Informed consent - DOC by tyndale




You have been invited to participate in this Prospective International Registry because,

based on your clinical history, electrocardiogram and additional tests, your physician

believes that you have Brugada syndrome.

Brugada syndrome is a hereditary (genetic) disease. The diagnosis is based on the

presence of a characteristic electrocardiogram. Patients with Brugada syndrome may

remain completely asymptomatic during their entire life or may develop symptoms.

Symptoms related to Brugada syndrome are caused by cardiac arrhythmias and may

include palpitations, syncope or cardiac arrest potentially leading to sudden death. At

the present time, it is not known what percentage of patients who have Brugada

syndrome will develop symptoms. Moreover, it is not known how to accurately identify

patients who are asymptomatic but are prone to develop dangerous arrhythmias in the

future. However, we do know that arrhythmia-related symptoms may occur at any age

but typically occur between 20 and 50 years of age and occur predominantly in males.

At the present time, we do not know what is the best treatment for patients with

asymptomatic Brugada syndrome and leading investigators of this disease disagree

about this important point. The main therapeutic options or alternatives for

asymptomatic Brugada syndrome include the following: 1) No therapy; 2) therapy with

medication (quinidine) for all patients with asymptomatic Brugada syndrome and 3)

risk-stratification of patients with the aid of electrophysiologic studies and therapy of

patients who have provocable arrhythmias during electrophysiologic studies with

quinidine or with an implantable cardioverter defibrillator (ICD).

The electrophysiologic study is a diagnostic procedure performed in the catheterization

room. Under local anesthesia, electrical catheters are inserted through a vein in the

inguinal region and advanced to the heart. The physician then attempts to provoke

(induce) ventricular arrhythmias in the heart using specific pacing protocols. The study

is considered "positive" if ventricular fibrillation requiring an electric shock for

termination is induced and "negative" if no arrhythmias can be provoked.

Electrophysiologic studies are not considered dangerous procedures and serious

complications from this procedure are extremely rare (one in a few thousand

procedures). The main drawback of the electrophysiologic studies is that the value of

the test results for predicting if spontaneous (real) arrhythmias will ever occur is limited

and debated. In fact, the great majority of asymptomatic patients who have inducible

ventricular arrhythmias during electrophysiologic studies will not have spontaneous

arrhythmias during follow-up. The results of different studies differ in terms of the

perceived risk for patients with positive electrophysiologic studies: some studies

suggesting that only 1% of patients with provocable (inducible) ventricular fibrillation

will have spontaneous arrhythmias, whereas other studies suggest that the risk could

be 12% by 5 years of follow-up.

The implantable cardioverter defibrillator (ICD) is a small electric device that is

implanted under the skin (or under the muscle) in the upper chest. The ICD is

connected to electric wires (electrodes) that are inserted through veins in the chest to

the heart. The procedure is performed under local anesthesia. If spontaneous

arrhythmias like ventricular fibrillation ever occur, the ICD senses and recognizes the

arrhythmia. If the ventricular fibrillation does not terminate spontaneously within a few

seconds, the ICD delivers a high-voltage electric shock. ICD-shocks are extremely

effective for terminating ventricualr fibrillation events that could otherwise be fatal.

Thus, the ICD is the most effective mean for protecting a patient against sudden death

from ventricular arrhythmias. However, serious complications may occur as a direct

consequence of ICD implantation, either during or shortly after the implantation

procedure or during long-term follow-up (see below). The list of complications includes

surgical complications like local bleeding (hematoma) at the surgical site, injury to the

lung (pneumothorax) during electrode insertion, perforation of the heart (very rarely)

and serious infection. In addition, the electrodes may dislodge (move from the correct

position in the heart). Repeated surgery may be required for correcting these

complications. In addition, fracture of the electrodes, or malfunction of the ICD, rarely

occur. Finally, for a number of reasons the ICD may sometimes deliver painful

inappropriate high-voltage electric shocks in the absence of true arrhythmias.

The standard of care for patients with asymptomatic Brugada syndrome in recent

years has been based on the results of studies published by Dr. Brugada and

colleagues (who first described this syndrome and have collected a large amount of

data from hundreds of patients with this disease). These studies suggest that patients

with asymptomatic Brugada syndrome who have inducible (provocable) ventricular

fibrillation during electrophysiologic studies are at higher risk for developing

spontaneous life-threatening ventricular arrhythmias than patients who have no

provocable arrhythmias during such studies. Accordingly, the standard approach in the

majority of medical centers in the world has been to recommend the performance of

electrophysiologic studies. Patients with negative electrophysiologic studies (that is,

patients who have no provocable arrhythmias) have been followed without specific

therapy. In contrast, prophylactic ICD implantation has been recommended for

patients who have inducible ventricular fibrillation during electrophysiologic studies.

However, several recent studies (also including hundreds of patients) have shown that

the results of electrophysiologic studies are of very little value for identifying patients

who will eventually develop arrhythmias during long-term follow-up. Also, a recent

multicenter European study showed that while only 1% of patients undergoing

prophylactic ICD implantation because of "asymptomatic Brugada syndrome with

inducible arrhythmias" actually benefited from this procedure (because the implanted

device terminated and treated spontaneous arrhythmias). In contrast, 28% of these

patients developed serious complications directly related to ICD implantation.

Consequently, more and more physicians in many important hospitals are questioning

the need for electrophysiologic studies and are seriously questioning the need for ICD

implantation for asymptomatic patients, even when they have positive

electrophysiologic studies.

All the physicians participating in this study agree that, at the present time, we do not

know what the best treatment of asymptomatic Brugada syndrome is. The purpose of

this Prospective International Registry is to collect information from patients receiving

different forms of therapy (see below) that will help define what the safest and most

effective therapy is. The Registry discourages the performance of electrophysiologic

studies because multicenter European, Japanese and Israeli studies suggest that the

information provided by electrophysiologic studies does not really help to identify

patients who will benefit from ICD implantation. Thus, two main forms of therapy are

proposed to patients entering this registry: 1) Therapy with quinidine and 2) No


Quinidine is one of the oldest available antiarrhythmic drugs. Quinidine appears to be

particularly suitable to treat Brugada syndrome because of all the following reasons: 1)

In laboratory (in-vitro) models of Brugada syndrome, quinidine effectively prevents

ventricular arrhythmias; 2) quinidine may partially normalize the pathologic

electrocardiogram of Brugada syndrome; 3) the vast majority (more than 85%) of

patients with Brugada syndrome who have provocable ventricular arrhythmias during

electrophysiologic studies in the absence of drugs, will have negative

electrophysiologic studies (that is, no arrhythmias will be provoked) if the

electrophysiologic study is repeated during quinidine therapy; 4) quinidine is one of the

most effective therapies for patients with Brugada syndrome who present with frequent

ventricular arrhythmias; 5) some studies from Israel and France suggest that patients

with Brugada syndrome that were considered to be at "high risk" for arrhythmias

(because they already had cardiac arrest with successful resuscitation before the

onset of therapy or because they had inducible ventricular arrhythmias during

electrophysiologic studies) can be safely treated with quinidine.

On the other hand, quinidine has side effects. Quinidine must be swallowed with a full

glass of water to avoid local irritation of the esophagus. The most common side effect

of quinidine is diarrhea. When large doses of quinidine are used, up to 40% of patients

may develop diarrhea, which resolves upon drug discontinuation or dose reduction.

Other side effects, like liver damage, anemia or thrombocytopenia are rarer but may

be dangerous. That is why blood tests are performed periodically to detect these

complications. The most serious risk of quinidine therapy relates to its potential to

provoke ventricular arrhythmias of a very specific type called torsade de pointes.

These ventricular arrhythmias may cause loss of consciousness or even arrhythmic

death. This is a very rare complication. In patients without organic heart disease the

risk is probably less than 4% and so far there have been no reports of torsade de

pointes in patients with Brugada syndrome treated with quinidine. To minimize the risk

of arrhythmias from quinidine the investigators of the Registry recommend taking the

following precautions: 1) hospitalization for 2 – 3 days for the initiation of therapy; 2)

avoidance of additional medications that may cause adverse drug interactions with

quinidine. The list of medications to be avoided when taking quinidine is available at

The option of clinical follow-up with no specific therapy for Brugada syndrome is also

acceptable to the investigators of the Registry because the risk for asymptomatic

patients appears to be small and because all the therapeutic options have risks of their

own (like complications from ICD implantation and adverse effects from quinidine).

If you decide to participate in this Prospective International Registry of Asymptomatic

Brugada Syndrome, you will be asked to provide your name and contact information,

as well as the contact information of your primary care physician and a close relative.

All patients participating in the registry agree to inform the investigators of the registry

of any important changes in clinical status, including the development of symptoms,

changes in therapy or hospitalizations. This will allow the investigators conducting this

prospective International Registry to continuously update the data from all the

participating patients. The investigators conducting this registry will periodically publish

the collected data to help you and/or patients like yourself decide what the best form of



The investigators of this Registry will not assign you to a specific form of therapy.

Instead, the decision as to the form of therapy will be yours, based on the

recommendations made by your treating physicians. The study investigators will be

happy to provide additional information that may help you with this decision.

Medications and/or automatic defibrillators will not be provided by the Registry.

After reading the information provided above I certify that I understand the aim of the

Prospective International Registry of Empiric Quinidine for Asymptomatic Brugada

Syndrome and I agree to participate. I understand that I am free to cancel my

participation in this study at any time.


Date and signature:

Name of physician

Date and signature:


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