Brugada Disease: Chronology Of Discovery And Paternity. Preliminary Observations And Historical Aspects

The Brugada disease, the last clinico-cardiologic entity described in the 20th century, initially called right bundle branch block syndrome with ST segment elevation from V1 to V2 or V3 and sudden cardiac death, is genetically determined in a dominant autosomal mode, and it affects the alpha subunit of the Na(+) channel by alteration of chromosome 3 and mutation in the SCN5A gene. In clinical diagnosis the mentioned electrocardiographic pattern in a patient without structural heart disease and positivity in pharmacological tests are considered major criteria. As minor criteria, the following are considered: positive family history, presence of syncope with unknown origin, documented episode of VT/VF, inducibility in electrophysiologic study and positivity of genetic study. The long-standing technology of ECG, with more than a century of existence, remains as the supplementary method with highest value in diagnosis, and currently new electrocardiographic criteria are suggested, which indicate high risk of VF. Natural history indicates a somber diagnosis in symptomatic patients with a high index of arrhythmic SCD secondary to very fast polymorphic ventricular tachycardia bursts, which degenerate into VF. Asymptomatic individuals with only a Brugada-type electrocardiographic pattern have a low risk. The prognosis seems to depend more on clinical facts, since a positive electrophysiologic study has an accuracy of just around 50%. We propose that this entity should be promoted to the category of disease, since it has a characteristic set of signs and symptoms, and an identified genetic defect

Chagas disease: State-of-the-art of diagnosis and management

Chagas’ disease or American trypanosomiasis, is a potentially lethal parasitic zoonosis prevalent and endemic only in Latin America, caused by the flagellate protozoa Trypanosoma cruzi. It has 3 differents stages, acute, indeterminate and chronic phase, with the chance of an etiological approach in the first stage and pharmacological and non-pharmacological treatment in the chronic phase. There are five main clinical forms of chronic chagasic cardiomyopathy: indeterminate, arrhythymogenic (predominantly dromotropic and extrasystolic), with ventricular dysfunction, thromboembolic and mixed forms. There are several diagnostic tests at the different stages, however, the ECG is the method of choice in longitudinal population studies in endemic areas because it is simple, with a low cost and a good sensitivity. Microscopic examination or parasitological diagnosis in the acute phase or immunodiagnostic tests are used to confirm the disease. The antiarrhythmic drug amiodarone, the most frequently prescribed agent for symptomatic ventricular arrhythmia treatment of Chagas’ disease patients, has also recently been shown to have antifungal activity. Cardiac device implantation is very common, and chronic Chagas disease patients require pacemaker implantation at a younger age in contrast with patients with other cardiac pathologies. In summary, Chagas disease is a social disease, endemic in Latin America and shows different prevalence rates in Latin American countries

Choroba Chagasa - aktualny stan wiedzy na temat rozpoznawania i postępowania terapeutycznego

Choroba Chagasa lub trypanosomoza amerykańska jest potencjalnie śmiertelną zoonozą pasożytniczą, występującą endemicznie jedynie w Ameryce Łacińskiej, wywoływaną przez Trypanosoma Cruzi - gatunek należący do uwicionych pierwotniaków. Przebieg tej choroby cechują 3 różne fazy: ostra, nieokreślona i przewlekła. W pierwszej fazie leczenie opiera się na podejściu etiologicznym. W fazie przewlekłej stosuje się różne metody leczenia farmakologicznego i niefarmakologicznego. Rozróżniono 5 głównych klinicznych form przewlekłych kardiomiopatii związanych z chorobą Chagasa: nieokreśloną, arytmogenną (głównie dromotropowa i ekstrasystoliczna), z dysfunkcją komory mięśnia sercowego, zakrzepowo-zatorową oraz postacie mieszane. Istnieje kilka testów diagnostycznych pozwalających na rozpoznanie choroby Chagasa w różnych jej fazach, jednak na podstawie przekrojowych badań populacyjnych przeprowadzonych na terenach endemicznych okazało się, że badanie elektrokardiograficzne jest metodą z wyboru, ze względu na łatwość wykonania, niski koszt oraz dobrą czułość. Badanie mikroskopowe, diagnostyka parazytologiczna w ostrej fazie choroby lub też testy immunodiagnostyczne są używane jedynie w celu potwierdzenia rozpoznania. W ostatnio przeprowadzonych badaniach wskazano, że amiodaron, najczęściej przepisywany lek przeciwaarytmiczny w leczeniu arytmii komorowych w przebiegu choroby Chagasa, wykazuje również aktywność przeciwgrzybiczą. W przebiegu choroby Chagasa dosyć często pojawia się konieczność implantacji stymulatora serca. Pacjenci z chorobą Chagasa, w porównaniu z osobami z innymi patologiami mięśnia sercowego, wymagają wszczepienia stymulatora w młodszym wieku. Podsumowując, choroba Chagasa to schorzenie społeczne, występujące endemicznie na terenach Ameryki Łacińskiej i wykazujące różny stopień rozpowszechnienia w poszczególnych krajach tego regionu

The management of Brugada syndrome patients

Brugada syndrome is a congenital electrical disorder characterised by the appearance of distinctive QRST-T patterns in the right precordial leads and an increased risk of sudden death (SCD) in young healthy adults. Although chamber enlargement is not apparent in most cases, autopsy and histological investigations have revealed structural abnormalities. The typical Brugada ECG manifestation is often concealed and may be revealed by Class IC anti-arrhythmic agents with the effect of blocking the fast component of sodium channel currents. The syndrome may also be unmasked or precipitated by a febrile state, vagotonic agents, α-adrenergic agonists, β-adrenergic blockers, tricyclic or tetracyclic antidepressants, a combination of glucose and insulin and hypokalaemia, as well as by alcohol and cocaine toxicity. Since the typical Brugada ECG pattern can be normalised by Class IA agents to block transient outward currents (Ito) or by isoproterenol and cilostazol to boost calcium channel currents, they have been considered pharmacological therapies aimed at rebalancing the ion channel currents during cardiac depolarisation and repolarisation. Case studies by intra-cardiac mappingguided ablation in the right ventricular outflow tract and Purkinje network have shown evidence of eliminating the substrate of ventricular tachycardia/fibrillation (VT/VF) in Brugada syndrome, which may be used as an adjunct to device therapy to abort electrical storms. At present the most effective therapy to prevent sudden cardiac death in Brugada syndrome is an implantable cardioverter defibrillator. (Cardiol J 2007; 14: 97–106

Propofol infusion syndrome and Brugada syndrome electrocardiographic phenocopy

This anesthetic drug may cause a rare condition named propofol infusion syndrome, characterized by unexplained lactic acidosis, lipemia, rhabdomyolysis, cardiovascular collapse and Brugada-like electrocardiographic pattern or Brugada electrocardiographic phenocopy changes following high-dose propofol infusion over prolonged periods of time. Several articles have contributed to our understanding of the cause of the syndrome, and the growing number of case reports has made it possible to identify several risk factors. Uncertainty remains as to whether a genetic susceptibility exists. The favorable recovery profile associated with propofol offers advantages over traditional anesthetics in clinical situations in which rapid recovery is important. Propofol is a safe anesthetic agent, but propofol infusion syndrome is a rare lethal complication. (Cardiol J 2010; 17, 2: 130-135

Early repolarization variant: Epidemiological aspects, mechanism, and differential diagnosis

Early repolarization variant (ERV or ERPV) is a enigmatic electrocardiographic phenomenon, characterized by prominent J wave and ST-segment elevation in multiple leads. Recently, there has been renewed interest in ERV because of similarities to the arrhythmogenic Brugada syndrome (BrS). Not much is known about the epidemiology of ERV and several studies have reported that this condition is associated with a good prognosis. Both syndromes exhibit some similarities including the ionic underlying mechanism, the analogous responses to changes in heart rate and autonomic tone, sympathicomimetics (isoproterenol test) as well as in sodium channel and beta-blockers. These observations raise the hypothesis that ERV may be not as benign as traditionally believed. Additionally, there are documents showing that ST-segment height in the man is greatly influenced by central sympathetic nervous activity, both at baseline and during physiologic and pharmacological stress. Central sympathetic dysfunction regularly results in multilead ST-segment elevation or J wave that decreases or below isoelectric baseline during low dose isoproterenol infusion. In this review, we describe the characteristics of ERV and the main differences with acute pericarditis, acute myocardial infraction/injury and Brugada syndrome. (Cardiol J 2008; 15: 4-16

Relationship among amiodarone, new class III antiarrhythmics, miscellaneous agents and acquired long QT syndrome

Class III drugs prolong the QT interval by blocking mainly the delayed rectifier rapid potassium outward current (IKr), with little effect on depolarization. This K+ channel in encoded by the human ether-a-go-go-related gene (hERG). Inhibition of hERG potassium currents by class III antiarrhythmic drugs causes lengthening of cardiac action potential, which produces a beneficial antiarrhythmic effect. Excessive prolongation of the action potential may lead to acquired long QT syndrome, which is associated with a risk of “torsade de pointes”. Class III agents can block all types of potassium channels: IKs, IKr, IKur and IK1. The main representing class III agent is amiodarone. It is the gold standard in the prevention of recurrence of atrial fibrillation. Although it is highly effective in treating many arrhythmias, large number of adverse effects limits its clinical use. Dronedarone is a synthetic amiodarone analogue, iodinefree compound, with fewer adverse effects, and shares amiodarone’s multichannel blocking effects, inhibiting transmembrane Na+, IKs, IKur, IK1, and slow Ca++L-type calcium currents. The main new generation class III drugs are: dofetilide, dronedarone, azimilide, and ibutilide. Oral dofetilide did not increase mortality in patients with a recent myocardial infarction or congestive heart failure. It is an alternative for the pharmacological conversion of atrial fibrillation and flutter. Azimilide blocks both rapid and slow potassium channels components. Azimilide is not a methanesulfonanilide compound. Trecitilide, tedisamil, ersentilide, ambasilide, chromanol and sematilide are class III miscellaneous agents. Old mixed agents are sotalol and bretylium. The present article reviews the main trials accomplished with these drugs. (Cardiol J. 2008; 14: 209–219

The enigmatic sixth wave of the electrocardiogram: The U wave

The U wave is the last, inconstant, smallest, rounded and upward deflection of the electrocardiogram. Controversial in origin, it is sometimes seen following the T wave with the TU junction along the baseline or fused with it and before P of the following cycle on the TP segment. In this review we will study its temporal location related to monophasic action potential, cardiac cycle and heart sounds, polarity, voltage or amplitude, frequency and shapecontour. We will analyze the clinical significance of negative, alternant, prominent U wave, and the difference between T wave with two peaks (T1–T2) and true U wave. Finally we will analyze the four main hypotheses about the source of U wave: repolarization of the intraventricular conducting system or Purkinje fibers system, delayed repolarization of the papillary muscles, afterpotentials caused by mechanoelectrical hypothesis or mechanoelectrical feedback, and the prolonged repolarization in the cells of the mid-myocardium (“M-cells”)

Idiopathic intrafascicular reentrant left ventricular tachycardia in an elite cyclist athlete

A 32 year-old Caucasian male, an elite athlete, was admitted to the emergency department because of a sudden onset of palpitations which had lasted more than 12 hours and were associated with chest discomfort. He had a two-year history of recurrent stress-induced palpitations. He denied either episodes of syncope or any family history of sudden death. Physical examination was normal. He had no evidence of structural heart disease. The electrocardiography (ECG) documented during the event supported the diagnosis of idiopathic reentrant left ventricular tachycardia. Ventricular tachycardia ablation was successful. This case demonstrates that a careful physical examination and correct ECG diagnosis can lead to an appropriate arrhythmia management

Aktualne sposoby leczenia zaburzeń rytmu u pacjentów z zespołem Brugadów

Zespół Brugadów jest chorobą uwarunkowaną genetycznie, charakteryzującą się obecnością typowych zmian elektrokardiograficznych u osób bez jawnej organicznej choroby serca oraz występowaniem złożonych komorowych zaburzeń rytmu, stanowiących najczęstszą przyczynę nagłego zgonu sercowego. Chociaż w większości przypadków nie stwierdza się powiększenia sylwetki serca ani innych cech kardiomiopatii, w badaniach przeprowadzonych u zmarłych osób z udokumentowanym zespołem wykazano obecność pewnych anomalii histopatologiczych, zwłaszcza w prawej komorze. U części pacjentów wyjściowy elektrokardiogram może być całkowicie prawidłowy. Typowy dla zespołu Brugadów obraz EKG może się ujawnić niekiedy dopiero po podaniu leków antyarytmicznych klasy IC - blokujących kanały sodowe. Nasilenie zmian elektrokardiograficznych w tej grupie chorych może wynikać również z gorączki, wzmożonego napięcia nerwu błędnego, hipokaliemii, zatrucia alkoholem lub kokainą, podawania glukozy z insuliną, a także stosowania leków działających α- i β-adrenergicznie oraz trój- i czteropierścieniowych preparatów przeciwdepresyjnych. Czynnikami przywracającymi zaburzoną równowagę na poziomie kanałów jonowych między okresami depolaryzacji i repolaryzacji komórek mięśnia sercowego, a tym samym zmniejszającymi typowe dla opisywanego zespołu uniesienie odcinka ST w oprowadzeniach V1-V3, są leki antyarytmiczne klasy IA, izoproterenol oraz zwiększający przepływ jonów przez kanały wapniowe cilostazol. Na podstawie tych danych zaproponowano stosowanie wyżej wymienionych preparatów w terapii pacjentów z zespołem Brugadów. Istnieją również pojedyncze doniesienia wskazujące na przydatność ablacji prądem o wysokiej częstotliwości ognisk w drodze odpływu prawej komory oraz włókien Purkiniego - jako zabiegów zmniejszających (poprzez modyfikację substratu arytmii) ryzyko wystąpienia "burzy elektrycznej" u pacjentów z implantowanym kardiowerterem-defibrylatorem serca. Obecnie najskuteczniejszą metodą zapobiegania nagłej śmierci sercowej u pacjentów z zespołem Brugadów nadal jest implantacja kardiowertera-defibrylatora serca