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Nuclear Cardiology andHeart Failure

in the Multimodality Arena

Nuclear Cardiology andHeart Failure

in the Multimodality Arena

Ioannis V. Vassiliadis, MD, Ph.D, FESC, FACC, FASNCDirector in Cardiology, Athens Euroclinic Hospital

• Despite improvement in health care systems morbidity and mortality remainhigh.

• The use of imaging techniques for patients with heart failure has evolvedsubstantially over the years. There is a need to identify imaging approachesthat have a positive impact on therapy decisions, patient outcomes andcosts.

Heart Failure represents the final commonpathway for most forms of heart disease .

Question to be answered in a particularpatient

• Ischemic vs non-ischemic etiology• Selection of therapy :Medical, intervention ,

viability indication for revascularization• Selection of candidates to device Therapy

CRT/ICD• Risk stratification

1) to determine the impact of emerging imaging strategies, on relevant clinical outcomes anddecision making in patients with HF

2) to establish standardization quality assurance (QA) measures and central databases in order toachieve reliable outcome driven research

3) to apply this as a platform for evaluation of new and emerging imaging biomarkers in HF.

OBJECTIVES

F. Caobelli, F.Bengel, J Nuc Cardiol 2015

The many Faces of Nuclear Cardiology in HF

Nuclear Cardiology in Heart Failure can be used:

TO DIAGNOSE THE CAUSE OF HF1. To detect myocardial ischemia/viability2. To diagnose the severity of LV systolic and diastolic dysfunction in HF3. Cardiac innervation – mIBG planar and SPECT4. To asses metabolism with free fatty acid imaging

TO ASSESS OR MONITOR THE IMPACT OF MEDICAL OR INTERVENTIONAL Tx

EMERGING APPLICATIONS OF SPECT-

1. Detection of arrythmogenic ventricular cardiomyopathy and to guide2. Resynchronization therapy ands ablation3. Heart transplantation4. Myocardial ACE and AT1R imaging

Coronary artery disease is the maincause of heart failure and thatreversibility of LV dysfunction dependson the amount of viable tissue.

Pts with ischemic HF have worseprognosis than those of any etiologybut may show dramatic improvementwith timely revascularization

Guidelines for Heart Failure JACC 1995;26Felker GM. J Am Coll Cardiol 2002,39,210

Tl-201SPECT STRESS-REST–REINJECTIONIMAGING

PET- Viability

PARR-2(PET and Recovery Following revascularization–

Phase 2) study, the first large randomized trialusing an FDG-PET–guided approach tomanagement of patients with coronarydisease and severe left ventriculardysfunction.Event rate 36%with standard carevs 30%with PET guided

Beanlands JACC 2007

gatedPET:LVEF 26%

Courtesy M. Schweiger

“Large ischemia” involving more than 20% ofthe LV volume

SPECT in Heart Failure can be used:1. To diagnose the cause of HF2. To detect myocardial ischemia/viability3. To diagnose the severity of LV systolic and diastolic dysfunction in HF4. Molecular tissue function (innervation) MIBG planar/SPECT and PET5. To asses metabolism with free fatty acid imaging6. To assess or monitor the impact of medical or interventional treatment7. Emerging Applications of SPECT-

Detection of arrythmogenic ventricular cardiomyopathy and to guideresynchronization therapy ands ablationHeart transplantationMyocardial ACE and AT1R imaging

Assessment of ventricular functionin pts with Heart failure


• Selection of patients for coronary arteryby pass surgery

• Detection of other causes of HF• Monitoring of thrombolytic therapy• Measures cardiotoxic effects of drug

treatment e.g. adriamycin

Role of ECG-Gating for MyocardialPerfusion SPECT

Role of ECG-Gating for MyocardialPerfusion SPECT

Improved diagnosticaccuracy for CAD(less equivocal

results,identification of

attenuation)

Incremental value for risk assessment(global functional parameters)

Enhancedviability

detection(additionalregional

functionalinformation)

Diagnosis and assessmentof ventricular aneurysm


Β-receptorSynaptic

cleft

ATP cAMPG-proteins

Nuclear scintigraphy is the only method currently available!

Υπολογισμός των H/M (heart to mediastinum ratio) και WR(washout rate) με επίπεδες εικόνες MIBG

H/M Ratio of MIBG Uptake:Measure of Specific to Non-specific Uptake

ADMIRE-HF Myocardial 123I-mIBG Imaging in HF. Jacobson et al. JACC 2010.

Regional Myocardial Sympathetic DenervationPredicts the Risk of Sudden Cardiac Arrest in

Ischemic Cardiomyopathy - PAREPET

Metabolic SPECT Imaging Tracer: I-123 BMIPPP ( Beta Methyl Iodo Phenyl

Pentadecanoic Acid) Indication : Assess myocardial viability in pts with

ischemic cardiomyopathy combined with a perfusiontracer (TL-201) , creating miss-math images

Image marker: Uptake and redistribution with longresidence time in the myokardium

Metabolic stunning memory: Depicts an ischemicevents in the detection of chest pain syndrome in theER that can be imaged later

SPECT Cardiac Imaging can be used:

1. To diagnose the cause of HF2. To detect myocardial ischemia/viability3. To diagnose the severity of LV systolic and diastolic dysfunction in HF4. Molecular tissue function (innervation) – mIBG planar and SPECT5. To asses metabolism with free fatty acid imaging6. F/u post heart transplantation7. To assess or monitor the impact of medical or interventional treatment8. Emerging Applications of SPECT- Detection of arrythmogenic ventricular

cardiomyopathy and to guide resynchronization therapy• Myocardial ACE and AT1R imaging• Image-guided VT ablation

C-11 HED: Reinnervation of Neuronal Fibers that areCut During Heart Transplantation

CT(left) /SPECT-MIBG(right) imaging of aheterotopic transplant.No uptake intransplanted heart ,mild uptake in thenativeKennethSK. J Heart Lung Transplant 2006

SPECT in Heart Failure can be used:

1. To diagnose the cause of HF2. To detect myocardial ischemia/viability3. To diagnose the severity of LV systolic and diastolic dysfunction in HF4. Cardiac innervation – mIBG planar and SPECT5. To asses metabolism with free fatty acid imaging6. F/u post heart transplantation7. To assess or monitor the impact of medical or interventional treatment8. Emerging applications of SPECT• Detection of arrythmogenic ventricular cardiomyopathy• Image-guided VT ablation and resynchronization therapy• Myocardial ACE and AT1R imaging

0

20

40

60

80

100

120

placebo metoprolol

MIB

G u

ptak

e (c

ts/v

oxel

)

baseline6 months

de Groot,, de Milliano, van Eck-Smit et al.J Nucl Cardiol 1999;6:S5

123I-MIBG in congestive heart failure:effect of metoprolol

123I-MIBG in congestive heart failure:effect of metoprolol

n=10 n=39

123I-MIBG in congestive heart failure:effect of enalapril

123I-MIBG in congestive heart failure:effect of enalapril

before 6 weeks treatment

Somsen et al, Heart 1996;76:218-22

SPECT in Heart Failure can be used:

1. To diagnose the cause of HF2. To detect myocardial ischemia/viability3. To diagnose the severity of LV systolic and diastolic dysfunction in HF4. Cardiac innervation – mIBG planar and SPECT5. To asses metabolism with free fatty acid imaging6. F/u post heart transplantation7. To assess or monitor the impact of medical or interventional treatment8. Emerging applications of SPECT• Detection of arrythmogenic ventricular cardiomyopathy• Image-guided VT ablation and resynchronization therapy• Myocardial ACE and AT1R imaging

Arrhythmiogenic Right VentricularCardiomyoparthy

The high probability of exercise-induced tachyarrhythmia orsudden cardiac death and its affinity to catecholamine effectconstitutes a strong indication of the sympathetic nervesystem contribution to the pathophysiology ofarrhythmogenesis

MIBG - SPECT και C-11 HED - PET provide evidence ofsegmental or global absence (defects) of sympatheticinnervation with reduce uptake and storage ofcatecholamines at pre-synaptic receptors of the left ventricleas well as diminution of beta meta-synaptic receptors.

Integration of 3-D Scar Models fromThallium SPECT to Guide VT Ablation

Results - mIBG GuidedSuccessful Ablation sites

Myocardial Sympathetic Innervation andLong-Term LV Mechanical Unloading

SPECT/CT Images of Over-expressedHuman ACE Mutant Transgenic Rat

Novel Imaging Targets of Local MyocardialSurface RAS for Exploratory Translation

Conclusions It is fair to say that no one modality at the moment can answer every

question we may have in this situation in one sitting Nuclear Cardiology Imaging can be used for the stratification of pts with

HF of CAD or CM origin and the assessment of treatment strategies Together with myocardial perfusion, imaging, cardiac sympathetic

function, provides information on the extent of regional cardiacdenervation which is often larger than that of ischemia/scar

Emerging applications such as molecular imaging of SPECT such asdetection of arhythmogenic ventricular cardiomyopathy , image-guidedVT ablation and resynchronization therapy, heart transplantationprograms and myocardial ACE and AT1R imaging is expected to gainmore widespread clinical use.

Unsettled issues regarding viability andprognosis

Does revascularization improve survival inpts with viable myocardium compared tomedical therapy?

The annual mortality was significantly lower inthose treated with revascularization (3.2%) thanthose treated medically (16%) irrespective of thediagnostic technique used

Does viability assessment improveselection of pts with LV dysfx forrevascularization?

Pts with viable myocardium undergoingrevascularization the annual mortality rate was3.2% compared to 7.7% in those withoutviability. Hence non-invasive evaluation iscrucial

Is improved oucomes afterrevascularization related to theimprovement of LV fx?

Lack of data addressing link between post-opimproved LV fx and improvement insurvival. STICH trial started 2002 will givethe answer in 2008!!!.

Bonow R. Ed.JACC 2002;39 Allman KC. JACC 2002;39

Results – Innervation Defect andVoltage Scar –

Results - Successful Ablation sites-

McMurray J. Eur J Heart Fail 2012;14:803–869.

BIOMARKERS: ST2 and galectin. Knowledge of the biomarker in general leads to no specific decision and thus is of verylimited clinical valueUdelson J. J Nucl Cardiol 2015;22:975–9.

CTA: CT-based assessment of FFR is an exciting development for evaluation of CAD, but it has not been studied in thesetting of HF and systolic dysfunction, and its correlation with downstream tissue viability—which is what we really needto know—is unknown.Min JK, . JAMA 2012;308:1237-45.

STRESS ECHO: The performance of stress echocardiography for detection of CAD in the setting of baseline abnormalitiesof regional or global function is modest as they point out. Techniques such as strain imaging, while of great interestpathophysiologically from an academic standpoint, have no clear practical implication in HF setting.Mullens W, Circulation 2009;119:62-70, Santos M, Circ Heart Fail 2015

NUCLEAR CARDIOLOGY: SPECT stress/rest imaging like echocardiography has modest performance for detectingCAD in the setting of HF but has high negative predictive value to rule out extensive CAD likely related directly to thecardiomyopathic state. SPECT and PET techniques for assessing viability and potential benefit of revascularization havea solid literature base and have been widely used for that purposeCaobelli F, J Nucl Cardiol 2015, Soman P, J Nucl Cardiol 2009;16:82-91

MOLECULAR NUCLEAR IMAGING : Imaging sympathetic innervation is theoretically attractive to potentially assessarrhythmic risk and perhaps guide ICD decisions as they suggest, but none of the data published to date are adequatelypowered to enable identification of low risk patients with sufficient confidence to allow a decision not to implant an ICD insomeone who otherwise has a clinical indication,Wessler BS, J Nucl Med 2015;56:20S-4S.

1) to determine the impact of emerging imaging strategies, on relevant clinical outcomes anddecision making in patients with HF

2) to establish standardization quality assurance (QA) measures and central databases in order toachieve reliable outcome driven research

3) to apply this as a platform for evaluation of new and emerging imaging biomarkers in HF.

OBJECTIVES

Level II ProjectICD: (Scar/Viability), (HED/MIBG)CRT: (Dysynchrony-Lateral scar-Metabolic reserve)

MYOCARDIAL VIABILITYMYOCARDIAL VIABILITY

“More than 50% of Q wave infarct regions on ECG,or of segments with persistent defects on TL-201scintigraphy or asynergy in ventriculography, haveresidual metabolic activity indicative of viablemyocardium”.

Marschall RC et al. Circulation 67:766, 1983Tamaki N et al. Eur. J. Nuc. Med. 11:246,1985Tillisch J et al. N. Engl. J. Med. 314:884, 1986

Brunken R et al. Circulation 73:951, 1986

What SPECT can do?

ISCHEMIC CASCADE

Information provided byradionuclide ventriculography

studies in pts with heart failure



• Left and right ventricular function• Volume of ventricular cavities• Regional wall contraction

Nuclear Cardiology in Heart Failure can be used:

TO DIAGNOSE THE CAUSE OF HF1. To detect myocardial ischemia/viability2. To diagnose the severity of LV systolic and diastolic dysfunction in HF3. Cardiac innervation – mIBG planar and SPECT4. To asses metabolism with free fatty acid imaging

TO ASSESS OR MONITOR THE IMPACT OF MEDICAL OR INTERVENTIONAL Tx

EMERGING APPLICATIONS OF SPECT-

1. Detection of arrythmogenic ventricular cardiomyopathy and to guide2. Resynchronization therapy ands ablation3. Heart transplantation4. Myocardial ACE and AT1R imaging

RNA MEASUREMENTSRNA MEASUREMENTS

1. Ejection fraction2. Wall motion abnormalities3. Volumes4. Diastolic function indices5. Dimensions

Differences in pathophysiologic substrate ofimaging modalities to detect viability

SPECT imaging reflects intracellular processes ,detecting the anatomic and functional integrityof cardiomiocytes membrane which transportskations

DES assesses ventricular contractile reserve PET images blood flow and metabolism MRI hyperenhancement identifies scarred

myocardium



• Selection of patients for coronary arteryby pass surgery

• Monitoring of thrombolytic therapy• Measures cardiotoxic effects of drug

treatment e.g. adriamycin

RNA MEASUREMENTSRNA MEASUREMENTS

1. Ejection fraction2. Wall motion abnormalities3. Volumes4. Diastolic function indices5. Dimensions





• Left and right ventricular function• Volume of ventricular cavities• Regional wall contraction

Myocardial Viability and Survivalin Ischemic Left Ventricular Dysfunction

Robert O. Bonow, MDOn behalf of the STICH Trial Investigators

Myocardial Viability and Survivalin Ischemic Left Ventricular Dysfunction

Robert O. Bonow, MDOn behalf of the STICH Trial Investigators

Postsynaptic CardiacImaging

Postsynaptic CardiacImaging

• PET or SPECT– Beta-receptors– Alpha-receptors (Alpha-1, Alpha-2)– Adenosine (A2A)– Muscarinic (M2)

Presynaptic CardiacImaging

Presynaptic CardiacImaging

• SPECT– I-123 MIBG

• PET– C-11-HED– F-18-Fluorodopamine– F-18-Fluoronorepinephrine

LV Ejection Fraction and Survivalin Chronic CAD

LV Ejection Fraction and Survivalin Chronic CAD

EF 50% (n=8640)EF 35-49% (n=2547)EF < 35% (n=1200) P<0.001

Time (years)

Surv

ival D

urin

g M

edica

l The

rapy

(%)

Emond et al. Circulation. 1994;90:2645-57

0

20

40

60

80

100

0 2 4 6 8 10 12 14

NeurotransmissionImaging in Cardiology

NeurotransmissionImaging in Cardiology

• Cardiac neuronal control is important– Autonomic regulation of LV and RV function

and perfusion– Receptor mediated effects of drugs

Nuclear scintigraphy is the onlymethod currently available!

I-123 mIBG: Imaging CardiacInnervation in Heart Failure

0

20

40

60

80

100

120

140

placebo (n=10) 50 mg (n=5) 100 mg (n=9) 150 mg (n=25)

MIB

G up

take

(cts

/vox

el)

baseline6 months

Figure 4

de Groot, de Milliano, van Eck-Smit et al,J Nucl Cardiol 1999;6:S5

123I-MIBG in congestive heart failure123I-MIBG in congestive heart failure

123I-MIBG in congestive heart failure123I-MIBG in congestive heart failure

normal congestive heart failure

Somsen, van der Wall, van Vlies et al,Int J Cardiac Imaging 1997;

ΜΕΛΕΤΗ ΣΥΜΠΑΘΗΤΙΚΗΣ ΕΝΝΕΥΡΩΣΗΣΤΗΣ ΚΑΡΔΙΑΣ

ΜΕΛΕΤΗ ΣΥΜΠΑΘΗΤΙΚΗΣ ΕΝΝΕΥΡΩΣΗΣΤΗΣ ΚΑΡΔΙΑΣ

• Η πρόσληψη επισημασμένων νευροδιαβιβαστών(νορεπινεφρινη-μεταραμινόλη) αντανακλά φυσιολογικήδραστηριότητα και τόνο του ΣΝΣ.

• Οι ραδιοισοτοπικές τεχνικές είναι οι μόνες από τιςαπεικονιστικές τεχνικές με αυτή τη δυνατότητα.Απεικονίζονται με SPECT 123I-metaiodobenzyl gua-nidine(MIBG). Με ΡΕΤ χρησιμοποιούνται 18F-metaraminol και11C-HED.

• Κλινική εφαρμογή στην πρόγνωση ασθενών με καρδιακήανεπάρκεια, με κοιλ. Αρρυθμίες/ηλεκτρικο θάνατο,αναδιαμόρφωση αρ. κοιλίας και σε μεταμοσχεύσεις.

SPECT for the detection of viabilityConclusions

Viability testing does not identify high risk patientssubgroups and predicts

- Respond to b-blockers therapy- Responnce to resynchronization therapy- Response to revascularization

Viability testing should not be considered a prerequisite fordecisions regarding medical vs surgical management inpatients with ischemic LV dysfunction

SPECT MPI is a good means to detect and predicts benefitfrom revascularization

Απεικόνιση της αδρενεργικής νεύρωσης του μυοκαρδίου:I-123 MIBG (μετα-ιωδο-βενζυλ-γουανιδίνη)

Συγγενής της νοραδρεναλίνης Kαρδιακή ανεπάρκεια ΝΟR MIBG MIBG σε ΕΜ, μυοκαρδιοπάθειες Επιτυχής θεραπεία με α-ΜΕΑ MIBG (ασχέτως NOR) MIBG = o καλύτερος δείκτης μακροζωίας (!)

Primary Endpoint Events

2-Year Cardiac Death and All-CauseMortality vs. H/M

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