Faculty Bibliography

BACKGROUND: Transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve demonstrates good 30 day clinical outcomes in patients with severe aortic stenosis who are at intermediate risk of surgical mortality. Here we report longer-term data in intermediate-risk patients given SAPIEN 3 TAVR and compare outcomes to those of intermediate-risk patients given surgical aortic valve replacement. METHODS: In the SAPIEN 3 observational study, 1077 intermediate-risk patients at 51 sites in the USA and Canada were assigned to receive TAVR with the SAPIEN 3 valve [952 [88%] via transfemoral access) between Feb 17, 2014, and Sept 3, 2014. In this population we assessed all-cause mortality and incidence of strokes, re-intervention, and aortic valve regurgitation at 1 year after implantation. Then we compared 1 year outcomes in this population with those for intermediate-risk patients treated with surgical valve replacement in the PARTNER 2A trial between Dec 23, 2011, and Nov 6, 2013, using a prespecified propensity score analysis to account for between-trial differences in baseline characteristics. The clinical events committee and echocardiographic core laboratory methods were the same for both studies. The primary endpoint was the composite of death from any cause, all strokes, and incidence of moderate or severe aortic regurgitation. We did non-inferiority (margin 7.5%) and superiority analyses in propensity score quintiles to calculate pooled weighted proportion differences for outcomes. FINDINGS: At 1 year follow-up of the SAPIEN 3 observational study, 79 of 1077 patients who initiated the TAVR procedure had died (all-cause mortality 7.4%; 6.5% in the transfemoral access subgroup), and disabling strokes had occurred in 24 (2%), aortic valve re-intervention in six (1%), and moderate or severe paravalvular regurgitation in 13 (2%). In the propensity-score analysis we included 963 patients treated with SAPIEN 3 TAVR and 747 with surgical valve replacement. For the primary composite endpoint of mortality, strokes, and moderate or severe aortic regurgitation, TAVR was both non-inferior (pooled weighted proportion difference of -9.2%; 90% CI -12.4 to -6; p<0.0001) and superior (-9.2%, 95% CI -13.0 to -5.4; p<0.0001) to surgical valve replacement. INTERPRETATION: TAVR with SAPIEN 3 in intermediate-risk patients with severe aortic stenosis is associated with low mortality, strokes, and regurgitation at 1 year. The propensity score analysis indicates a significant superiority for our composite outcome with TAVR compared with surgery, suggesting that TAVR might be the preferred treatment alternative in intermediate-risk patients. FUNDING: None.

BACKGROUND: Female sex is associated with poorer outcomes after surgical aortic valve replacement (SAVR). Data on sex-specific differences after transcatheter aortic valve replacement (TAVR) are conflicting. OBJECTIVE: To examine sex-specific differences in patients undergoing TAVR in the PARTNER (Placement of Aortic Transcatheter Valves) trial. DESIGN: Secondary analysis of the randomized and nonrandomized portions of the PARTNER trial. (ClinicalTrials.gov: NCT00530894). SETTING: 25 hospitals in the United States, Canada, and Germany. PATIENTS: High-risk and inoperable patients (1220 women and 1339 men). INTERVENTION: TAVR. MEASUREMENTS: Demographic characteristics, cardiac and noncardiac comorbidities, mortality, stroke, rehospitalization, vascular complications, bleeding complications, and echocardiographic valve parameters. RESULTS: At baseline, women had lower rates of hyperlipidemia, diabetes, smoking, and renal disease but higher Society of Thoracic Surgeons Predicted Risk of Mortality scores (11.9% vs. 11.1%; P < 0.001). After TAVR, women had more vascular complications (17.3% vs. 10.0%; difference, 7.29 percentage points [95% CI, 4.63 to 9.95 percentage points]; P < 0.001) and major bleeding (10.5% vs. 7.7%; difference, 2.8 percentage points [CI, 0.57 to 5.04 percentage points]; P = 0.012) but less frequent moderate and severe paravalvular regurgitation (6.0% vs. 14.3%; difference, -8.3 percentage points [CI, -11.7 to -5.0 percentage points]; P < 0.001). At 30 days, the unadjusted all-cause mortality rate (6.5% vs. 5.9%; difference, 0.6 percentage point [CI, -1.29 to 2.45 percentage points]; P = 0.52) and stroke incidence (3.8% vs. 3.0%; difference, 0.8 percentage point [CI, -0.62 to 2.19 percentage points]; P = 0.28) were similar. At 1 year, all-cause mortality was significantly lower in women than in men (19.0% vs. 25.9%; hazard ratio, 0.72 [CI, 0.61 to 0.85]; P < 0.001). LIMITATION: Secondary analysis that included nonrandomized trial data. CONCLUSION: Despite a higher incidence of vascular and bleeding complications, women having TAVR had lower mortality than men at 1 year. Thus, sex-specific risk in TAVR is the opposite of that in SAVR, for which female sex has been shown to be independently associated with an adverse prognosis. PRIMARY FUNDING SOURCE: Edwards Lifesciences.

BACKGROUND: This study sought to evaluate the impact of atrial fibrillation (AF) on clinical outcomes in patients undergoing transcatheter aortic valve replacement. METHODS AND RESULTS: Data were evaluated in 1879 patients with baseline and discharge ECGs who underwent transcatheter aortic valve replacement in the Placement of AoRTic TraNscathetER Valve (PARTNER) trial. A total of 1262 patients manifested sinus rhythm (SR) at baseline/SR at discharge, 113 SR baseline/AF discharge, and 470 AF baseline/AF discharge. Patients who converted from SR to AF by discharge had the highest rates of all-cause mortality at 30 days (P<0.0001 across all groups; 14.2% SR/AF versus 2.6% SR/SR; adjusted hazard ratio [HR]=3.41; P=0.0002) and over 2-fold difference at 1 year (P<0.0001 across all groups; 35.7% SR/AF versus 15.8% SR/SR; adjusted HR=2.14; P<0.0001). The presence of AF on baseline or discharge ECG was a predictor of 1-year mortality (adjusted HR=2.14 for SR/AF group and HR=1.88 for AF/AF groups; P<0.0001 for both groups versus SR/SR). For patients discharged in AF, those with lower ventricular response (ie, <90 bpm) experienced less 1-year all-cause mortality (HR=0.74; P=0.04). CONCLUSIONS: After transcatheter aortic valve replacement, the presence of AF at discharge, and particularly, the conversion to AF by discharge and higher ventricular response are associated with increased mortality. These data underscore the deleterious impact of AF, as well as the need for targeted interventions to improve clinical outcomes, in patients undergoing transcatheter aortic valve replacement. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

OBJECTIVES: Del Nido cardioplegia in adult cardiac surgery has not been studied although it has been in common use as a "single" dose cardioplegia in pediatric heart surgery. We retrospectively assessed the short-term (in-hospital) clinical outcomes of patients undergoing aortic valve replacement (AVR) using del Nido cardioplegia solution, comparing it to conventional multi-dose whole blood cardioplegia. METHODS: We switched our cardioplegia protocol from conventional whole blood cardioplegia exclusively to del Nido solution in May 2011. In 2011, 240 consecutive patients underwent isolated AVR. One hundred and seventy-eight of them were operated on with the use of del Nido cardioplegia (del Nido group) and whole blood cardioplegia (conventional group) was used in the other 62 patients. Isolated AVR was chosen as a cohort because of its relative simplicity and the similarity of surgical techniques among surgeons. Propensity-score matching identified 54 matched pairs for analysis. RESULTS: The retrograde cardioplegia technique was used in 19 cases (35.2%) in the del Nido group and 52 cases (96.3%) in the conventional group (p<0.001). Mean cardiopulmonary bypass time and mean aortic cross-clamp time were significantly shorter in the del Nido group compared to the conventional group: 71 +/- 16 min vs. 84 +/- 28 min (p<0.01), 52 +/- 14 min vs. 60 +/- 16 min (p<0.01), respectively. Postoperative inotropic support was required in 11 patients (20.4 %) in the del Nido group and 13 patients (24.1 %) in the conventional group (p=0.82) with no statistical difference. No patient required a postoperative intra-aortic balloon pump and in-hospital mortality was 0% in both groups. There was no significant difference in postoperative complications between the two groups. CONCLUSIONS: Short-term outcomes in adult cardiac surgery using del Nido solution were acceptable and comparable to conventional multi-dose whole blood cardioplegia. The del Nido cardioplegia technique was associated with shortened cross-clamp times and less frequent utilization of the retrograde cardioplegia delivery technique.

OBJECTIVES/OBJECTIVE:The purpose of this study was to identify predictors and clinical implications of permanent pacemaker (PPM) implantation after transcatheter aortic valve replacement (TAVR). BACKGROUND:Cardiac conduction disturbances requiring PPM are a frequent complication of TAVR. However, limited data is available regarding this complication after TAVR with a balloon-expandable valve. METHODS:The study included patients without prior pacemaker who underwent TAVR in the PARTNER (Placement of AoRtic TraNscathetER Valves) trial and registry and investigated predictors and clinical effect of new PPM. RESULTS:Of 2,559 TAVR patients, 586 were excluded due to pre-existing PPM. A new PPM was required in 173 of the remaining 1,973 patients (8.8%). By multivariable analysis, predictors of PPM included right bundle branch block (odds ratio [OR]: 7.03, 95% confidence interval [CI]: 4.92 to 10.06, p < 0.001), prosthesis diameter/left ventricular (LV) outflow tract diameter (for each 0.1 increment, OR: 1.29, 95% CI: 1.10 to 1.51, p = 0.002), LV end-diastolic diameter (for each 1 cm, OR: 0.68, 95% CI: 0.53 to 0.87, p = 0.003), and treatment in continued access registry (OR: 1.77, 95% CI: 1.08 to 2.92, p = 0.025). Patients requiring PPM had a longer mean duration of post-procedure hospitalization (7.3 ± 2.7 days vs. 6.2 ± 2.8 days, p = 0.001). At 1 year, new PPM was associated with significantly higher repeat hospitalization (23.9% vs. 18.2%, p = 0.05) and mortality or repeat hospitalization (42.0% vs. 32.6%, p = 0.007). There was no difference between groups in LV ejection fraction at 1 year. CONCLUSIONS:PPM was required in 8.8% of patients without prior PPM who underwent TAVR with a balloon-expandable valve in the PARTNER trial and registry. In addition to pre-existing right bundle branch block, the prosthesis to LV outflow tract diameter ratio and the LV end-diastolic diameter were identified as novel predictors of PPM after TAVR. New PPM was associated with a longer duration of hospitalization and higher rates of repeat hospitalization and mortality or repeat hospitalization at 1 year. (THE PARTNER TRIAL: Placement of AoRtic TraNscathetER Valves Trial; NCT00530894).

B-type natriuretic peptide (BNP) levels have shown a correlation with outcomes in studies of aortic valve surgery. Results from multicenter trials of BNP in transcatheter aortic valve surgery (TAVR) are lacking. The aim of this study was to investigate the prognostic role of serial measurement of BNP in transfemoral TAVR. A total of 1,097 patients who underwent TAVR via transfemoral access were analyzed by tertile of baseline BNP. Of those, 933 with BNP levels at 30 days were divided into 2 groups on the basis of increases (334 patients) or decreases or no change (599 patients) in BNP compared with baseline. Patients in the low-tertile BNP group had a lower rate of death at 1 year than those in the higher tertile group (15.0% vs 23.0%, p<0.01) which was not significant in multivariate analysis. Over 1 year, BNP decreased from 1,258.13±2,988.33 to 594.37±1,087.30 (p<0.01) in the entire group. Patients in the BNP-rise group had higher rates of death at 1 year (20.3% vs 11.4%, p<0.01) and an overall increase in moderate or severe aortic regurgitation over 1 year (p<0.01). Multivariate predictors of 1-year mortality were moderate or severe aortic regurgitation (hazard ratio 2.04, 95% confidence interval 1.36 to 3.05, p<0.01), increase in BNP at 30 days (hazard ratio 1.82, 95% confidence interval 1.26 to 2.62, p<0.01) and Society of Thoracic Surgeons score (hazard ratio 1.05, 95% confidence interval 1.01 to 1.10, p=0.03). In conclusion, increase in BNP at 30 days from baseline and moderate or severe aortic regurgitation at 30 days in patients who undergo transfemoral TAVR are independently associated with 1-year mortality. Increase in BNP at 30 days should prompt evaluation for causes of elevated wall stress, including aortic regurgitation.

OBJECTIVES/OBJECTIVE:Chronic kidney disease (CKD) is prevalent in patients undergoing aortic valve replacement (AVR). We sought to evaluate the impact of AVR on estimated glomerular filtration rate (eGFR) levels and determine the impact of reversibility of CKD on postoperative outcomes. METHODS:We retrospectively reviewed 2169 patients who underwent isolated AVR between 2000 and 2012. eGFR was calculated using the CKD-EPI formula. Based on preoperative eGFR, patients were divided into three groups: NoCKD (eGFR >60, n = 1417), ModCKD (eGFR = 30-60, n = 619) and SevCKD (eGFR = 15-30, n = 86). End-stage renal disease patients (eGFR <15 and/or dialysis, n = 47) were excluded from the study. RESULTS:Before AVR, eGFR in the NoCKD, ModCKD and SevCKD groups was 81.3 ± 14.2, 48.9 ± 8.10 and 25.3 ± 4.12 ml/min/1.73 m(2), respectively. NoCKD patients showed a decline in eGFR during the first month postoperatively; thereafter, eGFR remained stable over 1 year. ModCKD and SevCKD patients demonstrated an initial improvement in eGFR, which peaked at 1 week postoperatively. In ModCKD, eGFR stabilized at a slightly lower level thereafter out to 1-year follow-up. In SevCKD, eGFR declined slightly out to 6 months postoperatively. Regardlessly, eGFR in ModCKD at 1 year and in SevCKD at 6 months postoperatively demonstrated sustained improvement over baseline eGFR. Reversibility of CKD was associated with a better long-term survival in the ModCKD group (P < 0.001) and short-term survival in the SevCKD group (P = 0.018). CONCLUSIONS:AVR confers a marked initial improvement in eGFR, which is sustained in patients with ModCKD and SevCKD, and is associated with a better survival. The reversible nature of CKD in certain patients warrants careful consideration during preoperative risk scoring and stratification.