Unexplained Chest Pain in a Patient with Recurrent Hospital Visits – Coronary Artery Disease Complicated by Anxiety and Depression

To the Editor: Currently, a large number of patients in China suffer from both anxiety and depression alongside cardiovascular diseases, and this number continues to rise. However, due to misdiagnosis and inaccurate identification, the majority of patients endure long-term pain and discomfort, frequently seeking medical attention.[1] In some cases, clinical symptoms persist or even worsen despite appropriate treatment for coronary artery lesions. Only about 15% of patients receive an accurate diagnosis, and even fewer undergo effective treatment. This case report presents a patient with chronic anxiety and depression syndrome and coronary artery disease (CAD) who experienced recurrent symptoms of chest pain and tightness. Despite multiple cardiovascular evaluations and interventions, including guideline-directed pharmacotherapy and drug-coated balloon (DCB) angioplasty, her symptoms failed to improve and gradually worsened. Eventually, she was referred to a psychocardiology unit, where she received an integrated therapeutic regimen, including optimized psychopharmacologic therapy, percutaneous coronary intervention (PCI), and cognitive-behavioral therapy (CBT), resulting in notable clinical improvement. Informed consent was obtained from the patient. The patient, a 55-year-old female, was admitted on September 14, 2024, due to “recurrent chest pain and tightness for 30 years, with exacerbation for half a month” She had experienced repeated episodes of chest pain and tightness, and dyspnea for 30 years, often accompanied by panic attacks. These symptoms were gradually relieved after a few minutes of rest. She frequently visited the cardiology department, but all physical examinations were normal, and she was prescribed oral lipid-lowering medication. 5 years ago, when her symptoms recurred, she underwent resting and pharmacological stress myocardial perfusion single-photon emission computed tomography imaging at a local hospital, which revealed negative findings. She was referred for psychiatric evaluation and subsequently diagnosed with “moderate depression with anxiety.” Treatment with paroxetine and escitalopram provided partial symptom relief, but the symptoms persisted with intermittent recurrence. Three years ago, the patient developed chest and back pain during household activities. Coronary angiography performed at a local hospital revealed “severe stenosis in the proximal to mid-segment of the left anterior descending (LAD) artery.” She underwent PCI with DCB angioplasty of the LAD. After discharge, she adhered to secondary preventive medication for CAD. However, her symptoms did not improve and instead worsened. Over the next 3 years, she sought care at multiple tertiary hospitals, yet no significant clinical improvement was achieved. 1 year ago, coronary CT angiography revealed “mild luminal stenosis in the proximal to mid-segment of the LAD.” The Deep Vessel Fractional Flow Reserve (DVFFR; lesions with DVFFR ≤ 0.80 may induce myocardial ischemia) values were: LAD 0.82, left circumflex artery (LCX) 0.85, and right coronary artery (RCA) 0.87, leading to no further treatment. Two weeks before admission, the patient experienced aggravated chest pain and tightness, accompanied by abdominal discomfort and dizziness. Symptoms were partially relieved by rest or slow walking for several minutes. For the past 30 years, she had suffered from poor sleep, frequent nightmares, and nocturnal awakenings. PAST MEDICAL HISTORY The patient had a total hysterectomy for endometrial hyperplasia at 39. She had hyperlipidemia for 15 years and moderate depression for 5 years, intermittently treated with paroxetine and escitalopram. 2 weeks ago, she developed a generalized rash and pruritus, diagnosed as eczema. Both parents had CAD, with no known genetic disorders in the family. PHYSICAL EXAMINATION ON ADMISSION On admission, vitals were temperature 36.3°C, pulse 60 beats per min (bpm), respiratory rate 13 breaths per min, and blood pressure 103/61 mmHg (1 mmHg = 0.133 kPa). Skin examination showed scattered papules, maculopapular eruptions, excoriations, and crusts on the trunk and limbs. The lungs were clear bilaterally, with no crackles, wheezes, or pleural friction rubs. The heart had a regular 60 bpm rhythm, with no murmurs or pericardial friction rubs. LABORATORY AND IMAGING FINDINGS Alanine aminotransferase was 111 U/L, and aspartate aminotransferase was 77 U/L. Serum creatinine was 88.4 mmol/L, and the estimated glomerular filtration rate (eGFR) was 63.3 mL/min/1.73 m2. The lipid profile showed triglycerides at 1.83 mmol/L and low-density lipoprotein cholesterol (LDL-C) at 0.4 mmol/L. Electrocardiography showed sinus rhythm (59 bpm) with normal ST segments and T waves. Echocardiography revealed no structural or functional abnormalities. Abdominal ultrasound detected moderate liver steatosis and multiple gallbladder polyps. Other parameters were unremarkable. PSYCHOMETRIC ASSESSMENT ON ADMISSION The Patient Health Questionnaire-9 (PHQ-9)[2] score was 17, indicating moderate-to-severe depression. The Generalized Anxiety Disorder-7 (GAD-7)[3] score was 14, suggesting moderate-to-severe anxiety. The Athens Insomnia Scale (AIS)[4] score was 8, indicating insomnia. DIAGNOSIS AND TREATMENT The patient was diagnosed with CAD, anxiety, and depression. She was prescribed aspirin 100 mg/day, clopidogrel 75 mg/day, and isosorbide mononitrate 20 mg twice daily for CAD. Psychotropic therapy included escitalopram 15 mg/day and olanzapine 5 mg/day. Additional medications included estazolam and g-oryzanol for sleep support, mecobalamin for neuroprotection, and folic acid 5 mg/day. For eczema, loratadine, cetirizine, and topical mometasone furoate were prescribed. CBT was initiated for maladaptive illness perceptions and emotional responses. After 1 week of treatment, the patient’s symptoms showed improvement; however, intermittent episodes of chest pain and tightness persisted. A complete preoperative evaluation and coronary angiography performed on September 21, 2024, revealed 95% stenosis in the proximal to mid-segment of the LAD. Two drug-eluting stents were implanted in tandem, successfully relieving the coronary stenosis. Following the intervention, the patient experienced marked resolution of chest pain, tightness, and pruritus and was discharged on September 23, 2024. A psychometric reassessment at discharge showed a PHQ-9 score of 3 (remission) and a GAD-7 score of 1 (no anxiety). After discharge, daily patient education materials were provided to reinforce an accurate perception of the illness. The patient was advised to regulate emotions through exercise, music therapy, and meditation to promote healthy lifestyle habits. At the 3-month telephone follow-up, psychometric scores were PHQ-9: 11, GAD-7: 7, and AIS: 8. Although residual symptoms persisted, their frequency and severity had significantly decreased compared to baseline. A single transient episode of a panic attack occurred shortly after discharge but resolved spontaneously. The patient reported that these symptoms “no longer caused substantial distress.” This patient had a 30-year medical history and had repeatedly presented to the cardiovascular department with chest pain and tightness as the chief complaints. However, due to the lack of effective interventions, the symptoms recurred, causing significant distress. For years, other patients with similar symptoms, such as chest tightness and pain, have sought help in cardiology departments, but many internists lack the tools and expertise for accurate diagnosis and treatment and primarily focus on diagnosing CAD through diagnostic tests, often overlooking the patients’ psychological state. Therefore, when cardiovascular examination results are negative, no further diagnosis or treatment is pursued, even if the patients continue to experience chest pain and tightness. Although the patient was diagnosed with anxiety and depression five years ago and prescribed psychotropic medications that offered partial symptomatic relief, a lack of adequate understanding of the illness resulted in poor medication adherence and irregular follow-up visits. As a result, long-term therapeutic outcomes remained suboptimal. For such patients, regular post-discharge follow-up, ongoing management, and structured patient education are essential. This approach not only allows for timely adjustments to the medication regimen but also incorporates cost-effective strategies, such as health education, to help patients gain a clearer understanding of their condition, cultivate healthy lifestyle habits, and reintegrate into daily life and society. This model exemplifies a comprehensive continuum of care that integrates treatment and rehabilitation. In our psychocardiology clinic, we address organic heart diseases as well as the psychological and emotional well-being of patients. Typically, the “three-question method” is used to quickly assess recent sleep patterns, emotional state, and interests or hobbies, allowing for a rapid screening of potential comorbid anxiety and depression. Subsequently, standardized scales such as the PHQ-9, GAD-7, and AIS were used to objectively assess the patient’s levels of anxiety, depression, and insomnia. For patients with CAD who also experience anxiety and depression, we address both the cardiovascular pathology and the associated psychological comorbidities. Briefly, in addition to treating CAD through coronary interventions and secondary prevention medications, we prescribe psychiatric medications and CBT to alleviate psychological symptoms. Moreover, after hospital discharge, we continue close follow-up and management, provide health education on disease awareness, monitor changes in the patient’s condition, and adjust medications as needed to achieve optimal treatment outcomes and prognosis.[1] Compared with traditional cardiovascular risk factors, depression and anxiety have stronger independent associations with cardiovascular disease.[5,6] As a chronic psychophysiological stressor, anxiety and depression can trigger a multilevel pathological cascade, including autonomic nervous system dysfunction, hypothalamic–pituitary–adrenal axis imbalance, and chronic inflammation. These mechanisms synergistically drive endothelial damage, endothelial lipid accumulation, and oxidative modification of LDL particles, thereby accelerating the development of cardiovascular disease.[5] Emerging evidence shows that three inflammatory mediators, including C-reactive protein (CRP), interleukin 6 (IL-6), and (IL-1b), are central coordinators of this pathophysiological cascade, mediating endothelial leukocyte adhesion, plaque vulnerability, and thrombotic tendency through cytokine-driven epigenetic reprogramming.[7,8] Although the patient had established cardiovascular risk factors, the progression of anxiety and depression syndrome became a key factor in accelerating coronary atherosclerosis. It is worth noting that the aggravation of paradoxical symptoms after PCI 3 years ago may be related to stress after PCI in terms of mechanism.[9] The patient’s coronary artery lesions have progressed rapidly in the past 3 years, and the aggravation of anxiety and depression has played a key role. Long-term anxiety and depression not only significantly increase the risk of cardiovascular disease but also have a poor prognosis and even a high risk of death.[10,11] Meanwhile, prolonged untreated anxiety and depression may lead to complications such as inflammatory skin conditions (e.g., eczema), thereby increasing disease complexity and treatment difficulty.[12] Therefore, for patients with cardiovascular disease, clinicians should not only pay attention to the control of organic lesions and traditional risk factors but also actively screen for complications. For patients with CAD diagnosed with anxiety and depression, prompt initiation of comprehensive treatment, including CBT and evidence-based psychotropic medication, is essential to reduce the recurrence of cardiovascular events and all-cause mortality.[13,14] Clinicians should note that some selective serotonin reuptake inhibitors, such as citalopram and serotonin–norepinephrine reuptake inhibitors, including duloxetine, may induce QT prolongation and ventricular arrhythmias, especially in the setting of acute myocardial infarction, requiring a judicious risk–benefit assessment.[1] When using certain cardiovascular medications, such as calcium channel blockers and diuretics, clinicians should be aware that they may increase the risk of anxiety and depression.[15] Anxiety and depression contribute to the onset and progression of cardiovascular diseases through multiple pathways. Without timely and effective intervention, these conditions lead to comorbidities and increased disease complexity. Therefore, for patients presenting with symptoms such as chest pain and tightness, psychological assessments should be promptly conducted. If anxiety or depression is detected, dual-heart therapy should be initiated immediately to reduce cardiovascular risk, improve clinical symptoms and subjective experiences, and ultimately lower medical visits and healthcare costs. Although the relationship between CAD and anxiety and depression is increasingly recognized, clinical practice still faces challenges, including misdiagnosis and the lack of standardized diagnostic and treatment guidelines. To address these shortcomings, routine psychological, cognitive, and sleep assessments should be established. Active follow-ups should be conducted to develop a full-cycle medical service model. In addition, strengthening basic research on the underlying mechanisms of anxiety and depression in cardiovascular diseases will provide more evidence-based tools for clinical practice. Author contributions All authors have significantly contributed toward the concept, design, definition of intellectual content, literature search, clinical studies, experimental studies, data acquisition, data analysis, statistical analysis, manuscript preparation, manuscript editing, and manuscript review. All authors have given final approval for the current version to be published. Ethical statement This study was conducted per the ethical principles of the Declaration of Helsinki. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her names and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed. Data availability statement All data generated or analyzed during this study are included in this published article. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest