Recovery of Left Ventricular Mechanics after Transcatheter Aortic Valve Implantation: Effects of Baseline Ventricular Function and Postprocedural Aortic Regurgitation

CLINICAL INVESTIGATIONS VALVULAR HEART DISEASE

Recovery of Left Ventricular Mechanics after Transcatheter Aortic Valve Implantation: Effects of Baseline Ventricular Function and Postprocedural Aortic Regurgitation Frederic Poulin, MD, MSc, Shemy Carasso, MD, Eric M. Horlick, MDCM, Harry Rakowski, MD, Ki-Dong Lim, MD, Heather Finn, MBBS, Christopher M. Feindel, MD, Matthias Greutmann, MD, Mark D. Osten, MD, Robert J. Cusimano, MD, and Anna Woo, MD, SM, Toronto, Ontario, Canada

Background: Impaired left ventricular (LV) myocardial deformation is associated with adverse outcome in patients with severe aortic stenosis (AS). The aim of this retrospective study was to assess the impact of transcatheter aortic valve implantation (TAVI) on the recovery of myocardial mechanics and the influence of postprocedural aortic regurgitation (AR). Methods: Speckle-tracking echocardiography was used to assess multidirectional myocardial deformation (longitudinal and circumferential strain) and rotational mechanics (apical rotation and twist) before and at midterm follow-up after TAVI. Predictors of myocardial recovery, defined as a $20% relative increase in the magnitude of global longitudinal strain compared with baseline, were examined. Results: Sixty-four patients (median age, 83 years; interquartile range, 77–86 years) with severe AS and high surgical risk (mean European System for Cardiac Operative Risk Evaluation score, 20 6 13%) were evaluated. Overall, LV longitudinal deformation was impaired at baseline compared with controls. At 5 6 3 months after TAVI, LV longitudinal deformation had significantly improved only in the group of patients with baseline LV ejection fractions (LVEF) # 55%: global longitudinal strain from
9.7 6 3.7% to
11.8 6 3.2% (P = .05), longitudinal strain rate from
0.44 6 0.14 sec
1 to
0.57 6 0.16 sec
1 (P = .001), and early diastolic strain rate from 0.38 6 0.17 sec
1 to 0.49 6 0.18 sec
1 (P = .01). In patients with normal LVEFs, LV twist was supraphysiologic at baseline and normalized after TAVI (from 16.1 6 6.9 to 11.9 6 6.2 , P = .004). In patients with baseline LVEFs # 55%, circumferential deformation was impaired before TAVI and improved after TAVI. Baseline LVEF (odds ratio, 0.56 per 10% increment; P = .02) and global longitudinal strain (odds ratio, 0.65 per absolute 1% increment; P < .001) were significant predictors of myocardial recovery. LV mass, volumes, and longitudinal strain failed to favorably remodel in patients with post-TAVI important AR (defined as new mild post-TAVI AR or moderate or severe post-TAVI AR [either preexisting or new AR]). Conclusions: TAVI restores LV function toward more physiologic myocardial mechanics in both normal- and depressed-LVEF groups. Patients with lower systolic function derive the most benefit in terms of longitudinal reverse remodeling. Postprocedural AR adversely affects LV structural and functional remodeling. (J Am Soc Echocardiogr 2014;27:1133-42.) Keywords: Aortic stenosis, Transcatheter aortic valve implantation, Speckle-tracking echocardiography, Myocardial mechanics, Strain, Paravalvular aortic regurgitation Aortic stenosis (AS) causes chronic pressure overload on the left ventricle, leading to concentric hypertrophy, subendocardial ischemia, myocardial fibrosis, impaired diastolic filling, and potentially

From the Peter Munk Cardiac Center, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada de ric Poulin, MD, MSc, Toronto General Hospital, 200 Elizabeth Reprint requests: Fre Street, 4N-506, Toronto, ON M5G 2C4, Canada (E-mail: [email protected]). 0894-7317/$36.00 Copyright 2014 by the American Society of Echocardiography. http://dx.doi.org/10.1016/j.echo.2014.07.001

systolic dysfunction.1 Transcatheter aortic valve implantation (TAVI) is a novel therapy for patients with severe AS at high risk for open-heart surgery.2 Patients who have undergone TAVI are older and have more serious comorbidities than patients who have been referred for conventional surgical aortic valve replacement (AVR).3 One potential disadvantage of TAVI is an increased incidence of postprocedural aortic regurgitation (AR), which is an independent predictor of shortand long-term mortality and which may have a negative impact on LV myocardial recovery.4,5 Speckle-tracking echocardiography (STE) allows the quantitative angle-independent assessment of myocardial mechanics in different axes and rotations. STE provides strain and strain rate (SR) 1133

1134 Poulin et al

measurements that are more sensitive markers of subtle alterAR = Aortic regurgitation ations in global and regional myocardial function.6 In the AS = Aortic stenosis setting of AS, studies have shown AVR = Aortic valve progressive impairment in global replacement longitudinal systolic strain (GLS) and SR, proportional to the GLS = Global longitudinal severity of AS, despite preserved systolic strain left ventricular (LV) ejection fracLV = Left ventricular tion (LVEF).7,8 Reduction in GLS LVEF = Left ventricular predicts a worsened prognosis in ejection fraction this population.9-13 Therefore, the assessment of OR = Odds ratio multidirectional myocardial reSR = Strain rate covery by STE after TAVI in this elderly population with a high STE = Speckle-tracking burden of comorbidities warechocardiography rants further characterization. TAVI = Transcatheter aortic We sought to determine the valve implantation intermediate-term impact of TAVI on myocardial mechanics by using comprehensive quantification of LV longitudinal, circumferential, and rotational deformation before and after TAVI in a population of symptomatic patients with severe AS. Our secondary objective was to assess the influence of postprocedural AR on the recovery of myocardial mechanics. Abbreviations

METHODS Study Design Study Population. This retrospective study consisted of patients undergoing TAVI for symptomatic severe AS at a single center (Toronto General Hospital, University of Toronto). Patients were included in this study if transthoracic echocardiograms obtained before TAVI and at medium-term follow-up (between 2 and 12 months) were available for review. Exclusion criteria for this study were (1) poor endocardial tracking with speckle-tracking echocardiographic analysis in at least two adjacent myocardial segments and (2) the presence of atrial fibrillation during the echocardiographic study. Twenty-one healthy patients $60 years of age studied previously using the same echocardiographic protocol served as the control group.14 The study protocol was approved by the local institutional research ethics board. TAVI. Eligibility criteria for TAVI were the presence of symptomatic severe native or prosthetic valve stenosis with an aortic valve area # 1.0 cm2 and/or mean systolic aortic gradient > 40 mm Hg. In the setting of LV systolic dysfunction and low-flow, low-gradient AS, the severity of AS was confirmed by low-dose dobutamine stress echocardiography. All potential candidates for TAVI were considered to have an excessively high risk for death with conventional open AVR, with an estimated operative mortality risk of >15%, as determined by a multidisciplinary team of experts. Clinical Data. Demographic characteristics, comorbidities, previous cardiac procedures, logistic European System for Cardiac Operative Risk Evaluation score,15 and functional status were prospectively collected in a database. Echocardiography. Transthoracic echocardiographic and Doppler studies were done before and after TAVI at our institution.

Journal of the American Society of Echocardiography November 2014

Two-dimensional echocardiographic, Doppler, and Doppler tissue imaging parameters were measured in accordance with published guidelines from the American Society of Echocardiography. LV volumes and LVEF were estimated using Simpson’s biplane method.16 Aortic valve area was calculated using the continuity equation. Peak and mean systolic transaortic gradients were calculated using the simplified Bernoulli equation.17 AR. Before patients underwent TAVI, native aortic valve regurgitation was ascertained by integrating information from the following available semiquantitative parameters: AR jet width of the LV outflow tract, AR jet cross-sectional area in the LV outflow tract, AR jet density, pressure half-time of AR, and diastolic flow reversal in the descending aorta.18 The categorization of pre-TAVI AR into mild, moderate, and severe groups was made according to recommendations of the American Society of Echocardiography.18 After the TAVI procedure, color, pulsed-wave, and continuous-wave Doppler imaging was performed to semiquantitatively evaluate the severity of post-TAVI AR. The categorization of post-TAVI paravalvular AR was based mainly on the proportion of the circumference of the aortic prosthetic ring occupied by the regurgitant jet in the parasternal short-axis view.19 Trivial paravalvular AR was defined as a pinpoint jet. We adopted the following classification scheme for the circumferential extent of the AR jet, which has been proposed by the Valve Academic Research Consortium–2 consensus document: (1) mild, <10%; (2) moderate, 10% to 29%; and (3) severe, $30%.19 Pulsed-wave signals of diastolic flow reversal in the descending thoracic aorta was also used to differentiate postTAVI AR, with the following criteria: (1) mild, absent or brief early diastolic flow reversal; (2) moderate, intermediate findings between mild and severe AR; and (3) severe, prominent and holodiastolic flow reversal.19 Finally, the density of the AR jet on continuous-wave Doppler was used to help differentiate the cases of post-TAVI AR: (1) mild, incomplete or faint AR jet density, or (2) moderate or severe, dense AR jet density.19 In cases of both valvular and paravalvular regurgitation seen in the postprocedural echocardiographic studies, the grading of AR reflected the summation of total regurgitation. In analyzing post-TAVI valvular regurgitation, we hypothesized that any new post-TAVI AR potentially affects LV recovery, because this valvular regurgitation represents a new insult, mimicking the hemodynamic changes of acute AR. New mild post-TAVI AR contrasts with preexisting mild AR (i.e., a patient with both pre-TAVI mild AR of the original aortic valve and post-TAVI mild AR of the new aortic bioprosthesis), in which the LV cavity presumably does not need to make any major hemodynamic adaptation to an unchanged degree of AR. Accordingly, we dichotomized patients into two subgroups: unimportant post-TAVI AR and important post-TAVI AR. We defined unimportant post-TAVI AR as (1) no or trivial post-TAVI AR or (2) preexisting mild post-TAVI AR (i.e., at least mild pre-TAVI AR and ongoing postTAVI mild AR). Important post-TAVI AR was defined as (1) new mild post-TAVI AR (i.e., no or trivial pre-TAVI AR that becomes mild AR after TAVI) or (2) moderate or severe post-TAVI AR (either preexisting or new AR). All images were digitally stored for offline analyses. Myocardial Mechanics. Multidirectional myocardial mechanics were compared in patients with normal and abnormal LVEFs, with a cutoff LVEF of >55% used to define the normal systolic function group. Quantitative assessment of LV subendocardial mechanics by STE was performed before and after TAVI using Velocity Vector Imaging version 3 (Siemens Medical Solutions USA, Mountain View, CA). Apical four-, three-, and two-chamber views were used to obtain longitudinal strain and SR, as previously described.14

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Table 1 Baseline characteristics Clinical characteristic

All patients (n = 64)

LVEF > 55% (n = 41)

LVEF # 55% (n = 23)

P*

Age (y) Men BMI (kg/m2) NYHA class III or IV Arterial hypertension Dyslipidemia Diabetes mellitus Coronary artery disease Peripheral vascular disease Cerebral vascular disease Previous AVR Mitral regurgitation (moderate or greater) Chronic lung disease Renal insufficiency (GFR # 50 mL/min) Logistic EuroSCORE (%)

83 (77–86) 37 (58%) 22 6 5 56 (87%) 48 (75%) 43 (67%) 16 (25%) 37 (58%) 8 (13%) 6 (9%) 3 (5%) 8 (13%) 6 (9%) 22 (34%) 20 6 13

82 (77–86) 20 (49%) 22 6 6 33 (80%) 31 (76%) 31 (76%) 9 (22%) 20 (49%) 5 (12%) 2 (5%) 1 (2%) 5 (12%) 5 (12%) 18 (44%) 16 6 12

83 (77–87) 17 (74%) 23 6 4 23 (100%) 17 (74%) 12 (52%) 7 (30%) 17 (74%) 3 (13%) 4 (17%) 2 (9%) 3 (13%) 1 (4%) 4 (17%) 25 6 15

.96 .05 .55 .04 .88 .06 .45 .05 1.00 .18 .29 1.00 .29 .03 .02

BMI, Body mass index; GFR, glomerular filtration rate; NYHA, New York Heart Association. Data are expressed as median (range), number (percentage), or mean 6 SD. *LVEF > 55% versus LVEF # 55%.

Parasternal short-axis planes were used to obtain circumferential strain, SR, rotational angles, and maximal instantaneous basal to apical angle difference (net LV twist). Physiologic counterclockwise apical rotation was expressed as a positive angle. Global peak systolic strain and SR and early diastolic SR values were derived from the time-strain and SR curves, averaging the 16 myocardial segments.

coefficient21 and the coefficient of variation. A level of significance of .05 was set for all analyses. All statistical analyses were conducted using SPSS version 20 (SPSS, Inc., Chicago, IL).

Intraobserver and Interobserver Variability. Offline twodimensional strain evaluations were done by a single operator (F.P.) blinded to patients’ clinical information. For intraobserver variability, 10 randomly selected studies were reanalyzed once by the same observer several months after the initial analysis. A second experienced observer, blinded to previously obtained data, analyzed the same patients and the exact same loops for the assessment of interobserver variability.

Study Population

Statistical Analyses Categorical variables are expressed as frequencies and percentages. Continuous variables are summarized as mean 6 SD or median (interquartile range), depending on the normality of distribution. Echocardiographic parameters before and after TAVI were compared using McNemar’s test for categorical variables and the paired t test or Wilcoxon’s signed-rank test for continuous variables, as appropriate. Univariate logistic regression models with relevant clinical and echocardiographic variables were used to identify predictors of favorable functional myocardial recovery after TAVI, defined as $20% relative increase in the magnitude of GLS compared with baseline (e.g., increase from
15% [baseline] to at least
18% [after TAVI]). Comparisons of the change in echocardiographic parameters after TAVI between patients with unimportant AR and those with important AR after TAVI were performed using analysis of covariance with the absolute difference from baseline as the outcome and preprocedural value and LVEF as the covariates. Mean percentage change from baseline is also reported to facilitate comparison between groups in clinically relevant terms.20 Intraobserver and interobserver variability was assessed by the intraclass correlation

RESULTS

Among the 121 patients who underwent TAVI for severe AS from 2007 to 2012, and who had available preprocedural and mid-term follow-up transthoracic echocardiograms, 64 were eligible for this study. The excluded individuals consisted of 28 patients because of the presence of atrial fibrillation at the time of echocardiography and 29 patients because of poor endocardial tracking with the Velocity Vector Imaging software (caused mainly by insufficient endocardial definition or tracking issues during the cardiac cycle). Baseline characteristics are depicted in Table 1. The median age was 83 years (interquartile range, 77–86 years) and 58% were men. The mean logistic European System for Cardiac Operative Risk Evaluation risk estimate was 20 6 13%. There was no significant difference between the 64 study patients and the 57 excluded patients. The comparison of patients in the normal- and abnormal-LVEF groups showed no significant differences in age (median, 82 years [interquartile range, 77– 86 years] vs 83 years [interquartile range, 77–87 years]; P = .96), prevalence of hypertension (76% vs 74%, P = .88), and diabetes (22% vs 30%, P = .45). However, patients in the abnormal-LVEF group had more severe functional limitation (New York Heart Association class III or IV in 100% vs 80%, P = .04), higher logistic European System for Cardiac Operative Risk Evaluation score (25 6 15% vs 16 612%, P = .02), and a trend toward a greater prevalence of coronary artery disease (74% vs 49%, P = .05), compared with those patients with preserved LVEFs, respectively. TAVI Transapical and transfemoral approaches were used in 39 (61%) and 23 (36%) patients, respectively. The direct transaortic approach was

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Table 2 Echocardiographic parameters before and after TAVI according to baseline LVEF LVEF # 55% (n = 23)

LVEF > 55% (n = 41) Echocardiographic parameter

Pre-TAVI

Post-TAVI

P

Pre-TAVI

Post-TAVI

P

Aortic valve area (cm2) Aortic valve area index (cm2/m2) Aortic mean gradient (mm Hg) LV end-diastolic diameter (cm) LV end-systolic diameter (cm) LV diastolic volume (mL) LV systolic volume (mL) LV mass index (g/m2) Stroke volume (mL/beat) LVEF (%) Lateral E0 (cm/sec) E/E0 ratio LA volume (mL/m2) RVSP (mm Hg)

0.67 6 0.15 0.39 6 0.10 52 6 16 4.2 6 0.7 2.7 6 0.7 86 6 27 32 6 12 127 6 41 54 6 16 63 6 5 7.7 6 3.2 12.8 6 5.8 51 6 19 42 6 12

1.69 6 0.41 0.97 6 0.22 12 6 5 4.3 6 0.7 2.8 6 0.7 94 6 32 37 6 23 119 6 35 58 6 15 63 6 9 7.8 6 2.2 13.9 6 7.0 50 6 17 44 6 13

<.001 <.001 <.001 .18 .31 .07 .16 .08 .13 .79 .90 .49 .61 .48

0.70 6 0.22 0.39 6 0.11 45 6 16 4.9 6 0.7 3.5 6 1.0 132 6 54 74 6 33 138 6 37 59 6 28 45 6 9 6.9 6 1.7 12.2 6 2.9 50 6 17 45 6 14

1.71 6 0.38 0.95 6 0.22 11 6 5 4.6 6 0.7 3.2 6 0.9 116 6 51 59 6 36 120 6 33 57 6 21 51 6 12 8.5 6 3.2 10.3 6 5.7 45 6 12 42 6 14

<.001 <.001 <.001 .008 .01 .09 .01 .008 .82 .04 .22 .40 .15 .41

BSA, Body surface area; LA, left atrial; RVSP, right ventricular systolic pressure. Data are expressed as mean 6 SD.

required in two patients. Edwards SAPIEN valves were implanted in 52 patients (81%) and Medtronic CoreValve devices in 12 patients (19%). Echocardiography Follow-up transthoracic echocardiographic studies were performed 5.6 6 3.5 months after the procedures, with no significant difference between the preserved- and depressed-LVEF subgroups (5.7 6 3.6 months vs 5.6 6 3.4 months, P = .90; Table 2). The mean aortic valve area increased (from 0.67 6 0.15 to 1.69 6 0.41 cm2 [P < .001] in the preserved-LVEF subgroup and from 0.70 6 0.22 to 1.71 6 0.38 cm2 [P < .001] in the depressed-LVEF subgroup), accompanied by a significant decrease in the mean transaortic pressure gradient (from 52 6 16 to 12 6 5 mm Hg [P < .001] in the preserved-LVEF subgroup and from 45 6 16 to 11 6 5 mm Hg [P < .001] in the depressed-LVEF subgroup) after TAVI. In addition, significant reduction in LV systolic volume (from 74 6 33 to 59 6 36 mL, P = .01), LV mass index regression (from 138 6 37 to 120 6 33 g/m2, P = .008), and improvement in LVEF (from 45 6 9% to 51 6 12%, P = .04) were observed in the abnormal-LVEF group. The proportion of patients with at least moderate mitral regurgitation at baseline and at followup was 13% and 11%, respectively. Myocardial Mechanics Longitudinal Deformation. Compared with the control group, the 64 patients with severe AS had lower GLS (
12.8 6 4.0% vs
19.4 6 2.7%, P < .001), lower global longitudinal systolic SR (
0.61 6 0.20 sec
1 vs
1.01 6 0.15 sec
1, P < .001), and lower early diastolic SR (0.51 6 0.20 sec
1 vs 0.93 6 0.17 sec
1, P < .001) (Table 3). When patients were analyzed according to baseline LVEF (Table 3), the 23 patients with depressed LVEFs (mean, 45 6 9%) had lower longitudinal strain and SR at baseline (before TAVI) compared with those with preserved LVEFs (mean, 63 6 5%). At follow-up, only patients with depressed LVEFs at baseline showed consistent improvement in longitudinal deformation: GLS from


9.7 6 3.7% to
11.8 6 3.2% (P = .05), global longitudinal systolic SR from
0.44 6 0.14 sec
1 to
0.57 6 0.16 sec
1 (P = .001), and early diastolic SR from 0.38 6 0.17 sec
1 to 0.49 6 0.18 sec
1 (P = .01) (Figure 1). The change in longitudinal strain parameters did not reach statistical significance in the preserved-LVEF group. Circumferential Deformation. Normal-LVEF Subgroup.–In patients with normal LVEFs at baseline, preprocedural circumferential deformation was significantly higher compared with those with LVEFs < 55%, likely reflecting physiologic compensation to maintain systolic function. After TAVI, restoration of lower systolic circumferential strain and SR at the apical level was observed (Table 3). Low-LVEF Subgroup.–The changes in circumferential mechanics in the low-LVEF group differed from those in patients with normal LVEFs. Parameters of systolic and diastolic circumferential myocardial deformation were markedly impaired at baseline in the low-LVEF group. Circumferential systolic strain and SR (both globally and regionally in all three short-axis planes) and early diastolic SR significantly improved after TAVI (Table 3). Rotation and Net LV Twist Angle. Normal-LVEF Subgroup.–In patients with normal LVEFs, net LV twist angle was supraphysiologic before TAVI (16.1 6 6.9 vs 11.0 6 4.5 , patients with AS versus controls, respectively, P = .003) and decreased toward normal values after TAVI (from 16.1 6 6.9 to 11.9 6 6.2 , P = .004). There was corresponding normalization of apical counterclockwise rotation (from 10.5 6 6.5 to 7.4 6 5.7 , P = .009) in these patients (Figure 2, Table 3). Low-LVEF Subgroup.–In contrast, pre-TAVI net LV twist was significantly lower in patients with depressed LVEFs and did not change after TAVI. Impact of Transapical versus Transfemoral Approach on Myocardial Mechanics. There was no difference in change of longitudinal and circumferential strain and SR, apical rotation, and

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Figure 1 Pre- versus post-TAVI longitudinal strain in a representative patient. Segmental longitudinal strain curves (apical twochamber view) are illustrated in a representative patient. Longitudinal systolic strain is reduced at baseline (A), with near normalization after TAVI (B).

Table 3 Myocardial mechanics before and after TAVI according to baseline LVEF LVEF # 55% (n = 23)

LVEF > 55% (n = 41) Variable

Longitudinal GLS (%) GLSR (sec
1) Early diastolic SR (sec
1) Circumferential GCS (%) Base Mid Apex GCSR (sec
1) Base Mid Apex Early diastolic SR (sec
1) Rotation ( ) Base Mid Apex Peak twist angle ( )

Pre-TAVI

Post-TAVI

P*

.19 .11 .19


9.7 6 3.7‡
0.44 6 0.14‡ 0.38 6 0.17‡


11.8 6 3.2
0.57 6 0.16 0.49 6 0.18

.05 .001 .01


29.2 6 6.3
24.5 6 5.9
28.1 6 7.5
33.1 6 10.0
1.85 6 0.56
1.33 6 0.38
1.55 6 0.47
1.99 6 0.76 1.84 6 0.63

.06 .60 .08 .03 .13 .37 .48 .03 .29


21.0 6 6.1‡
17.5 6 6.0‡
18.8 6 7.4‡
24.1 6 9.7‡
1.29 6 0.36‡
0.87 6 0.29‡
0.97 6 0.38‡
1.36 6 0.57‡ 1.31 6 0.39‡


25.1 6 8.8
21.1 6 7.6
23.8 6 9.3
27.6 6 13.3
1.65 6 0.67
1.11 6 0.42
1.35 6 0.64
1.78 6 0.88 1.61 6 0.65

.03 .03 .03 .15 .01 .002 .01 .02 .03


4.6 6 5.8 0.9 6 5.2 7.4 6 5.7 11.9 6 6.2

.183 .26 .009 .004


3.6 6 3.1 2.1 6 5.0 7.7 6 3.9‡ 10.6 6 4.8‡


5.4 6 5.4 0.4 6 4.5 4.1 6 6.3 10.0 6 5.1

.30 .12 .02 .71

Controls (n = 21)

Pre-TAVI

Post-TAVI


19.4 6 2.7
1.01 6 0.15 0.93 6 0.17


14.6 6 2.9†
0.70 6 0.16† 0.57 6 0.19†


15.4 6 4.0
0.76 6 0.22 0.62 6 0.21


31.2 6 4.3
26.1 6 5.4
30.6 6 5.1
35.9 6 6.2
1.90 6 0.39
1.50 6 0.31
1.78 6 0.38
2.27 6 0.61 1.74 6 0.46


31.2 6 6.1
25.1 6 6.1
30.4 6 7.4
38.3 6 9.3
1.98 6 0.61
1.26 6 0.34†
1.61 6 0.53
2.45 6 1.25 2.00 6 0.69


4.0 6 2.3 2.5 6 2.9 8.0 6 3.8 11.0 6 4.5


5.5 6 4.7 1.6 6 5.6 10.5 6 6.5 16.1 6 6.9†

P*

GCS, Global circumferential strain; GCSR, global circumferential SR; GLSR, global longitudinal systolic SR. Data are expressed as mean 6 SD. *Pre-TAVI versus post-TAVI. † P < .05, AS with LVEF > 55% versus control. ‡ P < .05, LVEF # 55% versus LVEF > 55%.

net LV twist in patients who underwent transapical versus transfemoral TAVI.

Echocardiographic Predictors of Favorable Myocardial Recovery after TAVI Longitudinal myocardial recovery after TAVI, defined as $20% relative increase in the magnitude of GLS compared with baseline, was observed in 23 patients (36%). By univariate logistic regression, age, gender, coronary artery disease, and the type of procedural approach

were not significantly associated with LV longitudinal recovery. Among the echocardiographic variables studied (LVEF, LV volumes, LV mass, GLS, baseline aortic valve area, baseline mean transaortic gradient, change in aortic valve area, and mean gradient at follow-up), four variables emerged as significant predictors of longitudinal myocardial recovery after TAVI: baseline LVEF (odds ratio [OR], 0.56 per 10% increment; P = .02), baseline GLS (OR, 0.65 per absolute 1% increment; P < .001), baseline mean transaortic gradient (OR, 1.45 per 10 mm Hg increment; P = .04), and change in mean transaortic gradient after TAVI (OR, 1.45 per 10 mm Hg reduction; P = .03). Because of the

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Figure 2 Pre- versus post-TAVI LV rotation and net twist angle in a representative patient with LVEF > 55%. Basal clockwise and apical counterclockwise rotation and net LV twist are illustrated in a representative patient with AS and preserved LVEF. Normalization of apical rotation and net LV twist angle after TAVI highlights the compensatory nature of these mechanisms in patients with severe AS and preserved systolic function.

small number of patients with myocardial recovery, the sample size requirement for performing a multivariate analysis was not met. Impact of Postprocedural AR on Cardiac Structure and Function No or trivial, mild, moderate, and severe post-TAVI AR was found in 24 (38%), 28 (44%), 11 (17%), and one (1%) patient, respectively. Patients were classified according to their post-TAVI AR. The unimportant post-TAVI AR subgroup consisted of 46 patients: (1) 24 patients with no or trivial post-TAVI AR and (2) 22 patients with preexisting at least mild pre-TAVI AR who now had ongoing postTAVI mild AR (18 had preexisting pre-TAVI mild AR that remained mild after TAVI, and four had preexisting pre-TAVI moderate AR that became mild AR after TAVI). The important post-TAVI AR group consisted of 18 patients: (1) six patients with new mild post-TAVI AR (i.e., there was no or trivial AR of the original aortic valve before TAVI, and mild AR developed after TAVI in the new aortic bioprosthesis, an

entity similar to acute AR) and (2) 12 patients with post-TAVI moderate or severe AR (Table 4). In those cases with at least mild AR after TAVI, it was identified as paravalvular (31 patients [78%]), valvular (one patient [2%]), or both (eight patients [20%]). After adjusting for pre-TAVI LV volumes and LVEF, patients with unimportant post-TAVI AR had lower end-diastolic volumes (mean, 95 6 39 vs 121 6 42 mL, respectively; P = .006), lower end-systolic volumes (mean, 41 6 28 vs 53 6 33 mL, respectively; P = .03), and lower LV mass indexes (mean, 114 6 33 vs 134 6 32 g/m2, respectively, P = .008) at follow-up compared with those with important post-TAVI AR. Functionally, analyses of changes in cardiac mechanics after TAVI revealed that patients with unimportant post-TAVI AR demonstrated a mild but statistically significant improvement in longitudinal deformation (GLS, global longitudinal systolic SR, and early diastolic SR), and normalization of apical rotation and net LV twist after the TAVI procedure. In contrast, patients with important post-TAVI AR showed no significant change in longitudinal deformation and in rotational mechanics.

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Table 4 LV remodeling after TAVI according to the presence of unimportant or important postprocedural AR Post-TAVI important AR† (n = 18)

Post-TAVI unimportant AR* (n = 46) Variable

Pre-TAVI

Post-TAVI

Mean % change

LV end-diastolic volume (mL) LV end-systolic volume (mL) LVEF (%) LV mass index (g/m2) LA volume index (mL/m2) RVSP (mm Hg) Longitudinal mechanics GLS (%) GLSR (sec
1) Early diastolic SR (sec
1) Circumferential mechanics GCS (%) GCSR (sec
1) Apical rotation ( ) Peak twist angle ( )

102 6 48 48 6 32 56 6 12 130 6 40 54 6 18 43 6 12

95 6 39 41 6 28 59 6 11 114 6 33 50 6 16 42 6 13

0 6 29
3 6 38 10 6 36
10 6 22
2 6 28 0 6 35

‡

P

‡

.19 .04 .07 <.001 .19 .40


12.7 6 4.3
14.1 6 4.2
0.60 6 0.21
0.69 6 0.23 0.52 6 0.23 0.60 6 0.22

25 6 64 24 6 53 29 6 55


27.6 6 8.1
28.3 6 7.8
1.75 6 0.64
1.80 6 0.58 9.6 6 5.4 6.1 6 6.4 14.0 6 6.9 11.3 6 5.6

9 6 41 12 6 46
36 6 119 0 6 75

Pre-TAVI

Post-TAVI

Mean % change‡

P‡

P§

105 6 34 45 6 24 59 6 8 133 6 38 47 6 13 43 6 14

121 6 42 53 6 33 58 6 11 134 6 32 44 6 16 47 6 14

20 6 42 27 6 64
1 6 17 3 6 20
6 6 29 18 6 40

.10 .21 .75 .96 .24 .36

.006 .03 .35 .008 .45 .13

11 6 37 17 6 47 17 6 51

.38 .31 .31 .63 .21 .29

.03
13.2 6 3.1
14.0 6 3.8 .003
0.63 6 0.17
0.69 6 0.21 .03 0.48 6 0.12 0.53 6 0.18 .53 .55 .02 .03


27.3 6 7.2
26.2 6 6.8
1.69 6 0.62
1.71 6 0.68 9.3 6 6.9 6.3 6 5.5 14.5 6 6.6 10.9 6 6.6

0 6 28 9 6 50
34 6 115 2 6 111

.53 .93 .18 .14

.38 .79 .93 .70

Data are expressed as mean 6 SD. LA, Left atrial; GCSR, global circumferential SR; GLSR, global longitudinal systolic SR; RVSP, right ventricular systolic pressure. *No or trace AR or preexisting mild AR. † New mild AR or any moderate or severe AR. ‡ Post-TAVI versus pre-TAVI. § Post-TAVI unimportant AR (no or residual mild AR) versus post-TAVI important AR (new mild or greater or residual moderate or greater AR).

Table 5 Reproducibility analysis (n = 10): ICC and coefficient of variation Interobserver variability

Intraobserver variability

Variable

ICC

Coefficient of variation (%)

ICC

Coefficient of variation (%)

GLS Global longitudinal SR Global circumferential strain Global circumferential SR Apical rotation Peak twist angle

0.90 0.93 0.98 0.96 0.95 0.95

7 6 3 5 11 12

0.95 0.89 0.98 0.98 0.96 0.92

6 6 3 3 8 14

ICC, Intraclass correlation coefficient.

Intraobserver and Interobserver Variability Analysis of intra- and interobserver variability demonstrated very good agreement between observations (Table 5).

DISCUSSION Our results demonstrate that patients with severe AS referred for TAVI have very abnormal LV myocardial mechanics, those with both normal and abnormal LV systolic function. In patients with AS and preserved LVEFs, there is an adaptive increase in net LV twist and maintenance of physiologic circumferential deformation, which contribute to preserve systolic function. In contrast, once patients with AS have developed LV systolic dysfunction, these compensatory mechanisms are exhausted, likely reflecting a more advanced stage of

disease. Importantly, we determined that TAVI consistently restores more physiologic multidirectional myocardial mechanics in both patients with preserved and those with impaired LVEFs. In the preserved-LVEF subgroup, circumferential deformation at the apical level is restored back to lower values. This is paralleled by normalization of apical rotation and net twist. In the impaired-LVEF subgroup, there is significant amelioration of the markedly abnormal longitudinal and circumferential strain and SR after TAVI. However, the presence of postprocedural paravalvular AR appears to limit LV structural and functional recovery. It is a plausible mechanism by which postTAVI AR adversely affects prognosis.

Myocardial Mechanics in AS In severe AS, long-standing pressure overload induces predictable changes in myocardial deformation. Initially, longitudinal strain decreases, mainly as a consequence of subendocardial ischemia in the longitudinally oriented subendocardial fibers.22 In patients with normal LVEFs, some investigators have recognized impaired myocardial deformation in the circumferential and radial directions,8,23,24 whereas others have suggested that increased circumferential strain at the mid-LV level serves as an early compensatory mechanism.25 Studies using myocardial tagging magnetic resonance24,26,27 and STE28 have demonstrated an adaptive increase in apical rotation and twist in patients with AS. In the present study, we have shown opposing longitudinal (decreased) and circumferential (maintained) mechanics in AS with preserved LVEFs. Net LV twist was also notably enhanced. These findings are compatible with a pattern of adaptive remodeling in response to pressure overload in which a compensatory increase in net twist and maintenance of circumferential deformation preserve systolic function. Net LV twist, a systolic wringing motion due to helical

1140 Poulin et al

orientation of the cardiac muscle fibers, increases in response to severe AS.6 Twisting of the LV cavity represents an energy-saving means of overcoming afterload mismatch and generating higher intracavitary pressure with minimal shortening of the muscle fibers.29 This adaptation of the myocardium to AS, illustrated in a previous study of patients (mean age, 71 years) undergoing open surgical AVR,28 is thus still possible in our cohort of patients, who were 10 years older with advanced valvular disease. We also showed that impaired LVEF is associated with the loss of these compensatory mechanisms. Myocardial Mechanics after TAVI The regression of hypertrophy and interstitial fibrosis and the reversibility of adaptive remodeling have important prognostic implications after AVR for AS.1 Candidates for TAVI are distinguished by their older age and more extensive comorbidities compared with patients who undergo conventional surgical AVR, raising the possibility of end-stage myocardial dysfunction.30 The favorable impact of TAVI on the regression of LV mass,31-34 and the improvement in systolic32,35 and diastolic31 function have already been documented. A number of studies have demonstrated an improvement in global or regional longitudinal myocardial function after TAVI.35-44 A greater magnitude of change in GLS after TAVI was associated with greater symptomatic improvement40 and a lower mortality rate.41 Our findings confirm the results of recent studies showing similar44 and even greater35,41 recovery of post-TAVI LV longitudinal systolic function in patients with pre-TAVI depressed LVEFs. However, there are key differences between the analyses performed in our study and those found in the literature. Other investigators have reported on the multiple directions of myocardial strain after TAVI, but these studies used a six-segment mid-LV model to assess circumferential and radial deformation.37,39,43,45 In addition, these studies consisted of smaller cohorts, focused mainly on patients with preserved LV function,37,39,43 and evaluated patients at a shorter follow-up time point (#3 months after TAVI). Recent work by Logstrup et al.41 concentrated on longitudinal strain and addressed the clinically relevant issue of relating the change in GLS to overall survival after TAVI. To the best of our knowledge, no previous study has comprehensively examined LV mechanics, including longitudinal, circumferential, and rotational deformation, beyond the subacute phase after TAVI. Our study characterizes the midterm impact of TAVI on multidirectional LV deformation, including rotation and twist, using a 16 segment LV model. We included a large series of patients with a wide spectrum of baseline LVEFs. Importantly, we report the changes in the preserved- and depressed-LVEF subgroups separately to highlight the compensatory role of some of the deformation mechanisms. We have shown that systolic longitudinal strain and SR and early diastolic longitudinal SR increased significantly after TAVI in the depressedLVEF subgroup. With regard to circumferential, rotational, and torsional mechanics, TAVI led to partial reversal of the abnormalities observed before the procedure, but in opposite directions in the preserved- and depressed-LVEF subgroups. Our results exemplify the need to take systolic function into account when evaluating myocardial mechanics. Finally, our study is distinct in its analysis of the detrimental effects of post-TAVI AR on LV remodeling and on longitudinal mechanics. The improvement we observed in myocardial mechanics was incomplete compared with the values obtained in normal control subjects. Progressive AS leads to subendocardial ischemia, myocyte degeneration, and interstitial fibrosis,30 which may even persist for several years after AVR.46 Therefore, reversibility in abnormal

Journal of the American Society of Echocardiography November 2014

myocardial mechanics in our cohort of patients with advanced disease, who are otherwise not candidates for conventional AVR, is an encouraging finding of our study. Our findings that lower LVEF and lower GLS are associated with myocardial recovery demonstrate the potential benefit of TAVI in patients with more advanced myocardial disease and support previous work.32,35,41,47 Finally, our study results complement the observations of other investigators who have demonstrated an amelioration in LV mass,48 some diastolic filling parameters,48,49 and left atrial function in patients after TAVI.49 Impact of Postprocedural AR Post-TAVI AR was common in our series and was predominantly mild in severity. Moderate, severe, and new mild post-TAVI AR appears to significantly affect cardiac remodeling. Despite the resolution of chronic pressure overload by TAVI, LV volumes and mass failed to favorably remodel in the group of patients with important post-TAVI AR. The sudden change from pressure to volume overload in a concentric hypertrophied ventricle5,50 thus does not appear to be well tolerated and prevents longitudinal myocardial recovery after TAVI. Our data suggest that even mild AR after TAVI affects LV recovery when it represents a new insult. These mechanistic observations generate plausible causal hypotheses linking post-TAVI AR to decreased responsiveness to therapy and suggest an important target for device and procedural improvements to avoid post-TAVI AR, which hampers the efficacy of this promising procedure.4 Limitations There were a number of limitations to this study. First, we had to exclude a significant proportion of potentially eligible patients. Selection bias is unlikely, however, because the excluded patients did not differ from the study population. Second, differences found in myocardial mechanics between our study cohort and the control group (mean age, 81 6 7 vs 66 6 6 years, respectively) may in part reflect age-related changes. Unfortunately, normal strain values for healthy patients aged >80 years were not available from our previous studies or from the current published literature. Third, inherent limitations with regard to a retrospective study also apply. For example, there was heterogeneity in the timing of the post-TAVI follow-up echocardiographic studies. However, the length of follow-up was similar in the preserved- and depressed-LVEF subgroups, and the follow-up time had no impact on the magnitude of change in GLS and on the incidence of post-TAVI important AR. Finally, quantitative assessment of the degree of AR was not routinely performed in these cases. Therefore, classification of the severity of AR was based on semiquantitative criteria.

CONCLUSIONS Our comprehensive analysis of cardiac mechanics in patients with severe AS indicates that the pattern of adaptive remodeling results in abnormal longitudinal, circumferential, and rotational deformation. At intermediate-term follow-up, TAVI leads to partial reversal of these processes, even in patients with depressed LVEFs. In fact, patients with lower LVEFs derive the most benefit in terms of longitudinal reverse remodeling. Postprocedural paravalvular AR was common and had an adverse impact on cardiac structure and function. Further studies are needed to understand how these changes in strain after TAVI affect patients’ clinical outcomes.

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Journal of the American Society of Echocardiography Volume 27 Number 11

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