Cardionerds: A Cardiology Podcast

405. Case Report: Like Mother, Like Son? Peripartum Cardiomyopathy and Infantile Hypertrophic Cardiomyopathy Lead to a Unifying Diagnosis – Mayo Clinic Arizona

13 Dec 2024

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CardioNerds (Dr. Dan Ambinder and guest host, Dr. Pooja Prasad) join Dr. Donny Mattia from Phoenix Children’s pediatric cardiology fellowship, Dr. Sri Nayak from the Mayo Clinic – Arizona adult cardiology fellowship, and Dr. Harrison VanDolah from the University of Arizona College of Medicine - Phoenix Med/Peds program for a sunrise hike of Piestewa Peak, followed by some coffee at Berdena’s in Old Town Scottsdale (before the bachelorette parties arrive), then finally a stroll through the Phoenix Desert Botanical Gardens to discuss a thought-provoking case series full of clinical cardiology pearls. Expert commentary is provided by Dr. Tabitha Moe. Episode audio was edited by Dan Ambinder. They discuss the following case: Cardiology is consulted by the OB team for a 27-year-old female G1, now P1, who has just delivered a healthy baby boy at 34 weeks gestation after going into premature labor. She is experiencing shortness of breath and is found to have a significant past cardiac history, including atrial fibrillation and preexcitation, now with a pacemaker and intracardiac defibrillator. We review the differential diagnosis for peripartum cardiomyopathy (PPCM) and then combine findings from her infant son, who is seen by our pediatric cardiology colleagues and is found to have severe hypertrophic cardiomyopathy (HCM). Genetic testing for both ultimately reveals a LAMP2 mutation consistent with Danon Disease. The case discussion focuses on the differential diagnosis for PPCM, HCM, pearls on Danon Disease and other HCM “phenocopies,” and the importance of good history. US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Case Media Pearls Peripartum cardiomyopathy is a diagnosis of exclusion – we must exclude other possible etiologies of heart failure! Be on the lookout for features of non-sarcomeric HCM – as Dr. Michelle Kittleson said in Episode 166, “LVH plus” states. HCM with preexcitation, heart block, strong family history, or extracardiac symptoms such as peripheral neuropathy, myopathy, or cognitive impairment should be evaluated for infiltrative/inherited cardiomyopathies! As an X-linked dominant disorder, Danon disease will present differently in males vs females, with males having much more severe and earlier onset disease with extracardiac features. Making the diagnosis for genetic disorders such as Danon disease is important for getting the rest of family members tested as well as the opportunity for specialized treatments such as gene therapy Up to 5% of Danon disease cases may be due to copy number variants, which may be missed in genetic testing that does not do targeted deletion/duplication analysis!). Notes What is the differential diagnosis for peripartum cardiomyopathy? Peripartum cardiomyopathy is a diagnosis of exclusion – we must exclude other possible etiologies of heart failure! First, ensure that you are not missing an acute life-threatening etiology of acute decompensated heart failure – pulmonary embolism, amniotic fluid embolism, ACS, and SCAD should all be ruled out. Second, a careful history can identify underlying heart disease or risk factors for the development of heart failure, such as substance use, high-risk behaviors that put one at risk for HIV infection, and family history that suggests an inheritable cardiomyopathy. Lastly, a careful review of echocardiographic imaging may also identify underlying etiologies that warrant a change in management. Diagnosis of peripartum cardiomyopathy is important to consider as within 7 days of onset, patients may be eligible for treatment with bromocriptine – consider referring the patient for enrollment in the ongoing RCT ReBIRTH. Check out Cardionerds Episode 113 and the great article linked below for more details on heart failure in pregnancy and postpartum! What is the differential diagnosis for hypertrophic cardiomyopathy? Though by far the most common differential diagnosis for HCM is simple LVH or athlete’s heart, as Dr. Michelle Kittleson taught us in CardioNerds Episode 166, we should “remain alert for “LVH+” states.” It is helpful to think of them in two buckets – sarcomeric mutations (classic HCM) or non-sarcomeric causes (“phenocopies”). If you see systemic signs like peripheral neuropathy, renal dysfunction, or skin changes – clues towards a systemic pathology (for adult colleagues, first think amyloidosis; for peds, colleagues, think genetic syndromes such as RASopathies like Noonan syndrome, glycogen, and lysosomal storage diseases like Fabry). Additionally, certain additional cardiac findings can point towards a non-sarcomeric HCM – recall way back in CardioNerds Episode 68 when our friends at VCU presented a man in his 60s with a history of WPW/preexcitation and HCM and was found to have a PRKAG2 mutation, which is a similar lysosomal vacuolopathy to Danon disease. Another example was seen in Episode 349 when we saw a patient with HCM and heart block who was found to have Fabry disease. What is Danon disease, and how does it present? Danon disease is a rare X-linked dominant genetic disorder due to deficiency in LAMP2, a glycoprotein involved in protecting the lysosome from its roles in endocytosis and autophagy When deficiency of LAMP2 occurs, products build up into vacuoles and lead to cardiomyocyte dysfunction and death. Interestingly, autophagy disruption is the suspected mechanism of cardiomyopathies from anthracyclines and hydroxychloroquine – Danon disease severity underscores the importance of this process! Estimated prevalence of Danon disease in adult patients with HCM is 1-4%, however when both HCM and pre-excitation are present, this rises to 17%. It is highly penetrant, meaning most patients with the mutation will show symptoms. There are several extracardiac features such as skeletal myopathy, retinopathy, and cognitive impairment – these correlated with areas in the body where LAMP2 is expressed more! Classic presentations – remember that X-linked inheritance results in differential expression between males and females!Males: young onset with severe LVH/HCM and extracardiac phenotype Females: isolated cardiomyopathy (can be either dilated or hypertrophic) with preexcitation arrhythmias with a family history suggesting X-linked dominant transmission (i.e., males more severely affected than females). When taking a family history, note that male-to-male transmission (can’t happen since males don’t pass on an X chromosome to their male children) or female-to-offspring transmission (suggests mitochondrial disease) should prompt alternate diagnosis. However, an estimated 1/3 of Danon disease cases are de novo mutations! See Episode 300 for a great in-depth overview of the pathophysiology of Danon disease How is Danon disease diagnosed? Though there are some proposed characteristic cardiac MRI findings (diffuse LGE sparing the interventricular septum), diagnosis is genetic with a loss-of-function mutation in LAMP2 paired with characteristic cardiac or extracardiac features (see below diagnostic algorithm from Hong et al. JACC 2023) LAMP2 is now included in most hypertrophic and dilated CM panels – if found, it is crucial to ensure the patient’s family members also undergo testing and potentially cardiac evaluation! (Note: up to 5% of Danon disease cases may be due to copy number variants, which may be missed in genetic testing that does not do targeted deletion/duplication analysis!) Differential DiagnosisSarcomeric HCM – the “classic” HCM, which has numerous genetic causes, all of which affect the sarcomere with age-related penetrance leading to three peaks in age at onset (infancy

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Cardionerds: A Cardiology Podcast

405. Case Report: Like Mother, Like Son? Peripartum Cardiomyopathy and Infantile Hypertrophic Cardiomyopathy Lead to a Unifying Diagnosis – Mayo Clinic Arizona

This episode hasn't been transcribed yet

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3ª PARTE | 17 DIC 2025 | EL PARTIDAZO DE COPE

13:00H | 21 DIC 2025 | Fin de Semana

12:00H | 21 DIC 2025 | Fin de Semana

10:00H | 21 DIC 2025 | Fin de Semana

13:00H | 20 DIC 2025 | Fin de Semana

12:00H | 20 DIC 2025 | Fin de Semana

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