Background
Symptomatic patients with severe aortic stenosis (AS) demonstrate abnormal left ventricular (LV) mechanics. The aim of this study was to compare mechanics in asymptomatic and symptomatic patients with severe AS using two-dimensional myocardial strain imaging.
Methods
One hundred fifty-four patients with severe AS (aortic valve area ≤ 1.0 cm 2 ) referred to a heart valve clinic from 2004 to 2011 were studied. Thirty patients were asymptomatic, with normal LV ejection fractions (≥55%), without other significant valvular disease or wall motion abnormalities. Thirty-two symptomatic patients who underwent early aortic valve replacement, with similar age, gender, LV ejection fraction, and aortic valve area, were selected for comparison. Both groups were also compared with 32 healthy subjects with similar age and gender distributions and normal echocardiographic results who served as controls. LV longitudinal and circumferential strain and rotation were measured using speckle-tracking software applied to archived echocardiographic studies. Conventional echocardiographic and myocardial mechanical parameters were compared among the study subgroups.
Results
Patients with asymptomatic severe AS demonstrated smaller reductions in longitudinal strain, higher (supernormal) apical circumferential strain (−38 ± 6% vs −35 ± 4%, P < .05), and extreme (supernormal) apical rotation (12.2 ± 4.9° vs 2.9 ± 1.7°, P < .0005) compared with symptomatic patients. Apical rotation < 6° was the single significant predictor of symptoms in logistic regression analysis of clinical, echocardiographic, and mechanical parameters. Twelve asymptomatic patients underwent eventual aortic valve replacement and showed decreases in strain and apical rotation compared with baseline values.
Conclusions
Longitudinal strain was uniformly low in patients with severe AS and lower in those with symptoms. Compensatory circumferential myocardial mechanics (increased apical circumferential strain and rotation) were absent in symptomatic patients. Thus, myocardial mechanics may help in the follow-up of patients with severe AS and timing of valve surgery.
Selective longitudinal functional impairment in patients with severe aortic stenosis (AS) was hypothesized some 3 decades ago. Using speckle-tracking analysis of two-dimensional (2D) echocardiographic images, longitudinal strain has been shown to be low, and a cutoff of <15% shortening has been suggested to identify subtle left ventricular (LV) dysfunction and assist in clinical decision making. In a previous study, we suggested that in patients immediately before aortic valve replacement (AVR) for symptomatic severe AS, normal LV ejection fraction (LVEF) is maintained, despite the decrease in longitudinal strain, by abnormally high circumferential strain. In a subsequent study of patients with severe AS and variable LV systolic function, we demonstrated gradual loss of circumferential compensation with lower LVEF. Because these abnormalities reversed after AVR, continuously decreasing longitudinal strain was viewed as the primary mechanical outcome of severe AS, while increased circumferential mechanics were regarded as a dynamic compensatory mechanism, peaking in patients with normal LVEFs. Patients with severe AS may remain asymptomatic for a long time before becoming symptomatic and requiring AVR. We hypothesized that although symptomatic and asymptomatic patients have similar 2D Doppler characteristics, myocardial mechanics may be quite different, showing variable longitudinal and circumferential mechanical patterns. Thus, we aimed to evaluate biplane LV mechanics in patients with asymptomatic versus symptomatic severe AS using 2D myocardial strain imaging.
Methods
Study Population
We retrospectively screened our clinic log for new referrals for clinical and echocardiographic evaluation before possible AVR between January 2004 and December 2011. Of 154 patients with severe AS (aortic valve area [AVA] ≤ 1.0 cm 2 ), 118 had either early AVR because of symptoms (64 patients with effort angina or syncope or admission for heart failure or New York Heart Association functional class ≥ III), abnormal baseline LV systolic function (LVEF < 55%) or wall motion abnormalities, or concomitant valvular and coronary disease requiring interventions (mitral valve replacement or repair, coronary artery bypass grafting, or moderate or greater aortic regurgitation). Thirty-six patients were asymptomatic and had normal baseline LVEFs (≥55%) and no other significant valvular heart disease or wall motion abnormalities, and their planned AVR was deferred. Six patients had echocardiographic studies that were not analyzable for strain, leaving 30 patients as our study group. Thirty-seven patients with similar demographics (age, gender) and echocardiographic (LVEF, AVA) characteristics underwent AVR only early after their initial clinic visits. Of these, 32 had strain-analyzable echocardiographic studies and served as our comparator group. As a normal control reference, we included 32 subjects with similar demographics (age, gender) who were referred for echocardiography for minor symptoms, did not have major illnesses or cardiovascular risk factors, and had normal results on 2D Doppler echocardiography. All patients had available echocardiographic studies in Digital Imaging and Communications in Medicine format. Patients’ hospital records were used to obtain clinical data. The study was approved by our institutional research ethics board.
Doppler Echocardiographic Studies
All patients had routine full Doppler echocardiographic studies including parasternal long-axis views, four levels of short-axis views (aortic level, mitral, midpapillary, and apical levels), three apical long-axis views (each view repeated to include the both left atrium and ventricle and decreased depth to focus on the left ventricle). Studies were acquired using all various machines available at our lab (Vivid 3 and Vivid 7 [GE Vingmed Ultrasound AS, Horten, Norway], Acuson [Siemens Medical Solutions USA Inc, Mountain View, CA], and iE33 [Philips Medical Systems, Best, The Netherlands]) and archived without temporal or spatial compression. All cine acquisitions were of two or three consecutive beats. Echocardiographic studies were interpreted at the time of acquisition. Two-dimensional Doppler parameters were measured according to guidelines of the American Society of Echocardiography. AVA was calculated using the continuity equation.
Strain, Strain Rate, and Rotation Evaluation
Strain measurements were performed using 2D tissue-tracking software (Velocity Vector Imaging; Siemens Medical Solutions USA Inc) from archived 2D echocardiographic studies. Longitudinal wall strain and strain rate were averaged from 18-segment measurements from the apical two-, three-, and four-chamber views. Circumferential strain, strain rate, and rotation angles were measured in six segments per short-axis plane at the parasternal mid-LV level and at the apical level obtained in a window between the parasternal and apical windows. All measurements were averaged for each short-axis level. Peak systolic rotation was defined as the peak angular short-axis myocardial displacement during systole. Peak myocardial systolic rotation angles were used to calculate midapical LV twist, defined as the maximal instantaneous mid to apical rotation angle difference. All myocardial mechanical analyses were automatically averaged on all consecutive beats available on stored cine clips. Velocity Vector Imaging strain analysis was not expected to depend on source acquisition hardware.
Reproducibility of Myocardial Mechanical Analysis
For intraobserver variability of strain, systolic and diastolic strain rate, and rotation, 10 randomly assigned patients were reanalyzed by the same observer 3 months after the initial analysis. Interobserver analysis was done <10 days after the initial analysis. For both intra- and interobserver variability, the same patients and the exact same multibeat cine loops were reanalyzed.
Statistical Analysis
The data were analyzed using MedCalc version 11.6.1 (MedCalc Software, Mariakerke, Belgium). Continuous data are reported as mean ± SD. Patient groups (normal healthy controls, asymptomatic and symptomatic patients with severe AS) were assessed by using analysis of variance with the Tukey post hoc test. Prediction of symptoms by clinical, echocardiographic, and strain variables was done by using binary logistic regression analysis. For test performance, intra- and interobserver variability, intraclass correlation coefficients with 95% confidence intervals were calculated, as they take the bias between observations into account.
Results
Demographics and Conventional Echo-Doppler Measurements
Both patient groups had demographic characteristics that were similar to those of normal controls ( Table 1 ). Asymptomatic patients were followed for 29 ± 23 months. During follow-up, 12 patients (40%) underwent AVR a mean of 17 ± 9 months after their initial clinic visits. Conventional echocardiographic parameters (LV and left atrial dimensions, systolic and diastolic function) were nearly identical in symptomatic and asymptomatic patients with severe AS. There was no significant differences in AVA and peak aortic gradient. They demonstrated LV hypertrophy, normal LVEFs, mildly enlarged left atria, similar mitral inflow parameters, and borderline pulmonary hypertension compared with normal controls.
| Variable | Normal controls ( n = 32) | Asymptomatic AS ( n = 30) | Symptomatic AS ( n = 32) |
|---|---|---|---|
| Men | 44% | 43% | 47% |
| Age (y) | 62 ± 10 | 69 ± 14 | 65 ± 13 |
| BSA (m 2 ) | 1.8 ± 0.2 | 1.9 ± 0.2 | 1.8 ± 0.2 |
| Heart rate (beats/min) | 64 ± 8 | 67 ± 10 | 67 ± 10 |
| Systolic blood pressure (mm Hg) | 137 ± 15 | 138 ± 26 | |
| Diastolic blood pressure (mm Hg) | 61 ± 9 | 76 ± 9 | |
| Echocardiography | |||
| LV diastolic diameter (cm) | 4.7 ± 0.3 | 4.7 ± 0.5 | 4.9 ± 0.5 |
| LV systolic diameter (cm) | 2.9 ± 0.3 | 2.9 ± 0.4 | 3.1 ± 0.5 |
| Septal thickness (cm) | 0.9 ± 0.1 | 1.3 ± 0.2 ∗ | 1.3 ± 0.2 ∗ |
| Posterior wall thickness (cm) | 0.8 ± 0.1 | 1.0 ± 0.1 ∗ | 1.0 ± 0.1 |
| LV mass (g) | 135 ± 26 | 196 ± 58 ∗ | 216 ± 54 ∗ |
| LA systolic diameter (cm) | 3.6 ± 0.4 | 4.2 ± 0.5 ∗ | 4.1 ± 0.5 |
| LVEF (%) | 66 ± 4 | 67 ± 5 | 68 ± 7 |
| Mitral inflow E/A ratio | 1 ± 0.3 | 1.0 ± 0.7 | 1.0 ± 0.7 |
| Mitral E deceleration time (msec) | 230 ± 55 | 255 ± 52 | 250 ± 83 |
| Pulmonary arterial pressure (mm Hg) | 27 ± 4 | 34 ± 5 ∗ | 36 ± 7 ∗ |
| Aortic valve mean gradient (mm Hg) | NA | 56 ± 19 | 56 ± 17 |
| Aortic valve peak gradient (mm Hg) | NA | 96 ± 28 | 94 ± 29 |
| Aortic valve peak velocity (m/sec) | 0.7 ± 0.1 | 4.9 ± 0.7 | 4.9 ± 0.7 |
| LV outflow velocity-time integral (cm) | NA | 27 ± 4 | 28 ± 5 |
| AVA (cm 2 ) | NA | 0.8 ± 0.1 | 0.8 ± 0.2 |
| AVA index (cm 2 /m 2 ) | NA | 0.46 ± 0.09 | 0.43 ± 0.06 |
Asymptomatic versus Symptomatic AS Mechanics
Changes in strain and strain rate are reported in relation to their absolute values (i.e., by stating that strain was increased, we describe a larger negative value, implying increased shortening).
Longitudinal and Circumferential Strain
Uniplane strains were abnormal in patients with severe AS. Average LV longitudinal strain was lower than normal and demonstrated a progressive decline in relation to symptomatic status (20% and 34% declines for asymptomatic and symptomatic patients, respectively). Midlevel circumferential strain remained in the normal range regardless of symptomatic status. Apical circumferential strain was significantly higher than normal in patients with severe AS. This increase was greater (19%) in asymptomatic patients and fell to near yet above normal values (10%) in symptomatic patients. Global mechanical measurements were consistent with segmental measurements that demonstrated changes similar in direction, magnitude, and statistical significance ( Table 2 , Figure 1 ).
| Variable | Normal controls ( n = 32) | Asymptomatic AS ( n = 30) | Symptomatic AS ( n = 32) |
|---|---|---|---|
| Longitudinal strain (%) | |||
| Average | −19.5 ± 2.6 | −15.5 ± 2.7 ∗ | −13.1 ± 1. 7 ∗† |
| Circumferential strain (%) | |||
| Mid | −29.7 ± 5.4 | −29.8 ± 4.2 | −27.6 ± 4.6 |
| Apex | −32.2 ± 4.5 | −38.3 ± 6.4 ∗ | −34.9 ± 4.3 ∗† |
| Average strain rate (%/sec) | |||
| Longitudinal systolic | −1.0 ± 0.1 | −0.8 ± 0.1 ∗ | −0.6 ± 0.1 ∗† |
| Circumferential systolic (mid) | −1.7 ± 0.4 | −1.5 ± 0.4 ∗ | −1.4 ± 0.3 ∗† |
| Circumferential systolic (apex) | −2.0 ± 0.7 | −2.6 ± 0.8 ∗ | −1.9 ± 0.4 † |
| Longitudinal early diastolic | 1.0 ± 0.2 | 0.7 ± 0.1 ∗ | 0.6 ± 0.1 ∗† |
| Circumferential early diastolic (mid) | 1.6 ± 0.4 | 1.4 ± 0.4 ∗ | 1.2 ± 0.3 ∗† |
| Circumferential early diastolic (apex) | 1.8 ± 0.7 | 2.1 ± 0.8 ∗ | 1.6 ± 0.4 ∗† |
| Early diastolic/systolic strain rate ratio | |||
| Longitudinal | 0.92 ± 0.23 | 0.89 ± 0.1 | 0.88 ± 0.13 |
| Circumferential (mid) | 0.89 ± 0.25 | 0.92 ± 0.18 | 0.87 ± 0.12 |
| Circumferential (apex) | 0.91 ± 0.29 | 0.84 ± 0.20 | 0.87 ± 0.18 |
| Mid rotation angle (°) | 2.7 ± 2.3 | 2.6 ± 3.4 | −1.2 ± 0.8 † |
| Apical rotation angle (°) | 7.6 ± 3.8 | 12.2 ± 4.9 ∗ | 2.9 ± 1.7 ∗† |
| Midapical twist (°) | 5.7 ± 4.1 | 10.2 ± 6.1 ∗ | 3.4 ± 1.9 ∗† |
∗ P < .05 compared with normal subjects.
Apical Rotational Mechanics
Apical rotation demonstrated a bimodal pattern. In asymptomatic patients, it was >50% above normal, whereas in symptomatic patients it was dramatically different, being >50% lower than normal and >75% lower than in asymptomatic patients. In a multivariate logistic regression model with stepwise evaluation of age, LV mass, average longitudinal strain, apical strain, and apical rotation angle, the latter was found to be the sole independent predictor of symptomatic state (B coefficient = −1.31 (95% confidence interval, 0.11–0.65); P = .004). An apical rotation cutoff of 6° was 96.2% predictive of symptomatic status (true positive + true negative) ( Table 2 , Figure 2 ).
Diastolic Mechanics (Early Diastolic to Systolic Strain Rate Ratio)
Longitudinal and circumferential systolic and early diastolic strain rate magnitude changes generally followed the changes observed in systolic strain. To observe systolic independent changes in early diastolic strain, we calculated an early diastolic to systolic SR ratio. All patient groups (normal controls, asymptomatic and symptomatic patients) had similar corrected early diastolic strain rates ( Table 2 ). Thus, diastolic mechanics changed in parallel to systolic myocardial mechanics.
Initially Asymptomatic Patients Undergoing AVR in Follow-up
During the study period (2004–2011), 12 of the asymptomatic patients (40%) eventually underwent AVR a mean of 17 ± 9 months after their initial clinic visits and echocardiographic studies. Table 3 summarizes their echocardiographic and myocardial mechanical characteristics at baseline and immediately before surgery, comparing them with those of the remaining 18 patients who did not undergo AVR during follow-up. Patients with eventual AVR were nearly a decade younger than those who did not undergo AVR. At baseline, there were no significant differences in conventional or myocardial mechanical parameters between patients with and without subsequent AVR. During follow-up, patients with subsequent AVR had nonsignificant increases in their peak transaortic gradients and decreases in their body surface area–indexed AVAs. Although global longitudinal strain trended toward a continuing decrease in magnitude, circumferential mechanical parameters (strain and rotation) demonstrated significant decreases. Follow-up pre-AVR apical circumferential strain and rotation decreased to normal values, and apical rotation angle remained larger than in patients who underwent early AVR (8.5 ± 2.8° vs 2.9 ± 1.7°, respectively P < .005).
