B-type natriuretic peptide is a major predictor of ventricular tachyarrhythmias
Introduction
Sudden cardiac death (SCD) accounts for approximately 50% of total cardiovascular mortality.1 Even with appropriate use of optimal medical therapy in patients with structural heart disease, the implantable cardioverter-defibrillator (ICD) remains the most effective therapy shown to reduce the rate of SCD in this population. Although practice guidelines have designated left ventricular ejection fraction (LVEF) as the most important factor to be used in determining patient candidacy for ICD implantation,2 consensus panels find LVEF neither sensitive nor specific for the prediction of SCD.3, 4 In addition to LVEF, most risk variables incorporated into the multivariate models identified in the Multicenter UnSustained Tachycardia Trial (MUSTT),5 Multicenter Automatic Defibrillator Implantation Trial-II (MADIT-II),6 and Sudden Cardiac Death-Heart Failure Trial (SCD-HeFT)7 did not identify patients specifically at high risk for SCD. Indeed, patients at highest mortality risk in the MADIT-II trial did not experience survival benefit from ICDs, probably because deaths due to ventricular tachyarrhythmias (ie, SCD) represented a relatively smaller proportion of mortality as overall risk increased.8 Identifying variables that might predict a higher relative risk for SCD would help identify patients most likely to benefit from ICDs and thus remains an important goal of clinical electrophysiology investigation.
B-type natriuretic peptide (BNP) is released by cardiomyocytes in response to myocardial stretch and increased preload.9 In patients with chronic heart failure, stable coronary artery disease (CAD), and acute coronary syndromes, BNP is known to predict mortality independent of LVEF.10 The possibility that BNP or N-terminal pro-B-type natriuretic peptide (NT-proBNP) might predict the occurrence of arrhythmia is a logical extension of the known link11 between clinical heart failure and ventricular arrhythmias (VA) and has been proposed alongside emerging data about the molecular basis of stretch-activated depolarizing cation channels in cardiomyocytes.12, 13 Consequently, BNP has recently been evaluated as a potential predictor of SCD and VA in patients with ICDs.14, 15, 16, 17, 18 However, whether elevated BNP levels predict SCD independent of CHF status or LVEF remains controversial with conflicting evidence.19, 20, 21 In addition, it is not yet clear whether the association of BNP with VA and SCD is solely due to its relation with patients having more advanced disease and therefore at risk for higher total mortality. We performed this retrospective study to assess the association between BNP and NT-proBNP levels and VA in relation to total mortality in patients who have had ICDs implanted at our institutions over the last 10 years.
Section snippets
Patient population and data collection
In this 2-center retrospective study, patients who had NT-proBNP levels available within 9 months of the date of ICD implantation or BNP levels available within 12 months of the date of ICD implantation were identified among a cohort of all patients who had undergone initial ICD implantation at Beth Israel Deaconess Medical Center or Tufts Medical Center between October 2003 and July 2012 for the primary prevention of SCD. Patients were included if they underwent ICD implantation for the
Study population
A total of 695 patients who underwent ICD implantation for the primary prevention of SCD were identified: 202 patients from Beth Israel Deaconess Medical Center with available NT-proBNP levels and 493 patients from Tufts Medical Center with available BNP levels. Of these patients, we excluded 73 of 695 patients (10.5%) owing to insufficient data regarding clinical variables and 57 of 695 patients (8.2%) owing to cardiogenic shock or a heart failure hospitalization between the date of biomarker
Discussion
In this study, baseline NT-proBNP and BNP were highly associated with appropriate ICD therapy. Furthermore, the risk for ICD therapy increased out of proportion to the risk for total mortality. Elevated NT-proBNP and BNP levels remained independent predictors of appropriate ICD therapies after adjustment for variables that themselves are associated with the risk for VA or heart failure status, such as LVEF and NYHA functional class. HRs for NT-proBNP and BNP levels in the highest quartiles were
Conclusion
We have found that BNP and its prohormone NT-proBNP served as independent markers of VT and VF resulting in ICD therapy more than total mortality in 2 populations of patients undergoing ICD implantation for the primary prevention of SCD. These observations suggest that the association of natriuretic peptides with SCD and VA are not merely due to more advanced cardiac disease and failure. The measurement of these peptides should be incorporated into future prospective studies of multivariable
Acknowledgment
We thank Ms Dorothy Williams for invaluable assistance throughout this work.
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