Extracellular volume and global longitudinal strain both associate with outcomes but correlate minimally

Fredrika Fröjdh, Yaron Fridman, Patrick Bering, Aatif Sayeed, Maren Maanja, Louise Niklasson, Eric Olausson, Hongyang Pi, Timothy C Wong, Peter Kellman, Brian Feingold, Adam Christopher, Miho Fukui, João L Cavalcante, Christopher Miller, Javed Butler, Martin Ugander, Erik B Schelbert

Research output: Contribution to journalArticlepeer-review


Objectives: We examined how extracellular volume (ECV) and global longitudinal strain (GLS) relate to each other and to outcomes.

Background: Among myriad changes occurring in diseased myocardium, left ventricular imaging metrics of either: a) the interstitium—such as ECV , or b) contractile function—such as GLS, may consistently associate with adverse outcomes yet correlate minimally with each other, suggesting that ECV and GLS potentially represent distinct domains of cardiac vulnerability.

Methods: In 1578 patients referred for cardiovascular magnetic resonance (CMR) without amyloidosis, we quantified how ECV associated with GLS in linear regression models. We then compared ECV and GLS in their associations with incident outcomes (death and hospitalization for heart failure (HHF)).

Results: ECV and GLS correlated minimally (R2=0.04). Over a median follow-up of 5.6 years, 339 patients experienced adverse events (149 HHF, 253 deaths, 63 with both). GLS (univariable HR 2.07 per 5% increment, (95%CI 1.86-2.29) and ECV (univariable HR 1.66 per 4% increment, (95%CI 1.51-4.82) were principal variables associating with outcomes in univariable and multivariable Cox regression models. We observed similar results in several clinically important subgroups. In the whole cohort, ECV added prognostic value beyond GLS in univariable and multivariable Cox regression models.

Conclusion: GLS and ECV may represent principal but distinct domains of cardiac vulnerability, perhaps reflecting their distinct cellular origins. Whether combining ECV and GLS may advance pathophysiologic understanding for a given patient, optimize risk stratification, and foster personalized medicine by targeted therapeutics requires further investigation.
Original languageEnglish
JournalJACC: Cardiovascular Imaging
Publication statusAccepted/In press - 10 Apr 2020


  • global longitudinal strain
  • interstitium
  • cardiac magnetice resonance
  • extracellular volume
  • myocardial fibrosis


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