374. Case Report: Unraveling the Mystery – When Childhood Chest Pain Holds the Key to a Genetic Heart Condition – Wayne State University

This case report explores the intricacies of familial hypercholesterolemia (FH), delving into its genetic basis, atherosclerotic cascade, and early-onset cardiovascular complications. It examines established diagnostic criteria and emphasizes personalized management, including statins, novel therapies, and lifestyle modifications.

CardioNerds cofounders (Drs. Amit Goyal and Danial Ambinder) join Dr. Irfan Shafi, Dr. Preeya Prakash, and Dr. Rebecca Theisen from the Wayne State University/DMC and Central Michigan University at Campus Martius in Downtown Detroit for some holiday ice-skating! They discuss an interesting pediatric case (see case synopsis below). Dr. Luis C Afonso provides the Expert CardioNerd Perspectives & Review segment for this episode. Audio editing by CardioNerds academy internPace Wetstein.

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374. Case Report: Unraveling the Mystery – When Childhood Chest Pain Holds the Key to a Genetic Heart Condition – Wayne State University

Case Synopsis

FH, a 9-year-old female with no previous medical history, recently moved back to the US from Iraq. She presented to establish care and discuss new-onset chest pain and dyspnea. A systolic ejection murmur was noted during her initial visit to the pediatrician, prompting cholesterol testing and a cardiology referral. Testing revealed, alarming cholesterol levels (Total Cholesterol: 802 mg/dL, LDL: 731 mg/dL, Triglycerides: 123 mg/dL) prompted concern for cardiac involvement.

Due to persistent symptoms, FH was transferred to Children’s Hospital of Michigan. Despite normal findings on EKG and chest x-ray, a 2/6 systolic murmur was noted. She was discharged with a cardiology clinic follow-up.

However, two days later, FH experienced severe chest pain at rest, sweating, and difficulty breathing. She was transported to Children’s Hospital again, and her troponin level measured 3000, and her total cholesterol was 695 mg/dL. An echocardiogram revealed valvar and supravalvar aortic stenosis, necessitating collaboration between Pediatric and Adult cardiology teams.

CTA thorax revealed severe supravalvular stenosis, a hypoplastic right coronary artery, and significant coronary artery obstructions. Diagnostic cardiac catheterization confirmed severe aortic stenosis and coronary artery disease, leading to the decision for surgical intervention.

FH underwent the Ross operation, left main coronary artery augmentation, and right coronary artery reimplantation. Intraoperatively, atherosclerotic plaques were observed in multiple cardiac structures.

FH’s recovery was uneventful, discharged on a regimen including Atorvastatin, Ezetimibe, evolocumab, and antiplatelet therapy. Persistent high LDL levels required regular plasmapheresis. Plans for evaluations in Genetics, Lipid Clinic, Endocrine, and Gastroenterology were made, potentially leading to a liver transplant assessment. Given the severity of her condition, a heart/liver transplant might be considered in the future.


This case of FH highlights the complex presentation of severe aortic stenosis and coronary artery disease in a pediatric patient. Urgent diagnosis, interdisciplinary collaboration, and aggressive management were crucial. The case underscores the importance of comprehensive care for pediatric patients with rare cardiac conditions, emphasizing collaboration between specialties for optimal outcomes and long-term well-being.

Case Media

Pearls – Familial Hypercholesterolemia

  • Mutations in LDLR, ApoB, or PCSK9 genes disrupt LDL-C clearance, leading to a cascade of events culminating in accelerated atherosclerosis and early-onset cardiovascular complications (e.g., CAD, aortic stenosis, PAD, stroke).
  • Diagnosis of familial hypercholesterolemia relies on a combination of clinical features (xanthomas, corneal arcus, high LDL-C), family history, and genetic testing guided by established criteria like DCLN or NLA recommendations.
  • Supravalvular aortic stenosis, while common in many congenital cases, should raise suspicion of homozygous familial hypercholesterolemia in the setting of extensively elevated LDL and unexpected coronary artery disease.
  • A multidisciplinary approach, including involvement of pediatric and adult cardiology teams, lipid specialists and cardiothoracic surgeons, should be involved in the overall evaluation and management of these patients, both at initiation of diagnosis, and in an outpatient setting.
  • In patients with FH, it is important to delineate between homozygous and heterozygous manifestations, as this can have extensive implications on treatment, management and the overall clinical prognosis and further disease sequelae that the patient may experience.

References – Familial Hypercholesterolemia

  1. Shah, N. (2020). Familial hypercholesterolemia: Early diagnosis and treatment is key for cardiovascular prevention.Cleveland Clinic Journal of Medicine, 87(5), 109-120. https://pubmed.ncbi.nlm.nih.gov/23469913/
  2. Turgeon, R. D., Barry, A. R., & Pearson, G. J. (2023). Familial hypercholesterolemia: Review of diagnosis,screening, and treatment. American Journal of Health-System Pharmacy, 80(11), 917-929.https://pubmed.ncbi.nlm.nih.gov/26796832/
  3. Collins, R. T. (2018). Cardiovascular disease in Williams syndrome. Current Opinion in Pediatrics, 30(5), 609-615. https://www.ncbi.nlm.nih.gov/books/NBK544278/
  4. Collins, R. T., Kaplan, P., Somes, G. W., & Rome, J. J. (2010). Long-term outcomes of patients with cardiovascular abnormalities and Williams syndrome. American Journal of Cardiology, 105(6), 874-878.https://pubmed.ncbi.nlm.nih.gov/30045083/
  5. Honjo, R. S., Monteleone, V. F., Aiello, V. D., Wagenfuhr, J., Issa, V. S., Pomerantzeff, P. M. A., Furusawa, E. A.,Zanardo, E. A., Kulikowski, L. D., Bertola, D. R., & Kim, C. A. (2022). Cardiovascular findings in Williams-Beuren Syndrome: Experience of a single center with 127 cases. American Journal of Medical Genetics. Part A,188(3), 676-682. https://www.ncbi.nlm.nih.gov/books/NBK544278/
  6. Pham, P. P., Moller, J. H., Hills, C., Larson, V., & Pyles, L. (2009). Cardiac catheterization and operative outcomes from a multicenter consortium for children with Williams syndrome. Pediatric Cardiology, 30(1), 9-14.https://pubmed.ncbi.nlm.nih.gov/19052807/
  7. Olsen, M., Fahy, C. J., Costi, D. A., Kelly, A. J., & Burgoyne, L. L. (2014). Anaesthesia-related haemodynamic complications in Williams syndrome patients: A review of one institution’s experience. Anaesthesia and Intensive Care, 42(6), 619-624. https://pubmed.ncbi.nlm.nih.gov/25233176/
  8. Harada-Shiba, M., Arai, H., Ishigaki, Y., Ishibashi, S., Okamura, T., Ogura, M., Dobashi, K., Nohara, A., Bujo, H.,Miyauchi, K., Yamashita, S., & Yokote, K. (2018). Guidelines for diagnosis and treatment of familial hypercholesterolemia 2017. Journal of Atherosclerosis and Thrombosis, 25(8), 751-770.https://pubmed.ncbi.nlm.nih.gov/29877295/
  9. Alnouri, F., & Santos, R. D. (2022). New trends and therapies for familial hypercholesterolemia. Journal of Clinical Medicine, 11(22), 6638. https://pubmed.ncbi.nlm.nih.gov/36431115/
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