Prognostic power of NT-proBNP in left ventricular non-compaction cardiomyopathy

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Abstract

Background

The risk of adverse events in patients with left ventricular non-compaction cardiomyopathy (LVNC) is substantial. This study was designed to determine the prognostic value of NT-proBNP, left ventricular ejection fraction (LVEF), NYHA class, and exercise capacity in LVNC patients.

Methods

Cox regression analyses were performed for evaluating the prognostic value of NT-proBNP, LVEF, NYHA class, and exercise capacity on the occurrence of death or heart transplantation. 153 patients were included.

Results

During 1013 person-years (longest follow-up 18.5 years) 23 patients (15%) died or underwent heart transplantation. We observed a significant relationship of NT-proBNP (adjusted HR 2.44, 95% CI 1.45–4.09, for every NT-proBNP doubling, p = 0.0007) and LVEF (adjusted HR for age 60 years: 2.68, 95% CI 1.62–4.41, p = 0.0001) with the risk of death or heart transplantation. Combined covariate analysis indicated a strong influence of NT-proBNP (adjusted 2.89, 95% CI 1.33–6.26, p = 0.007), whereas LVEF was no longer significant (adjusted HR 0.82, 95% CI 0.42–1.67, p = 0.66) demonstrating a favorable prognostic power of NT-proBNP over LVEF. An increase in NYHA class was associated with a worse outcome, and exercise capacity revealed a trend in the same direction. For all the abovementioned analyses, similar results were obtained when assessing the values at first presentation.

Conclusion

This study provides evidence that an increase in NT-proBNP is a strong predictor of outcome in patients with LVNC. The prognostic power of NT-proBNP is at least as good as that of LVEF, indicating that routine NT-proBNP measurement may improve risk assessment in LVNC.

Introduction

Left ventricular non-compaction cardiomyopathy (LVNC) is a distinct primary cardiomyopathy characterized by a thin, compacted, outer (epicardial) layer and a thick, non-compacted, inner (endocardial) layer with deep recesses between prominent trabeculations [1], [2], [3]. Since its first description, the awareness of LVNC has increased [4], [5]. With wider recognition of the disease and systematic family screening the number of asymptomatic patients diagnosed with LVNC is increasing. Symptomatic patients typically present with heart failure, ventricular arrhythmias or thromboembolic events [6], [7], [8]. However, overall event rates and predictors of outcome remain ill defined. Mortality rates in earlier studies range from 2% to 35%, over median follow-up periods ranging from 2.3 to 4.5 years [9], [10], [11], [12], [13]. These studies observed an association between presentation with symptoms, reduced left ventricular ejection fraction and the risk for adverse outcomes [7], [8], [10], [11], [12]. Nevertheless, quantitative data allowing a reliable assessment of a patient's risk is scarce.

In cardiomyopathies other than LVNC, parameters like left ventricular ejection fraction, heart failure symptoms, and exercise capacity correlate with clinical outcome. Due to its low prevalence, the value of such parameters in LVNC is not as well defined, and the prognostic relevance of the heart failure marker N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP) as well as that of exercise capacity have not been examined so far.

The aim of this study was to determine the prognostic value of NT-proBNP in LVNC patients per se and in comparison with left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class, and exercise capacity. In addition, clinically established cut-off values (LVEF 55% and LVEF 30%, specified standard values for NT-proBNP) as well as cut-off points providing the best prognostic discrimination in regard to death and heart transplantation were assessed.

Section snippets

Patients

All patients diagnosed with isolated LVNC between 1988 and 2015, identified from the clinical and imaging databases at the University Hospitals Zurich and Basel were included in this retrospective analysis. The study was approved by the local ethical committees of Zurich and Basel and informed consent was obtained. The echocardiographic criteria described by Jenni et al. were applied to establish the diagnosis [14]. These criteria include 1) a thickened, two-layered myocardium with a compacted

Patients

During 1013 person-years (longest follow-up 18.5 years) 23 patients (15%) died or underwent heart transplantation. An overview of the study population, patient groups, measurements, follow-up, and outcome is provided in Table 1.

Prohormone brain natriuretic peptide

The median NT-proBNP level in all non-event associated measurements (all values except event-preceding values) was 292 ng/l. Median NT-proBNP level at the last measurement preceding an event was 6416 ng/l (Fig. 1A).

Cox regression revealed a highly significant relationship

Discussion

The predictors of mortality remain ill-defined in patients with LVNC. This study determined the prognostic value of NT-proBNP in comparison with other markers of left ventricular function such as LVEF, NYHA functional class, and exercise capacity in the largest LVNC cohort published to date, with 153 patients and a median follow-up duration of > 6 years. The overall mortality and heart transplantation rate in our cohort was 15%, which is in the range of previous studies reporting rates between 2%

Funding sources

No specific funding.

Disclosures

None.

Conflicts of interest

There are no potential conflicts of interest, including related consultancies, shareholdings, and funding grants.

Acknowledgments

None.

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    1

    These authors contributed equally to this work.

    2

    This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

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