The Combination of Carboxy-terminal Propeptide of Procollagen Type I Blood Levels and Late Gadolinium Enhancement at Cardiac Magnetic Resonance Provides Additional Prognostic Information in Idiopathic Dilated Cardiomyopathy - A Multilevel Assessment...

Overview

Journal Eur J Heart Fail

Publisher Wiley

Specialty Cardiology & Vascular Diseases

Date 2021 Apr 30

PMID 33928704

Citations 24

Authors

Anne G Raafs

Job A J Verdonschot

Michiel T H M Henkens

Bouke P Adriaans

Ping Wang

Kasper Derks

Myrurgia A Abdul Hamid

Christian Knackstedt

Vanessa P M van Empel

Javier Diez

Hans-Peter Brunner-La Rocca

Han G Brunner

Arantxa Gonzalez

Sebastiaan C A M Bekkers

Stephane R B Heymans

Mark R Hazebroek

Affiliations

Soon will be listed here.

Abstract

Aims: To determine the prognostic value of multilevel assessment of fibrosis in dilated cardiomyopathy (DCM) patients.

Methods And Results: We quantified fibrosis in 209 DCM patients at three levels: (i) non-invasive late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR); (ii) blood biomarkers [amino-terminal propeptide of procollagen type III (PIIINP) and carboxy-terminal propeptide of procollagen type I (PICP)], (iii) invasive endomyocardial biopsy (EMB) (collagen volume fraction, CVF). Both LGE and elevated blood PICP levels, but neither PIIINP nor CVF predicted a worse outcome defined as death, heart transplantation, heart failure hospitalization, or life-threatening arrhythmias, after adjusting for known clinical predictors [adjusted hazard ratios: LGE 3.54, 95% confidence interval (CI) 1.90-6.60; P < 0.001 and PICP 1.02, 95% CI 1.01-1.03; P = 0.001]. The combination of LGE and PICP provided the highest prognostic benefit in prediction (likelihood ratio test P = 0.007) and reclassification (net reclassification index: 0.28, P = 0.02; and integrated discrimination improvement index: 0.139, P = 0.01) when added to the clinical prediction model. Moreover, patients with a combination of LGE and elevated PICP (LGE+/PICP+) had the worst prognosis (log-rank P < 0.001). RNA-sequencing and gene enrichment analysis of EMB showed an increased expression of pro-fibrotic and pro-inflammatory pathways in patients with high levels of fibrosis (LGE+/PICP+) compared to patients with low levels of fibrosis (LGE-/PICP-). This would suggest the validity of myocardial fibrosis detection by LGE and PICP, as the subsequent generated fibrotic risk profiles are associated with distinct cardiac transcriptomic profiles.

Conclusion: The combination of myocardial fibrosis at CMR and circulating PICP levels provides additive prognostic value accompanied by a pro-fibrotic and pro-inflammatory transcriptomic profile in DCM patients with LGE and elevated PICP.

Citing Articles

The Pathobiology of Myocardial Recovery and Remission: From Animal Models to Clinical Observations in Heart Failure Patients.

Park A, Mann D Methodist Debakey Cardiovasc J. 2024; 20(4):16-30.

PMID: 39184167 PMC: 11342835. DOI: 10.14797/mdcvj.1389.

Recent Progresses in the Multimodality Imaging Assessment of Myocardial Fibrosis.

Zhu H, Xie K, Qian Y, Zou Z, Jiang M, Pu J Rev Cardiovasc Med. 2024; 25(1):5.

PMID: 39077665 PMC: 11262344. DOI: 10.31083/j.rcm2501005.

Serum Concentrations of Matrix Metalloproteinase-1 and Procollagen Type I Carboxy Terminal Propeptide Discriminate Infarct-Like Myocarditis and Non-ST-Segment-Elevation Myocardial Infarction.

Bacmeister L, Cavus E, Bohnen S, Tahir E, Wolf H, Buellesbach A J Am Heart Assoc. 2024; 13(14):e034194.

PMID: 38989835 PMC: 11292779. DOI: 10.1161/JAHA.124.034194.

Usformer: A small network for left atrium segmentation of 3D LGE MRI.

Lin H, Lopez-Tapia S, Schiffers F, Wu Y, Gunasekaran S, Hwang J Heliyon. 2024; 10(7):e28539.

PMID: 38596055 PMC: 11002571. DOI: 10.1016/j.heliyon.2024.e28539.

Precision therapy in dilated cardiomyopathy: Pipedream or paradigm shift?.

Javed S, Halliday B Camb Prism Precis Med. 2024; 1:e34.

PMID: 38550947 PMC: 10953759. DOI: 10.1017/pcm.2023.24.

References

Szekely Y, Arbel Y . A Review of Interleukin-1 in Heart Disease: Where Do We Stand Today?. Cardiol Ther. 2018; 7(1):25-44. PMC: 5986669. DOI: 10.1007/s40119-018-0104-3. View

Hazebroek M, Moors S, Dennert R, van den Wijngaard A, Krapels I, Hoos M . Prognostic Relevance of Gene-Environment Interactions in Patients With Dilated Cardiomyopathy: Applying the MOGE(S) Classification. J Am Coll Cardiol. 2015; 66(12):1313-23. DOI: 10.1016/j.jacc.2015.07.023. View

Lopez B, Gonzalez A, Diez J . Circulating biomarkers of collagen metabolism in cardiac diseases. Circulation. 2010; 121(14):1645-54. DOI: 10.1161/CIRCULATIONAHA.109.912774. View

Fiordelisi A, Iaccarino G, Morisco C, Coscioni E, Sorriento D . NFkappaB is a Key Player in the Crosstalk between Inflammation and Cardiovascular Diseases. Int J Mol Sci. 2019; 20(7). PMC: 6480579. DOI: 10.3390/ijms20071599. View

Cooper L, Baughman K, Feldman A, Frustaci A, Jessup M, Kuhl U . The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Endorsed by the Heart Failure.... J Am Coll Cardiol. 2007; 50(19):1914-31. DOI: 10.1016/j.jacc.2007.09.008. View

Ravassa S, Trippel T, Bach D, Bachran D, Gonzalez A, Lopez B . Biomarker-based phenotyping of myocardial fibrosis identifies patients with heart failure with preserved ejection fraction resistant to the beneficial effects of spironolactone: results from the Aldo-DHF trial. Eur J Heart Fail. 2018; 20(9):1290-1299. DOI: 10.1002/ejhf.1194. View

Nakamori S, Dohi K, Ishida M, Goto Y, Imanaka-Yoshida K, Omori T . Native T1 Mapping and Extracellular Volume Mapping for the Assessment of Diffuse Myocardial Fibrosis in Dilated Cardiomyopathy. JACC Cardiovasc Imaging. 2017; 11(1):48-59. DOI: 10.1016/j.jcmg.2017.04.006. View

Massoullie G, Sapin V, Ploux S, Rossignol P, Mulliez A, Jean F . Low fibrosis biomarker levels predict cardiac resynchronization therapy response. Sci Rep. 2019; 9(1):6103. PMC: 6465309. DOI: 10.1038/s41598-019-42468-4. View

Zannad F, Alla F, Dousset B, Perez A, Pitt B . Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales Investigators. Circulation. 2000; 102(22):2700-6. DOI: 10.1161/01.cir.102.22.2700. View

10.

Verdonschot J, Hazebroek M, Ware J, Prasad S, Heymans S . Role of Targeted Therapy in Dilated Cardiomyopathy: The Challenging Road Toward a Personalized Approach. J Am Heart Assoc. 2019; 8(11):e012514. PMC: 6585365. DOI: 10.1161/JAHA.119.012514. View

11.

Aoki T, Fukumoto Y, Sugimura K, Oikawa M, Satoh K, Nakano M . Prognostic impact of myocardial interstitial fibrosis in non-ischemic heart failure. -Comparison between preserved and reduced ejection fraction heart failure.-. Circ J. 2011; 75(11):2605-13. DOI: 10.1253/circj.cj-11-0568. View

12.

Maceira A, Prasad S, Khan M, Pennell D . Normalized left ventricular systolic and diastolic function by steady state free precession cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2006; 8(3):417-26. DOI: 10.1080/10976640600572889. View

13.

Suthahar N, Meijers W, Sillje H, de Boer R . From Inflammation to Fibrosis-Molecular and Cellular Mechanisms of Myocardial Tissue Remodelling and Perspectives on Differential Treatment Opportunities. Curr Heart Fail Rep. 2017; 14(4):235-250. PMC: 5527069. DOI: 10.1007/s11897-017-0343-y. View

14.

Schneider C, Rasband W, Eliceiri K . NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012; 9(7):671-5. PMC: 5554542. DOI: 10.1038/nmeth.2089. View

15.

Shanbhag S, Greve A, Aspelund T, Schelbert E, Cao J, Danielsen R . Prevalence and prognosis of ischaemic and non-ischaemic myocardial fibrosis in older adults. Eur Heart J. 2018; 40(6):529-538. PMC: 6657269. DOI: 10.1093/eurheartj/ehy713. View

16.

Xu Y, Li W, Wan K, Liang Y, Jiang X, Wang J . Myocardial Tissue Reverse Remodeling After Guideline-Directed Medical Therapy in Idiopathic Dilated Cardiomyopathy. Circ Heart Fail. 2020; 14(1):e007944. DOI: 10.1161/CIRCHEARTFAILURE.120.007944. View

17.

Kanoupakis E, Manios E, Kallergis E, Mavrakis H, Goudis C, Saloustros I . Serum markers of collagen turnover predict future shocks in implantable cardioverter-defibrillator recipients with dilated cardiomyopathy on optimal treatment. J Am Coll Cardiol. 2010; 55(24):2753-9. DOI: 10.1016/j.jacc.2010.02.040. View

18.

Cleland J, Ferreira J, Mariottoni B, Pellicori P, Cuthbert J, Verdonschot J . The effect of spironolactone on cardiovascular function and markers of fibrosis in people at increased risk of developing heart failure: the heart 'OMics' in AGEing (HOMAGE) randomized clinical trial. Eur Heart J. 2020; 42(6):684-696. PMC: 7878013. DOI: 10.1093/eurheartj/ehaa758. View

19.

Gonzalez A, Schelbert E, Diez J, Butler J . Myocardial Interstitial Fibrosis in Heart Failure: Biological and Translational Perspectives. J Am Coll Cardiol. 2018; 71(15):1696-1706. DOI: 10.1016/j.jacc.2018.02.021. View

20.

Flett A, Hasleton J, Cook C, Hausenloy D, Quarta G, Ariti C . Evaluation of techniques for the quantification of myocardial scar of differing etiology using cardiac magnetic resonance. JACC Cardiovasc Imaging. 2011; 4(2):150-6. DOI: 10.1016/j.jcmg.2010.11.015. View