Myocardial extracellular volume fraction quantified by cardiovascular magnetic resonance is increased in diabetes and associated with mortality and incident heart failure admission

Timothy C. Wong, Kayla M. Piehler, Ian A. Kang, Ajay Kadakkal, Peter Kellman, David S. Schwartzman, Suresh R. Mulukutla, Marc A. Simon, Sanjeev G. Shroff, Lewis H. Kuller, Erik B. Schelbert

Research output: Contribution to journalArticle

158 Citations (Scopus)

Abstract

AimsDiabetes may promote myocardial extracellular matrix (ECM) expansion that increases vulnerability. We hypothesized that: (i) type 2 diabetes would be associated with quantitative cardiovascular magnetic resonance (CMR) measures of myocardial ECM expansion, i.e. extracellular volume fraction (ECV); (ii) medications blocking the renin-angiotensin-aldosterone system (RAAS) would be associated with lower ECV; and (iii) ECV in diabetic individuals would be associated with mortality and/or incident hospitalization for heart failure.Methods and resultsWe enrolled 1176 consecutive patients referred for CMR without amyloidosis and computed ECV from measures of the haematocrit and myocardial and blood T1 pre- and post-contrast. Linear regression modelled ECV; Cox regression modelled mortality and/or hospitalization for heart failure. Diabetic individuals (n = 231) had higher median ECV than those without diabetes (n = 945): 30.2% (IQR: 26.9-32.7) vs. 28.1% (IQR: 25.9-31.0), respectively, P < 0.001). Diabetes remained associated with higher ECV in models adjusting for demographics, comorbidities, and medications (P < 0.001). Renin-angiotensin-aldosterone system blockade was associated with lower ECV (P = 0.028) in multivariable linear models. Over a median of 1.3 years (IQR: 0.8-1.9), 38 diabetic individuals had events (21 incident hospitalizations for heart failure; 24 deaths), and ECV was associated with these events (HR: 1.52, 95% CI: 1.21-1.89 per 3% ECV increase) in multivariable Cox regression models.ConclusionDiabetes is associated with increased ECV. Extracellular volume fraction detects amelioration of ECM expansion associated with RAAS blockade, and is associated with mortality and/or incident hospitalization for heart failure in diabetic individuals. Extracellular matrix expansion may be an important intermediate phenotype in diabetic individuals that is detectable and treatable.

Original languageEnglish (US)
Pages (from-to)657-664
Number of pages8
JournalEuropean Heart Journal
Volume35
Issue number10
DOIs
StatePublished - 2014

Fingerprint

Extracellular Matrix
Hospitalization
Magnetic Resonance Spectroscopy
Renin-Angiotensin System
Heart Failure
Mortality
Linear Models
Amyloidosis
Hematocrit
Proportional Hazards Models
Type 2 Diabetes Mellitus
Comorbidity
Demography
Phenotype

Keywords

  • collagen
  • diabetes
  • extracellular matrix
  • extracellular volume fraction
  • fibrosis
  • MRI

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Myocardial extracellular volume fraction quantified by cardiovascular magnetic resonance is increased in diabetes and associated with mortality and incident heart failure admission. / Wong, Timothy C.; Piehler, Kayla M.; Kang, Ian A.; Kadakkal, Ajay; Kellman, Peter; Schwartzman, David S.; Mulukutla, Suresh R.; Simon, Marc A.; Shroff, Sanjeev G.; Kuller, Lewis H.; Schelbert, Erik B.

In: European Heart Journal, Vol. 35, No. 10, 2014, p. 657-664.

Research output: Contribution to journalArticle

Wong, TC, Piehler, KM, Kang, IA, Kadakkal, A, Kellman, P, Schwartzman, DS, Mulukutla, SR, Simon, MA, Shroff, SG, Kuller, LH & Schelbert, EB 2014, 'Myocardial extracellular volume fraction quantified by cardiovascular magnetic resonance is increased in diabetes and associated with mortality and incident heart failure admission', European Heart Journal, vol. 35, no. 10, pp. 657-664. https://doi.org/10.1093/eurheartj/eht193
Wong, Timothy C. ; Piehler, Kayla M. ; Kang, Ian A. ; Kadakkal, Ajay ; Kellman, Peter ; Schwartzman, David S. ; Mulukutla, Suresh R. ; Simon, Marc A. ; Shroff, Sanjeev G. ; Kuller, Lewis H. ; Schelbert, Erik B. / Myocardial extracellular volume fraction quantified by cardiovascular magnetic resonance is increased in diabetes and associated with mortality and incident heart failure admission. In: European Heart Journal. 2014 ; Vol. 35, No. 10. pp. 657-664.
@article{ac5cdc7e315440319f2c76c657d137ff,
title = "Myocardial extracellular volume fraction quantified by cardiovascular magnetic resonance is increased in diabetes and associated with mortality and incident heart failure admission",
abstract = "AimsDiabetes may promote myocardial extracellular matrix (ECM) expansion that increases vulnerability. We hypothesized that: (i) type 2 diabetes would be associated with quantitative cardiovascular magnetic resonance (CMR) measures of myocardial ECM expansion, i.e. extracellular volume fraction (ECV); (ii) medications blocking the renin-angiotensin-aldosterone system (RAAS) would be associated with lower ECV; and (iii) ECV in diabetic individuals would be associated with mortality and/or incident hospitalization for heart failure.Methods and resultsWe enrolled 1176 consecutive patients referred for CMR without amyloidosis and computed ECV from measures of the haematocrit and myocardial and blood T1 pre- and post-contrast. Linear regression modelled ECV; Cox regression modelled mortality and/or hospitalization for heart failure. Diabetic individuals (n = 231) had higher median ECV than those without diabetes (n = 945): 30.2{\%} (IQR: 26.9-32.7) vs. 28.1{\%} (IQR: 25.9-31.0), respectively, P < 0.001). Diabetes remained associated with higher ECV in models adjusting for demographics, comorbidities, and medications (P < 0.001). Renin-angiotensin-aldosterone system blockade was associated with lower ECV (P = 0.028) in multivariable linear models. Over a median of 1.3 years (IQR: 0.8-1.9), 38 diabetic individuals had events (21 incident hospitalizations for heart failure; 24 deaths), and ECV was associated with these events (HR: 1.52, 95{\%} CI: 1.21-1.89 per 3{\%} ECV increase) in multivariable Cox regression models.ConclusionDiabetes is associated with increased ECV. Extracellular volume fraction detects amelioration of ECM expansion associated with RAAS blockade, and is associated with mortality and/or incident hospitalization for heart failure in diabetic individuals. Extracellular matrix expansion may be an important intermediate phenotype in diabetic individuals that is detectable and treatable.",
keywords = "collagen, diabetes, extracellular matrix, extracellular volume fraction, fibrosis, MRI",
author = "Wong, {Timothy C.} and Piehler, {Kayla M.} and Kang, {Ian A.} and Ajay Kadakkal and Peter Kellman and Schwartzman, {David S.} and Mulukutla, {Suresh R.} and Simon, {Marc A.} and Shroff, {Sanjeev G.} and Kuller, {Lewis H.} and Schelbert, {Erik B.}",
year = "2014",
doi = "10.1093/eurheartj/eht193",
language = "English (US)",
volume = "35",
pages = "657--664",
journal = "European Heart Journal",
issn = "0195-668X",
publisher = "Oxford University Press",
number = "10",

}

TY - JOUR

T1 - Myocardial extracellular volume fraction quantified by cardiovascular magnetic resonance is increased in diabetes and associated with mortality and incident heart failure admission

AU - Wong, Timothy C.

AU - Piehler, Kayla M.

AU - Kang, Ian A.

AU - Kadakkal, Ajay

AU - Kellman, Peter

AU - Schwartzman, David S.

AU - Mulukutla, Suresh R.

AU - Simon, Marc A.

AU - Shroff, Sanjeev G.

AU - Kuller, Lewis H.

AU - Schelbert, Erik B.

PY - 2014

Y1 - 2014

N2 - AimsDiabetes may promote myocardial extracellular matrix (ECM) expansion that increases vulnerability. We hypothesized that: (i) type 2 diabetes would be associated with quantitative cardiovascular magnetic resonance (CMR) measures of myocardial ECM expansion, i.e. extracellular volume fraction (ECV); (ii) medications blocking the renin-angiotensin-aldosterone system (RAAS) would be associated with lower ECV; and (iii) ECV in diabetic individuals would be associated with mortality and/or incident hospitalization for heart failure.Methods and resultsWe enrolled 1176 consecutive patients referred for CMR without amyloidosis and computed ECV from measures of the haematocrit and myocardial and blood T1 pre- and post-contrast. Linear regression modelled ECV; Cox regression modelled mortality and/or hospitalization for heart failure. Diabetic individuals (n = 231) had higher median ECV than those without diabetes (n = 945): 30.2% (IQR: 26.9-32.7) vs. 28.1% (IQR: 25.9-31.0), respectively, P < 0.001). Diabetes remained associated with higher ECV in models adjusting for demographics, comorbidities, and medications (P < 0.001). Renin-angiotensin-aldosterone system blockade was associated with lower ECV (P = 0.028) in multivariable linear models. Over a median of 1.3 years (IQR: 0.8-1.9), 38 diabetic individuals had events (21 incident hospitalizations for heart failure; 24 deaths), and ECV was associated with these events (HR: 1.52, 95% CI: 1.21-1.89 per 3% ECV increase) in multivariable Cox regression models.ConclusionDiabetes is associated with increased ECV. Extracellular volume fraction detects amelioration of ECM expansion associated with RAAS blockade, and is associated with mortality and/or incident hospitalization for heart failure in diabetic individuals. Extracellular matrix expansion may be an important intermediate phenotype in diabetic individuals that is detectable and treatable.

AB - AimsDiabetes may promote myocardial extracellular matrix (ECM) expansion that increases vulnerability. We hypothesized that: (i) type 2 diabetes would be associated with quantitative cardiovascular magnetic resonance (CMR) measures of myocardial ECM expansion, i.e. extracellular volume fraction (ECV); (ii) medications blocking the renin-angiotensin-aldosterone system (RAAS) would be associated with lower ECV; and (iii) ECV in diabetic individuals would be associated with mortality and/or incident hospitalization for heart failure.Methods and resultsWe enrolled 1176 consecutive patients referred for CMR without amyloidosis and computed ECV from measures of the haematocrit and myocardial and blood T1 pre- and post-contrast. Linear regression modelled ECV; Cox regression modelled mortality and/or hospitalization for heart failure. Diabetic individuals (n = 231) had higher median ECV than those without diabetes (n = 945): 30.2% (IQR: 26.9-32.7) vs. 28.1% (IQR: 25.9-31.0), respectively, P < 0.001). Diabetes remained associated with higher ECV in models adjusting for demographics, comorbidities, and medications (P < 0.001). Renin-angiotensin-aldosterone system blockade was associated with lower ECV (P = 0.028) in multivariable linear models. Over a median of 1.3 years (IQR: 0.8-1.9), 38 diabetic individuals had events (21 incident hospitalizations for heart failure; 24 deaths), and ECV was associated with these events (HR: 1.52, 95% CI: 1.21-1.89 per 3% ECV increase) in multivariable Cox regression models.ConclusionDiabetes is associated with increased ECV. Extracellular volume fraction detects amelioration of ECM expansion associated with RAAS blockade, and is associated with mortality and/or incident hospitalization for heart failure in diabetic individuals. Extracellular matrix expansion may be an important intermediate phenotype in diabetic individuals that is detectable and treatable.

KW - collagen

KW - diabetes

KW - extracellular matrix

KW - extracellular volume fraction

KW - fibrosis

KW - MRI

UR - http://www.scopus.com/inward/record.url?scp=84897948375&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897948375&partnerID=8YFLogxK

U2 - 10.1093/eurheartj/eht193

DO - 10.1093/eurheartj/eht193

M3 - Article

VL - 35

SP - 657

EP - 664

JO - European Heart Journal

JF - European Heart Journal

SN - 0195-668X

IS - 10

ER -