Plasma BNP Levels Research Articles

Plasma natriuretic peptide level is an independent determinant of major clinical outcomes in atrial fibrillation patients without heart failure: the Fushimi AF Registry

Abstract Background Atrial fibrillation (AF) increases the risk of death, stroke/systemic embolism and heart failure (HF). Plasma natriuretic peptide (NP) level is an important prognostic marker in HF patients. However, little is known regarding the prognostic significance of plasma NP level in AF patients without HF. Purpose The aim of this study is to investigate the relationship between plasma NP level and clinical outcomes such as all-cause death, stroke/systemic embolism and HF hospitalization during follow-up period in AF patients without HF. Methods The Fushimi AF Registry is a community-based prospective survey of AF patients in our city. The inclusion criterion of the registry is the documentation of AF at 12-lead electrocardiogram or Holter monitoring at any time, and there are no exclusion criteria. We started to enroll patients from March 2011, and follow-up data were available for 4,466 patients by the end of November 2019. From the registry, we excluded 1,220 patients without a pre-existing HF (defined as having one of the following; prior hospitalization for HF, New York Heart Association class ≥2, or left ventricular ejection fraction <40%). Among 3,246 AF patients without HF, we investigated 1,189 patients with the data of plasma BNP (n=401) or N-terminal pro-BNP (n=788) level at the enrollment. We divided the patients according to the quartile of each plasma BNP or NT-pro BNP level and compared the backgrounds and outcomes between these 4 groups stratified by plasma NP level. Results Of 1,189 patients, the mean age was 72.1±10.2 years, 454 (38%) were female and 684 (58%) were paroxysmal AF. The mean CHADS2 and CHA2DS2-VASc score were 1.6±1.1 and 2.9±1.5, respectively. Oral anticoagulants were prescribed in 671 (56%) at baseline. The median (interquartile range) BNP and N-terminal pro-BNP level were 84 (38, 176) and 500 (155, 984) pg/ml, respectively. Patients with high plasma NP level were older, and demonstrated lower prevalence of paroxysmal AF, higher CHADS2 and CHA2DS2-VASc scores and higher prevalence of chronic kidney disease and oral anticoagulants prescription (all P<0.01). A total of 165 all-cause death, 114 stroke/systemic embolism and 103 HF hospitalization occurred during the median follow-up period of 5.0 years. Kaplan-Meier curves demonstrated that higher plasma NP level was significantly associated with the incidences of all-cause death, stroke/systemic embolism and HF hospitalization in AF patients without HF (Figure 1A). Multivariable Cox regression analysis revealed that plasma NP level could stratify the risk of clinical outcomes even after adjustment by type of AF, CHA2DS2-VASc score, chronic kidney disease and oral anticoagulant prescription (Figure 1B). Conclusion Plasma NP level is a significant prognostic marker for all-cause death, stroke/systemic embolism and HF hospitalization in AF patients without HF, suggesting the importance of measuring plasma NP level in AF patients even without HF. Figure 1 Funding Acknowledgement Type of funding source: None

Donepezil markedly prevents the progression of chronic heart failure and renal dysfunction in renal artery stenosis-induced hypertensive rats

Abstract Introduction Parasympathetic activation by donepezil has been shown to improve prognosis in chronic heart failure (CHF) rats following myocardial infarction. We examined whether donepezil is effective in the treatment of another CHF model complicated with renal artery stenosis (RAS)-induced hypertension. Methods RAS was created by ligating the left renal artery up to 50% in SD rats, at the same time, we implanted a blood pressure (BP) transmitter for confirming RAS-induced hypertension (7-week post-RAS: systolic BP = 154±7 mmHg; diastolic BP = 115±8 mmHg). In the 11th week after induction of RAS, surviving animals were randomly assigned to untreated (UT, n=10) or donepezil treated [DT, n=10, dissolved in drinking water (3mg/kg/day)] group. After a 6-week treatment, the effects of donepezil were evaluated by hemodynamics, blood levels of neurohumoral markers, and morphology. Results Compared with UT, DT significantly prevented the progression of the left kidney atrophy (2.38±0.13 vs. 1.51±0.34 g/kg, P<0.05) and kidney fibrosis (left: −64%, P<0.001; right: −55%, P<0.01). DT also significantly prevented the progression of CHF, through suppressing cardiac hypertrophy (2.30±0.06 vs. 2.57±0.08 g/kg, P<0.01), cardiac fibrosis (−70%, P<0.01), and cardiac dysfunction [cardiac index: 102±3 vs. 86±3 ml/min/kg, P<0.05; left ventricular (LV) end-diastolic pressure: 12±2 vs. 20±2 mmHg, P<0.05; LV dp/dtmin: 5856±259 vs. 4924±227 mmHg/sec, P<0.05]. DT not only decreased serum levels of creatinine (0.54±0.02 vs. 0.63±0.03 mg/dl, P<0.05) and uric acid (1.4±0.2 vs. 1.9±0.2 mg/dl, P<0.05); but also decreased plasma levels of norepinephrine (273±38 vs. 846±242, P<0.01), AVP (2729±347 vs. 4783±695 pg/ml, P<0.05), BNP (360±13 vs. 460±39 pg/ml, P<0.05), angiotensin II and aldosteron, and suppressed the systemic inflammation. Conclusions Donepezil treatment markedly prevented the progression of CHF and renal dysfunction, and improved the neurohumoral markers in the CHF rat model complicated with RAS-induced hypertension, suggesting that donepezil may be used as a new pharmacotherapy for CHF patients complicated with RAS-induced hypertension. Funding Acknowledgement Type of funding source: None

Inflammation and fibrosis biomarkers are related to atrial dysfunction in patients at risk of atrial fibrillation

Abstract Introduction Arterial hypertension mitral regurgitation and endurance training are risks factors for incidental atrial fibrillation (AF). Left atrial (LA) remodeling in the context of volume and pressure overload may be the substrate for AF development. Inflammation and subsequent fibrosis may be related to the development of this atrial remodeling. Our aim was to analyze if there is any correlation between inflammation and fibrosis biomarkers and left atrial dysfunction in blood samples of subjects with hypertension or mitral regurgitation and in endurance athletes. Methods A population of 478 subjects at risk of atrial fibrillation were enrolled to this study. The cohort was composed by 275 endurance athletes, 185 patients with arterial hypertension and 32 with moderate to severe mitral regurgitation. All patients underwent 2D (two-dimensional) echocardiography with speckle-tracking analysis (LA strain and LA strain-rate) and 3D (three-dimensional) echocardiography to assess LA volume and volume-based function. Furthermore, blood samples were obtained to measure plasma levels of BNP, troponin-I and the following fibrosis and inflammatory biomarkers: MMP-9 (Matrix Metalloproteinase 9), CXCL16 (CXC chemokine), CXCL6, FABP3, PIGF, OSM, endocan-1. The whole cohort was divided into quartiles according to their reservoir strain value (surrogate of atrial relaxation impairment), and correlation between biomarkers, atrial 2D volumes and 3D volumes was calculated. Results Quartile ranges regarding reservoir strain (RS) were: 1st quartile (<28.9%), 2nd quartile (28,9%-32,1%), 3rd quartile (32,95–35,4), 4th quartile (>35,4%). The first quartile (worse left atrial reservoir function) was mainly composed by hypertensive and mitral regurgitation subjects while the 4th quartile (with larger left atrium but better reservoir function) was mostly integrated by athletes. The 1st quartile (worse atrial function) showed higher levels of fibrotic (MMP-9) and inflammatory biomarkers (CXCL16, FABP3, PIGF, BNP, Troponin-I and PIGF) as compared to the other quartiles. Conclusions Inflammation and fibrosis biomarkers (CXCL16, FABP3, PIGF and MMP-9) are higher in subjects with worse LA reservoir function. This suggests a correlation among inflammation (fibrosis) and atrial dysfunction in a population at risk for AF development. Biomarkers according RS quartiles Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Fundaciό La Maratό de TV3

Artificial Intelligence Uncovered Clinical Factors for Cardiovascular Events in Myocardial Infarction Patients with Glucose Intolerance.

Glucose intolerance (GI), defined as either prediabetes or diabetes, promotes cardiovascular events in patients with myocardial infarction (MI). Using the pooled clinical data from patients with MI and GI in the completed ABC and PPAR trials, we aimed to identify their clinical risk factors for cardiovascular events. Using the limitless-arity multiple testing procedure, an artificial intelligence (AI)-based data mining method, we analyzed 415,328 combinations of < 4 clinical parameters. We identified 242 combinations that predicted the occurrence of hospitalization for (1) percutaneous coronary intervention for stable angina, (2) non-fatal MI, (3) worsening of heart failure (HF), and (4) all causes, and we analyzed combinations in 1476 patients. Among these parameters, the use of proton pump inhibitors (PPIs) or plasma glucose levels > 200 mg/dl after 2 h of a 75 g oral glucose tolerance test were linked to the coronary events of (1, 2). Plasma BNP levels > 200 pg/dl were linked to coronary and cardiac events of (1, 2, 3). Diuretics use, advanced age, and lack of anti-dyslipidemia drugs were linked to cardiovascular events of (1, 3). All of these factors were linked to (4). Importantly, each finding was verified by independently drawn Kaplan-Meier curves, indicating that the determined factors accurately affected cardiovascular events. In most previous MI patients with GI, progression of GI, PPI use, or high plasma BNP levels were linked to the occurrence of coronary stenosis or recurrent MI. We emphasize that use of AI may comprehensively uncover the hidden risk factors for cardiovascular events.

Artificial Intelligence Uncovered Clinical Factors for Cardiovascular Events in Myocardial Infarction Patients with Glucose Intolerance in the Cohort of Two Large-Scale ABC and PPAR Clinical Trials

Background: Glucose intolerance (GI), defined as either prediabetes or diabetes, promotes cardiovascular events in patients with myocardial infarction (MI). Using the pooled clinical data from patients with MI and GI in the completed ABC and PPAR trials, we aimed to identify their clinical risk factors for cardiovascular events. Methods: Using the limitless-arity multiple testing procedure, an artificial intelligence (AI)-based data mining method, we analyzed 415,328 combinations of <4 clinical parameters. Findings: We identified 242 combinations that predicted the occurrence of hospitalization for (1) percutaneous coronary intervention for stable angina, (2) non-fatal MI, (3) worsening of heart failure (HF), and (4) all causes, and we analyzed combinations in 1,476 patients. Among these parameters, plasma glucose levels >200 mg/dl after 2 hours of a 75g oral glucose tolerance test or the use of proton pump inhibitors (PPIs) predicted the coronary events of (1, 2). Plasma BNP levels >200pg/dl predicted coronary and cardiac events of (1, 2, 3). Diuretics use, advanced age, and lack of anti-dyslipidemia drugs were predictors of cardiovascular events of (1, 3). These factors were linked to (4). Importantly, each finding was verified by independently drawn Kaplan–Meier curves, indicating that the determined factors accurately predicted cardiovascular events. Interpretation: In most previous MI patients with GI, progression of GI or PPI use predicted the occurrence of coronary stenosis; recurrent MI and high plasma BNP levels predicted the subsequent worsening of HF. We emphasize that use of AI is effective to comprehensively uncover the clinical risk factors of cardiovascular events. Trial Registration: This study was a sub-analysis of the ABC Study (Alpha-glucosidase-inhibitor Blocks Cardiac Events in Patients with Myocardial Infarction and Impaired Glucose Tolerance; ClinicalTrials.gov identification number: NCT00212017) and the Pioglitazone Protects DM Patients Against Re-Infarction Study (PPAR; Clinicaltrials.gov identification number: NCT00212004 and UMIN: No. 000091). Funding Statement: Grants-in-Aid from the Ministry of Health, Labour and Welfare of Japan; Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and Grants-in-Aid from the Japan Agency for Medical Research and Development. Declaration of Interests: No relationship to industry for K.S., H.F, Y.M.,J.K., S.I, and T.W. MK reports grants from Japanese government, grants from Japan Heart Foundation, grants from Japan Agency for Medical Research and Development , personal fees from Daiichi-Sankyo, personal fees from Pfizer, grants and personal fees from Ono, personal fees from Bayer, grants and personal fees from Novartis, grants and personal fees from Bheringer, grants and personal fees from Tanabe-Mitubishi, personal fees from Japan Medical Data Center, grants and personal fees from Takeda, grants and personal fees from Astra Zeneca, outside the submitted work. Ethics Approval Statement: Approval was obtained from the institutional review boards and ethics committees of all involved hospitals and all patients provided written informed consent. The study was performed in accordance with the principles of the Declaration of Helsinki and the Japanese Ethical Guidelines for Clinical Research.

Effects of different doses of atorvastatin, rosuvastatin, and simvastatin on elderly patients with ST-elevation acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI).

To conduct a randomized double-blind prospective study to investigate effect of different doses of atorvastatin, rosuvastatin, and simvastatin on elderly patients with ST-elevation AMI after PCI. One hundred and ninety-two AMI patients over 60 years old who underwent PCI were randomly divided into six groups: the low atorvastatin group, high atorvastatin group; low rosuvastatin group; high rosuvastatin group; low simvastatin group; high simvastatin group. Demographic data and clinical information as well as coronary angiography parameters were recorded. Plasma levels of CK-MB, BNP, ALT, and TnI were measured at 12 hr, 24 hr, and 1 week after PCI. Major cardiovascular events (MACE) were recorded and analyzed using Kaplan-Meier (K-M) curve. No significant differences were observed in angiographic and procedural characteristics. In all high dose groups, all levels of CK-MB, BNP, ALT, and TnI were significantly lower. However, after 1 week of PCI, only CK-MB, BNP, and TnI showed significant difference between high and low dose groups. Patients in high dose groups had significantly lower rates for surgical or percutaneous intervention, recurrence of angina, and rehospitalization. K-M curve analysis also showed cumulative incidence freedom time of overall MACE in high dose groups was significantly longer. No significant differences were found among different drugs with the same doses. Patients with higher doses had lower level of CK-MB, BNP, ALT, and TnI and lower occurrence of MACE after PCI.

Plasma BNP Levels and Diuretics Use as Predictors of Cardiovascular Events in Patients with Myocardial Infarction and Impaired Glucose Tolerance.

Although impaired glucose tolerance (IGT) promotes cardiovascular events, our Alpha-glucosidase-inhibitor Blocks Cardiac Events in Patients with Myocardial Infarction and Impaired Glucose Tolerance (ABC) study showed that alpha-glucosidase inhibitors do not prevent cardiovascular events in patients with myocardial infarction (MI) and IGT. The aim of the present study was to identify potential clinical factors for cardiovascular events in patients with MI and IGT. Using the limitless-arity multiple testing procedure, an artificial intelligence (AI)-based data mining method, we analyzed 385,391 combinations of fewer than four clinical parameters. We identified 380 combinations predicting the occurrence of (1) all-cause hospitalization, (2) hospitalization due to worsening of heart failure (HF), (3) hospitalization due to non-fatal MI, and (4) hospitalization due to percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for stable angina among 385,391 combinations in 853 patients. Among these, either plasma BNP levels ≥ 200 pg/dl or diuretic use exclusively predicted (1) all-cause hospitalization, (2) hospitalization due to worsening of HF, and (3) hospitalization due to a non-fatal MI, with plasma BNP levels ≥ 200 pg/dl being the sole predictor of hospitalization due to PCI and CABG. Importantly, each finding was verified by independently drawn Kaplan-Meier curves, revealing the unexpected role of plasma BNP levels in the progression of coronary stenosis determined as the necessity of PCI and CABG for stable angina. In patients with MI and IGT, high plasma BNP levels predicted the occurrence of coronary stenosis, recurrent MI, and worsening of HF, whereas diuretic use did not predict the progression of coronary stenosis but non-fatal MI and worsening of HF.

Comparison of questionnaire and accelerometer-based assessments of physical activity in patients with heart failure with preserved ejection fraction: clinical and prognostic implications

Objective. (i) To compare daily physical activity (PA) levels evaluated by the International Physical Activity Questionnaire (IPAQ) and by triaxial accelerometry in heart failure with preserved ejection fraction (HFpEF) patients; (ii) to describe daily PA patterns based in objective measurements; and (iii) to observe the association between prognostic indicators and PA measurements. Design. This is a cross-sectional study with 24 stable HFpEF patients. PA was assessed through the IPAQ short version and triaxial accelerometer. Time spent in moderate-to-vigorous PA (MVPA) from IPAQ was computed as self-reported walking and MVPA. Prognostic indicators were: distance on the 6-minute-walking test (6MWT), oxygen consumption (VO2) during the test, quality of life (QoL), BNP plasma level, and E/e′ ratio. Results. Compared to accelerometry, IPAQ underestimated sedentary time (253 ± 156 vs. 392 ± 104 min/day, p = .001) and overestimated MVPA (44 ± 56 vs. 19.3 ± 26 min/day, p < .001). Accelerometer-derived data showed that HFpEF patients spent 50% of their waking time in sedentary behaviours and 2.5% in MVPA. Of measured surrogate prognostic markers, functional capacity (6MWT, r = 0.652, p = .04; VO2, r = 0.512, p = .02) and QoL (r=−0.490, p = .04) were correlated with MVPA. Conclusions. The IPAQ underestimated sedentary time and over-estimated MVPA in HFpEF patients. Using accelerometer-derived data, HFpEF patients spent only a minority of their time involved in MVPA, which was the only PA pattern positively associated with prognostic indicators.

Assessment of Left Ventricular Functions in Hypertensive Diabetic Patients by Speckle Tracking Imaging: Correlation with Brain Natriuretic Peptide Levels

<i>Background</i>: Hypertension and diabetes are major contributors to structural changes including myocardial fibrosis and progressive alteration of LV systolic and diastolic functions. Two-dimensional speckle tracking echocardiography is a reliable imaging modality that overcomes the limitations of Tissue Doppler imaging and allows a more accurate assessment of myocardial deformation at the global and regional levels. <i>Objectives</i>: The investigation aims to assess Left Ventricular functions in patients with hypertension and/or diabetes who have apparently preserved LV systolic function; using speckle tracking echocardiography, and correlate the findings with plasma Brain Natriuretic Peptide levels. <i>Methods</i>: Twenty healthy subjects were enrolled as a control group. Sixty patients with hypertension and/or diabetes were recruited and assembled as three equal groups, hypertensives, diabetics, and hypertensive-diabetics. 2D-STE was performed to assess LV longitudinal strain and strain rate. Plasma BNP levels were measured for all subjects. <i>Results</i>: Global systolic longitudinal strain was significantly reduced in patients compared to controls (P=0.001). It was more reduced in group 4. Global systolic SR was reduced in patients compared to controls, being more significantly reduced in groups 2 and 4 (P=0.001). Global early diastolic SR was reduced in patients compared to controls (P=0.001). Meanwhile, Global late diastolic SR values were higher among patients, especially groups 2 and 4 (P=0.001). BNP levels were significantly higher in group 4 compared to group 1 (P=0.000), group 2 (P=0.000), and group 3 (P=0.000). BNP levels and global systolic strain in group 4 were significantly correlated. <i>Conclusion</i>: LV systolic dysfunction was found among all patients groups, confirmed by the significant reduction in LV global longitudinal systolic SR. Hypertensive-diabetics exhibited lower global strain than patients with hypertension only and patients with diabetes only, even though their EF showed no apparent difference. Elevated BNP levels, being the highest among group 4, indicate the presence of ventricular dysfunction, even before chamber failure occurs.

Application of Capnography Waveform Analyses for Evaluation of Recovery Process in a Patient with Heart Failure: A Case Report

Resting end-tidal CO2 levels obtained from capnography are associated with the severity of heart failure (HF). It has not been fully investigated whether other respiratory parameters acquired from detailed capnography waveform analyses could evaluate the recovery process in HF patients. In this case, the analysis of nasal capnography waveforms (diurnal five minutes recording) was performed to monitor and analyze end-tidal CO2 (ETCO2) values, inspiratory/expiratory ratio and respiratory intervals. We observed that these three parameters increased concurrently with decreasing plasma BNP levels during the recovery stage of HF. The kurtosis of frequency distributions of capnography waveforms became larger as HF improved. Proper utilization of these analyses could evaluate HF severity during the recovery process in patients with HF.

N-terminal pro-brain natriuretic peptide as a biomarker for differentiating cardiac and pulmonary disease in term neonates with respiratory distress

ObjectiveBrain natriuretic peptide (BNP) is synthesized in the cardiac ventricles and released in response to volume or pressure load. The aim of the study was to determine whether plasma level of N-terminal pro BNP (NT-pro BNP) can distinguish between cardiac and pulmonary disease (PD) among neonates with respiratory distress (RD). Patients and methodsThe study included 48 term neonates in the first month of life with signs of RD. They were recruited from Neonatal Intensive Care Unit of Al-Galaa Teaching Hospital. Twenty-six healthy neonates were included as a control group. The degree of RD was assessed using Silverman–Anderson score. Chest X-ray, echocardiography, and laboratory measurement of NT-pro BNP were performed. ResultsAccording to the underlying disease, neonates with RD were divided into 28 neonates with PD and 20 neonates with congenital heart disease (CHD). Regardless the etiology of RD, NT-pro BNP was significantly higher in the RD group than in the control (p = 0.001). There was a significant difference between and within the three groups regarding NT-pro BNP (p = 0.001). NT-pro BNP was significantly higher in the CHD group than in the PD group (p = 0.001). There was a significant difference between and within RD subgroups. The NT-pro BNP is a very useful test for identification of CHD in neonates with RD. Area under the receiver operating characteristic curve for CHD was 0.857 (p = 0.01), sensitivity 66%, specificity 85%, and cutoff point was 24.5 pg/mL. The area under the curve for PD was 0.646 (p = 0.1) with poor sensitivity and specificity, indicating that NT-pro BNP is a poor test for identification of PD in neonates with RD. ConclusionTerm neonates with RD have increased plasma levels of NT-pro BNP. NT-pro BNP is a very good test for identification of CHD in neonates with RD, in comparison with PD. Therefore, plasma NT-pro BNP can be used to differentiate between cardiac and pulmonary cause of RD.

4328Short-term effects of dapagliflozin versus canagliflozin on acute decompensated heart failure in patients with type 2 diabetes

Abstract Background The CANVAS program and DECLERE-TIMI 58 reported that SGLT2i had been demonstrated to reduce hospitalization for heart failure (HF) in type 2 diabetic mellitus (T2DM) patients with high cardiovascular disease risk. However, it remains unclear whether the effectiveness of SGLT2i on acute decompensated HF is also observed in T2DM patients irrespective of acting types of SGLT2i. Methods In this single center, open-label, prospective study, fifty-eight T2DM patients hospitalized due to decompensated HF were enrolled (mean age 73 years, HbA1c 7.2%). After treatment for HF, 5mg/day of dapagliflozin (n=24, from February 2016 to February 2017) or 100mg/day of canagliflozin (n=34, from March 2017 to July 2018) was administered and clinical parameters about HF and T2DM were followed for 7 days. Statistical comparison of parameters between groups taking dapagliflozin or canagliflozin was performed using the two-way repeated measures analysis of variance (MANOVA). Results In both groups, urine glucose excretion increased significantly after administration of SGLT2i. Fasting blood glucose level tended to be decreased in both groups. Urine volume increased significantly one day after administration of SGLT2i, and returned to the baseline after one week in both groups. Interestingly, urine volume one day after administration of SGLT2i tended to increase more in the group taking canagliflozin than in the group taking dapagliflozin (interaction P value = 0.088). Importantly, plasma BNP levels and Nt-proBNP levels were decreased significantly in both groups. Parameters before and after treatment Baseline Day 7 (Day 1) P value Interaction P value Fasting blood glucose, mg/dL All 137±57 122±51 0.013 0.900 Dapa 144±64 133±53 0.089 Cana 128±64 118±40 0.069 log BNP All 5.31±1.11 4.91±1.09 &lt;0.001 0.102 Dapa 5.48±1.04 4.94±1.00 &lt;0.001 Cana 5.20±1.15 4.89±1.16 &lt;0.001 log Nt-proBNP All 7.25±1.35 6.96±1.41 &lt;0.001 0.735 Dapa 7.54±1.16 7.22±1.25 0.048 Cana 7.04±1.45 6.79±1.50 0.005 Urine volume (Day 1), mL/24h All 1218±523 1584±614 &lt;0.001 0.088 Dapa 1261±564 1486±568 0.038 Cana 1186±498 1654±644 &lt;0.001 Urine volume (Day 7), mL/24h All 1218±523 1305±408 0.128 0.428 Dapa 1261±564 1295±468 0.700 Cana 1186±498 1313±367 0.097 Urine glucose, g/24h All 1.6±5.5 23.7±23.5 &lt;0.001 0.330 Dapa 1.7±6.8 20.3±21.7 &lt;0.001 Cana 1.5±4.6 26.0±24.7 &lt;0.001 Conclusion SGLT2i are useful for correcting volume overload and recovering from the decompensated state in HF patients with T2DM irrespective of acting types of SGLT2i.

P5406Impact of the albumin level on the prognostic value of diuretic response in patients admitted for acute decompensated heart failure: a prospective study

Abstract Background The reduced diuretic response (DR) has been shown to be associated with poor clinical outcome in patients with acute decompensated heart failure (ADHF). In addition, hypoalbuminemia, which is related to DR, has been also reported to predict poor prognosis in ADHF patients. However, there is no information available on the impact of albumin level on the prognostic value of DR in patients with ADHF. Methods We prospectively studied 296 consecutive patients who were admitted for ADHF and survived to discharge. The patients were divided into 2 groups according to the presence or absence of hypoalbuminemia at the admission, defined as the serum level of albumin at admission &lt;3.5g/dl, and DR was defined as weight loss per 40mg intravenous dose and 80mg oral dose of furosemide up to day 4. The endpoint was a composite of all-cause mortality and unplanned hospitalization for worsening heart failure. Results There were 144 patients with hypoalbuminemia and 152 patients without hypoalbuminemia. During a mean follow-up period of 2.2±1.5 years, 88 patients with hypoalbuminemia and 53 patients without hypoalbuminemia reached the endpoint. In group with hypoalbuminemia, DR was significantly smaller in patients with than without the endpoint (0.85 [0.50–1.50] vs 1.60 [0.76–2.70] kg/40mg furosemide, p=0.003), while there was no significant difference in DR between them in group without hypoalbuminemia (1.17 [0.59–1.66] vs 1.07 [0.75–1.88] kg/40mg furosemide, p=0.381). At multivariate Cox analysis, in group with hypoalbuminemia, DR was significantly associated with the endpoint, independently of age, left ventricular ejection fraction, and serum creatinine and plasma BNP levels. On the other hand, in group without hypoalbuminemia, DR showed no significant association with the endpoint at univariate Cox analysis. Kaplan-Meier analysis showed that patients with poor DR (≤1.08 kg/40mg furosemide: median value) had a significantly higher risk of the endpoint in group with hypoalbuminemia, but not in group without hypoalbuminemia (Figure). Figure 1 Conclusion Our results suggested that prognostic value of DR in ADHF patients is affected by the presence or absence of hypoalbuminemia.

P1025Clinical predictors for the improvement of left ventricular ejection fraction and prognosis after catheter ablation of atrial fibrillation in patients with systolic dysfunction

Abstract Background Catheter ablation (CA) of atrial fibrillation (AF) improves left ventricular ejection fraction (LVEF) and clinical outcomes in patients with left ventricular systolic dysfunction (LVSD). However, predictors of the improvement of LV function and clinical outcomes by CA were poorly understood. Purpose We examined the efficacy of CA in AF patients with LVSD and predictive factors associated with clinical outcomes. Method Among consecutive 795 patients undergone initial RFCA at our hospital, we studied 51 patients with LVSD (LVEF ≤50%). Improved LVEF more then 5% at 1-year after CA was classified as “responder” to CA. We analyzed clinical variables and echocardiographic parameters before and after the CAs. Results In the responder group, LVEF was significantly improved 1-year after catheter ablation compared with the non-responder group. (ΔLVEF 22±12% vs. −1±4%, p&lt;0.001). The responder group was significantly younger, had more non-paroxysmal AF, smaller LV systolic diameter and lower plasma BNP level before CA (Table). Late gadolinium enhancement (LGE)-positive rate in cardiovascular magnetic resonance imaging (CMR) before CA was higher in the non-responder group than in the responder group (100% [6/6] vs. 38% [5/13], p&lt;0.005). After CAs of AF, event-free survival from hospitalization for heart failure was significantly higher in the responder group (Figure) with less AF recurrence (27% vs. 47%, p=0.04) than in the non-responder group. Baseline characteristics Responder (N=35) Non-Responder (N=16) P value Age, y 62±11 69±8 p&lt;0.01 Male, n (%) 26 (74) 13 (76) NS Non-pAF 26 (74) 4 (24) p&lt;0.01 LAD, mm 48±7 48±8 NS LAVI, ml/m2 54±17 58±20 NS LVDd, mm 54±7 58±10 NS LVDs, mm 43±7 48±10 p=0.05 EF, % 37±8 38±8 NS BNP (pg/ml) 278±225 684±848 p&lt;0.05 Conclusion Younger age, absence of LV dilatation, lower plasma BNP, or absence of LGE may well predict favorable clinical outcomes after CA in patients with LVSD.

P915Clinical characteristics, natural history and predictors of disease progression in patients with degenerative mitral stenosis

Abstract Background Mitral annular calcification (MAC) is a common echocardiographic finding and an increasingly recognized cause of degenerative mitral stenosis (DMS). However, little is known about the natural history and predictors of disease progression of DMS, especially compared with rheumatic mitral stenosis (RMS). Purpose To compare the clinical characteristics and disease progression among patients with DMS and those with RMS, and to investigate the determinants of disease progression in DMS patients. Methods We retrospectively reviewed consecutive MS patients with a trans-mitral mean gradient ≥2 mmHg who underwent echocardiography at our institution between January 2014 and December 2017. We selected patients who had an initial and follow-up echocardiography with a ≥3-month interval and without prior and interim mitral valve intervention. DMS was defined as MS with MAC with normal or minimally reduced leaflet motion without tips restriction. RMS was defined as MS with tip restriction, thickening and restriction of leaflet mainly. We defined MAC severity as mild (focal), moderate (marked density &gt;1/3 but &lt;1/2 of the mitral annulus) and severe (marked density involving &gt;1/2 of the mitral annulus) based on previous reports. We calculated disease progression from the annual increase rate of trans-mitral mean gradient. First, we compared the backgrounds and disease progression between DMS group and RMS group. Second, we investigated the predictors of disease progression in DMS group. Results We enrolled 111 patients (64 in DMS group and 47 in RMS group) with a mean follow-up period of 2.1 years. Patients in DMS group were significantly older (79±9 vs. 70±10 years; P&lt;0.01), had higher prevalence of hypertension (P&lt;0.01) and coronary artery disease (P=0.02), and had higher plasma BNP level (P&lt;0.01) than those in RMS group. Baseline trans-mitral mean gradient was slightly lower in DMS group than in RMS group (3.9±1.9 vs. 4.7±1.8 mmHg; P=0.02). There were wide variations among individuals in progression rate (range: 0 to 3.5 mmHg/year in DMS group and 0 to 5.8 mmHg/year in RMS group, respectively), and the progression rate was comparable between DMS group and RMS group (0.49±0.79 vs. 0.61±1.37 mmHg/year; P=0.59). In DMS group, higher prevalence of dyslipidemia (P=0.01) and lower baseline trans-mitral mean gradient (P&lt;0.01) were significantly associated with disease progression even after adjustment for age and sex. Unexpectedly, there was no significant difference in the disease progression regardless of the MAC severity among DMS group (Picture). MAC severity and disease progression Conclusions Progression in DMS group is highly variable, but generally slow as that in RMS group. Initial mean gradient was inversely associated with disease progression in DMS group. Furthermore, baseline MAC severity did not correlate with the progression, suggesting the importance of follow-up echocardiography in spite of the MAC severity and initial mean gradient.

4089Prognostic value of cardiac metabolic activity assessed by 18F-FDG PET in patients with cardiac sarcoidosis

Abstract Background Sarcoidosis is a systemic granulomatous disease that affects multiple organs. Among these,the presenceof cardiac involvementis recognized as a determinant of worse clinical outcomes. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a valuable modality for detecting active inflammatory lesions associated with cardiac sarcoidosis (CS). Generally,the maximum standardized uptake value (SUV) is suitable for evaluating disease activity in CS, but this quantitative method had limitations because it does not integrate both volume and intensity of FDG uptake simultaneously. Cardiac metabolic activity (CMA), which is quantitative measures of FDG volume-intensity, could be a diagnostic tool in the evaluation of CS. However, its prognostic implication in patients with CS is unclear. Purpose We sought to investigate whether CMA assessed by FDG-PET was associated with long-term worse clinical outcomes in patients with CS. Methods A total of 76 consecutive patients suspected CS who underwent FDG-PET between January 2010 and April 2018 in our university hospital were registered. We excluded patients whodid not meet the Japanese Ministry of Health and Welfare 2007 criteria (n=9) and those who received oral corticosteroids at the time of FDG-PET (n=5). Ultimately, 62 CS patients with definitively diagnosed were included in this study.We used a dedicated software to analyze SUV. Cardiac metabolic volume (CMV) was defined as the volume within the boundary determined by the threshold (SUV mean of blood pool × 1.5). CMA was calculated by multiplying CMV by SUV mean. The primary outcome of interest was the composite of advanced atrioventricular block, ventricular tachycardia, ventricular fibrillation, heart failure hospitalization, and all-cause death. Results During a median follow-up period of 1287 (IQR 806–1809) days after the first FDG-PET, the adverse events occurred in 12 patients (19%). Events group had significantly higher CMA compared to no events group (83 [IQR 11–330] vs. 354 [IQR 70–577]) (Figure A). Based on ROC analysis, the optimal cut-off value of CMA for the discrimination of the adverse events was 244 ml, and c-index was 0.71 (95% CI, 0.55–0.87). Patients with high CMA (≥244 ml, n=23) had lower LVEF, and higher prevalence of New York Heart Association functional class III or IV, and higher plasma BNP level compared to those with low CMA (&lt;244 ml, n=39). Kaplan-Meier analysis revealed that composite adverse events more frequently occurred in patients with high CMA compared to those with low CMA (Figure B).Univariable Cox regression analysis showed that higher CMA was associated with increased subsequent risk of adverse events (HR 1.47, 95% CI 1.06–2.24). Conclusions Higher CMA assessed by FDG-PET was associated with worse clinical long-term outcomes in patients with CS, suggesting that measurement of the volume-intensity of abnormal FDG uptake may be useful for risk stratification in patients with CS.

Reduced diffusing capacity for carbon monoxide predicts borderline pulmonary arterial pressure in patients with systemic sclerosis.

Early intervention in pulmonary arterial hypertension associated with systemic sclerosis (SSc) may improve its prognosis. We aimed to establish an algorithm to detect mean pulmonary artery pressure (mPAP) > 20mmHg using non-invasive examinations in SSc patients by modifying the DETECT algorithm. This study included SSc patients who underwent right heart catheterization (RHC) in our hospital during 2010-2018. Following variables were assessed for performance to predict mPAP ≥ 25mmHg or > 20mmHg; anti-centromere or U1-RNP antibody, plasma BNP level, serum urate level, right axis deviation, forced vital capacity (FVC)/diffusing capacity for carbon monoxide (DLCO) ratio, and tricuspid regurgitation velocity. Of 58 patients enrolled in this study, 24 had mPAP of ≥ 25mmHg and 9 had mPAP of 21-24mmHg. Among variables tested, only FVC/DLCO elevated similarly in patients with mPAP of ≥ 25mmHg (median 2.5) and those with mPAP of 21-24mmHg (median 2.5) compared to those with mPAP of ≤ 20mmHg (median 1.5). Given the particularly good correlation between DLCO and mPAP of > 20mmHg, each variable was weighted according to its odds ratio and the total weighted score was calculated. The total weighted score exhibited a good predictive performance for mPAP of > 20mmHg with its sensitivity of 87.5% and specificity of 92%. Among conventional risk factors for PAH, decreased DLCO may predict mPAP > 20mmHg with priority in SSc patients. Weighting DLCO may improve the performance of screening algorithm for early SSc-PAH.

Plasma BNP and Diuretics As Predictors of Cardiovascular Events in Patients with MI and IGT

Background: Impaired glucose tolerance (IGT) promotes cardiovascular events in myocardial infarction (MI) patients. However, our randomized trial (the ABC study) showed that alpha-glucosidase inhibitors do not prevent cardiovascular events in patients with MI and IGT. The aim of the present study is to identify potential clinical factors for cardiovascular and coronary events in patients with a MI and IGT. Methods: Using the limitless-arity multiple testing procedure, an artificial intelligence (AI)-based data mining method, we analyzed 385,391 combinations of fewer than four clinical parameters. Findings: We identified 380 combinations predicting the occurrence of (1) all-cause hospitalisation, (2) hospitalisation due to worsening of heart failure (HF), (3) hospitalisation due to non-fatal MI, and (4) hospitalisation due to percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for stable angina among 385,391 combinations in 853 patients. Among these, either plasma BNP levels >200 pg/dl or diuretic use exclusively predicted (1) all-cause hospitalisation, (2) hospitalisation due to worsening of HF, and (3) hospitalisation due to a non-fatal MI, with plasma BNP levels >200 pg/dl being the sole predictor of hospitalisation due to PCI and CABG. Importantly, each finding was verified by independently drawn Kaplan-Meier curves, revealing the unexpected role of plasma BNP levels in the progression of coronary stenosis determined as the necessity of PCI and CABG for stable angina. Interpretation: In patients with MI and IGT, plasma BNP levels >200 pg/dl predicted the occurrence of coronary stenosis, recurrent MI and worsening of HF, whereas diuretic use did not predict the progression of coronary stenosis but non-fatal MI and worsening of HF We also demonstrated the use of AI in cardiovascular medicine. Funding: Grants-in-Aid from the Ministry of Health, Labour and Welfare of Japan; and Grants-in-Aid from the Japan Agency for Medical Research and Development. Declaration of Interest: Relationships to industry do not exist for K.S., H.F., T.H., S.I., A.I., M.A., J.K., H.A., O.T. and T.W. M.K. reports grants and personal fees from Takeda, during the conduct of the study; grants from Japanese government, grants from Japan Heart Foundation, grants from Japan Cardiovascular Research Foundation, grants and personal fees from Asteras, grants and personal fees from Sanofi, personal fees from Daiichi-sankyo, grants and personal fees from Pfizer, grants and personal fees from Ono, personal fees from Bayer, grants and personal fees from Novartis, personal fees from Bheringer, grants and personal fees from Tanabe-mitubishi, personal fees from Kowa, grants and personal fees from Kyowa-hakko-kirin, personal fees from Dainihon-sumitomo, personal fees from Sawai, personal fees from MSD, grants and personal fees from Abott, grants and personal fees from Otsuka, grants from Calpis, grants from Nihon Kohden, personal fees from Shionogi, personal fees from Astrazeneca, personal fees from Asahikasei Med., personal fees from Novo nordisk, personal fees from Fuji-film RI, personal fees from Japan Medical Data, outside the submitted work. Ethical Approval: Approval had been obtained from the institutional review boards and ethics committees of all involved hospitals. All patients provided written informed consent. The study was performed in accordance with the principles of the Declaration of Helsinki and the Japanese ethical guidelines for clinical research.

Effect of isosorbide mononitrate combined with metoprolol in the treatment of heart failure in patients with coronary heart disease

Objective To observe the clinical effect of isosorbide mononitrate combined with metoprolol in the treatment of coronary heart failure. Methods From January 2015 to May 2017, 100 patients with coronary heart failure treated in the Second People's Hospital of Yuyao were randomly divided into two groups according to the digital table, with 50 cases in each group.The conventional group was treated with conventional therapy.The observation group was treated with isosorbide mononitrate combined with metoprolol on the basis of conventional treatment for 30 days.The clinical efficacy, cardiac function index and plasma BNP level were compared between the two groups. Results The total effective rate of the observation group was 96.0%(48/50), which was higher than 78.0%(39/50) in the conventional group(χ2=7.161, P<0.01). After treatment, the cardiac drainage index(CI)[(3.14±0.53)L·min-1·(m2)-1], cardiac output blood volume(CO)[(5.62±0.95)L/min], each stroke volume(SV)[(79.24±2.56)mL], left ventricular ejection fraction(LVEF)[(61.62±4.95)%]in the observation group were better than those in the conventional group[(2.41±0.45)L·min-1·(m2)-1, (4.79±0.23)L/min, (72.30±2.78)mL, (53.79±4.23)%, t=7.043, 5.696, 12.318, 8.066, all P<0.05]. The BNP level of the observation group was (172.17±10.36)pg/mL, which was lower than (215.47±12.48)pg/mL of the conventional group (t=17.908, P<0.05). Conclusion The treatment of coronary heart failure with isosorbide mononitrate and metoprolol can improve the clinical effect and improve cardiac function. Key words: Coronary disease; Heart failure; Isosorbide mononitrate; Metoprolol

The risk of arrhythmia by calculating with new electrocardiographic parameters in pregnant women with heart failure

Aim: To evaluate cardiac arrhythmias with surface 12 lead electrocardiography (ECG) parameters during pregnancy in women with mild heart failure. Material and Cardiovascular deaths usually occur in older pregnancies and arrhythmia is the third most common cause. Our study aimed to determine whether the risk of arrhythmia increases in pregnancy with advanced age.Go to:Methods:This cross-sectional study was approved by the local ethics committee of bicard clinic and our hospital 53 consecutive patients were accepted. All patients were admitted to hospital for cesarean section. Patients were grouped to heart failure (group 1) and control (group 2) (healthy group). A 12 lead ECG and N-terminal pro B-type natriuretic peptide (NT-pro BNP) plasma levels was recorded for every woman at 48 hour before cesarean section. They were evaluated P wave, qt, qtc and Twave peak to end, preoperative NT-pro BNP and compared statistically.In total, 280 pregnant women, of whom 98 were of advanced age and 182 were under 35 years of age were included in the study. The risk of arrhythmia was evaluated by calculating the electrocardiographic P-wave duration, QT interval, T peak-to-end interval, and the Tp-e/QT ratio.Go to:Results: There were statistically significant differences in the Tp–e interval and Tp-e/QTc ratio between the two groups, the maximum QTc, minimum QTc, and QTc dispersion values, P wave dispersion were significantly higher in group-1 compared to the group-2. In addition, preoperative NT-pro BNP plasma levels was greater in the group 1 pregnant women. And there was a positive correlation between ECG parameters and NT-pro BNP plasma levels in group 1.Although there were no differences in the Tp-e interval and Tp-e/QTc ratio between the groups, the maximum QTc, minimum QTc, and QTc dispersion values were significantly higher in advanced-age pregnancies compared to the control group. In addition, the P dispersion was greater in advanced-age pregnancies. In correlation analysis, the increased dispersion of QTc and P were positively correlated with maternal age. Multiple linear regression analysis showed that QTc dispersion was independently associated with maternal age.Go to: Conclusion: In conclusion, repolarization parameters were increased in patients with heart failure with elevated NT-pro BNP. Pregnancy and heart failure has known risk for pregnant women. But there is no clear cut atrial and ventricular arrhythmias risk scoring parameters for these kind patients. We found that ECG parameters which had significantly different in pregnant women with heart failure than control group and these changes correlated with NT-pro BNP levels. This is pathological; arrhythmia risk scorings should be established to reduce mortality and morbidity in heart failure patients with elevated BNP levels.