Detection of orofacial pain of cardiac origin due to coronary artery disease: A case report and literature review

doi:10.21203/rs.3.rs-2597128/v1

Background. When diagnosing orofacial pain, clinicians should also consider non-odontogenic origin and systemic diseases as possible etiological factors, along with odontogenic origin. This case report aimed to provide information for early detection of orofacial pain of cardiac origin by dentists, when pain due to coronary artery disease is the only presenting symptom.

Case Presentation. A 60-year-old male patient with unexplained isolated bilateral jaw pain was referred to a dentist by an anesthesiologist whosuspected temporomandibular joint disorder. Oral examination and radiography of the temporomandibular joints revealed no bony abnormalities. Eventually, the patient was referred to a cardiologist for further evaluation since his pain was induced by physical activity. Coronary artery disease (CAD) was diagnosed using coronary computed tomographyangiography, and the pain was considered to be angina pectoris. Percutaneous coronary intervention was successfully done for the patient, after which his orofacial symptoms disappeared.

Conclusions. Isolated craniofacial pain of cardiac origin may lead to patients seeking dental care or visiting orofacial pain clinics. In these settings, dentists and orofacial pain specialists may contribute to the diagnosis of CAD and refer patients for cardiac evaluation and appropriate management.

Cardiac

Coronary artery disease

Jaw pain

Non-odontogenic

Orofacial pain

Percutaneous coronary intervention

Temporomandibular disorder

During the diagnosis and treatment of orofacial pain, dentists should also consider non-odontogenic etiologies, such as heart diseases, based on pain characteristics, which can be life-threatening. Medical emergencies during dental practice includes serious life-threatening events, including acute coronary syndrome (ACS), anaphylaxis, airway obstruction, and stroke. Approximately 57% of these medical emergencies are associated with ACS [1]. The estimated risk of encountering a patient death by British dentists in a 40-year career is reportedly between 1:12 and 1:19 [2]. According to the Global Burden of Disease, Risk Factors and Injuries study, age-standardized male ischemic heart disease (IHD) mortality per 100,000 individuals in the East Asia region was reported as 61, 83, and 84 in the years 1990, 2005, and 2010, respectively, (38% increase) in spite of the overall reduction in IHD mortality worldwide [3].

Coronary artery disease (CAD), also known as IHD, is defined as myocardial impairment due to an imbalance between coronary blood flow and myocardial requirements caused by changes in the coronary circulation [4]. CAD is characterized by substernal pain that may be described as squeezing, heaviness, pressure, weight, vise-like aching, burning, or tightness which radiates to the left arm, shoulder, neck, jaw, and epigastrium [5]. The pain can be precipitated by physical exercise or emotional stress and relieved by rest or nitroglycerin use. Dyspnea and fatigue may also be associated with this condition [6]. Some reports have stated that the pain may be isolated or spread to the orofacial region, especially the jaws and teeth (Table 1) [7-16]. Throat, followed by left mandible, right mandible, left temporomandibular joint (TMJ)/ear region, and teeth are the most commonly reported locations of orofacial pain radiating from heart diseases [16, 17].

Patients with orofacial pain referred from cardiac ischemia are likely to seek dental or otolaryngological treatment. Misdiagnosis or delayed diagnosis of such orofacial pain can result in a myriad of problems, ranging from unnecessary dental treatment to life-threatening situations, before receiving appropriate medical care [18]. The suspicion or diagnosis of orofacial pain of cardiac origin by dentists has been rarely reported. However, cardiac diseases can cause referred pain in the orofacial region via the vagus nerve, and if not accurately diagnosed, may result in worsening the patient's pain condition. This case report highlights a case of exertional angina that presented as isolated bilateral jaw pain without any cardiac symptoms or medical history.

Patient

A 60-year-old male patient was referred to the Orofacial Pain Clinic, Department of Oral Medicine and Oral Diagnosis, Seoul National University Dental Hospital, by an anesthesiologist at the Seoul National University Hospital for the evaluation of suspected temporomandibular disorder (TMD) for orofacial pain that had persisted for the past 5 years. The patient complained of excruciating bilateral jaw pain of 5-minute durations, which he described as feeling “like the lower jaw was about to fall out.” The intensity of pain was reported to be 10 on a visual analog scale by the patient. However, no sleep disturbances were reported. The orofacial symptoms had been present for the preceding five years, and the pain had worsened over the last two months. The pain was disturbing and exasperating to the point that on two different occasions, he sought treatment in the hospital and also consulted otolaryngology, neurology, and anesthesiology specialists. Pain was first perceived in the preauricular regions, which then radiated down to the masseter muscles. Pain was precipitated by ordinary daily activities including walking and the symptoms usually resolved at rest. However, the patient did not complain of paresthesia, numbness, local fever, or swelling in the orofacial region associated with the pain. The patient’s past medical and dental history were unremarkable. He had been a smoker for almost 30 years, was normotensive, and had a body mass index of 25.76 kg/m² (174 cm/78 kg).

Intra/extraoral examination and TMJ imaging

Intraoral examination of the patient was unremarkable. Routine laboratory blood tests, including complete blood cell and differential counts, erythrocyte sedimentation rate, showed normal results. Skull radiological examination, ultrasonography, urine tests, blood tests, and hearing tests performed at other hospitals also provided no plausible explanation for his pain. Extraoral examinations were conducted according to the Research Diagnostic Criteria/TMD (RDC/TMD). The maximum mandibular opening recoded was 42 mm. No chin deviation was observed during mouth opening. No abnormal joint noises or crepitus were elicited, and TMJ movements were normal. Occlusion check using an 8 μm thick film showed a sound occlusion. On palpating the temporalis, masseter, sternocleidomastoid, and trapezius muscles, no jaw pain was elicited. The patient reported unilateral sleeping and chin-buttressing habits during the investigation as possible contributing factors. The Symptom Check List-90-Revised was applied for psychological evaluation [19], and yielded normal results. Radiographs, including an orthopantomogram and a transcranial view, revealed no bony abnormalities (Figure 1).

Initial diagnosis and magnetic resonance imaging (MRI)

The patient was initially diagnosed nowhere within the RDC/TMD, and comprehensively treated using conservative methods like physical therapy, exercise, behavioral control, and muscle relaxants. MRI was performed at the patient’s request, which revealed no abnormal findings (Figure 2).

However, the orofacial symptoms still persisted two weeks after the MRI. The possibility of cardiac etiology was considered due to lack of local etiology of pain, and since the pain worsened with physical movement. No improvement was observed after typical physical exercise. He was then referred to the Internal Medicine and Cardiovascular Center of the Seoul National University Hospital.

Medical examination, coronary computed tomography (CT), treadmill test, and final diagnosis

Physical examination revealed a regular pulse of 74 beats per minute and blood pressure of 124/80 mmHg. The remaining physical examination results were unremarkable. Although the patient did not complain of chest pain or dyspnea on exertion, the cardiologist ordered a coronary CT angiography (CCTA) and an exercise treadmill test since the pain was induced by exercise and relieved with rest. CCTA revealed significant CAD affecting all three of his coronary vessels (Figure 3). There was 70–80% stenosis with mixed plaque at the proximal left anterior descending (LAD) artery, near total occlusion or total occlusion of the first diagonal vessel, 50–70% stenosis with mixed plaque at the proximal left circumflex artery (LCx), near total or total occlusion of the distal LCx, 50–70% stenosis at the proximal right coronary artery (RCA), and near total occlusion of the RCA. The exercise treadmill test results were also positive, and the patient was classified as high risk according to the Duke treadmill score.

Further questioning revealed a positive family history of vascular heart disease. Stable angina, also known as angina pectoris was diagnosed. The patient was admitted, and coronary angiography was performed. There was 70% tubular stenosis at the proximal LAD, near total occlusion at the first diagonal branch and 50% diffused stenosis at the proximal LCx. Moreover, a total occlusion of the distal LCx with Thrombolysis in Myocardial Infarction III flow collaterals from other coronary vessels was observed along with 50% tubular stenosis at the proximal RCA, 70% tubular stenosis, and focal 90% stenosis at the mid-RCA. To evaluate the functional significance of the lesions, fractional flow reserve (FFR) measurements were performed at the LAD and RCA. FFR were 0.75 and 0.62 when hyperemia was induced by adenosine infusion at LAD and RCA, respectively.

Surgical treatment and prognosis

The benefits of percutaneous coronary intervention (PCI) as an initial treatment strategy in patients with stable CAD remains controversial [20, 21].FFR-guided PCI have been reported to improve the outcomes compared to medical therapy alone in patients with stable CAD [22]. PCI was performed and 3 × 32 mm² and 3 × 26 mm² drug eluting coronary stents were placed at the proximal LAD lesion and mid-RCA lesion, respectively. The procedure was performed successfully, after which all the orofacial symptoms disappeared, confirming that they were caused by CAD.

Unlike previous case reports, this study highlights bilateral jaw pain induced by significant CAD, which was resolved after PCI. Pain of cardiac origin is pressure-like and burning in nature, while odontogenic pain is described as pulsatile and sharp, with no sex differences. Bilateral referral pattern of cardiac origin has been reported six times more frequently than unilateral complaint in craniofacial lesions has [23].

Orofacial pain of cardiac origin is considered to result from afferent fibers of the vagus nerve that transmit nociceptive stimuli to the cervical neuron cells [24, 25]. In animal studies, noxious electrical and chemical stimulation of cardiac branches of the left vagus nerve reportedly cause the activation of the left spinothalamic tract cells at the level of the trigeminothalamic tract [26, 27][20]. Based on extensive documentation, both somatic and visceral synapses to the same second-order sensory neurons are found in the outer layers of the dorsal horn [28, 29]. Connections between thoracic and cervical dermatomes (from C2 to T1 roots), and between the cervical dermatomes and the trigeminal nerve are purportedly the cause of referred jaw pain of cardiac origin [30, 31].

Ischemia induces anaerobic metabolism and triggers inflammation, leading to the release of cellular substances such as bradykinin, lactate, proton production (H+), adenosine, and substance P [32, 33]. It is believed that one of these substances activates and/or sensitizes the spinal and vagal cardiac afferents, ultimately leading to the sensation of angina and pain referred to the somatic areas [30]. Animal studies using rat models have revealed that ischemia may directly sensitize the afferent nociceptors via a subcategory of capsaicin receptors, the transient potential vanilloid 1 [34].

An uneven distribution of vagal and sympathetic afferent fibers has been observed in different regions of the heart, with a greater concentration of vagal afferent fibers terminating in the inferior-posterior wall of the left ventricle [35, 36]. Experimental evidence from animal studies suggests that the activation of vagal afferent fibers most likely occurs when myocardial ischemia involves the inferior-posterior regions of the left ventricle [37].However, these proposed mechanisms of referred cardiac pain are insufficient to explain the clinical findings of the present case.

Chest pain or discomfort, whether typical or atypical, is one of the most disconcerting symptoms due to its association with potentially critical heart disease and the risk of death. Ironically, the absence of chest pain is considered a main predisposing factor for delayed or missed diagnoses in acute myocardial infarction [38]. Orofacial pain is reported either independently (6%) or in conjunction with other types of pain (30%) [17]. However, this prospective case study had some limitations. First, the patient was not questioned about his medical history in terms of typical angina symptoms, including pain provoked by exercise. Second, other associated symptoms, such as dyspnea, diaphoresis, fatigue, and vomiting, were not reported and might not have been assessed. Third, patients biased towards anatomic description of pain might have been involved using a diagram [39].

A thorough medical and family history, including relevant symptoms, is crucial in diagnosing craniofacial pain of cardiac origin [40]]. Several epidemiologic studies have demonstrated a link between certain risk factors and cardiovascular disease. Causally linked risk factors include tobacco consumption, elevated low-density cholesterol, low high-density cholesterol, high blood pressure, elevated glucose levels, physical inactivity, obesity, and diet. Risk markers that have shown an association are low socioeconomic status, elevated prothrombotic factors (fibrinogen, plasminogen activator inhibitor 1), markers of infection or inflammation, elevated homocysteine levels, elevated lipoproteins, psychological factors (depression, anger proneness, hostility, stress, acute life events), and breakdown in social status (loss of social support and cohesion) [41]. Age, sex, diabetes, hypertension, dyslipidemia, family history of CAD, current smoking status, and symptom type can be easily elicited with careful history taking. In this case report, a full family history that included the history of CAD was identified at the second visit.

Turner et al. recommend that if the signs, symptoms, and investigations of facial pain do not provide a diagnosis, rare causes of facial pain should be considered, such as cardiac ischemia, before diagnosing it as atypical facial pain [9]. It seems plausible that craniofacial pain of cardiac origin is usually accompanied by other symptoms or by a suggestive history such as pain provoked by exercise. The importance of thoroughly assessing a patient’s medical history and physical status cannot be overemphasized in the diagnostic process for orofacial pain due to cardiac ischemia. Furthermore, it is necessary to conduct broader studies with a larger sample of patients to determine the characteristics of craniofacial pain of cardiac origin, to avoid unnecessary dental treatments such as tooth extractions and non-indicated temporomandibular dysfunction therapies, and to not delay the correct diagnosis of heart disease.

In conclusion, craniofacial pain of cardiac origin may lead to patients seeking dental care. Pain provoked by physical exercise is crucial for the diagnosis, with a thorough medical history for identifying potential differential diagnoses. In these settings, dentists may contribute to the diagnosis of CAD-related orofacial pain and refer patients for cardiovascular evaluation.

TMJ- Temporomandibular joint

CAD- Coronary artery disease

CCTA- Coronary computed tomography angiography

PCI- Percutaneous Coronary Intervention

ACS- Acute coronary syndrome

IHD- Ischemic heart disease

TMD- Temporomandibular disorder

RDC/TMD- Research Diagnostic Criteria for Temporomandibular Disorders

MRI- Magnetic resonance imaging

CT- Computed tomography

LAD- Left anterior descending artery

LCx- Left circumflex artery

RCA- Right coronary artery

FFR- Fractional flow reserve

Ethics approval and consent to participate

This study was approved by the Institutional Review Board of Seoul National University Dental School, South Korea (S-D20150026).

Consent for publication

Written consent was obtained from the patient.

Availability of data and materials

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Funding

This work was supported by the Korea Medical Device Development Fund funded by the Korean government (the Ministry of Science and ICT, Ministry of Trade, Industry and Energy, Ministry of Health & Welfare, and Ministry of Food and Drug Safety, Republic of Korea) under project number KMDF_PR_20200901_0023, 9991006696, National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (no. NRF-2020R1F1A1070072), and Kyung Hee University in 2021 (no. KHU20211863).

Author’s contributions

Conceived and designed the study; Eunhye Choi, Collected the data; Yeon-Hee Lee, Prepared data or figures; Eunhye Choi and Yeon-Hee Lee, Prepared table; Eunhye Choi, and Wrote the paper; Eunhye Choi and Yeon-Hee Lee, Revised manuscript; Eunhye Choi and Yeon-Hee Lee.

Acknowledgement

None.

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Table 1. Summary of previous case reports
*Case number* [Ref], Year	*Age/Sex*	*Craniofacial pain location (radiation)*	*Other pain symptoms* *(radiation)*	*Precipitating factors*	*Associated symptom*	*Medical history,* *family history*	*Cardiac treatment*	*Final diagnosis*
1[7], 1963	62/F	Bilateral Mn, neck, zygoma, temporal area)	None	Unknown	Vomit, syncope	HTN	Death of arteriosclerotic heart disease	MI
2 [8], 1981	67/M	Bilateral Mn	None	(+): walking back to work after lunch	Unknown	Unknown	Propranolol, nitrates	AP
3 [8], 1981	56/F	Bilateral anterior Mx, infraorbital	Neck, shoulder pain	No association with exertion	Dyspnea, orthopnea	Mild scleroderma	Aortocoronary bypass	AP, MI
4[8], 1981	79/M	Bilateral Mn	Chest pain	(-): isosorbide dinitrate	Unknown	Unknown	Unknown	MI
5^[42], 1998	56/M	Teeth, Mn	None	(-): sublingual nitroglycerine	Unknown	Spinal cord injury	CABG	AP
6^[24], 2008	63/F	Left teeth	None	Unknown	Unknown	Grave’s disease, chronic depression	Unknown	Referred pain from vagus nerve
7^[43], 2011	48/M	Bilateral TMJ pain	None	Unknown	Unknown	Car accident	CABG	AP
8^[9], 2013	59/F	All teeth, bilateral Mn, Mx	None	(+): walking, (-): rest	Nausea	RA, OA, discoid lupus, HTN, IHD family history	Isosorbide mononitrate, statin	AP
9^[10], 1970	72/F	Right Mn	Chest pain on exertion	(+): effort or stress (-): rest and vasodilator	Unknown	Unknown	Unknown	AP
10^[11], 1975	32/M	Left Mx posterior teeth	Chest pain (shoulder, back pain)	(+): physical activities (-): Nitroglycerine	Unknown	None	CABG	AP, MI
11^[12], 2005	50/F	Bilateral Mn, Mx, Left temporal area	Chest pain (neck, arm pain)	(+): exercise emotion (-): relax	Unknown	DM, CABG	Unknown	AP
12^[13], 2006	65/F	Bilateral zygoma, (Mn and left temporal region)	Chest pain, arm pain (neck pain)	(+): mandibular movement, walking, climbing stairs	Nausea, diaphoresis, vomiting	Thyroidectomy, MI	Propranolol, isosorbide dinitrate, aspirin	MI, AP
13^[14], 2006	61/F	Bilateral Mx, Mn(eye)	Chest pain	Unknown	Unknown	DM, HTN, smoking hypothyroidism	Stent in left coronary artery	AP
14 [44], 2010	80/M	The area of dental extraction (forehead and neck)	Chest pain	(+): walking	Unknown	DM, HTN	Angioplasty of the circumflex artery with implantation of a sirolimus eluting stent	AP
15^[16], 2012	54/M	Third quadrant including teeth	Chest, neck, and shoulder pain	Unknown	Unknown	NSAIDs (neck and back pain), HTN, type II DM, smoking (15 cigarettes/day), moderate drinker	Medication	Unstable Angina
16 [16], 2012	79/M	Left Mn	Left arm	Unknown	Unknown	Type II DM, left knee prosthesis,	Unknown	IHD

Mn, mandible; Mx, maxilla; HTN, hypertension; DM, diabetes mellitus; RA, rheumatoid arthritis; OA, osteoarthritis; MI, myocardial infarction; AP, angina pectoralis; IHD, ischemic heart disease; Ref, reference; CABG, coronary artery bypass graft; (+), aggravating factor; (-), relieving factor.

No competing interests reported.

Detection of orofacial pain of cardiac origin due to coronary artery disease: A case report and literature review

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Abstract

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Background

Case Presentation

Discussion And Conclusions

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