Cardiac cephalalgia: a case series of four patients and updated literature review

The interaction between the brain and the heart is an emerging area of clinical interest. Cardiac damage is common in patients with acute brain injury. Neurogenic stress cardiomyopathy (also known as neurogenic stunned myocardium) is widely recognized in patients with acute neurological disease [1]; however, little is known regarding cardiac-induced neurological symptoms. In 1997, Lipton et al. reported two cases of exertional headache associated with myocardial ischemia; based on these and a review of five similar previous ones, they coined the term “cardiac cephalgia” (“cardiac cephalalgia” in the current classification) [2]. In the International Classification of Headache, Third Edition (ICHD-III) [3], cardiac cephalalgia is classified as a headache caused by impaired homeostasis (Table 1). Cardiac cephalalgia is described as migraine-like headache that occurs during an episode of myocardial ischemia and is usually aggravated by exercise. The diagnosis can be challenging because cardiac cephalalgia is uncommon and the headache is not always associated with exertion; headache may occur at rest without chest symptoms [4‐6]. Only a few reported cases of cardiac cephalalgia presented with sudden severe headache (thunderclap headache), which mimics subarachnoid hemorrhage (SAH) [7‐10]. Both myocardial ischemia and SAH are potentially life-threatening; therefore, early recognition with appropriate treatment is critically important. Consequently, it is essential to understand the characteristics of cardiac cephalalgia as a neurological emergency and accurately diagnose it to enable appropriate intervention. This report presents four patients diagnosed with cardiac cephalalgia and reviews the relevant literature to summarize the disease characteristics and current evidence regarding the diagnosis and treatment of this uncommon clinical entity.

This report presents four cases of cardiac cephalalgia that resulted from AMI. Two patients (cases 2 and 3) reported chest discomfort with associated triggers. In contrast, the other two (cases 1 and 4) presented with sudden severe headache that met the diagnostic criteria for a thunderclap headache without an identifiable trigger. The latter two lost consciousness after the headache and had no cardiac symptoms; therefore, SAH was initially suspected. After head CT confirmed no intracranial hemorrhage, emergency CAG was performed, followed by PCI. Notably, three patients presented with low blood pressure and one developed VF. Because all four exhibited abnormal findings on ECG and echocardiography, the diagnosis of cardiac cephalalgia was straightforward. Early cooperation with cardiologists enabled prompt cardiovascular examination and treatment. The headache resolved after successful coronary reperfusion in all cases.

In a study of 1546 AMI patients, headache was present (along with other symptoms) in 5.2% and was the primary complaint in 3.4% [55]. Differentiation of cardiac cephalalgia from migraine without aura has been emphasized in patients without chest symptoms. Vasoconstrictor medications (e.g., triptans, ergots) are contraindicated in patients with ischemic heart disease, while migraine-like headache may be triggered by angina treatments such as nitroglycerine [3].

The typical manifestation of cardiac cephalalgia is migraine-like pain on exertion. However, it may present as a thunderclap headache without a trigger, although this is not common. In a systemic review of thunderclap headache, more than 100 different causes were reported; cardiac cephalalgia was highlighted as an important causative systemic condition [56]. Above all, SAH is the most common cause of secondary thunderclap headache and should be the focus of initial assessment given its significant morbidity and mortality [57].

Early differentiation of SAH and AMI is crucial because both are potentially life-threatening. Rapid diagnosis and appropriate treatment are therefore critical. Because cardiac cephalalgia is not always associated with chest symptoms or ECG abnormalities, the diagnosis should be considered in middle-aged or older patients with coronary risk factors presenting with a first-episode headache.

Confusingly, SAH patients can also present with cardiac symptoms. ECG abnormalities are common in these patients and left ventricular wall motion abnormalities may develop in the absence of organic coronary artery stenosis. Echocardiography may show takotsubo-like or other types of abnormal wall motion. This manifestation is transient and has been called neurogenic stunned myocardium [58], which is often associated with hypotension and elevated myocardial enzyme concentration [59]. Accordingly, hypotension, ECG abnormalities, abnormal cardiac wall motion, and mildly elevated cardiac enzyme concentration do not preclude SAH. For patients with thunderclap headache, emergency head CT is indispensable; if no significant findings are detected, a cardiac workup should be initiated. ECG, echocardiography, measurement of cardiac enzyme concentrations, and coronary artery evaluation should be performed when cardiac cephalalgia is suspected.

Several mechanisms to explain the headache induced by myocardial ischemia have been hypothesized: 1) referred pain through the convergence of vagal afferents from the heart with trigeminal neurons in the spinal trigeminal nucleus or somatic afferents from C1–C3 in the upper spinothalamic tract [2, 4, 60]; 2) elevated intracranial pressure because of venous stasis resulting from ischemia-induced ventricular hypofunction and reduced cardiac output [2, 4]; 3) vasodilation within the brain secondary to myocardial ischemia-induced release of serotonin, bradykinin, histamine, and substance P [2, 4]; 4) presence of vasospasm in both coronary and cerebral arteries [4]; and 5) reversible contraction of microvessels or cortical spreading depolarization induced by cerebral hypoperfusion [6]. The last hypothesis is based on confirmation of cerebral hypoperfusion during a headache attack in the presence of normal cerebral arteries on MR angiography [6]. CT angiography and MR angiography in the patients reported here did not reveal constriction of visible cerebral arteries either.

Headache in cardiac cephalalgia does not present with uniform clinical characteristics. Some patients visit the outpatient clinic complaining of recurrent exertional headaches, while others are brought to the emergency room in shock or a comatose state. Cardiac symptoms may be absent and ECG may be normal, even with standard stress testing [34]. To diagnose cardiac cephalalgia, clinicians must be aware of it and also suspect its presence. Interestingly, among the 48 articles reporting cardiac cephalalgia, 28 were published in neurology journals and 17 in cardiovascular journals. This may reflect the fact that patients are usually initially seen by neurologists. Overlooked or delayed diagnosis can lead to serious consequences. First-line health care professionals should be aware of cardiac cephalalgia. When it is suspected, early collaboration with cardiologists is warranted.

Cardiac cephalalgia resulting from AMI can present with or without chest discomfort and even mimic the classic thunderclap headache associated with SAH. It should be recognized as an emergency and treated without delay.