HISTORY, CURRENT DISEASE AND PHYSICAL EXAMINATION
A 37-year-old male of Indian origin with no cardiovascular risk factors (CVRF) was referred to our hospital with a diagnosis of hypertrophic cardiomyopathy and Wolff-Parkinson-White syndrome.
The patient made his debut at the age of 16 years (in 1990) with syncope while playing football. He had no family history of sudden death or relevant diseases. An electrocardiogram (ECG) showed signs of left ventricular (LV) hypertrophy with negative T waves in the precordial leads and pre-excitation. Severe concentric ventricular hypertrophy was corroborated on echocardiography, with a maximum IVS diameter of 22 mm, diastolic dysfunction and mild biventricular systolic dysfunction. He subsequently presented with an episode of pre-excited atrial fibrillation (AF) at more than 200 bpm, and electrophysiological studies demonstrated the existence of a posteroseptal/medioseptal accessory pathway (near the normal conduction system) that could not be ablated by radiofrequency after three unsuccessful attempts in three different procedures, so he was managed with medical treatment.
In 2012 (aged 27 years) he presented with an episode of acute pain in the right lower limb, being diagnosed by angio-CT of an acute thrombosis in the femoral artery, presumably due to an embolism secondary to a paroxysm of AF, so treatment with warfarin was started.
To better define the myocardium, cardiac magnetic resonance imaging (CMR) was performed and showed severe biventricular hypertrophy with a maximum IVS thickness of up to 30 mm; slightly depressed LVEF and extensive diffuse fibrosis in the areas of hypertrophy.
Several 24-hour Holter recordings were performed during the evolution without detecting ventricular tachycardias or frequent ventricular extrasystoles or new episodes of AF, although the patient reported palpitations about twice a month.
On arrival at our centre, to which he was referred as a referral unit for cardiomyopathies and other familial heart diseases, the patient had blood pressure (BP) 136/89 mmHg, RS at 52 bpm, without jugular venous engorgement. On auscultation, cardiac tones were rhythmic without murmurs, with preserved vesicular murmur and no pathological sounds. The lower limbs showed no oedema or signs of deep vein thrombosis. There were no skin lesions suggestive of cardio-cutaneous syndromes such as Fabry or Leopard.

COMPLEMENTARY TESTS
ECG: sinus bradycardia at 47 bpm. PR 140 ms with positive delta wave in V1 suggestive of left accessory pathway. QRS 160 ms. Left axis. Elevated R wave voltages especially in left precordial and deep negative T waves from V1 to V6, in I and aVL and flattened in inferior face.
ECG in pre-excited AF: irregular wide QRS tachycardia at more than 200 bpm, with irregularity in QRS morphology and width and in RR.
First transthoracic echocardiogram (TTE): concentric hypertrophy of 22 mm and midcavitary obliteration. Severe diastolic dysfunction. Dilated left atrium (LA). LVEF 57%. Moderate right ventricular (RV) dysfunction.
CMR: short axis and 4 chambers showing severe biventricular hypertrophy. 3C, D and E: sagittal plane, 4 chambers and short axis late gadolinium enhancement showing extensive and diffuse uptake in areas of hypertrophy.
First 24-hour Holter: sinus rhythm at 45-87 bpm. No significant pauses.
Low density ventricular extrasystoles. Frequent atrial extrasystoles. Absence of ventricular arrhythmias or AF. No symptoms reported in the diary.
First electrophysiological study (EPS): the posteroseptal/medioseptal accessory pathway was identified and radiofrequency ablation was attempted. The procedure was performed in two phases, but neither operator was able to achieve even transient block of the accessory pathway.
Ergometry: Bruce protocol. The test was stopped after 6 minutes due to fatigue, having reached 53% of maximum heart rate (HR). Normal blood pressure response. No arrhythmias, repolarisation disturbances or chest pain.
Last TTE: dilated left ventricle (LV), concentric hypertrophy more striking in the septum with apical and lateral hypertrabeculation, severe systolic dysfunction (Simpson biplane 10-15%). Mild-moderate mitral insufficiency (MI), biauricular dilatation, severely dilated RV with poor systolic function, moderate tricuspid insufficiency (TI), estimated pulmonary systolic pressure 51-56 mmHg.

CLINICAL EVOLUTION
At the first assessment in our centre (2013), an ECG was performed which showed the previously described findings and a new echocardiogram, where in addition to severe hypertrophy, biauricular dilatation, severe biventricular systolic dysfunction and diastolic dysfunction with signs of increased filling pressures were observed. An exercise stress test was performed and stopped after 6 minutes due to pain in MID, having reached 53% of target HR, with normal blood pressure response, no chest pain and no repolarisation abnormalities.
Due to the atypical presentation of the clinical picture, with severe concentric biventricular hypertrophy, diffuse late enhancement, systolic and diastolic dysfunction, onset of AF at an early age and presence of pre-excitation, the differential diagnosis of hypertrophic cardiomyopathy was made due to pathogenic variants in the sarcomeric genes with other possible aetiologies. A genetic study was performed in which a pathogenic variant in PRKAG2 was found.
In 2015 he was admitted again for asthenia and general malaise, and severe sinus bradycardia with complete paroxysmal AVB was detected. Due to the need for pacing and the high risk of sudden death (severe biventricular hypertrophy, systolic dysfunction, dilated LA, non-ablatable accessory pathway with antegrade conduction at more than 200 bpm, a confirmed episode of pre-excited AF and cardiogenic syncope), it was decided to implant an implantable cardioverter-defibrillator (ICD).
During the evolution, diastolic and systolic dysfunction progressed to become severe despite optimal medical treatment with angiotensin-converting enzyme inhibitors (ACE inhibitors), antialdosterone and beta-blockers, and the patient, aged 40 years, is currently in a pre-transplant cardiac situation.

DIAGNOSIS
Severe biventricular hypertrophy. Pathogenic variant in PRKAG2.
Extensive myocardial fibrosis in CMR.
Wolff-Parkinson-White syndrome by left posteromedial accessory pathway.
Episode of pre-excited AF.
Cardiogenic syncope of unfiliated aetiology: pre-excited AF vs VT.
Progressive biventricular systolic dysfunction and diastolic dysfunction.
Embolism in right femoral artery possibly secondary to AF paroxysm.
