Patients with nonobstructive hypertrophic cardiomyopathy (nHCM) often experience a high burden of symptoms; however, there are no proven pharmacological therapies. By altering the contractile ...mechanics of the cardiomyocyte, myosin inhibitors have the potential to modify pathophysiology and improve symptoms associated with HCM.
MAVERICK-HCM (Mavacamten in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy) explored the safety and efficacy of mavacamten, a first-in-class reversible inhibitor of cardiac-specific myosin, in nHCM.
The MAVERICK-HCM trial was a multicenter, double-blind, placebo-controlled, dose-ranging phase II study in adults with symptomatic nHCM (New York Heart Association functional class II/III), left ventricular ejection fraction (LVEF) ≥55%, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥300 pg/ml. Participants were randomized 1:1:1 to mavacamten at a pharmacokinetic-adjusted dose (targeting plasma levels of 200 or 500 ng/ml), or placebo for 16 weeks, followed by an 8-week washout. Initial dose was 5 mg daily with 1 dose titration at week 6.
Fifty-nine participants were randomized (19, 21, 19 patients to 200 ng/ml, 500 ng/ml, placebo, respectively). Their mean age was 54 years, and 58% were women. Serious adverse events occurred in 10% of participants on mavacamten and in 21% participants on placebo. Five participants on mavacamten had reversible reduction in LVEF ≤45%. NT-proBNP geometric mean decreased by 53% in the pooled mavacamten group versus 1% in the placebo group, with geometric mean differences of -435 and -6 pg/ml, respectively (p = 0.0005). Cardiac troponin I (cTnI) geometric mean decreased by 34% in the pooled mavacamten group versus a 4% increase in the placebo group, with geometric mean differences of -0.008 and 0.001 ng/ml, respectively (p = 0.009).
Mavacamten, a novel myosin inhibitor, was well tolerated in most subjects with symptomatic nHCM. Furthermore, treatment was associated with a significant reduction in NT-proBNP and cTnI, suggesting improvement in myocardial wall stress. These results set the stage for future studies of mavacamten in this patient population using clinical parameters, including LVEF, to guide dosing. (A Phase 2 Study of Mavacamten in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy MAVERICK-HCM; NCT03442764).
Aims
We examined the prognostic importance of N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) and troponin T (TnT) in heart failure patients with and without diabetes.
Methods and results
We ...measured NT‐proBNP and TnT in the biomarker substudy of the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM‐HF). Of 1907 patients, 759 (40%) had diabetes. Median TnT in patients with diabetes was 18 (interquartile range 11–27) ng/L and 13 (9–21) ng/L in those without (P < 0.001). The TnT frequency‐distribution curve was shifted to the right in patients with diabetes, compared to those without diabetes. By contrast, NT‐proBNP did not differ between patients with and without diabetes. Diabetes and each biomarker were predictive of worse outcomes. Thus, patients with diabetes, an elevated TnT and a NT‐proBNP level in the highest tertile (9% of all patients) had an absolute risk of cardiovascular death or heart failure hospitalization of 265 per 1000 person‐years, compared to a rate of 42 per 1000 person‐years in those without diabetes, a TnT < 18 ng/L and a NT‐proBNP in the lowest tertile (16% of all patients). TnT remained an independent predictor of adverse outcomes in multivariable analyses including NT‐proBNP.
Conclusion
TnT is elevated to a greater extent in heart failure patients with diabetes compared to those without (whereas NT‐proBNP is not). TnT and NT‐proBNP are additive in predicting risk and when combined help identify diabetes patients at extremely high absolute risk.
Aim.
To study the relationship between the level of N-terminal pro-brain natriuretic peptide (NT-proBNP) and myocardial abnormalities in patients with cardiac arrhythmias due to undifferentiated ...connective tissue disease (UCTD).
Material
and
methods.
This cross-sectional comparative study included young and middle-aged patients with arrhythmias due to UCTD: group 1 (18-44 years old, n=127), group 3 (45-59 years old, n=10). The control groups (n=30, group 2; n=8, group 4) included volunteers with single phenotypic signs of UCTD, comparable in age and sex. A standard clinical examination, 72-hour electrocardiographic monitoring, Speckletracking echocardiography, and NT-proBNP level assessment were performed.
Results.
In patients of groups 1 and 3, a significant increase in the concentration of NT-proBNP was noted compared to the control groups. At the same time, the average NT-proBNP level in the study groups did not exceed the reference values. Significant correlations were revealed between NT-proBNP and heart rate (r
1
=0,462, p=0,010; r
3
=0,397, p=0,034), UCTD diagnostic cut-off level (r
1
=0,496, p=0,001; r
3
=0,401, p=0,043), the presence of mitral valve prolapse (r
1
=0,469, p=0,002) and mitral regurgitation (r
1
=0,53, p=0,008), premature ventricular contractions (PVCs) of class III (r
1
=0,582, p=0,045), IVa (r
1
= 0,39, p=0,042) and V (r
1
=0,397, p=0,037); cardiac index (r
1
=-0,329, p=0,037) and ejection fraction (r
1
=-0,407, p=0,044). However, no significant correlation was found between the left ventricular global longitudinal strain and NT-proBNP level.
Conclusion.
The study demonstrated the association of NT-proBNP level with UCTD diagnostic cut-off level, mitral valve prolapse, mitral regurgitation, and PVCs, which makes possible the use of this biomarker as an additional diagnostic criterion for myocardial changes in against the background of UCTD.
Background
Associations of diet with dilated cardiomyopathy are under investigation.
Objectives
That cardiac assessment would show abnormalities in healthy dogs eating grain‐free (GF) diets or diets ...with Food and Drug Administration (FDA)‐listed ingredients of concern (peas, lentils, or potatoes) as top 10 ingredients (FDA‐PLP), but not in dogs eating grain‐inclusive (GI) diets or diets without FDA‐listed ingredients of concern (PLP) in the top 10 ingredients (NoFDA‐PLP).
Animals
One hundred eighty‐eight healthy Doberman Pinschers, Golden Retrievers, Miniature Schnauzers, and Whippets.
Methods
This study was an observational cross‐sectional study. Echocardiograms, cardiac biomarkers, and blood and plasma taurine concentrations were compared between dogs eating GF (n = 26) and GI (n = 162) diets, and between FDA‐PLP (n = 39) and NoFDA‐PLP (n = 149) diets, controlling for age and breed. Demographic characteristics, murmurs, genetic status, and ventricular premature complexes (VPCs) during examination were compared between dogs eating different diet types.
Results
No differences in echocardiographic variables, N‐terminal pro‐B‐type natriuretic peptide or whole blood taurine were noted between dogs eating different diet types. Dogs eating GF diets had higher median high‐sensitivity cardiac troponin I (hs‐cTnI) (GF 0.076 ng/mL Interquartile range (IQR), 0.028‐0.156 vs. GI 0.048 IQR, 0.0026‐0.080; P < .001) and higher median plasma taurine (GF 125 nmol/mL IQR, 101‐148 vs GI 104 IQR, 86‐123; P = .02) than dogs eating GI diets. Dogs eating FDA‐PLP diets had higher median hs‐cTnI (0.059 ng/mL IQR, 0.028‐0.122) than dogs eating NoFDA‐PLP diets (0.048 IQR, 0.025‐0.085; P = .006). A greater proportion of dogs eating FDA‐PLP diets (10%) had VPCs than dogs eating NoFDA‐PLP diets (2%; P = .04).
Conclusions and Clinical Importance
Higher hs‐cTnI in healthy dogs eating GF and FDA‐PLP diets might indicate low‐level cardiomyocyte injury.
Background
Treatment is indicated in dogs with preclinical degenerative mitral valve disease (DMVD) and cardiomegaly (stage B2). This is best diagnosed using echocardiography; however, relying upon ...this limits access to accurate diagnosis.
Objectives
To evaluate whether cardiac biomarker concentrations can be used alongside other clinical data to identify stage B2 dogs.
Animals
Client‐owned dogs (n = 1887) with preclinical DMVD prospectively sampled in Germany, the United Kingdom, and the United States.
Methods
Dogs that met inclusion criteria and were not receiving pimobendan (n = 1245) were used for model development. Explanatory (multivariable logistic regression) and predictive models were developed using clinical observations, biochemistry, and cardiac biomarker concentrations, with echocardiographically confirmed stage B2 disease as the outcome. Receiver operating characteristic curves assessed the ability to identify stage B2 dogs.
Results
Age, appetite, serum alanine aminotransferase activity, body condition, serum creatinine concentration, murmur intensity, and plasma N‐terminal propeptide of B‐type natriuretic peptide (NT‐proBNP) concentration were independently associated with the likelihood of being stage B2. The discriminatory ability of this explanatory model (area under curve AUC, 0.84; 95% confidence interval CI, 0.82‐0.87) was superior to NT‐proBNP (AUC, 0.77; 95% CI, 0.74‐0.80) or the vertebral heart score alone (AUC, 0.76; 95% CI, 0.69‐0.83). A predictive logistic regression model could identify the probability of being stage B2 (AUC test set, 0.86; 95% CI, 0.81‐0.91).
Conclusion and Clinical Importance
Our findings indicate accessible measurements could be used to screen dogs with preclinical DMVD. Encouraging at‐risk dogs to seek further evaluation could result in a greater proportion of cases being appropriately managed.
Intense physical exercise is known to increase cardiac biomarkers; however, it is unclear, whether this phenomenon is physiological, or if it indicates myocardial tissue injury. The aim of our study ...was to investigate the effects of seven consecutive days of excessive endurance exercise on continuous assessment of cardiac biomarkers, function, and tissue injury. During a 7‐day trail‐running competition (Transalpine Run, distance 267.4 km, altitude ascent/descent 15556/14450 m), daily blood samples were obtained for cardiac biomarkers (hs‐TnT, NT‐proBNP, and suppression of tumorigenicity‐2 protein (ST2)) at baseline, after each stage and 24–48 h post‐race. In addition, echocardiography was performed every second day, cardiac magnetic resonance imaging (CMR) before (n = 7) and after (n = 16) the race. Twelve (eight males) out of 17 healthy athletes finished all seven stages (average total finish time: 43 ± 8 h). Only NT‐proBNP increased significantly (3.6‐fold, p = 0.009) during the first stage and continued to increase during the race. Hs‐TnT revealed an incremental trend during the first day (2.7‐fold increase, p = 0.098) and remained within the pathological range throughout the race. ST2 levels did not change during the race. All cardiac biomarkers completely returned to physiological levels post‐race. NT‐proBNP kinetics correlated significantly with mild transient reductions in right ventricular function (assessed by TAPSE, tricuspid annular plane systolic function; r = −0.716; p = 0.014). No significant echocardiographic changes in LV dimensions, LV function, or relevant alterations in CMR were observed post‐race. In summary, this study shows that prolonged, repetitive, high‐volume exercise induced a transient, significant increase in NT‐proBNP associated with right ventricular dysfunction without corresponding left ventricular functional or structural impairment.
Aims
There is a lack of specific studies assessing the impact of natriuretic peptide monitoring in the post‐discharge management of patients with heart failure (HF) and preserved ejection fraction ...(HFpEF), throughout the vulnerable phase following acute HF hospitalization. The NICE study aims to assess the clinical benefit of incorporating N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) into the post‐discharge management of HFpEF patients.
Methods and results
Individuals admitted with HFpEF (left ventricular ejection fraction >50%) were included in a multicentre randomized controlled study employing an open‐label design with event blinding (NCT02807168). Upon discharge, 157 patients were randomly allocated to either NT‐proBNP monitoring (n = 79) or no access to NT‐proBNP (control group, n = 78) during pre‐scheduled visits at 2, 4 and 12 weeks. Clinical endpoints were evaluated at 6 months. The primary endpoint of HF rehospitalizations occurred in 12.1% patients, without significant differences observed between the NT‐proBNP monitoring group (12.8%) and the control group (11.4%) (hazard ratio HR 1.15, 95% confidence interval CI 0.47–2.81, p = 0.760). Regarding secondary endpoints, the NT‐proBNP monitoring group demonstrated a significantly lower risk of death (1.3% vs. 10.1%; HR 0.12, 95% CI 0.02–0.98; p = 0.048), whereas non‐HF hospitalizations (12.8% vs. 19.0%, p = 0.171) and any adverse clinical event (26.9% vs. 36.7%, p = 0.17) did not reach statistical significance Correction added on 29 April 2024, after first online publication: In the preceding sentence, “95% CI 0.02 ‐ 0.09” has been corrected to “95% CI 0.02 ‐ 0.98; p = 0.048” in this version.. Awareness of NT‐proBNP levels were associated with higher doses of diuretics and renin–angiotensin system inhibitors (angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers) in the NT‐proBNP monitoring group.
Conclusions
Post‐discharge monitoring of NT‐proBNP in HFpEF patients did not exhibit an association with reduced rates of HF hospitalization in this study. Nonetheless, it appears to enhance global clinical management by optimizing medical therapies and contributing to improved overall survival.
Effects of incorporating N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) into clinical visits during the post‐discharge period of patients with heart failure (HF) and preserved ejection fraction (HFpEF). ACEi, angiotensin‐converting enzyme inhibitor; AHF, acute heart failure; ARB, angiotensin II receptor blocker; i.v. intravenous; LVEF, left ventricular ejection fraction.
Background: Heart failure (HF) is one of the leading causes of hospitalizations in both developed as well as developing nations. The natriuretic peptide N-terminal pro-BNP (NT-proBNP) has long been ...used for diagnosing and managing HF. The study aimed to determine the correlation of NT-proBNP levels with clinical and echocardiographic features in evaluation of patients admitted with heart failure. Methods: This is retrospective observational study of 37 patients admitted to the hospital with acute onset dyspnea, over a period of 18 months. In addition to detailed history and physical examination, complete blood counts, random blood sugar, blood biochemistry, and electrocardiography (ECG), bedside echocardiography and x-ray chest were performed on admission to the hospital. Measurement of serum NT-proBNP level was performed as part of evaluation of dyspnea. Results: Average age of the study population was 64 years. The co morbidities among the patients were hypertension (91%), diabetes mellitus (68%), obstructive airway disease (21%), coronary artery disease (16%) and chronic kidney disease (4%). The mean NT-proBNP for each group was LVEF ≥ 50%= 2272, LVEF 40–49% = 8161.5, and LVEF < 40% = 17302.7 (pg/ml). Conclusion: NT-proBNP levels are proven to be useful in diagnosing and management of heart failure. However, the levels can be affected by many factors such as age, renal function, anaemia and body mass. When interpreting NT-proBNP levels, these factors have to be taken into account while making clinical decision and initiation of appropriate therapy.
Objective
To investigate the association between N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and changes in cognition and global brain structure.
Methods
In the Rotterdam Study, baseline ...NT‐proBNP was assessed at baseline from 1997 to 2008. Between 1997 and 2016, participants without dementia or stroke at baseline (n = 9566) had repeated cognitive tests (every 3–6 years) for global cognitive function, executive cognitive function, fine manual dexterity, and memory. Magnetic resonance imaging of the brain was performed repeatedly at re‐examination visits between 2005 and 2015 for 2607 participants to obtain brain volumes, focal brain lesions, and white matter microstructural integrity as measures of brain structure.
Results
Among 9566 participants (mean age 65.1 ± 9.8 years), 5444 (56.9%) were women, and repeated measures of cognition were performed during a median follow‐up time of 5.5 (range 1.1–17.9) years, of whom 2607 participants completed at least one brain imaging scan. Higher levels of NT‐proBNP were associated with a faster decline of scores in the global cognitive function (p value = 0.003) and the Word‐Fluency test (p value = 0.003) but were not related to a steeper deterioration in brain volumes, global fractional anisotropy, and mean diffusivity, as indicators of white matter microstructural integrity, or focal brain lesions.
Conclusions
Higher baseline NT‐proBNP levels were associated with a faster decline in cognition; however, no association with global brain structure was found.
Background: Despite comprehensive study, the aetiology of stroke is not identified in 35% of cases. Aims: We conducted a study to assess the diagnostic capacity of N-terminal pro-B-type natriuretic ...peptide (NT-proBNP) in the identification of ischaemic stroke of cardioembolic origin. The secondary purpose of the study was to evaluate the prognostic value of NT-proBNP for predicting 90-day all-cause mortality. Methods: We designed a prospective observational study including patients hospitalised due to stroke between March 2019 and March 2020. Blood samples were collected on admission to the emergency department and serum NT-proBNP levels were determined. Statistical analysis was performed using a bivariate logistic regression model and receiver operating characteristic (ROC) and Kaplan–Meier curves. Statistical significance was established at p < .05. Results: The study included 207 patients with first ischaemic stroke. Plasma NT-proBNP levels were significantly higher (p < .001) in the cardioembolic stroke group (2069 pg/mL ± 488.5). ROC curves showed that NT-proBNP > 499 pg/mL was the optimum value for diagnosing cardioembolic ischaemic stroke (sensitivity, 82%; specificity, 80%). Moreover, plasma NT-proBNP levels > 499 pg/mL were independently associated with cardioembolic stroke (OR: 9.881; p = .001). Finally, NT-proBNP > 1500 pg/mL was useful for predicting 90-day mortality (sensitivity, 70%; specificity, 93%). Conclusions: NT-proBNP was independently associated with cardioembolic stroke and should be quantified in blood tests within 24 h of stroke onset. High plasma levels (>499 pg/mL) may indicate an underlying cardioembolic cause, which should be further studied, while NT-proBNP >1500 pg/mL was associated with increased 90-day mortality. Resumen: Introducción: A pesar de un completo y exhaustivo estudio, la etiología de un 35% de los ictus isquémicos es desconocida. Objetivos: Evaluar la capacidad de diagnóstico del NT-proBNP en la identificación del ictus isquémico de origen cardioembólico. El objetivo secundario fue evaluar el valor pronóstico del NT-proBNP como predictor de mortalidad de cualquier causa tras 90 días del ictus. Métodos: Diseñamos un estudio observacional prospectivo, incluyendo pacientes hospitalizados por ictus. El periodo de reclutamiento fue de marzo de 2019 a marzo de 2020. Se obtuvieron muestras de sangre a su admisión en Urgencias y se midieron los niveles plasmáticos de NT-proBNP. El análisis estadístico fue realizado mediante un modelo bivariado de regresión logística, curva de la característica operativa del receptor (curvas ROC) y curvas Kaplan-Meier. Se consideraron significativas diferencias con p < 0,05. Resultados: Fueron incluidos 207 pacientes con un primer episodio de ictus isquémico agudo. Los niveles de NT-proBNP fueron significativamente mayores (p < 0,001) en el grupo de ictus isquémico cardioembólico (2.069 ± 488,5). Las curvas ROC mostraron que un NT-proBNP > 499 pg/mL es el valor óptimo para el diagnóstico de ictus isquémico cardioembólico (sensibilidad 82%, especificidad 80%). Además, los niveles plasmáticos de NT-proBNP > 499 pg/mL estaban asociados de forma independiente con el ictus isquémico cardioembólico (OR = 9.881, p = 0,001). Finalmente, un valor de NT-proBNP > 1.500 pg/mL fue útil para predecir la mortalidad de cualquier causa 90 días tras el ictus isquémico (sensibilidad = 70%, especificidad = 93%). Conclusiones: El valor de NT-proBNP estaba asociado independientemente al ictus isquémico de origen cardioembólico y debería ser considerado su análisis en las primeras 24 h desde el inicio del ictus. Niveles elevados (NT-proBNP > 499 pg/mL) pueden indicar un origen cardioembólico subyacente, el cual debería ser estudiado con mayor detalle, mientras que niveles de NT-proBNP > 1.500 pg/mL se asociaron con un incremento de la mortalidad a los 90 días del ictus.
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