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• Previous medication was withdrawn and the patient was put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!