Assessing early left ventricular remodeling in pediatric hypertension: A study using transthoracic echocardiography combined with two-dimensional speckle tracking echocardiography in an immature rabbit model

Abstract

This study explored the value of routine transthoracic echocardiography (TTE) combined with two-dimensional speckle tracking echocardiography (2D-STE) for the early evaluation of left ventricular remodeling in the hypertensive immature rabbit model. Twenty-seven New Zealand white rabbits were divided into Group A (sham-operated group), Group B (mild group), and Group C (severe group), with 9 rabbits per group. The hypertension model was constructed using the “two kidneys one clip” method. Changes in left ventricular function and the degree of left ventricular wall thickening were observed by TTE at 1, 4, and 8 weeks after modeling. The global longitudinal strain (GLS-AVG, GLS-A4C, GLS-A2C, and GLS-LAX) of the left ventricle (LV) and the longitudinal strain (LS) of the 18 segments of left ventricular myocardium were analyzed using 2D-STE. Concurrently, LV myocardial tissue was sampled for HE staining and Masson staining. Receiver operating characteristic (ROC) curves were plotted to evaluate the accuracy of 2D-STE parameters in predicting myocardial fibrosis. The model group exhibited varying degrees of left ventricular remodeling. GLS-A4C, GLS-A2C, GLS-LAX, and GLS-AVG in the model group increased at 1 week after modeling (P < 0.01), with LS abnormalities concentrated in the apical segments. GLS-AVG showed a significant positive correlation with both IVSd and CVF (P < 0.01). The area under the curve (AUC) values of GLS-AVG, GLS-A4C, GLS-A2C, and GLS-LAX were 0.850, 0.827, 0.839, and 0.800, respectively. This study demonstrates the promise of TTE combined with 2D-STE for the early and comprehensive evaluation of left ventricular myocardial damage in hypertensive children in the clinical setting.

Keywords

2D-STE / echocardiography / left ventricular remodeling / myocardial fibrosis / pediatric hypertension

References

[1] Song P-G, Zhang Y, Yu J-Y, et al. Global prevalence of hypertension in children: a systematic review and meta-analysis. JAMA Pediatr. 2019; 173(12): 1154-1163.

[2] Tran AH, Urbina EM. Hypertension in children. Curr Opin Cardiol. 2020; 35(4): 376-380.

[3] Machackova J, Barta J, Dhalla NS. Myofibrillar remodeling in cardiac hypertrophy, heart failure and cardiomyopathies. Can J Cardiol. 2006; 22(11): 953-968.

[4] Messerli FH, Rimoldi SF, Bangalore S. The transition from hypertension to heart failure: contemporary update. JACC Heart Fail. 2017; 5(8): 543-551.

[5] Rabi DM, McBrien KA, Sapir-Pichhadze R, et al. Hypertension Canada’s 2020 comprehensive guidelines for the prevention, diagnosis, risk assessment, and treatment of hypertension in adults and children. Can J Cardiol. 2020; 36(5): 596-624.

[6] Li Y, Haseler E, Chowienczyk P, Sinha MD. Haemodynamics of hypertension in children. Curr Hypertens Rep. 2020; 22(8): 60.

[7] Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American society of echocardiography and the European association of cardiovascular imaging. Eur Heart J Cardiovasc Imaging. 2015; 16(3): 233-270.

[8] Goldblatt H, Lynch J, Hanzal RF, Summerville WW. Studies on experimental hypertension: i. the production of persistent elevation of systolic blood pressure by means of renal ischemia. J Exp Med. 1934; 59(3): 347-379.

[9] Wagenseil JE, Knutsen RH, Li DY, Mecham RP. Elastin-insufficient mice show normal cardiovascular remodeling in 2K1C hypertension despite higher baseline pressure and unique cardiovascular architecture. Am J Physiol Heart Circ Physiol. 2007; 293(1): H574-H582.

[10] Guimaraes DA, Rizzi E, Ceron CS, et al. Doxycycline dose-dependently inhibits MMP-2-mediated vascular changes in 2K1C hypertension. Basic Clin Pharmacol Toxicol. 2011; 108(5): 318-325.

[11] Nwabuo CC, Vasan RS. Pathophysiology of hypertensive heart disease: beyond left ventricular hypertrophy. Curr Hypertens Rep. 2020; 22(2): 11.

[12] Stanton T, Dunn FG. Hypertension, left ventricular hypertrophy, and myocardial ischemia. Med Clin. 2017; 101(1): 29-41.

[13] Huang J, Yan Z-N, Fan L, Rui Y-F, Song X-T. Left ventricular longitudinal function assessment in rabbits after acute occlusion of left anterior descending coronary artery by two-dimensional speckle tracking imaging. BMC Cardiovasc Disord. 2017; 17(1): 219.

[14] Biering-Sørensen T, Biering-Sørensen SR, Olsen FJ, et al. Global longitudinal strain by echocardiography predicts long-term risk of cardiovascular morbidity and mortality in a low-risk general population: the Copenhagen city heart study. Circ Cardiovasc Imaging. 2017; 10(3):e005521.

[15] Potter E, Marwick TH. Assessment of left ventricular function by echocardiography: the case for routinely adding global longitudinal strain to ejection fraction. JACC Cardiovasc Imaging. 2018; 11(2 Pt 1): 260-274.

[16] Uppu SC, Shah A, Weigand J, et al. Two-dimensional speckle-tracking-derived segmental peak systolic longitudinal strain identifies regional myocardial involvement in patients with myocarditis and normal global left ventricular systolic function. Pediatr Cardiol. 2015; 36(5): 950-959.

[17] Tran AH, Flynn JT, Becker RC, et al. Subclinical systolic and diastolic dysfunction is evident in youth with elevated blood pressure. Hypertension. 2020; 75(6): 1551-1556.

[18] Lisi M, Cameli M, Mandoli GE, et al. Detection of myocardial fibrosis by speckle-tracking echocardiography: from prediction to clinical applications. Heart Fail Rev. 2022; 27(5): 1857-1867.

[19] Yildiz M, Oktay AA, Stewart MH, Milani RV, Ventura HO, Lavie CJ. Left ventricular hypertrophy and hypertension. Prog Cardiovasc Dis. 2020; 63(1): 10-21.

[20] Li L, Zhao Q, Kong W. Extracellular matrix remodeling and cardiac fibrosis. Matrix Biol. 2018; 68-69: 490-506.

[21] Frangogiannis NG. Cardiac fibrosis. Cardiovasc Res. 2021; 117(6): 1450-1488.

[22] Krämer J, Niemann M, Liu D, et al. Two-dimensional speckle tracking as a non-invasive tool for identification of myocardial fibrosis in Fabry disease. Eur Heart J. 2013; 34(21): 1587-1596.

[23] Afonso L, Kondur A, Simegn M, et al. Two-dimensional strain profiles in patients with physiological and pathological hypertrophy and preserved left ventricular systolic function: a comparative analyses. BMJ Open. 2012; 2(4):e001390.

RIGHTS & PERMISSIONS

2024 The Authors. Pediatric Discovery published by John Wiley & Sons Australia, Ltd on behalf of Children's Hospital of Chongqing Medical University.