Giuseppe De Luca, MD, PhD

Professore Associato di Cardiologia

Responsabile Laboratorio di Emodinamica

Universitario

AOU Maggiore della Carità

Novara, Italy

TAVI: Nuovi Orizzonti

New generation TAVI devices

Expanding TAVI Indications: low-risk vs SurgeryMODERATE SVA WITH HEART FAILURE Asyntomatic SVALow-Flow Low GradientBicuspid valveAortic regurgitation

Comparing TAVI options

Simplifying the TAVI procedure

Stroke and CEREBROVASCULAR EMBOLIC PROTECTION

Antithrombotic therapy post-TAVI

VALVE LEAFLET INTEGRITY, THICKENING AND THROMBOSIS

TAVI: Nuovi orizzonti

AVR Risk

Low High

TAVI Med Rx

Inoperable

Utility Futility

Too Sick

STS >10%ES ≥20%

AVR

Irrational

Moderate

?

STS ≥4%

? NoYesOK

TAVI: To Whom?

TAVIAVR

Leon MB et al, NEJM 2016

PARTNER II TrialAll procedures – Primary Outcome

Leon MB et al, NEJM 2016

PARTNER II TrialTransfemoral procedures – Primary Outcome

Leon MB et al, NEJM 2016

1746 pts

All-Cause Mortality or Disabling Stroke

SURTAVI TrialAll-Cause Mortality or Disabling Stroke at 24 Months

Thourani et al, Lancet 2016

p value<0.01

Thourani et al, Lancet 2016

AVR Risk

Low High

TAVI Med Rx

Inoperable

Utility Futility

Too Sick

STS >10%ES ≥20%

AVR

Irrational

Intermediate

STS ≥4%

OK NoYesYes

TAVI: To Whom?

TAVI or AVR TAVIAVR

AVR Risk

Low High

TAVI Med Rx

Inoperable

Utility Futility

Too Sick

STS >10%ES ≥20%

?

See you in 5 yrs

Intermediate

STS ≥4%

Yes NoYesYes

TAVI: To Whom?

TAVIAVR

TAVIAVR

ALL-CAUSE MORTALITY IN LOW-TO-INTERMEDIATE RISK PATIENTS

EARLY TAVR Trial

TAVR UNLOAD Trial

EPIDEMIOLOGIA

Il giusto timing di intervento per questa popolazione rimane controverso

Circa il 50 % degli individui con stenosi aortica severa è asintomatico

La stenosi aortica severa sintomatica non curata si associa a bassa sopravvivenza

La prevalenza della stenosi aortica e del 5% degli adulti con età > 65 aa

STORIA NATURALE DELLA STENOSI AORTICA ASINTOMATICA

Registro di Taniguchi et al.- 1.517 pazienti trattati conservativamente con AS asintomatica i tassi di sopravvivenza ad 1 anno e 5 anni sono del 92,8% e 73,6% rispettivamente

Nei pazienti con stenosi artica asintomatica grave, la sopravvivenza ad 1 anno e 5 anni riportata in letteratura oscilla dal 67% al 97%(1 aa) e dal 38% al 83%(2 aa)

A 5 anni circa il 75% dei pazienti diventa sintomatico 75% di questi morirà o farà la AVR/ TAVI

I pazienti asintomatici hanno una prognosi migliore rispetto a quelli sintomatici

Rischio di morte improvvisa 1-1,5% anno

PROBLEMI PRATICI CON LA STRATEGIA DI ‘’WATCHFUL WAITING’’

Il cardiologo spesso ha paura di fare lo stress test in pz con stenosi aortica asintomatica

Lo stress test richiede expertise ed un personale addestrato che non tutte le cardiologie hanno

Spesso il follow up non è ottimale e molti pazienti sono persi durante lo stesso

Molte morti per morte improvvisa si verificano in pazienti asintomatici e senza precedenti

N=2486

METANALISI DI STUDI CHE METTONO A CONFRONTOLA EARLY AVR VS STRATEGIA DI

OSSERVAZIONE IN PZ CON STENOIS AORTICA ASINTOMATICA

EARLY TAVR Trial

TAVR UNLOAD Trial

Three active-controlled randomised trials of TAVI devices are underway to generate efficacy

data to support Food and Drug Administration clearance of transcatheter heart valves already

approved for commercial use in Europe

All of these studies will target high- and extreme-risk patients with severe aortic stenosis:

1) PORTICO IDE (N=908, NCT02000115) is comparing the Portico™ (St. Jude Medical, St.

Paul, MN, USA) valve and either SAPIEN or CoreValve systems;

2) SALUS (TranScatheter Aortic Valve RepLacement System Pivotal Trial The Safety and

Effectiveness of the Direct Flow Medical Transcatheter Aortic Valve System) (N=649,

NCT02163850) is comparing the Direct Flow Medical® (Direct Flow Medical, Santa Rosa,

CA, USA) with the SAPIEN or CoreValve systems;

3) REPRISE III (Repositionable Percutaneous Replacement of Stenotic Aortic Valve Through

Implantation of Lotus™ Valve System) (N=1,032, NCT02202434) is a comparison of the

Lotus™ (Boston Scientific, Marlborough, MA, USA) and CoreValve systems. A small

investigator-initiated trial named REBOOT (REpositionable Versus BallOOn-expandable

Prosthesis for Trans-catheter Aortic Valve Implantation) (N=240, NCT02668484) is

comparing the Lotus and SAPIEN 3 valves with respect to the incidence of new pacemaker

implantation at 30 days. An industry-driven randomised trial of the ACURATE neo™ valve

(Symetis, Ecublens, Switzerland) vs. other TAVI systems is also planned.

Other new TAVI systems are in earlier phases of clinical testing as part of ongoing single-arm

studies. These include the Centera valve (Edwards Lifesciences), whose safety and

performance are the object of CENTERA-EU (N=200, NCT02458560), and the JenaValve

Pericardial TAVR System (JenaValve, Munich, Germany), which will be tested in two

feasibility trials of

CONCLUSIONSTAVI has revolutioned the management of aortic stenosis

TAVI has replaced Surgery in high and intermediate risk patients.

Several studies are ongoing to further expand the indication to low-riskpatients, asyntomatic patients and those with moderate SVA and Leftventricular dysfunction. Additonal studies are certainly needed inthose LFLG

The evolving technology will certainly contribute to simplify theproceudre, reduce complications, increase durability and enlarge theindication.

While the availability of several valves will facilitate a tailoredapproach, large randomized trials are certainly needed to define asuperiority of a valve over the others.