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Myocardial fibrosis and prognosis in heart failure with preserved ejection fraction: a pooled analysis of 12 cohort studies

  • Cardiac
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Abstract

Objectives

Heart failure with preserved ejection fraction (HFpEF) is a syndrome with significant clinical heterogeneity. Myocardial fibrosis has been considered a common pathological process in the development and progress of HFpEF. This study aimed to consolidate data on the prognostic effect of myocardial fibrosis, evaluated by cardiovascular magnetic resonance (CMR) imaging in patients with HFpEF.

Methods

Three medical databases were searched for potentially related articles up to February 28, 2023. Cohort studies reporting associations between myocardial fibrosis and risk of all-cause mortality or composite major adverse cardiac outcomes (MACE) were included. Cardiac fibrosis was evaluated by CMR metrics, including late gadolinium enhancement (LGE) or myocardial extracellular volume (ECV). The hazard ratios (HRs) and 95% confidence intervals (CI) of the outcomes for higher myocardial fibrosis were calculated.

Results

Twelve studies with 2787 patients with HFpEF were included for analysis. After a median follow-up duration of 31.2 months, a higher level of cardiac fibrosis was associated with a significant increase in the risk of MACE (HR = 1.34, 95% CI = 1.14–1.57) and all-cause mortality (HR = 1.74, 95% CI = 1.27–2.39), respectively. Furthermore, the increased risk of outcomes was both observed when cardiac fibrosis was defined according to LGE or ECV, respectively.

Conclusions

Higher burden of myocardial fibrosis evaluated by CMR can predict a poor prognosis in patients with HFpEF. Evaluation of LGE or ECV based on CMR could be recommended in these patients for risk stratification and guiding further treatment.

Clinical relevance statement

Inclusion of cardiovascular magnetic resonance examination in the diagnostic and risk-evaluation algorithms in patients with heart failure with preserved ejection fraction should be considered in clinical practice and future studies.

Key Points

• Myocardial fibrosis is a common pathological process in heart failure with preserved ejection fraction.

• A higher myocardial fibrosis burden on cardiac magnetic resonance predicts a poor prognosis in patients with heart failure with preserved ejection fraction.

• Evaluation of myocardial fibrosis may be useful in patients with heart failure with preserved ejection fraction for risk stratification and treatment guidance.

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Abbreviations

CI:

Confidence intervals

CMR:

Cardiovascular magnetic resonance

ECV:

Myocardial extracellular volume

HFpEF:

Heart failure with preserved ejection fraction

HFrEF:

Heart failure with reduced ejection fraction

HRs:

Hazard ratios

LGE:

Late gadolinium enhancement

MACE:

Major adverse cardiac event

MOLLI:

Modified Look-Locker inversion recovery sequence

QUIPS:

Quality in Prognosis Studies

RRs:

Relative risks

SEs:

Standard errors

References

  1. Wu J, Zheng H, Liu X et al (2020) Prognostic value of secreted frizzled-related protein 5 in heart failure patients with and without type 2 diabetes mellitus. Circ Heart Fail 13:e7054

    Google Scholar 

  2. Wu J, Qiu M, Sun L et al (2021) Alpha-linolenic acid and risk of heart failure: a meta-analysis. Front Cardiovasc Med 8:788452

    CAS  PubMed  Google Scholar 

  3. Mai L, Wen W, Qiu M et al (2021) Association between prediabetes and adverse outcomes in heart failure. Diabetes Obes Metab 23:2476–2483

    PubMed  Google Scholar 

  4. Choy M, Liang W, He J et al (2022) Phenotypes of heart failure with preserved ejection fraction and effect of spironolactone treatment. ESC Heart Fail 9:2567–2575

    PubMed  PubMed Central  Google Scholar 

  5. Uijl A, Savarese G, Vaartjes I et al (2021) Identification of distinct phenotypic clusters in heart failure with preserved ejection fraction. Eur J Heart Fail 23:973–982

    PubMed  Google Scholar 

  6. Brann A, Tran H, Greenberg B (2020) Contemporary approach to treating heart failure. Trends Cardiovasc Med 30:507–518

    CAS  PubMed  Google Scholar 

  7. Kruszewska J, Cudnoch-Jedrzejewska A, Czarzasta K (2022) Remodeling and fibrosis of the cardiac muscle in the course of obesity-pathogenesis and involvement of the extracellular matrix. Int J Mol Sci 23:4195

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Assadi H, Jones R, Swift AJ, Al-Mohammad A, Garg P (2021) Cardiac MRI for the prognostication of heart failure with preserved ejection fraction: a systematic review and meta-analysis. Magn Reson Imaging 76:116–122

    PubMed  PubMed Central  Google Scholar 

  9. Kanagala P, Cheng A, Singh A et al (2018) Diagnostic and prognostic utility of cardiovascular magnetic resonance imaging in heart failure with preserved ejection fraction - implications for clinical trials. J Cardiovasc Magn Reson 20:4

    PubMed  PubMed Central  Google Scholar 

  10. Roy C, Slimani A, de Meester C et al (2018) Associations and prognostic significance of diffuse myocardial fibrosis by cardiovascular magnetic resonance in heart failure with preserved ejection fraction. J Cardiovasc Magn Reson 20:55

    PubMed  PubMed Central  Google Scholar 

  11. Yang S, Chen H, Tan K et al (2020) Secreted frizzled-related protein 2 and extracellular volume fraction in patients with heart failure. Oxid Med Cell Longev 2020:2563508

    PubMed  PubMed Central  Google Scholar 

  12. Pezel T, Hovasse T, Sanguineti F et al (2021) Long-term prognostic value of stress CMR in patients with heart failure and preserved ejection fraction. JACC Cardiovasc Imaging 14:2319–2333

    PubMed  Google Scholar 

  13. van Woerden G, van Veldhuisen DJ, Gorter TM et al (2022) The clinical and prognostic value of late gadolinium enhancement imaging in heart failure with mid-range and preserved ejection fraction. Heart Vessels 37:273–281

    PubMed  Google Scholar 

  14. Rush CJ, Berry C, Oldroyd KG et al (2021) Prevalence of coronary artery disease and coronary microvascular dysfunction in patients with heart failure with preserved ejection fraction. JAMA Cardiol 6:1130–1143

    PubMed  Google Scholar 

  15. Garg P, Assadi H, Jones R et al (2021) Left ventricular fibrosis and hypertrophy are associated with mortality in heart failure with preserved ejection fraction. Sci Rep 11:617

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Nitsche C, Kammerlander AA, Binder C et al (2020) Native T1 time of right ventricular insertion points by cardiac magnetic resonance: relation with invasive haemodynamics and outcome in heart failure with preserved ejection fraction. Eur Heart J Cardiovasc Imaging 21:683–691

    PubMed  Google Scholar 

  17. Kanagala P, Cheng A, Singh A et al (2019) Relationship between focal and diffuse fibrosis assessed by CMR and clinical outcomes in heart failure with preserved ejection fraction. JACC Cardiovasc Imaging 12:2291–2301

    PubMed  Google Scholar 

  18. Murtagh G, Laffin LJ, Beshai JF et al (2016) Prognosis of myocardial damage in sarcoidosis patients with preserved left ventricular ejection fraction: risk stratification using cardiovascular magnetic resonance. Circ Cardiovasc Imaging 9:e3738

    Google Scholar 

  19. Kato S, Saito N, Kirigaya H et al (2015) Prognostic significance of quantitative assessment of focal myocardial fibrosis in patients with heart failure with preserved ejection fraction. Int J Cardiol 191:314–319

    PubMed  Google Scholar 

  20. Duca F, Kammerlander AA, Zotter-Tufaro C et al (2016) Interstitial fibrosis, functional status, and outcomes in heart failure with preserved ejection fraction: insights from a prospective cardiac magnetic resonance imaging study. Circ Cardiovasc Imaging 9:e005277

    PubMed  Google Scholar 

  21. Schelbert EB, Fridman Y, Wong TC et al (2017) Temporal relation between myocardial fibrosis and heart failure with preserved ejection fraction: association with baseline disease severity and subsequent outcome. JAMA Cardiol 2:995–1006

    PubMed  PubMed Central  Google Scholar 

  22. Stroup DF, Berlin JA, Morton SC et al (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283:2008–2012

    CAS  PubMed  Google Scholar 

  23. Jiang C, Wang Y, Fu W et al (2022) Association between sarcopenia and prognosis of hepatocellular carcinoma: a systematic review and meta-analysis. Front Nutr. 14(9):978110

    Google Scholar 

  24. Perais J, Agarwal R, Evans JR et al (2023) Prognostic factors for the development and progression of proliferative diabetic retinopathy in people with diabetic retinopathy. Cochrane Database Syst Rev 2:D13775

    Google Scholar 

  25. Yang Y, Li W, Zhu H et al (2020) Prognosis of unrecognised myocardial infarction determined by electrocardiography or cardiac magnetic resonance imaging: systematic review and meta-analysis. BMJ 369:m1184

    PubMed  PubMed Central  Google Scholar 

  26. Cai X, Sun L, Liu X et al (2021) Non-alcoholic fatty liver disease is associated with increased risk of chronic kidney disease. Ther Adv Chronic Dis 12:364072937

    Google Scholar 

  27. Trejo-Velasco B, Cruz-González I, Barreiro-Pérez M et al (2022) Mean velocity of the pulmonary artery as a clinically relevant prognostic indicator in patients with heart failure with preserved ejection fraction. J Clin Med 11:491

    PubMed  PubMed Central  Google Scholar 

  28. Li Y, Liu X, Yang F et al (2021) Prognostic value of myocardial extracellular volume fraction evaluation based on cardiac magnetic resonance T1 mapping with T1 long and short in hypertrophic cardiomyopathy. Eur Radiol 31:4557–4567

    PubMed  Google Scholar 

  29. Liu J, Zhao S, Yu S et al (2022) Patterns of replacement fibrosis in hypertrophic cardiomyopathy. Radiology 302:298–306

    PubMed  Google Scholar 

  30. Liu X, Gao Y, Guo YK et al (2022) Cardiac magnetic resonance T1 mapping for evaluating myocardial fibrosis in patients with type 2 diabetes mellitus: correlation with left ventricular longitudinal diastolic dysfunction. Eur Radiol 32:7647–7656

    PubMed  Google Scholar 

  31. Golukhova E, Bulaeva N, Alexandrova S, Gromova O, Berdibekov B (2022) Prognostic value of characterizing myocardial tissue by cardiac MRI with T1 mapping in HFpEF patients: a systematic review and meta-analysis. J Clin Med 11:2531

    PubMed  PubMed Central  Google Scholar 

  32. Cai X, Liu X, Sun L et al (2021) Prediabetes and the risk of heart failure: a meta-analysis. Diabetes Obes Metab 23:1746–1753

    PubMed  Google Scholar 

  33. Kasiakogias A, Rosei EA, Camafort M et al (2021) Hypertension and heart failure with preserved ejection fraction: position paper by the European Society of Hypertension. J Hypertens 39:1522–1545

    CAS  PubMed  Google Scholar 

  34. Joslin JR, Lioudaki E, Androulakis E (2022) Interrelation between heart failure with preserved ejection fraction and renal impairment. Rev Cardiovasc Med 23:69

    PubMed  Google Scholar 

  35. Leyva F, Zegard A, Okafor O et al (2022) Myocardial fibrosis predicts ventricular arrhythmias and sudden death after cardiac electronic device implantation. J Am Coll Cardiol 79:665–678

    PubMed  Google Scholar 

  36. Rubis PP, Dziewiecka EM, Banys P et al (2021) Extracellular volume is an independent predictor of arrhythmic burden in dilated cardiomyopathy. Sci Rep 11:24000

    CAS  PubMed  PubMed Central  ADS  Google Scholar 

  37. Scott PA, Rosengarten JA, Curzen NP, Morgan JM (2013) Late gadolinium enhancement cardiac magnetic resonance imaging for the prediction of ventricular tachyarrhythmic events: a meta-analysis. Eur J Heart Fail 15:1019–1027

    CAS  PubMed  Google Scholar 

  38. Jiang M, Xie X, Cao F, Wang Y (2021) Mitochondrial metabolism in myocardial remodeling and mechanical unloading: implications for ischemic heart disease. Front Cardiovasc Med 8:789267

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Smiseth OA, Morris DA, Cardim N et al (2022) Multimodality imaging in patients with heart failure and preserved ejection fraction: an expert consensus document of the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 24(23):e34–e61

    Google Scholar 

  40. Del Torto A, Guaricci AI, Pomarico F et al (2022) Advances in multimodality cardiovascular imaging in the diagnosis of heart failure with preserved ejection fraction. Front Cardiovasc Med 9(9):758975

    PubMed  PubMed Central  Google Scholar 

  41. He J, Yang W, Jiang Y, Sun X et al (2023) Heart failure with preserved ejection fraction assessed by cardiac magnetic resonance: From clinical uses to emerging techniques. Trends Cardiovasc Med 33(3):141–147

    PubMed  Google Scholar 

  42. Arnold JR, Kanagala P, Budgeon CA et al (2022) Prevalence and prognostic significance of microvascular dysfunction in heart failure with preserved ejection fraction. JACC Cardiovasc Imaging 15:1001–1011

    PubMed  Google Scholar 

  43. Gonzalez JA, Kramer CM (2015) Role of imaging techniques for diagnosis, prognosis and management of heart failure patients: cardiac magnetic resonance. Curr Heart Fail Rep 12:276–283

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Kalra R, Gupta K, Sheets R et al (2020) Cardiac function and sudden cardiac death in heart failure with preserved ejection fraction (from the TOPCAT Trial). Am J Cardiol 129:46–52

    PubMed  Google Scholar 

  45. Ferreira JP, Rossello X, Eschalier R et al (2019) MRAs in elderly HF patients: individual patient-data meta-analysis of RALES, EMPHASIS-HF, and TOPCAT. JACC Heart Fail 7:1012–1021

    PubMed  Google Scholar 

  46. Young MJ, Kanki M, Karthigan N, Konstandopoulos P (2021) The role of the mineralocorticoid receptor and mineralocorticoid receptor-directed therapies in heart failure. Endocrinology 162(11):bqab105

  47. Schulz A, Schuster A (2022) Visualizing diastolic failure: non-invasive imaging-biomarkers in patients with heart failure with preserved ejection fraction. EBioMedicine 86:104369

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Barison A, Aimo A, Todiere G, Grigoratos C, Aquaro GD, Emdin M (2022) Cardiovascular magnetic resonance for the diagnosis and management of heart failure with preserved ejection fraction. Heart Fail Rev 27:191–205

    PubMed  Google Scholar 

  49. Zhang S, Zhou Y, Han S, Ma Y, Wang C, Hou Y (2023) The diagnostic and prognostic value of cardiac magnetic resonance strain analysis in heart failure with preserved ejection fraction. Contrast Media Mol Imaging 2023:5996741

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Emily Woodhouse, PhD, from Liwen Bianji (Edanz) (www.liwenbianji.cn) for editing the English text of a draft of this manuscript.

The datasets and/or analyses during the current study are available from the corresponding author on reasonable request.

Funding

This study was supported by the National Natural Science Foundation of China (no.: 82270384), Guangdong Basic and Applied Basic Research Fund (Key project of Guangdong-Foshan Joint Fund) (2019B1515120044), the Scientific Research Start-up Plan of Southern Medical University (CX2018N202), the Clinical Research Startup Program of Shunde Hospital, Southern Medical University (CRSP2019001), and the Outstanding Young Medical Staff in Guangdong Province (600001).

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Author notes

  1. Xiaojie Zhang, Shaomin Yang, and Shali Hao contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Shunde Hospital, Southern Medical University (the First People’s Hospital of Shunde), Jiazhi Road, Lunjiao Town, Shunde District, Foshan, 528300, China

    Xiaojie Zhang, Shali Hao, Jiahuan Li, Min Qiu & Yuli Huang

  2. Department of Radiology, Lecong Hospital of Shunde, Foshan, China

    Shaomin Yang

  3. Department of Radiology, Shunde Hospital, Southern Medical University (the First People’s Hospital of Shunde), Jiazhi Road, Lunjiao Town, Shunde District, Foshan, 528300, China

    Haixiong Chen

  4. Faculty of Medicine, The George Institute for Global Health, University of New South Wales, Sydney, Australia

    Yuli Huang

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Correspondence to Haixiong Chen or Yuli Huang.

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The scientific guarantor of this publication is Yuli Huang.

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Statistics and biometry

No complex statistical methods were necessary for this paper.

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Not required. The study is a meta-analysis of published studies, and written informed consent is not applicable.

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Not applicable. The study is a meta-analysis of published studies, and ethical compliance is not applicable.

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Zhang, X., Yang, S., Hao, S. et al. Myocardial fibrosis and prognosis in heart failure with preserved ejection fraction: a pooled analysis of 12 cohort studies. Eur Radiol 34, 1854–1862 (2024). https://doi.org/10.1007/s00330-023-10218-w

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