Early hemodynamic and neurohormonal response after transcatheter aortic valve implantation

Valvular and Congenital Heart Disease

Early hemodynamic and neurohormonal response after transcatheter aortic valve implantation Mohammad A. Sherif, MD, a,b Mohamed Abdel-Wahab, MD, a,b Omar Awad, MD, b Volker Geist, MD, a Ghada El-Shahed, MD, b Reinhard Semmler, MD, c Mazen Tawfik, MD, b Ahmed A. Khattab, MD, b Doreen Richardt, MD, d Gert Richardt, MD, a and Ralph To ¨ lg, MD a Bad Segeberg, and Lübeck, Germany; and Cairo, Egypt

Background The conventional surgical aortic bioprostheses used for treatment of aortic stenosis (AS) are inherently stenotic in nature. The more favorable mechanical profile of the Medtronic CoreValve bioprosthesis may translate into a better hemodynamic and neurohormonal response. Patients and Methods The early hemodynamic and neurohormonal responses of 56 patients who underwent successful transcatheter aortic valve implantation (TAVI) using the Medtronic CoreValve bioprosthesis for severe symptomatic AS were compared with those of 36 patients who underwent surgical aortic valve replacement (SAVR) using tissue valves in the same period. Results At baseline, patients in the TAVI and SAVR group had comparable indexed aortic valve area (0.33 ± 0.1 vs 0.34 ± 0.1 cm2, respectively; P = .69) and mean transvalvular gradient (51.1 ± 16.5 vs 53.1 ± 14.3 mm Hg, respectively; P = .56). At 30-day follow-up, mean transvalvular gradient was lower in the TAVI group than in the SAVR group (10.3 ± 4 vs 13.1 ± 6.2 mm Hg, respectively; P = .015), and the indexed aortic valve area was larger in the TAVI group (1.0 ± 0.14 vs 0.93 ± 0.13 cm2/m2; P = .017). There was a trend toward a higher incidence of moderate patient-prosthesis mismatch in the surgical group compared with the TAVI group (30.5% vs 17.8%, respectively; P = .11). The overall incidence of prosthetic regurgitation (any degree) was higher in the TAVI group than in the SAVR group (85.7% vs 16.7%, respectively; P b .00001). The left ventricular mass index decreased after TAVI (175.1 ± 61.8 vs 165.6 ± 57.2 g/m2; P = .0003) and remained unchanged after SAVR (165.1 ± 50.6 vs 161 ± 64.8 g/m2; P = .81). Similarly, NT-ProBNP decreased after TAVI (3,479 ± 2,716 vs 2,533 ± 1,849 pg/mL; P = .033) and remained unchanged after SAVR (1,836 ± 2,779 vs 1,689 ± 1,533 pg/mL; P = .78). There was a modest correlation between natriuretic peptides and left ventricular mass index in the whole cohort (r = 0.4, P = .013). Conclusion

In patients with severe AS, TAVI resulted in lower transvalvular gradients and higher valve areas than SAVR. Such hemodynamic performance after TAVI may have contributed to early initiation of a reverse cardiac remodeling process and a decrease in natriuretic peptides. (Am Heart J 2010;160:862-9.)

Severe symptomatic aortic stenosis (AS) is a proven indication for surgical aortic valve replacement (SAVR).1 Certain patients, however, cannot take advantage of this therapeutic option due to comorbidities or other conditions rendering them at high risk for surgery.

From the aCardiology Department, Segeberger Kliniken GmbH, Bad Segeberg, Germany, b Cardiology Department, Ain-Shams University Hospitals, Cairo, Egypt, cCardiovascular Surgery Department, Segeberger Kliniken GmbH, Bad Segeberg, Germany, and d Cardiovascular Surgery Department, Schleswig-Holstein University Hospital, Lübeck, Germany. Submitted March 14, 2010; accepted July 13, 2010. Reprint requests: Mohammad A. Sherif, MD, Herz-Kreislauf-Zentrum, Segeberger Kliniken GmbH, Am Kurpark 1, 23795 Bad Segeberg, Germany. E-mail: [email protected] 0002-8703/$ - see front matter © 2010, Mosby, Inc. All rights reserved. doi:10.1016/j.ahj.2010.07.017

Transcatheter aortic valve implantation (TAVI) has emerged as an alternative treatment for severe AS in patients considered at high surgical risk with promising early and midterm results.2 BNP and its N-terminal fragment (NT-ProBNP) are neurohormones synthesized and secreted mainly from ventricular myocardium. Stimulus for their release is an increase in ventricular wall stress.3 The causes of natriuretic peptide elevation in patients with AS and how SAVR affects their levels were the focus of many studies.4-7 Although currently available prostheses used for TAVI have favorable mechanical profiles, little is known about the effect of TAVI on the natriuretic peptides levels. Therefore, we sought to shed light on the hemodynamic and neurohormonal performance of the Medtronic CoreValve bioprosthesis in comparison to surgically implanted bioprostheses for the treatment of severe AS.

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Methods Study design and patients Between September 2007 and May 2009, 56 consecutive patients with severe symptomatic AS (aortic valve area [AVA] b1 cm2 or body surface area indexed AVA [iAVA] b0.6 cm2/m2) underwent successful TAVI using the Medtronic CoreValve (Medtronic CoreValve, Irvine, CA) bioprosthesis via the transfemoral route. Clinical and anatomical selection criteria and device size selection were in line with the published investigational study for the third-generation (18F) CoreValve device.8,9 Description of the device and technical aspects of the procedure have been previously published.8,10 Selection of the prosthetic valve size (26-mm inflow device for 20- to 23-mm annulus or 29-mm inflow device for 24- to 27-mm annulus) was based on the measurements of the diameter of the aortic valve annulus obtained by transesophageal echocardiography (TEE). To control for the results after TAVI, we evaluated 36 patients with severe symptomatic AS who underwent successful SAVR (±coronary artery bypass surgery) in the same period. All procedures were performed by 1 experienced operator in a standard manner using aortic valve bioprostheses. The choice of the prosthesis was left to the operator's discretion. Three types of aortic valve bioprosthesis were used: the Hancock II porcine (Medtronic, Minneapolis, MN) stented valve, The Medtronic Mosaic (Medtronic) stented bioprosthesis, and the Sorin Pericarbon Freedom Stentless aortic valve (Sorin Biomedica Cardio S.p.A., Saluggia, Italy).

Transoesophageal and transthoracic echocardiography A standard transthoracic echocardiography was performed preoperatively and at 30-day follow-up. Two independent echocardiographers reviewed the results. Velocity-Time integral (cm), peak aortic velocity (cm/s), peak instantaneous gradient (mm Hg) (by using the modified Bernoulli equation, dP = 4v2), and mean transvalvular gradient (mm Hg) were measured. The AVA was estimated using the continuity equation.11 Color flow Doppler and continuous wave Doppler were used to quantify aortic regurgitation (AR) and mitral regurgitation (MR).1 Left ventricular mass (LVM; g) was estimated using the formula proposed by Devereux et al12: 1.04 ({left ventricular end-diastolic diameter + posterior wall diameter + interventricular septal diameter}3 − {left ventricular end-diastolic diameter}3) − 14 and was normalized to body surface area (LVM index [LVMI], g/m2). The diameters of the aortic valve annulus, ascending aorta, and left ventricular (LV) outflow tract were obtained using TEE. Postoperatively, the severity of AR was graded as I for mild, II for moderate, III for moderate to severe, and IV for severe.13

Natriuretic peptides assay Blood samples were drawn preprocedurally and at 30-day postprocedure. The NT-ProBNP was analyzed using a commercially available kit (The Elecsys proBNP, Roche Diagnostics, Mannheim, Germany). Cutoff values for NTProBNP were defined as follows: b125 pg/mL, heart failure ruled out; 125 to 342 pg/mL, heart failure possible; N342 pg/mL, heart failure present.

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Table I. Baseline clinical characteristics for 92 patients who underwent aortic valve replacement according to type of intervention

Age, mean ± SD, y Gender, male EuroSCORE Logistic, mean ± SD, % Standard, mean ± SD Length, mean ± SD, cm Weight, mean ± SD, kg BSA, mean ± SD, m2 BMI, mean ± SD, kg/m2 Sinus rhythm AF Pacemaker Diabetes mellitus Hypertension Previous PCI Previous CABG Previous stroke Previous myocardial infarction Peripheral vascular disease Carotid artery disease Coronary artery disease No Yes 1-Vessel 2-Vessel 3-Vessel NYHA mean grade, mean ± SD

TAVI (n = 56)

SAVR (n = 36)

P

80.5 ± 7.5 51.7

71.9 ± 7.7 58.3

b0001 .57

22.6 ± 11.3 11.1 ± 2.3 170 ± 8.2 76.6 ± 14.6 1.9 ± 0.21 26.4 ± 4.5

7.6 ± 5.3 6.7 ± 2.4 172.8 ± 9.7 83.3 ± 14.7 2 ± 0.22 27.7 ± 3.8

b.001 b.001 .14 .034 .03 .199

78.5 12.5 9 26.8 92.8 60.7 23.2 12.5 28.5

88.9 11.1 0 27.7 72.2 75 5.5 11 11

.18 .77 .06 .91 b.01 .16 .028 .77 .06

19.6

5.5

.07

17.8

22.2

.6

21.4 78.6 19.6 28.5 30.5 3.35 ± 0.55

44.4 55.6 19.4 16.6 19.6 2.77 ± 0.68

.02 .02 .9 .19 .28 b.001

Values are expressed as percentage unless otherwise indicated. BSA, Body surface area; BMI, body mass index; AF, atrial fibrillation; PCI, percutaneous coronary intervention; CABG, coronary artery bypass surgery.

Definitions and data collection Baseline clinical, echocardiographic, and procedural characteristics were recorded for all enrolled patients. Echocardiographic 1-month follow-up was obtained in 100% of the patients. Procedural success was defined as implantation of a functioning prosthetic valve within the aortic annulus and without intraprocedural mortality. Patient-Prosthesis mismatch was defined as mild (0.9 b iAVA b 1 cm2/m2), moderate (0.6 b iAVA b 0.9 cm2/m2), and severe (iAVA b 0.6 cm2/m2), as proposed by Rahimtoola.14

Statistical analysis Continuous variables were summarized as mean ± SD and compared by use of Student t test. Categorical variables were displayed as percentages and compared by use of Fisher exact test and χ2 test. The differences were measured before and after the procedures and compared intraindividually and between groups. A 2-sided value of P b .05 was considered statistically significant. All the factors that might have influence on the natriuretic peptides levels were pooled from the whole cohort, and Pearson correlation rho (r) coefficient was calculated to examine the relation between natriuretic peptides levels and these variables.

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Table II. Baseline hemodynamic and neurohormonal characteristics for 92 patients who underwent aortic valve replacement according to type of intervention

EF, % Peak transvalvular gradient, mm Hg Mean transvalvular gradient, mm Hg AVA, cm2 iAVA, cm2/m2 Systolic PAP, mm Hg LV wall thickness Septum, mm Posterior wall, mm LVEDD, mm LVMI, g/m2 Annulus diameter by TEE, mm Aortic regurgitation mean grade 0, % I, % II, % III, % IV, % MR mean grade Laboratory NT-ProBNP, pg/mL

TAVI (n = 56)

SAVR (n = 36)

P

47.4 ± 13.2 82.6 ± 21.25

58.3 ± 8.5 88 ± 19.3

b.001 .23

51.1 ± 16.5

53.1 ± 14.3

.56

0.63 ± 0.18 0.33 ± 0.1 50.7 ± 14.7

0.68 ± 0.21 0.34 ± 0.1 44.2 ± 11.8

.18 .69 .033

14.3 ± 3.1 13.7 ± 2.1 53.1 ± 10.2 175.1 ± 61.8 22.3 ± 1.8

14.1 ± 2.5 14.3.1 ± 3 50.7 ± 9.2 165.1 ± 50.6 22.4 ± 2

.83 .26 .36 .52 .43

0.9 ± 0.68

0.86 ± 1

.86

26.8 59 12.5 1.7 0 1.14 ± 0.64

44.4 36.1 13.9 0 5.5 0.58 ± 0.6

.08 .03 .8 .4 .07 b.001

3479 ± 2716

1836 ± 2779

b.001

Values are expressed as means ± SD unless otherwise indicated.

The authors are solely responsible for the design and conduct of this study, all study analyses, and the drafting and editing of the paper and its final contents. No extramural funding was used to support this work.

Results Baseline hemodynamic and neurohormonal characteristics Baseline clinical, hemodynamic, and neurohormonal characteristics are shown in Tables I and II. The TAVI patients, according to patient selection, had a higher mean logistic EuroSCORE15 (22.6% vs 6.7%; P b .001), were 8 years older, and had worse New York Heart Association (NYHA) class (P b .001) compared with SAVR patients. At baseline, patients in the TAVI and SAVR groups had comparable iAVA (0.33 ± 0.1 vs 0.34 ± 0.1 cm2/m2, respectively; P = .69) and mean transvalvular gradient (51.1 ± 16.5 vs 53.1 ± 14.3 mm Hg, respectively; P = .56). Twenty-three patients in the TAVI group underwent percutaneous coronary intervention within 1 week before valve implantation. Patients in the TAVI group had lower baseline mean ejection fraction (EF; P b .001), higher systolic pulmonary artery pressure (PAP; P = .033), and higher mean grade of MR (P b .0001). The TAVI patients had higher values of NT-ProBNP (P b .001). At baseline, only 2% of patients in the TAVI group and 5% of patients in the SAVR group had normal NT-ProBNP values (P = .42).

Table III. Procedural characteristics for 92 patients who underwent aortic valve replacement according to type of intervention No. of patients TAVI Transfemoral access Right Left Balloon diameter (mean ± SD) No. of balloon inflations before implantation (mean ± SD) Size 29-mm inflow 26-mm inflow Postimplantation dilatation Periprocedural mortality Aortic regurgitation (angiographically): 0 I II III IV SAVR CABG + AVR Type of valve Freedom Sorin Hancock Med (stented) Mosaic Med (stented) Size of valve 21 mm 23 mm 25 mm 27 mm 29 mm Periprocedural mortality

56 50 6 22.4 ± 1.6 1.3 ± 0.7

25 31 8 1 7 35 13 1 0 18 8 11 17 2 8 14 11 1 1

CABG, Coronary artery bypass graft; AVR, aortic valve replacement.

Procedure-related outcome Procedural details are shown in Table III. About 45% of the TAVI patients received a 29-mm valve, and 55% received a 26-mm valve. Postimplantation dilatation was done in 8 cases in the TAVI group. The 25- and 27-mm valves were the most commonly implanted in the SAVR group. Half of the SAVR patients underwent coronary artery bypass surgery. The overall procedural success rates were 98.2% and 97.25% in the TAVI and SAVR groups, respectively (P = .7). Periprocedural mortality was reported in 1 patient in each group (P = .66). Importantly, the degree of angiographic AR reported in Table III represents an assessment after valve implantation or after postimplant dilatation; all patients in the TAVI group, except one, had grade 2 or less AR at the end of the procedure (Table III). Hemodynamic and neurohormonal response at 1-month follow-up Doppler echocardiography and neurohormonal data at 1 month for both groups are shown in Tables IV and V. There was a lower mean transvalvular gradient in the

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Table IV. Hemodynamic and neurohormonal characteristics for patients who underwent TAVI at 30-day follow-up in comparison to baseline Pre-TAVI

Post- TAVI

EF, % 47.4 ± 13.2 49.4 ± 11 Peak transvalvular 82.6 ± 21.25 18.5 ± 7.2 gradient, mm Hg Mean transvalvular 51.1 ± 16.5 10.3 ± 4.4 gradient, mm Hg AVA, cm2 0.63 ± 0.18 1.9 ± 0.16 iAVA, cm2/m2 0.33 ± 0.1 1 ± 0.14 Systolic PAP, mm Hg 50.7 ± 14.7 44.3 ± 8.26 LV -wall thickness Septum, mm 14.3 ± 3.1 14.1 ± 2.8 Posterior wall, mm 13.7 ± 2.1 13.7 ± 1.97 LVEDD, mm 53.1 ± 10.2 50.45 ± 8.86 LVMI, g/m2 175.1 ± 61.8 165.6 ± 57.2 Aortic regurgitation mean grade 0.9 ± 0.68 1.1 ± 0.66 0, % 26.8 14.3 I, % 59 59 II, % 12.5 21.4 III, % 1.7 1.7 IV, % 0 0 MR mean grade 1.14 ± 0.64 1.47 ± 0.72 NYHA mean grade 3.35 ± 0.55 1.2 ± 0.66 NT-ProBNP, pg/mL 3479 ± 2716 2533 ± 1849

Figure 1

P .023 b.001 b.001 b.001 b.001 .04 .72 .98 b.001 .001 .09 .09 1 .26 1 .013 b.001 .033

Incidence and degree of aortic regurgitation (0-IV) at 30-day followup in the TAVI group compared with the SAVR group using echocardiography.

Table VI. Changes of hemodynamic and neurohormonal parameters for patients who underwent TAVI at 30-day follow-up in comparison to baseline according to EF Pre-TAVI

Values are expressed as means ± SD unless otherwise indicated.

Table V. Hemodynamic and neurohormonal characteristics for patients who underwent SAVR at 30-day follow-up in comparison to baseline

EF, % Peak transvalvular gradient, mm Hg Mean transvalvular gradient, mm Hg AVA, cm2 iAVA, cm2/m2 Systolic PAP, mm Hg LV wall thickness Septum, mm Posterior wall, mm LVEDD, mm LVMI, g/m2 Aortic regurgitation 0, % I, % II, % III, % IV, % MR mean grade NYHA mean grade NT-ProBNP, pg/mL

Pre-SAVR

Post-SAVR

P

58.3 ± 8.5 88 ± 19.3

55.7 ± 7.7 23.45 ± 10.4

.18 b.001

53.1 ± 14.3

13.1 ± 6.2

b.001

0.68 ± 0.21 0.34 ± 0.1 44.2 ± 11.8

1.85 ± 0.16 0.93 ± 0.13 39.1 ± 10.5

b.001 b.001 .08

14.1 ± 2.5 14.3.1 ± 3 50.7 ± 9.2 165.1 ± 50.6 0.86 ± 1 44.4 36.1 13.9 0 5.5 0.58 ± 0.6 2.77 ± 0.68 1836 ± 2779

13.9 ± 1.8 14.1 ± 2.7 48 ± 6.6 161 ± 64.8 0.12 ± 0.4 83.3 5.5 2.7 0 0 0.7 ± 0.68 0.9 ± 0.45 1689 ± 1533

.7 .98 .28 .81 b.001 .001 .002 .09 .14 .46 b.001 .78

Values are expressed as means ± SD unless otherwise indicated.

TAVI group (10.3 ± 4 mm Hg) than in the SAVR group (13.1 ± 6.2 mm Hg) (P = .015) and a larger iAVA in the TAVI group (1.0 ± 0.14 vs 0.93 ± 0.13 cm2/m2; P = .017). Severe patient-prosthesis mismatch (PPM) was not

EF b40% (n. 16) Mean PG, mm Hg AVA, cm2 EF, % LVEDD, mm LVMI, g/m2 ProBNP, pg/mL EF ≥ 40 (n. 39) Mean PG, mm Hg AVA, cm2 EF, % LVEDD, mm LVMI, g/m2 ProBNP, pg/mL

Post-TAVI

P

45.7 0.65 31.5 59.7 189 3564

± 11 ± 0.19 ± 5.6 ± 7.1 ± 31.5 ± 2344

9.7 1.9 39 55.5 170 4333

± 5.2 ± 0.18 ± 8.6 ±6 ± 28.7 ± 1766

b.001 b.001 b.001 .001 .002 .38

54 0.6 53.3 50.2 169.7 2761

± ± ± ± ± ±

10.3 1.9 53.5 48 158 1855

± ± ± ± ± ±

b.001 b.001 .8 .004 .014 .054

17.7 0.18 10 10.3 69.9 2181

3.8 .014 9 9 63 1093

Values are expressed as means ± SD. PG, Pressure gradient.

reported in any group, but moderate PPM was present in 11 cases (30.5%) in the surgical group and 10 cases in the TAVI group (17.8%) (P = .11). The overall incidence of prosthetic regurgitation was higher in the TAVI group (85.7%) than in the SAVR group (16.7%), (P b .001). Consequently, the mean grade of AR was higher in the TAVI group (1.1 ± 0.66 vs 0.12 ± 0.4; P b .0001) (Figure 1). Ejection fraction showed some improvement in the TAVI group (47.4% ± 13.2% vs 49.4% ± 11%; P = .023), whereas it remained stable in the SAVR group (58.3% ± 8.5% vs 55.7% ± 7.7%, P = .18) (Tables IV and V). The systolic PAP decreased in both groups, but the decrease was statistically significant only in the TAVI group (Tables IV and V). The overall mean grade of MR was higher in the TAVI group as compared with the SAVR group (1.47 ± 0.72 vs 0.7 ± 0.68, respectively; P b .0001). Noteworthy, the mean degree of MR significantly increased after TAVI,

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Figure 2

Changes in NYHA class at 30-day follow-up after TAVI (left panel) in comparison to SAVR (right panel).

whereas it remained unchanged after SAVR. The LVMI and LV end-diastolic diameter (LVEDD) decreased after TAVI and remained unchanged after SAVR (Tables IV and V). The NT-ProBNP modestly decreased in the TAVI group (3,479 ± 2,716 vs 2,533 ± 1,849 pg/mL; P = .033) (Table V). On the other hand, there were no changes in NT-ProBNP after SAVR (Table VI). None of the patients in the SAVR group had a normal postoperative NTProBNP value, and only 5% of patients in the TAVI group had normal values at 1 month. Noteworthy, a remarkable relief of symptoms was observed in both groups with a decline from a mean NYHA functional class of 3.35 ± 0.55 before to 1.2 ± 0.66 in the TAVI group and of 2.77 ± 0.68 to 0.9 ± 0.45 in the SAVR group (all P b .00001) (Figure 2).

Hemodynamic and neurohormonal response in the TAVI group according to EF In patients with moderately to severely impaired EF, there was a notable improvement in the systolic function associated with a decrease in LVEDD and LVMI, but the levels of NT-ProBNP did not decrease (Table VI). On the other hand, in patients with normal or mildly impaired EF, there was no improvement in EF after TAVI, but both LVEDD and LVMI decreased, associated with a decrease in NT-ProBNP levels (Table VI). The relation between natriuretic peptides and hemodynamic variables A poor correlation was found between NT-ProBNP and mean PG (r = 0.15, P = .08) (Figure 3) even after adjustment for age, sex, PAP, renal impairment, and NYHA class (r = 0.25, P = .005). There was no correlation between NT-ProBNP and AVA (r = −0.18, P = .15). We also found a poor negative correlation between NT-ProBNP and EF (r = −0.22, P = .012) (Figure 4). A modest positive correlation between

Figure 3

Relationship between mean pressure gradient (mm Hg) (x-axis) and NT-ProBNP (pg/mL) (y-axis), r = 0.15, P = .08.

NT-ProBNP and LVMI was found in the whole cohort (r = 0.4, P = .013) (Figure 5) that tended to be stronger after adjustment for age, sex, PAP, EF, renal impairment, and NYHA class (r = 0.55, P = .001).

Discussion The short-term hemodynamic and neurohormonal results of this study demonstrate the efficacy of TAVI using the Medtronic CoreValve bioprosthesis in managing high surgical risk patients who have severe calcific AS.

Hemodynamic performance after TAVI Transcatheter aortic valve implantation was associated with excellent hemodynamic results, with a mean

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Figure 4

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Figure 5

Relationship between EF (%) (x-axis) and NT-ProBNP (pg/mL) (y-axis), r = −0.22, P = .01.

Relationship between LVMI (x-axis) and NT-ProBNP (y-axis), r = 0.4, P = .013.

residual transvalvular gradient of 10 mm Hg and a mean AVA of 1.9 cm2. Several studies have reported similar hemodynamic results after TAVI, with transvalvular gradients b11 mm Hg and AVAs N1.5 cm2.8,16 The hemodynamic performance of the surgically implanted aortic bioprostheses goes along with previous studies.17 Our results agree in part with Clavel et al,18 who found that TAVI using Edwards SAPIEN valve (Edwards Lifesciences, Inc, Irvine, CA) provided superior hemodynamic performance compared with the surgical bioprostheses in terms of transvalvular gradient. The lower gradients and larger AVA after TAVI may be explained by the fact that—at least in our study—most of the used surgical bioprostheses are stented valves, whereas the transcatheter valves are functionally similar to the stentless surgical valves because of the low profile of their stent frame. The present study shows that such a reduction of the gradient may result in an early improvement of LV function in patients with impaired systolic function before TAVI. On the other hand, we found that TAVI did not prevent the occurrence of PPM in our study population. Our findings agree with Jilaihawi et al,19 who reported PPM after TAVI using CoreValve, but in a higher incidence than we reported (32% vs 17.8%) and related this to the suboptimal position of the device after implantation. Transcatheter aortic valve implantation using the Medtronic CoreValve bioprosthesis has been associated with a high rate of paravalvular prosthetic regurgitation, usually mild, with an incidence ranging from 66% to 100%,16,20 which is much higher than that observed after SAVR.21 In our study, the occurrence of any degree of AR was more common after TAVI (82.1%) than after SAVR

(8.2%). However, the degree of residual AR was mild in most (72%) TAVI patients, with no cases of severe AR. Importantly, these mild paravalvular regurgitations appear to be clinically insignificant. Rallidis et al21 showed that trivial or mild paraprosthetic regurgitation occurring after SAVR did not have any significant impact on clinical outcomes at 5-year follow-up. It has been noted that 69% to 82% of patients undergoing SAVR and preexisting MR have an improvement in the degree of MR after the operation.22 We found that the mean MR severity did not change after SAVR. On the other hand, the mean MR severity increased after TAVI. It is postulated that the impact of the ventricular end of the CoreValve frame on the motion of the anterior mitral leaflet may induce or adversely affect MR.23

Reverse cardiac remodeling and neurohormonal response after TAVI Synthesis and release of natriuretic peptides in AS seem to result from a complex interplay between pressure overload, ventricular hypertrophy, increase in LV wall stress, and other still unknown factors. Some studies showed that, in patients with AS, BNP and NT-ProBNP elevations correlate with AVA,7 transvalvular gradient,24 extent of LV hypertrophy,7 and functional status.6 On the other hand, Liska et al25 found that pulmonary hypertension is the most important independent predictor of natriuretic peptide elevation in patients with AS irrespective of the severity per se. Moreover, the effect of SAVR on the levels of natriuretic peptides remains controversial and time dependent.5,26 Qi et al5 found no significant decrease in NT-ProBNP 4 and 12 months after SAVR.

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Similarly, at 30-day follow-up, we observed no significant changes in natriuretic peptides values after SAVR, whereas we found a decrease in the levels of NT-ProBNP after TAVI. This early decrease in the levels of natriuretic peptides can be explained by a better reduction in the pressure overload by TAVI, which results in a decrease in the LV dimensions and LVMI, probably promoting an earlier reverse cardiac remodeling process. Interestingly, reduction of NT-ProBNP after TAVI was restricted to those patients with mildly depressed or preserved systolic LV function (EF ≥40%) despite the fact that those patients with poor systolic function had a marked decrease in LVEDD and LVMI, as well as a significant improvement in their ejection fraction.

Study limitations The differences observed in valve gradients and valve areas for the TAVI and SAVR groups are statistically significant, but we cannot definitely relate these small differences to the changes observed in LVMI and natriuretic peptide levels. Furthermore, the follow-up period was relatively short, which may have biased the results against the SAVR group because a significant part of the early postoperative period would be spent in the recovery phase, and future studies with more long-term data are certainly needed to assess the durability of the acute hemodynamic and neurohormonal results. Finally, the nonrandomized nature of the study may also be criticized.

Conclusion In patients with severe AS, TAVI resulted in lower transvalvular gradients and higher valve areas than SAVR. Such hemodynamic performance after TAVI may have contributed to an earlier initiation of the reverse cardiac remodeling process and a decrease in natriuretic peptides.

Acknowledgement Our thanks to the clinical research group at the Heart and Vascular Centre, Segeberger Kliniken GmbH, especially Mrs Daniela Schuermann-Kuchenbrandt and Mr Guido Kassner.

References 1. Vahanian A, Baumgartner H, Bax J, et al. Guidelines on the management of valvular heart disease: The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology. Eur Heart J 2007;28:230-68. 2. Patel JH, Mathew ST, Hennebry TA. Transcatheter aortic valve replacement: a potential option for the nonsurgical patient. Clin Cardiol 2009;32:296-301. 3. Ikeda T, Matsuda K, Itoh H, et al. Plasma levels of brain and atrial natriuretic peptides elevate in proportion to left ventricular end-systolic wall stress in patients with aortic stenosis. Am Heart J 1997;133:307-14.

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4. Weber M, Hausen M, Arnold R, et al. Prognostic value of N-terminal pro-B-type natriuretic peptide for conservatively and surgically treated patients with aortic valve stenosis. Heart 2006;92:1639-44. 5. Qi W, Mathisen P, Kjekshus J, et al. The effect of aortic valve replacement on N-terminal natriuretic propeptides in patients with aortic stenosis. Clin Cardiol 2002;25:174-80. 6. Gerber IL, Stewart RA, Legget ME, et al. Increased plasma natriuretic peptide levels reflect symptom onset in aortic stenosis. Circulation 2003;107:1884-90. 7. Qi W, Mathisen P, Kjekshus J, et al. Natriuretic peptides in patients with aortic stenosis. Am Heart J 2001;142:725-32. 8. Grube E, Schuler G, Buellesfeld L, et al. Percutaneous aortic valve replacement for severe aortic stenosis in high-risk patients using the second- and current third-generation self-expanding CoreValve prosthesis: device success and 30-day clinical outcome. J Am Coll Cardiol 2007;50:69-76. 9. Piazza N, Otten A, Schultz C, et al. Adherence to patient selection criteria in patients undergoing transcatheter aortic valve implantation with the 18F CoreValve ReValving System. Heart 2010;96:19-26. 10. de Jaegere P, van Dijk LC, Laborde JC, et al. True percutaneous implantation of the CoreValve aortic valve prosthesis by the combined use of ultrasound guided vascular access, Prostar(R) XL and the TandemHeart(R). EuroIntervention 2007;2:500-5. 11. Otto CM, Pearlman AS, Comess KA, et al. Determination of the stenotic aortic valve area in adults using Doppler echocardiography. J Am Coll Cardiol 1986;7:509-17. 12. Devereux RB, Alonso DR, Lutas EM, et al. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986;57:450-8. 13. Zoghbi WA, Enriquez-Sarano M, Foster E, et al. Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 2003;16:777-802. 14. Rahimtoola SH. Valve prosthesis-patient mismatch: an update. J Heart Valve Dis 1998;7:207-10. 15. Nashef SA, Roques F, Michel P, et al. European System for Cardiac Operative Risk Evaluation (EuroSCORE). Eur J Cardiothorac Surg 1999;16:9-13. 16. De Jaegere PP, Piazza N, Galema TW, et al. Early echocardiographic evaluation following percutaneous implantation with the self-expanding CoreValve ReValving System aortic valve bioprosthesis. EuroIntervention 2008;4:351-7. 17. Gegouskov VA, Eckstein FS, Kipfer B, et al. The Sorin pericardial bioprosthesis—a stentless aortic valve with very good hemodynamic performance. Swiss Surg 2003;9:247-52. 18. Clavel MA, Webb JG, Pibarot P, et al. Comparison of the hemodynamic performance of percutaneous and surgical bioprostheses for the treatment of severe aortic stenosis. J Am Coll Cardiol 2009;53:1883-91. 19. Rahimtoola SH. Is severe valve prosthesis-patient mismatch (VP-PM) associated with a higher mortality? Eur J Cardiothorac Surg 2006; 30:1. 20. Piazza N, Grube E, Gerckens U, et al. Procedural and 30-day outcomes following transcatheter aortic valve implantation using the third generation (18 Fr) CoreValve ReValving System: results from the multicentre, expanded evaluation registry 1-year following CE mark approval. EuroIntervention 2008;4:242-9. 21. Rallidis LS, Moyssakis IE, Ikonomidis I, et al. Natural history of early aortic paraprosthetic regurgitation: a five-year follow-up. Am Heart J 1999;138:351-7. 22. Caballero-Borrego J, Gomez-Doblas JJ, Cabrera-Bueno F, et al. Incidence, associated factors and evolution of non-severe functional

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