Myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterisation and left ventricular function on cardiovascular magnetic resonance

Abstract

Background Myocardial fibrosis occurs in end-stage heart failure secondary to mitral regurgitation (MR), but it is not known whether this is present before onset of symptoms or myocardial dysfunction. This study aimed to characterise myocardial fibrosis in chronic severe primary MR on histology, compare this to tissue characterisation on cardiovascular magnetic resonance (CMR) imaging, and investigate associations with symptoms, left ventricular (LV) function, and exercise capacity. Methods Patients with class I or IIa indications for surgery underwent CMR and cardiopulmonary exercise testing. LV biopsies were taken at surgery and the extent of fibrosis was quantified on histology using collagen volume fraction (CVFmean) compared to autopsy controls without cardiac pathology. Results 120 consecutive patients (64 ± 13 years; 71% male) were recruited; 105 patients underwent MV repair while 15 chose conservative management. LV biopsies were obtained in 86 patients (234 biopsy samples in total). MR patients had more fibrosis compared to 8 autopsy controls (median: 14.6% [interquartile range 7.4–20.3] vs. 3.3% [2.6–6.1], P < 0.001); this difference persisted in the asymptomatic patients (CVFmean 13.6% [6.3–18.8], P < 0.001), but severity of fibrosis was not significantly higher in NYHA II-III symptomatic MR (CVFmean 15.7% [9.9–23.1] (P = 0.083). Fibrosis was patchy across biopsy sites (intraclass correlation 0.23, 95% CI 0.08–0.39, P = 0.001). No significant relationships were identified between CVFmean and CMR tissue characterisation [native T1, extracellular volume (ECV) or late gadolinium enhancement] or measures of LV function [LV ejection fraction (LVEF), global longitudinal strain (GLS)]. Although the range of ECV was small (27.3 ± 3.2%), ECV correlated with multiple measures of LV function (LVEF: Rho = − 0.22, P = 0.029, GLS: Rho = 0.29, P = 0.003), as well as NTproBNP (Rho = 0.54, P < 0.001) and exercise capacity (%PredVO2max: R = − 0.22, P = 0.030). Conclusions Patients with chronic primary MR have increased fibrosis before the onset of symptoms. Due to the patchy nature of fibrosis, CMR derived ECV may be a better marker of global myocardial status. Clinical trial registration Mitral FINDER study; Clinical Trials NCT02355418, Registered 4 February 2015, https://clinicaltrials.gov/ct2/show/NCT02355418

Reverse Myocardial Remodeling Following Valve Repair in Patients With Chronic Severe Primary Degenerative Mitral Regurgitation

“…93 patients attended followup investigations at 8.8 [7.4-10.6] months postoperative (Figure 1). The mean histological collagen volume fraction (CVFmean) of this patient cohort, quantified via invasive myocardial biopsy at the time of surgery, has previously been reported (5). A statistically significant correlation was present between CVFmean and ECV% (n=56, rho=0.33, P=0.015) when limiting analyses to biopsy samples containing only myocardium (without endocardial contamination).…”

“…It has been widely proposed that the accumulation of myocardial fibrosis is associated with subclinical LV systolic and diastolic dysfunction (18,19). This relationship is supported by animal models of volume overload induced myocardial fibrosis (20)(21)(22), and has been specifically documented in primary MR (5). Furthermore, ECV% offers incremental prognostic value compared to traditional parameters of ventricular structure and function in mutliple cardiovascular diseases (23).…”

“…Furthermore, previous imaging studies linked the presence of DIF to LV dilatation and reduced ejection fraction, raising the possibility that this could be a risk factor to improve decision-making in timing interventions in primary MR (2). Although the occurrence of DIF has since been confirmed on histology in patients with asymptomatic severe MR, it is not known whether this fibrosis changes following surgical correction of MR (5). Moreover, it is not known whether the presence of DIF on CMR predicts post-repair myocardial function or patient response.…”

Valvular Cardiomyopathy: The Value of Cardiovascular Magnetic Resonance Imaging

“…is finding has been confirmed in another large study comprised of 120 patients with chronic primary MR, which demonstrated that fibrosis, as quantified by ECV, occurs before the onset of symptoms [33].…”

Osteopathic Palpation of the Heart

“…We must remember that all the landmarks illustrated are but a point of reference and not an absolute constraint, as we must take into account the person who is lying on the bed (age, morphological conformation of the chest and spine, pathologies). The presence of pathologies that change the cardiac morphology are capable of altering the cardiac position, as well as the presence of pulmonary or diaphragmatic pathologies (hernias or inspiratory or expiratory attitudes) [ 41 - 42 ]. With palpation, it is necessary to keep present the passive tensions of the pericardium and the tensions produced by the neighboring tissues in fascial connection with the pericardium; we do not have to hear the heartbeat but how the heart moves inside the pericardium and how the latter behaves inside the mediastinum.…”