Coronary Arterial Spasm During Pulsed Field Ablation to Treat Atrial Fibrillation.

BACKGROUND: Pulsed field ablation (PFA) has a unique safety profile when used to treat atrial fibrillation, largely related to its preferentiality for myocardial tissue ablation, in particular, esophageal sparing. A pentaspline catheter was the first such PFA system studied clinically for atrial fibrillation ablation; in these initial regulatory trials, the catheter was used for pulmonary vein isolation and left atrial posterior wall ablation. Since its regulatory approval in Europe, in clinical practice, physicians have ablated beyond pulmonary vein isolation and left atrial posterior wall ablation to expanded lesion sets in closer proximity to coronary arteries. This is an unstudied important issue because preclinical and clinical data have raised the potential for coronary arterial spasm. Herein, we studied the vasospastic potential of PFA lesion sets, both remote from and adjacent to coronary arteries. METHODS: During routine atrial fibrillation ablation using the pentaspline PFA catheter, coronary angiography was performed before, during, and after pulsed field applications. The lesion sets studied included: (1) those remote from the coronary arteries such as pulmonary vein isolation (n=25 patients) and left atrial posterior wall ablation (n=5), and (2) ablation of the cavotricuspid isthmus (n=20) that is situated adjacent to the right coronary artery. RESULTS: During pulmonary vein isolation and left atrial posterior wall ablation, coronary spasm did not occur, but cavotricuspid isthmus ablation provoked severe subtotal vasospasm in 5 of 5 (100%) consecutive patients, and this was relieved by intracoronary nitroglycerin in 5.5±3.5 minutes. ST-segment elevation was not observed. However, no patient (0%, P=0.004) had severe spasm if first administered parenteral nitroglycerin, either intracoronary (n=5) or intravenous (n=10), before treatment. CONCLUSIONS: Coronary vasospasm was not provoked during PFA at locations remote from coronary arteries, but when the energy is delivered adjacent to a coronary artery, PFA routinely provokes subclinical vasospasm. This phenomenon is attenuated by nitroglycerin, administered either post hoc to treat spasm or as prophylaxis.

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.

Pathophysiology and Treatment of Intraseptal-Course Left Coronary Anomaly: Surgery for All?

Intraseptal-course, ectopic coronary anomalies are not well characterized as to anatomy, function, prognosis, and treatment. Recently, a revolutionary but unsupported new theory is claiming that most patients with a Left Anomalous Coronary Artery originating from the Opposite Sinus with anomalous Intra-Septal course (L-ACAOS-IS)-even small children-have significant stenoses and require open-heart surgery to prevent acute myocardial infarction and death. This surprising view has spurred ongoing discussions among adult and pediatric cardiologists and cardiac surgeons, compelling us (the conservative party in the discussion) to offer an in-depth and comprehensive review of this anomaly, based on objective but opposite data. We and other adult cardiologists have followed numerous L-ACAOS-IS patients for many years and have observed none of the claimed catastrophes. Rather, we have consistently found that L-ACAOS-IS generally has a benign clinical prognosis. We present the general principle of coronary artery dysfunction in anatomical congenital anomalies (that only significant luminal coronary stenosis can have clinical repercussions). We then review anatomical and functional details of L-ACAOS-IS related to prognosis and treatment indications, which could explain many of the clinical presentations recently mentioned. Finally, we encourage our more liberal colleagues to recognize that, compared with normal coronary arteries, those with anomalies of origin and course are associated with frequent coronary spasm. In particular, we underscore that some of the ischemic manifestations and other results might actually be caused by pressure wire-induced artifacts (rigid wires tend to cause coronary spasm when advanced into tortuous coronary arteries).

Vasospastic angina following COVID-19 vaccine-related myocarditis: an underlying cause of chest pain.

We present a 13-year-old boy who had recurrent chest pain with elevated cardiac enzymes and abnormal ST segments in electrocardiogram 36 hours after the second dose of BNT162b2 vaccination. Cardiac MRI and coronary angiography with acetylcholine provocation confirmed myocarditis and vasospastic angina, respectively. Coronary vasospasm may play a pivotal role in the chest pain in COVID-19 vaccine-related myocarditis.

Kounis syndrome: an underestimated emergency.

Summary: Background. Kounis syndrome (KS) is defined as a rare cause of an acute coronary syndrome associated with systemic allergic reactions. To establish the prevalence of KS among the patients with diagnosis of anaphylaxis, we described clinical features, cardiological and allergological outcomes of patients evaluated in our allergy outpatient clinic. Methods. A retrospective study was carried out in the Allergy Unit of Novara hospital, from January 2008 to March 2020. Skin tests and in vitro tests were performed with suspected etiological agents. Results. We found 9 adults with KS (2%) out of 444 subjects who had experienced anaphylactic reactions (4/9 to Hymenoptera stings, 5/9 to drugs). Conclusions. The present study highlights the importance of suspicion of KS that appears not so uncommon in patients with anaphylaxis. KS seems to be a rare disease because unrecognized in diagnosis of anaphylaxis.

Increased plasma glutamate in non-smokers with vasospastic angina pectoris is associated with plasma cystine and antioxidant capacity.

Objectives. Endothelial dysfunction caused by oxidative stress plays an important role in the development of vasospastic angina pectoris (VSAP). Glutamate causes endothelial dysfunction by generating oxidative stress, and it inhibits cystine import into endothelial cells via the cystine/glutamate antiporter (XC-), which leads to depletion of antioxidant glutathione. However, whether glutamate and cystine are implicated in the pathogenesis of VSAP remains unclear. We investigated plasma glutamate and cystine levels, oxidative stress markers and antioxidant capacity in non-smoker patients with VSAP to determine whether glutamate and cystine are associated with the development of VSAP. We assessed 49 non-smokers assigned to groups with (n = 27) and without (n = 22) VSAP, and also measured plasma glutamate, cystine, nitrotyrosine, reactive oxygen metabolites and biological antioxidant potential. Results. Plasma glutamate and cystine values were significantly higher in the group with, than without VSAP (59.8 ± 25.7 vs. 43.5 ± 18.7 µmol/L, p = .016 and 35.3 ± 14.2 vs. 25.2 ± 9.1 µmol/L, p = .0056, respectively). Plasma glutamate and cystine values were significantly and positively associated (r = 0.32, p = .027). Levels of the oxidative stress markers nitrotyrosine and reactive oxygen metabolites, and biological antioxidant potential of as a measure of antioxidant capacity, did not significantly differ between the two groups. However, glutamate and biological antioxidant potential values were significantly and negatively associated (r = -0.3, p = .036). Conclusion. Plasma glutamate levels were increased in patients with VSAP who did not smoke, and they were positively associated with plasma cystine and negatively associated with the biological antioxidant potential levels.

Analysis of clinical characteristics of Kounis syndrome induced by contrast media.

BACKGROUND: Understanding the relationship between contrast agents and Kounis syndrome (KS) is mainly based on case reports. The purpose of this research is to explore the clinical characteristics of contrast media induced KS. METHODS: We searched for contrast-induced KS case reports through Chinese and English databases from 1991 to October 31, 2021. RESULTS: A total of 26 patients (19 men and 7 women,) were included, with a median age of 60 years (range 30-83). The contrast agents that cause KS mainly included gadolinium-based contrast agent (7 cases), iodine-containing contrast media (12 cases). KS mainly occurred within 30 min after administration and mainly manifests as chest pain and allergic reactions. Electrocardiogram (ECG) mainly showed ST elevation. Echocardiography mainly revealed normal. Coronary angiography showed normal, coronary vasospasm, stent thrombosis, occlusion and stenosis. After treatment with steroids, antihistamines and anti-ischemic therapy, 24 patients recovered completely and 2 patients died. CONCLUSIONS: KS is a rare adverse reaction of contrast media. Radiologists should recognize this rare but serious disease to ensure rapid diagnosis and proper management.

Mechanisms of Coronary Ischemia in Women.

PURPOSE OF REVIEW: Obstructive coronary artery disease is a major cause of ischemia in both men and women; however, women are more likely to present with ischemia in the setting of no obstructive coronary arteries (INOCA) and myocardial infarction with no obstructive coronary arteries (MINOCA), conditions that are associated with adverse cardiovascular prognosis despite absence of coronary stenosis. In this review, we focus on mechanisms of coronary ischemia that should be considered in the differential diagnosis when routine anatomic clinical investigation leads to the finding of non-obstructive coronary artery disease on coronary angiography in the setting of acute myocardial infarction. RECENT FINDINGS: There are multiple mechanisms that contribute to MINOCA, including atherosclerotic plaque disruption, coronary artery spasm, coronary microvascular dysfunction (CMD), coronary embolism and/or thrombosis, and spontaneous coronary artery dissection. Non-coronary causes such as myocarditis or supply-demand mismatch should also be considered on the differential when there is an unexplained troponin elevation. Use of advanced imaging and diagnostic techniques to determine the underlying etiology of MINOCA is feasible and helpful, as this has the potential to guide management and secondary prevention. Failure to identify the underlying cause(s) may result in inappropriate treatment and inaccurate counseling to patients. MINOCA predominates in young women and is associated with a guarded prognosis. The diagnosis of MINOCA should prompt further investigation to determine the underlying cause of troponin elevation. Patients with INOCA and MINOCA are heterogeneous, and response to treatments can be variable. Large randomized controlled trials to determine longer-term optimal medical therapy for management of these conditions are under investigation.

Mental Stress-Induced Myocardial Ischemia.

PURPOSE OF REVIEW: To summarize recent evidence on mental stress-induced myocardial ischemia (MSIMI), its mechanisms, and clinical significance. RECENT FINDINGS: MSIMI can occur in patients with normal cardiac stress testing, is only weakly related to severity of coronary artery disease (CAD), and it is often silent. Among patients with CAD, MSIMI is associated with a twofold increased risk of major adverse cardiovascular events compared to those who do not have MSIMI. Certain groups such as young women with myocardial infarction and those with psychological comorbidities are more susceptible to MSIMI. Abnormal microvascular vasoreactivity and inflammation are implicated mechanisms in MSIMI. Increased brain activity in regions that modulate autonomic reactivity to emotional stress and fear is associated with MSIMI. MSIMI has important prognostic implications in patients with CAD. Stress can no longer be ignored as a risk factor in cardiology care. Clinical trials testing effective strategies to target MSIMI are needed.

Allergen-Related Coronary Vasospasm "Kounis Syndrome" Requiring Administration of Epinephrine and a Coronary Vasodilator.

Kounis syndrome is an anaphylactic reaction leading to acute coronary syndrome. The acute treatment of anaphylaxis is epinephrine; however, epinephrine may cause coronary vasoconstriction, reduce coronary blood flow, increase myocardial oxygen demand, and worsen myocardial ischemia. On the other hand, coronary vasodilation, a treatment for acute coronary syndrome, can aggravate hypotension in patients with anaphylaxis. Herein, the authors report a case of type II Kounis syndrome, with vasospasm in a patient with coronary disease, requiring the administration of epinephrine and a coronary vasodilator for resuscitation. The authors administered intravenous epinephrine continuously from lower dosages and performed delicate titration. The coronary vasodilator nicorandil, which has little effect on hemodynamics, also was administered. These treatments improved hemodynamics without complications. Circulatory management that considers both anaphylaxis and coronary lesions is crucial to improve prognosis in this syndrome.

Kounis Syndrome Following Hypnale zara (Hump-Nosed Pit Viper) Bite in Sri Lanka.

A 47-y-old man was bitten by a hump-nosed viper (Hypnale zara) and gradually developed retrosternal chest pain associated with ST segment elevation on electrocardiogram. He had normal troponin I levels and no evidence of coagulopathy. Initially, he was managed as having anterior ST elevation myocardial infarction with thrombolysis. Later, because troponin levels were normal, he was suggested to have the type I variant of Kounis syndrome (allergic coronary artery spasm). This was supported by high eosinophil counts in peripheral blood. He was successfully managed with supportive treatment and discharged 6 d after the snakebite. Cardiac complications are rarely reported after hump-nosed viper bites, and clinical reports of coronary vasospasm after snakebites are extremely rare in the literature. This is the first known report of Kounis syndrome after a hump-nosed viper bite.

Diagnostic approach in patients with angina and no obstructive coronary artery disease: emphasising the role of the coronary function test.

BACKGROUND: Many patients with angina do not have obstructive coronary artery disease (CAD), also referred to as "Ischaemia with No Obstructive Coronary Arteries" (INOCA). Coronary vascular dysfunction is the underlying cause of this ischaemic heart disease in as much as 59-89% of these patients, including the endotypes of coronary microvascular dysfunction and epicardial coronary vasospasm. Currently, a coronary function test (CFT) is the only comprehensive diagnostic modality to evaluate all endotypes of coronary vascular dysfunction in patients with INOCA. OBJECTIVE: In this paper we discuss the relevance of performing a CFT, provide considerations for patient selection, and present an overview of the procedure and its safety. METHODS: We reviewed the latest published data, guidelines and consensus documents, combined with a discussion of novel original data, to present this point of view. RESULTS: The use of a CFT could lead to a more accurate and timely diagnosis of vascular dysfunction, identifies patients at risk for cardiovascular events, and enables stratified treatment which improves symptoms and quality of life. Current guidelines recommend considering a CFT in patients with INOCA and persistent symptoms. The safety of the procedure is comparable to that of a regular coronary angiography with physiological measurements. Non-invasive alternatives have limited diagnostic accuracy for the identification of coronary vascular dysfunction in patients with INOCA, and a regular coronary angiography and/or coronary computed tomography scan cannot establish the diagnosis. CONCLUSIONS: A complete CFT, including acetylcholine and adenosine tests, should be considered in patients with INOCA.

Contemporary Diagnosis and Management of Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease: A Scientific Statement From the American Heart Association.

Myocardial infarction in the absence of obstructive coronary artery disease is found in ≈5% to 6% of all patients with acute infarction who are referred for coronary angiography. There are a variety of causes that can result in this clinical condition. As such, it is important that patients are appropriately diagnosed and an evaluation to uncover the correct cause is performed so that, when possible, specific therapies to treat the underlying cause can be prescribed. This statement provides a formal and updated definition for the broadly labelled term MINOCA (incorporating the definition of acute myocardial infarction from the newly released "Fourth Universal Definition of Myocardial Infarction") and provides a clinically useful framework and algorithms for the diagnostic evaluation and management of patients with myocardial infarction in the absence of obstructive coronary artery disease.

Cardiac Lymphatic Dysfunction Causes Drug-Eluting Stent-Induced Coronary Hyperconstricting Responses in Pigs In Vivo.

Objective- We have previously demonstrated that coronary adventitial inflammation plays important roles in the pathogenesis of coronary vasomotion abnormalities, including drug-eluting stent (DES)-induced coronary hyperconstricting responses. Importantly, the adventitia also harbors lymphatic vessels, which may prevent inflammation by transporting extravasated fluid and inflammatory cells. We thus aimed to examine the roles of coronary adventitial lymphatic vessels in the pathogenesis of DES-induced coronary hyperconstricting responses in a porcine model in vivo. Approach and Results- We performed 2 experimental studies. In protocol 1, 15 pigs were divided into 3 groups with or without DES and with bare metal stent. Nonstented sites 20 mm apart from stent implantation also were examined. In the protocol 2, 12 pigs were divided into 2 groups with or without lymphatic vessels ligation followed by DES implantation at 2 weeks later (n=6 each). We performed coronary angiography 4 weeks after DES implantation, followed by immunohistological analysis. In protocol 1, the number and the caliber of lymphatic vessels were greater at only the DES edges after 4 more weeks. In protocol 2, coronary hyperconstricting responses were further enhanced in the lymphatic vessels ligation group associated with adventitial inflammation, Rho-kinase activation, and less adventitial lymphatic vessels formation. Importantly, there were significant correlations among these inflammation-related changes and enhanced coronary vasoconstricting responses. Conclusions- These results provide evidence that cardiac lymphatic vessel dysfunction plays important roles in the pathogenesis of coronary vasoconstrictive responses in pigs in vivo.

ST segment elevation in an adult chest pain patient: A case of coronary artery vasospasm.

Chest pain is one of the most common symptoms of patients presenting to the emergency department (ED) in the United States, accounting for up to eight million cases annually. We present a 55-year-old male who was brought in to the ED with sudden onset chest pain and was found to have ST-segment elevations in the infero-lateral leads on electrocardiogram (ECG). These changes resolved with nitroglycerin. Coronary artery vasospasm was diagnosed as coronary angiogram was normal. Calcium channel blocker was prescribed with good symptom relief. The most important teaching point is, coronary vasospasm as a cause of ST-segment elevation is missed frequently and should be considered among the differentials in patients presenting with chest pain. Nitrates and/or calcium channel blockers along with avoidance of triggers can help in symptom management.

Vasospasm-related Sudden Cardiac Death Has Outcomes Comparable with Coronary Stenosis in Out-of-Hospital Cardiac Arrest.

BACKGROUND: Characteristics of coronary vasospasm-related sudden cardiac death are not well understood. We aimed to compare the characteristics and clinical outcomes between coronary vasospasm and stenosis, in out-of-hospital cardiac arrest (OHCA) survivors, who underwent coronary angiogram (CAG). METHODS: We conducted a multicenter retrospective observational registry-based study at 8 Korean tertiary care centers. Data of OHCA survivors undergoing CAG between 2010 and 2015 were extracted. Patients were divided into vasospasm and stenosis (stenosis > 50%) groups based on CAG findings. The primary and the secondary outcomes were survival and a good neurologic outcome at 30 days after OHCA. Patients in the vasospasm and stenosis groups were propensity score matched. RESULTS: Of the 413 included patients, vasospasm and stenosis groups comprised 87 and 326 patients, respectively. There were 279 (66.7%) survivors and 206 (49.3%) patients with good neurologic outcomes. The vasospasm group had better clinical characteristics for outcome (younger age, less diabetes and hypertension, more prehospital restoration of spontaneous circulation, higher Glasgow Coma Scale, less ST segment elevation, and less requirement of circulatory support). The vasospasm group had better survival (75/87 vs. 204/326, P < 0.001) and good neurologic outcomes (62/87 vs. 144/326, P < 0.001). However, vasospasm was not independently associated with survival (odds ratio [OR], 0.980; 95% confidence interval [CI], 0.400-2.406) or neurologic outcomes (OR, 0.870; 95% CI, 0.359-2.108) after adjustment and vasospasm was not associated with survival and neurologic outcome in propensity score-matched cohorts. CONCLUSION: Our analysis of propensity score-matched cohorts finds that vasospasm OHCA survivors have survival and neurologic outcomes comparable with those of stenotic OHCA survivors.

Ischaemia with no obstructive coronary arteries.

Ischaemia with no obstructive coronary arteries (INOCA) is a common ischaemic heart disease with a female preponderance, mostly due to underlying coronary vascular dysfunction comprising coronary microvascular dysfunction and/or epicardial coronary vasospasm. Since standard ischaemia detection tests and coronary angiograms are not suitable to diagnose coronary vascular dysfunction, INOCA is often overlooked in current cardiology practice. Future research, including large outcome trials, is much awaited. Yet, adequate diagnosis is possible and treatment options are available and vital to reduce symptoms and most probably improve cardiovascular prognosis. This review intends to give a brief overview of the clinical presentation, underlying pathophysiology, and the diagnostic and treatment options in patients with suspected INOCA.

Vancomycin-induced Kounis Syndrome.

Kounis Syndrome is a rare allergic reaction that results in coronary vasospasm and may occur in patients with and without coronary artery disease. A 57-year-old man receiving pre-operative vancomycin for osteomyelitis and gangrene of the foot experienced an episode of anginal symptoms associated with transient ischemic 12-lead electrocardiogram (ECG) changes. The patient's symptoms and ECG changes abated with discontinuation of vancomycin and subsequent coronary angiography revealed no evidence of coronary artery disease. Treatment of Kounis Syndrome begins with cessation of the causative agent. Consensus guidelines for the management of Kounis Syndrome have not been established but treatment should both dilate the coronary vessels and suppress the allergic response. Coronary vasospasm after administration of antibiotics, including vancomycin, is a rare but serious reaction. It is important that Emergency Physicians recognize Kounis Syndrome as an uncommon yet dramatic and consequential reaction to such a commonly-administered antibiotic.

Intracoronary focal nitroglycerin injection through drilled balloon is very effective in the resolution of coronary spasm versus into proximal coronary artery: A prospective randomized comparison study.

BACKGROUND: In this study, we aimed to compare the effectiveness and safety of NTG administration via catheter and local NTG infusion through a perforated balloon in order to prevent coronary spasm from developing during percutaneous intervention. METHOD: The study began with 1:1 randomization into two groups of a total of 1688 patients scheduled for PCT. A total of 91 patients in the proximal group who developed lesions received 500 mcg NTG through a catheter, while 85 patients in the local group with lesions developed during the procedure received 500 mcg local NTG through a perforated balloon. After excluding patients who did not develop lesions during the procedure, and those without any change in the lesion with NTG application, the study was completed with 74 patients in the local group, and 70 patients in the proximal group. RESULTS: Both groups were similar in terms of basic characteristics. Incidences of procedure-related hypotension (10% vs 52%, P < 0.001) and tachycardia (20% vs 57%, P < 0.001) were significantly lower in the local NTG group. Success in addressing spasm was significantly higher in the local NTG than in the proximal NTG group (91.66 ± 14.09% vs 75.99 ± 16.86%, P < 0.001). DISCUSSION: Intracoronary injection with a perforated balloon, a simple technique introduced worldwide with our publication, can be used for administration of local NTG. Using this method, NTG can be better delivered with the perforated balloon to the vascular epithelium because of lower output, higher eruption rate, and perpendicularity to the endothelium. In this application, the balloon can better deliver drugs to the desired area via back-and-forth movements using a 0.014 guidewire. CONCLUSION: The local administration of NTG to a spasming area through a perforated balloon is more effective and safer than the proximal administration of NTG.