HISTORY, CURRENT ILLNESS AND PHYSICAL EXAMINATION

History
61-year-old woman. Personal history: No known drug allergies. No cardiovascular risk factors. Recent admission to internal medicine for community-acquired pneumonia and debut of heart failure. No surgical interventions. Other history: depressive syndrome, vertiginous syndrome since 2017, dorsalgia (followed up by rehabilitation). Usual treatment: betahistine 8 mg (1-0-1), bromazepam and paracetamol/codeine on demand. Family history: diabetic father, with CKD requiring haemodialysis and unspecified heart disease. Mother with atrial fibrillation and brother with acute non-ST-segment elevation myocardial infarction (NSTEMI) at 54 years of age.   Current illness: Consultation for several months of dyspnoea progressing to minimal effort with orthopnoea, paroxysmal nocturnal dyspnoea (PND), cough with purulent expectoration, decreased diuresis and dysthermic sensation.

Physical examination
Vital signs: blood pressure 124/72 mmhg, heart rate 98 bpm, respiratory rate 24 rpm, temperature 36°C. Good general condition. No jugular ingurgitation. Cardiac auscultation: rhythmic sounds with systolic murmur intensity II/VI in aortic focus. Pulmonary auscultation: diminished sounds in the right base and scarce bilateral crackles. Extremities without oedema.

COMPLEMENTARY TESTS
Urgent laboratory tests: haemogram: leucocytes 9,800 /μl (79.8% neutrophils), haemoglobin 12.4 g/dl, haematocrit 37.3%, platelets 160,000. Biochemistry: glucose 90 mg/dl, creatinine 0.5 mg/dl, urea 33 mg/dl, bilirubin 1.26 mg/dl, GOT 21 U/l, GPT 33 U/l, Na 144 mEq/l, K 1.5 mEq/l, Cl 104 mEq/l, CRP 0.47, TSH 1.04. Cardiac markers: ultrasensitive troponin I 10.2, NT-proBNP 8026 pg/ml. Antigenuria: pneumococcal antigen positive, Legionella pneumophila serogroup 1 antigen negative. SARS-CoV-2 PCR: negative. Chest X-ray on admission: normal cardiac silhouette, small interstitial infiltrate in the right base and small pleural effusion. ECG: sinus rhythm at 90 bpm, normal PR, right axis, incomplete right bundle branch block of the HH, Rs in V2-V4, without repolarisation disorders. Laboratory tests on the hospital ward: serum proteinogram: total proteins 6.4, albumin 3.37 g/dl (52.6%), alpha-1-globulins 0.35 g/dl (5.5%), alpha-2-globulins 0.79 g/dl (12.5%), B-globulins 1.14 g/dl (17.8%), gamma-globulins 0.75 g/dl (11.7%), monoclonal band in the beta region of 7.1% (0.45 g/dl), corresponds to an IgA kappa band. Serum free kappa light chains 4040 mg/l, serum free lambda light chains < 5 mg/l. Immunoglobulins: IgG 413 mg/dl, IgA 952 mg/dl, IgM < 20 mg/dl. Autoimmunity profile: negative. Urine study: protein/creatinine ratio 0.61, proteinuria in 24 hours 480 mg, kappa light chains in urine 17.7 mg/dl, lambda light chains < 1.5 mg/dl. Transthoracic echocardiogram (videos 1 and 2): left ventricle of preserved dimensions, with severely increased concentric wall thickness (16 mm), LVEF 68%, no segmental contractility defects. Diastolic dysfunction grade II, psudonormalised pattern (E/A 1.8 E/e" 17). Severe mitral insufficiency, dilated left atrium (50 mm). Right ventricle of preserved dimensions and systolic function, estimated PAPS 52 mmHg. Reduced global longitudinal Strain, preserved in apical segments, with deterioration in the basal region. Cardiac magnetic resonance (CMR): anterior ascending (AD) area in 4C 25 cm2, right ventricle (RV) 76X46X52 mm. Left atrium (LA) area 28 cm2, left ventricle (LV) 50X40X69 mm. T1 non-enhanced. Interventricular septum 19.5 mm, slight circumferential pericardial effusion of subcentimetric thickness. Non-dilated left ventricle, with severe septal hypertrophy and moderate circumferential hypertrophy at baso-medial level, contractility without segmental deficits. After i.v. contrast, difficulty in myocardial signal cancellation in LL sequence, showing diffuse endocardial enhancement of basal predominance, almost transmural in basal lateral face and mid-apical transmural mottling, with some respect for the basal septum. Probable endocardial enhancement in left atrium. Slightly hypertrophic right ventricle with tricuspid insufficiency (TI), mitral insufficiency (MI) and LVOT acceleration jet, without clear SAM. Brain magnetic resonance imaging (MRI): broad-based bony overgrowth affecting the posterior wall of the left internal auditory canal, compatible with exostosis. Pyrophosphate cardiac scan: Perugini grade 1 uptake. Abdominal subcutaneous cellular tissue biopsy: no relevant lesions, Congo red negative. Bone marrow biopsy: Congo red negative, slightly hypercellular with mature forms of the three series and mild-moderate interstitial plasmacytosis (21-24%) and restriction of kappa light chains.

CLINICAL EVOLUTION
The patient was admitted to the internal medicine department for symptoms compatible with community-acquired pneumonia with associated small pleural effusion. Antibiotics were administered with ceftriaxone plus clarithromycin for 7 days, with partial improvement of cough, but still with persistent dyspnoea, orthopnoea and development of oedema in the lower limbs. A control chest X-ray showed a slight increase in pleural effusion. In addition, blood tests showed an elevation of NT-proBNP disproportionate to the clinical picture. Following the findings observed in the echocardiogram, cardiology assessment was requested and the patient was transferred to the cardiology department. During admission to the cardiology ward, the patient remained stable, but persisted with occasional dizziness and oedema in the lower limbs despite diuretic treatment. The echocardiogram showed symmetric concentric hypertrophy of the left ventricle associated with diastolic dysfunction, high filling pressures and altered strain. In the aetiological study of the condition, CMR was performed with findings highly suggestive of cardiac amyloidosis. To establish a differential diagnosis between AL cardiac amyloidosis and ATTR, pyrophosphate scintigraphy was performed, which showed mild myocardial uptake, as well as a proteinogram and immunofixation in blood and urine, which detected a monoclonal IgA kappa-type component. Abdominal fat biopsy with Congo red stain was negative for amyloidosis. Bone marrow biopsy was then performed with plasmacytosis greater than 20%. These findings were compatible with multiple myeloma. Finally, a salivary gland biopsy was performed and was positive for amyloidosis. The patient was transferred to haematology and started treatment with bortezomib-cyclophosphamide-dexamethasone protocol.

DIAGNOSIS
Acute heart failure with preserved LVEF.
AL cardiac amyloidosis.
Multiple myeloma IgA kappa.
Community-acquired pneumonia.
