Brugada syndrome

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Classification according to ICD-10
I49.8 Other specified cardiac arrhythmias
ICD-10 online (WHO version 2019)
Autosomal dominant inheritance

The Brugada syndrome or Brugada Brugada syndrome is a rare and usually while autosomal - dominant , but typically with incomplete penetrance hereditary disease of the heart. It is assigned to the "primary congenital cardiomyopathies " and there the so-called ion channel diseases. Patients with this condition appear to have a completely healthy heart, but can suffer sudden cardiac death in adolescence and early adulthood . An effective symptomatic therapy is the implantation of an automatic defibrillator (ICD) in particularly vulnerable patients; however, patients have already been treated effectively with ablation therapy.

history

Brugada syndrome was only identified as a presumably independent disease in the 1990s.

In 1989, cardiologists from Padua described six patients between the ages of 14 and 35 who had suffered an unexplained cardiac arrest from ventricular fibrillation between 1977 and 1988 and who had been successfully resuscitated. All six patients were supposed to have a healthy heart; three of them showed abnormal elevations of the ST segment in leads V 1-2 in the electrocardiogram (EKG) .

The syndrome was named after the brothers Pedro and Josep Brugada , who were active in Belgium at the time and who described eight patients in 1992 who had also been successfully resuscitated after cardiac arrest. They all showed a special form of right bundle branch block in the EKG , but otherwise showed no signs of organic heart disease. The cause of the syndrome was still unclear at the time.

In a 2006 updated classification of cardiomyopathies by the American Heart Association (AHA), the Brugada syndrome, like the QT syndrome, is assigned to the “congenital primary cardiomyopathies”.

Epidemiology

The prevalence of Brugada syndrome is unknown; the incidence is given as five to 66 per 10,000 population. In Southeast Asia, where it appears to be more common than Europe and North America, the syndrome is eight times more common in men than women. Cardiac arrhythmias occur there on average in the 40th year of life, with the range from the first to the 77th year of life.

Pathogenesis and pathophysiology

Meanwhile, the Brugada syndrome, along with some other rare genetically determined heart diseases such as the QT syndrome and the familial sinus node syndrome , are counted among the ion channel diseases ( English channelopathies ). They have in common is a genetic variation of the protein molecules ( proteins ) that the ion transport regulated by the cell membranes of the heart muscle. They lead to an increased ( gain-of-function ) or decreased ( loss-of-function ) transport mainly of sodium and potassium ions and thereby change the electrical properties of the cells.

A responsible genetic defect has so far only been identified in a small proportion of patients with Brugada syndrome: 15 to 25 percent of them show a mutation in the SCN5A gene, which is encoded on the third chromosome (gene locus 3p21).

Symptoms and course of the disease

The repolarization disorder of the heart muscle cells on which the syndrome is based cannot be felt, so that some of the patients do not notice any symptoms. The main symptoms of sudden unconsciousness ( syncope ) and cardiac arrest occur only through cardiac arrhythmias such as polymorphic ventricular tachycardias or ventricular fibrillation , which are favored by the changed repolarization. Individual cases with a very early onset of symptoms in newborns have been described, but the symptoms usually appear for the first time in the third or fourth decade of life.

diagnosis

ECG leads V 1-3
A Normal findings
B in Brugada syndrome
Arrow: tent-shaped ST elevation

The only diagnostic signs of Brugada syndrome are an ECG with a right bundle branch block -like image, typically an incomplete right bundle branch block, as well as characteristic changes in the ST segment in leads V 1-3 .

These ECG changes can vary in severity and only exist temporarily. They can be enhanced or unmasked by administering drugs that block the sodium channel (so-called sodium channel blockers) such as ajmaline , flecainide or procainamide . These drugs are assigned to the class I antiarrhythmics according to Vaughan / Williams.

The ECG changes are divided into three different types (see table), which have a different specificity for the diagnosis of Brugada syndrome.

EKG changes in Brugada syndrome
"Type 1" "Type 2" "Type 3"
J amplitude ≥ 0.2 mV ≥ 0.2 mV ≥ 0.2 mV
T-wave negative positive or biphasic positive
ST-T configuration curved ( coved ) saddle-shaped ( saddleback ) saddle-shaped ( saddleback )
terminal ST segment slightly sloping raised ≥ 0.1 mV raised <0.1 mV

Since the ECG changes are not observed at all in some patients and only temporarily in others, the diagnosis of Brugada syndrome is difficult and inconsistent. In 2000 a working group of the European Society of Cardiology proposed the following criteria:

  1. The combination of a coved ST segment elevation ("type 1") in more than one right-precordial chest wall lead (V 1-3 ) and one of the following events makes Brugada syndrome likely: documented ventricular fibrillation, polymorphic ventricular tachycardia, sudden cardiac death in blood relatives less than 45 years of age, syncope, eligibility during the electrophysiological examination or arched ST segment elevation in a blood relative. The ECG changes may have occurred under the influence of or without a sodium channel blocker, but other possible causes of the changes should be ruled out.
  2. ST segment elevation of "type 2" or "type 3", which change to a "type 1" elevation after administration of a sodium channel blocker, are to be assessed as such. A medication-induced increase in the ST segment of at least 0.2 millivolts (mV) makes Brugada syndrome appear possible if one of the above. clinical criteria exist. In patients without changes in the ST segment after administration of a sodium channel blocker, Brugada syndrome is very unlikely; ST changes of less than 0.2 mV are considered unsafe.
Epsilon wave (red arrow) at ARCM

In the differential diagnosis, the ST elevation called “J-wave” in Brugada syndrome must be differentiated from a similar - if not identical in terms of a “phenotype overlap” - looking “epsilon wave” as an indication of arrhythmogenic right ventricular cardiomyopathy (ARVCM), what technical difficulties can arise especially if an ARVCM is only segmental. Further clinical pictures to be considered are RVOT-VT (right ventricular outflow tract ventricular tachycardia) and so-called idiopathic ventricular fibrillation, which is typically triggered by vagotonic irritation.

An expert consensus from 2013 dispensed with a clinical criterion and required ECG changes in just one lead (type 1 ECG in V 1 or V 2 , positioned in the 2nd, 3rd or 4th ICR ).

Genotype-phenotype relation

A defect in the SCN5A gene can be detected in around a fifth of patients with Brugada syndrome, the remaining patients cannot yet be genotypically assigned. Patients with the SCN5A mutation differ phenotypically from those without the SCN5A mutation in that they have an extended PQ time and an extended HV interval. A PQ time of ≥ 210 milliseconds (ms) and a HV interval of ≥ 60 ms in the ECG indicate an SCN5A mutation. In addition, the administration of a class I antiarrhythmic resulted in a significantly longer PQ time and QRS duration in carriers of the SCN5A mutation. With regard to demographic variables, medical history and family history, however, no differences were found between the groups.

therapy

The only measure that has been proven effective against sudden cardiac death is the implantation of an automatic defibrillator (ICD) . It is useful for all patients with already documented serious arrhythmias. It is unclear whether previously asymptomatic patients should also receive an ICD as soon as the typical ECG changes are noticed.

Beta blockers are believed to be contraindicated in most patients with Brugada syndrome, as low heart rates increase the risk of ventricular fibrillation. Patients with recurrent ventricular fibrillation episodes can occasionally be treated successfully, at least temporarily, with sympathomimetic medication (e.g. orciprenaline perfusor). In some patients, the action potential-prolonging effect of quinidine can lead to a decrease in typical ECG changes and possibly a reduction in the risk of ventricular fibrillation.

In addition, it should be pointed out that in individual cases the sclerosing (ablation) of electrophysiologically measured trigger areas in the heart muscle of patients in whom Brugada syndrome was known, should have resulted in them no longer having dangerous cardiac arrhythmias from this moment on suffered.

literature

Individual evidence

  1. ↑ B. Martini et al. a .: Ventricular fibrillation without apparent heart disease: description of six cases . In: Am Heart J . (1989) 118, pp. 1203-1209. PMID 2589161 .
  2. ^ P. Brugada, J. Brugada: Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. In: J Am Coll Cardiol . (1992) 20 (6), pp. 1391-1396. PMID 1309182 .
  3. ^ BJ Maron u. a .: Contemporary Definitions and Classification of the Cardiomyopathies . In: Circulation . (2006) 113, pp. 1807-1816. PMID 16567565
  4. ↑ a b A. A. Wilde: Proposed diagnostic criteria for the Brugada syndrome: consensus report . In: Circulation. (2002) 106, pp. 2514-2519. PMID 12417552 .
  5. ↑ A. Sarkozy, P. Brugada: Sudden cardiac death and inherited arrhythmia syndromes . In: J Cardiovasc Electrophysiol. (2005) 16 Suppl 1, pp. S8-S20. PMID 16138889 .
  6. ↑ Domenico Corrado, Cristina Basso, Gianfranco Buja, Andrea Nava, Gaetano Thiene: Brugada syndrome: relationship to other arrhythmogenic syndromes. In: Charles Antzelevitch: The Brugada Syndrome: From Bench to Bedside. Blackwell Publishing Professional, 2005, pp. 111-118.
  7. ↑ JP Smits et al. a .: Genotype-phenotype relationship in Brugada syndrome: electrocardiographic features differentiate SCN5A-related patients from non-SCN5A-related patients . In: J Am Coll Cardiol. (2002) 40 (2), pp. 350-356. PMID 12106943 .
  8. ↑ Li-Fern Hsu, Bruno Cauchemez, Prashanthan Sanders, Mélèze Hocini, Philippe Maury, Jose Angel Cabrera, Fabrice Extramiana, Christophe Scavée, Y. Takahashi, M. Rotter, JL. Pasquie, J. Victor, Stéphane Garrigue, Jacques Clémenty, Michel Haïssaguerre: Potential for ablation therapy in patients with Brugada syndrome. In: Charles Antzelevitch: The Brugada Syndrome: From Bench to Bedside. Blackwell Publishing Professional, 2005, ISBN 1-4051-2778-3 , pp. 212-220.