HISTORY, CURRENT ILLNESS AND PHYSICAL EXAMINATION

History
No drug allergies. Cardiovascular risk factors: type 2 diabetes mellitus, hypertension, dyslipidaemia. No toxic habits. Cardiological history: ischaemic heart disease: triple bypass in September 2015 due to severe disease of the trunk and three vessels, proximal anterior descending, proximal-medial circumflex and posterior interventricular. He had lost clinical follow-up, with last transthoracic echocardiography (TTE) in 2018: left ventricle with moderate concentric hypertrophy, LVEF 50% with hypokinesia of lower middle and basal segments, no valvulopathies and normal right ventricular function. Paroxysmal atrial fibrillation diagnosed in 2012. He had recently undergone electrical cardioversion (ECV). Other medical and surgical history: vertebrobasilar ischaemic stroke in 2017, with no sequelae.
Chronic kidney disease (CKD) 3bA1 probably secondary to nephroangiosclerosis. Polyposis of the colon with multiple endoscopic exeresis. Hyperuricaemia with gout crisis. Surgical interventions: coronary bypass, right inguinal herniorrhaphy, cataracts. Current treatment: insulin glargine 22 IU/24 h, linagliptin 5 mg/24 h, pitavastatin 2 mg/24 h, enalapril 5 mg/24 h, bisoprolol 5 mg/24 h, acenocoumarol 2 mg/24 h, amiodarone 200 mg/24 h, pantoprazole 20 mg/24 h, febuxostat 80 mg/24 h.

Present illness
A 78-year-old man came to the emergency department for progressive dyspnoea of months of evolution, more marked in the last 20 days until minimal effort (baseline NYHA I-II/IV, consultation in functional class III/IV), despite a course of furosemide 2 tablets a day for the last week by his primary care physician. He had an increase in his baseline orthopnoea and episodes of paroxysmal nocturnal dyspnoea (PND), as well as progressive oedematisation of the lower limbs since the previous month. He reported clinical symptoms compatible with exertional angina, consisting of oppressive central thoracic and epigastric pain, non-radiating, without vegetative cortex, which had subsided after 15 minutes with rest since approximately 4 months previously, stable with no recent progression. He denied palpitations. No fever or other infectious symptoms on physical examination.

Physical examination
Blood pressure 115/69 mmHg, heart rate 60 bpm, oxygen saturation 94% (with O2 through nasal goggles at 2 l/min). Afebrile. Good general condition. Conscious and oriented. Skin pallor. Eupneic at rest. No jugular engorgement. Cardiac auscultation: regular heart sounds, no murmurs. Pulmonary auscultation: generalised hypophonesis, bibasal crackles. Abdomen soft and depressible, not painful, no masses or megaliths. Lower limbs with oedema up to the root of the limbs.

COMPLEMENTARY TESTS
Electrocardiogram (ECG) on admission: sinus rhythm at 70 bpm, signs of left atrial enlargement, PR 240 ms, QRS 100 ms, precordial R progression defect, QS in inferior face. Chest X-ray on admission: no infiltrates or masses, increased cardiothoracic index (CTI), slight right costophrenic sinus impingement, median sternotomy sutures.

Laboratory tests: haemogram: red cells 4.13 10*12/l, haemoglobin 12.8 g/dl, haematocrit 39.1 %, MCV 94.8 fl, MCH 30.9 pg, ADE 15%, leukocytes 5.8 10*9/l, neutrophils 4.1 10*9/l, lymphocytes 1.1 10*9/l, monocytes 0.4 10*9/l, eosinophils 0.1 10*9/l, basophils 0 10*9/l, platelets 150 10*9/l. Biochemistry: glucose 88 mg/dl, sodium 140 mEq/l, potassium 3.5 mEq/l, chlorine 106 mEq/l, GPT 40 U/l, urea 83 mg/dl, creatinine 1.67 mg/dl, transferrin saturation index 17%, ferritin 47 mcg/l, C-reactive protein 0.8 mg/dl. Haemostasis: Quick's index 32%, INR 2.22, aPTT 35.7 s, derived fibrinogen 464 mg/dl. Serum proteinogram: albumin 53.5%, alpha 1 globulin 4.5%, alpha 2 globulin 13.6%, beta globulin 12%, gamma globulin 16.4%, albumin/globulin ratio 1.1%. No monoclonal peak is observed. Free light chains in serum and urine negative. TTE: severe concentric left ventricular hypertrophy with preserved global systolic function. Hypokinesia in lower mid-basal segments. Diastolic pattern with single E wave with data suggestive of increased filling pressures. Trivial mitral regurgitation. Mild aortic insufficiency. Mild left atrial dilatation. Right ventricle with preserved systolic function. Mild tricuspid insufficiency (TI) allowing estimation of systolic pulmonary artery pressure (PAPS) of approximately 35-40 mmHg. Plethoric inferior vena cava (IVC). Exploration in atrial fibrillation (AF) with RV as 80 bpm.

Cardiac MRI (video 3, images 3 and 4): left ventricle (LV) of normal volumes (LVOT 85 ml/m2, STV 32 ml/m2) with increased myocardial mass (LVMI 114 g/m2) and concentric hypertrophy (septum 21 mm and posterior wall 17 mm) with basal and mid inferior hypokinesia with preserved global systolic function (LVEF 62%). STIR sequences show mild myocardial oedema at anterior, anteroseptal, mid inferoseptal, anterior and apical septal levels. Right ventricle (RV) not dilated (RVOT 94 ml/m2, STV 41 ml/m2) with preserved global systolic function (RVEF 56%). Aorta and great vessels of normal diameter and morphology. Left atrium slightly dilated. Estimated normal pulmonary vascular resistance (mean pulmonary velocity 11 cm/s). Gadoteric acid (0.15 mM/kg) is administered: well tolerated by the patient. Necrosis and viability detection study: presence of myocardial late gadolinium enhancement (LGE) suggestive of subendocardial necrosis at anterior segment level with diffuse epicardial fibrosis at septal and inferior basal, middle and apical segments; as well as difficulty in myocardial nulling on viability sequences suggesting diffuse intramyocardial fibrosis with subendocardial RV LGE. Whole body bone scan: after 3 hours of tracer infusion (99mTc-HDP) increased uptake is observed at the level of the cardiac silhouette of greater intensity than the surrounding bone structures (score 3). Genetic study: study of the TTR gene, ruling out the presence of a mutation.

CLINICAL EVOLUTION
A diagnosis of decompensated heart failure was made in the emergency department and treatment with intravenous diuretics was started. Diuretic response was poor, requiring oxygen therapy to maintain oxygen saturation, and the patient was admitted to the cardiology ward to complete the study and treatment. The patient's evolution was slowly favourable with depletive treatment. Renal function deteriorated secondary to heart failure and intensive use of diuretics. In addition, iron deficiency anaemia was detected, so a single dose of 1,000 mg of iron carboxymaltose was administered. Echocardiography showed severe left ventricular hypertrophy with a granular pattern, compatible with infiltrative cardiomyopathy, and cardiac MRI was performed, identifying a pattern suggestive of amyloidosis. Therefore, a serum proteinogram and detection of free light chains in serum and urine were performed, which, being negative, ruled out the diagnosis of AL amyloidosis. With the suspicion of amyloidosis due to TTR, a bone scan with bisphosphonates was requested. After recovery of renal function to baseline levels, the patient was discharged from hospital with follow-up by the heart failure unit. The patient underwent outpatient scintigraphy, showing increased uptake in the cardiac silhouette of greater intensity than in the bone structures, establishing the diagnosis of amyloidosis due to TTR. A genetic study was performed, which was negative. At subsequent visits, the patient has remained stable in NYHA functional class II/IV.

DIAGNOSIS
Decompensated heart failure.
Cardiac amyloidosis due to wtTTR.

Other diagnoses:
Exacerbated chronic kidney disease.
Normocytic anaemia with iron deficiency.
Chronic ischaemic heart disease.
