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British Journal of Healthcare and Medical Research - Vol. 11, No. 3

Publication Date: June 25, 2024

DOI:10.14738/bjhmr.113.16940.

Cillis, N. I., Park, C. J., Amjad, A., & Sundaravel, S. H. (2024). All That Light Up Are Not Sarcoidosis – The Great Masquerader: A Case

of LMNA Cardiomyopathy. British Journal of Healthcare and Medical Research, Vol - 11(3). 97-102.

Services for Science and Education – United Kingdom

All That Light Up Are Not Sarcoidosis – The Great Masquerader: A

Case of LMNA Cardiomyopathy

Nicole I. Cillis, D.O., M.P.H.

Department of Internal Medicine, Atrium Health

Wake Forest Baptist Medical Center, Winston-Salem, NC

Carolyn J. Park, M.D.

Section of Cardiovascular Medicine, Atrium Health

Wake Forest Baptist Medical Center, Winston Salem, NC

Aysha Amjad, M.D.

Department of Heart Failure and Transplantation,

Intermountain Heart Institute, Salt Lake City, Utah

Swethika H. Sundaravel, M.D.

Section of Cardiovascular Medicine, Atrium Health

Wake Forest Baptist Medical Center, Winston Salem, NC

ABSTRACT

Lamin A/C (LMNA) cardiomyopathy is a rare cause of non-ischemic dilated

cardiomyopathy (DCM), caused by a gene mutation in Lamin A/C. It manifests with

electrical abnormalities before the onset of heart failure, much like cardiac

sarcoidosis (CS). Both have similar imaging findings. Detailed family history and

genetic testing are crucial in making the correct diagnosis.

Keywords: infiltrative cardiomyopathy, dilated cardiomyopathy, Lamin A/C gene, cardiac

sarcoidosis, FDG PET

INTRODUCTION

Dilated cardiomyopathies (DCM) are a common cause of heart failure, with up to 40-50% of

familial cardiomyopathies attributed to genetic mutations [1]. Among the genetic

cardiomyopathies, LMNA gene mutation is the second most common cause of familial DCM after

titin truncating mutations [1,2]. This gene encodes proteins in the nuclear membrane involved

in gene transcription and regulation [1,2]. LMNA mutation is attributed to 5-8% of genetic DCM

cases, usually presents in the 3rd-4th decade of life, with almost 100% age-dependent

penetrance [1].

The LMNA cardiomyopathy initially manifests with electrical abnormalities, such as heart

block, brady-tachy syndrome, and atrial/supraventricular/ventricular arrhythmias before the

onset of heart failure due to pump dysfunction [2]. LMNA mutation carriers often have a poor

prognosis due to progression of heart failure and risk of sudden cardiac death due to malignant

arrhythmias [1]. Interestingly, the LMNA DCM variant can have similar inflammatory findings

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British Journal of Healthcare and Medical Research (BJHMR) Vol 11, Issue 03, June-2024

Services for Science and Education – United Kingdom

on cardiac imaging to sarcoidosis, which can confound and delay the correct diagnosis of LMNA

DCM [5]. As such, it is important for early detection and appropriate treatment for patients

affected by LMNA DCM.

CLINICAL CASE

A 57-year-old woman with hypertension, Grave’s disease status post radiofrequency ablation,

tobacco use disorder, and obstructive sleep apnea on continuous positive airway pressure

(CPAP) therapy was referred to cardiology by her primary care doctor for evaluation of an

abnormal electrocardiogram (ECG). During an outpatient colonoscopy, she was noted to have

1st degree AV block and premature ventricular contractions (Figure 1) on a routine pre- operative ECG. Upon presentation, she noted exertional shortness of breath and easy

fatigability. At this visit, blood pressure was 126/73 mmHg, heart rate 55 beats per minute,

oxygen saturation of 98% on room air, and BMI of 37.6 kg/m2. Physical exam findings were

notable for jugular venous pressure of 5 cm of water, physiologic split of S2, clear breath sounds,

and no peripheral edema. She had no rashes, red eyes, or lymphadenopathy. She denied any

significant family history of sudden cardiac death or heart failure at this time.

Figure 1: ECG. Pre-operative 12 lead EKG with 1st degree grade AV block and premature

ventricular contractions.

A cardiac work-up included a transthoracic echocardiogram (TTE) which noted a moderately

depressed left ventricle ejection fraction (LVEF) of 35-40% with global hypokinesis of the left

ventricle. The left ventricle was mildly dilated with an internal diameter of 5.8cm. Right and left

heart catheterization noted non-obstructive coronary artery disease and elevated intracardiac

filling pressures, with preserved cardiac output. Cardiac magnetic resonance imaging (cMRI)

showed patchy late gadolinium enhancement (LGE) in the basal anteroseptum and inferolateral

left ventricular segments (Figures 2A and B).

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Cillis, N. I., Park, C. J., Amjad, A., & Sundaravel, S. H. (2024). All That Light Up Are Not Sarcoidosis – The Great Masquerader: A Case of LMNA

Cardiomyopathy. British Journal of Healthcare and Medical Research, Vol - 11(3). 97-102.

URL: http://dx.doi.org/10.14738/bjhmr.113.16940.

Figure 2: Cardiac MRI Images. (A) Cardiac MRI late gadolinium (phase sensitive inversion

recovery sequence) short axis basal slice showing transmural late gadolinium enhancement of

the basal anteroseptum and inferolateral left ventricular segments. (B) Corresponding apical 4

chamber showing enhancement of the basal to mid lateral segments.

The initial positron emission tomography (PET) scan noted fluorodeoxyglucose (FGD) uptake

in the corresponding areas, suggestive of cardiac sarcoidosis (CS) (Figure 3A). She had no

extracardiac uptake to suggest systemic sarcoidosis. Ambulatory heart monitor showed salvos

of non-sustained ventricular tachycardia and episodes of atrial fibrillation. She refused to

undergo invasive endomyocardial biopsy. Given the clinical and imaging findings she was

presumed to have isolated CS. She was empirically started on prednisone daily for treatment of

CS. An implantable cardiac resynchronization therapy defibrillator was placed for primary

prevention. She had no improvement on a 12 week follow up PET scan. She was then started on

methotrexate. Again, she had no improvement in symptoms or improvement on follow up PET

scan (Figure 3B). Unfortunately, during the course of patient’s treatment, her 48-year-old sister

passed away due to a heart attack. Upon further probing, the patient revealed her grandmother

may have had congestive heart failure and her father had a defibrillator. This prompted

additional work up and genetic testing which revealed a pathogenic variant in the LMNA gene.

She was then transitioned to guideline-directed medical therapy (GDMT), including