Posts Tagged ‘European Society of Cardiology’

Pacemakers, Implantable Cardioverter Defibrillators (ICD) and Cardiac Resynchronization Therapy (CRT)

Posted in Bio Instrumentation in Experimental Life Sciences Research, Cardiac and Cardiovascular Surgical Procedures, Electrophysiology, FDA Regulatory Affairs, FDA, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, GLP, ISO 14155, Frontiers in Cardiology and Cardiovascular Disorders, ISO 10993 for Product Registration: FDA & CE Mark for Development of Medical Devices and Diagnostics, Medical Devices R&D Investment, Origins of Cardiovascular Disease, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Uncategorized, tagged arrhythmia, Artificial cardiac pacemaker, Boston Scientific, Cardiac dysrhythmia, Cardiovascular Disorders, Cathode ray tube, Defibrillation, Ejection Fraction, Electrocardiography, European Society of Cardiology, Heart Failure, ICD, Implantable cardioverter-defibrillator, Left bundle branch block, Magnetic resonance imaging, QRS, QRS complex, The New England Journal of Medicine on July 22, 2013| 2 Comments »

Pacemakers, Implantable Cardioverter Defibrillators (ICD) and Cardiac Resynchronization Therapy (CRT)

Curators: Justin D Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

Updated on 2/16/2015

Mild, non-ischemic heart failure might be more deadly than thought, an Austrian group found, calling for broader ICD use.

SOURCE

http://www.medpagetoday.com/Cardiology/Strokes/50048?isalert=1&uun=g99985d3527R5099207u&utm_source=breaking-news&utm_medium=email&utm_campaign=breaking-news&xid=NL_breakingnews_2015-02-16

 

The voice of our Series A Content Consultant: Justin D Pearlman, MD, PhD, FACC

Pacemakers place one or more wires into heart muscle to trigger electro-mechanically coupled contraction. A single wire to the right atrium is called an AAI pacemaker (atrial sensing, atrial triggering, inhibit triggering if sensed). A single wire to the right ventricle is called a VVI pacemaker (ventricular sensing, ventricular triggering, inhibit if sensed). With two wires to the heart more combinations are possible, including atrial-ventricular sequential activation, a closer mimic to normal function (DDDR pacemaker: dual sensing, dual triggering, dual functions, and rate-responsive to mimic exercise adjustment of heart rate). Three wires are used for synchronization: one to the right atrium, one to the right ventricle apex, and a third lead into a distal branch of the coronary sinus to activate the far side of the left ventricle. Resynchronization is used to compensate for a dilated ventricle, especially one with conduction delays, where the timing of activation is so unbalanced that the heart contraction approaches a wobbling motion rather than a well coordinated contraction. Adjusting timing of activation of the right ventricle and left ventricle can offset dysynchrony (unbalanced timing) and thereby increase the amount of blood ejected by each heart beat contraction (ejection fraction). Patients with dilated cardiomyopathy and significant conduction delays can improve the ejection fraction by 10 or more percentage points, which offers a significant improvement in exertion tolerance and heart failure symptoms.

Patients with ejection fraction below 35%, among others, have an elevated risk of life-ending arrhythmias such as ventricular tachycardia. Ventricular tachycardia is an extreme example of a wobbling heart in which the electrical activation sequence circles around the heart sequentially activating a portion and blocking its ability to respond until the electric signal comes around again. Whenever a portion of the heart is activated, ions shift location, and further activation of that region is not possible until sufficient time passes so that the compartmentalized ion concentrations can be restored (repolarization). Pacing can interrupt ventricular tachycardia by depolarizing a region that supported the circular activation pattern. Failing that, an electric shock can stop an ineffective rhythm. After all regions stop activation, they will generally reactivate in the normal pulsatile synchronous manner. An implanted cardiac defibrillator is a device designed to apply an internal electric shock to pause all activation and thereby interrupt ventricular tachycardia.
UPDATED on 12/31/2013

Published on Friday, 27 December 2013

S-ICD – Subcutaneous Implantable Cardioverter Defibrillator – Boston Scientific

S-ICD – Subcutaneous Implantable Cardioverter Defibrillator – Boston Scientific

‘Regular’ Pacemaker/ICD with Leads and a ‘Can’

When we think of Pacemakers and ICD’s we naturally think of a ‘Can’ and Leads that track down into the heart. Whilst these devices work fantastically well and will continue to do so. Unfortunately the ‘lead’ part of the device opens the door for a few complications to possibly arise. Those who have a Pacemaker or ICD will probably be familiar with concerns over;

1. Systemic Infection – Infections travelling down the Leads into the Heart
2. Lead Displacement – The Lead moving away from the heart tissue and thus becoming pretty useless.
3. Vascular/Organ Injury – Damage to the blood vessels being used for access or perforation of heart wall.
4. Pneumothorax (damage to the lining around the Lung), Haemothorax (build up of blood in the chest cavity), and air embolism (air bubble trapped in a blood vessel).

These complications are one of the key motivations behind developing ‘leadless’ devices the first of which the St Jude Nanostim, a small VVI Pacemaker that fits directly into the heart.

Another device to address these issues is the Boston Scientific S-ICD

What is the Boston Scientific S-ICD?

The S-ICD is what is sometimes referred to as a ‘shock box’ it does not have the pacemaker functionality that many other ICD’s do have. It is ONLY there to terminate dangerous Arrhythmias.

*It does not have the pacing functionality of traditional ICD‘s because it DOES NOT HAVE A LEAD THAT ENTERS THE HEART.*

It is not a Pacemaker!

 

Without the lead(s) ENTERING the heart via a blood vessel there is a reduction in the risks mentioned previously that are associated traditional device. Another of the benefits is that the S-ICD is positioned and implanted using anatomical landmarks (visible parts of your body) and not Fluoroscopy (video X-Ray) which reduces radiation exposure to the patient.

Positioning of the S-ICD.

The ‘Can‘ (metal box that contains all the circuitry and battery), is buried under the skin on the outside of the ribs. Put your arms down by your sides, the device would go where your ribs meet the middle of your bicep. A lead is then run under the skin to the centre of your chest where its is anchored and then north, under the skin again until the tip of the lead is roughly at the top of the sternum.

For you physicians out there the ‘can’ is positioned at the mid-axillary line between the 5th and 6th intercostal spaces, the lead is then tunnelled to a small Xiphoid incision and then tunnelled north to a superior incision.

How is an S-ICD Implanted?

VIEW VIDEO

http://www.thepad.pm/2013/12/boston-scientific-s-icd.html#!

Having spoken to Boston Scientific it is becoming more apparent that the superior incision (cut at the top of the chest) may actually be removed from the procedure guidance as simply tunnelling the lead and ‘wedging’ the tip at that point is satisfactory – THIS IS NOT CONFIRMED AT THE MOMENT AND IS THEREFORE NOT PROCEDURE ADVICE.

Image Courtesy of http://www.bostonscientific.com/

How does the S-ICD Work?

A ‘Shock Box’ basically needs to do 2 things. Firstly be able to SENSE if the heart has entered a Dangerous Arrhythmia and Secondly, be able to treat it.

The treatment part of the functionality is the easy bit – it delivers an electric shock across a ‘circuit’ that involves a large amount of the tissue in the heart. The lead has two ‘electrodes’ and the ‘Can’ is a third electrode allowing you different shocking ‘vectors’. By vectors we mean directions and area through which the electricity travels during a shock. This gives us extra options when implanting a device as some vectors will work better than others for the treatment of dangerous arrhythmias.

Shocking Vectors?

This is a concept you are familiar with without even thinking about it… when you are watching ER or another TV program and they Defibrillate the patient using the metal paddles, where do they position them? One either side of the heart? Precisely!! this is creating a ‘vector’ across the heart to involve the cardiac tissue. The paddles would be a lot less effective if you put one on the knee and one on the foot!

Now because the ‘Vectors’ used by the S-ICD are over a larger area than those with a traditional device – more energy has to be delivered to have the same desired affect. The upshot of this is that a larger battery is required to deliver the 80J! Bigger Battery = Bigger Box. This image shows a demo device but this is the exact size compared to a One Pound Coin! Now yes it is big but because of the extra room where they place the device it is pretty discrete and hidden in even slender patients.

STAT ATTACK!

The S-ICD System delivers up to 5 shocks per episode at 80 J with up to 128 seconds of ECG storage per episode and storage of up to 45 episodes.

The heart rate that the S-ICD is told to deliver therapy is programable between 170 and 250 bpm. Quite cleverly the device is able to also deliver a small amount of ‘pacing’ after a shock, when the heart can often run slowly. This is external pacing and will be felt!! It can run for 30s.

Sensing in an S-ICD.

 

The S-ICD uses its electrodes to produce an ECG similar to a surface ECG. 

 

Now the Sensing functionality is the devices ability to determine what Rhythm the heart is in! Without a lead in the heart to give us really accurate information the device is using a large area of heart, ribs and muscle. This means there is more potential for ‘artefact’. Artefact is the electrical interference and confusion – that could potentially lead to a patient being shocked when they do not require it – or not being shocked when they do…

Boston Scientific have come up with a very clever software/algorithm called ‘Insight’. Insight uses 3 separate methods to determine the nature of a heart rhythm.

• Normal Sinus Rhythm Template (Do your heart beats look as they should)
• Dynamic Morphology Analysis (A live comparison of heart beat to previous heart beat, do they all look the same or do they keep changing?)
• QRS Width analysis (Are the tall ‘peaks’ on your ECG, the QRS’, wider than they normally are?)

These questions (with some very complex maths) and the rate of a rhythm are used to decide whether to ‘shock’ or not.

Image Courtesy of  http://www.bostonscientific.com/

How does Insight and the S-ICD compare to other ICD Devices?

The statistics for treatment success and inappropriate shocks (an electrocuted patient that did not need to be) actually compare very similarly if not favourably compared to other devices on the market – these two studies are well worth a read if you have the time 🙂

1. Burke M, et al. Safety and Efficacy of a Subcutaneous Implantable-Debrillator (S-ICD System US IDE Study). Late-Breaking Abstract Session. HRS 2012.

2. Lambiase PD, et al. International Experience with a Subcutaneous ICD; Preliminary Results of the EFFORTLESS S-ICD Registry. Cardiostim 2012.

3. Gold MR, et al. Head-to-head comparison of arrhythmia discrimination performance of subcutaneous and transvenous ICD arrhythmia detection algorithms: the START study. J Cardiovasc Electrophysiol. 2012;23;4:359-366.

Who qualifies?

Template used to assess eligibility! Image Courtesy of http://www.bostonscientific.com/

Well essentially anyone who qualifies for a normal ‘shock box’ ICD but with one other requirement. The Insight Software requires that a person has certain characteristics on their ECG. This is essentially showing that they have tall enough and narrow enough complexes to allow the algorithm to perform effectively. A simple 12 lead ECG Laying and Standing will be obtained and then a ‘Stencil’ is passed over the Print out – If the complexes fit within the boundaries marked on the ‘stencil’ then you potentially qualify. If your ECG does not meet requirements then it will not be recommended for you to have the S-ICD.

There you have it a quick overview of the Boston Scientific S-ICD.

Thanks for Reading

Cardiac Technician

SOURCE

http://www.thepad.pm/2013/12/boston-scientific-s-icd.html#!

UPDATED on 10/15/2013

Frequency and Determinants of Implantable Cardioverter Defibrillator Deployment Among Primary Prevention Candidates With Subsequent Sudden Cardiac Arrest in the Community

1. Kumar Narayanan, MD;
2. Kyndaron Reinier, PhD;
3. Audrey Uy-Evanado, MD;
4. Carmen Teodorescu, MD, PhD;
5. Harpriya Chugh, BS;
6. Eloi Marijon, MD;
7. Karen Gunson, MD;
8. Jonathan Jui, MD, MPH;
9. Sumeet S. Chugh, MD

+Author Affiliations

1. 
   
   From The Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA (K.N., K.R., A.U.-E., C.T., H.C., E.M., S.S.C.); and Departments of Pathology (K.G.) and Emergency Medicine (J.J.), Oregon Health and Science University, Portland, OR.

1. Correspondence to Sumeet S. Chugh, MD, Cedars-Sinai Medical Center, The Heart Institute, AHSP Suite A3100, 127 S. San Vicente Blvd., Los Angeles, CA 90048, Los Angeles, CA 90048. E-mail sumeet.chugh@cshs.org

Abstract

Background—The prevalence rates and influencing factors for deployment of primary prevention implantable cardioverter defibrillators (ICDs) among subjects who eventually experience sudden cardiac arrest in the general population have not been evaluated.

Methods and Results—Cases of adult sudden cardiac arrest with echocardiographic evaluation before the event were identified from the ongoing Oregon Sudden Unexpected Death Study (population approximately 1 million). Eligibility for primary ICD implantation was determined from medical records based on established guidelines. The frequency of prior primary ICD implantation in eligible subjects was evaluated, and ICD nonrecipients were characterized. Of 2093 cases (2003–2012), 448 had appropriate pre– sudden cardiac arrest left ventricular ejection fraction information available. Of these, 92 (20.5%) were eligible for primary ICD implantation, 304 (67.9%) were ineligible because of left ventricular ejection fraction >35%, and the remainder (52, 11.6%) had left ventricular ejection fraction ≤35% but were ineligible on the basis of clinical guideline criteria. Among eligible subjects, only 12 (13.0%; 95% confidence interval, 6.1%–19.9%) received a primary ICD. Compared with recipients, primary ICD nonrecipients were older (age at ejection fraction assessment, 67.1±13.6 versus 58.5±14.8 years, P=0.05), with 20% aged ≥80 years (versus 0% among recipients, P=0.11). Additionally, a subgroup (26%) had either a clinical history of dementia or were undergoing chronic dialysis.

Conclusions—Only one fifth of the sudden cardiac arrest cases in the community were eligible for a primary prevention ICD before the event, but among these, a small proportion (13%) were actually implanted. Although older age and comorbidity may explain nondeployment in a subgroup of these cases, other determinants such as socioeconomic factors, health insurance, patient preference, and clinical practice patterns warrant further detailed investigation.

Key Words:

• death, sudden
• epidemiology
• heart arrest
• implantable defibrillators
• population
• utilization

• Received March 11, 2013.
• Accepted August 21, 2013

http://circ.ahajournals.org/content/128/16/1733.abstract

UPDATED on 9/15/2013

based on 9/6/2013 Trials and Fibrillations — The Heart.org

http://www.theheart.org/columns/trials-and-fibrillations-with-dr-john-mandrola/new-post-39.do#!

Echo-CRT trial: Most important study released at ESC 2013

Cardiac resynchronization therapy (CRT) is a multilead pacing device that can extend lives and improve the quality of life of selected patients who suffer from reduced performance of the heart due to adverse timing of contraction (wobbling motion from conduction delays that cause asynchrony or  delayed activation of one portion of the left ventricle compared to others reducing net blood ejection).

The degree of benefit in CRT responders depends not only on the degree of asynchrony, but also on the delayed activity location in relation to the available locations for lead placement. CRT is an adjustment in the timing of muscle activiation to improve the concerted impact on blood ejection. Only patients likely to improve should be exposed to the risks and costs of CRT.

The Echo-CRT trial, presented September 3, 2013 at the European Society of Cardiology (ESC) 2013 Congressand simultaneously published in the New England Journal of Medicine, helps identify which patients may benefit from CRT devices. (See Steve Stiles’ report on heartwire),

Echo-CRT trial summary

Background is important

Previous CRT studies enrolled patients with QRS duration >120 or >130 ms for synchronizing biventricular pacing. Additional work confirmed the greatest benefit occurred in patients with QRS durations >150 ms and typical left bundle branch block (LBBB). Conflicting observational and small randomized trials were less clear for patients with shorter QRS durations—the majority of heart-failure patients. What’s more, most cardiologists have seen patients with “modest” QRS durations respond to CRT. In theory, wide QRS is only expected if the axis of significant delay projects onto the standard ECG views, whereas significant opportunity for benefit can be missed if the axis of significant delay is not wide in the standard views. CRT implanters have heard of patients with normal-duration QRS where echo shows marked dyssynchrony. This raised the  question: Are there CHF patients with mechanical dyssynchrony (determined by echo) but no electrical delay (as measured by the ECG) benefit from CRT?Unfortunately, echo does not resolve the issue either. Thus there is the residual question of who should be evaluated by a true 3D syncrhony assessment by cardiac MRI.

Echocardiographic techniques held promise to identify mechanical dyssynchrony, but like the standard 12 lead ECG, they also utilize limited orientations of views of the heart and hence the directions in which delays can be detected. Cardiac MRI Research (not limited in view angle) by JDPearlman showed that the axis of maximal delay in patients with asynchrony is within 30 degrees of the ECG and echo views in a majority of patients with asynchrony, but it can be 70-110 degrees away from the views used by echocardiography and by ECG in 20% of cases. Hence some patients who may benefit can be missed by ECG or Echo criteria.

Methodology

Echo-CRT was an industry-sponsored (Biotronik) investigator-initiated prospective international randomized controlled trial. All patients had mechanical dyssynchrony by echo, QRS <130 ms, and an ICD indication. CRT-D devices were implanted in all patients. Blinded randomization to CRT-on (404 patients) vs CRT-off (405 patients) was performed after implantation. Programming in the CRT-off group was set to minimize RV pacing. The primary outcome was a composite of all-cause mortality or hospitalization.

Six key findings

1. Although entry criteria for the trial was a QRS duration <130 ms, the mean QRS duration of both groups was 105 ms.

2. The data safety monitoring board terminated the trial prematurely because of an increased death rate in the CRT group.

3. No differences were noted in the primary outcome.

4. More patients died in the CRT group (hazard ratio=1.8).

5. The higher death rate in the CRT group was driven by cardiovascular death.

6. More patients in the CRT group were hospitalized, due primarily to device-related issues.

These findings send clear and simple messages to all involved with treating patients with heart failure. My interpretation of Echo-CRT is as follows:

Do not implant CRT devices in patients with “narrow” QRS complexes.

The signal of increased death was strong. A hazard ratio of 1.8 translates to an almost doubling of the risk of death. This finding is unlikely to be a statistical anomaly, as it was driven by CV death. The risks of CRT in nonresponders are well-known and include: increased RV pacing, possible proarrhythmia from LV pacing, and the need for more device-related surgery. Patients who do not respond to CRT get none of the benefits but all the potential harms—an unfavorable ratio indeed.

Echo is not useful for assessing dyssynchrony in patients with narrow QRS complexes.

Dr Samuel Asirvatham explains the concept of electropathy in a review article in the Journal of Cardiovascular Electrophysiology. He teaches us that the later the LV lateral wall is activated relative to the RV, the more the benefit of preexciting the lateral wall with an LV lead. That’s why the benefit from CRT in many cases increases with QRS duration, because—in a majority—a wide QRS means late activation of the lateral LV.

Simple triumphs over complicated—CRT response best estimated with the old-fashioned ECG.

In a right bundle branch block, the left ventricle is activated first; in LBBB, the LV lateral wall is last, and with a nonspecific ICD, there’s delayed conduction in either the His-Purkinje system or in ventricular muscle. What does a normal QRS say? It says the wave front of activation as projected onto the electric views obtained activates the LV and RV simultaneously. If those views capture the worst delay then they can eliminate the  need for resynchrony.

CRT benefit with mild-moderate QRS prolongation still not settled

Dr Robert Myerburg (here and here) teaches us to make a distinction between trial entry criteria and the actual values of the cohort.

Consider how this applies to QRS duration:  COMPANION and CARE-HF are clinical trials that showed definitive CRT benefit. Entry required a QRS duration >120 ms (130 ms in CARE-HF). But the actual mean QRS duration of enrolled patients was 160 ms. A meta-analysis of CRT trials confirmed benefit at longer QRS durations and questioned it below 150 ms. CRT guideline recommendations incorporate study entry criteria, not the mean values of actual patients in the trial. Patients enrolled in Echo-CRT had very narrow QRS complexes (105 ms). What to recommend in the common situation when a patient with a typical LBBB has a QRS duration straddling 130 ms is not entirely clear. The results of Echo-CRT might have been different had the actual QRS duration values been closer to 130 ms.

Conclusion

Echo-CRT study reinforces expectations based on cardiac physiology. In the practice of medicine, it’s quite useful to know when not to do something.

The trial should not dampen enthusiasm for CRT. Rather, it should focus our attention to patient selection—and the value of the 12-lead ECG.

 References

Rethinking QRS Duration as an Indication for CRT

SMITA MEHTA M.D.^{1 and} SAMUEL J. ASIRVATHAM M.D., F.A.C.C.^2,3

Author Information

1. Department of Pediatric Cardiology, Cleveland Clinic, Cleveland, Ohio, USA
2. Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
3. Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, USA

^*Samuel J. Asirvatham, M.D., Division of Cardiovascular Diseases, Department of Internal Medicine and Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. E-mail: asirvatham.samuel@mayo.edu

J Cardiovasc Electrophysiol, Vol. 23, pp. 169-171, February 2012.

http://onlinelibrary.wiley.com/doi/10.1111/j.1540-8167.2011.02163.x/full

Indications for Implantable Cardioverter-Defibrillators Based on Evidence and Judgment FREE

Robert J. Myerburg, MD; Vivek Reddy, MD; Agustin Castellanos, MD

 

J Am Coll Cardiol. 2009;54(9):747-763. doi:10.1016/j.jacc.2009.03.078

Implantable Cardioverter–Defibrillators after Myocardial Infarction

Robert J. Myerburg, M.D.

Division of Cardiology, University of Miami Miller School of Medicine, Miami.

N Engl J Med 2008; 359:2245-2253 November 20, 2008DOI: 10.1056/NEJMra0803409

END OF UPDATE

Electrical conduction of the Human Heart

• Physiology and
• Genetics

were explained by us in the following articles:

Genetics of Conduction Disease: Atrioventricular (AV) Conduction Disease (block): Gene Mutations – Transcription, Excitability, and Energy Homeostasis

On Devices and On Algorithms: Prediction of Arrhythmia after Cardiac Surgery and ECG Prediction of an Onset of Paroxysmal Atrial Fibrillation

Dilated Cardiomyopathy: Decisions on implantable cardioverter-defibrillators (ICDs) using left ventricular ejection fraction (LVEF)

Reduction in Inappropriate Therapy and Mortality through ICD Programming

Below, we present the following complementary topics:

Options for Cardiac Resynchronization Therapy (CRT) to Arrhythmias:

• Implantable Pacemaker
• Insertable Programmable Cardioverter Defibrillator (ICD)

UPDATED 8/6/2013

Medtronic Pacemaker Recall

 

17/07/2013

Australia’s regulatory authority, the Therapeutic Goods Administration (TGA) has issued a hazard alert pertaining to one of Medtronic’s pacing devices, the Consulta® Cardiac Resynchronization Therapy Pacemaker (CRT-P). The alert coincides somewhat with Medtronic’s own issuance of a field safety notice concerning Consulta and Syncra® CRT-P devices.

Background

Consulta and Syncra CRT-Ps are implantable medical devices used to treat heart failure. The devices provide pacing to help coordinate the heart’s pumping action and improve blood flow.

The two devices are the subject of a global manufacturer recall after Medtronic had identified an issue with a subset of both during production, although as yet there had been no reported or confirmed device failures. However, because of the potential for malfunction, Medtronic is requiring the return of non-implanted devices manufactured between April 1 and May 13, 2013 for re-inspection.

Seemingly this manufacturing issue could compromise the sealing of the device. Should an out-of-spec weld fail this could result in body fluids entering the device, which could cause it to malfunction leading to loss of pacing output. This could potentially see the return of symptoms including

• fainting or lightheadedness,
• dyspnoea (shortness of breath),
• fatigue and
• oedema.

Medtronic’s recall is thought to relate to 265 devices, 44 of which have been implanted in the US.

The Australian warning letter, issued by the TGA states that only one “at risk” Consulta CRT-P device has been implanted in the country and there have been no reports of device failures or patient injuries relating to this issue.

Neither Medtronic nor the TGA are suggesting any specific patient management measures other than routine follow-up in accordance with labelling instructions.

 http://www.remtecsearch.com/news/industry-news/medtronic-pacemaker-recall

http://www.medlatest.com/2013/07/17/medtronic-pacemaker-recall/

Pacemaker/Implantable Cardioverter Defibrillator (ICD) Insertion

Procedure Overview What is a pacemaker/implantable cardioverter defibrillator (ICD) insertion? A pacemaker/implantable cardioverter defibrillator (ICD) insertion is a procedure in which a pacemaker and/or an ICD is inserted to assist in regulating problems with the heart rate (pacemaker) or heart rhythm (ICD). Pacemaker When a problem develops with the heart’s rhythm, such as a slow rhythm, a pacemaker may be selected for treatment. A pacemaker is a small electronic device composed of three parts: a generator, one or more leads, and an electrode on each lead. A pacemaker signals the heart to beat when the heartbeat is too slow. Click Image to Enlarge A generator is the “brain” of the pacemaker device. It is a small metal case that contains electronic circuitry and a battery. The lead (or leads) is an insulated wire that is connected to the generator on one end, with the other end placed inside one of the heart’s chambers. The electrode on the end of the lead touches the heart wall. In most pacemakers, the lead senses the heart’s electrical activity. This information is relayed to the generator by the lead. If the heart’s rate is slower than the programmed limit, an electrical impulse is sent through the lead to the electrode and the pacemaker’s electrical impulse causes the heart to beat at a faster rate. When the heart is beating at a rate faster than the programmed limit, the pacemaker will monitor the heart rate, but will not pace. No electrical impulses will be sent to the heart unless the heart’s natural rate falls below the pacemaker’s low limit. Pacemaker leads may be positioned in the atrium or ventricle or both, depending on the condition requiring the pacemaker to be inserted. An atrial dysrhythmia/arrhythmia (an abnormal heart rhythm caused by a dysfunction of the sinus node or the development of another atrial pacemaker within the heart tissue that takes over the function of the sinus node) may be treated with an atrial pacemaker. Click Image to Enlarge A ventricular dysrhythmia/arrhythmia (an abnormal heart rhythm caused by a dysfunction of the sinus node, an interruption in the conduction pathways, or the development of another pacemaker within the heart tissue that takes over the function of the sinus node) may be treated with a ventricular pacemaker whose lead wire is located in the ventricle. It is possible to have both atrial and ventricular dysrhythmias, and there are pacemakers that have lead wires positioned in both the atrium and the ventricle. There may be one lead wire for each chamber, or one lead wire may be capable of sensing and pacing both chambers. A new type of pacemaker, called a biventricular pacemaker, is currently used in the treatment of congestive heart failure. Sometimes in heart failure, the two ventricles (lower heart chambers) do not pump together in a normal manner. When this happens, less blood is pumped by the heart. A biventricular pacemaker paces both ventricles at the same time, increasing the amount of blood pumped by the heart. This type of treatment is called cardiac resynchronization therapy. Implantable cardioverter defibrillator (ICD) An implantable cardioverter defibrillator (ICD) looks very similar to a pacemaker, except that it is slightly larger. It has a generator, one or more leads, and an electrode for each lead. These components work very much like a pacemaker. However, the ICD is designed to deliver an electrical shock to the heart when the heart rate becomes dangerously fast, or €œfibrillates.” An ICD senses when the heart is beating too fast and delivers an electrical shock to convert the fast rhythm to a normal rhythm. Some devices combine a pacemaker and ICD in one unit for persons who need both functions. The ICD has another type of treatment for certain fast rhythms called anti-tachycardia pacing (ATP). When ATP is used, a fast pacing impulse is sent to correct the rhythm. After the shock is delivered, a “back-up” pacing mode is used if needed for a short while. The procedure for inserting a pacemaker or an ICD is the same. The procedure generally is performed in an electrophysiology (EP) lab or a cardiac catheterization lab. Other related procedures that may be used to assess the heart include resting and exercise electrocardiogram (ECG), Holter monitor, signal-averaged ECG, cardiac catheterization, chest x-ray, computed tomography (CT scan) of the chest, echocardiography, electrophysiology studies, magnetic resonance imaging (MRI) of the heart, myocardial perfusion scans, radionuclide angiography, and ultrafast CT scan. The heart’s electrical conduction system Click Image to Enlarge The heart is, in the simplest terms, a pump made up of muscle tissue. Like all pumps, the heart requires a source of energy in order to function. The heart’s pumping energy comes from an indwelling electrical conduction system. An electrical stimulus is generated by the sinus node (also called the sinoatrial node, or SA node), which is a small mass of specialized tissue located in the right atrium (right upper chamber) of the heart. The sinus node generates an electrical stimulus regularly at 60 to 100 times per minute under normal conditions. This electrical stimulus travels down through the conduction pathways (similar to the way electricity flows through power lines from the power plant to your house) and causes the heart’s chambers to contract and pump out blood. The right and left atria (the two upper chambers of the heart) are stimulated first and contract a short period of time before the right and left ventricles (the two lower chambers of the heart). The electrical impulse travels from the sinus node to the atrioventricular (AV) node, where it stops for a very short period, then continues down the conduction pathways via the “bundle of His” into the ventricles. The bundle of His divides into right and left pathways to provide electrical stimulation to both ventricles. What is an ECG? This electrical activity of the heart is measured by an electrocardiogram (ECG or EKG). By placing electrodes at specific locations on the body (chest, arms, and legs), a tracing of the electrical activity can be obtained. Changes in an ECG from the normal tracing can indicate one or more of several heart-related conditions. Dysrhythmias/arrhythmias (abnormal heart rhythms) are diagnosed by methods such as EKG, Holter monitoring, signal-average EKG, or electrophysiological studies. These symptoms may be treated with medication or procedures such as a cardiac ablation (removal of a location in the heart that is causing a dysrhythmia by freezing or radiofrequency). Reasons for the Procedure A pacemaker may be inserted in order to provide stimulation for a faster heart rate when the heart is beating too slowly, and when other treatment methods, such as medication, have not improved the heart rate. An ICD may be inserted in order to provide fast pacing (ATP), cardioversion (small shock), or defibrillation (larger shock) when the heart beats too fast. Problems with the heart rhythm may cause difficulties because the heart is unable to pump an adequate amount of blood to the body. If the heart rate is too slow, the blood is pumped too slowly. If the heart rate is too fast or too irregular, the heart chambers are unable to fill up with enough blood to pump out with each beat. When the body does not receive enough blood, symptoms such as fatigue, dizziness, fainting, and/or chest pain may occur. Some examples of rhythm problems for which a pacemaker or ICD might be inserted include: atrial fibrillation – occurs when the atria beat irregularly and too fast ventricular fibrillation – occurs when the ventricles beat irregularly and too fast bradycardia – occurs when the heart beats too slow tachycardia – occurs when the heart beats too fast heart block – occurs when the electrical signal is delayed after leaving the SA node; there are several types of heart blocks, and each one has a distinctive ECG tracing There may be other reasons for your physician to recommend a pacemaker or ICD insertion. Risks of the Procedure Possible risks of pacemaker or ICD insertion include, but are not limited to, the following: bleeding from the incision or catheter insertion site damage to the vessel at the catheter insertion site infection of the incision or catheter site pneumothorax – air becomes trapped in the pleural space causing the lung to collapse If you are pregnant or suspect that you may be pregnant, you should notify your physician. If you are lactating, or breastfeeding, you should notify your physician. Patients who are allergic to or sensitive to medications or latex should notify their physician. For some patients, having to lie still on the procedure table for the length of the procedure may cause some discomfort or pain. There may be other risks depending upon your specific medical condition. Be sure to discuss any concerns with your physician prior to the procedure. Before the Procedure Your physician will explain the procedure to you and offer you the opportunity to ask any questions that you might have about the procedure. You will be asked to sign a consent form that gives your permission to do the test. Read the form carefully and ask questions if something is not clear. You will need to fast for a certain period of time prior to the procedure. Your physician will notify you how long to fast, usually overnight. If you are pregnant or suspect that you are pregnant, you should notify your physician. Notify your physician if you are sensitive to or are allergic to any medications, iodine, latex, tape, or anesthetic agents (local and general). Notify your physician of all medications (prescription and over-the-counter) and herbal supplements that you are taking. Notify your physician if you have heart valve disease, as you may need to receive an antibiotic prior to the procedure. Notify your physician if you have a history of bleeding disorders or if you are taking any anticoagulant (blood-thinning) medications, aspirin, or other medications that affect blood clotting. It may be necessary for you to stop some of these medications prior to the procedure. Your physician may request a blood test prior to the procedure to determine how long it takes your blood to clot. Other blood tests may be done as well. You may receive a sedative prior to the procedure to help you relax. If a sedative is given, you will need someone to drive you home afterwards. The upper chest may be shaved or clipped prior to the procedure. Based upon your medical condition, your physician may request other specific preparation. During the Procedure Chest X-ray with Implanted Pacemaker A pacemaker or implanted cardioverter defibrillator may be performed on an outpatient basis or as part of your stay in a hospital. Procedures may vary depending on your condition and your physician’s practices. Generally, a pacemaker or ICD insertion follows this process: You will be asked to remove any jewelry or other objects that may interfere with the procedure. You will be asked to remove your clothing and will be given a gown to wear. You will be asked to empty your bladder prior to the procedure. An intravenous (IV) line will be started in your hand or arm prior to the procedure for injection of medication and to administer IV fluids, if needed. You will be placed in a supine (on your back) position on the procedure table. You will be connected to an electrocardiogram (ECG or EKG) monitor that records the electrical activity of the heart and monitors the heart during the procedure using small, adhesive electrodes. Your vital signs (heart rate, blood pressure, breathing rate, and oxygenation level) will be monitored during the procedure. Large electrode pads will be placed on the front and back of the chest. You will receive a sedative medication in your IV before the procedure to help you relax. However, you will likely remain awake during the procedure. The pacemaker or ICD insertion site will be cleansed with antiseptic soap. Sterile towels and a sheet will be placed around this area. A local anesthetic will be injected into the skin at the insertion site. Once the anesthetic has taken effect, the physician will make a small incision at the insertion site. A sheath, or introducer, is inserted into a blood vessel, usually under the collarbone. The sheath is a plastic tube through which the pacer/ICD lead wire will be inserted into the blood vessel and advanced into the heart. It will be very important for you to remain still during the procedure so that the catheter placement will not be disturbed and to prevent damage to the insertion site. The lead wire will be inserted through the introducer into the blood vessel. The physician will advance the lead wire through the blood vessel into the heart. Once the lead wire is inside the heart, it will be tested to verify proper location and that it works. There may be one, two, or three lead wires inserted, depending on the type of device your physician has chosen for your condition. Fluoroscopy, (a special type of x-ray that will be displayed on a TV monitor), may be used to assist in testing the location of the leads. Once the lead wire has been tested, an incision will be made close to the location of the catheter insertion (just under the collarbone). You will receive local anesthetic medication before the incision is made. The pacemaker/ICD generator will be slipped under the skin through the incision after the lead wire is attached to the generator. Generally, the generator will be placed on the non-dominant side. (If you are right-handed, the device will be placed in your upper left chest. If you are left-handed, the device will be placed in your upper right chest). The ECG will be observed to ensure that the pacer is working correctly. The skin incision will be closed with sutures, adhesive strips, or a special glue. A sterile bandage/dressing will be applied. After the Procedure In the hospital After the procedure, you may be taken to the recovery room for observation or returned to your hospital room. A nurse will monitor your vital signs for a specified period of time. You should immediately inform your nurse if you feel any chest pain or tightness, or any other pain at the incision site. After the specified period of bed rest has been completed, you may get out of bed. The nurse will assist you the first time you get up, and will check your blood pressure while you are lying in bed, sitting, and standing. You should move slowly when getting up from the bed to avoid any dizziness from the period of bedrest. You will be able to eat or drink once you are completely awake. The insertion site may be sore or painful, but pain medication may be administered if needed. Your physician will visit with you in your room while you are recovering. The physician will give you specific instructions and answer any questions you may have. Once your blood pressure, pulse, and breathing are stable and you are alert, you will be taken to your hospital room or discharged home. If the procedure is performed on an outpatient basis, you may be allowed to leave after you have completed the recovery process. However, if there are concerns or problems with your ECG, you may stay in the hospital for an additional day (or longer) for monitoring of the ECG. You should arrange to have someone drive you home from the hospital following your procedure. At home You should be able to return to your daily routine within a few days. Your physician will tell you if you will need to take more time in returning to your normal activities. In addition, you should not do any lifting or pulling on anything for a few weeks. You may be instructed not to lift your arms above your head for a period of time. You will most likely be able to resume your usual diet, unless your physician instructs you differently. It will be important to keep the insertion site clean and dry. Your physician will give you specific bathing instructions. Your physician will give you specific instructions about driving. If you had an ICD, you will not be able to drive until your physician gives you approval. Your physician will explain these limitations to you, if they are applicable to your situation. You will be given specific instructions about what to do if your ICD discharges a shock. For example, you may be instructed to dial 911 or go to the nearest emergency room in the event of a shock from the ICD. Ask your physician when you will be able to return to work. The nature of your occupation, your overall health status, and your progress will determine how soon you may return to work. Notify your physician to report any of the following: fever and/or chills increased pain, redness, swelling, or bleeding or other drainage from the insertion site chest pain/pressure, nausea and/or vomiting, profuse sweating, dizziness and/or fainting palpitations Your physician may give you additional or alternate instructions after the procedure, depending on your particular situation. Pacemaker/ICD precautions The following precautions should always be considered. Discuss the following in detail with your physician, or call the company that made your device: Always carry an ID card that states you are wearing a pacemaker or an ICD. In addition, you should wear a medical identification bracelet that states you have a pacemaker or ICD. Use caution when going through airport security detectors. Check with your physician about the safety of going through such detectors with your type of pacemaker. In particular, you may need to avoid being screened by hand-held detector devices, as these devices may affect your pacemaker. You may not have a magnetic resonance imaging (MRI) procedure. You should also avoid large magnetic fields. Abstain from diathermy (the use of heat in physical therapy to treat muscles). Turn off large motors, such as cars or boats, when working on them (they may temporarily €œconfuse” your device). Avoid certain high-voltage or radar machinery, such as radio or television transmitters, electric arc welders, high-tension wires, radar installations, or smelting furnaces. If you are having a surgical procedure performed by a surgeon or dentist, tell your surgeon or dentist that you have a pacemaker or ICD, so that electrocautery will not be used to control bleeding (the electrocautery device can change the pacemaker settings). You may have to take antibiotic medication before any medically invasive procedure to prevent infections that may affect the pacemaker. Always consult your physician if you have any questions concerning the use of certain equipment near your pacemaker. When involved in a physical, recreational, or sporting activity, you should avoid receiving a blow to the skin over the pacemaker or ICD. A blow to the chest near the pacemaker or ICD can affect its functioning. If you do receive a blow to that area, see your physician. Always consult your physician when you feel ill after an activity, or when you have questions about beginning a new activity.

SOURCE

http://stanfordhospital.org/healthLib/greystone/heartCenter/heartProcedures/pacemakerImplantableCardioverterDefibrillatorICDInsertion.html

In Summary: Who Needs a Pacemaker?

Doctors recommend pacemakers for many reasons. The most common reasons are bradycardia and heart block.

Bradycardia is a heartbeat that is slower than normal. Heart block is a disorder that occurs if an electrical signal is slowed or disrupted as it moves through the heart.

Heart block can happen as a result of aging, damage to the heart from a heart attack, or other conditions that disrupt the heart’s electrical activity. Some nerve and muscle disorders also can cause heart block, including muscular dystrophy.

Your doctor also may recommend a pacemaker if:

• Aging or heart disease damages your sinus node’s ability to set the correct pace for your heartbeat. Such damage can cause slower than normal heartbeats or long pauses between heartbeats. The damage also can cause your heart to switch between slow and fast rhythms. This condition is called sick sinus syndrome.
• You’ve had a medical procedure to treat an arrhythmia called atrial fibrillation. A pacemaker can help regulate your heartbeat after the procedure.
• You need to take certain heart medicines, such as beta blockers. These medicines can slow your heartbeat too much.
• You faint or have other symptoms of a slow heartbeat. For example, this may happen if the main artery in your neck that supplies your brain with blood is sensitive to pressure. Just quickly turning your neck can cause your heart to beat slower than normal. As a result, your brain might not get enough blood flow, causing you to feel faint or collapse.
• You have heart muscle problems that cause electrical signals to travel too slowly through your heart muscle. Your pacemaker may provide cardiac resynchronization therapy (CRT) for this problem. CRT devices coordinate electrical signaling between the heart’s lower chambers.
• You have long QT syndrome, which puts you at risk for dangerous arrhythmias.

Doctors also may recommend pacemakers for people who have certain types ofcongenital heart disease or for people who have had heart transplants. Children, teens, and adults can use pacemakers.

Before recommending a pacemaker, your doctor will consider any arrhythmia symptoms you have, such as dizziness, unexplained fainting, or shortness of breath. He or she also will consider whether you have a history of heart disease, what medicines you’re currently taking, and the results of heart tests.

Diagnostic Tests

Many tests are used to detect arrhythmias. You may have one or more of the following tests.

EKG (Electrocardiogram)

An EKG is a simple, painless test that detects and records the heart’s electrical activity. The test shows how fast your heart is beating and its rhythm (steady or irregular).

An EKG also records the strength and timing of electrical signals as they pass through your heart. The test can help diagnose bradycardia and heart block (the most common reasons for needing a pacemaker).

A standard EKG only records the heartbeat for a few seconds. It won’t detect arrhythmias that don’t happen during the test.

To diagnose heart rhythm problems that come and go, your doctor may have you wear a portable EKG monitor. The two most common types of portable EKGs are Holter and event monitors.

Holter and Event Monitors

A Holter monitor records the heart’s electrical activity for a full 24- or 48-hour period. You wear one while you do your normal daily activities. This allows the monitor to record your heart for a longer time than a standard EKG.

An event monitor is similar to a Holter monitor. You wear an event monitor while doing your normal activities. However, an event monitor only records your heart’s electrical activity at certain times while you’re wearing it.

For many event monitors, you push a button to start the monitor when you feel symptoms. Other event monitors start automatically when they sense abnormal heart rhythms.

You can wear an event monitor for weeks or until symptoms occur.

Echocardiography

Echocardiography (echo) uses sound waves to create a moving picture of your heart. The test shows the size and shape of your heart and how well your heart chambers and valves are working.

Echo also can show areas of poor blood flow to the heart, areas of heart muscle that aren’t contracting normally, and injury to the heart muscle caused by poor blood flow.

Electrophysiology Study

For this test, a thin, flexible wire is passed through a vein in your groin (upper thigh) or arm to your heart. The wire records the heart’s electrical signals.

Your doctor uses the wire to electrically stimulate your heart. This allows him or her to see how your heart’s electrical system responds. This test helps pinpoint where the heart’s electrical system is damaged.

Stress Test

Some heart problems are easier to diagnose when your heart is working hard and beating fast.

During stress testing, you exercise to make your heart work hard and beat fast while heart tests, such as an EKG or echo, are done. If you can’t exercise, you may be given medicine to raise your heart rate.

SOURCE

http://www.nhlbi.nih.gov/health/health-topics/topics/pace/whoneeds.html

What Are the Risks of Pacemaker Surgery?

Pacemaker surgery generally is safe. If problems do occur, they may include:

• Swelling, bleeding, bruising, or infection in the area where the pacemaker was placed
• Blood vessel or nerve damage
• A collapsed lung
• A bad reaction to the medicine used during the procedure

Talk with your doctor about the benefits and risks of pacemaker surgery.

How Does a Pacemaker Work?

A pacemaker consists of a battery, a computerized generator, and wires with sensors at their tips. (The sensors are called electrodes.) The battery powers the generator, and both are surrounded by a thin metal box. The wires connect the generator to the heart.

A pacemaker helps monitor and control your heartbeat. The electrodes detect your heart’s electrical activity and send data through the wires to the computer in the generator.

If your heart rhythm is abnormal, the computer will direct the generator to send electrical pulses to your heart. The pulses travel through the wires to reach your heart.

Newer pacemakers can monitor your blood temperature, breathing, and other factors. They also can adjust your heart rate to changes in your activity.

The pacemaker’s computer also records your heart’s electrical activity and heart rhythm. Your doctor will use these recordings to adjust your pacemaker so it works better for you.

Your doctor can program the pacemaker’s computer with an external device. He or she doesn’t have to use needles or have direct contact with the pacemaker.

Pacemakers have one to three wires that are each placed in different chambers of the heart.

• The wires in a single-chamber pacemaker usually carry pulses from the generator to the right ventricle (the lower right chamber of your heart).
• The wires in a dual-chamber pacemaker carry pulses from the generator to the right atrium (the upper right chamber of your heart) and the right ventricle. The pulses help coordinate the timing of these two chambers’ contractions.
• The wires in a biventricular pacemaker carry pulses from the generator to an atrium and both ventricles. The pulses help coordinate electrical signaling between the two ventricles. This type of pacemaker also is called a cardiac resynchronization therapy (CRT) device.

Cross-Section of a Chest With a Pacemaker

The image shows a cross-section of a chest with a pacemaker. Figure A shows the location and general size of a double-lead, or dual-chamber, pacemaker in the upper chest. The wires with electrodes are inserted into the heart’s right atrium and ventricle through a vein in the upper chest. Figure B shows an electrode electrically stimulating the heart muscle. Figure C shows the location and general size of a single-lead, or single-chamber, pacemaker in the upper chest.

Types of Pacemaker Programming

The two main types of programming for pacemakers are

• demand pacing and
• rate-responsive pacing.

A demand pacemaker monitors your heart rhythm. It only sends electrical pulses to your heart if your heart is beating too slow or if it misses a beat.

A rate-responsive pacemaker will speed up or slow down your heart rate depending on how active you are. To do this, the device monitors your

• sinus node rate,
• breathing,
• blood temperature, and
• other factors to determine your activity level.

Your doctor will work with you to decide which type of pacemaker is best for you.

SOURCE

http://www.nhlbi.nih.gov/health/health-topics/topics/pace/howdoes.html

What To Expect During Pacemaker Surgery

Placing a pacemaker requires minor surgery. The surgery usually is done in a hospital or special heart treatment laboratory.

Before the surgery, an intravenous (IV) line will be inserted into one of your veins. You will receive medicine through the IV line to help you relax. The medicine also might make you sleepy.

Your doctor will numb the area where he or she will put the pacemaker so you don’t feel any pain. Your doctor also may give you antibiotics to prevent infection.

First, your doctor will insert a needle into a large vein, usually near the shoulder opposite your dominant hand. Your doctor will then use the needle to thread the pacemaker wires into the vein and to correctly place them in your heart.

An x-ray “movie” of the wires as they pass through your vein and into your heart will help your doctor place them. Once the wires are in place, your doctor will make a small cut into the skin of your chest or abdomen.

He or she will slip the pacemaker’s small metal box through the cut, place it just under your skin, and connect it to the wires that lead to your heart. The box contains the pacemaker’s battery and generator.

Once the pacemaker is in place, your doctor will test it to make sure it works properly. He or she will then sew up the cut. The entire surgery takes a few hours.

SOURCE

http://www.nhlbi.nih.gov/health/health-topics/topics/pace/during.html

What To Expect After Pacemaker Surgery

Expect to stay in the hospital overnight so your health care team can check your heartbeat and make sure your pacemaker is working well. You’ll likely have to arrange for a ride to and from the hospital because your doctor may not want you to drive yourself.

For a few days to weeks after surgery, you may have pain, swelling, or tenderness in the area where your pacemaker was placed. The pain usually is mild; over-the-counter medicines often can relieve it. Talk to your doctor before taking any pain medicines.

Your doctor may ask you to avoid vigorous activities and heavy lifting for about a month after pacemaker surgery. Most people return to their normal activities within a few days of having the surgery.

SOURCE

http://www.nhlbi.nih.gov/health/health-topics/topics/pace/after.html

How Will a Pacemaker Affect My Lifestyle?

Once you have a pacemaker, you have to avoid close or prolonged contact with electrical devices or devices that have strong magnetic fields. Devices that can interfere with a pacemaker include:

• Cell phones and MP3 players (for example, iPods)
• Household appliances, such as microwave ovens
• High-tension wires
• Metal detectors
• Industrial welders
• Electrical generators

These devices can disrupt the electrical signaling of your pacemaker and stop it from working properly. You may not be able to tell whether your pacemaker has been affected.

How likely a device is to disrupt your pacemaker depends on how long you’re exposed to it and how close it is to your pacemaker.

To be safe, some experts recommend not putting your cell phone or MP3 player in a shirt pocket over your pacemaker (if the devices are turned on).

You may want to hold your cell phone up to the ear that’s opposite the site where your pacemaker is implanted. If you strap your MP3 player to your arm while listening to it, put it on the arm that’s farther from your pacemaker.

You can still use household appliances, but avoid close and prolonged exposure, as it may interfere with your pacemaker.

You can walk through security system metal detectors at your normal pace. Security staff can check you with a metal detector wand as long as it isn’t held for too long over your pacemaker site. You should avoid sitting or standing close to a security system metal detector. Notify security staff if you have a pacemaker.

Also, stay at least 2 feet away from industrial welders and electrical generators.

Some medical procedures can disrupt your pacemaker. These procedures include:

• Magnetic resonance imaging, or MRI
• Shock-wave lithotripsy to get rid of kidney stones
• Electrocauterization to stop bleeding during surgery

Let all of your doctors, dentists, and medical technicians know that you have a pacemaker. Your doctor can give you a card that states what kind of pacemaker you have. Carry this card in your wallet. You may want to wear a medical ID bracelet or necklace that states that you have a pacemaker.

Physical Activity

In most cases, having a pacemaker won’t limit you from doing sports and exercise, including strenuous activities.

You may need to avoid full-contact sports, such as football. Such contact could damage your pacemaker or shake loose the wires in your heart. Ask your doctor how much and what kinds of physical activity are safe for you.

Ongoing Care

Your doctor will want to check your pacemaker regularly (about every 3 months). Over time, a pacemaker can stop working properly because:

• Its wires get dislodged or broken
• Its battery gets weak or fails
• Your heart disease progresses
• Other devices have disrupted its electrical signaling

To check your pacemaker, your doctor may ask you to come in for an office visit several times a year. Some pacemaker functions can be checked remotely using a phone or the Internet.

Your doctor also may ask you to have an EKG (electrocardiogram) to check for changes in your heart’s electrical activity.

Battery Replacement

Pacemaker batteries last between 5 and 15 years (average 6 to 7 years), depending on how active the pacemaker is. Your doctor will replace the generator along with the battery before the battery starts to run down.

Replacing the generator and battery is less-involved surgery than the original surgery to implant the pacemaker. Your pacemaker wires also may need to be replaced eventually.

Your doctor can tell you whether your pacemaker or its wires need to be replaced when you see him or her for followup visits.

SOURCE

http://www.nhlbi.nih.gov/health/health-topics/topics/pace/lifestyle.html

Clinical Trial on Pace Makers

clinical trials related to pacemakers, talk with your doctor. You also can visit the following Web sites to learn more about clinical research and to search for clinical trials:

• http://clinicalresearch.nih.gov
• www.clinicaltrials.gov
• www.nhlbi.nih.gov/studies/index.htm
• www.researchmatch.org

For more information about clinical trials for children, visit the NHLBI’s Children and Clinical Studies Web page.

SOURCE

http://www.nhlbi.nih.gov/health/health-topics/topics/pace/trials.html

RESOUCES on PaceMakers

Links to Other Information About Pacemakers

NHLBI Resources

• Arrhythmia (Health Topics)
• Atrial Fibrillation (Health Topics)
• Heart Block (Health Topics)
• How the Heart Works (Health Topics)
• Implantable Cardioverter Defibrillator (Health Topics)
• Long QT Syndrome (Health Topics)

Non-NHLBI Resources

• Pacemaker (MedlinePlus)
• Pacemakers and Implantable Defibrillators (MedlinePlus)
• Pacemaker Interactive Tutorial (MedlinePlus—Patient Education Institute)

Clinical Trials

• Children and Clinical Studies
• Clinical Trials (Health Topics)
• Current Research (ClinicalTrials.gov)
• NHLBI Clinical Trials
• NIH Clinical Research Trials and You (National Institutes of Health)
• ResearchMatch (funded by the National Institutes of Health)

SOURCE

http://www.nhlbi.nih.gov/health/health-topics/topics/pace/links.html

 

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Heart Failure: New Research in Treatment Strategies Cardiology, Cambridge Research Center, London

Posted in Cardiac & Vascular Repair Tools Subsegment, Cardiac and Cardiovascular Surgical Procedures, Cell Biology, Signaling & Cell Circuits, Ecosystems & Industrial Concentration in the Medical Device Sector, Electrophysiology, Frontiers in Cardiology and Cardiovascular Disorders, Infectious Disease & New Antibiotic Targets, Mechanical Assist Devices: LVAD, RVAD, BiVAD, Artificial Heart, Medical Devices R&D Investment, Origins of Cardiovascular Disease, tagged ACC, American College of Cardiology, American Society of Echocardiography, Cardiology, European Society of Cardiology, Heart Failure, Internal Medicine on July 5, 2013| Leave a Comment »

Reporter: Aviva Lev-Ari, PhD, RN

Heart Failure

Heart Failure and Dietary Sodium: Do we know as much as we think?

Samar Sheth,1 Alan B. Weder2 and Scott L. Hummel2,3; 1. Department of Internal Medicine, University of Michigan; 2. Division of Cardiovascular Medicine, Department of Medicine, University of Michigan Medical School; 3. Staff Cardiologist, Department of Veterans Affairs Medical Center, Ann Arbor, Michigan

Treatment Strategies Cardiology, Volume 3 Issue 1, 44-48

Depolarisation Reserve: A New Identification Concept of Responders to Biventricular Stimulation.

Philippe Chevalier and Alina Scridon; Centre de Référence des Troubles du Rythme Cardiaque Héréditaires, Hôpital Cardiologique Louis Pradel, Bron Cedex

Treatment Strategies Cardiology, Volume 3 Issue 2, 65-70

Selective Site Pacing During Cardiac Resynchronization Therapy

Leonidas Tzogias and Attila Roka, Hospital of St. Raphael, New Haven, Connecticut

Treatment Strategies Cardiology, Volume 4 Issue 1, 37-40

The Clinical Utility of BNP with Heart Failure in the European Physician Oce Setting

Treatment Strategies Cardiology, Volume 4 Issue 2, 49-52

The Treatment of Virus-associated Inammatory Cardiomyopathy

Uwe Kühl and Heinz-Peter Schultheiss, Department of Cardiology and Pulmonology, Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin

Treatment Strategies Cardiology, Volume 4 Issue 2, 63-68

TREATMENT STRATEGIES – CARDIOLOGY

Treatment Strategies – Cardiology is a print (on request) and online eBook publication that provides its readership with a collection of comprehensive and thought-provoking articles from the most respected key opinion leaders, leading doctors and authorities in the cardiology field. The series informs and educates clinicians on the latest therapeutic and technological advances. Published in line with the foremost cardiology congresses, the editorial content includes an unbiased, independent inbound supplement reviewing either the ESC or ACC congress. The review is dedicated to bringing readers the latest cardiology breaking news, exhibition highlights, awards and prizes and research developments from the key-note presentations at the congress.

Treatment Strategies – Cardiology (European and US edition) is available online as a free-to-view eBook providing its readers with an exciting interactive experience. Easily accessible, user friendly and free-to-print, the eBook can provide you with a wide range of dynamic features, including links to external websites, newsletters and email addresses to direct readers to your specialist products and services forming strong links with media partnerships. Importantly, an eBook can be sent out to clients worldwide in an organised and professional layout that allows a far-reaching distribution of your products. The eBook also offers you the opportunity to include, on any page, videos and podcasts of current events such as symposium proceedings that you may wish to highlight for the readership. The latest eBook also permits the advertiser to track statistical data for each page and publication; including the number of unique visits, click though pages, geographical location of the visitor and average time spent viewing.

Advisory Panel

 Treatment Strategies – Cardiology is shaped by an advisory panel of world-renowned specialists from the leading associations and societies, including experts from:

American College of Cardiology (ACC)
American Society of Echocardiography (ASE)
European Association of Cardiothoracic Anaesthesiologists (EACTA)
European Association of Echocardiography (EAE)

European Society of Cardiology (ESC)

Nicholas Antony Boon, Consultant Cardiologist, Royal Infirmary of Edinburgh, Honorary Reader, University of Edinburgh and former President of the British Cardiovascular Society

 (BCS)

Carl J. Pepine, Professor of Medicine, Division of Cardiovascular Medicine, University of Florida; Past-President, American College of Cardiology (ACC)

Bertram Pitt, University of Michigan Medical Center, William Beaumont Hospital, Ann Arbor, Michigan; President of the Michigan Chapter of American College of Cardiology, Chairman, Young Investigator’s Award Committee of the American College of Cardiology, Chairman of the Reveal Committee of the ACC

For our full Editorial Advisory Panel list please click here.

US Edition

Treatment Strategies – Cardiology Volume 5 Issue 1 will include an unbiased, independent inbound supplement reviewing the ACC Congress, taking place in San Francisco in March. The inbound supplement will present the readers with the latest news, exhibition highlights, awards and prizes and research developments from the key-note presentations from the ACC. The publication will be published in April 2013.

European Edition

Treatment Strategies – Cardiology Volume 5 Issue 2 will include an independently written review of the ESC congress taking place in Amsterdam in August. The review is dedicated to bringing readers the latest cardiology news, exhibition highlights, awards and prizes and research developments from the key-note presentations at the congress. Please click on the image (below) to view the media pack as an eBook. Volume 5 Issue 2 will be published in September 2013.

SOURCE

http://www.cambridgeresearchcentre.co.uk/all-publications/cardiology/

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Outcomes in High Cardiovascular Risk Patients: Prasugrel (Effient) vs. Clopidogrel (Plavix); Aliskiren (Tekturna) added to ACE or added to ARB

Posted in CABG, Cell Biology, Signaling & Cell Circuits, Chemical Biology and its relations to Metabolic Disease, Disease Biology, Small Molecules in Development of Therapeutic Drugs, FDA Regulatory Affairs, Frontiers in Cardiology and Cardiovascular Disorders, Health Economics and Outcomes Research, Health Law & Patient Safety, HTN, Origins of Cardiovascular Disease, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Pharmacotherapy of Cardiovascular Disease, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, tagged American College of Cardiology, Antiplatelet drug, Clopidogrel, Coronary artery bypass surgery, Daiichi Sankyo, Eli Lilly, European Society of Cardiology, myocardial infarction, New England Journal of Medicine, Prasugrel, ST elevation, Ticagrelor on August 27, 2012| 7 Comments »

Reporter and Curator: Aviva Lev-Ari, PhD, RN

WOEST (What is the Optimal Antiplatelet and Anticoagulant Therapy in Patients with Oral Anticoagulantion and Coronary Stenting): Get Rid Of The Aspirin In Triple Therapy

According to current guidelines and clinical practice, PCI patients already taking an oral anticoagulant generally end up on triple therapy comprising the anticoagulant plus clopidogrel and aspirin. However, there is no supporting evidence base for this approach and the triple therapy regimen is known to increase bleeding complications. Now a new study– the first randomized trial to address this situation, according to the investigators–  may have a large impact on clinical practice by demonstrating that the omission of aspirin in this context appears to be safe and may reduce adverse events.

Results of the WOEST (What is the Optimal Antiplatelet and Anticoagulant Therapy in Patients with Oral Anticoagulantion and Coronary Stenting) trial were presented by Willem Dewilde at the ESC in Munich today. Investigators in the Netherlands and Belgium randomized 573 patients to triple therapy or dual therapy of an anticoagulant plus clopidogrel for at least one month after implantation of a bare-metal stent or one year after a drug-eluting stent. Two-thirds of the patients were receiving oral anticoagulation for atrial fibrillation.

The primary endpoint, the total number of bleeding events, was dramatically reduced in the dual therapy group at one year:

• 44.9% in the triple therapy group versus 19.5% (HR 0.36, CI 0.26-0.50)

There were 3 intracranial bleeds in each group. Most of the difference in bleeding occurred in TIMI minor and minimal bleeding. The difference in TIMI major bleeding (3.3% versus 5.8%) did not achieve statistical significance.

Clinical events, the trials’s secondary endpoint, were numerically lower in the dual therapy group. The difference in mortality achieved statistical significance.

• Mortality: 7 deaths (2.6%) in the dual therapy group versus 18 deaths (6.4%) in the triple therapy group, p=0.027
• MI: 3.3% versus 4.7%, p=0.382
• TVR: 7.3% versus 6.8%, p=0.876
• Stroke: 1.1% versus 2.9%, p=0.128)
• Stent thrombosis: 1.5% versus 3.2%, p=0.165

“The WOEST study demonstrates that omitting aspirin leads to less bleedings but does not increase the risk of stent thrombosis, stroke or myocardial infarction,” said Dewilde in an ESC press release. “Although the number of patients in the trial is limited, this is an important finding with implications for future treatment and guidelines in this group of patients known to be at high risk of bleeding and thrombotic complications.”

David Holmes said the trial addressed “an incredibly important issue” and predicted that it would “change the way we practice medicine, it will change practice right away.” Keith Fox said that the evidence base prior to WOEST was extremely limited and that the trial showed that there was no hazard in doing without aspirin. The ESC discussant, Marco Valgimigli, said the trial showed it was safe to drop aspirin and provided another demonstration that “we have hit the wall” with anticoagulation.

Republished with permission from CardioExchange, a NEJM group publication.

http://www.forbes.com/sites/larryhusten/2012/08/28/woest-get-rid-of-the-aspirin-in-triple-therapy/

European Society of Cardiology: Prasugrel Can’t Top Clopidogrel in ACS

 By Todd Neale, Senior Staff Writer, MedPage Today

Published: August 26, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

MUNICH — For patients with unstable angina or non-ST-segment elevation myocardial infarction (non-STEMI) who do not undergo revascularization, increasing platelet inhibition may not improve outcomes, a randomized trial showed.

Added to a background of low-dose aspirin, prasugrel (Effient) did not significantly reduce the rate of MI, stroke, or cardiovascular death compared with clopidogrel (13.9% versus 16%, HR 0.91, 95% CI 0.79 to 1.05), according to Matthew Roe, MD, of Duke University in Durham, N.C.

The risk of severe bleeding was similar with both drugs, although minor and moderate bleeding were increased with prasugrel, Roe reported at the European Society of Cardiology meeting here. The findings were published simultaneously online in the New England Journal of Medicine.

“I think the outcome is a bit surprising because we think usually that more aggressive antiplatelet therapy, conceivably, in the face of an acute coronary syndrome and non-ST-elevation would lead to lesser adverse outcome from acute myocardial infarction or death,” said William Zoghbi, MD, from Methodist DeBakey Heart Center in Houston and president of the American College of Cardiology.

But he said clinicians need to respect the data “and start thinking about pathogenesis and what we’re trying to do with any of our new interventions.”

In patients with unstable angina or non-STEMI, practice guidelines call for angiography within 48 to 72 hours with provisional revascularization. Many of these patients do not ultimately undergo revascularization, placing them at greater risk compared with those who have their arteries opened with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG).

Recommended medical therapy is with clopidogrel and aspirin, which is an approach that will not change from the current findings, Zoghbi said.

The purpose of the TRILOGY ACS trial was to explore whether using a more powerful platelet inhibitor — prasugrel — would improve outcomes compared clopidogrel (Plavix) in this high-risk patient subset.

The primary analysis involved 7,243 patients younger than 75 (mean age 62) who were receiving aspirin and were randomized to prasugrel 10 mg daily (or 5 mg daily for those weighing less than 132 pounds) or to clopidogrel 75 mg daily. The researchers recommended a daily aspirin dose of 100 mg or less.

A secondary, exploratory analysis involved 2,083 patients, 75 or older, who were randomized to prasugrel 5 mg daily or to clopidogrel 75 mg daily.

The lack of efficacy seen in the primary analysis of patients younger than 75 remained when patients of all ages were combined. There were no between-group differences for any of the components of the primary endpoint.

A prespecified secondary analysis taking multiple recurrent ischemic events into consideration showed a lower risk of MI, stroke, and cardiovascular death with prasugrel in the younger patients (HR 0.85, 95% CI 0.72 to 1.00, P=0.04), a finding consistent with the main results of the TRITON-TIMI 38 trial, which involved patients treated with PCI. The apparent benefit appeared after 12 months of treatment.

“Although this observation is exploratory, it raises the question of whether investigation of the multiplicity of ischemic events is warranted in future secondary-prevention trials, rather than solely analyzing the time to the first event, as has been traditional in studies involving patients who have had an acute coronary event,” the researchers wrote.

Rates of GUSTO severe or life threatening bleeding and TIMI major bleeding — as well as intracranial hemorrhage — were similar in the two groups in both the younger patients and in the overall study population. When minor and moderate bleeding events were added, the bleeding rate was higher with prasugrel.

There were no widespread differences between the groups in rates of nonhemorrhagic serious adverse events, but heart failure was more frequent with clopidogrel (1.8% versus 1.3%, P=0.045).

Douglas Weaver, MD, of Henry Ford Health System, said that he does not think the findings will have any impact on the use of prasugrel, which is not indicated for the patient population included in the study.

“It just doesn’t pass muster in improving value over clopidogrel,” said Weaver, a past president of the American College of Cardiology.

From a clinical perspective, he said, an important message from the study is the evidence of the safety of a reduced dose of prasugrel in the patients 75 and older, which is a consideration when prescribing prasugrel for patients undergoing PCI.

In comments following Roe’s presentation, Raffaele De Caterina, MD, PhD, of the G. d’Annunzio University in Chieti, Italy, provided context about how the findings fit in with the rest of the literature.

He compared the current results to those of a substudy of the PLATO trial, which involved ticagrelor (Brilinta).

In that trial, ticagrelor significantly reduced vascular death, MI, and stroke (HR 0.85, 95% CI 0.73 to 1.00, P=0.045) — the primary endpoint — and all-cause death (HR 0.75, 95% CI 0.61 to 0.93).

He then highlighted the ESC guidelines on treating patients with acute coronary syndromes without persistent ST-segment elevation.

In those, ticagrelor is recommended for all patients at moderate-to-high risk of ischemic events, regardless of initial treatment strategy and including those pre-treated with clopidogrel, and prasugrel is recommended for those who have not taken another P2Y12 inhibitor, who have a known coronary anatomy, and who are proceeding to PCI.

“I believe such statements and recommendations of the guidelines should not be changed,” De Caterina said.

TRILOGY ACS was funded by Eli Lilly and Daiichi Sankyo.

Roe reported relationships with Daiichi Sankyo, Eli Lilly, AstraZeneca, Bristol-Myers Squibb, Janssen Pharmaceuticals, Merck, Hoffmann-La Roche, and sanofi-aventis. The other authors reported numerous relationships with industry.

Primary source: New England Journal of Medicine

Source reference:
Roe M, et al “Prasugrel versus clopidogrel for acute coronary syndromes without revascularization” N Engl J Med2012; DOI: 10.1056/NEJMoa1205512.

http://www.medpagetoday.com/MeetingCoverage/ESCCongress/34375?utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=WC&xid=NL_DHE_2012-08-27&eun=g99985d0r&userid=99985&email=avivalev-ari@alum.berkeley.edu&mu_id=5099207

Prematurely halted ALTITUDE trial showed When added to monotherapy with either an ACE inhibitor or an angiotensin receptor blocker (ARB), aliskiren (Tekturna) did not improve outcomes in patients with type 2 diabetes who had high cardiovascular and renal risk

ESC: Aliskiren Onboard No Help in T2D

By Todd Neale, Senior Staff Writer, MedPage Today

Published: August 26, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

MUNICH — When added to monotherapy with either an ACE inhibitor or an angiotensin receptor blocker (ARB), aliskiren (Tekturna) did not improve outcomes in patients with type 2 diabetes who had high cardiovascular and renal risk, the prematurely halted ALTITUDE trial showed.

Through an average follow-up of 32 months, a composite of various cardiovascular and renal outcomes occurred in 17.9% of patients receiving the direct renin inhibitor and 16.8% of those receiving placebo (HR 1.08, 95% CI 0.98 to 1.20), according to Hans-Henrik Parving, MD, DMSc, of the University of Copenhagen and Aarhus University in Denmark.

As a Hot Line presentation European Society of Cardiology meeting here, Parving reported that there were no significant differences on any of the individual components of the endpoint — cardiovascular death, resuscitated sudden death, MI, stroke, unplanned hospitalization for heart failure, doubling of baseline serum creatinine, and onset of end-stage renal disease — or all-cause death.

The rate of stroke — mostly ischemic stroke — was numerically higher with aliskiren, although the result fell short of statistical significance (3.4% versus 2.8%; HR 1.25, 95% CI 0.98 to 1.60,P=0.07).

Thus, Parving said, using aliskiren with ACE inhibitors or ARBs in these high-risk patients “is not recommended and may even be harmful.”

The data monitoring committee for the ALTITUDE trial decided to stop the study early in December 2011 both for futility and for adverse events. Then, earlier this year, the FDA issued a warning about using aliskiren with ACE inhibitors or ARBs and changed the drug label to reflect a contraindication for such combinations in patients with diabetes or renal impairment.

The trial included 8,561 patients with type 2 diabetes who had a high risk of cardiovascular or renal disease who were randomized to aliskiren — at 150 mg daily for 1 month followed by 300 mg daily thereafter — or placebo in addition to monotherapy with either an ACE inhibitor or an ARB (but not both).

Adding aliskiren did not improve outcomes, and in fact, may have caused harm, Parving said, as indicated by the apparent increase in stroke risk.

He said that could be explained by the impaired autoregulation of patients with diabetes or by chance, as there are no indications of a stroke risk in other studies of the drug.

Johannes Mann, of Friedrich Alexander University in Erlangen, Germany, and McMaster University in Hamilton, Ontario, who served as the discussant following Parving’s presentation, agreed that it could be a chance finding, but said that it could also be a direct effect of aliskiren itself.

He concluded that the stroke risk was not explained, however, by dual renin system inhibition, because such a signal was not seen in the ONTARGET trial, which compared the combination of ramipril (an ACE inhibitor) and telmisartan (an ARB) with each drug as monotherapy.

As noted when the trial was halted last year, adverse events were more frequent in the aliskiren group.

The percentage of patients who had a potassium level of 5.5 to less than 6.0 mmol/L was greater with active treatment (21% versus 16%), as was the percentage of those with a potassium level of 6.0 mmol/L or greater (8.8% versus 5.6%).

Aliskiren carried higher risks of hyperkalemia (38.7% versus 28.6%), hypotension (12.1% versus 8%), diarrhea (9.6% versus 7.2%), and falls (2.8% versus 2.6%). There was one death caused by hyperkalemia.

Douglas Weaver, MD, of the Henry Ford Health System in Detroit, said that the findings were disappointing, but that they likely wouldn’t change how aliskiren is used in practice.

“I don’t think this is going to have a negative or a positive effect on it,” said Weaver, who is a past president of the American College of Cardiology.

ALTITUDE was sponsored by Novartis Pharma AG.

The executive committee and other investigators or their institutions received a consultancy fee. Some of the authors are employees of Novartis and therefore eligible for stock and stock options.

Primary source: European Society of Cardiology
Source reference:
Parving H-H, et al “The Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE)” ESC 2012; Abstract 399.

http://www.medpagetoday.com/MeetingCoverage/ESCCongress/34388?utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=WC&xid=NL_DHE_2012-08-27&eun=g99985d0r&userid=99985&email=avivalev-ari@alum.berkeley.edu&mu_id=5099207

 

Aliskiren

From Wikipedia, the free encyclopedia

Aliskiren

Systematic (IUPAC) name
(2S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2,2-dimethylethyl)-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-2-(propan-2-yl)nonanamide
Aliskiren (INN) (trade names Tekturna, U.S.; Rasilez, U.K. and elsewhere) is the first in a class of drugs called direct renin inhibitors. Its current licensed indication is essential (primary) hypertension.

Aliskiren was co-developed by the Swiss pharmaceutical companies Novartis and Speedel.^[1][2] It was approved by the U.S. Food and Drug Administration in 2007 for the treatment of primary hypertension.^[3]

In December 2011, Novartis had to halt a clinical trial of the drug after discovering increased incidence of non-fatal stroke, renal complications, hyperkalemia and hypotension in patients with diabetes and renal impairment.^[4]

The following recommendations are being added to the drug labels for aliskiren-containing products as of 4/20/12:

I) A new contraindication against the use of aliskiren with ARBs or ACEIs in patients with diabetes because of the risk of renal impairment, hypotension, and hyperkalemia. II) A warning to avoid use of aliskiren with ARBs or ACEIs in patients with moderate to severe renal impairment (i.e., where glomerular filtration rate [GFR] < 60 mL/min).

Mechanism of Action

Renin is the first enzyme in the renin-angiotensin-aldosterone system which plays a role in blood pressure control. Renin cleaves angiotensinogen to angiotensin I, which is in turn converted by angiotensin-converting enzyme (ACE) toangiotensin II. Angiotensin II has both direct and indirect effects on blood pressure. It directly causes arterial smooth muscle to contract, leading to vasoconstriction and increased blood pressure. Angiotensin II also stimulates the production of aldosterone from the adrenal cortex, which causes the tubules of the kidneys to increase reabsorption of sodium, with water following thereby increasing plasma volume and blood pressure.

Aliskiren binds to the S3^bp binding pocket of renin, essential for its activity.^[5] Binding to this pocket prevents the conversion of angiotensinogen to angiotensin I.

Aliskiren is also available as combination therapy with hydrochlorothiazide.^[6]

Many drugs control blood pressure by interfering with angiotensin or aldosterone. However, when these drugs are used chronically, the body increases renin production, which drives blood pressure up again. Therefore, doctors have been looking for a drug to inhibit renin directly. Aliskiren is the first drug to do so.^[7][8]

Aliskiren may have renoprotective effects that are independent of its blood pressure−lowering effect in patients with hypertension, type 2 diabetes, and nephropathy who are receiving the recommended renoprotective treatment. According to the AVOID study, researchers found that treatment with 300 mg of aliskiren daily, as compared with placebo, reduced the mean urinary albumin-to-creatinine ratio by 20% (95% confidence interval, 9 to 30; P<0.001), with a reduction of 50% or more in 24.7% of the patients who received aliskiren as compared with 12.5% of those who received placebo (P<0.001). Furthermore, the AVOID trial shows that treatment with 300 mg of aliskiren daily reduces albuminuria in patients with hypertension, type 2 diabetes, and proteinuria who are receiving the recommended maximal renoprotective treatment with losartan and optimal antihypertensive therapy. Therefore, direct renin inhibition will have a critical role in strategic renoprotective pharmacotherapy, in conjunction with dual blockade of the renin−angiotensin−aldosterone system with the use of ACE inhibitors and angiotensin II–receptor blockers, very high doses of angiotensin II−receptor blockers, and aldosterone blockade.^[9]

Adverse effects

• Angioedema
• Hyperkalemia (particularly when used with ACE inhibitors in diabetic patients)
• Hypotension (particularly in volume-depleted patients)
• Diarrhea and other GI symptoms
• Headache
• Dizziness
• Cough
• Rash
• Elevated uric acid, gout, and renal stones
• Rarely: allergic swelling of the face, lips or tongue and difficulty breathing

Contraindications

• Pregnancy: other drugs such as ACE inhibitors, also acting on the renin-angiotensin system have been associated with fetal malformations and neonatal death^[10]
• Breast feeding: during animal studies, the drug has been found present in milk.^[10]

Aliskiren has not yet been evaluated in patients with significantly impaired renal function.

Drug interactions

Aliskiren is a minor substrate of CYP3A4 and, more important, P-glycoprotein:

• Reduces furosemide blood concentration.
• Atorvastatin may increase blood concentration, however no dose adjustment needed.
• Possible interaction with ciclosporin (the concomitant use of ciclosporin and aliskiren is contraindicated).
• Caution should be exercised when aliskiren is administered with ketoconazole or other moderate P-gp inhibitors (itraconazole, clarithromycin, telithromycin, erythromycin, amiodarone).
• Doctors should stop prescribing aliskiren-containing medicines to patients with diabetes (type 1 or type 2) or with moderate to severe kidney impairment who are also taking an ACE inhibitor or ARB, and should consider alternative antihypertensive treatment as necessary.^[11]

References

1. ^ Gradman A, Schmieder R, Lins R, Nussberger J, Chiang Y, Bedigian M (2005). “Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients”. Circulation 111 (8): 1012–8. doi:10.1161/01.CIR.0000156466.02908.ED. PMID 15723979.
2. ^ Straessen JA, Li Y, and Richart T (2006). “Oral Renin Inhibitors”. Lancet 368 (9545): 1449–56. doi:10.1016/S0140-6736(06)69442-7. PMID 17055947.
3. ^ “First Hypertension Drug to Inhibit Kidney Enzyme Approved”. CBC. 2007-03-06. Retrieved 2007-03-14.^{[dead link]}
4. ^ Healthzone.ca: Blood-pressure drug reviewed amid dangerous side effects
5. ^ “Chemistry & Biology : Structure-based drug design: the discovery of novel nonpeptide orally active inhibitors of human renin”. ScienceDirect. Retrieved 2010-01-20.
6. ^ Baldwin CM, Plosker GL.[1]. doi:10.2165/00003495-200969070-00004. Drugs 2009; 69(7):833-841.
7. ^ Ingelfinger JR (June 2008). “Aliskiren and dual therapy in type 2 diabetes mellitus”. N. Engl. J. Med. 358 (23): 2503–5. doi:10.1056/NEJMe0803375.PMID 18525047.
8. ^ PharmaXChange: Direct Renin Inhibitors as Antihypertensive Drugs
9. ^ Parving HH, Persson F, Lewis JB, Lewis EJ, Hollenberg NK. “Aliskiren Combined with Losartan in Type 2 Diabetes and Nephropathy,” N Engl J Med 2008;358:2433-46.
10. ^ ^a b Drugs.com: Tekturna
11. ^ European Medicines Agency recommends new contraindications and warnings for aliskiren-containing medicines.

External links

• Prescribing Information for Tekturna
• aliskiren at the US National Library of Medicine Medical Subject Headings (MeSH)
• Chemical synthesis

 http://en.wikipedia.org/wiki/Aliskiren

 

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