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)

Alan Cheng, Yiyi Zhang, Elena Blasco-Colmenares, Darshan Dalal, Barbara Butcher, Sanaz Norgard, Zayd Eldadah, Kenneth A. Ellenbogen, Timm Dickfeld, David D Spragg, Joseph Marine, Eliseo Guallar, Gordon F. Tomaselli

Research output: Contribution to journalArticle

Abstract

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. 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 multivariableadjusted models, higher interleukin-6 levels increased the risk of appropriate ICD shocks. In contrast, C-reactive protein, interleukin-6, tumor necrosis factor-α 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. 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.

Original languageEnglish (US)
Pages (from-to)1084-1091
Number of pages8
JournalCirculation: Arrhythmia and Electrophysiology
Volume7
Issue number6
DOIs
StatePublished - Dec 1 2014

Fingerprint

Implantable Defibrillators
Primary Prevention
Observational Studies
Biomarkers
Prospective Studies
Shock
Proteins
Mortality
Interleukin-6
Systolic Heart Failure
Inflammation
Troponin T
Tumor Necrosis Factor Receptors
Brain Natriuretic Peptide
Sudden Cardiac Death
Wounds and Injuries
Serum
Tachycardia
Stroke Volume
C-Reactive Protein

Keywords

  • Arrhythmias, cardiac
  • Death, sudden, cardiac
  • Defibrillators, implantable
  • Inflammation
  • Prevention & control

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

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). / Cheng, Alan; Zhang, Yiyi; Blasco-Colmenares, Elena; Dalal, Darshan; Butcher, Barbara; Norgard, Sanaz; Eldadah, Zayd; Ellenbogen, Kenneth A.; Dickfeld, Timm; Spragg, David D; Marine, Joseph; Guallar, Eliseo; Tomaselli, Gordon F.

In: Circulation: Arrhythmia and Electrophysiology, Vol. 7, No. 6, 01.12.2014, p. 1084-1091.

Research output: Contribution to journalArticle

Cheng, Alan ; Zhang, Yiyi ; Blasco-Colmenares, Elena ; Dalal, Darshan ; Butcher, Barbara ; Norgard, Sanaz ; Eldadah, Zayd ; Ellenbogen, Kenneth A. ; Dickfeld, Timm ; Spragg, David D ; Marine, Joseph ; Guallar, Eliseo ; Tomaselli, Gordon F. / 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). In: Circulation: Arrhythmia and Electrophysiology. 2014 ; Vol. 7, No. 6. pp. 1084-1091.
@article{d832eb9aaa1e45d9af1bbd19c15a0ab7,
title = "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)",
abstract = "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. 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 multivariableadjusted models, higher interleukin-6 levels increased the risk of appropriate ICD shocks. In contrast, C-reactive protein, interleukin-6, tumor necrosis factor-α 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. 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.",
keywords = "Arrhythmias, cardiac, Death, sudden, cardiac, Defibrillators, implantable, Inflammation, Prevention & control",
author = "Alan Cheng and Yiyi Zhang and Elena Blasco-Colmenares and Darshan Dalal and Barbara Butcher and Sanaz Norgard and Zayd Eldadah and Ellenbogen, {Kenneth A.} and Timm Dickfeld and Spragg, {David D} and Joseph Marine and Eliseo Guallar and Tomaselli, {Gordon F.}",
year = "2014",
month = "12",
day = "1",
doi = "10.1161/CIRCEP.113.001705",
language = "English (US)",
volume = "7",
pages = "1084--1091",
journal = "Circulation: Arrhythmia and Electrophysiology",
issn = "1941-3149",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Protein biomarkers identify patients unlikely to benefit from primary prevention implantable cardioverter defibrillators

T2 - Findings from the prospective observational study of implantable cardioverter defibrillators (PROSE-ICD)

AU - Cheng, Alan

AU - Zhang, Yiyi

AU - Blasco-Colmenares, Elena

AU - Dalal, Darshan

AU - Butcher, Barbara

AU - Norgard, Sanaz

AU - Eldadah, Zayd

AU - Ellenbogen, Kenneth A.

AU - Dickfeld, Timm

AU - Spragg, David D

AU - Marine, Joseph

AU - Guallar, Eliseo

AU - Tomaselli, Gordon F.

PY - 2014/12/1

Y1 - 2014/12/1

N2 - 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. 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 multivariableadjusted models, higher interleukin-6 levels increased the risk of appropriate ICD shocks. In contrast, C-reactive protein, interleukin-6, tumor necrosis factor-α 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. 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.

AB - 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. 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 multivariableadjusted models, higher interleukin-6 levels increased the risk of appropriate ICD shocks. In contrast, C-reactive protein, interleukin-6, tumor necrosis factor-α 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. 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.

KW - Arrhythmias, cardiac

KW - Death, sudden, cardiac

KW - Defibrillators, implantable

KW - Inflammation

KW - Prevention & control

UR - http://www.scopus.com/inward/record.url?scp=84925713809&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925713809&partnerID=8YFLogxK

U2 - 10.1161/CIRCEP.113.001705

DO - 10.1161/CIRCEP.113.001705

M3 - Article

VL - 7

SP - 1084

EP - 1091

JO - Circulation: Arrhythmia and Electrophysiology

JF - Circulation: Arrhythmia and Electrophysiology

SN - 1941-3149

IS - 6

ER -