Plasma BNP Research Articles

MO721: Correlation of Serum BNP Levels with Blood Pressure Variability using ABPM in Patients NAÏVE on Haemodialysis

Abstract BACKGROUND AND AIMS Plasma BNP levels are thought to correlate with blood pressure monitoring in patients on maintenance haemodialysis. An adequate BP control results in decline in mortality rates in these patients. To correlate plasma BNP levels and blood pressure variability using ABPM with echocardiographic findings in non-hypertensive patients with end-stage renal disease naïve on haemodialysis. METHOD Type of study: Institutional-based, a single-centre cross-sectional observational study. Study period : January 2017–2019. Sample size: 80. RESULTS In our study, 75% were males and 25% were females. Out of 80 patients type 2 diabetes mellitus was present in 13 (16.3%), hypertension was present (based on office BP) in 36 (45%), 86.3% of patients had azotemia symptoms at presentation, 72.5% of patients were underweight (BMI < 18.5 kg/m2), 42.5% of patients were categorized as CKD G5A3, hyperuricemia was present in 31.3%. Mean age was 47.6 years, mean height was 165 cm, mean weight was 47.8 kg, mean BMI was 17.54 kg/m2 mean SBP was 129.10 mmHg and mean DBP was 78.05 mmHg. During passive phase ABPM readings, double product was low in 50% of cases, HBI diagnosed hypertension and isolated systolic hypertension, isolated diastolic hypertension in 62.3%, 11.3% and 3.8% of cases, respectively. ABPM diagnosis of non-hypertension or hypertension under control was observed in 22.55 of cases during passive phase. Mean total cholesterol was significantly more in HTN compared with patients without HTN; P < 0.05. Mean BNP was significantly higher in patients with HTN compared with patients without HTN; P < 0.05. There was a significant negative correlation observed between BNP and EF on 2D ECHO, LVH on 2D ECHO and EF (%) on 2D ECHO; P < 0.05. No factor was found to be associated statistically significant with outcome. Comparison of mean BNP levels in relation to dipping status on ABPM in all six groups i.e. HTN group containing three subgroups (non-dippers, normal dippers and reverse dippers) and non-HTN group containing three subgroups (non-dippers, normal dippers and reverse dippers) did not reveal any significance (P > 0.05). Comparison of mean BNP levels in relation to dipping status on ABPM in all six groups, i.e. HTN group containing 3 subgroups (non-dippers, normal dippers and reverse dippers) and non-HTN group containing three subgroups (non-dippers, normal dippers and reverse dippers) did not reveal any significance (P > 0.05). ABPM readings diagnosed underlying masked hypertension in 19 out of 44 (43.1%) patients with normal office BP readings. Subgroup analysis of plasma BNP relation to this masked hypertension patients and actual non-hypertension patients also did not reveal any significant difference in plasma BNP levels (ROC—best cut-off of 23.05 ng/L with sensitivity of 88% and specificity of 26.3%). CONCLUSION ABPM is useful to diagnose significant number of masked hypertension patients in those naïve on dialysis. Plasma BNP level has a low sensitivity and specificity as a screening tool to identify dipping status or to predict outcomes in ESRD patients naïve to haemodialysis.

Cardiac Natriuretic Peptide And Cgmp Impairment In Human Decompensated Heart Failure: Employing A Novel Ex Vivo Natriuretic Peptide/GC-A/cGMP Potency Assay To Evaluate Natriuretic Peptide Therapeutic Capacity

Cardiac Natriuretic Peptide And Cgmp Impairment In Human Decompensated Heart Failure: Employing A Novel Ex Vivo Natriuretic Peptide/GC-A/cGMP Potency Assay To Evaluate Natriuretic Peptide Therapeutic Capacity

Angiotensin II As A Natural Suppressor On Cardiac Natriuretic Peptide System: Molecular Insights And Novel Therapeutic Design

<h3>Introduction</h3> Therapeutic strategies harnessing both renin-angiotensin system (RAS) and natriuretic peptide system (NPS) mediated effects, such as Sacubitril/Valsartan, has been proven to be promising in treating human heart failure (HF). However, molecular understanding of the interaction between RAS and NPS remains to be fully elucidated. While angiotensin II (ANGII), the central RAS hormone, is thought to interact with NPS at multiple levels, whether and how it may influence the actions of particulate guanylyl cyclase A (pGC-A), the only functional receptor for both atrial and b-type natriuretic peptide (ANP and BNP), has not been investigated. <h3>Hypothesis</h3> We hypothesize that ANGII naturally suppresses pGC-A and the inhibition of this crosstalk would be a novel therapeutic strategy to combat cardiovascular disease (CVD) of which RAS hyperactivation is a hallmark feature. <h3>Methods</h3> Plasma ANP, BNP, cGMP, and ANGII were measured in 128 healthy humans to define the balance between ANGII and NPS. cGMP responses to acute infusion of ANP alone and in the presence of ANGII was characterized in normal rats. The molecular mechanisms including involvement of ANGII type I receptor (AT1R) and its downstream target protein kinase C (PKC) were investigated in HEK293 cell overexpressing pGC-A and together with AT1R. CRRL-58, an innovative dual-functional peptide was designed to activate pGC-A and inhibit PKC, and tested for cGMP generation in HEK293 cells. <h3>Results</h3> In healthy human, plasma cGMP was positively associated with ANP or BNP only in low (≤ 4.5 pg/mL) but not those with high (> 4.5 pg/mL) ANGII levels (see Figure). Infusion of ANP (300 pmol/kg/min) in normal rats increased plasma and urinary cGMP, however ANP mediated cGMP generation was reduced in the presence of ANGII (50 pmol/kg/min). Notably, the suppressive effect of ANGII on pGC-A was recapitulated in HEK293 cell overexpressing both pGC-A and AT1R, but not in HEK293 cell overexpressing pGC-A alone. Meanwhile, we found PKC, a well-established downstream target of AT1R, was a key mediator for this observed crosstalk, as the suppression effect of ANGII was largely ablated by Go6983, a pan PKC inhibitor. Notably, CRRL-58 had superior potency in cGMP generation compared to the currently best-in-class ANP-analog, MANP, in vitro. <h3>Conclusions</h3> Our human and experimental data demonstrate that ANGII is a natural suppressor of pGC-A activation via AT1R and PKC signaling, but not via pGC-A per se. Moreover, we report for the first time that CRRL-58, an innovative bioengineered peptide that activates pGC-A receptor while inhibiting PKC signaling, potently generates cGMP. Together, our study provides new insights into the interaction between RAS and NPS, and highlights a novel and mechanism-based therapeutic avenue for treating HF and other CVDs.

Kinetics of atrial and brain natriuretic peptides during hemodialysis are regulated in association with different cardiac functional changes.

The blood levels of atrial and brain natriuretic peptides (ANP and BNP) are both increased markedly in hemodialysis patients, but the kinetics of the two are not always parallel. The present study investigated the association of changes in ANP and BNP levels before and after dialysis with changes in cardiac function in hemodialysis patients. A total of 57 patients (mean age 64years, 47 males and 10 females) on maintenance hemodialysis with sinus rhythm were enrolled. Blood samples were taken at the beginning and end of dialysis, and plasma levels of ANP and BNP were measured. Changes in cardiac function during dialysis were examined by echocardiography performed just before and after dialysis. Both plasma ANP and BNP concentrations decreased significantly after hemodialysis, but the rate of decrease in BNP [mean ± SD, 555 ± 503 to 519 ± 477pg/mL (-6.4%), P = 0.011] was much smaller than that in ANP [233 ± 123 to 132 ± 83pg/mL (-43.4%), P < 0.001]. As for the relation to the changes in echocardiographic parameters before and after dialysis, the decrease in inferior vena cava diameter had a close correlation with the decrease in ANP (r = 0.528, P < 0.001), but not BNP. In contrast, the decrease in left ventricular end-diastolic volume index was correlated only with the decrease in BNP (r = 0.297, P = 0.035). The peak velocity ratio of early diastolic to atrial filling decreased with preload reduction by dialysis, and its decrease was more strongly correlated with the decrease in BNP (r = 0.407, P = 0.002) than that in ANP (r = 0.273, P = 0.040). These results demonstrated that in hemodialysis patients, the decrease in plasma ANP by a single dialysis was essentially caused by blood volume reduction, while BNP decrease was mainly induced by the reduction of left ventricular overload. Our findings indicate that the kinetics of both peptides during dialysis are regulated by different cardiac and hemodynamic factors.

Clinically Administered Doses of Pitavastatin and Rosuvastatin.

Clinical studies have indicated that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, can potentially inhibit chronic heart failure. In the Stat-LVDF study, a difference was noted in terms of the effect of lipophilic pitavastatin (PTV) and hydrophilic rosuvastatin (RSV) on plasma BNP, suggesting that statin lipophilicity and pharmacokinetics change the pleiotropic effect on heart failure in humans. Therefore, we assessed the beneficial effects of PTV on hypertrophy in cardiac myocytes compared with RSV at clinically used doses. Cultured cardiomyocytes were stimulated with 30 μM phenylephrine (PE) in the presence of PTV (250 nM) or RSV (50 nM). These doses were calculated based on the maximum blood concentration of statins used in clinical situations in Japan. The results showed that PTV, but not RSV, significantly inhibits the PE-induced increase in cell size and leucine incorporation without causing cell toxicity. In addition, PTV significantly suppressed PE-induced mRNA expression of hypertrophic response genes. PE-induced ERK phosphorylation was inhibited by PTV, but not by RSV. Furthermore, PTV significantly suppressed the angiotensin-II-induced proline incorporation in primary cultured cardiac fibroblasts. In conclusion, a clinical dose of PTV was noted to directly inhibit cardiomyocyte hypertrophy and cardiac fibrosis, suggesting that lipophilic PTV can be a potential drug candidate against chronic heart failure.

Abstract 11877: Arrhythmogenic Right Ventricular Cardiomyopathy Patients with a Markedly Enlarged RV Compressing LV to Left Side Have an Atypical Distribution of Epsilon Waves and Elevated Plasma BNP

Introduction: Epsilon waves on V1-3 leads are specific ECG findings in patients with arrhythmogenic right ventricular (RV) cardiomyopathy (ARVC). 4D cardiac CT visualizes ARVC characteristics, such as fibro-fatty invasion into RV and left ventricular (LV) myocardium (RVM, LVM), an enlarged RV, reduced RV motion, and bulging. Hypothesis: We hypothesize that epsilon waves in V4-6 leads suggest LV invasion in ARVC. Alternatively, extreme RV enlargement may compress the LV and cause clockwise rotation; an enlarged RV may itself cause epsilon waves in V4-6 leads. Methods: Retrospective analysis of 17 patients (11 males, 57±17 yrs) with suspected ARVC undergoing cardiac CT and ECG, 9 of whom met 2010 ARVC task force criteria. Result: All 9 patients had epsilon waves ; 5 had fibro-fatty invasion into the LVM. We divided the 9 into 5 groups by CT: 1) markedly enlarged RV compressing the LV to the left side with fibro-fatty changes exclusively in RVM (N=1); 2) similar findings in both RVM and LVM (N=2); 3) moderately enlarged RV without compression of the LV to the left side and fibro-fatty changes exclusively in RVM (N=3); 4) the same in both RVM and LVM (N=2); 5) severe mitral valve regurgitation, a markedly enlarged LV, and a fibro-fatty change in both RVM and LVM (N=1). The patient in group (gp) 1 showed epsilon waves in V1-6 leads, patients in gp 2 had epsilon waves in V1-6 (N=1), and V3-5 (N=1) leads; patients in gp 3 had epsilon waves in V1-4 (N=2), and V1-3 (N=1) leads, patients in gp 4 had epsilon waves in V1-3 (N=1), and V1, 2 (N=1) leads; finally, the patient in gp 5 had epsilon waves in V4-6 leads. Plasma BNP levels were significantly greater in patients in gp 1 &amp; 2 than gp 3 &amp; 4 (1255±838 vs 80±52 pg/ml, P=0.016). Conclusions: ARVC patients with a markedly enlarged RV compressing the LV to the left side (gp 1,2) had a broad (V1-6) or different range (V3-5) distribution of epsilon waves and significantly elevated plasma BNP independent of fibro-fatty invasion of the LV, different from typical ARVC (gp 3,4).

Abstract 10507: Pyridoxamine Protects Against Cardiotoxicity After Doxorubicin Chemotherapy

Introduction: Although doxorubicin (DOX) is an efficient anthracycline agent used to treat cancer, it induces cardiotoxicity and mortality in cancer survivors. Cardioprotection is inadequate. The vitamin B 6 -derivative pyridoxamine (PM) has shown to be cardioprotective in diverse cardiac diseases. Whether PM offers cardioprotection after DOX treatment is unknown. We hypothesized that PM limits cardiac impairment after DOX treatment by reducing cardiac fibrosis and inflammation. Methods: Female Sprague Dawley rats were weekly treated with 2 mg/kg DOX or saline IV for 8 weeks. At DOX treatment onset, 2 extra groups received PM (1 g/L) via the drinking water. Echocardiographic (4D) and hemodynamic parameters were assessed at week 8, together with plasma BNP. PCR analysis was performed on left ventricular tissue to evaluate fibrosis and inflammation. Data were compared using 1-way ANOVA, Kruskal-Wallis test or 2-way ANOVA with post-hoc tests as appropriate. Results: As shown in Table 1, cardiac impairment by DOX was prevented by PM. In addition, DOX significantly increased the expression of fibrosis markers, such as TGFβ (0.29 ± 0.02 vs. 0.69 ± 0.09 a.u., p&lt;0.0001), LOX (0.055 ± 0.002 vs. 0.590 ± 0.174 a.u., p&lt;0.01), collagen type 1 (0.21 ± 0.02 vs. 0.62 ± 0.11 a.u., p&lt;0.001) and interstitial collagen (4.6 ± 0.3 vs. 7.7 ± 0.6%, p&lt;0.001). DOX also increased the inflammation marker IL-6 (0.13 ± 0.03 vs. 0.73 ± 0.13 a.u., p&lt;0.01). PM treatment significantly lowered all these parameters (p&lt;0001, p&lt;0.001, p&lt;0.01, p&lt;0.01 and p&lt;0.01 respectively). Conclusions: In conclusion, our data show that DOX causes dilated cardiomyopathy with reduced ejection fraction, accompanied by cardiac fibrosis and myocarditis. As PM limits this adverse phenotype, it could be a novel cardioprotective strategy for DOX-treated cancer patients.

Abstract 9175: Clinical Significance of Resting Heart Rate on Exercise Capacity and Prognosis: Comparison Among Heart Failure Patients with Reduced, Preserved and Mid-Range Ejection Fraction

Introduction: Resting heart rate (rHR) has a big influence on clinical outcomes and exercise capacity in patients with chronic heart failure (CHF). However, the association of rHR with exercise capacity and prognosis has not been fully elucidated in patients with heart failure with reduced, preserved and mid-range ejection fraction (HFrEF, HFpEF and HFmrEF). Aims: We aimed to determine the differences in the association of rHR with exercise capacity and prognosis in patients with HFrEF, HFpEF and HFmrEF. Methods: 877 CHF patients with sinus rhythm (SR) were divided into four groups according to rHR (G1: rHR &lt; 60 /min, G2: 60&lt;rHR &lt; 70 /min, G3: 70&lt;rHR &lt; 80 /min and G4: rHR&lt;80 /min) in HFrEF, HFpEF and HFmrEF, respectively. We compared the parameters of cardiopulmonary exercise testing and adverse cardiac event rates (cardiac death and re-hospitalizations for worsening heart failure) among HFrEF, HFpEF and HFmrEF. Results: Of 877 CHF patients, 388 were in HFrEF, 360 in HFpEF and 179 in HFmrEF. Patients with HFrEF were the youngest among three groups. Patients with HFrEF had the highest plasma BNP level and the lowest estimated glomerular filtration rate, followed by those with HFmrEF and HFpEF. Patients with HFrEF had the lowest peak oxygen consumption (PVO 2 ) , heart rate reserve (HRR: [peak HR-rHR] / [predicted max HR-rHR]) and oxygen uptake efficiency slope (OUES) , and the highest minute ventilation and carbon dioxide production (VE/VCO 2 ) slope, followed by those with HFmrEF and HFpEF. In HFrEF, patients with rHR from 70 to 80 /min had the highest PVO 2 and HRR and the lowest VE/VCO 2 slope. On the other hands, as rHR increased, adverse cardiac event rates increased. In HFpEF, patients with rHR less than 60 had the lowest PVO 2 , HRR and OUES, and the highest VE/VCO 2 slope and adverse cardiac event rates. In HFmrEF, patients with rHR less than 60 had the lowest PVO 2 , HRR and OUES and the highest VE/VCO 2 slope. In contrast, adverse cardiac event rate was not significant different in relation to rHR. Conclusions: rHR was associated with exercise capacity and clinical outcomes in patients with CHF and SR. However, influence of rHR on exercise capacity and adverse clinical outcomes were different among HFrEF, HFpEF and HFmrEF.

Abstract 8914: Selective Phosphodiesterase-9 Inhibition With IMR-687 Mitigates Cardiac Hypertrophy and Renal Injury in Preclinical Mouse Models of Heart Failure With Preserved Ejection Fraction

Introduction: Through degradation of the cardio- and renal-protective second messenger cyclic GMP, phosphodiesterase-9 (PDE9) excess may contribute to cardiomyocyte hypertrophy, fibrosis, and renal dysfunction, common features in heart failure with preserved ejection fraction (HFpEF) development and progression. Hypothesis: Selective PDE9 inhibition with IMR-687 mitigates an adverse cardiac and renal phenotype in mouse models of HFpEF. Methods: Cardiac and renal responses to IMR-687 (60 mg/kg, 100 mg/kg) compared with vehicle were examined over 6-8 weeks in 3 adult male mouse models of HFpEF (1.5 mg/kg/d angiotensin-II infusion [ang-II]; uninephrectomy + 0.30 ug/h d-aldosterone infusion + 1% NaCl drinking water [neph-aldo]; and db/db [db]). Phenotyping included wheat germ agglutinin staining for cardiomyocyte cross-sectional area (CSA); RT-PCR for myocardial PDE9, natriuretic peptide, inflammatory and fibrosis marker transcript abundances; ELISA for plasma natriuretic peptides; and urinary albumin to creatinine ratio (UACR). Results: IMR-687 reduced median cardiomyocyte size (CSA) by 54, 58, and 35% compared with vehicle in the ang-II, neph-aldo, and db models, respectively; p &lt; 0.003 for all. Myocardial PDE9, NPPA, NPPB, COL3A1, and IL-1β expression were decreased by IMR-687 in all models (Table). Median plasma BNP levels (pg/mL) were lower in IMR-687 vs. vehicle treated mice in all models (ang-II: 2376 vs. 5757; neph-aldo: 1216 vs. 1860; db: 830 vs. 1216); p &lt; 0.007 for all, with similar findings for ANP (Table). UACR was lower in IMR-687 compared with vehicle treated mice in all models (Table). Heart rate and blood pressure did not differ between IMR-687 and vehicle treated mice. Conclusion: Selective PDE9 inhibition with IMR-687 was effective for prevention and treatment of cardiac hypertrophy and renal dysfunction in 3 different preclinical models of HFpEF. IMR-687 may be a promising candidate therapy for testing in clinical trials of human HFpEF.

Molecular ratio of mature B-type natriuretic peptide in acute heart failure: an indicator for ventricular contractile recovery.

AimsThe methodology to distinguish between the heart failure (HF) with recovered ejection fraction (HFrecEF) and those with continuously reduced ejection fraction (EF) (HFcrEF) on admission has not been established. We recently demonstrated that the ratio of plasma levels of pro‐B‐type natriuretic peptide (proBNP) to total BNP (proBNP plus mature BNP) is decreased on admission in patients with mild acute HF, but not in severe acute HF as a compensatory mechanism for activating cyclic GMP via increases of bioactive mature BNP. We aimed to test the hypothesis that the ratio of bioactive mature BNP to total BNP is associated with reverse remodelling capacity in patients with HF with reduced EF.Methods and resultsPlasma proBNP and total BNP were measured in patients with acute decompensated HF by using specific and sensitive enzyme immunochemiluminescent assay. Estimated percent mature BNP (%emBNP) was calculated as ([total BNP − proBNP]/total BNP) × 100. We retrospectively identified the patients with reduced EF (≤40%, on admission) who had echocardiographic data after discharge (n = 93). We defined patients with increased EF by >10% during the follow‐up term (median, 545 days) after the admission as HFrecEF group. We compared patient characteristics, %emBNP, and other biomarkers between HFrecEF and HFcrEF. Of the enrolled patients with HFrecEF (n = 32) and HFcrEF (n = 61), on admission, %emBNP was significantly higher in HFrecEF than in HFcrEF (44.1% vs. 36.9%; P < 0.05). There were no significant differences in left ventricular EF on admission between the two groups. The univariate analysis revealed that %emBNP on admission was associated with HFrecEF occurrence rate (P < 0.05), in contrast both total BNP and high‐sensitive cardiac troponin‐T levels were not associated with HFrecEF occurrence rate.ConclusionsThe ratio of mature BNP to total BNP in plasma at the time of hospital admission may be predictive of left ventricular contractile recovery. Preservation of the capacity to convert proBNP to mature BNP, but not myocardial injury itself, is associated with future ventricular contractile recovery.

Compare the Serum Level of BNP between Weaning Successful and Weaning Failed Patients

Background: Weaning is the term frequently used to describe the gradual reduction of ventilatory support from patient who’s pulmonary and other conditions are improving. Delayed weaning from ventilatory support expose patients to unnecessary complications. Patients should therefore be weaned from mechanical ventilation as quickly as possible. Objective: The purpose of the study was to compare the serum level of BNP between weaning successful and weaning failed patients. Methodology: This study was a prospective cohort study. This study was conducted in the Department of Anesthesia, Analgesia and Intensive Care Medicine at Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh over a period of 2 years. Study population was selected for weaning from mechanical ventilation support for the first time in the age group of more than 18 years with both sexes. Patients with pre-existing diseases that elevate the plasma BNP level were excluded from the study. Weaning criteria was selected by ICU consultant following the standard ICU protocol for every patients enrolled in this study. Patients were subdivided into weaning success and weaning failure groups according to the outcome of weaning process. Plasma BNP level of all patients was measured before and after 2 hours of spontaneous breathing trial. Each blood sample (3ml) was collected by ICU lab technician into a vacutainer with EDTA for anticoagulation. Blood samples were sent to the biochemistry lab and analysis was done by chemiluminescent microparticle immunoassay (CMIA). Serial arterial blood gases done within ICU lab before and after 2hours of SBT and 12hourly up to 48 hours. Patients who were extubated would be followed up for 48 hours after SBT. Result: A total number of 30 patients were recruited for this study. One-third (33.3%) of the patients failed on SBT. The mean age of weaning success and failure groups were 54.90±9.787 years and 57.60±10.091 years respectively. The mean percent changes ............

Role of Serum B-type Natriuretic Peptide before and after 2hours of Spontaneous Breathing Trial among Patients under Mechanical Ventilation

Background: Weaning of a patient from mechanical ventilation is very important for the outcomes of the patients.&#x0D; Objective: The purpose of the study was to evaluate the serum level of BNP before and after 2hours of spontaneous breathing trial (SBT) among patients under mechanical ventilation.&#x0D; Methodology: This prospective cohort study was conducted in the Department of Anesthesia, Analgesia and Intensive Care Medicine at Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh over a period of 2 years. Study population was selected for weaning from mechanical ventilation support for the first time in the age group of more than 18 years with both sexes. Plasma BNP level of all patients was measured before and after 2 hours of spontaneous breathing trial.&#x0D; Results: A total number of 30 patients were recruited for this study. One-third (33.3%) of the patients failed on SBT. The mean percent changes of BNP (pg/ml) during 2-h of SBT in weaning success and failure groups were 38.41±9.379 and 59.51±2.940 respectively (p=0.01). The receiver-operating characteristic curve analysis for BNP as a predictor of weaning outcome, showed that the area under the curve (AUC) was 0.89.&#x0D; Conclusion: In conclusion BNP is currently a good predictor of different cardiac diseases.&#x0D; Journal of Current and Advance Medical Research, July 2021;8(2):125-129

Retrospective Analysis of High-Dose Melphalan and Autologous Stem Cell Transplantation for Systemic Light-Chain Amyloidosis: A Single Center 63 Cases

[Background]High-dose melphalan and autologous stem cell transplantation (HDM/ASCT) show significant efficacy in systemic immunoglobulin light-chain (AL) amyloidosis. However, there have been few reports demonstrating efficacy of HDM/ASCT for AL amyloidosis patients in Asia, because of scarcity of AL amyloidosis. We retrospectively analyzed 63 cases of AL amyloidosis who received HDM/ASCT.[Patients and methods]We retrospectively analyzed 63 patients with AL amyloidosis who received HDM and ASCT between 2006 and 2017. Patients with plasma BNP<1000 pg/ml and <IVST 15mm were determined transplant eligible from 2007. The median age was 54 years old (range, 32-70). Cardiac, renal and gastrointestinal involvement were 24(38.1%), 42(66.7%) and 29(48%) patients, respectively. The percentage of more than 2 organ involvement was 69.8%. Cardiac response was defined as more than 30% of BNP decline. Because NTproBNP was measured only in limited number of patients, we used BNP instead of NTproBNP to analyze cardiac response. Also, BNP was well correlated to NTproBNP (spearman correlation = 0.922). Hematological and kidney response was defined as previously described (Comenzo RL et al, Leukemia, 2012). Briefly, a difference between the involved FLC and uninvolved FLC of 50mg/dl and more than 0.5g of 24-hour urine protein were defined as measurable for hematological and renal response.[Results]2-year and 4-year overall survival was 88.2% and 80.9%, respectively. Cardiac response was achieved in 9 of 22(40.9%). Hematological responses were evaluated in 25 cases and were 15(60%) sCR, 3(12%) VGPR and 6(24%) PR. More than 11mm of IVST affected worse OS(p=0.032) in line with previous reports. Also, more than 1mg/dl of serum creatinine (sCre) showed worse OS (p=0.022).Mortality within 100 days after ASCT was observed in 5 patients (1 MOF, 1 arrhythmia, 1 heart failure and 2 infection). 4 out of 5 patients showed cardiac involvement (median BNP value = 732.3).[Conclusions]Our analysis revealed comparable OS rate with other institutions in US and EU countries. Patients with cardiac involvement and higher sCre level showed worse prognosis. More than 11 mm of interventricular septum thickness (IVST) affected worse OS. Careful patient selection and experienced management are important for HDM/ASCT for AL amyloidosis. DisclosuresIshida:Bristol-Myers Squibb: Honoraria; Janssen: Honoraria; Takeda: Honoraria; ONO: Honoraria; Celgene: Honoraria. Suzuki:Bristol-Myers K.K: Honoraria; Novarltis: Honoraria; Celgen: Honoraria; Ono: Honoraria; Fujimoto: Honoraria; Takeda: Honoraria.

BNP LEVELS AND LEFT VENTRICULAR MORPHOLOGY AND FUNCTION IN HYPERTENSIVE PATIENTS BEFORE AND AFTER AN INTRAVENOUS SALINE LOAD

Objective: Previous studies have reported a relationship between BNP levels and left ventricular (LV) morphology and function in essential hypertension (EH), but results are conflicting. The aim of the study was to investigate the relationships between BNP levels measured before and after a standard saline load (SLT), plasma aldosterone (PA), active renin (AR), and LV variables in EH patients without heart failure or valvular disease. Design and method: In 155 EH patients (age 48 ± 12 years, 92 males, 64 treatment-naïve, the remaining 91 after drug wash-out), a SLT (0.9% saline, 2 L in 4 hours) was performed with baseline and post-SLT measurement of PA, AR, BNP pre- and post-test (pre-BNP, post-BNP). Echocardiography with Tissue Doppler Imaging (TDI) was performed, with measurement of indexed LV mass (LVMI), ejection fraction (EF), TDI-S velocity, E/A and E/e’ ratios, and TDI-e’ velocity. Results: Pre-BNP level was higher in females than males, and in patients with previous antihypertensive treatment than in naive patients. Pre-BNP level was significantly and directly related to age, LVMI, E/e’, and inversely related to glomerular filtration (GFR), AR, TDI-S, E/A, and TDI-e’. Post-BNP levels was higher in females and in previously treated patients, and it was positively related to age, E/e’ ratio, and inversely related to GFR, AR, TDI-S, E/A, and TDI-e’. At multivariate analysis pre-BNP level was independently associated with age, female gender, GFR, and AR, while post-BNP level was independently associated with age, AR, and previous antihypertensive treatment. Conclusions: In EH patients, plasma BNP is related with LVMI and LV systolic and diastolic function before and after a SLT, but this relationship seems to be limited to female sex and older subjects. Measurement of BNP might be useful for identification and follow-up of subclinical LV abnormalities in these patients.

DOUBLE PRODUCT CAN BE REDUCED BY CPAP IN SLEEP APNEA SYNDROME PATIENTS

Objective: Sleep apnea syndrome (SAS) is associated with increased cardiovascular mortality mediated by intermittent hypoxia, oxidative stress, endothelial dysfunction, and sympathetic nerve activation. Continuous positive airway pressure (CPAP) therapy has been established as the treatment of SAS. Double product (W-P = systolic blood pressure x heart rate) was reported to be a good predictor for cardiovascular disease. This study was designed to test whether CPAP could reduce W-P in SAS patients. Design and method: Patients diagnosed as SAS by polisomnography (PSG) examined in our hospital from April 2016 to April 2018 were enrolled (N = 67, male 78.3%, 60.4 ± 14.3 years). 11 cases of the subjects had examined PSG under wearing CPAP. W-P was calculated by casual blood pressure and heart rate measured on the PSG enforcement day. The association between W-P and parameters including age, sex, BMI, abdominal circumference, blood tests date, urine albumin, and various SAS indexes were examined. Results: Casual blood pressure and heart rate were 124.8 ± 19.2/79.1 ± 15.9 mmHg and 78.6 ± 13.4 bpm. W-P in the group with CPAP (8786.7 ± 1451.7) was significantly decreased compared with the group without CPAP (10127.7 ± 2826.5, p &lt; 0.05). The urine protein level (R = 0.43, p &lt; 0.05) and the plasma BNP level (R = 0.45, p &lt; 0.005) were related to W-P. Multivariate regression analysis adjusted for known risk factors also indicated that the urine protein level was independent factor to determine elevated W-P (beta = 0.57, p &lt; 0.05). Conclusions: W-P was related to a hypertensive target organ damage in SAS patient. The CPAP therapy can decrease W-P and may reduce the risk of future cardiovascular disease.

Integrative characterization of asymptomatic vs. symptomatic patients with moderate-severe primary mitral regurgitation

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by NHLBI and Specialized Centers of Clinically Oriented Research grant in cardiac dysfunction, by Department of Veteran Affairs for Merit Review and NIH Grant P01. Background Optimal timing for surgery in primary mitral regurgitation (PMR) is a subject of debate. Purpose Use a combination of imaging, circulating biomarkers and histology to define the transition from asymptomatic (asx) to symptomatic (sx) stage in moderate-severe PMR. Methods 57 controls, 82 sx and 47 asx patients with moderate to severe PMR underwent cardiac MR(CMR), plasma BNP, levels of xanthine oxidase (XO) activity, and circulating markers of collagen (Col) synthesis (propeptide of procollagen type I, PICP) and degradation (Col type I fibers, ICTP). Results A progressive worsening in the severity of adverse LV remodeling was noted based on CMR indices listed in Table 1. The 3D mid-wall LV endocardial curvature to wall thickness was lower in normal and similar in asx and sx patients.Plasma BNP was progressively higher in normal vs. asx vs sx (Figure 1A). The levels of XO activity were higher in sx vs. asx (Figure 1B,1C). Levels of PICP were similar among the three; levels of ICTP were significantly higher in the sx vs the asx (Figure 1D,1E). LV biopsies revealed large areas of patchy replacement fibrosis and areas devoid of interstitial Col (Figure 1F). From the subgroup of 56 patients who underwent CMR 6 months after surgery, 27% had LVEF &amp;lt; 50%. The preoperative LVEF, LVESV, LVESD and LA emptying fraction were predictors of postoperative drop in LVEF. Conclusion Increased COl breakdown coupled with markers of oxidative stress and CMR-based LV remodeling characterize the transition from asx to sx PMR. Longitudinal studies are needed to define cutoff"s for patient selection and optimal timing for MV surgery. CMR indices in normal, asx and sx PMR. Normal (57) Moderate/Severe MR Asymptomatic (56) Pre-Surgery MR Symptomatic (81) P-value Age 48 (34, 55) 54 (46, 62) * 57 (50, 67) * &amp;lt;0.0001 Female/Male 30(53%)/27(47%) 35(63%)/21(38%) 25(31%)/56(69%) LVEF (%) 64 (61, 67) 62 (59, 66) 63 (59, 67) 0.3482 LV EDV (mL/m2) 71 (61, 76) 89 (73, 103) * 100 (83, 123) *# &amp;lt;0.0001 LV ESV (mL/m2) 24 (21, 29) 32 (26, 38) * 36 (28, 47) * &amp;lt;0.0001 LVSV (mL/m2) 43 (37, 50) 54 (43, 66) * 60 (54, 77) *# &amp;lt;0.0001 LVED Mass/Volume 0.7 (0.6, 0.8) 0.6 (0.5, 0.7) * 0.6 (0.6, 0.7) * 0.0012 LVED Mass/Vol x SI 1.29 (1.05, 1.50) 0.97 (0.77, 1.15) * 0.94 (0.77, 1.14) * &amp;lt;0.0001 Regurgitant Volume (mL) ― 38 (26, 54) 57 (38, 83) # 0.001 Regurgitant Fraction (%) ― 39 (28, 50) 46 (36, 56) # 0.042 Table 1 shows the CMR indices of LV remodeling in normal, asymptomatic and symptomatic patients with moderate-severe PMR. p-values *vs. Normal; # vs. Asymptomatic. Kruskal-Wallis test or unpaired t-test Abstract Figure 1.

AST-120 Improves Cardiac Dysfunction in Acute Kidney Injury Mice via Suppression of Apoptosis and Proinflammatory NF-κB/ICAM-1 Signaling.

PurposeAcute kidney injury (AKI) is a devastating disorder associated with considerably high morbidity and mortality. Reports have shown that AST-120, an oral charcoal adsorbent, can reduce oxidative stress by lowering serum indoxyl sulfate levels. The effects of AST-120 and indoxyl sulfate on kidney injury and cardiac dysfunction were investigated in vivo and in vitro.Patients and MethodsPatients were tracked for enrollment upon receiving a diagnosis of AKI. Plasma was collected to determine the renal and inflammatory parameters. Renal ischemia/reperfusion (I/R) induced AKI or sham operation was performed in C57BL/6J mice. Animals were divided into sham, AKI+vehicle, and AKI+AST-120 groups. Plasma and tissues were assembled after 48 h to assess apoptotic and inflammatory responses. We also conducted human umbilical vein endothelial cell (HUVECs) and HL-1 cardiomyocyte culture studies to determine the underlying mechanisms of indoxyl sulfate’s effects. Echocardiography, histopathology, biochemical indexes, ELISA, terminal dUTP nick-end labeling (TUNEL) and Western blot analysis were performed.ResultsThe cohort included 25 consecutive patients with AKI and 25 non-AKI. Plasma levels of creatinine, indoxyl sulfate, IL-1β and ICAM-1 were significantly higher in patients with AKI than in non-AKI controls. Plasma levels of blood urea nitrogen, creatinine, indoxyl sulfate, IL-1β and renal tubular injury were increased in mice after renal I/R and were decreased by AST-120 treatment. In addition, AST-120 therapy not only improved the parameters assessed by echocardiography but also substantially attenuated the elevation of plasma BNP. Oral administration of AST-120 significantly downregulated NF-κB/ICAM-1 expression and reduced cell apoptosis in both kidney and heart after renal I/R injury.ConclusionOur investigations demonstrated that AST-120 administration improves cardiac dysfunction in AKI mice via the suppression of apoptosis and proinflammatory NF-κB/ICAM-1 signaling.

Abstract 13077: Higher Occurrence of Right Ventricular Fibrosis in Right Ventricular Outflow Tract-dominant Than Diffuse Hypertrophic Types: A Pulmonary Hypertension Study Using Cardiac Computed Tomography

Introduction: On cardiac CT of pulmonary hypertension (PH), two right ventricular (RV) hypertrophic (RVH) morphological types are seen, namely RV outflow tract-dominant and RV-diffuse. However, clinical significance of this difference is unclear. Hypothesis: These two morphological RVH types have different effects on myocardial characteristics, clinical severity and prognosis in PH patients. Methods: We retrospectively analyzed 43 PH patients (33 females, 55±15yrs, 31 chronic thromboembolic PH (CTEPH), 7 idiopathic pulmonary arterial (PA) hypertension). On CT, RV fibrosis was defined as contrast defects in early phase and abnormal enhancement in late phase. Cases were divided into 3 groups: RV outflow tract-dominant RVH (gp 1), RVH-diffuse (gp 2), and no RVH (gp 3). Mean follow up was 39.3±20.1, 58.3±17.7, 68.2±11.9 months, respectively. Results: There were 6, 26, 11 patients in gps 1, 2, 3, respectively. There were no significant differences in these percentages between CTEPH and idiopathic PA hypertension or between ages ≥60 and &lt;60 yrs. There were no significant differences of R/S wave ratio on ECG V1 lead, maximum RV wall thickness on end-diastole (CT), plasma BNP and estimated PA systolic pressure (PASP) on TTE between gps 1 and 2. There were significant positive correlations between maximum RV wall thickness in end-diastole and plasma BNP in gp 1 (R=0.44) but no correlations in gp 2 (R=0.05). Similarly, there were significant positive correlations between maximum RV wall thickness in end-diastole and estimated PASP in gp 1 (R=0.38) but no correlations in gp 2 (R= -0.08). RV fibrosis was detected in 3 patients (50%) (gp1) and 1 patient (4%) (gp2) (P=0.003). Zero, 2, and 1 patients died due to PH during follow-up periods in gps 1, 2, 3 , respectively, and there were no significant differences in these percentages on Kaplan Meier analysis and log rank testing. Interobserver agreement between two observers was 91% in gp 1 and 77% in both gps 2 and 3. Conclusions: In PH patients, RV outflow tract-dominant RVH was relatively easy to diagnose and manifested with greater occurrence of RV fibrosis than diffuse-type. RV outflow tract-dominant RVH showed significant positive correlations of maximum RV wall thickness in end-diastole with plasma BNP and estimated PASP.

Abstract 14515: The Prognostic Impact of Human Epididymis Protein 4 Levels in Patients With Dilated Cardiomyopathy

Introduction: Interstitial fibrosis of myocardium is an important component of cardiac dysfunction. Myofibroblasts, which are activated fibroblasts, contribute to interstitial fibrosis in dilated cardiomyopathy (DCM). Recently, human epididymal body protein 4 (HE4) has attracted attention as a marker specific to myofibroblasts. Hypothesis: We hypothesized that the circulating serum HE4 levels were associated with future cardiac events in DCM. Methods: We enrolled 44 DCM patients with stable heart failure (HF) condition. Patients with cancer were excluded. We collected blood samples from peripheral vain (PV), ascending aorta (Ao), and coronary sinus (CS) during cardiac catheterization. They were divided into two groups at the median of PV HE4 levels: High PV group (&gt;69 pmol/L); n=22, Low PV group (&lt;69 pmol/L); n=22. Furthermore, they were also divided into groups with median of CS-Ao HE4 levels: High CS-Ao group (&gt;-0.15 pmol/L); n=22, Low CS-Ao group (&lt;-0.15 pmol/L); n=22. Cardiac events were defined as composite of cardiac deaths and hospitalization for worsening HF. Results: The mean age, left ventricular ejection fraction (LVEF), and plasma BNP level were 56 years, 32%, and 205 pg/mL. Between two groups, there were no significant differences in age, gender, LVEF, left ventricular end-diastolic diameter, cardiac index, and pulmonary capillary wedge pressure. However, estimated glomerular filtration rate was significantly lower in the High PV group (p=0.025). Survival analysis revealed that the High PV group had a higher rate of cardiac events ( Figure ). However, there was no difference between two CS-Ao groups. As for the pathological analysis, not only the peripheral HE4 level but CS-Ao HE4 level did not significantly correlate with collagen volume fraction in biopsy samples. Conclusion: Elevated circulating HE4 is associcated with poor prognosis in ambulatory patients with NIDCM. However, transcardiac gradient of plasma HE4 level might not be associated.

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 &amp;lt;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&amp;lt;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