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.

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.

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.

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.

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.

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.

Pyridostigmine-induced coronary artery spasm in early-onset myasthenia gravis: a case presentation and review of the literature.

We present a case of pyridostigmine-induced coronary artery spasm in a woman with early-onset myasthenia gravis (MG) who suffered from acute chest discomfort a few days after pyridostigmine dose up-titration. Twelve-lead ECG demonstrated ST-segment elevation in inferior limb leads together with sinus arrest. Sublingual nitrate was immediately given, which rapidly relieved her symptoms concomitantly with the resolution of abnormal ECG findings. Coronary angiography showed normal coronary arteries reflecting the transient nature of the disease. A small dose of pyridostigmine was rechallenged under close monitoring in the coronary care unit and reproduced her chest discomfort. After the substitution of pyridostigmine with immunosuppressive agents and prescription of long-acting nitrate, she had no recurrence of chest discomfort, as well as well-controlled MG symptoms.

The efficacy and safety of cardio-protective therapy in patients with 5-FU (Fluorouracil)-associated coronary vasospasm.

BACKGROUND: Coronary vasospasm is a known side effect of 5-FU (fluorouracil) therapy. Beyond switching to non-5FU-based chemotherapy, there are no established treatments for 5-FU associated coronary vasospam. Our objective was to assess the safety and efficacy of re-challenge with 5-FU after pre-treatment with calcium channel blockers (CCBs) and long-acting nitrates among patients 5-FU associated coronary vasospasm. METHODS: We conducted a retrospective study of patients with 5-FU coronary vasospasm at a single academic center. By protocol, those referred to cardio-oncology received pre-treatment with either combination [nitrates and CCBs] or single-agent therapy [nitrates or CCBs]) prior to re-challenge with 5-FU. Our primary outcome was overall survival. Other important outcomes included progression-free survival and safety. RESULTS: Among 6,606 patients who received 5-FU from January 2001 to Dec 2020, 115 (1.74%) developed coronary vasospasm. Of these 115 patients, 81 patients continued 5-FU therapy, while 34 stopped. Of the 81 who continued, 78 were referred to cardio-oncology and prescribed CCBs and/or nitrates prior to subsequent 5-FU, while the remaining 3 continued 5-FU without cardiac pre-treatment. Of the 78, 56.4% (44/78) received both nitrates and CCBs, 19.2% (15/78) received CCBs alone, and 24.4% (19/78) received nitrates alone. When compared to patients who stopped 5-FU, those who continued 5-FU after pre-treatment (single or combination therapy) had a decreased risk of death (HR 0.42, P = 0.005 [95% CI 0.23-0.77]) and a trend towards decreased cancer progression (HR 0.60, P = 0.08 [95% CI 0.34-1.06]). No patient in the pre-treatment group had a myocardial infarct after re-challenge; however, chest pain (without myocardial infarction) recurred in 19.2% (15/78) among those who received cardiac pre-treatment vs. 66.7% (2/3) among those who did not (P = 0.048). There was no difference in efficacy or the recurrence of vasospasm among patients who received pre-treatment with a single agent (nitrates or CCBs) or combination therapy (14.7% (5/34) vs. 25.0% (11/44), P = 0.26). CONCLUSION: Re-challenge after pre-treatment with CCBs and nitrates guided by a cardio-oncology service was safe and allowed continued 5-FU therapy.

Perioperative Presentations of Kounis Syndrome: A Systematic Literature Review.

Kounis syndrome commonly is described as a complex multisystem phenomenon mainly affecting coronary arteries, resulting in coronary vasospasm in the context of an allergic manifestation. This article reviews the literature regarding perioperative presentations of the syndrome. A systematic search in MEDLINE and Embase databases was performed for case reports through June 16, 2021, on Kounis syndrome triggered by medications administered in the perioperative setting. The authors' search resulted in 35 perioperative reports of Kounis syndrome, with the majority of the cases occurring in men between 40 and 80 years of age, manifesting within 20 minutes following the administration of the suspected trigger. Chest pain and ischemic changes on the electrocardiograph were the most frequent presentations, while intravenous antibiotics and neuromuscular blocking agents were the most common triggers. In most instances, the patients had a good recovery following the event. Coronary vasospasm is often less frequently recognized as a form of allergic manifestation in the perioperative setting. Many potential triggers, such as antibiotics and neuromuscular blocking agents, are routinely administered during surgery. Awareness of this condition, early diagnosis, and effective management of this condition can lead to good outcomes.

Vasospastic Angina: An Immune-related Adverse Event.

A 54-year-old Japanese woman was admitted to our ward because of recurrent chest pain at rest for 2 months. She had been treated with nivolumab, an immune checkpoint inhibitor for inoperable advanced hypopharyngeal cancer for 21 months. She had no chest pain after cessation of nivolumab treatment. Cardiac catheterization confirmed the presence of vasospastic angina. Benidipine 8 mg was started, and she had no chest pain even after resuming therapy with nivolumab. Vasospastic angina is an adverse effect of nivolumab.

Sex-related Differences in Patients with Positive Coronary Spasm as Identified by Acetylcholine Testing.

Objective A pathological acetylcholine (ACh) test was observed at lower ACh doses in females compared with males in European populations. We retrospectively analyzed the sex-related differences in Japanese patients with provoked positive spasm by ACh spasm provocation testing. Methods We performed the ACh spasm provocation tests in 1,854 patients from Jan 1991 until Mar 2019. ACh was injected in incremental doses of 20/50/100/200 µg into the left coronary artery and 20/50/80 µg into the right coronary artery. Positive spasm was defined as >90% stenosis and usual chest pain or ischemic ECG changes. We compared the clinical characteristics, angiographical findings during ACh testing, and clinical outcomes between female and male patients with and without provoked positive spasm. Results Positive provoked spasm was diagnosed in 917 patients including 737 (80.4%) males and 180 (19.6%) females. The incidence of provoked positive spasm in females was significantly lower than that in males (33.5% vs. 56.0%, p<0.001). Female patients with provoked positive spasm tended to be older, have less history of smoking, less provoked spasm in the left circumflex artery, or less focal type spasm than male patients with provoked positive spasm. The incidence of ST elevation during ACh testing in male patients was significantly higher than that in female patients, whereas the frequency of ST depression in females was remarkably higher than that in males. The mean maximum used ACh dose for provoked positive spasm on both coronary arteries in female patients was significantly higher than that in male patients. The observed major complications during ACh testing did not differ substantially between the sexes. In addition, the prognosis in females with provoked positive spasm was not different from males. Conclusion Provoked positive spasm by ACh test was obtained at lower mean maximum ACh doses in males compared with females in Japanese patients.

Spontaneous coronary artery dissection in association with cabergoline therapy.

Spontaneous coronary artery dissection (SCAD) is a rare but increasingly recognised cause of acute coronary syndrome. While numerous risk factors are associated with SCAD, one potential cause is coronary artery vasospasm. The use of cabergoline-an ergot derivative and dopamine agonist that may induce vasospasm-has been associated with SCAD in one other case report worldwide. Here, we describe SCAD in a 37-year-old woman on long-term cabergoline therapy with no other cardiac risk factors. Cabergoline-induced SCAD should be considered in patients presenting with an acute coronary syndrome who are treated with this medication.

ST-elevation during head up tilt test: a challenging case in syncope unit.

A 65-year-old woman, during an elective head up tilt test, after the sublingual nitrate administration, experienced electrocardiogram alteration with ST elevation in the inferior leads, that returned normal when the patient was laid supine after few minutes. Serial cardiac markers were not elevated and coronary angiography revealed normal epicardial coronary arteries. Paradoxical vasospastic response to nitrates in vasospastic angina patients represents a rare but very challenging condition and the best therapeutic approach in this subgroup of patients remains unclear.

Coronary artery spasms due to tyrosine kinase inhibitors used in chronic myeloid leukemia.

Tyrosine kinase inhibitors (TKIs) have changed the landscape of treatment for patients with chronic myeloid leukemia (CML) leading to a life expectancy comparable to the general population. Side effects commonly encountered during TKI treatment are pleural effusion due to use of dasatinib and vascular side effects due to nilotinib and ponatinib. Coronary artery spasm (CAS), although encountered during treatment with other chemotherapeutic drugs, have to our knowledge never been reported during TKI treatment. Here, we describe two cases of coronary artery spasms which are likely due to TKIs.

Enhanced coronary arteriolar contraction to vasopressin in patients with diabetes after cardiac surgery.

OBJECTIVE: Cardioplegic arrest (CP) and cardiopulmonary bypass (CPB) are associated with vasomotor dysfunction of coronary arterioles in patients with diabetes (DM) undergoing cardiac surgery. We hypothesized that DM may up-regulate vasopressin receptor expression and alter the contractile response of coronary arterioles to vasopressin in the setting of CP/CPB. METHODS: Right atrial tissue samples of patients with DM and without (ND) (n = 8 in each group) undergoing cardiac surgery were harvested before and after CP/CPB. The isolated coronary arterioles (80-150 µm) dissected from the harvested right atrial tissue samples were cannulated and pressurized (40 mm Hg) in a no-flow state. The changes in diameter were measured with video microscopy. The protein expression/localization of vasopressin 1A receptors (V1A) and vasopressin 1B receptors (V1B) in the atrial tissue were measured by immune-blotting and immunohistochemistry. RESULTS: The pre-CP/CPB contractile responses of the coronary arterioles to vasopressin were significantly increased post-CP/CPB in both the ND and DM groups. This effect was more pronounced in the vessels from patients in the DM group than that of vessels from patients in the ND group (P < .05). Vasopressin-induced contractile response of the coronary arterioles was inhibited in the presence of the specific V1A antagonist SR 49059 (10-7 M) in both ND and DM vessels (P < .05). The post-CP/CPB protein levels of V1A were significantly increased compared with pre-CP/CPB values in both the ND and DM groups (P < .05), whereas this increase was greater in DM than that of ND (P < .05). Immunohistochemistry staining further indicates that V1B were mainly expressed in the myocardium but not in vascular smooth muscle. CONCLUSIONS: CP/CPB and DM are both associated with up-regulation in V1 receptor expression/localization in human myocardium. Vasopressin may induce coronary arteriolar constriction via V1A. This alteration may lead to increased coronary arteriolar spasm in patients with DM undergoing CP/CPB and cardiac surgery.

Angioscopic differences of coronary intima between diffuse and focal coronary vasospasm: Comparison of optical coherence tomography findings.

BACKGROUND: Coronary artery vasospasm (CS) can be identified as either a diffuse type or focal type; however, the difference in endothelial characteristics between these spasm types remains unclear. The features of coronary intima associated with diffuse spasm and focal spasm using coronary angioscopy (CAS) were evaluated and the optical coherence tomography (OCT) findings were compared. METHODS: CAS and/or OCT observational analysis was performed in 55 patients (mean age: 61.4 years, 31 men) who had acetylcholine-provoked CS (diffuse CS, 31 patients; focal CS, 24 patients). The yellowness of the intima, presence of thrombus in CAS, and intimal characteristics based on the OCT results were evaluated. RESULTS: CAS showed more atherosclerotic yellow plaques at the focal spasm segment than at the diffuse spasm segment (p=0.032). Moreover, there were more thrombi at the focal spasm segment (p=0.039). In addition, OCT results revealed that the intima area, maximum intima thickness, and lipid content in the focal CS group were larger than the diffuse CS group (4.22±1.67mm2 vs. 3.45±2.36mm2; 0.71±0.29mm vs. 0.53±0.30mm; 55.9% vs. 32.0%, p<0.001, respectively). CONCLUSIONS: These results indicate that the presence of atherosclerotic plaques at the spasm site is likely to be related to the occurrence of a focal vasospasm. This may support the difference of features between focal CS and diffuse CS and contribute to precise treatment for each spasm type.

Myocardial infarction during anaphylaxis in a young healthy male with normal coronary arteries- is epinephrine the culprit?

BACKGROUND: Anaphylaxis is an acute, potentially fatal medical emergency. Myocardial injury or infarction in the setting of an anaphylaxis can be due the anaphylaxis itself, when it is known as Kounis syndrome or it can also be due to the effect of epinephrine treatment. Epinephrine is considered as the cornerstone in management of anaphylaxis. Myocardial infarction secondary to therapeutic doses of adrenaline is a rare occurrence and only a few cases have been reported in literature. The mechanism of myocardial injury was considered to be due to coronary vasospasm secondary to epinephrine as the coronary angiograms were normal on these occasions. CASE PRESENTATION: A 21-year- old previously healthy male got admitted to the local hospital with an urticarial rash and difficulty in breathing, one hour after ingestion of prawns for which he was known to be allergic. He was treated with 0.5 ml of intramuscular adrenaline (1:1000) which was administered to the lateral side of the thigh, following which he developed palpitations and tightening type central chest pain. Electrocardiogram showed ST segment depressions in leads III, aVF and V1 to V5 and he was transferred to a tertiary care hospital. The second electrocardiogram, done 2 h later, showed resolution of ST segment depressions but new T inversions in leads I and aVL. Troponin I was elevated with a titer of 2.15 ng/ml. He was treated with sublingual GTN in the emergency treatment unit and the symptoms resolved. Transthoracic 2D echocardiogram and stress testing with treadmill was normal and CT coronary angiogram revealed normal coronary arteries. CONCLUSION: Here we present a case of a young healthy adult with no significant risk factors for coronary artery disease who developed myocardial infarction following intramuscular administration of therapeutic dose of adrenalin for an anaphylactic reaction. The postulated mechanism is most likely an alpha receptor mediated coronary vascular spasm. However the use of adrenaline in the setting of life threatening anaphylaxis is life saving and the benefits far outweigh the risks of adverse effects. Therefore the purpose of reporting this case is not to discourage the use of adrenaline in anaphylaxis but to make aware of this potential adverse effect which can occur in the acute setting.

Echocardiographic Epicardial Adipose Tissue Thickness Is Associated with Symptomatic Coronary Vasospasm during Provocative Testing.

BACKGROUND: Epicardial adipose tissue (EAT) is the ectopic visceral fat surrounding the heart, which plays an important role in atherosclerosis of the coronary arteries via endothelial damage. Several studies have also suggested that vasospasm with angina (VSA) causes endothelial dysfunction in the coronary arteries. The aim of this study was to evaluate the thickness of EAT in the anterior interventricular groove (EAT-AIG) using echocardiography in patients who had no obstructive coronary artery disease and were suspected of having VSA. METHODS: Sixty-five patients who underwent intracoronary acetylcholine provocation testing for clinical indications were prospectively enrolled. VSA was diagnosed by coronary artery stenosis increase of >90% and the presentation of chest pain with ischemic changes on electrocardiography. RESULTS: Subjects were divided into two groups, with and without significant coronary spasm (VSA group, 30 patients; non-VSA group, 35 patients), consistent with acetylcholine provocation testing. EAT-AIG thickness was significantly greater in the VSA group than in the non-VSA group (8.2 ± 2.7 vs 6.1 ± 2.5 mm, P = .002). By receiver operating characteristic analysis, EAT-AIG thickness had a high C statistic (area under the curve = 0.81, P < .001) after adjustment for conventional risk factors (smoking, diabetes mellitus, and dyslipidemia). EAT-AIG thickness had incremental diagnostic value over other conventional risk factors (area under the curve = 0.81 vs 0.64, P for comparison = .020). CONCLUSIONS: EAT-AIG thickness, which is noninvasively and easily measured using transthoracic echocardiography, can be one of multiple clinical variables associated with VSA.