Outstanding Study

Outcomes in patients operated on for severe aortic stenosis

The Outstanding study (OUTcomes evaluation of current therapeutic STrategies for severe Aortic valve steNosis and the ageING population in ITALY), conducted within the Cardiology Network, investigated the treatment options for patients with severe aortic valve stenosis: TAVI (Transcatheter Aortic Valve Implantation) vs SAVR (Surgical Aortic Valve Replacement).
The study, led by principal investigator Marco Ranucci (director of Cardiac Anaesthesia and ICU at Policlinico San Donato), was supported by IRCCS Policlinico San Donato (371 patients), San Raffaele (10 patients), Humanitas (32 patients), Fondazione Maugeri Pavia e Montescano (18 patients), and ISMETT Palermo (69 patients), and enrolled patients with a minimum age of 66 years.

OUTCOMES

Quality of life

Results already submitted to the European Journal of Preventive Cardiology. Quality of life (QoL) was assessed at one year by measuring the change in each individual patient based on the total change in their standard deviation. At one year, there was no difference between TAVI and SAVR in the SF-12 mental and physical components.

At 4 years, there was a significant difference in the risk of deterioration in the mental component in favour of surgery (higher risk for TAVI). However, correction of the data for confounding factors (Cox regression) showed no difference. There was no significant difference in the physical component in the univariate analysis, but in reality, after correction for confounding factors, there was a medium/long-term advantage for SAVR (20% deterioration for TAVI and 10% for surgery). It has been found that, in surgery, after the first year in which some indicators worsen due to the effect of the invasive procedure, they return to normal over time, leaving the pool of risk of deterioration.

Neurocognitive function and QoL

A second analysis involves neurocognitive function 2 to 3 months after the procedure. In patients with neurocognitive deterioration, observed in both TAVI and SAVR cases, a significant deterioration in the mental component of QoL is observed after one year. The practical implication is that, in the event of early neurocognitive deterioration, it would be reasonable to refer the patient for neurocognitive rehabilitation.

Overall Outcome SAVR vs TAVI

Many randomised controlled comparative studies suggest that there are no major differences between TAVI and SAVR at one year. In this context, a real-world study was published, essentially carried out by Mario Negri’s group, which had access to the mortality data databases of the Lombardy (5,290 patients) and Puglia (2,000 patients) regions. The population included subjects aged 65-80 years with aortic stenosis who underwent aortic valve replacement (SAVR or TAVI) from 2018 to 2021. Two comparable groups were created using propensity matching. At 5 years, SAVR was superior to TAVI in terms of all-cause mortality. In Puglia, in the first few months, there was an advantage in favour of TAVI due to immediate surgical mortality, but after 2 years, a clear advantage for surgery emerged.

These data are similar to those reported in other large “real world” analyses2,3 but appear to contrast with those published in some randomised controlled trials.

‘At 5 years, randomised data report a TAVI mortality rate of 40-45% and 40% for surgery: our study confirms the data for TAVI, while SAVR mortality stands at 20%. ‘There is also a study of 40,000 low-risk patients reporting a 5-year SAVR mortality rate of 7.1%. Real-world data essentially suggest the superiority of surgery in the long term.’ Marco Ranucci, Director of Cardiac Anaesthesia and ICU at Policlinico San Donato

In the prospective arm of Oustanding, there are currently (May 2025) 4,172 patients who, together with the Mario Negri data, bring the total number of people analysed with different techniques in the study to more than 10,000.

Neurocognitive function

Differences in neurocognitive (NC) outcome 3 months after surgery. Study already published in 20245. Approximately 100 patients received MoCA (Montreal Cognitive Assessment) pre- and post-procedure. On average, there was an improvement in NC functions post-procedure, but some patients worsened, especially on memory indices: 28% had NC deterioration. No significant difference at 3 months between TAVI and SAVR on MoCA components.

Analysing a wide range of parameters, the only finding was that patients who had received more transfusion units had a higher risk of neurocognitive impairment.

Rehabilitation process

A further study published in 2024 (San Donato and Maugeri) looked at post-surgical rehabilitation within the Network. There was no difference in the walking test on admission and discharge. The only difference was in age, with obese patients tending to be younger. The percentages of deterioration in the walking test were similar between obese and non-obese patients.

Amyloidosis

Another arm of Outstanding, managed by Professor Eloisa Arbustini of San Matteo in Pavia, studies the amyloid component of the heart valve. On samples of surgically excised valves.

The Outstanding study also includes the analysis of mortality outcomes in the prospective arm of 2,214 patients and the evaluation of valvular amyloidosis.

 

Reference

  1. Ranucci M et al. When Real-World Outcomes Do Not Meet the Results of Clinical Trials: Transfemoral Transcatheter vs. Surgical Aortic Valve Replacement in an Intermediate-Age Population (The Outstanding Italy Study). J Clin Med 2025 May 15;14(10):3471. doi: 10.3390/jcm14103471 
  2. Cardiac Interventions Today. STS Reports Study Findings of SAVR Versus TAVR in Patients Aged < 60 Years. Available online: https://citoday.com/news/sts-reports-study-findings-of-savr-versus-tavr-in-patients-aged-60-years (accessed on 30 April 2024).
  3. Auer, J.; Krotka, P.; Reichardt, B.; Traxler, D.; Wendt, R.; Mildner, M.; Ankersmit, H.J.; Graf, A. Selection for transcatheter versus surgical aortic valve replacement and mid-term survival: Results of the AUTHEARTVISIT study. Eur. J. Cardiothorac. Surg. 2024, 66, ezae214.
  4. Thourani, V.H.; Habib, R.; Szeto, W.Y.; Sabik, J.F.; Romano, J.C.; MacGillivray, T.E.; Badhwar, V. Survival After Surgical Aortic Valve Replacement in Low-Risk Patients: A Contemporary Trial Benchmark. Ann. Thorac. Surg. 2024, 117, 106–112. 
  5. Ranucci L et al. Neurocognitive function in procedures correcting severe aortic valve stenosis: patterns and determinants Front Cardiovasc Med. 2024 Apr 12;11:1372792. doi: 10.3389/fcvm.2024.1372792 
  6. Ranucci M et al. Moderate obesity is not a limiting factor in cardiac rehabilitation after aortic valve replacement for severe stenosis. Eur J Prev Cardiol. 2024. PMID: 38513061