Aims
HELIOS‐A was a Phase 3, open‐label study of vutrisiran, an RNA interference therapeutic, in patients with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy. This analysis ...evaluated vutrisiran's impact on exploratory cardiac endpoints in HELIOS‐A patients.
Methods and results
Patients were randomized 3:1 to subcutaneous vutrisiran 25 mg every 3 months or intravenous patisiran 0.3 mg/kg every 3 weeks (reference group) for 18 months. Exploratory cardiac endpoints included change from baseline in N‐terminal prohormone of brain‐type natriuretic peptide (NT‐proBNP) and echocardiographic parameters versus external placebo (APOLLO study). The modified intent‐to‐treat (mITT) population comprised randomized patients receiving any study drug (n = 122). A cardiac subpopulation with evidence of cardiac amyloid involvement (n = 40) was prespecified. 99mTc scintigraphy exploratory assessments in a planned vutrisiran‐treated cohort at select sites were compared with baseline. At Month 18, vutrisiran demonstrated beneficial effects on NT‐proBNP versus external placebo in the mITT and cardiac subpopulations (adjusted geometric mean fold change ratio 95% confidence interval 0.480 0.383–0.600, p = 9.606 × 10−10 and 0.491 0.337–0.716, p = 0.0004, respectively). Benefits or trends towards benefit in echocardiographic parameters versus external placebo were observed for both populations. In 99mTc scintigraphy assessments, 32/47 (68.1%) and 31/48 (64.6%) patients exhibited reduced normalized left ventricular total uptake and heart‐to‐contralateral lung ratio, respectively. Perugini grade was reduced or unchanged versus baseline in 55/57 (96.5%) evaluable patients. No increase in cardiac adverse events was observed with vutrisiran versus external placebo.
Conclusions
Vutrisiran demonstrated evidence of potential benefit on cardiac manifestations in patients with ATTRv amyloidosis with polyneuropathy, with an acceptable safety profile.
Vutrisiran demonstrated beneficial effects on N‐terminal prohormone of brain‐type natriuretic peptide (NT‐proBNP) and other prespecified exploratory echocardiographic parameters versus external placebo in both a modified intent‐to‐treat (mITT) population and a cardiac subpopulation at Month 18. In a planned cohort undergoing 99mTc scintigraphy assessments, a majority of vutrisiran‐treated patients experienced reduced or stabilized radiotracer uptake versus baseline. Vutrisiran demonstrated evidence of potential benefit on cardiac manifestations in patients with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy, and an acceptable safety profile, including no cardiac safety concerns. CI, confidence interval; LV, left ventricular; Q3M, every 3 months; SC, subcutaneous. aIn a planned cohort.
•Identified measurement variability in CRP and NT-proBNP.•Highlighted gaps in standardization protocols.•Urged for robust international guidelines.•Advocated for standardized collection protocols.
...The harmonization of laboratory biomarkers is pivotal in ensuring consistent and reliable diagnostic outcomes across different clinical settings. This systematic review examines the harmonization of C-Reactive Protein (CRP) and N-Terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) measurements, both of which are jointly utilized in the diagnosis and management of cardiovascular diseases. To identify relevant studies, we searched the PubMed electronic database using specific medical subject headings and keywords such as C-Reactive Protein, CRP, high sensitivity C-Reactive Protein (hs-CRP), N-terminal pro B-type natriuretic peptide, and NT-proBNP, focusing on publications from June 1 to September 26, 2021. The query filtered studies to include only those in English involving human subjects. From our search, 97 articles met the inclusion criteria and were included for in-depth analysis. Despite their widespread use, significant variability remains in the measurements of CRP and NT-proBNP due to a lack of standardized pre-analytical, analytical, and post-analytical practices. This review highlights the consequences of this variability on clinical decision-making and patient outcomes and emphasizes the need for international standards and guidelines to achieve better harmonization. Our findings advocate for the establishment of universal protocols to enhance the reliability of these biomarker measurements across different clinical environments, ensuring improved healthcare delivery.
Morbidity and mortality of patients with immunoglobulin light chain (AL) amyloidosis are strongly associated with the severity of cardiac involvement, especial in patients with cardiac stage IIIb, ...but the real-world data on these patients is still limited.
A retrospective analysis was conducted on 77 patients diagnosed with cardiac stage IIIb AL amyloidosis at our center. We analyzed the clinical characteristics, treatment and outcome of the patients.
The median age of patients was 57 years and 49.4% were male. Median serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) were 13,384 ng/L and 0.166 ug/L, and 42 (54.5%) patients had heart failure at diagnosis. Fifty-seven (74.0%) patients received antiplasma cell treatment, and the main treatment options include bortezomib or thalidomide combined with dexamethasone. The hematologic overall response rate was 70% (28/40), and at 6-month landmark analysis, patients with hematologic responses had a higher survival rate. Cardiac and renal responses were achieved in 14 (37.8%) and 13 (32.5%) patients, respectively. After a median follow-up of 10 months (range 1-115 months), median overall survival (OS) was 18 months, and the estimated survival rates at 3, 6, and 12 months were 79.9%, 75.6%, and 54.5%, respectively. In Cox regression models, age, hypotension and cTnT were independently predictive of mortality after adjusting for heart failure.
The hematologic, cardiac and renal responses were relative lower in patients with cardiac stage IIIb AL amyloidosis. The overall prognosis of patients was poor, and age, hypotension, and cTnT can be used to predict mortality.
The clinical characteristics, treatment modalities and outcomes of Chinese patients with cardiac stage IIIb AL amyloidosis have not been fully investigated. Through consulting the electronic medical record system and telephone follow-up, we documented hematologic and organ responses after treatment in 77 patients diagnosed at our center. The unsatisfactory prognosis of these patients suggests that a rapid-acting and safe therapy is needed for these patients.
•NT-proBNP and HFABP levels in postmortem urine were compared.•HFABP was significantly elevated in CHF, sepsis, and hyperthermia cases.•NT-proBNP was significantly high in AMI, CHF, sepsis, and ...hyperthermia cases.•Postmortem urinary NT-proBNP and HFABP levels showed a positive correlation.•The degree of HFABP/NTpro-BNP ratio differed between the causes of death.
The clinical use of N-terminal pro-brain natriuretic peptide (NT-proBNP) and blood concentrations of heart-type fatty acid-binding protein (HFABP) is well-established in diagnosing heart conditions. However, their applicability in forensics is controversial due to postmortem changes. NT-proBNP and HFABP are excreted in the urine due to their small molecular weights and may be found in postmortem urine samples; however, their correlation has not been evaluated. In this study, we compared the concentrations of urinary NT-proBNP and HFABP in 386 forensic autopsy cases. The urinary NT-proBNP levels were significantly higher in acute myocardial infarction (AMI), congestive heart failure (CHF), sepsis, and hyperthermia cases, with the highest levels in CHF cases. Similarly, HFABP concentration was significantly higher in CHF, sepsis, and hyperthermia cases, with the highest level observed in hyperthermia cases. However, the difference in urinary HFABP levels between the AMI and control cases was not significant. Our analysis revealed a correlation between postmortem urine NT-proBNP and HFABP levels, and the NT-proBNP/HFABP ratio was high in patients with CHF and sepsis cases and low in those with hyperthermia. The difference between the ratios was possibly due to the combined release of ventricular myocardial cells in response to ventricular wall stress and myocardial injury for NT-proBNP, as well as myocardial and skeletal muscle injuries for HFABP. This study, for the first time, demonstrates the utility of postmortem measurements of urinary NT-proBNP and HFABP levels, offering valuable insights for improving the accuracy of postmortem diagnosis in forensic medicine.
Aim
To investigate the use of biomarkers providing independent information regarding physiology in acutely decompensated heart failure (ADHF) for assessment of risk.
Methods and results
This was a ...prospective study of 107 patients hospitalized with ADHF (mean age 72 ± 13 years, 44% male, left ventricular ejection fraction 47 ± 15%). Blood samples were collected on presentation to measure soluble (s)ST2, high-sensitivity troponin T (hsTnT), and amino-terminal pro-B type natriuretic peptide (NT-proBNP) levels. Clinical follow-up was obtained for all patients over a median period of 739 days, and all-cause mortality was registered. Concentrations of sST2 per 10 ng/mL, hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.04-1.13; P< 0.001, hsTnT (per 0.1 ng/mL, HR 1.16, 95% CI 1.09-1.24; P< 0.001), and NT-proBNP (per 100 pg/mL, HR 1.01, 95% CI 1.003-1.01; P< 0.001) were each predictive of a higher risk of death. In bootstrapped models, each biomarker retained independent predictive value for mortality. Patients with all three biomarkers below their optimal cut-off at presentation were free of death (0%) during follow-up, whereas 53% of those with elevations of all three biomarkers had died. For each elevated marker (from 0 to 3) adjusted analysis suggested a tripling of the risk of death (for each elevated marker, HR 2.64, 95% CI 1.63-4.28, P< 0.001). Integrated discrimination analyses indicated that the use of these three markers in a multimarker approach uniquely improved prediction of death.
Conclusions
Biomarkers reflecting remodelling (sST2), myonecrosis (hsTnT), and myocardial stretch (NT-proBNP) provide complementary prognostic information in patients with ADHF. When used together, these novel markers provide superior risk stratification.
To evaluate left ventricular function and measure N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) levels in women with hypertensive disorders of pregnancy (HDP) in comparison to normotensive ...women and correlate these with maternal and neonatal outcomes. This was a prospective observational case–control study from 2018 to 2020 in an Indian tertiary care hospital and included antenatal women beyond 20 weeks of pregnancy with 160 women with HDP as cases and 160 normotensive women as controls. Echocardiography was performed to assess left ventricular structure and function. Quantitative analysis of NT‐proBNP levels was performed based on fluorescence immunochromatography. Women with HDP were observed to have a significant difference in the value of left ventricular structure and function (P < 0.001). Mild systolic dysfunction was found in 13 (8.1%) women in the HDP group 8 (20%) women with severe pre‐eclampsia and 5 (33.3%) women with eclampsia). Significantly lower values of left ventricular ejection fraction and higher values of NT‐proBNP were recorded in women with HDP who developed maternal complications and had adverse neonatal outcomes (P < 0.001). Echocardiography and NT‐proBNP levels have been shown to have a significant role in women with severe forms of HDP to detect early signs of cardiac dysfunction.
Synopsis
Hypertensive disorders of pregnancy are associated with significant structural and functional left ventricular changes and higher N‐terminal pro b‐type natriuretic peptide levels compared with normotensive women.
Aims
We investigated which serum amino‐terminal pro‐B‐type‐natriuretic peptide (NT‐proBNP) levels inform heart failure (HF) risk in a community‐based population at increased cardiovascular disease ...(CVD) risk.
Methods and results
Inclusion criteria were age ≥ 60 years with one or more of self‐reported hypertension, diabetes, heart disease, abnormal heart rhythm, cerebrovascular disease, or renal impairment. Exclusion criteria were known HF, ejection fraction (EF) < 50%, or more than mild valve abnormality. NT‐proBNP levels were measured in 3842 participants on enrolment. HF was diagnosed in 162 participants at a median of 4.5 (interquartile range 2.7–5.4) years after enrolment, 73 with HF with preserved EF (HFpEF), 53 with HF with reduced EF (HFrEF), and 36 with valvular HF (VHF). Areas under the receiver operating characteristic curve (AUC) for 5‐year prediction of total HF were similar for NT‐proBNP alone (0.79, 95% confidence interval 0.74–0.83) and a 7‐parameter multivariable model (0.82, 0.77–0.86, P = 0.035). NT‐proBNP cut‐points of 11, 16, and 25 pmol/L for individuals aged 60–69, 70–79, and ≥ 80 years, respectively, achieved sensitivities > 76% and specificities of 47–69% for 5‐year prediction of total HF in men and women in all three age groups. Sensitivities were ≥ 75% in most subgroups according to body mass index, estimated glomerular filtration rate, and the presence or absence of atrial fibrillation, pacemaker, or CVD, and for the prediction of HFpEF, HFrEF and VHF.
Conclusion
Age‐specific serum NT‐proBNP levels inform prognosis, and hence therapeutic decisions, regarding HF risk in individuals at increased CVD risk.
Background
Although orthostatic hypotension (OH) is a well‐recognized manifestation of neuropathy and hypovolemia, its contribution to cardiovascular disease (CVD) risk is controversial.
Methods and ...Results
Participants with OH, defined as a decrease in blood pressure (systolic ≥20 mm Hg or diastolic ≥10 mm Hg) from the supine to standing position, were identified during the first visit of the ARIC (Atherosclerosis Risk in Communities) Study (1987–1989) within 2 minutes of standing. All participants were followed up for the development of myocardial infarction, heart failure, stroke, fatal coronary heart disease (CHD), any CHD (combination of silent, nonfatal, and fatal CHD or cardiac procedures), and all‐cause mortality. Participants were assessed for carotid intimal thickness and plaque during the first visit. Detectable high‐sensitivity troponin T (≥5 ng/L) and elevated NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide; ≥100 pg/mL) were determined in blood collected during the second visit (1990–1992). All associations were adjusted for known CVD risk factors. In 9139 participants (57% women; 23% black; mean age, 54±5.7 years), 3% had OH. During follow‐up (median, 26 years), OH was associated with myocardial infarction (hazard ratio HR, 1.88; 95% confidence interval CI, 1.44–2.46), congestive heart failure (HR, 1.65; 95% CI, 1.34–2.04), stroke (HR, 1.83; 95% CI, 1.35–2.48), fatal CHD (HR, 2.77; 95% CI, 1.93–3.98), any CHD (HR, 2.00; 95% CI, 1.64–2.44), and all‐cause mortality (HR, 1.68; 95% CI, 1.45–1.95). OH was also associated with carotid intimal thickness (β, 0.05 mm; 95% CI, 0.04–0.07 mm), carotid plaque (odds ratio, 1.51; 95% CI, 1.18–1.93), detectable high‐sensitivity troponin T (odds ratio, 1.49; 95% CI, 1.16–1.93), and elevated NT‐proBNP (odds ratio, 1.92; 95% CI, 1.48–2.49).
Conclusions
OH identified in community‐dwelling middle‐aged adults was associated with future CVD events and subclinical CVD. Further research is necessary to establish a causal role for OH in the pathogenesis of CVD.
Aims
Anthracyclines increase heart failure (HF) risk, but the long‐term prevalence of myocardial dysfunction in young breast cancer (BC) survivors is unknown. Early measures of left ventricular ...myocardial dysfunction are needed to identify BC patients at risk of symptomatic HF.
Methods and results
Within an established cohort, we studied markers for myocardial dysfunction among 569 women, who were 5–7 years (n = 277) or 10–12 years (n = 292) after BC treatment at ages 40–50 years. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were assessed by echocardiography. N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) was measured in serum. Associations between patient‐related and treatment‐related risk factors and myocardial dysfunction were evaluated using linear and logistic regression. Median ages at BC diagnosis and cardiac assessment were 46.7 and 55.5 years, respectively. Anthracycline‐treated patients (n = 313), compared to the no‐anthracycline group (n = 256), more often had decreased LVEF (10% vs. 4%), impaired GLS (34% vs. 27%) and elevated NT‐proBNP (23% vs. 8%). GLS and LVEF declined in a linear fashion with increasing cumulative anthracycline dose (GLS: +0.23 and LVEF: −0.40 per cycle of 60 mg/m2; P < 0.001) and GLS was worse for patients with left breast irradiation. The risk of NT‐proBNP >125 ng/L was highest for patients who received 241–300 mg/m2 anthracycline dose compared to the no‐anthracycline group (odds ratio: 3.30, 95% confidence interval: 1.83–5.96).
Conclusion
Impaired GLS and increased NT‐proBNP levels are present in a substantial proportion of young BC survivors treated with anthracyclines. Whether this will lead to future cardiac disease needs to be evaluated by longitudinal assessment.
Background
Red blood cell distribution width (RDW) and N‐terminal pro brain natriuretic peptide (NT‐proBNP) may predict the prognosis of heart failure (HF). However, the impact of combined RDW and ...NT‐proBNP levels as a prognostic marker of HF remains unclear and the significance of this combination at various time‐points has not been sufficiently studied.
Hypothesis
RDW can predict prognosis in HF at various time‐points and combination with NT‐proBNP improves the prognostic value.
Methods
Patients admitted to HF care unit of Fuwai Hospital CAMS&PUMC (Beijing, China) with a diagnosis of HF from November 2008 to November 2018 were analyzed retrospectively.
Results
In total, 3231 patients with available RDW data at admission were evaluated (median age 58 years, 71.9% males, 39.7% coronary heart disease, 68.6% New York Heart Association NYHA III or IV). Median RDW and NT‐proBNP at admission were 13.4% (interquartile range IQR: 12.7%–14.5%), and 1723.00 pg/ml (IQR: 754.00–4006.25 pg/ml), respectively. During 2.9‐year median follow‐up, all‐cause death occurred in 1075 (33.27%) patients. Kaplan–Meier survival curve and Cox proportional‐hazard models, showed patients in the top quarter RDW had a 32.0% increased mortality compared to the bottom quarter (hazard ratio: 4.39, 95% confidence interval: 3.59–5.38; p <.001). The top quarter RDW retained independent prognostic value across HF with reduced ejection fraction HFrEF, HF with mid‐range ejection fraction HFmrEF, and HF with preserved ejection fraction HFpEF subgroups. Patients were subsequently divided into four groups by median RDW and NT‐proBNP. Comparison of Kaplan–Meier survival curves for various groups showed good risk stratification (p < .001).
Conclusions
RDW is an independent predictor of mortality among patients with HF in the short‐, medium‐, and long‐term. Combination of RDW and NT‐proBNP improves the prognostic value. This is true across all clinical subtypes of heart failure (HFrEF, HFmrEF, HFpEF), and among most subgroups of patients with various comorbidities (infection, diabetes, hypertension).
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