Eugenio Picano Institute of Clinical Physiology, CNR Pisa, Italy Gramado, Brazil , 19 May 2016,h 10 am Stress echo 2020: above and beyond coronary artery disease Eugenio Picano Institute of Clinical Physiology, CNR Pisa, Italy

Stress echo lab 1.0: One patient, one technology, one sign Rest Stress Adapted from Picano E. Am J Med 2003

Stress echo lab 2.0: versatility (Picano E, Pellikka P, Eur Heart J 2014) Stress echo lab 2.0: versatility Ischemia Viability CFVR Mitral Insufficiency 200 LV elastance Extravascular lung water CAD CMD Valvular HD Congenital HD Athletes, divers, climbers Secondary pulmonary hypertension (SScl, PPH) Heart Transplant pts

Stressecho beyond CAD Started as early as stress echo in CAD (in the eighties, mainly on mitral stenosis and valves) Small part (<1/10 ) of stress echo guidelines (ASE 2007 Pellikka et al; EACVI 2008 Sicari et al) Special Focus in EHJ clinical review 2014 (Picano E, Pellikka P, EHJ 2014) Targeted by joint ASE-EACVI recommendation (Lancellotti P., Pellikka P, Tsutsui J, Picano E et al, EHJ-CV imaging 2016) Now it is multicenter trial time: SE 2020 Exercise-induced symptons Exercise-induced hypotension ECG changes LVOT obstruction development New wall motion abnormalities Coronary flow velocity reserve (CFRV) 4

Stress echo 2020 pedigree: si parva licet componere magnis … SE 2020 a step-child of GISSI: 1 - Sponsored by a respected, independent, not-for-profit national professional society (it was ANMCO; it is SIEC) 2 - Scientific coordination from a distinguished research institute (it was Mario Negri in Milan, it is CNR-IFC Pisa) 3 - Inclusivity (it was all CCU’s, it is all SE labs of the nation) 4 – Emphasis on clinical relevant outcomes changing patient care (it was thrombolytic therapy in acute myocardial infarction, it is cardiac imaging within and beyond CAD) Braunwald E, Am Heart J, 2004: The GISSI twentieth birthday

EPIC, the father of Stress echo 2020 1 - simple protocols without economic induction can change guidelines (it was in CAD, it is also beyond CAD for SE 2020) 2 - Italians do it (SE) better, we have cultural and technological infrastructure (it was analogic dip and dob, it is digital and also semi-supine exercise) 3 - Echo people like to do extra-work that make their practice better if clinically worthwhile (it was RWMA , it is also CFVR, B-lines, SPAP, LV elastance index, etc) 4 – We need the fruit of effectiveness (real world data), not the seed of efficacy (virtual reality of journals written by enthousiastic fellows and presented by gray-haired opinion leaders paid by industry) to feed our patients 30 EPIC-EDIC papers with over 75 authors of 4 continents and 12 countries on top-ranked journals over a 20 years span (1992- 2012) changing clinical practice

The 10 protocols, 100 centers and 10,000 patients STRESSECHO 2020 The 10 protocols, 100 centers and 10,000 patients Running title : Italians still do it better? (10-100-10,000)

Contractile reserve and CRT response (Ciampi Q et al, 2016, ESC abstract)

Stress B- lines in Heart Failure Scali MC,Marzilli M et al, ESC 2016 (abstract)

Stress echo in HCM : coronary flow reserve makes the difference Ciampi Q et al, ESC meeting 2016

HFrEF: EDV reserve matters (diastolic pressure-volume better than pressure only!) HFpEF HFrEF Controls (Shimiaie et al, JACC heart fail 2015)

Beneficial effects of TAVI on MR Costantino F et al, CardioUltra 2015

Stress echo Outdoor * * * 5130 4790 3440 1350 1350 m s.l. days 18 subjects (10 males) mean age 45±10 years m s.l. Gokyo 5130 Namche Bazaar 4790 * Gorak Shep 3440 * Kathmandu * 1350 Kathmandu 1350 days Cardiac and chest echo Pratali L. et al Critical Care Medicine 2010 13

SE in adult repaired ToF RV FAC decreases at exercise RV FAC increases at exercise RV FAC at Rest RV FAC at Exercise RV FAC at Rest RV FAC at Exercise NON RESPONDERS (49 pts) RESPONDERS (74 pts) L. Ait Ali et al, J Am Soc Echocardiogr. 2014

SE in patients at risk for pulmonary arterial hypertension Figure 2. Changes in PASP values from rest to peak exercise for each individual patient. Luna Gargani, Alberto Pignone, Gergely Agoston, Antonella Moreo, Eugenia Capati, Luigi P. Badano, Marica Doveri, Laura Bazzichi, Marco Fabio Costantino, Andrea Pavellini, Francesco Pieri, Francesco Musca, Denisa Muraru, Oscar Epis, Eleonora Bruschi, Benedetta De Chiara, Federico Perfetto, Fabio Mori, Oberdan Parodi, Rosa Sicari, Stefano Bombardieri, Albert Varga, Marco Matucci Cerinic, Eduardo Bossone, Eugenio Picano American Heart Journal, Volume 165, Issue 2, 2013, 200–207 http://dx.doi.org/10.1016/j.ahj.2012.10.020

Incremental value of CFR over wall motion to predict mortality Cortigiani. JACC Cardiovasc Imaging 2012;5:1079

Genetic stress echo in HCM, PPH and DCM

Stress Echo Computerized Software 2.0

Allo studio partecipano alcuni dei migliori ricercatori italiani nei rispettivi settori, di tutte le età (dai 30 ai 60 anni), tutte le appartenenze (ospedalieri, universitari, CNR) e tutte le provenienze geografiche (da Potenza a Venezia), secondo un principio elementare (ma raramente applicato) di rispetto delle competenze, condivisione dei saperi e ottimizzazione delle risorse

Conclusions Stress-echo 2020 will help the Italian SE community in tailoring the right stress to the right patient with the right technology, used by the right (properly trained and certified) cardiologist. SE has today an unprecedented advantage of economic sustainability, lack of radiation, portability and versatility making it potentially dominant in the current era of societal pressures on cardiac imaging costs and risks. Stressecho 2020 will recruit 10,000 patients by 2020 spread over 10 subprojects and should create a SE lab without walls 20

Nunca procures saber por quem os sinos dobram; eles dobram por ti Marco Antonio, Liz, Monica, Pedro, Adriana, Patricia, Leticia, Wilson, Lucas, and many others: EPIC EDIC and Brazil, 20 years after here we go again Nunca procures saber por quem os sinos dobram; eles dobram por ti