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Eugenio Picano Institute of Clinical Physiology, CNR Pisa, Italy

Roma, 23 Settembre 2016. Stress echo 2020. 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. (Picano E, Pellikka P, Eur Heart J 2014).

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Eugenio Picano Institute of Clinical Physiology, CNR Pisa, Italy

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  1. Roma, 23 Settembre 2016 Stress echo 2020 Eugenio Picano Institute of Clinical Physiology, CNR Pisa, Italy

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

  3. (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 Pulmonaryarterial hypertension CAD HFrEF HFpEF Valvular HD Congenital HD Extremephysiology HCM

  4. 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, Picano E et al, EHJ-CV imaging 2016) • Now it is multicenter trial time: SE 2020

  5. DEC 14, 2009 Projected Cancer Risks From Computed Tomographic Scans Performed in the United States in 2007 Amy Berrington de Gonzalez, Mahadevappa Mahesh, Kwang-Pyo Kim, Mythreyi Bhargavan, Rebecca Lewis, Fred Mettler, Charles Land Overall, we estimated that approximately 29000 (95% UL, 15000-45000) future cancers could be related to CT scans performed in the US in 2007 (2 % of all US cancers). DEC 7, 2010 Myocardial perfusion scans: projected population cancer risks from current levels of use in the United States. Berrington de Gonzalez A, Kim KP, Smith-Bindman R, McAreavey D 9 million perfusion scans in US could result in 7400 (95 CI: 330-13700) additional future cancers In USA, the 85 millions CT scans in 2012 will produce 46,750 cancers in the lifetime with an extra-cost of 150 million US dollars (Kuo P et al, American Roentgen Ray Society 2016 meeting)

  6. % Abnormal SE in suspected CAD and Therapy Trends Carpeggiani C, Picano E et al, Int J Cardiol 2016

  7. Risk stratification beyond regional wall motion abnormalities - + ++ 1 – 2 segments ≥ 3 segments Ø ESC guidelines 2013 Hard CV events/ year <1% >3% Resting WMSI > 1.4 On therapy CFVR < 2.0 LVCR < 2.0 B-Lines Resting WMSI 1.0 Off therapy CFVR > 2.0 LVCR > 2.0 A-Lines Titrating negativity(No RWMA) 4% 0.2% Titrating positivity( RWMA) 15% 0.5% Resting WMSI > 1.4 On therapy CFVR < 2.0 LVCR < 2.0 B-Lines > 15 Resting WMSI 1.0 Off therapy CFVR > 2.0 LVCR > 2.0 A-Lines No RWMA RWMA

  8. ASE Cardiovascular Technology Research summit: A roadmap for 2020 1- Administrative/Infrastructure : “Explore the development of imaging registries that interface with other clinical and research sets” 4- Research Topics “Conduct clinical trials demonstrating the impact on outcome of echocardiography” Pellikka P, Douglas P, Miller J et al, JASE 2013;26: 325 -338

  9. ASE Cardiovascular Technology and Research summit : A roadmap for 2020 Recommendations: “The development of a registry of echocardiographic information (and eventually images) that can serve as a platform for quality improvement and clinical research” “Such registry data would be accessible to the research community facilitating a broad range of clinical research on the effectiveness of echocardiography for the improvement of patient management and outcome” Pellikka P, Douglas P, Miller J et al, JASE 2013;26: 325 -338

  10. Stress echo 2020 pedigree: EPIC and GISSI 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

  11. 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

  12. 10 protocols ,10 patients: from telephone to smart-phone 10 - GENES 1- CHEF 2- BHEF 9 - DITSE 3- SERCA 6- DOPSAH 5 - SETA 4 - SEDIA 7 - SETOF 6-SEO

  13. United Colors of Stress Echo

  14. Figure 1

  15. Il Cammino di Quirino Lab accreditation (EACVI,National societies) Quality Control for Regional Wall Motion Abnormalities 10,000 patients enrolled N= 3,000 N= 1,500 N= 500 2020 N= 7,000 2018 2017 2019 SECS 2.0Software High Volume labs (>100/year) Declaration of interest for SE2020 from head of lab 2016 Start recruiting B-lines HCM CRT Diastolicheartfailure Post-TAVI Se2020 ExtremePhysiology RepairedToF PAH Genetic SE Triple imaging in CAD

  16. Stress echo 2020 Gantt chart

  17. Stress Echo 2020 : covering the full spectrum of disease CHEF, SETA, BHEF SETOF, SEDIA, SEHCA DOPSAH, DITSE Project SEO GENES Worried well Patients status Well Suspected sick Very sick Sick Years Patient age 30 40 60 70 80

  18. ESC August 2016, kick-off Euroecho December 2014, the sparkle Porto Alegre May 2016, Brazilian Chapter foundation ESC August 2016, Olympic stadium, outdoor stress echo

  19. Acronym: CHEF Project 1 : Contractile reserve predicts CRT response in Heart Failure patients

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

  21. Flow Chart CHEF #1 , 05.02.2016 EF < 35% HF (NYHA 3-4) ScheduledforCRT without CAD,or CAD without ischemia SE (exer or dob or dip ) Studyhypothesis NON-RESPONDERS NON RESPONDERS Higher Lower WMSI decrease EF increase Lower Higher Lower LVEl increase Higher Resting TTE 4 Resting TTE 2 Resting TTE 3 Resting TTE 1 6 Months Baseline 2 Months 1 Year

  22. Acronym: BHEF Project 2 : B-lines in Heart Failure patients (with depressed or preserved systolic function)

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

  24. Flow Chart Protocol #2 , BHEF HEART FAILURE, NYHA class 1 , 2 , 3 Preserved or depressed LV function EXERCISE (dip or dob) Yearly TTE follow-up Studyhypothesis EVENTS NO EVENTS More • B-lines Less • Severe MR More Less Higher • TAPSE Lower Higher • E/e’ Lower Lower Higher • LV elastance

  25. Acronym: SEHCA Project 3 : Stress echo in Hypertrophic cardiomyopathy for risk stratification through ischemia-related and hemodynamic parameters

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

  27. Flow Chart Protocol # 3 , SEHCA HCM,NYHA class 1 or 2,EF > 45%, no CAD TTE EXERCISE (dip or dob) Yearly TTE follow-up Studyhypothesis EVENTS NO EVENTS More ? • LVOTG Less ? • Severe MR More Less More • WMSI >1 Less Higher • E/e’ Lower Higher Lower • CFVR

  28. Acronym: SEDIA Project 4 : Stress echo in diastolic heart failure

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

  30. Flow Chart Protocol # 4 , SEDIA Dyspnea NYHA class 2 or 3, EF ≥ 50%, LVEDVI < 97mL/m2, LVESV < 43 mL/m2, E/e’ < 13 Clinical criteria: anemia and COPD TTE (no severe VHD or R WMA): E/e’ < 13.Possible LVH and LA dilation (> 34 mL/m2) COPD: chronic obstructive pulmonary disease, CR: contractile reserve; HCM: hypertrophic cardiomyopathy LVEDVI:left ventricular end-diastolic volume index LVOTG: left ventricular outflow tract gradient MR: mitral regurgitation RWMA: regional wall motion abnormalities VHD: valvular heart disease TTE exclusion criteria: HCM or RWMA or severe VHD EXERCISE (dip or dob): No LVOTG > 50 mmHg; No severe MR; No RWMA; No LV elas <2 SE exclusion criteria . LVOTG > 50 mmHg; Severe MR; Inducible RWMA; Subnormal CR (LVel<2.0) Yearly TTE follow-up Studyhypothesis EVENTS NO EVENTS Higher • E/e’ Stress Lower • PASP Stress Higher Lower Shorter • DT Stress Longer Smaller • EDVI Stress Larger Less More • B-lines Stress

  31. Acronym: SETA Project 5 : Stress echo after TAVI: focus on mitral regurgitation

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

  33. Flow Chart Protocol # 3 , SEHCA Severe Aortic stenosis (baseline resting TTE), NYHA 2 or 3 post-TAVI or SAVR Low level EXERCISE Yearly TTE follow-up Studyhypothesis MORE EVENTS Less EVENTS Post-TAVI rest MR More ? Less ? Less Post-TAVI stress MR More Post-TAVI rest AoGr Post-TAVI stress AoG More Less ? Less More

  34. Acronym: SEO Project 6 : Stress Echo Outdoor with pocket size echo to detect subclinical pulmonary edema in extreme physiology setting (high altitude, apnea, marathon runners)

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

  36. LUS-driven therapy and expected results Study protocol

  37. Acronym: SETOF Project 7 : Stress echo in operated tetralogy of Fallot

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

  39. Flow Chart Protocol # 7 , SETOF Repaired ToF or TOF-like, age >10 years, NYHA 1 or 2 TTE EXERCISE (dip or dob) RV reserve is important ! But LV systolic and diastolic reserve can also be important Yearly TTE follow-up Studyhypothesis MORE EVENTS Less EVENTS RV TAPSE stress Lower Higher Higher RV FAC % stress Lower LV Peak stress E/e’ LV Δ EF Higher Lower Lower Higher

  40. Acronym: DOPSAH Project 8 : Doppler Stress echo for prediction of Pulmonary Arterial Hypertension

  41. 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

  42. Flow Chart Protocol #8, DOPSAH GROUP A : Subjects at risk of PAH without diagnosis of PAH (Group 1 ESC GL) Without contraindications to exercise GROUP B: Patients with diagnosis of PAH (Group 1 ESC GL) Without contraindications to exercise + Subgroup of borderline patients (invasive mPAP 21-24 mmHg and PCWP≤15) Without contraindications to exercise EXERCISE Yearly clinical TTE follow-up Studyhypothesis • Echo PASP increase/will be PAH (Group A) • More events (Group B) • No echo PASP increase/no PAH (Group A) • Less events (Group B) Peak exercise PASP Higher ? Lower? Mean PAP/CO slope Higher Lower Higher Mean PAP/ min exercise Lower RV contractile reserve Lower Higher

  43. Acronym: DITSE Project 9 : Diagnosis of CAD by Triple imaging Stress Echo (wall motion, coronary flow reserve and left ventricular elastance) in patients with normal resting left ventricular function

  44. Incrementalvalueof CFR overwallmotiontopredictmortality n = 4,313 p < 0.0001 Cortigiani. JACC Cardiovasc Imaging 2012;5:1079

  45. Flow Chart Protocol #9, DITSE “All-comers” with chest pain syndrome Preserved or depressed LV function EXERCISE or DIP or ADO or DOB Yearly clinical follow-up Studyhypothesis EVENTS NO EVENTS Higher • WMSI Lower • CFVR Lower Higher Lower • LV elastance Higher

  46. Acronym: GENES Project 10 : Genetic stress echo in hypertrophic cardiomyopathy, familial dilated cardiomyopathy and familial pulmonary hypertension

  47. Genetic stress echo in HCM, PPH and DCM

  48. Flow Chart Protocol # 10 , GENES Asymptomatic first-degree relatives with genetic testing of a known proband with disease TTE: normal EXERCISE or DIP or DOB Yearly clinical follow-up Studyhypothesis Genotype pos Genotype neg High LVOTG,Low CFVR in HCM Higher Lower Lower Higher PASP e PAP/CO slope in PAH LV elast ance and CFVR in DC Lower Higher Will develop disease at f-up More likely with SE+ More likely with SE +

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