Evidence from the placement of aortic transcatheter valve (PARTNER) trial—can we just dismiss it?

In a recent review titled “TAVI—thick on technology but thin on evidence,” Dr. Sarkar has raised many pertinent issues related to the adoption of transcatheter aortic valve implantation (TAVI) in general and the placement of aortic transcatheter valve (PARTNER) trial in particular [1].

The review has to be lauded for highlighting some very important issues regarding lack of data transparency and publication bias and bringing forward the many clinical concerns with transcatheter aortic valve replacement (TAVR) or TAVI. However, some of the criticism is a little harsh, and for the benefit of the readership, the positives of the trial need to be stressed upon too.

One of the criticisms of the trial in the review was lack of any substantive differences between the inoperable (cohort B) and high-risk operable groups (cohort A), implying that the criteria to choose who was high risk and who was deemed inoperable was flawed. However, the inoperability was decided not just on clinical but also on anatomical grounds. In the inoperable group, the incidence of extensively calcified aorta was 15.1% as opposed to 0.9% in the high-risk group. Similarly, the effects of chest wall irradiation (8.7% vs. 0.9%) and chest wall deformity (6.7% vs. 0.2%) were disproportionately high in the group deemed inoperable by the two surgeons responsible for deciding inoperability. Even clinically, the incidence of oxygen-dependent chronic obstructive pulmonary disease (COPD) was much higher in the inoperable group (cohort B) at 23.5% versus only 8.2% in the high-risk group (cohort A). Also, inoperable patients were significantly more frail compared to the high-risk patients (23.1% vs. 16.6%). So, these groups were in fact different, both from an anatomical point of view and important clinical parameters [1].

It is also mentioned that “incidence of comorbidities was noticeably higher in the surgical AVR group.” This may have been an unfortunate typographical error as there was not a single statistically significant difference between the groups undergoing TAVR or surgical aortic valve replacement (SAVR) in the high-risk group [2]. Probably it has been confused with the groups undergoing TAVR and standard therapy (i.e., balloon aortic valvuloplasty) in the inoperable group [3].

Lastly, there have been suggestions that one of the principal investigators was a financial beneficiary from the industry. As a matter of fact, not one but 15 of the investigators, including both the principal investigators of the trial, were beneficiaries from the industry, not necessarily from the sponsor of the study. Moreover, they have disclosed their financial affiliations as part of the disclosure norm, and thus, the question of financial impropriety does not arise in the context of the trial [2, 3].

Despite all the criticism heaped upon the PARTNER trial, we have to acknowledge that it is one of the most diligent and well conducted trials in recent time. The trial was carried out across 22 centers in the United States of America (USA), 2 centers in Canada, and 1 in Germany which were all centers of excellence. The entire data was sent for analysis to independent consulting biostatisticians, and independent core laboratories analyzed all echocardiograms and electrocardiograms [2].

With regard to TAVI, the relevant question is not whether TAVI is good or bad but how can we make good use of TAVI? The message we need to take from the PARTNER trial is that the patients who benefit most from TAVI are the anatomically inoperable patients. We also have to be aware that a certain subset (cohort C) has been recognized recently who do not benefit from TAVI. These are inoperable patients with aortic stenosis who have serious comorbidities including frailty, malnutrition, cachexia, recent malignancy, stroke, dementia, and dialysis that make a return to semi-independent living very unlikely after TAVR, and thus, these patients do not benefit from TAVR [4].

Even though the mortality in the PARTNER trial was at the time the lowest ever reported in medical literature for TAVR (high-risk operable patients, as-treated mortality 3.7%; inoperable patients 6.4%), Dr. Sarkar’s concerns about stroke, paravalvular leaks, and vascular injury are genuine and deserve critical evaluation. However, it has to be seen in the context that most of the participating US centers in the PARTNER trial had no previous experience with TAVI. It is likely that with newer valves (SAPIEN 3 and the Medtronic CoreValve) improved delivery systems and with further experience at implanting these valves, the current complications of TAVI will decline. Emerging evidence from other trials has already shown that TAVR using newer devices, such as the Edwards SAPIEN 3 (Edwards Lifesciences, Irvine, CA, USA), is associated with lower mortality, stroke, and regurgitation at 1 year (PARTNER S3i trial) [5]. As the numbers of implantations increase and newer manufacturers enter the fray, the cost concern perhaps will also be addressed.

While most of the concerns raised in the manuscript are fair, we cannot lose sight of the fact that the cardiac surgical world around us is changing rapidly. SAVR numbers in the USA continued to rise since 2005 and reached its peak in 2013, but has undergone a slight decline in the last few years and stood at 28,037 in 2016. Contrast this with the meteoric rise in the number of TAVR which stood at 37,113 in 2016. This entire comparison between SAVR and TAVR is eerily reminiscent of an earlier era when cardiac surgery stood at a similar watershed moment with percutaneous coronary interventions, and it may be history repeating itself, if we chose to be dismissive about the evolving technology of TAVR. In fact, a judicious, ethical, and scientific embracing of this technology might be in the interest of the patients we strive to serve as well as the specialty we are skilled in.

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Conflict of interest

The author declares no conflict of interest.

Ethical approval

The invited editorial does not mention any patient or patient details, and hence, formal ethical approval is not required.