Profound Coronary Vasospasm Associated with Intraoperative Ketamine Administration: A Case Report.

We report a case of a 62-year-old woman with a decade-long history of atypical chest pain resulting in a largely negative cardiac workup, who developed significant angiographically demonstrated coronary vasospasm thought to be due to a small dose of intravenous ketamine. In patients with a history of atypical chest pain despite a reassuring cardiac evaluation, providers should carefully consider medications that may precipitate coronary vasospasm and be prepared to treat it accordingly.

Relation of Vasoreactivity in the Left and Right Coronary Arteries During Acetylcholine Spasm Provocation Testing.

The diagnosis of vasospastic angina (VSA) according to Japanese guidelines involves an initial intracoronary acetylcholine (ACh) provocation test in the left coronary artery (LCA) followed by testing in the right coronary artery (RCA). However, global variations in test protocols often lead to the omission of ACh provocation in the RCA, potentially resulting in the underdiagnosis of VSA. This study assessed the validity of the LCA-only ACh provocation approach for the VSA diagnosis and whether vasoreactivity in the LCA aids in determining further provocation in the RCA. A total of 273 patients who underwent sequential intracoronary ACh provocation testing in the LCA and RCA were included. Patients with a positive ACh provocation test in the LCA were excluded. Relations between vasoreactivity in the LCA and ACh test outcomes (positivity and adverse events) in the RCA were evaluated. In patients with negative ACh test results in the LCA, subsequent ACh testing was positive in the RCA in 23 of 273 (8.4%) patients. In patients with minimal LCA vasoconstriction (<25%), only 3.0% had a positive ACh test in the RCA, whereas the ACh test in the RCA was positive in 13.5% of those with LCA constriction of 25% to 90% (p = 0.002). No major adverse events occurred during ACh testing in the RCA. In conclusion, for the VSA diagnosis, the omission of ACh provocation in the RCA may be clinically acceptable, particularly when vasoconstriction induced by ACh injection was minimal in the LCA. Further studies are needed to define ACh provocation protocols worldwide.

Ponatinib-Related Vasospastic Angina.

Tyrosine kinase inhibitors (TKIs) are essential drugs for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Cardiovascular or arteriothrombotic adverse events have been reported in patients treated with TKIs. We report 3 cases of Ponatinib-related vasospastic angina, in which prophylactic administration of nitrates or calcium channel blockers was effective.

Safety and potential usefulness of sequential intracoronary acetylcholine and ergonovine administration for spasm provocation testing.

BACKGROUND: Although guidelines recommend intracoronary acetylcholine (ACh) and ergonovine (ER) provocation testing for diagnosis of vasospastic angina, the feasibility and safety of sequential (combined) use of both pharmacological agents during the same catheterization session remain unclear. OBJECTIVES: In this study, we investigated the feasibility and safety of sequential intracoronary ACh and ER administration for coronary spasm provocation testing. METHODS: The study included 235 patients who showed positive results on ACh and ER provocation testing. Initial intracoronary ACh administration was followed by ER administration for left coronary artery (LCA) spasm provocation testing. Subsequently, the right coronary artery (RCA) was subjected to sequential ACh and ER administration for provocation testing. The primary outcome of the study was the safety of sequential intracoronary ACh and ER provocation testing, which was assessed based on a composite of all-cause death, sustained ventricular tachycardia and fibrillation, and cardiogenic shock. RESULTS: Even in patients with negative results on sequential intracoronary ACh and ER provocation testing in the LCA and only ACh administration into the RCA, additional administration of ER into the RCA showed a positive provocation test result in 33 of 235 (14.0%) patients; three (1.3%) patients developed adverse effects (cardiogenic shock occurred in all cases) during LCA provocation testing. We observed no deaths attributable to spasm provocation testing. CONCLUSION: Sequential administration of intracoronary ACh and ER was associated with a relatively low major complication rate and may be safe and potentially useful for diagnosis of vasospastic angina.

Safety and potential usefulness of novel coronary spasm provocation testing protocolCoronary spasm represents a subtype of ischemic heart disease, potentially leading to heart attack. Although guidelines recommend intracoronary administration of different pharmacological agents, acetylcholine (ACh) and ergonovine (ER), for coronary spasm provocation testing, the feasibility and safety of sequential (combined) use of both drugs are unclear. In the present study, we showed that sequential administration of intracoronary ACh and ER was associated with a relatively low major complication rate and may be safe and potentially useful for diagnosis of coronary vasospasm.

Atherosclerosis Vindicated: A Case of Chest Pain Due to Capecitabine-Induced Coronary Artery Spasm.

BACKGROUND Capecitabine and other 5-fluorouracil prodrugs are medications widely employed in treating solid tumors, including breast and colorectal cancer. However, they carry a notable risk for cardiotoxicity, including coronary vasospasm, possibly related to their impact on vascular endothelium and smooth muscle. CASE REPORT We present a case of a 45-year-old male with a pancreatic neuroendocrine tumor who developed exertional chest pain after starting capecitabine. Initial evaluations in the emergency department, including a 12-lead electrocardiogram and cardiac enzymes, were normal, but suspicion for coronary vasospasm persisted due to the temporal relationship with drug initiation and symptom characteristics. A graded exercise test reproduced his symptoms, accompanied by hyperacute peaked T waves and subsequent ST segment elevations in the inferior leads. Coronary angiography revealed patent coronary arteries, rendering provocative testing unnecessary due to a high clinical suspicion of capecitabine-induced vasospasm. Discontinuing the patient's medication was a more efficient approach than continuing additional cardiac workup while the drug was still administered. After multidisciplinary discussion, capecitabine was discontinued, leading to symptom resolution and a negative repeat graded exercise test. CONCLUSIONS This case underscores the potential for capecitabine to induce coronary artery vasospasm, emphasizing the importance of prompt medication cessation. Patients receiving capecitabine therapy and experiencing chest pain should undergo an evaluation with consideration of capecitabine-induced vasospasm in the differential diagnosis. Prompt recognition and medication cessation are critical to prevent serious cardiovascular complications including death. In our patient, discontinuing capecitabine resolved his symptoms, emphasizing the significance of discontinuing the causative drug and seeking alternative chemotherapy regimens.

What is the meaning of provoked spasm phenotypes by vasoreactivity testing?

Coronary artery epicardial spasm is involved in the pathogenesis of many cardiac disorders. Vasoreactivity testing, such as intracoronary injection of acetylcholine (ACH) or ergonovine (ER), is the gold standard method for the diagnosis of vasospastic angina. Provoked epicardial spasm phenotypes are classified as focal spasm and diffuse spasm. Multiple factors, including sex, ethnicity, and use of coronary vasoactive stimulators, are related to the provoked phenotypes of epicardial spasm. Diffuse-provoked spasm is often observed in females, where focal-provoked spasm is markedly more common in males. ACH provokes more diffuse and distal spasms, whereas ER induces more focal and proximal spasms. Yellow plaque and coronary thrombi are often observed in lesions with focal spasms, and intimal thickness with a sonolucent zone is significantly more common in lesions with focal spasm. Furthermore, clinical outcomes in patients with focal spasm are unsatisfactory compared with those in patients with diffuse spasm. However, the reproducibility and eternality of provoked spasm phenotypes by vasoreactivity testing is uncertain. Coronary atherosclerosis or endothelial damage may affect coronary vasomotor tone. Although coronary artery spasm may persist in the same coronary artery, provoked coronary spasm phenotypes may exhibit a momentary coronary reaction by intracoronary ACH or ER testing.

Omitting 50 µg of intracoronary acetylcholine injection in the left coronary artery during spasm provocation test.

BACKGROUND: Although guidelines recommend intracoronary administration of acetylcholine (ACh) with incremental doses of 20, 50, and 100 µg into the left coronary artery (LCA) during spasm provocation test for diagnosing vasospastic angina, 50 µg of ACh rarely induced significant coronary vasospasm when no vasoconstriction was observed with 20 µg of ACh in a previous report. The aim of this study was to evaluate the safety and feasibility of omitting 50 µg according to the vasoreactivity by 20 µg of ACh in the LCA. METHODS: A total of 556 patients undergoing ACh provocation test with 20 µg followed by 50 and/or 100 µg were retrospectively included. Injection of 50 µg of ACh was primarily omitted when vasoconstriction <25 % was observed with 20 µg, which was left to operator's discretion. Adverse events were defined as a composite of ventricular fibrillation, sustained ventricular tachycardia, and cardiogenic shock during ACh test in the LCA. RESULTS: Positive ACh test in the LCA was observed in 245 (44.1 %) patients. Overall, patients with LCA constriction <25 % by 20 µg of ACh had a lower rate of positive ACh test than their counterpart (24.0 % vs. 88.4 %, p < 0.001). In patients with LCA constriction ≥25 % by 20 µg, the incidence of adverse events was significantly higher than in those with LCA constriction <25 % during the provocation test at doses of 50 and 100 µg (2.3 % vs. 0 %, p = 0.009). CONCLUSIONS: Omitting 50 µg of ACh in the LCA may be safe and feasible when little vasoconstriction was observed with preceding injection of 20 µg of ACh during spasm provocation test for diagnosing vasospastic angina. However, we believe that 50 µg of ACh should not be omitted when 20 µg of ACh induced LCA constriction ≥25 %.

Refractory hypotension and coronary artery spasm induced by antipsychotic drugs: A challenging case and treatment consideration: A case report and literature review.

RATIONALE: Coronary artery spasms may result from supply-demand mismatch due to hypotension. Norepinephrine is more effective in ameliorating antipsychotic-induced refractory hypotension. PATIENT CONCERNS: Postoperative difficult-to-correct hypoperfusion occurs in patients with comorbid depression and coronary spasm; the use of norepinephrine and epinephrine for rapidly raising blood pressure needs to be considered. DIAGNOSES: Electrocardiogram is an auxiliary tool and Digital Substraction Angiography is the gold standard for the diagnosis. INTERVENTIONS: Surgery and correct choice of raising blood pressure are the main treatment methods. OUTCOMES: Hypotension induced by the use of antipsychotics after angiography is difficult to correct with dobutamine, and the above scenario is relatively rare in the clinic, where norepinephrine could be a potential therapeutic option. LESSONS: Based on the lessons learnt from this case, caution must be exercised when dealing with patients on multiple antipsychotics during the perioperative period, while pressor-boosting medications should not be limited to conventional drugs such as dopamine. Norepinephrine may be more effective in dealing with difficult-to-correct hypoperfusion.

Refractory cardiac arrest caused by type I Kounis syndrome treated with adrenaline and nicorandil: A case report.

RATIONALE: Kounis syndrome is a rare but life-threatening anaphylactic reaction that can lead to acute coronary syndrome and cardiac arrest, and requires prompt diagnosis. Adrenaline, which is used to treat anaphylaxis, may cause coronary vasoconstriction and worsen ischemia, whereas coronary vasodilators may dilate systemic vessels and exacerbate hypotension. Delayed diagnosis of Kounis syndrome and inadequate therapeutic intervention may thus lead to a poor outcome. PATIENT CONCERNS: A 59-year-old man was treated for sepsis due to a liver abscess. Following administration of daptomycin, the patient developed severe anaphylactic shock leading to refractory cardiac arrest. Because conventional cardiopulmonary resuscitation was ineffective, extracorporeal cardiopulmonary resuscitation was considered as an alternative approach. DIAGNOSES: On bedside monitoring during cardiopulmonary resuscitation, unexpected ST-segment elevation was found on lead II electrocardiogram. Accordingly, the patient was clinically diagnosed with Kounis syndrome. INTERVENTIONS: Nicorandil (6 mg/h), a coronary vasodilator with minimal blood pressure effects, was administered along with high doses of vasopressors, including adrenaline 0.2 µg/kg/min. OUTCOMES: After the initiation of nicorandil administration, the patient achieved return of spontaneous circulation and did not require extracorporeal cardiopulmonary resuscitation. Based on the elevated serum tryptase level, normal creatine kinase-MB range, and lack of stenosis on coronary angiography, the patient was definitively diagnosed with type I (coronary vasospasm) Kounis syndrome. He was subsequently transferred to the referring hospital without neurological sequelae. LESSONS: If anaphylaxis leads to refractory shock and cardiac arrest, ischemic changes on the electrocardiogram should be investigated to identify underlying Kounis syndrome. In addition to adrenaline, coronary dilators are the definitive treatment. Nicorandil may be a useful treatment option because of its minimal effect on blood pressure.

Role of polyunsaturated fatty acids in Japanese patients with coronary spastic angina.

BACKGROUND: n-3 polyunsaturated fatty acids (PUFAs) reduce the risk of ischemic heart disease. However, there are few reports of a relationship between n-3 PUFAs and coronary spastic angina (CSA). This study aimed to assess the age-dependent role of serum levels of fatty acid in patients with CSA. METHODS AND RESULTS: We enrolled 406 patients who underwent ergonovine tolerance test (ETT) during coronary angiography for evaluation of CSA. All ETT-positive subjects were diagnosed as having CSA. We categorized the patients by age and results of ETT as follows: (1) young (age ≤ 65 years) CSA-positive (n = 32), (2) young CSA-negative (n = 134), (3) elderly (age > 66 years) CSA-positive (n = 36), and (4) elderly CSA-negative (n = 204) groups. We evaluated the serum levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid, and dihomo-gamma-linolenic acid. In the young groups, the serum levels of EPA (64.3 ±â€¯37.7 µg/mL vs. 49.4 ±â€¯28.8 µg/mL, p = 0.015) and DHA (135.7 ±â€¯47.6 µg/mL vs. 117.4 ±â€¯37.6 µg/mL, p = 0.020) were significantly higher in the CSA-positive group than in the CSA-negative group, respectively. However, this was not the case with elderly groups. In the multivariate analysis in young groups, the serum levels of EPA (p = 0.028) and DHA (p = 0.049) were independently associated with the presence of CSA, respectively. CONCLUSION: Our results suggested that the higher serum levels of EPA and/or DHA might be involved in the pathophysiology of CSA in the young population but not in the elderly population.

J wave dynamicity during coronary angiography and intracoronary acetylcholine administration.

BACKGROUND: J-waves may be observed during coronary angiography (CAG) or intracoronary acetylcholine (ACh) administration, but their significance is unknown. METHODS: Forty-nine patients, 59.1 ± 11.5 years old and 59% male, were studied on suspicion of vasospastic angina, and J wave dynamicity was compared between CAG and Ach administration. RESULTS: Diagnostic (≥0.1 mV) or nondiagnostic (<0.1 mV) J waves in 9 and 3 patients, respectively, were augmented, and J waves were newly observed in 2 patients during CAG and Ach administration. Similar changes in the J-wave amplitude were observed: from 0.10 ± 0.09 mV to 0.20 ± 0.15 mV (p < .002) and from 0.10 ± 0.10 mV to 0.20 ± 0.16 mV (p < .001) during CAG and Ach administration, respectively. J waves were located in the inferior leads and changed only during the right coronary interventions. In the remaining 35 patients, J waves were absent before and during the coronary interventions. Augmentation of J waves was found when the RR interval was shortened in some patients. Injection of anoxic media into the coronary artery might induce a conduction delay from myocardial ischemia that manifests as augmentation or new occurrence of J waves. CONCLUSIONS: Both CAG and intracoronary Ach administration affected J waves similarly in the same individuals. A myocardial ischemia-induced conduction delay may be responsible for the changes in J waves, but further studies are needed.

Post-partum myocardial ischemia due to intramuscular methylergonovine-induced coronary vasospasm: case report.

BACKGROUND: Methylergonovine is a vasoconstrictive agent historically used as a provocative agent in the lab for coronary vasospasm; it is also a first line uterotonic agent for management of postpartum hemorrhage. CASE PRESENTATION: A 29-year-old female with history of smoking and idiopathic thrombocytopenia received intramuscular methylergonovine after delivery of twins for intrauterine hemorrhage management. Subsequently, she had episodes of chest pain with high sensitivity Troponin I elevation to 1509 ng/L with accompanying septal T wave inversions, decreased left ventricular ejection fraction to 49% and basal septal wall hypokinesis. Computed tomography (CT) coronary angiogram showed patent coronary arteries and no coronary arterial dissection. The patient was conservatively managed with aspirin and metoprolol, and on follow up had fully recovered left ventricular function with resolution of wall motion abnormalities. Given this, coronary vasospasm due to intramuscular methylergonovine is the most likely cause of patient's chest pain and associated myocardial ischemia. CONCLUSIONS: Intramuscular, intrauterine, intravenous, and even oral methylergonovine can rarely cause coronary vasospasm leading to myocardial ischemia. Cardiologists caring for postpartum patients should be aware of these potential lethal complications; prompt identification and administration of sublingual nitroglycerin can prevent severe complications of arrythmias, heart block, or cardiac arrest.

Intraoperative Kounis Syndrome and Fixation Errors: A Case Report.

Postinduction hypotension, though frequently due to anesthetic medications, has a variety of causes. We present a case of presumed intraoperative Kounis syndrome, or anaphylaxis-induced coronary vasospasm, in which the patient's perioperative course was initially attributed to anesthesia-induced hypotension and iatrogenic rebound hypertension leading to Takotsubo cardiomyopathy. A second anesthetic event with immediate recurrence of hypotension after the patient received levetiracetam appears to confirm the diagnosis of Kounis syndrome. In this report, we discuss the fixation error that led to this patient's original misdiagnosis.

Life-threatening Vasospastic Angina Induced by Carteolol Eye Drops.

Vasospastic angina (VSA) can be worsened by oral nonselective beta-blockers. Ophthalmic carteolol eye drops are nonselective beta-blockers and effective against glaucoma and ocular hypertension. Systemic effects of ophthalmic beta-blockers on VSA have not yet been reported. We herein report a case of VSA that developed after a patient started carteolol eye drops for ocular hypertension. Even though benidipine, a calcium channel blocker, was started, a VSA attack with incessant non-sustained ventricular tachycardia occurred. Once the carteolol eyedrops were discontinued, the VSA resolved. This case demonstrates that carteolol eye drops can induce life-threatening VSA.

Intra-brachial ergonovine, not acetylcholine, is associated with radial artery vasospasm in patients with coronary vasospasm.

BACKGROUND: The intracoronary provocation test is expensive and may cause complications. Therefore, we investigated the sensitivity, specificity and safety of different drug- and dose-peripheral artery provocation tests in the diagnosis of coronary artery spasm (CAS). METHODS: The patients who had repeated chest pain as well as both coronary and radial stenoses <50% were selected. These patients were divided into CAS group (n = 24) and control group (n = 33) after the intracoronary ergonovine provocation test. All patients underwent radial artery provocation tests at different dose-acetylcholine (200 µg, 400 µg and 800 µg) and ergonovine (60 µg, 100 µg and 160 µg). The predictive values of radial provocation tests for CAS diagnosis were analysed using receiver operator characteristic (ROC) curves. RESULTS: In radial acetylcholine provocation tests, 200 µg of acetylcholine failed to induce radial artery spasm, and the radial artery stenosis degree was not significantly different between the CAS group and control group at 400 µg and 800 µg of acetylcholine (all p > 0.05). In the radial artery ergonovine provocation tests, the radial artery stenosis degree was all significantly higher in the CAS group than in the control group at the three different doses (all p < 0.05). The specificity and sensitivity of radial ergonovine provocation tests were 90.91% and 50.00% at 60 µg, 96.97% and 66.67% at 100 µg, and 90.91% and 95.83% at 160 µg. Only the radial 160 µg-ergonovine provocation test caused CAS in one case. CONCLUSION: The radial acetylcholine provocation test has no diagnostic value for CAS. The radial 160 µg-ergonovine provocation test has higher sensitivity and specificity for CAS diagnosis, but its safety should be paid attention to.

Cardiac arrest due to coronary vasospasm after sugammadex administration -a case report.

BACKGROUND: Sugammadex is a widely used medication for the reversal of aminosteroid neuromuscular blockades. Although sugammadex is generally regarded to be safe, concerns about the risk of serious complications have emerged. CASE: A 57-year-old man without a history of coronary disease was scheduled for general anesthesia to undergo cardiac radiofrequency catheter ablation due to symptomatic persistent atrial fibrillation and flutter. At the end of the procedure, he was given 400 mg of sugammadex. A little later, the electrocardiogram showed a sudden ST elevation on the inferior leads, followed by cardiac arrest. The urgent coronary angiography demonstrated total collapse of the right coronary artery. After two injections of intra-coronary nitroglycerin, the vasospasm of the right coronary artery was completely resolved. The patient recovered without sequelae and was discharged on postoperative day 5. CONCLUSIONS: Clinicians should pay close attention to the potential risk of coronary vasospasm, even cardiac arrest, after sugammadex administration.

Managing life-threatening 5-fluorouracil cardiotoxicity.

5-Fluorouracil (5-FU), a known cardiotoxin, is the backbone for the treatment of colorectal cancer. It is associated with arrhythmias, myocardial infarction and sudden cardiac death. Most commonly, it is associated with coronary vasospasm secondary to direct toxic effects on vascular endothelium.A woman with metastatic colon cancer, originally treated with a 5-FU infusion as part of the FOLFIRI (Folinic acid, 5-Fluorouracil, Irinotecan) regimen, was unable to tolerate the chemotherapy due to chest pain. She was transitioned from infusional 5-FU to inferior 1-hour bolus 5-FU, in an attempt to minimise cardiotoxicity, but had disease progression. A multidisciplinary decision was made to again trial 5-FU infusion and pretreat with diltiazem. She tolerated chemotherapy without adverse events. A multidisciplinary discussion is recommended for co-management of reversible 5-FU-associated cardiotoxicity. After coronary artery disease (CAD) risk stratification and treatment, empiric treatment with calcium channel blockers and/or nitrates may allow patients with suspected coronary vasospasm, from 5-FU, to continue this vital chemotherapy.

Coronary Spasm During Postoperative Sedation With Dexmedetomidine.

This is a case report of an 81-year-old woman who underwent tracheostomy, bilateral cervical dissection, partial tongue resection, radial forearm free flap reconstruction, and split-thickness skin grafting under general anesthesia. After successful surgery, she was moderately sedated postoperatively with intravenous dexmedetomidine (DEX) and fentanyl. The fentanyl was discontinued 5 hours postoperatively. Eight hours after the operation, an atrioventricular junctional rhythm, a 2-mm elevation of the ST segment, and biphasic T waves were detected in lead II that lasted approximately 3 minutes. Hypotension and bradycardia were observed simultaneously with the abnormal electrocardiogram. The next day, a cardiologist examined the patient and suggested that coronary spasm had occurred based on those findings. The transient coronary spasm was likely caused by a combination of various factors including surgical stress and altered autonomic function. However, it is possible that stimulation of α-2 adrenergic receptors induced by DEX may also be linked to the coronary vasospasm that occurred.