We used a national multicenter registry including all patients aged from 50 to 65 years who underwent isolated AVR in 27 Spanish centers during January 2000 and September 2018. We excluded dndocarditis, nonelective interventions and surgery due to isolated aortic regurgitation. Each center had 2 researchers responsible for collecting pre-, intra-, postoperative data and follow-up in all patients. The variables collected in this registry were reported for another study at ClinicalTrials.gov: NCT03595423. Follow-up was collected from February to July 2019. Telephone contacts with the patient/family, contacts with their physicians and information based on medical reports were used. Only 3 patients were lost to follow-up. For these patients, we considered the last date they were known to be alive.

We compared the long-term observed survival of these patients who underwent isolated AVR with the expected survival of the general population from Spain matched by age, sex, and year of surgery. To match for these factors, we used the data freely available and provided by the National Institute of Statistics.6 This method has been previously used.1

In an attempt to expand knowledge, we selected another sample and repeated all analyses. This sample was formed by patients who survived the postoperative period, did not suffer major postoperative complications and who were able to have a straightforward postoperative course. These individuals did not have a permanent pacemaker, aortic regurgitation (mild or more severe), stroke, new-onset atrial fibrillation, and their ventricular function did not worsen more than 10% compared with previous function and the total hospital stay was less than 10 days.

This study complies with the Declaration of Helsinki, was approved by the IRB (Comité de Ética de Investigación de Málaga, reference: 2806/2018, informed consent was not needed due to the retrospective nature of the study) and the design, aims and main estimates were registered online.7

To compare observed with expected survival in patients aged 50 to 65 years who underwent isolated AVR.

To determine whether the long-term survival of patients aged 50 to 65 years who underwent isolated AVR, survived the postoperative period and had no postoperative complications was similar to that of the general population.

To Identify the main risk factors for long-term mortality in this population.

Categorical and quantitative variables are described as No. (%) and mean±SD, respectively. We compared observed survival, calculated by the usual actuarial estimate (intervals of 0.1 years), with expected survival, calculated by the Ederer II method. This method, considered the best for this purpose,8 is able to estimate the expected survival of the sample in the theorical assumption that they did not have the disease. This method was previously used in other works.1,9,10 If the 95% confidence interval (95%CI) of the observed survival included the expected survival, no difference can be shown. For the calculations, we used the data provided by the National Institute of Statistics.6 With these data, we created a database with the annual risk of death by sex, year (2000-2019), and age (50-84 years).

The mortality in a sample may be due to the disease under study or to other unrelated causes. Consequently, usual Kaplan-Meier survival curves, without comparison with the general population, provide little information. One method that estimates the proportion of patients who die only due to the disease is the relative survival (RS). An RS of 100% indicates that there are no deaths related to the disease (all patients survive). An RS of 60% would indicate that 40% of the patients died because of the disease.1,11–13 We calculated the RS with its 95%CI. If the CI includes the value 100%, no excess of mortality can be shown. RS results from the division between the observed and the expected survival and therefore it can exceed 100%.

Risk factors for long-term mortality were identified using a multivariate Cox-regression analysis. All baseline characteristics were included in the model and the proportion hazards assumption was tested.

All analyses were performed with STATA v.15 (StataCorp, United States) and the strs12 command was used to calculate these estimates.

A total of 5084 patients underwent isolated AVR during the study period. The mean age was 59.3±4.3 years and 1618 (31.8%) were women. Baseline characteristics are described in table 1. In all, 152 (2.99%) patients died during the postoperative period with a logistic EuroSCORE of 3.1±7.5.

Median follow-up of the censored observations was 97.6 months. Observed survival at 1, 5, 10 and 15 years of follow-up was 96.7% (95%CI, 96.2%-97.2%), 92.5% (95%CI, 91.7%-93.2%), 85.3% (95%CI, 84.1%-86.4%), and 73.7% (95%CI, 71.6%-75.6%). Expected survival for these years was 99.3%, 95.9%, 90.1%, and 82.1%. Observed and expected survival curves are represented in figure 1.

Figure 1.

Observed and expected survival in the overall sample. 95%CI, 95% confidence interval; AVR, aortic valve replacement.

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The cumulative RS for 1, 5, 10 and 15 years of follow-up was 97.4% (95%CI, 96.9%-97.9%), 96.5% (95%CI, 95.7%-97.3%), 94.7% (95%CI, 93.3%-95.9%), and 89.8% (95%CI, 87.3%-92.1%). The cumulative RS for different years of follow-up and stratified by age ranges can be observed in figure 2A-D.

Figure 2.

Overall sample. A-D: cumulative relative survival at different times of follow-up. (A: 50-55 years; B:55-60 years; C:60-65 years; D: total sample). AVR, Aortic valve replacement.

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The same analyses were performed for patients who survived the postoperative period (Results and figure 1 of the supplementary data). Stratified analyses by sex and type of prosthesis were also calculated (figure 2 and 3 of the supplementary data). In addition, the main risk factors for long-term mortality are shown in Results of the supplementary data.

A total of 1657 fulfilled the criteria. The mean age was 59.4±4.4 years and 517 (31.2%) were women.

Observed survival at 1, 5, 10 and 15 years was 99.6% (95%CI, 99.1%-99.8%), 94.8% (95%CI, 93.5%-95.8%), 87.8% (95%CI, 85.6%-89.7%), and 75.7% (95%CI, 71.1%-79.6%). Expected survival at 1, 5, 10 and 15 years was 99.3%, 95.9%, 90.2%, and 82.2%. Observed and expected survival curves are shown in figure 3A.

Figure 3.

A: Observed and expected survival in patients who survived the postoperative period and who had no complications; B: cumulative relative survival in these patients. 95%CI, 95% confidence interval AVR, aortic valve replacement; RS, relative survival.

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Cumulative RS for 1, 5, 10 and 15 years was 100.3% (95%CI, 99.8%-100.5%), 98.9% (95%CI, 97.6%-99.9%), 97.3% (95%CI, 94.9%-99.4%), and 91.9% (95%CI, 86.5%-96.8%). Cumulative RS during the follow-up is presented in figure 3B.

Stratified analyses by sex and type of prosthesis were also calculated. These results can be consulted in figure 4 and figure 5 of the supplementary data. The number of complications by patient can be consulted in the table 1 of the supplementary data.

In this study, we present the largest sample of relatively young patients undergoing AVR and compared their long-term survival with that of the general population matched by age, sex, year of surgery, and nation. Our sample was formed only by isolated AVR and therefore it is more homogeneous than that presented in other samples with concomitant coronary surgery.

However, this study has several limitations. This is a retrospective work and is therefore subject to intrinsic biases of this type of study. There was no objective way to know whether patients’ surgery was easy and straightforward. We selected this group of patients based on the available postoperative variables. Nevertheless, we acknowledge that the selection of these factors was substantially subjective. Some important postoperative complications such as reoperation due to severe bleeding were not present in the registry so we could not take them into account. Finally, different centers may lead to different surgical results and our conclusions are only an average of the observed and expected survival at the national level.