Prosthesis-related events and echocardiographic data throughout 9 years follow up after TAVI. Luca Testa, MD, PhD IRCCS Pol. S. Donato, Milan, Italy luctes@gmail.com

Potential conflicts of interest Speaker's name: Luca Testa I do not have any potential conflict of interest to report:

Why this study? The introduction of transcatheter aortic valve implantation (TAVI) technology has determined a paradigm shift in the treatment of degenerative severe aortic stenosis. However, data on long term valve performance are lacking, as a consequence of a high rate of overall mortality in the elderly population treated with TAVI.

We sought to evaluate: What did we study? the rate of clinical events related to transcatheter aortic valve bioprostheses, and inherent echocardiographic parameters up to 9-year follow up.

How was the study executed? Starting in June 2007, all consecutive patients with severe aortic stenosis undergoing TAVI with the CoreValve and EvolutR devices in 13 Italian centers were prospectively included in the Clinical Service Project. (Clinical Trial Registration Information: http://clinicaltrials.gov/ct2/show/NCT01007474). The ClinicalService® Project is a national data repository that was approved by each site’s Institutional Review Board Clinical and echocardigraphic follow up has been done under the responsibility of each participating center. Time points were: post procedure, 1 month, 6 months, 12 months and then yearly. All the clinical events and, whereas available the autopsy findings, were recorded in order to outline the prosthesis related ones.

How was the study executed? All the cardiac deaths and the hospitalizations possibly related to the prosthesis have been reviewed to assess the presence of endocarditis, thrombosis and/or worsening (stenosis/regurgitation) valve parameters, and eventually included in the analysis. These events were defined as “prosthesis-related clinical events”. Endpoints of interest were: the occurrence of the prosthesis-related clinical events, and the changes over time of echocardiographic parameters, such as the aortic valve area, the mean gradient and rates of moderate and severe PVL.

What are the essential results? From June 2007 to December 2016, 2343 patients have been treated in the 13 participating Italian Centers. Longest follow up reached 9 years while the mean FU was 22 months and the total exposure time was 4325 years. Clinical Characteristics TOTAL (n=2343) Age at procedure (yrs), Mean ± SD 82 ± 6 Male, % 45.8 BMI, Mean ± SD 26 ± 5 Log-Euroscore, Mean ± SD 22 ± 15 STS Score, Mean ± SD 9 ± 9 Creatinine>2 (mg/dL), (%) 9.9 GFR<30, (%) 21.9 NYHA 3-4, (%) 76.5 Kidney Disease, (%) 49.5 Hypertension, (%) 81.2 Diabetes, (%) 30.1% Prior Stroke, (%) 7.9% CAD, (%) 40.7% Prior MI, (%) 17.2% Prior PCI, (%) 27.8% Severe COPD, (%) 21.9% Prior CABG, (%) 14.6% Mean Aortic Gradient (Mean ± SD) 51 ± 16 Aortic regurgitation = 2+ (%) 2.5 Mitral regurgitation = 2+ (%) 42.3 LVEF (Mean ± SD) 51 ± 13 sPAP > 60 mmHg (%) 10.9 LBBB (%) 10.5 RBBB (%) 6.5 PM (%) 13.1 Procedural Characteristics TOTAL (n=2343) Access Femoral (%) 83.3 Subclavian (%) 11.5 Aortic (%) 4.8 Other 0.3 Type of Anesthesia Local Anesthesia (%) 73.5 General Anesthesia (%) 26.5 Prosthesis Size 23 (%) 2.4 26 (%) 44.7 29 (%) 43.7 31 (%) 9.2 Post-dilatation (%) 23.5 Device success (%)* 93.3 Procedural success (%)* 94.9 Contrast media (m, Mean ± SD) 186 ± 112 Periprocedural regurgitation None/Trace (%) 29.6 Mild (%) 53.8 Moderate (%) 14.1 Severe (%) * VARC 2

What are the essential results? At 7 year follow-up, overall mortality was 68.1% (62.9-73.2). Up to 9-year FU, 4 more fatalities have been recorded, however, the number of patients at risk was very low as compared to the initial population so that it was statistically sound to trunk the plots at 7 years.

What are the essential results? 20 prosthesis related clinical events occurred with an annual rate ranging from 0.2% to 1.5%; the 7 years incidence of events was 3.2% (1.51-6.71%)

What are the essential results? 6 prosthesis related fatalities (all patients were hospitalized presenting progressive worsening of hemodynamic parameters up to end stage heart failure): 3 endocarditis with isolation of the pathogen have been diagnosed at 3, 6, and 24 months In all other cases, no signs of infection were detected but a severe degeneration of the bioprosthesis performance (1 case of severe intraprosthetic regurgitation after 72 months and 2 cases of severe stenosis after 26 and 89 months). 14 prosthesis-related events led to a new hospitalization for heart failure: 2 endocarditis with isolation of the pathogen have been diagnosed, after 9 and 16 months, respectively. The first  urgent SAVr. ; the second  medical Tx In the remaining 12 cases, 8 “Valve-in-Valve procedure”, 2 SAVr, and 2 medical Tx. After 7 years up to 9-year follow up, no further prosthesis related clinical events have been recorded.

What are the essential results? The rates of mild and moderate PVL did not change from discharge (53.8% and 14.1%) to last available follow up (51% and 16%), p=0.65.

Why it is important? The future application of the TAVI technology in younger and less sick patients can only be imagined in the presence of data showing the life span of the available bioprosthesis Our data suggest a very low rate of “clinically relevant” bioprosthesis failure, and provide evidence about a reassuring long term performance.

The essentials to remember Take Home: Why? Data concerning the life span of a TAVI, and its long term performance are lacking. What? We sought to evaluate the rate of prosthesis related clinical events, and echocardiographic parameters at long term after TAVI How? Within the framework of the ClinicalService Project, i.e. a nation- based clinical data repository and medical care project (Clinicaltrial.gov: NCT01007474). What are the results? The rate of prosthesis related clinical events ranges between 0.2 % to 1.5%/year; echocardiographic parameters are stable long after TAVI. Why is this important? The future application of TAVI to younger patients needs long term data.

Participating Centers: ▪ Spedali Civili Brescia ▪ Policlinico San Donato ▪ Ospedale San Raffaele ▪ Humanitas ▪ Ospedale Civile di Legnano ▪ Ospedale Niguarda ▪ Cardiologico Monzino ▪ Ospedale Poma ▪ Maria Cecilia Hospital ▪ Ospedale Cisanello ▪ Ospedale Le Scotte I wish to thank all those involved in the procedures, follow ups, data management and analysis. ▪ AO Gemelli ▪ Ospedale San Camillo Participating Centers: • 1 Dept. of Cardiology, IRCCS Pol San Donato, San Donato Milanese, Milan, Italy: Dr. Francesco Bedogni, Dr. RA Latini 2 Interventional Cardiology Unit, San Raffaele Hospital and EMO-GVM Centro Cuore Columbus, Milan, Italy: Dr. A. Latib, Prof. A. Colombo 3 Ospedale Civile, Legnano, Italy: Dr. A. Poli 4 Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy: Dr. C. Giannini, Prof. AS Petronio 5 Azienda Ospedaliera-Universitaria Senese, Pol. Le Scotte, Siena, Italy : Dr. A. Iadanza 6 Ferrarotto Hospital, Catania, Italy : Dr. M. Barbanti, Prof. C. Tamburino 7 Ospedale San Giovanni di Dio Ruggi d'Aragona, Salerno, Italy: Dr. Giudice P 8 Osp. S. Camillo, Roma, Italy: Dr. Boschetti C 9 Niguarda Ca Granda Hospital, Milan, Italy : Dr. Bruschi G 10 Humanitas Research Hospital, Rozzano, Italy: Dr. Reimers B 11 Pol. A Gemelli, Roma, Italy: Dr. C. Trani 12 Centro Cardiologico Monzino, Milano, Italy: Dr. Fabbiocchi F. 13 Spedali civili, Brescia, Italy: Dr. C. Fiorina, Dr. M Adamo. ▪ AO San Giovanni di Dio • • ▪ Ospedale Ferrarotto • •

THANKS FOR THE ATTENTION Luca Testa, MD, PhD IRCCS Pol. S. Donato, Milan, Italy luctes@gmail.com