Prosthesis-patient mismatch — when a patient with aortic stenosis is given a valve prosthesis with an effective orifice area that is too small in relation to body size — is associated with higher risk of mortality, even in patients undergoing transcatheter valve replacement, a new meta-analysis suggests.

“We found that mismatch in patients undergoing transcatheter aortic valve replacement (TAVR) is associated with a negative impact on survival, and this is particularly important if there is severe mismatch,” lead author Michel Pompeu Sá, MD, PhD, Lankenau Institute for Medical Research, Wynnewood, Pennsylvania, told theheart.org | Medscape Cardiology.

“There is a narrative out there that mismatch is only a problem for surgical valves. But we found that this is not the case,” Pompeu Sá said. “It also occurs with TAVR, and it has an impact on survival.

“Our results show that we should not accept mismatch in TAVR either, as it is associated with worse outcomes,” he added.

Pompeu Sá is presenting the meta-analysis at the Transcatheter Cardiovascular Therapeutics 2022 meeting this weekend in Boston. The analysis is also published online today in JACC: Cardiovascular Imaging.

Prosthesis-Patient Mismatch

“When implanting an aortic valve, a very large person will need a different sized valve than a very small person. If the wrong size valve is used (smaller than what the patient needs), we call that prothesis-patient mismatch,” Pompeu Sá explained. 

“A small 23-mm valve may be fine in a small person, but a much heavier person requires a greater blood flow and will therefore require a valve with a larger orifice.”

The matching of a valve to a patient is based on the ratio between the valve orifice area (which is measured in cm²) and the patient’s body surface area (which is measured in m²). The orifice area of the valve is divided by the surface area of the body to give the indexed effective orifice area (iEOA).

“In non-obese people, the iEOA needs to be above 0.85 cm²/m². If values of this ratio are below 0.85 cm²/m^2, then we say there is mismatch. If patients have a ratio of 0.65 to 0.85 cm²/m², then this is moderate mismatch, and if the ratio is below 0.65, then this is severe mismatch,” Pompeu Sá noted.

In obese people, the iEOA needs to be above 0.70 cm²/m². Values of 0.55 to 0.70 cm²/m² are classified as moderate mismatch and under 0.55 cm²/m² is severe mismatch.

“We know mismatch occurs frequently and is a big problem in patients undergoing surgical valve replacement. We also know that mismatch occurs much less frequently in TAVR but whether or not it has an effect on outcomes in TAVR patients has not been so clear-cut,” Pompeu Sá said.

For the current analysis, investigators pooled individual-patient data from 23 studies comparing patients with and without prosthesis-patient mismatch after TAVR to evaluate its effect on the all-cause mortality risk.

“To the best of our knowledge, this is the first pooled meta-analysis of reconstructed time-to-event data analyzing the impact of prosthesis-patient mismatch on outcomes after TAVR,” they say.

The analysis included 81,969 patients (19,612 with prosthesis-patient mismatch and 62,357 without prosthesis-patient mismatch).

Results showed that patients with moderate/severe prosthesis-patient mismatch had a significantly higher risk for mortality compared with those without mismatch (hazard ratio [HR], 1.09, 95% CI, 1.04 – 1.14; P < .001).

In the first 30 months after the procedure, mortality rates were significantly higher in the moderate/severe mismatch group (HR, 1.1). In contrast, results beyond 30 months were not statistically significantly different.

The researchers suggest these different effects at different times may be a result of the time taken for the hypertrophied left ventricle to go through the process of reverse remodeling.

In a sensitivity analysis, severe mismatch showed a higher risk for mortality in comparison with no mismatch (HR, 1.25; P < .001). However, moderate mismatch was not associated with a statistically significant difference for mortality (HR, 1.03; P = .398).

“Severe Mismatch Is Not to Be Tolerated”

“Our results suggest that we might be able to tolerate moderate mismatch, but this needs to be investigated further. However, severe mismatch is not to be tolerated under any circumstances,” Pompeu Sá commented.

“These findings need to be taken seriously. It is not difficult to calculate the appropriate size of the valve needed for a certain body size during the preprocedural planning,” he said. “The size of the effective orifice area for a certain body size is one the most important things to take into account when selecting a valve.”

In an accompanying editorial in JACC: Cardiovascular Imaging, Linda Gillam, MD, Gagnon Cardiovascular Institute at Morristown Medical Center, Morristown, New Jersey, notes that although there have been other meta-analyses on this topic, this is the first to reconstruct time-to-event data from a pooled analysis of Kaplan Meier estimated individual patient data rather than merging hazard ratios produced with different time points.

“Time-to-event outcomes take into account that both the event and its timing are important, which is clearly the case in the setting of TAVI-associated mortality,” she says.

Gillam also points out that lower recommended cutoffs for obese patients were not universally used in studies included in the meta-analysis, so the confidence with which mismatch is accurately identified is problematic. And the severe mismatch cutoff of 0.65 cm² was somewhat arbitrary, so “it is almost certain that the pool of patients with ‘severe’ prosthesis-patient mismatch is a mixed bag, including those with moderate or even no prosthesis-patient mismatch,” she adds.

“Perhaps, therefore, a more practical interpretation of the results of this meta-analysis, is a simpler one: the smaller the indexed effective orifice area, the more likely it is to have an impact on outcomes,” she concludes.

To put this meta-analysis in context, Gillam notes that severe prosthesis-patient mismatch is not a rare phenomenon, reported as 10.9% in this study.

Although the reported prevalence has varied considerably depending on methods for calculating and adjusting iEOA, she cites estimates that severe PPM is present in at least 1 in 100 to 1 in 20 patients.

The current meta-analysis “underscores the clinical importance of severe prosthesis-patient mismatch,” Gillam writes.

“This study, and its first time-to-event individual patient data approach, is thus an important contribution to understanding the impact of prosthesis-patient mismatch and supports ongoing efforts to reduce its occurrence,” she concludes.

This study was supported by the Sharpe-Strumia Research Foundation (Bryn Mawr Hospital). Pompeu Sá receives support from The Thoracic Surgery Foundation (charitable arm of The Society of Thoracic Surgeons) through the TSF Every Heartbeat Matters Global Structural Heart Fellowship Award for the project “Structural Heart/Minimally Invasive Cardiac Surgery.”

Transcatheter Cardiovascular Therapeutics 2022. To be presented
September 19, 2022.

JACC Cardiovasc. Imaging. Published online September 16. Abstract, Editorial 

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