
We present the case of a 72-year-old male pacemaker user with complete atrioventricular (AV) block who presented to the emergency department with heart failure and constitutional syndrome.

HISTORY, CURRENT DISEASE AND PHYSICAL EXAMINATION

History
Cardiovascular risk factors: hypertension (HT), dyslipidaemia and type 2 diabetes mellitus (DM2) treated with oral antidiabetics. No toxic habits.
Cardiologic history: VDD pacemaker holder since 2003 due to complete AVB. Generator replacement in March/2019. Last cardiology consultation in January 2020, when severe ventricular dysfunction was observed with marked asynchrony due to ventricular stimulation by MCP, and he was referred to the arrhythmia unit for evaluation of upgrade to tri-chamber pacemaker (TRC).

Other medical and surgical history:
Obstructive sleep apnoea syndrome (OSA) with nocturnal continuous positive airway pressure (CPAP).
Anaemia and dysphagia under study by digestive medicine and internal medicine.
Gastroscopy and colonoscopy negative. Pending thoraco-abdomino-pelvic CT scan and oesophageal manometry.
Current treatment: atorvastatin 30 mg 1 tablet at dinner, vildagliptin/metformin 50/850 mg 1 tablet per day, omeprazole 20 mg 1 capsule at breakfast, ramipril 10 mg 1 tablet per day. Since the January consultation: bisoprolol 5 mg 1 tablet at breakfast, eplerenone 25 mg 1 tablet at breakfast, furosemide 40 mg 1 tablet at breakfast.

Present illness
A 72-year-old man came to the emergency department for dyspnoea. He reported progressive deterioration of his functional class (basically NYHA I) for 5 months, with marked worsening in the last two months, presenting dyspnoea on minimal effort, subjective decrease in diuresis and nocturia, without orthopnoea, PND, oedema or other symptoms of congestion. He had asthenia, intermittent dysthymic sensation and weight loss of 20 kg during this period. Absence of improvement after initiation of diuretics by departmental cardiology following echocardiographic findings.

Physical examination
Blood pressure (BP) 100/60 mmHg, heart rate (HR) 85 bpm, SpO2 93% (with O2 through nasal goggles at 2 L/min).
Afebrile. Good general condition. Conscious and oriented. Skin pallor. Eupneic at rest, tolerates decubitus. No jugular engorgement. Cardiac auscultation: regular heart sounds, systolic murmur III/VI in left sternal border and mitral focus. Pulmonary auscultation: bibasal crackles, rest of lung fields with preserved vesicular murmur. Abdomen soft and depressible, no palpable masses or megaliths, no peritoneal irritation, preserved peristalsis.
Lower limbs with discrete tibiomalleolar oedema.

COMPLEMENTARY TESTS
Electrocardiogram (ECG) on admission: sinus rhythm at 75 bpm with ventricular conduction mediated by electrostimulation, wide QRS with morphology of left bundle branch block, secondary repolarisation alterations. Ventricular extrasystoles.
Chest X-ray on admission: slightly increased cardiothoracic index (CTI), prominent hilarity, no alveolar consolidation or pleural effusion. Pacemaker lead normally positioned in the right ventricle.

Laboratory tests:
CBC: red cells 4.19 10*12/l; Hb 10.2 g/dl (nadir 8); Htc 31.6%; MCV 75.3 fl; leukocytes 6000/L (PMN 76.7%; nadir 100 cells/μL); platelets 109000/l; MPV 8.8 fl; platelets (citrate) 89 10*9/L (nadir 31000).
Biochemistry: glucose 139 mg/dl; sodium 135 mEq/l; potassium 3.9 mEq/l; chlorine 101 mEq/l; urea 74 mg/dl; creatinine 0.98 mg/dl, estimated GFR (CKD-EPI) 76.71 ml/min/1.73 m2; total bilirubin 0.82 mg/dl, GPT 26 U/l, GOT 21 U/l, GGT 24 U/l; protein 5.8 g/dl; CRP 10.9 mg/dl.
Coagulation: prothrombin time (PT) 15.6 sec; Quick index 69%; INR 1.33; aPTT 30.2 sec; ratio (aPTT) 1.01; derived fibrinogen 410 mg/dl.
Serial blood cultures during the entire admission, in standard and special media, for bacteria and fungi: negative.
Bacterial and viral serologies: negative.
Autoimmunity, including ANA, ANCA, rheumatoid factor, antiphospholipid antibodies: negative.
Haemolysis markers such as LDH, haptoglobin and reticulocytes: negative.
Bone marrow aspirate: no significant alterations observed. Correct myeloerythroid quotient. Microbiological cultures and parasite study negative.
Cultures of resected valve material and explanted pacemaker wire: negative.

Thoracic-abdominal-pelvic CT with contrast: thorax: both main and lobar pulmonary arteries show normal morphology and calibre. No repletion defects are observed. No axillary, mediastinal or hilar adenopathies of significant size are identified. Hypoventilation bands in both lower lobes. No pleural effusion. Abdomen-pelvis: liver with lobulated contours and slightly heterogeneous density, suggestive of chronic liver disease. Pancreas and adrenal glands are normal.
Bilateral simple renal cysts. Lithiasis in the right kidney, with no significant impact on the excretory tract. Splenomegaly of 16.6 cm with several foci of infarction inside. No retroperitoneal or mesenteric adenopathy. No free intra-abdominal fluid.
Diverticulosis of the sigma.

Transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE): left ventricle with moderate eccentric hypertrophy (TIV and PPVI 14 mm, DTDVI 62 mm), increased volumes (VTD BP 170 mL) and severe depression of global systolic function (LVEF BP 27%) with marked asynchrony, wide anomalous septoapical movement by electrostimulation. Slight aortic root dilatation without valve dysfunction.
endocarditis over native pulmonary valve: large pedunculated vegetation with a maximum diameter of 40 mm, with deflected edges, with great mobility and systodiastolic protrusion over the pulmonary valve. No significant valvular involvement was observed. No vegetations or other pathological changes were observed on the tricuspid valve or pacemaker lead.
endocarditis on mitral valve with vegetation image on anterior mitral leaflet of 11 mm. Moderate mitral insufficiency (ORE by PISA 0.3 cm2) due to slight eversion of the leaflet, with rupture of the chordae tendineae and eccentric jet directed to the posterior face of the atrium. Diastolic pattern compatible with impaired relaxation (E 90 cm/s, A 113 cm/s), with significant increase in filling pressures (E/e' 17). Biauricular dilatation. Right ventricle of normal diameters with preserved global systolic function (TAPSE 22 mm). Mild TR allowing estimation of PAPs of approximately 50 mmHg (moderate PHT). Inferior vena cava plethora (IVC).
Coronary angiography: Truncus description: normal. Anterior descending description: severe stenosis in proximal segment. Diagonal branch distal to the lesion very developed (double DA system). Circumflex description: normal. Right coronary description: dominant. No stenosis.

CLINICAL EVOLUTION
The patient was initially admitted to the cardiology ward with depletive and disease-modifying treatment for heart failure. In view of the constitutional syndrome, a thoracic-abdominal-pelvic CT scan was requested to rule out concomitant neoplasia. There were no findings compatible with neoplastic disease. However, splenomegaly with foci of splenic infarction was noted.
In view of these findings, a repeat TTE was performed, which revealed, in addition to the ventricular dysfunction already observed in the study performed in the previous 3 weeks, a large mobile mass in the pulmonary valve and moderate mitral insufficiency on a valve with a small mass compatible with endocarditis. Transesophageal echocardiography was performed, confirming the diagnosis, so serial blood cultures were taken and empirical antibiotic therapy was started with vancomycin (20 mg/kg/12 hours i.v.) and gentamicin (3 mg/kg/day i.v.).
In the first days of admission, the patient remained very symptomatic, with dyspnoea on minimal exertion and episodes of sudden dyspnoea, although afebrile. Chest CT angiography was performed on suspicion of septic embolism, which was ruled out.
The case was discussed at a medical-surgical session and scheduled for surgery. However, the patient evolved unfavourably, presenting an episode of acute pulmonary oedema and requiring transfer to the coronary unit for stabilisation.
Progressive blood tests showed significant anaemisation, with a drop to 8 g/dl, requiring transfusion given the clinical condition. In addition, severe neutropenia and thrombopenia were observed (nadir of 100 cells/μl and 31000/l, respectively). Because of this, it was decided to postpone surgery. He was assessed by haematology, started on treatment with granulocyte colony-stimulating factors (G-CSF), and a bone marrow aspirate was performed.
Due to neutropenia, meropenem 1g/8h i.v. was added to the treatment, with the appearance of a generalised maculopapular rash that forced its interruption. Meanwhile, the result of the aspirate showed no pathological findings, so it was considered that the origin of the haematological alteration could be drug-related, and it was decided to replace vancomycin with daptomycin (10 mg/kg/day i.v.).
With this measure and the administration of G-CSF, the patient showed progressive analytical improvement.
Coronary angiography was performed as part of the preoperative study, showing a severe lesion in the proximal anterior descending artery, which was left for surgical revascularisation.
All blood cultures in standard and special media for fungi and bacteria were negative. Serology and even autoimmunity tests were performed, all of which were negative and the microorganism responsible could not be identified. Nuclear medicine tests were considered in view of the lack of an aetiological diagnosis; however, given the patient's clinical situation, they were not carried out.
Finally, clinical stability was achieved, and surgery was performed to replace the mitral and pulmonary valves with biological prostheses. In addition, the pacemaker lead and generator were removed and epicardial leads were implanted in the AD, RV and LV for resynchronisation, with placement of a new generator in the right abdominal subcostal region. Bypass over the LAD was ruled out as the vessel could not be adequately exposed due to the presence of abundant epicardial fat, so percutaneous coronary intervention (PCI) over the LAD will be performed at a later date. The valve debris and the distal end of the wire were sent to microbiology.
The patient was transferred to cardiac resuscitation, where he progressed favourably, was transferred to the ward and was discharged after 2 weeks, with follow-up in the heart failure unit and arrhythmia unit.

DIAGNOSIS
Endocarditis on native pulmonary and mitral valves, with moderate mitral insufficiency with eversion of the anterior leaflet due to rupture of the chordae tendineae.
Heart failure with depressed ejection fraction with marked asynchrony due to ventricular electrostimulation.
Splenic infarcts secondary to infective endocarditis.
Agranulocytosis and thrombopenia of probable drug origin.
Toxicoderma due to meropenem.
