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Myocardial Fibrosis and LV Remodeling After TAVR for Severe AS
Quick Takes
- Pre-TAVR myocardial fibrosis (MF) was an independent predictor of cardiovascular and all-cause mortality.
- Although patients with MF above the median (>11%) had more advanced heart failure based on clinical and imaging parameters, post-TAVR improvements in LVEF, exercise tolerance, and quality of life occurred in this group.
Study Questions:
What is the relationship of biopsy-proven myocardial fibrosis (MF) with left ventricular (LV) remodeling and recovery, and with patient mortality, following transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS)?
Methods:
Between January 2017 and October 2018, this prospective, single-center German study enrolled consecutive patients with severe AS who were scheduled for transfemoral TAVR. Based on transthoracic echocardiogram (TTE) results, AS was classified into four hemodynamic subgroups:
- Normal ejection fraction, high-gradient (NEF-HG)
- Low ejection fraction, high-gradient (LEF-HG)
- Low ejection fraction, low-gradient (LEF-LG)
- Paradoxical (preserved ejection fraction) low-flow, low-gradient (PLF-LG)
A subset of patients underwent cardiovascular magnetic resonance (CMR). Following TAVR deployment, LV biopsies were harvested from the basal anteroseptum. MF was assessed in a blinded fashion using quantitative morphometry (percentage of blue area in Masson’s trichrome-stained biopsy sections). The primary clinical endpoint was cardiovascular mortality.
Results:
Among the 100 study participants, mean age was 78 ± 7 years, 35% were women, and 70% had coronary artery disease (CAD). Hemodynamic subgroups were as follows: 1) NEF-HG AS: 40 patients; 2) NEF-HG AS: 14 patients; LEF-LG AS: 26 patients; PLF-LG AS: 16 patients. Moderate-to-severe AS based on retrospective classification: patients (excluded from subtype analyses).
MF burden was greatest among patients with LEF-HG and LEF-LG AS (25.6 ± 23.3% and 29.5 ± 26.4%, respectively), and smallest in the NEF-HG group (13.5 ± 16%; p = 0.03 for comparison with LEF-HG and p = 0.003 for comparison with LEF-LG). Median MF burden in all subjects was 11%. In the entire cohort, CAD was not significantly associated with MF. Patients with MF above the median more frequently had diabetes mellitus (61% vs. 27%, p = 0.001), had shorter 6-minute walk distances (179 ± 122 m vs. 245 ± 112 m, p = 0.01), and had lower LVEFs (44 ± 17% vs. 55 ± 11%, p = 0.0002), as well as a higher prevalence of eccentric LV hypertrophy (24% vs. 4%, p = 0.004).
Among the 40 patients who underwent baseline CMR, quantitative late gadolinium enhancement (LGE) correlated with histological MF (r2 = 0.20, p = 0.004), but extracellular volume (ECV) quantification based on T1 mapping did not (r2 = 0.02, p = 0.41). Only LGE correlated with echocardiographic parameters including EF and global longitudinal strain.
At 6 months post-TAVR, 14/100 patients had died (0% procedural mortality), and follow-up was completed in 67 patients. Improvements in LV global longitudinal strain and reductions in LV mass index occurred in patients with MF burdens above and below the median, but only those in the below-median group exhibited significant reductions in LV end-diastolic volume (125 ± 31 ml at baseline vs. 109 ± 31 ml at 6 months, p = 0.02). Improvements in 6-minute walk distance, N-terminal pro–B-type natriuretic peptide levels, and Minnesota Living With Heart Failure Questionnaire scores were seen in both groups, but follow-up findings remained more favorable in the below-median group. Over a mean follow-up period of 11 months, MF above the median was a significant, independent predictor of cardiovascular mortality (hazard ratio [HR], 17.3; 95% confidence interval [CI], 2.8-23.4; p = 0.0001) and all-cause mortality (HR, 2.8; 95% CI, 1.2-6.6; p = 0.02).
Conclusions:
Pre-TAVR MF was an independent predictor of cardiovascular and all-cause mortality. Although patients with greater degrees of MF had more advanced heart failure based on clinical and imaging parameters, post-TAVR improvements in LVEF, exercise tolerance, and quality of life occurred in the whole cohort. CMR LGE correlated modestly with histological MF, while CMR ECV did not. Further work will be needed to develop CMR techniques to identify MF.
Perspective:
This study is unique in that MF was identified by endomyocardial biopsy at the time of TAVR. Myocardial remodeling is a nearly universal finding in severe AS, but noninvasive identification of MF remains difficult. On CMR, LGE primarily detects focal or patchy MF, rather than diffuse MF, for which T1 mapping is the technique of choice. As T1 mapping is not well standardized and has been slower to gain traction in the clinical realm, practical experience with this technique remains limited. Future studies employing CMR in AS patients should explore use of various ECV sequences and analysis methods, and based on the results of the present study, histologic correlation would likely be feasible.
Clinical Topics: Cardiac Surgery, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Valvular Heart Disease, Atherosclerotic Disease (CAD/PAD), Aortic Surgery, Cardiac Surgery and Heart Failure, Cardiac Surgery and VHD, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Interventions and Coronary Artery Disease, Interventions and Imaging, Interventions and Structural Heart Disease, Echocardiography/Ultrasound
Keywords: Aortic Valve Stenosis, Contrast Media, Coronary Artery Disease, Diabetes Mellitus, Diagnostic Imaging, Echocardiography, Endomyocardial Fibrosis, Exercise Tolerance, Fibrosis, Gadolinium, Geriatrics, Heart Failure, Heart Valve Diseases, Hypertrophy, Natriuretic Peptide, Brain, Quality of Life, Stroke Volume, Transcatheter Aortic Valve Replacement
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