Introduction / Hypothesis
Identify the etiology of vasospastic angina. Investigate the mechanism and incidence of chemotherapy on coronary vasospasm. Assess the incidence, risk factors, and prognostic implications of 5-FU coronary vasospasm among patients receiving 5-FU regimens.

Patient is a 61 y.o. Caucasian female with known diagnosis of adenocarcinoma of the rectum stage III and hypothyroidism. Patient was admitted for chemotherapy with CAPOX when she developed acute onset of substernal chest pain while undergoing chemotherapy. Cardiology was consulted for evaluation. Patient reports developing acute onset of substernal squeezing chest pain following chemo infusion with capecitabine and 5-fluorouracil. She described her symptoms as substernal chest pressure radiating to left arm. Severity an 8/10 in severity. Associated shortness of breath. Non-exertional. Symptoms occurred at rest. No aggravating or alleviating factors. Patient had never had chest pain like this before. Patient was given a full dose aspirin 324 mg x 1 and sublingual nitroglycerin. Following the sublingual nitroglycerin her chest pain resolved. Patient has no prior cardiac history. Denies prior MI, CAD, stents, CABG, CVA, hypertension, hyperlipidemia or diabetes mellitus. Former tobacco use for 7 years prior, quit many years ago. Family hx MI and CAD, Father in 60s. Medications at time of admission were ibuprofen and levothyroxine.

Vital signs stable with BP 103/58, HR 76 bpm, oxygen 91% on 4L NC, and afebrile temp 36.3. Labs notable for hgb 13.2, plt 251, wbc 10.4, neutrophils 7.54, Na+ 139, K 4.2, BUN 18.6, Cr 0.64, normal LFTs, Mg 2.4. Troponin T 27, 30, 10 (normal < 10). LDL elevated at 144. EKG showed normal sinus rhythm with hyperacute T waves in precordial leads. CXR no cardiopulmonary abnormality. A coronary CTA was ordered which showed normal coronaries, no evidence of plaque or stenosis. CAD RADS 0. An echocardiogram was performed revealing left ventricular ejection fraction 55%, no regional wall motion abnormalities. Borderline strain at -17%. No hemodynamically significant valvular heart disease.

Methods
Clinical presentation is suggestive of coronary vasospasm angina associated with capecitabine. Disaccharidase affect is usually observed during initial phase of treatment. Patient was started on amlodipine 5 mg daily and crestor 10 mg QHS. Recommendation was for patient to take sublingual nitroglycerin as needed for recurrent chest pain. Patient continued to follow with outpatient oncology and cardiology team.

Results
Patient followed with her oncologist and recommendation was to rechallenge with 5-Fluorouracil in the inpatient setting. Patient was re-admitted to undergo monitoring with 5-fluororuracil infusion. This was further complicated by severe 8/10 chest pain described as a tightness radiating to left arm during infusion. Associated nausea. She was given sublingual nitroglycerin with relief of symptoms. An extra dose of amlodipine 5 mg was given. Vital signs were stable. TnT 6, 11, 14. EKG showed normal sinus rhythm HR 81 bpm, nonspecific ST/T changes. 5-FU infusion was ultimately discontinued. A repeat limited echo was performed which showed no significant change compared to prior. EF 55%, no hemodynamically significant valvular disease. Ultimately both chemotherapeutic agents were discontinued in the setting of severe coronary vasospasm.

Conclusion
Capecitabine is an oral prodrug of 5-fluorouracil (5-FU) which is approved for early-stage and advanced colorectal cancer. Cardiotoxocity is common and multiple cases of coronary vasospasm have been reported. The mechanism of coronary vasospasm is thought to be a result of endothelial dysfunction caused by 5-Fluorouracil and its active metabolites. According to a publication in JACC Cardio Oncology in 2021, approximately 4,019 individual patients who received 5-FU from 2009 to 2019 at a single center, 87 (2.16%) developed vasospasm. Patients who developed vasospasm were younger (age 58 +/- 13 years vs. 64 +/- 13 years; p = 0.001) and were less likely to have any cardiovascular risk factors (70.1 percent vs. 84.5 percent; p = 0.007). Patients with vasospasm and patients without vasospasm were otherwise similar in terms of types of cancer, stage of cancer, sex, and race. There was no significant difference in progression-free survival, overall mortality or cancer specific mortality between patients who developed vasospasm versus those who did not. Additional proposed mechanisms underlying cardiotoxicity induced by 5-fluorouracil (5-FU) includes vascular endothelial damage followed by thrombus formation, ischemia secondary to coronary artery vasospasm, direct toxicity on myocardium and thrombogenicity. In patients with angina and electrocardiographic evidence of myocardial ischemia due to chemotherapy-related coronary artery vasospasm, termination of chemotherapy and administration of calcium channel blockers or nitrates can improve ischemic symptoms. As depicted in this clinical case, coronary artery vasospasm can reoccur with 5-FU re-administration with limited effectiveness of vasodilator prophylaxis observed.

**Introduction / Hypothesis**
Identify the etiology of vasospastic angina. Investigate the mechanism and incidence of chemotherapy on coronary vasospasm. Assess the incidence, risk factors, and prognostic implications of 5-FU coronary vasospasm among patients receiving 5-FU regimens.

Patient is a 61 y.o. Caucasian female with known diagnosis of adenocarcinoma of the rectum stage III and hypothyroidism. Patient was admitted for chemotherapy with CAPOX when she developed acute onset of substernal chest pain while undergoing chemotherapy. Cardiology was consulted for evaluation. Patient reports developing acute onset of substernal squeezing chest pain following chemo infusion with capecitabine and 5-fluorouracil. She described her symptoms as substernal chest pressure radiating to left arm. Severity an 8/10 in severity. Associated shortness of breath. Non-exertional. Symptoms occurred at rest. No aggravating or alleviating factors. Patient had never had chest pain like this before. Patient was given a full dose aspirin 324 mg x 1 and sublingual nitroglycerin. Following the sublingual nitroglycerin her chest pain resolved. Patient has no prior cardiac history. Denies prior MI, CAD, stents, CABG, CVA, hypertension, hyperlipidemia or diabetes mellitus. Former tobacco use for 7 years prior, quit many years ago. Family hx MI and CAD, Father in 60s. Medications at time of admission were ibuprofen and levothyroxine.

Vital signs stable with BP 103/58, HR 76 bpm, oxygen 91% on 4L NC, and afebrile temp 36.3. Labs notable for hgb 13.2, plt 251, wbc 10.4, neutrophils 7.54, Na+ 139, K 4.2, BUN 18.6, Cr 0.64, normal LFTs, Mg 2.4. Troponin T 27, 30, 10 (normal < 10). LDL elevated at 144. EKG showed normal sinus rhythm with hyperacute T waves in precordial leads. CXR no cardiopulmonary abnormality. A coronary CTA was ordered which showed normal coronaries, no evidence of plaque or stenosis. CAD RADS 0. An echocardiogram was performed revealing left ventricular ejection fraction 55%, no regional wall motion abnormalities. Borderline strain at -17%. No hemodynamically significant valvular heart disease.

**Methods**
Clinical presentation is suggestive of coronary vasospasm angina associated with capecitabine. Disaccharidase affect is usually observed during initial phase of treatment. Patient was started on amlodipine 5 mg daily and crestor 10 mg QHS. Recommendation was for patient to take sublingual nitroglycerin as needed for recurrent chest pain. Patient continued to follow with outpatient oncology and cardiology team.

**Results**
Patient followed with her oncologist and recommendation was to rechallenge with 5-Fluorouracil in the inpatient setting. Patient was re-admitted to undergo monitoring with 5-fluororuracil infusion. This was further complicated by severe 8/10 chest pain described as a tightness radiating to left arm during infusion. Associated nausea. She was given sublingual nitroglycerin with relief of symptoms. An extra dose of amlodipine 5 mg was given. Vital signs were stable. TnT 6, 11, 14. EKG showed normal sinus rhythm HR 81 bpm, nonspecific ST/T changes. 5-FU infusion was ultimately discontinued. A repeat limited echo was performed which showed no significant change compared to prior. EF 55%, no hemodynamically significant valvular disease. Ultimately both chemotherapeutic agents were discontinued in the setting of severe coronary vasospasm.

**Conclusion**
Capecitabine is an oral prodrug of 5-fluorouracil (5-FU) which is approved for early-stage and advanced colorectal cancer. Cardiotoxocity is common and multiple cases of coronary vasospasm have been reported. The mechanism of coronary vasospasm is thought to be a result of endothelial dysfunction caused by 5-Fluorouracil and its active metabolites. According to a publication in JACC Cardio Oncology in 2021, approximately 4,019 individual patients who received 5-FU from 2009 to 2019 at a single center, 87 (2.16%) developed vasospasm. Patients who developed vasospasm were younger (age 58 +/- 13 years vs. 64 +/- 13 years; p = 0.001) and were less likely to have any cardiovascular risk factors (70.1 percent vs. 84.5 percent; p = 0.007). Patients with vasospasm and patients without vasospasm were otherwise similar in terms of types of cancer, stage of cancer, sex, and race. There was no significant difference in progression-free survival, overall mortality or cancer specific mortality between patients who developed vasospasm versus those who did not. Additional proposed mechanisms underlying cardiotoxicity induced by 5-fluorouracil (5-FU) includes vascular endothelial damage followed by thrombus formation, ischemia secondary to coronary artery vasospasm, direct toxicity on myocardium and thrombogenicity. In patients with angina and electrocardiographic evidence of myocardial ischemia due to chemotherapy-related coronary artery vasospasm, termination of chemotherapy and administration of calcium channel blockers or nitrates can improve ischemic symptoms. As depicted in this clinical case, coronary artery vasospasm can reoccur with 5-FU re-administration with limited effectiveness of vasodilator prophylaxis observed.

Chemotherapy induced chest pain ? ACS vs Vasospasm