Search Results (70)

S-nitrosoglutathione (GSNO), a promising S-nitrosothiol, has been recognized for its ability to modulate vascular tone through its vasodilatory, antiplatelet, and antiproliferative effects. However, data on its vasodilatory effects in human vessels remain limited, and its mechanisms of action have yet to be fully elucidated. In this study, we aimed to investigate the vasorelaxant effect of GSNO and its underlying mechanisms, with particular focus on the soluble guanylate cyclase (sGC)/nitric oxide (NO) pathway and potassium channels in isolated human saphenous veins (SVs) obtained from patients undergoing coronary artery bypass grafting (CABG). GSNO (10⁻⁸–10⁻⁴ M) produced concentration-dependent relaxations in SV rings precontracted with phenylephrine. These relaxations were unaffected by NO synthase inhibition with L-NAME (10⁻⁴ M, 30 min) or NO scavenging with PTIO (10⁻⁴ M, 30 min), but were significantly reduced by the sGC inhibitor, ODQ (10⁻⁵ M, 30 min). Inhibition of ATP-sensitive (glibenclamid; 10⁻⁵ M, 30 min.), high-conductance Ca²⁺-activated (charybdotoxin; 10⁻⁷ M, 30 min), small-conductance Ca²⁺-activated (apamin; 10⁻⁶ M, 30 min), or voltage-dependent (4-aminopyridine; 10⁻³ M, 30 min) potassium channels did not alter the maximum relaxant responses to GSNO. Furthermore, pretreatment with GSNO (10⁻⁴ M, 30 min) significantly attenuated both the contractile response and sensitivity to phenylephrine. Collectively, these findings demonstrate that GSNO exerts acute vasorelaxant and modulatory effects in human SV primarily via cGMP-dependent mechanisms, highlighting its potential as a local therapeutic agent for preventing graft spasm in CABG. Full article

Coronary microvascular obstruction and dysfunction (CMVO) frequently arise following primary percutaneous coronary intervention (PCI), particularly in individuals with myocardial infarction. Despite the restoration of epicardial blood flow, microvascular perfusion might still be compromised, resulting in negative clinical outcomes. CMVO is a complex condition resulting from a combination of ischemia, distal thrombotic embolization, reperfusion injury, and individual susceptibilities such as inflammation and endothelial dysfunction. The pathophysiological features of this condition include microvascular spasm, endothelial swelling, capillary plugging by leukocytes and platelets, and oxidative stress. Traditional angiographic assessments, such as Thrombolysis in Myocardial Infarction (TIMI) flow grade and myocardial blush grade, have limited sensitivity. Cardiac magnetic resonance imaging (CMR) stands as the gold standard for identifying CMVO, while the index of microvascular resistance (IMR) is a promising invasive option. Treatment approaches involve powerful antiplatelet drugs, anticoagulants, and supersaturated oxygen, yet no treatment has been definitively shown to reverse established CMVO. CMVO remains a significant therapeutic challenge in coronary artery disease management. Enhancing the comprehension of its core mechanisms is vital for the development of more effective and personalized treatment strategies. Full article

Despite significant advances in understanding and management, cardiovascular diseases remain the leading cause of mortality worldwide. Historically, diagnostic and therapeutic strategies have typically targeted obstructive coronary arteries. However, growing evidence supports the pivotal role of non-obstructive mechanisms in myocardial ischemia, prompting a new classification that distinguishes Acute Myocardial Ischemic Syndromes from Non-Acute Myocardial Ischemic Syndromes. In this evolving context, Optical Coherence Tomography (OCT) plays an important diagnostic role in the assessment of both obstructive and non-obstructive ischemic mechanisms. In Acute Myocardial Ischemic Syndromes, OCT enables the identification of major plaque destabilization mechanisms and contributes to the diagnosis of Myocardial Infarction with Non-Obstructive Coronary Arteries, helping to differentiate between atherosclerotic and non-atherosclerotic causes. In Non-Acute Myocardial Ischemic Syndromes, OCT assists in evaluating stenosis severity, plaque morphology, vulnerability, and healing, and may contribute to the diagnosis of Ischemia with Non-Obstructive Coronary Arteries, identifying myocardial bridge and epicardial spasm alongside conventional functional assessment of intermediate stenoses. This narrative review outlines the expanding clinical applications of OCT across the full spectrum of ischemic syndromes, emphasizing its role in bridging obstructive and non-obstructive pathophysiology and supporting a more comprehensive diagnostic approach to ischemic heart disease. Full article

Background and Objectives: Radial artery spasm (RAS) is a frequent complication during invasive angiography using the transradial approach, leading to patient discomfort and procedural challenges. While intra-arterial nitroglycerine (NTG) effectively reduces RAS after sheath insertion, preprocedural prevention strategies are limited. This study evaluates the efficacy of topical NTG in improving radial artery puncture success and reducing RAS incidence. Materials and Methods: In a randomized, double-blind single-center study 100 patients undergoing angiography were pretreated with either topical NTG or placebo. Outcomes assessed included RAS incidence, radial artery puncture success, number of attempts, procedural duration, patient discomfort, and complications. RAS was evaluated angiographically and clinically, with additional subgroup analyses for diabetic and smoking patients. Results: Topical NTG significantly reduced RAS incidence (53.2% vs. 73.6%; p = 0.0349) and increased radial puncture success on the first attempt (89.4% vs. 77.4%; p = 0.0488). Diabetic patients particularly benefited from NTG application, with lower RAS rates (36.4% vs. 76.2%; p = 0.0296). No significant differences were observed in procedural duration, patient discomfort, or complication rates between groups. The placebo group demonstrated a higher incidence of diffuse RAS (p = 0.0109). Conclusions: Preprocedural topical NTG application is a safe, non-invasive intervention that improves radial artery access success and reduces RAS, especially in high-risk subgroups such as diabetics. These findings support its potential as a procedural optimization tool in cardiovascular interventions, particularly in patients with heart failure, who often require repeated and reliable vascular access. Full article

Coronary artery spasm (CAS) is a reversible vasoconstriction of normal or atherosclerotic epicardial coronary arteries with a subsequent reduction in myocardial blood flow, leading to myocardial ischemia, myocardial infarction, severe arrhythmias, or even sudden death. It is an entity that should be recognized based on a particular clinical presentation. Numerous differences exist between CAS and obstructive coronary disease in terms of mechanisms, risk factors, and therapeutic solutions. The gold standard for CAS diagnosis is represented by transitory and reversible occlusion of the coronary arteries at spasm provocation test, which consists of an intracoronary administration of Ach, ergonovine, or methylergonovine during angiography. The pathophysiology of CAS is not fully understood. However, the core of CAS is represented by vascular smooth muscle cell contraction, with a circadian pattern. The initiating event of this contraction may be represented by endothelial dysfunction, inflammation, or autonomic nervous system unbalance. Our study explores the intricate balance of these factors and their clinical relevance in the management of CAS. Full article

(1) Background: Prevalence of patent foramen ovale (PFO) in the general population is estimated at around 24%. We hypothesized that right-to-left shunting (RLS) resulting from PFO might contribute to angina symptoms in patients with coronary artery spasm (CAS), potentially triggered by vasoactive metabolites. Therefore, the aim of this study was to investigate the prevalence of PFO-related RLS in patients with documented CAS. (2) Methods: This single-center prospective cohort study included patients with documented CAS undergoing transthoracic echocardiography (TTE), including a contrast bubble study between 2021 and 2023. The Seattle Angina Questionnaire (SAQ) and Migraine Disability Assessment (MIDAS) were used to survey patients. (3) Results: RLS (PFO group) was observed in 11 of the 48 patients included (23%). In the PFO group, 64% had epicardial spasm and 36% microvascular spasm. Furthermore, RLS was more prevalent in patients with CAS and concomitant migraine (29%). Remarkably, the density plot of the SAQ summary score showed a worse score for patients with RLS (median of 38 [Q1–Q3: 31–49]) than patients without RLS (median of 49 [Q1–Q3: 41–55]) (p = 0.0282). (4) Conclusions: The prevalence of RLS due to PFO in patients with CAS was in line with the PFO prevalence in the general population, and patients with RLS are more symptomatic according to the SAQ summary score. Whether PFO closure could be beneficial to patients with CAS and concomitant migraine requires further investigation. Full article

Arterial and venous graft spasm can occur during harvesting or immediately after coronary artery bypass grafting (CABG), leading to increased perioperative morbidity and affecting graft patency rates. Bypass grafts harvested from diabetic patients are particularly prone to spasm. This study aimed to elucidate the functional characteristics of human bypass grafts for the internal mammary artery (IMA) and saphenous vein (SV), from both diabetic and non-diabetic patients, and to determine how diabetes affected their responses to spasmogenic and relaxant agents. SV and IMA graft rings isolated from diabetic and non-diabetic patients during CABG were placed in an isolated organ bath system. Contractions to potassium chloride (10–100 mM) and phenylephrine (10⁻⁸–10⁻⁴ M) were evaluated, and relaxation responses to acetylcholine (10⁻⁹–10⁻⁴ M) and sodium nitroprusside (10⁻⁸–10⁻⁴ M) were assessed to evaluate endothelial and smooth muscle function, respectively. We observed increased responses to phenylephrine, an alpha-1 adrenoceptor agonist, in both IMAs and SVs, as well as an increased responses to potassium chloride, a non-receptor agonist, in SVs in diabetic patients compared to non-diabetic patients. We did not observe any deterioration in endothelium-dependent relaxations in either SV or IMA grafts under diabetic conditions. This study is the first to demonstrate that diabetes exacerbates potassium chloride-induced contractions in human SV grafts. Understanding the differences in potassium chloride-induced contraction profiles between arterial and venous grafts is essential in optimizing graft spasm management and improving the patency rates of bypass grafts. Full article

Background: Diagnostic angiography of coronary arteries is one of the most common procedures in invasive cardiology and is mainly performed via the radial artery. Rapid improvements in the quality of the equipment and operator’s experience have changed the landscape of this procedure. Methods: In this study, 284 patients were analyzed to determine whether heparin administration should be a necessity for all patients to prevent radial artery occlusion (RAO). Moreover, the possible influence of 51 other factors on RAO was analyzed. Results: This study revealed that heparin administration does not have a significant impact on RAO incidence (p = 0.131). However, it was found that a longer fluoroscopy time (p < 0.001) and smaller (5F) vascular sheath (p = 0.001) might serve as protective factors against RAO. On the other hand, a greater number of catheters (p < 0.001), greater compression time (p = 0.001), wider (6F) vascular sheath (p = 0.002), spasm occurrence (p = 0.001), spasmolytic administration (p < 0.001) and atherosclerotic changes in the radial artery (p = 0.005) were risk factors for RAO. Conclusions: This study demonstrates the need for a more personalized approach to the patient when analyzing the individual risk of RAO. In our opinion, it is possible to omit heparin in cases of patients with an initial low risk of RAO or possible adverse drug reactions during diagnostic angiography. Full article

Background/Objectives: The diagnosis of coronary artery spasm (CAS) frequently requires invasive provocation testing, typically utilising acetylcholine (ACh). Although the left coronary artery (LCA) is routinely assessed as a part of the testing protocol, assessment of the right coronary artery (RCA) is often avoided since it requires the insertion of a temporary pacing wire. We sought to compare the prevalence of inducible CAS in the LCA and RCA, among patients with CAS undergoing multivessel spasm provocation testing with ACh. Methods: A local multi-institutional ANOCA (angina and non-obstructive coronary arteries) database was analysed, which included 316 patients with angina and suspected CAS who underwent provocation testing (single vessel n = 266, multivessel n = 50) with incremental bolus doses of intracoronary ACh (25, 50, 100 μg in the LCA; 25, 50 μg in the RCA). CAS was defined as >90% constriction of the epicardial coronary artery as assessed visually on coronary angiography. Results: In the 50 patients (55 ± 10 years, 77% female) who underwent multivessel spasm provocation testing, CAS was induced in 20 patients (40%), with ACh provoking CAS only in the LCA system in 45%, only in the RCA system in 35%, and both LCA/RCA in 20%. Conclusions: These findings demonstrate that assessing only the LCA may miss up to one-third of CAS cases. Therefore, it is essential to routinely evaluate the RCA, particularly when no inducible spasm is detected in the LCA. Full article

Coronary artery disease is one of the leading public health problems in the world in terms of mortality and economic burden from the disease. Traditionally, the focus of research and clinical pathways leading to the diagnosis and treatment of coronary artery disease was on the more common variant of the disease resulting from atherosclerosis in the epicardial coronary arteries. However, coronary microvasculature, representing the vast majority of the total heart circulation, has the greatest influence on overall coronary resistance and, therefore, blood flow. Coronary microvascular dysfunction (CMD), characterized by structural or functional abnormalities in the microvasculature, significantly impacts myocardial perfusion. Endothelial dysfunction results in inadequate coronary dilation during exercise or spontaneous spasm in the microvasculature or epicardial arteries. A significant proportion of people presenting for coronary angiography in the context of angina have unobstructed epicardial coronary arteries yet are falsely reassured about the benign nature of their condition. Meanwhile, increasing evidence indicates that patients diagnosed with CMD as well as vasospastic angina (VSA) face an increased risk of Major Adverse Cardiovascular Events (MACEs), including death. The aim of this review is to outline the current practice with regard to invasive and non-invasive methods of CMD and VSA diagnosis and assess the evidence supporting the existing treatment strategies. These include endotype-specific pharmacological therapies, a holistic approach to lifestyle modifications and risk factor management and novel non-pharmacological therapies. Furthermore, the review highlights critical gaps in research and suggests potential areas for future investigation, to improve understanding and management of these conditions. Full article

Myocardial infarction (MI) is a significant cardiovascular event caused by the decrease in or complete cessation of blood flow to a portion of the myocardium. It can arise from a variety of etiological factors, including pharmacological triggers. This review aims to explore the diverse drugs and substances that might lead to drug-induced myocardial infarction, focusing on their mechanisms of action and the pathophysiological processes involved. Various established and emerging pharmacological agents that could elevate the risk of myocardial infarction, such as nonsteroidal anti-inflammatory drugs, hormonal therapies, anticoagulants, and antipsychotic medications, are discussed. The role of drug-induced endothelial dysfunction, coronary artery spasm, and thrombosis are presented in order to highlight the underlying mechanisms. This review emphasizes the need for increased awareness among healthcare professionals to mitigate the risks associated with different pharmacological therapies to improve patient outcomes. Full article

Gender medicine has increasingly underscored the necessity of addressing sex-based differences in disease prevalence and management, particularly within cardiovascular conditions and drug intolerance. Women often present cardiovascular diseases distinctively from men, with a higher prevalence of non-obstructive coronary artery disease and varied ischemic manifestations, such as coronary microvascular dysfunction and epicardial or microvascular coronary spasm. This disparity is further exacerbated by elevated drug intolerance rates among women, influenced by hormonal, genetic, and psychosocial factors. The 2024 ESC guidelines for managing chronic coronary syndromes stress the need for personalized approaches to treat angina and ischemia with non-obstructive coronary artery disease (ANOCA/INOCA), recommending a combination of antianginal medications. Despite standard treatments, up to 40% of ANOCA/INOCA patients experience refractory angina, necessitating a multifaceted approach that often involves multiple antianginal drugs, which can increase the likelihood of drug intolerances. Future research should focus on including women in drug studies and addressing sex-specific differences, while healthcare providers must be equipped to manage gender-specific drug intolerances. Enhanced awareness, individualized treatment strategies, and gender-sensitive healthcare policies are crucial for improving outcomes and bridging the gender gap in cardiovascular medicine. Full article

Background: Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis usually affects small blood vessels and is characterized by the presence of circulating autoantibodies (c-ANCA or p-ANCA). The risk of cardiovascular events is threefold higher compared to general population, and cardiac manifestations include myocarditis, pericarditis, valvulitis, aortitis, or coronary arteritis. Coronary involvement is very rare, but it is a potentially life-threatening manifestation. Methods: We present an atypical cardiac scenario of p-ANCA vasculitis. Results: A 68-year-old woman with known p-ANCA vasculitis and stage 5 chronic kidney disease (CKD) on hemodialysis presented with dizziness accompanied by low blood pressure and chest pain. Electrocardiogram on arrival showed slightly ST-T changes, with negative cardiac biomarkers and no abnormalities in cardiac regional wall motion. Five hours after presentation, the patient repeated chest pain, accompanied by a drop in blood pressure and junctional escape rhythm. The highly sensitive cardiac troponin I (hs-cTnI) was raised at 560 ng/L. Coronary angiography showed coronary arteries without significant stenosis. The provocative test with intracoronary ergonovine demonstrated coronary vasospasm of the anterior descending artery accompanied by chest pain, with resolution after intracoronary nitroglycerin. Under amlodipine, nitrate, acetylsalicylic acid, statin and corticosteroids the patient did not experience the recurrence of angina. Conclusions: This case illustrates coronary involvement, manifested as coronary spasm with favorable outcomes, in systemic vasculitis. The underlying mechanism is immune-mediated inflammation in vascular walls. Full article

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a clinical entity characterized by the absence of significant coronary artery obstruction in epicardial arteries (<50%) on coronary angiography in the setting of acute myocardial infarction (AMI). This article aims to provide a narrative review of the pathophysiological mechanisms, diagnostic challenges, and prognosis associated with MINOCA based on pathophysiology regarding the atherosclerotic and non-atherosclerotic causes. Etiological factors, including thromboembolism, coronary artery spasm, spontaneous coronary artery dissection, coronary microvascular disease, and supply–demand mismatch, are addressed. Imaging modalities such as echocardiography, advances in coronary angiography like intravascular ultrasound (IVUS) and optical coherence tomography (OCT), cardiac magnetic resonance (CMR), and coronary computed tomography angiography (CCTA) are also analyzed. MINOCA patients have a better short-term prognosis compared to those with obstructive coronary artery disease but face significant long-term risks, underscoring the need for precise diagnosis and management strategies. Elevated inflammatory markers and specific genetic predispositions are also associated with adverse outcomes in MINOCA. This review focused on MINOCA from a pathophysiological perspective on the diverse underlying mechanisms, the challenges in achieving accurate diagnosis, the importance of a tailored therapeutic approach and the necessity for further investigation of clinical outcomes. Full article

Acute adverse reactions to COVID-19 mRNA vaccines are a major concern, as autopsy reports indicate that deaths most commonly occur on the same day of or one day following vaccination. These acute reactions may be due to cytokine storms triggered by lipid nanoparticles (LNPs) and anaphylaxis induced by polyethene glycol (PEG), both of which are vital constituents of the mRNA-LNP vaccines. Kounis syndrome, in which anaphylaxis triggers acute coronary syndrome (ACS), may also be responsible for these cardiovascular events. Furthermore, COVID-19 mRNA-LNP vaccines encompass adjuvants, such as LNPs, which trigger inflammatory cytokines, including interleukin (IL)-1β and IL-6. These vaccines also produce spike proteins which facilitate the release of inflammatory cytokines. Apart from this, histamine released from mast cells during allergic reactions plays a critical role in IL-6 secretion, which intensifies inflammatory responses. In light of these events, early reduction of IL-1β and IL-6 is imperative for managing post-vaccine cytokine storms, ACS, and myocarditis. Corticosteroids can restrict inflammatory cytokines and mitigate allergic responses, while colchicine, known for its IL-1β-reducing capabilities, could also prove effective. The anti-IL-6 antibody tocilizumab also displays promising treatment of cytokine release syndrome. Aside from its significance for treating anaphylaxis, epinephrine can induce coronary artery spasms and myocardial ischemia in Kounis syndrome, making accurate diagnosis essential. The upcoming self-amplifying COVID-19 mRNA-LNP vaccines also contain LNPs. Given that these vaccines can cause a cytokine storm and allergic reactions post vaccination, it is crucial to consider corticosteroids and measure IL-6 levels for effective management. Full article