Study Population
Patients’ mean age was 74 SD 8 years, and the study cohort was predominantly male (54%). There were no significant differences in the clinical and demographic variables among the three AS types, except for SBP (p = 0.001) and pulse pressure (p = 0.001), which showed higher values in the HG-AS group than in other two groups (Table 1 and Additional file 1 supplemental material Table 1).
The most frequent cause of initial exclusion was the inability to perform CPET (36.3 %), followed by a poor echocardiographic window (9.9%). The other reasons are found in Figure 1. From the 113 patients analyzed, 63 presented MAS (55.8%), 29 presented HG-AS (25.7%), and 21 presented PLGAS (18.6%).
Results of the cardiopulmonary exercise testing according to the aortic stenosis classification
In total, 44.2% of the patients had abnormal CPET. According to the AS types, 66.7%, 55.2%, and 31.7% of the PLGAS, HG-AS and MAS groups, respectively, had abnormal CPET, with the differences being significant (p<0.05) (Table 1).
Significant differences were found in baseline SBP during CPET (p = 0.001), maximum SBP during CPET (p <0.05), and decrease in ST segment ≥2 mm (p <0.005) (Table 1 and Additional file 2). All of the 19 patients with a decrease in ST segment underwent a coronary angiography, and only one had coronary artery disease. Post-hoc analysis revealed that patients with MAS had a lower proportion of abnormal CPET than patients with HG-AS and PLGAS (p<0.05). Patients with HG-AS had CPET basal SBP, and, CPET SBP during maximum effort greater in than in those with MAS and PLGAS (p <0.05 and 0.001, respectively). There were no significant differences in the CPET variables (Additional file 1 supplemental Table 1).
Result of echocardiographic variables according to the aortic stenosis classification
In the post-hoc analysis, we observed that the HG-AS group had greater left ventricular mass (LVM) indexed by body-surface area (BSA) than the MAS and PLGAS groups (p <0.001 and p <0.05, respectively) (Table 1, Additional file 1 supplemental material Table 2, and Additional file 3: Figure A).
The relative wall thickness (RWT) was >0.42 in all groups, but it was more prominent in the HG-AS group than in the MAS and PLGAS groups. This finding was consistent with the increase in the left atrium, with the HG-AS group showing higher increased compared to the other groups (Additional file 3: Figure B).
The MAS patients had a lower valvuloarterial impedance (ZVA) than the HG-AS (p <0.001) and PLGAS (p <0.001) patients (Table 1 and Additional file 3: Figure C).
Results of echocardiographic variables of myocardial deformation according to the aortic stenosis classification
The HG-AS group had worst LV global longitudinal strain rate (GLSR) than the MAS group [-0.62 (-0.72 to -0.55) vs. -0.77 (-0.86 to -0.65), respectively (p <0.05)]. The PLGAS group also had a worst GLSR than the MAS group [-0.60 (-0.68 to -0.54) vs. -0.77 (-0.86 to -0.65), respectively (p = 0.001)] (Table 1).
The HG-AS and PLGAS groups had worst global basal longitudinal strain than the MAS group (both p <0.05). The GLS of the LV worst in the PLGAS group than in the MAS group (-12.65 SD 1.8 vs. -14.37 SD 2.65 respectively, p <0.05).
We did not observe a difference in the distribution of the circumferential and radial deformities of the LV among the three groups (Additional file 1 supplemental material Table 2).
Bland-Altman analysis showed good intra- and inter-observer agreement with a non-significant bias. The intraobserver and interobserver variabilities for GLS were 1.18% (95% CI, 1.09%-1.31%) and 1.31% (95% CI, 1.15%-1.82%) respectively.
Univariate multinomial logistic regression analysis
Among the differences observed between PLGAS and MAS, the following data were prominent in PLGAS: higher number of abnormal CPET (p <0.05), higher ZVA (p <0.001), worst GLS (p <0.05), worst GLSR (p <0.05), and worst global basal longitudinal strain (p <0.05) (Table 2 and Additional file 1 supplemental material Table 3).
When comparing the PLGAS and HG-AS groups, the PLGAS group had lower SBP (p = 0.001), lower pulse pressure (p = 0.001), lower basal SBP during CPET (p = 0.001), lower maximum SBP during CPET (p <0.05), lower LVM indexed by BSA (p <0.05), and lower left atrial diameter (p = <0.05).
Multivariate multinomial logistic regression analysis
When comparing MAS with the reference category (PLGAS), MAS showed lower ZVA (OR = 0.262 CI = 0.12-0.59, p = 0.001), lesser abnormal CPET (OR = 0.198 CI = 0.06-0.69, p <0.05), and better GLSR of LV (OR = 0.003 CI = 0.00-0.35, p <0.05); these variables characterized the difference between the two groups (Table 2).
With PLGAS used as the reference category, the most powerful variable in establishing a difference with respect to HG-AS was the LVM indexed by BSA (OR = 1.04 CI = 1.01-1.06, p <0.05), with HG-AS showing a greater indexed LVM than PLGAS.
Study of the overall diagnostic accuracy with ROC curves
The ROC curve analysis of the LVM indexed by BSA to differentiate between HG-AS and PLGAS is shown in Figure 2A, with an area under the ROC curve of 0.71 (95% CI: 0.56-0.83, p <0.012). The best cut-off point was 108.4 g/m2, with a diagnostic sensitivity of 72.4% (95% CI: 63-80%) and a specificity of 52.4% (95% CI: 42-62%). The area under the ROC curve for ZVA and GLSR to differentiate between MAS and PLGAS was 0.77 (95% CI: 0.65-0.88, p <0.001) (Figure 2B) and 0.75 (95% CI: 0.63-0.86 p = 0.001) (Figure 2C), respectively.