Abstract
Acromegaly—a rare endocrine disorder—results when a growth hormone–secreting somatotroph pituitary adenoma leads to increased insulin-like growth factor 1 production. Acromegaly is known to cause left ventricular hypertrophy. We present a case of acromegaly with massive left ventricular hypertrophy that was determined to be coexistent with gene-positive hypertrophic obstructive cardiomyopathy. (Level of Difficulty: Intermediate.)
Key Words: cardiomyopathy, genetic disorders, mitral valve
Central Illustration
A 61-year-old woman with a history of hypothyroidism presented with worsening dyspnea on exertion and orthopnea. She reported enlarging facial features, hands, and feet over several years. Coarse facial features with prognathism, prominent brow ridge, remarkable distance between teeth, and macroglossia were observed. A grade 3/6 systolic ejection murmur, which increased to 4/6 intensity with Valsalva maneuvers, was heard at the left sternal border.
Laboratory test results were significant for N-terminal pro–B-type natriuretic peptide of 4,522 pg/mL (reference: ≤125 pg/mL); high-sensitivity troponin of 2,857 ng/L (reference: <52 ng/L); and insulin-like growth factor-1 of 639 ng/mL (reference: 43-220 ng/mL). Electrocardiography demonstrated normal sinus rhythm with left ventricular hypertrophy (LVH). Chest x-ray film demonstrated mild pulmonary edema.
Transthoracic echocardiography (TTE) revealed massive asymmetric septal hypertrophy (43 mm) with reverse septal curvature, posterior wall thickness of 19 mm, and LV mass of 395 g/m2 (Figure 1A). LV ejection fraction was 76%. LV outflow tract obstruction with severe mitral systolic anterior motion was present with a peak gradient of 40 mm Hg at rest and 75 mm Hg with Valsalva maneuvers. A flail segment of the posterior mitral leaflet and severe anteriorly directed mitral regurgitation were observed. Transesophageal echocardiography confirmed a flail P3 scallop of the mitral valve with torrential regurgitation (Figures 1B and 1C, Video 1).
Figure 1.
Multimodality Imaging of Massive Left Ventricular Hypertrophy
(A) A presurgery transthoracic echocardiogram in the parasternal long-axis view in end diastole with ultrasound enhancing agent demonstrates severe septal hypertrophy measuring 43 mm (double-headed arrow). (B) Torrential anteriorly directed mitral regurgitation (arrow) is seen on a presurgery transesophageal echocardiogram. (C) A presurgery 3-dimensional transesophageal echocardiogram shows the mitral valve with flail P3 scallop prolapsing into the left atrium (black arrow). (D) A 4-chamber cardiovascular magnetic resonance image using steady-state free precession shows severe asymmetric septal hypertrophy measuring 43 mm (double-headed arrow) with reverse septal morphology. (E) Cardiovascular magnetic resonance in the mid short-axis view with high-resolution late gadolinium enhancement demonstrates extensive, patchy, midmyocardial delayed gadolinium enhancement (arrow) in the septal and anterior walls. (F) A transthoracic echocardiogram in the parasternal long-axis view during diastole performed at the 1-year follow-up visit demonstrates reverse septal hypertrophy measuring 36 mm (double-headed arrow). Figures from Tilkens BL, Wang D, Solis J, Crouch JD, Sanders H, Tajik AJ. A masquerade of acromegaly with underlying hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol. 2023;81(suppl 8):3183. LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.
Cardiovascular magnetic resonance showed extensive fibrosis throughout the septum and midanterior wall, ∼30% of the total LV mass (Figures 1D and 1E). Coronary angiography demonstrated no obstructive coronary disease. Brain magnetic resonance imaging demonstrated a 15 × 16 × 23–mm pituitary macroadenoma. Genetic testing, performed to distinguish phenotype vs phenocopy of massive hypertrophy in a patient with acromegaly, revealed a pathogenic variant of the autosomal dominant MYBPC3 gene for hypertrophic cardiomyopathy (HCM).
The patient underwent transaortic septal myectomy, mitral valve repair with a Gore-Tex neochord (W. L. Gore & Associates), and annuloplasty with a 32-mm 3D Memo ring (LivaNova). An implantable cardioverter-defibrillator was placed for primary prevention of sudden cardiac death. Four weeks later, a neurosurgeon performed an endoscopic endonasal resection of the pituitary adenoma. Surgical pathology results were consistent with somatotroph adenoma. The patient was discharged on atenolol 50 mg and spironolactone 12.5 mg daily.
At 1 year, symptoms had resolved. Computed tomography demonstrated no sign of recurring pituitary mass. Repeat laboratory workups and TTE demonstrated significant improvements (Supplemental Table 1), including asymmetric septal hypertrophy measuring 36 mm (Figure 1F), no LV outflow tract gradient, and mild residual mitral regurgitation.
LVH with chamber enlargement is observed in ∼16% of patients with acromegaly. Surgical resection of the macroadenoma causes significant reduction in LV mass and hypertrophy.1 A Mayo Clinic study included HCM patients who underwent septal myectomy with pre- and postoperative TTE. After 2 years, the average LV mass index regression was about 20%.2 In our patient, there was a 25% regression in LV mass index 1 year after pituitary tumor resection and septal myectomy. Regression in LV mass index without complete resolution of LVH suggests that both acromegaly and HCM contributed to the massive LVH. This case demonstrates that the primary diagnosis may not be the only diagnosis.
Funding Support and Author Disclosures
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Acknowledgments
The authors thank Dr Dajun Wang for contributing to the care of this patient. The authors also thank the following from Aurora Cardiovascular and Thoracic Services: Jennifer Pfaff and Sarah Kennedy for editorial preparation of the manuscript and Brian Miller and Brian Schurrer for assistance with the figures.
Footnotes
This case was presented at the American College of Cardiology in March 2023.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
Appendix
For a supplemental table and video, please see the online version of this paper.
Appendix
Pre-Surgery Transesophageal Echocardiogram
Imaging with and without color Doppler demonstrating a redundant anterior mitral valve leaflet with flail P3 scallop and torrential anteriorly directed mitral regurgitation.
References
- 1.Goldberg M.D., Vadera N., Yandrapalli S., Frishman W.H. Acromegalic cardiomyopathy: an overview of risk factors, clinical manifestations, and therapeutic options. Cardiol Rev. 2018;26:307–311. doi: 10.1097/CRD.0000000000000215. [DOI] [PubMed] [Google Scholar]
- 2.Deb S.J., Schaff H.V., Dearani J.A., Nishimura R.A., Ommen S.R. Septal myectomy results in regression of left ventricular hypertrophy in patients with hypertrophic obstructive cardiomyopathy. J Ann Thorac. 2004;78:2118–2122. doi: 10.1016/j.athoracsur.2004.05.063. [DOI] [PubMed] [Google Scholar]
Associated Data
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Supplementary Materials
Pre-Surgery Transesophageal Echocardiogram
Imaging with and without color Doppler demonstrating a redundant anterior mitral valve leaflet with flail P3 scallop and torrential anteriorly directed mitral regurgitation.