, Yüksel Çavuşoğlu 2
, Gamze Babur Güler 3
, Serkan Ünlü 4
, Özlem Yıldırımtürk 5
, Dilek Çiçek Yılmaz 6
, Cihan Örem 7
, İbrahim Başarıcı 8
, Omaç Tüfekçioğlu 9
, Lale Tokgözoğlu 10
, Uğur Nadir Karakulak 10
, İrem Dinçer 11
, Gamze Çapa Kaya 12
, İlknur Ak Sivriöz 13
, Selda Murat 2
, Arda Güler 3
, Ayşe Çolak 1
, Mürsel Şahin 7
, Elmas Kaplan 9
, Dursun Akaslan 14
, Ayçe Türer Cabbar 15
, Murat Sünbül 14
, Yüksel Kaya 16
, Cafer Sadık Zorkun 17
, Fahriye Vatansever Ağca 18
, Barış İkitimur 19
, Alper Onbaşılı 20
, Alev Kılıçgedik 21
, Hakan Altay 22
, Elif Eroğlu Büyüköner 23
, Muzaffer Değertekin 15
2Department of Cardiology, Eskişehir Osmangazi University Faculty of Medicine, Eskişehir, Türkiye
3Department of Cardiology, Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, İstanbul, Türkiye
4Department of Cardiology, Gazi University Faculty of Medicine, Ankara, Türkiye
5Department of Cardiology, Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Training and Research Hospital, İstanbul, Türkiye
6Department of Cardiology, Mersin University Faculty of Medicine, Mersin, Türkiye
7Department of Cardiology, Karadeniz Technical University Farabi Hospital, Trabzon, Türkiye
8Department of Cardiology, Akdeniz University Faculty of Medicine, Antalya, Türkiye
9Department of Cardiology, Ankara Bilkent City Hospital, Ankara, Türkiye
10Department of Cardiology, Hacettepe University Faculty of Medicine, Ankara, Türkiye
11Department of Cardiology, Ankara University Faculty of Medicine, Ankara, Türkiye
12Department of Nuclear Medicine, Dokuz Eylül University, Faculty of Medicine, İzmir, Türkiye
13Department of Nuclear Medicine, Eskişehir Osmangazi University Faculty of Medicine, Eskişehir, Türkiye
14Department of Cardiology, Marmara University Faculty of Medicine, İstanbul, Türkiye
15Department of Cardiology, Yeditepe University Faculty of Medicine, İstanbul, Türkiye
16Department of Cardiology, Van Yüzüncü Yıl University Faculty of Medicine, Van, Türkiye
17Department of Cardiology, İstanbul University İstanbul Medical Faculty, İstanbul, Türkiye
18Department of Cardiology, University of Health Sciences Bursa Yüksek İhtisas Training and Research Hospital, Bursa, Türkiye
19Department of Cardiology, İstanbul University-Cerrahpaşa, Cerrahpaşa Medical Faculty, İstanbul, Türkiye
20Department of Cardiology, Aydın Adnan Menderes University Faculty of Medicine, Aydın, Türkiye
21Department of Cardiology, Başakşehir Çam and Sakura City Hospital, İstanbul, Türkiye
22Department of Cardiology, Başkent University İstanbul Hospital, İstanbul, Türkiye
23Department of Cardiology, Acıbadem Mehmet Ali Aydinlar University Faculty of Medicine, İstanbul, Türkiye
Abstract
Background: Cardiac amyloidosis (CA) is an increasingly recognized disease. Several recent advanced imaging techniques and parameters have been introduced into the diagnosis of CA. However, the first step in using those techniques is clinical suspicion. Left ventricular hypertrophy (LVH) is the main entity in rising the suspicion of CA in routine echocardiography, although it is not a diagnosis for CA. The aim of this study is to investigate the prevalence of CA and its subtypes and predictive value of clinical and echocardiographic red flags of CA among consecutive adult patients with LVH identified during routine echocardiographic examination in 25 tertiary institutions in Türkiye.
Methods: This was a prospective observational multicenter, national registration study.
Patients with LVH (interventricular septum thickness ≥13 mm or >15 mm in those with hypertension) were screened for CA stepwise. The first step was a clinical questionnaire for the red flags of CA. Those having ≥2 red flags were further analyzed by detailed echocardiography, blood tests, Tc-pyrophosphate (PYP) bone scintigraphy, and histopathological examination if needed. Parameters associated with CA were evaluated via univariate and multivariate analyses. Wild-type transthyretin (wTTR) vs. mutant-type TTR (mTTR), CA discriminators were also evaluated in the same manner.
Results: A total of 420 patients meeting these criteria were included in the study. With a standardized algorithmic approach, 27.1% (114) of patients received a CA diagnosis. Among these patients with CA, 50.8% (58) were diagnosed with immunoglobulin free chain (AL) CA, 38.6% (44) with wTTR CA, and 7% (8) with mTTR CA. Left ventricular apical sparing pattern and restrictive type LV filling on echocardiography, low QRS voltage on ECG, bilateral carpal tunnel syndrome, low blood pressure, right ventricular diameter, and an increased basal heart rate (HR) were independent predictors for CA diagnosis. When it
comes to diagnosis of wTTR CA; advanced age (age >75), lower troponin values, absence of pericardial effusion and absence of proteinuria were the independent predictors.
Conclusion: Cardiac amyloidosis is highly prevalent in a patient population with LVH and 2 red flags who underwent a standardized algorithmic approach, in which apical sparing, restrictive filling pattern, low QRS voltage, carpal tunnel syndrome, low blood pressure, and increased HR are the highly suggestive signs of CA. Among this pool of newly diagnosed CA patients in Türkiye, AL-CA constituted 50.8%, wTTR CA 38.6%, and mTTR CA 7%, emphasizing that approximately 1 in 2 patients diagnosed with CA may have TTR CA.