Rihal, C.

Abstract Background The MITRAL Trial (Mitral Implantation of TRAnscatheter vaLves) evaluates the safety and feasibility of balloon-expandable aortic transcatheter heart valves in patients with severe mitral valve disease with mitral annular calcification (MAC), failed surgical rings or failed bioprostheses. Purpose We sought to evaluate 4-year outcomes of patients enrolled in the MITRAL trial. Methods This is a prospective study that enrolled 91 high surgical risk patients at 13 sites in the U.S. 30 patients underwent Mitral Valve-in-Valve (MViV), 30 Valve-in-Ring (MViR) and 31 Valve-in-MAC (ViMAC). 4-year outcomes of these patients were evaluated in this analysis. Primary endpoints and key serious adverse events including deaths were adjudicated by an independent Clinical Events Committee. Cardiac computed tomography (CT) and echocardiographic images were evaluated by independent CT and Echocardiographic Core Laboratories. Results Mean age was 74.3±8.9 years. Most patients undergoing MViV and ViMAC were female (MVIV=63.3%, MViR=36.7% and ViMAC=71%). Mean STS score was 9.2±6.6% (MViV 10.2±6.5%, MViR 8.7±4.7%, ViMAC=8.6±8.2%). All-cause mortality at 4 years was higher for ViMAC and MViR: MViV=6.9% (cardiovascular 3.4%), MViR=48.1% (cardiovascular 18.5%), ViMAC=51.9% (cardiovascular 29.6%), p=0.002 (Figure 1). At 4 years, all survivors had ≤1+ mitral regurgitation and most had none or trace mitral regurgitation (MViV=87.5, MViR=33.3% and ViMAC=100%). Mean mitral valve gradients remained stable (MViV=5.9±2.2 mmHg, MViR= 6.6±5.1 mmHg, ViMAC=5.1±1.0 mmHg), Figure 2. Most survivors experienced significant improvement of symptoms and were in NYHA class I-II at 4-year follow-up (MViV=78.9%, MViR=66.7% and ViMAC=66.7%). Conclusions MViV is associated with excellent outcomes at 4 years. MViR and ViMAC were associated with higher mortality at 4 years. However, most survivors in all groups experienced sustained improvement of symptoms and stable THV performance at 4 years. Whether survival bias had an impact on THV performance and improved symptoms at follow-up is not known and deserves further evaluation. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Unrestricted Research Grant from Edwards Lifesciences.

Abstract Background There is a paucity of data about the prevalence and natural history of mitral annular calcification (MAC). Purposes In a large cohort of patients undergoing clinically-indicated echocardiography, we aimed to evaluate the prevalence and the natural history of MAC, and the frequency of associated mitral valve dysfunction (MVD). Methods Retrospective review of all patients who underwent echocardiographic evaluation at our institution between January 1st and December 31st 2015. The patients were stratified into 3 groups: MAC with MVD, MAC without MVD, no MAC. MVD was defined as moderate or greater mitral regurgitation (MR) or stenosis (MS). The 3 groups were compared for baseline clinical and echocardiographic characteristics and all-cause mortality during follow-up. Results Of 24,415 evaluated patients, 5478 (22%) had MAC. Patients with MAC were older (75±10 vs. 60±16 years, p<0.01) and more often female (46% vs. 43%, p<0.01). MVD was more frequently observed in patients with MAC (16% vs. 7%, p<0.01); moderate or greater MR was found in 10% of patients with MAC vs. 6% without MAC (p<0.01) and MS in 7% vs. 0.5% (p<0.01). In patients with MAC, those with MVD were more often female and more frequently had creatinine ≥2mg/dl and moderate or greater aortic stenosis (AS) than those without MVD (Fig. A). Kaplan-Meier survivals at 1 year were 75% in patients with MAC and MVD, 87% in those with MAC without MVD, and 92% in those without MAC (Fig B). Adjusted for age, sex, diabetes, creatinine ≥2 mg/dl, coronary artery disease, left ventricular ejection fraction <50%, and AS, MAC was associated with higher all-cause mortality (adjusted hazard ratio1.4, 95% confidence interval: 1.3–1.5, p<0.01); combined MAC and MVD was associated with the highest mortality during follow-up of 2.5±1.8 years. Conclusion In a large cohort of patients undergoing echocardiographic evaluation, the prevalence of MAC was 22%. MV dysfunction was more than twice as prevalent in patients with MAC as without. Patients with MAC had higher all-cause mortality than patients without MAC. Among patients with MAC and mitral valvular dysfunction, adjusted mortality was two-fold higher compared to those without MAC. Funding Acknowledgement Type of funding source: None

Abstract Background/Introduction TAILOR-PCI is the largest cardiovascular genotype-based randomized trial (NCT#01742117) investigating whether genotype-guided selection of oral P2Y12 inhibitor therapy improves ischemic outcomes after percutaneous coronary intervention (PCI). The TAILOR-PCI Digital Sub-Study tests the feasibility of extending original follow-up of 1 year to 2 years using state-of-the-art digital solutions. Deep phenotyping acquired during a clinical trial can be leveraged by extending follow-up in an efficient and cost-effective manner using digital technology. Purpose Our objective is to describe onboarding and engagement of participants initially recruited in a large, pragmatic, international, multi-center clinical trial to a digital registry. Methods TAILOR-PCI participants, within 23 months of their index PCI, were invited by letters containing a URL to the Digital Sub-Study website (http://tailorpci.eurekaplatform.org). These invitations were followed by phone calls, if no response to the letter, to determine reason for non-participation. A NIH-funded direct-to-participant digital research platform (the Eureka Research Platform) was used to onboard, consent and enroll participants for the digital follow-up. Participants were asked to answer health-related surveys at fixed intervals using the Eureka mobile app and desktop platform. To capture hospitalizations, participants could enable geofencing to allow background location tracking, which triggered surveys if a hospitalization was detected. Result(s) Letters were mailed to 893 of 929 eligible participants across 22 sites in the United States and Canada leading to 226 homepage visits and 118 registrations. There were 107 consents (12.0% of invited; mean age: 66.4±9.0; 19 females [18%]): 47 (44%) participants consented after the letter, 36 (34%) consented after the 1st call and 24 (22%) consented after a 2nd call. Among those who consented, 100 were eligible (7 did not have a smartphone) 81 downloaded the study mobile app and 73 agreed for geofencing (Figure 1). Among the 722 invited participants who were surveyed, 354 declined participation: due to lack of time (146; 20.2%), lack of smartphone (125; 17.3%), difficulty understanding (41; 5.7%), concern about using smartphone (34; 4.7%), concern of data privacy (14; 1.9%), concerns of location tracking (6; 0.8%) and other reasons (57; 7.9%). Conclusion Extended follow-up of a clinical trial using a digital platform is feasible but uptake in this study population was limited largely due to lack of time or a smartphone among participants. Based on data from other digital studies, uptake may also have been limited since digital follow-up consent was not incorporated at the time of consent for the main trial. Figure 1. Onboarding of the digital substudy Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institute of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)