Thourani, Vinod H.

ObjectivesTo identify number of cases needed to maximize device success and minimize adverse events after transfemoral transcatheter aortic valve replacement (TF‐TAVR), and determine if adverse events were linked to the technical performance learning curve.BackgroundTF‐TAVR is a complex procedure with an incompletely characterized learning curve for clinical outcomes.MethodsFrom 4/2007–2/2012, 1521 patients underwent TF‐TAVR in the PARTNER‐I trial. Outcomes learning curves were defined as number of cases needed to reach a plateau for device success, adverse events, and post‐procedure length of stay. Institutional variation was accounted for by mixed‐model non‐linear techniques, which were also used to identify contribution of the procedure time learning curve to 30‐day major adverse events and length of stay.ResultsEighty percent device success was achieved after 22 cases; major vascular complications fell below 5% after 70 cases and major bleeding below 10% after 25 cases. It took an average of 28 cases to achieve a consistent low risk of 30‐day major adverse events, but institutions entering in the middle of the trial achieved it after about 26. The most significant correlate of 30‐day major adverse events and post‐procedure length of stay was procedure time (P < 0.0001). However, this association was related to patient and unmeasured variables, not the procedure time learning curve (P = 0.6).ConclusionsBy end of trial, a consistent low risk of adverse events was achieved after ∼26 cases. However, these improved results were due to change in patient risk profile; outcomes were not linked to the technical performance learning curve. © 2015 Wiley Periodicals, Inc.

Objective Pulmonary hypertension (PH) is associated with increased mortality after surgical or transcatheter aortic valve replacement (TAVR) for aortic stenosis (AS), and when the pulmonary artery pressure is particularly elevated, there may be questions about the clinical benefit of TAVR. We aimed to identify clinical and haemodynamic factors associated with increased mortality after TAVR among those with moderate/severe PH. Methods Among patients with symptomatic AS at high or prohibitive surgical risk receiving TAVR in the Placement of Aortic Transcatheter Valves (PARTNER) I randomised trial or registry, 2180 patients with an invasive measurement of mean pulmonary artery pressure (mPAP) recorded were included, and moderate/severe PH was defined as an mPAP ≥35 mm Hg. Results Increasing severity of PH was associated with progressively worse 1-year all-cause mortality: none (n=785, 18.6%), mild (n=838, 22.7%) and moderate/severe (n=557, 25.0%) (p=0.01). The increased hazard of mortality associated with moderate/severe PH was observed in females, but not males (interaction p=0.03). In adjusted analyses, females with moderate/severe PH had an increased hazard of death at 1 year compared with females without PH (adjusted HR 2.14, 95% CI 1.44 to 3.18), whereas those with mild PH did not. Among males, there was no increased hazard of death associated with any severity of PH. In a multivariable Cox model of patients with moderate/severe PH, oxygen-dependent lung disease, inability to perform a 6 min walk, impaired renal function and lower aortic valve mean gradient were independently associated with increased 1-year mortality (p<0.05 for all), whereas several haemodynamic indices were not. A risk score, including these factors, was able to identify patients with a 15% vs 59% 1-year mortality. Conclusions The relationship between moderate/severe PH and increased mortality after TAVR is altered by sex, and clinical factors appear to be more influential in stratifying risk than haemodynamic indices. These findings may have implications for the evaluation of and treatment decisions for patients referred for TAVR with significant PH. Trial registration NCT00530894.

ObjectivesTo assess technical performance learning curves of teams performing transfemoral transcatheter aortic valve replacement (TF‐TAVR).BackgroundTF‐TAVR is a new procedure for treating severe aortic stenosis. The number of cases required for procedural efficiency is unknown.MethodsIn the PARTNER‐I trial, 1,521 patients underwent TF‐TAVR from 4/2007–2/2012. Learning curve analysis of technical performance metrics was performed using institution‐specific patient sequence number, interval between procedures, and institutional trial entry date. Learning curve characteristics were assessed using semi‐parametric and parametric mixed‐effects models.ResultsAs patient sequence number increased, average procedure time decreased from 154 to 85 minutes (P < 0.0001), and fluoroscopy time from 28 to 20 minutes (P < 0.0001). Procedure time plateaued at an average of 83 minutes (range 52–140). Procedure time plateau was dynamic during the course of the trial, averaging 25 cases (range 21–52) by its end. The later institutions enrolled in the trial, the shorter the initial procedure time. During the trial, percutaneous rather than surgical access increased from 7.9% to 69%.ConclusionsTechnical performance learning curves exist for TF‐TAVR; procedural efficiency increased with experience, with concomitant decreases in radiation and contrast media exposure. The number of cases needed to achieve efficiency decreased progressively, with optimal procedural performance reached after approximately 25 cases for late‐entering institutions. Knowledge and experience accumulated by early TF‐TAVR institutions were disseminated, shortening the learning curve of late‐entering institutions. Technological advances resulting from learning during the trial moved the field from initial conservative surgical cut‐down to percutaneous access for most patients. © 2015 Wiley Periodicals, Inc.

Background— Tricuspid regurgitation (TR) and right ventricular (RV) dysfunction adversely affect outcomes in patients with heart failure or mitral valve disease, but their impact on outcomes in patients with aortic stenosis treated with transcatheter aortic valve replacement has not been well characterized. Methods and Results— Among 542 patients with symptomatic aortic stenosis treated in the Placement of Aortic Transcatheter Valves (PARTNER) II trial (inoperable cohort) with a Sapien or Sapien XT valve via a transfemoral approach, baseline TR severity, right atrial and RV size and RV function were evaluated by echocardiography according to established guidelines. One-year mortality was 16.9%, 17.2%, 32.6%, and 61.1% for patients with no/trace (n=167), mild (n=205), moderate (n=117), and severe (n=18) TR, respectively ( P <0.001). Increasing severity of RV dysfunction as well as right atrial and RV enlargement were also associated with increased mortality ( P <0.001). After multivariable adjustment, severe TR (hazard ratio, 3.20; 95% confidence interval, 1.50–6.82; P =0.003) and moderate TR (hazard ratio, 1.60; 95% confidence interval, 1.02–2.52; P =0.042) remained associated with increased mortality as did right atrial and RV enlargement, but not RV dysfunction. There was an interaction between TR and mitral regurgitation severity ( P =0.04); the increased hazard of death associated with moderate/severe TR only occurred in those with no/trace/mild mitral regurgitation. Conclusions— In inoperable patients treated with transcatheter aortic valve replacement, moderate or severe TR and right heart enlargement are independently associated with increased 1-year mortality; however, the association between moderate or severe TR and an increased hazard of death was only found in those with minimal mitral regurgitation at baseline. These findings may improve our assessment of anticipated benefit from transcatheter aortic valve replacement and support the need for future studies on TR and the right heart, including whether concomitant treatment of TR in operable but high-risk patients with aortic stenosis is warranted. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01314313.

Background— The higher risk of adverse outcomes after transapical (TA) versus transfemoral (TF) transcatheter aortic valve replacement (TAVR) could be attributable to TA-TAVR being an open surgical procedure or to clinical differences between TA- and TF-TAVR patients. We compared outcomes after neutralizing patient differences using propensity score matching. Methods and Results— From April 2007 to February 2012, 1100 Placement of Aortic Transcatheter Valves (PARTNER)-I patients underwent TA-TAVR and 1521 underwent TF-TAVR with Edwards SAPIEN balloon-expandable bioprostheses. Propensity matching based on 111 preprocedural variables, exclusive of femoral access morphology, identified 501 well-matched patient pairs (46% of possible matches), 95% of whom had peripheral arterial disease. Matched TA-TAVR patients experienced more adverse procedural events, longer length of stay (5 versus 8 days; P <0.0001), and slower recovery (New York Heart Association class I, 31% versus 38% at 30 days, equalizing by 6 months at 51% versus 47%); stroke risk was similar (3.4% versus 3.3% at 30 days and 6.0% versus 6.7% at 3 years); mortality was elevated for the first 6 postprocedural months (19% versus 12%; P =0.01); but aortic regurgitation was less (34% versus 52% mild and 8.9% versus 12% moderate to severe at discharge, P =0.001; 36% versus 50% mild and 10% versus 15% moderate to severe at 6 months, P <0.0001). Conclusions— The likelihood of adverse periprocedural events and prolonged recovery is greater after TA-TAVR than TF-TAVR in vasculopathic patients after accounting for differences in cardiovascular risk factors, although stroke risk is equivalent and aortic regurgitation is less. As smaller delivery systems permit TF-TAVR in many of these patients, we recommend a TF-first access strategy for TAVR when anatomically feasible. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00530894.

BackgroundTranscatheter aortic valve replacement (TAVR) with the balloon‐expandable Sapien transcatheter heart valve improves survival compared to standard therapy in patients with severe aortic stenosis (AS) and is noninferior to surgical aortic valve replacement (AVR) in patients at high operative risk. Nonetheless, a significant proportion of patients may require pre‐emptive or emergent support with cardiopulmonary bypass (CPB) and/or intra‐aortic balloon pump (IABP) during TAVR due to pre‐existing comorbid conditions or as a result of procedural complications. Objectives: We hypothesized that patients who required CPB or IABP would have increased periprocedural complications and reduced long‐term survival. In addition, we sought to determine whether preprocedural variables could predict the need for CPB and IABP. Methods: The study population included 2,525 patients in the PARTNER Trial (Cohort A and B) and the continuing access registry (CAR). Patients that received CPB or IABP were compared to patients that did not receive either, and then further divided into those that received support pre‐TAVR and those that were placed on support emergently. Results: One‐hundred sixty‐three patients (6.5%) were placed on CPB and/or IABP. The use of CPB or IABP was associated with higher 1 year mortality (49.1% vs. 21.6%, P < 0.001). In multivariable analysis, utilization of CPB or IABP was an independent predictor of 30 day (HR 6.95) and 1‐year (HR 2.56) mortality. Although mortality was highest in emergent cases, mortality was also greater in planned CPB and IABP cases compared with non‐CPB/IABP cases (53.3% and 40.3% vs. 21.6%, P < 0.001). Conclusions: These findings indicate that CPB and IABP use in TAVR portends a poor prognosis and its utilization, particularly in the setting of pre‐emptive use, needs reconsideration. © 2015 Wiley Periodicals, Inc.

Background— In patients with severe aortic stenosis, transcatheter aortic valve replacement (TAVR) improves survival when compared with nonsurgical therapy but with higher in-hospital and lifetime costs. Complications associated with TAVR may decrease with greater experience and improved devices, thereby reducing the overall cost of the procedure. Therefore, we sought to estimate the effect of periprocedural complications on in-hospital costs and length of stay of TAVR. Methods and Results— Using detailed cost data from 406 TAVR patients enrolled in the Placement of Aortic Transcatheter Valve (PARTNER) I trial, we developed multivariable models to estimate the incremental cost and length of stay associated with specific periprocedural complications. Attributable costs and length of stay for each complication were calculated by multiplying the independent cost of each event by its frequency in the treatment group. Mean cost for the initial hospitalization was $79 619±40 570 ($50 891 excluding the valve); 49% of patients had ≥1 complication. Seven complications were independently associated with increased hospital costs, with major bleeding, arrhythmia, and death accounting for the largest attributable cost per patient. Renal failure and the need for repeat TAVR, although less frequent, were also associated with substantial incremental and attributable costs. Overall, complications accounted for $12 475 per patient in initial hospital costs and 2.4 days of hospitalization. Conclusions— In the PARTNER trial, periprocedural complications were frequent, costly, and accounted for ≈25% of non-implant–related hospital costs. Avoidance of complications should improve the cost-effectiveness of TAVR for inoperable and high-risk patients, but reductions in the cost of uncomplicated TAVR will also be necessary for optimal efficiency. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00530894.

Background— The objective was to evaluate the effects of aortic annulus size on valve hemodynamics and clinical outcomes in those patients included in the Placement of Aortic Transcatheter Valves (PARTNER) randomized controlled trial cohort A and the nonrandomized continued access cohort. Methods and Results— Patients included the randomized controlled trial (n=574) and nonrandomized continued access (n=1358) cohorts were divided in tertiles according to aortic annulus diameter (small aortic annulus tertile, medium aortic annulus tertile, and large aortic annulus tertile [LAA], respectively) as measured by transthoracic echocardiography. Severe prosthesis–patient mismatch was defined as an effective aortic orifice area of <0.65 cm 2 /m 2 . In the randomized controlled trial cohort, patients in the small aortic annulus tertile who underwent transcatheter aortic valve replacement had a lower incidence of severe prosthesis–patient mismatch (19.7% versus 37.5%; P =0.03) and only a trend toward a higher incidence of moderate-to-severe paravalvular leaks compared with surgical aortic valve replacement (5.7% versus 0%; P =0.06). In the LAA tertile, there were no differences in the rate of prosthesis–patient mismatch between groups, and a significant increase in moderate-to-severe paravalvular leaks was associated with transcatheter aortic valve replacement (9% versus 0%; P =0.01). There were no differences in mortality between transcatheter aortic valve replacement and surgical aortic valve replacement. In the nonrandomized continued access cohort, there were no differences in prosthesis–patient mismatch between the small aortic annulus and LAA tertiles, but a higher rate of moderate-to-severe paravalvular leaks was observed in the LAA tertile (5.9% versus 11.5%; P =0.009). Patients in the LAA tertile had a higher mortality rate at 1-year follow-up ( P =0.02), and differences persisted in multivariable analysis ( P =0.048 for LAA versus medium aortic annulus tertile, P =0.035 for LAA versus small aortic annulus tertile). Conclusions— Aortic annulus size had a major impact on valve hemodynamics and clinical outcomes after transcatheter aortic valve replacement and surgical aortic valve replacement. This study highlights the importance of considering aortic annulus size in the evaluation of high-risk patients who are candidates for aortic valve replacement. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00530894.

Objective Multiple-valve (MUV) procedures currently exhibit higher operative mortality than do single-valve procedures, but a paucity of scientific information exists to explain the observation. This topic was examined using The Society of Thoracic Surgeons Database. Methods All patients in the The Society of Thoracic Surgeons data set undergoing valve surgery (except pulmonary valve and aortic root operations) from 1993 through 2007 were identified (N = 623,039). Baseline characteristics and postoperative outcomes were contrasted between all seven combinations of single-valve and MUV procedures involving aortic, mitral, and tricuspid valves. Seven independent logistic regression analyses were performed, based on the seven procedures, and multivariable risk factors for mortality were compared, with emphasis on single-valve versus MUV procedures. Results Baseline characteristics for MUV procedures (n = 67,926) shared many similarities to those for single-valve procedures (n = 555,113), including age, ejection fraction, and comorbidities. Preoperative renal failure, New York Heart Association class III to IV, nonelective presentation, and reoperation were slightly more common in MUV subsets, and coronary bypass was less frequent. Operative mortality was almost double for MUV as compared with single-valve procedures (10.7% vs 5.7%, P = 0.0001). Categorical predictors with the largest odds ratios for mortality were emergency status, renal failure, and second reoperation. However, predictors for mortality were generally consistent in order and magnitude between the single-valve and MUV subgroups. Conclusions Despite similarities in preoperative profiles of the patients undergoing single-valve and MUV procedures, mortality for MUV surgery remains considerably higher. Determinants of operative mortality and morbidity differ little across the procedural groups, and these findings serve as a benchmark for future studies, as well as suggest a continued search for explanations of poorer MUV outcomes.