Optimizando el uso de la cardiología nuclear en la amiloidosis cardíaca:
ejemplos clínicos
Optimizing the use of nuclear cardiology in cardiac amyloidosis:
clinical examples
Fernando Mut, MD, FASNC - Uruguay
Amiloidosis Cardíaca en Latinoamérica: Lectura con Expertos Cardiac Amyloidosis in Latin America: Read With the Experts
Marzo/March 9, 2021
Case 1
How does CA diagnosis affect patient outcome in heart failure?
• 75 y.o. man with no previous history of cardiac disease
• Hypertension, dyslipidemia, hypothyroidism
• Progressive dyspnea, for which he is admitted
Clinical presentation
• ECG: Sinus rhythm 63 bpm, normal P waves and
P-R interval, RBBB, RAHB. Normal QRS voltage.
• Doppler 2D Echo: Severe wall thickness (15mm),
LVEF 43%, severe diastolic dysfunction.
ECG and Echo
• Hb 16,2 - Leuk 6,740 - Plat 165,000
• Urea 72 - Creat 1,64
• Na 129 - K 4,2 - Uric acid 8,4
• HbA1c 6,2% - Glyc 180
• TC 136 - LDL 51 - HDL 66 - Triglyc 107
• T4L 1,5 - TSH 3,4 - 25-OH-Vit D 34
• NT-ProBNP 3,643
Laboratory findings
The patient was put on:
• Calcium channel blockers
• Beta-blockers
• Angiotensin-2 receptor blockers Symptoms worsened:
• Fatigue and weakness
• Legs, ankles and feet edema
• Palpitations
• Persistent cough
Follow-up
• Heterogeneous late gadolinium enhancement
(LGE)
• Increased native T1 values (~1167ms)
• Increased extracellular volume (ECV) (~ 66%)
Cardiac Amyloidosis suspected
Cardiac Magnetic Resonance
• Serum protein immunofixation and urinary protein electrophoresis:
absence of monoclonal components
• Electromyography (EMG): sensitive-motor polyneuropathy / medial
nerves dysfunction at carpal tunnel – bilateral
99mTc-PYP suggested
Additional workup
99mTc-Pyrophosphate cardiac scintigraphy
Planar 1 hour
SPECT
Visual score = 3
H/CL ratio = 1.84
H CL
Anterior view
Planar 1 hour
Semi-quantitative evaluation – H/CL ratio
• Cardiac amyloidosis TTR type was diagnosed
• Previous medication was withdrawn and the patient was put
on a combination of a loop diuretic (furosemide) and a
mineralocorticoid receptor antagonist (spironolactone), with
clinical improvement
Follow-up
Teaching points
• The diagnosis of CA is essential to differentiate it from other causes of heart failure, since common
treatment for heart failure is not well tolerated by these patients.
• β-Blockers reduce cardiac output due to blunting of the compensatory tachycardic response to the fixed
stroke volume and can produce heart block in these patients already prone to conduction abnormalities.
• Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers are poorly tolerated
due to a low cardiac output, orthostatic hypotension, presence of autonomic neuropathy, and the frequent
coexistence of renal dysfunction in this population.
• Calcium channel blockers bind avidly to amyloid fibrils and carry the risk of worsening heart failure,
severe hypotension, and syncope.
• The combined findings of grade 2 or 3 myocardial 99mTc-PYP uptake and the absence of a
monoclonal protein in serum or urine has very high specificity and positive predictive values for ATTR.
Case 2
Is SPECT really necessary for ATTR diagnosis?
• 80 y.o. woman with no previous history of cardiac disease
• Obesity, hypertension, dyslipidemia, type II diabetes
• Chronic renal failure
• Fatigue and shortness of breath
• LVEF reduction in the last weeks
Clinical presentation
ECG
• Sinus tachycardia 102 bpm • 1st degree A-V block • RBBB • Inferior wall infarction
Courtesy Dr. G Grossman
Transthoracic Echocardiogram
• Ascending aorta dilatation • Thickened aortic valve with no significant obstruction, mild regurgitation • LV mildly dilated, borderline wall thickness, mild systolic /moderate diastolic dysfunction • Left atrial dilatation, normal RV.
LVEF = 48%
Courtesy Dr. G Grossman
99mTc-Pyrophosphate cardiac scintigraphy
1h images 3h images
Visual score = 1-2
Courtesy Dr. G Grossman
99mTc-Pyrophosphate SPECT/CT
Blood pool activity – negative for ATTR
Courtesy Dr. G Grossman
Teaching points
• In the context of an equivocal planar 99mTc-PYP study, SPECT images can
easily differentiate between true myocardial uptake and persistent blood pool
activity
• Blood pool activity can last for long in patients with heart failure and/or renal
failure due to delayed plasmatic clearance of the radiotracer
Case 3
Is 99mTc-PYP uptake always related to CA-TTR?
• 68 y.o. woman with Sjögren’s syndrome, on hydroxycholoquine for 15 ys.
• Hypertension, dyslipidemia
• Presents with congestive heart failure
Clinical presentation
Transthoracic Echocardiogram
Concentric left ventricular wall thickening and abnormal averaged longitudinal peak systolic strain at −10%, most preserved at the apex.
Chang ICY et al. Circ Cardiovasc Imaging 2017
99mTc-PYP scintigraphy
Visual score = 2 H/CL ratio = 1.8
SPECT/CT = myocardial uptake, most pronounced in the lateral wall
Chang ICY et al. Circ Cardiovasc Imaging 2017
• H&E–stained sections of the endomyocardial biopsy shows sarcoplasmic vacuolization of cardiac myocytes. • Amyloid not present on special stains, including sulfated Alcian blue stain and Congo red stains. • Electron microscopy demonstrates the presence of myelinoid and curvilinear bodies, in keeping with
hydroxychloroquine-mediated cardiotoxicity (instead of a presumed diagnosis of cardiac ATTR)
Endomyocardial biopsy
Chang ICY et al. Circ Cardiovasc Imaging 2017
• Hydroxychloroquine has been found to have a beneficial effect in rheumatoid arthritis and systemic lupus erythematosus, possibly through interfering T cell activation
• Despite its potential cardiac toxicity and not having received approval for treatment or prevention, hydroxychloroquine has been extensively used worldwide during the current COVID-19 pandemic
• With the increasing use of 99mTc-PYP cardiac scintigraphy, hydroxychloroquine toxicity may thus become a recognized cause of false-positive results during CA workup
• Although being very high, the true specificity of 99mTc-scintigraphy for amyloidosis remains unclear, since non-CA myocardial uptake has been reported in a variety of other conditions (other than the well-known situation of myocardial infarction)
Teaching points
Gracias! Thank you!