Prosthesis-patient mismatch (PPM) occurs when the effective orifice area (EOA) of a normally functioning prosthetic valve is too small in relation to the patient’s body size. Transcatheter aortic valve replacement (TAVR) has been shown to have less PPM than surgical aortic valve replacement (SAVR).1 Severe PPM occurs after 2% to 20% of SAVRs,1-3 and increased perioperative and overall mortality have been well described.1,3-5 Recent data from the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) registry showed that severe TAVR PPM, defined as an indexed EOA (iEOA) < 0.65 cm2/m2 (Table 1), occurred in 12.1% of patients and was associated with increased mortality (hazard ratio [HR], 1.19; 95% confidence interval, 1.09–1.310; P < .001).6 However, in the randomized TAVR trials, there has been no significant mortality signal with TAVR PPM for the balloon-expandable (BE) Sapien valve (Edwards Lifesciences),1 whereas TAVR PPM with the self-expanding (SE) CoreValve (Medtronic) and SAVR PPM were both associated with increased mortality.1,7 Which patients are at risk for PPM? Is there really a difference in outcomes of TAVR PPM compared with SAVR PPM? Why is there a difference between the “real-world” STS/ACC TVT registry and randomized trials? Is there increased mortality associated with PPM in TAVR? Is PPM different for different valve types? This article attempts to answer some of these questions.


Given the definitions of PPM, the most obvious characteristics that could be associated with a higher incidence of PPM include factors associated with small aortic annular dimensions that would dictate the size of the prosthesis, inherent valve design features that dictate the EOA for any given annular size, and higher body mass index (BMI). Predictors of PPM in one meta-analysis that included both SAVR and TAVR patients were older age, female sex, hypertension, diabetes, renal failure, larger body surface area, higher BMI, and the use of a bioprosthesis (vs mechanical valve).5 The impact of PPM on mortality appears to be more important in patients aged < 70 years and/or those undergoing concomitant coronary artery bypass grafting and less pronounced in patients with a higher BMI (> 28 kg/m2) compared to those with a lower BMI. The latter finding supports the use of different iEOA criteria depending on body mass (Table 1). TAVR studies have confirmed that predictors of PPM are younger age, non-white/Hispanic ethnicity, and small prosthesis (< 23 mm diameter).6,8


Similar to common practice with surgical prostheses, a complete assessment of prosthetic valve function requires an understanding of the construct and appearance of each transcatheter heart valve (THV) and the normal function of each type and size of implanted valve.9,10 Normative expected gradient, valve area, and Doppler index of commercially available THVs by valve type and size have been reported11 based on echocardiographic core lab–assessed hemodynamic data from early randomized trials and registries.4,12,13 The precise methodology for assessing post-TAVR valve area used by the different echocardiographic core labs was delineated for both BE and SE valves and was very similar.11 The ideal measurement protocol uses the outer-to-outer border of the stented valve at its ventricular tip as the measure of left ventricular outflow tract (LVOT), which is consistent with the methodology used for prosthetic surgical valves. Pulsed-wave Doppler is then performed by placing the sample volume just apical to the THV stent, and the stroke volume across the valve is calculated.

There are multiple pitfalls to this measurement protocol, such as (1) obtaining on-axis sagittal plane images of a circular or elliptical stent frame (ie, bisecting the largest dimension in systole); (2) ill-defined LVOT diameter in the setting of a THV positioned below the annulus (ie, with the stent frame protruding into the left ventricular outflow space) that might cause overestimation of stroke volume if the native anatomy is used to calculate the valve area; and (3) inaccurate positioning of the pulsed-wave Doppler sample volume (ie, either too apical or within the stent frame). The echocardiographic core labs in various randomized trials offer the “most accurate” data on expected valve areas and, thus, should provide the best “expected” valve areas for each valve type and size. Unlike a surgical valve with a fixed size and sewing ring, transcatheter valves are sized by the native annular area,14,15 with the expectation of expanding the valve to fit securely into the annulus. Thus, the normative data reported by Hahn et al11 were the first to report valve area by quintiles of annular dimensions from CT-based measurements of native annular area and perimeter.

The measurement of EOA required for determination of PPM could theoretically be calculated using a number of different methods:

  1. Use of only echocardiographic measurement of gradients and valve area
  2. Use of only catheterization measurements of gradients and valve area (not typically performed after TAVR or SAVR)
  3. Assumed LVOT diameter for echocardiographic calculations using the THV size or the baseline annular dimension pre-TAVR
  4. Use of the predicted EOA from the normative echocardiographic data manuscript for THV size or annular size.

Differences in between-study outcomes would depend not only on the methods of calculating EOA but also the inherent variability of the measurements. Site-reported data from the STS/ACC TVT database use method 1, which likely introduced significant measurement variability. Reduced measurement variability by echocardiographic core lab assessment could explain why no randomized TAVR study has shown a mortality signal for PPM. To reduce the variability of nonechocardiographic core lab–assessed calculations, the use of predicted EOA (method 4) could provide another method for evaluating PPM prevalence and outcomes. In fact, the reported incidence of SAVR PPM from the STS database is also based on predicted EOA.2

The prevalence and impact of PPM may be overestimated after TAVR because of low flow state (ie, pseudo-PPM), pressure recovery, and obesity.16 As noted, PPM occurs when the EOA of a normally functioning prosthetic valve is too small in relation to the patient’s body size; however, the flow requirements for muscle are not the same as for fat. Thus, using different indexed cutoffs for grading PPM severity has been advocated by the Valve Academic Research Consortium-2 consensus document.17 Many studies have failed to use different cutoffs for PPM severity and, thus, not only overestimated the prevalence of the PPM but may have underestimated the impact of PPM in patients with normal body weight.


Previous studies have suggested that PPM is more prevalent in SAVR compared with TAVR (Table 2).16 This makes anatomic sense when considering that a stented THV will expand to the size of the native annulus and has a thinner stent frame than a surgical sewing ring. However, in the most recent PARTNER 3 trial,18 larger SAVR valves were used and more aortic root enlargements were performed compared to earlier trials, which likely resulted in smaller TAVR EOAs compared with SAVR EOAs (1.7 ± 0.02 cm2 vs 1.8 ± 0.02 cm2). Despite higher TAVR ejection fraction (84.2% ± 0.71% vs 76.6% ± 0.81%) and stroke volume index (41.9 ± 0.35 mL/m2 vs 38.0 ± 0.40 mL/m2), PPM was still more severe for SAVR compared with TAVR (6.3% vs 4.3%). This counterintuitive finding suggests that SAVR may be associated with low-flow pseudo-PPM, and the clinical impact of this entity is unknown. In the low-risk Evolut trial, severe PPM occurred at 12 months in 1.8% of patients in the TAVR group and in 8.2% of patients in the surgery group.19

Multiple studies and meta-analyses have shown an increased perioperative and overall mortality in the SAVR population with severe PPM.1,3-5 In addition, PPM is associated with slower and less complete regression of left ventricular hypertrophy and pulmonary hypertension, worse functional class, reduced exercise capacity, and reduced quality of life, as well as more cardiac events.20,21 PPM may also predispose patients to structural valve deterioration.22


Few direct comparisons of THV designs evaluate possible differences in the incidence of PPM with different valve types. When looking at the reported incidences of PPM by valve type, PPM is more common with BE versus SE TAVR (Table 2).16 However, outcomes associated with PPM appear less significant with BE compared to SE TAVR (HR, 0.58–1.2 vs approximately 1.7, respectively). Some of these differences could relate to differences in valve design and pressure recovery.

Pressure recovery downstream of the aortic valve constitutes an important factor affecting the calculation of pressure gradient across the valve and, therefore, the aortic valve area.23 The pressure gradient measured at the vena contracta (ie, the pressure gradient measured by echo Doppler) represents the greatest pressure difference across a stenotic orifice; however, downstream from the vena contracta, the kinetic energy of the blood is converted back to potential energy (pressure) with pressure recovery in the ascending aorta. Although both the vena contracta gradient and pressure recovered gradients exist in vivo, the recovered pressure represents the net pressure seen by the left ventricle and may be the most relevant hemodynamic measurement.9 The amount of pressure recovery is dictated by several factors, such as turbulence,24 velocity of blood at the orifice, and the geometry of the aorta.25

In a recent in vitro study of the two commercially available THVs, Hatoum et al showed that while gradients at the vena contracta are higher with the BE THV, in part because of a slight increase in gradient within the stent frame, the net gradient after pressure recovery was significantly lower compared with SE THV.26 Thus, efficiency of pressure recovery significantly depends on valve type, likely due to stent interference with the recovering blood flow,27 and the calculated EOA using the vena contracta gradients underestimates the downstream valve area and overestimates the severity of PPM for the BE valve. These findings could explain why severe PPM in the PARTNER IA trial was associated with increased risk of mortality in the SAVR arm but not in the TAVR arm,1 whereas severe PPM was associated with increased risk of mortality in both arms in the CoreValve pivotal high-risk trial.7


Although using the predicted iEOA for a given THV can be performed using the normative data that have been published, this discussion raises significant issues with the clinical value of such an exercise for every THV type. For the SE valve, in which severe PPM is associated with increased short- and midterm mortality, using the tables for expected valve area by annular measurement or planned THV size will predict the occurrence of PPM. In addition, a recent presentation of data based on the CoreValve pivotal and SURTAVI trial data showed that a Doppler velocity index (DVI) ≤ 0.5 occurred in 32% of SE TAVR and 50% of SAVR patients and was associated with a higher 3-year mortality rate in TAVR (20% vs 18.5%; P = .025).28 Thus, using the tables of expected normal values for the SE valve11 to estimate expected EOA, iEOA, and DVI in order to predict outcomes would be appropriate.

For the BE valve, the association of PPM with mortality is more tenuous, with randomized trials suggesting no significant mortality and nonrandomized data showing a risk for increased mortality. The hemodynamic differences between the SE and BE valves continue to be studied but may be in part a result of the underestimation of BE THV EOA due to pressure recovery. The tables of expected normal values for the BE valve11 may be important for follow-up, particularly in the absence of patient-specific post-TAVR data, but may not be as useful for predicting outcomes prior to valve implantation.


The measurement of PPM is nuanced, with multiple hemodynamic variables affecting quantitation of prosthetic EOA. The grading of PPM should use EOA indexed to body surface area, with different cutoffs depending on BMI. Other confounders (pseudo-PPM due to low flow, pressure recovery) require further study. TAVR is associated with less PPM than SAVR, and severe PPM in SAVR is consistently associated with increased mortality. The adverse outcomes of PPM associated with the SE THV have not been seen with the BE THV, and differences in valve construct and hemodynamics may help explain these discordant results. Thus, an individualized approach to valve choice should always be made while considering these differences in outcomes related to PPM, as well as differences in incidence and outcomes associated with other complications, such as paravalvular regurgitation and stroke.

1. Pibarot P, Weissman NJ, Stewart WJ, et al. Incidence and sequelae of prosthesis-patient mismatch in transcatheter versus surgical valve replacement in high-risk patients with severe aortic stenosis: a PARTNER trial cohort-A analysis. J Am Coll Cardiol. 2014;64:1323-1334.

2. Fallon JM, DeSimone JP, Brennan JM, et al. The incidence and consequence of prosthesis-patient mismatch after surgical aortic valve replacement. Ann Thorac Surg. 2018;106:14-22.

3. Head S, Mokhles M, Osnabrugge R, et al. The impact of prosthesis-patient mismatch on long-term survival after aortic valve replacement: a systematic review and meta-analysis of 34 observational studies comprising 27,186 patients with 133,141 patient-years. Eur Heart J. 2012;33:1518-1529.

4. Hahn RT, Pibarot P, Stewart WJ, et al. Comparison of transcatheter and surgical aortic valve replacement in severe aortic stenosis: a longitudinal study of echocardiography parameters in cohort A of the PARTNER trial (placement of aortic transcatheter valves). J Am Coll Cardiol. 2013;61:2514-2521.

5. Dayan V, Vignolo G, Soca G, et al. Predictors and outcomes of prosthesis-patient mismatch after aortic valve replacement. JACC Cardiovasc Imaging. 2016;9:924-933.

6. Herrmann HC, Daneshvar SA, Fonarow GC, et al. Prosthesis-patient mismatch in patients undergoing transcath-eter aortic valve replacement: from the STS/ACC TVT registry. J Am Coll Cardiol. 2018;72:2701-2711.

7. Zorn GL 3rd, Little SH, Tadros P, et al. Prosthesis-patient mismatch in high-risk patients with severe aortic stenosis: a randomized trial of a self-expanding prosthesis. J Thorac Cardiovasc Surg. 2016;151:1014-1022, 1023.e1-3.

8. Stamou SC, Chen K, James TM, et al. Predictors and outcomes of patient-prosthesis mismatch after transcatheter aortic valve replacement. J Cardiac Surg. 2020;35:360-366.

9. Lancellotti P, Pibarot P, Chambers J, et al. Recommendations for the imaging assessment of prosthetic heart valves: a report from the European Association of Cardiovascular Imaging endorsed by the Chinese Society of Echocardiography, the Inter-American Society of Echocardiography, and the Brazilian Department of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2016;17:589-590.

10. Doherty JU, Kort S, Mehran R, et al. ACC/AATS/AHA/ASE/ASNC/HRS/SCAI/SCCT/SCMR/STS 2017 appropriate use criteria for multimodality imaging in valvular heart disease: a report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2017;70:1647-1672.

11. Hahn RT, Leipsic J, Douglas PS, et al. Comprehensive echocardiographic assessment of normal transcatheter valve function. J Am Coll Cardiol Imag. 2019;12:25-34.

12. Douglas PS, Hahn RT, Pibarot P, et al. Hemodynamic outcomes of transcatheter aortic valve replacement and medical management in severe, inoperable aortic stenosis: a longitudinal echocardiographic study of cohort B of the PARTNER trial. J Am Soc Echocardiogr. 2015;28:210-7.e1-9.

13. Oh JK, Little SH, Abdelmoneim SS, et al. Regression of paravalvular aortic regurgitation and remodeling of self-expanding transcatheter aortic valve: an observation from the CoreValve U.S. pivotal trial. JACC Cardiovasc Imaging. 2015;8:1364-1375.

14. Willson AB, Webb JG, Labounty TM, et al. 3-dimensional aortic annular assessment by multidetector computed tomography predicts moderate or severe paravalvular regurgitation after transcatheter aortic valve replacement: a multicenter retrospective analysis. J Am Coll Cardiol. 2012;59:1287-1294.

15. Hahn RT, Khalique O, Williams MR, et al. Predicting paravalvular regurgitation following transcatheter valve replacement: utility of a novel method for three-dimensional echocardiographic measurements of the aortic annulus. J Am Soc Echocardiogr. 2013;26:1043-1052.

16. Pibarot P, Clavel MA. Prosthesis-patient mismatch after transcatheter aortic valve replacement: it is neither rare nor benign. J Am Coll Cardiol. 2018;72:2712-2716.

17. Kappetein AP, Head SJ, Genereux P, et al. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document (VARC-2). Eur J Cardiothoracic Surg. 2012;42:S45-S60.

18. Mack MJ, Leon MB, Thourani VH, et al. Transcatheter aortic-valve replacement with a balloon-expandable valve in low-risk patients. N Engl J Med. 2019;380:1695-1705.

19. Popma JJ, Deeb GM, Yakubov SJ, et al. Transcatheter aortic-valve replacement with a self-expanding valve in low-risk patients. N Engl J Med. 2019;380:1706-1715.

20. Pibarot P, Dumesnil JG. Hemodynamic and clinical impact of prosthesis-patient mismatch in the aortic valve position and its prevention. J Am Coll Cardiol. 2000;36:1131-1141.

21. Pibarot P, Dumesnil JG. Prosthesis-patient mismatch: definition, clinical impact, and prevention. Heart. 2006;92:1022-1029.

22. Urso S, Calderon P, Sadaba R, et al. Patient-prosthesis mismatch in patients undergoing bioprosthetic aortic valve implantation increases risk of reoperation for structural valve deterioration. J Cardiac Surg. 2014;29:439-444.

23. Bahlmann E, Cramariuc D, Gerdts E, et al. Impact of pressure recovery on echocardiographic assessment of asymptomatic aortic stenosis: a SEAS substudy. JACC Cardiovasc Imaging. 2010;3:555-562.

24. Bach DS. Echo/Doppler evaluation of hemodynamics after aortic valve replacement: principles of interrogation and evaluation of high gradients. JACC Cardiovasc Imaging. 2010;3:296-304.

25. Chambers J. Is pressure recovery an important cause of “Doppler aortic stenosis” with no gradient at cardiac catheterisation? Heart .1996;76:381.

26. Hatoum H, Hahn RT, Lilly S, Dasi LP. Differences in pressure recovery between balloon expandable and self-expandable transcatheter aortic valves. Ann Biomedical Engin. 2020;48:860-867.

27. Hatoum H, Lilly S, Maureira P, et al. The hemodynamics of transcatheter aortic valves in transcatheter aortic valves [published online October 31, 2019]. J Thorac Cardiovasc Surg.

28. Van Mieghem N, Popma J, Søndergaard L, et al. CRT-600.06 clinical outcomes and valve hemodynamics following transcatheter and surgical aortic valve replacement. JACC Cardiovasc Interv. 2020;13:S48.

Rebecca T. Hahn, MD, FACC
Columbia University Medical Center
NewYork-Presbyterian Hospital
New York, New York
Disclosures: Echo Core Lab Director for multiple TAVR trials for which she receives no direct compensation.