Hemorrhagic Stroke Caused by Moyamoya Disease in a Patient with Obstructive Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is a well-known cardiac condition characterized by thickening of the heart muscle, particularly the interventricular septum. While HCM is primarily associated with an increased risk of ischemic stroke, hemorrhagic stroke is an exceedingly rare complication in these patients. This report presents a unique case of a 42-year-old woman with obstructive HCM who experienced a hemorrhagic stroke due to underlying moyamoya disease, a rare cerebrovascular disorder. The coexistence of these two conditions is exceptionally rare, with only one prior case reported in the literature.
The patient initially presented with exertional dyspnea, chest pain, and dizziness. She had a 10-year history of obstructive HCM, managed with metoprolol, and was consistently found in sinus rhythm. Her family history was notable for HCM in her mother, who was diagnosed at the age of 30 but declined further investigations. On admission, echocardiography revealed asymmetrical left ventricular (LV) hypertrophy with a peak pressure gradient of 79 mmHg in the LV outflow tract (LVOT). Cardiac magnetic resonance imaging (MRI) further confirmed the diagnosis, showing remarkable hypertrophy of the interventricular septum with a maximum thickness of 32 mm and focal late gadolinium enhancement. The imaging also demonstrated a narrowed LVOT at mid-systole, consistent with obstructive HCM.
The patient underwent a modified Morrow surgery, a procedure aimed at relieving LVOT obstruction, and recovered successfully. She remained asymptomatic during an 8-month follow-up period. However, she was readmitted following a sudden onset of unconsciousness. A computed tomography (CT) scan of the brain confirmed the presence of a left parietal lobe hemorrhage with intraventricular extension. Transcatheter angiography revealed the characteristic features of moyamoya disease, including steno-occlusion of the distal parts of the bilateral internal carotid arteries and the presence of moyamoya-associated collateral networks at the base of the brain.
Genetic analysis through whole-exome sequencing identified two significant mutations. The first was a single-site mutation (p.G407C, c.1219G>T) in the myosin heavy chain 7 (MYH7) gene, the most frequently implicated gene in HCM. This mutation results in an amino acid change from glycine to cysteine, which disrupts the secondary structure of the protein and is considered likely pathogenic. The second mutation (p.R2954H, c.8834G>A) was found in the ring finger protein 213 (RNF213) gene, the first susceptibility gene identified for moyamoya disease. The p.R2954H variant has not been previously reported in moyamoya disease, and the exact mechanisms by which RNF213 variants contribute to the development of moyamoya remain unclear.
HCM is a monogenic heart disease with a prevalence of 0.07% to 0.2% in the general population. It is associated with an increased risk of atrial fibrillation, primarily due to advanced diastolic dysfunction and left atrial remodeling. While HCM is an independent risk factor for ischemic stroke, hemorrhagic stroke is a rare complication in these patients, with mechanisms yet to be fully elucidated. Moyamoya disease, on the other hand, is a rare cerebrovascular disorder characterized by chronic steno-occlusion of the distal internal carotid arteries and the development of fragile collateral vessels. This condition predisposes patients to both ischemic and hemorrhagic strokes, with hemorrhagic stroke being the more common presenting type in Asian adults.
The coexistence of HCM and moyamoya disease is exceptionally rare. Prior to this case, only one other instance had been reported in the literature, involving a 14-year-old boy in 1985. The rarity of this combination underscores the importance of this case report in expanding our understanding of the potential complications and genetic underpinnings of these conditions.
In conclusion, this case highlights the rare but significant association between obstructive HCM and moyamoya disease, leading to hemorrhagic stroke in a 42-year-old woman. The genetic mutations identified in the MYH7 and RNF213 genes provide valuable insights into the potential molecular mechanisms underlying these conditions. Further research is needed to elucidate the precise role of these genetic variants in the pathogenesis of HCM and moyamoya disease and to explore potential therapeutic targets.
doi.org/10.1097/CM9.0000000000000997
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