Alan Zajarias

Two-year outcomes after transcatheter or surgical aortic-valve replacement.

BACKGROUND The Placement of Aortic Transcatheter Valves (PARTNER) trial showed that among high-risk patients with aortic stenosis, the 1-year survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical replacement. However, longer-term follow-up is necessary to determine whether TAVR has prolonged benefits. METHODS At 25 centers, we randomly assigned 699 high-risk patients with severe aortic stenosis to undergo either surgical aortic-valve replacement or TAVR. All patients were followed for at least 2 years, with assessment of clinical outcomes and echocardiographic evaluation. RESULTS The rates of death from any cause were similar in the TAVR and surgery groups (hazard ratio with TAVR, 0.90; 95% confidence interval [CI], 0.71 to 1.15; P=0.41) and at 2 years (Kaplan-Meier analysis) were 33.9% in the TAVR group and 35.0% in the surgery group (P=0.78). The frequency of all strokes during follow-up did not differ significantly between the two groups (hazard ratio, 1.22; 95% CI, 0.67 to 2.23; P=0.52). At 30 days, strokes were more frequent with TAVR than with surgical replacement (4.6% vs. 2.4%, P=0.12); subsequently, there were 8 additional strokes in the TAVR group and 12 in the surgery group. Improvement in valve areas was similar with TAVR and surgical replacement and was maintained for 2 years. Paravalvular regurgitation was more frequent after TAVR (P<0.001), and even mild paravalvular regurgitation was associated with increased late mortality (P<0.001). CONCLUSIONS A 2-year follow-up of patients in the PARTNER trial supports TAVR as an alternative to surgery in high-risk patients. The two treatments were similar with respect to mortality, reduction in symptoms, and improved valve hemodynamics, but paravalvular regurgitation was more frequent after TAVR and was associated with increased late mortality. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.).

Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients

BACKGROUND Previous trials have shown that among high-risk patients with aortic stenosis, survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. We evaluated the two procedures in a randomized trial involving intermediate-risk patients. METHODS We randomly assigned 2032 intermediate-risk patients with severe aortic stenosis, at 57 centers, to undergo either TAVR or surgical replacement. The primary end point was death from any cause or disabling stroke at 2 years. The primary hypothesis was that TAVR would not be inferior to surgical replacement. Before randomization, patients were entered into one of two cohorts on the basis of clinical and imaging findings; 76.3% of the patients were included in the transfemoral-access cohort and 23.7% in the transthoracic-access cohort. RESULTS The rate of death from any cause or disabling stroke was similar in the TAVR group and the surgery group (P=0.001 for noninferiority). At 2 years, the Kaplan-Meier event rates were 19.3% in the TAVR group and 21.1% in the surgery group (hazard ratio in the TAVR group, 0.89; 95% confidence interval [CI], 0.73 to 1.09; P=0.25). In the transfemoral-access cohort, TAVR resulted in a lower rate of death or disabling stroke than surgery (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P=0.05), whereas in the transthoracic-access cohort, outcomes were similar in the two groups. TAVR resulted in larger aortic-valve areas than did surgery and also resulted in lower rates of acute kidney injury, severe bleeding, and new-onset atrial fibrillation; surgery resulted in fewer major vascular complications and less paravalvular aortic regurgitation. CONCLUSIONS In intermediate-risk patients, TAVR was similar to surgical aortic-valve replacement with respect to the primary end point of death or disabling stroke. (Funded by Edwards Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313.).

Outcomes and Safety of Percutaneous Aortic Valve Replacement

The concept of transcatheter aortic valve replacement was developed with the goal of offering a therapeutic solution to patients with severe symptomatic aortic stenosis who are not considered good candidates for surgical valve replacement. Initial attempts were complicated by vascular access problems and lack of appropriate tools. With time and experience, early problems were solved and the concepts of valve sizing, valve positioning, and patient selection were defined. Technological improvements allowed the use of smaller arterial sheaths to decrease vascular trauma, special catheters to facilitate valve delivery, and treatments on the valve prostheses that would ensure longer durability. After 5 years, the number of transcatheter aortic valve replacements has grown significantly, and will likely continue as this technology becomes increasingly available. Currently, 2 valve models, the Edwards SAPIEN valve (Edwards Lifescience, Irvine, California) and the CoreValve ReValving system (CoreValve Inc., Irvine, California), have been used in over 4,000 cases worldwide for the treatment of symptomatic aortic stenosis. Midterm follow-up shows no evidence of restenosis or prosthetic valve dysfunction. Transfemoral and transapical delivery routes can be selected depending on the quality of vascular access and the type of prosthesis used. Randomized trials that are currently underway will confirm procedural safety and guide the applicability of this technology.

Paravalvular regurgitation after transcatheter aortic valve replacement with the Edwards sapien valve in the PARTNER trial: characterizing patients and impact on outcomes

AIM The impact of paravalvular regurgitation (PVR) following transcatheter aortic valve replacement (TAVR) remains uncertain. In this analysis, we sought to evaluate the impact of varying degrees of PVR on both mortality and changes in ventricular geometry and function. METHODS AND RESULTS Clinical and echocardiographic outcomes of patients who underwent TAVR from the randomized cohorts and continued access registries in the PARTNER trial were analysed after stratifying by severity of post-implant PVR, which was graded as none/trace in 52.9% (n = 1288), mild in 38.0% (n = 925), and moderate/severe in 9.1% (n = 221). There were significant differences in baseline clinical and echocardiographic characteristics. After TAVR, all the patients demonstrated increase in left ventricular (LV) function and reduction in the LV mass index, although the magnitude of mass regression was lower in the moderate/severe PVR group. The 30-day mortality (3.1 vs. 3.4 vs. 4.5%, P = 0.56) and stroke (3.4 vs. 3.7 vs. 2.3%, P = 0.59) were similar in all groups (none/trace, mild, and moderate/severe). At 1 year, there was increased all-cause mortality (15.9 vs. 22.2 vs. 35.1%, P < 0.0001), cardiac mortality (6.1 vs. 7.4% vs. 16.3%, P < 0.0001) and re-hospitalization (14.4 vs. 23.0 vs. 31.3%, P < 0.0001) with worsening PVR. A multivariable analysis indicated that the presence of moderate/severe PVR (HR: 2.18, 95% CI: 1.57-3.02, P < 0.0001) or mild PVR (HR: 1.37, 95% CI: 1.14-1.90, P = 0.012) was associated with higher late mortality. CONCLUSION Differences in baseline characteristics in patients with increasing severities of PVR may increase the risk of this complication. Despite these differences, multivariable analysis demonstrated that both mild and moderate/severe PVR predicted higher 1-year mortality.

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)

OBJECTIVES This study sought to compare health status and quality-of-life outcomes for patients with severe aortic stenosis (AS) and high surgical risk treated with either transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (AVR). BACKGROUND For high-risk patients with severe AS, TAVR has been shown to result in similar 12-month survival but differing adverse events compared with AVR. METHODS We evaluated the health status of 628 patients with severe, symptomatic AS at high risk of surgical complications who were randomized to either TAVR or AVR in the PARTNER Trial. Health status was assessed at baseline and 1, 6, and 12 months using the Kansas City Cardiomyopathy Questionnaire, the Short Form-12, and the EuroQol-5D. RESULTS The primary outcome, the Kansas City Cardiomyopathy Questionnaire summary score, improved more rapidly with TAVR, but was similar for the 2 groups at 6 and 12 months. However, there was a significant interaction between the benefit of TAVR and access site (transapical vs. transfemoral). Patients eligible for transfemoral TAVR demonstrated significant health status benefits with TAVR versus AVR at 1 month (difference, 9.9 points; 95% confidence interval: 4.9 to 14.9; p < 0.001), whereas patients treated via the TA approach demonstrated no benefits with TAVR compared with AVR at any time point. Results for Kansas City Cardiomyopathy Questionnaire subscales and generic measures demonstrated similar patterns. CONCLUSIONS In high-risk patients with severe AS, health status improved substantially between baseline and 1 year after either TAVR or AVR. TAVR via the transfemoral, but not the transapical route, was associated with a short-term advantage compared with surgery. (Placement of AoRTic TraNscathetER Valve [PARTNER] trial; NCT00530894).

Predictive factors, management, and clinical outcomes of coronary obstruction following transcatheter aortic valve implantation: Insights from a large multicenter registry

OBJECTIVES This study sought to evaluate the main baseline and procedural characteristics, management, and clinical outcomes of patients from a large cohort of patients undergoing transcatheter aortic valve implantation (TAVI) who suffered coronary obstruction (CO). BACKGROUND Very little data exist on CO following TAVI. METHODS This multicenter registry included 44 patients who suffered symptomatic CO following TAVI of 6,688 patients (0.66%). Pre-TAVI computed tomography data was available in 28 CO patients and in a control group of 345 patients (comparisons were performed including all patients and a cohort matched 1:1 by age, sex, previous coronary artery bypass graft, transcatheter valve type, and size). RESULTS Baseline and procedural variables associated with CO were older age (p < 0.001), female sex (p < 0.001), no previous coronary artery bypass graft (p = 0.043), the use of a balloon-expandable valve (p = 0.023), and previous surgical aortic bioprosthesis (p = 0.045). The left coronary artery was the most commonly involved (88.6%). The mean left coronary artery ostia height and sinus of Valsalva diameters were lower in patients with obstruction than in control subjects (10.6 ± 2.1 mm vs. 13.4 ± 2.1 mm, p < 0.001; 28.1 ± 3.8 mm vs. 31.9 ± 4.1 mm, p < 0.001). Differences between groups remained significant after the case-matched analysis (p < 0.001 for coronary height; p = 0.01 for sinus of Valsalva diameter). Most patients presented with persistent severe hypotension (68.2%) and electrocardiographic changes (56.8%). Percutaneous coronary intervention was attempted in 75% of the cases and was successful in 81.8%. Thirty-day mortality was 40.9%. After a median follow-up of 12 (2 to 18) months, the cumulative mortality rate was 45.5%, and there were no cases of stent thrombosis or reintervention. CONCLUSIONS Symptomatic CO following TAVI was a rare but life-threatening complication that occurred more frequently in women, in patients receiving a balloon-expandable valve, and in those with a previous surgical bioprosthesis. Lower-lying coronary ostium and shallow sinus of Valsalva were associated anatomic factors, and despite successful treatment, acute and late mortality remained very high, highlighting the importance of anticipating and preventing the occurrence of this complication.

Predictors of Poor Outcomes After Transcatheter Aortic Valve Replacement Results From the PARTNER (Placement of Aortic Transcatheter Valve) Trial

Background— Transcatheter aortic valve replacement (TAVR) is a less invasive option for treatment of high-risk patients with severe aortic stenosis. We sought to identify patients at high risk for poor outcome after TAVR using a novel definition of outcome that integrates quality of life with mortality. Methods and Results— Among 2137 patients who underwent TAVR in the PARTNER (Placement of Aortic Transcatheter Valve) trial or its associated continued access registry, quality of life was assessed with the Kansas City Cardiomyopathy Questionnaire–Overall Summary Scale (KCCQ-OS; range 0–100, where a higher score equates to a better quality of life) at baseline and at 1, 6, and 12 months after TAVR. A poor 6-month outcome (defined as death, KCCQ-OS score <45, or ≥10-point decrease in KCCQ-OS score compared with baseline) occurred in 704 patients (33%). Using a split-sample design, we developed a multivariable model to identify a parsimonious set of covariates to identify patients at high risk for poor outcome. The model demonstrated moderate discrimination (c-index=0.66) and good calibration with the observed data, performed similarly in the separate validation cohort (c-index=0.64), and identified 211 patients (10% of the population) with a ≥50% likelihood of a poor outcome after TAVR. A second model that explored predictors of poor outcome at 1 year identified 1102 patients (52%) with ≥50% likelihood and 178 (8%) with ≥70% likelihood of a poor 1-year outcome after TAVR. Conclusions— Using a large, multicenter cohort, we have developed and validated predictive models that can identify patients at high risk for a poor outcome after TAVR. Although model discrimination was moderate, these models may help guide treatment choices and offer patients realistic expectations of outcomes based on their presenting characteristics. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.Background— Transcatheter aortic valve replacement (TAVR) is a less invasive option for treatment of high-risk patients with severe aortic stenosis. We sought to identify patients at high risk for poor outcome after TAVR using a novel definition of outcome that integrates quality of life with mortality. Methods and Results— Among 2137 patients who underwent TAVR in the PARTNER (Placement of Aortic Transcatheter Valve) trial or its associated continued access registry, quality of life was assessed with the Kansas City Cardiomyopathy Questionnaire–Overall Summary Scale (KCCQ-OS; range 0–100, where a higher score equates to a better quality of life) at baseline and at 1, 6, and 12 months after TAVR. A poor 6-month outcome (defined as death, KCCQ-OS score <45, or ≥10-point decrease in KCCQ-OS score compared with baseline) occurred in 704 patients (33%). Using a split-sample design, we developed a multivariable model to identify a parsimonious set of covariates to identify patients at high risk for poor outcome. The model demonstrated moderate discrimination ( c -index=0.66) and good calibration with the observed data, performed similarly in the separate validation cohort ( c -index=0.64), and identified 211 patients (10% of the population) with a ≥50% likelihood of a poor outcome after TAVR. A second model that explored predictors of poor outcome at 1 year identified 1102 patients (52%) with ≥50% likelihood and 178 (8%) with ≥70% likelihood of a poor 1-year outcome after TAVR. Conclusions— Using a large, multicenter cohort, we have developed and validated predictive models that can identify patients at high risk for a poor outcome after TAVR. Although model discrimination was moderate, these models may help guide treatment choices and offer patients realistic expectations of outcomes based on their presenting characteristics. Clinical Trial Registration— URL: . Unique identifier: [NCT00530894][1]. # CLINICAL PERSPECTIVE {#article-title-31} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00530894&atom=%2Fcirculationaha%2F129%2F25%2F2682.atom

Impact of Preoperative Moderate/Severe Mitral Regurgitation on 2-Year Outcome After Transcatheter and Surgical Aortic Valve Replacement Insight From the Placement of Aortic Transcatheter Valve (PARTNER) Trial Cohort A

Background— The effect of preoperative mitral regurgitation (MR) on clinical outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) is controversial. This study sought to examine the impact of moderate and severe MR on outcomes after TAVR and surgical aortic valve replacement (SAVR). Methods and Results— Data were drawn from the randomized Placement of Aortic Transcatheter Valve (PARTNER) Trial cohort A patients with severe, symptomatic aortic stenosis undergoing either TAVR (n=331) or SAVR (n=299). Both TAVR and SAVR patients were dichotomized according to the degree of preoperative MR (moderate/severe versus none/mild). At baseline, moderate or severe MR was reported in 65 TAVR patients (19.6%) and 63 SAVR patients (21.2%). At 30 days, among survivors who had isolated SAVR/TAVR, moderate/severe MR had improved in 25 SAVR patients (69.4%) and 30 TAVR patients (57.7%), was unchanged in 10 SAVR patients (27.8%) and 19 TAVR patients (36.5%), and worsened in 1 SAVR patient (2.8%) and 4 TAVR patients (5.8%; all P=NS). Mortality at 2 years was higher in SAVR patients with moderate or severe MR than in those with mild or less MR (49.8% versus 28.1%; adjusted hazard ratio, 1.73; 95% confidence interval, 1.01–2.96; P=0.04). In contrast, MR severity at baseline did not affect mortality in TAVR patients (37.0% versus 32.7%, moderate/severe versus none/mild; hazard ratio, 1.14; 95% confidence interval, 0.72–1.78; P=0.58; P for interaction=0.05). Conclusions— Both TAVR and SAVR were associated with a significant early improvement in MR in survivors. However, moderate or severe MR at baseline was associated with increased 2-year mortality after SAVR but not after TAVR. TAVR may be a reasonable option in selected patients with combined aortic and mitral valve disease. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.Background— The effect of preoperative mitral regurgitation (MR) on clinical outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) is controversial. This study sought to examine the impact of moderate and severe MR on outcomes after TAVR and surgical aortic valve replacement (SAVR). Methods and Results— Data were drawn from the randomized Placement of Aortic Transcatheter Valve (PARTNER) Trial cohort A patients with severe, symptomatic aortic stenosis undergoing either TAVR (n=331) or SAVR (n=299). Both TAVR and SAVR patients were dichotomized according to the degree of preoperative MR (moderate/severe versus none/mild). At baseline, moderate or severe MR was reported in 65 TAVR patients (19.6%) and 63 SAVR patients (21.2%). At 30 days, among survivors who had isolated SAVR/TAVR, moderate/severe MR had improved in 25 SAVR patients (69.4%) and 30 TAVR patients (57.7%), was unchanged in 10 SAVR patients (27.8%) and 19 TAVR patients (36.5%), and worsened in 1 SAVR patient (2.8%) and 4 TAVR patients (5.8%; all P =NS). Mortality at 2 years was higher in SAVR patients with moderate or severe MR than in those with mild or less MR (49.8% versus 28.1%; adjusted hazard ratio, 1.73; 95% confidence interval, 1.01–2.96; P =0.04). In contrast, MR severity at baseline did not affect mortality in TAVR patients (37.0% versus 32.7%, moderate/severe versus none/mild; hazard ratio, 1.14; 95% confidence interval, 0.72–1.78; P =0.58; P for interaction=0.05). Conclusions— Both TAVR and SAVR were associated with a significant early improvement in MR in survivors. However, moderate or severe MR at baseline was associated with increased 2-year mortality after SAVR but not after TAVR. TAVR may be a reasonable option in selected patients with combined aortic and mitral valve disease. Clinical Trial Registration— URL: . Unique identifier: [NCT00530894][1]. # Clinical Perspective {#article-title-27} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00530894&atom=%2Fcirculationaha%2F128%2F25%2F2776.atom

How to Define a Poor Outcome After Transcatheter Aortic Valve Replacement Conceptual Framework and Empirical Observations From the Placement of Aortic Transcatheter Valve (PARTNER) Trial

Background—Transcatheter aortic valve replacement (TAVR) has emerged as a less invasive option for valve replacement of patients with severe aortic stenosis. Although it has been recommended that TAVR should not be offered to patients who will not improve functionally or derive meaningful survival benefit from the procedure, no guidance exists on how best to identify such patients. The first step in this process is to define a poor outcome that can then be used as a foundation for subsequent case identification. We sought to evaluate potential definitions of a poor outcome after TAVR that combine both mortality and quality of life components. Methods and Results—Using data from 463 patients who underwent TAVR as part of the Placement of AoRTic TraNscathetER Valve (PARTNER) trial, we evaluated 6-month mortality and quality of life outcomes using the Kansas City Cardiomyopathy Questionnaire to explore potential definitions of a poor outcome. We then compared the strengths and weaknesses of each potential definition by examining the relationship between baseline and 6-month Kansas City Cardiomyopathy Questionnaire scores for each patient. Based on these analyses, we argue that the most appropriate definition of a poor outcome after TAVR is (1) death, (2) Kansas City Cardiomyopathy Questionnaire overall summary score <45, or (3) Kansas City Cardiomyopathy Questionnaire decrease of ≥10 points, which best reflects a failure to achieve the therapeutic goals of TAVR. Conclusions—Using empirical data on a large number of patients enrolled in the PARTNER trial, we propose a definition for poor outcome after TAVR that combines both mortality and quality of life measures into a single composite end point. Use of this end point (or other similar end points) in future studies can facilitate development of predictive models that may be useful to identify patients who are poor candidates for TAVR and to provide such patients and their families with appropriate expectations of functional recovery after TAVR.

Effects of Phosphodiesterase Type 5 Inhibition on Systemic and Pulmonary Hemodynamics and Ventricular Function in Patients With Severe Symptomatic Aortic Stenosis

Background— Pressure overload resulting from aortic stenosis causes maladaptive ventricular and vascular remodeling that can lead to pulmonary hypertension, heart failure symptoms, and adverse outcomes. Retarding or reversing this maladaptive remodeling and its unfavorable hemodynamic consequences has the potential to improve morbidity and mortality. Preclinical models of pressure overload have shown that phosphodiesterase type 5 inhibition is beneficial; however, the use of phosphodiesterase type 5 inhibitors in patients with aortic stenosis is controversial because of concerns about vasodilation and hypotension. Methods and Results— We evaluated the safety and hemodynamic response of 20 subjects with severe symptomatic aortic stenosis (mean aortic valve area, 0.7±0.2 cm2; ejection fraction, 60±14%) who received a single oral dose of sildenafil (40 or 80 mg). Compared with baseline, after 60 minutes, sildenafil reduced systemic (−12%; P<0.001) and pulmonary (−29%; P=0.002) vascular resistance, mean pulmonary artery (−25%; P<0.001) and wedge (−17%; P<0.001) pressures, and increased systemic (13%; P<0.001) and pulmonary (45%; P<0.001) vascular compliance and stroke volume index (8%; P=0.01). These changes were not dose dependent. Sildenafil caused a modest decrease in mean systemic arterial pressure (−11%; P<0.001) but was well tolerated with no episodes of symptomatic hypotension. Conclusions— This study shows for the first time that a single dose of a phosphodiesterase type 5 inhibitor is safe and well tolerated in patients with severe aortic stenosis and is associated with improvements in pulmonary and systemic hemodynamics resulting in biventricular unloading. These findings support the need for longer-term studies to evaluate the role of phosphodiesterase type 5 inhibition as adjunctive medical therapy in patients with aortic stenosis. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01060020.