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Internal Medicine
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Internal Medicine
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Internal Medicine
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Clinical Science
Abstract
Background: Non-ischemic cardiomyopathy (NICM), can arise from various causes, including hemodynamic pathology, infections, immunologic abnormalities, toxic injuries, and genetic factors. Determining the prevalence of NICM is challenging due to varying definitions and diagnostic criteria, selection bias, and geographic variation. MYBPC3 is the primary gene known to cause restrictive cardiomyopathy, dilated cardiomyopathy, and left ventricular non-compaction. This gene encodes cMyBP-C, a structural protein of the heart muscle that interacts with actin, myosin, and titin to maintain sarcomeric integrity. While loss-of-function mutations are common, MYBPC3 missense variants of uncertain significance (VUS) are also prevalent. Individuals with MYBPC3 missense VUS predicted to disrupt subdomain folding (STRUM+) exhibit high incidences of adverse clinical outcomes similar to pathogenic MYBPC3 variants.
Case Presentation: A 49-year-old Hispanic male with hypertension, and hyperlipidemia, who denies smoking, alcohol, or substance abuse, presented with shortness of breath and fatigue. He experienced a syncopal episode in February while on a ladder, with lightheadedness, racing heart, sharp chest pains, and difficulty swallowing, losing consciousness upon reaching the ground. The physical exam showed BP 110/65 mmHg, HR 108 bpm, RR 20 bpm, and JVD. EKG showed a left bundle branch block, and an echocardiogram revealed an ejection fraction
Conclusion: Dilated cardiomyopathy can result from rare genetic mutations like VUS MYBPC3. Genetic testing is crucial for NICM patients to inform family members about the necessity of genetic testing. MYBPC3 missense VUS predicted to disrupt subdomain folding (STRUM+) presents high incidences of adverse outcomes. While MYBPC3 mutations are common in HCM, our patient presented with heart failure, possibly indicating HCM progression to heart failure or primary heart failure due to the gene mutation. GDMT and device therapy are essential in treating NICM while awaiting a heart transplant.
Presentation Type
Talk
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This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 International License.
Recommended Citation
Ngo, Khiem D.; Alejos, Carlos; Rojas, Jennifer; Memon, Sobia; and Stone, James, "Unraveling Dilated Cardiomyopathy Linked to an Enigmatic MYBPC3 Variant" (2024). Research Colloquium. 14.
https://scholarworks.utrgv.edu/colloquium/2024/talks/14
Unraveling Dilated Cardiomyopathy Linked to an Enigmatic MYBPC3 Variant
Background: Non-ischemic cardiomyopathy (NICM), can arise from various causes, including hemodynamic pathology, infections, immunologic abnormalities, toxic injuries, and genetic factors. Determining the prevalence of NICM is challenging due to varying definitions and diagnostic criteria, selection bias, and geographic variation. MYBPC3 is the primary gene known to cause restrictive cardiomyopathy, dilated cardiomyopathy, and left ventricular non-compaction. This gene encodes cMyBP-C, a structural protein of the heart muscle that interacts with actin, myosin, and titin to maintain sarcomeric integrity. While loss-of-function mutations are common, MYBPC3 missense variants of uncertain significance (VUS) are also prevalent. Individuals with MYBPC3 missense VUS predicted to disrupt subdomain folding (STRUM+) exhibit high incidences of adverse clinical outcomes similar to pathogenic MYBPC3 variants.
Case Presentation: A 49-year-old Hispanic male with hypertension, and hyperlipidemia, who denies smoking, alcohol, or substance abuse, presented with shortness of breath and fatigue. He experienced a syncopal episode in February while on a ladder, with lightheadedness, racing heart, sharp chest pains, and difficulty swallowing, losing consciousness upon reaching the ground. The physical exam showed BP 110/65 mmHg, HR 108 bpm, RR 20 bpm, and JVD. EKG showed a left bundle branch block, and an echocardiogram revealed an ejection fraction
Conclusion: Dilated cardiomyopathy can result from rare genetic mutations like VUS MYBPC3. Genetic testing is crucial for NICM patients to inform family members about the necessity of genetic testing. MYBPC3 missense VUS predicted to disrupt subdomain folding (STRUM+) presents high incidences of adverse outcomes. While MYBPC3 mutations are common in HCM, our patient presented with heart failure, possibly indicating HCM progression to heart failure or primary heart failure due to the gene mutation. GDMT and device therapy are essential in treating NICM while awaiting a heart transplant.