HISTORY, CURRENT ILLNESS AND PHYSICAL EXAMINATION
57-year-old male, no known allergies, active, currently unemployed.

History
Cardiovascular risk factors (CVRF): obesity grade II (BMI of 39). Active smoker of 10 cigarettes/day (12 packs/year). Hypertension diagnosed 3 years ago. Dyslipidaemia diagnosed 10 years ago. Diabetes mellitus (DM) type 2 diagnosed at 38 years of age, with poor metabolic control over the years. As a result, she has diabetic retinopathy and diabetic nephropathy.
Chronic obstructive pulmonary disease (COPD) GOLD 2 and sleep apnoea hypopnoea syndrome (SAHS) treated with nocturnal continuous positive airway pressure (CPAP).
From the cardiological point of view, in 2017 he had presented an episode of persistent atrial fibrillation associated with tachycardiomyopathy (LVEF 35% with normal sized LV) with LVEF recovery to normal after effective reversion to sinus rhythm and without subsequent cardiology follow-up.
He is currently on home treatment with: acenocoumarol 4 mg as prescribed; atorvastatin 20 mg/24 hours; fenofibrate 145 mg/24 hours; bisoprolol 5 mg/24 hours; olmesartan-amlodipine 40/5 mg/24 hours; formoterol-budesonin 160/4.5 mg inhaled/12 hours; insulin novomix 30: 36-36-34 IU breakfast-lunch-dinner sc; dulaglutide 1.5 mg/weekly sc; metformin 1000 mg/24 hours; salbutamol on demand; bromazepam 3 mg/24 hours.

Present illness
Consultation at the emergency department of our centre due to increased dyspnoea for approximately 4-6 weeks, with two-pillow orthopnoea, bendopnoea and episodes of paroxysmal nocturnal dyspnoea. She does not report subjective oliguria but progressive oedematisation of the lower limbs. No palpitations or chest pain. No loss of appetite. No associated fever or other concurrent symptoms.

Physical examination
Blood pressure (BP) 90-95/60-65; heart rate (HR) 156 bpm; oxygen saturation in ambient air 90%, temperature 36.2 oC.
Conscious, oriented, sweating, with skin pallor, although not deep. Tachypneic, with abdominal breathing.
No jugular ingurgitation.
Cardiac auscultation: arrhythmic and tachycardic, no audible murmurs.
Pulmonary auscultation: generalised hypophonesis with bilateral crackling rales up to midfields.
Abdomen distended, soft, not painful on palpation. No visceromegaly. Hydro-aerial sounds present.
Oedema with fovea up to both knees, no signs of deep vein thrombosis (DVT) and weak symmetrical pedal pulses.

COMPLEMENTARY TESTS
Laboratory tests on admission:
Haemogram Hb 12.7 g/dl. Red cells 6.29 x10E6/μl. MCV 70.3 fl. MCH 20.2 pg. MCHC 28.7 g/dl. Leucocytes 14.18 x10E3/μl. Neutrophils (blood-%): 65.4%. Neutrophils 9.27 x10E3/μl. Lymphocytes (%) 22.8%. Lymphocytes 3.24 x10E3/μl. Monocytes (blood-%) 10.8%. Monocytes 1.53 x10E3/μl. Eosinophils (blood-%) 0.6 %. Basophils (blood-%) 0.4%. Immature granulocytes % 1.10 %. Immature granulocytes 0.15 x10E3/μl. UPLAQ platelets 205 x10E3/μ. VPM 11.5 fL. SR R.D.W. coefficient of variation 19.3%. Haematocrit 44.2%. Biochemistry: glucose 146 mg/dl. Urea 76 mg/dl. Creatinine 1.87 mg/dl. FGR (CKD-EPI) 39 ml/min/1.73 m . Sodium ion 141 mmol/l. Plasma potassium ion 7 mmol/l, Creatine kinase 404 U/l. Troponin T 112 ng/l. NT-proBNP 2298. Procalcitonin 0.08. Heparin plasma C-reactive protein 0.5 mg/dl.
Coagulation: Prothrombin T. 27.10 sec, INR 2.36. Prothrombin T. (%) 31.0%. Partial thromboplastin time 32.30 sec. Derived fibrinogen 457. D-dimer: 616 ng/m. Blood gases: pH (arterial blood gas) 7.43. pO2 (arterial blood gas) 75 mmHg. pCO2 (arterial blood gas) 31 mmHg. Total CO2 (arterial gas) 21.9 mmol/l. Bicarbonate (arterial gas) 22.4 mmol/l. Excess bases (arterial gas) -3.3 mmol/l. Oxyhaemoglobin saturation (arterial gas) 95%.
Electrocardiogram (ECG) on admission: atrial fibrillation at 150 bpm with narrow QRS and secondary repolarisation disorders.
Postcardioversion ECG: sinus rhythm at 70 bpm with normal PR, P wave widening suggestive of atrial enlargement. Late progression of R in precordial leads. Intraventricular conduction disturbance with QRS 110ms. QTc 443 ms.

Chest X-rays PA and LAT on admission: very enlarged CTI, no condensation or masses were observed. Diffuse interstitial pattern with perihilar deflections suggestive of heart failure. Free costophrenic sinuses.
Echocardiograms during admission: dilated left ventricle (DTd 6.3 cm; VolTd 203 ml), slightly hypertrophic, with severe left ventricular systolic dysfunction (EF by Simpson bp 29%) and transmitral pattern suggestive of pseudonormalisation with high filling pressures. Right ventricle with slightly reduced systolic function (TAPSE 15 mm). Biauricular dilatation. No significant valvular heart disease. No pericardial effusion.
Coronary angiography: coronary arteries with diffuse atheromatosis without significant lesions.

CLINICAL EVOLUTION
In the history prior to admission, the patient had taken a certain amount of hypoglycaemic drugs over the previous 4 years:
Until 2015 the patient was taking metformin 1000 mg every 12 hours, with poor follow-up and therapeutic adherence during years of illness.
At the end of that year, after visiting the health centre, his primary care doctor managed to recover some follow-up and associated insulin therapy: Lantus SoloStar 100 IU/ml, 30 IU in the morning, and referred him to the endocrinology department.
In February 2016, he had an Hb1Ac of 10.8%, BMI of 40 and weight of 110 kg, eGFR of 55 ml/min/1.73 m, so the endocrinologist implemented a diabetology education course, and changed Lantus to Novomix 30/70 at 20-20-18 IU breakfast-lunch-dinner, while associating metformin/vildagliptin 50/1000 mg every 12 hours.
June 2016, insulinisation takes effect and Hb1Ac is reduced to 8.5%. BMI remains at 40. Novomix 30 is maintained, increasing the doses to 26-26-24 IU breakfast-lunch-dinner. The analysis showed a GFR estimated by CDK-EPI of 40 ml/min/1.73 cm2, so it was decided to discontinue metformin/vildagliptin 50/1000 mg, maintaining only metformin 1000 mg/24 hours.
In June 2017 during admission to cardiology for an episode of rapid atrial fibrillation, associated with tachycardiomyopathy. Hb1Ac is 7.1%. The eGFR had decreased by 28 ml/min/1.73 m . Metformin was discontinued.
In February 2018 after cardiology review she had fully recovered LVEF. Renal function had improved (eGFR 51 ml/min/1.73 m2). Hb1Ac 8.3%. BMI was still 40. Discussion with endocrinology, the patient's profile is optimal for starting a GLP1 analogue: diabetic with > 10 years of evolution, with metabolic syndrome, obesity (BMI > 35 kg/m2) and previous cardiovascular disease. It was decided to start dulaglutide 0.75 mg weekly subcutaneously and progressively increased to 1.50 mg weekly, without gastrointestinal side effects, with good adaptation and tolerance to the drug. Metformin was restarted at the same time. Novomix therapy was maintained.
Six months later, the patient was reviewed and reported a weight loss of 5 kg, he was more animated, with Hb1Ac 7%. Metformin was again discontinued due to reduced glomerular filtration rate.
Returning to the current cardiology admission in 2020, the patient presented adequate clinical evolution in hospitalisation after intravenous diuretic treatment, improving from the point of view of heart failure. A transthoracic echocardiogram was performed showing a dilated left ventricle (DTd 6.3 cm; VolTd 203 ml) with severe left ventricular systolic dysfunction (EF by Simpson bp 29%) and transmitral pattern suggestive of pseudonormalisation with high filling pressures. Right ventricle with slightly reduced systolic function (TAPSE 15 mm). Biauricular dilatation. No significant valvular heart disease. No pericardial effusion. Coronary angiography with diffuse atheromatosis in the coronary arteries without significant lesions. It was therefore interpreted as suggestive of a priori non-ischaemic dilated cardiomyopathy decompensated by rapid AF, and outpatient magnetic resonance imaging (MRI) was requested to complete the study. He was treated with amiodarone 200 mg/24 hours orally, remaining in sinus rhythm, without new falls in atrial fibrillation. In the admission blood test, Hb1Ac was 8.1%. The BMI was 39.7. On discharge, as this was a male with a clear metabolic syndrome and diabetes mellitus with poor control, the treatment was optimised as much as possible, and as an option, treatment with dulaglutide was replaced with semaglutide 0.5 mg weekly (and progressively after 4 weeks the dose was increased to 1 mg) in an attempt to improve weight loss and metabolic control, maintaining the same insulin units, as blood glucose levels during admission were in range and his HbA1c was >8%. Metformin is not associated as the glomerular filtration rate at discharge is 39 ml/min by CDK-EPI, with urine albuminuria of 146 mg/g. Finally, atorvastatin 40 mg/24 hours, which the patient was taking, was replaced by rosuvastatin 20 mg/24 hours.
Over the last 4 years, the patient has undergone various hypoglycaemic treatments, with frequent changes, mainly due not to side effects but to variable renal function. The advantage of GLP1 analogues is that they are not limited by this fact. CKD is often present in long-standing diabetic patients with poor control, since, as we know, diabetic nephropathy is one of their vascular complications. This can lead to frequent changes in medication, which are associated with treatment errors and poorer long-term adherence of patients to medications. To get the most benefit from therapy, it is important to know the indications, limitations, adverse effects and to tailor the decision of which drug to prescribe to the patient's profile.

DIAGNOSIS
Type 2 diabetes mellitus that is difficult to control.
Metabolic syndrome.
Heart failure with reduced LVEF.
Non-ischemic dilated cardiomyopathy decompensated by rapid AF (associated tachycardiomyopathy component).
Persistent cardioverted persistent atrial fibrillation electrically anticoagulated with vitamin K antagonists.
Stage IIIb A2 chronic kidney disease.
