We report the case of a patient with HOCM presenting with MINOCA. Despite the presence of AMI and diffuse fibrosis, extended septal myectomy was performed to relieve ventricular outflow tract obstruction and the patient’s symptoms. This case highlighted that treatment for MINOCA in HOCM should be individualized based on the patients’ specific conditions, including the infarct size, obstructive severity, and fibrosis level.
The diagnosis of MINOCA requires an ischemic basis for the clinical presentation—i.e., a diagnosis of AMI should be made first [3]. Specifically, the universal AMI definition requires clinical evidence of myocardial necrosis and ischemia [15]. In this case, typical symptoms, ischemic ECG changes, and regional wall motion abnormalities were evidence of acute myocardial ischemia, while dynamic troponin I release and infarcted nuclear imaging supported myocardial necrosis. One distinct characteristic is that ST-segment elevation was always present in precordial V1-V6 leads in this patient. During an acute angina attack, this phenomenon could be misleading and confusing. However, a few days later, T-wave inversion, a sign of postischemic stunning, was observed in these precordial leads (LAD distributed). One shortcoming of this case report was that we did not perform optical coherence tomography (OCT) or intravascular ultrasound (IVUS) imaging to confirm the evidence of nonobstructive atherosclerosis, plaque rupture and erosion on the angiogram [3]. However, the interventional cardiologist confirmed that obstructive disease was not overlooked, as shown in the coronary angiogram.
Previously, some case reports also demonstrated AMI in HCM with a normal coronary artery or diminutive coronary artery [5,6,7]. However, MINOCA in HCM is rare and requires further study to uncover the underlying mechanism [7]. The most likely reason is that ischemia results from an imbalanced oxygen supply and demand at the microvascular level without acute epicardial obstruction [8]. The pathophysiological changes include distortion of the arteriolar architecture, intramural small vessel disease, inadequate capillary density in relation to the increased myocardial mass, and impairment of endothelium-dependent vasodilation [8,9,10]. Additionally, LVOT obstruction might enhance thrombin generation and platelet activity, accounting for micro or transient thrombus/embolism formation in the coronary artery [13]. Another suggested mechanism is that in HOCM, increased wall stress leads to coronary spasm and squeezing, and decreased coronary flow, causing microvascular disorder and myocardial infarction [12]. In this patient, extreme hypertrophy combined with biventricular obstruction may have resulted in a compromised blood supply of the LAD branch that manifested as slow blood flow.
In HCM patients, the prevalence of significant epicardial coronary artery disease (CAD) was up to 20% [9]. However, the incidence and prevalence of AMI in the HCM population, which could be caused either by obstructive epicardial CAD or MINOCA, have not been investigated in large studies. Theoretically, HCM with MINOCA is different from HCM with AMI caused by obstructive CAD. Therefore, their prognoses are considered different. However, no studies have compared the two phenotypes. Nevertheless, a previous study showed that adult HCM patients with concomitant severe CAD are at a higher risk of death than their counterparts [9]. In summary, coronary angiography is necessary for HCM patients with concomitant AMI to clarify the underlying cause and determine the following treatment plan.
Patients with HOCM and MINOCA are challenging to treat, particularly in the presence of a large area of myocardial infarction. First, the infarcted myocardium cannot be saved by revascularization, because no epicardial coronary stenotic lesions exist. Additionally, no effective treatments are currently available to reverse myocardial infarction mediated by other mechanisms. Second, the healthy viable myocardium is significantly reduced once massive myocardial infarction occurs. As shown in this case, the presence of biventricular obstruction makes the clinical scenario more complex. On the one hand, if septal reduction therapy is performed, part of the healthy viable myocardium may be cut off, and the normal viable myocardium will be reduced further, possibly leading to cardiac dysfunction after surgery. On the other hand, if septal reduction therapy is not performed, patients will continue to show severe LVOT obstruction and have a high risk of sudden death. Biventricular obstruction will also aggravate myocardial ischemia and worsen cardiac function. No consensus exists regarding the choice of treatment for these patients [16]. Individualized treatment is the focus for HCM patients. More studies on treatment is needed for this population in the future. In this case, the final decision was to perform extended septal myectomy to solve the current main problem of ventricular outflow tract obstruction. This not only relieved outflow tract obstruction and symptoms but also reduced the rate of sudden death and avoided left ventricular dysfunction after surgery [17,18,19].
In addition to MINOCA, this patient showed diffuse myocardial fibrosis as indicated by LGE on CMR. According to previous studies, LGE is identified in approximately 60% of the adult overt HCM population [20]. The molecular pathways leading to myocardial fibrosis remain incompletely understood. LV hypertrophy may be an important factor associated with LGE because LGE is seldom observed in mutation carriers without LV hypertrophy [21,22,23]. Recent studies have demonstrated that the maximal LV wall thickness is the only independent predictor of the presence and extent of LGE [23]. Myocardial fibrosis displayed on LGE might be the manifestation of ischemia. Whether patients with severe hypertrophy have recurrent ischemic attacks and/or focal infarctions is unknown. However, LGE has been extensively studied and found to be associated with adverse outcomes [20, 24]. Thus, this extremely hypertrophic and biventricular obstructive HCM patient, with extensive myocardial fibrosis superimposed by MINOCA, might have the worst prognosis.
This patient had a family history of HCM, and the genetic test results suggested a heterozygous variant of uncertain significance in KCNJ2, which encodes the Kir2.1 potassium channel [25]. This gene has not been previously reported to be associated with HCM. Previously, this gene variant was reported to enhance the function of Kir2.1 and was related to atrial fibrillation [26]. The relationship between this gene variant and HCM phenotype remains unclear. Further basic studies are required to verify the variant’s function.
In summary, this patient with extremely hypertrophic and biventricular obstructive HCM had a MINOCA attack superimposed on extensive myocardial fibrosis. We made individualized treatment decisions according to the characteristics of the patient. Septal reduction surgery was performed cautiously in this scenario to improve the patient’s symptoms.