Myocardial fibrosis in asymptomatic patients undergoing surgery for mitral and aortic valve regurgitation.
Aortic Valve
/ diagnostic imaging
Aortic Valve Insufficiency
/ diagnostic imaging
Cardiomyopathies
Cardiomyopathy, Dilated
/ complications
Fibrosis
Heart Valve Diseases
Humans
Mitral Valve Insufficiency
/ diagnostic imaging
Ventricular Dysfunction, Left
/ diagnostic imaging
Ventricular Function, Left
Journal
Journal of cardiovascular medicine (Hagerstown, Md.)
ISSN: 1558-2035
Titre abrégé: J Cardiovasc Med (Hagerstown)
Pays: United States
ID NLM: 101259752
Informations de publication
Date de publication:
01 08 2022
01 08 2022
Historique:
pubmed:
30
7
2022
medline:
3
8
2022
entrez:
29
7
2022
Statut:
ppublish
Résumé
Chronic heart valve regurgitation induces left ventricular (LV) volume overload, leading to the development of hypertrophy and progressive dilatation of the ventricle to maintain physiological cardiac output. In order to prevent potential irreversible LV structural changes, the identification of the best timing for treatment is pivotal. To assess the presence and extent of fibrosis in myocardial tissue in asymptomatic patients with valvular heart disease (VHD) and preserved LV dimensions and function undergoing cardiac surgery. Thirty-nine patients were enrolled. Sixteen patients were affected by aortic or mitral regurgitation: they were all asymptomatic, undergoing valve surgery according to VHD European Society of Cardiology guidelines. Twenty-three patients with end-stage nonischemic dilated cardiomyopathy (DCM) and severe LV dysfunction undergoing cardiac surgery for implantation of a durable left ventricular assist device (LVAD) served as controls. During surgery, VHD patients underwent three myocardial biopsies at the level of the septum, the lateral wall and LV apex, while in LVAD patients the coring of the apex of the LV was used. For both groups, the tissue samples were analyzed on one section corresponding to the apical area. All slides were stained with hematoxylin and eosin and Masson's trichrome staining and further digitalized. The degree of fibrosis was then calculated as a percentage of the total area. Of 39 patients, 23 met the inclusion criteria: 12 had mitral or aortic insufficiency with a preserved ejection fraction and 11 had idiopathic dilated cardiomyopathy. Quantitative analysis of apical sections revealed a myocardial fibrosis amount of 10 ± 6% in VHD patients, while in LVAD patients the mean apical myocardial fibrosis rate was 38 ± 9%. In VHD patients, fibrosis was also present in the lateral wall (9 ± 4%) and in the septum (9 ± 6%). Our case series study highlights the presence of tissue remodeling with fibrosis in asymptomatic patients with VHD and preserved LV function. According to our results, myocardial fibrosis is present at an early stage of the disease, well before developing detectable LV dysfunction and symptoms. Since the relationship between the progressive magnitude of myocardial fibrosis and potential prognostic implications are not yet defined, further studies on this topic are warranted.
Sections du résumé
BACKGROUND
Chronic heart valve regurgitation induces left ventricular (LV) volume overload, leading to the development of hypertrophy and progressive dilatation of the ventricle to maintain physiological cardiac output. In order to prevent potential irreversible LV structural changes, the identification of the best timing for treatment is pivotal.
OBJECTIVE
To assess the presence and extent of fibrosis in myocardial tissue in asymptomatic patients with valvular heart disease (VHD) and preserved LV dimensions and function undergoing cardiac surgery.
METHODS
Thirty-nine patients were enrolled. Sixteen patients were affected by aortic or mitral regurgitation: they were all asymptomatic, undergoing valve surgery according to VHD European Society of Cardiology guidelines. Twenty-three patients with end-stage nonischemic dilated cardiomyopathy (DCM) and severe LV dysfunction undergoing cardiac surgery for implantation of a durable left ventricular assist device (LVAD) served as controls. During surgery, VHD patients underwent three myocardial biopsies at the level of the septum, the lateral wall and LV apex, while in LVAD patients the coring of the apex of the LV was used. For both groups, the tissue samples were analyzed on one section corresponding to the apical area. All slides were stained with hematoxylin and eosin and Masson's trichrome staining and further digitalized. The degree of fibrosis was then calculated as a percentage of the total area.
RESULTS
Of 39 patients, 23 met the inclusion criteria: 12 had mitral or aortic insufficiency with a preserved ejection fraction and 11 had idiopathic dilated cardiomyopathy. Quantitative analysis of apical sections revealed a myocardial fibrosis amount of 10 ± 6% in VHD patients, while in LVAD patients the mean apical myocardial fibrosis rate was 38 ± 9%. In VHD patients, fibrosis was also present in the lateral wall (9 ± 4%) and in the septum (9 ± 6%).
CONCLUSION
Our case series study highlights the presence of tissue remodeling with fibrosis in asymptomatic patients with VHD and preserved LV function. According to our results, myocardial fibrosis is present at an early stage of the disease, well before developing detectable LV dysfunction and symptoms. Since the relationship between the progressive magnitude of myocardial fibrosis and potential prognostic implications are not yet defined, further studies on this topic are warranted.
Identifiants
pubmed: 35904996
doi: 10.2459/JCM.0000000000001347
pii: 01244665-202208000-00002
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
505-512Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.
Références
Vahanian A, Beyersdorf F, Praz F, et al. ESC/EACTS Scientific Document Group; ESC Scientific Document Group. 2021 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J 2022; 46:561–632.
Otto CM, Nishimura RA, Bonow RO, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2021; 143:e72–e227.
Kang DH, Kim JH, Rim JH, et al. Comparison of early surgery versus conventional treatment in asymptomatic severe mitral regurgitation. Circulation 2009; 119:797–804.
Quintana E, Suri RM, Thalji NM, et al. Left ventricular dysfunction after mitral valve repair--the fallacy of ‘normal’ preoperative myocardial function. J Thorac Cardiovasc Surg 2014; 148:2752–2760.
Enriquez-Sarano M, Suri RM, Clavel MA, et al. Is there an outcome penalty linked to guideline-based indications for valvular surgery? Early and long-term analysis of patients with organic mitral regurgitation. J Thorac Cardiovasc Surg 2015; 150:50–58.
Liu B, Edwards NC, Neal DAH, et al. A prospective study examining the role of myocardial fibrosis in outcome following mitral valve repair in degenerative mitral regurgitation: rationale and design of the mitral FINDER study. BMC Cardiovasc Disord 2017; 17:282.
Milano DA, Faggian G, Dodonov M, et al. Prognostic value of myocardial fibrosis in patients with severe aortic stenosis. J Thorac Cardiovasc Surg 2012; 144:830–837.
Rosenhek R, Rader F, Klaar U, et al. Outcome of watchful waiting in asymptomatic severe mitral regurgitation. Circulation 2006; 113:2238–2244.
Turk R, Varadarajan P, Kamath A, et al. Survival benefit of aortic valve replacement in older patients with asymptomatic chronic severe aortic regurgitation. Ann Thorac Surg 2010; 89:731–737.
Zheng J, Chen Y, Pat B, et al. Microarray identifies extensive downregulation of noncollagen extracellular matrix and profibrotic growth factor genes in chronic isolated mitral regurgitation in the dog. Circulation 2009; 119:2086–2095.
Chen YW, Pat B, Gladden JD, et al. Dynamic molecular and histopathological changes in the extracellular matrix and inflammation in the transition to heart failure in isolated volume overload. Am J Physiol Heart Circ Physiol 2011; 300:H2251–H2260.
Zheng J, Yancey DM, Ahmed MI, et al. Increased sarcolipin expression and adrenergic drive in humans with preserved left ventricular ejection fraction and chronic isolated mitral regurgitation. Circ Heart Fail 2014; 7:194–202.
McCutcheon K, Dickens C, van Pelt J, et al. Dynamic changes in the molecular signature of adverse left ventricular remodeling in patients with compensated and decompensated chronic primary mitral regurgitation. Circ Heart Fail 2019; 12:e005974.
Cannata’ A, Merlo M, Artico J, et al. Cardiovascular aging: the unveiled enigma from bench to bedside. J Cardiovasc Med 2018; 19:517–526.
Gharacholou SM, Slusser JP, Lennon RJ, et al. Factors associated with change in frailty scores and long-term outcomes in older adults with coronary artery disease. J Geriatr Cardiol 2021; 18:196–203.
Travers JG, Kamal FA, Robbins J, et al. Cardiac fibrosis: the fibroblast awakens. Circ Res 2016; 118:1021–1040.
Weber KT. Fibrosis and hypertensive heart disease. Curr Opin Cardiol 2000; 15:264–272.
Chaturvedi RR, Herron T, Simmons R, et al. Passive stiffness of myocardium from congenital heart disease and implications for diastole. Circulation 2010; 121:979–988.
Espira L, Czubryt MP. Emerging concepts in cardiac matrix biology. Can J Physiol Pharmacol 2009; 87:996–1008.
de Bakker JM, van Capelle FJ, Janse MJ, et al. Fractionated electrograms in dilated cardiomyopathy: origin and relation to abnormal conduction. J Am Coll Cardiol 1996; 27:1071–1078.
Spach MS, Boineau JP. Microfibrosis produces electrical load variations due to loss of side-to-side cell connections: a major mechanism of structural heart disease arrhythmias. Pacing Clin Electrophysiol 1997; 20:397–413.
McCrohon JA, Moon JC, Prasad SK, et al. Differentiation of heart failure related to dilated cardiomyopathy and coronary artery disease using gadolinium-enhanced cardiovascular magnetic resonance. Circulation 2003; 108:54–59.
Bello D, Fieno DS, Kim RJ, et al. Infarct morphology identifies patients with substrate for sustained ventricular tachycardia. J Am Coll Cardiol 2005; 45:1104–1108.
Bello D, Shah DJ, Farah GM, et al. Gadolinium cardiovascular magnetic resonance predicts reversible myocardial dysfunction and remodeling in patients with heart failure undergoing beta-blocker therapy. Circulation 2003; 108:1945–1953.
Kim RJ, Wu E, Rafael A, et al. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med 2000; 343:1445–1453.
Assomull RG, Prasad SK, Lyne J, et al. Cardiovascular magnetic resonance, fibrosis, and prognosis in dilated cardiomyopathy. J Am Coll Cardiol 2006; 48:1977–1985.
Gulati A, Jabbour A, Ismail TF, et al. Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy. JAMA 2013; 309:896–908.
Masci PG, Schuurman R, Andrea B, et al. Myocardial fibrosis as a key determinant of left ventricular remodeling in idiopathic dilated cardiomyopathy: a contrast-enhanced cardiovascular magnetic study. Circ Cardiovasc Imaging 2013; 6:790–799.
Barison A, Del Torto A, Chiappino S, et al. Prognostic significance of myocardial extracellular volume fraction in nonischaemic dilated cardiomyopathy. J Cardiovasc Med 2015; 16:681–687.
Shafii AE, Gillinov AM, Mihaljevic T, et al. Changes in left ventricular morphology and function after mitral valve surgery. Am J Cardiol 2012; 110:403–408.
Foglieni C, Rusconi R, Mantione ME, et al. Early left atrial tissue features in patients with chronic mitral regurgitation and sinus rhythm: alterations of not remodeled left atria. Int J Cardiol 2016; 219:433–438.
Frustaci A, Chimenti C, Bellocci F, et al. Histological substrate of atrial biopsies in patients with lone atrial fibrillation. Circulation 1997; 96:1180–1184.
Marsan NA, Maffessanti F, Tamborini G, et al. Left atrial reverse remodeling and functional improvement after mitral valve repair in degenerative mitral regurgitation: a real-time 3-dimensional echocardiography study. Am Heart J 2011; 161:314–321.
Nudi F, Iskandrian AE, Schillaci O, et al. Noninvasive cardiovascular imaging for myocardial necrosis, viability, stunning and hibernation: evidence from an umbrella review encompassing 12 systematic reviews, 286 studies, and 201,680 patients. Minerva Cardiol Angiol 2021; 69:191–200.
Francone M, Aquaro G, Barison A, et al. Appropriate use criteria for cardiovascular MRI: SIC – SIRM position paper. Part 2. Myocarditis, pericardial disease, cardiomyopathies and valvular heart disease. J Cardiovasc Med 2021; 22:515–529.
Çelik SF. Early impairment left ventricular mechanics in children with mitral valve prolapse. Am J Cardiol 2019; 123:1992–1998.
Öz TK, Abdelnabi M, Fiore C, et al. Assessment of sacubitril/valsartan effects on left ventricular dynamics using 3D echocardiography and 3D strain in heart failure with reduced ejection fraction patients. Minerva Cardiol Angiol 2021; doi: 10.23736/S2724-5683.21.05802-6.
doi: 10.23736/S2724-5683.21.05802-6
Seferović PM, Fragasso G, Petrie M, et al. Sodium-glucose co-transporter 2 inhibitors in heart failure: beyond glycaemic control. A position paper of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2020; 22:1495–1503.