Pathophysiological mechanisms of Brugada syndrome: depolarization disorder, repolarization disorder, or more?

After its recognition as a distinct clinical entity, Brugada syndrome is increasingly recognized worldwide as an important cause of sudden cardiac death. Brugada syndrome exhibits autosomal dominant inheritance with SCN5A, which encodes the cardiac sodium channel, as the only gene with a proven involvement in 20-30% of patients. Its signature feature is ST segment elevation in right precordial ECG leads and predisposition to malignant ventricular tachyarrhythmias. The pathophysiological mechanism of ST elevation and ventricular tachyarrhythmia, two phenomena strongly related, is controversial. Here, we review clinical and experimental studies as they provide evidence to support or disprove the two hypotheses on the mechanism of Brugada syndrome that currently receive the widest support: (1) nonuniform abbreviation of right ventricular epicardial action potentials ("repolarization disorder"), (2) conduction delay in the right ventricular outflow tract ("depolarization disorder"). We also propose a schematic representation of the depolarization disorder hypothesis. Moreover, we review recent evidence to suggest that other derangements may also contribute to the pathophysiology of Brugada syndrome, in particular, right ventricular structural derangements. In reviewing these studies, we conclude that, similar to most diseases, it is likely that Brugada syndrome is not fully explained by one single mechanism. Rather than adhering to the notion that Brugada syndrome is a monofactorial disease, we should aim for clarification of the contribution of various pathophysiological mechanisms in individual Brugada syndrome patients and tailor therapy considering each of these mechanisms.     

Irritable bowel syndrome or endometriosis, or both?

Both irritable bowel syndrome and endometriosis are common conditions, although symptomatic gastrointestinal endometriosis is extremely rare. We report the case of a patient initially thought to have irritable bowel syndrome, in whom the diagnosis of endometriosis only became clear following a laparotomy for small bowel obstruction. This case highlights the need to question the diagnosis in patients with irritable bowel syndrome when there is any uncertainty, and also to appreciate that other pathology can arise, even when the diagnosis is secure.     

What is new in Brugada syndrome?

The Brugada syndrome (BrS) and the long QT syndrome are the most frequently diagnosed genetically-conditioned arrhythmogenic syndromes. It is a primary disorder of electric cardiac activity which is demonstrated by elevation of the ST segment in the right precordial leads connected to an increased risk of sudden death in patients without a structural damage of the heart. In this article, an overview of genetic heterogeneity, pathophysiology, ECG diagnostics and therapy possibilities are discussed, including the innovations of the recent years. A brief case report of a patient presenting with syncope and ST segment elevation is described.     

Susac's syndrome or catastrophic antiphospholipid syndrome?

Susac's syndrome is a microangiopathic disorder of unknown pathogenesis presenting with encephalopathy, hearing loss and branch retinal artery occlusions. The term 'catastrophic' antiphospholipid syndrome (APS) is used to define a subset of the APS characterized by thrombotic microangiopathy with clinical evidence of three or more organ involvement developed in a short period of time. We describe a patient with typical features of Susac's syndrome, that appeared in less than a week, in whom aPL were detected, thus fulfilling criteria for 'probable' catastrophic APS.     

Economy-class syndrome or Immobile Traveler's syndrome?

Economy class syndrome describes the situation of patients who suffer pulmonary embolism following prolonged immobility in a long distance flight. The objective of the present study was to analyze whether there is a risk of pulmonary thromboembolism after a long overland journey. The study consecutively enrolled 100 patients diagnosed with pulmonary thromboembolism. Nine of them had previously undertaken a long journey (>5 h), 6 of which had been over land. Consequently, we think that the preventative measures recommended for airline passengers should be extended to users of other means of transport.     

Early repolarization syndrome and Brugada syndrome: is there any linkage?

Early repolarization syndrome (ERS) is characterized by the presence, in most cases in mid-to-lateral precordial leads, of a J wave on the downsloping portion of the QRS complex, followed by an elevation of the ST-segment with upward concavity. ERS is considered a benign electrocardiographic pattern of ventricular repolarization and, thus far, clinical interest in this syndrome has been confined to its differential diagnosis from myocardial infarction and pericarditis. Brugada syndrome (BS), an inherited cardiac disease first described in 1992, exhibits a characteristic electrocardiographic pattern consisting of a J wave mimicking a right bundle branch block with typical ST-segment elevation in the right precordial leads. Believed to be a normal repolarization variant for more than three decades, the syndrome is now known instead to be associated with a high incidence of life-threatening ventricular tachyarrhythmias and is responsible for a number of sudden deaths in young adults worldwide. Although clinical findings seem to differentiate the two syndromes, similarities between BS and ERS in terms of response to heart rate, pharmacologic agents, and neuromodulation could suggest a linkage in their pathophysiological mechanism. The authors review the clinical and experimental data in order to test this hypothesis.     

Cogan syndrome or sarcoidosis?

INTRODUCTION: The Cogan's syndrome is characterized by the association of vestibulo-auditory dysfunction, non syphilitic interstitial keratitis or another significant inflammatory eye lesion. Some authors consider this disease as a vasculitis, because it is frequently associated with systemic manifestations. Based on Cogan's diagnostic criteria, Cogan's syndrome may be part of other systemic diseases, as polyarteritis nodosa or Wegener's granulomatosis. EXEGESIS: We report the case of a patient who presented with a Cogan's syndrome and developed further sarcoidosis. CONCLUSION: If Cogan's syndrome is characterized as systemic disease because of its association with aortitis or other vasculitis, on the other hand, clinical presentation may be part of many other systemic diseases.     

Brugada electrocardiographic pattern: Reality or fiction?

In many cases, failure to perform an electrocardiogram according to established standards can lead to incorrect diagnosis. When this error involves a disease that can result in sudden death such as Brugada syndrome, diagnostic procedures are not without risk for the patient.