Abstract
Myocardial fibrosis is the major determinant of diastolic property of the left ventricle (LV). Experimental and clinical studies have suggested that angiotensin receptor blockers attenuate myocardial fibrosis in various heart diseases. The integrated backscatter signal (IBS) represents a promising ultrasonic method for assessing the characterization of myocardial tissue: cardiac cycle–dependent variation of the IBS (IBS-CV) is negatively correlated with myocardial collagen deposition in hypertensive hearts. Using non-invasive echocardiographic techniques, we performed a prospective, multi-center trial to examine whether long-term treatment with valsartan would improve myocardial fibrosis and diastolic dysfunction in hypertensives. This study included 43 hypertensive patients who had impaired diastolic function (transmitral Doppler flow early to late filling velocity ratio [E/A ratio] <1.0) and preserved systolic function (LV ejection fraction [LVEF] >50%). Twelve-month valsartan treatment reduced blood pressure (BP) and LV mass index. Valsartan significantly increased not only IBS-CV but also E/A ratio without changing LVEF. The effects of valsartan were compared between two subgroups: one with low IBS-CV (IBS-CV <5.08 dB [the average of 43 patients at baseline]), the other with high IBS-CV (IBS-CV >5.08 dB). At baseline, BP, LV mass index, LVEF, and E/A ratio were similar in the two groups. Valsartan significantly increased IBS-CV and E/A ratio in the low IBS-CV group, but not in the high IBS-CV group, despite comparable reductions in BP and LV mass. In conclusion, long-term valsartan treatment attenuated myocardial fibrosis and improved diastolic dysfunction in hypertensives. It is suggested that in the low IBS-CV group, improvement of diastolic dysfunction by valsartan may be caused by attenuation of myocardial fibrosis, and not by regression of LV hypertrophy.
Similar content being viewed by others
Article PDF
References
Levy D, Larson MG, Vasan RS, Kannel WB, Ho KK : The progression from hypertension to congestive heart failure. JAMA 1996; 275: 1557–1562.
Gaasch WH, Zile MR : Left ventricular diastolic dysfunction and diastolic heart failure. Annu Rev Med 2004; 55: 373–394.
Kuwahara F, Kai H, Tokuda K, et al: Transforming growth factor-β function blocking prevents myocardial fibrosis and diastolic dysfunction in pressure-overloaded rats. Circulation 2002; 106: 130–135.
Kuwahara F, Kai H, Tokuda K, et al: Hypertensive myocardial fibrosis and diastolic dysfunction—another model of inflammation—. Hypertension 2004; 43: 739–745.
Kai H, Mori T, Tokuda K, et al: Pressure overload–induced transient oxidative stress mediates perivascular inflammation and cardiac fibrosis through angiotensin II. Hypertens Res 2006; 29: 711–718.
Varo N, Iraburu MJ, Varela M, Lopez B, Etaya LC, Diez J : Losartan inhibits posttranscriptional synthesis of collagen type I and reverses left ventricular fibrosis in spontaneously hypertensive rats. J Hypertens 1999; 17: 107–114.
Tokuda K, Kai H, Kuwahara F, et al: Pressure-independent effects of angiotensin II on hypertensive myocardial fibrosis. Hypertension 2004; 43: 499–503.
Kai H, Kuwahara F, Tokuda K, Imaizumi T : Diastolic dysfunction in hypertensive hearts: roles of perivascular inflammation and reactive myocardial fibrosis. Hypertens Res 2005; 28: 483–490.
Lopez B, Querejeta R, Varo N, et al: Usefulness of serum carboxy-terminal propeptide of procollagen type I in assessment of the cardioreparative ability of antihypertensive treatment in hypertensive patients. Circulation 2001; 104: 286–291.
Diez J, Querejeta R, Lopez B, Gonzalez A, Larman M, Martinez Ubago JL : Losartan-dependent regression of myocardial fibrosis is associated with reduction of left ventricular chamber stiffness in hypertensive patients Circulation 2002; 105: 2512–2517.
Ciulla MM, Paliotti R, Esposito A, et al: Different effects of antihypertensive therapies based on losartan or atenolol on ultrasound and biochemical markers of myocardial fibrosis: results of a randomized trial. Circulation 2004; 110: 552–557.
Müller-Brunotte R, Kahan T, López B, et al: Myocardial fibrosis and diastolic dysfunction in patients with hypertension: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA). J Hypertens 2007; 25: 1958–1966.
Maceira AM, Barba J, Varo N, Beloqui O, Diez J : Ultrasonic backscatter and serum marker of cardiac fibrosis in hypertensives. Hypertension 2002; 39: 923–928.
Maceira AM, Barba J, Beloqui O, Diez J : Ultrasonic backscatter and diastolic function in hypertensive patients. Hypertension 2002; 40: 239–243.
Masugata H, Senda S, Goda F, et al: Left ventricular diastolic dysfunction as assessed by echocardiography in metabolic syndrome. Hypertens Res 2006; 29: 897–903.
Hoyt RM, Skorton DJ, Collins SM, Melton HE Jr : Ultrasonic backscatter and collagen in normal ventricular myocardium. Circulation 1984; 69: 775–782.
Hoyt RH, Collins SM, Skorton DJ, Ericksen EE, Conyers D : Assessment of fibrosis in infarcted human hearts by analysis of ultrasonic backscatter. Circulation 1985; 71: 740–744.
Vered Z, Barzilai B, Mohr GA, et al: Quantitative ultrasonic tissue characterization with real-time integrated backscatter imaging in normal human subjects and in patients with dilated cardiomyopathy. Circulation 1987; 76: 1067–1073.
Masuyama T, St Giar FG, Tye TL, Oppenheim G, Schnittger I, Popp RL : Ultrasound tissue characterization of human hypertrophied hearts in vivo with cardiac cycle–dependent variation in integrated backscatter. Circulation 1989; 80: 925–934.
Ciulla M, Paliotti R, Hess DB, et al: Echocardiographic patterns of myocardial fibrosis in hypertensive patients: endomyocardial biopsy versus ultrasonic tissue characterization. J Am Soc Echocardiogr 1997; 10: 657–664.
Di Bello V, Giorgi D, Talini E, et al: Incremental value of ultrasonic tissue characterization (backscatter) in the evaluation of left ventricular myocardial structure and mechanics in essential arterial hypertension. Circulation 2003; 107: 74–80.
Gigli G, Lattanzi F, Lucarini AR, et al: Normal ultrasonic myocardial reflectivity in hypertensive patients. A tissue characterization study. Hypertension 1993; 21: 329–334.
Laurent GJ : Dynamic state of collagen: pathways of collagen degradation in vivo and their possible role in regulation of collagen mass. Am J Physiol 1987; 252: C1–C9.
Rocha R, Martin-Berger CL, Yang P, Scherrer R, Delyani J, McMahon E : Selective aldosterone blockade prevents angiotensin II/salt-induced vascular inflammation in the rat hearts. Endocrinology 2002; 143: 4828–4836.
Ilgenli TF, Kilicaslan F, Kirilmaz A, Uzun M : Bisoprolol improves echocardiographic parameters of left ventricular diastolic function in patients with systemic hypertension. Cardiology 2006; 106: 127–131.
DÃez J, Laviades C, Mayor G, Gil MJ, Monreal I : Increased serum concentrations of procollagen peptides in essential hypertension. Relation to cardiac alterations. Circulation 1995; 91: 1450–1456.
Laviades C, Varo N, Fernández J, et al: Abnormalities of the extracellular degradation of collagen type I in essential hypertension. Circulation 1998; 98: 535–540.
Pearlman ES, Wber KT, Janicki JS, Pietra GG, Fishman AP : Muscle fiber orientation and connective tissue content in the hypertrophied human heart. Lab Invest 1982; 46: 158–164.
Wickline SA, Thomas LJ 3rd, Miller JG, Sobel BE, Perez JE : A relationship between ultrasound integrated backscatter signal and myocardial contractile function. J Clin Invest 1985; 76: 2151–2160.
Takahashi M, Sasayama S, Kawai C, Kotoura H : Contractile performance of the hypertrophied ventricle in patients with systemic hypertension. Circulation 1980; 62: 116–126.
Cockcroft DW, Gault MH : Prediction of creatinine clearance from serum creatinine. Nephron 1976; 13: 31–41.
Author information
Authors and Affiliations
Consortia
Corresponding author
Rights and permissions
About this article
Cite this article
Mizuta, Y., Kai, H., Mizoguchi, M. et al. Long-Term Treatment with Valsartan Improved Cyclic Variation of the Myocardial Integral Backscatter Signal and Diastolic Dysfunction in Hypertensive Patients: The Echocardiographic Assessment. Hypertens Res 31, 1835–1842 (2008). https://doi.org/10.1291/hypres.31.1835
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1291/hypres.31.1835
Keywords
This article is cited by
-
Diagnosis and Management of Left Ventricular Diastolic Dysfunction in the Hypertensive Patient
American Journal of Hypertension (2011)
-
Myocardial ultrasonic tissue characterization in patients with thyroid dysfunction
Cardiovascular Ultrasound (2010)