Article Text

Download PDFPDF

Familial apical dilated cardiomyopathy in a young man: a novel phenotype of Takatsubo syndrome or a new entity altogether?
  1. Dibbendhu Khanra1,
  2. Yash Shrivastava1,
  3. Bhanu Duggal1 and
  4. Kanwar Kumar Kapoor2
  1. 1 Cardiology, All India Institute of Medical Sciences, Rishikesh, India
  2. 2 Cardiology, The Heart Clinic, Noida, India
  1. Correspondence to Dr Bhanu Duggal, bhanuduggalbmj{at}gmail.com

Statistics from Altmetric.com

Description

A 24-year-old man was admitted to cardiac intensive care unit (ICU) with Stevenson’s type C acute decompensated heart failure (ADHF).1 His shortness of breath has progressed over 10 days to New York heart association class 4 associated with orthopnoea. On taking detailed history, the patient had gradually progressive exertional shortness of breath for the last 3 months. He did not suffer any chest pain, nor did he have any history of fever. There was no recent physical or emotional trauma to the patient recently. There was no history of psychiatric disease in the past. There was history of sudden cardiac deaths in the family among multiple first and second degree family members at a premature age. On admission, his jugular venous pressure was elevated, blood pressure was 90/60 mm Hg and pulse rate was 100 beats/min. Chest auscultation revealed extensive bilateral rales throughout the lungs. On cardiac auscultation S3 was audible.

Serum troponin I level was 1 ng/dL (normal <0.4 ng/mL) and Brain Nitriuretic Peptide (BNP) was 3000 pg/dL (normal <100 pg/mL). ECG showed no ST/T changes. Skiagram of chest corroborated with severe pulmonary oedema. Trans-thoracic echocardiography (TTE) revealed dilated left ventricle (LV) with global hypokinesia with left ventricular ejection fraction (LVEF) of 35%. The left ventricular myocardium was showing numerous trabeculations in short-axis view (figure 1A). There was no evidence of LV hypertrophy or mid-cavity gradient or thrombus (figure 1B). LV apex was ballooned out and dyskinetic (figure 1C). The patient was treated with ionotropic and vasopressor support along with diuretics and he became haemodynamically stable gradually over the course of 1 week. Echocardiography of two of his younger brothers also revealed global hypokinesia and dilated LV cavity (involving apex) with reduced LVEF. A 24-hour ECG tape of the patient did not reveal any arrhythmia.

Figure 1

Three-dimensional trans-thoracic echocardiography revealed dilated left ventricle (LV) with global hypokinesia with left ventricular ejection fraction (LVEF) of 35%. The left ventricular myocardium was showing numerous trabeculations in short-axis view (A). There was no evidence of LV hypertrophy or mid-cavity gradient or thrombus (B). LV apex was ballooned out and dyskinetic (C). Parametric imaging showing relatively preserved basal contractility but apical ballooning and dyskinesia with global LVEF of 46.6% (D).

After the patient was stabilised and shifted out of ICU, detailed three-dimensional (3D) TTE was done showing relatively preserved basal contractility but apical ballooning and dyskinesia with global LVEF of 46.6%. Parametric imaging confirmed apical dysknesia with basal sparing (figure 1D). The similar patterns were noted in the echocardiography of his two younger brothers. A coronary angiogram was done which ruled out coronary artery disease. We did a myocardial contrast echocardiography (MCE) using sulphur hexafluoride microbubble (SonoVue, Bracco) of the patient which ruled out left ventricular non-compaction (LVNC) and confirmed apical ballooning and dyskinesia with preserved basal contractility (figure 2A,Bvideos 1 and 2). Blood for total cardiac genetic profile was sent which did not find mutation of any conventional gene known for inherited cardiomyopathy. The patient is under follow-up for 8 weeks now with good functional status and on guideline-directed medical therapy. Both of his brothers were asymptomatic.

Figure 2

Myocardial contrast echocardiography ruled out left ventricular non-compaction (A) and confirmed apical ballooning and dyskinesia with preserved basal contractility (B).

Video 1

Myocardial contrast echocardiography ruled out left ventricular non-compaction.

Video 2

Myocardial contrast echocardiography confirmed apical ballooning.

The diagnosis of the patient described above remained elusive as we thought of viral myocarditis but we could not find evidence of such causing isolated apical dyskinesia despite extensive literature search. However, the familial pattern of cardiac involvement led us to consider inherited cardiomyopathy. However, we could not link that to any particular gene mutation. Apical cardiomyopathies are reported in literature but they are either in the form of hypertrophic or restrictive.2 3 But the patient in our case, did not have evidence of LV hypertrophy. Sometimes, mid-cavity obstruction may lead to apical aneurysm complicated with apical thrombus and arrhythmia but we could not demonstrate any features of obstructive LV gradient either.2

We acknowledge that the clinical and echocardiographic presentation of the patient resembles of Takatsubo Syndrome (TTS). But it was difficult to establish in absence of chest pain, ST elevation and physical/emotional stress in a young male patient.4 Cases of TTS have been reported to have familial associations in the literature but all of them were females.5–7 Sharkey et al genotyped three adrenergic receptor (AR) polymorphisms in a cohort of 41 female patients with TTS and their data suggest that AR polymorphisms do not mediate the sympathetic nervous system hyperactivity in TTS patients.8 In the dataset reported by Murakami et al, cardiac complications appeared to be more common in male patients than female patients with TTS during hospitalisation which was in line with the poor haemodynamic status of the young man in our case.9 In the same database, the age of the male TTS patients ranged from 64 to 81 years.9 However, familial TTS-like cardiomyopathy with apical ballooning in a young male patient is never reported before in the literature.

Our case also emphasised the role of MCE in exploring cardiac pathologies involving LV apex. Short-axis images in TTE may not be perpendicular to the LV long axis and can produce the morphologic appearance of prominent trabeculations that mimic LVNC.10 Thus, we excluded LVNC by MCE in our case which can be comparable to cardiac magnetic resonance imaging in resource-limited setting.11 Multi-disciplinary team was against the diagnosis of LVNC in view of absence of prominent trabecular formations (more than 3 is the cut-off) along the left ventricular endocardial border in end-diastole, distinct from papillary muscles, false tendons or aberrant bands; isolated apical involvement (in LVNC lateral wall is more affected); preserved contraction of all the segments of left ventricle (LVNC is characterised by global hypokinesia); no LV clot (which is quite common in LVNC), and genetic testing did not reveal any Tafazzin mutation (or any mutation conventionally known to cause familial cardiomyopathy).

And contrary to conventional ventriculogram to diagnose apical ballooning in TTS, parametric imaging using 3D TTE could be informative. This saved our patient from cathlab radiation, contrast and invasive diagnostic procedure in an unstable state of ADHF. In a study by Cai et al, TTS patients were found to have lower values of global longitudinal strain in the mid-inferolateral, mid-inferior, apical-lateral and apical-inferior segments than those of left anterior descending coronary artery ischemia or infarction.12

The authors are not committed to a final diagnosis of TTS and the case is open for discussion. However, our case challenges the very pathogenesis of TTS in multiple fronts. First, TTS is known to cause stress-induced cardiomyopathy but our patient did not have any form of physical or emotional stress. Second, TTS presents acutely but in our case the patient had a progressive deterioration of symptoms followed by ADHF. Third, TTS has been described among men but never in such a young age of 24 years. And fourth, familial association of TTS has been described but asymptomatic TTS pattern in echocardiography without symptoms is a thing to ponder. And last but not the least, the role of MCE and parametric imaging of 3D TTE in diagnosis of apical cardiomyopathies including TTS has been emphasised.

Learning points

  • Short-axis images in trans-thoracic echocardiography (TTE) may not be perpendicular to the left ventricular long axis and can produce the morphologic appearance of prominent trabeculations that mimic non-compaction.

  • Myocardial contrast echocardiography can be very useful in assessment of apical pathologies and in distinguishing left ventricular non-compaction and thus can be comparable to cardiac magnetic resonance imaging in resource-limited setting.

  • Parametric imaging using three-dimensional TTE can be a non-invasive alternative of ventriculogram to diagnose Takatsubo syndrome and can be undertaken without need of cathlab, radiation or contrast.

References

Footnotes

  • Contributors Conception: BD, KKK; case report: YS, DK; investigations: BD, DK; discussion: YS, DK and critical appraisal: BD, KKK.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Patient consent for publication Obtained.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.