The patient was diagnosed with ICH. After cranial decompression surgery, symptoms such as nausea and chest tightness, and neurologic abnormalities improved. However, her hypertension persisted. She was additionally diagnosed with pheochromocytoma and treated by adrenalectomy. Finally, she was discharged and remained clinically stable.
Her initial symptoms were nausea and vomiting, which are not typical but are common to ICH and MI. Her initial diagnosis in the emergency room (ER) was NSTEMI, based on the cardiac marker elevation and ST depression seen on the EKG. Early CAG was performed to determine the cause of MI and coronary artery stenosis. CAG showed no apparent coronary artery stenosis.
There is an increased interest in the diagnosis of MINOCA. MINOCA is defined by the 2016 European Society of Cardiology position paper [6] as an MI without obstructive coronary artery disease and no other clinical findings suggestive of alternative causes for the elevated cardiac biomarkers. The prognosis of MINOCA is not favorable compared to the conventional causes of MI. In a nationwide prospective study of the Korean Acute Myocardial Infarction- National Institutes of Health registry [12], MINOCA and MI with coronary artery occlusive disease had similar frequencies of in-hospital events, rates of mortality, and recurrent MI within 2 years. Thus, after ruling out other causes, clinicians should identify the etiology of MINOCA, such as plaque disruption, coronary artery dissection, epicardial or microvascular spasm, and coronary thromboembolism [6, 13]. When we saw this patient’s nonobstructive coronary arteries, we considered performing the ergonovine provocation test to rule out vasospasm, but we decided to defer this test due to her unstable condition. In our case, MINOCA may have been suspected upon ruling out non-cardiac causes of myocardial damage. The decreasing biomarkers prior to CAG suggests that the MI was improving. It is assumed that the myocardial damage improved as the coronary artery spasms decreased when the catecholamine concentration fluctuated. MINOCA is a working diagnosis and refers to an MI with coronary artery problems but without significant occlusion on CAG [13]. It corresponds to a diagnosis that highlights the need to ascertain the causes of coronary vasospasm and dissection. A diagnosis of MINOCA is excluded if there are other specific causes for the MI, such as ICH and pheochromocytoma surge, as in our case. Since we were not aware of the existence of an ICH until after a brain CT was performed and after a CAG confirmed it, we suspected MINOCA immediately after the CAG. As ICH and pheochromocytoma were eventually confirmed, this patient does not fit the criteria for MINOCA. We attempted to look at the non-cardiac possibilities by performing abdominopelvic CT, brain CT, and additional physical examinations. On the other hand, a cardiac MRI is not only a good option for diagnosing MINOCA but also has the added advantage of helping predict the prognosis by identifying the extent of myocardial damage [14]. However, in our patient, since the cardiac biomarkers improved, a cardiac MRI was not performed as there was no evidence of deteriorating cardiac function.
A detailed evaluation revealed an ICH and a pheochromocytoma as the causes of raised cardiac biomarkers and other symptoms. Neurogenic stunned myocardium (NSM) is a cardiac complication that occurs after a neurologic event due to the dysregulation of the autonomic nervous system [15]. NSM presents with ischemic EKG changes, elevated cardiac markers, and ventricular wall motion abnormalities, similarly to MI. The potential mechanism of NSM involves a catecholamine surge after damage to the regions of the brain governing the autonomic system. Meanwhile, MI is due to coronary artery blockage. Significant coronary artery obstruction is absent in NSM [16]. Recent cases of ICH mimicking STEMI have been reported [17]. The signs and symptoms of MI and ICH, such as nausea, vomiting, and syncope, are ambiguous and may confuse the diagnosis.
There are several reported cases with similar or related pathophysiology to our case. In addition, cocaine-induced MI and stress-induced cardiomyopathy (SCMP) [18] presenting similarly to a myocardial injury as a result of an underlying ICH [17] and pheochromocytoma [19, 20], respectively, have also been reported.
A characteristic feature seen in our patient which differs from other similar cases is that our patient who developed an acute MI had an underlying ICH and a pheochromocytoma. Cases of NSM that appear as a part of the clinical course of ICH, and MI due to pheochromocytoma have been reported as mentioned above [16, 17, 19, 20]; however, there were no cases in which the two conditions appeared together. MI resulting from an ICH and a pheochromocytoma have in common that both are a result of a catecholamine rush. The order of the myocardial injury in this case is unclear (Fig. 7). Considering the clinical course, one of the two hypotheses is that the pheochromocytoma crisis occurred after the wine intake, and the ICH developed as a result. In this case, the myocardial injury confirmed upon admission to the ER was thought to be related to the catecholamines derived from the pheochromocytoma or ICH. Another hypothesis is that only the ICH occurred initially, and the pheochromocytoma crises developed after the surgery. In this case, it is presumed that the catecholamine release, which is one of the mechanisms of NSM, caused the myocardial injury.
Cocaine-induced MI appears as a normal coronary artery, vasospasm, or a coronary artery thrombosis [21]. Supply-demand mismatch caused by the catecholamine rush and coronary artery spasm caused by the cocaine’s adrenergic reuptake blockade are similar to our case, but the difference is that a thrombotic component [22] is likely to coexist in cases of cocaine abuse.
In general, SCMP or catecholamine associated CMP (NSM, cocaine, pheochromocytoma) shows regional wall motion abnormalities that do not fit well with coronary artery territories [13]. This is also a good indication when diagnosing SCMP. However, early echocardiography in our patient showed hypokinesia of the inferior wall. A possible explanation for this is, first, that the cases of stress-induced CMP appearing in a single vessel territory are rare but have been reported [23]. Although the diagnosis of SCMP is excluded in the presence of a pheochromocytoma or an NSM, it is also accepted that a catecholamine surge plays a part in the pathophysiology of SCMP [24]. Therefore, if an SCMP appears as a single vessel territory, a single vessel territory hypokinesia is possible even in the case of a pheochromocytoma or an NSM. On the other hand, a follow-up echocardiogram performed 3 months later showed a base to mid inferior wall hypokinesia. In the CAG, despite an inferior wall hypokinesia, the right coronary artery was normal without stenosis. The cerebral hemorrhage was resolved and the pheochromocytoma was resected.
In our case, the patient’s nausea persisted, and further evaluation identified a lateral gaze palsy. If brain CT was performed early in the ER, heparin and dual antiplatelet therapy, which increase the risk of bleeding, could be avoided. Also, the surgery for the cerebral hemorrhage could have been performed earlier. However, when our patient presented to the ER, her complaints did not include any specific neurological symptoms, such as headache or decreased consciousness. Thus, it was difficult to ascertain a neurological diagnosis.
Pheochromocytoma may have caused the cerebral hemorrhage and the abrupt elevation of blood pressure that followed. Pheochromocytoma is a rare tumor derived from the chromaffin cells. It is characterized by the production of catecholamines and other neuropeptides [25]. The clinical presentation of pheochromocytoma differs from blood pressure fluctuations due to an MI. The catecholamine surge induces vascular constriction and myocardial inotrope effects, which result in myocardial damage [26]. Pheochromocytoma is aggravated by consuming foods or beverages, such as wine, that are rich in tyramine [27]. At admission, her heart rate was 68 bpm, which is lower than what we anticipated considering pheochromocytoma. Moreover, blood pressure and pulse rate may fluctuate even during a pheochromocytoma crisis. Therefore, one hypothesis is that the patient developed a cerebral hemorrhage and cardiomyopathy initially during the crisis, and upon arrival to the hospital, the catecholamine surge had decreased temporarily. After the surgical treatment of the cerebral hemorrhage and the treatment of hypothermia, it is presumed that the adrenal surge was not revealed, and hypertension due to the pheochromocytoma was revealed again. Another hypothesis is that the pheochromocytoma was initially not a problem, but after the surgical treatment of the cerebral hemorrhage, it was stimulated by a stressful condition resulting in elevated blood pressure.
Both hypotheses suggest that the postoperative hypertension is due to the pheochromocytoma. This is based on the fluctuations in the patient’s blood pressure and pulse rate were generally parallel post-surgery (Fig. 6). Moreover, before visiting the ER, the patient had experienced increased blood pressure at home, but this was not documented in the hospital setting. This intermittent blood pressure elevation was likely a manifestation of the pheochromocytoma.
After the ICH treatment, her cardiac marker values normalized. Moreover, the resection of the pheochromocytoma reduced the number of anti-hypertensives required. Therefore, we assumed a catecholamine surge triggered by ingesting a tyramine-rich beverage caused paroxysmal hypertension and resulted in an ICH. Myocardial damage occurred as a direct effect of the catecholamine surge associated with pheochromocytoma. NSM from ICH also induced myocardial damage in this patient (Fig. 7).
