Faculty Bibliography

OBJECTIVES: This study sought to clarify the clinical and echocardiographic prognostic implication of myocardial injury after transcatheter aortic valve replacement (TAVR). BACKGROUND: The clinical significance of cardiac biomarker elevation after TAVR remains unclear. METHODS: Patients treated with TAVR in the PARTNER (Placement of Aortic Transcatheter Valves) trial were divided into tertiles (T1, T2, T3) based on the difference between the values on post-procedure day 1 and the baseline values of 2 cardiac biomarkers: cardiac troponin I (DeltacTnI); and creatine kinase-myocardial band (DeltaCK-MB) fraction. Patients were stratified according to their access route: transfemoral (TF) (n = 1,840) or transapical (TA) (n = 1,173). RESULTS: At 30 days after TF-TAVR, patients in the highest tertile (T3) of cardiac biomarker elevation had a higher rate of all-cause mortality (DeltacTnI: T3: 5.4% vs. T1: 0.5%, p = 0.006; DeltaCK-MB: T3: 5.7% vs. T1: 0.9%, p = 0.006) and cardiovascular mortality (DeltacTnI: T3: 4.9% vs. T1: 0.5%, p = 0.01; DeltaCK-MB: T3: 3.9% vs. T1: 0.5%, p = 0.02). At 1 year, only patients in the highest CK-MB tertile had higher rates of all-cause (25.4% vs. 16.8%, p = 0.02) and cardiovascular (10.3% vs. 5.0%) mortality. Multivariable analysis demonstrated that greater release of cardiac biomarkers was independently associated with increased mortality in the TF population. After TA-TAVR, being in the highest tertile of cardiac biomarker elevation had no influence on clinical and echocardiographic outcomes at 30 days and 1 year. CONCLUSIONS: After TF-TAVR, a greater degree of myocardial injury was associated with higher rates of 30-day all-cause and cardiovascular mortality. At 1 year, being in the highest tertile of DeltaCK-MB was correlated with a higher rate of all-cause and cardiac mortality. Finally, the level of myocardial injury after TA-TAVR had no impact on clinical and echocardiographic outcomes.

BACKGROUND: Echocardiographic calculation of effective orifice area (EOA) after transcatheter aortic valve replacement is integral to the assessment of transcatheter heart valve (THV) function. The aim of this study was to determine the most accurate method for calculating the EOA of the Edwards SAPIEN and SAPIEN XT THVs. METHODS: One hundred intraprocedural transesophageal echocardiograms were analyzed. To calculate the post-transcatheter aortic valve replacement left ventricular outflow tract (LVOT) stroke volume (SV), four diameters were measured using two-dimensional echocardiography: (1) baseline LVOT diameter (LVOTd_PRE), (2) postimplantation LVOT diameter, (3) native aortic annular diameter, and (4) THV in-stent diameter. Four corresponding areas were planimetered by three-dimensional echocardiography. Two LVOT velocity-time integrals (VTI) were measured with the pulsed-wave Doppler sample volume at (1) the proximal (apical) edge of the valve stent or (2) within the valve stent at the level of the THV cusps. LVOT velocity-time integral with the sample volume at the proximal edge of the valve stent was used with the LVOT and aortic annular measurements above, whereas in-stent VTI was paired with the in-stent THV diameter to yield eight different SVs. Right ventricular outflow tract (RVOT) SV was calculated using RVOT diameter and RVOT VTI and was used as the primary comparator. Transaortic VTI was obtained by continuous-wave Doppler, and EOA calculations using each SV measurement were compared with (1) EOA calculated using RVOTSV and (2) planimetered aortic valve area using three-dimensional echocardiography (AVAplanimetry3D). RESULTS: Post-transcatheter aortic valve replacement EOA calculated using LVOTd_PRE was not significantly different from EOA calculated using RVOTSV (1.88 +/- 0.33 vs 1.86 +/- 0.39 cm2, P = .36) or from AVAplanimetry3D (1.85 +/- 0.28, P = .38, n = 34). All other two-dimensional EOA calculations were statistically larger than EOA calculated using RVOTSV. All three-dimensional echocardiography-based EOA calculations were statistically different from AVAplanimetry3D. CONCLUSIONS: The most accurate EOA after implantation of a balloon-expandable THV is calculated using preimplantation LVOT diameter and VTI.

OBJECTIVE: Many patients undergoing transcatheter aortic valve implantation (TAVI) have a pre-existing, permanent pacemaker (PPM) or receive one as a consequence of the procedure. We hypothesised that chronic pacing may have adverse effects on TAVI outcomes. METHODS AND RESULTS: Four groups of patients undergoing TAVI in the Placement of Aortic Transcatheter Valves (PARTNER) trial and registries were compared: prior PPM (n=586), new PPM (n=173), no PPM (n=1612), and left bundle branch block (LBBB)/no PPM (n=160). At 1 year, prior PPM, new PPM and LBBB/no PPM had higher all-cause mortality than no PPM (27.4%, 26.3%, 27.7% and 20.0%, p<0.05), and prior PPM or new PPM had higher rehospitalisation or mortality/rehospitalisation (p<0.04). By Cox regression analysis, new PPM (HR 1.38, 1.00 to 1.89, p=0.05) and prior PPM (HR 1.31, 1.08 to 1.60, p=0.006) were independently associated with 1-year mortality. Surviving prior PPM, new PPM and LBBB/no PPM patients had lower LVEF at 1 year relative to no PPM (50.5%, 55.4%, 48.9% and 57.6%, p<0.01). Prior PPM had worsened recovery of LVEF after TAVI (Delta=10.0 prior vs 19.7% no PPM for baseline LVEF <35%, p<0.0001; Delta=4.1 prior vs 7.4% no PPM for baseline LVEF 35-50%, p=0.006). Paced ECGs displayed a high prevalence of RV pacing (>88%). CONCLUSIONS: In the PARTNER trial, prior PPM, along with new PPM and chronic LBBB patients, had worsened clinical and echocardiographic outcomes relative to no PPM patients, and the presence of a PPM was independently associated with 1-year mortality. Ventricular dyssynchrony due to chronic RV pacing may be mechanistically responsible for these findings. TRIAL REGISTRATION NUMBER: (ClinicalTrials.gov NCT00530894).

BACKGROUND: When transcatheter aortic valve replacement (TAVR) cannot be carried out through transfemoral access, alternative access TAVR is indicated. The purpose of this study was to explore inhospital and 1-year outcomes of patients undergoing alternative access TAVR through the transapical (TA) or transaortic (TAo) techniques in the United States. METHODS: Clinical records of 4,953 patients undergoing TA (n = 4,085) or TAo (n = 868) TAVR from 2011 to 2014 in The Society of Thoracic Surgeons (STS)/American College of Cardiology Transcatheter Valve Therapy Registry were linked to Centers for Medicare and Medicaid Services hospital claims. Inhospital and 1-year clinical outcomes were stratified by operative risk; and the risk-adjusted association between access route and mortality, stroke, and heart failure repeat hospitalization was explored. RESULTS: Mean age for all patients was 82.8 +/- 6.8 years. The median STS predicted risk of mortality was significantly higher among patients undergoing TAo (8.8 versus 7.4, p < 0.001). When compared with TA, TAo was associated with an increased risk of unadjusted 30-day mortality (10.3% versus 8.8%) and 1-year mortality (30.3% versus 25.6%, p = 0.006). There were no significant differences between TAo and TA for inhospital stroke rate (2.2%), major vascular complications (0.3%), and 1-year heart failure rehospitalizations (15.7%). Examination of high-risk and inoperable subgroups showed that 1-year mortality was significantly higher for TAo patients classified as inoperable (p = 0.012). CONCLUSIONS: Patients undergoing TAo TAVR are older, more likely female, and have significantly higher STS predicted risk of mortality scores than patients operated on by TA access. There were no risk-adjusted differences between TA and TAo access in mortality, stroke, or readmission rates as long as 1 year after TAVR.

OBJECTIVES: The study objectives were to (1) compare the safety of high-risk surgical aortic valve replacement in the Placement of Aortic Transcatheter Valves (PARTNER) I trial with Society of Thoracic Surgeons national benchmarks; (2) reference intermediate-term survival to that of the US population; and (3) identify subsets of patients for whom aortic valve replacement may be futile, with no survival benefit compared with therapy without aortic valve replacement. METHODS: From May 2007 to October 2009, 699 patients with high surgical risk, aged 84 +/- 6.3 years, were randomized in PARTNER-IA; 313 patients underwent surgical aortic valve replacement. Median follow-up was 2.8 years. Survival for therapy without aortic valve replacement used 181 PARTNER-IB patients. RESULTS: Operative mortality was 10.5% (expected 9.3%), stroke 2.6% (expected 3.5%), renal failure 5.8% (expected 12%), sternal wound infection 0.64% (expected 0.33%), and prolonged length of stay 26% (expected 18%). However, calibration of observed events in this relatively small sample was poor. Survival at 1, 2, 3, and 4 years was 75%, 68%, 57%, and 44%, respectively, lower than 90%, 81%, 73%, and 65%, respectively, in the US population, but higher than 53%, 32%, 21%, and 14%, respectively, in patients without aortic valve replacement. Risk factors for death included smaller body mass index, lower albumin, history of cancer, and prosthesis-patient mismatch. Within this high-risk aortic valve replacement group, only the 8% of patients with the poorest risk profiles had estimated 1-year survival less than that of similar patients treated without aortic valve replacement. CONCLUSIONS: PARTNER selection criteria for surgical aortic valve replacement, with a few caveats, may be more appropriate, realistic indications for surgery than those of the past, reflecting contemporary surgical management of severe aortic stenosis in high-risk patients at experienced sites.

BACKGROUND: This study describes short-term and mid-term outcomes of nonagenarian patients undergoing transfemoral or transapical transcatheter aortic valve replacement (TAVR) in the Placement of Aortic Transcatheter Valve (PARTNER)-I trial. METHODS: From April 2007 to February 2012, 531 nonagenarians, mean age 93 +/- 2.1 years, underwent TAVR with a balloon-expandable prosthesis in the PARTNER-I trial: 329 through transfemoral (TF-TAVR) and 202 transapical (TA-TAVR) access. Clinical events were adjudicated and echocardiographic results analyzed in a core laboratory. Quality of life (QoL) data were obtained up to 1 year post-TAVR. Time-varying all-cause mortality was referenced to that of an age-sex-race-matched US population. RESULTS: For TF-TAVR, post-procedure 30-day stroke risk was 3.6%; major adverse events occurred in 35% of patients; 30-day paravalvular leak was greater than moderate in 1.4%; median post-procedure length of stay (LOS) was 5 days. Thirty-day mortality was 4.0% and 3-year mortality 48% (44% for the matched population). By 6 months, most QoL measures had stabilized at a level considerably better than baseline, with Kansas City Cardiomyopathy Questionnaire (KCCQ) 72 +/- 21. For TA-TAVR, post-procedure 30-day stroke risk was 2.0%; major adverse events 32%; 30-day paravalvular leak was greater than moderate in 0.61%; and median post-procedure LOS was 8 days. Thirty-day mortality was 12% and 3-year mortality 54% (42% for the matched population); KCCQ was 73 +/- 23. CONCLUSIONS: A TAVR can be performed in nonagenarians with acceptable short- and mid-term outcomes. Although TF- and TA-TAVR outcomes are not directly comparable, TA-TAVR appears to carry a higher risk of early death without a difference in intermediate-term mortality. Age alone should not preclude referral for TAVR in nonagenarians.

BACKGROUND: In the Placement of AoRTic TraNscathetER Valve (PARTNER) randomized controlled trial (RCT), which represented the first exposure to transapical transcatheter aortic valve replacement (TA-TAVR) for many clinical sites, high-risk patients undergoing TA-TAVR derived similar health-related quality of life (HRQoL) outcomes when compared with surgical aortic valve replacement (SAVR). With increasing experience, it is possible that HRQoL outcomes of TA-TAVR may have improved. METHODS AND RESULTS: We evaluated HRQoL outcomes at 1-, 6-, and 12-month follow-ups among 875 patients undergoing TA-TAVR in the PARTNER nonrandomized continued access (NRCA) registry and compared these outcomes with those of the TA-TAVR and SAVR patients in the PARTNER RCT. HRQoL was assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Medical Outcomes Study Short-Form 12, and the EuroQoL-5D, with the KCCQ overall summary score serving as the primary end point. The NRCA TA-TAVR and RCT TA-TAVR and SAVR groups were generally similar. The primary outcome, the KCCQ summary score, did not differ between the NRCA TA-TAVR and the RCT TA-TAVR group at any follow-up timepoints, although there were small differences in favor of the NRCA cohort on several KCCQ subscales at 1 month. There were no significant differences in follow-up HRQOL between the NRCA-TAVR and the RCT SAVR cohorts on the KCCQ overall summary scale or any of the disease-specific or generic subscales. CONCLUSIONS: Despite greater experience with TA-TAVR in the NRCA registry, HRQoL outcomes remained similar to those of TA-TAVR in the original RCT cohort and no better than those with SAVR. These findings have important implications for patient selection for TAVR when transfemoral access is not an option. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

BACKGROUND: Based on the early results of the Placement of Aortic Transcatheter Valves (PARTNER) trial, transcatheter aortic valve replacement (TAVR) is an accepted treatment for patients with severe aortic stenosis who are not suitable for surgery. However, little information is available about the late clinical outcomes in such patients. METHODS: We did this randomised controlled trial at 21 experienced valve centres in Canada, Germany, and the USA. We enrolled patients with severe symptomatic inoperable aortic stenosis and randomly assigned (1:1) them to transfemoral TAVR or to standard treatment, which often included balloon aortic valvuloplasty. Patients and their treating physicians were not masked to treatment allocation. The randomisation was done centrally, and sites learned of the assignment only after a patient had been screened, consented, and entered into the database. The primary outcome of the trial was all-cause mortality at 1 year in the intention-to-treat population, here we present the prespecified findings after 5 years. This study is registered with ClinicalTrials.gov, number NCT00530894. FINDINGS: We screened 3015 patients, of whom 358 were enrolled (mean age 83 years, Society of Thoracic Surgeons Predicted Risk of Mortality 11.7%, 54% female). 179 were assigned to TAVR treatment and 179 were assigned to standard treatment. 20 patients crossed over from the standard treatment group and ten withdrew from study, leaving only six patients at 5 years, of whom five had aortic valve replacement treatment outside of the study. The risk of all-cause mortality at 5 years was 71.8% in the TAVR group versus 93.6% in the standard treatment group (hazard ratio 0.50, 95% CI 0.39-0.65; p<0.0001). At 5 years, 42 (86%) of 49 survivors in the TAVR group had New York Heart Association class 1 or 2 symptoms compared with three (60%) of five in the standard treatment group. Echocardiography after TAVR showed durable haemodynamic benefit (aortic valve area 1.52 cm(2) at 5 years, mean gradient 10.6 mm Hg at 5 years), with no evidence of structural valve deterioration. INTERPRETATION: TAVR is more beneficial than standard treatment for treatment of inoperable aortic stenosis. TAVR should be strongly considered for patients who are not surgical candidates for aortic valve replacement to improve their survival and functional status. Appropriate selection of patients will help to maximise the benefit of TAVR and reduce mortality from severe comorbidities. FUNDING: Edwards Lifesciences.

BACKGROUND: The Placement of Aortic Transcatheter Valves (PARTNER) trial showed that mortality at 1 year, 2 years, and 3 years is much the same with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) for high-risk patients with aortic stenosis. We report here the 5-year outcomes. METHODS: We did this randomised controlled trial at 25 hospitals, in Canada (two), Germany (one), and the USA (23). We used a computer-generated randomisation sequence to randomly assign high-risk patients with severe aortic stenosis to either SAVR or TAVR with a balloon-expandable bovine pericardial tissue valve by either a transfemoral or transapical approach. Patients and their treating physicians were not masked to treatment allocation. The primary outcome of the trial was all-cause mortality in the intention-to-treat population at 1 year, we present here predefined outcomes at 5 years. The study is registered with ClinicalTrials.gov, number NCT00530894. FINDINGS: We screened 3105 patients, of whom 699 were enrolled (348 assigned to TAVR, 351 assigned to SAVR). Overall mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 11.7%. At 5 years, risk of death was 67.8% in the TAVR group compared with 62.4% in the SAVR group (hazard ratio 1.04, 95% CI 0.86-1.24; p=0.76). We recorded no structural valve deterioration requiring surgical valve replacement in either group. Moderate or severe aortic regurgitation occurred in 40 (14%) of 280 patients in the TAVR group and two (1%) of 228 in the SAVR group (p<0.0001), and was associated with increased 5-year risk of mortality in the TAVR group (72.4% for moderate or severe aortic regurgitation vs 56.6% for those with mild aortic regurgitation or less; p=0.003). INTERPRETATION: Our findings show that TAVR as an alternative to surgery for patients with high surgical risk results in similar clinical outcomes. FUNDING: Edwards Lifesciences.