Prognosis after surgical replacement with a bioprosthetic aortic valve in patients with severe symptomatic aortic stenosis: systematic review of observational studies (original) (raw)

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  3. Prognosis after surgical replacement with a bioprosthetic aortic valve in patients with severe symptomatic aortic stenosis: systematic review of observational studies

Research BMJ 2016;354 doi: https://doi.org/10.1136/bmj.i5065 (Published 28 September 2016) Cite this as: BMJ 2016;354:i5065

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  1. Farid Foroutan, master student1 2,
  2. Gordon H Guyatt, distinguished professor1,
  3. Kathleen O’Brien, undergraduate student2,
  4. Eva Bain, undergraduate student2,
  5. Madeleine Stein, undergraduate student2,
  6. Sai Bhagra, physician2,
  7. Daegan Sit, medical student1,
  8. Rakhshan Kamran, undergraduate student1,
  9. Yaping Chang, PhD student1,
  10. Tahira Devji, PhD student1,
  11. Hassan Mir, physician1,
  12. Veena Manja, physician1 3 4,
  13. Toni Schofield, physician2,
  14. Reed A Siemieniuk, physician1 5,
  15. Thomas Agoritsas, assistant professor1 6,
  16. Rodrigo Bagur, assistant professor7,
  17. Catherine M Otto, professor8,
  18. Per O Vandvik, associate professor9 10
  19. 1Department of Clinical Epidemiology and Biostatistics, McMaster University, 1280 Main St West, Hamilton, Ontario, Canada L8S 4L8
  20. 2Heart Failure/Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
  21. 3Department of Internal Medicine, State University of New York at Buffalo, Buffalo, USA
  22. 4VA WNY Health Care System at Buffalo, Department of Veterans Affairs, USA
  23. 5Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  24. 6Division of General Internal Medicine, and Division of Clinical Epidemiology, University Hospitals of Geneva, Geneva, Switzerland
  25. 7Division of Cardiology, London Health Sciences Centre and Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada N6A 5W9
  26. 8Division of Cardiology, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA
  27. 9Department of Internal Medicine, Innlandet Hospital Trust-division Gjøvik, Norway
  28. 10Institute of Health and Society, Faculty of Medicine, University of Oslo, Norway
  29. Correspondence to: F Foroutan farid.foroutan{at}uhn.ca

Abstract

Objective To determine the frequency of survival, stroke, atrial fibrillation, structural valve deterioration, and length of hospital stay after surgical replacement of an aortic valve (SAVR) with a bioprosthetic valve in patients with severe symptomatic aortic stenosis.

Design Systematic review and meta-analysis of observational studies.

Data sources Medline, Embase, PubMed (non-Medline records only), Cochrane Database of Systematic Reviews, and Cochrane CENTRAL from 2002 to June 2016.

Study selection Eligible observational studies followed patients after SAVR with a bioprosthetic valve for at least two years.

Methods Reviewers, independently and in duplicate, evaluated study eligibility, extracted data, and assessed risk of bias for patient important outcomes. We used the GRADE system to quantify absolute effects and quality of evidence. Published survival curves provided data for survival and freedom from structural valve deterioration, and random effect models provided the framework for estimates of pooled incidence rates of stroke, atrial fibrillation, and length of hospital stay.

Results In patients undergoing SAVR with a bioprosthetic valve, median survival was 16 years in those aged 65 or less, 12 years in those aged 65 to 75, seven years in those aged 75 to 85, and six years in those aged more than 85. The incidence rate of stroke was 0.25 per 100 patient years (95% confidence interval 0.06 to 0.54) and atrial fibrillation 2.90 per 100 patient years (1.78 to 4.79). Post-SAVR, freedom from structural valve deterioration was 94.0% at 10 years, 81.7% at 15 years, and 52% at 20 years, and mean length of hospital stay was 12 days (95% confidence interval 9 to 15).

Conclusion Patients with severe symptomatic aortic stenosis undergoing SAVR with a bioprosthetic valve can expect only slightly lower survival than those without aortic stenosis, and a low incidence of stroke and, up to 10 years, of structural valve deterioration. The rate of deterioration increases rapidly after 10 years, and particularly after 15 years.

Introduction

Aortic valve replacement is the treatment of choice for patients with severe symptomatic aortic stenosis.1 Surgical aortic valve replacement (SAVR) reduces morbidity and mortality related to aortic stenosis and has been the procedure of choice for younger, low to intermediate risk patients, typically defined by the Society of Thoracic Surgeons predicted risk of mortality (STS-PROM) score of 8% or less.1 Because such patients require lifelong treatment with oral anticoagulants,2 use of mechanical valves has decreased and most SAVR procedures now use bioprosthetic valves.

Options facing patients with severe aortic stenosis include delaying any major procedure, undergoing SAVR with a mechanical valve, undergoing SAVR with a bioprosthetic valve, and undergoing transcatheter aortic valve implantation. Crucial to this decision is mortality after SAVR and structural valve deterioration resulting in heart failure, with possible need for a second valve replacement.

A recent systematic review and meta-analysis of observational studies reporting on long term outcomes with bioprosthetic valves suggest a low incidence for early and late mortality (5.03% per patient year and 1.68% per patient year, respectively) and a very low rate of reintervention (0.75% per patient year).3 Limitations of this review included failure to age stratify for mortality, the unlikely assumption of a constant hazard for the incidence rate for reintervention, failure to address outcomes of stroke and atrial fibrillation incidence, and failure to formally address the quality of evidence underlying the findings.

We therefore initiated our own systematic review of the prognosis of patients undergoing SAVR with a bioprosthetic valve. We conducted the review in parallel with systematic reviews addressing relative effects of transcatheter aortic valve implantation versus bioprosthetic SAVR in low and intermediate risk patients,4 and a related review of patients’ values and preferences.5 Our review addressed patient important outcomes of survival, stratified by patients’ age, and of stroke, atrial fibrillation, length of hospital stay, and structural valve deterioration with SAVR. These outcomes were chosen with the participation of patients who had undergone SAVR.

We conducted these reviews to inform recommendations6 for the first in a new series in The BMJ of trustworthy recommendations published in response to potentially practice changing evidence,7 so called Rapid Recommendations. For such recommendations, the panel overseeing the new series requires estimates of absolute risk obtained by applying relative risk estimates from randomised trials to best estimates of baseline risk. Such baseline risks ideally come from observational studies that typically enrol more representative patients than do randomised trials, and follow patients for far longer.

Methods

Data sources and searches

We created the search strategy informed by a previously published comprehensive systematic search,8 with modifications to capture observational studies. We searched Medline, Embase, PubMed (non-Medline records only), Cochrane Database of Systematic Reviews, and Cochrane CENTRAL from conception to 30 June 2016. Supplementary appendix A presents the search strategy. We identified additional references by searching the reference lists of included publications and relevant narrative reviews.

Study selection

Eligible observational studies enrolled adults (≥18 years) with symptomatic aortic stenosis undergoing SAVR using a bioprosthetic valve. We included studies reporting on patients with mechanical valves if results in patients receiving bioprosthetic valves were reported separately or if 80% or greater of the participants received bioprosthetic valves. Patient important outcomes were identified by the Rapid Recommendations panel responsible for creating recommendations, composed of clinicians, researchers, methodologists, and patients.6 Eligible SAVR studies, unrestricted by language, reported on mortality, stroke, atrial fibrillation, structural valve deterioration, index admission length of stay, or postoperative pain. To ensure that our review was relevant to current technologies, we included only studies published after 2006; for the sake of efficiency, we excluded studies enrolling fewer than 50 patients. When more than one study reported on the same population, we used data from all studies that provided relevant comprehensive information.

Seven reviewers, working in pairs, independently screened titles and abstracts of identified citations, evaluating the full text of potentially eligible articles using a standardised screening form (see supplementary appendix B). The Covidence systematic review platform provided software for screening.9

Data abstraction and risk of bias assessment

Ten reviewers, working in pairs and using a standardised form, independently extracted data from eligible studies, including source of data, time frame of recruitment, definition and number of events, and population characteristics, including age, sex, history of coronary artery disease, chronic obstructive pulmonary disease, diabetes, hypertension, atrial fibrillation, and left ventricular ejection fraction, New York Heart Association classification, prior coronary artery bypass grafting, prior myocardial infarction, prior percutaneous coronary intervention, prior stroke or transient ischemic attack, logistic EuroSCORE, STS-PROM score, and concomitant coronary artery bypass grafting. For survival and structural valve deterioration post-SAVR, we applied Digitizeit10 to published Kaplan-Meier curves to obtain patient level freedom-from-event estimates over time. For stroke, atrial fibrillation, and structural valve deterioration in studies not presenting Kaplan-Meier curves, we collected the total number of events along with median follow-up time and incidence rates per 100 patient years, and captured information on postoperative length of hospital stay. Data from the Social Security Administration of United States of America11 provided life expectancy for the general population for comparison with estimates of survival post-SAVR obtained in our review.

The quality in prognostic studies (QUIPS)12 instrument provided criteria for assessing risk of bias in individual studies, including patient selection, study attrition, measurement of prognostic factors, outcome measurement, study confounding, and statistical analysis and reporting (see supplementary appendix C). The instrument rates studies as high, moderate, or low risk of bias. We classified studies with five or six low risk domains as at overall low risk of bias, studies with two or more high risk domains as at overall high risk of bias, and remaining studies as at overall moderate risk of bias.

The grading of recommendations, assessment, development, and evaluation (GRADE) system provided the structure for assessing confidence in prognostic risk estimates13 as high, moderate, low, or very low based on considerations of risk of bias, consistency, precision, directness, and publication bias. The last was assessed using visual inspection of funnel plots.

Data synthesis and statistical analysis

Using an established algorithm, we estimated and pooled individual patient data to obtain an overall estimate of survival and freedom from structural valve deterioration.14 Owing to the lack of Kaplan-Meier curves for stroke and atrial fibrillation, we combined and presented the study results as incidence rates per 100 patient years post-intervention for each outcome using Metaprop’s DerSimonian and Laird random effects model, with a binomial distribution to model within study variability or stabilise variances by applying Freeman-Tukey double arcsine transformation.15

We addressed statistical heterogeneity through consistency of point estimates and extent of overlap of confidence intervals. Heterogeneity was not assessed with I2 statistics, as this is typically not useful in prognostic studies with a large sample size and resulting precise estimates.13 To identify potential sources of heterogeneity, we performed subgroup analyses for age, valve type, and risk of bias, specified a priori. We hypothesised higher adverse event rates in older patients, in studies that included only bioprosthetic valves versus studies that also included mechanical valves. We established age thresholds consistent with the requirements for Rapid Recommendations: study mean or median age of ≤65, 65 to <75, 75 to <85, and ≥85.6 For survival estimates, we used the log-rank test to compare survival across the different age groups. We defined a half weighted threshold age in which close to 50% of the total sample, within each age subgroup, is above and below this threshold. For these age thresholds, we obtained life expectancy estimates from the Social Security Administration of United States of America.11 We compared our median survival estimates with life expectancy estimates of the US general population.

A two sided P value of 0.05 or less was considered statistically significant. Review Manager 5 and STATA16 17 provided software for statistical analyses, as well as forest plots and funnel plots.

Patient involvement

The parallel Rapid Recommendations guideline panel, which included two patients, requested this meta-analysis and included two people with experience of severe aortic stenosis. The patient panel members helped choose the outcomes examined in this systematic review and uniquely highlighted pain and physical function. We were unable to find direct evidence for either of those outcomes. Feedback from the community panel members guided the interpretation and dissemination of our results.

Results

Study selection and characteristics

The 93 eligible studies enrolled patients from 1977 to 2013 and reported on 53 884 predominantly male patients with aortic stenosis (mean age 53 to 92 years) undergoing aortic valve replacement. Figure 1⇓ presents the flow diagram for study selection following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) format. Supplementary appendix C summarizes the characteristics of the eligible studies.

Figure1

Risk of bias in individual studies

Supplementary appendix D summarizes the quality assessment of individual studies. Of the 93 studies, 51 proved at overall low risk of bias.18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 Twenty one of the remaining 42 proved at overall moderate risk of bias69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 and 21 at overall high risk of bias.90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110

Survival post-SAVR

All 85 studies that reported survival post-SAVR analyzed data using a Kaplan-Meier method. Studies provided pooled survival estimates of 89.7% at two years, 78.4% at five years, 57.0% at 10 years, 39.7% at 15 years, and 24.7% at 20 years. Supplementary appendix H provides the life table that informed estimates for Rapid Recommendations.6 A subgroup analysis comparing studies with a mean or median age of ≤65, 65 to 75, 75 to 85, and more than 85 showed survival at five years of 83.7%, 81.4%, 67.4%, and 52.2%, respectively (interaction P<0.001, fig 2⇓). Studies provided approximate median survival estimates of 16 years in patients aged 65 or less (half weighted group age 59, US general population life expectancy 22.2), 12 years in those aged 65 to 75 (half weighted group age 68, US general population life expectancy 15.6), seven years in those aged 75 to 85 (median age 79, half weighted US general population life expectancy 8.7), and six years in those aged more than 85 (mean age 92, US general population life expectancy 3.5).11 Studies provided similar estimates of survival across risk of bias and valve type. The overall confidence in the estimate of mortality is moderate (table1⇓), with the main limitation being serious inconsistency in survival estimates across individual studies.

Table 1

GRADE evidence profile on risk estimates summarizing findings from observational studies of surgical aortic valve replacement in patients with severe aortic stenosis

Stroke post-SAVR

The seven studies reporting stroke post-SAVR23 36 40 62 64 69 90 provided number of events both within and beyond the postoperative period as well as median follow-up time, allowing for calculation of incidence rate per 100 patients years. Studies provided a pooled estimate for incidence of stroke of 0.25 per 100 patient years (95% confidence interval 0.06 to 0.54, table 1⇑). Subgroup analysis comparing studies revealed that chance easily explained differences between studies restricted to patients receiving bioprosthetic valves and those including patients receiving mechanical valves (bioprosthetic only, 0.38 per 100 patients years, 0.22 to 0.58; mixed population, 0.12 per 100 patients years, 0.00 to 0.49; interaction P=0.26), and based on age categories (<75, 0.28 per 100 patients years, 0.08 to 0.57; >75, 0.55 per 100 patient years, 0.15 to 1.15; interaction P=0.26). The overall confidence in the estimate of stroke is moderate because of imprecision (table 1⇑).

Atrial fibrillation post-SAVR

Two studies including a total of 177 patients reported that 21 developed atrial fibrillation post-SAVR.23 106 The pooled incidence rate of these studies was 2.90 per 100 patient years (1.78 to 4.79) (table 1⇑). The small number of studies precluded subgroup analysis. The overall confidence in the estimate of atrial fibrillation is low owing to serious risk of bias and imprecision (table 1⇑).

Structural valve deterioration

Twelve studies21 22 25 26 27 33 53 68 69 81 85 90 with published Kaplan-Meier curves including 7603 patients reported on structural valve deterioration after SAVR. Supplementary appendix F presents the definition for structural valve deterioration across all 12 studies. Although the definitions are worded slightly differently, they all objectively defined valve dysfunction as severe stenosis or regurgitation through echocardiographic assessment. Studies estimated a cumulative incidence of 6.0% by 10 years, 19.3% by 15 years, and 48.0% by 20 years (fig 3⇓). Risk of bias assessment deemed all but one study to be at low risk of bias. The overall confidence in the estimates of structural valve deterioration post-SAVR is high.

Figure3

Fig 3 Freedom from structural valve deterioration after surgical aortic valve replacement with a bioprosthetic valve. Individual patient data estimated using algorithm developed by Guyot et al 201214

Length of hospital stay

The pooled mean estimate for length of hospital stay in 11 studies20 23 31 3962 64 65 75 85 101 103 that enrolled 6405 patients undergoing SAVR was 13 days (95% confidence interval 10 to 16, table 1⇑). Subgroup analysis comparing studies at low risk of bias with those at moderate and high risk of bias showed an interaction P value of 0.05 (low risk of bias, 12 days, 95% confidence interval 9 to 15; high risk of bias, 15 days, 14 to 16). Given the P value on the test for interaction, we considered the low risk of bias studies to be more trustworthy, providing high confidence in the estimate of length of hospital stay (table 1⇑).

Postoperative pain

No eligible studies reported on postoperative pain.

Discussion

In this systematic review and meta-analysis of outcomes after surgical aortic valve replacement (SAVR) we provide prognostic estimates for patient important outcomes needed to determine absolute effects of SAVR for patient important outcomes. The timeliness of the review is underscored by the potentially practice changing evidence emerging from the Partner 2 trial concerning transcatheter aortic valve implantation as an alternative to SAVR in patients at low to intermediate risk of perioperative mortality.111 Our findings, together with linked systematic reviews on treatment effects and patient preferences and values, inform trustworthy recommendations for clinical practice developed in the new The BMJ series Rapid Recommendations.6

Principal findings

From the time of surgery, the approximate median survival in patients undergoing SAVR is 16 years in those aged 65 or less years, 12 years in patients aged 65 to 75, seven years in those aged 75 to 85, and six years in those older than 85 (fig 2⇑). The median survival in patients aged 65 or less years is approximately five years less than that of the general population, but it is similar to the general population in patients older than 65. Evidence in patients with an average age of more than 85, taken from a single study, suggested a longer life span than that of the general population of the same age. This likely reflects that only exceptionally healthy patients of this advanced age were considered for SAVR.

Over the decade after SAVR, patients participating in these studies experienced a risk of stroke less than 3%, a risk of atrial fibrillation less than 30%, and a risk of structural valve deterioration less than 10%. The rate of structural valve deterioration, however, increases rapidly after 10 years, with deterioration occurring in almost 50% of patients by 20 years.

Age has a strong association with mortality; estimates differed according to risk of bias only for duration of hospital stay (lower risk of bias studies reported shorter hospital stay). With respect to stroke, age did not influence the frequency. We found only one study reporting on stroke in patients of mean age 65 or less, and no studies of mean age 85 or more. Thus there is need for future research to better understand the extent to which risk of stroke varies across age groups.

In these studies, patients undergoing SAVR stayed in hospital an average of 12 days (95% confidence interval 9 to 15 days). We found one study to be an outlier, with a mean length of stay post-SAVR of five days.39 Most patients in this study were in New York Heart Association class I and II (89%). The relatively normal functional status of these patients may be responsible for the shorter length of stay post-surgery. One study, from the German registry on SAVR (not included in our systematic review because it was published after we had completed our search), reported an average length of stay of 12 days, in keeping with our results.112

Strengths and limitations of this review

Strengths of our systematic review include a comprehensive search of databases for all observational studies and a review of citations of not only eligible studies but prior narrative reviews. Reviewers abstracted data and applied the QUIPS instrument for risk of bias, independently and in duplicate. We conducted subgroup analyses exploring the impact of age, risk of bias, and population (all bioprosthetic or mixed) on outcomes. We also rated the confidence in prognostic estimates for each outcome using guidance from the GRADE working group.13

One limitation of this review is that the method we used for pooling survival across studies using published Kaplan-Meier curves assumes a constant rate of censoring through time.14 The algorithm underlying this method does not consider the standard error in survival estimates and thus the variability in results across studies. This method therefore does not account for the varying sample sizes from which the individual patient data are estimated. Thus we are unable to generate confidence intervals around survival estimates and cumulative incidences. Another limitation of this method is the inability to perform competing risk analysis, which would require individual patient data from source studies. The current analysis captures mortality as a censored event when the outcome of interest is structural valve deterioration. As a result, this modifies the probability of structural valve deterioration, resulting in inaccurate cumulative incidence for this event.

In our survival analysis, we subclassified studies based on prespecified age categories. We classified studies using the reported mean or median age. It is possible for some studies to be classified in one category but have patients that belong to another age category (based on the distribution of age). This likely underestimates differences in survival according to age. Furthermore, only one study had participants with a mean age of 92, and thus the age group 85 or older is informed by very few patients (n=119).

Our calculation of incidence rate depended on mean or median follow-up and assumed a constant incidence over time. When this is not the case (as it clearly is not for atrial fibrillation and structural valve deterioration) the incidence rates may be misleading.

For instance, two studies reported the absolute number of patients with new onset atrial fibrillation during the follow-up period. Collectively, they provided an incidence rate of 2.90 per 100 patient years. Based on this incidence rate, the risk of new onset atrial fibrillation by four years is 12%. In the PARTNER 2A trial, approximately 27 of 100 patients developed atrial fibrillation by two years.111 Our incidence rate is based on a longer median follow-up (four years, versus two years maximum follow-up in PARTNER 2A). The hazard for atrial fibrillation is highest in the postoperative period and much lower thereafter; this to some extent explains the difference in estimates. Other explanations include differences between the demographics of patients included in our review and those included in the PARTNER 2A trial. For instance, the average age of patients undergoing SAVR in the PARTNER 2A trial is 81.7 years; the two cohorts that inform our atrial fibrillation incidence rate enrolled patients of mean age 58 and 77 years.

We presented our estimate for length of hospital stay post-SAVR using the mean. The length of stay might be expected to have an upward skewed distribution, necessitating the use of median for reporting the central tendency. Therefore, our reported mean length of stay may be an overestimation as a result of improper statistical reporting of source studies.

We found high quality evidence for length of hospital stay and structural valve deterioration. Imprecision was a common limitation in other outcomes, which also limits subgroup analyses (for instance, we found no association between age and risk of stroke, likely because the analysis was underpowered).

Comparison with other findings

Our current paper and the previous systematic review and meta-analysis by Huygens et al both address prognosis after SAVR with bioprosthetic valves over a similar period.3 The study by Huygens et al, however, failed to age stratify for mortality; our results, not surprisingly, show large differences in mortality across age groups. The study by Huygens et al focused on reinterventions, ignoring the functional deterioration that accompanies structural valve deterioration in those who do not undergo reintervention. In addressing reintervention, these authors made the unlikely assumption of a constant hazard. We utilized a novel method to obtain estimates for structural valve deterioration at all time points post-SAVR, and demonstrate the low rate of structural valve deterioration in the first decade after operation and the rapid increase thereafter, particularly after 15 years. In addition, our review addressed the additional patient important outcomes of atrial fibrillation, stroke, and length of hospital stay. Finally, we utilized the GRADE approach to evaluate confidence in our estimates for all outcomes, establishing that some evidence (structural valve deterioration, stroke) is high quality (and thus trustworthy), some (mortality, stroke) is moderate quality, and some (atrial fibrillation) only low quality.

Conclusion

For patients who undergo SAVR using a bioprosthetic valve, evidence with moderate to high confidence suggests a survival close to that of general populations of the same age, a low incidence of stroke, and infrequent structural valve deterioration for the first decade, with increasing incidence thereafter.

Linked articles in this BMJ Rapid Recommendations cluster

What is already known on this topic

What this study adds

Footnotes

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.

References

  1. ↵
    Nishimura RA, Otto CM, Bonow RO, et al. ACC/AHA Task Force Members. 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation2014;129:2440-92. doi:10.1161/CIR.0000000000000029 pmid:24589852.
  2. ↵
  3. ↵
    Huygens SA, Mokhles MM, Hanif M, et al. Contemporary outcomes after surgical aortic valve replacement with bioprostheses and allografts: a systematic review and meta-analysis. Eur J Cardiothorac Surg2016;ezw101. doi:10.1093/ejcts/ezw101 pmid:27026750.
  4. ↵
    Siemieniuk RA, Agoritsas T, Manja V, et al. Transcatheter versus surgical aortic valve replacement in patients with severe aortic stenosis at low and intermediate risk: systematic review and meta-analysis.BMJ;2016:354:i5130.
  5. ↵
    Lytvyn L, Guyatt GH, Manja V, et al. Patient values and preferences on transcatheter or surgical aortic valve replacement therapy for aortic stenosis: a systematic review. BMJ Open2016;6:e014327.
  6. ↵
    Vandvik PO, Otto CM, Siemieniuk RA, et al. Transcatheter or surgical aortic valve replacement for patients with severe, symptomatic, aortic stenosis at low to intermediate surgical risk: a clinical practice guideline. BMJ2016:354:i5085.
  7. ↵
    Siemieniuk RA, Macdonald H, Agoritsas T, Guyatt GH, Brandt L, Vandvik PO. Introduction to BMJ Rapid Recommendations. BMJ2016;354:i5191.
  8. ↵
    Cao C, Liou KP, Pathan FK, et al. Transcatheter Aortic Valve Implantation versus Surgical Aortic Valve Replacement: Meta-Analysis of Clinical Outcomes and Cost-Effectiveness. Curr Pharm Des2016;22:1965-77. doi:10.2174/1381612822666160219120713 pmid:26891807.
  9. ↵
    Fabián J, Bass K, Fischer V, et al. [Dilated cardiomyopathy and heart transplantation]. Bratisl Lek Listy1997;98:243-7.pmid:9296828.
  10. ↵
  11. ↵
  12. ↵
  13. ↵
    Iorio A, Spencer FA, Falavigna M, et al. Use of GRADE for assessment of evidence about prognosis: rating confidence in estimates of event rates in broad categories of patients. BMJ2015;350:h870. doi:10.1136/bmj.h870 pmid:25775931.
  14. ↵
    Guyot P, Ades AE, Ouwens MJ, Welton NJ. Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves. BMC Med Res Methodol2012;12:9. doi:10.1186/1471-2288-12-9 pmid:22297116.
  15. ↵
  16. ↵
    Review Manager (RevMan). (The Nordic Cochrane Centre, The Cochrane Collaboration, 2014).
  17. ↵
  18. ↵
    Accola KD, Scott ML, Palmer GJ, et al. Surgical management of aortic valve disease in the elderly: A retrospective comparative study of valve choice using propensity score analysis. J Heart Valve Dis2008;17:355-64, discussion 365.pmid:18751463.
  19. ↵
    Ali A, Patel A, Ali Z, et al. Enhanced left ventricular mass regression after aortic valve replacement in patients with aortic stenosis is associated with improved long-term survival. J Thorac Cardiovasc Surg2011;142:285-91. doi:10.1016/j.jtcvs.2010.08.084 pmid:21272899.
  20. ↵
  21. ↵
    Aupart MR, Mirza A, Meurisse YA, Sirinelli AL, Neville PH, Marchand MA. Perimount pericardial bioprosthesis for aortic calcified stenosis: 18-year experience with 1133 patients. J Heart Valve Dis2006;15:768-75, discussion 775-6.pmid:17152784.
  22. ↵
    Auriemma S, D’Onofrio A, Brunelli M, et al. Long-term results of aortic valve replacement with Edwards Prima Plus stentless bioprosthesis: eleven years’ follow up. J Heart Valve Dis2006;15:691-5.pmid:17044376.
  23. ↵
    Aydin E, Yerlikhan OA, Tuzun B, Ozen Y, Sarikaya S, Kirali MK. How to approach aortic valve disease in the elderly: a 25-year retrospective study. Cardiovasc J Afr2014;25:244-8. doi:10.5830/CVJA-2014-051 pmid:25629541.
  24. ↵
    Barone-Rochette G, Piérard S, De Meester de Ravenstein C, et al. Prognostic significance of LGE by CMR in aortic stenosis patients undergoing valve replacement. J Am Coll Cardiol2014;64:144-54. doi:10.1016/j.jacc.2014.02.612 pmid:25011718.
  25. ↵
    Benhameid O, Jamieson WR, Castella M, et al. CarboMedics Mitroflow pericardial aortic bioprosthesis - performance in patients aged 60 years and older after 15 years. Thorac Cardiovasc Surg2008;56:195-9. doi:10.1055/s-2008-1038385 pmid:18481236.
  26. ↵
  27. ↵
    Bourguignon T, Lhommet P, El Khoury R, et al. Very long-term outcomes of the Carpentier-Edwards Perimount aortic valve in patients aged 50-65 years. Eur J Cardiothorac Surg2016;49:1462-8. doi:10.1093/ejcts/ezv384 pmid:26530269.
  28. ↵
    Rubio Alvarez J, Sierra Quiroga J, Vega Fernandez M, et al. Up to twenty-five-year survival after aortic valve replacement with size 19 mm valves. Interact Cardiovasc Thorac Surg2010;10:32-5. doi:10.1510/icvts.2009.209197 pmid:19770137.
  29. ↵
    Christ T, Grubitzsch H, Claus B, Heinze G, Dushe S, Konertz W. Hemodynamic behavior of stentless aortic valves in long term follow-up. J Cardiothorac Surg2014;9:197. doi:10.1186/s13019-014-0197-2 pmid:25527116.
  30. ↵
    Concistrè G, Dell’aquila A, Pansini S, et al. Aortic valve replacement with smaller prostheses in elderly patients: does patient prosthetic mismatch affect outcomes?J Card Surg2013;28:341-7. doi:10.1111/jocs.12136 pmid:23691967.
  31. ↵
  32. ↵
  33. ↵
  34. ↵
    ElBardissi AW, Shekar P, Couper GS, Cohn LH. Minimally invasive aortic valve replacement in octogenarian, high-risk, transcatheter aortic valve implantation candidates. J Thorac Cardiovasc Surg2011;141:328-35. doi:10.1016/j.jtcvs.2010.08.056 pmid:21047646.
  35. ↵
    Elhmidi Y, Piazza N, Mazzitelli D, Wottke M, Lange R, Bleiziffer S. Sex-related differences in 2197 patients undergoing isolated surgical aortic valve replacement. J Card Surg2014;29:772-8. doi:10.1111/jocs.12442 pmid:25264220.
  36. ↵
  37. ↵
    Flameng W, Herregods MC, Vercalsteren M, Herijgers P, Bogaerts K, Meuris B. Prosthesis-patient mismatch predicts structural valve degeneration in bioprosthetic heart valves. Circulation2010;121:2123-9. doi:10.1161/CIRCULATIONAHA.109.901272 pmid:20439787.
  38. ↵
  39. ↵
  40. ↵
    Glauber M, Gilmanov D, Farneti PA, et al. Right anterior minithoracotomy for aortic valve replacement: 10-year experience of a single center. J Thorac Cardiovasc Surg2015;150:548-56.e2. doi:10.1016/j.jtcvs.2015.06.045 pmid:26215359.
  41. ↵
    Grupper A, Beigel R, Maor E, et al. Survival after intervention in patients with low gradient severe aortic stenosis and preserved left ventricular function. J Thorac Cardiovasc Surg2014;148:2823-7. doi:10.1016/j.jtcvs.2014.03.039 pmid:24787695.
  42. ↵
  43. ↵
  44. ↵
    Hong S, Yi G, Youn YN, Lee S, Yoo KJ, Chang BC. Effect of the prosthesis-patient mismatch on long-term clinical outcomes after isolated aortic valve replacement for aortic stenosis: a prospective observational study. J Thorac Cardiovasc Surg2013;146:1098-104. doi:10.1016/j.jtcvs.2012.07.101 pmid:22959323.
  45. ↵
    Howell NJ, Keogh BE, Ray D, et al. Patient-prosthesis mismatch in patients with aortic stenosis undergoing isolated aortic valve replacement does not affect survival. Ann Thorac Surg2010;89:60-4. doi:10.1016/j.athoracsur.2009.07.037 pmid:20103206.
  46. ↵
    Iturra SA, Suri RM, Greason KL, et al. Outcomes of surgical aortic valve replacement in moderate risk patients: implications for determination of equipoise in the transcatheter era. J Thorac Cardiovasc Surg2014;147:127-32. doi:10.1016/j.jtcvs.2013.08.036 pmid:24094915.
  47. ↵
    Kapadia SR, Tuzcu EM, Makkar RR, et al. Long-term outcomes of inoperable patients with aortic stenosis randomly assigned to transcatheter aortic valve replacement or standard therapy. Circulation2014;130:1483-92. doi:10.1161/CIRCULATIONAHA.114.009834 pmid:25205802.
  48. ↵
    Kato Y, Tsutsumi Y, Kawai T, Goto T, Takahashi Y, Ohashi H. Aortic valve replacement for aortic stenosis in the elderly: influence of prosthesis-patient mismatch on late survival and left ventricular mass regression. Gen Thorac Cardiovasc Surg2008;56:397-403. doi:10.1007/s11748-008-0261-8 pmid:18696205.
  49. ↵
    Kobayashi KJ, Williams JA, Nwakanma L, Gott VL, Baumgartner WA, Conte JV. Aortic valve replacement and concomitant coronary artery bypass: assessing the impact of multiple grafts. Ann Thorac Surg2007;83:969-78. doi:10.1016/j.athoracsur.2006.10.027 pmid:17307443.
  50. ↵
    Kulik A, Burwash IG, Kapila V, Mesana TG, Ruel M. Long-term outcomes after valve replacement for low-gradient aortic stenosis: impact of prosthesis-patient mismatch. Circulation2006;114(Suppl):I553-8.pmid:16820636.
  51. ↵
    Levy F, Laurent M, Monin JL, et al. Aortic valve replacement for low-flow/low-gradient aortic stenosis operative risk stratification and long-term outcome: a European multicenter study. J Am Coll Cardiol2008;51:1466-72. doi:10.1016/j.jacc.2007.10.067 pmid:18402902.
  52. ↵
    Linneweber J, Heinbokel T, Christ T, Claus B, Kossagk C, Konertz W. Clinical experience with the ATS 3F stentless aortic bioprosthesis: five years’ follow up. J Heart Valve Dis2010;19:772-7.pmid:21214103.
  53. ↵
    Matsumoto Y, Fujita T, Hata H, Shimahara Y, Sato S, Kobayashi J. Hemodynamic Performance and Durability of Mosaic Bioprostheses for Aortic Valve Replacement, up to 13 Years. Circ J2015;79:1044-51. doi:10.1253/circj.CJ-14-0990 pmid:25740500.
  54. ↵
    McLean RC, Briggs AH, Slack R, et al. Perioperative and long-term outcomes following aortic valve replacement: a population cohort study of 4124 consecutive patients. Eur J Cardiothorac Surg2011;40:1508-14. doi:10.1016/j.ejcts.2011.01.088. pmid:21493086.
  55. ↵
    Muneretto C, Alfieri O, Cesana BM, et al. A comparison of conventional surgery, transcatheter aortic valve replacement, and sutureless valves in “real-world” patients with aortic stenosis and intermediate- to high-risk profile. J Thorac Cardiovasc Surg2015;150:1570-7, discussion 1577-9. doi:10.1016/j.jtcvs.2015.08.052 pmid:26384753.
  56. ↵
    Muneretto C, Bisleri G, Moggi A, et al. Treating the patients in the ‘grey-zone’ with aortic valve disease: a comparison among conventional surgery, sutureless valves and transcatheter aortic valve replacement. Interact Cardiovasc Thorac Surg2015;20:90-5. doi:10.1093/icvts/ivu340 pmid:25320140.
  57. ↵
    Nyawo B, Graham R, Hunter S. Aortic valve replacement with the Sorin Pericarbon Freedom stentless valve: five-year follow up. J Heart Valve Dis2007;16:42-8.pmid:17315382.
  58. ↵
  59. ↵
  60. ↵
    Papadopoulos N, Schiller N, Fichtlscherer S, et al. Propensity matched analysis of longterm outcomes following transcatheter based aortic valve implantation versus classic aortic valve replacement in patients with previous cardiac surgery. J Cardiothorac Surg2014;9:99. doi:10.1186/1749-8090-9-99 pmid:24915763.
  61. ↵
    Petrov G, Dworatzek E, Schulze TM, et al. Maladaptive remodeling is associated with impaired survival in women but not in men after aortic valve replacement. JACC Cardiovasc Imaging2014;7:1073-80. doi:10.1016/j.jcmg.2014.06.017 pmid:25306541.
  62. ↵
    Redlich K, Khaladj N, Peterss S, et al. Conventional aortic valve replacement in patients with concomitant coronary artery disease and previous coronary artery bypass grafting in the era of interventional approaches. Eur J Cardiothorac Surg2011;40:455-62. doi:10.1016/j.ejcts.2010.11.067. pmid:21256760.
  63. ↵
    Schymik G, Heimeshoff M, Bramlage P, et al. A comparison of transcatheter aortic valve implantation and surgical aortic valve replacement in 1,141 patients with severe symptomatic aortic stenosis and less than high risk. Catheter Cardiovasc Interv2015;86:738-44. doi:10.1002/ccd.25866 pmid:25641398.
  64. ↵
    Wenaweser P, Pilgrim T, Kadner A, et al. Clinical outcomes of patients with severe aortic stenosis at increased surgical risk according to treatment modality. J Am Coll Cardiol2011;58:2151-62. doi:10.1016/j.jacc.2011.05.063 pmid:22078420.
  65. ↵
  66. ↵
    Christ T, Grubitzsch H, Claus B, Konertz W. Long-term follow-up after aortic valve replacement with Edwards Prima Plus stentless bioprostheses in patients younger than 60 years of age. J Thorac Cardiovasc Surg2014;147:264-9. doi:10.1016/j.jtcvs.2012.10.032 pmid:23158257.
  67. ↵
  68. ↵
    Joshi V, Prosser K, Richens D. Early prosthetic valve degeneration with Mitroflow aortic valves: determination of incidence and risk factors. Interact Cardiovasc Thorac Surg2014;19:36-40. doi:10.1093/icvts/ivu033 pmid:24667584.
  69. ↵
  70. ↵
    Beholz S, Repossini A, Livi U, et al. The Freedom SOLO valve for aortic valve replacement: clinical and hemodynamic results from a prospective multicenter trial. J Heart Valve Dis2010;19:115-23.pmid:20329497.
  71. ↵
    Dagenais F, Mathieu P, Doyle D, Dumont É, Voisine P. Moderate aortic stenosis in coronary artery bypass grafting patients more than 70 years of age: to replace or not to replace?Ann Thorac Surg2010;90:1495-9, discussion 1499-500. doi:10.1016/j.athoracsur.2010.06.036 pmid:20971247.
  72. ↵
    Ding WH, Lam YY, Pepper JR, et al. Early and long-term survival after aortic valve replacement in septuagenarians and octogenarians with severe aortic stenosis. Int J Cardiol2010;141:24-31. doi:10.1016/j.ijcard.2008.11.126 pmid:19138807.
  73. ↵
    Dubois C, Coosemans M, Rega F, et al. Prospective evaluation of clinical outcomes in all-comer high-risk patients with aortic valve stenosis undergoing medical treatment, transcatheter or surgical aortic valve implantation following heart team assessment. Interact Cardiovasc Thorac Surg2013;17:492-500. doi:10.1093/icvts/ivt228 pmid:23702465.
  74. ↵
    Ennker JA, Ennker IC, Albert AA, Rosendahl UP, Bauer S, Florath I. The Freestyle stentless bioprosthesis in more than 1000 patients: a single-center experience over 10 years. J Card Surg2009;24:41-8. doi:10.1111/j.1540-8191.2008.00732.x pmid:19120674.
  75. ↵
    George I, Yerebakan H, Kalesan B, et al. Age alone should not preclude surgery: contemporary outcomes after aortic valve replacement in nonagenarians. J Thorac Cardiovasc Surg2014;148:1360-1369.e1. doi:10.1016/j.jtcvs.2014.01.015 pmid:24560419.
  76. ↵
    Glaser N, Franco-Cereceda A, Sartipy U. Late haemodynamic performance and survival after aortic valve replacement with the Mosaic bioprosthesis. Interact Cardiovasc Thorac Surg2014;19:756-62. doi:10.1093/icvts/ivu238 pmid:25016530.
  77. ↵
  78. ↵
    Higgins J, Jamieson WR, Benhameid O, et al. Influence of patient gender on mortality after aortic valve replacement for aortic stenosis. J Thorac Cardiovasc Surg2011;142:595-601, 601.e1-2. doi:10.1016/j.jtcvs.2010.05.056. pmid:21247593.
  79. ↵
    Horst M, Easo J, Hölzl PP, et al. The Freedom SOLO valve: mid-term clinical results with a stentless pericardial valve for aortic valve replacement. J Heart Valve Dis2011;20:704-10.pmid:22655502.
  80. ↵
    Luciani GB, Viscardi F, Cresce GD, Faggian G, Mazzucco A. Seven-year performance of the Edwards Prima Plus stentless valve with the intact non-coronary sinus technique. J Card Surg2008;23:221-6. doi:10.1111/j.1540-8191.2008.00592.x pmid:18435636.
  81. ↵
    Milano AD, Dodonov M, Celiento M, et al. The Sorin freedom stentless pericardial valve: clinical and echocardiographic performance at 10 years. Int J Artif Organs2012;35:481-8. doi:10.5301/ijao.5000103 pmid:22661113.
  82. ↵
    Nguyen TC, Babaliaros VC, Razavi SA, et al. Transcatheter aortic valve replacement has improved short-term but similar midterm outcomes in isolated aortic valve replacement after prior coronary artery bypass grafting. Ann Thorac Surg2014;98:1316-24. doi:10.1016/j.athoracsur.2014.05.081 pmid:25149053.
  83. ↵
    Rodés-Cabau J, Pibarot P, Suri RM, et al. Impact of aortic annulus size on valve hemodynamics and clinical outcomes after transcatheter and surgical aortic valve replacement: insights from the PARTNER Trial. Circ Cardiovasc Interv2014;7:701-11. doi:10.1161/CIRCINTERVENTIONS.114.001681 pmid:25270901.
  84. ↵
    Scherner M, Madershahian N, Kuhr K, et al. Aortic valve replacement after previous heart surgery in high-risk patients: transapical aortic valve implantation versus conventional aortic valve replacement-a risk-adjusted and propensity score-based analysis. J Thorac Cardiovasc Surg2014;148:90-7. doi:10.1016/j.jtcvs.2013.07.046 pmid:24125091.
  85. ↵
    Sénage T, Le Tourneau T, Foucher Y, et al. Early structural valve deterioration of Mitroflow aortic bioprosthesis: mode, incidence, and impact on outcome in a large cohort of patients. Circulation2014;130:2012-20. doi:10.1161/CIRCULATIONAHA.114.010400 pmid:25355912.
  86. ↵
    Stassano P, Di Tommaso L, Vitale DF, et al. Aortic valve replacement and coronary artery surgery: determinants affecting early and long-term results. Thorac Cardiovasc Surg2006;54:521-7. doi:10.1055/s-2006-924467 pmid:17151966.
  87. ↵
  88. ↵
    Wang TKM, Sathananthan J, Chieng N, Gamble GD, Haydock DA, Ruygrok PN. Aortic valve replacement in over 70- and over 80-year olds: 5-year cohort study. Asian Cardiovasc Thorac Ann2014;22:526-33. doi:10.1177/0218492313497950 pmid:24867025.
  89. ↵
    Zannis K, Joffre J, Czitrom D, et al. Aortic valve replacement with the perceval S bioprosthesis: single-center experience in 143 patients. J Heart Valve Dis2014;23:795-802.pmid:25790630.
  90. ↵
    Amabile N, et al. Long-term results of freestyle stentless bioprosthesis in the aortic position: A single center cohort of 500 patients. Eur Heart J2014;35:686. doi:10.1093/eurheartj/ehu324. pmid:24474738.
  91. ↵
    Bernet FH, Baykut D, Grize L, Zerkowski HR. Single-center outcome analysis of 1,161 patients with St. Jude medical and ATS open pivot mechanical heart valves. J Heart Valve Dis2007;16:151-8.pmid:17484464.
  92. ↵
    D’Onofrio A, Salizzoni S, Agrifoglio M, et al. Medium term outcomes of transapical aortic valve implantation: results from the Italian Registry of Trans-Apical Aortic Valve Implantation. Ann Thorac Surg2013;96:830-5, discussion 836. doi:10.1016/j.athoracsur.2013.04.094 pmid:23870695.
  93. ↵
    Dewey TM, Brown D, Ryan WH, Herbert MA, Prince SL, Mack MJ. Reliability of risk algorithms in predicting early and late operative outcomes in high-risk patients undergoing aortic valve replacement. J Thorac Cardiovasc Surg2008;135:180-7. doi:10.1016/j.jtcvs.2007.09.011 pmid:18179938.
  94. ↵
    Englberger L, Carrel TP, Doss M, et al. Clinical performance of a sutureless aortic bioprosthesis: five-year results of the 3f Enable long-term follow-up study. J Thorac Cardiovasc Surg2014;148:1681-7. doi:10.1016/j.jtcvs.2014.03.054 pmid:24787699.
  95. ↵
  96. ↵
  97. ↵
    Hosono M, Sasaki Y, Hirai H, et al. Risk factors for late valve-related mortality after aortic valve replacement in elderly patients. Ann Thorac Cardiovasc Surg2013;19:368-74. doi:10.5761/atcs.oa.12.01983 pmid:23237930.
  98. ↵
    Kobayashi KJ, Williams JA, Nwakanma LU, et al. EuroSCORE predicts short- and mid-term mortality in combined aortic valve replacement and coronary artery bypass patients. J Card Surg2009;24:637-43. doi:10.1111/j.1540-8191.2009.00906.x pmid:20078709.
  99. ↵
    Koos R, Reinartz S, Mahnken AH, et al. Impact of aortic valve calcification severity and impaired left ventricular function on 3-year results of patients undergoing transcatheter aortic valve replacement. Eur Radiol2013;23:3253-61. doi:10.1007/s00330-013-2961-4 pmid:23821024.
  100. ↵
    Orłowska Baranowska E, Abramczuk E, Grabowski M, et al. Factors affecting long-term survival after aortic valve replacement. Kardiol Pol2012;70:1120-9.pmid:23180519.
  101. ↵
    Santarpino G, Pfeiffer S, Jessl J, et al. Clinical Outcome and Cost Analysis of Sutureless Versus Transcatheter Aortic Valve Implantation With Propensity Score Matching Analysis. Am J Cardiol2015;116:1737-43. doi:10.1016/j.amjcard.2015.08.043 pmid:26433277.
  102. ↵
    Sezai A, Osaka S, Yaoita H, et al. Early and Long-Term Outcomes in Japanese Patients Aged 80 Years or Older Undergoing Conventional Aortic Valve Replacement. Ann Thorac Cardiovasc Surg2015;21:247-53. doi:10.5761/atcs.oa.15-00067 pmid:26004118.
  103. ↵
    Subramanian S, Rastan AJ, Holzhey D, et al. Conventional aortic valve replacement in transcatheter aortic valve implantation candidates: a 5-year experience. Ann Thorac Surg2012;94:726-9, discussion 729-30. doi:10.1016/j.athoracsur.2012.04.068 pmid:22818966.
  104. ↵
    Svennevig JL, Abdelnoor M, Nitter-Hauge S. Twenty-five-year experience with the Medtronic-Hall valve prosthesis in the aortic position: a follow-up cohort study of 816 consecutive patients. Circulation2007;116:1795-800. doi:10.1161/CIRCULATIONAHA.106.677773 pmid:17893279.
  105. ↵
  106. ↵
    Umezu K, Saito S, Yamazaki K, Kawai A, Kurosawa H. Cardiac valvular surgery in dialysis patients: comparison of surgical outcome for mechanical versus bioprosthetic valves. Gen Thorac Cardiovasc Surg2009;57:197-202. doi:10.1007/s11748-008-0365-1 pmid:19367452.
  107. ↵
    Vohra HA, Whistance RN, Bolgeri M, et al. Mid-term evaluation of Sorin Soprano bioprostheses in patients with a small aortic annulus <or=20 mm. Interact Cardiovasc Thorac Surg2010;10:399-402. doi:10.1510/icvts.2009.217844 pmid:19952015.
  108. ↵
    Yakubov SJ, Adams DH, Watson DR, et al. CoreValve United States Clinical Investigators. 2-Year Outcomes After Iliofemoral Self-Expanding Transcatheter Aortic Valve Replacement in Patients With Severe Aortic Stenosis Deemed Extreme Risk for Surgery. J Am Coll Cardiol2015;66:1327-34. doi:10.1016/j.jacc.2015.07.042 pmid:26383718.
  109. ↵
    Yamashita MH, Ye J, Jamieson WR, Cheung A, Lichtenstein SV. Conventional aortic valve replacement remains a safe option in patients aged > or = 70 years: a 20-year experience. J Heart Valve Dis2012;21:148-55.pmid:22645847.
  110. ↵
  111. ↵
    Leon MB, Smith CR, Mack MJ, et al. PARTNER 2 Investigators. Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients. N Engl J Med2016;374:1609-20. doi:10.1056/NEJMoa1514616 pmid:27040324.
  112. ↵

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