Ibutilide is an antiarrhythmic drug that was recently marketed for the rapid conversion of atrial fibrillation and atrial flutter. After intravenous administration, ibutilide is moderately effective in achieving prompt cardioversion to sinus rhythm, with greater efficacy in patients who have atrial flutter. Like other drugs that prolong ventricular repolarization, ibutilide administration carries a risk of excessive QT prolongation, or the acquired long-QT syndrome, with associated polymorphic ventricular tachycardia (torsade de pointes), necessitating careful patient selection and clinical monitoring during drug administration.
For each patient with AF, the two principal goals of therapy are symptom control and the prevention of thromboembolism.
Rate- and rhythm-control strategies improve symptoms, but neither has been conclusively shown to improve survival compared to the other.
In this ppt i am going to discuss various spotters, including ECG, X-ray, fluroscopy images and there answers. These spotter now days asked in various DM cardiology exam conducted all over India, so it will help you in your DM Cardiology exam preperationn.
For each patient with AF, the two principal goals of therapy are symptom control and the prevention of thromboembolism.
Rate- and rhythm-control strategies improve symptoms, but neither has been conclusively shown to improve survival compared to the other.
In this ppt i am going to discuss various spotters, including ECG, X-ray, fluroscopy images and there answers. These spotter now days asked in various DM cardiology exam conducted all over India, so it will help you in your DM Cardiology exam preperationn.
SGLT2 inhibitors in Heart failure: A prized addition to HF treatment optionsahvc0858
Early Diabetes and Dyslipidaemia Treatment Optimisation.
Presentation by Dr Chan Wan Xian
Cardiologist, Echocardiologist
Heart Failure Intensivist
Asian Heart & Vascular Centre
www.ahvc.com.sg
#flozins
🫀DAPA 🆚placebo in HFpEF
Now we have a positive trial!
⬇️18% in CV☠️ death or
worsening HF among LVEF>40%
⬇️ 21%heart failure
💥Results same for LVEF> 60% 🆚LVEF<60%
This highly energetic lecture presents the pathophysiology of S-T elevation myocardial infarction in an easy to understand style to help you best identify, triage and treat patients presenting with acute coronary syndromes. Using the latest research behind the AHA Guidelines changes, AHA National Faculty Rom Duckworth will help you better coordinate with you partners along the continuum of cardiac care. Emphasis is placed on risk factors, recognizing truly sick patients and coordinating care with hospital personnel.
Learning Objectives: Students will learn:
-The pathophysiology of S-T elevation myocardial infarction.
-The difference between STEMI, NSTEMI and unstable angina.
-Differing treatment methods and priorities for different cardiac syndromes.
-The function and importance of 12 lead ECG and prehospital diagnostic testing.
-The roles and responsibilities of EMS providers as the key element in “door-to-balloon” and “door-to-needle” time for STEMI patients.
www.romduck.com
www.RescueDigest.com
SGLT2 inhibitors in Heart failure: A prized addition to HF treatment optionsahvc0858
Early Diabetes and Dyslipidaemia Treatment Optimisation.
Presentation by Dr Chan Wan Xian
Cardiologist, Echocardiologist
Heart Failure Intensivist
Asian Heart & Vascular Centre
www.ahvc.com.sg
#flozins
🫀DAPA 🆚placebo in HFpEF
Now we have a positive trial!
⬇️18% in CV☠️ death or
worsening HF among LVEF>40%
⬇️ 21%heart failure
💥Results same for LVEF> 60% 🆚LVEF<60%
This highly energetic lecture presents the pathophysiology of S-T elevation myocardial infarction in an easy to understand style to help you best identify, triage and treat patients presenting with acute coronary syndromes. Using the latest research behind the AHA Guidelines changes, AHA National Faculty Rom Duckworth will help you better coordinate with you partners along the continuum of cardiac care. Emphasis is placed on risk factors, recognizing truly sick patients and coordinating care with hospital personnel.
Learning Objectives: Students will learn:
-The pathophysiology of S-T elevation myocardial infarction.
-The difference between STEMI, NSTEMI and unstable angina.
-Differing treatment methods and priorities for different cardiac syndromes.
-The function and importance of 12 lead ECG and prehospital diagnostic testing.
-The roles and responsibilities of EMS providers as the key element in “door-to-balloon” and “door-to-needle” time for STEMI patients.
www.romduck.com
www.RescueDigest.com
While low to moderate doses are generally safe, caffeine is addictive and users can become dependent on it and find it difficult to quit or even cut back.Caffeine dependence was even named as a new mental disorder this year. Anyone who's ever quit cold turkey knows it can trigger pounding headaches, mental fuzziness and fatigue for a couple of days until the body adjusts.
This official textbook of the European Association of Echocardiography (EAE) serves the educational requirements of cardiologists and all clinical medical professionals, underpinning the structural training in the field in accordance with EAE aims and goals, and reflecting the EAE Core Syllabus. Published in partnership with the European Society of Cardiology, and written by a team of expert authors from across Europe, it is a valuable resource to support not only those with an interest in echocardiography but specifically those seeking the information needed for accreditation and training through the EAE.
Join live classes, download study aids, sell your documents, join or host your own classes online, get tutoring, tutor students, take practices tests and more at Examville.com
This powerpoint is a case presentation, that explains the case of ADCHF, with comorbidities, comprising HTN, CAD and DLP.
A summary on the recent advancements in HF management, along with justification of therapy provided, has been elucidated.
A note on home remedies and counselling tips has also been provided.
Formulary recommendations for an MAPD plan, based on the evaluation of its clinical benefits & possible
place in therapy amongst other beta blockers
Wellens syndrome. Wellens syndrome (also referred to as LAD coronary T-wave syndrome) refers to an ECG pattern specific for critical stenosis of the proximal left anterior descending artery. The anomalies described occur in patients with recent anginal chest pain, and do not have chest pain when the ECG is recorded.
Congenital defects can put a strain on the heart, causing it to work harder. To stop your heart from getting weaker with this extra work, your doctor may try to treat you with medications. They are aimed at easing the burden on the heart muscle. You need to control your blood pressure if you have any type of heart problem.
Changing your lifestyle can help control and manage high blood pressure. Your health care provider may recommend that you make lifestyle changes including:
Eating a heart-healthy diet with less salt
Getting regular physical activity
Maintaining a healthy weight or losing weight
Limiting alcohol
Not smoking
Getting 7 to 9 hours of sleep daily
CRISPR technologies have progressed by leaps and bounds over the past decade, not only having a transformative effect on
biomedical research but also yielding new therapies that are poised to enter the clinic. In this review, I give an overview of (i)
the various CRISPR DNA-editing technologies, including standard nuclease gene editing, base editing, prime editing, and epigenome editing, (ii) their impact on cardiovascular basic science research, including animal models, human pluripotent stem
cell models, and functional screens, and (iii) emerging therapeutic applications for patients with cardiovascular diseases, focusing on the examples of Hypercholesterolemia, transthyretin amyloidosis, and Duchenne muscular dystrophy.
A post-splenectomy patient suffers from frequent infections due to capsulated bacteria like Streptococcus
pneumoniae, Hemophilus influenzae, and Neisseria meningitidis despite vaccination because of a lack of
memory B lymphocytes. Pacemaker implantation after splenectomy is less common. Our patient underwent
splenectomy for splenic rupture after a road traffic accident. He developed a complete heart block after
seven years, during which a dual-chamber pacemaker was implanted. However, he was operated on seven
times to treat the complication related to that pacemaker over a period of one year because of various
reasons, which have been shared in this case report. The clinical translation of this interesting observation
is that, though the pacemaker implantation procedure is a well-established procedure, the procedural
outcome is influenced by patient factors like the absence of a spleen, procedural factors like septic measures,
and device factors like the reuse of an already-used pacemaker or leads.
Transcatheter closure of patent ductus arteriosus (PDA) is feasible in low-birth-weight infants. A female baby was born prematurely with a birth weight of 924 g. She had a PDA measuring 3.7 mm. She was dependent on positive pressure ventilation for congestive heart failure in addition to the heart failure medications. She could not be discharged from the hospital even after 79 days of birth, and even though her weight reached 1.9 kg in the neonatal intensive care unit. We attempted to plug the PDA using an Amplatzer Piccolo Occluder, but the device failed to anchor. Then, the PDA was plugged using a 4-6 Amplatzer Duct Occluder using a 6-Fr sheath which was challenging.
Accidental misplacement of the limb lead electrodes is a common cause of ECG abnormality and may simulate pathology such as ectopic atrial rhythm, chamber enlargement or myocardial ischaemia and infarction
A Case of Device Closure of an Eccentric Atrial Septal Defect Using a Large D...Ramachandra Barik
Device closure of an eccentric atrial septal defect can be challenging and needs technical modifications to avoid unnecessary complications. Here, we present a case of a 45-year-old woman who underwent device closure of an eccentric defect with a large device. The patient developed pericardial effusion and left-sided pleural effusion due to injury to the junction of right atrium and superior vena cava because of the malalignment of the delivery sheath and left atrial disc before the device was pulled across the eccentric defect despite releasing the left atrial disc in the left atrium in place of the left pulmonary vein. These two serious complications were managed conservatively with close monitoring of the case during and after the procedure.
Trio of Rheumatic Mitral Stenosis, Right Posterior Septal Accessory Pathway a...Ramachandra Barik
A 57-year-old male presented with recurrent palpitations. He was diagnosed with rheumatic mitral stenosis, right posterior septal accessory pathway and atrial flutter. An electrophysiological study after percutaneous balloon mitral valvotomy showed that the palpitations were due to atrial flutter with right bundle branch aberrancy. The right posterior septal pathway was a bystander because it had a higher refractory period than the atrioventricular node.
Percutaneous balloon dilatation, first described by
Andreas Gruentzig in 1979, was initially performed
without the use of guidewires.1 The prototype
balloon catheter was developed as a double lumen
catheter (one lumen for pressure monitoring or
distal perfusion, the other lumen for balloon inflation/deflation) with a short fixed and atraumatic
guidewire at the tip. Indeed, initially the technique
involved advancing a rather rigid balloon catheter
freely without much torque control into a coronary
artery. Bends, tortuosities, angulations, bifurcations,
and eccentric lesions could hardly, if at all, be negotiated, resulting in a rather frustrating low procedural success rate whenever the initial limited
indications (proximal, short, concentric, noncalcified) were negated.2 Luck was almost as
important as expertise, not only for the operator,
but also for the patient. It is to the merit of
Simpson who, in 1982, introduced the novelty of
advancing the balloon catheter over a removable
guidewire, which had first been advanced in the
target vessel.3 This major technical improvement
resulted overnight in a notable increase in the procedural success rate. Guidewires have since evolved
into very sophisticated devices.
Optical coherence tomography-guided algorithm for percutaneous coronary intervention. Vessel diameter should be assessed using the external elastic lamina (EEL)-EEL diameter at the reference segments, and rounded down to select interventional devices (balloons, stents). If the EEL cannot be identified, luminal measures are used and rounded up to 0.5 mm larger for selection of the devices. Optical coherence tomography (OCT)-guided optimisation strategies post stent implantation per EEL-based diameter measurement and per lumen-based diameter measurement are shown. For instance, if the distal EEL-EEL diameter measures 3.2 mm×3.1 mm (i.e., the mean EEL-based diameter is 3.15 mm), this number is rounded down to the next available stent size and post-dilation balloon to be used at the distal segment. Thus, a 3.0 mm stent and non-compliant balloon diameter is selected. If the proximal EEL cannot be visualised, the mean lumen diameter should be used for device sizing. For instance, if the mean proximal lumen diameter measures 3.4 mm, this number is rounded up to the next available balloon diameter (within up to 0.5 mm larger) for post-dilation. MLA: minimal lumen area; MSA: minimal stent area;NC: non-compliant
Brugada syndrome (BrS) is an inherited cardiac disorder,
characterised by a typical ECG pattern and an increased
risk of arrhythmias and sudden cardiac death (SCD).
BrS is a challenging entity, in regard to diagnosis as
well as arrhythmia risk prediction and management.
Nowadays, asymptomatic patients represent the majority
of newly diagnosed patients with BrS, and its incidence
is expected to rise due to (genetic) family screening.
Progress in our understanding of the genetic and
molecular pathophysiology is limited by the absence
of a true gold standard, with consensus on its clinical
definition changing over time. Nevertheless, novel
insights continue to arise from detailed and in-depth
studies, including the complex genetic and molecular
basis. This includes the increasingly recognised
relevance of an underlying structural substrate. Risk
stratification in patients with BrS remains challenging,
particularly in those who are asymptomatic, but recent
studies have demonstrated the potential usefulness
of risk scores to identify patients at high risk of
arrhythmia and SCD. Development and validation of
a model that incorporates clinical and genetic factors,
comorbidities, age and gender, and environmental
aspects may facilitate improved prediction of disease
expressivity and arrhythmia/SCD risk, and potentially
guide patient management and therapy. This review
provides an update of the diagnosis, pathophysiology
and management of BrS, and discusses its future
perspectives.
The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative medicine. Here we outline the HDCA initiative and the challenges of mapping and modelling human development using state-of-the-art technologies to create a reference atlas across gestation. Similar to the Human Genome Project, the HDCA will integrate the output from a growing community of scientists who are mapping human development into a unified atlas. We describe the early milestones that have been achieved and the use of human stem-cell-derived cultures, organoids and animal models to inform the HDCA, especially for prenatal tissues that are hard to acquire. Finally, we provide a roadmap towards a complete atlas of human development.
The treatment of patients with advanced acute heart failure is still challenging.
Intra-aortic balloon pump (IABP) has widely been used in the management of
patients with cardiogenic shock. However, according to international guidelines, its
routinary use in patients with cardiogenic shock is not recommended. This recommendation is derived from the results of the IABP-SHOCK II trial, which demonstrated
that IABP does not reduce all-cause mortality in patients with acute myocardial infarction and cardiogenic shock. The present position paper, released by the Italian
Association of Hospital Cardiologists, reviews the available data derived from clinical
studies. It also provides practical recommendations for the optimal use of IABP in
the treatment of cardiogenic shock and advanced acute heart failure.
Left ventricular false tendons (LVFTs) are fibromuscular
structures, connecting the left ventricular
free wall or papillary muscle and the ventricular
septum.
There is some discussion about safety issues during
intense exercise in athletes with LVFTs, as these
bands have been associated with ventricular arrhythmias
and abnormal cardiac remodelling. However,
presence of LVFTs appears to be much more common
than previously noted as imaging techniques
have improved and the association between LVFTs
and abnormal remodelling could very well be explained
by better visibility in a dilated left ventricular
lumen.
Although LVFTsmay result in electrocardiographic abnormalities
and could form a substrate for ventricular
arrhythmias, it should be considered as a normal
anatomic variant. Persons with LVFTs do not appear
to have increased risk for ventricular arrhythmias or
sudden cardiac death.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
2. Ibutilide
Ibutilide is the first 'pure' class III anti-arrhythmic drug to be
available. [1]
Approved by the USFDA in Dec.1995
June 2016 (Zuventus Health Care Ltd) received manufacturing &
marketing approval from DCGI India.
API as well as finished product developed through “in house R&D”
Marketed as “Fibricor”
1. Drugs. 1997 Aug;54(2):312-30.
3. “Pure Class III”
• Ibutilide: “cardiac electrophysiological actions” Only.
• Ibutilide: "Pure" action potential–prolonging drug
• It has no “negative inotropic” effects
Goodman & Gilman's The Pharmacological Basis of Therapeutics - 12th Ed
Amiodarone Dronadarone and sotalol are
mixed acting class-III drugs.
Sotalol: Has class II and III activities
Amiodarone: Has Class I, II, III and IV activities and
has multiple cardiac (electrophysiologic
characteristics of all 4 classes) & systemic side
effects.
Dronaderon: Similar to Amiodarone
5. Unique mechanism of action
• Ibutilide, at nanomolar concentrations (10-8), “prolongs repolarization by
activation of a slow, inward current (predominantly sodium).”
• It blocks Potassium channels at 1000 times concentration i.e. (10-5)
• Plasma levels achieved after 1mg infusion are in the range of (10-8)
• This mechanism of action is “unique among available class III drugs”
Naccarelli GV. Am J Cardiol. 1996 Oct 17;78(8A):12-6.
Ibutilide does not have a sodium-
blocking, Antiadrenergic, and
Calcium blocking activity
6. Unique Mechanism of Action among
available class III drugs
Activation of a late
inward sodium current
Increased sodium influx
Shah D. Eur Heart J. 2016 May 21;37(20):1622-5.
Prolongation of the
myocardial action
potential duration.
+
-
V Max
plateau
Slow Na
(Ibutilide)CaNa
N
T
QT
APD
Action Potential Duration
K+ (other class III)
Repolarization
7. No Hemodynamic Effects
No clinically significant Hemodynamic effect (at doses up to
0.03 mg/kg) demonstrated on
– Cardiac output,
– Mean pulmonary arterial pressure
– Capillary wedge pressure
Katherine T. Murray. Ibutilide. Circulation 1998;97;493-497.
8. Ibutilide: Electrophysiological
Effects
No clinically significant effect on QRS (at the recommended dosage)
A dose related prolongation of the QT interval
Prolongation of QT interval is similar in men & women
Prolongs action potential duration and effective refractory periods in both
atria and ventricles
Nair M. J Am Board Fam Med. 2011 Jan-Feb;24(1):86-92.
9. Pharmacokinetics
• Ibutilide is intravenously (i.v.)
administered
• Due to its high first-pass
metabolism, its not given orally
Katherine T. Murray. Ibutilide. Circulation 1998;97;493-497.
.http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-491S003.pdf
• The pharmacokinetics of Ibutilide
is similar regardless of
• The type of atrial arrhythmia,
• Age, sex
• Left ventricular ejection fraction,
• Occurrence of polymorphic
ventricular tachycardia
• The concomitant use of digoxin,
CCBs, or β-blockers.
10. After IV infusion, Ibutilide plasma concentrations rapidly decrease in a
multiexponential fashion.
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-491S003.pdf
Pharmacokinetics
12. Ibutilide: Dosage & Administration
Ibutilide infusion should be stopped as soon as the presenting arrhythmia is terminated
or in the event of sustained or nonsustained ventricular tachycardia, or marked
prolongation of QT or QTc.
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-491S003.pdf
13. Dilution
Solutions used
for dilution →
Ibutilide Injection 10 ml one Vial
+ 50 ml of 5 % Dextrose Injection
Ibutilide Injection 10 ml one Vial +
50 ml of 0.9 % NaCl Injection
Ibutilide Injection may be administered undiluted or diluted in 50 mL of diluent
Admixtures of the product, with approved diluents, are chemically and physically stable for 24
hours at room temperature (15°to 30°C )
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-491S003.pdf
14. Clinical settings for Ibutilide usage
(cardioversion in AF and AFL)
1. Recent onset atrial fibrillation or flutter
2. Persistent atrial fibrillation or flutter
a) As standalone therapy
b) In patients already on oral amiodarone
c) To facilitate electrical cardioversion
d) To facilitate cardioversion of atrial flutter by overdrive atrial pacing
3. Post-operative atrial fibrillation or flutter
4. Pre-excited atrial fibrillation in patients with WPW syndrome
5. Atrial fibrillation or flutter during an electrophysiological study
or ablation procedure
6. Children and those with congenital heart disease
7. Elderly patients with atrial fibrillation or flutter
Kartikeya Bhargava. Role of Ibutilide in Atrial Fibrillation Supplement Issue on Atrial Fibrillation . JAPI • August 2016 • Vol. 64.
16. Warnings & Precautions
• Potential to prolong refractoriness When
given with Class Ia and other class III
antiarrhythmic, concomitantly or within 4
hours post infusion
• Class I and III agents may be withheld for at
least 5 half-lives prior to ibutilide infusion
• Potential for Proarrhythmia when given
with drugs that prolong the QT interval, such
as
– Phenothiazines,
– Tricyclic or Tetracyclic antidepressants
– Antihistamines- terfenadine, Astemizole
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-491S003.pdf
• Doses of more than two infusions are
not recommended in a single setting
due to the risk of QT prolongation
• Not recommended in
– Patients with QTc intervals > 440
msec.
– Patients with H/O polymorphic
ventricular tachycardias (e.g.,
torsades de pointes).
• More rapid infusion is not recommended.
18. Common Non-arrhythmic Toxicity
of most frequently used anti-arrhythmic agents in AF/AFL
Ibutilide Nausea
Amiodarone Tremor, peripheral neuropathy, pulmonary inflammation,
hypothyroidism and hyperthyroidism, photosensitivity
Dofetilide Nausea
Propafenone Taste disturbance, dyspepsia, nausea, vomiting
Flecainide Dizziness, nausea, headache, decreased myocardial contractility
Sotalol Hypotension, bronchospasm
Harrison's Principles of Internal Medicine, 18th Ed. Chapter 233. The Tachyarrhythmias >
19. Pro-arrhythmic Manifestations
Amiodarone
Sinus bradycardia, AV block, increase in defibrillation threshold
Rare: long QT and torsades des pointes, 1:1 ventricular conduction with
atrial flutter
Ibutilide Long QT and torsades de pointes
Flecainide 1:1 Ventricular response to atrial flutter; increased risk of some ventricular
tachycardias in patients with structural heart disease; sinus bradycardia
Dofetilide Long QT and torsades des pointes
Propafenone 1:1 Ventricular response to atrial flutter; increased risk of some ventricular
tachycardias in patients with structural heart disease; sinus bradycardia
Sotalol Long QT and torsades des pointes, sinus bradycardia
Harrison's Principles of Internal Medicine, 18th Ed. Chapter 233. The Tachyarrhythmias
20. How to reduce Torsades de pointes
Pretreatment with Class IC drugs
Class IC drugs: Flecainide and Propafenone.
• Ibutilide effect is mediated through the delay of slow Na(+) current
inactivation.1
• Pretreatment with IC agents can reduce the increase in QTc seen with
Ibutilide2
• There is lower risk of Proarrhythmia since the class IC drugs induced
slow conduction by blocking sodium channels which exert somewhat
protective effect against Ibutilide toxicity.
• Ibutilide has been safely used in patients who are already on class IC
drugs.
1. Kartikeya Bhargava. Supplement Issue on Atrial Fibrillation . JAPI • August 2016 • Vol. 64. 2. Reiffel JA. J Cardiovasc Pharmacol Ther. 2000 Jul;5(3):177-81.
21. • Combined therapy of iv esmolol and Ibutilide vs.
Ibutilide alone in patients with recent onset AF showed
a higher rate of conversion to sinus rhythm (67% vs.
46%), reduced rate of immediate recurrence and a
lower risk of proarrhythmia1
• The addition of Esmolol reduces QTc prolongation and
diminishes the risk of ventricular tachycardia
• Magnesium prevents significant prolongation of QT interval
and therefore reduces the risks of torsade de pointes2
1. Fragakis N. Europace 2009; 11:70. 2. Wang A. Pharm Pract (Granada). 2012 Apr;10(2):65-71. 21
How to reduce Torsades de pointes
Ibutilide in combination with Esmolol or MgSO4
22. Predictor of successful cardioversion
with Ibutilide
1. Recent onset of arrhythmia
2. Atrial flutter rhythm
3. Relatively high heart rate
4. Lack of a H/O of CHF
5. Lack of concomitant digoxin therapy
6. Female gender and younger age
Zaqqa M. Am J Cardiol. 2000 Jan 1;85(1):112-4, A9.
23. Geriatric Use
• Usually start at the low end of the dosing
range, because of
– Decreased hepatic or renal function
– Decreased Cardiac function
– Concomitant disease or other drug therapy.
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-491S003.pdf
• Clinical experience shows no difference in responses
between the elderly & younger patients.
24. Use in Patients with Hepatic or Renal
Dysfunction
• The safety, effectiveness & pharmacokinetics
of Ibutilide have not been established in
patients with hepatic or renal dysfunction.
• It is unlikely that dosing adjustments would be
necessary in patients with compromised renal
or hepatic function
• Patients with abnormal liver function should be
monitored for >4-hour period.
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-491S003.pdf
27. Recommendation from AHA/ACC/HRS
Guidelines 2014
Anti-arrhythmic
Drugs
Class of Recommendation in following Indications
Atrial Fibrillation/Flutter
Wolff Parkinson White
and
Pre-excitation
Syndrome
Post operative
Cardiac & Thoracic
Surgery induced AF
Ibutilide Class I Class I Class IIa
Amiodarone Class IIa Not recommended Not recommended
Flecainide
Class I (in Hospital)
Class IIa (outside hospital
with β-blocker)
Not recommended Not recommended
Dofetilide Class I Not recommended Not recommended
Propafenone
Class I (in Hospital)
Class IIa (outside hospital
with β-blocker)
Not recommended Not recommended
Class-I Recommendation:Benefit >>> Risk ;Procedure/treatment SHOULD be performed/administered
Class-II Recommendation: CLASS II a - Benefit >> Risk Additional studies with focused objectives needed ; IT IS REASONABLE to perform procedure/administer
treatment; CLASS II b -Benefit ≥ Risk ;Additional studies with broad objectives needed; additional registry data would be helpful Procedure/treatment MAY BE
CONSIDERED
Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol.2014;64(21):2246-2280.
29. IBUTILIDE Rescue for failed Amiodarone therapy
S
N
Title N Drugs Primary Endpoint Results
1 Marcus G. Hennersdorf et
al. Conversion of recent
onset atrial fibrillation or
flutter with ibutilide after
amiodarone has failed.
Intensive Care Med. 2002
Jul;28(7):925-9.
26 Ibutilide (1 mg or, 2
mg i.v.) after
Amiodarone (150 mg
i.v.) failed in Persistent
arrhythmia
Conversion of
recent onset atrial
fibrillation or
flutter
after amiodarone
has failed.
Ibutilide led “Sinus
Rhythm” conversion in
81.5% of patients where
Amiodarone had failed
29
30. • 70 pts on longterm oral amiodarone for
cardioversion in “Afib” (57/70) or “Afl” (13/70)
• Patients administered 2 mg i.v. Ibutilide.
• 55 patients (79%) had structural heart
disease.
• Patients on amiodarone:153 days
• Patients with arrhythmia for 196 days
before cardioversion.
Kathy Glatter. Circulation. 2001;103:253-257.
Patients converted within 30 minutes of infusion.
AFib- 22 of 57 (39%) and
AFl -7 of 13 (54%)
only 1 episode of torsade de pointes occurred
Ibutilide Add-on to long term Oral Amiodarone
30
31. Ibutilide Vs. Amiodarone (i.v.) in AF & AFl
N= 152 (Ibutilide n=79, Amiodarone n= 73)
Duration of AF or Afl: 3-48 h
Conversion to SR
All patients
Ibutilide: 63 of 79 pts (80%)
Amiodarone: 42 of 73 pts (57%)
In AFL
Ibutilide: 20 of 23 pts (87%)
Amiodarone: 6 of 21 pts (29%)
In AF
Ibutilide:43 of 56 pts (77%)
Amiodarone: 36 of 52 pts (69%)
80%
57%
77%
69%
87%
29%
Ibutilide is more effective than amiodarone in converting recent-onset AF or AFl to Sinus Rhythm
Kafkas NV. Int J Cardiol. 2007 Jun 12;118(3):321-5. 31
32. Ibutilide: Shorter Arrhythmia Termination Time
Kafkas NV, Int J Cardiol. 2007 Jun 12;118(3):321-5.
Atrial Fibrillation
53.4 min
492 min
Atrial Flutter
28.4 min
762 min
32
33. Ibutilide vs. Propafenone
SN Title N Drugs Primary
Endpoint
Results
1 Zhang HC et al. Immediate
cardioversion of atrial fibrillation and
atrial flutter lasting less than 90 days
by ibutilide versus propafenone: a
multicentre study. Zhonghua Yi
Xue Za Zhi. 2005 Mar
30;85(12):798-801.
212 Ibutilide (1 mg)
(n = 107), 75 AF & 32 AFL
Propafenone
(70 mg)
(n = 105, 76 AF & 29 AFL
IV over 10 mins
Cardioversion AFL conversion rate
Ibutilide = 78.1%
Propafenone 48.3%
33
34. Ibutilide vs. Propafenone
Ibutilide 1 mg or Propafenone 70 mg
[2 infusions, 10 min apart]
N= 82 pts with AF
Onset : 2 h to 90 days
The treatment was considered successful if sinus rhythm occurred within 90 mins
p = 0.043
Zhang N. Int J Clin Pract. 2005 Dec;59(12):1395-400.
Ibutilide is more effective than intravenous propafenone for the cardioversion
34
35. Sun JL. Cardiovasc Drugs Ther. 2005 Jan;19(1):57-64.
Ibutilide was superior to propafenone for treating atrial flutter (90% vs. 30%).
n=40
Ibutilide-20
Propafenone-20
Bradycardia &
hypotension were more
common side effects with
propafenone.
Randomized to receive
Ibutilide 1 mg
Propafenone 70mg
Ibutilide vs. Propafenone
35
36. Ibutilide with Propafenone
3 John A. Chiladaki et al.
Ibutilide added to
propafenone for the
conversion of atrial
fibrillation and atrial
flutter. J Am Coll
Cardiol. 2004 Aug
18;44(4):859-63.
202 Oral propafenone
N=202
With AF/AFL without left
ventricular dysfunction.
IV Ibutilide (1mg)
N=104
(48 pts with paroxysmal
arrhythmia, & 56 with
chronic arrhythmia)
Safety &
efficacy of
Ibutilide when
added to
propafenone
Ibutilide offered an overall
conversion efficacy of 66.3%.
•70.8% for patients with
paroxysmal AF/AFL
•62.5% for patients with chronic
AF/AFL.
36
37. Ibutilide 2mg
Cardioversion of pts on Class IC Agents
• Total 71 pts. AF (n=48) & AFL (n= 23)
• Pts. on Propafenone 300 to 900 mg/day (n=46) or Flecainide 100 to 300
mg/day (n= 25)
Conversion rates:
AF - 23 of 48 pts (47.9%)
AFL- 17 of 23 pts (73.9%)
No pts needed to stop of Ibutilide infusion
for ventricular dysrhythmia or excessive QT
prolongation.
Attenuation of Ibutilide-induced QTC prolongation:
Class IC agents block slow inward INa in addition to fast INa
In this study mean Ibutilide-induced QTC interval prolongation was 20
ms as compared to 47 to 90ms (reported in literature)
This attenuation is without decrease in Ibutilide efficacy
Hongo RH. J Am Coll Cardiol. 2004 Aug 18;44(4):864-8.
37
38. Ibutilide Vs. Procainamide
ADVERSE EVENTS :
More common with procainamide (46.2%) than with Ibutilide group -29.0%
Ibutilide - Extrasystole occurred .
Procainamide - Headache, hypotension, flushing, dizziness and hypesthesia
Volgman AS. J Am Coll Cardiol. 1998 May;31(6):1414-9.
Combined Conversion rates
Ibutilide –58%
Procainamide - 18%
Atrial Flutter
Ibutilide -76%
Procainamide -14%
Atrial Fibrillation
Ibutilide - 51%
Procainamide -21%
Study Establishes The Superior Efficacy Of Ibutilide Over Procainamide
Total N= 120 , Ibutilide n=60 procainamide n=60
38
39. Randomized, double-blinded comparative study- 136 patients treated :
• i.v. Ibutilide (n=73)
•placebo (n=22)
•iv procainamide (n=53)
Bruce S. Stambler et al. Circulation. 1997;96:4298-4306
Ibutilide Vs. Procainamide
In AFL
Ibutilide converted 29 of 45 pts= 64%
Procainamide & placebo converted 0%
In AF
Ibutilide converted 9 of 28 pts 32%
Procainamide converted in 1 of 20 5%
Placebo converted 0%
39
40. Ibutilide vs. Procainamide
S
N
Title N Drugs Primary
Endpoint
Results
3 Stambler BS et al.;
Comparative efficacy of iv
Ibutilide versus procainamide for
enhancing termination of atrial
flutter by atrial overdrive pacing
Am J Cardiol. 1996 May
1;77(11):960-6.
54 Ibutilide n=15 or
Procainamide
n=33 or
Placebo n =11
Termination
of atrial
flutter
Pacing converted SR
18% placebo, 87%
ibutilide, (88%)
procainamide
40
41. Ibutilide vs. Sotalol
Vos M. et al. Heart. 1998;79(6):568-575.]
• Ibutilide (given in 1 or 2 mg doses over 10 mins Rapidly terminates persistent AF
or AFL.
• Ibutilide (2 mg) was superior to Sotalol in both atrial flutter and fibrillation
• Ibutilide vs Sotalol in Atrial flutter (70% vs. 19%),
• Ibutilide vs Sotalol in Atrial Fibrillation (44% v 11%)
Double blind, randomised
study.
308 patients with atrial
fibrillation (n = 251) or atrial
flutter (n = 57)
(duration 3 hrs to 45 days) .
three groups :
1 mg ibutilide (n = 99)
2 mg ibutilide (n = 106)
1.5 mg/kg DL-sotalol (n = 103)
41
42. Magnesium as an adjunct to Ibutilide,
improves efficacy & minimize toxicity
1. Magnesium have intrinsic
antiarrhythmic properties
2. Potential to increase the
efficacy of class III
antiarrhythmics
3. Delays AV node conduction,
without significant effect on
the sinus node
3. Efficacy of magnesium &
Ibutilide combination is due
to the additive potassium
blockade effect
4. Side effects of magnesium
are usually mild : e.g. minor
tingling, flushing & dizziness
Wang A. Pharm Pract (Granada). 2012 Apr;10(2):65-71.
42
43. Magnesium as an adjunct for Ibutilide…..
• Therefore, magnesium with Ibutilide involves
minimal risks with monitoring of vital signs &
ECG.
• Magnesium prevents significant prolongation
of QT interval and therefore reduces the risks
of torsade de pointes
The administration of magnesium makes Ibutilide a much safer
agent, & magnesium increased the conversion efficacy of Ibutilide
Wang A. Pharm Pract (Granada). 2012 Apr;10(2):65-71.
4 g of magnesium may be given within 2 hrs prior to initiation of
Ibutilide for conversion of AF or typical flutter
43
44. Ibutilide and Magnesium Combination
Therapy
Article Study
Design
Groups Doses of magnesium
used
Rates of Successful
Cardioversion
Kalus JS. Am J
Health Syst
Pharm. 2003 Nov
15;60(22):2308-
12.
Retrospective
, cohort
N = 321
1. Control: Ibutilide
alone
N = 214
2. Treatment:
Ibutilide & MgSO4
N = 107
Mean total dose: 2.2 + 1
grams Magnesium was
given within 2 hours
before or during ibutilide
therapy
Treatment group: 72%
Control group: 60.3%
p = 0.04
Patsilinakos S.
Am J
Cardiol. 2010 Sep
1;106(5):673-6.
Prospective
N = 476
1) Ibutilide alone
N = 229
2] Ibutilide & MgSO4
N = 247
5 grams given 1 hour
prior to first dose of
Ibutilide, followed by
another 5 grams given
over 2 hours
Treatment group: 76.5%
Control group: 67.3%
p = 0.033
Steinwender C.
Int J Cardiol. 2010
Jun
11;141(3):260-5.
Randomized,
placebo
controlled
N = 117
1. Ibutilide and
placebo
N = 59
2. Ibutilide & MgSO4
N = 58
Magnesium 4 grams or
placebo given 20
minutes prior to first
dose of ibutilide
Treatment group (typical
AF): 85%
Control group (typical
AF): 59%
p = 0.017
Tercius AJ.
Pacing Clin
Electrophysiol 2007
Nov;30(11):1331-5.
Retrospective
cohort
N = 229
1. Ibutilide only
N = 88
2. Ibutilide & MgSO4
N = 141
Magnesium 1-4 grams
within 2 hours prior to
ibutilide
78% more chances of
conversion with
combination versus
59.8% without MgSO4
44
45. 1
Stavros E. Et al.
Ibutilide to expedite ED
therapy for recent-onset
atrial fibrillation flutter
Am J Emerg Med.2006
Jul;24(4):407-12.
Total = 36
(AFib = 26)
&
(AFl = 10)
Ibutilide 1 mg
Successful
conversion
within 1 hour
90% patients with AFl and
61.5% patients with AFib
converted to sinus rhythm
No significant complications
occurred.
2
Amy Eversole.et al.
Ibutilide: Efficacy and Safety
in Atrial Fibrillation and Atrial
Flutter in a General
Cardiology Practice. Clin.
Cardiol. 2001;24,521-
525
Total = 54
Afib (n=34)
Afl (n= 20)
Ibutilide
1 mg for pts ≥
60 kg & 0.1
mg/kg for pts
< 60 kg
Successful
cardioversion
70.6% pts with AFib & 75%
with AFl converted to SR.
Conversion of AFib to SR
more likely if duration of AFib
= 96 h versus >96 h (81 %
vs. 17%).
3
Gowda RM.et al. Use
of ibutilide for cardioversion of
recent-onset atrial fibrillation and
flutter in elderly.
Am J Ther. 2004 Mar-
Apr;11(2):95-7.
Total = 32
AFib n=19
AFl n =13
Ibutilide 1 mg Cardioversion
Successful Arrhythmia
Termination = 59%.
63% in patients with AFib &
54% in AFl
The mean conversion time was
33 +/- 45 minutes.
Efficacy of Ibutilide
45
46. 44 patients (75%) converted to SR after Ibutilide
31 on single dose (53%) & 13 on double dose (22%)
Ibutilide in AFL- Single vs Double Dose
Andò G. Minerva Cardioangiol. 2004 Feb;52(1):37-42.
The mean time to the 2nd dose was
34 min in responders
46
N= 59 patients
dose- 1 mg Ibutilide.
47. • 266 pts with AF (n = 133) or flutter (n = 133),
• Arrhythmia duration - 3 hrs to 45 days
• Randomized to receive up to two 10-min infusions of
– Ibutilide (1.0 and 0.5 mg) or
– Ibutilide (1.0 and 1.0 mg)
– Placebo
• The conversion rate
– 47% after Ibutilide &
– 2% after placebo
• Efficacy was higher in AFl than fibrillation (63% versus 31%)
• Arrhythmia termination - 27 min after start of the infusion
• Of 180 Ibutilide-treated patients, 15 (8.3%) developed polymorphic ventricular
tachycardia during or soon after the infusion
Efficacy and safety of Repeated I.V. doses of
Ibutilide
Ibutilide given in repeated doses is effective in rapidly terminating
AF & AFl
Stambler B et al. Circulation 1996;94:1613-1621. 47
48. Ibutilide Vs. Placebo
SN Title N
Drugs Primary
Endpoints Results & conclusion
1
Abi-Mansour P.et al. Am
Heart J. 1998 Oct;136(4
Pt 1):632-42.
n=250 Ibutilide 1 mg
(n=209)
or
Placebo
(n=41)
Termination of
atrial fibrillation
or flutter
34.9% of ibutilide Pts had
cardioversion within 1.5 hrs
0% of placebo Pts
At 24 Hrs, 86.3% of Ibutilide
recipients remained in SR
2
James T. VanderLugt.et al.
Efficacy and Safety of Ibutilide
Fumarate for the Conversion of
Atrial Arrhythmias After Cardiac
Surgery. Circulation.
1999;100: 369-375.
n = 302
AFib=20
1
AFl=101
Ibutilide (n= 218)
(0.25, 0.5, or 1.0 mg)
or
Placebo (n=84)
Conversion
within 90 mins
Conversion rates = Placebo 15%;
Ibutilide 0.25 mg 40%, 0.5 mg 47%,
and 1.0 mg 57%
Mean time to conversion decreased
as the Ibutilide dose was increased
48
50. Pretreatment with Ibutilide facilitate
Electrical cardioversion
• It increases the conversion rate1
• Reduces the energy required to cardiovert2
• Reduces the number of attempts at cardioversion1
• Successful cardioversion in patients who failed initial
shock without Ibutilide pretreatment1
• 100% with Ibutilide versus 72 % without Ibutilide
1. Oral H. N Engl J Med 1999; 340:1849–54.
2. Mazzocca G. J Cardiovasc Med 2006; 7:124–8.
51. Ibutilide 1 mg with electrical cardioversion
51
n =100
Transthoracic cardioversion
with or without pre-
treatment
Pretreatment reduced mean
energy required for
defibrillation (166 J vs. 228 J
without pretreatment)
Oral H. N Engl J Med. 1999 Jun 17;340(24):1849-54.
52. Ibutilide for conversion after Cardiac Surgery
Ibutilide: Higher conversion rates than placebo, efficacy was dose related
Polymorphic ventricular tachycardia - in Ibutilide group 1.8% vs. 1.2% in placebo group
N= 302, Fibrillation- 201, flutter- 101
Ibutilide is a safe treatment alternative for Post cardiac surgery Atrial Arrhythmias
VanderLugt JT. Circulation. 1999 Jul 27;100(4):369-75.
52
53. Ibutilide in children & patients with
Congenital Heart Disease
RESULTS:
– 74 episodes of AFl and 4 episodes of AF
(median episodes / patient was 1, range
1-31).
– Ibutilide converted 55 of all the
episodes (71%).
– Success during its first-ever
administration in 12 of 19 patients: 63%.
– One patient went into torsade de pointes.
Hoyer AW. Pacing Clin Electrophysiol. 2007 Aug;30(8):1003-8.
19 patients (age 6 mths to 34 years) who received Ibutilide between 1996-2005
15 patients with CHD (14 had prior heart surgery); 4 children had normal heart
structure.
Ibutilide - effective in selected paedo pts for cardioversion of AFL
53
54. • Ibutilide successfully terminated AF in 95% of
patients (including children) during
electrophysiology study of accessory pathways
that were subsequently ablated. 1
• Ibutilide an alternative to Procainamide for
cardioversion in stable pts with preexcited AF.2
Ibutilide in Preexcited AF in WPW Syndrome
1. Glatter KA. Circulation. 2001 Oct 16;104(16):1933-9. 2. Varriale P. Pacing Clin Electrophysiol. 1999 Aug;22(8):1267-9.
54
55. Ibutilide Enhances Termination of AFl by
Burst Atrial Overdrive Pacing
• 26 patients for “pacing termination” with standard
protocol of “Burst Atrial Overdrive Pacing”
• Ibutilide enhanced pacing-induced termination of
AFl compared to placebo (p <0.001) .
• PACING CONVERSION:
– 2 of 11 patients (18%) on placebo
– 13 of 15 patients (87%) on Ibutilide.
Stambler BS. Am J Cardiol. 1996 May 1;77(11):960-6.
55
56. n=87 (AFL duration 2 hr to 30 days)
randomized :
Group 1—i.v. Ibutilide treatment, up to 2 mg
Group 2—ATP with “burst” and “ramp” pacing
protocols
Andrea Mazza et al. Europace 2004;6:301-30656
Ibutilide vs. Transoesophageal Atrial Pacing
57. Andrea Mazza et al. Europace 2004;6:301-306
Group 1:
i.v. ibutilide
Group 2:
Transoesophageal atrial
pacing
Rate of sinus rhythm restoration
Ibutilide appears to be the best choice in AFL
Ibutilide vs. Transoesophageal Atrial Pacing
59. Ibutilide after Radiofrequency Ablation
SN Title N
Drugs Primary
Endpoints
Results & conclusion
1
Tian XC.et al. Efficacy
of ibutilide for cardioversion
of persistent Afib during
radiofrequency ablation.
Zhonghua Xin Xue Guan
Bing Za Zhi. 2011 Nov;
39(11):1029-32.
AFib
(n = 18)
Pts treated with 1 mg
Ibutilide within 10
minutes after
unsuccessful ablation
Cardioversion Ibutilide is highly effective and safe
for cardioversion in pts where
ablation failed.
After Ibutilide administration
61.11% converted to SR.
The average conversion time was
13.80 min.
2
Hou Yu.et al. Single dose
of ibutilide for conversion
of persistent Atrial
fibrillation after
radiofrequency ablation.
Chin Med J (Engl). 2011
Mar;124(5):710-713
AFib
(n = 40)
Pts whose AFib was
not converted to
sinus rhythm after
radiofrequency
ablation were given
1mg Ibutilide.
Rate of
conversion
Ibutilide converted 72.5% patients
to sinus rhythm.
Mean conversion time = 13 mins.
No cases of serious arrhythmias or
other adverse reactions were
found.
59
60. The Modified Ablation Guided by Ibutilide Use in
Chronic Atrial Fibrillation (MAGIC-AF) Study
• International multicenter RCT
• Assessed the utility of the intraprocedural
administration of 0.25 mg of
iv Ibutilide before performing Complex
fractionated atrial electrograms (CFAE)
ablation
Singh SM. Eur Heart J. 2016 May 21;37(20):1614-21.
200 pts undergoing a first-ever persistent AF catheter ablation procedure
were randomly assigned to receive either
0.25 mg of iv Ibutilide or
saline placebo
CFAE sites were then targeted with ablation. 60
61. MAGIC-AF Study continued……
When CFAE ablation was guided by Ibutilide
administration it results into
– Reduction in CFAE area and
– Greater AF termination (75 vs. 57%)
Singh SM. Eur Heart J. 2016 May 21;37(20):1614-21.
61
62. Ibutilide for AF and flutter in cancer pts.
RESULTS:
• Successful cardioversion in 75% of
patients
• 68 patients (84%) were on at least 1
medication that prolonged the QT interval at
the time of Ibutilide administration
• No significant changes in the corrected QT
interval post Ibutilide cardioversion
Bickford CL. Am J Med Sci. 2014 Apr;347(4):277-81.
Centre: University of Texas MD Anderson Cancer Center
81 patients received Ibutilide for AF/AFL from January 2002 to May 2006
Ibutilide is safe and effective in cancer pts.
Despite the use of multiple drugs that can potentially prolong the QT interval,
no patient experienced serious rhythm disturbances or significant QT
prolongation during Ibutilide administration
62
63. Ibutilide in CAD (Coronary Artery Disease)
MVD (Mitral Valve Disease) and LAH (Left Atrial Hypertrophy)
The response rate in patients with CAD was higher than in patients without CAD
(23/30= 77%, vs. 33/71= 46%)
Das MK. Clin Cardiol. 2002 Sep;25(9):411-5.
n=101
63
64. Continued……..
Ibutilide success rate:
Presence of MVD- 37.7% (23/61 pts)
Absence of MVD- 82.5% (33/40 pts)
(p <0.01)
Ibutilide Response rate:
85% (29 of 34 ) in pts without MVD &
without markedly enlarged LA
Ibutilide is most effective in patients with CAD or in patients without MVD and/or without
markedly enlarged LA
Das MK. Clin Cardiol. 2002 Sep;25(9):411-5.
64
65. Fibricor Summary
1. Ibutilide is Pure class III antiarrhythmic drug for AFL and AF
2. Quick onset of action (with in minutes)
3. Best in class III antiarrythmics
4. Easy and rapid administration
5. Low incidence of adverse effects
6. A good alternative to electrical cardioversion
7. Ibutilide Pretreatment increases electrical conversion from 72% to 100%
8. Can be used safely in AF/ AFL patients receiving oral amiodarone
9. Accessory pathway-mediated AF- the conversion rate of Ibutilide is 95%.
10.Safe and effective in post-cardiac surgery AF patients
11.Risk of torsades de pointes (TDP)- up to 4%
12.Proarrhythmia prevented by Class IC drugs (Flecainide & Propafenone)
or IV Esmolol or Mg SO4
13.Monitor at least for 4 hrs or until QTc has returned to baseline
14.The anticoagulation strategy is the same as for any other mode of
cardioversion
65