Download - STRESS ECHO 2020

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)
Stress echo lab 2.0: versatility
Ischemia
Viability
CFVR
.54
Mitral Insufficiency
8
.23
10
200
LV elastance
Extravascular
lung water
CAD
HFrEF
HFpEF
Valvular HD
Congenital HD
Extreme physiology
Pulmonary arterial
hypertension
HCM
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
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)
% Abnormal SE in suspected CAD and Therapy Trends
100
75
50
25
0
1983
1992
2001
SE Positivity
Carpeggiani C, Picano E et al, Int J Cardiol 2016
Therapy
Risk stratification beyond regional wall motion abnormalities
-
+
++
Ø
1 – 2 segments
≥ 3 segments
ESC guidelines 2013
Hard CV events/ year
<1%
Resting WMSI 1.0
Off therapy
CFVR > 2.0
LVCR > 2.0
A-Lines
>3%
Resting WMSI > 1.4
On therapy
CFVR < 2.0
LVCR < 2.0
B-Lines
Titrating negativity
(No RWMA)
4%
0.2%
Titrating positivity
( RWMA)
0.5%
Resting WMSI 1.0
Off therapy
CFVR > 2.0
LVCR > 2.0
A-Lines
No RWMA
15%
Resting WMSI > 1.4
On therapy
CFVR < 2.0
LVCR < 2.0
B-Lines > 15
RWMA
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
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
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
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)
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
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
10 protocols ,10 patients: from telephone to smart-phone
10 - GENES
1- CHEF
2- BHEF
9 - DITSE
3- SERCA
6- DOPSAH
4 - SEDIA
7 - SETOF
6-SEO
5 - SETA
United Colors of Stress Echo
Figure 1
Il Cammino di Quirino
Lab accreditation
(EACVI,National
societies)
Quality Control
for Regional Wall
Motion
Abnormalities
10,000
patients
enrolled
N= 500
N= 1,500
N= 7,000
2017
High Volume
Declaration of interest
labs
for SE2020 from head of lab
(>100/year)
SECS 2.0
Software
2016
Start recruiting
N= 3,000
2018
2019
2020
Stress echo 2020 Gantt chart
Stress Echo 2020 : covering the full spectrum of disease
Project
SEO
GENES
DOPSAH,
DITSE
SETOF,
SEDIA,
SEHCA
CHEF,
SETA,
BHEF
Patients
status
Well
Worried
well
Suspected
sick
Sick
Very
sick
Years
Patient age
30
40
60
70
80
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
Acronym:
CHEF
Project 1 : Contractile reserve predicts CRT response
in Heart Failure patients
Contractile reserve and CRT response
(Ciampi Q et al, 2016, ESC abstract)
Flow Chart CHEF #1 , 05.02.2016
HF
(NYHA
3-4)
EF <
35%
without
CAD,or
CAD
without
ischemia
Scheduled
for
CRT
SE
(exer or dob
or dip )
Study hypothesis
NON-RESPONDERS
NON RESPONDERS
WMSI decrease
Lower
Higher
EF increase
Lower
Higher
LVEl increase
Lower
Higher
Resting TTE 1
Baseline
Resting TTE 2
Resting TTE 3
Resting TTE 4
2 Months
6 Months
1 Year
Acronym:
BHEF
Project 2 : B-lines in Heart Failure patients (with
depressed or preserved systolic function)
Stress B- lines in Heart Failure
Scali MC, Marzilli M, Picano E et al, ESC 2016 (abstract)
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
Study hypothesis
EVENTS
NO EVENTS
•
B-lines
More
Less
•
Severe MR
More
Less
•
TAPSE
Higher
Lower
•
E/e’
Higher
Lower
•
LV elastance Higher
Lower
Acronym:
SEHCA
Project 3 : Stress echo in Hypertrophic
cardiomyopathy for risk stratification through
ischemia-related and hemodynamic parameters
Stress echo in HCM : coronary flow reserve makes the difference
Ciampi Q et al, ESC meeting 2016
Flow Chart Protocol # 3 , SEHCA
HCM,NYHA class 1 or 2,EF > 45%, no CAD
TTE
EXERCISE
(dip or dob)
Yearly TTE follow-up
Study hypothesis
EVENTS
NO EVENTS
•
LVOTG
More ?
Less ?
•
Severe MR
More
Less
•
WMSI >1
More
Less
•
E/e’
Higher
Lower
•
CFVR
Lower
Higher
Acronym:
SEDIA
Project 4 : Stress echo in diastolic heart failure
HFrEF: EDV reserve matters (diastolic pressure-volume better than pressure only!)
HFpEF
HFrEF
Controls
(Shimiaie et al, JACC heart fail 2015)
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
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 (no severe VHD or R
WMA): E/e’ < 13.Possible
LVH and LA dilation (> 34
mL/m2)
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
Study hypothesis
EVENTS
NO EVENTS
•
E/e’ Stress
Higher
Lower
•
PASP Stress Higher
Lower
•
DT Stress
Shorter
Longer
•
EDVI Stress Smaller
Larger
•
B-lines Stress
More
Less
Acronym:
SETA
Project 5 : Stress echo after TAVI:
focus on mitral regurgitation
Beneficial effects of TAVI on MR
Costantino F et al, CardioUltra 2015
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
Study hypothesis
MORE EVENTS
Less EVENTS
Post-TAVI rest MR
More ?
Less ?
Post-TAVI stress MR
More
Less
Post-TAVI rest AoGr
More
Less ?
Post-TAVI stress AoG
More
Less
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)
Stress echo Outdoor
•18 subjects (10 males)
•mean age 45±10 years
Gokyo
m s.l. 6000
5130
5000
Namche Bazaar
4790
4000
*
60
3440
50
Gorak Shep
3000
*
*
40
30
2000
1350
20
1000
Kathmandu
Kathmandu
1350
10
0
0
2
Cardiac and chest echo
6
10
14
20
Pratali L. et al Critical Care Medicine 2010
days
LUS-driven therapy and expected results
Study protocol
Acronym:
SETOF
Project 7 : Stress echo in operated tetralogy of Fallot
SE in adult repaired ToF
RV FAC decreases at exercise
75
70
65
60
55
50
45
40
35
30
25
20
15
10
RV FAC increases at exercise
75
70
65
60
55
50
45
40
35
30
25
20
15
10
RV FAC1.00
at Rest
RV FAC at Exercise
NON RESPONDERS (49 pts)
1.00
RV FAC
at Rest
RV FAC at Exercise
RESPONDERS (74 pts)
L. Ait Ali et al, J Am Soc Echocardiogr. 2014
Flow Chart Protocol # 7 , SETOF
Repaired ToF or TOF-like, age >10 years, NYHA 1 or 2
TTE
RV reserve is important !
But LV systolic and diastolic
reserve can also be
important
EXERCISE
(dip or dob)
Yearly TTE follow-up
Study hypothesis
MORE EVENTS
Less EVENTS
RV TAPSE stress
Lower
Higher
RV FAC % stress
Lower
Higher
LV Peak stress E/e’
Higher
Lower
Lower
Higher
LV Δ EF
Acronym:
DOPSAH
Project 8 : Doppler Stress echo for prediction of
Pulmonary Arterial Hypertension
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
Flow Chart Protocol #8, DOPSAH
GROUP A : Subjects at risk of PAH
without diagnosis of PAH
(Group 1 ESC GL)
GROUP B: Patients with diagnosis of PAH
(Group 1 ESC GL)
Without contraindications to exercise
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
Study hypothesis
•
•
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
Mean PAP/ min exercise
Higher
Lower
RV contractile reserve
Lower
Higher
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
Incremental value of CFR over wall motion to predict mortality
Overall mortality %
50
n = 4,313
p < 0.0001
40
39
30
20
12
10
7
3
0
0
Subjects at risk
SE + / CFR <2
SE + / CFR >2
SE - / CFR <2
SE - / CFR >2
516
249
903
2645
12
2
365
730
1095
3
Follow-up (years)
120
108
513
2018
53
69
316
1292
24
42
209
799
Cortigiani. JACC Cardiovasc Imaging 2012;5:1079
1460
4
10
23
125
405
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
Study hypothesis
EVENTS
NO EVENTS
•
WMSI
Higher
Lower
•
CFVR
Lower
Higher
•
LV elastance Lower
Higher
Acronym:
GENES
Project 10 : Genetic stress echo
in hypertrophic cardiomyopathy, familial dilated
cardiomyopathy and familial pulmonary hypertension
Genetic stress echo in HCM, PPH and DCM
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
Study hypothesis
Genotype pos
Genotype neg
High LVOTG,Low CFVR in HCM
Higher
Lower
PASP e PAP/CO slope in PAH
Lower
Higher
LV elast ance and CFVR in DC
Will develop disease at f-up
Lower
More likely with SE+
Higher
More likely with SE +
“Now, here, you see, it takes all the running you can do, to
keep in the same place. If you want to get something else,
you must run at least twice as fast as that “
(Lewis Carroll, Through the looking glass)
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