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Relation between serum N-terminal pro-brain natriuretic peptide and prognosis in patients with hypertrophic cardiomyopathy

Pro-B-type natriuretic peptide  (proBNP) is a cardiac neurohormone synthesized and secreted mainly from ventricles in response to increased wall stress. In hypertrophic cardiomyopathy (HCM) the neurohormone is expressed in ventricular myocites especially with high levels in the setting of obstructive cases or forms with diastolic dysfunction. Preliminary data show that its concentrations may correlate with markers of disease severity and exercise intolerance (1-3).  Although BNP concentrations in tissue and plasma are also associated with fibrosis and evolution towards sytolic dysfunction (4,5), its has been suggested that this neurohormone has a limited role in the diagnosis and management of HCM because concentrations only weakly correlate with clinical symptoms and markers of systolic and diastolic function (6). However available studies are small and there are limited data on its real prognostic role.
In a recently published prospective observational, single-centre cohort study (7), 847 patients (mean 53 years; 67% male) with HCM (28% with left ventricular outflow tract obstruction≥30 mmHg at rest) were followed for  a median duration of 3.5 years. The median NT-proBNP concentration was 78 pmol/L (range <5–1817 pmol/L and IQR 312-183 pmol/L). Mean NT-proBNP concentrations were higher across all age groups compared with reference values. Six hundred and sixty-eight (79%) patients had an abnormal NT-proBNP concentration, of which 147 (17%) had a left ventricular EF <50%.
Patients were followed for a median duration of 3.5 years (IQR 2.5– 4.5 years). During this time, 68 patients (8%) died or underwent cardiac transplantation. There were 8 SCDs (mean age 42 +/- 13 years); 16 HF deaths (55 + 14 years), and 7 cardiac transplants (45+12 years).
Patients with an abnormal NT-proBNP had a seven-fold increased risk of death or transplantation (relative risk 6.7, 95% CI 1.7–27.2, P=0.0074) compared with those with a normal NT-proBNP. N- terminal pro-brain natriuretic peptide levels predicted the primary endpoint with an area under the ROC curve of 0.78 (95% CI 0.73 – 0.84). A cut-off of ,100 pmol/L had a 96% negative predictive value. N-terminal pro-brain natriuretic peptide concentration was higher in patients who were transplanted or died from HF (median 274 pmol/L, IQR 153–446) than in those who died suddenly or received an appropriate ICD shock (median 184 pmol/ L, IQR 62–277) during the follow-up period. Univariable Cox regression found Log NT-proBNP was a significant predictor of HF and transplant-related deaths (n= 23; HR 3.03, 95% CI 1.99– 4.60, P <0.001) but not sudden death or appropriate ICD shock (n=11; HR 1.54, 95% CI 0.91–2.60, P = 0.111). Multivariable Cox proportional hazards model analysis identified three independent predictors of all-cause mortality or transplantation: NYHA class III/IV (HR 2.10, 95% CI 1.21–3.65, P =0.008), ejection fraction (HR 0.98, 95% CI 0.96–1.00, P =0.035), and logNT-proBNP (HR 2.04, 95% CI 1.56–2.66, P< 0.001).
Myocardial Disease

This is a very important study showing in a sufficiently large sample of patients with HCM that NT-proBNP is a significant predictor of HF and transplant-related deaths but not sudden death or appropriate ICD shock. As pointed out, this observation is important because most contemporary studies suggest that HF has become the predominant mechanism of premature mortality in patients with HCM and there is, therefore, a need for sensitive early biomarkers that can be used to target early preventative therapies. An additional important issue is that severe symptoms and NT-proBNP were independent predictors of adverse outcome in this study, suggesting that they provide complementary informations on disease severity and progression. Additional studies are warranted to assess the value of serial NT-proBNP measurements in patients with HCM.


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6. Binder J, Ommen SR, Chen HH, Ackerman MJ, Tajik AJ, Jaffe AS. Usefulness of brain natriuretic peptide levels in the clinical evaluation of patients with hypertrophic cardiomyopathy. Am J Cardiol 2007;100:712–714.

7. Coats CJ, Gallagher MJ, Foley M, O'Mahony C, Critoph C, Gimeno J, Dawnay A, McKenna WJ, Elliott PM. Relation between serum N-terminal pro-brain natriuretic peptide and prognosis in patients with hypertrophic cardiomyopathy. Eur Heart J.  2013 Mar 8. [Epub ahead of print].

Notes to editor

Presented by : Massimo Imazio, MD, FESC. Cardiology Department. Maria Vittoria Hospital. Torino, Italy.
Eur Heart J. 2013 Mar 8. [Epub ahead of print]
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.