Michael A. Mussallem
Chairman & Chief Executive Officer at Edwards Lifesciences
Thank you, Mark. We're proud of our performance in 2021. Although, hospitals continue to be impacted by COVID, it was a year of significant milestones and investment for Edwards and our teams were relentless. In TAVR, we made important strides in executing our long-term strategy. In particular, we invested in increasing awareness, pursued further therapy expansion and advanced new technologies. We completed enrollment of the EARLY TAVR trial, an important pivotal study, studying the treatment of severe aortic stenosis patients before their symptoms develop. Separately, we initiated enrollment in our PROGRESS trial for moderate AS patients, and we received FDA approval for our ALLIANCE pivotal trial to start our next-generation TAVR technology, SAPIEN X4.
In TMTT, we achieved our significant 2021 milestones, as we continue to make meaningful progress on advancing our three key value drivers; a portfolio of pioneering therapies for patients, positive pivotal trial results to support approvals and adoption, and favorable real-world clinical outcomes.
We are pleased to have treated over 3,000 patients in 2021, with our differentiated portfolio of TMTT therapies, gaining valuable learnings through both our clinical and commercial experiences. Each of our platforms demonstrated promising outcomes and clinical performance. I'm also pleased to announce that we completed enrollment of our CLASP IID pivotal trial in 2021, an important milestone that keeps us on track for U.S. approval late this year.
In Surgical Structural Heart, we extended our leadership position through the adoption of our premium technologies. We also implemented valuable additions to our smart monitoring advancements in critical care. Most importantly in 2021, even more patients benefited from Edwards' life-saving technologies than ever before. I'm also proud to say that throughout the year, our employees remain dedicated to keeping our commitments to patients and to one another. Despite the ongoing pandemic that fueled global challenges, our employees found innovative ways to support hospital procedures and to ensure our ability to supply our life-saving therapies was not impacted. And through their efforts, we were able to get our technologies into the hands of our trusted partners around the world, so they could serve their patients.
Now I'd like to cover several 2021 financial highlights, before I get into the quarterly details. In 2021, we were pleased to achieve all of our key financial expectations. Underlying sales increased 18% to $5.2 billion, driven by balanced organic sales growth in each region. We achieved 19% growth in adjusted earnings per share, while also increasing R&D, 19%. The significant increase in R&D and infrastructure investments this year, helped strengthen our long-term outlook. And as you heard at our investor conference last month, we are as convinced as ever about the tremendous opportunity we have, to enhance patients' lives and bring significant value to the healthcare system.
Turning to our financial results; fourth quarter sales of $1.3 billion increased 13% on a constant currency basis versus the year ago period. Growth was driven by our portfolio of innovative technologies, although at the lower end of our October expectations, due to the pronounced impact of Omicron on hospital resources in December, especially in the U.S.
Full year 2021 global TAVR sales of $3.4 billion increased 18% on an underlying basis versus the prior year. Despite intermittent challenges associated with the pandemic throughout the year, sales were in line with our original guidance of $3.2 billion to $3.6 billion, and were driven by increased awareness of the benefits of TAVR therapy with our SAPIEN platform. In the fourth quarter, our global TAVR sales were $872 million, an increase of 13% on an underlying basis, with impressive strengths outside the U.S. We estimated, global TAVR procedure growth was comparable with our growth. And globally, average selling prices were stable, as we maintained our disciplined pricing strategy. In the U.S., our TAVR sales grew 10% year-over-year in the fourth quarter, and we estimate that our share of procedures was stable.
As previously mentioned, the Omicron variant had a noticeable impact on hospital resources in December as cases were postponed or limited in a number of hospitals. Growth in the U.S. was highest in small to mid-volume centers, which are helping provide access to a broader population of aortic stenosis patients.
Outside the U.S., in the fourth quarter our sales grew approximately 20% year-over-year on an underlying basis and we estimate total TAVR procedure growth was comparable. We continue to be encouraged by the strong international adoption of TAVR broadly in all regions. In Europe, Edwards' growth was in the mid-teens, and we estimate that our competitive position was stable. Growth was broad-based across the region.
It's worth noting that a recent cost-effectiveness study, demonstrated that TAVR with SAPIEN 3 was economically dominant, when compared to surgical aortic valve replacement, in treating French patients with severe symptomatic aortic stenosis, who are at low surgical mortality -- who are at low risk of surgical mortality. We're also encouraged by the recently published guidelines from the European Association of Cardiothoracic Surgery, which now definitively recommend TAVR for patients over 75. We believe both of these developments represents an important long-term opportunity to bring TAVR therapy to even more patients in need.
Sales growth in Japan was also strong, where therapy adoption is still relatively low. Several important milestones were achieved in Q4. For the first time, the number of TAVR procedures performed in Japan was comparable with the surgical aortic valve replacements. Furthermore, in each prefecture in Japan, there is now at least one hospital offering SAPIEN. Following the recent reimbursement approval for the treatment of patients at low surgical risk, we remain focused on expanding the availability of TAVR therapy throughout the country. Longer term, we see excellent opportunities for continued O-U.S. growth as we believe global adoption of TAVR therapy remains quite low.
In addition to our geographic expansion of our TAVR therapies, we remain focused on indication expansion. In Q4, we completed enrollment of our EARLY TAVR pivotal trial, which is focused on the treatment of asymptomatic AS patients. Separately, we initiated enrollment in PROGRESS, an important pivotal trial for moderate aortic stenosis to determine the optimal time to treat patients who have this progressive disease. We believe that some patients may benefit from earlier treatment, before they have symptoms or before their AS becomes severe, rather than risking irreversible damage to their heart, as the disease progresses.
We also took steps to advance our innovative product portfolio. In Q4, we received FDA approval for our ALLIANCE pivotal trial to study our next-generation TAVR device, SAPIEN X4. Additionally, in Q4, we received FDA approval to use SAPIEN 3 with our Alterra adaptive pre-stent for congenital heart patients. This should result in a quality-of-life improvement and a reduction in the number of procedures that these younger patients will require over their lifetime.
In summary, despite a slower-than-expected start to the year, we continue to anticipate 2022 underlying TAVR sales growth of 12% to 15%, consistent with the range we shared at our December investor conference. Our outlook assumes COVID-related challenges early in 2022, turning to more normalized growth environment, as headwinds from Omicron subside and hospital resource constraints stabilize. We remain confident in this large global opportunity will double to $10 billion by 2028, which implies a compounded annual growth rate in the low double-digit range.
Turning to TMTT; as I mentioned, in the fourth quarter, we completed enrollment of our CLASP IID pivotal trial, and we remain on track to present data in the second half of 2022. This important milestone keeps us on track for U.S. approval late this year of PASCAL, for patients with degenerative mitral regurgitation. We also continue to expect European approval of our next-generation PASCAL Precision System later this year.
At the PCR London Valves conference in Q4, PASCAL 30-day outcomes from our MiCLASP post-market approval study of more than 250 patients in Europe were presented. The data highlighted safe and effective MR reduction in a post-market setting. We also progressed on the enrollment of our CLASP IIF pivotal trial for patients with functional mitral disease. In mitral replacement, we continue to expand our experience with both our transcatheter mitral replacement therapies through the ENCIRCLE pivotal trial for SAPIEN M3 and the MISCEND study for EVOQUE Eos. Early experience with these sub-French transfemoral therapies, increase our confidence in both platforms.
Turning to transcatheter tricuspid therapies, results from the TRISCEND study were presented at the Annual TCT Conference in November and demonstrated that early patient outcomes with the EVOQUE tricuspid were favorable and sustained at six months. We are encouraged by the procedural success rates and also the significant TR reduction and sustained improvements in quality of life measures experienced by these patients.
We continue to make meaningful progress in enrolling our two tricuspid pivotal trials, the TRISCEND II pivotal trial for the EVOQUE system and the CLASP II TR pivotal trial with PASCAL, in patients with symptomatic severe tricuspid regurgitation. We anticipate a late 2022 approval of EVOQUE tricuspid in Europe, and remain committed to providing solutions for these patients that have very poor prognosis and few treatment options today.
Turning to the sales performance of TMTT; fourth quarter revenue of $25 million grew sequentially from the third quarter, as we saw increased adoption of the PASCAL system despite the negative COVID impact in December. Full year 2021 global sales more than doubled to $86 million, as we continue to expand the availability of PASCAL to more centers in Europe, we are pleased with the excellent outcomes for patients supported by our high touch model.
We look forward to continuing our progress toward advancing our vision to transform the lives of patients with mitral and tricuspid valve disease in 2022, with the milestones that we outlined in our recent investor conference.
Despite the COVID impact so far this year, we continue to expect TMTT sales of $140 million to $170 million for 2022. We estimate that global TMTT opportunity will grow to approximately $5 billion by 2028, and we remain committed to bringing our groundbreaking portfolio of therapies to patients with these life-threatening diseases. We are confident our portfolio strategy positions us well for leadership.
In Surgical Structural Heart, full year global sales were $889 million, up 15% on an underlying basis versus the prior year. Fourth quarter 2021 global sales of $221 million increased 9% on an underlying basis over the prior year. Although, we saw that hospital staffing shortages continued to worsen throughout the quarter, especially in the U.S., life-saving surgical therapies continue to be prioritized over elective procedures. We're excited about the continued global adoption of INSPIRIS RESILIA aortic surgical valve, the KONECT RESILIA aortic tissue valve conduit and our MITRIS RESILIA valve.
We remain encouraged by the growing evidence that supports Edwards RESILIA tissue valves, including two studies being presented at the Society of Thoracic Surgeons Conference this weekend. The COMMENCE study demonstrates excellent hemodynamics of this tissue technology across all aortic valve sizes at five years. While a European economic value study, shows a cost reduction with the use of INSPIRIS versus mechanical valves.
In summary, we continue to expect that our full year 2022 underlying sales growth will be in the mid single digit range for Surgical Structural Heart, driven by adoption of our premium technologies and procedure growth. Even as TAVR adoption expands, we're excited about our ability to provide innovative surgical treatment options for patients, extend our global leadership and be the partner of choice for cardiac surgeons.
Turning to Critical Care; full year global sales of $835 million increased 14% on an underlying basis versus the prior year. 2021 growth was driven by balanced contributions from all product lines, led by HemoSphere sales, as capital spending resumed. Our TruWave disposable pressure monitoring devices used in the ICU, also remained in high demand, due to the elevated COVID hospitalizations in both the U.S. and Europe.
Fourth quarter Critical Care sales of $212 million increased 8% on an underlying basis, driven by strong demand for HemoSphere. Demand for our broad portfolio of smart recovery sensors also remained robust in the fourth quarter, including ClearSight, our non-invasive finger cuff, which achieved sustained performance at or above pre-COVID levels. As discussed at our recent investor conference, the integration of a full range of technologies, creates a unique offering of enhanced recovery tools and predictive analytics capabilities, to further strengthen our leadership in hemodynamic monitoring.
In summary, we continue to expect mid-single-digit underlying sales growth for 2022, and we remain excited about our pipeline of innovative critical care products.
And now, I'll turn the call over to Scott.