Cardiac pheochromocytomas (CPs) are very rare primary neuroendocrine catecholamine-secreting tumors that arise from the sympathetic paraganglia, which is made up of (chromaffin) cells. Paraganglia are non-neuronal cells that originated from the neural crest. The incidence of primary cardiac tumors ranges from 0.01 to 0.3% by autopsy.. Thus far, CP is the rarest form of primary cardiac tumors. Nearly 98% of pheochromocytomas are found in the abdomen, with the adrenal gland being the most common site). Less than 2% of pheochromocytomas are found in the chest, with the heart being the least common site. Most of the reported cases of CP were benign. Although malignant pheochromocytomas are uncommon, the ones arising from the heart appear more aggressive and difficult to resect. In a small clinical data of 158 patients, where 137 of these patients had detailed imagings, 85% (117/137) of the patients were found to have an intra-pericardiac tumor, either arose from branchiomeric paraganglia (in the roots of the great vessels including pulmonary artery, pulmonary vein, vena cava, and aorta) or visceral autonomic paraganglia( interatrial or interventricular groove). CP is an extremely vascular tumor that mostly obtains its blood supply from the coronary circulation (right coronary artery > left circumflex artery > left coronary artery > left anterior descending artery).
Although there is no clear data available, recent data reports that genetic mutations and familial etiology contribute up to 25% to 50% of pheochromocytomas. In the literature review, one case of cardiac pheochromocytoma was associated with multiple endocrine neoplasia (MEN) was reported . The following syndromes have been found to be associated with pheochromocytomas in general. Multiple endocrine neoplasia type 2 (RET gene), neurofibromatosis 1 (NF1), Von Hippel-Lindau disease (VHL gene), adrenocortical adenoma and/or endocrines tumors as in Carney’s triad and paraganglioma syndromes type 1, 3, and 4 (SDH gene). Thirty percent (30%) of patients with malignant adrenal pheochromocytomas and forty-eight percent (48%) of patients with malignant paragangliomas (extra-adrenal pheochromocytomas) are found to have germline mutations of succinate dehydrogenase subunit B (SDH). It is possible that CPs are also associated with the above syndromes.
Cardiac pheochromocytomas (CPs) represent the rarest form of primary cardiac tumors. The incidence of primary cardiac tumors ranges from 0.01 to 0.3% by autopsy. Only less than 2% of pheochromocytomas are found in the chest, and of these, CP accounts the least of all. Less than 300 patients with CP are described in the PubMed database. The mean age at diagnosis is 40 years (ranges from 12 to 85 years) with equal distribution in both genders, although data is limited. In general, catecholamine-secreting tumors occur less than 0.2% of patients with hypertension.
Cardiac pheochromocytomas are catecholamine secreting tumors that arise from chromaffin cells of the sympathetic paraganglia in the heart. They are often characterized by excessive, often episodic catecholamine production and/or secretion (Like epinephrine, dopamine, and norepinephrine) that can lead to signs and symptoms like hypertension, sweating, headache, dizziness, perspiration, palpitations, and tachycardia.
The most common presentations of cardiac pheochromocytomas are catecholamine-related symptoms: palpitations, sweating, diaphoresis, hypertension, tachycardia, dizziness, headache, syncope, perspiration, and flushing. Unlike other primary cardiac tumors, shortness of breath is uncommon. Although uncommon, some patients may present with chest pain. The likely explanation of the chest pain is that the tumor itself may mimic angina if it does not get enough blood supply. Sometimes initial presentation can be nonspecific: fever, fatigue, and weight loss. These tumors are rarely asymptomatic.
Once there is a suspicion of a pheochromocytoma, one should keep in mind that 98% of these tumors are intra-abdominal (90% in the adrenal medulla), and less than 2% are found in the chest. Of these in the chest, CP is one of the rarest ones.
The most difficult part of this tumor is not by diagnosing it but to localize it. There is a number of imagings (including but not limited to CT or enhanced CT, PET scan, MRI, echocardiogram, labeled metaiodobenzylguanidine (MIBG), or Tc labeled octreotide) that can be used. The most important imagings for CP localization will be reviewed below.
In summary: MIBG, MRI, and coronary angiogram are indispensable pre-operative imaging modalities for tumor localization after laboratory confirmation.
The most effective treatment of cardiac pheochromocytomas is surgical resection. However, blood pressure has to be controlled pre-operatively. Blood pressure normalization can be achieved with alpha-blockers (doxazosin, urapidil, phenoxybenzamine) initiating 2 to 3 weeks prior to the surgery. Other medications that can be used are calcium channel blockers (amlodipine, nifedipine) and angiotensin-converting enzyme inhibitors (ramipril). It is very important to avoid using beta blockers until good blood pressure control with alpha-blockers. Isolated beta-blocker use can cause a catecholamine storm and hypertensive crisis. It is recommended to start beta-blockers 2 days prior to surgery to control heart rate. There is no known role for chemoradiation.
In general, differential diagnosis of pheochromocytomas is broad, and these include but not limited to adrenal pheochromocytomas, hyperthyroidism, thyroid storm, cardiac arrhythmias, carcinoid tumor, migraine, stroke, medullary thyroid carcinoma, mastocytosis, etc.
In patients with a confirmed cardiac mass, the differential diagnosis may include pericardial mass, abscess, or metastasis.
The most effective treatment of cardiac pheochromocytomas is surgical resection.
The one- year and 5- year survival rate date of 91 patients who had benign CP were 98.2% and 78.8%, respectively. Although data is limited, overall prognosis and recovery are quite good after complete resection. For malignant CP, the prognosis is not clear yet, as not enough data is available.
Complications can be related to either the disease itself or the procedure. Since it is a catecholamine-secreting tumor, if not treated, it can cause ischemic heart disease, myocardial infarction, cardiac arrhythmias, cardiomyopathy, pulmonary edema, stroke, and hypertensive crisis. The procedure is high risk. CP is a highly vascular tumor. In data of 100 patients, 5 died due to massive intraoperative bleeding.
An interprofessional approach including a cardiologist, a cardiothoracic surgeon, an oncologist, an electrophysiologist, an intensivist, an internist, and the nurse is required for proper care and management of patients with CP. The overall prognosis is quite good after total resection.
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