Red flags
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When to suspect
Raise suspicion
There are several common “red flags” that can raise suspicion of underlying ATTR-CM. Some of these are listed below.[1][2][3]
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Male over 65 or female
over 70 years with HF
Suspicion should be raised in men older than 65 years or women older than 70 years with HF and other “red flag” signs or symptoms. A significant male predominance has been reported in both ATTRwt and ATTRv amyloidosis.[2]
Septum thickness
over 12–14 mm
Increased wall thickness caused by deposition of amyloid fibrils is a prominent characteristic of ATTR-CM. This can lead to ventricular stiffening and left ventricle diastolic dysfunction.[6]
Increased
biomarker levels
Cardiac biomarkers, such as troponin and NT-proBNP, are useful prognostic markers of cardiac function in ATTR amyloidosis.[1][2][3]
Poor response to
common HF drugs
Most drugs commonly used for the treatment of HF are neither effective or well-tolerated in patients with AL amyloidosis and ATTR amyloidosis.[1][4][5]
Non-cardiac
involvement
Carpal tunnel syndrome, lumbar spinal stenosis, and bicep tendon rupture are all common extracardiac manifestations in ATTR-CM.[1][2][3]
Discordance between
LV wall thickness
and QRS voltage
One clue to cardiac CA is the discrepancy between LV wall thickness and QRS voltages on a standard 12-lead electrocardiogram (ECG). Many ATTR-CM patients have normal followed by low QRS voltages.[1][2][3]
A heart disease hidden in plain sight
ATTR-CM can reveal itself in many shapes and forms. Despite this, the diagnosis of ATTR-CM is often delayed or missed. Below are three examples of fairly common clinical situations in which ATTR-CM can present itself. Have a look at these case presentations and see if you can identify any “red flags” typical to ATTR-CM.
Try to identify the “red flags”
The referral
A 68-year-old man made a scheduled follow-up visit to his GP because of newly discovered diabetes type 2 (DM2). Apart from DM2 and a chronic back ache due to magnetic resonance imaging (MRI)-verified spinal stenosis, the patient is well. Blood pressure at the initial visit had been normal but findings on the ECG were a bit unclear (possible conduction impairment). The patient was referred for an ECHO, some lab tests, and scheduled for a follow-up.
Examination of the recent ECHO findings showed a thickened left ventricle despite normal QRS voltage on ECG but no other pathology. Lab tests showed elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) but all other standard lab values (excluding HbA1c and fasting glucose) were normal. The patient is troponin T negative and was put on angiotensin converting enzyme inhibitors (ACEis) and metformin after his last visit, but the response seems poor.
At the re-visit the patient tells his GP that he has been feeling lightheaded with increased exertional dyspnea, fatigue, and weakness for the past few weeks. Physical examination reveals no pathological findings. The GP writes a referral to the cardiology department asking for further investigation of “heart failure of unknown cause”.
The primary care visit
A 75-year-old man sits in the waiting room for a re-visit to his GP. He was diagnosed with atrial fibrillation (AF), high blood pressure (170/100), and HF 4 weeks ago and started on novel oral anticoagulants (NOACs), beta blockers and ACEis on a titration schedule. He is booked for an ECHO examination in 2 weeks.
The walk from his home to the primary health care center took him almost half an hour. He is now a bit thirsty and he gets up from the chair to have a glass of water when he suddenly blacks-out and falls to the floor. The attending nurse rushes to his help and the man is put on a stretcher and wheeled into the examination room.
An ECG shows normal QRS voltage, AF 110/min, and blood pressure is 80/70. Hemoglobin and glucose levels are normal. Both Troponin T and NTpro-BNP are elevated. He is a bit pale but otherwise fine. A quick physical examination shows no injuries from the fall, he has no headache, and a brief neurological check-up reveals a normal status.
The GP decides to send the patient to the hospital. You are the attending doctor. Upon arrival, the patient’s level of consciousness is Glasgow Coma Scale 15, an ECG shows AF 105/min, and saturation is 98%. The man tells you that he has been “very compliant to his new medications”, which rapidly took him to the maximum dose of both beta blockers and ACEis.
The ward
A 71-year-old woman was admitted last night due to acute chest pain. It is Tuesday morning and time for medical rounds when the nurse tells you about this new patient on the ward. The ECG revealed deep Q waves in leads V1–V2 with T wave flattening. Troponin I was slightly above the limit and since the attending emergency room physician felt unsure, he called the catheterization laboratory for a coronary angiogram, which revealed no pathology. ECG monitoring during the night and morning has been uneventful.
Having exchanged some courtesy phrases, the woman tells you that she is previously healthy apart from a bilateral carpal tunnel surgery 5 years ago and some minor gastrointestinal problems. She has had no sequelae post surgery and no new symptoms. In addition, she says she has started to get a tingling feeling in her fingers and toes and that someone in the family suffers from “a kind of progressive nerve disease”.
A clinical bed-side examination reveals no pathological findings and this morning’s laboratory tests are mostly fine, but still showing slightly elevated Troponin I. One of your junior colleagues tells you of a recent case report involving “the heart and a bilateral carpal tunnel syndrome” but he is unable to recall any further details.
