cardiovascular-agents and Tachycardia--Supraventricular

To date, up to 65% of drugs used in neonates and infants are off-label or unlicensed, as they were implemented in clinical care without the usual regulatory phases of pharmacological drug development. Pharmacotherapy in this age group is still mainly based on the individual clinical expertise of specialized pediatricians. Pharmacological trials involving neonates are indeed more difficult to perform: appropriate dosing is hampered by the rapid physiological changes occurring at this stage of development, and the selection of proper end-points and biomarkers is complicated by the limited knowledge of the pathophysiology of the specific diseases of infancy. Moreover, there are many ethical challenges in planning and conducting drug studies in pediatric patients (especially in newborns and infants). In the current review, we address some challenges and discuss possible perspectives to stimulate scientific and clinical pharmacological research in neonates and infants. We hereby aim to illustrate the add on value of the regulatory framework for model-based neonatal medicinal development currently used in Europe and the United States. We provide several examples of successful recent pharmacological trials performed in neonates and infants. In these examples, success was ensured by the implementation of specific pharmacokinetic assessments, thanks to accurate drug dosing achieved with a combination of dose validation, population pharmacokinetics and mathematical models of drug clearance and distribution; moreover, age-specific pharmacodynamics was considered via appropriate evaluations of drug efficacy with end-points adapted to the peculiar pathophysiology of diseases in this age group. These "pharmacological" challenges add to the ethical challenges that are always present in planning and conducting clinical studies in neonates and infants and support the opinion that clinical research in pediatrics should be evaluated by ad hoc ethical committees with specific expertise.

Topics: Anti-Bacterial Agents; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Dose-Response Relationship, Drug; Drug Discovery; Humans; Infant; Infant, Newborn; Pediatrics; Pharmaceutical Research; Tachycardia, Supraventricular

Paroxysmal supraventricular tachycardia (PSVT) is a well-known and thoroughly studied clinical syndrome, characterized by regular tachycardia rhythm with sudden onset and abrupt termination. Most patients present with palpitations and dizziness, and their electrocardiogram demonstrates a narrow QRS complex and regular tachycardia with hidden or inverted P waves. PSVT is caused by re-entry due to the presence of inhomogeneous, accessory, or concealed conducting pathways. Hemodynamically stable patients are treated by vagal maneuvers, intravenous adenosine, diltiazem, or verapamil, hemodynamically unstable patients are treated by cardioversion. Patients with symptomatic and recurrent PSVT can be treated with long-term drug treatment or catheter ablation.

Topics: Cardiovascular Agents; Disease Management; Electrocardiography; Humans; Tachycardia, Paroxysmal; Tachycardia, Supraventricular

Supraventricular tachycardia (SVT) is a common cardiac rhythm disturbance; it usually presents with recurrent episodes of tachycardia, which often increase in frequency and severity with time. Although SVT is usually not life-threatening, many patients suffer recurrent symptoms that have a major impact on their quality of life. The uncertain and sporadic nature of episodes of tachycardia can cause considerable anxiety - many patients curtail their lifestyle as a result, and many prefer curative treatment. SVT often terminates before presentation, and episodes may be erroneously attributed to anxiety. Sudden-onset, rapid, regular palpitations characterise SVT and, in most patients, a diagnosis can be made with a high degree of certainty from patient history alone. Repeated attempts at electrocardiographic documentation of the arrhythmia may be unnecessary. Treatment of SVT may not be necessary when the episodes are infrequent and self-terminating, and produce minimal symptoms. When episodes of tachycardia occur frequently, are prolonged or are associated with symptoms that affect quality of life, catheter ablation is the first choice of treatment; it is a low-risk procedure with a high success rate. Long-term preventive pharmacotherapy is an alternative approach in some patients.

Topics: Adenosine; Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Cardiovascular Agents; Diltiazem; Electrocardiography; Electrocardiography, Ambulatory; Heart Conduction System; Humans; Pre-Excitation Syndromes; Tachycardia, Atrioventricular Nodal Reentry; Tachycardia, Supraventricular; Verapamil

Over decades, anesthesiologists have used intravenous adenosine as mainstay therapy for diagnosing or treating supraventricular tachycardia in the perioperative setting. More recently, specific adenosine receptor therapeutics or gene-targeted mice deficient in extracellular adenosine production or individual adenosine receptors became available. These models enabled physicians and scientists to learn more about the biologic functions of extracellular nucleotide metabolism and adenosine signaling. Such functions include specific signaling effects through adenosine receptors expressed by many mammalian tissues; for example, vascular endothelia, myocytes, hepatocytes, intestinal epithelia, or immune cells. At present, pharmacological approaches to modulate extracellular adenosine signaling are evaluated for their potential use in perioperative medicine, including attenuation of acute lung injury; renal, intestinal, hepatic and myocardial ischemia; or vascular leakage. If these laboratory studies can be translated into clinical practice, adenosine receptor-based therapeutics may become an integral pharmacological component of daily anesthesiology practice.

Topics: Adenosine; Anesthesia; Animals; Cardiovascular Agents; Extracellular Space; Humans; Hypoxia; Intraoperative Complications; Perioperative Care; Signal Transduction; Tachycardia, Supraventricular

Atrial fibrillation occurs and maintains itself in the context of a morphologically and functionally altered atrial substrate that can be induced by stressors such as underlying diseases (cardiac or noncardiac) or aging. The resultant structural remodeling is a slow process that progressively affects myocytes and the myocardial interstitium, and takes place from as early as the first days of atrial tachyarrhythmia. The left atrium, and particularly its posterior wall, is the location where remodeling is concentrated to the greatest extent. The mechanisms that underlie the remodeling process in atrial fibrillation have not yet been completely elucidated, although experimental and clinical investigations have indicated a number of signaling systems, inflammation, oxidative stress, atrial stretching and ischemia as factors involved in the cascade of events that leads to atrial fibrillation. The aim of this Review is to provide a comprehensive overview of the morphological changes that characterize the fibrillating atrial myocardium at histological and ultrastructural levels, and the established and hypothetical pathogenetic mechanisms involved in structural remodeling. This article also highlights the emerging therapies being developed to prevent progression of atrial fibrillation.

Topics: Animals; Atrial Fibrillation; Atrial Function; Cardiovascular Agents; Catheter Ablation; Cell Death; Connexins; Disease Models, Animal; Disease Progression; Fibrosis; Heart Atria; Humans; Inflammation; Myocardial Ischemia; Myocardium; Oxidative Stress; Risk Factors; Tachycardia, Supraventricular; Treatment Outcome

Ivabradine has been approved for the treatment of chronic heart failure and chronic stable angina pectoris in Europe. Based on adverse outcomes of reproductive animal studies and the lack of human data, ivabradine is considered contraindicated during pregnancy. The aim of this observational study is to analyse ivabradine use before and during pregnancy.. We evaluated all ivabradine-related requests to the German Embryotox Institute from 2007 to 2019. Exposed pregnancies were analysed as to their outcome.. Off-label use for supraventricular tachycardia was frequent in women of childbearing age. Of 38 prospectively ascertained pregnancies with ivabradine exposure and completed follow-up, 32 resulted in live births, 3 in spontaneous abortions, and 3 were electively terminated. One neonate presented with major birth defects (atrial septal defect and cleft palate). In 33/38 patients, ivabradine was discontinued after confirmation of pregnancy without cardiac deterioration and 5/38 women continued ivabradine throughout pregnancy. In addition, there were 3 retrospectively reported pregnancies including one major birth defect (tracheal atresia).. This case series represents the largest cohort of ivabradine-exposed pregnancies, published so far. According to our findings, ivabradine appears not to be a major teratogen. However, established drugs of choice with strong evidence of low risk for the unborn should be preferred in women planning pregnancy. After inadvertent exposure during pregnancy or lack of treatment alternatives, fetal ultrasound for structural anomalies and growth restriction is recommended. In addition, close monitoring is necessary in pregnant women with supraventricular arrhythmias or cardiac disease.

Topics: Abortion, Spontaneous; Adult; Cardiovascular Agents; Congenital Abnormalities; Female; Humans; Ivabradine; Pregnancy; Pregnancy Outcome; Retrospective Studies; Tachycardia, Supraventricular

Topics: Action Potentials; Cardiomyopathies; Cardiovascular Agents; Defibrillators, Implantable; Electric Countershock; Electrocardiography; Female; Heart Rate; Humans; Immunosuppressive Agents; Middle Aged; Tachycardia, Supraventricular; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Incessant focal atrial tachycardia (FAT), if untreated, can lead to ventricular dysfunction and heart failure (tachycardia-induced cardiomyopathy). Drug therapy of FAT is often difficult and ineffective. The efficacy of ivabradine has not been systematically evaluated in the treatment of FAT.. The study group consisted of patients with incessant FAT (lasting >24 hours) and structurally normal hearts. Patients with ventricular dysfunction as a consequence of FAT were not excluded. All antiarrhythmic drugs were discontinued at least 5 half-lives before the initiation of ivabradine. Oral ivabradine (adults, 10 mg twice 12 hours apart; pediatric patients: 0.28 mg/kg in 2 divided doses) was initiated in the intensive care unit under continuous electrocardiographic monitoring. A positive response was defined as the termination of tachycardia with the restoration of sinus rhythm or suppression of the tachycardia to <100 beats per minute without termination within 12 hours of initiating ivabradine.. Twenty-eight patients (mean age, 34.6±21.5 years; women, 60.7%) were included in the study. The most common symptom was palpitation (85.7%) followed by shortness of breath (25%). The mean atrial rate during tachycardia was 170±21 beats per minute, and the mean left ventricular ejection fraction was 54.7±14.3%. Overall, 18 (64.3%) patients responded within 6 hours of the first dose of ivabradine. Thirteen of 18 ivabradine responders subsequently underwent successful catheter ablation. FAT originating in the atrial appendages was a predictor of ivabradine response compared with those arising from other atrial sites (P=0.046).. Ivabradine-sensitive atrial tachycardia constitutes 64% of incessant FAT in patients without structural heart disease. Incessant FAT originating in the atrial appendages is more likely to respond to ivabradine than that arising from other atrial sites. Our findings implicate the funny current in the pathogenesis of FAT.

Topics: Administration, Oral; Adult; Atrial Function, Left; Cardiovascular Agents; Dose-Response Relationship, Drug; Electrocardiography; Female; Follow-Up Studies; Heart Atria; Heart Rate; Humans; Ivabradine; Male; Prospective Studies; Tachycardia, Supraventricular; Treatment Outcome

Topics: Adolescent; Adult; Cardiovascular Agents; Catheter Ablation; Child; Child, Preschool; Combined Modality Therapy; Cost-Benefit Analysis; Decision Making; Diagnostic Techniques, Cardiovascular; Disease Management; Electrocardiography; Evidence-Based Medicine; Female; Humans; Male; Pregnancy; Pregnancy Complications, Cardiovascular; Quality of Life; Tachycardia, Supraventricular; Young Adult

Topics: Adolescent; Adult; Cardiovascular Agents; Catheter Ablation; Child; Child, Preschool; Combined Modality Therapy; Cost-Benefit Analysis; Decision Making; Diagnostic Techniques, Cardiovascular; Disease Management; Electrocardiography; Evidence-Based Medicine; Female; Humans; Male; Pregnancy; Pregnancy Complications, Cardiovascular; Quality of Life; Tachycardia, Supraventricular; Young Adult

Atrial fibrillation induced by electroconvulsive therapy (ECT) is rare, with only 3 reported cases. None of those cases involved either young healthy patients or right unilateral ECT. We report a 46-year-old healthy male observed to be in atrial fibrillation immediately after electrical induction of the 25th administration of right unilateral ECT. Diltiazem was administered, and he spontaneously cardioverted. After a negative cardiology workup, he safely resumed ECT. Atrial fibrillation was most likely triggered by autonomic imbalance due to the combination of electrical induction, seizure, and medication.

Topics: Anesthesia; Atrial Fibrillation; Cardiovascular Agents; Diltiazem; Electrocardiography; Electroconvulsive Therapy; Electroencephalography; Functional Laterality; Glycopyrrolate; Humans; Male; Middle Aged; Muscarinic Antagonists; Stress Disorders, Post-Traumatic; Suicidal Ideation; Tachycardia, Supraventricular

Slow coronary flow is an angiographic phenomenon characterized by delayed opacification of vessels in the absence of any evidence of obstructive epicardial coronary disease. In this article, we present serious clinical manifestations of extremely slow coronary flow in two hypertensive patients with preserved ejection fraction in echocardiographical examination: a 57 year-old woman with acute coronary syndrome and temporary ST elevation; and a 65 year-old man with atrial tachycardia which was leading to sudden arrest of circulation. The woman was admitted to hospital due to recurrent syncope and chest pain. Because of severe bradycardia, an AAI pacemaker was implanted. Coronary angiography without evident obstructive lesion revealed extremely slow flow of dye through arteries. The man was admitted to hospital because of heart palpitations (paroxysmal atrial tachycardia, PAT) followed by chest pain. During hospitalization, a sudden arrest of circulation in the course of supraventricular tachycardia of 220/min with atrioventricular conduction of 1:1 occurred. Coronary arteriography did not show any occlusions in the coronary arteries, although extremely slow dye flow was seen. Electrophysiological examination revealed arrhythmia of the left atrial (PAT) (tricuspid valve anulus mapping) without induced ventricular arrhythmia. Because of symptomatic bradyarrhythmia, a VVI heart pacemaker was implanted. Over a 12-month observation, his heart rate remained under control, and the patient did not complain of chest pains or heart palpitations.

Topics: Acute Coronary Syndrome; Aged; Angina Pectoris; Blood Flow Velocity; Bradycardia; Cardiac Pacing, Artificial; Cardiovascular Agents; Combined Modality Therapy; Coronary Angiography; Coronary Circulation; Coronary Disease; Drug Therapy, Combination; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Syncope; Tachycardia, Paroxysmal; Tachycardia, Supraventricular; Treatment Outcome

Accurate prehospital diagnosis and early initiation of emergency medical treatment for pediatric patients found to have supraventricular tachycardia is a reasonable task to accomplish and one that does not have to be anxiety-provoking. The most important point to remember is that the standard approach to resuscitation and stabilization for pediatric patients with narrow complex tachycardias (and those with aberrant or wide complexes identifiable as WPW) applies to all variations of SVT; thus, it is not necessary to precisely diagnose the variant prior to initiation of treatment, except for WPW, in which adenosine administration is contraindicated. Once the dysrhythmia is identified as SVT, the patient must rapidly be categorized as stable or unstable, which will then lead the EMS provider down the correct branch of the treatment algorithm. Every attempt should be made to perform a 12-lead ECG pre- and post-resuscitation, as well at to administer sedation prior to emergent synchronized cardioversion. Dosages of medications need not be memorized, provided that a readily available guide, such as a Broselow tape or regional tertiary care center laminated resuscitation card, is at hand. Finally, while termination of pediatric SVT, whether spontaneous or by EMS intervention, will also likely terminate the EMS provider's own palpitations, it is essential that these patients be seen in an emergency department immediately in order to accurately diagnose their medical condition and provide the patient and family with an appropriate disposition based on the events surrounding the incident.

Topics: Cardiovascular Agents; Child; Diagnosis, Differential; Electrocardiography; Emergency Medical Services; Emergency Treatment; Female; Heart; Humans; Pediatrics; Tachycardia, Supraventricular; United States

Topics: Adenosine; Cardiovascular Agents; Humans; Tachycardia, Supraventricular

Ventricular tachyarrhythmias present a unique set of stimuli to arterial and cardiopulmonary baroreceptors by increasing cardiac filling pressures and decreasing arterial pressure. The net effect on the control of sympathetic nerve activity (SNA) in humans is unknown. The purpose of this study was to determine the relative roles of cardiopulmonary and arterial baroreceptors in controlling SNA and arterial pressure during ventricular pacing in humans.. Two experiments were performed in which SNA and hemodynamic responses to ventricular pacing were compared with nitroprusside infusion (NTP) in 12 patients and studied with and without head-up tilt or phenylephrine to normalize the stimuli to either the arterial or cardiopulmonary baroreceptors in 9 patients. In experiment 1, the slope of the relation between SNA and mean arterial pressure was greater during NTP (-4.7+/-1.4 U/mm Hg) than during ventricular pacing (-3.4+/-1.1 U/mm Hg). Comparison of NTP doses and ventricular pacing rates that produced comparable hypotension showed that SNA increased more during NTP (P=0.03). In experiment 2, normalization of arterial pressure during pacing resulted in SNA decreasing below baseline (P<0.05), whereas normalization of cardiac filling pressure resulted in a greater increase in SNA than pacing alone (212+/-35% versus 189+/-37%, P=0. 04). Conclusions--These data demonstrate that in humans arterial baroreflex control predominates in mediating sympathoexcitation during ventricular tachyarrhythmias and that cardiopulmonary baroreceptors contribute significant inhibitory modulation.

Topics: Action Potentials; Adult; Baroreflex; Blood Pressure; Cardiac Catheterization; Cardiac Pacing, Artificial; Cardiotonic Agents; Cardiovascular Agents; Humans; Middle Aged; Nitroprusside; Peroneal Nerve; Phenylephrine; Reflex, Abnormal; Sympathetic Nervous System; Tachycardia, Supraventricular; Tachycardia, Ventricular; Tilt-Table Test; Vasodilator Agents; Ventricular Dysfunction, Left

Topics: Adenosine; Anti-Arrhythmia Agents; Cardiovascular Agents; Contraindications; Digoxin; Drug Interactions; Humans; Infant, Newborn; Tachycardia, Supraventricular; Ventricular Fibrillation; Wolff-Parkinson-White Syndrome