doppler - cip determining optimal non-invasive parameters for the prediction of left ventricular...
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DOPPLER - CIP
Determining Optimal non-invasive Parameters for the Prediction of Left vEntricular morphologic and functional Remodeling in Chronic Ischemic Patients
DOPPLER - CIP
KU Leuven, Belgium Frank RademakersKU Leuven, Belgium Jan DhoogeTurku University Hospital, Finland Juhani KnuutiSERMAS, Madrid, Spain Jose ZamoranoCNR, Pisa, Italy Rosa SicariUniversity of Pisa, Italy Vitantonio Di BelloKing’s College London, UK Mark MonaghanUniversity Linkoping, Sweden Jan EngvallRikshospitalet Oslo, Norway Thor EdvardsenKing’s College London, UK Eike Nagel
AMID, Sulmona, Italy Giovanni Tonti
Objective• Which non-Invasive Parameters
– Which parameters: clinical, exercise, morphology, function, perfusion, …
– Which method/technique: echo, nuclear, MR
Predict• Remodeling
– Morphological– Functional
Dilated (failing) heart
IschemiaInfarctionLoadingValve diseaseMyopathies…
Objective
• Which non-Invasive Parameters– Which parameters: clinical, exercise, morphology,
function, perfusion, …– Which method/technique: echo, nuclear, MR
Predict• Remodeling
– Morphological: EDV increase– Functional
Patient in/exclusion criteria Inclusion: Antecedents of myocardial ischemia defined as any one of the following:
• Positive stress testing according to individual center’s criteria (MR, Mibi, cycloergometry, stress TTE)
• PTCA/CABG in history• Infarction in history
Exclusion: • ACS in 3 preceding months• Valvular disease more than moderate• Pacemaker/permanent Afib• Conditions limiting 2-year survival
Study Design
• Multi – centre– Stratification: CAD with/without previous MI ± EF
impact
• Anonymized core-lab analysis• ECG bicycle (with VO2 max)
• Quality of Life questionnaire• Clinical data• 2 or more imaging tests including stress
Imaging performed
Modalities Combined stress studies
Follow - up
• Clinical: optimal treatment based on guidelines, using imaging data
• 2-year evaluation– Clinical events– Quality of Life– Imaging to determine remodeling
Inclusion Fup
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
2010 2011 2012
Inclusion
Period: end january 2010 – end December 2012 (3years)Total number of patients: 676
• 617 patients with follow-up (drop-out: 8% (N= 59))• 10 patients died during 2y follow-up
- 2 acute coronary syndromes- 8 non cardiovascular causes
• 291 (47%) were hospitalized
•174 (28%) received invasive coronary treatment (80% elective PCI)
Definition of Remodeling• Using re-test data: remodeling threshold for relative change and for absolute change in an
'average' patient
• EDV mean change for remodeller using cascade definition with relative change– 35 % or 39 ml
Re-test 2.0*SD
MethodICC
SD of Standardized
Difference
Absolute Increase
Relative Increase
MRI 0.99 0.059 14 ml 12 %
E3D 0.74 0.200 30 ml 40 %
A4CH 0.65 0.191 34 ml 38 %
A2CH 0.64 0.198 33 ml 40 %
PARA 0.71 0.142 25 ml 28 %
% of patients 15 percent 20 percent
Statistics• Group parameters in physiologic categories:
– Clinical– Exercise– LV morphology– LA morphology– Global systolic function– Global diastolic function– Regional function– Perfusion– Loading
• Principal component analysis of all parameters per group• Compare groups of parameters using cross-validated c-
statistics
Baseline Parameters
LV EDVMeasured with MR
120 140 160 180 200
EDV
0.2
0.3
0.4
0.5E
stim
ated
Pro
bab
ility
95% Confidence IntervalPredicted Probability of EDV Remodeling
Plot of Predicted Probability of Remodelling According to Logistic Regression Model using relative change
LV EDV @ BL
Est
ima
ted
pro
ba
bili
ty f
or
Re
lativ
e c
ha
ng
e E
DV
120 140 160 180 200
xVar
0.0
0.2
0.4
0.6
0.8
Est
imat
ed P
roba
bilit
y
YesNoYesNoPrior MI
p(Interaction)=0.7254
p(Prior MI)=0.1648
Previous Myocardial InfarctionE
stim
ate
d p
rob
ab
ility
fo
r R
ela
tive
ch
an
ge
ED
V
LV EDV @ BL
Focus on small LV EDV (<145ml)“REMODELERS” @ BL have
• Higher NYHA, lower QoL• Similar risk profile but higher Troponin• No more reported previous MI• Borderline more scar on MR LE• Smaller LV with higher LV mass• No worse global function by EF but
– Lower global strain and strain rate– Worse regional function @ rest and during low stress
• More angina during exercise test• No regional ischemia on SPECT or MR perfusion
0.5 1.0 1.5 2.0 2.5
EDVm
0.2
0.4
0.6
0.8E
stim
ated
Pro
babi
lity
95% Confidence IntervalPredicted Probability of EDV Remodeling
Remodeling versus EDV/LVM in EDV < 145ml
LV EDV/LVM @ BL
Est
ima
ted
pro
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ty f
or
Re
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e E
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Effect LVM in model with EDV for EDV <145ml
80 100 120 140 160
LVM
0.1
0.2
0.3
0.4
Est
imat
ed P
roba
bilit
y
95% Confidence IntervalPredicted Probability of EDV Remodeling
LV Mass @ BL
Est
ima
ted
pro
ba
bili
ty f
or
Re
lativ
e c
ha
ng
e E
DV
Conclusion In this group of stable CAD patients
– Morphologic remodeling is best predicted by morphologic characteristics of the LV, in particular EDV
– EDV measured by MRI showed to be the most prognostic.– Remodeling is frequently observed– Occurs often in normally sized ventricles with
• Decreased EDV/LVM– Goes against hypothesis of increased wall stress as cause/mechanism for
remodeling – Potentially related to
• Ongoing ischemia due to microvascular dysfunction• Optimization of wall stress
– Quantification of perfusion needed: • CFR , microvascular dysfunction?
DOPPLER-CIP team
Leuven
AMIDGianni PedrizzettiGiovanni Tonti
Frank RademakersJan D’hoogePiet ClausValerie RobesynRuta JasaityteOana MireaJens-Uwe VoigtKaatje GoetschalckxAn BelmansAna DarabanLieven HerbotsTom Standaert
Linkoping
Jan EngvallTino EbbersGidby GunborgLars-Ake LevinMagnus Husberg
London - KCL
Eike NagelValentina PuntmannRadmila Maksimovic
London - KCH
Mark MonaghanMichelle AndrewsAlexandros PapachristidisPeter Pearson
Madrid
Pepe ZamoranoCovadonga Fernandez-GolfinLuis Miguel Rincon Diaz
Oslo
Thor EdvardsenMargareth RibeSebastian Imre SarvariNina Hasselberg
Pisa - CNR
Rosa SicariLuna GarganiGennaro D’AngeloMauro Raciti
Uni Pisa
Vitantonio Di BelloIacopo FabianiLorenzo Conte
TurkuHeikki UkkonenJuhani Knuuti