A-fib

[Largehearted]

Below is a link to an interesting article regarding a new a-fib medication. Since I have recurring bouts of a-fib every year or so I try to stay up on what treatments are available. What this article does not address is whether the medication they are developing is appropriate for those of us with HCM. Non-the-less it is well worth the read.

Peace,

Leon

http://www.medscape.com/viewarticle/504950

[williamm]

Dear Leon,

This article is in a protected area only available to registered users. Maybe it could useful to paste its text directly here in the forum.

Best regards,

William.

[fausto.freire]

Dear William:

It's a long article with tables. You can register for free at medscape and gain access to the article.

Anyhow I copied below the first three paragraphs.

Fausto

ACT 1: Atrial Arrhythmia Conversion Trial 1 - A New Antiarrhythmic Agent

May 16, 2005 — The rate- vs rhythm-control trials may support a strategy of rate control, but restoration of sinus rhythm (SR) in patients with atrial fibrillation (AF) is still a desirable goal. Now, a novel mixed ion channel antagonist, RSD1235, has demonstrated its effectiveness to convert recent-onset AF to SR in a large, international, phase 3, randomized, placebo-controlled clinical trial. Furthermore, the first presentation of the results of the Atrial arrhythmia Conversion Trial 1 (ACT 1)[1] confirm that RSD1235 has a rapid onset of action and is well tolerated.

RSD1235 is a novel, frequency-dependent sodium and early-activating potassium-channel blocker under joint development by Cardiome (Vancouver, Canada) and its partner, Astellas Pharma US (Deerfield, Illinois). The agent is intended as an acute-use, intravenous (IV) administration treatment to terminate AF and restore SR in AF patients. An oral formulation of RSD1235 is also under development for the long-term maintenance of normal SR following termination of AF.

ACT 1 was a phase 3, randomized, placebo-controlled, double-blind, multicenter trial initiated in August 2003 and carried out in 45 centers in Canada, Scandinavia, and the United States. Cochairs of the study steering committee were Denis Roy, MD (Montreal Heart Institute, Montreal, Quebec, Canada) and Craig M. Pratt, MD (Baylor College of Medicine, Houston, Texas). The study included patients aged > 18 years with electrocardiographic-documented AF (ranging in duration from 3 hrs to 45 days); patients were hemodynamically stable and on adequate anticoagulation therapy by US and European practice guidelines. Patients were excluded if they had long-QT syndrome, torsade de pointes, Brugada syndrome; bradycardia or sick sinus syndrome, unstable NYHA class IV heart failure; myocardial infarction, acute coronary syndrome, or cardiac surgery within the previous 30 days; failed electrical cardioversion; or typical atrial flutter.

[Sarah]

http://www.cardiome.com/RSD1235.php is the drug company's site with a free, unregistered fact sheet on the trial.

still early days and the stats are not any better than any other drug, just a different mechanism.

[williamm]

Thanks Fausto and Sarah,

Even with no better stats, something similar to Amiodarone but with less side effects still would be great for many of us. But we don't know if that's the case for this new experimental med.

William.

[Sarah]

well, it IS a potassium channel blocker like amio and the preliminary results are that it has fewer side effects (i don't think it would be possible for anything to have more!) but I don't think the stats are better ---however it would be great to have something else to try before going to "the dark side."

[progers]

Gee,

I sure hope someting else comes along soon as I am now in my third week of taking Amiodarone. So far just a few side effects, but at only 35 the prospect of taking this medicince for the next few decades is not appealing, epecially since it is, according to one article I read, 'the most toxic drug in medicine'. Unfortunately, I don't really have a choice because Sotalol failed for me once and some of the other effective drugs are not available here in Australia (such as Disopyramide).

And just to think I NEVER had a-fib prior to my myectomy 11 weeks ago!!

Paul

[fausto.freire]

Paul:
How much are you taking per day?
Amiodarone is very dangerous in particular for high doses, such us 600mg/day. ut for small doses, sometimes it takes a long time before major problems.

I was having 200mg 5 days a week for near 3 years without any major side-effect (besides sun sensitivity). I was taking it to gain some time before the next a-fib attack. Unfortunately it did not work for a long time. To tell the true I feel now much worse with the permanent a-fib, even that I did not want to take amio for a long time.

Paul, perhaps amiodarone can give you some time without a-fib before you discover a procedure which can cure your a-fib. I am still hoping for that myself, but with much lower chances since as you know being in a-fib reduces the chances of curing it.

But some good news: there is a new drug very similar to amiodarone, but hopefully without the side effects of amio. It is called dronedarone. It is currently in phase III development (last phase before being commercially available). It is very similar to amio but it does not contain iodine in its structure

Some links with more information:

http://www.news-medical.net/?id=4381

http://www.drugdevelopment-technolog...s/Dronedarone/

Fausto

[Cynaburst]

I believe that dronedarone was found to have problems (I can't remember specifically what they were) and the trials of it were suspended. It is no longer on track to replace amiodarone.

[Sarah]

There is another drug called dofetilide (Tikosyn is the brand name) that has been around for about three or four years now and it is a potassium channel blocker like amio but without the side effects.

It does have a slightly higher rate of elongated QT intervals and must be carefully monitored and your compliance must be 100%. I took it for two years successfully before it started to fade out and stop working.

I didn't have any other side effects besides the slightly widened QT which is ok as long as it is under 500ms. They watch you in the hosptial for three days when you start it to make sure you won't "go too far."

[progers]

Hi Fausto,

I am taking 400 mg per day right now. I will be on that dose for 3 more weeks, then down to 200 mg per day.

Fausto, did you take Amiodarone but it didn't work for you. Or you stopped taking it and went back into a-fib? If so, why will you not take it again?

For some of us with HCOM, the risks associated with Amiodarone are probably much less than with staying in a-fib. Ultimately, a-fib leads to heart failure for many, particularly those who rely on the left atrium for cardiac output; this means those with significant diastolic dysfunction.

I am also trying to buy myself some time so that I can realise the benefits of my myectomy 11 weeks ago. If I stay in sinus rhythm, there is a chance that I will be among the 50% of patients in whom a-fib stops. It is possible that myectomy improves diastolic function, leads to a reduction in left atrial size and perhaps no more a-fibs (see ACC/European Concensus on HCM).

Fausto, perhaps myectomy is something you should look seriously at, particularly since you are so young? (you are obstructed right??).

Take care and keep in touch,

Paul

[fausto.freire]

First about dronedarore:
Yes there were some problems but not when it was used for afib. More details below: One of the several studies being done with dronedarone was discontinued in the beginning of 2003. That study was called the ANDROMEDA (Antiarrhythmic trial with DROnedarone in Moderate to severe CHF Evaluating morbidity DecreAse) study. However, other studies with dronedarone have continued and are now in the final phase, namely: 2 trials in the maintenance of sinus rhythm in patients with atrial fibrillation EURIDIS (in Europe) and ADONIS (in North America, South America, Australia and South Africa).

The results of these trials were presented last year showing that “Dronedarone is effective and well-tolerated in prevention of AF recurrence” http://www.eurekalert.org/pub_releas...c2_4082904.php

Nonetheless, some doctors (including mine) said that the results were somehow disappointing and Dronedarone is not as effective as hoped (http://heartdisease.about.com/od/pal...ronedarone.htm). “Dronedarone may turn out to be reasonably useful as an antiarrhythmic drug - but apparently it's not going to be the "non-toxic amiodarone" we've all been waiting for.”

Fausto

[fausto.freire]

Hi Paul:
You are now in the amio load phase. In the fist few weeks taking amio, higher doses are used to impregnate amio in your body organs Yes, unfortunately in the entire body and not only in the hearth muscle.

Your situation is different than mine regarding that you had afib after having a myectomy. Thus, I wish that in the future you don’t have afib again. Hopefully with time you atrium will reduce more in size since, as you know, an enlarged atrium is a very bad prognosis for recurrence of afib.

Answering your questions: I was taking amio when I had all my afib episodes (except the first, of course). My last cardioversion did not work. That’s why I am not taking amio anymore. Now my afib treatment is for rate control since it is assumed sinus rhythm cannot be restored unless some sort of RF ablation or surgery is performed.

About my case: You have raised a question that I have been thinking, but never asked my doctor or here in the forum.

Before having afib, I did not have many symptoms or problems. My maximum gradient is 30-40 mmhg and my septum is about 18-19mm. Thus I don’t think (but I am no sure?) if a myectomy could help. Does anyone had a myectomy with this type of values?

Next month I will do an echo to see how my mitral valve is working and how much is my mitral regurgitation. I think it should be a lot, since my left atrium is so enlarged (65mm). On July 12, I will have an appointment with my cardiologist to see if I need a mitral valve surgery and something more (maze?).

This raise a question that I would like to pose to the forum (perhaps I should create a new post). What is more important for left atrium enlargement: genetics or degree of obstruction?

Fausto

PS I am waiting for new data (my next echo) to formulate more questions to the forum regarding my own situation

[progers]

Hi Fausto,

Good to hear from you again. I don't know the answer to the last question you asked. Perhaps others have an idea?

Are you obstructed? It sounds as though you may be if you have a pressure gradient. I have also heard of people having a myectomy with an 18 or 19 mm septum. Remember that the normal septum measures around 10 mm so yours is almost twice the normal (mine was 30 mm before my surgery). Both the obstruction and mitral regurgitation put back pressure on the left atrium causing it to enlarge. This is why people who have mitral valve surgery and/or myectomy usually experience a decrease in atrium size and a reduction in a-fib.

I have just read an older paper that suggests that those who undergo myectomy before 40 years of age are more likely to have a decrease in their left atrium size and a reduction in a-fib, when compared with those over 40. It may be that surgery can really help you as you are so young still. The paper is:

Watson, C., et al. (1977). 'Effects of Operation on Left Atrial Size
and the Occurrence of Atrial Fibrillation in Patients with Hypertrophic Subaortic Stenosis', in Circulation, Vol 55(1): 178-181.

If you would like to read this I can email you a pdf copy.

I will also meet with my Electrophysiologist on Thursday. He has talked with other specialists about my case, so I will give you a detailed report on what he says about the lates procedures for people like you and I.

Take care and stay in touch.

Paul[/i]

[williamm]

Hi Fausto,

I don't know about other cardiologic centers but here in Brazil, septal reduction is mainly indicated in people with gradient over 50mmHg at rest AND if dual chamber pacemaker therapy has failed to decrease this gradient. And different from USA (I think), septal ablation has been the first choice due to its less invasive method. I hope you find soon a way to revert your a-fib. You were correct saying that as the more time you keep in a-fib is more difficult to revert it. But as you should know, the RF ablation process are evolving very fast. I have some friends here in Brazil that perform RF ablation and they was talking that a few years ago the maximum atrial diameter to perform this process was 50mm and with a very small success rate. Today is common to use this method in people with atrial diameter of 60mm and with a higher success rate. That will depend how many "wrong patways" has been created in your atrium and where they are localized.

Best Regards,

William.