Myocardial Fibrosis and Cardiac Decompensation in Aortic Stenosis

Abstract

ObjectivesCardiac magnetic resonance (CMR) was used to investigate the extracellular compartment and myocardial fibrosis in patients with aortic stenosis, as well as their association with other measures of left ventricular decompensation and mortality.BackgroundProgressive myocardial fibrosis drives the transition from hypertrophy to heart failure in aortic stenosis. Diffuse fibrosis is associated with extracellular volume expansion that is detectable by T1 mapping, whereas late gadolinium enhancement (LGE) detects replacement fibrosis.MethodsIn a prospective observational cohort study, 203 subjects (166 with aortic stenosis [69 years; 69% male]; 37 healthy volunteers [68 years; 65% male]) underwent comprehensive phenotypic characterization with clinical imaging and biomarker evaluation. On CMR, we quantified the total extracellular volume of the myocardium indexed to body surface area (iECV). The iECV upper limit of normal from the control group (22.5 ml/m2) was used to define extracellular compartment expansion. Areas of replacement mid-wall LGE were also identified. All-cause mortality was determined during 2.9 ± 0.8 years of follow up.ResultsiECV demonstrated a good correlation with diffuse histological fibrosis on myocardial biopsies (r = 0.87; p < 0.001; n = 11) and was increased in patients with aortic stenosis (23.6 ± 7.2 ml/m2 vs. 16.1 ± 3.2 ml/m2 in control subjects; p < 0.001). iECV was used together with LGE to categorize patients with normal myocardium (iECV <22.5 ml/m2; 51% of patients), extracellular expansion (iECV ≥22.5 ml/m2; 22%), and replacement fibrosis (presence of mid-wall LGE, 27%). There was evidence of increasing hypertrophy, myocardial injury, diastolic dysfunction, and longitudinal systolic dysfunction consistent with progressive left ventricular decompensation (all p < 0.05) across these groups. Moreover, this categorization was of prognostic value with stepwise increases in unadjusted all-cause mortality (8 deaths/1,000 patient-years vs. 36 deaths/1,000 patient-years vs. 71 deaths/1,000 patient-years, respectively; p = 0.009).ConclusionsCMR detects ventricular decompensation in aortic stenosis through the identification of myocardial extracellular expansion and replacement fibrosis. This holds major promise in tracking myocardial health in valve disease and for optimizing the timing of valve replacement. (The Role of Myocardial Fibrosis in Patients With Aortic Stenosis; NCT01755936)

Imaging of Myocardial Fibrosis and Its Functional Correlates in Aortic Stenosis: A Review and Clinical Potential

“…AS is characterized by a significant increase in DMF, with a large variation in interindividual values [6, 17]. The extent of DMF has been shown to be an independent predictor of adverse clinical outcomes both before and after AVR as well [15, 18, 19]. Notably, patients with paradoxical low-flow low-gradient AS have a higher degree of myocardial fibrosis and LV longitudinal dysfunction than patients with normal-flow high-gradient AS [16, 20].…”

“…It is noteworthy that AS-induced DMF starts at the subendocardial level, affecting mainly longitudinal LV function. Since it is predominantly determined by radial function, the LV ejection fraction can be normal for a long time even in the presence of extensive subendocardial fibrosis [6, 15, 19]. Accordingly, the LV ejection fraction, i.e., the class I guideline recommendation for AVR, cannot be used for early risk stratification in asymptomatic AS patients.…”

“…First of all, GLS was found to be related to biomarkers of myocardial fibrosis such as those expressing calcification, collagen formation, or breakdown and inflammation [42, 43]. Several studies have also reported significant associations between LV systolic function and both FMF and DMF at CMR or myocardial histology [3, 14, 15, 18, 19, 24, 29, 44-46] (Table 2). Former studies have investigated the relationship between FMF and LV contractile function [14, 44, 45].…”

“…A GLS ≤−11.6% showed a sensitivity of 65% and a specificity of 75% to predict significant FMF (LGE > 10%) [43]. The majority of studies dealing with this issue have focused on DMF [15, 19, 24, 46, 47]. Of the conventional echocardiography-derived parameters, DMF seems to show a significant, though weak, correlation only with LV mass and the LV mass index [23, 24].…”

The Prognostic Role of T1 Mapping Sequences: Can T1 Mapping Parameters Have a Role in Risk Stratification?

“…In addition, elderly persons and those with chronic kidney disease are very common in cases with severe aortic stenosis, so native T1 without contrast could provide helpful information without the use of gadolinium contrast media [57,58]. Chin et al [59] used total extracellular volume indexed by body surface area (iECV) was together with LGE to categorize patients with normal myocardium (iECV<22.5 mL/m 2 ; 51% of patients), extracellular expansion (iECV≥22.5 mL/m 2 ; 22%), and replacement fibrosis (presence of mid-wall LGE, 27%). In that study, categorization by ECV was of prognostic value with stepwise increases in unadjusted all-cause mortality (8 deaths/1000 patient-years vs. 36 deaths/1000 patient-years vs. 71 deaths/1,000 patientyears, respectively; p=0.009).…”