HISTORY, CURRENT ILLNESS AND PHYSICAL EXAMINATION

PERSONAL HISTORY
77-year-old woman, allergic to propifenazone, with a history of arterial hypertension for more than 20 years and dyslipidaemia, both under medical treatment with good control. No other cardiovascular risk factors.

Cardiological history
Diagnosed with persistent atrial fibrillation in October 2011, with mild hypertensive heart disease (left ventricle [LV] of normal size, slightly hypertrophic, normal left ventricular ejection fraction [LVEF] with moderately dilated left atrium [LA] on transthoracic echocardiography [TTE]), which required pharmacological cardioversion in March 2012 and pulmonary vein ablation in October 2012. He initially remained in sinus rhythm under antiarrhythmic treatment with flecainide (50 mg, half a tablet every 12 hours), which was discontinued in October 2013, and anticoagulation with dabigatran (150 mg every 12 hours).
He subsequently presented arrhythmic recurrence in the form of atrial fibrillation and left flutter in early June 2014, which required reablation of the left atrial substrate, atrial roof line and mitral isthmus. Recurrence of left flutter at the end of June 2014, which required new electrical cardioversion in the same month. On admission, antiarrhythmic treatment was started with a loading dose of intravenous amiodarone with facial flushing and discomfort, so the infusion was stopped and outpatient management with oral flecainide (100 mg, half a tablet every 12 hours) and atenolol (50 mg, one and a half tablets every 24 hours) was decided.
She was reviewed in February 2015 for an episode of clumsiness in the right leg that temporarily coincided with arrhythmic recurrence in the form of atrial fibrillation. In view of this situation, a referral to neurology was requested and a diagnosis of transient ischaemic attack was made following a cranial MRI in which acute/subacute ischaemic lesions were ruled out. Since then, amiodarone 200 mg every 8 hours was started as a loading dose for a week and then 200 mg every 24 hours. Since then in sinus rhythm.
In August 2015 antiacogulation is changed from dabigatran (150 mg every 12 hours) to rivaroxaban (15 mg, every 24 hours) due to worsening renal function.
Other relevant background information
On the other hand, in January 2016, there were episodes of copious and recurrent anterior epistaxis with significant anaemisation, despite the treatment applied by the otorhinolaryngology department (cauterisation with silver nitrate and placement of spogostan and bactroban film).
In view of this situation, percutaneous closure of the left atrial appendage was decided in February 2016 with a 28 mm Amulet device. Treatment was started with acetylsalicylic acid 100 mg and clopidogrel 75 mg every 24 hours and anti-clotting agents were discontinued. In April 2016, double antiplatelet therapy was discontinued and single antiplatelet therapy was maintained with acetylsalicylic acid (100 mg, every 24 hours).

Medical treatment
Amiodarone 200 mg (1 tablet at breakfast), acetylsalicylic acid 100 mg (1 tablet at lunch) and valsartan 50 mg (1 tablet at breakfast).

CURRENT ILLNESS
Asymptomatic for dyspnoea, palpitations and chest pain until August 2018, at which time she attended the emergency department reporting progressive exertional dyspnoea and dry cough, which prevented her from carrying out her daily activities.

PHYSICAL EXAMINATION
Blood pressure (BP) 150/90 mmHg, heart rate (HR) 65 bpm, SatO2 92%, temperature 37.5 ̊C.
Acceptable general condition. Conscious and oriented in the three spheres. Normal colour, normohydrated and normoperfused.
Carotids rhythmic and symmetrical. No jugular ingurgitation.
Cardiac auscultation: rhythmic tones without murmurs or extratonos.
Pulmonary auscultation: vesicular murmur abolished in lung bases with dry crackles up to midfields.
Abdomen: hydro-aerial sounds present, soft and depressible, not painful on deep palpation. No masses or megaliths.
Lower extremities: No oedema. Peripheral pulses present. No signs of deep vein thrombosis.

COMPLEMENTARY TESTS
CBC: glucose 88 mg/d, urea 44 mg/dl, Cr 1.2 mg/dl, MDRD 46 ml/min 1.73m2, Na 142 mEq/l, K 4.4 mEq/l, Cl 104 mEq/l, CO2 23 mEq/l, GOT 16 IU/l, GPT 10 IU/l, gamma-glutamyltransferase 8 IU/l, alkaline phosphatase 110 IU/l, LDH 410 IU/l, total bilirubin 0.76 mg/dl, TSH 0.74 μU/ml, C-reactive protein 5.31 mg/dl, procalcitonin 0.068 ng/ml, proBNP 320 pg/ml, Hb 11.9 mg/dl, Hto. 37.37%, MCV 84.9 fl, platelets 462 109/l, leukocytes 11.6 109/l, neutrophils 8.31 109/l.
Electrocardiogram: sinus rhythm at 65 bpm. Left axis. Left anterior hemiblock.
Posteroanterior and lateral chest X-ray: atheromatosis of the aortic arch. Aortic elongation. Borderline cardiothoracic index with percutaneous left atrial appendage closure device. Areas of bibasal consolidation with interstitial pattern up to midfields and mild bilateral pleural effusion. Rest of lung parenchyma with acceptable aeration.
TTE 08/18: left ventricle slightly dilated, mild hypertrophy and normal systolic function. Ejection fraction 62%. No regional contractility abnormalities. Pseudonormal filling pattern, high filling pressures (E/E ́ 19). Right ventricle with normal morphology and systolic function. Severe left atrial dilatation. Minimal mitral and aortic regurgitation. Minimal tricuspid insufficiency that allows estimating a systolic pulmonary artery pressure (PAPs) within the normal range. No signs of pericardial pathology. Vena cava of normal calibre collapsing with inspiration. Atrial appendage closure device.
Chest computed tomography (CT) 08/18: pulmonary involvement characterised by areas of pulmonary consolidation with alveolar pattern and air bronchogram predominantly peripheral and in lower lobes, patchy foci of ground glass and small nodular opacities. It is associated with a peripheral coarse reticular interstitial pattern and traction bronchiectasis, suggestive of chronicity. Compatible with cryptogenic organised pneumonia. No pleural effusion is observed. Left atrial appendage closure device. Main trunk of pulmonary artery of 29 mm, at the high limit of normality. Multinodular goitre at the expense of the left lobe, partially endothoracic, with the largest nodule measuring 20 mm in the left thyroid lobe.
Diffuse increased attenuation of the liver parenchyma (study without contrast).
Bronchoscopy: normal. Bronchoalveolar lavage with predominantly neutrophilic phenotype, no microbiological isolates and pathological anatomy with fatty macrophages.
Respiratory function tests 08/18: mild restrictive ventilatory abnormality. Severe decrease in diffusing capacity.
6 minute walk test 08/18:
Respiratory function tests after corticosteroid treatment 09/18: normal respiratory function tests. Isolated moderate decrease in diffusing capacity. Improvement of 3 ml/mmHG/min in diffusing capacity compared to previous tests.
6-minute walk test after corticosteroid treatment 09/18:
Chest CT scan 10/18: persistent peripheral pattern of predominance in bases, interstitial, ground glass and with thickening of interlobar septa, which shows a clear improvement compared to the August scan, with almost complete disappearance of the areas of consolidation. Nodular goitre predominantly on the left with some endothoracic component. Left atrial closure device. Dilatation of the left atrium. No pleural or pericardial effusion was observed.

CLINICAL EVOLUTION
In view of the elevated inflammatory parameters and the radiological pulmonary alterations (areas of bibasal consolidation and bilateral pleural effusion), it was decided to admit the patient to the cardiology ward for aetiological study and treatment.
Due to increased inflammatory parameters, it was decided to administer intravenous amoxicillin/clavulanic acid 1,000 mg every 8 hours and oral azithromycin 500 mg every 24 hours for three days. In addition, despite no clinical signs of systemic congestion, given the mildly elevated pro-BNP and the possible association of incipient heart failure in the context of primary pulmonary pathology, intravenous furosemide was added as part of the initial treatment. Amiodarone was also suspended due to suspicion of pulmonary toxicity until the aetiology of the pulmonary involvement and its evolution were known.
During the first 48 hours, there was no improvement in her clinical condition, and a thoracic CT scan was completed, which showed a pulmonary pattern compatible with cryptogenic organised pneumonia with fibrotic changes of chronic profile.
The patient was assessed by pulmonology during admission and studies of interstitial lung disease were completed. Respiratory function tests showed a mild restrictive ventilatory abnormality, and a severe decrease in diffusing capacity, with a 6-minute walk test with desaturation of up to 83-84% over a maximum distance covered of 390m. They also performed a bronchoscopy which revealed no pathological findings, with bronchoalveolar lavage showing a predominantly neutrophilic phenotype, no microbiological isolates and pathological anatomy with fatty macrophages.
With the diagnosis of cryptogenic organised pneumonia probably related to amiodarone (suspended on admission), corticosteroid treatment with intravenous methylprednisolone (40 mg/24 hours) was started during admission.
Prior to discharge, a thyroid ultrasound was requested, which showed multiple benign nodules with normal thyroid function.
She was discharged after 7 days of admission, with partial improvement of her respiratory symptoms with outpatient steroid treatment (oral methylprednisolone, 40 mg until further review in one month). The rest of the treatment at discharge was as follows: pantoprazole 40 mg at breakfast, acetylsalicylic acid 100 mg at lunch, valsartan 80 mg at dinner and calcium and vitamin D3 1250 mg at breakfast.
She came for a check-up at the end of September 2018, reporting a clear improvement in respiratory function. Complete respiratory function tests were repeated, showing an improvement in respiratory function (normal function, with an improvement in diffusion capacity of 3 ml/mmHg with respect to the previous test) and in the 6-minute walk test in which she was able to complete 445 metres. A chest CT scan was performed in October 2018 in which a peripheral interstitial pattern persisted, predominantly basal, in ground glass, with thickening of the interlobar septa, although with a clear improvement compared to the previous CT scan, with almost complete disappearance of the areas of consolidation.

DIAGNOSIS
Interstitial pneumonitis probably secondary to pharmacological toxicity due to amiodarone.
Hypertensive heart disease with normal ventricular function, without signs of heart failure.
Systemic arterial hypertension with good pharmacological control.
Persistent atrial fibrillation treated by ablation in 2012 and 2014. Arrhythmic recurrence with low afterload. Currently in sinus rhythm.
History of recurrent epistaxis under treatment with oral anticoagulation. Carrier of Amulet 28 mm atrial appendage closure device and on treatment with simple antiplatelet therapy.
Benign thyroid nodules without alterations in thyroid function.
