Left ventricular reverse remodeling after transcatheter aortic valve implantation: a cardiovascular magnetic resonance study

Twenty-seven patients who underwent successful TAVI using the Medtronic CoreValve (Medtronic CoreValve Percutaneous System, Medtronic CV) or Edwards SAPIEN (Edwards Lifesciences Inc, Irvine, CA, USA) bioprostheses were assessed with CMR before the procedure and at six-month follow up (Figure 1). The institutional ethics committee approved the study protocol and all patients gave informed consent. All patients were informed about the potential risks of CMR [17] and gave their written consent. Inclusion and exclusion criteria were previously reported [18].

Left ventricular mass indexed to body surface area (LVMi), left ventricular end diastolic volume indexed to body surface area (LVEDVi), stroke volume (SV), left ventricular ejection fraction (LVEF) and mass/volume ratio were assessed at baseline and six months. The occurrence of subendocardial fibrosis was assessed in terms of late gadolinium enhancement (LGE) at baseline and six months.

All CMR studies were performed with a 1.5 Tesla Magnetic Resonance Imaging scanner (Achieva, Philips Medical Systems, Netherlands) with a flexible cardiac five-element phased-array coil and a vector electrocardiogram for R wave triggering using a standard MRI imaging protocol. In brief, multiple short axis (SAX) cine images using a breath-hold steady state free precession sequence with parallel imaging (balanced Fast Field Echo (FFE); Repetition time (TR)/Echo time (TE) = 3.1/1.56 ms; slice thickness 8 mm; matrix 180 x 175 ; flip angle 60°; acquisition voxel-size = 1.78 × 1.82 × 8 mm³ ; reconstructed voxel-size = 1.25 × 1.25 × 8 mm³ acquisition; sensitivity encoding (SENSE)-factor = 2) were acquired after the acquisition of true two- and four- chamber planes for the assessment of left ventricular ejection fraction (LVEF %).The CMR images were analyzed off-line using a commercial software (Philips Medical Systems Extended MK Word Space Version 2.6.3.1) by a blinded experienced CMR reader unaware of patients’ clinical data. For assessment of left ventricular function, the end-diastolic and end-systolic cine frames were identified for each slice and the endocardial and epicardial borders were manually traced. The end-diastolic and end-systolic volumes were then calculated using the Simpson’s rule (i.e., sum of cavity sizes across all continuous slices) and indexed to body surface area. LVEF was calculated as (end-diastolic volume - end-systolic volume)/end-diastolic volume. LVMi was derived via the Simpson’s method multiplied by the specific gravity of myocardium (1.055 g/ml) and indexed to the body surface area. LVMi was divided by the LVEDVi to obtain the mass/volume ratio. Normal values used in this study for both LV systolic function and mass were those reported by Maceira et al. [19]. Left ventricular reverse remodeling was defined as a significant reduction in LVMi between baseline and 6 months.

To evaluate LGE, an intravenous bolus dose of 0.2 mmol/kg body weight of gadobutrol (Gadovist, Bayer Schering Pharma, Berlin, Germany) was administered at a rate of 3 ml/s by a power injector (MedradSpectris Solaris, Medrad, USA). Ten minutes after gadolinium injection, a ‘Look Locker’ sequence was performed to obtain the most appropriate inversion time to null the signal intensity of normal myocardium. LGE images were then acquired using the following parameters: fast gradient echo, repetition time 6.1 ms, echo time 3 ms, flip angle 25°, field of view 320 mm, slices thickness 10 mm, acquired in the left ventricular short axis over 2 RR intervals and no interslice gap. LGE was evaluated by visual assessment in short-axis slices and further characterized by spatial location, pattern, and LGE quantification (1–25%, 25–50%, 50–75%, >75%) [20].

Quantitative data were presented as mean ± standard deviations and were compared using the Student t paired test. Univariate and multivariate correlates of left ventricular reverse remodeling were analyzed by logistic regression. To explore their significance as baseline predictors, LVMi (< or ≥ 89 g/m²) and LVEF (< or ≥ 55%) were dichotomyzed as previously described [19]. A two-sided p value of < 0.05 was considered to indicate statistical significance. All data were processed using the Statistical Package for Social Sciences, version 15 (SPSS, Chicago, IL, USA).

All patients well tolerated CMR and no clinical adverse event was recorded during the examination both at baseline and at 6 months. The images quality was diagnostic in 100% of examinations. The mass/volume ratio decreased significantly from baseline to follow-up (P=0.001) (Table 2, Figure 3). Figure 4 displays changes in CMR endpoints from baseline to follow up. LVMi decreased from 84.5±25.2 g/m² to 69.4±18.4 g/m² (P<0.001). Conversely, LVEDVi, SV and LVEF did not change significantly (Table 2, Figure 4). After entering in a multivariable model all potential baseline confounding factors with p<0.20 at univariate analysis, no significant predictors of left ventricular reverse remodeling was identified.

Because myocardial fibrosis may significantly impact clinical outcomes [21], we repeated the analysis by excluding patients with fibrosis of ischemic or non ischemic nature (N=10) and found a consistent evidence of significant LVMi reduction (83.9 ± 28.9 g/m²vs 69.5± 22.3 g/m², P <0.001), with no significant changes for other parameters (Table 3).

Gadolinium was not administered to 3 patients due to severe renal failure (creatinine clearance <30 ml/min). At baseline, evidence of LGE was present in 10 (41.6%) of 24 cases. Causes for LGE were ischemic in 8 cases, and non-ischemic in 2 cases (Figure 5). At follow up, there were no new cases of LGE related to the intervention although one patient did have a pre-procedural myocardial infarction with new LGE at follow up.