Diagnostic and prognostic value of N-terminal pro B-type natriuretic peptide (NT-proBNP) in patients with chronic aortic regurgitation

doi:10.1016/j.ijcard.2007.07.174

International Journal of Cardiology

Volume 127, Issue 3, 21 July 2008, Pages 321-327

https://doi.org/10.1016/j.ijcard.2007.07.174 Get rights and content

Abstract

Background

BNP and its N-terminal fragment NT-proBNP have proven to be of diagnostic and prognostic value in patients with valvular aortic stenosis. Data regarding those biomarkers in patients with chronic aortic regurgitation (AR) are sparse. Thus it was the aim of the present study to evaluate the diagnostic and the long term prognostic value of NT-proBNP in patients presenting with AR.

Methods and results

This study included 60 patients with isolated AR of varying severity (AR I mild, AR II moderate and AR III severe) and preserved left ventricular function. Patients were followed over a median period of 824 (770–921) days.

NT-proBNP at baseline was related to disease severity and to functional status (161 (70–456) pg/ml in AR I, 226 (100–666) pg/ml in AR II and 1268 (522–5446) pg/ml in AR III (p = 0.003)). Patients (n = 6) experiencing an adverse event had higher NT-proBNP values at baseline as event free survivors (1271 (613–2992) pg/ml vs. 215 (92–534) pg/ml; p = 0.034). The AUC of the ROC curve for NT-proBNP as a predictor for an adverse event was 0.76 (p < 0.036) with an optimised cut-off value of 602 pg/ml. Consequently, in Kaplan–Meier analysis NT-proBNP values dichotomised at this cut-off were able to discriminate patients with an adverse outcome in the entire study group (Log rank 9.98, p = 0.0016) and even better in the conservative group (Log rank 26.92, p < 0.001).

Conclusion

NT-proBNP is linked to disease severity in patients with chronic aortic regurgitation reflecting hemodynamic stress due to volume overload. It provides prognostic information for the clinical outcome and thus might be a useful biomarker for risk stratification.

Section snippets

Background

Aortic regurgitation (AR) is a common heart disease with a relatively high prevalence of 4.9% in the Framingham Heart Study [1] and 10% in the Strong Heart Study [2]. The major therapeutic option is aortic valve replacement (AVR). Even though there are clearly defined indications for aortic valve surgery in patients with aortic regurgitation [3] there are some areas of uncertainty on the optimal timing of AVR. The effect of severity assessed by echocardiography to clinical outcome is unknown,

Patients

This study included 60 consecutive patients recruited from April 2002 until February 2004 who were referred for further evaluation of isolated chronic aortic regurgitation. All patients had preserved or mildly reduced left ventricular function (ejection fraction > 45%) documented by echocardiography. Patients with concomitant moderate or severe mitral regurgitation respectively an aortic stenosis with a maximum flow velocity of more than 200 cm/s were excluded. Functional status was assessed and

Results

A total of 60 patients with chronic aortic regurgitation were included. According to the above mentioned definition 27 patients were classified to have mild AR (AR I), 22 patients moderate AR (AR II) and 11 patients severe AR (AR III). The detailed baseline characteristics of the patients are shown in Table 1. Baseline values of NT-proBNP were related to severity of AR (161 (70–456) pg/ml in AR I, 226 (100–666) pg/ml in AR II and 1268 (522–5446) pg/ml in AR III (p = 0.003)) (Table 1, Fig. 1) and

Discussion

In the present study we could demonstrate that NT-proBNP, a biomarker reflecting myocardial stress, is elevated in patients with chronic aortic regurgitation in relation to severity and to clinical status. Furthermore, it is the first clinical outcome study showing that NT-proBNP assessment in these patients provides prognostic information for an unfavourable clinical course.

The results of our study are confirming and extending data of previously published reports of an elevation of BNP

Conclusion

NT-proBNP is elevated in patients with chronic aortic regurgitation linked to disease severity and functional status of the patients. Elevated values decrease after valve replacement but remain unchanged in conservatively treated patients. Thus NT-proBNP can be used as a biomarker reflecting hemodynamic stress due to volume overload caused by aortic regurgitation. Furthermore, NT-proBNP provides prognostic information for the clinical outcome in patients with isolated aortic regurgitation

Limitations

The main limitation of the present study is the small number of patients included and in consequence the small number of adverse events. Therefore, the results have to be evaluated with caution. Thus, the study needs to be considered as a pilot study warranting larger scaled studies.

Acknowledgements

This study was supported by Roche Diagnostics Germany who provided the assays for NT-proBNP without charge. Special thanks concerns to B. Rabenau and S. Vogt for the tremendous work they have done in the laboratory. Furthermore, we are indebted to A. Berkowitsch for statistical advice.

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The objective of our prospective and multicenter study is to determine whether patients at risk of early clinical deterioration as per CMR assessment will benefit from early surgical treatment. The study is designed as a superiority trial to demonstrate that early surgical treatment is safe and more effective than the standard treatment. A total of 217 asymptomatic patients with severe AR, but without current guidelines-based surgical indication, will be enrolled across all centers. We expect 24 % of patients identified as high clinical risk and therefore eligible for 1:1 randomization to early surgical treatment within 3 months or a watchful waiting strategy. Follow-up will be annual. We expect a complete restoration of LV size and function along with improved quality of life and physical performance in a short-term follow-up of 12 months. The primary endpoint will be a composite safety and efficacy with all criteria mandatory: 15 % or larger reduction of baseline CMR-derived LV end-diastolic volume index, LV ejection fraction >50 %, and no major adverse cardiovascular events. The annual follow-up will continue for a minimum of 4 years until the required number of endpoints is achieved to show a statistically significant difference in cardiovascular morbidity and mortality in early surgically treated patients.
The ELEANOR trial is the first multicenter randomized controlled study to compare early surgical treatment with a watchful waiting strategy in asymptomatic patients with chronic severe AR at high risk of early clinical deterioration as per CMR assessment but without guidelines-based indications for surgical treatment.
Imaging Methods for Evaluation of Chronic Aortic Regurgitation in Adults: JACC State-of-the-Art Review
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A global multidisciplinary workshop was convened to discuss the multimodality diagnostic evaluation of aortic regurgitation (AR). Specifically, the focus was on assessment tools for AR severity and analyzing evolving data on the optimal timing of aortic valve intervention. The key concepts from this expert panel are summarized as: 1) echocardiography is the primary imaging modality for assessment of AR severity; however, when data is incongruent or incomplete, cardiac magnetic resonance may be helpful; 2) assessment of left ventricular size and function is crucial in determining the timing of intervention; 3) recent evidence suggests current cutpoints for intervention in asymptomatic severe AR patients requires further scrutiny; 4) left ventricular end-systolic volume index has emerged as an additional parameter that has promise in guiding timing of intervention; and 5) the role of additional factors (including global longitudinal strain, regurgitant fraction, and myocardial extracellular volume) is worthy of future investigation.
Optimizing Timing of Valve Intervention in Patients With Asymptomatic Severe Valvular Heart Disease
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The management of valvular heart disease has changed dramatically over the past decade with advances in cardiac imaging, the use of novel biomarkers, and the development of transcatheter valve repair and replacement technology. International society guidelines have kept pace to provide recommendations for diagnosis, follow-up, and timing of intervention. The most challenging patient cohort for clinicians are patients with asymptomatic severe disease in whom the optimal timing of intervention can be ill-defined. It is a fine balance between the risks of early intervention on asymptomatic patients and improving patient outcomes by preventing long-term cardiac complications. The key in optimal patient management is gathering the necessary information on patient risk and combining that with the risk, efficacy, and durability of valve interventions to arrive at the appropriate timing for intervention. This group of patients will be the focus of this review as we delve into the natural history, recommended follow-up, and indications for intervention in patients with degenerative aortic and mitral valve disease.
La prise en charge de la cardiopathie valvulaire a considérablement évolué au cours de la dernière décennie grâce aux progrès de l'imagerie cardiaque, à l'utilisation de nouveaux biomarqueurs et au développement de la technologie de réparation et de remplacement de valve par cathéter. Les lignes directrices de la société internationale ont évolué au même rythme pour fournir des recommandations sur le diagnostic, le suivi et le moment de l'intervention. La cohorte de patients la plus difficile à appréhender pour les cliniciens est celle des patients atteints d'une maladie grave asymptomatique chez lesquels le moment optimal de l'intervention peut être difficile à définir. Il s'agit d'un équilibre délicat entre les risques d'une intervention précoce chez les patients asymptomatiques et l'amélioration du pronostic des patients en prévenant les complications cardiaques à long terme. L’élément clé de la prise en charge optimale des patients consiste en un regroupement des informations nécessaires concernant le risque du patient et de les combiner avec le risque, l'efficacité et la durabilité des interventions valvulaires pour déterminer un moment approprié pour l'intervention. Ce groupe de patients sera au centre de cette revue de littérature, et nous explorerons les antécédents, le suivi recommandé et les indications d'intervention chez les patients atteints de valvulopathie aortique et mitrale dégénérative.
Prognostic Value of N-Terminal Pro–B-Type Natriuretic Peptide in Elderly Patients With Valvular Heart Disease
2020, Journal of the American College of Cardiology
N-terminal pro–B-type natriuretic peptide (NT-proBNP) may reflect early prognosis in patients with valvular heart disease (VHD).
The aim of this study was to examine the association between NT-proBNP and mortality in elderly patients with VHD.
A total of 5,983 elderly patients (age ≥60 years) with moderate or severe VHD underwent echocardiography and NT-proBNP measurement. VHD examined included aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid regurgitation, and multivalvular heart disease. NT-proBNP ratio was defined as measured NT-proBNP relative to the maximal normal values specific to age and sex. Disease-specific thresholds were defined on the basis of penalized splines and maximally selected rank statistics.
The cohort had a mean age of 71.1 ± 7.6 years. At 1-year follow-up, 561 deaths (9.4%) had occurred. In penalized splines, relative hazards showed a monotonic increase with greater NT-proBNP ratio for death with different VHDs (p < 0.001 for all) except mitral stenosis. Higher NT-proBNP ratio, categorized by disease-specific thresholds, was independently associated with mortality (overall adjusted hazard ratio: 1.99; 95% confidence interval: 1.76 to 2.24; p < 0.001). Different subtypes of VHD all incurred excess mortality with elevated NT-proBNP ratio, with the strongest association detected for aortic stenosis (adjusted hazard ratio: 10.5; 95% confidence interval: 3.9 to 28.27; p < 0.001). The addition of NT-proBNP ratio to the prediction algorithm including traditional risk factors improved outcome prediction (overall net reclassification index = 0.28; 95% CI: 0.24 to 0.34; p < 0.001; likelihood ratio test p < 0.001). Results remained consistent in patients under medical care, with normal left ventricular ejection fractions, and with primary VHD.
NT-proBNP provides incremental prognostic information for mortality in various VHDs. It could aid in risk stratification as a pragmatic and versatile biomarker in elderly patients.
Early changes in N-terminal pro-B-type natriuretic peptide levels after transcatheter aortic valve replacement and its impact on long-term mortality
2018, International Journal of Cardiology
Citation Excerpt :
Its release is related to left ventricular wall stress and it is used for the diagnosis and prognosis of acute and chronic heart failure [15–17]. Additionally, NT-proBNP correlates with the severity of AS and chronic aortic regurgitation (AR) [18,19]. Patients with higher pre-operative NT-proBNP concentrations show higher morbidity and mortality after surgical AVR [20] or TAVR [21–23].
N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) levels correlate with higher peri-procedural mortality after transcatheter aortic valve replacement (TAVR). The long-term prognostic value of NT-proBNP within the first days after TAVR, however, remains unclear. This study examined early changes in NT-proBNP prior to and within 6 days after TAVR, the diagnostic value of this biomarker regarding aortic regurgitation (AR), and its prognostic value regarding one-year mortality.
NT-proBNP concentrations were measured in 504 consecutive patients undergoing transapical (TA) or transfemoral (TF) TAVR before and directly after TAVR as well as 4 h and 1, 2, 3, and 6 days after TAVR. The follow-up period was 1 year. NT-proBNP was elevated in all patients at baseline (median 2141 ng/L [IQR 1021–5319 ng/L]). NT-proBNP changes in the first 6 days after TAVR showed significant differences depending on the approach, with a greater and more prolonged rise evident in TA-TAVR patients. NT-proBNP was an independent predictor of mortality in TA patients with AR, with an AUC of 0.794 (95% CI 0.663–0.925; P = 0.003) when measured on day 3 after TAVR. For TF patients with AR and reduced left ventricular systolic function, the AUC for prediction of mortality was 0.897 (95% CI 0.778–1.0; P = 0.004) on day 2.
The prognostic information of early post-procedural NT-proBNP concentrations is superior to pre-procedural values regarding all-cause mortality within 1 year. Post-procedural NT-proBNP must be interpreted in relation to the TAVR approach. NT-proBNP predicts mortality in TF-TAVR patients with AR and reduced left ventricular function.
Global Longitudinal Strain in Asymptomatic Chronic Aortic Regurgitation: The Missing Piece for the Watchful Waiting Puzzle? <sup>∗</sup>
2018, JACC: Cardiovascular Imaging

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Diagnostic and prognostic value of N-terminal pro B-type natriuretic peptide (NT-proBNP) in patients with chronic aortic regurgitation

Abstract

Background

Methods and results

Conclusion

Section snippets

Background

Patients

Results

Discussion

Conclusion

Limitations

Acknowledgements

Am J Cardiol

J Am Coll Cardiol

Am Heart J

Am Heart J

Am Heart J

Am J Cardiol

Am J Cardiol

Am J Cardiol

J Am Coll Cardiol

J Am Soc Echocardiogr

Clin Chim Acta