HISTORY, CURRENT ILLNESS AND PHYSICAL EXAMINATION

PERSONAL HISTORY
We present the case of an 80-year-old female patient, autonomous and without cognitive impairment. She had a history of hypertension under treatment with lisinopril/hydrochlorothiazide 20/12.5 mg daily; type 2 diabetic with good metabolic control and without micro or macrovascular complications under treatment with metformin 1000 mg/sitagliptin 50 mg at breakfast and dinner; and dyslipidaemia under treatment with simvastatin 20 mg at dinner.
In addition, he has stage IV colorectal adenocarcinoma with lung metastases (metastatic debut in 2015) on third-line treatment with binimetanib and nivolumab since September 2018.

Current history
She consulted the ED three weeks after initiation of immunotherapy for progressive picture of exertional dyspnoea and two-pillow orthopnoea along with anorexia, asthenia and dizziness. He denied angina, syncope, as well as infectious focality or fever. He also reported no palpitations or other typical cardiological symptoms.

PHYSICAL EXAMINATION
Blood pressure (BP) 95/63 mmHg. Heart rate (HR) 85 bpm. External jugular ingurgitation in the middle third, eupneic in decubitus at 45 ̊ with O2 saturation 94% ambient air.
Rhythmic cardiac auscultation without murmurs. Pulmonary auscultation with good bilateral ventilation, moist crackles in the bases. Oedema with bilateral pretibial fovea.

COMPLEMENTARY TESTS
Electrocardiogram (ECG) on arrival at the emergency department: sinus rhythm at 80 bpm, normal PR. Wide QRS of 120 ms with BRD morphology and secondary repolarisation alterations. QTc 465ms.
PA and lateral chest X-ray on admission: cardiothoracic index not increased, bilateral perihilar thickening with vascular redistribution without occupation of costophrenic sinuses.
Emergency laboratory tests: haemoglobin 9.9 g/dl, MCV 89.4 fl, leukocytes 5880/μl with normal formula, platelets 132000/μl. INR 0.93, APTT 29.2 sec. Glucose 178 mg/dl, ALT 42 U/l, GGT 50 U/l, alkaline phosphatase 101 U/l, bilirubin 0.3 mg/dl, albumin 4 g/dl, creatinine 1.45 mg/dl, sodium 142 mmol/l, potassium 4.6 mmol/l, C-reactive protein 7.8 mg/dl, CK 2423 U/l, ultrasensitive troponin I 640.4 ng/l (VN < 21 ng/l), NT-proBNP 1509 ng/l.
Transthoracic echocardiogram: left ventricle neither dilated nor hypertrophic, normofunctioning with hypokinesia of basal and medial inferolateral segments. Mitral filling pattern with impaired relaxation. Non-dilated left atrium. Normal right chambers. Normal mitral valve. Trivalve aortic valve, with mild sclerosis and slightly elevated gradients (peak 20 mmHg). No evidence of pulmonary hypertension. IVT in RV outflow tract=23 cm (normal). No pericardial effusion. Inferior cava not dilated, physiologically collapsed.
Cardiac MRI with contrast: left ventricle of normal size, with slightly increased wall thickness. No alterations of segmental contraction. Practical systolic collapse of the distal cavity, hyperdynamic, with left ventricular ejection fraction (LVEF) 72%. In STIR sequences, predominantly mid-distal signal hyperintensity. Data suggestive of diffuse inflammation in T2 maps. Late enhancement without alterations.
Triceps muscle biopsy: H-E shows several necrotic fibres with myophagocytosis and scant clustering of nuclei. The HE technique identifies a slight inflammatory infiltrate composed mainly of histiocytes. Immunohistochemistry revealed CD68 positive and HLA-1 positive patchy HLA-1 predominantly in the perifascicular region. CD3 negative. Findings globally compatible with the diagnosis of necrotising inflammatory myopathy.
ECG at discharge (image 6): sinus rhythm at 70 bpm with normal PR and normopositioned narrow QRS with adequate progression in precordials without repolarisation alterations.
Blood tests at discharge: haemoglobin 10.4 g/dl, MCV 91.2 fl, leukocytes 7200/μl with normal formula, platelets 225000/μl. INR 0.81, APTT 27.7 sec. Glucose 101 mg/dl, ALT 42 U/l, GGT 19 U/l, alkaline phosphatase 76 U/l, bilirubin 0.3 mg/dl, albumin 3.8 g/dl, creatinine 0.97 mg/dl, sodium 141 mmol/l, potassium 3.7 mmol/l, C-reactive protein 0.4 mg/dl, CK 67 U/l, ultrasensitive troponin I 11 ng/l (VN < 21 ng/l), NT-proBNP 149 ng/l.
Anti-striated muscle antibodies (immunofluorescence): positive.

CLINICAL EVOLUTION
On arrival, and given the suspected diagnosis, empirical treatment was started with high-dose corticosteroids (methylprednisolone 2 mg/kg/day), oral diuretic at medium doses and telemetry monitoring.
During admission, there was a progressive normalisation of electrocardiographic alterations and markers of myocardial damage, as well as an evident parallel clinical improvement, tolerating a subsequent tapering regimen of systemic corticosteroids. Transthoracic echocardiography and magnetic resonance imaging showed preserved biventricular function, without valvular heart disease or late enhancement. Diffuse oedema predominantly mediodistal on T2-STIR sequences compatible with a myocarditis-type inflammatory process with no apparent sequelae. In addition, the positive result of anti-striated muscle antibodies and triceps brachii biopsy were consistent with the diagnosis of myositis.
It is worth mentioning that neither coronary angiography nor endomyocardial biopsy was necessary in this case since the clinical, analytical and ECG alterations, completely reversible with anti-inflammatory drugs, together with the autoimmunity, the muscle biopsy and the data from the T2-STIR sequences and maps are sufficiently important to establish the diagnosis of myocarditis due to immunotherapy (nivolumab).
Months later, she is still under outpatient follow-up in cardio-oncology outpatient clinics, asymptomatic, with normal ECG and troponins. Nivolumab, suspended after admission, has not been restarted.

DIAGNOSIS
Myocarditis and myositis due to nivolumab.
Metastatic colorectal adenocarcinoma.
Essential arterial hypertension. Type 2 diabetes mellitus.
