Terminal Pro B-type Natriuretic Peptide Research Articles

Angiotensin-Neprilysin Inhibition in Patients With Mildly Reduced or Preserved Ejection Fraction and Worsening Heart Failure

BackgroundU.S. guidelines recommend consideration of sacubitril/valsartan in chronic heart failure (HF) and mildly reduced or preserved ejection fraction (EF). Whether initiation is safe and effective in EF >40% after a worsening heart failure (WHF) event is unknown. ObjectivesPARAGLIDE-HF (Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF) assessed sacubitril/valsartan vs valsartan in EF >40% following a recent WHF event. MethodsPARAGLIDE-HF is a double-blind, randomized controlled trial of sacubitril/valsartan vs valsartan in patients with EF >40% enrolled within 30 days of a WHF event. The primary endpoint was time-averaged proportional change in amino terminal pro–B-type natriuretic peptide (NT-proBNP) from baseline through Weeks 4 and 8. A secondary hierarchical outcome (win ratio) consisted of: 1) cardiovascular death; 2) HF hospitalizations; 3) urgent HF visits; and 4) change in NT-proBNP. ResultsIn 466 patients (233 sacubitril/valsartan; 233 valsartan), time-averaged reduction in the NT-proBNP was greater with sacubitril/valsartan (ratio of change: 0.85; 95% CI: 0.73-0.999; P = 0.049). The hierarchical outcome favored sacubitril/valsartan but was not significant (unmatched win ratio: 1.19; 95% CI: 0.93-1.52; P = 0.16). Sacubitril/valsartan reduced worsening renal function (OR: 0.61; 95% CI: 0.40-0.93) but increased symptomatic hypotension (OR: 1.73; 95% CI: 1.09-2.76). There was evidence of a larger treatment effect in the subgroup with EF ≤60% for NT-proBNP change (0.78; 95% CI: 0.61-0.98) and the hierarchical outcome (win ratio: 1.46; 95% CI: 1.09-1.95). ConclusionsAmong patients with EF >40% stabilized after WHF, sacubitril/valsartan led to greater reduction in plasma NT-proBNP levels and was associated with clinical benefit compared with valsartan alone, despite more symptomatic hypotension. (Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF; NCT03988634)

NT-proBNP levels as a predictor of higher left ventricular end-diastolic pressure in children with small perimembranous ventricular septal defect

The decision to close small ventricular septal defect is still controversial. Previous study showed that ventricular dysfunction in adulthood is correlated with small perimembranous ventricular septal defect. N terminal pro B-type natriuretic peptide (NT-proBNP) is a neurohormone secreted primarily from the ventricles in response to increased left and right ventricular pressure and volume load. The left ventricular end-diastolic pressure will reflect ventricular performance. This study aimed to evaluate the correlation between left ventricular end-diastolic pressure and the NT-proBNP in children with small perimembranous ventricular septal defect. Level of NT-proBNP in 41 patients with small perimembranous ventricular septal defect was measured before transcatheter closure procedure. We also measured the left ventricular end-diastolic pressure in each patients during catheterisation. We investigated the value of NT-proBNP in patients with small perimembranous ventricular septal defect and its correlation with the level of left ventricular end-diastolic pressure. We found positive correlation between NT-proBNP and left ventricular end-diastolic pressure (r = 0.278, p = 0.046). The median of NT-proBNP at left ventricular end-diastolic pressure < 10 was lower than at left ventricular end-diastolic pressure ≥ 10 (0.87 ng/ml versus 1.83 ng/ml, p = 0.023). The results of the NT-proBNP diagnostic test for predicting left ventricular end-diastolic pressure ≥ 10 using Receiver Operating Characteristic (ROC) analysis showed the area under the curve value of 0.715 (95% CI: 0.546-0.849). The cut-off value >0.99 ng/ml of NT-proBNP has 75.0% sensitivity and 72.2% specifity. Level of NT-proBNP higher than 0.99 ng/ml was correlated significantly with left ventricular end-diastolic pressure ≥10 in children with small perimembranous ventricular septal defect.

Rhabdomyolysis following Nuss Procedure: A Prospective Study in Children.

Postoperative rhabdomyolysis (RML) has been documented after several surgical procedures in adults. Musculoskeletal remodeling after Nuss procedure for pectus excavatum (PE) could cause RML. We evaluated the incidence of RML after Nuss procedure in children. This study was a prospective study from 2018 to 2021. We enrolled all otherwise healthy patients who underwent PE correction with only one bar. Studied variables included demographic and clinical data, duration of surgery, complications, and length of hospitalization. The patients included underwent serial measurements of serum creatine kinase (CK), troponin I, N terminal pro B-type natriuretic peptide (NT-proBNP), serum creatinine, urea, and glomerular filtration rate at 6 and 48 hours postoperatively, and hospital discharge. Forty-six patients met criteria (40 males/6 females), with a mean age of 15.1 ± 1.4 years. Mean duration of surgery was 74 ± 28 minutes, and length of hospitalization was 4.6 ± 1.6 days. RML was diagnosed in 30.4% of patients at 6 hours, 91.3% at 48 hours, and 21.7% at hospital discharge. Mean preoperative CK value was 181.1 ± 141.6 IU/L, and postoperative values were 863.3 ± 302.6 IU/L at 6 hours, 1,675.2 ± 561 IU/L at 48 hours, and 850 ± 683.7 IU/L at hospital discharge, with statistically significant differences (p = 0.001). High-sensitivity troponin I and NT-proBNP levels increased significantly during the postoperative time (p = 0.001). Renal function remained stable (p = 0.55). Nuss technique produces RML without kidney injury in healthy patients. This knowledge should be considered for patients at increased risk of developing acute kidney injury and other complications.

101 Differentiating Type 1 from Type 2 Acute Myocardial Infarction in the Emergency Department Using the N-terminal Pro B-type Natriuretic Peptide/High-sensitivity Cardiac Troponin T Ratio

Acute myocardial infarction (AMI) is currently further diagnosed as being a type 1 (T1), caused by coronary artery atherosclerosis with thrombosis or a type 2 (T2), resulting from cardiac oxygen supply and demand imbalance. It is hypothesized that patients with T2 might develop earlier and increased cardiac wall stressing before the development of AMI as compared to those with T1, resulting in higher N- terminal pro B-type natriuretic peptide (NT-proBNP)/high sensitivity cardiac troponin T (hs-cTnT) ratios.

B-39 | BNP as a biomarker for pulmonary hypertension in a pediatric population

Amino terminal pro B-type natriuretic peptide (NT-proBNP) and brain B-type natriuretic peptide (BNP) are used as lab markers of cardiac wall tension and early studies indicate that it may be useful as a screening or surveillance test for pediatric pulmonary hypertension. This study is a prospective study of whether the serum level of BNP or NT-pro-BNP was associated with the severity and reactivity of pulmonary hypertension during catheterization of a population of pediatric patients with known or suspected pulmonary hypertension.

Sex Differences in the Non-infarct-Related Artery-Based Quantitative Flow Ratio in Patients With ST-Elevation Myocardial Infarction: A Retrospective Study.

Introduction: It has been reported that sex has well-established relationships with the prevalence of coronary artery disease (CAD) and the major adverse cardiovascular events. Compared with men, the difference of coronary artery and myocardial characteristics in women has effects on anatomical and functional evaluations. Quantitative flow ratio (QFR) has been shown to be effective in assessing the hemodynamic relevance of lesions in stable coronary disease. However, its suitability in acute myocardial infarction patients is unknown. This study aimed to evaluate the sex differences in the non-infarct-related artery (NIRA)-based QFR in patients with ST-elevation myocardial infarction (STEMI).Methods: In this study, 353 patients with STEMI who underwent angiographic cQFR assessment and interventional therapy were included. According to contrast-flow QFR (cQFR) standard operating procedures: reliable software was used to modeling the hyperemic flow velocity derived from coronary angiography in the absence of pharmacologically induced hyperemia. 353 patients were divided into two groups according to sex. A cQFR ≤0.80 was considered hemodynamically significant, whereas invasive coronary angiography (ICA) luminal stenosis ≥50% was considered obstructive. Demographics, clinical data, NIRA-related anatomy, and functional cQFR values were recorded. Clinical outcomes included the NIRA reclassification rate between men and women, according to the ICA and cQFR assessments.Results: Women were older and had a higher body mass index (BMI) than men. The levels of diastolic blood pressure, troponin I, peak creatine kinase-MB, low-density lipoprotein cholesterol, N terminal pro B-type natriuretic peptide, stent diameter, and current smoking rate were found to be significantly lower in the female group than in the male group. Women had a lower likelihood of a positive cQFR ≤0.80 for the same degree of stenosis and a lower rate of NIRA revascularization. Independent predictors of positive cQFR included male sex and diameter stenosis (DS) >70%.Conclusions: cQFR values differ between the sexes, as women have a higher cQFR value for the same degree of stenosis. The findings suggest that QFR variations by sex require specific interpretation, as these differences may affect therapeutic decision-making and clinical outcomes.

Diagnostic performance of miR-214, BNP, NT-proBNP and soluble ST2 in acute heart failure.

This study aimed to investigate the potential diagnostic value of miR-214, B-type natriuretic peptide (BNP), N terminal-pro BNP (NT-proBNP) and soluble ST2 (sST2) in acute heart failure (AHF). This study included 176 patients as the AHF group and 60 healthy subjects as the control group from February 2018 to February 2020. Patients in the AHF group were classified according to the New York Heart Association (NYHA) functional classification, including 60 level II patients, 59 level III patients and 57 level IV patients. The expression level of miR-214, BNP, NT-proBNP and sST2 of both groups were recorded and analysed. The morbidity of cardiovascular diseases was significantly higher in the AHF group than in the control group (P<.05). The expression level of miR-214, BNP, NT-proBNP and sST2 in the AHF group were all significantly higher than in the control group (P<.05). Besides, the expression level of all the molecules in level IV was significantly higher than that of level III and level II, respectively (P<.001, P<.001). In addition, the expression level of all the molecules in level III was significantly higher than that of level II (P<.001). The area under the ROC curve of miR-214, BNP, NT-proBNP and sST2 were 0.913, 0.836, 0.849 and 0.855, respectively, indicating good diagnostic value. MiR-214, BNP, NT-proBNP and sST2 can be used as effective biomarkers for AHF, providing a new strategy for diagnosis and for judging the severity of AHF.

Evaluation of the Role of Routine Laboratory Biomarkers in COVID-19 Patients: Perspective from a Tertiary Care Hospital in India.

To evaluate the role of routine laboratory biomarkers like C Reactive Protein (CRP), Lactate Dehydrogenase (LDH), Interleukin 6 (IL6), Ferritin, Creatinine, Procalcitonin (PCT), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Serum Albumin, Total Bilirubin (T Bil), High Sensitive Troponin I (hs troponin I), N Terminal-pro B-type Natriuretic Peptide (NT proBNP), Blood Urea Nitrogen (BUN) and Blood Gases in COVID 19 patients who are admitted with SARS CoV-2 positive test results by real-time reverse transcriptase polymerase chain reaction (rRT PCR) in Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute, Mumbai, India. 100 individuals detected with COVID-19 belonging to the age group 12–83 years (median age 62 years) within the period of 1st March 2020 to 10th July 2020 were studied. The case group consisted of 72 males and 28 females. 40 healthy adults without any history or clinical evidence suggestive of COVID-19 and without any comorbidities, like diabetes, hypertension chronic lung disease, cardiac disease, cancer, and immune-compromised individuals were considered as a control group for the study. Routine laboratory findings of these 100 patients were used to evaluate the abnormalities found in COVID-19 patients. Statistical analysis was carried out on the data after determining whether the data had a normal/log-normal distribution and their significance was determined by calculating the p-value. The percentage of patients showing a decrease or increase from the normal value was calculated. Trend analysis was carried out for the 100 patients considered in the case group. Among them, 6 patients were used as representatives to show the trend in these biomarkers during the course of hospital stay. These 5 severe cases consisted of 2 adult males, 2 adult females, and 1 adolescent girl. This selection is to demonstrate the representation of COVID-19 infection in adult males and females and pediatric multisystem inflammatory syndrome associated with COVID-19 in the younger age group. One mild case (adult male) was also selected in the case study. We found a significant increase in mean values of AST, ALT, Total Billirubin, Creatinine, CRP, PCT, LDH, IL6, Ferritin, Lactate, hsTroponin I, NT Pro BNP and decrease in mean values of Albumin, SO2, and PO2 in COVID 19 cases than control. We applied Receiver Operating Curve (ROC) curve to discriminate case population more precisely than the control population. Therefore, Routine laboratory biomarkers appear to play a significant role in COVID-19 patients.

Clinical Efficacy and Safety of Shensong Yangxin Capsule-Amiodarone Combination on Heart Failure Complicated by Ventricular Arrhythmia: A Meta-Analysis of Randomized Controlled Trials.

Background: Shensong Yangxin capsule (SSYX) is a well-known traditional Chinese patent medicine for treating arrhythmia. Recently, a flurry of randomized controlled trials (RCTs) of SSYX combined with amiodarone (SSYX-amiodarone) was reported in the treatment of heart failure (HF) complicated by ventricular arrhythmia (VA) in China. However, these RCTs have not been systematically evaluated. Therefore, this study aimed to evaluate the efficacy and safety of SSYX-amiodarone in the treatment of heart failure complicated by ventricular arrhythmia (HF-VA). Methods: Seven electronic literature databases (the Cochrane Library, PubMed, EMBASE, China Biomedical database web, China National Knowledge Infrastructure Databases, Chinese Scientific Journal database and Wanfang database) were searched from their inceptions to June 1, 2020 to identify RCTs of SSYX-amiodarone in the treatment of HF-VA. The primary outcomes included the total effective rate and adverse events (ADRs). The secondary outcomes included the frequency of ventricular premature complexes, left ventricular ejection fraction, N terminal pro Btype natriuretic peptide (NT-proBNP), and QT dispersion (QTd). The quality of the included RCTs was assessed using the Cochrane risk-of-bias tool. All data was analyzed using RevMan 5.3 software. The registration number of this protocol is PROSPERO CRD42020196689. Results: There are Eighteen trials involving 1,697 patients were included in this study. Meta-analysis showed that SSYX-amiodarone group was superior to the amiodarone group in improving the total effective rate [RR = 1.21; 95%CI (1.16, 1.27); p < 0.01], meanwhile reducing the ADRs [RR = 0.65; 95%CI (0.45, 0.95); p = 0.03], VPCs [MD = 170.96; 95%CI (159.88, 182.04); p < 0.01] and QTd [MD = 8.39; 95%CI (6.91, 9.87); p < 0.01]. No significant difference of enhancing LVEF [MD = 4.32; 95%CI (−0.56, 9.20); p = 0.08] and reducing NT-proBNP [SMD = 0.17; 95%CI (−0.81, 1.14); p = 0.73] was observed between SSYX-amiodarone and amiodarone group. Conclusions: Despite the apparent positive findings reported, the evidence provided by this meta-analysis was still insufficient to support the routine use of SSYX-amiodarone for HF-VA due to the poor methodological quality of included studies. The overall effect should to be verified in further through more well-design clinical studies with reasonable sample and good methodological quality.

The effects of saxagliptin on cardiac structure and function using cardiac MRI (SCARF)

A recent large cardiovascular outcome trial in patients with type 2 diabetes (T2DM) demonstrated excess heart failure hospitalization with saxagliptin. We sought to evaluate the impact of saxagliptin on cardiac structure and function using cardiac magnetic resonance imaging (CMR) in patients with T2DM without pre-existing heart failure. In this prospective study, patients with T2DM without heart failure were prescribed saxagliptin as part of routine guideline-directed management. Clinical assessment, CMR imaging and biomarkers were assessed in a blinded fashion and compared following 6months of continued treatment. The primary outcome was the change in left ventricular (LV) ejection fraction (LVEF) after 6months of therapy. Key secondary outcomes included changes in LV and right ventricular (RV) end-diastolic volume, ventricular mass, LV global strain and cardiac biomarkers [N terminal pro B-type natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hsCRP)] over 6 months. The cohort (n = 16) had a mean age of 59.9years with 69% being male. The mean hemoglobin A1c (HbA1c) was 8.3%. Mean baseline LVEF was 57% ± 3.4, with no significant change over 6months (- 0.2%, 95% CI - 2.5, 2.1, p = 0.86). Detailed CMR analyses that included LV/RV volumes, LV mass, and feature tracking-derived strain showed no significant change (all p > 0.50). NT-proBNP and hsCRP levels did not significantly change (p > 0.20). In this cohort of stable ambulatory patients with T2DM without heart failure, saxagliptin treatment was not associated with adverse ventricular remodeling over 6months as assessed using CMR and biomarkers.

N Terminal-Pro B Type Natriuretic Peptide (NT- PRO BNP) levels and severity of disease in elderly with heart failure

Background: Heart failure is a major health problem in the world. It is associated with high morbidity and high mortality especially in elderly patients. Most studies reported using N terminal pro-B type natriuretic peptide (NT-proBNP) in diagnosis of heart failure, but about of these tests in determining classification of severity of heart failure in the elderly remain unclear.Objective: To determine the differences NT-pro BNP levels based on the severity of diease of heart failure in elderly patients.Methods: This is an observational study with cross sectional design. Subjects were patients with diagnosed heart failure and aged = 60 years. Patients were divided into two groups, mild and severe heart failure groups according to severity of heart failure in New York Heart Association (NYHA) class. The NT Pro-BNP levels were measured for all subjects in both groups. Data was analyzed with using unpaired t test and was considered significant if p Results: This study involved 24 subjects, consisting of 2 gorups, there were mild heart failure groups (NYHA class I-II) and groups of patients with severe heart failure (NYHA III-IV). The mean age of the subjects was 64.50 ± 4.65 years with a minimum age of 60 years and a maximum of 78 years. The NT pro-BNP levels in the severe heart failure group (1.2587.58 ± 574.85 pg / ml) was higher than the mild heart failure group (867.83 ± 333.27 pg / ml), it was statistically significant with p = 0.040.Conclusion: The levels of NT-pro BNP serum in elderly patients with severe heart failure (NYHA III-IV) were significantly higher than in patients with mild heart failure (NYHA I-II).

Heart Failure Results in Inspiratory Muscle Dysfunction Irrespective of Left Ventricular Ejection Fraction

Background: Exercise intolerance in heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) results from both cardiac dysfunction and skeletal muscle weakness. Respiratory muscle dysfunction with restrictive ventilation disorder may be present irrespective of left ventricular ejection fraction and might be mediated by circulating pro-inflammatory cytokines. Objective: To determine lung and respiratory muscle function in patients with HFrEF/HFpEF and to determine its associations with exercise intolerance and markers of systemic inflammation. Methods: Adult patients with HFrEF (n = 22, 19 male, 61 ± 14 years) and HFpEF (n = 8, 7 male, 68 ± 8 years) and 19 matched healthy control subjects underwent spirometry, measurement of maximum mouth occlusion pressures, diaphragm ultrasound, and recording of transdiaphragmatic and gastric pressures following magnetic stimulation of the phrenic nerves and the lower thoracic nerve roots. New York Heart Association (NYHA) class and 6-min walking distance (6MWD) were used to quantify exercise intolerance. Levels of circulating interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured using ELISAs. Results: Compared with controls, both patient groups showed lower forced vital capacity (FVC) (p < 0.05), maximum inspiratory pressure (PI_max), maximum expiratory pressure (PE_max) (p < 0.05), diaphragm thickening ratio (p = 0.01), and diaphragm strength (twitch transdiaphragmatic pressure in response to supramaximal cervical magnetic phrenic nerve stimulation) (p = 0.01). In patients with HFrEF, NYHA class and 6MWD were both inversely correlated with FVC, PI_max, and PE_max. In those with HFpEF, there was an inverse correlation between amino terminal pro B-type natriuretic peptide levels and FVC (r = −0.77, p = 0.04). In all HF patients, IL-6 and TNF-α were statistically related to FVC. Conclusions: Irrespective of left ventricular ejection fraction, HF is associated with respiratory muscle dysfunction, which is associated with increased levels of circulating IL-6 and TNF-α.

Inspiratory muscle dysfunction and restrictive lung function impairment in congenital heart disease: Association with immune inflammatory response and exercise intolerance

BackgroundIn adult patients with congenital heart disease (ACHD), both underlying disease and lung restriction contribute to exercise intolerance. In ACHD the yet incompletely understood mechanism underlying restricted ventilation may be inspiratory muscle weakness. Therefore, this study comprehensively evaluated inspiratory muscle function in ACHD and associations with systemic inflammation and the clinical severity of exercise intolerance. Methods30 ACHD patients (21 men, 35 ± 12 years) and 30 healthy controls matched for age, gender and body mass index underwent spirometry, measurement of mouth occlusion pressures, and diaphragm ultrasound. Six-minute walking distance (6MWD) and New York Heart Association functional class were used to quantify exercise intolerance. Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels were measured using enzyme-linked immunosorbent assays. ResultsACHD patients showed lower forced vital capacity (FVC), and maximum inspiratory (PImax) and expiratory (PEmax) pressures compared with controls (all p < 0.05). On ultrasound, ACHD patients showed a lower diaphragm thickening ratio (2.3 ± 0.5 vs. 2.8 ± 0.9, p < 0.01) and lower diaphragm excursion velocity during a voluntary sniff maneuver (5.7 ± 2.2 vs. 7.6 ± 2.0 cm/s, p < 0.01). Respiratory parameters, such as FVC (r = 0.53; p < 0.01) and PImax (r = 0.43; p = 0.02), correlated with 6MWD. Furthermore, amino terminal pro B-type natriuretic peptide levels were inversely correlated with FVC (r = −0.54; p < 0.01). Circulating pro-inflammatory cytokines were markedly increased, and IL-6 was correlated with 6MWD, dyspnea, and biomarkers of heart, lung and inspiratory muscle function (all p < 0.05). ConclusionsOur findings show that diaphragm dysfunction is present in ACHD and relates to restrictive ventilation disorder and exercise intolerance, possibly mediated by increased IL-6 levels.

Inflammation and Circulating Natriuretic Peptide Levels.

NPs (natriuretic peptides) are cardiac-derived hormones that promote natriuresis, diuresis, and vasodilation. Preclinical evidence suggests that nonhemodynamic triggers for NP release exist, with a few studies implicating inflammatory stimuli. We examined the association between inflammation and NP levels in humans. The associations between inflammation and NP levels were examined in 3 independent studies. First, in 5481 MESA (Multi-Ethnic Study of Atherosclerosis) participants, the cross-sectional (exam 1) and longitudinal (exams 1 to 3) associations between circulating IL6 (interleukin-6) and NT-proBNP (N terminal pro B-type natriuretic peptide) levels were examined in multivariable-adjusted models. Second, in a prospective study of 115 healthy individuals, changes in NP levels were quantified following exposure to lipopolysaccharide as an inflammatory stimulus. Third, in 13 435 hospitalized patients, the association between acute inflammatory conditions and circulating NP levels was assessed using multivariable-adjusted models. At the baseline MESA exam, each 1-unit higher natural log IL6 was associated with 16% higher NT-proBNP level ([95% CI, 10%-22%]; P=0.002). Each 1-unit higher baseline natural log IL6 level also associated with 6% higher NT-proBNP level ([95% CI, 1%-11%]; P=0.02) at 4-year follow-up. In the lipopolysaccharide study, median NT-proBNP levels rose from 21 pg/mL pre-lipopolysaccharide to 54 pg/mL post-lipopolysaccharide, P<0.001. In the hospitalized patient study, acute inflammatory conditions were associated with 36% higher NP levels ([95% CI, 17%-60%]; P<0.001). Inflammation appears to be associated with NP release. Interpretation of NP levels should therefore take into account inflammatory conditions.

2-OR: Impact of N Terminal Pro B-Type Natriuretic Peptide and High Sensitivity Cardiac Troponin on the Prediction of Death and Cardiovascular Events in High-Risk Patients with Type 2 Diabetes

We assessed the relative contributions of N-terminal pro-B-type natriuretic peptide (NTBNP) and high sensitivity cardiac troponin (hsTnT) to the prediction of death and cardiovascular (CV) events in 5597 (with complete data) of 8561 patients with type 2 diabetes (T2DM) and CV disease (CVD) and/or chronic kidney disease (CKD) enrolled in the Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints (ALTITUDE). We analysed Harrell’s C-statistics (Cs) to estimate Cox model performance to predict death (n= 473) and a CV composite outcome (CVCO: CV death, resuscitated cardiac arrest, nonfatal myocardial infarction, stroke or heart failure hospitalization, n= 1129) after a median follow-up of 2.6 years, using a base model (BM) of 19 clinical baseline variables. The Cs for predicting death in the BM (0.724) was augmented by adding hsTnT (0.744, p= 0.002) which was further improved by NTBNP (0.779, p &amp;lt;0.001). Similarly, the BM for predicting CVCO Cs (0.716) was improved by hsTnT (0.732, p= 0.001) and enhanced further by including NTBNP in the model (0.763, p &amp;lt;0.001). Notably, NTBNP by itself was as predictive as BM plus hsTNT for predicting death (both 0.744, p= 1.0) and the CVCO (0.732 vs. 0.721, p= 0.27). In patients with T2DM and CVD or/and CKD, NTBNP was the major prognostic factor and should be considered for risk stratification. Disclosure M.V.B. Malachias: Speaker’s Bureau; Self; Biolab Sanus Farmaceutica, Libbs Farmaceutica. P. Jhund: Advisory Panel; Self; Cytokinetics Inc. Research Support; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Novartis AG. Other Relationship; Self; AstraZeneca. B. Claggett: None. M.O. Wijkman: None. R. Bentley-Lewis: Consultant; Self; Novo Nordisk Inc. Research Support; Self; Janssen Pharmaceuticals, Inc. P.C. Brunel: Consultant; Self; Novartis AG. N. Chaturvedi: Consultant; Self; AstraZeneca. A.S. Desai: Consultant; Self; Abbott, Alnylam Pharmaceuticals, AstraZeneca, Biofourmis, Boehringer Ingelheim Pharmaceuticals, Inc., Boston Scientific, DalCor Pharmaceuticals, Merck &amp; Co., Inc., Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Relypsa, Inc. Research Support; Self; Alnylam Pharmaceuticals, AstraZeneca, Novartis Pharmaceuticals Corporation. S.M. Haffner: None. H.D. Parving: None. M.F. Prescott: Employee; Self; Novartis Pharmaceuticals Corporation. S. Solomon: Consultant; Self; AstraZeneca, Theracos, Inc. Research Support; Self; AstraZeneca, Theracos, Inc. D. de Zeeuw: Advisory Panel; Self; AbbVie Inc., Bayer AG, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Janssen Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation. J.J. McMurray: Other Relationship; Self; AbbVie Inc., Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Bristol-Myers Squibb, Cardurion, GlaxoSmithKline plc., Novartis Pharmaceuticals Corporation, Theracos, Inc. M.A. Pfeffer: Consultant; Self; AstraZeneca, CinCor, Correvio, Corvidia, DalCor Pharmaceuticals, GlaxoSmithKline plc., Innovative Science, Jazz Pharmaceuticals, MyoKardia, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., PharmaScience, Sanofi US, Servier, Takeda Development Center Americas, Inc. Research Support; Self; Novartis Pharmaceuticals Corporation. Funding Novartis Pharmaceuticals (NCT00549757)

Clinical Analysis of Cardiac Involvement in 53 Patients With Multiple Myeloma Coexistent With Light Chain Amyloidosis

BackgroundWe identified 53 patients with multiple myeloma (MM) who had biopsy evidence of light chain amyloidosis (AL), and studied their cardiac involvement and outcomes. Patients and MethodsOur cohort consisted of 53 patients in whom MM and AL were initially diagnosed from July 1, 2006 to June 30, 2016.The diagnosis of MM required > 10% of clonal plasma cells in bone marrow and 1 of the CRAB symptoms, meanwhile, the diagnosis of AL must meet pathologic diagnostic criteria and monoclonal immunoglobulin light chain. Echocardiograms and cardiac biomarker such as N terminal pro B-type natriuretic peptide was used for evaluation of cardiac damage on the baseline and before every cycle of the regimen. ResultsThere were 36 men and 17 women with a median age of 59 years; their main organ involvement was kidney (72%) and heart (62%). Of these, 22 patients were treated with a bortezomib-based regimen, and the response rate was more effective than the other 21 patients who received non-bortezomib-based regimens (64% vs. 29%). The median overall survival (OS) for the total cohort was 12 months (P < .05). The median OS of the MM cohort with International Staging System stage I and II together was 34 months, which was longer than that of patients with stage III of 8 months. The median OS in Mayo stages I, II, and III was 38, 8, and 1 months, respectively (P < .05). Cardiac involvement significantly adversely affected survival (6 vs. 40 months), as did systolic blood pressure (< 90 mmHg, 3 vs. 8.5 months). ConclusionsPatients coexistent with MM and AL is rare; AL has a negative impact on survival for the total cohort. Especially, cardiovascular dysfunction caused by AL maybe a major determinant of shortening survival.

Relation of Dietary Sodium Intake With Subclinical Markers of Cardiovascular Disease (from MESA)

The associations between dietary sodium intake and markers of subclinical cardiovascular disease (CVD), such as high-sensitivity cardiac troponin T (hs-cTnT) and amino terminal pro b-type natriuretic peptide (NT-proBNP), may provide mechanistic insight into the relation between dietary sodium and cardiovascular events. We studied 6,131 participants of the Multi-Ethnic Study of Atherosclerosis, who were free of clinical CVD at baseline. Food frequency questionnaires were used to assess estimated sodium intake (ESI) at baseline. We tested the associations between 5 quintiles of ESI (quintile 1: 0.2 to 1.3 grams/day, quintile 2: 1.3 to 1.8 grams/day, quintile 3: 1.8 to 2.4 grams/day, quintile 4: 2.4 to 3.2 grams/day, and quintile 5: 3.2 to 9.9 grams/day) with cross-sectional and 5-year longitudinal change in hs-cTnT and NT-proBNP concentrations. Restricted cubic spline plots were utilized to explore the shape of the associations between ESI and biomarker outcomes. A cross-sectional association between baseline sodium intake and hs-cTnT (but not NT-proBNP) was observed, driven predominantly by a strong positive relation at an intake range of 0.2 to 2.4 g/day. Conversely, a longitudinal association between baseline sodium intake and NT-proBNP (but not hs-cTnT) was observed, driven predominantly by a strong positive relation at intake levels ≥2.4 g/day. In conclusion, temporal shifts in the association between increased ESI and markers of subclinical CVD, hs-cTnT in the short term and NT-proBNP in the longer term, point to the complex pathobiology of the association between sodium intake and CVD. There was also no consistent evidence supporting a J-curve (i.e., excess biomarker values at very low ESI).

Outcomes and Effect of Treatment According to Etiology in HFrEF: An Analysis of PARADIGM-HF

ObjectivesThe purpose of this study was to compare outcomes (and the effect of sacubitril/valsartan) according to etiology in the PARADIGM-HF (Prospective comparison of angiotensin-receptor-neprilysin inhibitor [ARNI] with angiotensin-converting-enzyme inhibitor [ACEI] to Determine Impact on Global Mortality and morbidity in Heart Failure) trial. BackgroundEtiology of heart failure (HF) has changed over time in more developed countries and is also evolving in non-Western societies. Outcomes may vary according to etiology, as may the effects of therapy. MethodsWe examined outcomes and the effect of sacubtril/valsartan according to investigator-reported etiology in PARADIGM-HF. The outcomes analyzed were the primary composite of cardiovascular death or HF hospitalization, and components, and death from any cause. Outcomes were adjusted for known prognostic variables including N terminal pro-B type natriuretic peptide. ResultsAmong the 8,399 patients randomized, 5,036 patients (60.0%) had an ischemic etiology. Among the 3,363 patients (40.0%) with a nonischemic etiology, 1,595 (19.0% of all patients; 47% of nonischemic patients) had idiopathic dilated cardiomyopathy, 968 (11.5% of all patients; 28.8% of nonischemic patients) had a hypertensive cause, and 800 (9.5% of all patients, 23.8% of nonischemic patients) another cause (185 infective/viral, 158 alcoholic, 110 valvular, 66 diabetes, 30 drug-related, 14 peripartum–related, and 237 other). Whereas the unadjusted rates of all outcomes were highest in patients with an ischemic etiology, the adjusted hazard ratios (HRs) were not different from patients in the 2 major nonischemic etiology categories; for example, for the primary outcome, compared with ischemic (HR: 1.00), hypertensive 0.87 (95% confidence interval [CI]: 0.75 to 1.02), idiopathic 0.92 (95% CI: 0.82 to 1.04) and other 1.00 (95% CI: 0.85 to 1.17). The benefit of sacubitril/valsartan over enalapril was consistent across etiologic categories (interaction for primary outcome; p = 0.11). ConclusionsJust under one-half of patients in this global trial had nonischemic HF with reduced ejection fraction, with idiopathic and hypertensive the most commonly ascribed etiologies. Adjusted outcomes were similar across etiologic categories, as was the benefit of sacubitril/valsartan over enalapril. (Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure; NCT01035255)

Progressive Elevation of NT-ProBNP During Chemotherapy Is Related to Asymptomatic Cardiovascular Events in Patients With Multiple Myeloma

BackgroundPatients with multiple myeloma (MM) are at risk of cardiovascular events (CVEs) as a result of disease burden– and treatment-related risk factors. Cardiac biomarkers have been reported to be more sensitive than left ventricular ejection fraction in detecting CVEs. We sought to explore CVEs risk factors in MM patients and to establish sensitive predictors of biomarkers. Patients and MethodsWe studied 116 newly diagnosed MM patients who received chemotherapy in our department. Echocardiograms were examined at baseline and after 4 cycles of treatment, as well as upon clinical suspicion of a cardiac event or after an adjustment of treatment regimens. Cardiac biomarkers, including troponin T, myohemoglobin, and N terminal pro B-type natriuretic peptide (NT-proBNP), were estimated before each cycle and within 24 hours after chemotherapy, which was provided for at least 4 cycles. ResultsThirteen patients (11.2%) experienced CVEs, seven of which were subclinical. There was no significant difference between the CVE group and the non-CVE group in terms of general patient characteristics, MM disease factors, or chemotherapy drugs. The baseline levels of left ventricular ejection fraction and NT-proBNP were comparable between the 2 groups. NT-proBNP levels increased rapidly after chemotherapy and fell to normal levels before administration of the next cycle in all patients (60 pg/mL vs. 446 pg/mL, P < .001). Patients with asymptomatic CVEs showed a significantly higher proportion of progressively elevated NT-proBNP compared to symptomatic CVE and non-CVE patients (57% vs. 0 vs. 6.1%, P = .035). ConclusionThe dynamic change in NT-proBNP may predict early asymptomatic cardiac damage and allow interventional strategies to avoid cardiac decompensation.

Prognostic value of Amino Terminal Pro B-type Natriuretic Peptide (NT-proBNP) in patient with severe sepsis and septic shock in an ICU of tertiary care hospital of Bangladesh.

Background: Severe sepsis and septic shock are the leading cause of ICU admission. Despite the adequate resuscitation, septic shock is frequently associated with multiple system organ failure (MSOF) and death. This study examined the clinical utility of the level of NT-proBNP as an indicator of outcome in severe sepsis and septic shock.Objectives: to find relationship between level of NT-Pro-BNP and the outcome of the patients of severe sepsis and septic shock.Design: This Prospective observational study done in ICU of BIRDEM General Hospital.Method: All consecutive patients who were diagnosed as severe sepsis and septic shock according to SSC (Surviving Sepsis Campaign) guidelines fulfilling the selection criteria were included in the study. Informed written consent was taken from patient’s first degree relatives. Just after admission of severe sepsis and septic shock patients into ICU and development of severe sepsis or septic shock of previously admitted ICU patients, blood sample for serum NT-proBNP level was sent to hospital laboratory. 28 days were taken as follow up period for all patients in this study. Outcome was measured by mortality. Those who were discharged or transferred were classified as survivors and those who were died, categorized as non survivors. Those who were neither discharged nor dead during the study period were classified as survivors. Patient’s resusci-tation and management were done according to the standard ICU protocol of BIRDEM General Hospital.Result: A total 127 of patients fulfilled the criteria of sepsis and septic shock and study inclusion criteria during the study period. The mean &amp; SD of age in this study was 63.69 ± 17.79 years. 52% (n = 66) were male &amp; 48% (n = 61) were female. Here DM was the most common (83.5%) comorbidity and predominant diagnoses were Pneumonia (58.3%) &amp; UTI (30.7%). Among 127 patients, 24.4% (n=31) were in septic shock and 75.6% (n= 96) patients present with severe sepsis. Level of NT-proBNP of severe sepsis patients were 4608.64 ± 7712.12 &amp; Level of NT-proBNP of septic shock patients were 19239.06 ± 13058.05 (P&lt;0.0001). Among 31 (24.4%) septic shock patients, 32.2% (n=10) patients were survivor and NT-proBNP level was 7333.50 ± 10624 pg/ml; 67.8% (n=21) patients were non survivor and NT-proBNP level was 24908.38 ± 10017.87 pg/ml (P &lt;0.001). In this study among 96 (75.6%) patients with severe sepsis, 88.7% (n=86) were survivor and NT-proBNP level was 2436.41 ± 3755.03 pg/ml; 11.3% (n=11) patients were non-survivors and NT-proBNP level was 21238.36 ± 10095.34 pg/ml (P&lt;0.0001).Conclusion: Severe sepsis and septic shock are the leading cause of ICU admission and also leading cause of death. Our study showed that, elderly with diabetes mellitus had developed more sepsis. Pneumonia and UTI are commonest cause of sepsis.Sepsis causes extreme inflammatory reactions involving all organs of whole body including heart, causing release of NT-proBNP. Raised level of this biomarker associated with increased rate of mortality.Bangladesh Crit Care J September 2018; 6(2): 65-70