ABC | Volume 114, Nº4, Suplement, April 2020

Case Report Syncope as a Phenotypic Expression of Hereditary Transthyretin Amyloidosis Val142Ile (Val122Ile) Nágela S. V. Nunes, 1, 2 João Paulo Moreira Carvalho, 3 Fernanda Salomão Costa, 4 Marcelo Souto Nacif, 1, 5 Joelma Dominato, 1 Claudio Tinoco Mesquita, 4, 5 Evandro Tinoco Mesquita 2,6 Complexo Hospitalar de Niterói – Cardiologia, 1 Niterói, RJ – Brazil Hospital Universitário Antônio Pedro, Departamento de Cardiologia (Ebserh/UFF), 2 Niterói, RJ – Brazil Labs a+ / Grupo Fleury RJ – Ecocardiografia, 3 Niterói, RJ – Brazil Hospital Pró-Cardíaco - Medicina Nuclear, 4 Rio de Janeiro, RJ – Brazil Hospital Universitário Antonio Pedro, Departamento de Radiologia (Ebserh/UFF), 5 Niteroi, Rio de Janeiro – Brazil Americas Medical City - Centro de Educação e Treinamento Edson Bueno, 6 Rio de Janeiro, RJ – Brazil Mailing Address: Nágela S. V. Nunes • Complexo Hospitalar de Niterói – Cardiologia - Rua La Sale, 12. Postal Code 24020-096, Centro, Niterói, RJ – Brazil E-mail: nvinhosa@me.com Manuscript received August 03, 2018, revised manuscript December 11, 2018, accepted December 19, 2018 Keywords Syncope; Amyloidosis, Familial/genetics; Amyloid Neuropathies, Familial; Cardiomyopathies/diagnosis; Diagnostic, Imaging/methods; Prevalence. DOI: https://doi.org/10.36660/abc.20180130 Introduction Transthyretin amyloidosis (ATTR) is a familial disease caused by one of more than 100 described mutations, where there is production of amyloids that are deposited in tissues. 1 Phenocopies include neuropathy (autonomic and peripheral), cardiomyopathy, renal, gastrointestinal, vitreous and meningeal involvement, which vary according to the genetic mutation, ethnicity and geographical origin, even among individuals with the same mutation or within the same family. 2 Syncope (transient loss of consciousness caused by global cerebral hypoperfusion) in the presence of heart disease confers risk of fatal events. 3 The Val142Ilemutation has heart failure with preserved ejection fraction (HFpEF) as the predominant clinical phenotype, with syncope being an uncommon symptom. 4,5 Case Report The patient was male, 64 years old, of white ethnicity, engineer, born in Rio de Janeiro. He reported an isolated episode of syncope when he quickly got up from a sitting position after running. There was a history of sudden death in the family (uncle at 60). He used to take escitalopram10mg/day and finasteride 5 mg/day. At physical examination: BMI of 21.8 kg/m 2 and jugular turgency at 45 o . BP: 140x80mmHg, HR: 85 bpm, RR: 18 breaths per minute, fourth heart sound, sustained and palpable apex beat in the 6 o intercostal space at the hemiclavicular line, clear lungs and ankle edema. Hewas inNYHA FC I. Blood: BNP: 233 pg/mL (NV: up to 100 pg/mL) and ultra‑sensitive Troponin: 0.135 ng/mL (NV: up to 0.01 ng/mL). The electrocardiogram (EKG) (Fig.1) showed sinus rhythm, HR: 84bpm, right bundle branch block, low voltage in frontal leads, and an pseudo-infarct pattern in precordial leads. The transthoracic Echocardiogram (TTE) showed left ventricular hypertrophy (LVH) - septum= 16 mm and posterior wall = 13 mm - mitral flow with type II relaxation deficit and LA indexed volume: 87 mL/m 2 (Figure 2). 24-h Holter and Exercise Test (ET) showed short and asymptomatic polymorphic ventricular tachycardia (PVT) outbreaks. Cardiac magnetic resonance imaging (CMRI) at rest and after stress with dipyridamole requested after TTE showed diffuse LVH and absence of myocardial ischemia, with areas of lateral and anterior mesocardial late enhancement (LE) and diffuse subendocardial LE in the LV, atria and interatrial septum (Figure 1). Evaluation of global longitudinal strain (GLS) after CMRI showed marked alterations in the basal and medial portions of all myocardial walls, sparing the LV apical regions, which was consistent with the described cardiac amyloidosis (CA) pattern. Abdominal fat and rectal biopsies confirmed the diagnosis of amyloidosis with Congo red staining. Immunofixation in blood and 24-h urine andmeasurement of light chains Imunoglobulins in the blood ruled out monoclonal gammopathy, after which cardiac technetium-99m pyrophosphate scintigraphy (99mTc-PYP) (Figure 1) was requested, witch showed intense radiotracer uptake in the myocardium (grade 3), suggesting Transthyretin CA (ATTR‑CA) etiology. Finally, the patient underwent genetic testing, which confirmed a heterozygous Val142Ile mutation for the TTR gene. Discussion When evaluating a syncope patient, it is a priority to stratify the risk of fatal events, 3 which take into account electro and echocardiographic alterations, which were present in this patient. The low voltage pattern found in the EKG (Figure 1), in the presence of LVH, are already warning signs for the diagnosis of CA. 1,4,6 Elevated BNP and troponin levels reflected increased intracavitary pressures and ongoing myocardial injury, which was indicative of heart disease. The TTE confirmed the suspected heart disease. The (Figure 2), family history of sudden death and the presence of PVT on exertion raised the suspicion of cardiac syncope and the main differential diagnoses would be hypertrophic cardiomyopathy (HCM), coronary artery disease (CAD) and CA. 3 The CMRI, which was subsequently requested, provided evidence that was strongly suggestive of CA, given the characteristic LE pattern, ruling out the hypotheses of HCM and 1