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.

Vasoespasmo en microcirugía: revisión de la literatura y recomendaciones para su manejo / Vasospasm in microsurgery: literature review and clinical recommendations

Introducción y objetivo: Los colgajos libres microquirúrgicos se han convertido en una herramienta indispensable en Cirugía Reconstructiva. El vasoespasmo es una entidad que puede producir fallo del colgajo. El objetivo de este trabajo es evaluar las distintas medidas terapéuticas para la prevención y tratamiento del vasoespasmo y proponer un algoritmo de manejo para esta complicación. Material y método: Revisión bibliográfica de estudios de diseño experimental o cuasi experimental que evalúen el efecto de distintas intervenciones para la prevención y el tratamiento del vasoespasmo. Resultados: Incluimos 31 estudios experimentales, de los cuales 5 analizan intervenciones no farmacológicas y 26 intervenciones farmacológicas. Todos los estudios experimentales fueron realizados en modelos animales. Dentro de las intervenciones no farmacológicas estudiadas, la adventicetomía y el adecuado control de la hemostasia mostraron ser medidas efectivas para la prevención del vasoespasmo. Dentro de las intervenciones farmacológicas tópicas, la lidocaína, la papaverina, el sulfato de magnesio al 10% y el verapamilo demostraron consistentemente su efectividad en la prevención y tratamiento del vasoespasmo. Dentro de las intervenciones farmacológicas sistémicas, la pentoxifilina y la prostaglandina E1 fueron las más efectivas para el manejo del vasoespasmo. Otros fármacos mostraron evidencia controvertida: nifedipino, nicardipino y prostaglandina E1 (todos de aplicación tópica); nicardipino, nifedipino y verapamilo (todos de aplicación sistémica). Conclusiones: La evidencia actual respecto a la efectividad de medidas orientadas al manejo del vasoespasmo en microcirugía se basan principalmente en estudios animales. El algoritmo de manejo del vasoespasmo que presentamos se sustenta en la experiencia clínica acumulada y la mejor evidencia actualmente disponible...

Background and objective: Microsurgical free flaps have become an indispensable tool in Reconstructive Surgery. Vasospasm is an entity that can cause flap failure. Our objective is to evaluate the different therapies for vasospasm prevention and treatment and to propose a management algorithm for this complication. Methods: Bibliographic review of studies of experimental or quasi-experimental design that assesed the effect of interventions for the prevention and treatment of vasospasm. Results: Thirty one experimental studies were included, of which 5 analyzed non-pharmacological interventions and 26 pharmacological interventions. All experimental studies were performed in animal models. Among the non-pharmacological interventions studied, adventicetomy and adequate control of hemostasis proved to be effective measures for the prevention of vasospasm. Within topical pharmacological interventions, lidocaine, papaverine, 10% magnesium sulfate, and verapamil consistently demonstrated their effectiveness in the prevention and treatment of vasospasm. Within the systemic pharmacological interventions, pentoxifylline and prostaglandin E1 were the most effective interventions for the management of vasospasm. Other drugs showed controversial evidence: nifedipine, nicardipine and prostaglandin E1 (topicallys); nicardipine, nifedipine and verapamil (systemics). Conclusions: The current evidence regarding the effectiveness of measu-res aimed at managing vasospasm in microsurgery is based mainly on animal studies. The vasospasm management algorithm presented is based on accumulated clinical experience and the best currently available evidence. Having this therapeutic strategy makes it possible to standardize management in clinical practice for rapid decision-making. Level of evidence 5c Therapeutic.(AU)

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.

Vasospastic angina: Past, present, and future.

Vasospastic angina (VSA) is characterized by episodes of rest angina that are responsive to short-acting nitrates and are attributable to coronary artery vasospasm. The condition is underdiagnosed as the provocation test is rarely performed. VSA, the most important component of non-obstructive coronary artery disease, can present with angina, be asymptomatic, or can even present with fatal arrhythmias and cardiac arrest. Although most patients with VSA respond well to vasodilating medications, prognosis does not improve as expected in most patients, suggesting the existence elusive prognostic factors and pathogenesis that warrant further exploration. Moreover, patients with either severe or refractory VSA barely respond to conventional treatment and may develop life-threatening arrhythmias or suffer sudden cardiac death during ischemic attacks, which are associated with immune-inflammatory responses and have been shown to achieve remission following glucocorticoid and immunoglobulin treatments. Our recent work revealed that inflammation plays a key role in the initiation and development of coronary spasms, and that inflammatory cytokines have predictive value for diagnosis. In contrast to the existing literature, this review both summarizes the theoretical and clinical aspects of VSA, and also discusses the relationship between inflammation, especially myocarditis and VSA, in order to provide novel insights into the etiology, diagnosis, and treatment of VSA.

Effect of Statins on Major Adverse Cardiovascular Events in Patients with Coronary Artery Spasm: A Meta-Analysis of the Asia Region.

Background: Whether statins can reduce major cardiovascular adverse events (MACE) in patients with coronary artery spasm (CAS) is controversial. And most of the relevant research to date has been conducted in Asia. Methods: We systematically searched electronic databases for studies on the effect of statins on MACE in patients with CAS in Asia and published up to September 2022. We included data on MACE in a statin therapy patient group and a no-statin therapy control group. We then evaluated the effect of statin therapy on MACE in patients with CAS in Asia by meta-analysis and trial sequential analysis (TSA). All statistical analyses were performed using Stata 16.0 software and TSA software. Results: A total of 10 studies (n = 9333 patients) were included in the final analysis. Meta-analysis showed that the use of statins had a significant effect on MACE in CAS patients (with RR, 0.70; 95% CI, 0.49-0.99), and the sensitivity analysis further confirmed this finding. Subgroup analysis suggested that the correlation between statin therapy and reduced MACE endpoint was stronger in Japanese patients and patients followed up for more than 4 years. But our TSA results indicated that the available samples were insufficient and further research is needed. Conclusions: Our meta-analysis suggests that statin therapy can reduce MACE in patients with CAS in Asia, and the correlation between the two was stronger in Japanese patients and patients followed up for more than 4 years.

Cardioprotective and Antianginal Efficacy of Nicorandil: A Comprehensive Review.

ABSTRACT: Angina pectoris remains a significant burden despite advances in medical therapy and coronary revascularization. Many patients (up to 30%) with angina have normal coronary arteries, with coronary microvascular disease and/or coronary artery vasospasm being major drivers of the myocardial demand-supply mismatch. Even among patients revascularized for symptomatic epicardial coronary stenosis, recurrent angina remains highly prevalent. Medical therapy for angina currently centers around 2 disparate goals, viz secondary prevention of hard clinical outcomes and symptom control. Vasodilators, such as nitrates, have been first-line antianginal agents for decades, along with beta-blockers and calcium channel blockers. However, efficacy in symptoms control is heterogenous, depending on underlying mechanism(s) of angina in an individual patient, often necessitating multiple agents. Nicorandil (NCO) is an antianginal agent first discovered in the late 1970s with a uniquely dual mechanism of action. Like a typical nitrate, it mediates medium-large vessel vasodilation through nitric oxide. In addition, NCO has adenosine triphosphate (ATP)-dependent potassium channel agonist activity (K ATP ), mediating microvascular dilatation. Hence, it has proven effective in both coronary artery vasospasm and coronary microvascular disease, typically challenging patient populations. Moreover, emerging evidence suggests that cardiomyocyte protection against ischemia through ischemic preconditioning may be mediated through K ATP agonism. Finally, there is now fairly firm evidence in favor of NCO in terms of hard event reduction among patients with stable coronary artery disease, following myocardial infarction, and perhaps even among patients with congestive heart failure. This review aims to summarize the mechanism of action of NCO, its efficacy as an antianginal, and current evidence behind its impact on hard outcomes. Finally, we review other cardiac and emerging noncardiac indications for NCO use.

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.

Comparison of various calcium antagonist on vasospastic angina: a systematic review.

BACKGROUND: Coronary artery vasospasm is an abnormal spasm of coronary arteries that cause transient or complete occlusion without exertion. It causes stable angina to ACS. However, this can be prevented by calcium channel blockers (CCBs) which suppress Ca2+ influx into the vascular muscle cells. Nevertheless, several CCBs adverse effects are harmful for these patients. Selecting the right CCBs would give the best clinical practice. METHOD: The studies were obtained from four major medical databases by various keywords. Inclusion and exclusion criteria were implemented as adult >18 years, observational study, English language and drug of interest. Duplicates were eliminated, and the remaining studies were reviewed. Final full-texts assessment was conducted independently by Newcastle-Ottawa Scale and Revised Cochrane. RESULTS: The search found 1378 articles. However, six studies were selected after implementing the study criteria. Diltiazem was found to decrease angina and increase quality of life until 12th week of treatment; however, some adverse effects include atrioventricular block and recurrent angina up till 4th week were found. Meanwhile, nifedipine was found to decrease vasospastic angina (VSA) by the fourth and eighth weeks of treatment. Nevertheless, it caused excessive drop in BP and increase heart rate by eighth week. In addition, slow-release preparation of both CCBs were found to increase efficacy and compliance. Lastly amlodipine was also found to decrease VSA by 17%±140% and 33% after 6 weeks, but further studies needed. CONCLUSION: Diltiazem, nifedipine and amlodipine are potent in decreasing VSA, however, tailoring specific CCBs adverse reactions to patient condition and the drug preparation would be substantially beneficial for the outcome.

Prognostic impact of nitrate therapy in patients with myocardial bridge and coexisting coronary artery spasm.

The aim of this study was to investigate the prognostic impact of nitrate therapy in patients with myocardial bridge (MB) and coexisting coronary artery spasm (CAS). MB often accompanies CAS. Nitrates have been widely used as anti-ischemic drugs in CAS patients, while it is not recommended in MB patients. Thus, we investigated the long-term impact of nitrate on clinical outcomes in patients with both CAS and MB. A retrospective observational study was performed using propensity score matching (PSM) in a total of 757 consecutive MB patients with positive acetylcholine (Ach) provocation test. Patients were divided into two groups according to the regular administration of nitrates (nitrate group: n = 504, No nitrate group; n = 253). The PSM was used to adjust for selection bias and potential confounding factors, and major clinical outcomes were compared between the two groups up to 5 years. Baseline characteristics were well-matched between the two groups following PSM (n = 211 for both groups). There was no significant difference in the incidence of death, myocardial infarction, and major adverse cardiovascular events (MACEs) between the two groups. However, the nitrate group showed a significantly higher rate of recurrent angina which subsequently needed re-evaluation of coronary arteries by follow-up angiography (15.7 vs. 5.7%, Log-rank p = 0.012) compared to the non-nitrate group. Long-term nitrate administration in patients with MB and coexisting CAS did not show benefit in reducing MACE, rather it was associated with a higher incidence of recurrent angina requiring follow-up angiography.

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.

Management of vasospastic angina.

Vasospastic angina is a well-established cause of chest pain that is caused by coronary artery spasm. It can be clinically diagnosed during a spontaneous episode by documenting nitrate-responsive rest angina with associated transient ischaemic ECG changes but more often requires provocative coronary spasm testing with acetylcholine during coronary angiography. Vasospastic angina may result in recurrent episodes of angina (including nocturnal angina), which can progress on to major adverse cardiac events. Calcium channel blockers are first-line therapy for this condition, given their anti-anginal and cardioprotective benefits. Despite an established diagnostic and therapeutic management pathway for vasospastic angina, this diagnosis is often overlooked in patients presenting with chest pain. Thus, there is need for increased clinical awareness of vasospastic angina to improve outcomes in affected patients.

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.

Effect of Statins on Clinical Outcomes in Patients With Coronary Artery Spasm: A Meta-Analysis.

PURPOSE: The purpose of this meta-analysis was to assess the effect of statins on major adverse cardiovascular events (MACE) related to coronary artery spasm (CAS) and to evaluate the effectiveness of statins in patients with CAS. METHODS: A systematic search of electronic databases, including Google Scholar, the Cochrane Central Register of Controlled Trials, and PubMed, was conducted. These studies were all published in English, and the databases were searched from inception to July 2021. All articles were evaluated independently by 2 researchers on the basis of inclusion and exclusion criteria. In the research, data about the incidence of major adverse cardiovascular events in CAS patients undergoing statin therapy was included and divided into different subgroups. A random effects model was conducted to synthesize the data. FINDINGS: Five cohort studies were included in the analysis. These results indicated that statins failed to reduce the incidence of stroke in patients with CAS in general. However, subgroup analysis revealed that statins were more effective in improving outcomes for CAS patients without severe coronary stenosis compared with those with severe coronary stenosis. IMPLICATIONS: Statins may have a potential benefit in patients with CAS who do not have coronary stenosis. To investigate these findings further, future prospective, randomized controlled research will be required.