Author + information
- Received September 17, 2019
- Revision received April 8, 2020
- Accepted April 9, 2020
- Published online June 17, 2020.
- Fredrika Fröjdh, MDa,
- Yaron Fridman, MDb,
- Patrick Bering, MDc,
- Aatif Sayeed, MDc,
- Maren Maanja, MDa,
- Louise Niklasson, MDa,
- Eric Olausson, MDa,
- Hongyang Pi, MDc,
- Ali Azeem, MDc,
- Timothy C. Wong, MD, MSc,d,e,f,
- Peter Kellman, PhDg,
- Brian Feingold, MD, MSf,h,
- Adam Christopher, MDh,
- Miho Fukui, MDi,
- João L. Cavalcante, MDi,
- Christopher A. Miller, MBBCh, PhDj,k,l,
- Javed Butler, MD, MPHm,
- Martin Ugander, MD, PhDa,n and
- Erik B. Schelbert, MD, MSc,d,e,f,∗ (, )@erik_schelbert
- aDepartment of Clinical Physiology, Karolinska University Hospital, and Karolinska Institutet, Stockholm, Sweden
- bAsheville Cardiology Associates, Mission Hospital, Asheville, North Carolina
- cUPMC Cardiovascular Magnetic Resonance Center, UPMC, Pittsburgh, Pennsylvania
- dDepartment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
- eHeart and Vascular Institute, UPMC, Pittsburgh, Pennsylvania
- fClinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
- gNational Heart Lung and Blood Institute, Bethesda, Maryland
- hDepartment of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
- iMinneapolis Heart Institute, Abbott Northwestern Hospital, Minneapolis, Minnesota
- jDivision of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom
- kManchester University NHS Foundation Trust, Wythenshawe, Manchester, United Kingdom
- lWellcome Centre for Cell-Matrix Research, Division of Cell-Matrix Biology & Regenerative Medicine, School of Biology, Faculty of Biology, Medicine & Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom
- mDepartment of Medicine, University of Mississippi, Jackson, Mississippi
- nKolling Institute, Royal North Shore Hospital, and Sydney Medical School, Northern Clinical School, University of Sydney, Sydney, Australia
- ↵∗Address for correspondence:
Dr. Erik B. Schelbert, University of Pittsburgh School of Medicine, 200 Lothrop Street, PUH E E354.2, Pittsburgh, Pennsylvania 15101.
Objectives This study examined how ECV and GLS relate to each other and to outcomes.
Background Among myriad changes occurring in diseased myocardium, left ventricular imaging metrics of either the interstitium (e.g., extracellular volume [ECV]) or contractile function (e.g., global longitudinal strain [GLS]) may consistently associate with adverse outcomes yet correlate minimally with each other. This scenario suggests that ECV and GLS potentially represent distinct domains of cardiac vulnerability.
Methods The study included 1,578 patients referred for cardiovascular magnetic resonance (CMR) without amyloidosis, and it quantified how ECV associated with GLS in linear regression models. ECV and GLS were then compared in their associations with incident outcomes (death and hospitalization for heart failure).
Results ECV and GLS correlated minimally (R2 = 0.04). Over a median follow-up of 5.6 years, 339 patients experienced adverse events (149 hospitalizations for heart failure, 253 deaths, and 63 with both). GLS (univariable hazard ratio: 2.07 per 5% increment; 95% CI: 1.86 to 2.29) and ECV (univariable hazard ratio: 1.66 per 4% increment; 95% CI: 1.51 to 1.82) were principal variables associating with outcomes in univariable and multivariable Cox regression models. Similar results were observed in several clinically important subgroups. In the whole cohort, ECV added prognostic value beyond GLS in univariable and multivariable Cox regression models.
Conclusions 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 pathophysiological understanding for a given patient, optimize risk stratification, and foster personalized medicine by targeted therapeutics requires further investigation.
- cardiac magnetic resonance
- extracellular volume
- global longitudinal strain
- myocardial fibrosis
This work was supported by several entities. Dr. Miller is funded by a Clinician Scientist Award (CS-2015-15-003) from the National Institute for Health (NIH) Research. Dr. Wong was supported by an American Heart Association Scientist Development grant and a Children’s Cardiomyopathy Foundation grant. Dr. Feingold was supported by an American Heart Association Enduring Hearts grant (14GRNT20380101) and a National Center for Advancing Translational Sciences of the NIH (KL2TR000146) grant. Dr. Schelbert was supported by a grant from The Pittsburgh Foundation (M2009-0068) and an American Heart Association Scientist Development grant (09SDG2180083) including a T. Franklin Williams Scholarship Award. Funding was provided by Atlantic Philanthropies, Inc., the John A. Hartford Foundation, the Association of Specialty Professors, and the American Heart Association. This work was also supported by grant UL1-TR-001857 from the National Center for Research Resources, a component of the NIH and the NIH Roadmap for Medical Research. Drs. Fröjdh, Maanja, Niklasson, Olausson, and Ugander were supported in part by grants (principal investigator: Dr. Ugander) from the Swedish Research Council, Swedish Heart and Lung Foundation, Stockholm County Council, and Karolinska Institutet. Dr. Butler is a consultant, speakerm, serves on steering committee, clinical events committee, and data safety monitoring for Abbott, Adrenomed, Amgen, Applied Therapeutics, Array, Astra Zeneca, Bayer, BerlinCures, Boehringer Ingelheim, Cardior, CVRx, Foundry, G3 Pharma, Imbria, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, NovoNordisk, Relypsa, Roche, Sanofi, Sequana Medical, V-Wave Limited, and Vifor. Dr. Miller received research support from Roche and Guerbet; and is an advisory board participant for Novartis. Dr. Schelbert has accepted contrast material from Bracco Diagnostics for research purposes; served on advisory boards for Merck and Bayer; and currently serves on the Scientific Advisory Board of Haya Therapeutics. Dr. Ugander is principal investigator on a research and development agreement regarding cardiovascular magnetic resonance between Siemens and Karolinska University Hospital. Dr. Cavalcante has received consulting fees from Boston Scientific, Medtronic, and Abbott Vascular; and research grant support from Abbott Vascular, Edwards Lifesciences, Medtronic, Boston Scientific, Circle Cardiovascular Imaging, Siemens Healthineers, and Medis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Cardiovascular Imaging author instructions page.
- Received September 17, 2019.
- Revision received April 8, 2020.
- Accepted April 9, 2020.
- 2020 American College of Cardiology Foundation
This article requires a subscription or purchase to view the full text. If you are a subscriber or member, click Login or the Subscribe link (top menu above) to access this article.