HISTORY, CURRENT ILLNESS AND PHYSICAL EXAMINATION

PERSONAL HISTORY
Cardiovascular risk factors: dyslipidaemia, type 2 diabetes mellitus.
Previous cardiological history:
Chronic ischemic cardiomyopathy. Debut in June 2018 as evolved anterior myocardial infarction, in Killip-Kimbal II haemodynamic situation. Two-vessel coronary artery disease completely revascularised percutaneously by implantation of two drug-eluting stents at the level of mid-first diagonal anterior descending (primary angioplasty) and posterior interventricular (second time). Severe left ventricular dysfunction on echocardiogram (left ventricular ejection fraction [LVEF] 30% at discharge).
Admission in August 2018 for symptoms compatible with Dressler syndrome.
Favourable evolution with the combination of high-dose salicylates and colchicine.
Subsequent follow-up in the heart failure clinic, where the medication has been titrated with prognostic impact. Start of sacubitril/valsartan in November 2018 due to persistence of New York Heart Association (NYHA) functional class II
Association (NYHA) functional class II.
Ergometry at the end of the cardiac rehabilitation programme clinically and electrically negative for ischaemia, in functional class I (12.67 METS).
No other comorbidities of interest.
Current treatment: omeprazole 20 mg/day, acetylsalicylic acid 100 mg/day, prasugrel 10 mg/day, sacubitril/valsartan 49/51 mg/12 hours, bisoprolol 5 mg/day, eplerenone 50 mg/day, metformin/empaglifozin 1000 mg/5 mg every 12 hours, rosuvastatin 10 mg/day, ezetimibe 10 mg/day.

CURRENT DISEASE
A 49-year-old man, with a coronary event at an early age, who came for a check-up at the heart failure clinic on 13 November 2018. He is asymptomatic in the cardiological sphere. He has not presented angina and has maintained excellent functional class (NYHA I) since starting sacubitrilo-valsartan.
On the other hand, since starting treatment with atorvastatin in June 2018, he has complained of significant pain and cramps in the calves and thighs, both at rest and when walking, with normal CPK values. She also presented progressive elevation of transaminases and cholestasis enzymes (with abdominal ultrasound that ruled out hepatobiliary pathology), so, given the suspicion that the symptoms and laboratory alterations could be related to taking atorvastatin, the doses were progressively reduced to 10 mg, without any improvement. Treatment with low doses of other statins (pitavastatin and simvastatin) has also been tried without success and she is currently only clinically tolerating 10 mg of rosuvastatin but with mild alteration of the hepatic profile. In addition to poor tolerance, LDL-C levels have remained persistently elevated at follow-up (LDL-C > 130 mg/dl), despite having associated ezetimibe to lipid-lowering therapy.

PHYSICAL EXAMINATION
At consultation (17/11/18):
Blood pressure 100/65 mmHg. Heart rate (sinus rhythm) 70 beats per minute.
Weight 83 kg. Height 189 cm. Abdominal waist 90 cm. Body mass index 23.2 kg/m2.
Eupneic at rest, tolerating decubitus. No jugular ingurgitation. Cardiac auscultation: regular heart sounds without murmurs or extratonos. Pulmonary auscultation: preserved vesicular murmur, no adventitial sounds. Abdomen: nondescript. Lower limbs: no oedema or signs of deep vein thrombosis (DVT). Pulses preserved and symmetrical. No stigmata of hyperlipaemia.

COMPLEMENTARY TESTS
Blood test in consultation (11/12/18): glucose 126 mg/dl. HbA1c 6.5%. ALT 82 U/l, AST 55 U/l. Bilirubin 0.8 mg/dl. Gamma-GT 108 U/l. Alkaline phosphatase 85 U/l. CK 92 U.
Creatinine 0.86 mg/dl, eGFR by MDRD-4 IDMS > 60 ml/min/1.73 m2. Sodium 142 mmol/l.
Potassium 4.8 mmol/l. NT-proBNP 544 ng/l. Lipid profile: triglycerides 100 mg/dl, total cholesterol 188 mg/dl, HDL-C 37 mg/dl, LDL-C 160 mg/dl. Apolipoprotein A1 145 mg/dl.
Apolipoprotein B 89 mg/dl. ApoB/ApoA1 ratio 0.6 mg/mg. Lipoprotein (a) 90 mg/dl.
ECG in consultation (17/11/18): sinus rhythm at 65 bpm. PR interval 140 ms. Narrow QRS with normopositioned axis. QS with residual submillimetric ST segment elevation in V1-V4, with negative T wave in I, aVL and flattened in V5-V6. Transition in V4. No other repolarisation alterations.
Echocardiogram in consultation (17/07/18): non-dilated left ventricle, with normal wall thickness except for the sigmoid septum. Moderately depressed global systolic function (LVEF estimated by Simpson biplane 40%). Apical akinesia and akinesia of the middle and distal segments of the anterior face and anterior septum. Hypokinesia of the distal third of the inferior septum. Transmitral filling pattern with impaired relaxation.
E/e`12 ratio. Non-dilated atria. Non-dilated right ventricle, with normal global systolic function (TAPSE 15 mm). No significant valvular heart disease. Pulmonary arterial systolic pressure (PSAP) not estimable. Inferior vena cava not dilated, with physiological inspiratory collapse. Aortic root not dilated. No pericardial effusion.
Cardiac magnetic resonance (CMR) (24/07/18): study compatible with chronic anteroseptal myocardial infarction with moderate ventricular dysfunction (LVEF 35%). Absence of viability in the territory of the anterior descending artery (transmural ischaemic scar of the apex, mid and distal segment of the anterior face and anterior septum, distal half of the inferior septum and distal segment of the inferior face).

CLINICAL EVOLUTION
Considering the prognostic benefit of the patient (young and at very high cardiovascular risk) and the inability to reach target LDL-C levels despite moderate doses of rosuvastatin and ezetimibe, it was decided to start treatment with evolocumab 140 mg (subcutaneous injection) fortnightly. Two weeks after starting evolocumab treatment, LDL-C levels dropped sharply from 160 to 9 mg/dL. The evolution of the lipid profile (including levels of lipoprotein a, Lp [a]) in the successive monthly controls up to the present were as follows:
December 2018: total cholesterol 69 mg/dl, HDLc 40 mg/dl, LDLc 9 mg/dl. Lp (a): 45 mg/dl. It is decided to reduce the dose of rosuvastatin from 10 mg to 5 mg.
January 2019: total cholesterol 75 mg/dl, HDL-C 42 mg/dl, LDL-C 18 mg/dl. Lp (a): 50 mg/dl.
It is decided to withdraw ezetimibe.
February 2019: total cholesterol 78 mg/dl, HDLc 39 mg/dl, LDLc 26 mg/dl. Lp (a): 56 mg/dl
March 2019: total cholesterol 83 mg/dl, HDL-C 40 mg/dl, LDL-C 25 mg/dl. Lp (a): 52 mg/dl.
For the time being (March/2019), the patient has not presented any adverse effects related to treatment with proprotein convertase subtilisin/kexin type 9 (iPCSK9) inhibitors; and after the rosuvastatin dose reduction, the hepatobiliary profile has normalised (ALT 22 U/l, AST 25 U/l. ) and the myalgias have disappeared. Other cardiovascular risk factors remain well controlled (blood pressure < 130/90 mmHg, baseline blood glucose < 100 mg/dl; HbA1c < 7%, BMI < 25 kg/m2, abdominal circumference < 94 cm). In light of the CMR results and the evolution of LVEF and functional class, the need for ICD implantation at follow-up remains to be considered.

DIAGNOSIS
Chronic ischaemic heart disease. Canadian Cardiovascular Society (CCS) functional class I/IV. Moderately depressed LVEF. Late transmural anteroseptal enhancement on CMR.
Two-vessel coronary artery disease completely revascularised percutaneously.
Drug-eluting stents in DAm-D1 and IVP.
Dyslipidaemia. Hypercholesterolemia. Elevation of lipoprotein (a).
Statin intolerance.
Optimal control of LDL-C and Lp(a) levels after initiation of treatment with iPCSK9.
Type 2 diabetes mellitus, with good glycaemic control.
