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Figure 1.
Adjusted Between-Group Differences Between the Transcatheter Aortic Valve Replacement (TAVR) and Surgical Aortic Valve Replacement (SAVR) Cohorts Stratified by Access Sites
Adjusted Between-Group Differences Between the Transcatheter Aortic Valve Replacement (TAVR) and Surgical Aortic Valve Replacement (SAVR) Cohorts Stratified by Access Sites

A, Differences between TAVR and SAVR on the disease-specific Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score as well as the Physical Limitations, Total Symptoms, Quality of Life, and Social Limitations Subscales. B, Differences in generic health status between TAVR and SAVR as assessed by the Medical Outcomes Study Short-Form-36 (SF-36) physical and mental component summary scores as well as EuroQOL-5D (EQ-5D) utilities. Scales described in the Measurement of Health Status subsection. Error bars denote 95% CIs. P values represent the interaction between treatment group and access site at each time point.

Figure 2.
The Proportions of Transcatheter Aortic Valve Replacement (TAVR) and Surgical Aortic Valve Replacement (SAVR) Patients Achieving Specific Levels of Change in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Scores
The Proportions of Transcatheter Aortic Valve Replacement (TAVR) and Surgical Aortic Valve Replacement (SAVR) Patients Achieving Specific Levels of Change in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Scores

Changes from baseline to 1 month, 1 year, and 2 years, as defined in the Measurement of Health Status subsection. Proportions are presented separately for patients in the transfemoral (A) and transthoracic (B) access cohorts. The P values were based on ordinal logistic regression.

Table 1.  
Baseline Characteristics of the Primary Analytic Cohort
Baseline Characteristics of the Primary Analytic Cohort
Table 2.  
Within-Group Change in Health Status After TAVR or SAVR
Within-Group Change in Health Status After TAVR or SAVR
Table 3.  
Rates of Substantial or Moderate Improvement Over Time After TAVR and SAVR
Rates of Substantial or Moderate Improvement Over Time After TAVR and SAVR
1.
Schwarz  F, Baumann  P, Manthey  J,  et al.  The effect of aortic valve replacement on survival.  Circulation. 1982;66(5):1105-1110.PubMedGoogle ScholarCrossref
2.
Sundt  TM, Bailey  MS, Moon  MR,  et al.  Quality of life after aortic valve replacement at the age of >80 years.  Circulation. 2000;102(19)(suppl 3):III70-III74.PubMedGoogle Scholar
3.
Khan  JH, McElhinney  DB, Hall  TS, Merrick  SH.  Cardiac valve surgery in octogenarians: improving quality of life and functional status.  Arch Surg. 1998;133(8):887-893.PubMedGoogle ScholarCrossref
4.
Leon  MB, Smith  CR, Mack  M,  et al; PARTNER Trial Investigators.  Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery.  N Engl J Med. 2010;363(17):1597-1607.PubMedGoogle ScholarCrossref
5.
Adams  DH, Popma  JJ, Reardon  MJ.  Transcatheter aortic-valve replacement with a self-expanding prosthesis.  N Engl J Med. 2014;371(10):967-968.PubMedGoogle ScholarCrossref
6.
Leon  MB, Smith  CR, Mack  MJ,  et al; PARTNER 2 Investigators.  Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.  N Engl J Med. 2016;374(17):1609-1620.PubMedGoogle ScholarCrossref
7.
Reynolds  MR, Magnuson  EA, Lei  Y,  et al; Placement of Aortic Transcatheter Valves (PARTNER) Investigators.  Health-related quality of life after transcatheter aortic valve replacement in inoperable patients with severe aortic stenosis.  Circulation. 2011;124(18):1964-1972.PubMedGoogle ScholarCrossref
8.
Osnabrugge  RL, Arnold  SV, Reynolds  MR,  et al; CoreValve US Trial Investigators.  Health status after transcatheter aortic valve replacement in patients at extreme surgical risk: results from the CoreValve US trial.  JACC Cardiovasc Interv. 2015;8(2):315-323.PubMedGoogle ScholarCrossref
9.
Arnold  SV, Reynolds  MR, Wang  K,  et al; CoreValve US Pivotal Trial Investigators.  Health status after transcatheter or surgical aortic valve replacement in patients with severe aortic stenosis at increased surgical risk: results from the CoreValve US Pivotal Trial.  JACC Cardiovasc Interv. 2015;8(9):1207-1217.PubMedGoogle ScholarCrossref
10.
Reynolds  MR, Magnuson  EA, Wang  K,  et al; PARTNER Trial Investigators.  Health-related quality of life after transcatheter or surgical aortic valve replacement in high-risk patients with severe aortic stenosis: results from the PARTNER (Placement of Aortic Transcatheter Valve) Trial (Cohort A).  J Am Coll Cardiol. 2012;60(6):548-558.PubMedGoogle ScholarCrossref
11.
O’Brien  SM, Shahian  DM, Filardo  G,  et al; Society of Thoracic Surgeons Quality Measurement Task Force.  The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 2–isolated valve surgery.  Ann Thorac Surg. 2009;88(1)(suppl):S23-S42.PubMedGoogle ScholarCrossref
12.
Soto  GE, Jones  P, Weintraub  WS, Krumholz  HM, Spertus  JA.  Prognostic value of health status in patients with heart failure after acute myocardial infarction.  Circulation. 2004;110(5):546-551.PubMedGoogle ScholarCrossref
13.
Kosiborod  M, Soto  GE, Jones  PG,  et al.  Identifying heart failure patients at high risk for near-term cardiovascular events with serial health status assessments.  Circulation. 2007;115(15):1975-1981.PubMedGoogle ScholarCrossref
14.
Arnold  SV, Spertus  JA, Lei  Y,  et al.  Use of the Kansas City Cardiomyopathy Questionnaire for monitoring health status in patients with aortic stenosis.  Circ Heart Fail. 2013;6(1):61-67.PubMedGoogle ScholarCrossref
15.
Spertus  J, Peterson  E, Conard  MW,  et al; Cardiovascular Outcomes Research Consortium.  Monitoring clinical changes in patients with heart failure: a comparison of methods.  Am Heart J. 2005;150(4):707-715.PubMedGoogle ScholarCrossref
16.
Ware  JE  Jr, Sherbourne  CD.  The MOS 36-Item Short-Form Health Survey (SF-36)—I; conceptual framework and item selection.  Med Care. 1992;30(6):473-483.PubMedGoogle ScholarCrossref
17.
Kiebzak  GM, Pierson  LM, Campbell  M, Cook  JW.  Use of the SF36 general health status survey to document health-related quality of life in patients with coronary artery disease: effect of disease and response to coronary artery bypass graft surgery.  Heart Lung. 2002;31(3):207-213.PubMedGoogle ScholarCrossref
18.
Failde  I, Ramos  I.  Validity and reliability of the SF-36 Health Survey Questionnaire in patients with coronary artery disease.  J Clin Epidemiol. 2000;53(4):359-365.PubMedGoogle ScholarCrossref
19.
Ware  JKM, Bjorner  JB, Turner-Bowkes  DM, Gandek  B, Maruish  ME.  Determining Important Differences in Scores: User’s Manual for the SF-36v2 Health Survery. Lincoln, RI: Quality Metric Inc; 2007.
20.
Shaw  JW, Johnson  JA, Coons  SJ.  US valuation of the EQ-5D health states: development and testing of the D1 valuation model.  Med Care. 2005;43(3):203-220.PubMedGoogle ScholarCrossref
21.
Chan  PS, Soto  G, Jones  PG,  et al.  Patient health status and costs in heart failure: insights from the eplerenone post-acute myocardial infarction heart failure efficacy and survival study (EPHESUS).  Circulation. 2009;119(3):398-407.PubMedGoogle ScholarCrossref
22.
Grossi  EA, Zakow  PK, Ribakove  G,  et al.  Comparison of post-operative pain, stress response, and quality of life in port access vs standard sternotomy coronary bypass patients.  Eur J Cardiothorac Surg. 1999;16(suppl 2):S39-S42.PubMedGoogle Scholar
23.
Diegeler  A, Walther  T, Metz  S,  et al.  Comparison of MIDCAP versus conventional CABG surgery regarding pain and quality of life.  Heart Surg Forum. 1999;2(4):290-295.PubMedGoogle Scholar
24.
Walther  T, Falk  V, Metz  S,  et al.  Pain and quality of life after minimally invasive versus conventional cardiac surgery.  Ann Thorac Surg. 1999;67(6):1643-1647.PubMedGoogle ScholarCrossref
25.
Thourani  VH, Kodali  S, Makkar  RR,  et al.  Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis.  Lancet. 2016;387(10034):2218-2225.PubMedGoogle ScholarCrossref
Original Investigation
August 2017

Health Status Benefits of Transcatheter vs Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis at Intermediate Surgical RiskResults From the PARTNER 2 Randomized Clinical Trial

Author Affiliations
  • 1Saint Luke’s Mid America Heart Institute, School of Medicine, University of Missouri, Kansas City
  • 2Cedars-Sinai Medical Center, Los Angeles, California
  • 3Hospital of University of Pennsylvania, Philadelphia
  • 4Columbia University Medical Center, New York, New York
  • 5Emory University School of Medicine, Atlanta, Georgia
  • 6Cleveland Clinic, Cleveland, Ohio
  • 7Baylor Scott and White Healthcare, Plano, Texas
  • 8Baylor Health Care System, Plano, Texas
JAMA Cardiol. 2017;2(8):837-845. doi:10.1001/jamacardio.2017.2039
Key Points

Question  What is the effect of transcatheter aortic valve replacement vs surgical aortic valve replacement on health status in patients with severe aortic stenosis at intermediate surgical risk?

Findings  In this substudy of the PARTNER 2 randomized clinical trial involving 1833 patients, transcatheter aortic valve replacement and surgical aortic valve replacement were associated with health status improvement at 2 years. Patients undergoing transfemoral transcatheter aortic valve replacement demonstrated better early health status than those who underwent surgical aortic valve replacement, but by 1 year, there was no significant difference between the procedures.

Meaning  In patients with severe aortic stenosis at intermediate risk, transcatheter aortic valve replacement results in long-term health status benefits similar to those of surgical aortic valve replacement.

Abstract

Importance  In patients with severe aortic stenosis (AS) at intermediate surgical risk, treatment with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) results in similar 2-year survival. The effect of TAVR vs SAVR on health status in patients at intermediate surgical risk is unknown.

Objective  To compare health-related quality of life among intermediate-risk patients with severe AS treated with either TAVR or SAVR.

Design, Setting, and Participants  Between December 2011 and November 2013, 2032 intermediate-risk patients with severe AS were randomized to TAVR with the Sapien XT valve or SAVR in the Placement of Aortic Transcatheter Valve 2 Trial and were followed up for 2 years. Data analysis was conducted between March 1, 2016, to April 30, 2017.

Main Outcomes and Measures  Health status was assessed at baseline, 1 month, 1 year, and 2 years using the Kansas City Cardiomyopathy Questionnaire (KCCQ) (23 items covering physical function, social function, symptoms, self-efficacy and knowledge, and quality of life on a 0- to 100-point scale; higher scores indicate better quality of life), Medical Outcomes Study Short Form-36 (36 items covering 8 dimensions of health status as well as physical and mental summary scores; higher scores represent better health status), and EuroQOL-5D (assesses 5 dimensions of general health on a 3-level scale, with utility scores ranging from 0 [death] to 1 [ideal health]). Analysis of covariance was used to examine changes in health status over time, adjusting for baseline status.

Results  Of the 2032 randomized patients, baseline health status was available for 1833 individuals (950 TAVR, 883 SAVR) who formed the primary analytic cohort. A total of 1006 (54.9%) of the population were men; mean (SD) age was 81.4 (6.8) years. Over 2 years, both TAVR and SAVR were associated with significant improvements in both disease specific (16-22 points on the KCCQ-OS scale) and generic health status (3.9-5.1 points on the SF-36 physical summary scale). At 1 month, TAVR was associated with better health status than SAVR, but this difference was restricted to patients treated via transfemoral access (mean difference in the KCCQ overall summary [KCCQ-OS] score, 14.1 points; 95% CI, 11.7 to 16.4; P < .01) and was not seen in patients treated via transthoracic access (mean difference in KCCQ-OS, 3.5 points; 95% CI, −1.4 to 8.4; P < .01 for interaction). There were no significant differences between TAVR and SAVR in any health status measures at 1 or 2 years.

Conclusions and Relevance  Among intermediate-risk patients with severe AS, health status improved significantly with both TAVR and SAVR through 2 years of follow up. Early health status improvement was greater with TAVR, but only among patients treated via transfemoral access. Longer term follow-up is needed to assess the durability of quality-of-life improvement with TAVR vs SAVR in this population.

Trial Registration  clinicaltrials.gov Identifier: NCT01314313

Introduction

Patients with severe, symptomatic aortic stenosis (AS) benefit from aortic valve replacement both in terms of survival and quality of life (QOL).1-3 While surgical aortic valve replacement (SAVR) has long been the standard of care for treatment of AS, over the past decade, transcatheter aortic valve replacement (TAVR) has also been shown to be a viable treatment option for patients who are not suitable for SAVR or are at high risk for surgical complications.4,5 With growing experience and technological evolution, TAVR has been increasingly performed in patients at lower surgical risk. Recently, the Placement of Aortic Transcatheter Valve (PARTNER) 2 Cohort A trial demonstrated similar rates of death or disabling stroke at 2 years in patients at intermediate surgical risk treated with either SAVR or TAVR.6

Although prolonged survival remains a key benefit of valve replacement for patients with AS, for many individuals (who are generally elderly and have multiple comorbid conditions), improved QOL is an equally important consideration. Prior studies have shown that TAVR results in substantial QOL benefits in patients with AS who are unsuitable for SAVR7,8 and an early QOL benefit compared with SAVR for patients at high surgical risk.9,10 However, this early QOL benefit has been restricted to patients treated via the transfemoral approach and has not been seen in patients treated via alternative access. Whether these results apply to patients at intermediate surgical risk is currently unknown. In particular, it is unclear whether differences in procedure-related complications (eg, bleeding, paravalvular regurgitation, or permanent pacemaker implantation) might result in long-term differences in health status between the 2 treatments. To address these gaps in knowledge, we performed a prospective study alongside the PARTNER 2A trial to compare both short- and long-term health status outcomes in intermediate-risk patients with AS treated with either TAVR or SAVR.

Methods
Study Design and Population

The design of the PARTNER 2A trial (NCT01314313) has been described.6 Briefly, PARTNER 2A enrolled patients with severe, symptomatic AS at intermediate surgical risk at 57 sites in the United States and Canada. Severe AS was defined as (1) aortic valve area of 0.8 cm2 or less or aortic valve area index 0.5 cm2/m2 or less and (2) mean aortic valve gradient greater than 40 mm Hg or peak aortic jet velocity greater than 4.0 m/s. Patients were considered to be at intermediate surgical risk if they had a predicted 30-day surgical mortality of 4% to 8% as determined by the Society of Thoracic Surgeons mortality risk model (possible range of risk, 0%-100%; higher percentages indicate greater risk)11 and a multidisciplinary heart team. Key exclusion criteria included patients with a congenitally bicuspid aortic valve, severe renal disease, predominant aortic regurgitation, or left ventricular ejection fraction less than 20%. All patients underwent imaging to determine eligibility for transfemoral or transthoracic access (direct aortic or transapical approach) for TAVR. Patients were then stratified according to access route and randomized 1:1 to undergo either TAVR, using the Sapien XT valve (Edwards LifeSciences) or SAVR. The trial was approved by the institutional review board at each site (eAppendix in Supplement), and written informed consent was obtained from all patients.

Measurement of Health Status

Health status was evaluated in all patients at baseline, 1 month, 1 year, and 2 years. Disease-specific health status was assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ). The KCCQ is a 23-item questionnaire that covers 5 key domains of health status in patients with heart failure (physical function, social function, symptoms, self-efficacy and knowledge, and quality of life) and is scored from 0 to 100, with higher scores indicating better QOL. The individual scales of the KCCQ may be converted into a single overall summary score (KCCQ-OS), which has been shown to correlate well with important clinical outcomes, including rehospitalization, health care costs, and death in heart failure populations.12,13 The KCCQ-OS has also been shown to correlate with New York Heart Association functional class as follows: class I, 75-100; class II, 60-74; class III, 45-59; and class IV, 0-44.14,15 Small, moderate, and large clinical improvements have been shown to correspond with changes in the KCCQ-OS of approximately 5, 10, and 20 points, respectively.15 Recent work by our group demonstrated the reliability and validity of this instrument for patients with AS.14

Generic health status was evaluated using the Medical Outcomes Study Short-Form 36 (SF-36) questionnaire and the EuroQOL-5D (EQ-5D). The SF-36 assesses 8 dimensions of health status and has been validated in patients with cardiovascular disease.16-18 In addition, the SF-36 provides physical and mental component summary scales, which are scored such that the US population mean (SD) is 50 (10), with higher scores representing better health status. The minimum clinically important differences for the SF-36 physical and mental summary scales are approximately 2 points.19 The EQ-5D is a multiattribute health status classification system that assesses 5 dimensions of general health, using a 3-level scale, that are then transformed into preference-based utility weights using validated population sampling methods.20 These utilities range from 0 (death) to 1 (ideal health).

Statistical Analysis

The primary analysis compared the health status of patients randomized to TAVR vs SAVR on an intention-to-treat basis. A secondary analysis was performed, which included only patients who underwent their assigned treatment (per-protocol population). The primary end point was the KCCQ-OS score. All other QOL scales were considered secondary end points. Baseline characteristics were compared between the cohorts using 2-tailed t tests for continuous variables and χ2 tests for categorical variables. Mean changes in health status scores at all time points were compared with baseline within each treatment group using paired t tests. For each health status measure, scores between treatment groups at each time point were compared using analysis of covariance, adjusting for differences in baseline health status. Since prior studies of TAVR have demonstrated that access site can be associated with different clinical and health status outcomes,9,10 the analytic plan specified that, if a significant interaction (P < .05) between access site and treatment was observed on the KCCQ-OS at any time point, then all analyses would be stratified according to access site.

Categorical analyses incorporating both health status and survival were also performed to provide further perspective on the effect of these interventions over time. For these analyses, ordinal categories based on previously established thresholds for clinically relevant changes in the KCCQ-OS score15 were defined: death, worse (decrease from baseline >5 points), no change (change between −5 and <5 points), mildly improved (increase between 5 and <10 points), moderately improved (increase between 10 and <20 points), and substantially improved (increase ≥20 points). The relative effect of TAVR vs SAVR on health status was then compared between the 2 cohorts, using ordinal logistic regression after stratification for access site. Rates of substantial improvement and moderate improvement among surviving patients were also compared between TAVR and SAVR in the transfemoral and transthoracic groups, using logistic regression.

Results
Study Population

Of the 2032 patients randomized in the PARTNER 2A trial, baseline health status was available for 1833 patients (950 TAVR; 883 SAVR) who formed the primary analytic cohort. Baseline characteristics of the analytic cohort are summarized in Table 1. Overall, the treatment groups were well matched. Mean (SD) age was 81.4 (6.8) years, and 1006 (54.9%) participants were men. The mean (SD) Society of Thoracic Surgeons mortality risk score was 5.8% (2.1%) for TAVR and 5.8% (1.9% for SAVR). Six hundred seventy-one (36.6%) patients had diabetes, 451 (24.6%) had undergone prior coronary artery bypass graft surgery, and 59 (3.2%) had chronic obstructive pulmonary disease requiring home oxygen. A total of 1393 (76.0%) patients were eligible for transfemoral access, and the remaining 440 (24.0%) required transthoracic access. Patients who required transthoracic access had higher rates of peripheral arterial disease, prior coronary artery bypass graft surgery, and prior stroke compared with transfemoral access patients.

Baseline health status was significantly impaired in both groups. The mean (SD) KCCQ-OS score was 53 (21.6), which corresponds to New York Heart Association functional class III symptoms. The mean SF-36 physical summary score was 36 (8.8), which is approximately 1.5 SDs below the US population mean. There were no significant differences in baseline health status between the TAVR and SAVR groups in either access stratum.

Within-Group Comparisons

Health status data were available for 95%, 92%, and 88% of patients in the TAVR group at 1 month, 1 year, and 2 years, respectively, and for 87%, 84% and 84% at 1 month, 1 year, and 2 years in the SAVR group (eTable 1 in the Supplement). Baseline clinical characteristics were similar between patients with and without 2-year follow-up health status data (eTable 2 in the Supplement).

Among surviving patients, both disease-specific and generic health status improved substantially by 1-year after TAVR or SAVR, regardless of access site (Table 2), with mean improvements of 16 to 22 points on the KCCQ-OS scale, 3.9 to 5.1 points on the SF-36 physical summary scale, and 1.6 to 3.3 points on the SF-36 mental summary scale. Similar improvements were seen among surviving patients at 2-year follow-up.

Between-Group Comparisons

The comparisons of health status between the TAVR and SAVR groups are shown in Figure 1A and B as well as eTable 3 in the Supplement. Since there was evidence of a significant interaction between access site and treatment group for several key health status measurements at 1 month, all analyses were stratified by access site.

In the transfemoral group, TAVR resulted in a significantly greater early health status improvement compared with SAVR according to the KCCQ-OS score (1-month mean adjusted difference, 14.1 points; 95% CI, 11.7-16.4; P < .01). Similar benefits of TAVR were seen in the SF-36 physical summary scale (mean adjusted difference, 4.6 points; 95% CI, 3.7-5.5; P < .01) and the SF-36 mental summary scale (mean adjusted difference, 5.5 points; 95% CI, 4.3-6.8; P < .01). At 1 and 2 years, however, there were no significant differences between TAVR and SAVR on any of the disease-specific or generic health status instruments. In the transthoracic group, there were no significant differences in health status between TAVR and SAVR at 1 month (mean difference in KCCQ-OS, 3.5 points; 95% CI, −1.4 to 8.4; P < .01 for interaction) or at any time point on any health status measure.

Per-protocol Results

Of the 1833 patients in the analytic cohort, 27 (1.5%) did not undergo the assigned procedure. The per-protocol cohort thus consisted of 1806 patients (945 TAVR; 861 SAVR). There were no meaningful differences in either the within-group or between-group comparisons in the per-protocol analyses compared with the intention-to-treat analyses (eTables 4 and 5 in the Supplement).

Categorical Analyses

The results of categorical analyses are summarized in Table 3 and Figure 2. At 1-month follow-up, the proportion of patients who experienced a substantial (≥20 points) improvement in the KCCQ-OS was significantly greater with transfemoral TAVR than SAVR (43.8% vs 26.9%; P < .01). No such benefit of TAVR was seen in the transthoracic cohort. At both 1- and 2-year follow-up, 45%-50% of surviving patients experienced a substantial improvement in the KCCQ-OS, with no significant difference between TAVR and SAVR in either the transfemoral or transthoracic cohorts. When change in health status was categorized as an ordinal variable with death as the worst possible outcome, transfemoral TAVR resulted in a substantial benefit compared with SAVR at 1 month and a small, but significant, benefit at 1 year and 2 years as well (Figure 2A). These benefits were driven by both small differences in survival as well as differences in the proportion of patients who experienced large health status benefits at the later time points. No significant differences were seen at any time point in the transthoracic cohort (Figure 2B).

Discussion

To our knowledge, this is the first study to compare the effects of TAVR with those of SAVR on detailed disease-specific and generic patient-reported health status in individuals with severe, symptomatic AS at intermediate surgical risk. In this population, patients who were treated with TAVR or SAVR demonstrated substantial and durable improvements in health status from baseline through 2 years. Among patients eligible for transfemoral access, TAVR was associated with significantly better health status compared with SAVR at 1 month. However, at both 1 and 2 years, there were no differences in health status between transfemoral-eligible patients treated with TAVR or SAVR. In contrast, among patients who required transthoracic access, there were no significant differences in health status between TAVR and SAVR at any time point. The similar 1- and 2-year health status outcomes of TAVR and SAVR in the intermediate-risk population are reassuring, especially given concerns about the higher rates of paravalvular aortic regurgitation and pacemaker implantation seen with TAVR in PARTNER 2A.6

The improvements in health status at 1- and 2-year follow-up were substantial with both TAVR and SAVR, regardless of access site. With more than 60% of surviving patients experiencing improvements of more than 10 points in the KCCQ-OS score at 2 years, these changes are not only statistically significant but also clinically meaningful, as prior studies in patients with heart failure have shown that improvements as small as 5 points on the KCCQ-OS are associated with reduced mortality and health care costs.12,21 The magnitude of improvement of QOL in the PARTNER 2A trial was smaller than that seen in both the PARTNER A and CoreValve US Pivotal trials (mean 1-year changes in KCCQ-OS of 19, 27, and 23 points, respectively).9,10 These findings are likely related to the worse baseline health status seen in patients at high surgical risk (baseline KCCQ-OS score, 39-45 points) compared with the intermediate-risk population in PARTNER 2A (baseline KCCQ-OS score, 53 points).

In interpreting our findings, it is important to recognize that the observed health status results apply only to surviving patients at each time interval. If a new treatment results in a survival benefit compared with the alternative, it may paradoxically appear to result in worse long-term health status than the alternative strategy owing to differential attrition of the sickest patients in the alternative treatment arm. As such, integrating both survival and QOL into a single outcome provides an important patient-centered metric by which to further evaluate the effects of TAVR vs SAVR. Indeed, when mortality and health status outcomes were analyzed as a single, ordinal end point, there was evidence of a statistically significant benefit of transfemoral TAVR over SAVR at both early (1 month) and later (1 and 2 years) time points in the transfemoral cohort. While the differences at the later time points were small and driven mainly by a trend toward lower mortality in the TAVR arm, these findings suggest that there may be a sustained overall benefit of transfemoral TAVR over SAVR in this population. Longer term follow-up is needed to assess whether this finding persists.

Although the magnitude of long-term health status benefit was similar with TAVR and SAVR at 1 and 2 years, early health status benefits favored TAVR, but only among patients who were suitable for transfemoral access. These results add to a growing literature demonstrating that TAVR via transthoracic access may not offer significant therapeutic advantages over SAVR.9,10 There are a number of possible reasons for these findings. First, although there were lower rates of acute kidney injury, disabling stroke, and atrial fibrillation in patients treated with TAVR vs SAVR in the transfemoral cohort at 1 month, there were no significant differences in complications between TAVR and SAVR in the transthoracic cohort.6 As such, a lower incidence of these complications could have contributed to more rapid improvement in health status in the transfemoral TAVR patients. Second, manipulation of the chest’s musculoskeletal frame required for transthoracic access (whether by lateral thoracotomy or ministernotomy) may cause more postoperative pain than expected. While it is intuitive that a smaller chest incision via a lateral thoracotomy or ministernotomy would be associated with an easier healing process than a traditional median sternotomy used for SAVR, prior studies do not support this hypothesis.22-24 Finally, it is possible that transthoracic TAVR results in an early health status benefit compared with SAVR that was not captured by our study, either through power issues or through using scales that were insensitive to modest differences in pain between transthoracic TAVR and SAVR during the early recovery period.

Limitations

Our study should be interpreted in light of several potential limitations. First, as noted above, the proportion of patients in the transthoracic cohort was low (24.0%). As such, the comparisons of transthoracic TAVR with SAVR may have been underpowered to detect modest differences in health status at both early and late time points. Second, the PARTNER 2A trial used the Sapien XT valve, which is a second-generation TAVR device. Since the conduct of this trial, a third-generation, balloon-expandable valve (Sapien 3) has been approved and offers several advantages over the Sapien XT valve, including a lower delivery profile and lower rates of paravalvular regurgitation.25 Whether use of the Sapien 3 valve would have led to greater health status benefits compared with SAVR is unknown. Third, PARTNER 2A was an unblinded trial, which could have influenced patient-reported health status during follow-up. Finally, there was a modest amount of missing health status data at 2 years (15.7% for SAVR; 11.9% for TAVR). While missing data could have contributed to responder bias, there was no difference in baseline characteristics between patients with and without available health status data at 2 years, thereby suggesting that the effect of responder bias is likely minimal.

Conclusions

Among patients with severe AS at intermediate surgical risk, TAVR and SAVR were associated with similar health status benefits through 2 years of follow-up. Although health status improvement was more rapid with TAVR compared with SAVR, this benefit was seen only in patients treated via transfemoral access. Further studies are needed to assess the durability of health status improvement of TAVR beyond 2 years and to understand the effects of third-generation TAVR devices on health status in patients with severe AS.

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Article Information

Accepted for Publication: May 4, 2017.

Corresponding Author: David J. Cohen, MD, MSc, Saint-Luke’s Mid America Heart Institute, School of Medicine, University of Missouri, Kansas City, 4401 Wornall Rd, Kansas City, MO 64111 (dcohen@saint-lukes.org).

Published Online: June 28, 2017. doi:10.1001/jamacardio.2017.2039

Author Contributions: Dr Cohen had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Baron, Thourani, Svensson, Mack, Smith, Cohen.

Acquisition, analysis, or interpretation of data: Baron, Arnold, Wang, Magnuson, Chinnakondepalli, Makkar, Herrmann, Kodali, Kapadia, Brown, Mack, Smith, Leon, Cohen.

Drafting of the manuscript: Baron, Chinnakondepalli, Mack, Cohen.

Critical revision of the manuscript for important intellectual content: Baron, Arnold, Wang, Magnuson, Makkar, Herrmann, Kodali, Thourani, Kapadia, Svensson, Brown, Mack, Smith, Leon.

Statistical analysis: Baron, Wang, Chinnakondepalli.

Obtained funding: Svensson, Cohen.

Administrative, technical, or material support: Makkar, Brown, Smith, Leon.

Supervision: Magnuson, Thourani, Kapadia, Mack, Smith, Cohen.

Funding/Support: The PARTNER 2 clinical trial and quality-of-life substudy were funded by a research grant from Edwards Lifesciences, Inc. Dr Arnold is supported by Career Development Grant Award K23 HL116799 from the National Heart, Lung, and Blood Institute.

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The PARTNER 2 Investigators are:

Arkansas Heart Hospital, Little Rock: David Mego, MD; Michael Nolen, MD. Austin Heart PLLC, Austin, Texas: Frank J. Zidar, MD; Faraz Kerendi, MD. Baptist Memorial Health Center, Memphis, Tennessee: H. Edward Garrett, MD; Basil Mantas Paulus, MD. Brigham and Women's Hospital, Boston, Massachusetts: Pinak Shah, MD. Cedars-Sinai Medical Center: Rajendra Makkar, MD; Alfredo Trento, MD. Cleveland Clinic Foundation, Cleveland, Ohio: E. Murat Tuzcu, MD; Lars Svensson, MD. Columbia University Medical Center, New York, New York: Susheel Kodali, MD; Isaac George, MD. Cooper University, Camden, New Jersey: Janah Aji, MD; Frank Bowen, MD. Cornell Medical Center, New York, New York: Shing Chiu Wong, MD; Arash Salemi, MD. Dartmouth–Hitchcock, Hanover, New Hampshire: James Devries, MD; Joseph DeSimone, MD. Duke University, Durham, North Carolina: John Kevin Harrison, MD; G. Charles Hughes, MD. East Carolina University, Greeneville, North Carolina: Andy Kiser, MD. Emory University Hospital, Atlanta, Georgia: Vinod Thourani, MD; Vasilis Babaliaros, MD. Henry Ford Medical Center, Detroit, Michigan: William O’Neill, MD; Gaetano Paone, MD. Indiana University Health, Indianapolis: Anjan Sinha, MD; Arthur Coffey, MD. Intermountain Medical Center, Salt Lake City, Utah: Brian Whisenant, MD; Kent Jones, MD. Jewish Hospital, Louisville, Louisville, Kentucky: Kendra Grubb, MD; Michael Flaherty, MD. Laval University, Quebec City, Quebec, Canada: Joseph Rodes-Cabau, MD; Daniel Doyle, MD. Massachusetts General Hospital, Boston, Massachusetts: Jonathan Passeri, MD. Mayo Clinic, Rochester, Minnesota: Kevin Greason, MD; David Holmes, MD. Medical City Dallas, Dallas, Texas: Todd Dewey, MD; Bruce Bowers, MD. Medical University of South Carolina, Charleston: Daniel Steinberg, MD; John Ikonomidis, MD. Medstar Union Memorial Hospital, Hyattsville, Maryland: Michael Fiocco, MD; John Wang, MD. Mercy General Hospital, Rancho Cordova, California: Frank Slachman, MD; Michael Chang, MD. Minneapolis Heart Institute Foundation, Minneapolis, Minnesota: Mario Goessl, MD; Vibhu Kshettry, MD. Morton Plant Hospital, Joshua Rovin, MD; Douglas Spriggs, MD. Morton Plant Hospital, Clearwater, Florida: Joshua Rovin, MD; Douglas Spriggs, MD. Nebraska Heart Institute, Lincoln: James Wudel, MD; Steven Martin, MD. Newark Beth Israel Medical Center, Newark, New Jersey: Marc Cohen, MD; Mark Russo, MD. Northshore University Health System, Evanston, Illinois: Ted Feldman, MD; Paul L. Pearson, MD. NorthShore LIJ Medical Group, New Hyde Park, New York: S. Jacob Scheinerman, MD. Northwestern University, Chicago, Illinois: Chris Malaisrie, MD; Charles Davidson, MD. Ochsner Clinic Foundation, New Orleans, Louisiana: Stephen Ramee, MD; Patrick Eugene Parrino, MD. Oklahoma Cardiovascular Research Group, Oklahoma City: Mark Bodenhamer, MD; Mohammad Ghani, MD. Prairie Education & Research, Springfield, Illinois: Gregory Mishkel, MD; John Gill, MD. Providence St Vincent Medical Center, Portland, Oregon: Jeffrey Swanson, MD; Robert Hodson, MD. Rush University Medical Center, Chicago, Illinois: Clifford J. Kavinsky, MD; Robert March, MD. Sentara Norfolk General Hospital, Norfolk, Virginia: Paul Mahoney, MD; Joseph R. Newton, MD. Scripps Green Hospital, La Jolla, California: Paul S. Teirstein, MD; Scot A. Brewster, MD. Scripps Memorial Hospital, Pasadena, California: Richard Stahl, MD; Jeffrey Cavendish, MD. Stanford University Medical Center, Palo Alto, California: D. Craig Miller, MD; Alan Yeung, MD. St Luke's Hospital, Kansas City, Missouri: Adnan Chhatriwalla, MD; Michael Borkon, MD. St Paul's Hospital, Vancouver, Canada: John Webb, MD; Jian Ye, MD. St Vincent Indianapolis Medical Group Inc, Indianapolis, Indiana: James Hermiller, MD; Sina Moainie, MD. The Christ Hospital, Cincinnati, Ohio: Dean Kereiakes, MD. University of California, Davis, Sacramento, California: Reginald Low, MD; Nilas Young, MD. University of Colorado, Denver: John Carroll, MD; David Fullerton, MD. University of Florida, Gainesville: Thomas Beaver, MD; R. David Anderson, MD. University of Iowa, Iowa City: Philip Horwitz, MD. University of Maryland, Baltimore: Anuj Gupta, MD. University of Miami, Miami, Florida: Mauricio Cohen, MD; Donald Williams, MD. University of Michigan, Ann Arbor: Stanley Chetcuti, MD; G. Michael Deeb, MD. The Heart Hospital Baylor Plano, Plano, Texas: William Brinkman, MD; David Brown, MD. University of Pennsylvania, Philadelphia: Joseph Bavaria, MD; Howard Hermann, MD. The University of Texas Health Science Center, Houston: Richard Smalling, MD; Anthony Estrera, MD. University of Texas, San Antonio: Steven Bailey, MD; Andrea Carpenter, MD. University of Virginia, Charlottesville: Irving L. Kron, MD. University of Washington, Seattle: Larry Dean, MD; Edward Verrier, MD. Washington Hospital Center, Hyattsville, Maryland: Lowell Satler, MD; Paul Corso, MD. Washington University, St Louis, Missouri (Barnes_Jewish Hospital): Alan Zajarias, MD; Hersh Maniar, Jr, MD. William Beaumont Hospital, Royal Oak, Michigan: George Hanzel, MD; Francis Shannon, MD. Winthrop University Hospital, Mineola, New York: Richard Schwartz, MD. University of Wisconsin, Madison: Giorgio Gimelli, MD; Lucian Lozonschi, MD. Wellspan Hospital, York, Pennsylvania: William Nicholson, MD; David Kaczorowski, MD.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Baron has received consulting fees from Edwards Lifesciences Inc and from St Jude Inc. Dr Makkir has received grants from Edwards Lifesciences and St Jude Medical Center and personal fees from Abbott Vascular, Cordis, and Medtronic. Dr Herrmann has received grants from Abbott Vascular, Edwards Lifesciences Inc, Boston Scientific, Medtronic, and St Jude Medical, and personal fees from Edwards Lifesciences Inc. Dr Kodali is a paid member of the scientific advisory boards of Dura Biotec, Thubrikar Aortic Valve, Inc, and BioTrace Medical, and is an unpaid consultant for Medtronic, Edwards Lifesciences Inc, Claret Medical, and Boston Scientific. Dr Thourani has received grants and personal fees from Edwards Lifesciences Inc. Dr Mack has received compensation from Edwards Lifesciences Inc. Dr Cohen has received grants and personal fees from Edwards Lifesciences Inc and Medtronic and grants from Abbott Vascular. No other conflicts were reported.

References
1.
Schwarz  F, Baumann  P, Manthey  J,  et al.  The effect of aortic valve replacement on survival.  Circulation. 1982;66(5):1105-1110.PubMedGoogle ScholarCrossref
2.
Sundt  TM, Bailey  MS, Moon  MR,  et al.  Quality of life after aortic valve replacement at the age of >80 years.  Circulation. 2000;102(19)(suppl 3):III70-III74.PubMedGoogle Scholar
3.
Khan  JH, McElhinney  DB, Hall  TS, Merrick  SH.  Cardiac valve surgery in octogenarians: improving quality of life and functional status.  Arch Surg. 1998;133(8):887-893.PubMedGoogle ScholarCrossref
4.
Leon  MB, Smith  CR, Mack  M,  et al; PARTNER Trial Investigators.  Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery.  N Engl J Med. 2010;363(17):1597-1607.PubMedGoogle ScholarCrossref
5.
Adams  DH, Popma  JJ, Reardon  MJ.  Transcatheter aortic-valve replacement with a self-expanding prosthesis.  N Engl J Med. 2014;371(10):967-968.PubMedGoogle ScholarCrossref
6.
Leon  MB, Smith  CR, Mack  MJ,  et al; PARTNER 2 Investigators.  Transcatheter or surgical aortic-valve replacement in intermediate-risk patients.  N Engl J Med. 2016;374(17):1609-1620.PubMedGoogle ScholarCrossref
7.
Reynolds  MR, Magnuson  EA, Lei  Y,  et al; Placement of Aortic Transcatheter Valves (PARTNER) Investigators.  Health-related quality of life after transcatheter aortic valve replacement in inoperable patients with severe aortic stenosis.  Circulation. 2011;124(18):1964-1972.PubMedGoogle ScholarCrossref
8.
Osnabrugge  RL, Arnold  SV, Reynolds  MR,  et al; CoreValve US Trial Investigators.  Health status after transcatheter aortic valve replacement in patients at extreme surgical risk: results from the CoreValve US trial.  JACC Cardiovasc Interv. 2015;8(2):315-323.PubMedGoogle ScholarCrossref
9.
Arnold  SV, Reynolds  MR, Wang  K,  et al; CoreValve US Pivotal Trial Investigators.  Health status after transcatheter or surgical aortic valve replacement in patients with severe aortic stenosis at increased surgical risk: results from the CoreValve US Pivotal Trial.  JACC Cardiovasc Interv. 2015;8(9):1207-1217.PubMedGoogle ScholarCrossref
10.
Reynolds  MR, Magnuson  EA, Wang  K,  et al; PARTNER Trial Investigators.  Health-related quality of life after transcatheter or surgical aortic valve replacement in high-risk patients with severe aortic stenosis: results from the PARTNER (Placement of Aortic Transcatheter Valve) Trial (Cohort A).  J Am Coll Cardiol. 2012;60(6):548-558.PubMedGoogle ScholarCrossref
11.
O’Brien  SM, Shahian  DM, Filardo  G,  et al; Society of Thoracic Surgeons Quality Measurement Task Force.  The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 2–isolated valve surgery.  Ann Thorac Surg. 2009;88(1)(suppl):S23-S42.PubMedGoogle ScholarCrossref
12.
Soto  GE, Jones  P, Weintraub  WS, Krumholz  HM, Spertus  JA.  Prognostic value of health status in patients with heart failure after acute myocardial infarction.  Circulation. 2004;110(5):546-551.PubMedGoogle ScholarCrossref
13.
Kosiborod  M, Soto  GE, Jones  PG,  et al.  Identifying heart failure patients at high risk for near-term cardiovascular events with serial health status assessments.  Circulation. 2007;115(15):1975-1981.PubMedGoogle ScholarCrossref
14.
Arnold  SV, Spertus  JA, Lei  Y,  et al.  Use of the Kansas City Cardiomyopathy Questionnaire for monitoring health status in patients with aortic stenosis.  Circ Heart Fail. 2013;6(1):61-67.PubMedGoogle ScholarCrossref
15.
Spertus  J, Peterson  E, Conard  MW,  et al; Cardiovascular Outcomes Research Consortium.  Monitoring clinical changes in patients with heart failure: a comparison of methods.  Am Heart J. 2005;150(4):707-715.PubMedGoogle ScholarCrossref
16.
Ware  JE  Jr, Sherbourne  CD.  The MOS 36-Item Short-Form Health Survey (SF-36)—I; conceptual framework and item selection.  Med Care. 1992;30(6):473-483.PubMedGoogle ScholarCrossref
17.
Kiebzak  GM, Pierson  LM, Campbell  M, Cook  JW.  Use of the SF36 general health status survey to document health-related quality of life in patients with coronary artery disease: effect of disease and response to coronary artery bypass graft surgery.  Heart Lung. 2002;31(3):207-213.PubMedGoogle ScholarCrossref
18.
Failde  I, Ramos  I.  Validity and reliability of the SF-36 Health Survey Questionnaire in patients with coronary artery disease.  J Clin Epidemiol. 2000;53(4):359-365.PubMedGoogle ScholarCrossref
19.
Ware  JKM, Bjorner  JB, Turner-Bowkes  DM, Gandek  B, Maruish  ME.  Determining Important Differences in Scores: User’s Manual for the SF-36v2 Health Survery. Lincoln, RI: Quality Metric Inc; 2007.
20.
Shaw  JW, Johnson  JA, Coons  SJ.  US valuation of the EQ-5D health states: development and testing of the D1 valuation model.  Med Care. 2005;43(3):203-220.PubMedGoogle ScholarCrossref
21.
Chan  PS, Soto  G, Jones  PG,  et al.  Patient health status and costs in heart failure: insights from the eplerenone post-acute myocardial infarction heart failure efficacy and survival study (EPHESUS).  Circulation. 2009;119(3):398-407.PubMedGoogle ScholarCrossref
22.
Grossi  EA, Zakow  PK, Ribakove  G,  et al.  Comparison of post-operative pain, stress response, and quality of life in port access vs standard sternotomy coronary bypass patients.  Eur J Cardiothorac Surg. 1999;16(suppl 2):S39-S42.PubMedGoogle Scholar
23.
Diegeler  A, Walther  T, Metz  S,  et al.  Comparison of MIDCAP versus conventional CABG surgery regarding pain and quality of life.  Heart Surg Forum. 1999;2(4):290-295.PubMedGoogle Scholar
24.
Walther  T, Falk  V, Metz  S,  et al.  Pain and quality of life after minimally invasive versus conventional cardiac surgery.  Ann Thorac Surg. 1999;67(6):1643-1647.PubMedGoogle ScholarCrossref
25.
Thourani  VH, Kodali  S, Makkar  RR,  et al.  Transcatheter aortic valve replacement versus surgical valve replacement in intermediate-risk patients: a propensity score analysis.  Lancet. 2016;387(10034):2218-2225.PubMedGoogle ScholarCrossref
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