PSCC RMH CARDIAC AMYLOD CARDIAC SARCOID PET/CT FDG

1. Cardiology Updates 2023
MCQs interactive session
DR IHAB SULIMAN FESC
Recertified CBNC 2016

2. XXXX
• Strongly Positive on all parameters

3. • 66y A+ 157cm 74kg 30.02kg/m² 1.80m²
• 66 years old lady with DM, HTN, DLP and CVA
and atypical CP referred for PET /CT stress test

4. ECG 16/5/2016

7. • She developed Ischemic Chest pain during
Regadenoson(lexiscan) infusion.

16. Conclusion
• PET/CT stress test is a very useful test to
detect and quantify myocardial ischemia.

17. • Sarcoidosis

18. • This is a 70 years old Female known to have
Non-Ischemic Cardiomyopathy asymptomatic
from cardiac point of view.
• Patient admitted 30/4 to ouside hospital
with syncope and VT and DC shock 100 J
once and subsequently AICD was inserted.

19. • F 71y B+ 147cm 52kg 24.06kg/m² 1.46m²

20. • A 70 year old female with history of previous
Normal Coronaries on 09/May/2016, and
AICD due to cardiac arrest , and with the
following risk factors: hypertension,
hyperlipidemia and diabetes; was referred for
perfusion PET study to evaluate for Cardiac
sarcoidosis.

21. • The patient was prepared for the test with high fat/low carbohydrate
diet. After 15 hours fast a rest rubidium 82 study was done. The p
atient was injected with IV UFH 50 units/kg. The patient was then i
njected with 5.55mCi of F-
18 Deoxy Glucose, and after standard uptake period of 120 minutes,
PET/CT imaging was performed.
The rest Rubidium images showed a severe perfusion defect in the b
asal anterior wall, and a moderate perfusion defect in the mid inferi
or wall.
FDG images showed 2 hot spots one in the mid inferior wall and an
other one in the mid anterior and basal anterolateral wall.
These findings are consistent with active inflammatory cardiac diseas
e.

25. CMR 11/5/2016

30. • PET/CT is a valuable technique to study and
aid in the diagnosis of Cardiac inflammatory
disease like cardiac sarciodosis.

31. • In cardiac PET-CT, when using F-18 FDG to
investigate cardiac sarcoid, a cardiac fasting
protocol is used to switch myocardial metabolism
from glucose to fatty acids. How long should the
patient fast for?
• 2 hours
• 6 hours
• 10 hours
• 18 hours
• 36 hours

32. • A cardiac fasting protocol to suppress
myocardial uptake typically involves a low
carbohydrate diet for 1 day followed by an
extended 18 hour fast, this switches the
heart from using glucose to fatty acids. Good
myocardial suppression helps to identify
pathological uptake within the heart.

33. Q2
• In the setting of progressive massive fibrosis
pattern on CT, which of the following would most
strongly favor sarcoidosis over silicosis as the
underlying cause?
• absence of lung parenchymal calcification
• elevation of the hila
• mediastinal lymph node calcification
• occupational history of mining
• pulmonary nodules

34. • Progressive massive fibrosis appears as conglomerate
mass-like opacities within the upper zones with volume
loss and elevation of the hila due to fibrosis. It can be
caused by silicosis (or other less common
pneumoconioses) or sarcoidosis.
• Both silicosis and sarcoidosis often result in mediastinal
lymph node calcification and pulmonary nodules,
however lung parenchymal calcification is a prominent
feature only in silicosis and is rarely present in
sarcoidosis, and therefore this can be a very useful
feature in distinguishing between the two causes. An
occupational history of mining would favor silicosis

35. Q3

37. • Correct Answer is B) : Patchy inflammation and no scar
There is evidence of multiple perfusion defects (Top
images) with enhanced FDG uptake in the same distribution
as the perfusion defects (Bottom images). This perfect
perfusion defects pattern with matched FDG uptake
pattern is the whole-mark of identification of inflammation
by PET.
Patient in addition had peri-hilar lymphnodes uptake which
were biopsied and confirmed the presence of pulmonary
sarcoidosis with now cardiac involvement.
•

38. Q4

39. • Correct Answer is D) : Necrosis in RCA and LCx territories
The pts was submitted to single day dipyridamole/rest CZT
scan. Baseline ECG showed q waves in DII, DIII and aVF. No
abnormalities at peak stress.
The images showed a a fixed defect indicative of infarction
without reversibility to suggest classical stress-related
ischemia.
Gated images indicated akinesia of inferior wall, lateral wall
and apex. Rest EF: 38%, stress 35%.
MRI confirmed the absence of viability in the same
territories.
The invasive coronary anatomy showed chronic proximal
occlusion of LCx (dominant) with hypoplasia of RCA.

40. Q5

42. • Correct Answer is B) : AL Amyloidosis
The images show a diffuse cardiac uptake
of [18F]-florbetaben, indicating the presence of
cardiac AL amyloidosis. [18F]-florbetaben is one
of the possible PET tracers that, according to the
published results, can be used for the evaluation
of AL Amyloidosis. Late static [18F]-florbetaben
PET acquisitions can discriminate cardiac
involvement due to AL amyloidosis from ATTR
amyloidosis and from other non-CA conditions
mimicking infiltrative disorders.

43. Q6
• 61 year old male, dyspnoea on effort
Previous revascularization by PCI on LAD and
RCA.
What is the best interpretation of these PET
images?
A) Ischemia on LAD
B) Ischemia on LCX
C) Ischemia on RCA
D) Ischemia on MVD

45. A6
• 61 year old male, dyspnoea on effort
Previous revascularization by PCI on LAD and
RCA.
What is the best interpretation of these PET
images?
D) Ischemia on MVD

46. Q7
• 56 yo man, with dyspnoea on effort and
vertigo.
Which is the best interpretation of these
images?
A) Cardiac Amyloidosis
B) Cardiac Endocarditis
C) Cardiac Sarcoidosis
D) Normal scan

48. A7

49. • Amyloidosis and sarcoidosis are systemic
diseases that affect multiple organ systems.
Accurate diagnosis of cardiac amyloidosis and
sarcoidosis is particularly important because
cardiac involvement can be fatal. Amyloidosis
is characterized by the deposition of amyloid
fibrils, and cardiac amyloidosis is classified
into amyloid immunoglobulin light chain (AL)
and amyloid transthyretin (ATTR) types.

50. Infiltrative Cardiomyopathy
O Characterized by the deposition of abnormal
substances (protein, cells, etc.) within the
heart causing myocardial dysfunction
O Diagnosis requires a high degree of suspicion
O Imaging and laboratory testing are essential
O Represents cardiac manifestation of a
systemic disease

51. Causes of Infiltrative CMs
OAmyloidosis
OSarcoidosis (and other inflammatory diseases)
O Hemochromatosis
O Fabry disease (lysosomal storage)
O Danon disease (LAMP2 deficiency)
O PRKAG2 deficiency
O Friedreich ataxia (frataxin mutation)
O Hypereosinophilic syndromes
O Carcinoid

52. Amyloidosis
• Systemic process resulting in extracellular
deposition of abnormal insoluble fibrils
• Derived from a variety of serum proteins
• Can affect one or more organs
• Results in organ dysfunction due to tissue
infiltration
Falk RH, Circulation 2005, 2011

53. Amyloidosis is a Multisystem
Disease
CNS MANIFESTATIONS
• Progressive dementia
• Headache
• Ataxia
• Seizures
• Spastic paresis
• Stroke-like episodes
AUTONOMIC NEUROPATHY
• Orthostatic hypotension
• Recurrent urinary tract
infection (due to urinary retention)
• Sexual dysfunction
• Sweating abnormalities
CV MANIFESTATIONS
• Conduction blocks
• Cardiomyopathy/cardiac hypertrophy
• Systolic and/or diastolic dysfunction
• Atrial and/or ventricular arrhythmias
• Mild valvular regurgitation
• Shortness of breath
• Fluid retention (edema, ascites)
PERIPHERAL SENSORY MOTOR NEUROPATHY
• Neuropathic pain
• Altered sensation (i.e., change
in sensitivity to pain and temperature)
• Numbness and paresthesia
• Muscle weakness
• Impaired balance
• Difficulty walking
RENAL
• Proteinuria
• Renal failure
CARPAL TUNNEL SYNDROME
OCULAR MANIFESTATIONS
• Vitreous opacification
• Glaucoma
• Abnormal conjunctival vessels
• Papillary abnormalities
GI MANIFESTATIONS
• Nausea and vomiting
• Changes in GI motility
(i.e., diarrhea, constipation,
gastroparesis, early satiety)
• Unintentional weight loss
Conceição et al. J Peripher Nerv Syst 2016;21:5–9

54. Cardiac Amyloidosis Presentations
• Heart failure (dyspnea, edema, etc)
• Angina
• Syncope/presyncope (conduction disease)
• Sudden death
• Unexplained “hypertrophy”
• ECG/Echo abnormalities
• Pericardial disease
• Thromboembolism/stroke Falk RH, Prog Cardiovasc Dis, 2010

55. Clues for Cardiac Amyloidosis
Shah KB et al., Circ HF 2016

56. Diagnostic Evaluation: Precursor Protein
Falk RH et al., JACC 2016

57. Slide courtesy of Lowell Satler

58. AL Cardiac Amyloid
Immunoglobulin Molecule

59. Giampaolo Merlini, M.D. (Kyoto Myeloma Conference, 2013)

60. Transthyretin (TTR) Cardiac
Amyloidosis
There are 2 forms of disease:
1. Wild type amyloidosis or senile systemic amyloidosis (ATTRwt)
2. Familial (Hereditary) amyloid cardiomyopathy (hATTR or ATTRm)
Ruberg FL, Berk JL, Circulation 2012

61. Mutant TTR
monomers
misfold
Formation of
insoluble
amyloid fibrils
and amyloid
deposition in
the nerves,
heart, and
other tissues
Mutant TTR
monomers
aggregate
TTR gene
mutation
destabilizes the
tetramer →
dissociation
Identical TTR
monomers
are
synthesized
in the liver
and form
tetramers
TTR tetramers
ATTR Amyloidosis
1. Hawkins et al. Ann Med 2015;47:625–38; 2. Hanna. Curr Heart Fail Rep 2014;11:50–7; 3. Damy et al. J Cardiovasc Transl Res 2015;8:117–27

62. THAOS Registry:
Distribution of ATTR Mutations
Maurer MS et al., Circulation 2017

63. ATTR Disease and Aortic Stenosis
Castano A et al., European Heart Journal 2017

64. ATTR Disease and HFpEF
Mohammed SF et al., JACC HF 2014

65. Cumulative Mortality
(WT vs. Val122Ile)
Maurer MS et al., JACC 2016

66. Diagnosis Requires Pattern
Recognition
Hanna M, Cleveland Clinic Journal of Medicine, 2017

67. Diagnostic Tools:
Electrocardiogram
Falk RH, Circulation, 2011

68. Echocardiography

69. Echo Strain Imaging
Falk RH et al., JACC 2016

70. Cardiac MRI
Esplin BL, Curr Probl Cardiol, 2013

71. Technetium Pyrophosphate Imaging
Bokhari S, J Nucl Cardiol, 2014

72. Slide courtesy of Lowell Satler

73. Proteomic Analysis of Biopsy Tissue
Vrana JA et al, Blood 2009

74. Diagnostic Algorithm
Hanna M, Cleveland Clinic Journal of Medicine, 2017

75. General Principles for Treatment
of Cardiac Amyloidosis
O Treatment depends on the identification of the precursor
protein
O Diuretics/sodium restriction
O Surveillance for and treatment of atrial/ventricular
arrhythmias
O Monitoring for conduction disease
O Avoidance of negative inotropic/chronotropic drugs (beta
blockers, calcium channel blockers)
O Avoidance of vasodilator therapy

76. Multidisciplinary Team
Approach

77. Mutant TTR
monomers
misfold
Formation of
insoluble
amyloid fibrils
and amyloid
deposition in
the nerves,
heart, and
other tissues
Mutant TTR
monomers
aggregate
TTR gene
mutation
destabilizes the
tetramer →
dissociation
Identical TTR
monomers
are
synthesized
in the liver
and form
tetramers
TTR tetramers
Treatment Strategies in TTR Disease
1. Hawkins et al. Ann Med 2015;47:625–38; 2. Hanna. Curr Heart Fail Rep 2014;11:50–7; 3. Damy et al. J Cardiovasc Transl Res 2015;8:117–27

78. Current and Emerging Therapies
for ATTR Amyloidosis
Buxbaum JN, NEJM 2018
207008

79. Slide courtesy of Lowell Satler

80. Tafamidis: ATTR-ACT Trial
Maurer MS et al, NEJM 2018
FDA-approved for treatment of ATTR cardiac
amyloidosis

81. ATTR-ACT Trial
NNT to prevent 1 death=7.5
NNT to prevent 1 hospitalization per year=4.5
Maurer MS et al, NEJM 2018

82. ATTR-ACT Trial: 6MWT Distance
Maurer MS et al, NEJM 2018

83. Tafamidis Survival by NYHA
Class
Maurer MS et al, NEJM 2018

84. Current and Emerging
Therapies for hATTR
Amyloidosis
Buxbaum JN, NEJM 2018

85. Patisiran (APOLLO Trial)
Adams D et al, NEJM 2018
FDA-approved for treatment of hATTR polyneuropathy

86. Patisiran:
Effects on Cardiac Parameters
Solomon SD et al, Circulation 2018

87. Inotersen: NEURO-TTR Trial
Benson M.D. et al, NEJM 2018
FDA-approved for treatment of hATTR polyneuropathy

88. Biomarker Staging System in Wild Type Cardiac
Amyloidosis (TnT and NT-proBNP)
Grogan M et al., JACC 2016

89. 0
1
2
3
4
5
Diagnosis of ATTR Amyloidosis
is Often Delayed
1. Adams et al. Amyloid 2012;19(Suppl. 1):61–4; 2. Plante-Bordeneuve et al. Neurology 2007;69:693–8; 3. Cappellari et al. J Periph Nerv Syst 2011;16:119–29;
4. Koike et al. J Neurol Neurosurg Psychiatry 2012;83:152–8; 5. Leibou et al. Isr Med Assoc J 2012;14:662–5; 6. Luigetti et al. Neurol Sci 2013;34:1057–63
(n=60)
Adams1
(n=15)
Luigetti6
(n=17)
Cappellari3
(n=50)
Koike4
(n=90
)
Plante-Bordeneuve2
(n=8)
Leibou5
Mean
Delay
in
Diagnosis
of
hATTR
Amyloidosis
(Years)
3.1
4.3
3.3
2.8
2.0
4.0

90. ATTR Amyloidosis: Delay from
Symptom Onset to Diagnosis
Early and
common
manifestation
Papoutsidakis et al. J Card Fail 2018;24:131–3

91. AL Cardiac Amyloidosis
Treatment
Chemotherapy is the cornerstone therapy
Hanna M, Cleveland Clinic Journal of Medicine, 2017

92. Treatment and Prognosis in AL
Amyloid
Maurer MS et al., Circulation 2017

93. Conclusions
• Cardiac amyloidosis (CA) results from extracellular
deposition of abnormal insoluble fibrils (immunoglobulin
light chain or transthyretin).
O Disease recognition requires a high degree of suspicion
(“pattern recognition”). Early diagnosis is the key to
improving survival.
O TTR CA can now be diagnosed without the need for
biopsy given improvements in non-invasive techniques.
O There are FDA-approved treatments for AL and TTR CA
that improve survival and QOL.

94. • Radionuclide tracers for amyloidosis
include (a) bone tracers, (b) amyloid-directed
molecules, and (c) PET amyloid agents.

95. • Bone tracers are particularly sensitive in
detection of ATTR type amyloidosis, whereas
PET amyloid agents show a higher affinity for
the AL type.

96. • In sarcoidosis, gallium 67 (67Ga) citrate
scintigraphy and fluorine 18 (18F)
fluorodeoxyglucose (FDG) PET are pivotal to
diagnosis of cardiac sarcoidosis, and 18F-FDG
PET/CT has particularly high efficacy in
detection of sarcoidosis and monitoring of
response to therapy.

97. • A major limitation of 18F-FDG is physiologic
uptake in the myocardium, which can remain
in approximately 20% of patients even after
elaborate preparation (eg, prolonged fasting
>12–18 hours, modification to a high-fat and
low-carbohydrate diet, and injection of
unfractionated heparin).

98. • This limitation has led to a search for potential
new tracers. Recently introduced tracers that
show promise include those used in
somatostatin receptor imaging and cellular
proliferation imaging, which provide
detectability as high as that for 18F-FDG
without requiring dietary restrictions and have
potential for monitoring disease activity.

105. Cardiac Sarcoidosis
• Sarcoidosis is a granulomatous disease that
affects multiple organs and has no clearly
defined etiology. It occurs most commonly in
patients who are 20–40 years old, with a
predominance of female patients .The
cardiovascular system is the third most
common site of sarcoidosis and is involved in
25%–50% of patients

106. The Role of PET/CT imaging in the diagnosis of cardiac sarcoidosis post cardiac arrest
I. Suliman1, M. Alfaris1 - (1) King Abdulaziz Cardiac Center, National Guard Hospital , Riyadh, Riyadh, Saudi Arabia
History:
A 70 year old female with history of
Ventricular tachycardia arrest, S/P Automatic
Internal Cardiac Defibrillator (AICD)
implantation, cardiac catheterization on May
2016 showed mild CAD, was referred for
PET/CT study to evaluate for possible cardiac
sarcoidosis after Cardiac MRI (GE-CASE-
8000) raised suspicion .
Procedure:
The patient was prepared for the test with high
fat/low carbohydrate diet. After 15 hours fast
a rest rubidium 82 study was done. The
patient was injected with IV Unfractionated
Heparin (UFH) 50 units/kg. The patient was
then injected with 5.55mCi of F-18
deoxyglucose, and after standard uptake
period of 120 minutes, PET/CT imaging was
performed.
Findings:
• The rest Rubidium images showed
a severe perfusion defect in the
basal anterior wall, and a moderate
perfusion defect in the mid inferior
wall.
• FDG images showed 2 hot spots
one in the mid inferior wall and
another one in the mid anterior and
basal anterolateral wall.
• These findings are consistent with
active inflammatory cardiac
disease.
Conclusion:
PET/CT is a valuable technique to
study and aid in the diagnosis of
Cardiac inflammatory disease like
cardiac sarciodosis.in addition to
cardiac MRI-DE.
Disclosure: Nothing to disclose

107. • Patients with heart failure have a particularly
poor prognosis .Because corticosteroid
therapy improves cardiac function and
prognosis accurate diagnosis and timely
intervention are vital for improving outcomes.
However, a definitive diagnosis of cardiac
sarcoidosis is difficult to make because of the
low sensitivity (≤25%) of endomyocardial
biopsy .

108. • This high false-negative rate has led the two
major diagnostic guidelines, published by the
Heart Rhythm Society and the Japanese
Circulation Society (revised in 2016) , to allow a
diagnosis of cardiac sarcoidosis without a positive
result from endomyocardial biopsy. As seen in ,
the radiologic imaging criteria (ie, cardiac MRI,
gallium 67 [67Ga]–citrate scintigraphy, and 18F-
fluorodeoxyglucose [FDG] PET) are essential to
diagnosis.

116. Potential Novel Tracers
• Although 18F-FDG PET/CT offers high diagnostic
value for detection of cardiac sarcoidosis,
accurate interpretation may be hampered by
physiologic accumulation of 18F-FDG in the
myocardium, which is seen in up to 20% of
patients even after elaborate preparation,
Also, 18F-FDG PET/CT is not suitable for patients
with uncontrolled diabetes. These inherent
limitations of 18F-FDG have led to a search for
new potential tracers.

117. • Somatostatin Receptor Imaging.—Radionuclide
agents that target somatostatin receptors (SSTRs)
are major candidates for tracers to compete
with 18F-FDG in evaluation of cardiac sarcoidosis.
The indium 111 (111In)–labeled somatostatin
analog (111In-pentetreotide) was the first tracer
introduced for SSTR imaging. 68Ga-labeled
tetraazacyclododecane tetraacetic acid (DOTA)
peptides (eg, 68Ga-DOTA-Tyr3-octreotide
[DOTATOC]) have recently been developed as PET
tracers.