HISTORY, CURRENT ILLNESS AND PHYSICAL EXAMINATION
The patient is a 72-year-old male, allergic to penicillin and intolerant to tramadol and metformin, with criteria of metabolic syndrome (with central obesity). He has been diagnosed with hypertension (HT), dyslipidaemia (DLP) and DM2 for a long time, with erratic control of these CVRF to date. Ex-smoker for about 8 years. Multifactorial chronic kidney disease (CKD) with creatinine levels around 1.5 mg/dl, chronic obstructive pulmonary disease (COPD) and sleep apnoea syndrome (OSAHS) with indication for CPAP. He had undergone lumbar canal surgery five years earlier (posterior cord electrostimulator, under follow-up by the pain unit) and resection of colon polyps (benign).
His cardiological history begins in the 1990s, when he was diagnosed with ischaemic heart disease (debut as AMI), with three-vessel disease on coronary angiography. He underwent surgical revascularisation by double bypass: internal mammary artery (IMA) to anterior descending artery (ADA) and saphenous vein to circumflex artery (ACx); without approaching the right coronary artery (RCA) due to severe and diffuse disease.
He was assessed for the first time in 2010 in the HF unit of his hospital due to clinical worsening, with the finding of ventricular dysfunction (LVEF 35-40%) in transthoracic echocardiography, unknown until then. Repeat coronary angiography showed patency of the AMI-ADA bypass, with occlusion of the saphenous vein graft to ACx (thin vessel and diffuse disease), which was considered for conservative management. First admission for HF in 2015, with decompensation occurring in the context of atrial flutter, which underwent cavotricuspid isthmus ablation. Implantation of a single-chamber ICD for primary prevention that same year, with no arrhythmic events to date. New admission for dyspnoea and chest pain in 2016, with no notable changes in the control coronary angiography. More than two admissions throughout 2017, with clear clinical deterioration, for which an assessment was requested in our HF unit two years ago.
On consultation, the patient reported minimal effort dyspnoea (NYHA III), chronic two-pillow orthopnoea and bendopnoea, without clear paroxysmal nocturnal dyspnoea. There were also signs of water retention, mainly oedema in the lower limbs (lower limbs). No clinical data suggestive of low output. Regular blood pressure control at home with ambulatory systolic blood pressure (SBP) of around 160 mmHg.
Physical examination showed good general condition. Conscious and oriented in all three spheres.
Tendency to hypertension (160/90 mmHg). Heart rate (HR) 70 bpm. Basal saturation 94%. Weight 119 kilograms (kg). Height 1.72 metres (m). Body mass index (BMI) 40.2 kg/m . Obesity class III. Auscultation is rhythmic and there are no murmurs. Minimal crackles at the bases. Abdomen soft and depressible, without palpable masses or megaliths. MMII with oedema from the knee. Acceptable distal capillary refill.
The treatment he was taking at the time is summarised below: acenocoumarol for target INR 2-3, acetylsalicylic acid (ASA) 100 mg 1-0-0, carvedilol 25 mg 0.5-0-0.5, enalapril 20 mg 1-0-1, eplerenone 25 mg 0-1-0, furosemide 40 mg 2-2-0, chlorthalidone 50 mg half tablet every other day, atorvastatin 40 mg 0-0-1, omeprazole 20 mg 1-0-0, tiotropium bromide one inhalation per day, insulin aapid 34-32-38, paracetamol and metamizole on demand.

COMPLEMENTARY TESTS
CBC 1 (initial): glucose 127 mg/dl (60.0-100.0), urea 64 mg/dl (21.0-50.0), creatinine 1.46 mg/dl (0.6-1.2), glomerular filtration rate 48 ml/min/1.73 m2, uric acid 7.8 mg/dl (3.4-7.0), cholesterol 183 mg/dl, hDL-C 32 mg/dl, LDL-C 107 mg/dl, triglycerides 221 mg/dl, total protein 7.4 g/dl (6.0-8.0), albumin 4.4 g/dl (3.5-5.0), sodium 142 mmol/l (135.0-145.0), potassium 4.2 mmol/l (3.5-5.0), total bilirubin 0.5 mg/dl (0.3-1.1), NT-proBNP 3463 pg/ml (10.0-125.0), LDH 335 U/l (230.0-460.0), ALT (GPT) 21 U/l (6.0-40.0), AST (GOT ) 25 U/l (6.0-40.0), alkaline phosphatase 96 U/l (40,0-128.0), gamma-glutamyltransferase 216 U/l (8.0-61.0), c-reactive protein 20.0 mg/l (0.1-10.0) glycohaemoglobin (HbA1c) 8.8%, leucocytes 8.92 x10E3/microL, haemoglobin 17.40 g/dl, platelets 245.00 10E3/microL, INR 1.47 R.N.
CBC 2 (at six months): glucose 117 mg/dl, urea 53 mg/dl, creatinine 1.36 mg/dl, glomerular filtration 53 mL/min/1.73 mE2, uric acid 6.6 mg/dl, cholesterol 160 mg/dl, HDL-C 34 mg/dl, LDL-C (calculated) 89 mg/dl, triglycerides 185 mg/dl, total protein 6.9 g/dl, albumin 4,1 g/dl, calcium 9.3 mg/dl, sodium 143 mmol/l, potassium 4.8 mmol/l, NT-proBNP 1010 pg/ml, LDH 333 U/l, ALT (GPT) 11 U/l, AST (GOT) 16 U/l, alkaline phosphatase 67 U/l, gamma-glutamyltransferase 80 U/l, glycohaemoglobin (HbA1c) 8.0 %, leucocytes 7.92 x10E3/microL, haemoglobin 18.40 g/dl, platelets 180.00 10E3/microL, INR 2.10 R.N.
CBC 3 (at one year): glucose 103 mg/dl, urea 50 mg/dl, creatinine 1.31 mg/dl, glomerular filtration 55 ml/min/1.73 mE2, uric acid 6.8 mg/dl, cholesterol 143 mg/dl, HDLc 35 mg/dl, LDL cholesterol (calculated) 76 mg/dl, triglycerides 163 mg/dl, total proteins 6.9 g/dl, albumin 4.2 g/dl, calcium 9.2 mg/dl, sodium 139 mmol/l, potassium 4.9 mmol/l, NT-proBNP 835 pg/ml, LDH 330 U/l, ALT (GPT) 13 U/l, AST (GOT ) 16 U/l, alkaline phosphatase 69 U/l, gamma-glutamyltransferase 71 U/l, glycohaemoglobin (HbA1c) 7.3%, leucocytes 6.46 x10E3/microL, haemoglobin 17.20 g/dl, platelets 202.00 10E3/microL, INR 2.6 R.N.
Electrocardiogram: sinus bradycardia at 50 bpm. Left axis. Atrial enlargement data. PR 200 ms. Wide QRS 120 ms. Inferior Q. Inferolateral ST rectified, flattening in DI and AvL. QTc 470 ms.
Chest X-ray: increased cardiothoracic index. Free costophrenic sinuses. Generator and electrode in normal position. No images of condensation or pleural effusion.
Transthoracic echocardiogram: study limited by poor acoustic window and obesity. Dilated cardiomyopathy with moderately dilated left ventricle (LV), with moderately depressed contractility. EF 35-38%. Extensive inferior, posterior and lateral akinesia. Diastolic dysfunction. Aortic valve sclerosis. Valvular flows without significant alterations. Minimal mitral insufficiency (MI) that does not allow estimation of PAPs, but without data of severe pulmonary hypertension (PHT) due to pulmonary acceleration. Implantable cardioverter defibrillator (ICD) lead in right cavities. Right ventricle (RV) apparently normal with preserved longitudinal systolic function. No pericardial effusion.

CLINICAL EVOLUTION
In the first consultation assessment and, given the clinical situation and analytical results (see analytical 1 in complementary tests), it was decided to start neurohormonal medication for HF with reduced ejection fraction (EFred), increasing the dose of beta-blocker (carvedilol was increased to 25 mg every 12 hours). Enalapril is replaced by sacubitril/valsartan 24/26 mg every 12 hours (with a blanking period due to prior treatment with ACE inhibitors). The dose of mineralocorticoid receptor antagonist (MRA) is doubled to 50 mg eplerenone daily. ASA was also discontinued, maintaining oral anticoagulation.
It was decided to add ezemitiba as lipid-lowering treatment for LDL outside the target range for ischaemic patients. Given the results of glycated haemoglobin (Hb1Ac) and given that this was a patient with HF, a sodium-glucose cotransporter receptor inhibitor (iSGLT2) was added: empagliflozin 10 mg every 24 hours.
Given the volemia situation in the consultation and, prioritising the titration of drugs for HF with FEred, the dose of furosemide was reduced to 2-1-0 and chlorthalidone was discontinued. On the other hand, a reduction in the need for diuretics was expected after starting iSGLT2.
The patient was assessed again after 6 months in consultations. He has not been admitted for decompensation of HF and suggests clinical stability. He reported improvement in functional class, with current dyspnoea on moderate exertion (NYHA II), although he was still limited by muscular pain related to his lumbar pathology. He also reports a significant reduction in oedema in the lower limbs and has lost about 8 kg in weight since the last visit (he acknowledges better dietary compliance). He periodically monitors his blood pressure, with TAS values of around 130-140 mmHg.
On examination, the patient is in good general condition. Haemodynamically
stable with BP 140/80 mmHg. HR 55 bpm. O2 saturation 95%. Weight 111 kg. Height 1.72 m. BMI 37.5 kg/m . Obesity class II. Minimal crackles on auscultation, with limitation of oedema to the bimalleolar area. Good distal capillary filling persists.
The clinical improvement corresponds with the analytical results (see analytical 2 in complementary tests), showing a reduction of NT-proBNP from 3463 pg/ml to 1010 pg/ml. Glycaemic and lipid control, although still outside target values, has also improved (HbA1c has been reduced to 8% and LDL is around 90 mg/dl).
At this visit, it was decided to increase the dose of sacubitril/valsartan to 49/51 mg every 12 hours due to good clinical and haemodynamic tolerance, with no deterioration in renal function. Atorvastatin was replaced by rosuvastatin in an attempt to achieve target LDL. Finally, given the clinical context (DM2 patient with obesity and poor glycaemic control, under treatment with insulin and iSGLT2), it was decided to add a 1glucagon-like peptide receptor agonist (aGLP1): subcutaneous liraglutide 0.6 mg/day for one week and then 1.2 mg/day.
At the new clinical review, the patient again reported subjective improvement, with no admissions for HF. He has lost another 7 kg in weight and is more agile, having started physical activity (he does pilates). He remains in NYHA functional class II, with better control of lumbar discomfort by the pain unit. His blood pressure continues to be in the target range (ambulatory blood pressure around 120-130 mmHg). No data suggesting water retention, with remission of oedema in the lower limbs. No adverse effects attributable to the use of iSGLT2 or ARGLP1.
At the consultation examination the patient weighs 104 kg, which means a reduction in BMI to 35.6 kg/m2 (class II obesity). Blood pressure 135/78 mmHg. HR 62 bpm. Sat 95%. No evidence of congestion or low output.
The blood test showed a reduction in NT-proBNP to 835 pg/ml. The evolution of Hb1Ac continues to be favourable (7%) and LDL is practically in the target range (76 mg/dl).
It was decided to continue outpatient follow-up, maintaining check-ups every 6-9 months in consultations, given the situation of clinical stability.

DIAGNOSIS
HF with reduced EF. Initial CF III with clinical and analytical improvement after titration of neuhormonal medication. Currently NYHA II.
Moderate left ventricular systolic dysfunction (LVEF 35%) of ischaemic aetiology. Surgically revascularised chronic ischaemic heart disease: IMA-ADA and saphenous bypass to ACx. Subsequent control coronary angiography with patency of the mammary graft and occlusion of the saphenous graft (severe and diffuse disease), for conservative management. ACD thin and diffusely diseased vessel, discouraged for revascularisation.
Metabolic syndrome with type III obesity and poor initial control of classic CVRFs. Improvement of metabolic control and weight reduction with medical treatment (aGLP1). Current BMI 35.6 kg/m2 (type II obesity).
DM2 better controlled after initiation of iSGLT2 and aGLP1.
Multifactorial chronic CKD with creatinine levels stable at around 1.3-1.5 mg/dl.
Ex-smoker.
