cardiovascular-agents and Hypersensitivity

The advent of drug-eluting stents (DES) has revolutionized the field of interventional cardiology. Their dramatic and persistent restenotic and target lesion revascularization advantages are unquestioned. However, concerns over the rare but potentially catastrophic risk of stent thrombosis (ST) have tempered universal acceptance of these devices. Although the precise mechanism of DES ST is undoubtedly multifactorial and as yet not fully elucidated, delayed or incomplete endothelial healing clearly plays a pivotal role. Detailed histopathological data have implicated a contributory allergic or hypersensitivity component, as verified by the Food and Drug Administration's Manufacturer and User Device Experience Center and the Research on Adverse Drug/device events And Reports (RADAR) project. These findings thus suggest a potential connection with the Kounis syndrome, the concurrence of acute coronary events with allergic, hypersensitivity, anaphylactic, or anaphylactoid reactions. Potential culprits responsible for this phenomenon include: arachidonic acid metabolites such as leukotrienes and thromboxane, proteolytic enzymes such as chymase and tryptase, histamine, cytokines, and chemokines. Additionally, inflammatory cells such as macrophages, T-lymphocytes, and mast cells are probably also contributory. Autopsy-confirmed infiltrates of various inflammatory cells including lymphocytes, plasma cells, macrophages, and eosinophils have been reported in all 3 vascular wall layers and are reminiscent of those associated with the Kounis syndrome. Although the concurrence of acute coronary syndromes with hypersensitivity reactions has been long established, the specific association with DES ST remains unproven. Potential incorporation of hypersensitivity suppressive agents might represent a promising paradigm shift from efficacy to safety in future DES designs.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Disease; Drug Hypersensitivity; Drug-Eluting Stents; Humans; Hypersensitivity; Metals; Practice Guidelines as Topic; Prosthesis Design; Risk Assessment; Risk Factors; Thrombosis; Treatment Failure

There is a fascinating and exceedingly important area of medicine that most of us have not been exposed to at any level of our medical training. This relatively new area is termed chronobiology; that is, how time-related events shape our daily biologic responses and apply to any aspect of medicine with regard to altering pathophysiology and treatment response. For example, normally occurring circadian (daily cycles, approximately 24 hours) events, such as nadirs in epinephrine and cortisol levels that occur in the body around 10 PM to 4 AM and elevated histamine and other mediator levels that occur between midnight and 4 AM, play a major role in the worsening of asthma during the night. In fact, this nocturnal exacerbation occurs in the majority of asthmatic patients. Because all biologic functions, including those of cells, organs, and the entire body, have circadian, ultradian (less than 22 hours), or infradian (greater than 26 hours) rhythms, understanding the pathophysiology and treatment of disease needs to be viewed with these changes in mind. Biologic rhythms are ingrained, and although they can be changed over time by changing the wake-sleep cycle, these alterations occur over days. However, sleep itself can adversely affect the pathophysiology of disease. The non-light/dark influence of biologic rhythms was first described in 1729 by the French astronomer Jean-Jacques de Mairan. Previously, it was presumed that the small red flowers of the plant Kalanchoe bloss feldiuna opened in the day because of the sunlight and closed at night because of the darkness. When de Mairan placed the plant in total darkness, the opening and closing of the flowers still occurred on its intrinsic circadian basis. It is intriguing to think about how the time of day governs the pathophysiology of disease. On awakening in the morning, heart rate and blood pressure briskly increase, as do platelet aggregability and other clotting factors. This can be linked to the acrophase (peak event) of heart attacks. During the afternoon we hit our best mental and physical performance, which explains why most of us state that "I am not a morning person." Even the tolerance for alcohol varies over the 24-hour cycle, with best tolerance around 5 pm (i.e. "Doctor, I only have a couple of highballs before dinner"). Thus, all biologic functions, from those of the cell, the tissue, the organs, and the entire body, run on a cycle of altering activity and function.(ABSTRACT TRUNCATED AT 400 W

Topics: Arthritis; Autonomic Nervous System Diseases; Cardiovascular Agents; Cardiovascular Diseases; Chronobiology Phenomena; Circadian Rhythm; Endocrine System Diseases; Female; Gastrointestinal Diseases; Hematologic Diseases; Humans; Hypersensitivity; Kidney Diseases; Male; Nervous System Diseases; Neuromuscular Diseases; Phototherapy; Respiratory Physiological Phenomena; Respiratory Tract Diseases; Sleep; Sleep Apnea Syndromes

A 54-year-old woman treated with cobalt-chromium everolimus eluting stents (CoCr-EES) for her left distal circumflex and diagonal branch lesions suffered from repeated in-stent restenosis in both lesions. Neointimal proliferation occurred rapidly and almost simultaneously in the two lesions. The cause was established to be metal allergy, as determined by patch tests which were strongly positive for bare metal stents and weakly positive for CoCr-EES. Following the third successive angioplasty, we initiated treatment with prednisolone (30 mg daily) and the anti-allergic and anti-proliferative drug tranilast (300 mg daily). An elective angiogram performed 3 months later showed no evidence of in-stent restenosis in any of the stented lesions. Furthermore, the patient has remained angina-free for 15 months. The unique features of this case include: (1) near-simultaneous repeated multivessel in-stent restenosis in a patient with skin test-documented metal allergy to cobalt-chromium stents; (2) adjunctive systemic medical therapy with prednisolone and tranilast appeared to terminate the malignant restenotic cycle.

Topics: Anti-Allergic Agents; Cardiovascular Agents; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug Therapy, Combination; Drug-Eluting Stents; Everolimus; Female; Glucocorticoids; Humans; Hypersensitivity; Middle Aged; Neointima; ortho-Aminobenzoates; Patch Tests; Percutaneous Coronary Intervention; Predictive Value of Tests; Prednisolone; Prosthesis Design; Recurrence; Risk Factors; Tomography, Optical Coherence; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Drug-Eluting Stents; Everolimus; Humans; Hypersensitivity; Myocardial Infarction; Paclitaxel; Prosthesis Design; Sirolimus; Syndrome; Thrombosis; Treatment Outcome

Topics: Alloys; Cardiovascular Agents; Clinical Trials as Topic; Coronary Restenosis; Drug-Eluting Stents; Humans; Hypersensitivity; Incidence; Paclitaxel; Platelet Aggregation Inhibitors; Risk Factors; Sirolimus; Thrombosis; Time Factors

A 74-year-old woman presented with effort-induced chest pain. Diagnostic coronary angiography revealed three-vessel disease. A successful angioplasty was performed with two sirolimus-eluting stents placed in the left anterior descending artery (LAD) and left circumflex artery (LCX). The right coronary artery (RCA) was treated with a bare-metal stent. Follow-up angiography and intravascular ultrasound (IVUS) assessment were performed 8 months later, which showed late stent malapposition (LSM) with marked positive vascular remodeling around the drug-eluting stents (DES) in both LAD and LCX lesions, but there was no evidence of ectatic area around the BMS in the RCA lesion. Compared with the baseline IVUS, a significant increase in external elastic membrane (EEM) cross-sectional area was found. Twenty-seven months later, we performed repeat follow-up angiography. Intravascular ultrasound still showed vessel malapposition. A previous report showed that aneurysmal dilatation of the stented segment with severe localized hypersensitivity reaction could be a potential cause of late thrombosis after DES implantation. If LSM is related to hypersensitivity of the DES, it may have a potential risk of adverse events. Although there is a paucity of data regarding malapposition as the cause of adverse events, careful long-term follow-up of patients with vessel enlargement after DES placement is recommended.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Drug-Eluting Stents; Female; Humans; Hypersensitivity; Metals; Prosthesis Design; Severity of Illness Index; Sirolimus; Stents; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Topics: Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Clinical Trials as Topic; Coronary Thrombosis; Endothelium, Vascular; Humans; Hypersensitivity; Regeneration; Stents; Vascular Diseases; Wound Healing

Topics: Autoimmune Diseases; Cardiovascular Agents; Humans; Hypersensitivity; Myocarditis

Topics: Adrenal Cortex Hormones; Cardiovascular Agents; Glucocorticoids; Hypersensitivity

Topics: Anaphylaxis; Anti-Allergic Agents; Antihypertensive Agents; Cardiovascular Agents; Dihydroergotamine; Ear Auricle; Ergot Alkaloids; Guinea Pigs; Heart; Hypersensitivity; Lysergic Acid Diethylamide; Reserpine

Topics: Anaphylaxis; Animals; Cardiovascular Agents; Ergot Alkaloids; Hypersensitivity; Immune System Diseases; Rabbits

Topics: Cardiovascular Agents; Hypersensitivity; Muscle Relaxants, Central; Seizures; Succinylcholine