The incidence and prognostic implications of worsening right ventricular function after surgical or transcatheter aortic valve replacement: insights from PARTNER IIA

The incidence and prognostic implications of worsening right ventricular function after surgical... Abstract Aims In patients randomized to transcatheter or surgical aortic valve replacement (TAVR, SAVR), we sought to determine whether SAVR is associated with worsening right ventricular (RV) function and whether RV deterioration is associated with mortality. Methods and results In 1376 patients from PARTNERIIA with paired baseline and 30-day core lab echocardiograms, worsening RV function was defined as decline by at least one grade from baseline to 30 days. Our primary outcome was all-cause mortality from 30 days to 2 years. Among 744 patients with TAVR, 62 (8.3%) had worsening RV function, compared with 156 of 632 patients with SAVR (24.7%) (P < 0.0001). In a multivariable model, SAVR [odds ratio (OR) 4.05, 95% confidence interval (CI) 2.55–6.44], a dilated RV (OR 2.38, 95% CI 1.37–4.14), and more than mild tricuspid regurgitation (TR) (OR 2.58, 95% CI 1.25–5.33) were associated with worsening RV function. There were 169 deaths, and patients with worsening RV function had higher all-cause mortality [hazard ratio (HR) 1.98, 95% CI 1.40–2.79]. This association remained robust after adjusting for clinical and echocardiographic variables. Among patients with worsening RV function, there was no mortality difference between TAVR and SAVR (HR 1.16, 95% CI 0.61–2.18). The development of moderate or severe RV dysfunction from baseline normal RV function conferred the worst prognosis (HR 2.87, 95% CI 1.40–5.89). Conclusion After aortic valve replacement, worsening RV function is more common in patients with baseline RV dilation, more than mild TR, and in patients treated with SAVR. Worsening RV function and the magnitude of deterioration have important prognostic implications. View largeDownload slide View largeDownload slide Transcatheter aortic valve replacement , Surgical aortic valve replacement , Worsening right ventricular function Introduction With the advent of transcatheter aortic valve replacement (TAVR) for severe symptomatic aortic stenosis (AS), echocardiographic parameters that inform prognosis have been emphasized.1 In general, these analyses have focused on the left ventricle, though more recently, progression to right ventricular (RV) damage has also shown prognostic importance.2 After cardiac surgery, the association between baseline RV dysfunction and poor outcomes is established.3 However, in the PARTNER II inoperable cohort, baseline RV dysfunction was associated with worse outcomes after TAVR on univariable, but not multivariable, analyses.4 In addition, deterioration in RV function has been noted after surgical aortic valve replacement (SAVR),5 but whether RV function worsens after TAVR remains unclear.6 Specifically, in patients randomized to TAVR or SAVR, the differential incidence of worsening RV function and possible associations with adverse outcomes have not been well studied. Given this limited understanding of the importance of the RV after aortic valve replacement (AVR), the objectives of the current study are two-fold. First, in patients from PARTNER IIA,7 we aim to delineate whether the approach to AVR has a differential impact on RV function. Second, we aim to determine whether worsening RV function after AVR is associated with adverse outcomes. Methods Study population The PARTNER IIA study design and results have been previously reported.7 In brief, 2032 patients with severe symptomatic AS were randomized to SAVR or TAVR with the Edwards Sapien XT valve. All patients were at intermediate risk, based on a Society of Thoracic Surgery (STS) predicted 30-day mortality of at least 4.0%. For this analysis, the logistic EuroSCORE was used instead of the STS score because the former includes the presence of pulmonary hypertension in calculating risk, an important parameter for right heart function. Our substudy included all patients with a core lab echocardiogram at baseline and at 30 days (n = 1384). We excluded patients with severe baseline RV dysfunction (n = 8), as we were specifically interested in patients with worsening RV function after AVR, yielding a final cohort of 1376 patients. The study protocol was approved by the institutional review board at each enrolling site, was compliant with the Declaration of Helsinki, and all patients provided written informed consent. Echocardiography An independent core laboratory prospectively analysed all echocardiograms with quality and measurement methodology as previously reported.8,9 In brief, the severity of AS was determined by measuring peak and mean gradients across the valve with the modified Bernoulli equation, and aortic valve area was calculated using the continuity equation. Ventricular size, left ventricular ejection fraction (LVEF), and left ventricular (LV) mass were measured according to the recommendations of the American Society of Echocardiography.10 The severity of aortic, mitral, and tricuspid regurgitation (TR) were determined by an integrated, semiquantitative approach, as recommended by the American Society of Echocardiography.11 RV size and function was also assessed with a guideline-endorsed multiparametric approach using visual assessment, right ventricular fractional area change when feasible, and tricuspid annular plane systolic excursion when available.12 RV function was categorized as normal, mildly, moderately or severely decreased. In patients with RV dysfunction, severity was primarily based on visual assessment. Similarly, in accordance with guidelines,12 RV enlargement was assessed visually, and dilation was defined from a dedicated apical view with linear dimensions if basal diameter was >42 mm, >35 mm at the mid level, or >86 mm in longitudinal dimension.12 Outcomes Worsening RV function was defined as deterioration by at least one grade between baseline and 30-day echocardiogram. To assess outcomes, we performed a landmark analysis with all events occurring at least 30 days after AVR. As our primary outcome, we assessed whether worsening RV function was associated with all-cause mortality between 30 days and 2 years. For our secondary outcome, we assessed whether worsening RV function was associated with cardiovascular mortality between 30 days and 2 years. Other secondary outcomes included cardiac rehospitalizations that were not related to study valve or procedurdal complications, Kansas City Cardiomyopathy Questionnaire (KCCQ)13 scores, and 6 min walk distance (m), all assessed between 30 days and 2 years. To assess whether complications may be related to worsening RV function, we also evaluated cardiac rehospitalizations that were related to the study valve or procedure. Statistics Continuous data were summarized as mean (standard deviation) or median (interquartile percentages) with comparisons using t-tests or Wilcoxon rank sum tests, and categorical data were expressed as n (%) with comparisons using the χ2 or Fisher exact tests, as appropriate. Multivariable logistic regression was performed to assess associations with worsening RV function. Time-to-event curves for 30 day to 2 year mortality were created using the Kaplan–Meier estimates with between group comparisons using the log-rank test. For time-to-event outcomes, univariable and multivariable Cox proportional hazards models were created, and the assumptions of proportional hazards were satisfied. All covariates for the multivariable models were chosen based on biologic plausibility. A two-sided P-value of <0.05 was considered statistically significant. All statistical analyses were performed with SAS software, version 9.4 (SAS Institute) or R Core Team (2017). Results Baseline clinical and echocardiographic findings From an initial 2032 patients, 1376 patients with paired baseline and 30 day echocardiograms were included in this study. Within the first 30 days, 34 patients with TAVR and 38 patients with SAVR died. As would be expected, patients alive and with echocardiograms at 30 days were slightly lower risk compared to PARTNER IIA patients not included in this substudy (see Supplementary material online, Table S1). Importantly, there were no statistically significant between group differences in TAVR and SAVR patients in this landmark analysis, except that SAVR patients were more likely to have atrial fibrillation at baseline (29.7% vs. 35.6%, P = 0.02)(see Supplementary material online, Table S2). Among 744 patients with TAVR, 62 (8.3%) had worsening RV function, compared with 156 of 632 patients with SAVR (24.7%) [odds ratio (OR) 3.61, 95% confidence interval (CI) 2.63–4.95]. In addition, 47 patients with TAVR (6.3%) and 26 patients with SAVR (4.1%) had improved RV function at 30 days (OR 1.57, 95% CI 0.96–2.57). Grades of RV function at 30 days are shown in Figure 1. At baseline, patients with worsening RV function were more likely to have atrial fibrillation, and there was a trend towards higher logistic EuroSCOREs, male sex, permanent pacemaker, and New York Heart Association (NYHA) Class III or IV symptoms (Table 1). Table 1 Baseline clinical and echocardiographic characteristics in patients with TAVR or SAVR, stratified by the presence of worsening RV function at 30 days TAVR: worsening RV function (n = 62) TAVR: no worsening RV function (n = 682) SAVR: worsening RV function (n = 156) SAVR: no worsening RV function (n = 476) P-value Age 81.9 (6.4) 81.7 (6.5) 81.7 (6.5) 81.7 (6.8) 0.99 Female sex 41.9% (26/62) 49.6% (338/682) 39.7% (62/156) 48.3% (230/476) 0.12 Body mass index (kg/m2) 28.3 (5.6) 28.2 (5.8) 27.8 (5.8) 28.0 (5.7) 0.84 Logistic EuroSCORE 8.1 (7.9) 6.1 (5.3) 6.9 (6.1) 6.3 (6.8) 0.06 NYHA Class III or IV 75.8% (47/62) 77.3% (527/682) 78.2% (122/156) 71.0% (338/476) 0.08 KCCQ 49.7 (24.5) 54.6 (21.3) 51.9 (21.0) 53.9 (21.6) 0.26 6 minute walk (m) 166.8 (112.0) 189.6 (117.7) 176.7 (129.4) 190.8 (122.9) 0.32 CAD 71.0% (44/62) 68.9% (470/682) 64.7% (101/156) 64.3% (306/476) 0.32 Peripheral vascular disease 33.9% (21/62) 26.0% (177/682) 30.8% (48/156) 30.7% (146/476) 0.21 Atrial fibrillation 32.3% (20/62) 28.2% (192/682) 41.0% (64/156) 32.8% (156/476) 0.01 Permanent Pacemaker 17.7% (11/62) 10.0% (68/682) 14.1% (22/156) 9.7% (46/476) 0.11 Hypertension 95.2% (59/62) 94.4% (644/682) 94.9% (148/156) 93.3% (444/476) 0.80 Dyslipidaemia 82.3% (51/62) 82.7% (564/682) 76.9% (120/156) 80.9% (385/476) 0.40 Diabetes mellitus 35.5% (22/62) 35.6% (243/682) 35.3% (55/156) 33.4% (159/476) 0.89 Previous or current smoker 59.7% (37/62) 45.7% (312/682) 49.4% (77/156) 48.5% (231/476) 0.18 COPD 37.1% (23/62) 30.1% (204/678) 27.6% (43/156) 29.4% (139/472) 0.57 Creatinine ≥2 mg/dL 1.6% (1/62) 4.4% (30/682) 7.1% (11/156) 5.5% (26/476) 0.30 Liver disease 1.6% (1/62) 2.1% (14/682) 4.5% (7/156) 2.7% (13/476) 0.34 ACEi 29.0% (18/62) 29.9% (204/682) 31.4% (49/156) 26.3% (125/476) 0.49 ARB 16.1% (10/62) 16.7% (114/682) 15.4% (24/156) 19.3% (92/476) 0.58 Beta-blockers 51.6% (32/62) 55.6% (379/682) 57.7% (90/156) 59.2% (282/476) 0.51 Diuretic 53.2% (33/62) 50.1% (342/682) 49.4% (77/156) 51.5% (245/476) 0.93 Statin 69.4% (43/62) 66.7% (455/682) 57.1% (89/156) 64.3% (306/476) 0.12 LVEF (%) 53 (11) 56 (11) 51 (12) 56 (11) <0.0001 LV mass index (g/m2) 118 (35) 120 (32) 120 (34) 121 (34) 0.92 Normal RV function 80.6% (50/62) 83.1% (567/682) 85.9% (134/156) 81.1% (386/476) 0.52 Normal RV size 67.7% (42/62) 83.6% (569/681) 69.2% (108/156) 87.2% (415/476) <0.0001 Aortic valve peak velocity (m/s) 4.4 (0.7) 4.4 (0.6) 4.3 (0.6) 4.4 (0.6) 0.18 Aortic valve area (cm2) 0.69 (0.19) 0.70 (0.17) 0.69 (0.20) 0.68 (0.19) 0.55 Moderate or severe AR 11.5% (7/61) 11.5% (75/654) 10.7% (16/150) 11.5% (52/453) 0.99 Moderate or severe MR 18.6% (11/59) 16.9% (108/639) 17.9% (26/145) 18.0% (79/440) 0.96 Moderate or severe TR 31.6% (18/57) 15.3% (94/616) 21.1% (31/147) 15.6% (65/416) 0.006 Right ventricular systolic pressure (mmHg) 44 (16) 37 (12) 37 (11) 37 (13) 0.01 TAVR: worsening RV function (n = 62) TAVR: no worsening RV function (n = 682) SAVR: worsening RV function (n = 156) SAVR: no worsening RV function (n = 476) P-value Age 81.9 (6.4) 81.7 (6.5) 81.7 (6.5) 81.7 (6.8) 0.99 Female sex 41.9% (26/62) 49.6% (338/682) 39.7% (62/156) 48.3% (230/476) 0.12 Body mass index (kg/m2) 28.3 (5.6) 28.2 (5.8) 27.8 (5.8) 28.0 (5.7) 0.84 Logistic EuroSCORE 8.1 (7.9) 6.1 (5.3) 6.9 (6.1) 6.3 (6.8) 0.06 NYHA Class III or IV 75.8% (47/62) 77.3% (527/682) 78.2% (122/156) 71.0% (338/476) 0.08 KCCQ 49.7 (24.5) 54.6 (21.3) 51.9 (21.0) 53.9 (21.6) 0.26 6 minute walk (m) 166.8 (112.0) 189.6 (117.7) 176.7 (129.4) 190.8 (122.9) 0.32 CAD 71.0% (44/62) 68.9% (470/682) 64.7% (101/156) 64.3% (306/476) 0.32 Peripheral vascular disease 33.9% (21/62) 26.0% (177/682) 30.8% (48/156) 30.7% (146/476) 0.21 Atrial fibrillation 32.3% (20/62) 28.2% (192/682) 41.0% (64/156) 32.8% (156/476) 0.01 Permanent Pacemaker 17.7% (11/62) 10.0% (68/682) 14.1% (22/156) 9.7% (46/476) 0.11 Hypertension 95.2% (59/62) 94.4% (644/682) 94.9% (148/156) 93.3% (444/476) 0.80 Dyslipidaemia 82.3% (51/62) 82.7% (564/682) 76.9% (120/156) 80.9% (385/476) 0.40 Diabetes mellitus 35.5% (22/62) 35.6% (243/682) 35.3% (55/156) 33.4% (159/476) 0.89 Previous or current smoker 59.7% (37/62) 45.7% (312/682) 49.4% (77/156) 48.5% (231/476) 0.18 COPD 37.1% (23/62) 30.1% (204/678) 27.6% (43/156) 29.4% (139/472) 0.57 Creatinine ≥2 mg/dL 1.6% (1/62) 4.4% (30/682) 7.1% (11/156) 5.5% (26/476) 0.30 Liver disease 1.6% (1/62) 2.1% (14/682) 4.5% (7/156) 2.7% (13/476) 0.34 ACEi 29.0% (18/62) 29.9% (204/682) 31.4% (49/156) 26.3% (125/476) 0.49 ARB 16.1% (10/62) 16.7% (114/682) 15.4% (24/156) 19.3% (92/476) 0.58 Beta-blockers 51.6% (32/62) 55.6% (379/682) 57.7% (90/156) 59.2% (282/476) 0.51 Diuretic 53.2% (33/62) 50.1% (342/682) 49.4% (77/156) 51.5% (245/476) 0.93 Statin 69.4% (43/62) 66.7% (455/682) 57.1% (89/156) 64.3% (306/476) 0.12 LVEF (%) 53 (11) 56 (11) 51 (12) 56 (11) <0.0001 LV mass index (g/m2) 118 (35) 120 (32) 120 (34) 121 (34) 0.92 Normal RV function 80.6% (50/62) 83.1% (567/682) 85.9% (134/156) 81.1% (386/476) 0.52 Normal RV size 67.7% (42/62) 83.6% (569/681) 69.2% (108/156) 87.2% (415/476) <0.0001 Aortic valve peak velocity (m/s) 4.4 (0.7) 4.4 (0.6) 4.3 (0.6) 4.4 (0.6) 0.18 Aortic valve area (cm2) 0.69 (0.19) 0.70 (0.17) 0.69 (0.20) 0.68 (0.19) 0.55 Moderate or severe AR 11.5% (7/61) 11.5% (75/654) 10.7% (16/150) 11.5% (52/453) 0.99 Moderate or severe MR 18.6% (11/59) 16.9% (108/639) 17.9% (26/145) 18.0% (79/440) 0.96 Moderate or severe TR 31.6% (18/57) 15.3% (94/616) 21.1% (31/147) 15.6% (65/416) 0.006 Right ventricular systolic pressure (mmHg) 44 (16) 37 (12) 37 (11) 37 (13) 0.01 AR, aortic regurgitation; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; KCCQ, Kansas City Cardiomyopathy Questionnaire; LV, left ventricle; LVEF, left ventricular ejection fraction; MR, mitral regurgitation; NYHA, New York Heart Association; RV, right ventricle; SAVR, surgical aortic valve replacement; TAVR, transcatheter aortic valve replacement; TR, tricuspid regurgitation. Table 1 Baseline clinical and echocardiographic characteristics in patients with TAVR or SAVR, stratified by the presence of worsening RV function at 30 days TAVR: worsening RV function (n = 62) TAVR: no worsening RV function (n = 682) SAVR: worsening RV function (n = 156) SAVR: no worsening RV function (n = 476) P-value Age 81.9 (6.4) 81.7 (6.5) 81.7 (6.5) 81.7 (6.8) 0.99 Female sex 41.9% (26/62) 49.6% (338/682) 39.7% (62/156) 48.3% (230/476) 0.12 Body mass index (kg/m2) 28.3 (5.6) 28.2 (5.8) 27.8 (5.8) 28.0 (5.7) 0.84 Logistic EuroSCORE 8.1 (7.9) 6.1 (5.3) 6.9 (6.1) 6.3 (6.8) 0.06 NYHA Class III or IV 75.8% (47/62) 77.3% (527/682) 78.2% (122/156) 71.0% (338/476) 0.08 KCCQ 49.7 (24.5) 54.6 (21.3) 51.9 (21.0) 53.9 (21.6) 0.26 6 minute walk (m) 166.8 (112.0) 189.6 (117.7) 176.7 (129.4) 190.8 (122.9) 0.32 CAD 71.0% (44/62) 68.9% (470/682) 64.7% (101/156) 64.3% (306/476) 0.32 Peripheral vascular disease 33.9% (21/62) 26.0% (177/682) 30.8% (48/156) 30.7% (146/476) 0.21 Atrial fibrillation 32.3% (20/62) 28.2% (192/682) 41.0% (64/156) 32.8% (156/476) 0.01 Permanent Pacemaker 17.7% (11/62) 10.0% (68/682) 14.1% (22/156) 9.7% (46/476) 0.11 Hypertension 95.2% (59/62) 94.4% (644/682) 94.9% (148/156) 93.3% (444/476) 0.80 Dyslipidaemia 82.3% (51/62) 82.7% (564/682) 76.9% (120/156) 80.9% (385/476) 0.40 Diabetes mellitus 35.5% (22/62) 35.6% (243/682) 35.3% (55/156) 33.4% (159/476) 0.89 Previous or current smoker 59.7% (37/62) 45.7% (312/682) 49.4% (77/156) 48.5% (231/476) 0.18 COPD 37.1% (23/62) 30.1% (204/678) 27.6% (43/156) 29.4% (139/472) 0.57 Creatinine ≥2 mg/dL 1.6% (1/62) 4.4% (30/682) 7.1% (11/156) 5.5% (26/476) 0.30 Liver disease 1.6% (1/62) 2.1% (14/682) 4.5% (7/156) 2.7% (13/476) 0.34 ACEi 29.0% (18/62) 29.9% (204/682) 31.4% (49/156) 26.3% (125/476) 0.49 ARB 16.1% (10/62) 16.7% (114/682) 15.4% (24/156) 19.3% (92/476) 0.58 Beta-blockers 51.6% (32/62) 55.6% (379/682) 57.7% (90/156) 59.2% (282/476) 0.51 Diuretic 53.2% (33/62) 50.1% (342/682) 49.4% (77/156) 51.5% (245/476) 0.93 Statin 69.4% (43/62) 66.7% (455/682) 57.1% (89/156) 64.3% (306/476) 0.12 LVEF (%) 53 (11) 56 (11) 51 (12) 56 (11) <0.0001 LV mass index (g/m2) 118 (35) 120 (32) 120 (34) 121 (34) 0.92 Normal RV function 80.6% (50/62) 83.1% (567/682) 85.9% (134/156) 81.1% (386/476) 0.52 Normal RV size 67.7% (42/62) 83.6% (569/681) 69.2% (108/156) 87.2% (415/476) <0.0001 Aortic valve peak velocity (m/s) 4.4 (0.7) 4.4 (0.6) 4.3 (0.6) 4.4 (0.6) 0.18 Aortic valve area (cm2) 0.69 (0.19) 0.70 (0.17) 0.69 (0.20) 0.68 (0.19) 0.55 Moderate or severe AR 11.5% (7/61) 11.5% (75/654) 10.7% (16/150) 11.5% (52/453) 0.99 Moderate or severe MR 18.6% (11/59) 16.9% (108/639) 17.9% (26/145) 18.0% (79/440) 0.96 Moderate or severe TR 31.6% (18/57) 15.3% (94/616) 21.1% (31/147) 15.6% (65/416) 0.006 Right ventricular systolic pressure (mmHg) 44 (16) 37 (12) 37 (11) 37 (13) 0.01 TAVR: worsening RV function (n = 62) TAVR: no worsening RV function (n = 682) SAVR: worsening RV function (n = 156) SAVR: no worsening RV function (n = 476) P-value Age 81.9 (6.4) 81.7 (6.5) 81.7 (6.5) 81.7 (6.8) 0.99 Female sex 41.9% (26/62) 49.6% (338/682) 39.7% (62/156) 48.3% (230/476) 0.12 Body mass index (kg/m2) 28.3 (5.6) 28.2 (5.8) 27.8 (5.8) 28.0 (5.7) 0.84 Logistic EuroSCORE 8.1 (7.9) 6.1 (5.3) 6.9 (6.1) 6.3 (6.8) 0.06 NYHA Class III or IV 75.8% (47/62) 77.3% (527/682) 78.2% (122/156) 71.0% (338/476) 0.08 KCCQ 49.7 (24.5) 54.6 (21.3) 51.9 (21.0) 53.9 (21.6) 0.26 6 minute walk (m) 166.8 (112.0) 189.6 (117.7) 176.7 (129.4) 190.8 (122.9) 0.32 CAD 71.0% (44/62) 68.9% (470/682) 64.7% (101/156) 64.3% (306/476) 0.32 Peripheral vascular disease 33.9% (21/62) 26.0% (177/682) 30.8% (48/156) 30.7% (146/476) 0.21 Atrial fibrillation 32.3% (20/62) 28.2% (192/682) 41.0% (64/156) 32.8% (156/476) 0.01 Permanent Pacemaker 17.7% (11/62) 10.0% (68/682) 14.1% (22/156) 9.7% (46/476) 0.11 Hypertension 95.2% (59/62) 94.4% (644/682) 94.9% (148/156) 93.3% (444/476) 0.80 Dyslipidaemia 82.3% (51/62) 82.7% (564/682) 76.9% (120/156) 80.9% (385/476) 0.40 Diabetes mellitus 35.5% (22/62) 35.6% (243/682) 35.3% (55/156) 33.4% (159/476) 0.89 Previous or current smoker 59.7% (37/62) 45.7% (312/682) 49.4% (77/156) 48.5% (231/476) 0.18 COPD 37.1% (23/62) 30.1% (204/678) 27.6% (43/156) 29.4% (139/472) 0.57 Creatinine ≥2 mg/dL 1.6% (1/62) 4.4% (30/682) 7.1% (11/156) 5.5% (26/476) 0.30 Liver disease 1.6% (1/62) 2.1% (14/682) 4.5% (7/156) 2.7% (13/476) 0.34 ACEi 29.0% (18/62) 29.9% (204/682) 31.4% (49/156) 26.3% (125/476) 0.49 ARB 16.1% (10/62) 16.7% (114/682) 15.4% (24/156) 19.3% (92/476) 0.58 Beta-blockers 51.6% (32/62) 55.6% (379/682) 57.7% (90/156) 59.2% (282/476) 0.51 Diuretic 53.2% (33/62) 50.1% (342/682) 49.4% (77/156) 51.5% (245/476) 0.93 Statin 69.4% (43/62) 66.7% (455/682) 57.1% (89/156) 64.3% (306/476) 0.12 LVEF (%) 53 (11) 56 (11) 51 (12) 56 (11) <0.0001 LV mass index (g/m2) 118 (35) 120 (32) 120 (34) 121 (34) 0.92 Normal RV function 80.6% (50/62) 83.1% (567/682) 85.9% (134/156) 81.1% (386/476) 0.52 Normal RV size 67.7% (42/62) 83.6% (569/681) 69.2% (108/156) 87.2% (415/476) <0.0001 Aortic valve peak velocity (m/s) 4.4 (0.7) 4.4 (0.6) 4.3 (0.6) 4.4 (0.6) 0.18 Aortic valve area (cm2) 0.69 (0.19) 0.70 (0.17) 0.69 (0.20) 0.68 (0.19) 0.55 Moderate or severe AR 11.5% (7/61) 11.5% (75/654) 10.7% (16/150) 11.5% (52/453) 0.99 Moderate or severe MR 18.6% (11/59) 16.9% (108/639) 17.9% (26/145) 18.0% (79/440) 0.96 Moderate or severe TR 31.6% (18/57) 15.3% (94/616) 21.1% (31/147) 15.6% (65/416) 0.006 Right ventricular systolic pressure (mmHg) 44 (16) 37 (12) 37 (11) 37 (13) 0.01 AR, aortic regurgitation; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; KCCQ, Kansas City Cardiomyopathy Questionnaire; LV, left ventricle; LVEF, left ventricular ejection fraction; MR, mitral regurgitation; NYHA, New York Heart Association; RV, right ventricle; SAVR, surgical aortic valve replacement; TAVR, transcatheter aortic valve replacement; TR, tricuspid regurgitation. Figure 1 View largeDownload slide Right ventricular function at 30 days, stratified by transcatheter aortic valve replacement or surgical aortic valve replacement, in patients with baseline normal (A) or abnormal (B) right ventricular function. (A) In patients with surgical aortic valve replacement and normal right ventricular function at baseline (red, n = 520), 74.2% had normal, 20.8% had mild, and 5.0% had moderate of severe right ventricular dysfunction at 30 days. In patients with transcatheter aortic valve replacement and normal right ventricular function at baseline (blue, n = 617), 91.9% had normal, 7.6% had mild, and 0.5% had moderate or severe right ventricular dysfunction at 30 days. (B) In patients with surgical aortic valve replacement and baseline right ventricular dysfunction (red, n = 112), 18.8% had normal, 53.6% had mild, and 27.7% had moderate or severe right ventricular dysfunction at 30 days. In patients with transcatheter aortic valve replacement and baseline right ventricular dysfunction (blue, n = 127), 26.0% had normal, 55.9% had mild, and 18.1% had moderate or severe right ventricular dysfunction at 30 days. Figure 1 View largeDownload slide Right ventricular function at 30 days, stratified by transcatheter aortic valve replacement or surgical aortic valve replacement, in patients with baseline normal (A) or abnormal (B) right ventricular function. (A) In patients with surgical aortic valve replacement and normal right ventricular function at baseline (red, n = 520), 74.2% had normal, 20.8% had mild, and 5.0% had moderate of severe right ventricular dysfunction at 30 days. In patients with transcatheter aortic valve replacement and normal right ventricular function at baseline (blue, n = 617), 91.9% had normal, 7.6% had mild, and 0.5% had moderate or severe right ventricular dysfunction at 30 days. (B) In patients with surgical aortic valve replacement and baseline right ventricular dysfunction (red, n = 112), 18.8% had normal, 53.6% had mild, and 27.7% had moderate or severe right ventricular dysfunction at 30 days. In patients with transcatheter aortic valve replacement and baseline right ventricular dysfunction (blue, n = 127), 26.0% had normal, 55.9% had mild, and 18.1% had moderate or severe right ventricular dysfunction at 30 days. Regarding echocardiographic parameters, worsening RV function was associated with lower LV systolic function, though most patients had normal LVEFs (Table 1). In addition, patients with worsening RV function were more likely to have dilated right ventricles at baseline, but there was no statistically detectable difference in baseline RV systolic function. Moderate or severe TR was also more common in patients who developed worsening RV function, and baseline estimated right ventricular systolic pressure (RVSP) was also higher, though absolute between group differences in RVSP were small (Table 1). Worsening right ventricular function In a multivariable model, SAVR was associated with a higher odds of worsening RV function compared with TAVR (OR 4.05, 95% CI 2.55–6.44). After adjustment, baseline clinical variables were not associated with worsening RV function, though the association with certain baseline echocardiographic variables remained significant. Specifically, patients with more than mild TR, lower LVEFs and dilated right ventricles at baseline were more likely to develop worsening RV function (Table 2). In stability analyses using the same covaraites but restricted to patients with either TAVR or SAVR, differential associations with worsening RV function were noted. For patients with TAVR, more than mild TR was associated with worsening RV function (OR 5.33, 95% CI 1.46–19.39), whereas an association with baseline RV dilation was not statistically detectable (OR 1.92, 95% CI 0.76-4.85) (see Supplementary material online, Table S3). Conversely, in patients with SAVR, baseline RV dilation was associated with worsening RV function (OR 2.77, 95% CI 1.35–5.68), and there was not a significant association with more than mild TR (OR 1.78, 95% CI 0.71–4.49) (see Supplementary material online, Table S4). Table 2 Multivariable analysis for worsening RV function after AVRa OR (95% CI) P-value SAVR vs. TAVR 4.05 (2.55–6.44) <0.0001 Age (years) 1.02 (0.98–1.06) 0.28 Male 0.75 (0.47–1.20) 0.23 BMI 1.01 (0.96–1.05) 0.78 Logistic EuroSCORE 1.02 (0.99–1.05) 0.18 Atrial fibrillation 1.43 (0.90–2.26) 0.13 Pacemaker 1.34 (0.69–2.61) 0.39 Liver disease 0.61 (0.13–2.96) 0.54 Baseline LVEF 0.97 (0.95–0.99) 0.007 Baseline right ventricular dilation 2.38 (1.37–4.14) 0.002 Baseline right ventricular systolic pressure 1.00 (0.98–1.02) 0.94 Baseline mitral valve regurgitation mild vs. none/trace 0.93 (0.54–1.62) 0.81 Baseline mitral valve regurgitation moderate/severe vs. none/trace 0.51 (0.24–1.05) 0.07 Baseline tricuspid valve regurgitation mild vs. none/trace 1.38 (0.78–2.47) 0.27 Baseline tricuspid valve regurgitation moderate/severe vs. none/trace 2.58 (1.25–5.33) 0.01 OR (95% CI) P-value SAVR vs. TAVR 4.05 (2.55–6.44) <0.0001 Age (years) 1.02 (0.98–1.06) 0.28 Male 0.75 (0.47–1.20) 0.23 BMI 1.01 (0.96–1.05) 0.78 Logistic EuroSCORE 1.02 (0.99–1.05) 0.18 Atrial fibrillation 1.43 (0.90–2.26) 0.13 Pacemaker 1.34 (0.69–2.61) 0.39 Liver disease 0.61 (0.13–2.96) 0.54 Baseline LVEF 0.97 (0.95–0.99) 0.007 Baseline right ventricular dilation 2.38 (1.37–4.14) 0.002 Baseline right ventricular systolic pressure 1.00 (0.98–1.02) 0.94 Baseline mitral valve regurgitation mild vs. none/trace 0.93 (0.54–1.62) 0.81 Baseline mitral valve regurgitation moderate/severe vs. none/trace 0.51 (0.24–1.05) 0.07 Baseline tricuspid valve regurgitation mild vs. none/trace 1.38 (0.78–2.47) 0.27 Baseline tricuspid valve regurgitation moderate/severe vs. none/trace 2.58 (1.25–5.33) 0.01 AVR, aortic valve replacement; BMI, body mass index; LVEF, left ventricular ejection fraction; RV, right ventricle; SAVR, surgical aortic valve replacement; TAVR, transcatheter aortic valve replacement. a c-statistic for this model is 0.77 with a P-value <0.0001. Table 2 Multivariable analysis for worsening RV function after AVRa OR (95% CI) P-value SAVR vs. TAVR 4.05 (2.55–6.44) <0.0001 Age (years) 1.02 (0.98–1.06) 0.28 Male 0.75 (0.47–1.20) 0.23 BMI 1.01 (0.96–1.05) 0.78 Logistic EuroSCORE 1.02 (0.99–1.05) 0.18 Atrial fibrillation 1.43 (0.90–2.26) 0.13 Pacemaker 1.34 (0.69–2.61) 0.39 Liver disease 0.61 (0.13–2.96) 0.54 Baseline LVEF 0.97 (0.95–0.99) 0.007 Baseline right ventricular dilation 2.38 (1.37–4.14) 0.002 Baseline right ventricular systolic pressure 1.00 (0.98–1.02) 0.94 Baseline mitral valve regurgitation mild vs. none/trace 0.93 (0.54–1.62) 0.81 Baseline mitral valve regurgitation moderate/severe vs. none/trace 0.51 (0.24–1.05) 0.07 Baseline tricuspid valve regurgitation mild vs. none/trace 1.38 (0.78–2.47) 0.27 Baseline tricuspid valve regurgitation moderate/severe vs. none/trace 2.58 (1.25–5.33) 0.01 OR (95% CI) P-value SAVR vs. TAVR 4.05 (2.55–6.44) <0.0001 Age (years) 1.02 (0.98–1.06) 0.28 Male 0.75 (0.47–1.20) 0.23 BMI 1.01 (0.96–1.05) 0.78 Logistic EuroSCORE 1.02 (0.99–1.05) 0.18 Atrial fibrillation 1.43 (0.90–2.26) 0.13 Pacemaker 1.34 (0.69–2.61) 0.39 Liver disease 0.61 (0.13–2.96) 0.54 Baseline LVEF 0.97 (0.95–0.99) 0.007 Baseline right ventricular dilation 2.38 (1.37–4.14) 0.002 Baseline right ventricular systolic pressure 1.00 (0.98–1.02) 0.94 Baseline mitral valve regurgitation mild vs. none/trace 0.93 (0.54–1.62) 0.81 Baseline mitral valve regurgitation moderate/severe vs. none/trace 0.51 (0.24–1.05) 0.07 Baseline tricuspid valve regurgitation mild vs. none/trace 1.38 (0.78–2.47) 0.27 Baseline tricuspid valve regurgitation moderate/severe vs. none/trace 2.58 (1.25–5.33) 0.01 AVR, aortic valve replacement; BMI, body mass index; LVEF, left ventricular ejection fraction; RV, right ventricle; SAVR, surgical aortic valve replacement; TAVR, transcatheter aortic valve replacement. a c-statistic for this model is 0.77 with a P-value <0.0001. Regarding complications leading to cardiac rehospitalization, 30 events were study-valve related and 31 events were procedure related. Worsening RV function was not associated with either study-valve related [hazard ratio (HR) 1.13, 95% CI 0.43–2.95] or procedure related rehospitalization (HR 1.56, 95% CI 0.67–3.61). To assess exposures that were specific to either TAVR or SAVR and potential associations with worsening RV function, further exploratory analyses were performed. In SAVR, cardiopulmonary bypass time was not increased in patients with worsening RV function (108 vs. 100 min, P = 0.16) (see Supplementary material online, Table S5). For TAVR, post-dilation was not associated with worsening RV function (24.6% vs. 20.6%, P = 0.46) (see Supplementary material online, Table S5). The need for a pacemaker after AVR was also not associated with worsening RV function after TAVR (16.1% vs. 11.6%, P = 0.22) or (SAVR 10.9% vs. 11.1%, P = 0.47) (see Supplementary material online, Table S5). Worsening right ventricular function and adverse events Between 30 days and 2 years, there were 169 deaths, and patients with worsening RV function had higher mortality (HR 1.98, 95% CI 1.40–2.79) (Take home figure). In comparing TAVR to SAVR, there was no difference in patients with (HR 1.16, 95% CI 0.61–2.18) or without RV worsening (HR 1.03, 95% CI 0.72–1.48) (P-value for interaction 0.76). Regarding cardiovascular death, there were 85 events. Results were similar with higher cardiovascular death among patients with worsening RV function (HR 2.11, 95% CI 1.22–3.66) (Figure 2). Regarding cardiac rehospitalizations that were not related to valve or procedural complications, there were 133 events, and there was not a statistically significant association with worsening RV function (HR 1.43, 95% CI 0.94–2.18). Take home figure View largeDownload slide The Kaplan–Meier survival curves for all-cause mortality in patients with and without worsening right ventricular function, stratified by randomization to transcatheter aortic valve replacement or surgical aortic valve replacement. Patients with worsening right ventricular function had higher all-cause mortality (hazard ratio 1.98, 95% confidence interval 1.40–2.79), though there was no difference in mortality in patients with worsening right ventricular function according to transcatheter aortic valve replacement or surgical aortic valve replacement (hazard ratio 1.16, 95% CI 0.61–2.18). Take home figure View largeDownload slide The Kaplan–Meier survival curves for all-cause mortality in patients with and without worsening right ventricular function, stratified by randomization to transcatheter aortic valve replacement or surgical aortic valve replacement. Patients with worsening right ventricular function had higher all-cause mortality (hazard ratio 1.98, 95% confidence interval 1.40–2.79), though there was no difference in mortality in patients with worsening right ventricular function according to transcatheter aortic valve replacement or surgical aortic valve replacement (hazard ratio 1.16, 95% CI 0.61–2.18). To further assess the association between worsening RV function after AVR and adverse events, baseline echocardiographic variable were added separately to a background model that included age, sex, logistic EuroSCORE, and LVEF. After additional adjustment for baseline RV function, mitral regurgitation, and TR, the association between worsening RV function and all-cause death remained significant in all models with an approximately two-fold increase in hazard (Table 3). Results were similar for cardiovascular death, though the association was attenuated following adjustment for RVSP (HR 1.82, 95% CI 0.95-3.48) (Table 4). Table 3 Worsening RV function and all-cause mortality HR (95% CI) P-value Worsening RV function (adjusted for background modela and baseline RV function)b 2.11 (1.40–3.19) 0.0004 Worsening RV function (adjusted for background modela and baseline MR)c 2.02 (1.32–3.08) 0.001 Worsening RV function (adjusted for background modela and baseline tricuspid TR)d 2.05 (1.34–3.12) 0.0009 Worsening RV function (adjusted for background modela and baseline RVSP)e 2.12 (1.33–3.37) 0.002 HR (95% CI) P-value Worsening RV function (adjusted for background modela and baseline RV function)b 2.11 (1.40–3.19) 0.0004 Worsening RV function (adjusted for background modela and baseline MR)c 2.02 (1.32–3.08) 0.001 Worsening RV function (adjusted for background modela and baseline tricuspid TR)d 2.05 (1.34–3.12) 0.0009 Worsening RV function (adjusted for background modela and baseline RVSP)e 2.12 (1.33–3.37) 0.002 CI, confidence interval; HR, hazard ratio; MR, mitral regurgitation; RV, right ventricle; RVSP, right ventricular systolic pressure; TR, tricuspid regurgitation. a Background model includes age, sex, logistic EuroSCORE, and LVEF. b c-statistic 0.62, P < 0.0001. c c-statistic 0.63, P < 0.0001. d c-statistic 0.62. e c-statistic 0.67, P < 0.0001. Table 3 Worsening RV function and all-cause mortality HR (95% CI) P-value Worsening RV function (adjusted for background modela and baseline RV function)b 2.11 (1.40–3.19) 0.0004 Worsening RV function (adjusted for background modela and baseline MR)c 2.02 (1.32–3.08) 0.001 Worsening RV function (adjusted for background modela and baseline tricuspid TR)d 2.05 (1.34–3.12) 0.0009 Worsening RV function (adjusted for background modela and baseline RVSP)e 2.12 (1.33–3.37) 0.002 HR (95% CI) P-value Worsening RV function (adjusted for background modela and baseline RV function)b 2.11 (1.40–3.19) 0.0004 Worsening RV function (adjusted for background modela and baseline MR)c 2.02 (1.32–3.08) 0.001 Worsening RV function (adjusted for background modela and baseline tricuspid TR)d 2.05 (1.34–3.12) 0.0009 Worsening RV function (adjusted for background modela and baseline RVSP)e 2.12 (1.33–3.37) 0.002 CI, confidence interval; HR, hazard ratio; MR, mitral regurgitation; RV, right ventricle; RVSP, right ventricular systolic pressure; TR, tricuspid regurgitation. a Background model includes age, sex, logistic EuroSCORE, and LVEF. b c-statistic 0.62, P < 0.0001. c c-statistic 0.63, P < 0.0001. d c-statistic 0.62. e c-statistic 0.67, P < 0.0001. Table 4 Worsening RV function and cardiac death HR (95% CI) P-value Worsening RV function (adjusted for background modela and baseline RV function)b 2.25 (1.30–3.90) 0.004 Worsening RV function (adjusted for background modela and baseline MR)c 1.97 (1.12–3.49) 0.02 Worsening RV function (adjusted for background modela and baseline tricuspid TR)d 2.05 (1.17–3.60) 0.01 Worsening RV function (adjusted for background model and baseline RVSP)e 1.82 (0.95–3.48) 0.07 HR (95% CI) P-value Worsening RV function (adjusted for background modela and baseline RV function)b 2.25 (1.30–3.90) 0.004 Worsening RV function (adjusted for background modela and baseline MR)c 1.97 (1.12–3.49) 0.02 Worsening RV function (adjusted for background modela and baseline tricuspid TR)d 2.05 (1.17–3.60) 0.01 Worsening RV function (adjusted for background model and baseline RVSP)e 1.82 (0.95–3.48) 0.07 CI, confidence interval; HR, hazard ratio; MR, mitral regurgitation; RV, right ventricle; RVSP, right ventricular systolic pressure; TR, tricuspid regurgitation. a Background model includes age, sex, logistic EuroSCORE, and LVEF. b c-statistic 0.63, P < 0.0001. c c-statistic 0.65, P < 0.0001. d c-statistic 0.65. e c-statistic 0.68, P < 0.0001. Table 4 Worsening RV function and cardiac death HR (95% CI) P-value Worsening RV function (adjusted for background modela and baseline RV function)b 2.25 (1.30–3.90) 0.004 Worsening RV function (adjusted for background modela and baseline MR)c 1.97 (1.12–3.49) 0.02 Worsening RV function (adjusted for background modela and baseline tricuspid TR)d 2.05 (1.17–3.60) 0.01 Worsening RV function (adjusted for background model and baseline RVSP)e 1.82 (0.95–3.48) 0.07 HR (95% CI) P-value Worsening RV function (adjusted for background modela and baseline RV function)b 2.25 (1.30–3.90) 0.004 Worsening RV function (adjusted for background modela and baseline MR)c 1.97 (1.12–3.49) 0.02 Worsening RV function (adjusted for background modela and baseline tricuspid TR)d 2.05 (1.17–3.60) 0.01 Worsening RV function (adjusted for background model and baseline RVSP)e 1.82 (0.95–3.48) 0.07 CI, confidence interval; HR, hazard ratio; MR, mitral regurgitation; RV, right ventricle; RVSP, right ventricular systolic pressure; TR, tricuspid regurgitation. a Background model includes age, sex, logistic EuroSCORE, and LVEF. b c-statistic 0.63, P < 0.0001. c c-statistic 0.65, P < 0.0001. d c-statistic 0.65. e c-statistic 0.68, P < 0.0001. A graded response to magnitude of worsening RV function was also noted. Patients who began with normal RV function and developed moderate to severe dysfunction (n = 29) had the highest hazard for all-cause death (HR 2.87, 95% CI 1.40–5.89), followed by patients who initially had normal RV function and then developed mild dysfunction (n = 108)(HR 2.05, 95% CI 1.38–3.04) (Figure 3). Similar results were obtained for cardiovascular death with the worst prognosis among patients with normal RV function who developed moderate to severe RV dysfunction (HR 4.37, 95% CI 1.87–10.2), followed by patients who worsened to mild RV dysfunction (HR 1.93, 95% CI 1.08–3.43) (Figure 4). In patients with mild RV dysfunction at baseline who improved to normal RV function at 30 days (n = 49), there was no significant association with all-cause (HR 0.76, 95% CI 0.28–2.05) or cardiac death (HR 0.85, 95% CI 0.18–3.10). Figure 2 View largeDownload slide The Kaplan–Meier survival curves for cardiovascular mortality in patients with and without worsening right ventricular function, stratified by randomization to transcatheter aortic valve replacement or surgical aortic valve replacement. Patients with worsening right ventricular function had higher cardiovascular mortality (hazard ratio 2.11, 95% confidence interval 1.22–3.66), though there was no difference in mortality in patients with worsening right ventricular function according to transcatheter aortic valve replacement or surgical aortic valve replacement (hazard ratio 1.09, 95% confidence interval 0.65–1.82). Figure 2 View largeDownload slide The Kaplan–Meier survival curves for cardiovascular mortality in patients with and without worsening right ventricular function, stratified by randomization to transcatheter aortic valve replacement or surgical aortic valve replacement. Patients with worsening right ventricular function had higher cardiovascular mortality (hazard ratio 2.11, 95% confidence interval 1.22–3.66), though there was no difference in mortality in patients with worsening right ventricular function according to transcatheter aortic valve replacement or surgical aortic valve replacement (hazard ratio 1.09, 95% confidence interval 0.65–1.82). Figure 3 View largeDownload slide Forest plots for magnitude of worsening right ventricular function and all-cause mortality. Normal to moderate/severe (n =29), normal to mild (n = 155), mild to moderate/severe (n = 28), mild to mild (n = 112), moderate to moderate/severe (n = 26). CI, confidence interval; HR, hazard ratio; RV, right ventricle; RVD, right ventricular dysfunction. Figure 3 View largeDownload slide Forest plots for magnitude of worsening right ventricular function and all-cause mortality. Normal to moderate/severe (n =29), normal to mild (n = 155), mild to moderate/severe (n = 28), mild to mild (n = 112), moderate to moderate/severe (n = 26). CI, confidence interval; HR, hazard ratio; RV, right ventricle; RVD, right ventricular dysfunction. Figure 4 View largeDownload slide Forest plots for magnitude of worsening RV function and cardiovascular mortality. Normal to moderate/severe (n =29), normal to mild (n = 155), mild to moderate/severe (n = 28), mild to mild (n = 112), moderate to moderate/severe (n = 26). CI, confidence interval; HR, hazard ratio; RV, right ventricle; RVD, right ventricular dysfunction. Figure 4 View largeDownload slide Forest plots for magnitude of worsening RV function and cardiovascular mortality. Normal to moderate/severe (n =29), normal to mild (n = 155), mild to moderate/severe (n = 28), mild to mild (n = 112), moderate to moderate/severe (n = 26). CI, confidence interval; HR, hazard ratio; RV, right ventricle; RVD, right ventricular dysfunction. In the entire cohort, patients with worsening RV function had a smaller increase in KCCQ scores from baseline to 30 days (6.1 vs. 11.1, P = 0.01). However, this association was related to smaller increases in KCCQ scores among patents with SAVR compared with TAVR (see Supplementary material online, Table S6). In addition, among SAVR patients with worsening RV function, there was less improvement in KCCQ scores compared with baseline at one (17.1 vs. 22.8, P = 0.02) and 2 years (15.9 vs. 20.4, P = 0.10), though none of these associations were significant after adjusting for multiple comparisons (see Supplementary material online, Table S6). Similarly, there were no significant differences in change in 6 min walk distance for patients with worsening RV function, stratified by TAVR or SAVR (see Supplementary material online, Table S7). With regards to the need for diuretics, in TAVR patients, there was no statistically detectable difference in those with and without worsening RV function at baseline, 30 days, 1 and 2 years (see Supplementary material online, Table S8). Conversely, in patients with SAVR, even though there were no statistically significant differences after adjusting for multiple comparisons, a trend was noted: patients with worsening RV function were numerically more likely to require diuretic therapy at one (OR 1.61, 95% CI 1.07–2.43) and 2 years (OR 1.40, 95% CI 0.91–2.16) (see Supplementary material online, Table S8). At 1-year, among patients with worsening RV function, 26 patients died, and 50 patients improved to normal RV function. When compared with TAVR, patients with SAVR were not more likely to improve to normal RV function at 1-year (OR 1.59, 95% CI 0.75–3.37). By two years of follow-up, 44 patients with worsening RV function had died, and 49 patients had normal RV function. Patients with SAVR were again not more likely to have normal RV function (OR 1.10, 95% CI 0.48–2.55). Discussion To the best of our knowledge, our study is the first to investigate adjusted analyses of worsening RV function after AVR and its association with adverse outcomes in patients randomized to SAVR or TAVR. Several observations are notable. First, after multivariable adjustment, the odds for worsening RV function was more than four times greater for SAVR compared to TAVR. Worsening RV function was also more common in patients with dilated RVs and at least moderate TR. After adjusting for baseline clinical and echocardiographic parameters, worsening RV function was associated with higher all-cause and cardiovascular mortality. Finally, a graded ‘dose’ response was noted. Patients who developed moderate or severe RV dysfunction from baseline normal RV function had the worst prognosis. Previous studies of aortic valve replacement and right ventricular function Right ventricular dysfunction after cardiac surgery is well-described, associated with adverse outcomes, and is generally attributed to ischaemia and myocardial depression following cardiopulmonary bypass without salutary unloading, as is often observed with the left ventricle when treating left-sided valvular lesions.14–16 With the advent of TAVR, the prognostic importance of the right ventricle has been further emphasized. Results have been discordant with several investigations demonstrating that right ventricular dilation and dysfunction are associated with increased mortality whereas other studies have not confirmed this association.4,17–19 These discrepant results are possibly related to differences in cohorts, variations in methodologies for RV assessment, and the approach to multivariable adjustment. Importantly, these studies assessed baseline RV function and adverse events without investigating whether deterioration in RV function after AVR is associated with poor outcomes. More recently, however, a single-centre study investigated RV dysfunction after TAVR in over 1000 patients.20 Their results are concordant with ours as Asami et al.20 demonstrated a gradient of increasing risk from patients with normal RV function, to patients with new RV dysfunction, to patients with persistent RV dysfunction after TAVR. Of note, this study did not include patients with SAVR. Therefore, the differential incidence and impact of worsening RV function according to mode of AVR could not be investigated. Additional studies have demonstrated that RV dysfunction is more common after SAVR compared to TAVR.5,6,21 However, these studies have either not involved randomized patients5,6 or did not perform adjusted analysis for worsening RV function after AVR.22 Furthermore, like previous investigations involving patients with TAVR,4,17–19,21 none of the prior studies addressed the possible association of worsening RV function after AVR and increased mortality.5,6,21 Limitations Notable limitations of this study warrant emphasis. First, this study is a landmark analysis of patients from PARTNERIIA who had echocardiograms at 30 days, and these patients were slightly lower risk compared with patients who did not have 30 day echocardiograms (see Supplementary material online, Table S1; median logistic EuroSCORE in analysis of 6.3 vs. 7.3 not in analysis). Of note, however, baseline characteristics of TAVR and SAVR patients in this analysis were well-balanced (see Supplementary material online, Table S2). Second, even though an integrated prospective echocardiographic approach was employed to evaluate RV function, guidelines to assess RV function have been updated since the initiation of PARTNERIIA23, and an even more accurate and reproducible assessment may be possible with global longitudinal strain and cardiac magnetic resonance imaging.24–26 In particular, our approach emphasized visual assessment to categorize RV dysfunction. However, this approach reflects clinical practice, and we speculate that a more precise assessment of RV function would only strengthen the associations that we have demonstrated. Third, even though LVEF was associated with worsening RV function, absolute between group differences were small, and the majority of patients had normal or mildly reduced LVEFs. Therefore, our results are not as generalizable to patients with more severely reduced LV systolic function. Fourth, invasive haemodynamic data were not available. Baseline cardiac indices and intracardiac pressures may have provided further insights regarding associations with worsening RV function and adverse outcomes. Finally, our longitudinal analyses regarding changes in RV function and quality of life assessments at one and two years should be considered as merely descriptive and exploratory for two analytical reasons. First, after correction for multiple hypothesis testing, none of the results are statistically significant. Second, there are competing risks and events are likely not independent, as patients who die during follow-up would also be expected to have a worse performance on quality of life measures. Clinical implications and future directions Among an intermediate-risk cohort with severe symptomatic AS, patients with dilated RVs, more than mild TR, and patients treated with SAVR are at-risk for developing worsening RV function after AVR. After AVR, the extent to which specific insults contribute to worsening RV function are not well understood. Possible risks specific to SAVR include cardioplegia and pericardiotomy, whereas LV and RV interaction as well as alterations in the geometry of the fibrous skeleton may contribute to worsening RV function after TAVR or SAVR.27–29 Even though these mechanisms are still being defined, and despite overall similar outcomes in patients with SAVR or TAVR once RV function has worsened, our results demonstrate that patients with worsening RV function after AVR have increased mortality. Exploratory analyses also suggested differential increased risks for worsening RV function in patients with TAVR or SAVR. With TAVR, more than mild TR, but not RV dilation, was associated with worsening RV function. Conversely, after SAVR, RV dilation, but not baseline TR, was associated with worsening RV function. Combined with other investigations and future studies, these results have implications regarding which intermediate risk patients may benefit from TAVR or SAVR. In addition, these results prompt the question of whether medical, surgical, and percutaneous treatment of concomitant TR can preserve RV function. Finally, our results should lead to further investigations of RV function after AVR in lower risk patients being considered for SAVR or TAVR. Most importantly, clinicians should recognize that patients with normal baseline RV function who develop moderate or severe dysfunction after AVR are at especially high risk. Supplementary material Supplementary material is available at European Heart Journal online. Conflict of interest: none declared. References 1 Douglas PS , Hahn RT , Pibarot P , Weissman NJ , Stewart WJ , Xu K , Wang Z , Lerakis S , Siegel R , Thompson C , Gopal D , Keane MG , Svensson LG , Tuzcu EM , Smith CR , Leon MB. Hemodynamic outcomes of transcatheter aortic valve replacement and medical management in severe, inoperable aortic stenosis: a longitudinal echocardiographic study of cohort B of the PARTNER trial . J Am Soc Echocardiogr 2015 ; 28 : 210 – 217.e1–9 . Google Scholar CrossRef Search ADS PubMed 2 Généreux P , Pibarot P , Redfors B , Mack MJ , Makkar RR , Jaber WA , Svensson LG , Kapadia S , Tuzcu EM , Thourani VH , Babaliaros V , Herrmann HC , Szeto WY , Cohen DJ , Lindman BR , McAndrew T , Alu MC , Douglas PS , Hahn RT , Kodali SK , Smith CR , Miller DC , Webb JG , Leon MB. Staging classification of aortic stenosis based on the extent of cardiac damage . Eur Heart J 2017 ; 38 : 3351 – 3358 . Google Scholar CrossRef Search ADS PubMed 3 Ternacle J , Berry M , Cognet T , Kloeckner M , Damy T , Monin JL , Couetil JP , Dubois-Rande JL , Gueret P , Lim P. Prognostic value of right ventricular two-dimensional global strain in patients referred for cardiac surgery . J Am Soc Echocardiogr 2013 ; 26 : 721 – 726 . Google Scholar CrossRef Search ADS PubMed 4 Lindman BR , Maniar HS , Jaber WA , Lerakis S , Mack MJ , Suri RM , Thourani VH , Babaliaros V , Kereiakes DJ , Whisenant B , Miller DC , Tuzcu EM , Svensson LG , Xu K , Doshi D , Leon MB , Zajarias A. Effects of tricuspid regurgitation and the right heart on survival after transcatheter aortic valve replacement: insights from the placement of aortic transcatheter valves II inoperable cohort . Circ Cardiovasc Interv 2015 ; 8 : e002073. Google Scholar CrossRef Search ADS PubMed 5 Kempny A , Diller GP , Kaleschke G , Orwat S , Funke A , Schmidt R , Kerckhoff G , Ghezelbash F , Rukosujew A , Reinecke H , Scheld HH , Baumgartner H. Impact of transcatheter aortic valve implantation or surgical aortic valve replacement on right ventricular function . Heart 2012 ; 98 : 1299 – 1304 . Google Scholar CrossRef Search ADS PubMed 6 Forsberg LM , Tamás E , Vánky F , Nielsen NE , Engvall J , Nylander E. Left and right ventricular function in aortic stenosis patients 8 weeks post-transcatheter aortic valve implantation or surgical aortic valve replacement . Eur J Echocardiogr 2011 ; 12 : 603 – 611 . Google Scholar PubMed 7 Leon MB , Smith CR , Mack MJ , Makkar RR , Svensson LG , Kodali SK , Thourani VH , Tuzcu EM , Miller DC , Herrmann HC , Doshi D , Cohen DJ , Pichard AD , Kapadia S , Dewey T , Babaliaros V , Szeto WY , Williams MR , Kereiakes D , Zajarias A , Greason KL , Whisenant BK , Hodson RW , Moses JW , Trento A , Brown DL , Fearon WF , Pibarot P , Hahn RT , Jaber WA , Anderson WN , Alu MC , Webb JG ; PARTNER 2 Investigators . Transcatheter or surgical aortic-valve replacement in intermediate-risk patients . N Engl J Med 2016 ; 374 : 1609 – 1620 . Google Scholar CrossRef Search ADS PubMed 8 Douglas PS , Waugh RA , Bloomfield G , Dunn G , Davis L , Hahn RT , Pibarot P , Stewart WJ , Weissman NJ , Hueter I , Siegel R , Lerakis S , Miller DC , Smith CR , Leon MB. Implementation of echocardiography core laboratory best practices: a case study of the PARTNER I trial . J Am Soc Echocardiogr 2013 ; 26 : 348 – 358.e343 . Google Scholar CrossRef Search ADS PubMed 9 Hahn RT , Pibarot P , Stewart WJ , Weissman NJ , Gopalakrishnan D , Keane MG , Anwaruddin S , Wang Z , Bilsker M , Lindman BR , Herrmann HC , Kodali SK , Makkar R , Thourani VH , Svensson LG , Akin JJ , Anderson WN , Leon MB , Douglas PS. Comparison of transcatheter and surgical aortic valve replacement in severe aortic stenosis: a longitudinal study of echocardiography parameters in cohort A of the PARTNER trial (placement of aortic transcatheter valves) . J Am Coll Cardiol 2013 ; 61 : 2514 – 2521 . Google Scholar CrossRef Search ADS PubMed 10 Lang RM , Bierig M , Devereux RB , Flachskampf FA , Foster E , Pellikka PA , Picard MH , Roman MJ , Seward J , Shanewise JS , Solomon SD , Spencer KT , Sutton MS , Stewart WJ ; Chamber Quantification Writing Group; American Society of Echocardiography's Guidelines and Standards Committee; European Association of Echocardiography . Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology . J Am Soc Echocardiogr 2005 ; 18 : 1440 – 1463 . Google Scholar CrossRef Search ADS PubMed 11 Zoghbi WA , Enriquez-Sarano M , Foster E , Grayburn PA , Kraft CD , Levine RA , Nihoyannopoulos P , Otto CM , Quinones MA , Rakowski H , Stewart WJ , Waggoner A , Weissman NJ ; American Society of Echocardiography . Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography . J Am Soc Echocardiogr 2003 ; 16 : 777 – 802 . Google Scholar CrossRef Search ADS PubMed 12 Rudski LG , Lai WW , Afilalo J , Hua L , Handschumacher MD , Chandrasekaran K , Solomon SD , Louie EK , Schiller NB. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography . J Am Soc Echocardiogr 2010 ; 23 : 685 – 713 . Google Scholar CrossRef Search ADS PubMed 13 Green CP , Porter CB , Bresnahan DR , Spertus JA. Development and evaluation of the Kansas City Cardiomyopathy Questionnaire: a new health status measure for heart failure . J Am Coll Cardiol 2000 ; 35 : 1245 – 1255 . Google Scholar CrossRef Search ADS PubMed 14 Haddad F , Couture P , Tousignant C , Denault AY. The right ventricle in cardiac surgery, a perioperative perspective: II. Pathophysiology, clinical importance and management . Anesth Analg 2009 ; 108 : 422 – 433 . Google Scholar CrossRef Search ADS PubMed 15 Kaul TK , Fields BL. Postoperative acute refractory right ventricular failure: incidence, pathogenesis, management and prognosis . Cardiovasc Surg 2000 ; 8 : 1 – 9 . Google Scholar CrossRef Search ADS PubMed 16 Hedman A , Alam M , Zuber E , Nordlander R , Samad BA . Decreased right ventricular function after coronary artery bypass grafting and its relation to exercise capacity: a tricuspid annular-motion based study . J Am Soc Echocardiogr 2004 ; 17 : 126 – 131 . Google Scholar CrossRef Search ADS PubMed 17 Griese DP , Kerber S , Barth S , Diegeler A , Babin-Ebell J , Reents W. Impact of right and left ventricular systolic dysfunction on perioperative outcome and long-term survival after transcatheter aortic valve replacement . J Interven Cardiol 2017 ; 30 : 217 – 225 . Google Scholar CrossRef Search ADS 18 Ito S , Pislaru SV , Soo WM , Huang R , Greason KL , Mathew V , Sandhu GS , Eleid MF , Suri RM , Oh JK , Nkomo VT. Impact of right ventricular size and function on survival following transcatheter aortic valve replacement . Int J Cardiol 2016 ; 221 : 269 – 274 . Google Scholar CrossRef Search ADS PubMed 19 Koifman E , Didier R , Patel N , Jerusalem Z , Kiramijyan S , Ben-Dor I , Negi SI , Wang Z , Goldstein SA , Lipinski MJ , Torguson R , Gai J , Pichard AD , Satler LF , Waksman R , Asch FM. Impact of right ventricular function on outcome of severe aortic stenosis patients undergoing transcatheter aortic valve replacement . Am Heart J 2017 ; 184 : 141 – 147 . Google Scholar CrossRef Search ADS PubMed 20 Asami M , Stortecky S , Praz F , Lans K , Raber L , Franzone A , Piccolo R , Siontis GCM , Heg D , Valgimigli M , Wenaweser P , Roost E , Windecker S , Pilgrim T. Prognostive value of right ventricular dysfunction on clinical outcomes after transcatheter aortic valve replacement . J Am Coll Cardiol 2018 ; doi:10.1016/j.jcmg.2017.12.015. 21 Lindsay AC , Harron K , Jabbour RJ , Kanyal R , Snow TM , Sawhney P , Alpendurada F , Roughton M , Pennell DJ , Duncan A , Di Mario C , Davies SW , Mohiaddin RH , Moat NE. Prevalence and prognostic significance of right ventricular systolic dysfunction in patients undergoing transcatheter aortic valve implantation . Circ Cardiovasc Interv 2016 ; 9 : e003486. Google Scholar CrossRef Search ADS PubMed 22 Little SH , Oh JK , Gillam L , Sengupta PP , Orsinelli DA , Cavalcante JL , Chang JD , Adams DH , Zorn GL 3rd , Pollak AW , Abdelmoneim SS , Reardon MJ , Qiao H , Popma JJ. Self-expanding transcatheter aortic valve replacement versus surgical valve replacement in patients at high risk for surgery: a study of echocardiographic change and risk prediction . Circ Cardiovasc Interv 2016 ; 9 : e003426. Google Scholar CrossRef Search ADS PubMed 23 Harjola V-P , Mebazaa A , Čelutkienė J , Bettex D , Bueno H , Chioncel O , Crespo-Leiro MG , Falk V , Filippatos G , Gibbs S , Leite-Moreira A , Lassus J , Masip J , Mueller C , Mullens W , Naeije R , Nordegraaf AV , Parissis J , Riley JP , Ristic A , Rosano G , Rudiger A , Ruschitzka F , Seferovic P , Sztrymf B , Vieillard-Baron A , Yilmaz MB , Konstantinides S. Contemporary management of acute right ventricular failure: a statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology . Eut J Heart Failure 2016 ; 18 : 226 – 241 . Google Scholar CrossRef Search ADS 24 Dahou A , Clavel MA , Capoulade R , Bartko PE , Magne J , Mundigler G , Bergler-Klein J , Burwash I , Mascherbauer J , Ribeiro HB , O'Connor K , Baumgartner H , Sénéchal M , Dumesnil JG , Rosenhek R , Mathieu P , Larose E , Rodés-Cabau J , Pibarot P. Right ventricular longitudinal strain for risk stratification in low-flow, low-gradient aortic stenosis with low ejection fraction . Heart 2016 ; 102 : 548 – 554 . Google Scholar CrossRef Search ADS PubMed 25 Lorenz CH , Walker ES , Morgan VL , Klein SS , Graham TP. Normal human right and left ventricular mass, systolic function, and gender differences by cine magnetic resonance imaging . J Cardiovasc Magn Reson 1999 ; 1 : 7 – 21 . Google Scholar CrossRef Search ADS PubMed 26 Bellenger NG , Burgess MI , Ray SG , Lahiri A , Coats AJ , Cleland JG , Pennell DJ. Comparison of left ventricular ejection fraction and volumes in heart failure by echocardiography, radionuclide ventriculography and cardiovascular magnetic resonance; are they interchangeable? Eur Heart J 2000 ; 21 : 1387 – 1396 . Google Scholar CrossRef Search ADS PubMed 27 Boldt J , Zickmann B , Ballesteros M , Dapper F , Hempelmann G. Right ventricular function in patients with aortic stenosis undergoing aortic valve replacement . J Cardiothorac Vasc Anesth 1992 ; 6 : 287 – 291 . Google Scholar CrossRef Search ADS PubMed 28 Unsworth B , Casula RP , Kyriacou AA , Yadav H , Chukwuemeka A , Cherian A , Stanbridge Rde L , Athanasiou T , Mayet J , Francis DP. The right ventricular annular velocity reduction caused by coronary artery bypass graft surgery occurs at the moment of pericardial incision . Am Heart J 2010 ; 159 : 314 – 322 . Google Scholar CrossRef Search ADS PubMed 29 Sonny A , Sessler DI , You J , Kashy BK , Sarwar S , Singh AK , Sale S , Alfirevic A , Duncan AE. Early left and right ventricular response to aortic valve replacement . Anesth Analg 2017 ; 124 : 406 – 418 . Google Scholar CrossRef Search ADS PubMed Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Heart Journal Oxford University Press

The incidence and prognostic implications of worsening right ventricular function after surgical or transcatheter aortic valve replacement: insights from PARTNER IIA

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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.
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Abstract

Abstract Aims In patients randomized to transcatheter or surgical aortic valve replacement (TAVR, SAVR), we sought to determine whether SAVR is associated with worsening right ventricular (RV) function and whether RV deterioration is associated with mortality. Methods and results In 1376 patients from PARTNERIIA with paired baseline and 30-day core lab echocardiograms, worsening RV function was defined as decline by at least one grade from baseline to 30 days. Our primary outcome was all-cause mortality from 30 days to 2 years. Among 744 patients with TAVR, 62 (8.3%) had worsening RV function, compared with 156 of 632 patients with SAVR (24.7%) (P < 0.0001). In a multivariable model, SAVR [odds ratio (OR) 4.05, 95% confidence interval (CI) 2.55–6.44], a dilated RV (OR 2.38, 95% CI 1.37–4.14), and more than mild tricuspid regurgitation (TR) (OR 2.58, 95% CI 1.25–5.33) were associated with worsening RV function. There were 169 deaths, and patients with worsening RV function had higher all-cause mortality [hazard ratio (HR) 1.98, 95% CI 1.40–2.79]. This association remained robust after adjusting for clinical and echocardiographic variables. Among patients with worsening RV function, there was no mortality difference between TAVR and SAVR (HR 1.16, 95% CI 0.61–2.18). The development of moderate or severe RV dysfunction from baseline normal RV function conferred the worst prognosis (HR 2.87, 95% CI 1.40–5.89). Conclusion After aortic valve replacement, worsening RV function is more common in patients with baseline RV dilation, more than mild TR, and in patients treated with SAVR. Worsening RV function and the magnitude of deterioration have important prognostic implications. View largeDownload slide View largeDownload slide Transcatheter aortic valve replacement , Surgical aortic valve replacement , Worsening right ventricular function Introduction With the advent of transcatheter aortic valve replacement (TAVR) for severe symptomatic aortic stenosis (AS), echocardiographic parameters that inform prognosis have been emphasized.1 In general, these analyses have focused on the left ventricle, though more recently, progression to right ventricular (RV) damage has also shown prognostic importance.2 After cardiac surgery, the association between baseline RV dysfunction and poor outcomes is established.3 However, in the PARTNER II inoperable cohort, baseline RV dysfunction was associated with worse outcomes after TAVR on univariable, but not multivariable, analyses.4 In addition, deterioration in RV function has been noted after surgical aortic valve replacement (SAVR),5 but whether RV function worsens after TAVR remains unclear.6 Specifically, in patients randomized to TAVR or SAVR, the differential incidence of worsening RV function and possible associations with adverse outcomes have not been well studied. Given this limited understanding of the importance of the RV after aortic valve replacement (AVR), the objectives of the current study are two-fold. First, in patients from PARTNER IIA,7 we aim to delineate whether the approach to AVR has a differential impact on RV function. Second, we aim to determine whether worsening RV function after AVR is associated with adverse outcomes. Methods Study population The PARTNER IIA study design and results have been previously reported.7 In brief, 2032 patients with severe symptomatic AS were randomized to SAVR or TAVR with the Edwards Sapien XT valve. All patients were at intermediate risk, based on a Society of Thoracic Surgery (STS) predicted 30-day mortality of at least 4.0%. For this analysis, the logistic EuroSCORE was used instead of the STS score because the former includes the presence of pulmonary hypertension in calculating risk, an important parameter for right heart function. Our substudy included all patients with a core lab echocardiogram at baseline and at 30 days (n = 1384). We excluded patients with severe baseline RV dysfunction (n = 8), as we were specifically interested in patients with worsening RV function after AVR, yielding a final cohort of 1376 patients. The study protocol was approved by the institutional review board at each enrolling site, was compliant with the Declaration of Helsinki, and all patients provided written informed consent. Echocardiography An independent core laboratory prospectively analysed all echocardiograms with quality and measurement methodology as previously reported.8,9 In brief, the severity of AS was determined by measuring peak and mean gradients across the valve with the modified Bernoulli equation, and aortic valve area was calculated using the continuity equation. Ventricular size, left ventricular ejection fraction (LVEF), and left ventricular (LV) mass were measured according to the recommendations of the American Society of Echocardiography.10 The severity of aortic, mitral, and tricuspid regurgitation (TR) were determined by an integrated, semiquantitative approach, as recommended by the American Society of Echocardiography.11 RV size and function was also assessed with a guideline-endorsed multiparametric approach using visual assessment, right ventricular fractional area change when feasible, and tricuspid annular plane systolic excursion when available.12 RV function was categorized as normal, mildly, moderately or severely decreased. In patients with RV dysfunction, severity was primarily based on visual assessment. Similarly, in accordance with guidelines,12 RV enlargement was assessed visually, and dilation was defined from a dedicated apical view with linear dimensions if basal diameter was >42 mm, >35 mm at the mid level, or >86 mm in longitudinal dimension.12 Outcomes Worsening RV function was defined as deterioration by at least one grade between baseline and 30-day echocardiogram. To assess outcomes, we performed a landmark analysis with all events occurring at least 30 days after AVR. As our primary outcome, we assessed whether worsening RV function was associated with all-cause mortality between 30 days and 2 years. For our secondary outcome, we assessed whether worsening RV function was associated with cardiovascular mortality between 30 days and 2 years. Other secondary outcomes included cardiac rehospitalizations that were not related to study valve or procedurdal complications, Kansas City Cardiomyopathy Questionnaire (KCCQ)13 scores, and 6 min walk distance (m), all assessed between 30 days and 2 years. To assess whether complications may be related to worsening RV function, we also evaluated cardiac rehospitalizations that were related to the study valve or procedure. Statistics Continuous data were summarized as mean (standard deviation) or median (interquartile percentages) with comparisons using t-tests or Wilcoxon rank sum tests, and categorical data were expressed as n (%) with comparisons using the χ2 or Fisher exact tests, as appropriate. Multivariable logistic regression was performed to assess associations with worsening RV function. Time-to-event curves for 30 day to 2 year mortality were created using the Kaplan–Meier estimates with between group comparisons using the log-rank test. For time-to-event outcomes, univariable and multivariable Cox proportional hazards models were created, and the assumptions of proportional hazards were satisfied. All covariates for the multivariable models were chosen based on biologic plausibility. A two-sided P-value of <0.05 was considered statistically significant. All statistical analyses were performed with SAS software, version 9.4 (SAS Institute) or R Core Team (2017). Results Baseline clinical and echocardiographic findings From an initial 2032 patients, 1376 patients with paired baseline and 30 day echocardiograms were included in this study. Within the first 30 days, 34 patients with TAVR and 38 patients with SAVR died. As would be expected, patients alive and with echocardiograms at 30 days were slightly lower risk compared to PARTNER IIA patients not included in this substudy (see Supplementary material online, Table S1). Importantly, there were no statistically significant between group differences in TAVR and SAVR patients in this landmark analysis, except that SAVR patients were more likely to have atrial fibrillation at baseline (29.7% vs. 35.6%, P = 0.02)(see Supplementary material online, Table S2). Among 744 patients with TAVR, 62 (8.3%) had worsening RV function, compared with 156 of 632 patients with SAVR (24.7%) [odds ratio (OR) 3.61, 95% confidence interval (CI) 2.63–4.95]. In addition, 47 patients with TAVR (6.3%) and 26 patients with SAVR (4.1%) had improved RV function at 30 days (OR 1.57, 95% CI 0.96–2.57). Grades of RV function at 30 days are shown in Figure 1. At baseline, patients with worsening RV function were more likely to have atrial fibrillation, and there was a trend towards higher logistic EuroSCOREs, male sex, permanent pacemaker, and New York Heart Association (NYHA) Class III or IV symptoms (Table 1). Table 1 Baseline clinical and echocardiographic characteristics in patients with TAVR or SAVR, stratified by the presence of worsening RV function at 30 days TAVR: worsening RV function (n = 62) TAVR: no worsening RV function (n = 682) SAVR: worsening RV function (n = 156) SAVR: no worsening RV function (n = 476) P-value Age 81.9 (6.4) 81.7 (6.5) 81.7 (6.5) 81.7 (6.8) 0.99 Female sex 41.9% (26/62) 49.6% (338/682) 39.7% (62/156) 48.3% (230/476) 0.12 Body mass index (kg/m2) 28.3 (5.6) 28.2 (5.8) 27.8 (5.8) 28.0 (5.7) 0.84 Logistic EuroSCORE 8.1 (7.9) 6.1 (5.3) 6.9 (6.1) 6.3 (6.8) 0.06 NYHA Class III or IV 75.8% (47/62) 77.3% (527/682) 78.2% (122/156) 71.0% (338/476) 0.08 KCCQ 49.7 (24.5) 54.6 (21.3) 51.9 (21.0) 53.9 (21.6) 0.26 6 minute walk (m) 166.8 (112.0) 189.6 (117.7) 176.7 (129.4) 190.8 (122.9) 0.32 CAD 71.0% (44/62) 68.9% (470/682) 64.7% (101/156) 64.3% (306/476) 0.32 Peripheral vascular disease 33.9% (21/62) 26.0% (177/682) 30.8% (48/156) 30.7% (146/476) 0.21 Atrial fibrillation 32.3% (20/62) 28.2% (192/682) 41.0% (64/156) 32.8% (156/476) 0.01 Permanent Pacemaker 17.7% (11/62) 10.0% (68/682) 14.1% (22/156) 9.7% (46/476) 0.11 Hypertension 95.2% (59/62) 94.4% (644/682) 94.9% (148/156) 93.3% (444/476) 0.80 Dyslipidaemia 82.3% (51/62) 82.7% (564/682) 76.9% (120/156) 80.9% (385/476) 0.40 Diabetes mellitus 35.5% (22/62) 35.6% (243/682) 35.3% (55/156) 33.4% (159/476) 0.89 Previous or current smoker 59.7% (37/62) 45.7% (312/682) 49.4% (77/156) 48.5% (231/476) 0.18 COPD 37.1% (23/62) 30.1% (204/678) 27.6% (43/156) 29.4% (139/472) 0.57 Creatinine ≥2 mg/dL 1.6% (1/62) 4.4% (30/682) 7.1% (11/156) 5.5% (26/476) 0.30 Liver disease 1.6% (1/62) 2.1% (14/682) 4.5% (7/156) 2.7% (13/476) 0.34 ACEi 29.0% (18/62) 29.9% (204/682) 31.4% (49/156) 26.3% (125/476) 0.49 ARB 16.1% (10/62) 16.7% (114/682) 15.4% (24/156) 19.3% (92/476) 0.58 Beta-blockers 51.6% (32/62) 55.6% (379/682) 57.7% (90/156) 59.2% (282/476) 0.51 Diuretic 53.2% (33/62) 50.1% (342/682) 49.4% (77/156) 51.5% (245/476) 0.93 Statin 69.4% (43/62) 66.7% (455/682) 57.1% (89/156) 64.3% (306/476) 0.12 LVEF (%) 53 (11) 56 (11) 51 (12) 56 (11) <0.0001 LV mass index (g/m2) 118 (35) 120 (32) 120 (34) 121 (34) 0.92 Normal RV function 80.6% (50/62) 83.1% (567/682) 85.9% (134/156) 81.1% (386/476) 0.52 Normal RV size 67.7% (42/62) 83.6% (569/681) 69.2% (108/156) 87.2% (415/476) <0.0001 Aortic valve peak velocity (m/s) 4.4 (0.7) 4.4 (0.6) 4.3 (0.6) 4.4 (0.6) 0.18 Aortic valve area (cm2) 0.69 (0.19) 0.70 (0.17) 0.69 (0.20) 0.68 (0.19) 0.55 Moderate or severe AR 11.5% (7/61) 11.5% (75/654) 10.7% (16/150) 11.5% (52/453) 0.99 Moderate or severe MR 18.6% (11/59) 16.9% (108/639) 17.9% (26/145) 18.0% (79/440) 0.96 Moderate or severe TR 31.6% (18/57) 15.3% (94/616) 21.1% (31/147) 15.6% (65/416) 0.006 Right ventricular systolic pressure (mmHg) 44 (16) 37 (12) 37 (11) 37 (13) 0.01 TAVR: worsening RV function (n = 62) TAVR: no worsening RV function (n = 682) SAVR: worsening RV function (n = 156) SAVR: no worsening RV function (n = 476) P-value Age 81.9 (6.4) 81.7 (6.5) 81.7 (6.5) 81.7 (6.8) 0.99 Female sex 41.9% (26/62) 49.6% (338/682) 39.7% (62/156) 48.3% (230/476) 0.12 Body mass index (kg/m2) 28.3 (5.6) 28.2 (5.8) 27.8 (5.8) 28.0 (5.7) 0.84 Logistic EuroSCORE 8.1 (7.9) 6.1 (5.3) 6.9 (6.1) 6.3 (6.8) 0.06 NYHA Class III or IV 75.8% (47/62) 77.3% (527/682) 78.2% (122/156) 71.0% (338/476) 0.08 KCCQ 49.7 (24.5) 54.6 (21.3) 51.9 (21.0) 53.9 (21.6) 0.26 6 minute walk (m) 166.8 (112.0) 189.6 (117.7) 176.7 (129.4) 190.8 (122.9) 0.32 CAD 71.0% (44/62) 68.9% (470/682) 64.7% (101/156) 64.3% (306/476) 0.32 Peripheral vascular disease 33.9% (21/62) 26.0% (177/682) 30.8% (48/156) 30.7% (146/476) 0.21 Atrial fibrillation 32.3% (20/62) 28.2% (192/682) 41.0% (64/156) 32.8% (156/476) 0.01 Permanent Pacemaker 17.7% (11/62) 10.0% (68/682) 14.1% (22/156) 9.7% (46/476) 0.11 Hypertension 95.2% (59/62) 94.4% (644/682) 94.9% (148/156) 93.3% (444/476) 0.80 Dyslipidaemia 82.3% (51/62) 82.7% (564/682) 76.9% (120/156) 80.9% (385/476) 0.40 Diabetes mellitus 35.5% (22/62) 35.6% (243/682) 35.3% (55/156) 33.4% (159/476) 0.89 Previous or current smoker 59.7% (37/62) 45.7% (312/682) 49.4% (77/156) 48.5% (231/476) 0.18 COPD 37.1% (23/62) 30.1% (204/678) 27.6% (43/156) 29.4% (139/472) 0.57 Creatinine ≥2 mg/dL 1.6% (1/62) 4.4% (30/682) 7.1% (11/156) 5.5% (26/476) 0.30 Liver disease 1.6% (1/62) 2.1% (14/682) 4.5% (7/156) 2.7% (13/476) 0.34 ACEi 29.0% (18/62) 29.9% (204/682) 31.4% (49/156) 26.3% (125/476) 0.49 ARB 16.1% (10/62) 16.7% (114/682) 15.4% (24/156) 19.3% (92/476) 0.58 Beta-blockers 51.6% (32/62) 55.6% (379/682) 57.7% (90/156) 59.2% (282/476) 0.51 Diuretic 53.2% (33/62) 50.1% (342/682) 49.4% (77/156) 51.5% (245/476) 0.93 Statin 69.4% (43/62) 66.7% (455/682) 57.1% (89/156) 64.3% (306/476) 0.12 LVEF (%) 53 (11) 56 (11) 51 (12) 56 (11) <0.0001 LV mass index (g/m2) 118 (35) 120 (32) 120 (34) 121 (34) 0.92 Normal RV function 80.6% (50/62) 83.1% (567/682) 85.9% (134/156) 81.1% (386/476) 0.52 Normal RV size 67.7% (42/62) 83.6% (569/681) 69.2% (108/156) 87.2% (415/476) <0.0001 Aortic valve peak velocity (m/s) 4.4 (0.7) 4.4 (0.6) 4.3 (0.6) 4.4 (0.6) 0.18 Aortic valve area (cm2) 0.69 (0.19) 0.70 (0.17) 0.69 (0.20) 0.68 (0.19) 0.55 Moderate or severe AR 11.5% (7/61) 11.5% (75/654) 10.7% (16/150) 11.5% (52/453) 0.99 Moderate or severe MR 18.6% (11/59) 16.9% (108/639) 17.9% (26/145) 18.0% (79/440) 0.96 Moderate or severe TR 31.6% (18/57) 15.3% (94/616) 21.1% (31/147) 15.6% (65/416) 0.006 Right ventricular systolic pressure (mmHg) 44 (16) 37 (12) 37 (11) 37 (13) 0.01 AR, aortic regurgitation; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; KCCQ, Kansas City Cardiomyopathy Questionnaire; LV, left ventricle; LVEF, left ventricular ejection fraction; MR, mitral regurgitation; NYHA, New York Heart Association; RV, right ventricle; SAVR, surgical aortic valve replacement; TAVR, transcatheter aortic valve replacement; TR, tricuspid regurgitation. Table 1 Baseline clinical and echocardiographic characteristics in patients with TAVR or SAVR, stratified by the presence of worsening RV function at 30 days TAVR: worsening RV function (n = 62) TAVR: no worsening RV function (n = 682) SAVR: worsening RV function (n = 156) SAVR: no worsening RV function (n = 476) P-value Age 81.9 (6.4) 81.7 (6.5) 81.7 (6.5) 81.7 (6.8) 0.99 Female sex 41.9% (26/62) 49.6% (338/682) 39.7% (62/156) 48.3% (230/476) 0.12 Body mass index (kg/m2) 28.3 (5.6) 28.2 (5.8) 27.8 (5.8) 28.0 (5.7) 0.84 Logistic EuroSCORE 8.1 (7.9) 6.1 (5.3) 6.9 (6.1) 6.3 (6.8) 0.06 NYHA Class III or IV 75.8% (47/62) 77.3% (527/682) 78.2% (122/156) 71.0% (338/476) 0.08 KCCQ 49.7 (24.5) 54.6 (21.3) 51.9 (21.0) 53.9 (21.6) 0.26 6 minute walk (m) 166.8 (112.0) 189.6 (117.7) 176.7 (129.4) 190.8 (122.9) 0.32 CAD 71.0% (44/62) 68.9% (470/682) 64.7% (101/156) 64.3% (306/476) 0.32 Peripheral vascular disease 33.9% (21/62) 26.0% (177/682) 30.8% (48/156) 30.7% (146/476) 0.21 Atrial fibrillation 32.3% (20/62) 28.2% (192/682) 41.0% (64/156) 32.8% (156/476) 0.01 Permanent Pacemaker 17.7% (11/62) 10.0% (68/682) 14.1% (22/156) 9.7% (46/476) 0.11 Hypertension 95.2% (59/62) 94.4% (644/682) 94.9% (148/156) 93.3% (444/476) 0.80 Dyslipidaemia 82.3% (51/62) 82.7% (564/682) 76.9% (120/156) 80.9% (385/476) 0.40 Diabetes mellitus 35.5% (22/62) 35.6% (243/682) 35.3% (55/156) 33.4% (159/476) 0.89 Previous or current smoker 59.7% (37/62) 45.7% (312/682) 49.4% (77/156) 48.5% (231/476) 0.18 COPD 37.1% (23/62) 30.1% (204/678) 27.6% (43/156) 29.4% (139/472) 0.57 Creatinine ≥2 mg/dL 1.6% (1/62) 4.4% (30/682) 7.1% (11/156) 5.5% (26/476) 0.30 Liver disease 1.6% (1/62) 2.1% (14/682) 4.5% (7/156) 2.7% (13/476) 0.34 ACEi 29.0% (18/62) 29.9% (204/682) 31.4% (49/156) 26.3% (125/476) 0.49 ARB 16.1% (10/62) 16.7% (114/682) 15.4% (24/156) 19.3% (92/476) 0.58 Beta-blockers 51.6% (32/62) 55.6% (379/682) 57.7% (90/156) 59.2% (282/476) 0.51 Diuretic 53.2% (33/62) 50.1% (342/682) 49.4% (77/156) 51.5% (245/476) 0.93 Statin 69.4% (43/62) 66.7% (455/682) 57.1% (89/156) 64.3% (306/476) 0.12 LVEF (%) 53 (11) 56 (11) 51 (12) 56 (11) <0.0001 LV mass index (g/m2) 118 (35) 120 (32) 120 (34) 121 (34) 0.92 Normal RV function 80.6% (50/62) 83.1% (567/682) 85.9% (134/156) 81.1% (386/476) 0.52 Normal RV size 67.7% (42/62) 83.6% (569/681) 69.2% (108/156) 87.2% (415/476) <0.0001 Aortic valve peak velocity (m/s) 4.4 (0.7) 4.4 (0.6) 4.3 (0.6) 4.4 (0.6) 0.18 Aortic valve area (cm2) 0.69 (0.19) 0.70 (0.17) 0.69 (0.20) 0.68 (0.19) 0.55 Moderate or severe AR 11.5% (7/61) 11.5% (75/654) 10.7% (16/150) 11.5% (52/453) 0.99 Moderate or severe MR 18.6% (11/59) 16.9% (108/639) 17.9% (26/145) 18.0% (79/440) 0.96 Moderate or severe TR 31.6% (18/57) 15.3% (94/616) 21.1% (31/147) 15.6% (65/416) 0.006 Right ventricular systolic pressure (mmHg) 44 (16) 37 (12) 37 (11) 37 (13) 0.01 TAVR: worsening RV function (n = 62) TAVR: no worsening RV function (n = 682) SAVR: worsening RV function (n = 156) SAVR: no worsening RV function (n = 476) P-value Age 81.9 (6.4) 81.7 (6.5) 81.7 (6.5) 81.7 (6.8) 0.99 Female sex 41.9% (26/62) 49.6% (338/682) 39.7% (62/156) 48.3% (230/476) 0.12 Body mass index (kg/m2) 28.3 (5.6) 28.2 (5.8) 27.8 (5.8) 28.0 (5.7) 0.84 Logistic EuroSCORE 8.1 (7.9) 6.1 (5.3) 6.9 (6.1) 6.3 (6.8) 0.06 NYHA Class III or IV 75.8% (47/62) 77.3% (527/682) 78.2% (122/156) 71.0% (338/476) 0.08 KCCQ 49.7 (24.5) 54.6 (21.3) 51.9 (21.0) 53.9 (21.6) 0.26 6 minute walk (m) 166.8 (112.0) 189.6 (117.7) 176.7 (129.4) 190.8 (122.9) 0.32 CAD 71.0% (44/62) 68.9% (470/682) 64.7% (101/156) 64.3% (306/476) 0.32 Peripheral vascular disease 33.9% (21/62) 26.0% (177/682) 30.8% (48/156) 30.7% (146/476) 0.21 Atrial fibrillation 32.3% (20/62) 28.2% (192/682) 41.0% (64/156) 32.8% (156/476) 0.01 Permanent Pacemaker 17.7% (11/62) 10.0% (68/682) 14.1% (22/156) 9.7% (46/476) 0.11 Hypertension 95.2% (59/62) 94.4% (644/682) 94.9% (148/156) 93.3% (444/476) 0.80 Dyslipidaemia 82.3% (51/62) 82.7% (564/682) 76.9% (120/156) 80.9% (385/476) 0.40 Diabetes mellitus 35.5% (22/62) 35.6% (243/682) 35.3% (55/156) 33.4% (159/476) 0.89 Previous or current smoker 59.7% (37/62) 45.7% (312/682) 49.4% (77/156) 48.5% (231/476) 0.18 COPD 37.1% (23/62) 30.1% (204/678) 27.6% (43/156) 29.4% (139/472) 0.57 Creatinine ≥2 mg/dL 1.6% (1/62) 4.4% (30/682) 7.1% (11/156) 5.5% (26/476) 0.30 Liver disease 1.6% (1/62) 2.1% (14/682) 4.5% (7/156) 2.7% (13/476) 0.34 ACEi 29.0% (18/62) 29.9% (204/682) 31.4% (49/156) 26.3% (125/476) 0.49 ARB 16.1% (10/62) 16.7% (114/682) 15.4% (24/156) 19.3% (92/476) 0.58 Beta-blockers 51.6% (32/62) 55.6% (379/682) 57.7% (90/156) 59.2% (282/476) 0.51 Diuretic 53.2% (33/62) 50.1% (342/682) 49.4% (77/156) 51.5% (245/476) 0.93 Statin 69.4% (43/62) 66.7% (455/682) 57.1% (89/156) 64.3% (306/476) 0.12 LVEF (%) 53 (11) 56 (11) 51 (12) 56 (11) <0.0001 LV mass index (g/m2) 118 (35) 120 (32) 120 (34) 121 (34) 0.92 Normal RV function 80.6% (50/62) 83.1% (567/682) 85.9% (134/156) 81.1% (386/476) 0.52 Normal RV size 67.7% (42/62) 83.6% (569/681) 69.2% (108/156) 87.2% (415/476) <0.0001 Aortic valve peak velocity (m/s) 4.4 (0.7) 4.4 (0.6) 4.3 (0.6) 4.4 (0.6) 0.18 Aortic valve area (cm2) 0.69 (0.19) 0.70 (0.17) 0.69 (0.20) 0.68 (0.19) 0.55 Moderate or severe AR 11.5% (7/61) 11.5% (75/654) 10.7% (16/150) 11.5% (52/453) 0.99 Moderate or severe MR 18.6% (11/59) 16.9% (108/639) 17.9% (26/145) 18.0% (79/440) 0.96 Moderate or severe TR 31.6% (18/57) 15.3% (94/616) 21.1% (31/147) 15.6% (65/416) 0.006 Right ventricular systolic pressure (mmHg) 44 (16) 37 (12) 37 (11) 37 (13) 0.01 AR, aortic regurgitation; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; KCCQ, Kansas City Cardiomyopathy Questionnaire; LV, left ventricle; LVEF, left ventricular ejection fraction; MR, mitral regurgitation; NYHA, New York Heart Association; RV, right ventricle; SAVR, surgical aortic valve replacement; TAVR, transcatheter aortic valve replacement; TR, tricuspid regurgitation. Figure 1 View largeDownload slide Right ventricular function at 30 days, stratified by transcatheter aortic valve replacement or surgical aortic valve replacement, in patients with baseline normal (A) or abnormal (B) right ventricular function. (A) In patients with surgical aortic valve replacement and normal right ventricular function at baseline (red, n = 520), 74.2% had normal, 20.8% had mild, and 5.0% had moderate of severe right ventricular dysfunction at 30 days. In patients with transcatheter aortic valve replacement and normal right ventricular function at baseline (blue, n = 617), 91.9% had normal, 7.6% had mild, and 0.5% had moderate or severe right ventricular dysfunction at 30 days. (B) In patients with surgical aortic valve replacement and baseline right ventricular dysfunction (red, n = 112), 18.8% had normal, 53.6% had mild, and 27.7% had moderate or severe right ventricular dysfunction at 30 days. In patients with transcatheter aortic valve replacement and baseline right ventricular dysfunction (blue, n = 127), 26.0% had normal, 55.9% had mild, and 18.1% had moderate or severe right ventricular dysfunction at 30 days. Figure 1 View largeDownload slide Right ventricular function at 30 days, stratified by transcatheter aortic valve replacement or surgical aortic valve replacement, in patients with baseline normal (A) or abnormal (B) right ventricular function. (A) In patients with surgical aortic valve replacement and normal right ventricular function at baseline (red, n = 520), 74.2% had normal, 20.8% had mild, and 5.0% had moderate of severe right ventricular dysfunction at 30 days. In patients with transcatheter aortic valve replacement and normal right ventricular function at baseline (blue, n = 617), 91.9% had normal, 7.6% had mild, and 0.5% had moderate or severe right ventricular dysfunction at 30 days. (B) In patients with surgical aortic valve replacement and baseline right ventricular dysfunction (red, n = 112), 18.8% had normal, 53.6% had mild, and 27.7% had moderate or severe right ventricular dysfunction at 30 days. In patients with transcatheter aortic valve replacement and baseline right ventricular dysfunction (blue, n = 127), 26.0% had normal, 55.9% had mild, and 18.1% had moderate or severe right ventricular dysfunction at 30 days. Regarding echocardiographic parameters, worsening RV function was associated with lower LV systolic function, though most patients had normal LVEFs (Table 1). In addition, patients with worsening RV function were more likely to have dilated right ventricles at baseline, but there was no statistically detectable difference in baseline RV systolic function. Moderate or severe TR was also more common in patients who developed worsening RV function, and baseline estimated right ventricular systolic pressure (RVSP) was also higher, though absolute between group differences in RVSP were small (Table 1). Worsening right ventricular function In a multivariable model, SAVR was associated with a higher odds of worsening RV function compared with TAVR (OR 4.05, 95% CI 2.55–6.44). After adjustment, baseline clinical variables were not associated with worsening RV function, though the association with certain baseline echocardiographic variables remained significant. Specifically, patients with more than mild TR, lower LVEFs and dilated right ventricles at baseline were more likely to develop worsening RV function (Table 2). In stability analyses using the same covaraites but restricted to patients with either TAVR or SAVR, differential associations with worsening RV function were noted. For patients with TAVR, more than mild TR was associated with worsening RV function (OR 5.33, 95% CI 1.46–19.39), whereas an association with baseline RV dilation was not statistically detectable (OR 1.92, 95% CI 0.76-4.85) (see Supplementary material online, Table S3). Conversely, in patients with SAVR, baseline RV dilation was associated with worsening RV function (OR 2.77, 95% CI 1.35–5.68), and there was not a significant association with more than mild TR (OR 1.78, 95% CI 0.71–4.49) (see Supplementary material online, Table S4). Table 2 Multivariable analysis for worsening RV function after AVRa OR (95% CI) P-value SAVR vs. TAVR 4.05 (2.55–6.44) <0.0001 Age (years) 1.02 (0.98–1.06) 0.28 Male 0.75 (0.47–1.20) 0.23 BMI 1.01 (0.96–1.05) 0.78 Logistic EuroSCORE 1.02 (0.99–1.05) 0.18 Atrial fibrillation 1.43 (0.90–2.26) 0.13 Pacemaker 1.34 (0.69–2.61) 0.39 Liver disease 0.61 (0.13–2.96) 0.54 Baseline LVEF 0.97 (0.95–0.99) 0.007 Baseline right ventricular dilation 2.38 (1.37–4.14) 0.002 Baseline right ventricular systolic pressure 1.00 (0.98–1.02) 0.94 Baseline mitral valve regurgitation mild vs. none/trace 0.93 (0.54–1.62) 0.81 Baseline mitral valve regurgitation moderate/severe vs. none/trace 0.51 (0.24–1.05) 0.07 Baseline tricuspid valve regurgitation mild vs. none/trace 1.38 (0.78–2.47) 0.27 Baseline tricuspid valve regurgitation moderate/severe vs. none/trace 2.58 (1.25–5.33) 0.01 OR (95% CI) P-value SAVR vs. TAVR 4.05 (2.55–6.44) <0.0001 Age (years) 1.02 (0.98–1.06) 0.28 Male 0.75 (0.47–1.20) 0.23 BMI 1.01 (0.96–1.05) 0.78 Logistic EuroSCORE 1.02 (0.99–1.05) 0.18 Atrial fibrillation 1.43 (0.90–2.26) 0.13 Pacemaker 1.34 (0.69–2.61) 0.39 Liver disease 0.61 (0.13–2.96) 0.54 Baseline LVEF 0.97 (0.95–0.99) 0.007 Baseline right ventricular dilation 2.38 (1.37–4.14) 0.002 Baseline right ventricular systolic pressure 1.00 (0.98–1.02) 0.94 Baseline mitral valve regurgitation mild vs. none/trace 0.93 (0.54–1.62) 0.81 Baseline mitral valve regurgitation moderate/severe vs. none/trace 0.51 (0.24–1.05) 0.07 Baseline tricuspid valve regurgitation mild vs. none/trace 1.38 (0.78–2.47) 0.27 Baseline tricuspid valve regurgitation moderate/severe vs. none/trace 2.58 (1.25–5.33) 0.01 AVR, aortic valve replacement; BMI, body mass index; LVEF, left ventricular ejection fraction; RV, right ventricle; SAVR, surgical aortic valve replacement; TAVR, transcatheter aortic valve replacement. a c-statistic for this model is 0.77 with a P-value <0.0001. Table 2 Multivariable analysis for worsening RV function after AVRa OR (95% CI) P-value SAVR vs. TAVR 4.05 (2.55–6.44) <0.0001 Age (years) 1.02 (0.98–1.06) 0.28 Male 0.75 (0.47–1.20) 0.23 BMI 1.01 (0.96–1.05) 0.78 Logistic EuroSCORE 1.02 (0.99–1.05) 0.18 Atrial fibrillation 1.43 (0.90–2.26) 0.13 Pacemaker 1.34 (0.69–2.61) 0.39 Liver disease 0.61 (0.13–2.96) 0.54 Baseline LVEF 0.97 (0.95–0.99) 0.007 Baseline right ventricular dilation 2.38 (1.37–4.14) 0.002 Baseline right ventricular systolic pressure 1.00 (0.98–1.02) 0.94 Baseline mitral valve regurgitation mild vs. none/trace 0.93 (0.54–1.62) 0.81 Baseline mitral valve regurgitation moderate/severe vs. none/trace 0.51 (0.24–1.05) 0.07 Baseline tricuspid valve regurgitation mild vs. none/trace 1.38 (0.78–2.47) 0.27 Baseline tricuspid valve regurgitation moderate/severe vs. none/trace 2.58 (1.25–5.33) 0.01 OR (95% CI) P-value SAVR vs. TAVR 4.05 (2.55–6.44) <0.0001 Age (years) 1.02 (0.98–1.06) 0.28 Male 0.75 (0.47–1.20) 0.23 BMI 1.01 (0.96–1.05) 0.78 Logistic EuroSCORE 1.02 (0.99–1.05) 0.18 Atrial fibrillation 1.43 (0.90–2.26) 0.13 Pacemaker 1.34 (0.69–2.61) 0.39 Liver disease 0.61 (0.13–2.96) 0.54 Baseline LVEF 0.97 (0.95–0.99) 0.007 Baseline right ventricular dilation 2.38 (1.37–4.14) 0.002 Baseline right ventricular systolic pressure 1.00 (0.98–1.02) 0.94 Baseline mitral valve regurgitation mild vs. none/trace 0.93 (0.54–1.62) 0.81 Baseline mitral valve regurgitation moderate/severe vs. none/trace 0.51 (0.24–1.05) 0.07 Baseline tricuspid valve regurgitation mild vs. none/trace 1.38 (0.78–2.47) 0.27 Baseline tricuspid valve regurgitation moderate/severe vs. none/trace 2.58 (1.25–5.33) 0.01 AVR, aortic valve replacement; BMI, body mass index; LVEF, left ventricular ejection fraction; RV, right ventricle; SAVR, surgical aortic valve replacement; TAVR, transcatheter aortic valve replacement. a c-statistic for this model is 0.77 with a P-value <0.0001. Regarding complications leading to cardiac rehospitalization, 30 events were study-valve related and 31 events were procedure related. Worsening RV function was not associated with either study-valve related [hazard ratio (HR) 1.13, 95% CI 0.43–2.95] or procedure related rehospitalization (HR 1.56, 95% CI 0.67–3.61). To assess exposures that were specific to either TAVR or SAVR and potential associations with worsening RV function, further exploratory analyses were performed. In SAVR, cardiopulmonary bypass time was not increased in patients with worsening RV function (108 vs. 100 min, P = 0.16) (see Supplementary material online, Table S5). For TAVR, post-dilation was not associated with worsening RV function (24.6% vs. 20.6%, P = 0.46) (see Supplementary material online, Table S5). The need for a pacemaker after AVR was also not associated with worsening RV function after TAVR (16.1% vs. 11.6%, P = 0.22) or (SAVR 10.9% vs. 11.1%, P = 0.47) (see Supplementary material online, Table S5). Worsening right ventricular function and adverse events Between 30 days and 2 years, there were 169 deaths, and patients with worsening RV function had higher mortality (HR 1.98, 95% CI 1.40–2.79) (Take home figure). In comparing TAVR to SAVR, there was no difference in patients with (HR 1.16, 95% CI 0.61–2.18) or without RV worsening (HR 1.03, 95% CI 0.72–1.48) (P-value for interaction 0.76). Regarding cardiovascular death, there were 85 events. Results were similar with higher cardiovascular death among patients with worsening RV function (HR 2.11, 95% CI 1.22–3.66) (Figure 2). Regarding cardiac rehospitalizations that were not related to valve or procedural complications, there were 133 events, and there was not a statistically significant association with worsening RV function (HR 1.43, 95% CI 0.94–2.18). Take home figure View largeDownload slide The Kaplan–Meier survival curves for all-cause mortality in patients with and without worsening right ventricular function, stratified by randomization to transcatheter aortic valve replacement or surgical aortic valve replacement. Patients with worsening right ventricular function had higher all-cause mortality (hazard ratio 1.98, 95% confidence interval 1.40–2.79), though there was no difference in mortality in patients with worsening right ventricular function according to transcatheter aortic valve replacement or surgical aortic valve replacement (hazard ratio 1.16, 95% CI 0.61–2.18). Take home figure View largeDownload slide The Kaplan–Meier survival curves for all-cause mortality in patients with and without worsening right ventricular function, stratified by randomization to transcatheter aortic valve replacement or surgical aortic valve replacement. Patients with worsening right ventricular function had higher all-cause mortality (hazard ratio 1.98, 95% confidence interval 1.40–2.79), though there was no difference in mortality in patients with worsening right ventricular function according to transcatheter aortic valve replacement or surgical aortic valve replacement (hazard ratio 1.16, 95% CI 0.61–2.18). To further assess the association between worsening RV function after AVR and adverse events, baseline echocardiographic variable were added separately to a background model that included age, sex, logistic EuroSCORE, and LVEF. After additional adjustment for baseline RV function, mitral regurgitation, and TR, the association between worsening RV function and all-cause death remained significant in all models with an approximately two-fold increase in hazard (Table 3). Results were similar for cardiovascular death, though the association was attenuated following adjustment for RVSP (HR 1.82, 95% CI 0.95-3.48) (Table 4). Table 3 Worsening RV function and all-cause mortality HR (95% CI) P-value Worsening RV function (adjusted for background modela and baseline RV function)b 2.11 (1.40–3.19) 0.0004 Worsening RV function (adjusted for background modela and baseline MR)c 2.02 (1.32–3.08) 0.001 Worsening RV function (adjusted for background modela and baseline tricuspid TR)d 2.05 (1.34–3.12) 0.0009 Worsening RV function (adjusted for background modela and baseline RVSP)e 2.12 (1.33–3.37) 0.002 HR (95% CI) P-value Worsening RV function (adjusted for background modela and baseline RV function)b 2.11 (1.40–3.19) 0.0004 Worsening RV function (adjusted for background modela and baseline MR)c 2.02 (1.32–3.08) 0.001 Worsening RV function (adjusted for background modela and baseline tricuspid TR)d 2.05 (1.34–3.12) 0.0009 Worsening RV function (adjusted for background modela and baseline RVSP)e 2.12 (1.33–3.37) 0.002 CI, confidence interval; HR, hazard ratio; MR, mitral regurgitation; RV, right ventricle; RVSP, right ventricular systolic pressure; TR, tricuspid regurgitation. a Background model includes age, sex, logistic EuroSCORE, and LVEF. b c-statistic 0.62, P < 0.0001. c c-statistic 0.63, P < 0.0001. d c-statistic 0.62. e c-statistic 0.67, P < 0.0001. Table 3 Worsening RV function and all-cause mortality HR (95% CI) P-value Worsening RV function (adjusted for background modela and baseline RV function)b 2.11 (1.40–3.19) 0.0004 Worsening RV function (adjusted for background modela and baseline MR)c 2.02 (1.32–3.08) 0.001 Worsening RV function (adjusted for background modela and baseline tricuspid TR)d 2.05 (1.34–3.12) 0.0009 Worsening RV function (adjusted for background modela and baseline RVSP)e 2.12 (1.33–3.37) 0.002 HR (95% CI) P-value Worsening RV function (adjusted for background modela and baseline RV function)b 2.11 (1.40–3.19) 0.0004 Worsening RV function (adjusted for background modela and baseline MR)c 2.02 (1.32–3.08) 0.001 Worsening RV function (adjusted for background modela and baseline tricuspid TR)d 2.05 (1.34–3.12) 0.0009 Worsening RV function (adjusted for background modela and baseline RVSP)e 2.12 (1.33–3.37) 0.002 CI, confidence interval; HR, hazard ratio; MR, mitral regurgitation; RV, right ventricle; RVSP, right ventricular systolic pressure; TR, tricuspid regurgitation. a Background model includes age, sex, logistic EuroSCORE, and LVEF. b c-statistic 0.62, P < 0.0001. c c-statistic 0.63, P < 0.0001. d c-statistic 0.62. e c-statistic 0.67, P < 0.0001. Table 4 Worsening RV function and cardiac death HR (95% CI) P-value Worsening RV function (adjusted for background modela and baseline RV function)b 2.25 (1.30–3.90) 0.004 Worsening RV function (adjusted for background modela and baseline MR)c 1.97 (1.12–3.49) 0.02 Worsening RV function (adjusted for background modela and baseline tricuspid TR)d 2.05 (1.17–3.60) 0.01 Worsening RV function (adjusted for background model and baseline RVSP)e 1.82 (0.95–3.48) 0.07 HR (95% CI) P-value Worsening RV function (adjusted for background modela and baseline RV function)b 2.25 (1.30–3.90) 0.004 Worsening RV function (adjusted for background modela and baseline MR)c 1.97 (1.12–3.49) 0.02 Worsening RV function (adjusted for background modela and baseline tricuspid TR)d 2.05 (1.17–3.60) 0.01 Worsening RV function (adjusted for background model and baseline RVSP)e 1.82 (0.95–3.48) 0.07 CI, confidence interval; HR, hazard ratio; MR, mitral regurgitation; RV, right ventricle; RVSP, right ventricular systolic pressure; TR, tricuspid regurgitation. a Background model includes age, sex, logistic EuroSCORE, and LVEF. b c-statistic 0.63, P < 0.0001. c c-statistic 0.65, P < 0.0001. d c-statistic 0.65. e c-statistic 0.68, P < 0.0001. Table 4 Worsening RV function and cardiac death HR (95% CI) P-value Worsening RV function (adjusted for background modela and baseline RV function)b 2.25 (1.30–3.90) 0.004 Worsening RV function (adjusted for background modela and baseline MR)c 1.97 (1.12–3.49) 0.02 Worsening RV function (adjusted for background modela and baseline tricuspid TR)d 2.05 (1.17–3.60) 0.01 Worsening RV function (adjusted for background model and baseline RVSP)e 1.82 (0.95–3.48) 0.07 HR (95% CI) P-value Worsening RV function (adjusted for background modela and baseline RV function)b 2.25 (1.30–3.90) 0.004 Worsening RV function (adjusted for background modela and baseline MR)c 1.97 (1.12–3.49) 0.02 Worsening RV function (adjusted for background modela and baseline tricuspid TR)d 2.05 (1.17–3.60) 0.01 Worsening RV function (adjusted for background model and baseline RVSP)e 1.82 (0.95–3.48) 0.07 CI, confidence interval; HR, hazard ratio; MR, mitral regurgitation; RV, right ventricle; RVSP, right ventricular systolic pressure; TR, tricuspid regurgitation. a Background model includes age, sex, logistic EuroSCORE, and LVEF. b c-statistic 0.63, P < 0.0001. c c-statistic 0.65, P < 0.0001. d c-statistic 0.65. e c-statistic 0.68, P < 0.0001. A graded response to magnitude of worsening RV function was also noted. Patients who began with normal RV function and developed moderate to severe dysfunction (n = 29) had the highest hazard for all-cause death (HR 2.87, 95% CI 1.40–5.89), followed by patients who initially had normal RV function and then developed mild dysfunction (n = 108)(HR 2.05, 95% CI 1.38–3.04) (Figure 3). Similar results were obtained for cardiovascular death with the worst prognosis among patients with normal RV function who developed moderate to severe RV dysfunction (HR 4.37, 95% CI 1.87–10.2), followed by patients who worsened to mild RV dysfunction (HR 1.93, 95% CI 1.08–3.43) (Figure 4). In patients with mild RV dysfunction at baseline who improved to normal RV function at 30 days (n = 49), there was no significant association with all-cause (HR 0.76, 95% CI 0.28–2.05) or cardiac death (HR 0.85, 95% CI 0.18–3.10). Figure 2 View largeDownload slide The Kaplan–Meier survival curves for cardiovascular mortality in patients with and without worsening right ventricular function, stratified by randomization to transcatheter aortic valve replacement or surgical aortic valve replacement. Patients with worsening right ventricular function had higher cardiovascular mortality (hazard ratio 2.11, 95% confidence interval 1.22–3.66), though there was no difference in mortality in patients with worsening right ventricular function according to transcatheter aortic valve replacement or surgical aortic valve replacement (hazard ratio 1.09, 95% confidence interval 0.65–1.82). Figure 2 View largeDownload slide The Kaplan–Meier survival curves for cardiovascular mortality in patients with and without worsening right ventricular function, stratified by randomization to transcatheter aortic valve replacement or surgical aortic valve replacement. Patients with worsening right ventricular function had higher cardiovascular mortality (hazard ratio 2.11, 95% confidence interval 1.22–3.66), though there was no difference in mortality in patients with worsening right ventricular function according to transcatheter aortic valve replacement or surgical aortic valve replacement (hazard ratio 1.09, 95% confidence interval 0.65–1.82). Figure 3 View largeDownload slide Forest plots for magnitude of worsening right ventricular function and all-cause mortality. Normal to moderate/severe (n =29), normal to mild (n = 155), mild to moderate/severe (n = 28), mild to mild (n = 112), moderate to moderate/severe (n = 26). CI, confidence interval; HR, hazard ratio; RV, right ventricle; RVD, right ventricular dysfunction. Figure 3 View largeDownload slide Forest plots for magnitude of worsening right ventricular function and all-cause mortality. Normal to moderate/severe (n =29), normal to mild (n = 155), mild to moderate/severe (n = 28), mild to mild (n = 112), moderate to moderate/severe (n = 26). CI, confidence interval; HR, hazard ratio; RV, right ventricle; RVD, right ventricular dysfunction. Figure 4 View largeDownload slide Forest plots for magnitude of worsening RV function and cardiovascular mortality. Normal to moderate/severe (n =29), normal to mild (n = 155), mild to moderate/severe (n = 28), mild to mild (n = 112), moderate to moderate/severe (n = 26). CI, confidence interval; HR, hazard ratio; RV, right ventricle; RVD, right ventricular dysfunction. Figure 4 View largeDownload slide Forest plots for magnitude of worsening RV function and cardiovascular mortality. Normal to moderate/severe (n =29), normal to mild (n = 155), mild to moderate/severe (n = 28), mild to mild (n = 112), moderate to moderate/severe (n = 26). CI, confidence interval; HR, hazard ratio; RV, right ventricle; RVD, right ventricular dysfunction. In the entire cohort, patients with worsening RV function had a smaller increase in KCCQ scores from baseline to 30 days (6.1 vs. 11.1, P = 0.01). However, this association was related to smaller increases in KCCQ scores among patents with SAVR compared with TAVR (see Supplementary material online, Table S6). In addition, among SAVR patients with worsening RV function, there was less improvement in KCCQ scores compared with baseline at one (17.1 vs. 22.8, P = 0.02) and 2 years (15.9 vs. 20.4, P = 0.10), though none of these associations were significant after adjusting for multiple comparisons (see Supplementary material online, Table S6). Similarly, there were no significant differences in change in 6 min walk distance for patients with worsening RV function, stratified by TAVR or SAVR (see Supplementary material online, Table S7). With regards to the need for diuretics, in TAVR patients, there was no statistically detectable difference in those with and without worsening RV function at baseline, 30 days, 1 and 2 years (see Supplementary material online, Table S8). Conversely, in patients with SAVR, even though there were no statistically significant differences after adjusting for multiple comparisons, a trend was noted: patients with worsening RV function were numerically more likely to require diuretic therapy at one (OR 1.61, 95% CI 1.07–2.43) and 2 years (OR 1.40, 95% CI 0.91–2.16) (see Supplementary material online, Table S8). At 1-year, among patients with worsening RV function, 26 patients died, and 50 patients improved to normal RV function. When compared with TAVR, patients with SAVR were not more likely to improve to normal RV function at 1-year (OR 1.59, 95% CI 0.75–3.37). By two years of follow-up, 44 patients with worsening RV function had died, and 49 patients had normal RV function. Patients with SAVR were again not more likely to have normal RV function (OR 1.10, 95% CI 0.48–2.55). Discussion To the best of our knowledge, our study is the first to investigate adjusted analyses of worsening RV function after AVR and its association with adverse outcomes in patients randomized to SAVR or TAVR. Several observations are notable. First, after multivariable adjustment, the odds for worsening RV function was more than four times greater for SAVR compared to TAVR. Worsening RV function was also more common in patients with dilated RVs and at least moderate TR. After adjusting for baseline clinical and echocardiographic parameters, worsening RV function was associated with higher all-cause and cardiovascular mortality. Finally, a graded ‘dose’ response was noted. Patients who developed moderate or severe RV dysfunction from baseline normal RV function had the worst prognosis. Previous studies of aortic valve replacement and right ventricular function Right ventricular dysfunction after cardiac surgery is well-described, associated with adverse outcomes, and is generally attributed to ischaemia and myocardial depression following cardiopulmonary bypass without salutary unloading, as is often observed with the left ventricle when treating left-sided valvular lesions.14–16 With the advent of TAVR, the prognostic importance of the right ventricle has been further emphasized. Results have been discordant with several investigations demonstrating that right ventricular dilation and dysfunction are associated with increased mortality whereas other studies have not confirmed this association.4,17–19 These discrepant results are possibly related to differences in cohorts, variations in methodologies for RV assessment, and the approach to multivariable adjustment. Importantly, these studies assessed baseline RV function and adverse events without investigating whether deterioration in RV function after AVR is associated with poor outcomes. More recently, however, a single-centre study investigated RV dysfunction after TAVR in over 1000 patients.20 Their results are concordant with ours as Asami et al.20 demonstrated a gradient of increasing risk from patients with normal RV function, to patients with new RV dysfunction, to patients with persistent RV dysfunction after TAVR. Of note, this study did not include patients with SAVR. Therefore, the differential incidence and impact of worsening RV function according to mode of AVR could not be investigated. Additional studies have demonstrated that RV dysfunction is more common after SAVR compared to TAVR.5,6,21 However, these studies have either not involved randomized patients5,6 or did not perform adjusted analysis for worsening RV function after AVR.22 Furthermore, like previous investigations involving patients with TAVR,4,17–19,21 none of the prior studies addressed the possible association of worsening RV function after AVR and increased mortality.5,6,21 Limitations Notable limitations of this study warrant emphasis. First, this study is a landmark analysis of patients from PARTNERIIA who had echocardiograms at 30 days, and these patients were slightly lower risk compared with patients who did not have 30 day echocardiograms (see Supplementary material online, Table S1; median logistic EuroSCORE in analysis of 6.3 vs. 7.3 not in analysis). Of note, however, baseline characteristics of TAVR and SAVR patients in this analysis were well-balanced (see Supplementary material online, Table S2). Second, even though an integrated prospective echocardiographic approach was employed to evaluate RV function, guidelines to assess RV function have been updated since the initiation of PARTNERIIA23, and an even more accurate and reproducible assessment may be possible with global longitudinal strain and cardiac magnetic resonance imaging.24–26 In particular, our approach emphasized visual assessment to categorize RV dysfunction. However, this approach reflects clinical practice, and we speculate that a more precise assessment of RV function would only strengthen the associations that we have demonstrated. Third, even though LVEF was associated with worsening RV function, absolute between group differences were small, and the majority of patients had normal or mildly reduced LVEFs. Therefore, our results are not as generalizable to patients with more severely reduced LV systolic function. Fourth, invasive haemodynamic data were not available. Baseline cardiac indices and intracardiac pressures may have provided further insights regarding associations with worsening RV function and adverse outcomes. Finally, our longitudinal analyses regarding changes in RV function and quality of life assessments at one and two years should be considered as merely descriptive and exploratory for two analytical reasons. First, after correction for multiple hypothesis testing, none of the results are statistically significant. Second, there are competing risks and events are likely not independent, as patients who die during follow-up would also be expected to have a worse performance on quality of life measures. Clinical implications and future directions Among an intermediate-risk cohort with severe symptomatic AS, patients with dilated RVs, more than mild TR, and patients treated with SAVR are at-risk for developing worsening RV function after AVR. After AVR, the extent to which specific insults contribute to worsening RV function are not well understood. Possible risks specific to SAVR include cardioplegia and pericardiotomy, whereas LV and RV interaction as well as alterations in the geometry of the fibrous skeleton may contribute to worsening RV function after TAVR or SAVR.27–29 Even though these mechanisms are still being defined, and despite overall similar outcomes in patients with SAVR or TAVR once RV function has worsened, our results demonstrate that patients with worsening RV function after AVR have increased mortality. Exploratory analyses also suggested differential increased risks for worsening RV function in patients with TAVR or SAVR. With TAVR, more than mild TR, but not RV dilation, was associated with worsening RV function. Conversely, after SAVR, RV dilation, but not baseline TR, was associated with worsening RV function. Combined with other investigations and future studies, these results have implications regarding which intermediate risk patients may benefit from TAVR or SAVR. In addition, these results prompt the question of whether medical, surgical, and percutaneous treatment of concomitant TR can preserve RV function. Finally, our results should lead to further investigations of RV function after AVR in lower risk patients being considered for SAVR or TAVR. Most importantly, clinicians should recognize that patients with normal baseline RV function who develop moderate or severe dysfunction after AVR are at especially high risk. Supplementary material Supplementary material is available at European Heart Journal online. Conflict of interest: none declared. References 1 Douglas PS , Hahn RT , Pibarot P , Weissman NJ , Stewart WJ , Xu K , Wang Z , Lerakis S , Siegel R , Thompson C , Gopal D , Keane MG , Svensson LG , Tuzcu EM , Smith CR , Leon MB. Hemodynamic outcomes of transcatheter aortic valve replacement and medical management in severe, inoperable aortic stenosis: a longitudinal echocardiographic study of cohort B of the PARTNER trial . J Am Soc Echocardiogr 2015 ; 28 : 210 – 217.e1–9 . Google Scholar CrossRef Search ADS PubMed 2 Généreux P , Pibarot P , Redfors B , Mack MJ , Makkar RR , Jaber WA , Svensson LG , Kapadia S , Tuzcu EM , Thourani VH , Babaliaros V , Herrmann HC , Szeto WY , Cohen DJ , Lindman BR , McAndrew T , Alu MC , Douglas PS , Hahn RT , Kodali SK , Smith CR , Miller DC , Webb JG , Leon MB. Staging classification of aortic stenosis based on the extent of cardiac damage . Eur Heart J 2017 ; 38 : 3351 – 3358 . Google Scholar CrossRef Search ADS PubMed 3 Ternacle J , Berry M , Cognet T , Kloeckner M , Damy T , Monin JL , Couetil JP , Dubois-Rande JL , Gueret P , Lim P. Prognostic value of right ventricular two-dimensional global strain in patients referred for cardiac surgery . J Am Soc Echocardiogr 2013 ; 26 : 721 – 726 . Google Scholar CrossRef Search ADS PubMed 4 Lindman BR , Maniar HS , Jaber WA , Lerakis S , Mack MJ , Suri RM , Thourani VH , Babaliaros V , Kereiakes DJ , Whisenant B , Miller DC , Tuzcu EM , Svensson LG , Xu K , Doshi D , Leon MB , Zajarias A. Effects of tricuspid regurgitation and the right heart on survival after transcatheter aortic valve replacement: insights from the placement of aortic transcatheter valves II inoperable cohort . Circ Cardiovasc Interv 2015 ; 8 : e002073. Google Scholar CrossRef Search ADS PubMed 5 Kempny A , Diller GP , Kaleschke G , Orwat S , Funke A , Schmidt R , Kerckhoff G , Ghezelbash F , Rukosujew A , Reinecke H , Scheld HH , Baumgartner H. Impact of transcatheter aortic valve implantation or surgical aortic valve replacement on right ventricular function . Heart 2012 ; 98 : 1299 – 1304 . Google Scholar CrossRef Search ADS PubMed 6 Forsberg LM , Tamás E , Vánky F , Nielsen NE , Engvall J , Nylander E. Left and right ventricular function in aortic stenosis patients 8 weeks post-transcatheter aortic valve implantation or surgical aortic valve replacement . Eur J Echocardiogr 2011 ; 12 : 603 – 611 . Google Scholar PubMed 7 Leon MB , Smith CR , Mack MJ , Makkar RR , Svensson LG , Kodali SK , Thourani VH , Tuzcu EM , Miller DC , Herrmann HC , Doshi D , Cohen DJ , Pichard AD , Kapadia S , Dewey T , Babaliaros V , Szeto WY , Williams MR , Kereiakes D , Zajarias A , Greason KL , Whisenant BK , Hodson RW , Moses JW , Trento A , Brown DL , Fearon WF , Pibarot P , Hahn RT , Jaber WA , Anderson WN , Alu MC , Webb JG ; PARTNER 2 Investigators . Transcatheter or surgical aortic-valve replacement in intermediate-risk patients . N Engl J Med 2016 ; 374 : 1609 – 1620 . Google Scholar CrossRef Search ADS PubMed 8 Douglas PS , Waugh RA , Bloomfield G , Dunn G , Davis L , Hahn RT , Pibarot P , Stewart WJ , Weissman NJ , Hueter I , Siegel R , Lerakis S , Miller DC , Smith CR , Leon MB. Implementation of echocardiography core laboratory best practices: a case study of the PARTNER I trial . J Am Soc Echocardiogr 2013 ; 26 : 348 – 358.e343 . Google Scholar CrossRef Search ADS PubMed 9 Hahn RT , Pibarot P , Stewart WJ , Weissman NJ , Gopalakrishnan D , Keane MG , Anwaruddin S , Wang Z , Bilsker M , Lindman BR , Herrmann HC , Kodali SK , Makkar R , Thourani VH , Svensson LG , Akin JJ , Anderson WN , Leon MB , Douglas PS. Comparison of transcatheter and surgical aortic valve replacement in severe aortic stenosis: a longitudinal study of echocardiography parameters in cohort A of the PARTNER trial (placement of aortic transcatheter valves) . J Am Coll Cardiol 2013 ; 61 : 2514 – 2521 . Google Scholar CrossRef Search ADS PubMed 10 Lang RM , Bierig M , Devereux RB , Flachskampf FA , Foster E , Pellikka PA , Picard MH , Roman MJ , Seward J , Shanewise JS , Solomon SD , Spencer KT , Sutton MS , Stewart WJ ; Chamber Quantification Writing Group; American Society of Echocardiography's Guidelines and Standards Committee; European Association of Echocardiography . Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology . J Am Soc Echocardiogr 2005 ; 18 : 1440 – 1463 . Google Scholar CrossRef Search ADS PubMed 11 Zoghbi WA , Enriquez-Sarano M , Foster E , Grayburn PA , Kraft CD , Levine RA , Nihoyannopoulos P , Otto CM , Quinones MA , Rakowski H , Stewart WJ , Waggoner A , Weissman NJ ; American Society of Echocardiography . Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography . J Am Soc Echocardiogr 2003 ; 16 : 777 – 802 . Google Scholar CrossRef Search ADS PubMed 12 Rudski LG , Lai WW , Afilalo J , Hua L , Handschumacher MD , Chandrasekaran K , Solomon SD , Louie EK , Schiller NB. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography . J Am Soc Echocardiogr 2010 ; 23 : 685 – 713 . Google Scholar CrossRef Search ADS PubMed 13 Green CP , Porter CB , Bresnahan DR , Spertus JA. Development and evaluation of the Kansas City Cardiomyopathy Questionnaire: a new health status measure for heart failure . J Am Coll Cardiol 2000 ; 35 : 1245 – 1255 . Google Scholar CrossRef Search ADS PubMed 14 Haddad F , Couture P , Tousignant C , Denault AY. The right ventricle in cardiac surgery, a perioperative perspective: II. Pathophysiology, clinical importance and management . Anesth Analg 2009 ; 108 : 422 – 433 . Google Scholar CrossRef Search ADS PubMed 15 Kaul TK , Fields BL. Postoperative acute refractory right ventricular failure: incidence, pathogenesis, management and prognosis . Cardiovasc Surg 2000 ; 8 : 1 – 9 . Google Scholar CrossRef Search ADS PubMed 16 Hedman A , Alam M , Zuber E , Nordlander R , Samad BA . Decreased right ventricular function after coronary artery bypass grafting and its relation to exercise capacity: a tricuspid annular-motion based study . J Am Soc Echocardiogr 2004 ; 17 : 126 – 131 . Google Scholar CrossRef Search ADS PubMed 17 Griese DP , Kerber S , Barth S , Diegeler A , Babin-Ebell J , Reents W. Impact of right and left ventricular systolic dysfunction on perioperative outcome and long-term survival after transcatheter aortic valve replacement . J Interven Cardiol 2017 ; 30 : 217 – 225 . Google Scholar CrossRef Search ADS 18 Ito S , Pislaru SV , Soo WM , Huang R , Greason KL , Mathew V , Sandhu GS , Eleid MF , Suri RM , Oh JK , Nkomo VT. Impact of right ventricular size and function on survival following transcatheter aortic valve replacement . Int J Cardiol 2016 ; 221 : 269 – 274 . Google Scholar CrossRef Search ADS PubMed 19 Koifman E , Didier R , Patel N , Jerusalem Z , Kiramijyan S , Ben-Dor I , Negi SI , Wang Z , Goldstein SA , Lipinski MJ , Torguson R , Gai J , Pichard AD , Satler LF , Waksman R , Asch FM. Impact of right ventricular function on outcome of severe aortic stenosis patients undergoing transcatheter aortic valve replacement . Am Heart J 2017 ; 184 : 141 – 147 . Google Scholar CrossRef Search ADS PubMed 20 Asami M , Stortecky S , Praz F , Lans K , Raber L , Franzone A , Piccolo R , Siontis GCM , Heg D , Valgimigli M , Wenaweser P , Roost E , Windecker S , Pilgrim T. Prognostive value of right ventricular dysfunction on clinical outcomes after transcatheter aortic valve replacement . J Am Coll Cardiol 2018 ; doi:10.1016/j.jcmg.2017.12.015. 21 Lindsay AC , Harron K , Jabbour RJ , Kanyal R , Snow TM , Sawhney P , Alpendurada F , Roughton M , Pennell DJ , Duncan A , Di Mario C , Davies SW , Mohiaddin RH , Moat NE. Prevalence and prognostic significance of right ventricular systolic dysfunction in patients undergoing transcatheter aortic valve implantation . Circ Cardiovasc Interv 2016 ; 9 : e003486. Google Scholar CrossRef Search ADS PubMed 22 Little SH , Oh JK , Gillam L , Sengupta PP , Orsinelli DA , Cavalcante JL , Chang JD , Adams DH , Zorn GL 3rd , Pollak AW , Abdelmoneim SS , Reardon MJ , Qiao H , Popma JJ. Self-expanding transcatheter aortic valve replacement versus surgical valve replacement in patients at high risk for surgery: a study of echocardiographic change and risk prediction . Circ Cardiovasc Interv 2016 ; 9 : e003426. Google Scholar CrossRef Search ADS PubMed 23 Harjola V-P , Mebazaa A , Čelutkienė J , Bettex D , Bueno H , Chioncel O , Crespo-Leiro MG , Falk V , Filippatos G , Gibbs S , Leite-Moreira A , Lassus J , Masip J , Mueller C , Mullens W , Naeije R , Nordegraaf AV , Parissis J , Riley JP , Ristic A , Rosano G , Rudiger A , Ruschitzka F , Seferovic P , Sztrymf B , Vieillard-Baron A , Yilmaz MB , Konstantinides S. Contemporary management of acute right ventricular failure: a statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology . Eut J Heart Failure 2016 ; 18 : 226 – 241 . Google Scholar CrossRef Search ADS 24 Dahou A , Clavel MA , Capoulade R , Bartko PE , Magne J , Mundigler G , Bergler-Klein J , Burwash I , Mascherbauer J , Ribeiro HB , O'Connor K , Baumgartner H , Sénéchal M , Dumesnil JG , Rosenhek R , Mathieu P , Larose E , Rodés-Cabau J , Pibarot P. Right ventricular longitudinal strain for risk stratification in low-flow, low-gradient aortic stenosis with low ejection fraction . Heart 2016 ; 102 : 548 – 554 . Google Scholar CrossRef Search ADS PubMed 25 Lorenz CH , Walker ES , Morgan VL , Klein SS , Graham TP. Normal human right and left ventricular mass, systolic function, and gender differences by cine magnetic resonance imaging . J Cardiovasc Magn Reson 1999 ; 1 : 7 – 21 . Google Scholar CrossRef Search ADS PubMed 26 Bellenger NG , Burgess MI , Ray SG , Lahiri A , Coats AJ , Cleland JG , Pennell DJ. Comparison of left ventricular ejection fraction and volumes in heart failure by echocardiography, radionuclide ventriculography and cardiovascular magnetic resonance; are they interchangeable? Eur Heart J 2000 ; 21 : 1387 – 1396 . Google Scholar CrossRef Search ADS PubMed 27 Boldt J , Zickmann B , Ballesteros M , Dapper F , Hempelmann G. Right ventricular function in patients with aortic stenosis undergoing aortic valve replacement . J Cardiothorac Vasc Anesth 1992 ; 6 : 287 – 291 . Google Scholar CrossRef Search ADS PubMed 28 Unsworth B , Casula RP , Kyriacou AA , Yadav H , Chukwuemeka A , Cherian A , Stanbridge Rde L , Athanasiou T , Mayet J , Francis DP. The right ventricular annular velocity reduction caused by coronary artery bypass graft surgery occurs at the moment of pericardial incision . Am Heart J 2010 ; 159 : 314 – 322 . Google Scholar CrossRef Search ADS PubMed 29 Sonny A , Sessler DI , You J , Kashy BK , Sarwar S , Singh AK , Sale S , Alfirevic A , Duncan AE. Early left and right ventricular response to aortic valve replacement . Anesth Analg 2017 ; 124 : 406 – 418 . Google Scholar CrossRef Search ADS PubMed Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com. 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European Heart JournalOxford University Press

Published: May 8, 2018

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