of loop diuretics (77.9% versus 67.8%; P=0.001). In the laboratory data, the benzodiazepine group demonstrated lower levels of hemoglobin (12.3 versus 13.0 g/dL; P=0.001), sodium (139.0 versus 140.0 mEq/L; P=0.018), and albumin (3.7 versus 3.9 g/dL; P=0.003). Kaplan-Meier analysis showed that both end points were higher in the benzodiazepine group (rehospitalization for HF, log-rank P=0.001; cardiac death, log-rank P=0.043). Multiple Cox proportional hazard analysis revealed that the use of benzodiazepines was an independent predictor of rehospitalization for HF (hazard ratio, 1.530; 95% CI, 1.025-2.284; P=0.038). Furthermore, rehospitalization for HF was higher in the benzodiazepine group after propensity score matching (log-rank P=0.036). Conclusions Benzodiazepine is associated with higher risk of rehospitalization for HF compared with Z-drugs in patients with HF.