HISTORY, CURRENT ILLNESS AND PHYSICAL EXAMINATION

History
Brother and nephew diagnosed with HCM.
No history of sudden death in first-degree relatives.
No known drug allergies.
Worked in newspaper distribution.
Smoker of 30 cigarettes per day, with a cumulative rate of 48 packs per year.
Cardiovascular risk factors: obesity grade I (body mass index [BMI] 32 kg/m2). No hypertension, diabetes or dyslipidaemia.
Follow-up in cardiology consultations for asymmetric obstructive HCM with inconclusive genetic study. At diagnosis, there was no significant obstruction. However, during subsequent follow-up and coinciding with a clear worsening of her functional class, a transthoracic echocardiogram (TTE) revealed a progressive increase in septal hypertrophy causing an obstructive dynamic gradient and systolic anterior motion (SAM) in the anterior leaflet of the mitral valve, leading to moderate mitral regurgitation. Cardiogenic syncope in 2019, for which it was decided to implant a DDDR implantable cardioverter-defibrillator (ICD) in primary prevention, given that the risk of sudden death at 5 years was 7.1%. In successive check-ups, close monitoring was carried out to control symptoms and drug titration, despite which dyspnoea and angina on exertion persisted.
Baseline: independent for basic activities of daily living. Higher functions preserved. Active life. Currently presents dyspnoea on usual exertion, in NYHA functional class III.
Usual treatment: omeprazole 20 mg/24 hours, disopriramide 100 mg/ 8 hours, verapamil 120 mg/12 hours.

Present illness
A 52-year-old patient returned to the emergency department of our hospital due to chest pain and an increase in his baseline dyspnoea to the point of minimal effort. He did not present orthopnoea, paroxysmal nocturnal dyspnoea crises, decreased diuresis or oedema in the lower limbs.
On arrival at the ED, the patient was haemodynamically stable, with slight tachypnoea at rest, maintaining oxygen saturation 98%. An electrocardiogram (ECG) was performed, with no changes with respect to those previously described, as well as serum markers of myocardial damage, which were normal. Admission to cardiology was decided.

Physical examination
Good general condition. Conscious and oriented. Normal colour, well hydrated and perfused. Afebrile. Haemodynamically stable (blood pressure [BP] 127/84 mmHg, heart rate [HR] 70 bpm). Eupneic at rest. Oxygen saturation 99% without oxygen therapy. Cardiorespiratory auscultation: rhythmic tones at a good frequency, with a panfocal systolic murmur that increases with the Valsalva manoeuvre. Good ventilation in both lung fields with no added pathological noises. Abdomen soft and depressible. No masses or megaliths palpable. Not painful. No signs of peritoneal irritation or peritonism. Lower limbs without oedema or signs of deep vein thrombosis. Pedial pulses present and symmetrical.

COMPLEMENTARY TESTS
Laboratory tests:
Biochemistry: glucose 106 mg/dl, urea 35 mg/dl, Cr 0.92 mg/dl, uric acid 6 mg/dl, GFR > 90 ml/min. Ionogram normal. Abdominal profile: total bilirubin 2.31 mg/dl, at the expense of indirect (1.69 mg/dl), rest normal. Total protein 6.9 g/dl. NT-proBNP 869 pg/ml. Serial myocardial damage markers: normal.
Lipid profile: total cholesterol 206 mg/dl, LDL 140 mg/dl, HDL 42 mg/dl, triglycerides 122 mg/dl.
PSA 0.16 ng/ml.
HbA1c 5.6%.
CBC: haemoglobin 14.4 g/dl, platelets 181x109/l, leucocytes 1073 x109/l with normal formula.
Electrocardiograms (ECG): emergency ECG: pacemaker stimulation at 60 bpm, evidence of left ventricular hypertrophy. QTc 440 ms.
ECG on the ward: in sinus rhythm 71 bpm. Normal PR. Positive Sokolow's criteria with overload data and negative T waves from V4 to V6, I and aVL.
TTE: severe and asymmetric ventricular hypertrophy with maximum myocardial thickness at septal level (26-27 mm) with clear SAM leading to moderate mitral regurgitation. Obstructive dynamic gradient at LVOT level with a gradient of 50 mmHg, which with Valsalva manoeuvres reaches 82 mmHg. Preserved left ventricular systolic function with an ejection fraction of 70%. Low echocardiographic probability of pulmonary hypertension.
Transesophageal echocardiogram (TEE) (videos 3 and 4): mitral valve with no structural alterations of note. No elongation of leaflets or subvalvular apparatus. Slight thickening of the anterior leaflet at the level of its A2 scallop. It presents an alteration of the dynamics consisting of retraction of both leaflets in closure by intraventricular dynamic gradient mechanism at the level of the left LVOT with SAM of both the anterior and posterior leaflets. This alteration of the dynamics generates a mitral insufficiency jet of at least moderate size. No other alterations were observed beyond those found in the HCM mechanism secondary to SAM with involvement of the entire valve apparatus.
Coronary angiography: angiographically normal coronary arteries. The second septal branch (of greater calibre and development) is selectively cannulated, as the first branch also fistulises the left ventricle in the angiographic image. After selective occlusion of this branch and injection of ultrasound contrast, TTE shows correct basal opacification of the septum, but with almost complete drainage of the contrast to the left ventricle.
Cardiac MRI: non-dilated left ventricle, with concentric increase of its mass and severe asymmetric hypertrophy of septal predominance. Maximum myocardial thickness in the basal anteroseptal (26 mm) and mid inferoseptal (24 mm) segments. Thicknesses in apical septal 16 mm, basal inferoseptal 16 mm and mid-anteroseptal 15 mm. Rest of segments with maximum thicknesses of 13 mm. Normal segmental contractility and end-systolic collapse of the ventricular cavity leading to hyperdynamic systolic function.
At LVOT level, there is systolic flow acceleration and SAM of the anterior mitral leaflet leading to mitral insufficiency conjet directed to the lateral wall of the left atrium. An intramyocardial crypt is seen in the mid segment of the inferior aspect. The ejection fraction measured with the Simpson method was 81%. LVEDV of 144 ml, indexed by body surface area of 72 ml/m, LVESV of 27 ml, indexed by body surface area of 13.5 ml/m
Cardiac output of 6.8 l/min. Myocardial mass 285 g, indexed by body surface area of 142 .g/m
Right ventricle neither dilated nor hypertrophic, with preserved global and segmental mobility.
Ejection fraction measured by Simpson's method of 81 % RVEDV of 104 ml, indexed by body surface area of 52 ml/m. VTSVD of 19 ml, indexed by body surface area of 9.5 ml/m . Dilated left atrium with an area of 41 cm, indexed by 20 cm/m . Normal right atrium (21 cm, indexed 10.5 cm/m). The first-pass perfusion sequence shows no baseline perfusion defects. Late enhancement/viability sequence shows no fibrosis or necrosis. Conclusion: Asymmetric obstructive HCM without fibrosis. Non-dilated left ventricle with preserved systolic function.

CLINICAL EVOLUTION
Patient diagnosed with asymmetric HCM in 2009 after consulting for palpitations, without correlating at that time with tachyarrhythmias. At the time of diagnosis, there was no significant LVOT obstruction. Since then, he has been followed up in cardiology outpatient clinics and was found to be asymptomatic after initiation of low-dose beta-blockers. Subsequent check-ups revealed a worsening of his functional class to the point of dyspnoea and angina on minimal exertion.
Beta-blockers were titrated to maximum doses on an outpatient basis and, taking advantage of the fact that the patient was a DDDR ICD user, the parameters of the latter were optimised to achieve left ventricular pacing greater than 90%. Despite this, the patient continued to be symptomatic and with a significant obstructive gradient of more than 50 mmHg. It was decided to start treatment with high doses of calcium antagonists associated with disopyramide and to titrate doses, and the possibility of septal ablation with alcohol or Morrow surgery was considered if there was no adequate clinical response.
However, the patient was finally admitted to our care due to worsening symptoms. During admission, it was decided to initiate the preliminary study to assess whether he was a candidate for septal ablation with alcohol or surgical myomectomy while continuing with the titration of medical treatment without being able to reach higher doses due to the presence of anticholinergic symptoms associated with disopyramide.
Finally, given the degree of ventricular hypertrophy and the absence of a septal branch suitable for alcohol septal ablation, surgical myomectomy was chosen.

DIAGNOSIS
Septal HCM with severe LVOT obstruction. Moderate mitral regurgitation due to SAM.
Exertional angina and dyspnoea in NYHA functional class III secondary to the above. DDDR ICD carrier in primary prevention (risk of sudden death at 5 years according to the European Society of Cardiology score: 7.1%).
