Valvular Heart Disease Research Papers

Valvular heart disease remained in the shadow of coronary artery disease for a long time. Vascular biology and Andreas Grüntzig’s seminal procedure 40 years ago in Zürich1 focused the interest of science and medicine for more than two decades on coronary artery disease. This changed at the turn of the century with the first experimental catheter-based valve implantation and the first-in-man transarterial aortic valve implantation or TAVI by Alain Cribier in Rouen in 2002.2 Over the last 15 years, the TAVI procedure has been refined and improved, as have its results in large centres3–5 and even in those without surgical back-up.6 Thus, it is timely to publish the updated ‘2017 ESC/EACTS Guidelines for the management of valvular heart disease: The Task Force for the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)’.7

In a FAST TRACK clinical research paper entitled ‘SOURCE 3: 1-year outcomes of post-transcatheter aortic valve implantation using the latest generation of the balloon-expandable transcatheter heart valve’, Olaf Wendler and colleagues from King’s College London in the UK note that TAVI has developed from a procedure for patients with aortic stenosis which is inoperable or who are high risk for surgery into a treatment option even for intermediate risk elderly patients. This development has been facilitated by the clinical learning curve and constant improvements of transcatheter heart valves used. They present total 1-year results of SOURCE 3, the European post-approval multicentre registry of the latest generation balloon-expandable Edwards SAPIEN 3TM valve.8 In total, 1946 patients with a mean age of 82 years were enrolled in 80 centres from 10 European countries. At 1 year, all-cause mortality was 12.6%, cardiovascular mortality 8.0%, stroke 3.1%, disabling stroke 1.4%, and rate of new pacemakers 13.2%. Causes of death were 62.0% cardiovascular and 38.0% non-cardiovascular, with heart failure and pulmonary complications being the main reasons for fatal outcomes. Multivariable analysis identified New York Heart Association (NYHA) class IV and renal insufficiency as predictors of mortality, while higher body mass indexes (BMIs) improved survival (Figure 1). Severe and moderate paravalvular leakage was noted in 2.6%. Thus, the latest generation balloon-expandable Edwards SAPIEN 3TM valve is associated with a low complication and mortality rate at 1 year. The clinical relevance of these findings are put into context in an Editorial by John G. Webb from St. Paul’s Hospital in Vancouver, Canada.9

Another type of TAVI valves are self-expandable valves. The ADVANCE study was designed to evaluate the safety and effectiveness of such a self-expanding bioprosthesis in real-world patients with symptomatic, severe aortic stenosis at high surgical risk. Ulrich Gerckens and colleagues from the University of Rostock in Germany look at this matter in another FAST TRACK manuscript entitled ‘Final 5-year clinical and echocardiographic results of treatment for severe aortic stenosis with a self-expanding bioprosthesis from the ADVANCE Study’.10 In total, 1015 patients with a mean age of 81 years and mean logistic EuroSCORE of 19% were enrolled from 44 experienced centres in 12 countries with 996 attempted TAVI procedures. Five-year follow-up was available in nearly half of the patients, at which point the rate of all-cause mortality was 51% and the rate of major stroke 5.4% (Figure 2). Haemodynamic measures remained consistent for paired patients, with a mean transvalvular gradient of 8.8 mmHg and an effective orifice area of 1.7 cm2. Aortic regurgitation11 decreased over time, and among paired patients dropped from 13% to 8% moderate aortic regurgitation at 5 years. At echocardiography or re-intervention, there were 2.6% meeting the VARC-2 criteria for valve dysfunction and 1.2% with a reintervention beyond 30 days. Thus, the 5-year results in real-world, elderly, high-risk patients undergoing TAVI with a self-expanding bioprosthesis provide evidence for continued valve durability with low rates of re-interventions and haemodynamic valve dysfunction.

Figure 2

Forest plot for multivariable analysis of predictors of all-cause mortality through 5 years.

Figure 2

Forest plot for multivariable analysis of predictors of all-cause mortality through 5 years.

In summary, the current guidelines as well as the ongoing improvements of the TAVI valves and the procedure clearly document that the future of this catheter-based valve replacement is bright12 and, provided that hypo-attenuated leaflet thickening13 will turn out to be harmless and valve durability will be further confirmed, will be used in middle and possibly even in low risk patients.

The editors hope that this issue of the European Heart Journal will be of interest of to its readers.

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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Introduction

The following are highlights from the new series, Circulation: Cardiovascular Quality and Outcomes Topic Reviews. This series will summarize the most important manuscripts, as selected by the Editor, which have been published in the Circulation portfolio. The objective of this new series is to provide our readership with a timely, comprehensive selection of important papers that are relevant to the quality and outcomes as well as general cardiology audience. The studies included in this article represent the most significant research in the area of valvular heart disease. (Circ Cardiovasc Quality and Outcomes. 2012;5:-e103.)

In recent years, no field of clinical cardiology has experienced a great influx of transformational therapeutic options as has the area of valvular heart disease. Treatment of severe aortic stenosis (AS) has been revolutionized by transcatheter aortic valve replacement (TAVR), which has been shown to improve life expectancy and functional outcomes in patients with inoperable AS1,2 and to have short-term outcomes comparable to surgical aortic valve replacement (AVR) in patients at high perioperative risk.3,4 Analogously, mitral valve disease has been amenable to percutaneous valve replacement,5,6 as well as clipping procedures7 that can substantively reduce severe mitral regurgitation (MR) and improve functional outcomes. Even right-sided heart disease involving valves in pulmonary8,9 and tricuspid10 positions has been treated successfully with endovascular techniques.

Yet, even with this growing focus on percutaneous valvular interventions, open surgical techniques remain the dominant treatment strategies and standard of care for most advanced lesions. Surgical valve repair and replacement account for 10% to 20% of all cardiac surgical procedures,11–13 approximately two thirds of which are for AS.11–13 For patients undergoing surgery, there remains considerable debate about risk stratification,14 intraoperative technique,15 and postoperative management.16 In addition, there remains significant controversy as to what is the optimal time in the natural history of disease to perform surgery,17 especially for patients who are asymptomatic.18 Ultimately, the field appears to be moving toward hybrid approaches for treatment that involve both cardiac surgeons and cardiology-trained structural interventionalists.

We have therefore dedicated the topic reviews in this article of Circulation: Cardiovascular Quality and Outcomes to the important subject of valvular heart disease. We have included articles on diverse topics including preoperative factors associated with adverse outcomes after tricuspid valve replacement (TVR),19 late results after percutaneous mitral commissurotomy (PMC),20 outcomes among patients with low-gradient severe AS,21 and health-related quality of life after TAVR.22

Long-term Outcomes of Mechanical Valve Replacement in Patients With Atrial Fibrillation: Impact of the Maze Procedure

Summary: The long-term benefits of the maze procedure in patients with chronic atrial fibrillation requiring lifelong anticoagulation who are undergoing mechanical valve replacement are unknown. The authors evaluated adverse outcomes including death, thromboembolic events, and a composite measure including death, thromboembolism, heart failure (HF), and valve-related complications in 569 patients with atrial fibrillation–related valvular heart disease undergoing mechanical valve replacement with (n=317) or without (n=252) the maze procedure. Patients were recruited from 1 center between 1999 and 2000. Those undergoing the maze procedure were placed on a postoperative rhythm control strategy, whereas others were placed on a rate control strategy. Propensity matching was used to minimize preoperative differences between groups. The authors found that patients undergoing the maze procedure were younger and less symptomatic than patients undergoing valve-only surgery. Patients undergoing maze were at similar risk of death and the composite outcome but at lower risk for thromboembolic events (hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.12–0.73) compared with patients undergoing valve replacement alone at a median follow-up of 63.6 months. Relative to patients undergoing valve replacement only, thromboembolism was less in maze patients with a European System for Cardiac Operative Risk Evaluation (EuroSCORE) of 0 to 3 (HR, 0.18; 95% CI, 0.04–0.93) and was equivalent in maze patients with a EuroSCORE of ≥4 (HR, 0.61; 95% CI, 0.17–2.18). Patients undergoing the maze procedure had superior left ventricular function (P<0.001) and less tricuspid regurgitation (P<0.001) at a median follow-up of 52.7 months.

Conclusion: The addition of the maze procedure to mechanical valve replacement is a reasonable strategy to reduce thromboembolic events in lower-risk patients with chronic atrial fibrillation requiring lifelong anticoagulation. However, this approach cannot be recommended universally because both death and the composite end point including death were not different between treatment groups. It is possible that the 2 treatment groups were incompletely matched, because the lower age and symptomatology among patients undergoing the maze procedure point to potentially important underlying differences between groups. Finally, because patients in the maze group also underwent a rhythm control strategy after surgery, it may be that pharmacologic therapy drove differences in outcomes between the treatment groups, not the maze procedure itself.23

Survival of Kidney Transplantation Patients in the United States After Cardiac Valve Replacement

Summary: This study assessed survival of US kidney transplantation recipients after cardiac valve replacement and compared outcomes among patients receiving bioprosthetic versus mechanical heart valves. Using the US Renal Data System, the authors identified 1335 kidney transplantation recipients hospitalized between 1991 and 2004 that underwent replacement of mitral and aortic valves. Mean follow-up was 34.4±34.5 months. Most patients (50.3%) were between 45 and 64 years of age. Most valve surgeries (52.4%) were performed between 2000 and 2004. Tissue valves were used in 28% of patients. Survival was estimated using the life-table method. The log-rank test was used to compare survival between groups receiving bioprosthetic and mechanical valves. A Cox proportional hazard model was used to identify predictors of survival with additional propensity matching to confirm results. For the entire cohort, estimated survival at 0.5, 1, 2, 3, 5, and 10 years was 75.3%, 70.8%, 60.1%, 52.8%, 38.4%, and 16.0%, respectively. Predictors of death included age >75 years (HR, 3.76; 95% CI, 2.62–5.39), age 65 to 74 years (HR, 2.11; 95% CI, 1.65–2.68), end-stage renal disease duration, and increased comorbidity. Mortality was lower for patients receiving tissue valves (HR, 0.83; 95% CI, 0.70–0.99). Estimates did not change significantly with additional propensity matching.

Conclusion: Mortality rates are extremely high after left-sided valve replacement in kidney transplant recipients. In this study, more than one quarter of patients are dead at 1 year after surgery, and almost one half are dead at 3 years. This finding will gain increased importance as the mean age of kidney transplant recipients continues to rise24 and valvular heart disease becomes more common. The improved outcomes associated with the use of bioprosthetic valves are of interest because patients with renal disease are at higher risk of hemorrhage when taking anticoagulation. However, these results will need to be confirmed because the US Renal Data System database provides relatively few clinical data that may be important in risk adjustment.25

Preoperative Factors Associated With Adverse Outcome After TVR

Summary: Little is known about the preoperative clinical and echocardiographic factors associated with increased mortality after TVR in patients with severe tricuspid regurgitation. The authors examined 189 patients (mean age, 67.5 years) with severe tricuspid regurgitation who underwent TVR at the Mayo Clinic (Minneapolis, MN) between 1997 and 2007. Patients were excluded if they had undergone previous tricuspid valve surgery, had congenital tricuspid valve disease, had carcinoid heart disease, had tricuspid stenosis, or underwent tricuspid valve repair rather than replacement. Operative mortality was 0% in New York Heart Association (NYHA) class II patients, 8.9% in NYHA class III patients, and 17.9% in NYHA class IV patients. NYHA class was the only significant predictor of early mortality when evaluating outcomes in all TVR patients, as well as the subset undergoing isolated TVR (68 patients). At a mean follow-up of 29.3±27.1 months, 30% of patients had died and 41% remained event free without death, hospital readmission for HF, or repeat tricuspid valve surgery. Increased NYHA class, increased comorbidity by the Charlson Index, and increased creatinine-predicted death on follow-up. Adjusted Cox analyses that included echocardiographic parameters showed that the right index of myocardial performance, a global estimate of right ventricular systolic and diastolic function, also predicted death and cardiac events. Five-year survival rates were 69.3%, 63.5%, and 36.3% in patients with NYHA functional class II, III, and IV, respectively.

Conclusion: Overall mortality at 29 months after TVR is high and is strongly correlated with NYHA functional class and other easily assessed patient characteristics, including comorbidities and serum creatinine. The additional use of echocardiographic parameters of right ventricular function can provide additional prognostic use. Although the authors indicate that surgery should be considered before the development of advanced HF or echocardiographic evidence of increased right ventricular filling pressure, these data cannot be used to plan timing of surgery in the absence of a control group; it is not surprising that sicker patients are more likely to experience adverse events.19

Mitral Valve Disease

Mitral valve disease, especially MR, is relatively common among Americans. More than 19% of participants in the Framingham Heart Study were found to have at least mild MR.26 In the year 2000, it was estimated that 2 to 2.5 million Americans had moderate to severe MR, with the number expected to increase because of population aging.27 Although mitral stenosis has declined in both incidence and prevalence in the United States and other industrialized countries because rheumatic fever has become increasingly rare, mitral stenosis remains an important valvular problem in the developing world.12,28

Research continues to define the clinical significance of mitral valve disease and opportunities for its correction. For example, ischemic MR has been found to be associated with worse outcomes among patients with coronary artery disease.29 However, it is unclear whether concomitant mitral surgery improves outcomes among patients undergoing coronary artery bypass grafting (CABG). Similarly, although PMC has been a major treatment option for patients with moderate to severe mitral stenosis and anatomy amenable to intervention, long-term follow-up data concerning the efficacy and safety of this procedure are limited.12

The summaries in this section pertain to articles examining outcomes related to concomitant mitral valve surgery in patients undergoing CABG, mitral valve repair and replacement in the elderly, and PMC.

Outcomes for Mitral Valve Surgery Among Medicare Fee-for-Service Beneficiaries, 1999–2008

Summary: The authors sought to analyze changes over time in rates of mitral valve surgery, postprocedural mortality, and 30-day readmissions through examination of a 100% sample of Medicare Fee-for-Service patients undergoing mitral valve surgery between 1999 and 2008. All patients were ≥65 years of age. Over the time period of analysis, the overall rate of mitral valve surgery per 100000 beneficiary-years declined (56 per 100000 beneficiary-years to 51 per 100000 beneficiary-years). The proportion of patients undergoing surgery who had mitral valve repair versus replacement increased from 24.7% to 46.9% (P<0.001). Among patients undergoing isolated mitral valve surgery, there were significant declines in risk-adjusted 30-day mortality (8.1%–4.2%; P<0.001 for trend) and 1-year mortality (15.3%–9.2%; P=0.003 for trend) over the study period. There also was a slight decline in rates of risk-adjusted 30-day readmission (23.0%–21.0%; P=0.035 for trend). Mortality rates decreased in all age, sex, and race subgroups, as well as among patients undergoing mitral valve repair or replacement. However, mortality remained high among patients ≥85 years of age, women, and nonwhites.

Conclusion: Using real-world data, the authors point to an encouraging trend of reduced 30-day and 1-year mortality among elderly patients undergoing mitral valve surgery. The reasons for this reduction are unknown, although it may be related to increased use of valve repair versus replacement and improved patient selection because we see that overall surgical rates are declining with time. Interestingly, readmission rates have remained relatively constant, indicating that the determinants of postprocedural mortality and readmission may differ. Reductions in readmissions may therefore be an appropriate target for further intervention.30

Influence of MR Repair on Survival in the Surgical Treatment for Ischemic Heart Failure Trial

Summary: MR can adversely affect the outcomes of patients undergoing CABG. Using data from the Surgical Treatment for Ischemic Heart Failure (STICH)31 trial, the authors reported multiple outcomes for patients in the medical therapy, CABG only, and CABG plus valve repair treatment groups as related to the underlying degree of MR. Of the 1212 patients in STICH, no/trace MR, mild MR, moderate MR, and severe MR were reported in 435, 554, 181, and 39 cases, respectively. Among the patients in the medical therapy arm, mortality was proportionally greater with increasing MR severity (32%, 44%, and 50% in patients with no/trace, mild, and moderate to severe MR, respectively). Among the surgical patients undergoing CABG only or CABG plus mitral valve repair, the mortality benefit for concomitant mitral valve surgery was significant only after adjustment for other prognostic factors (adjusted HR, 0.41; 95% CI, 0.22–0.77; P=0.006). There was also a nonsignificant trend toward reduced mortality with CABG plus mitral valve surgery compared with medical therapy alone.

Conclusion: This study provides a large amount of information about medical and surgical outcomes in patients with various degrees of MR. Natural history data in patients who were medically managed are particularly useful. However, because the decision to perform mitral valve repair was not randomized and the criteria for distinction of MR severity may have varied across enrolling sites, it would be prudent to use additional data when making treatment decisions. Two ongoing studies by the Cardiothoracic Surgical Trials Network should be better able to clarify the benefits of treatment of ischemic MR during CABG.29,32

Late Results of PMC up to 20 Years: Development and Validation of a Risk Score Predicting Late Functional Results From a Series of 912 Patients

Summary: PMC is a standard procedure in areas with a high prevalence of mitral stenosis. In a single-center study, the authors determined the 20-year outcomes in a population of 1024 patients who underwent PMC. In patients with good immediate PMC results (n=912, with postprocedure valve area ≥1.5 cm2 and MR <2/4), the 20-year rate of good functional outcome (survival free from repeat PMC, mitral surgery, or NYHA functional class of III or IV) was 30.2±2.0%. The median duration between PMC and a second intervention was 8.4 years. A Cox model with interaction terms found 7 predictors of late outcomes, six of which consisted of interactions between variables, including age–valve area interaction (P<0.0001) with lower impact at higher age and sex–valve calcification interaction (P<0.0001) with stronger impact of calcification in men. High residual transmitral gradient also predicted poor functional results (P<0.0001). The authors additionally developed a risk score for prediction of favorable outcomes among 609 randomly selected patients. The risk score was later validated in the remaining 303 patients, with an overall C index of 0.71 (95% CI, 0.58–0.80).

Conclusion: The study provides unique insight into natural history of patients undergoing PMC. Successful intervention can delay further procedures for >8 years. However, fewer than one third of patients maintain a good functional status at 20 years postprocedure. Study findings are limited by the fact that results can be extrapolated only to highly experienced centers. In addition, the derived risk score is very complex to interpret with multiple interaction terms. Finally, no investigation was done to identify the predictors of poor short-term results.20

Aortic Valve Disease

Aortic valve disease is common in the United States and affects ≈5.2 million adults >65 years of age.33,34 Patients with symptomatic AS have a limited lifespan after the onset of symptoms such as angina, syncope, or dyspnea,35 and prognosis is poor when these patients are treated medically.36 For this reason, surgical AVR has long been the standard of care. Prognosis in younger elderly patients without significant comorbidities is excellent after surgical AVR and mirrors age-matched control subjects without aortic valve disease.37 Prognosis after surgical AVR is also very good even in high-risk patients >70 years of age in whom median survival is ≈6 years.38 Yet some patients still remain ineligible for surgery because of high operative risks.39

However, the choice of therapeutic options has increased in recent years with the development of TAVR. In 2002, Cribier et al40 successfully performed the first human TAVR in a 57-year-old male patient with severe calcific AS who was ineligible for surgical AVR because of significant comorbidities. Since then, TAVR has been performed many thousands of times with good short-term results.41 Randomized data with the Edwards SAPIEN valve42 have shown better short-term outcomes with TAVR compared with medical management in patients with inoperable AS,43 as well as a 1-year outcome comparable to surgical AVR in patients with high perioperative risk.1 Further trials are testing the safety and efficacy of the Medtronic CoreValve for patients with symptomatic AS at high risk for surgical AVR. Additional postmarketing surveillance of both Edwards and Medtronic valves is ongoing in Europe.41

In light of the expanding therapeutic options for aortic valve disease, increased attention is being directed to patients with severe but asymptomatic AS. Despite being asymptomatic, this population has been found to have a yearly risk of sudden death of ≈1%44,45 and a risk of postoperative mortality of ≈3% to 4%.46 Although some retrospective data suggest a possible benefit to early surgical AVR in patients with asymptomatic severe AS,47 this intervention does not receive a Class I or IIa recommendation from European13 or US guidelines.48 Further prospective studies are needed to identify subsets of asymptomatic patients who are at higher risk of cardiac events and may therefore benefit from early intervention.

Given the explosion of articles pertinent to AS with the increasing focus on TAVR, we have included multiple articles on aortic valve disease. Topics include long-term outcomes after surgical AVR,38 the cost-effectiveness of TAVR in patients with severe AS,43 predictors of mortality after TAVR, the natural history of asymptomatic AS, and many others.

Long-term Survival After AVR Among High-risk Elderly Patients in the United States: Insights From the Society of Thoracic Surgeons Adult Cardiac Surgery Database, 1991–2007

Summary: AVR has long been the standard of care for patients with operable aortic valve disease. However, there exists no benchmark of long-term survival after surgical AVR in elderly patients. This study examined long-term survival in 145911 patients ≥65 years of age (median, 76 years of age) undergoing AVR (61530 isolated AVR; 84381 AVR with CABG) at 1026 centers included in the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database during 1991–2007. To identify long-term outcomes, patient records were linked to Medicare claims files using indirect patient identifiers in a previously validated algorithm, and results were stratified by age, comorbidities, and STS perioperative risk of mortality. The authors found that median survival for patients 65 to 69, 70 to 79, and ≥80 years of age undergoing isolated AVR was 13, 9, and 6 years, respectively, which was nearly identical to the age-matched general population for the 70 to 79- and ≥80-year age groups. Median survival of patients in each group undergoing AVR plus CABG was slightly worse at 10, 8, and 6 years, respectively. Severe lung disease, renal failure, left ventricular dysfunction, and prior cardiac surgery were associated with significant reductions in median survival. STS perioperative risk of mortality was moderately predictive of long-term survival overall (C index, 0.71 over 10 years). However, intermediate- and high-risk patients by STS perioperative risk of mortality were found to have similar median survival times.

Conclusion: Study results support AVR as the standard of care for operative aortic valve disease because long-term survival is excellent for all patients ≥65 years of age. In particular, the survival of patients 70 to 79 and ≥80 years of age is nearly identical to that of the age-matched general population. A limitation of the study was the indirect identifier approach used to match patients in the STS database to Medicare denominator files; 25% of patients were unable to be matched, resulting in a study cohort that may not be representative of the overall surgical population with possible unmeasured confounders. Interestingly, STS perioperative risk of mortality did not appear to accurately differentiate intermediate- and high-risk patients when median survival was considered, implying that perioperative and long-term outcomes may be influenced by different factors.38

AVR in the Elderly: Determinants of Late Outcome

Summary: AVR is common in the elderly, but few studies have evaluated long-term outcomes in older patients undergoing AVR. The authors studied late survival and complications of 2890 patients ≥70 years of age (mean, 78±5 years) who underwent AVR (92% bioprosthesis; 8% mechanical valves) at the Mayo Clinic between 1993 and 2007. Five-, 10-, and 15-year survival rates were 68%, 34%, and 8%, respectively. Multivariable analysis identified 11 significant risk factors for late death, with age and renal failure being the 2 most important by HR. When risk-stratified by these factors, the lowest-risk group showed a survival rate (55%) similar to that of a matched general population, whereas higher-risk groups had lower-than-expected survival. A comparison of patients receiving mechanical and bioprosthetic valves showed no significant difference in overall survival but found lower survival in the highest-risk patients receiving mechanical prostheses. The overall incidence of bioprosthetic valve deterioration was found to be low at 2.9% over the 15-year follow-up period based on the combined end points of reoperation or echocardiographic evidence of either prosthetic stenosis or moderate to severe regurgitation. However, late echocardiographic follow-up (mean interval, 4.4±3.2 years) was available in only 63% of patients.

Conclusion: The overall survival of patients after AVR is strongly influenced by age and several other mostly nonmodifiable factors, suggesting that earlier surgical referral may be a strategy that merits further testing. Attention to risk in patients with chronic kidney disease also seems to be particularly important. The lack of validation of study results using a multi-institutional cohort is an important limitation because survival after surgery performed at the Mayo Clinic may not be generalizable to community practice. Similar efficacy of bioprosthetic and mechanical valves in this population is reassuring and consistent with current guidelines.48,49

Cost-effectiveness of TAVR Compared With Standard Care Among Inoperable Patients With Severe AS: Results From the Placement of Aortic Transcatheter Valves Trial (Cohort B)

Summary: The Placement of Aortic Transcatheter Valve (PARTNER) trial randomized patients to receive TAVR (n=179) or standard therapy that consisted of medical management or percutaneous aortic valvuloplasty as required (n=179). This substudy from the PARTNER trial evaluates the cost-effectiveness of TAVR in symptomatic patients with inoperable severe AS (cohort B) compared with standard therapy. Life expectancy, quality-adjusted life expectancy, and lifetime medical care costs were calculated on the basis of the survival, quality of life, medical resource use, and hospital cost data collected during the duration of the trial. The authors also calculated incremental cost-effectiveness for TAVR in the US context. For patients treated with TAVR, mean cost for the initial hospitalization was $78542. Follow-up cost through 12 months was lower with TAVR compared with routine therapy ($29289 versus $53621) because of reduced hospitalization rates, but cumulative 1-year cost remained higher ($106076 versus $53621) because of the increased initial cost of the procedure. Discounted life expectancy was projected to be increased by 1.6 years (1.3 quality-adjusted life-years) at an incremental cost of $79837 by TAVR. The incremental cost-effectiveness ratio for TAVR was thus estimated at $50200 per year of life gained or $61889 per quality-adjusted life-year gained. These results were stable across a broad range of uncertainty and sensitivity analyses.

Conclusion: In the current challenging financial context, studies assisting physicians in the delivery of high-value, cost-conscious care are critical. This analysis finds that TAVR is a justifiable intervention from a cost-effectiveness perspective because it meets the commonly accepted incremental cost-effectiveness ratio threshold of $50000. Because improved technology and operator experience improve valve function and procedure-related morbidity, respectively, incremental cost-effectiveness may further improve with time. Limitations of this study include the lack of long-term follow-up and its inclusion of a highly selected clinical trial population.43

Health-Related Quality of Life After TAVR in Inoperable Patients With Severe AS

Summary: The authors sought to evaluate improvement in health-related quality of life with TAVR compared with routine therapy consisting of medical management or aortic valvuloplasty in patients with inoperable symptomatic severe AS of the PARTNER trial. Health-related quality of life was assessed at baseline and at 1, 6, and 12 months with the Kansas City Cardiomyopathy Questionnaire and the 12-item Short Form-12 General Health Survey. The mean Kansas City Cardiomyopathy Questionnaire summary scores (35±20) and 12-item Short Form-12 General Health Survey physical summary scores (28±7) at baseline were markedly depressed in the study population compared with the general US population. The improvement of summary scores was greater after TAVR compared with routine therapy at 1 month (mean between-group difference, 13 points; 95% CI, 8–19; P<0.001) with larger benefits at 6 months (mean difference, 21 points; 95% CI, 15–27; P<0.001) and 12 months (mean difference, 26 points; 95% CI, 19–33; P<0.001). At 12 months, TAVR patients also reported higher 12-item Short Form-12 General Health Survey physical and mental health scores with mean differences compared with standard care of 5.7 and 6.4 points, respectively (P<0.001).

Conclusion: In this preplanned substudy from the PARTNER trial, TAVR was associated with a significant improvement in quality of life among patients with symptomatic severe AS who were deemed inoperable. Because studies have shown that the great majority of inoperable patients undergoing TAVR survive beyond 1 year postprocedure,1,43 it is important to know whether quality-of-life benefits are sustained beyond the 12 months studied in this article. Because TAVR technology improves and the procedure becomes less morbid, it is likely that quality-of-life improvement relative to medical management will become further pronounced.22

Incidence and Predictors of Early and Late Mortality After Transcatheter Aortic Valve Implantation in 663 Patients With Severe AS

Summary: Information on the incidence and predictors of both early mortality at 30 days and late mortality between 30 days and 1 year after transcatheter aortic valve implantation (TAVI) with the self-expanding CoreValve Revalving prosthesis remains scarce. Using data from a multicenter registry, the authors sought to provide information on incidence and predictors of early and late mortality in a total of 663 patients (mean age, 81.0±7.3 years) with symptomatic severe AS undergoing TAVI at 14 Italian centers. Procedural success and intraprocedural death occurred in 98% and 0.9% of patients, respectively. The cumulative incidence of mortality was 5.4% at 30 days, 12.2% at 6 months, and 15.0% at 1 year. Independent predictors of mortality at 30 days included conversion to open heart surgery (odds ratio [OR], 38.68), cardiac tamponade (OR, 10.97), major access site complications (OR, 8.47), left ventricular ejection fraction <40% (OR, 3.51), prior balloon valvuloplasty (OR, 2.87), and diabetes mellitus (OR, 2.66). Prior stroke (HR, 5.47), postprocedural paravalvular leak ≥2+ (HR, 3.79), prior acute pulmonary edema (HR, 2.70), and chronic kidney disease (HR, 2.53) were independent predictors of mortality between 30 days and 1 year. The discriminative ability of the logistic EuroSCORE for predicting risks of 30-day and 1-year mortality was weak (c statistic 0.55 for both).

Conclusion: This study describes long-term predictors of success after TAVI with the third-generation CoreValve Revalving System. Not surprisingly, the data indicate that early mortality was largely affected by procedural complications, whereas late mortality was influenced significantly by comorbidities. Importantly, the logistic EuroSCORE showed a weak discriminative ability in predicting both 30-day and 1-year mortality, highlighting the need for novel TAVI-specific scores such as the recently proposed Karnofsky index used in the post-TAVI setting.50 Comparative study of the predictors of mortality when using different TAVI bioprostheses would provide additional light on whether the covariates identified in this article maintain their significance across different device types.51

Correlates and Causes of Death in Patients With Severe Symptomatic AS Who Are Not Eligible to Participate in a Clinical Trial of TAVI

Summary: This single-center study aimed to detect the incidence and correlates of mortality in patients ineligible to participate in TAVI trial. From April 2007 to July 2009, 362 patients with severe AS who did not meet the necessary inclusion criteria for TAVI were screened and classified into 2 groups: Group 1 received medical treatment with or without balloon aortic valvuloplasty, and group 2 was intended to receive surgery. Groups 1 and 2 included 274 and 88 patients, respectively. In group 1, 97 patients (35.4%) were treated medically and 177 patients (64.6%) were treated with valvuloplasty. This group was of significantly higher periprocedural risk than the surgical group, with significantly higher STS scores (12.8±7.0 versus 8.5±5.1; P<0.001) and logistic EuroSCORE (42.4±22.8 versus 24.4±18.1; P<0.001). After 1-year follow-up, mortality rate in group 1 was 37.2%, and mortality rate in group 2 was 21.5%. After multivariate adjustment, renal failure (HR, 5.60) and NYHA class IV (HR, 5.88) were identified as independent correlates for mortality in the medical group, whereas renal failure (HR, 7.45), STS score (HR, 1.09), and logistic EuroSCORE (HR, 1.45) were correlates of mortality in the surgical group.

Conclusion: Study results demonstrate that patients with severe symptomatic AS formerly ineligible for TAVI trials will experience high mortality rates even when undergoing surgical AVR. Renal failure was an important predictor of risk in both surgical and nonsurgical patients. It is possible that indication creep in typical practice may lead to a number of these medically managed patients receiving TAVI in the future. For these patients, it is unknown whether outcomes would be similar to those receiving TAVI the PARTNER B trial.43,52

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