Aims
Dapagliflozin reduced the risk of the composite of cardiovascular (CV) death or hospitalization for heart failure (HHF) in patients with type 2 diabetes mellitus in DECLARE‐TIMI 58. We ...hypothesized that baseline N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) and high‐sensitivity troponin T (hsTnT) levels would help identify patients who are at higher baseline risk and we describe the treatment effects of dapagliflozin in patients according to their baseline NT‐proBNP and hsTnT levels.
Methods and results
This was a pre‐specified biomarker study from DECLARE‐TIMI 58, a randomized, double‐blind, placebo‐controlled CV outcomes trial of dapagliflozin. Baseline NT‐proBNP and hsTnT levels were measured in the TIMI Clinical Trials Laboratory in 14 565 patients. Among the included patients, 9143 patients (62.8%) were male, 1464 (10.1%) had a history of heart failure and the mean age was 63.9 years. The median baseline NT‐proBNP and hsTnT levels were 75 pg/mL interquartile range (IQR) 35–165 and 10.2 pg/mL (IQR 6.9–15.5), respectively. Patients with higher NT‐proBNP and hsTnT quartiles had higher rates of CV death/HHF (Q4 vs. Q1: NT‐proBNP: 4‐year Kaplan–Meier event rates 13.7% vs. 1.0%; hsTnT: 11.8% vs. 1.4%; P‐trend <0.001). Dapagliflozin consistently reduced the relative risk of CV death/HHF regardless of baseline NT‐proBNP (P‐interaction 0.72) or hsTnT quartiles (P‐interaction 0.93). Given their higher baseline risk, patients with NT‐proBNP and/or hsTnT levels above the median derived larger absolute risk reductions with dapagliflozin (NT‐proBNP 1.9% vs. 0%, P‐interaction 0.010; hsTnT 1.8% vs. 0.1%, P‐interaction 0.026).
Conclusion
Patients with type 2 diabetes mellitus and higher NT‐proBNP or hsTnT levels are at increased risk of CV death and HHF. Dapagliflozin reduced the relative risk of CV death/HHF irrespective of NT‐proBNP and hsTnT levels, with greater absolute risk reductions seen in patients with higher baseline biomarker levels.
Summary
Kawasaki disease (KD) vasculitis is an acute febrile illness of childhood characterized by systemic vasculitis of unknown origin, and is the most common cause of acquired heart disease among ...children in the United States. While histological evidence of myocarditis can be found in all patients with acute KD, only a minority of patients are clinically symptomatic and a subset demonstrate echocardiographic evidence of impaired myocardial function, as well as increased left ventricular mass, presumed to be due to myocardial edema and inflammation. Up to a third of KD patients fail to respond to first‐line therapy with intravenous immunoglobulin (IVIG), and the use of interleukin (IL)‐1 receptor antagonist (IL‐1Ra, anakinra) is currently being investigated as an alternative therapeutic approach to treat IVIG‐resistant patients. In this study, we sought to investigate the effect of IL‐1Ra on myocardial dysfunction and its relation to myocarditis development during KD vasculitis. We used the Lactobacillus casei cell‐wall extract (LCWE)‐induced murine model of KD vasculitis and investigated the effect of IL‐1Ra pretreatment on myocardial dysfunction during KD vasculitis by performing histological, magnetic resonance imaging (MRI) and echocardiographic evaluations. IL‐1Ra pretreatment significantly reduced KD‐induced myocardial inflammation and N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) release. Both MRI and echocardiographic studies on LCWE‐injected KD mice demonstrated that IL‐1Ra pretreatment results in an improved ejection fraction and a normalized left ventricular function. These findings further support the potential beneficial effects of IL‐1Ra therapy in preventing the cardiovascular complications in acute KD patients, including the myocarditis and myocardial dysfunction associated with acute KD.
Here we show that similar to what is observed in children with Kawasaki Disease (KD), LCWE‐induced KD vasculitis in mice is also associated with myocarditis and myocardial dysfunction with ventricular enlargement. We found that treatment with the IL‐1R antagonist (Anakinra) improved myocardial function, ejection fraction and left ventricular function in this experimental mouse model of KD vasculitis. These findings further support the potential beneficial effects of IL‐1Ra therapy in preventing the cardiovascular complications in acute KD patients, including the myocarditis and myocardial dysfunction associated with acute KD.
Excess risk of adverse outcomes in heart failure with high and low levels of NT-proBNP.
Display omitted
This study investigated excess risk in patients with heart failure with reduced left ...ventricular ejection fraction (HFrEF) with or without elevated levels of NT-proBNP (N-terminal pro-brain natriuretic peptide).
Patients with HFrEF from the NorthStar cohort (n = 1120) were matched on age, sex, and presence of AF (atrial fibrillation/flutter) to five controls without HFrEF from The Danish National Patient Registries. Patients were compared with controls before and after stratification according to baseline NT-proBNP levels, with cutoffs defined as </≥ 600 pg/ml in patients with sinus rhythm and </≥ 900 pg/ml in patients with AF. The primary composite endpoint was a 7-year risk of cardiovascular death or HF admission.
In the HFrEF cohort, 704 patients had high NT-proBNP (median age, 73; mean left ventricular ejection fraction (LVEF), 33%). 416 patients had low NT-proBNP (median age, 65; LVEF, 30%). Patients from both groups were in NYHA class I-III. The primary endpoint occurred in 531 patients (75.4%) with HFrEF and elevated NT-proBNP, and 748 controls (21.3%) (risk difference, 54.2%; 95% confidence interval (CI) 50.7–57.6%). In comparison, it occurred in 199 patients (47.9%) with HFrEF and without elevated NT-proBNP, and 185 controls (8,9%) (risk difference, 38.9%; 95% CI 34.0–43.9%). Risk differences for all secondary endpoints were significant, except for overall mortality in the low NT-proBNP group (risk difference, 3.8%; 95% CI, −0.4–8.0%).
This study identified a significant excess risk in patients with HFrEF across various endpoints, which persisted after stratification into high and low levels of NT-proBNP.
Background and purpose
Atrial fibrillation (AF) often remains undiagnosed in cryptogenic stroke (CS), mostly because of limited availability of cardiac long‐term rhythm monitoring. There is an unmet ...need for a pre‐selection of CS patients benefitting from such work‐up. A clinical risk score was therefore developed for the prediction of AF after CS and its performance was evaluated over 1 year of follow‐up.
Methods
Our proposed risk score ranges from 0 to 16 points and comprises variables known to be associated with occult AF in CS patients including age, N‐terminal pro‐brain natriuretic peptide, electrocardiographic and echocardiographic features (supraventricular premature beats, atrial runs, atrial enlargement, left ventricular ejection fraction) and brain imaging markers (multi‐territory/prior cortical infarction). All CS patients admitted to our Stroke Unit between March 2018 and August 2019 were prospectively followed for AF detection over 1 year after discharge.
Results
During the 1‐year follow‐up, 24 (16%) out of 150 CS patients with AF (detected via electrocardiogram controls, n = 18; loop recorder monitoring, n = 6) were diagnosed. Our predefined AF Risk Score (cutoff ≥4 points; highest Youden's index) had a sensitivity of 92% and a specificity of 67% for 1‐year prediction of AF. Notably, only two CS patients with <4 score points were diagnosed with AF later on (negative predictive value 98%).
Conclusions
A clinical risk score for 1‐year prediction of AF in CS with high sensitivity, reasonable specificity and excellent negative predictive value is presented. Generalizability of our score needs to be tested in external cohorts with continuous cardiac rhythm monitoring.
Occult atrial fibrillation (AF) often remains undiagnosed in cryptogenic stroke (CS), mostly because of limited availability of cardiac long‐term rhythm monitoring. In this prospective study, a clinical risk score for the prediction of AF in CS patients was developed. The Graz AF Risk Score was then evaluated in 150 CS patients, who were followed over 1 year for the diagnosis of AF. Our score reached a high sensitivity and reasonable specificity for predicting AF in CS patients, and had an excellent negative predictive value (98%).
Aim
. To establish the correlations of the soluble suppression of tumorigenicity 2 protein (sST2) and N-terminal pro-brain natriuretic peptide (NT-proBNP) with some clinical and paraclinical ...characteristics of patients with heart failure (HF).
Material and methods
. The study included 130 patients with HF (men — 54, women — 76, mean age, 64,3±8,3 years) from the regional registry of HF patients in the Voronezh Oblast. All patients underwent echocardiography and general clinical investigations. In addition, the serum levels of sST2 and NT-proBNP were determined and their correlations with other parameters were studied.
Results
. The blood level of sST2 in HF patients was 339,8 266;405 pg/ml. In the study sample of patients with HF, sST2 levels correlated with right atrial (r=0,49) and right ventricular (r=0,32) sizes, left ventricular end-diastolic dimension (r=0,34) and volume (r=0,33), left ventricular early diastolic filling rate (r=-0,35), blood calcium level (r=-0,55) and functional class of exertional angina (r=-0,37).
Conclusion
. The data obtained may indicate a pathogenetic relationship between sST2 and systolic and diastolic dysfunction of the left ventricle and right heart.
The introduction of novel biomarkers necessitates their detailed study in patients with different heart failure (HF) phenotypes as part of a personalized approach to assessing the disease severity ...and predicting outcomes.
Aim
. To assessthe activity of following neurohormonal systems: N-terminal probrain natriuretic peptide (NT-proBNP) and galectin-3 in HF with preserved, mildly reduced and reduced ejection fraction (EF).
Material and methods
. In 69 patients with NYHA class II-IV HF, along with a general clinical examination, the level of NT-proBNP and serum galectin-3 was determined by enzyme immunoassay.
Results
. Patients included in the study were divided into 3 groups: preserved EF (HFpEF) — 23 patients, mildly reduced EF (HFmrEF) — 26 patients, and reduced EF (HFrEF) — 20 patients. In patients with HF, the level of galectin-3 did not directly depend on EF, but was associated with NT-proBNP level as follows: there was a tendency to increase the concentration of galectin-3 in the tertile groups of NT-proBNP. Correlation analysis revealed significant feedback (r=-0,41, p<0,05) between galectin-3 and left ventricular EF only in patients with preserved systolic function. In the same group of HFpEF patients, the maximum values of serum galectin-3 indices were noted, reaching 10,5 6,5; 14,5 ng/ml.
Conclusion
. Analysis of neurohormonal activity demonstrated a unidirectional increase in NT-proBNP and galectin-3 in patients with HF, regardless of left ventricular EF, while the maximum values of galetin-3 were observed in patients with HFpEF.
Aims
The TIM‐HF2 study showed less days lost due to unplanned cardiovascular hospitalization or all‐cause death and improved survival in patients randomly assigned to remote patient management (RPM) ...instead of standard of care.
Methods and results
This substudy explored whether the biomarkers mid‐regional pro‐adrenomedullin (MR‐proADM) and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) could be used to identify low‐risk patients unlikely to benefit from RPM, thereby allowing more efficient allocation of the intervention. For 1538 patients of the trial (median age 73 years, interquartile range 64–78 years, 30% female), baseline biomarkers were used to select subpopulations recommended for RPM with various safety endpoints (100%, 98%, 95% sensitivity), and efficacy of RPM was assessed. Both biomarkers were strongly associated with events. The primary endpoint of lost days increased from 1.0% (1.4%) in the lowest to 17.3% (17.6%) in the highest quintile of NT‐proBNP (MR‐proADM). After combining biomarkers to identify patients recommended for RPM with 95% sensitivity, in the most efficient scenario (excluding 27% of patients; NT‐proBNP < 413.7 pg/mL and MR‐proADM < 0.75 nmol/L), the effect of RPM on patients was highly similar to the original trial (ratio of lost days: 0.78, hazard ratio for all‐cause death: 0.68). Number needed to treat for all‐cause death was lowered from 28 to 21. Rates of emergencies and telemedical efforts were significantly lower among patients not recommended for RPM. Biomarker guidance would have saved about 150 h effort/year per 100 patients of the eligible population.
Conclusions
The combined use of MR‐proADM and NT‐proBNP may allow safe, more precise, effective and cost‐saving allocation of patients with heart failure to RPM and warrants further prospective studies.
B-type natriuretic peptide (BNP) is an itch-selective neuropeptide that was shown to play a role in both histaminergic and nonhistaminergic itch in mice. It was also shown that elevated serum BNP is ...linked to increased pruritus in nondiabetic hemodialysis patients. This study examined plasma BNP levels of 77 patients and N-terminal pro-BNP levels of 33 patients with differing types of chronic itch to see whether BNP and N-terminal pro-BNP levels can correlate with itch severity. Plasma BNP and N-terminal pro-BNP levels of all patients with itch correlated with itch numerical rating scale and in particular for patients with chronic pruritus of unknown origin. On the basis of this clinical observation, this study further showed that increasing pathophysiological levels of BNP in mice by intravenous or osmotic pump induced significant scratching. In addition, pharmacological and ablation strategies determined that BNP acts centrally by activating the natriuretic peptide receptor A in the dorsal horn of the spinal cord. These data support that BNP and N-terminal pro-BNP levels are associated with chronic itch and may be used in clinical setting.
Aim
To create and validate a prediction model to identify patients with type 2 diabetes (T2D) at high risk of new‐onset heart failure (HF), including those treated with a sodium‐glucose ...cotransporter‐2 (SGLT2) inhibitor.
Methods
A prediction model was developed from the Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints (ALTITUDE), a trial in T2D patients with albuminuria or cardiovascular disease. We included 5081 patients with baseline N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) measurement and no history of HF. The model was developed using Cox regression and validated externally in the placebo arm of the Canagliflozin Cardiovascular Assessment Study (CANVAS), which included 996 participants with T2D and established cardiovascular disease or high cardiovascular risk, and in patients treated with canagliflozin.
Results
ALTITUDE participants (mean age 64 ± 9.8 years) had a median serum NT‐proBNP level of 157 (25th–75th percentile 70–359) pg/mL. Higher NT‐proBNP level, troponin T (TnT) level and body mass index (BMI) emerged as significant and independent predictors of new‐onset HF in both cohorts. The model further contained urinary albumin‐to‐creatinine ratio, glycated haemoglobin, age, haematocrit, and use of calcium channel blockers. A prediction model including these variables had a C‐statistic of 0.828 (95% confidence interval CI 0.801–0.855) in ALTITUDE and 0.800 (95% CI 0.720–0.880) in CANVAS. The C‐statistic of this model increased to 0.847 (95% CI 0.792–0.902) in patients after 1 year of canagliflozin treatment.
Conclusion
In patients with T2D, higher NT‐proBNP level, TnT level and BMI are independent and externally validated predictors of new‐onset HF, including patients using an SGLT2 inhibitor. This newly developed model may identify patients at high risk of new‐onset HF, contributing to early recognition and possibly prevention.
PDF
