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Correlation to NT-ProBNP and remodeling after cardiac surgery

Abstracts

BACKGROUND: Few data are available on diastolic function in patients with aortic stenosis (AOS) with indication of surgical treatment. A potential correlation between biomarkers and diastolic function has not been established. OBJECTIVE: The aim of our study was to evaluate diastolic function in patients with AOS waiting for aortic valve replacement (AVR) echocardiographically, and to verify its correlation with serum brain natriuretic peptide (NT-proBNP). METHODS: Thirty-one AOS patients (11 male), 21 to 81 years old (mean age, 61±15 years old) were studied before and after AVR. Diastolic function was assessed with Doppler methods: transvalvar mitral flow, tissue Doppler imaging (TDI) and pulmonary venous Doppler (PVD), correlating with serum brain natriuretic peptide (NT-proBNP) before and 6 months after AVR. RESULTS: Comparing pre to post-operative period, we observed an increase of the left atrial ejection fraction and isovolumetric relaxation time (IRT), and the decrease of the mitral velocity to early diastolic velocity of the mitral annulus ratio (E/E'), the difference between the pulmonary A wave duration and mitral A duration, left atrial systolic volume, left atrial systolic volume index, left ventricular diastolic diameter, left ventricular systolic diameter, end diastolic volume (LVEDV), left ventricular mass index, left ventricular volume and mass index ratio. The values of NT-proBNP were positively correlated to diastolic dysfunction, both before and after surgery. CONCLUSION: AOS patients' ventricular diastolic function improved after AVR. The biomarker NT-proBNP might be a useful biomarker of diastolic function in these patients, before and after AVR. NT-proBNP values show a positive correlation with echocardiographic variables that determine diastolic dysfunction, and is a good marker for the characterization of this dysfunction in AOS patients.

Aortic Valve Stenosis; Ventricular Dysfunction; Natriuretic Peptide, Brain


FUNDAMENTO: A função diastólica em portadores de estenose aórtica (EAO) é pouco estudada. Não é possível estabelecer uma possível correlação entre biomarcadores e disfunção diastólica. OBJETIVO: Avaliar a função diastólica em portadores de EAO submetidos à troca valvar através de ecocardiografia transtorácica e correlacionar com valores de NT-proBNP. MÉTODOS: Estudamos 31 pacientes com EAO (11 homens), com idade entre 21 e 81 anos (média de 61±15 anos), submetidos a tratamento cirúrgico de EAO. Foi realizada dosagem sérica de NT-proBNP e o resultado, comparado com variáveis ecocardiográficas obtidas pelo Doppler pulsado em fluxo mitral, Doppler pulsado em veias pulmonares e Doppler tecidual, tanto no pré quanto no pós-operatório. RESULTADOS: Observou-se melhora na Fração de Ejeção (FE) de AE e Tempo de Relaxamento Isovolumétrico (TRIV), além de redução nos seguintes parâmetros: a) Relação da velocidade diastólica precoce mitral (onda E) com a velocidade do anel mitral (onda E´) (E/E'), b) Volume sistólico de átrio esquerdo (AE), c) Volume sistólico de AE indexado, d) Diâmetro diastólico de ventrículo esquerdo (DDVE), e) Diâmetro sistólico de VE (DSVE), f) Volume diastólico final (VDF), g) Massa indexada de VE e h) Relação Volume/Massa de ventrículo esquerdo (VE). Os valores do NT-proBNP correlacionaram-se de modo positivo com os diversos graus de disfunção diastólica, tanto no pré como no pós-operatório. CONCLUSÃO: 1) A cirurgia de troca valvar para correção de EAO resultou em melhora significativa da função diastólica ventricular. 2) Os valores de NT-proBNP correlacionaram-se positivamente com as variáveis ecocardiográficas que determinam disfunção diastólica, sendo o NT-proBNP um bom marcador para caracterizar essa disfunção em portadores de EAO.

Estenose Aórtica; Disfunção Ventricular; Peptídeo Natriurético Encefálico


Instituto do Coração (InCor), São Paulo, SP - Brasil

Mailing address

ABSTRACT

BACKGROUND: Few data are available on diastolic function in patients with aortic stenosis (AOS) with indication of surgical treatment. A potential correlation between biomarkers and diastolic function has not been established.

OBJECTIVE: The aim of our study was to evaluate diastolic function in patients with AOS waiting for aortic valve replacement (AVR) echocardiographically, and to verify its correlation with serum brain natriuretic peptide (NT-proBNP).

METHODS: Thirty-one AOS patients (11 male), 21 to 81 years old (mean age, 61±15 years old) were studied before and after AVR. Diastolic function was assessed with Doppler methods: transvalvar mitral flow, tissue Doppler imaging (TDI) and pulmonary venous Doppler (PVD), correlating with serum brain natriuretic peptide (NT-proBNP) before and 6 months after AVR.

RESULTS: Comparing pre to post-operative period, we observed an increase of the left atrial ejection fraction and isovolumetric relaxation time (IRT), and the decrease of the mitral velocity to early diastolic velocity of the mitral annulus ratio (E/E'), the difference between the pulmonary A wave duration and mitral A duration, left atrial systolic volume, left atrial systolic volume index, left ventricular diastolic diameter, left ventricular systolic diameter, end diastolic volume (LVEDV), left ventricular mass index, left ventricular volume and mass index ratio. The values of NT-proBNP were positively correlated to diastolic dysfunction, both before and after surgery.

CONCLUSION: AOS patients' ventricular diastolic function improved after AVR. The biomarker NT-proBNP might be a useful biomarker of diastolic function in these patients, before and after AVR. NT-proBNP values show a positive correlation with echocardiographic variables that determine diastolic dysfunction, and is a good marker for the characterization of this dysfunction in AOS patients.

Keywords: Aortic Valve Stenosis / surgery; Ventricular Dysfunction; Natriuretic Peptide, Brain.

Introduction

Left ventricle diastolic function is related both to its relaxation and filling. In general, it is quantified by Echo-Doppler1-4.

An additional manner of evaluating cardiac function is by measuring the serum concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP). NT-proBNP levels are increased in patients with both systolic and diastolic LV dysfunction5. Januzzi et al6 showed a correlation between NT-proBNP serum levels and prognosis in systolic heart failure. However, NT-proBNP measurement cannot differentiate systolic from diastolic heart failure. Thus, NT-proBNP exerts an important role in the evaluation of diastolic dysfunction only when combined with echocardiographic evaluation.

Patients submitted to surgery for correction of aortic stenosis (AOS) present immediate improvement of systolic function. On the other hand, diastolic dysfunction remains and can ever worsen, since myocardial hypertrophy reversal occurs faster than interstitial fibrosis reduction7-9.

As for LV mass increase, left atrial (LA) function can be considered a marker of diastolic dysfunction severity. Lubien et al10 observed higher BNP levels when LA increase is combined to LV hypertrophy.

However, the relationship between biomarkers and LV remodeling, specifically in AOS patients submitted to aortic valve replacement has not yet been established10-13 Some studies suggest that NT-proBNP can be used in diagnostic and prognostic applications. Fisher et al14 observed that patients with congestive heart failure and higher than average NT-proBNP values had a 1-year mortality rate of 53%, as compared to a 11% rate registered for patients with lower than average values.

Biomarkers, particularly NT-proBNP, have not been accurately evaluated in AOS. The present study aims to analyze LV mass reduction and left atrial and ventricular remodeling in patients submitted to aortic valve replacement surgery due to significant AOS, as well as correlating NT-proBNP levels with various levels of diastolic dysfunction, both before and after surgery.

Methods

Study design

This is a longitudinal observational study of patients with significant AOS who have indication of surgical treatment.

Patients

Thirty-one NYHA class III or IV AOS patients (11 male) aged 21 to 81 years old (mean age, 61±15 years old) with preserved systolic function and indication of surgical treatment of the valvular heart disease were included.

Exclusion criteria

a) Severe coronary failure

b) Other moderate or severe valvular heart disease

c) Atrial fibrillation

Hypothyroidism, neoplasia, chronic renal insufficiency or severe chronic obstructive pulmonary disease.

Transthoracic echocardiography

The exams were carried out with the patient lying in the left side position, both 1 to 3 months before and 6 months after surgery. The equipment (HDI 5000 [Philips Medical Systems, Andover, MA, USA], with multi frequency electronic sector transducer, pulsed, tissue and continuous Doppler and colored flow mapping) used is commercially available. The patients were submitted to simultaneous electrocardiographic monitoring and the exams were performed according to the recommendations of the American Society of Echocardiography15.

At least three measurements were obtained for each variable and the mean values were used for each one.

The echocardiographic variables used both in the pre- and postoperative periods were:

1- LV end-systolic diameter and end-diastolic diameter.

2- End-diastolic septal and LV posterior wall thickness, used for calculating LV mass index (according to Devereux formula)15.

3- LV systolic function, calculated as LV ejection fraction (LVEF), according to Simpson rule (bidimensional measurement)16.

4- Aortic valve area, calculated by the continuity equation16.

5- LV diastolic function:

5.1 Pulsed Doppler study of the mitral transvalvar flow: mitral transvalvar flow was assessed at the apical four-chamber view, with the pulsed Doppler probe placed in the LV entry pathway, at the distal mitral valve leaflets, with 2-mm sample volume. The following parameters were evaluated:

5.1.a) Protodiastolic LV filling velocity (E wave), in cm/s.

5.1.b) Telediastolic LV filling velocity (A wave), in cm/s.

5.1.c) Telediastolic LV wave duration (A wave measured by pulsed Doppler), in ms.

5.1.d) Ratio between E and A wave (E/A)

5.1.e) LV filling flow deceleration time (DT), in ms.

5.2 Isovolumetric relaxation time (IVRT).

5.3. Pulsed Doppler study of pulmonary venous flow, evaluating the following parameters:

5.3.a) Pulmonary venous flow systolic component (S wave), in cm/s.

5.3.b) Pulmonary venous flow diastolic component (D wave), in cm/s.

5.3.c) Atrial wave contraction duration (A wave time), in ms.

5.3.d) Atrial contraction peak (A wave), in cm/s.

5.4. Tissue Doppler mitral ring study: the image was obtained by tissue Doppler at apical 2- and 4-chamber view, 1-2 mm sample volume.

The maximum myocardial displacement speed was measured at the beginning and at the end of diastole (E' and A' waves, respectively), and during systole (S' wave), at the septal, lateral, inferior, anterior and rings and the VD lateral ring17,18.

LA volume was measured at apical 2- and 4-chamber view. LA systolic and diastolic volumes were measured for calculating LA emptying fraction, using a method similar to Simpson's18.

Statistical analysis

A descriptive analysis was performed on the data obtained from the 31 patients, taking into account demographics, echocardiographic variables and NT-proBNP values before and after surgery.

The mean value found for each variable was compared among AOS patients, before and after surgery. For mean comparison, the Wilcoxon test was used since the variables do not follow a normal distribution, with the exception of the BNP logarithm (compared by the Student t-test).

Results

Study population

Thirty one patients (21 female; mean age 61±15 years old) with significant aortic stenosis were included.

AOS patients mean age was 61.5±14.72 years old (ranging from 21 to 81 years).

Of the study patients, 26 had atherodegenerative AOS, 4 had congenital AOS and 1 had rheumatic AOS.

Echocardiographic data

Improvement of echocardiographic parameters between the pre- and postoperative periods can be observed on analyzing data on Table 1.

Diastolic dysfunction and NT-proBMP correlation

Diastolic dysfunction improved between the pre- and postoperative periods, although values were not yet normal at the study period (Table 2).

NT-proBNP levels decreased postoperatively in comparison to the pre-operative period (Table 3). After classification in three levels (I, II and III), the sample was evaluated for the difference among the groups according to log-NT-proBNP value. ANOVA test showed significance between groups (F=3.850, p=0.027) and the Bonferroni post hoc test demonstrated a difference on log-NT-proBNP values between Grade I (mean 4.58) and Grade II (mean 4.69) (p=0.025). However, no statistically significance difference was found between Grades II (mean 4.69) and III (mean 4.70) on log-NT-proBNP values (p=0.08) (Table 4).

Using Pearson linear correlation and Spearman correlation, we have observed that the variables E/E', EF/LA, LA systolic volume, indexed LA systolic volume, LVSD, indexed LV mass and volume/mass ratio show a correlation with log-NT-proBNP (Table 5). The variables E/E', LA systolic volume, indexed LA systolic volume, LVSD and indexed LV mass show a positive correlation, indicating that NT-proBNP logarithm increases with increasing values of the respective variables. On the other hand, NT-proBNP logarithm decreases when the variables mitral A time-pulmonary A time, LAEF and volume/mass ratio increase.

The variables with significant Spearman and Pearson correlations are the same. The variables behavior is identical to the one observed previously, and NT-proBNP logarithm also increases with LVSD increase.

When verification is done on a logistic regression model (Table 6), the risk of diastolic dysfunction in a patient with log-NT-proBNP equal to 4.78 (BNP=119.10) is 92.01% [CI 955, 83.45%; 96.33%], the risk of diastolic dysfunction increases 2.64 times [CI 95%, 1.21; 5.78] for each 1-unit increase in log-NT-proBNP.

Discussion

The relationship between LV geometry in AOS and remodeling after aortic valve replacement is not known. In the early postoperative period, few patients present LV mass reduction, but 18 months after the procedure LV hypertrophy and end-diastolic volume decrease19,20.

Mitral transvalvar flow velocity is an important parameter for evaluating filling pressures; however, it can be modified or influenced by various factors and the same is true for pulmonary venous flow. Tissue Doppler analysis and LA volume evaluation21 were included in the present study for minimizing these limitations and increasing diastolic dysfunction diagnostic precision21.

It was possible to verify an improvement of LAEF in the postoperative period (as compared to the findings before surgery), meaning an improvement in diastolic function after valve replacement surgery due to LV mass regression and adaptation of the heart to the new post-load values22. LA dilation follows LV diastolic dysfunction development and is an important predictor of adverse events, particularly arrhythmias. On the other hand, LA volume reduction and LAEF improvement suggest that reverse remodeling occurred, implying that cardiovascular risk was reduced.

Indexed LV mass reduction, in turn, is also a strong (and the most consistent) predictor of events after valve replacement surgery, independently from gender, age and valve replacementtype23.

According to the European Society of Cardiology11, besides considering the symptoms of HF with normal LVEF, diastolic HF can be diagnosed by tissue Doppler (on which E/E' ratio is essential), combined with evaluation of mitral transvalvar flow and pulmonary venous flow by pulsed Doppler. LV mass index and LA indexed volume corroborate the diagnosis. Nagueh et al24 showed that, in patients with preserved LVEF, E/E' ratio is 8 to 15 and that other measurements are required for diagnosing diastolic dysfunction. We must now highlight that, despite the applicability of diastolic function evaluation by Doppler, the method has some limitations. Doppler methods depend on the insonation angle and require experienced physicians. NT-proBNP values correlate to morphofunctional behavior and echocardiographic variables changes after surgical treatment of AOS, and decreased levels of this biomarker can be observed on the postoperative period. The results of the study by Nagueh et al11 support this statement. This behavior can be explained by a reduction of blood flow resistance and LV hypertrophy after surgery, leading to a reduction in LV mass and diastolic wall tension, consequently reducing natriuretic peptide release. The peptides, though, do not return to normal levels due to the aortic-LV pressure gradient generated by the aortic valve prosthesis11.

In a postoperative study, Frederiksen et al25 showed a good correlation between E/E' echocardiographic ratio and NT-proBNP levels, something that was not seen for the E/A ratio. The prognostic importance and predictive ability for cardiovascular events of natriuretic peptides such as NT-proBNP have been recently considered a study subject on the medical literature. Berger-Klein et al12 had already studied NT-proBNP in the postoperative evolution of symptomatic AOS patients and observed its predictive effect, independent from survival. Besides, Gerber et al26 suggested an predictive effect of symptoms development in AOS patients.

The present study showed a correlation between the different echocardiographic variables that characterize diastolic dysfunction27 and NT-proBNP serum levels. We were also able to demonstrate that high preoperative NT-proBNP levels predict greater LV mass regression after surgical treatment, in spite of the indexed LV mass values. This fact suggests that NT-proBNP measurement may be good prognostic marker in AOS patients. Also, diastolic function echocardiographic changes in AOS patients precede LV mass increase. When these changes indicate moderate to severe LV dysfunction, they are considered an independent factor for late mortality after valve replacement surgery.

Vasan et al28 proposed a criterion for diagnosing diastolic HF that includes signs and symptoms of HF, preserved LVEF and evidences of diastolic dysfunction (BNP measurement and echocardiographic changes). This, high BNP values can help in the diagnosis of diastolic heart failure in patients with normal systolic function echocardiographic parameters and abnormal diastolic function.

Conclusions

There was an improvement of diastolic function and reduction of LV mass in AOS patients submitted to valve replacement surgery. Besides that, negative LA remodeling and LAEF improvement in the postoperative period were observed compared to pre-procedure values. NT-proBNP values showed a positive correlation with the various degrees of diastolic dysfunction, both pre- and postoperatively.

References

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  • Correlation to NT-ProBNP and remodeling after cardiac surgery

    Berta Paula Napchan Boer; Marcelo Luiz Campos Vieira; Roney Orismar Sampaio; Henry Abensur; Alessandra Gomes de Oliveira; João Ricardo Fernandes; Max Grinberg
  • Publication Dates

    • Publication in this collection
      12 Apr 2013
    • Date of issue
      May 2013

    History

    • Received
      14 May 2012
    • Accepted
      17 Dec 2012
    • Reviewed
      16 Nov 2012
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    E-mail: revista@cardiol.br