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Background Little is known about the hemodynamic performance of Edwards Sapien-3 (S3) valve after Transcatheter Aortic Valve Replacement (TAVR). Doppler velocity index (DVI) is a better indicator of prosthetic valve function as it is independent of valve size and flow, unlike mean gradient and peak velocity which are flow-dependent. Methods In this study, we compare outcomes based on differences in DVI among a consecutive series of patients who underwent S3 TAVR between April 2015 and December 2018. Our institutional review board approved the study and informed consents were obtained from the subjects. Results Among 921 patients who had follow-up echocardiograms within 30 days after TAVR, 60.8% had DVI ≤0.5, while 39.2% had DVI >0.5. The median 30-day DVI was 0.47 with a standard deviation of 0.11 and mean 0.49 and interquartile range 0.41–0.55. The baseline clinical and procedural characteristics were similar between both groups with the exception of less post-dilation (36.8% vs. 47.4%; p=0.001) and greater implantation depth (2.59±1.99 vs. 2.31±1.9mm; p=0.031) with DVI ≤0.5. The rates of aortic valve calcification, pre dilation, pre-TAVR aortic regurgitation (AR) were similar. At baseline, there were no differences between both groups in mean or peak gradients or aortic velocity time integral (VTI). At 1 year, mean gradients were higher with DVI ≤0.5 (12.7±5.6 vs. 11.1±4.6 mmHg; p=0.001). DVI ≤0.5 was associated with higher peak gradients (24.2±10.2 vs. 21.4±8.7 mmHg; p=0.002), and aortic VTI (51.4±13.5 vs. 46.8±12.2 cm; p0.5 group, patients in DVI0.5 were lower (6.6% vs. 10.6%; log-rank p=0.033), however no difference was noted at both 2 years (17.3% vs. 20.1%; log-rank p=0.151), and 3 years after TAVR (30.7% vs. 31.2%; log-rank p=0.333). Conclusions DVI Funding Acknowledgement Type of funding sources: None. Figure 1. All-cause SurvivalFigure 2. Hemodynamic Data

Background A novel hemodynamic parameter obtained from the cardiopulmonary exercise testing (CPET), the hemodynamic gain index (HGI), was developed and shown to be a strong independent predictor of all-cause mortality in a large male cohort. The HGI also strongly correlates with exercise parameters such as peak oxygen consumption and metabolic equivalents (METs). However, prognostic implications of the HGI have not been externally validated with subgroup analyses based on sex, heart failure (HF), coronary artery disease (CAD) and the use of beta-blockers. Purpose We aimed to validate the prognostic value of the HGI in men, women, and patients with and without HF, CAD, and beta-blocker use. Methods We identified 126,356 consecutive patients undergoing treadmill exercise testing for symptom evaluation between 1/1/1991–02/27/2015. HGI was calculated using the formula, [(SBPpeak x HRpeak) − (SBPrest x HRrest)] / (SBPrest x HRrest). Univariable and multivariable cox regression models were used to determine the associations between the HGI stratified by quartiles and all-cause mortality at 10 years with adjustment for cardiovascular risk factors (age, sex, diabetes, hypertension, dyslipidemia, chronic kidney disease, smoking status and body mass index) and exercise testing parameters (chronotropic reserve index, METs, abnormal heart rate recovery, and total exercise time). Results In our study cohort, mean age was 53.5±12.6 years. There were 74,724 (59.1%) male, 5,940 (4.7%) HF, 21,123 (16.7%) CAD, and 30,568 (24.2%) beta-blocker-using patients. During the mean follow up of 8.7 years, 9,929 (7.9%) died. Mean HGI was 2.0±1.2 bpm/mmHg. Lower HGI was associated with all-cause mortality in the entire cohort (Figure 1A, log rank p Conclusions HGI is an independent predictor of long-term mortality after adjusted for traditional cardiovascular risk factors, and exercise performance across patient subgroups. Funding Acknowledgement Type of funding sources: None. Figure 1. Kaplan-Meier curve and Cox regression

Background Exercise capacity, as measured by metabolic equivalents of task [METs], varies with gender and is an independent predictor of mortality. We sought to investigate gender differences in the protocol selected, the estimated exercise capacity, and the prognostic value of METs. Purpose Investigate the gender differences in the protocol chosen (adjusting for age and comorbidities), the METs achieved (also adjusting for the protocol selected), and the predictive value of exercise capacity adjusted to METs achieved. Methods In a 25-year stress testing registry spanning from 1991 to 2015, we identified 120,705 patients who underwent exercise stress testing. Protocols were split into Bruce vs. non-Bruce. METs were estimated based on established gender-specific formulas (the St James Take Heart Project formula for women, and the Veterans Affairs cohort formula for men).The primary outcome was all-cause mortality. Results The mean age was 53.3±12.5 years, and 59% were male. Table 1 presents the baseline characteristics and exercise parameters. A total of 8426 death occurred over 8.7 years of mean follow-up duration. Females were more commonly referred for non-Bruce protocols [adjusted OR 2.6; 95% CI (2.5–2.7)] even after adjusting for age and comorbidities. Within the same protocol chosen, females achieved lower estimated METs [Beta −1.4; 95% CI (−1.43 to −1.37)]. Exercise capacity was inversely related to mortality in both genders and across protocols (figure 1), however, after adjusting for age, comorbidities, protocol chosen, and the number of METs achieved, the HR for death was significantly lower for women [adjusted HR=0.44; 95% CI (0.41–0.46)]. Conclusion After adjusting for age and comorbidities, women tend to be more commonly referred for non-Bruce protocols, achieve less estimated METs (after adjusting for the protocol chosen), and have half the mortality for the same METs achieved. Death vs. Exercise capacity by gender Funding Acknowledgement Type of funding source: None

Background A variety of exercise stress testing protocols with various workloads are available. The test protocol is typically selected according to patient's expected exercise performance. Purpose We sought to assess whether the choice of the protocol is by itself independently associated with mortality even after adjusting for clinical variables and estimated workload achieved in metabolic equivalents of task (METS). Methods In a 25-year stress testing registry spanning from 1991 to 2015, we identified 120,705 patients who underwent 7 different standardized exercise protocols: Bruce, Modified Bruce, Cornell 0%, 5%, and 10%, Naughton, and modified Naughton. The choice of the protocol was dependent on the supervising exercise physiologist, mainly according to patient's expected exercise performance. The primary outcome was all-cause mortality. Results Mean age was 53.3±12.5 years and 59% were male. There were 74953 Bruce, 8368 modified Bruce, 2648 Cornell 0%, 9972 Cornell 5%, 20425 Cornell 10% 1226 Naughton, and 3113 modified Naughton protocols. A total of 8426 death occurred over 8.7 years of mean follow-up duration. Table 1 presents the baseline characteristics by protocol. After adjusting for the number of METs, age, gender, hypertension, diabetes, coronary disease, end-stage renal disease, smoking, and statin use, the protocol selected remained predictive of mortality. Figure 1 shows the adjusted HR for death by protocol selected when compared to Bruce. Baseline characteristics by protocol Variable Bruce (n=74953) Modified Bruce (n=8368) Cornell 0% (n=2648) Cornell 5% (n=9972) Cornell 10% (n=20425) Naughton (n=1226) Modified Naughton (n=3113) Age, mean ± SD 49.4±11.3 61.3±10.3 66.4±11.7 62.5±11.8 57.2±11.5 67.5±9.8 55.5±11.9 Male, % 64.6 51.8 37.8 42.3 51.7 49 66.7 Coronary disease, % 8.7 32.5 31.7 26.7 21.1 49.7 45.6 Diabetes mellitus, % 7.6 16.5 25.3 20 14.2 27.2 26.2 Hypertension, % 41.7 64 85.4 77.9 67.1 82.5 97.5 Smoker, % 40.9 55 50.7 50.9 50.8 56.9 60.6 ESRD, % 0.7 1 3.7 2.4 1.6 2.7 8.1 Mets, mean ± SD 10.3±2.4 7.2±1.7 5.2±1.6 6.7±1.5 8.3±1.9 4.8±1.5 4.6±1.5 Statin use, % 22.4 15.2 41.8 38.3 35.1 19 40.1 ESRD = end-stage renal disease; METS = metabolic equivalents of task. Adjusted HR by protocol selected Conclusion The choice of the stress testing protocol, which is in large part dependent on patient's expected exercise performance is in itself independently associated with mortality even after adjustment for METs achieved and patients' demographics and comorbidities. The choice of the modified-Naughton is associated with the greatest risk of mortality, likely chosen based on limited functional capacity

Background While the Bruce protocol has been extensively validated, other modified exercise protocols with less workload burden are commonly used, though their prognostic value is not well established. Purpose We sought to assess whether exercise capacity (or workload achieved in metabolic equivalents of task [METs]) remains predictive of mortality across various exercise stress testing protocols. Methods In a 25-year stress testing registry spanning from 1991 to 2015, we identified 120,705 patients who underwent 7 different standardized symptom-limited exercise stress testing protocols: Bruce, Modified Bruce, Cornell 0%, Cornell 5%, Cornell 10%, Naughton, and modified Naughton. The choice of the protocol was dependent on the supervising exercise physiologist according to purpose of the test and the individual patient. The primary outcome was all-cause mortality. Results Mean age was 53.3±12.5 years and 59% were male. There were 74953 Bruce, 8368 modified Bruce, 2648 Cornell 0%, 9972 Cornell 5%, 20425 Cornell 10% 1226 Naughton, and 3113 modified Naughton individual protocols. A total of 8426 death occurred over 8.7 years of mean follow-up duration. Figure 1 shows that there was an inverse relationship between peak METs achieved and mortality across all 7 protocols. On multivariable analysis, increasing METs remained protective against death [adjusted HR of 0.46; 95% CI (0.44 - 0.48); p METS vs. mortality by protocol Conclusion Across 7 different exercise protocols with various workloads, the predicted exercise capacity remained predictive of mortality irrespective of the protocol chosen, patients' demographics and comorbidities. Different testing choices likely represent different estimated functional capacity.