Protein biomarkers identify patients unlikely to benefit from primary prevention implantable cardioverter defibrillators: findings from the Prospective Observational Study of Implantable Cardioverter Defibrillators (PROSE-ICD).
Protein biomarkers identify patients unlikely to benefit from primary prevention implantable cardioverter defibrillators: findings from the Prospective Observational Study of Implantable Cardioverter Defibrillators (PROSE-ICD).
Available online from MWHC library: 2008 - present
BACKGROUND: Primary prevention implantable cardioverter defibrillators (ICDs) reduce all-cause mortality, but the benefits are heterogeneous. Current risk stratification based on left ventricular ejection fraction has limited discrimination power. We hypothesize that biomarkers for inflammation, neurohumoral activation, and cardiac injury can predict appropriate shocks and all-cause mortality in patients with primary prevention ICDs. CLINICAL TRIAL REGISTRATION URL: clinicaltrials.gov; Unique Identifier: NCT00733590.Copyright � 2014 American Heart Association, Inc. CONCLUSIONS: An increase in serum biomarkers of inflammation, neurohumoral activation, and myocardial injury increased the risk for death but poorly predicted the likelihood of an ICD shock. These findings highlight the potential importance of serum-based biomarkers in identifying patients who are unlikely to benefit from primary prevention ICDs. METHODS AND RESULTS: The Prospective Observational Study of Implantable Cardioverter Defibrillators (PROSe-ICD) enrolled 1189 patients with systolic heart failure who underwent ICD implantation for primary prevention of sudden cardiac death. The primary end point was an ICD shock for adjudicated ventricular tachyarrhythmia. The secondary end point was all-cause mortality. After a median follow-up of 4.0 years, 137 subjects experienced an appropriate ICD shock and 343 participants died (incidence rates of 3.2 and 5.8 per 100 person-years, respectively). In multivariable-adjusted models, higher interleukin-6 levels increased the risk of appropriate ICD shocks. In contrast, C-reactive protein, interleukin-6, tumor necrosis factor-alpha receptor II, pro-brain natriuretic peptide (pro-BNP), and cardiac troponin T showed significant linear trends for increased risk of all-cause mortality across quartiles. A score combining these 5 biomarkers identified patients who were much more likely to die than to receive an appropriate shock from the ICD.
English
1941-3084
*Blood Proteins/an [Analysis]
*Death, Sudden, Cardiac/pc [Prevention & Control]
*Defibrillators, Implantable
*Electric Countershock/is [Instrumentation]
*Primary Prevention/is [Instrumentation]
Aged
Biological Markers/bl [Blood]
Chi-Square Distribution
Death, Sudden, Cardiac/et [Etiology]
Female
Humans
Inflammation Mediators/bl [Blood]
Linear Models
Male
Middle Aged
Multivariate Analysis
Myocardium/me [Metabolism]
Natriuretic Peptide, Brain/bl [Blood]
Patient Selection
Predictive Value of Tests
Primary Prevention/mt [Methods]
Proportional Hazards Models
Prospective Studies
Protein Precursors/bl [Blood]
Risk Assessment
Risk Factors
United States/ep [Epidemiology]
MedStar Heart & Vascular Institute
Journal Article
Multicenter Study
Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Available online from MWHC library: 2008 - present
BACKGROUND: Primary prevention implantable cardioverter defibrillators (ICDs) reduce all-cause mortality, but the benefits are heterogeneous. Current risk stratification based on left ventricular ejection fraction has limited discrimination power. We hypothesize that biomarkers for inflammation, neurohumoral activation, and cardiac injury can predict appropriate shocks and all-cause mortality in patients with primary prevention ICDs. CLINICAL TRIAL REGISTRATION URL: clinicaltrials.gov; Unique Identifier: NCT00733590.Copyright � 2014 American Heart Association, Inc. CONCLUSIONS: An increase in serum biomarkers of inflammation, neurohumoral activation, and myocardial injury increased the risk for death but poorly predicted the likelihood of an ICD shock. These findings highlight the potential importance of serum-based biomarkers in identifying patients who are unlikely to benefit from primary prevention ICDs. METHODS AND RESULTS: The Prospective Observational Study of Implantable Cardioverter Defibrillators (PROSe-ICD) enrolled 1189 patients with systolic heart failure who underwent ICD implantation for primary prevention of sudden cardiac death. The primary end point was an ICD shock for adjudicated ventricular tachyarrhythmia. The secondary end point was all-cause mortality. After a median follow-up of 4.0 years, 137 subjects experienced an appropriate ICD shock and 343 participants died (incidence rates of 3.2 and 5.8 per 100 person-years, respectively). In multivariable-adjusted models, higher interleukin-6 levels increased the risk of appropriate ICD shocks. In contrast, C-reactive protein, interleukin-6, tumor necrosis factor-alpha receptor II, pro-brain natriuretic peptide (pro-BNP), and cardiac troponin T showed significant linear trends for increased risk of all-cause mortality across quartiles. A score combining these 5 biomarkers identified patients who were much more likely to die than to receive an appropriate shock from the ICD.
English
1941-3084
*Blood Proteins/an [Analysis]
*Death, Sudden, Cardiac/pc [Prevention & Control]
*Defibrillators, Implantable
*Electric Countershock/is [Instrumentation]
*Primary Prevention/is [Instrumentation]
Aged
Biological Markers/bl [Blood]
Chi-Square Distribution
Death, Sudden, Cardiac/et [Etiology]
Female
Humans
Inflammation Mediators/bl [Blood]
Linear Models
Male
Middle Aged
Multivariate Analysis
Myocardium/me [Metabolism]
Natriuretic Peptide, Brain/bl [Blood]
Patient Selection
Predictive Value of Tests
Primary Prevention/mt [Methods]
Proportional Hazards Models
Prospective Studies
Protein Precursors/bl [Blood]
Risk Assessment
Risk Factors
United States/ep [Epidemiology]
MedStar Heart & Vascular Institute
Journal Article
Multicenter Study
Observational Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't