Lim, Scott

Introduction: Pulmonary hypertension (PH) is associated with increased mortality after surgical or transcatheter aortic valve replacement (TAVR) for aortic stenosis (AS). Hypothesis: We hypothesized that clinical or hemodynamic factors might influence the relationship between significant PH and increased mortality. Methods: Among patients with symptomatic AS at high or prohibitive surgical risk receiving TAVR in the PARTNER I randomized trial or registry, 2180 patients with an invasive measurement of mean pulmonary artery pressure (mPAP) recorded were included. PH was defined as: none (mPAP<25 mmHg), mild (25 to <35), and mod/sev (≥35). Results: One year all-cause mortality was worse with increasing severity of PH: none (n=785, 18.6%), mild (n=838, 22.7%), and mod/sev (n=557, 25.0%) (p=0.01). The association between mod/sev PH (vs. no PH) and 1y mortality varied by sex and renal function (interaction p=0.03 and p=0.06, respectively). In females, mod/sev PH was associated with increased mortality (24.6% vs. 14.1%, HR 1.89, 95% CI 1.32-2.73); in males it was not (24.9% vs. 22.2%, HR 1.12, 95% CI 0.82-1.52). Additionally, mod/sev PH was associated with mortality in those with glomerular filtration rate (GFR) <40 (HR 1.76, 95% CI 1.28-2.42), but not in those with GFR ≥40. In a multivariable Cox PH model of patients with mod/sev PH, oxygen dependent lung disease, cerebrovascular disease, lower GFR, and lower baseline transvalvular mean gradient were each independently associated with increased 1y mortality (p<0.05 for all), whereas pulmonary artery compliance was the only hemodynamic variable associated with mortality (p=0.043) (Table). Conclusions: The relationship between mod/sev PH and increased mortality after TAVR is altered by sex and renal function. While lower pulmonary artery compliance is associated with increased mortality in patients with significant PH, clinical factors appear to be more influential in stratifying risk than hemodynamic indices.

Background: In the initial PARTNER trial (Placement of Aortic Transcatheter Valves) of transcatheter aortic valve replacement for high-risk (HR) and inoperable patients, mortality at 1 year was 24% in HR and 31% in inoperable patients. A recent report of the 30-day outcomes with the low-profile SAPIEN 3 transcatheter aortic valve replacement system demonstrated very low rates of adverse events, but little is known about the longer-term outcomes with this device. Methods: Between October 2013 and September 2014, 583 HR (65%) or inoperable (35%) patients were treated via the transfemoral (84%) or transapical/transaortic (16%) access route at 29 US sites. Major clinical events at 1 year were adjudicated by an independent clinical events committee, and echocardiographic results were analyzed by a core laboratory. Results: Baseline characteristics included age of 83 years, 42% female, and median Society of Thoracic Surgeons score of 8.4%. At the 1-year follow-up, survival (all-cause) was 85.6% for all patients, 87.3% in the HR subgroup, and 82.3% in the inoperable subgroup. Survival free of all-cause and cardiovascular mortality in the transfemoral patients from the HR cohort was 87.7% and 93.3%, respectively. There was no severe paravalvular leak. Moderate paravalvular leak (2.7%) was associated with an increase in mortality at 1 year, whereas mild paravalvular leak had no significant association with mortality. Symptomatic improvement as assessed by the percentage of patients in New York Heart Association class III and IV (90.1% to 7.7% at 1 year; P <0.0001) and by Kansas City Cardiomyopathy Questionnaire overall summary score (improved from 46.9 to 72.4; P <0.0001) was marked. Multivariable predictors of 1-year mortality included alternative access, Society of Thoracic Surgeons score, and disabling stroke. Conclusions: In this large, adjudicated registry of SAPIEN 3 HR and inoperable patients, the very low rates of important complications resulted in a strikingly low mortality rate at 1 year. Between 30 and 365 days, the incidence of moderate paravalvular aortic regurgitation did not increase, and no association between mild paravalvular leak and 1-year mortality was observed, although a small increase in disabling stroke occurred. These results, which likely reflect device iteration and procedural evolution, support the use of transcatheter aortic valve replacement as the preferred therapy in HR and inoperable patients with aortic stenosis. Clinical Trial Registration : URL: http://www.clinicaltrials.gov . Unique identifier: NCT01314313.

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