Abstract
The purpose of this investigation was to evaluate the influence of aortic stenosis (AS) on right ventricular (RV) strain and particularly the importance of arterial hypertension on this association. This cross‐sectional study included 107 patients with moderate and severe AS (with and without hypertension) and preserved left ventricular ejection fraction (>50%) and 82 age‐matched normotensive and hypertensive controls who underwent comprehensive echocardiographic examination. AS patients were divided into normotensive and hypertensive groups. Left ventricle (LV) mass index gradually increased from the controls, across the moderate AS to the severe AS. There was a trend of reduction of RV global and layer‐specific longitudinal strain of the whole ventricle and RV free wall from the controls, across the moderate AS to the severe AS. RV global longitudinal strain, as well as layer‐specific RV longitudinal strains, was significantly lower in the patients with severe AS than the controls and the normotensive patients with moderate AS. Endocardial and epicardial RV strains were lower in hypertensive than in normotensive patients with moderate AS. In patients with severe AS, there was no difference between normotensive and hypertensive patients. LV mass index and mean aortic valve gradient were associated with RV global longitudinal strain in AS patients independently of systolic blood pressure, LV ejection fraction (EF), age, and body mass index (BMI). In conclusion, RV mechanics was deteriorated in the patients with moderate and severe AS. There was a trend of RV longitudinal strain worsening in the hypertensive patients with AS in comparison with their normotensive counterparts. Severity of AS, expressed by the mean AV gradient, was related with RV longitudinal strain.
Keywords: aortic stenosis, arterial hypertension, right ventricle, strain
1. INTRODUCTION
The importance of right ventricular (RV) structure and function has been underestimated in comparison with left ventricular remodeling for a long time. However, studies have shown that its structure and function is very important in patients with congenital heart disease and pulmonary hypertension, but afterward, the important role of RV remodeling has been proved in the patients with heart failure, heart transplantation, cardiomyopathies, and valvular heart disease.1, 2 The influence of aortic stenosis (AS) and particularly of AS severity on RV remodeling is still debatable, and the data are scarce.3, 4, 5, 6 Recently, several studies regarding the prognostic importance of RV structure and function in AS patients after surgical replacement or catheter aortic valve implantation have been published.4, 5, 6
Epidemiological studies demonstrated significant prevalence of arterial hypertension (HT) in AS patients, which reaches almost 80% in the older population.7 The impact of HT on AS severity assessment is still controversial.8 It is known that changes in blood pressure induce concomitant changes in transvalvular flow rate that results in over‐ or underestimation of AS severity. The impact of HT on progression and prognosis in AS patients is also recognized.8 However, the effect of HT on already significantly changed and remodeled left ventricle is difficult to assess.
Even though the role of arterial hypertension on RV structure, function, and mechanics has not been completely enlightened, several studies demonstrated the presence of important RV remodeling in patients with HT.9, 10, 11, 12 However, the influence of arterial HT on the relationship between AS and RV structure and function is still unknown.
The main hypothesis of this investigation was that the AS patients with arterial HT had more pronounced RV functional and mechanical remodeling than the normotensive AS patients. Therefore, the aim of this study was to investigate RV structure, function, and mechanics in patients with moderate and severe AS and also the importance of HT on the association between AS and RV remodeling.
2. METHODOLOGY
This cross‐sectional study included 107 patients with moderate (n = 43) and severe AS (n = 64) and preserved left ventricle (LV) ejection fraction (>50%) and 82 age‐matched normotensive (n = 34) and hypertensive (n = 48) controls matched by age and sex. In total, there were 6 groups: normotensive and hypertensive controls; normotensive and hypertensive patients with moderate AS; and normotensive and hypertensive patients with severe AS.
Exclusion criteria were heart failure, symptomatic coronary artery disease, atrial fibrillation, congenital heart disease, more than mild valvular heart disease (other than aortic stenosis), artificial valves, previous myocardial revascularization, simultaneous coronary artery bypass surgery, chronic obstructive bronchitis or asthma, sleep‐apnea syndrome, liver or kidney failure. Diabetes was an exclusion criterion in the normotensive control group.
Arterial pressure values were obtained by measuring the average value of two consecutive measurements obtained by a conventional sphygmomanometer. HT was defined when blood pressure was ≥ 140/90 mm Hg or when the patient was taking antihypertensive therapy. Anthropometric measures (height and weight) and laboratory analyses (level of fasting glucose, blood creatinine and urea, total cholesterol, and triglycerides) were obtained from all the subjects included in the study. The data regarding medication were obtained from all study participants. Body mass index (BMI) and body surface area (BSA) were calculated for each patient. The study was approved by the local Ethics Committee, and informed consent was obtained from all the participants.
2.1. Echocardiography
Echocardiographic examinations were performed by using a commercially available Vivid 7 (GE Vingmed, Horten, Norway) ultrasound machine.
Left ventricle diameters, posterior wall and septum thickness, were measured according to the current recommendations.13 Relative wall thickness was calculated according to the formula. LV ejection fraction (EF) was calculated by using the biplane method of disks (modified Simpson's rule).13 LV mass was calculated by using the American Society for Echocardiography's formula13 and indexed for the body surface area.
Pulsed‐wave Doppler assessment of transmitral LV was obtained in the apical 4‐chamber view according to the guidelines.14 Tissue Doppler imaging was used to obtain LV myocardial velocities in the apical 4‐chamber view, with a sample volume placed at the septal and lateral segments of the mitral annulus during early diastole (e′)m. The average of the peak early diastolic relaxation velocity (e′)m of the septal and lateral mitral annulus was calculated, and the E/e′m ratio was computed.
Continuous‐wave Doppler was used to assess the peak aortic velocity, the peak, and mean transaortic pressure gradient which were calculated using the simplified Bernoulli equation.15 Peak aortic velocity and gradients were assessed in the apical 5‐chamber or right parasternal view that provided the highest velocity signal and gradients. Aortic valve area (AVA) was calculated from the continuity equation using the ratio of the velocity time interval across the valve and in the LV outflow tract.15 Moderate AS was defined when 1.0 ≤ AVA < 1.5 cm2 and severe AS when AVA < 1 cm2.15
2.2. Right ventricle
The RV basal diameter was measured in the apical four‐chamber view in end‐diastole.16 RV thickness was measured in the subcostal view.16 Tricuspid inflow (Et) and tissue Doppler velocities of RV free wall (et, st) were evaluated in the apical 4‐chamber view,16 and E/e′t ratio was calculated.
Systolic pulmonary artery pressure (PAP) was assessed in the patients with minimal/mild tricuspid regurgitation. PAP was determined according to the current guidelines using formula: PAP = (TR velocity)2 + RA pressure. RV global systolic function was assessed as the tricuspid annular plane systolic excursion (TAPSE).16 The RA pressure was estimated from vena cava inferior (IVC) diameter and its collapsibility: (a) IVC diameter < 2.1 cm with >50% collapse with a sniff indicated normal RA pressure of 3 mm Hg; (b) IVC diameter > 2.1 cm with <50% collapse with a sniff indicated increased RA pressure of 15 mm Hg; (c) in other scenarios, RA pressure was intermediate (8 mm Hg).13
2.3. Two‐dimensional right ventricular strain
2DE strain imaging was performed by using 3 consecutive cardiac cycles of 2DE images in the apical 4‐chamber view. EchoPAC 2.1 (GE‐Healthcare, Horten, Norway) was used for the 2DE strain analysis. The study was done only in one center in Belgrade, and only one type of echo machine and the same software were used. The RV speckle tracking analysis was done after the endocardial border was manually traced in the four‐chamber view, therefore, delineating a region of interest, composed by six segments. The software generated six longitudinal strain curves for each RV segment.16 The global longitudinal strain for the RV free wall and global RV were determined separately. RV free wall longitudinal strain was calculated as the average of 3 segments that belong to RV free wall. The global value for RV longitudinal strain was provided by the software.
Multilayer longitudinal strain was determined by modified 2DE strain software. The modified 2DE strain speckle tracking includes the delineation of the endocardial border, similarly to the traditional 2DE strain, but instead of a single chain of nodes, the myocardial wall is automatically defined by multiple chains of nodes, allowing investigation of 3 myocardial layers: endocardial, mid‐myocardial, and epicardial.
2.4. Statistical analysis
All the parameters were tested for normal distribution using the Kolmogorov‐Smirnov test. Continuous variables were presented as mean ± standard deviation and compared by the analysis of covariance (ANCOVA), as they showed normal distribution. Tukey HSD post hoc analysis was used for the comparison between different groups. The differences in proportions were compared by using the chi‐square or Fisher test, where appropriate. The correlation was used to determine the association between different echocardiographic and clinical parameters and RV strain in the patients with AS. Two examiners (MT and VK) performed all echocardiographic examinations, but only one investigator (MT) performed RV strain analysis. The inter‐ and intra‐observer agreements were determined by evaluation of the intra‐class correlation coefficients (ICC) in 15 randomly chosen subjects (5 participants from each of the three groups: controls, moderate, and severe AS). The other investigator (VK) performed RV analysis in these 15 randomly chosen patients in order to determine inter‐observer variability. The P‐value < 0.05 was considered statistically significant.
3. RESULTS
No difference was noticed in age, BMI, and sex distribution among the observed groups (Table 1). Plasma glucose level and total cholesterol level were significantly higher in the subjects with AS than in the control group (Table 1). As expected, considering the classification of the patients, all hypertensive patients (with and without AS) had significantly higher blood pressure values (Table 1). Diabetes was equally distributed in all groups except the normotensive control group in which diabetes was excluded by definition. Antihypertensive medication groups and statins were equally presented in all hypertensive patients—without and with AS (Table 1).
Table 1.
Demographic characteristics and clinical parameters of study population
| No AS | Moderate AS | Severe AS | ||||
|---|---|---|---|---|---|---|
| Controls (n = 34) | Hypertension (n = 48) | No hypertension (n = 18) | Hypertension (n = 25) | No hypertension (n = 26) | Hypertension (n = 38) | |
| Age (years) | 67 ± 9 | 67 ± 10 | 66 ± 9 | 67 ± 9 | 69 ± 9 | 69 ± 10 |
| Sex (% male) | 20 (59) | 24 (50) | 10 (56) | 15 (60) | 15 (58) | 21 (55) |
| BMI (kg/m2) | 25.7 ± 3.4 | 26.6 ± 3.7 | 26.1 ± 3.6 | 26.5 ± 3.3 | 26.2 ± 3.3 | 26.7 ± 3.7 |
| Plasma glucose (mmol/L) | 5.0 ± 0.9 | 5.3 ± 1.0 | 5.7 ± 1.2 | 6.2 ± 1.2 c | 6.1 ± 1.3 c | 6.2 ± 1.4 a , b , c |
| Total cholesterol (mmol/L) | 5.3 ± 0.9 | 5.7 ± 0.7 | 5.8 ± 1.0 | 6.4 ± 1.1 a | 6.2 ± 1.0 c | 6.3 ± 1.2 a , b |
| SBP (mm Hg) | 129 ± 8 | 145 ± 12a | 128 ± 9 b | 144 ± 11a , d , e | 126 ± 8 b | 143 ± 12a , d , e |
| DBP (mm Hg) | 74 ± 9 | 87 ± 10a | 75 ± 9b | 86 ± 10a , d , e | 76 ± 10b | 91 ± 11 a , d , e |
| Diabetes (%) | ‐ | 12 (25) | 5 (28) | 5 (20) | 7 (27) | 9 (24) |
| Antihypertensives (%) | ‐ | 26 (55) | ‐ | 14 (56) | ‐ | 23 (61) |
| Statins (%) | ‐ | 28 (58) | 2 (11) | 16 (64) d , e | 6 (23) | 25 (66) d , e |
ACE‐I, angiotensin‐converting enzyme inhibitor; ARB, angiotensin II receptor antagonist; AS, aortic stenosis; BMI, body mass index; BP, blood pressure; CCB, calcium channel blocker therapy; DBP, diastolic blood pressure; SBP, systolic blood pressure.
P < 0.01 for comparison with controls.
P < 0.01 for comparison with hypertensive patients without AS.
P < 0.05 for comparison with controls.
P < 0.01 for comparison with moderate AS without hypertension.
P < 0.01 for comparison with severe AS without hypertension.
3.1. Echocardiography
There was no difference in LV diameter across the observed groups (Table 2). The parameters of LV hypertrophy (LV wall thickness and LV mass index) gradually increased from the controls across the moderate to the severe AS patients (Table 2). LV relative wall thickness and LV mass index gradually increased from the controls, across the patients with moderate AS, to the patients with severe AS (Table 2). EF was significantly lower in the severe AS than in the controls (Table 2). The parameter of LV diastolic function (E/e′)m was significantly higher in the patients with severe AS than in the controls.
Table 2.
Echocardiographic parameters of LV and RV structure and function in the study population
| No AS | Moderate AS | Severe AS | ||||
|---|---|---|---|---|---|---|
| Controls (n = 34) | Hypertension (n = 48) | No hypertension (n = 18) | Hypertension (n = 25) | No hypertension (n = 26) | Hypertension (n = 38) | |
| Left ventricle | ||||||
| LVEDD (mm) | 48.4 ± 5.0 | 49.0 ± 5.2 | 48.8 ± 5.6 | 49.6 ± 5.4 | 49.0 ± 5.2 | 49.9 ± 5.6 |
| IVS (mm) | 9.1 ± 0.9 | 10.2 ± 1.2 a | 10.8 ± 1.0a | 11.5 ± 1.2a , b | 12.0 ± 1.1a , b , d | 12.8 ± 1.2a , b , d |
| RWT | 0.37 ± 0.03 | 0.40 ± 0.04f | 0.44 ± 0.03a , b | 0.46 ± 0.04 a , b | 0.48 ± 0.04a , b , c | 0.50 ± 0.05 a , b , d |
| LAVI (mL/m2) | 29.5 ± 3.7 | 32.3 ± 4.6 | 31.0 ± 4.0 | 35.0 ± 5.2a | 33.8 ± 4.8a | 38.3 ± 6.2a , b , d |
| LVMI(g/m2) | 76.9 ± 9.2 | 88.1 ± 10.2 a | 99.1 ± 15.2 a | 106.5 ± 18.2a , b | 110.8 ± 20.8 a , b | 122.4 ± 24.1 a , b , d , e |
| EF (%) | 61 ± 3 | 62 ± 3 | 61 ± 3 | 60 ± 4 | 59 ± 3 b | 58 ± 3 a , b |
| (E/e′)m | 9.1 ± 2.2 | 11.2 ± 3.1 | 12.3 ± 3.3 f | 13.5 ± 3.5a , g | 13.8 ± 4.3 a , g | 15.0 ± 4.5a , b |
| Aortic valve parameters | ||||||
| Mean AV gradient (mm Hg) | 3 ± 2 | 4 ± 2 | 28 ± 10 a , b | 27 ± 9a , b | 45 ± 12a , b , d , e | 48 ± 15a , b , d , e |
| Peak AV gradient (mm Hg) | 5 ± 3 | 6 ± 3 | 46 ± 15a , b | 45 ± 13a , b | 75 ± 16a , b , d , e | 79 ± 18a , b , d , e |
| AVA (cm2) | 2.68 ± 0.33 | 2.61 ± 0.32 | 1.25 ± 0.22a , b | 1.21 ± 0.18 a , b | 0.77 ± 0.19a , b , d , e | 0.70 ± 0.22a , b , d , e |
| SVi (mL/m2) | 47 ± 4 | 45 ± 5 | 42 ± 4a | 40 ± 4a , b | 40 ± 3a , b | 38 ± 3a , b , d |
| Right ventricle | ||||||
| RV basal diameter (mm) | 34.6 ± 3.6 | 35.1 ± 3.7 | 35.7 ± 3.8 | 35.4 ± 3.7 | 36.2 ± 4.1 | 36.5 ± 4.3 |
| RV thickness (mm) | 4.4 ± 0.5 | 4.7 ± 0.7 | 4.6 ± 0.8 | 4.9 ± 0.7 | 5.1 ± 0.9 a | 5.3 ± 1.1a , b , d |
| TAPSE (mm) | 23 ± 4 | 24 ± 5 | 23 ± 4 | 22 ± 4 | 22 ± 4 | 21 ± 4 g |
| FAC (%) | 45 ± 5 | 44 ± 4 | 44 ± 5 | 43 ± 4 | 44 ± 3 | 42 ± 3 |
| Et/e′t | 4.5 ± 1.5 | 5.1 ± 1.4 | 4.9 ± 1.6 | 5.5 ± 1.7 | 5.3 ± 1.7 | 5.7 ± 1.5f |
| st (cm/s) | 14 ± 3 | 13 ± 3 | 13 ± 3 | 12 ± 2 | 12 ± 3 | 12 ± 2f |
| PAP (mm Hg) | 29 ± 5 | 28 ± 4 | 31 ± 5 | 31 ± 4 | 32 ± 5b | 33 ± 5a , b |
AS, aortic stenosis; AVA, aortic valve area; AV, aortic valve; e′, early diastolic flow velocity across the septal segment of mitral (e′m) annulus (tissue Doppler); E, early diastolic mitral/tricuspid flow (pulse Doppler); EF, ejection fraction; FAC, fractional area shortening; IVS, interventricular septum thickness; LAVI, left atrial volume index; LVEDD, left ventricle end‐diastolic diameter; LVMI, left ventricular mass index; PAP, pulmonary arterial pressure; RV, right ventricle; RWT, relative wall thickness; SVi, stroke volume index; TAPSE, tricuspid annular plane systolic excursion.
P < 0.01 for comparison with controls.
P < 0.01 for comparison with hypertensive patients without AS.
P < 0.05 for comparison with moderate AS without hypertension.
P < 0.01 for comparison with moderate AS without hypertension.
P < 0.01 for comparison with moderate AS with hypertension.
P < 0.05 for comparison with controls.
P < 0.05 for comparison with hypertensive patients without AS.
By definition, AV gradients significantly increased and AV area decreased from the controls, throughout the moderate, to the severe AS patients (Table 2). Significant difference in AV gradients or AV area between the normotensive and the hypertensive patients with moderate and severe AS was not noticed (Table 2). Stroke volume was lower in the patients with moderate and severe AS patients than in the controls.
3.2. Right ventricle
There was no difference in RV basal diameter between the observed groups (Table 2). RV thickness was significantly higher in the severe AS patients than in the controls (Table 2). The parameters of RV systolic (FAC, st, TAPSE) were similar between the groups (Table 2). The parameters of longitudinal RV systolic function (st and TAPSE) were significantly lower in the hypertensive patients with severe AS patients than in the controls, but not in comparison with the other groups (Table 2). The parameter of RV diastolic function (Et/e′t) was significantly higher only in the hypertensive patients with severe AS than in the controls (Table 2). PAP was significantly higher in the patients with severe AS patients than in the controls.
3.3. Speckle tracking imaging
Global longitudinal strain of the RV and RV free wall gradually decreased from the controls, across the moderate AS, to the severe AS (Table 3 and 1). The same trend exists also in the layer‐specific RV longitudinal strain of the whole ventricle and of the RV free wall (Table 3). The normotensive and hypertensive patients with AS had significantly lower RV longitudinal strains (global and layer‐specific) than the normotensive patients with moderate AS. Significant difference between the normotensive and the hypertensive patients was present only among the subjects with moderate AS, but not in those with severe AS. The hypertensive patients with severe AS showed significantly lower RV longitudinal global and layer‐specific strains than the normotensive or the hypertensive patients with moderate AS (Table 3). However, there was no significant difference between the normotensive and the hypertensive patients with severe AS.
Table 3.
2D RV strain in the study population
| No AS | Moderate AS | Severe AS | ||||
|---|---|---|---|---|---|---|
| Controls (n = 34) | Hypertension (n = 48) | No hypertension (n = 18) | Hypertension (n = 25) | No hypertension (n = 26) | Hypertension (n = 38) | |
| Global RV strain (%) | ||||||
| Global RV | −23.4 ± 3.1 | −21.8 ± 2.8 g | −21.2 ± 2.6a | −19.2 ± 2.3a , b | −18.8 ± 2.0a , b , c | −17.1 ± 2.0a , b , d , h |
| Lateral wall | −26.2 ± 3.8 | −24.9 ± 3.6 | −23.7 ± 3.5 | −20.8 ± 3.0 a , b , f | −20.3 ± 2.7 a , b , d | −19.0 ± 2.4 a , b , d |
| Longitudinal global RV strain (%) | ||||||
| Endocardial | −26.0 ± 4.1 | −24.5 ± 4.2 | −23.6 ± 4.0a | −21.4 ± 3.8 a , b , c | −20.8 ± 3.6a , b , c | −18.7 ± 3.3 a , b , e , f |
| Mid‐myocardial | −23.4 ± 3.0 | −21.9 ± 2.7 g | −21.0 ± 2.5a | −19.0 ± 2.2a , b | −18.7 ± 2.1a , b , c | −16.9 ± 2.0a , b , d , h |
| Epicardial | −21.1 ± 2.9 | −19.0 ± 2.5a | −18.9 ± 2.8g | −16.5 ± 2.4 a , b , c | −16.6 ± 2.3 a , b , c | −14.9 ± 1.8 a , b , d |
| Longitudinal free wall RV strain (%) | ||||||
| Endocardial | −29.7 ± 4.6 | −28.2 ± 4.5 | −25.2 ± 4.4a | −23.0 ± 4.0 a , b | −21.8 ± 3.5 a , b | −20.0 ± 3.4a , b , d , h |
| Mid‐myocardial | −26.0 ± 3.7 | −24.8 ± 3.6 | −23.6 ± 3.4 | −21.0 ± 3.1a , b | −20.1 ± 2.6 a , b , d | −18.9 ± 2.4 a , b , d |
| Epicardial | −22.8 ± 3.0 | −21.6 ± 3.2 | −22.2 ± 3.3 | −18.7 ± 2.9a , b , d | −18.9 ± 2.8 a , b , d | −18.0 ± 2.6 a , b , d |
AS, aortic stenosis; LV, left ventricle; RV, right ventricle.
P < 0.01 for comparison with controls.
P < 0.01 for comparison with hypertensive patients without AS.
P < 0.05 for comparison with moderate AS without hypertension.
P < 0.01 for comparison with moderate AS without hypertension.
P < 0.01 for comparison with moderate AS with hypertension.
P < 0.05 for comparison with severe AS without hypertension.
P < 0.05 for comparison with controls.
P < 0.05 for comparison with moderate AS with hypertension.
Figure 1.
Global right ventricular longitudinal strain across the observed groups. AS, aortic stenosis, HT, arterial hypertension
3.4. Correlation and regression analysis
Systolic blood pressure, LV EF, LV mass index, Em/e′m, RV wall thickness, and mean AV gradient significantly correlated with RV global longitudinal strain (Table 4). However, after adjustment for age and BMI only LV mass index and AV gradient remained significantly associated with RV global longitudinal strain (Table 4). Similar results are also obtained for free wall RV longitudinal strain (Table 4). The only additional independent variable significantly associated with RV free wall longitudinal strain besides LV mass index and AV gradient that was not independently associated with RV global longitudinal strain was RV free wall thickness.
Table 4.
Influence of different demographic, clinical and echocardiographic parameters on RV and RV free wall global longitudinal strain in AS patients
| RV GLS (%) | RV free wall longitudinal strain (%) | |||
|---|---|---|---|---|
| r | β | r | β | |
| Age (years) | −0.077 | −0.068 | −0.085 | −0.060 |
| SBP (mm Hg) | −0.184a | −0.111 | −0.174a | −0.082 |
| BMI (kg/m2) | −0.102 | −0.093 | −0.096 | −0.069 |
| LV EF (%) | 0.157a | 0.109 | 0.169a | 0.111 |
| LV mass index (g/m2) | −0.293b | −0.192a | −0.203b | −0.182a |
| Em/e′m | −0.160a | −0.109 | −0.148a | −0.080 |
| RV wall thickness (mm) | −0.165a | −0.097 | −0.180a | −0.127a |
| PAP (mm Hg) | −0.099 | −0.088 | −0.087 | −0.051 |
| Mean AV gradient (mm Hg) | −0.250b | −0.179a | −0.207b | −0.151a |
| r 2 | 0.40 | 0.36 | ||
BMI, body mass index; EF, ejection fraction; Em/em′, the ratio between early flow across mitral annulus measured with pulsed and tissue Doppler; LV, left ventricle; PAP, systolic arterial pulmonary pressure; RV GLS, global longitudinal strain of the right ventricle; RV, right ventricle; SBP, systolic blood pressure.
P < 0.05.
P < 0.01.
3.5. Intra‐observer variability
The intra‐observer variability was high for RV global longitudinal strain: ICC (95% CI) = 0.922 (0.908‐0.954), P < 0.001; as well as for RV global subendocardial longitudinal strain: ICC (95% CI) = 0.936 (0.916‐0.962), P < 0.001; RV global mid‐myocardial longitudinal strain: ICC (95% CI) = 0.924 (0.910‐0.959), P < 0.001; RV global subepicardial longitudinal strain: ICC (95% CI) = 0.818 (0.785‐0.969), P < 0.001.
3.6. Inter‐observer variability
The inter‐observer variability was high for RV global longitudinal strain: ICC (95% CI) = 0.908 (0.894‐0.940), P < 0.001; RV global subendocardial longitudinal strain: ICC (95% CI) = 0.920 (0.885‐0.958), P < 0.001; RV global mid‐myocardial longitudinal strain: ICC (95% CI) = 0.910 (0.897‐0.939), P < 0.001; RV global subepicardial longitudinal strain: ICC (95% CI) = 0.779 (0.722‐0.875), P < 0.001.
4. DISCUSSION
The present investigation revealed several important findings: (a) RV global longitudinal strain is significantly impaired in patients with moderate and severe AS; (b) RV layer‐specific longitudinal strain is also deteriorated in patients with significant AS; (c) the significant difference in RV global and multilayer longitudinal strain between the normotensives and the hypertensives was observed only in the subjects with no AS and among the patients with moderate AS, but not in those with severe AS; (d) AS severity, determined by mean AV gradient, was independently of other clinical and echocardiographic parameters associated with global and free wall RV longitudinal strain.
The RV function was proved to be an important predictive factor of mortality in patients after transcatheter aortic valve implantation (TAVI).3 However, Lindsay et al3 used cardiac magnetic resonance (CMR) and RV ejection fraction for the assessment of RV function, and not echocardiographic evaluation as in our study. Musa et al5 also used CMR as a referent method showing that RV mass was the only independent predictor of mortality after TAVI procedure. Cavalcante et al17 revealed that RV dysfunction, defined by reduced TAPSE (<16 mm), was independent risk of all‐cause mortality in the specific population of patients with low‐flow low‐gradient AS. Galli et al6 included only severe AS patients showing that RV dysfunction defined as TAPSE ≤ 17 mm and/or st ≤ 9 cm/s was one of the strongest predictors of adverse event. The strongest predictor was biventricular dysfunction (TAPSE ≤ 17 mm and LVEF < 50%).6 In our study, the traditional echocardiographic parameters of RV systolic function (TAPSE, st, and FAC) were reduced only in the hypertensive patients with severe AS, but not in other AS subgroups. On the other hand, RV thickness was higher in the normo‐ and the hypertensive AS patients and was independently related with RV free wall longitudinal strain, which confirms the importance of RV hypertrophy. These findings suggested that severe AS might induce RV hypertrophy and impaired RV systolic function.
The role of RV strain is significantly less investigated. In the unique population of patients with low‐flow low‐gradient AS, Dahou et al18 showed that rest RV longitudinal strain < |13%| was related with worse 2‐year survival, but stress RV longitudinal strain < |14%| (measured during low‐dose dobutamine stress echocardiography) was an even stronger predictor of mortality and provided incremental prognostic value beyond that obtained from the rest RV longitudinal strain.
Our study showed that RV longitudinal strain—global and layer‐specific was significantly reduced in the patients with significant AS (moderate and severe AS) in comparison with the patients with no AS and no arterial hypertension. Additionally, RV global longitudinal strain was lower in the patients with severe AS than in those with moderate AS. This refers to RV global longitudinal strain, as well as to RV free wall longitudinal strain, and also to multilayer strain of global RV and RV free wall. The reduction of strain was noticed in all three myocardial layers, which implies that all layers are impacted by AS. However, normal transmural gradient from RV endocardium to epicardium was maintained, which suggests unique effect of AS on RV mechanics.
There are several mechanisms that could potentially explain the effect of AS on RV remodeling: first, there is strong interdependence between LV and RV through interventricular septum and common pericardial sac; second, chronic elevation in LV afterload induces LV fibrosis and hypertrophy, causing a progressive worsening in LV longitudinal function and ultimately to the LVEF reduction; third, retrograde transmission of LV filling pressure on the pulmonary circulation and further to the RV could increase RV stiffness and deteriorate RV function and strain. This was partly confirmed in our study, which showed significant correlation between Em/e′m and RV strain, even though this relationship vanished after adjustment in multivariate analysis. All these LV changes are easily transmitted to the RV across the interventricular septum.
The role of arterial HT on the relationship between AS and RV remodeling has been unknown. It is proved that HT is associated with RV remodeling,9, 10, 11, 12 but there are no data in the patients with AS and arterial hypertension. Our results showed that RV global and layer‐specific strains were significantly lower in the hypertensive than in the normotensive patients with moderate AS. There was the same trend among the patients with severe AS, but probably due to the limited number of patients (n = 64), the statistical significance was not reached. Similar results were obtained for global and free wall. These results imply that not only interventricular dependence was responsible for RV remodeling, but also other intrinsic factors might have important role. Perhaps common molecular mechanisms that are important for LV remodeling in AS and HT could provide an answer about this intriguing relationship. Growth‐stimulating signals such as angiotensin I and catecholamines produced in the hypertrophic LV and outside LV in AS and even more in HT might induce RV remodeling and functional deterioration in AS.8, 19, 20 The hemodynamic change is common for AS and HT—significant increase in afterload and well‐known activation of the renin‐angiotensin‐aldosterone system could also have an important role in further deterioration of RV function in AS patients. This is supported by our previous findings that showed RV wall thickening and deterioration in RV longitudinal strain in hypertensive patients.9, 10, 11, 12
Our previous study group showed that RV endocardial and mid‐myocardial longitudinal strains were reduced in the hypertensive patients.21, 22 In the current study, all three layers are impacted, which again indicates that AS and HT have a cumulative negative effect on RV mechanics.
Our study has emphasized the importance of evaluation of RV function and mechanics in patients with AS and implies that better blood pressure control should be applied in AS patients because HT has an additive negative effect on RV function. The primary structural changes in the patients with AS and arterial HT occur in the LV. These unfavorable alterations are apparently extending to the RV along the anatomical and functional ventricular continuum, and therefore aggravate the prognosis of AS patients.
The present study has several important clinical messages: (a) more detailed evaluation of RV structure, function, and strain (when possible and feasible) in the patients with moderate and severe AS is advisable due to impact of AS on RV remodeling; (b) arterial hypertension is additionally deteriorating RV mechanics in the patients with significant AS (moderate and severe); (c) more strict blood pressure control should be considered in the AS patients with arterial hypertension.
4.1. Limitations
The current study has several limitations. The investigation included a limited number of patients. However, found a significant difference between various groups. Echocardiographic evaluation of RV strain could be significantly influenced by the acquisition quality. The main challenge is obtaining adequate image of RV free wall. However, echosonographers who performed this study are experienced and they used some of well‐known maneuvers for improving image quality (changing the angle of probe, taking images during end‐expiration or breath holding, etc.). Focused RV image significantly helped us to resolve many problems in regard to the RV.
Asymptomatic coronary artery disease could not be excluded because coronary angiography was not done in all patients, mostly in those who did not undergo AV replacement. The cross‐sectional nature of our study limits the ability to assume any causal relationship between AS, arterial HT, and RV strain. The potential limitation refers to the fact that the hypertensive group comprised treated and untreated patients. Antihypertensive treatment may exert some influence on RV mechanics.
5. CONCLUSIONS
RV strain was significantly deteriorated in patients with moderate and severe AS. RV global and layer‐specific longitudinal strains were significantly reduced in the AS patients in comparison with the subjects with no AS and without hypertension. There was a trend of gradual reduction of RV longitudinal strain from the controls (normotensive subjects without AS), across the moderate AS, to the severe AS patients. There was also a trend of lower layer‐specific longitudinal strains (endocardial, mid‐myocardial, and epicardial) in the hypertensive rather than in the normotensive patients in all three groups (controls, moderate, and severe AS). The statistical significance in the patients with severe AS was probably not achieved due to the limited number of subjects. Considering the high prevalence of HT in AS patients and the predictive value of RV longitudinal strain, it would be important to conduct a follow‐up study that would show if RV global and layer‐specific strain have importance as predictors in AS patients with HT, as well as to address the question of the influence of more strict blood pressure control on outcome in patients with severe AS.
CONFLICT OF INTEREST
None.
Tadic M, Cuspidi C, Pencic B, et al. Right ventricular mechanics in patients with aortic stenosis and preserved ejection fraction: Is arterial hypertension a new player in the game?. J Clin Hypertens. 2019;21:516‒523. 10.1111/jch.13513
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