HISTORY, CURRENT ILLNESS AND PHYSICAL EXAMINATION

History
No known adverse drug reactions. Cardiovascular risk factors: hypertension, type 2 diabetes mellitus. Dyslipidaemia. Smoker of 1 pack a day. Alcoholic habit of 1-2 standard drink units per day. Obesity. Chronic ischaemic heart disease. 2-vessel disease. In 2015, due to stable angina, proximal anterior descending artery was revascularised with a drug-eluting stent. Subsequently in 2019, as a result of acute hypertensive pulmonary oedema, a new lesion was found in the circumflex ostium treated with a drug-eluting stent and a moderate lesion in the dominant right coronary artery that was not treated. Follow-up by the heart failure unit with severely depressed LVEF (recovered) of mixed aetiology (tachycardiomyopathy and ischaemic) in baseline functional class NYHA II. Paroxysmal atypical atrial flutter. Last electrical cardioversion (ECV) in October 2020, effective.

*** Last echocardiography 2019: left ventricle, with preserved diameters, volumes and global systolic function (EF 63%) with anterolateral medial and apical hypokinesia with preserved contractility of the remaining segments. Aortic sclerosis without significant functional repercussions. Diastolic pattern with single E wave with indirect data of slightly increased filling pressures. Dilated left atrium. Right ventricle with normal diameters and global systolic function. Mild tricuspid regurgitation, systolic pulmonary artery pressure approximately 65-70 mmHg (severe pulmonary hypertension [PHT]). Normal inferior vena cava.

Other history: Chronic obstructive pulmonary disease moderate emphysema phenotype. Obstructive sleep apnoea hypopnoea syndrome with use of nocturnal CPAP. Bladder tumour pT1G3 + CIS in follow-up by urology. Stage IIIA chronic kidney disease (CKD) (baseline creatinine around 1.2) with exacerbation in the context of excessive blood pressure control. Chronic constipation with haemorrhoids and anal fissure. Normocytic-normochromic anaemia with gastrocolonoscopy with colon polyps, chronic gastritis and hyperemic erythematous duodenitis (last colonoscopy in 2017). Peripheral arterial disease: chronic ischaemia of lower limbs. Aortobifemoral thrombosis in February 2015. Benign prostatic hyperplasia. Chronic glaucoma. Depressive disorder Usual treatment: sacubitril/valsartan 97/103 mg (1 tablet every 12 hours), bisoprolol 5 mg (1 tablet every 12 hours), furosemide 40 mg (1 tablet every 12 hours), amlodipine 10 mg (1 tablet per day), spironolactone 25 mg (2 tablets daily), edoxaban 60 mg (1 tablet daily), pantoprazole 40 mg (1 capsule daily), amiodarone 200 mg (1 tablet daily), insulin glargine 36 IU daily, atorvastatin/ezetimibe 40/10 mg (1 tablet daily), indacaterol/glycopyrronium bromide 85/43 micrograms (1 capsule daily), silodosin 4 mg (1 tablet daily), allopurinol 300 mg (half a tablet daily), brinzolamide (1 drop every 12 hours), saflutan/taptiqom (1 drop daily), venlafaxine 75 mg (1 tablet daily), cholecalciferol 25000 IU (1 ampoule every 30 days), lipase/amylase/protease 25000 (2 capsules after each meal).

Present illness
65-year-old male admitted to the coronary unit for acute hypertensive pulmonary oedema. The patient reported deterioration of functional class over 2 weeks of evolution to dyspnoea on light exertion, with orthopnoea and paroxysmal nocturnal dyspnoea (attenuated by nocturnal CPAP), with increased peripheral oedema without subjective decrease in diuresis in the context of decompensated CHF with no clear apparent trigger, although it could be related to uncontrolled arterial hypertension (AHT) at home. On arrival at the ED he presented with dyspnoea at rest in a situation of global respiratory failure in the context of acute hypertensive pulmonary oedema (165/95 mmHg). Depletive treatment was intensified with perfused furosemide together with non-invasive mechanical ventilation in BiPAP mode, achieving progressive negative balances and clinical improvement. During his stay, a right thoracentesis was also performed with an output of 1,000 ml of serous fluid with clinical improvement without complications. After clinical improvement and haemodynamic and respiratory stability, the patient was discharged to the cardiology ward. Four days later, the patient's dyspnoea worsened again with the need for NIMV, and bedside echocardiography was performed in the acute phase, describing significant acute mitral insufficiency due to asymmetrical posterior tethering.   Physical examination Conscious and oriented, eupneic at rest with NIMV in BiPAP mode. Adequate diuresis with furosemide perfusion.

Blood pressure 160/95 mmHg, heart rate 65 bpm, peripheral oxygen saturation 93% (FiO2 35%). Cardiac auscultation: regular sounds, systolic murmur II/VI. Pulmonary auscultation: preserved vesicular murmur, bilateral midbasal crackles, scattered rhonchi, right basal hypophonasis. Extremities: tibiomalleolar oedema with fovea, no signs of deep vein thrombosis.

COMPLEMENTARY TESTS
AP chest X-ray: signs of venous congestion, bilateral intersticioalveolar infiltrate predominantly basal, bilateral pleural effusion predominantly right. 12-lead electrocardiogram: sinus rhythm at 60 bpm, PR 200 ms, QRS 100 ms, poor septal vector progression, QS in V1-V2, ST-segment depression with asymmetric negative T in II, III, aVF, V5-V6, ST-segment elevation in aVR. Transthoracic echocardiogram at bedside: suboptimal examination due to sitting position. Left ventricle of normal diameters and volumes with slightly depressed global function secondary to anterolateral and lower middle basal hypokinesia with preserved contractility of the rest of the segments. Moderate-severe mitral insufficiency due to asymmetric posterior tethering. Aortic sclerosis without significant functional repercussions. Diastolic pattern with indirect data of increased filling pressures. Dilated left atrium. Right ventricle with normal diameters and global systolic function. Mild tricuspid regurgitation, systolic pulmonary artery pressure approximately 65-70 mmHg (severe PHT). Plethoric inferior vena cava. Diffuse bilateral B-lines.

Blood tests (ED): CBC: haemoglobin 11.4 g/dl, haematocrit 34.2%, MCV 90fl, leucocytes 10.9 10*9/l, neutrophils 10 10*9/l, lymphocytes 0.3 10*9/l, platelets 250 10*9/l. Haemostasis: INR 2.15, Quick index 33%. Biochemistry: glucose 90 mg/dl, sodium 132 mEq/l, potassium 5.1 mEq/l, chlorine 96 mEq/l, total bilirubin 1.46 mg/dl, GPT 8 U/l, urea 107 mg/dl, creatinine 2.23 mg/dl, C-reactive protein 1.2 mg/dl. Arterial blood gases (FiO2 50% in Ventimask): pH 7.42, pCO2 35, pO2 48 mmHg, HCO3a 22.7 mmol/l, lactate 1.8 mmol/l. Arterial blood gas (1 hour BiPAP control): pH 7.37, pCO2 39 mmHg, pO2 74 mmHg, HCO3a 22.5 mmol/l, lactate 0.8 mmol/l. NT-proBNP 11955 pg/ml. Troponin I (hsTnI): 43 mg/dl (0- 21 mg/dl).

Blood analysis (admitted): CBC: red cells * 3.55 10*12/l, haemoglobin * 12.2 g/dl, haematocrit * 37.1%, MCV 91 fl, leukocytes 8.5 10*9/l, neutrophils 7.1 10*9/l, lymphocytes * 0.6 10*9/l, monocytes 0.7 10*9/l, eosinophils 0.1 10*9/l, basophils 0.1 10*9/l, platelets 211 10*9/l. Haemostasis: prothrombin time (PT) * 26.6 sec, Quick's index * 31%, INR * 2.24, aPTT 36.5 sec, ratio (aPTT) * 1.22. Derived fibrinogen 433 mg/dl. Glycosylated haemoglobin (HbA1c): 7.4%. Biochemistry: glucose * 146 mg/dl, sodium 140 mEq/l, potassium 4.2 mEq/l, chlorine * 96 mEq/l, magnesium * 1.5 mg/dl, total bilirubin * 1.5 mg/dl, aspartate aminotransferase GOT 19 U/l, alanine aminotransferase GPT 10 U/l, alkaline phosphatase * 167 U/l, gamma-glutamyl transferase * 203 U/l, urea * 70 mg/dl, creatinine 1.11 mg/dl, alkaline reserve 26 mmol/l, estimated GFR CKD-EPI 69.8 ml/min/1.73 m2, calcium 10.2 mg/dl, phosphorus 3.7 mg/dl, uric acid 6.8 mg/dl, protein 6.8 g/dl, albumin 4.2 g/dl, prealbumin 20.1 mg/dl, C-reactive protein * 0.7 mg/dl. Iron profile: ferritin * 304 μg/l, iron * 60 μg/dl, total Fe binding capacity 338 ug/dl, transferrin saturation index * 17.8%, latent Fe binding capacity 278 ug/dl. Lipid profile: total cholesterol 107 mg/dl, triglycerides 83 mg/dl, HDL cholesterol 47 mg/dl, non-HDL cholesterol 55 mg/dl. Urine: spot creatinuria 63.0 mg/dl, spot albuminuria 1.07 mg/dl, albuminuria/creatinuria index 17 mg/g creatinine. Vitamins: vitamin B12 465 pg/ml, folic acid 4.3 ng/ml. Nasopharyngeal exudate RT PCR SARS-CoV-2: negative. Catheterisation (videos 2-4): dominance: right dominant. Coronary arteries: significant stenosis. Truncus description: with atheromatosis without stenosis. Anterior descending description: good late result of the stent implanted on LD-CT. Circumflex description (CX): new ostial restenosis 90%, so new angioplasty is performed with implantation of ULTIMASTER TANSEI- sirolimus 3.0/12 mm drug-eluting stent, with minimal protrusion in LMCA and ending with post-dilatation in kissing balloon to avoid displacement of struts of the LMCA-AD stent. Right coronary description: dominant vessel unchanged with respect to previous exploration, with 50% lesion in proximal segment. Left radial with EBU 3.5 6F, BMW guides to DA and CX, predilatation with 3 balloons in kissing and implantation of ULTIMASTER TANSEI stent (3x12) with stopper balloon in TCI-DA and final postdilatation in kissing. Conclusions: recurrent in-stent restenosis in CX ostium. PTCA on the SIRS with sirolimus DES implantation and final post-dilatation in kissing. Moderate lesion persists in proximal DC with no changes with respect to the previous exploration.

CLINICAL EVOLUTION
On re-admission he was desaturated, with intense respiratory work and mildly obnubilised, so non-invasive mechanical ventilation (NIV) was started with a very good initial response and perfusion of furosemide. After clinical and blood pressure stabilisation, a new echocardiogram was performed which showed normalisation of the previously described alterations in segmental contractility and a decrease in the degree of mitral regurgitation to mild. Due to suspicion of acute mitral insufficiency (echocardiography in 2019 did not reveal mitral insufficiency) in the context of ischaemia due to high blood pressure, coronary angiography was performed, revealing in-stent restenosis in the circumflex ostium, which was treated with a new drug-eluting stent. Control tests showed recovery of renal function to baseline and correction of initial mild hyperkalaemia to mild hypokalaemia, requiring supplementary potassium, and a red blood cell concentrate due to anaemia without active bleeding. The patient continued to progress favourably until transferred to a conventional hospital ward and was subsequently discharged home. In a patient with high ischaemic risk (cardiovascular risk factors, chronic ischaemic heart disease and previous peripheral artery disease and in-stent restenosis) and high haemorrhagic risk (normocytic-normochromic anaemia due to digestive losses, bladder tumour under follow-up, poorly controlled hypertension at home and chronic kidney disease), double therapy was prescribed with apixaban 5 mg every 12 hours and clopidogrel 75 mg daily; triple therapy was used during hospitalisation. The change from edoxaban to apixaban is due to the consideration of the European guidelines for atrial fibrillation of the use of apixaban or dabigatran 110 mg due to the lower rate of gastrointestinal bleeding compared to warfarin. As an obese patient with type 2 diabetes mellitus under suboptimal treatment with HbA1c of 7.4%, semaglutide 0.25 mg weekly subcutaneously is started for 4 weeks with a view to increasing to 0.5 and 1 mg thereafter. In addition, metformin/empagliflozin 1,000 mg/5 mg every 12 h is added (and if tolerated will be increased to 1,000 mg/12.5 mg every 12 h). Subsequently, insulin therapy is reduced according to requirements. The patient continues with controls in the heart failure unit without incident.

DIAGNOSIS
Acute pulmonary oedema in the context of acute ischaemic mitral insufficiency.
In-stent restenosis of the circumflex artery.
Type 2 diabetes mellitus with suboptimal treatment.
