Progression of myocardial fibrosis in hypertrophic cardiomyopathy

mechanisms and clinical implications

Betty Raman, Rina Ariga, Marco Spartera, Sanjay Sivalokanathan, Kenneth Chan, Sairia Dass, Steffen E. Petersen, Matthew J. Daniels, Jane Francis, Robert Smillie, Adam J. Lewandowski, Eric O. Ohuma, Christopher Rodgers, Christopher M. Kramer, Masliza Mahmod, Hugh Watkins, Stefan Neubauer

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Aims: Myocardial fibrosis as detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a powerful prognostic marker in hypertrophic cardiomyopathy (HCM) and may be progressive. The precise mechanisms underlying fibrosis progression are unclear. We sought to assess the extent of LGE progression in HCM and explore potential causal mechanisms and clinical implications. Methods and results: Seventy-two HCM patients had two CMR (CMR1-CMR2) at an interval of 5.7 ± 2.8 years with annual clinical follow-up for 6.3 ± 3.6 years from CMR1. A combined endpoint of heart failure progression, cardiac hospitalization, and new onset ventricular tachycardia was assessed. Cine and LGE imaging were performed to assess left ventricular (LV) mass, function, and fibrosis on serial CMR. Stress perfusion imaging and cardiac energetics were undertaken in 38 patients on baseline CMR (CMR1). LGE mass increased from median 4.98 g [interquartile range (IQR) 0.97-13.48 g] to 6.30 g (IQR 1.38-17.51 g) from CMR1 to CMR2. Substantial LGE progression (ΔLGE ≥ 4.75 g) occurred in 26% of patients. LGE increment was significantly higher in those with impaired myocardial perfusion reserve (<MPRI 1.40) and energetics (phosphocreatine/adenosine triphosphate <1.44) on baseline CMR (P ≤ 0.01 for both). Substantial LGE progression was associated with LV thinning, increased cavity size and reduced systolic function, and conferred a five-fold increased risk of subsequent clinical events (hazard ratio 5.04, 95% confidence interval 1.85-13.79; P = 0.002). Conclusion: Myocardial fibrosis is progressive in some HCM patients. Impaired energetics and perfusion abnormalities are possible mechanistic drivers of the fibrotic process. Fibrosis progression is associated with adverse cardiac remodelling and predicts an increased risk of subsequent clinical events in HCM.

Original languageEnglish
Pages (from-to)157-167
Number of pages11
JournalEuropean Heart Journal Cardiovascular Imaging
Volume20
Issue number2
DOIs
Publication statusPublished - 1 Feb 2019
Externally publishedYes

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Hypertrophic Cardiomyopathy
Gadolinium
Fibrosis
Magnetic Resonance Spectroscopy
Perfusion
Perfusion Imaging
Phosphocreatine
Ventricular Tachycardia
Left Ventricular Function
Hospitalization
Heart Failure
Adenosine Triphosphate
Confidence Intervals

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

Progression of myocardial fibrosis in hypertrophic cardiomyopathy : mechanisms and clinical implications. / Raman, Betty; Ariga, Rina; Spartera, Marco; Sivalokanathan, Sanjay; Chan, Kenneth; Dass, Sairia; Petersen, Steffen E.; Daniels, Matthew J.; Francis, Jane; Smillie, Robert; Lewandowski, Adam J.; Ohuma, Eric O.; Rodgers, Christopher; Kramer, Christopher M.; Mahmod, Masliza; Watkins, Hugh; Neubauer, Stefan.

In: European Heart Journal Cardiovascular Imaging, Vol. 20, No. 2, 01.02.2019, p. 157-167.

Research output: Contribution to journalArticle

Raman, B, Ariga, R, Spartera, M, Sivalokanathan, S, Chan, K, Dass, S, Petersen, SE, Daniels, MJ, Francis, J, Smillie, R, Lewandowski, AJ, Ohuma, EO, Rodgers, C, Kramer, CM, Mahmod, M, Watkins, H & Neubauer, S 2019, 'Progression of myocardial fibrosis in hypertrophic cardiomyopathy: mechanisms and clinical implications', European Heart Journal Cardiovascular Imaging, vol. 20, no. 2, pp. 157-167. https://doi.org/10.1093/ehjci/jey135
Raman, Betty ; Ariga, Rina ; Spartera, Marco ; Sivalokanathan, Sanjay ; Chan, Kenneth ; Dass, Sairia ; Petersen, Steffen E. ; Daniels, Matthew J. ; Francis, Jane ; Smillie, Robert ; Lewandowski, Adam J. ; Ohuma, Eric O. ; Rodgers, Christopher ; Kramer, Christopher M. ; Mahmod, Masliza ; Watkins, Hugh ; Neubauer, Stefan. / Progression of myocardial fibrosis in hypertrophic cardiomyopathy : mechanisms and clinical implications. In: European Heart Journal Cardiovascular Imaging. 2019 ; Vol. 20, No. 2. pp. 157-167.
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abstract = "Aims: Myocardial fibrosis as detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a powerful prognostic marker in hypertrophic cardiomyopathy (HCM) and may be progressive. The precise mechanisms underlying fibrosis progression are unclear. We sought to assess the extent of LGE progression in HCM and explore potential causal mechanisms and clinical implications. Methods and results: Seventy-two HCM patients had two CMR (CMR1-CMR2) at an interval of 5.7 ± 2.8 years with annual clinical follow-up for 6.3 ± 3.6 years from CMR1. A combined endpoint of heart failure progression, cardiac hospitalization, and new onset ventricular tachycardia was assessed. Cine and LGE imaging were performed to assess left ventricular (LV) mass, function, and fibrosis on serial CMR. Stress perfusion imaging and cardiac energetics were undertaken in 38 patients on baseline CMR (CMR1). LGE mass increased from median 4.98 g [interquartile range (IQR) 0.97-13.48 g] to 6.30 g (IQR 1.38-17.51 g) from CMR1 to CMR2. Substantial LGE progression (ΔLGE ≥ 4.75 g) occurred in 26{\%} of patients. LGE increment was significantly higher in those with impaired myocardial perfusion reserve (<MPRI 1.40) and energetics (phosphocreatine/adenosine triphosphate <1.44) on baseline CMR (P ≤ 0.01 for both). Substantial LGE progression was associated with LV thinning, increased cavity size and reduced systolic function, and conferred a five-fold increased risk of subsequent clinical events (hazard ratio 5.04, 95{\%} confidence interval 1.85-13.79; P = 0.002). Conclusion: Myocardial fibrosis is progressive in some HCM patients. Impaired energetics and perfusion abnormalities are possible mechanistic drivers of the fibrotic process. Fibrosis progression is associated with adverse cardiac remodelling and predicts an increased risk of subsequent clinical events in HCM.",
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T1 - Progression of myocardial fibrosis in hypertrophic cardiomyopathy

T2 - mechanisms and clinical implications

AU - Raman, Betty

AU - Ariga, Rina

AU - Spartera, Marco

AU - Sivalokanathan, Sanjay

AU - Chan, Kenneth

AU - Dass, Sairia

AU - Petersen, Steffen E.

AU - Daniels, Matthew J.

AU - Francis, Jane

AU - Smillie, Robert

AU - Lewandowski, Adam J.

AU - Ohuma, Eric O.

AU - Rodgers, Christopher

AU - Kramer, Christopher M.

AU - Mahmod, Masliza

AU - Watkins, Hugh

AU - Neubauer, Stefan

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Aims: Myocardial fibrosis as detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a powerful prognostic marker in hypertrophic cardiomyopathy (HCM) and may be progressive. The precise mechanisms underlying fibrosis progression are unclear. We sought to assess the extent of LGE progression in HCM and explore potential causal mechanisms and clinical implications. Methods and results: Seventy-two HCM patients had two CMR (CMR1-CMR2) at an interval of 5.7 ± 2.8 years with annual clinical follow-up for 6.3 ± 3.6 years from CMR1. A combined endpoint of heart failure progression, cardiac hospitalization, and new onset ventricular tachycardia was assessed. Cine and LGE imaging were performed to assess left ventricular (LV) mass, function, and fibrosis on serial CMR. Stress perfusion imaging and cardiac energetics were undertaken in 38 patients on baseline CMR (CMR1). LGE mass increased from median 4.98 g [interquartile range (IQR) 0.97-13.48 g] to 6.30 g (IQR 1.38-17.51 g) from CMR1 to CMR2. Substantial LGE progression (ΔLGE ≥ 4.75 g) occurred in 26% of patients. LGE increment was significantly higher in those with impaired myocardial perfusion reserve (<MPRI 1.40) and energetics (phosphocreatine/adenosine triphosphate <1.44) on baseline CMR (P ≤ 0.01 for both). Substantial LGE progression was associated with LV thinning, increased cavity size and reduced systolic function, and conferred a five-fold increased risk of subsequent clinical events (hazard ratio 5.04, 95% confidence interval 1.85-13.79; P = 0.002). Conclusion: Myocardial fibrosis is progressive in some HCM patients. Impaired energetics and perfusion abnormalities are possible mechanistic drivers of the fibrotic process. Fibrosis progression is associated with adverse cardiac remodelling and predicts an increased risk of subsequent clinical events in HCM.

AB - Aims: Myocardial fibrosis as detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a powerful prognostic marker in hypertrophic cardiomyopathy (HCM) and may be progressive. The precise mechanisms underlying fibrosis progression are unclear. We sought to assess the extent of LGE progression in HCM and explore potential causal mechanisms and clinical implications. Methods and results: Seventy-two HCM patients had two CMR (CMR1-CMR2) at an interval of 5.7 ± 2.8 years with annual clinical follow-up for 6.3 ± 3.6 years from CMR1. A combined endpoint of heart failure progression, cardiac hospitalization, and new onset ventricular tachycardia was assessed. Cine and LGE imaging were performed to assess left ventricular (LV) mass, function, and fibrosis on serial CMR. Stress perfusion imaging and cardiac energetics were undertaken in 38 patients on baseline CMR (CMR1). LGE mass increased from median 4.98 g [interquartile range (IQR) 0.97-13.48 g] to 6.30 g (IQR 1.38-17.51 g) from CMR1 to CMR2. Substantial LGE progression (ΔLGE ≥ 4.75 g) occurred in 26% of patients. LGE increment was significantly higher in those with impaired myocardial perfusion reserve (<MPRI 1.40) and energetics (phosphocreatine/adenosine triphosphate <1.44) on baseline CMR (P ≤ 0.01 for both). Substantial LGE progression was associated with LV thinning, increased cavity size and reduced systolic function, and conferred a five-fold increased risk of subsequent clinical events (hazard ratio 5.04, 95% confidence interval 1.85-13.79; P = 0.002). Conclusion: Myocardial fibrosis is progressive in some HCM patients. Impaired energetics and perfusion abnormalities are possible mechanistic drivers of the fibrotic process. Fibrosis progression is associated with adverse cardiac remodelling and predicts an increased risk of subsequent clinical events in HCM.

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