Padrão de Brugada em doente medicada com lamotrigina

The authors report the case of a 52-year-old woman with depressive syndrome, treated with lamotrigine for about five months, who went to the emergency department for atypical precordial pain. The electrocardiogram (ECG) revealed a 2-mm downsloping ST-segment elevation and negative T waves in V1 and V2. Due to suspicion of ST-elevation acute coronary syndrome, cardiac catheterization was performed, which revealed normal coronary arteries. The initial ECG was suggestive of type 1 Brugada pattern, but subsequent serial ECGs were less typical. A flecainide test showed the same pattern.After discontinuation of lamotrigine reversal of the typical Brugada ECG pattern was observed.Although not currently contraindicated in Brugada syndrome, the antidepressant lamotrigine blocks sodium channels, which are usually inactivated in heart cell membranes in Brugada syndrome, and may be responsible for the expression of type 1 Brugada pattern.     

Normal conventional electrocardiogram with negative pharmacological stress test does not rule out Brugada syndrome

The diagnosis of Brugada syndrome, or right bundle-branch block with an elevated ST segment and negative T waves in V1-3, is obscured by the transitory normalization of the electrocardiogram, which can be unmasked by administering sodium-channel blockers. It has been recently reported that the condition can be underdiagnosed if only conventional precordial leads are used. We present the cases of two asymptomatic patients, a mother and son, with a family history of sudden cardiac death in first-degree relatives. Baseline ECGs obtained in conventional leads and one and two intercostal spaces above conventional electrode sites were similar, normal in the mother and saddle-like in the son. A flecainide stress test elicited the characteristic pattern of Brugada syndrome in both patients, but only in the high leads. Pharmacological stress testing with conventional precordial lead recordings does not rule out Brugada syndrome. We recommend that ECG recordings should include leads in the second and third intercostal spaces.     

Tpeak-Tend and Tpeak-Tend dispersion as risk factors for ventricular tachycardia/ventricular fibrillation in patients with the Brugada syndrome.

OBJECTIVES: Our objective in this study was to evaluate Tpeak-Tend interval (Tp-e) and other electrocardiographic parameters as risk factors for recurrence of life-threatening cardiac events in patients with the Brugada syndrome (BS). BACKGROUND: The Tp-e interval in the electrocardiogram (ECG) has been reported to predict life-threatening arrhythmias in the long QT syndrome. METHODS: Twenty-nine patients with the ECG pattern of BS and 29 healthy age- and gender-matched controls were studied. The follow-up period was 42.65 +/- 24.42 months (range 11 to 108 months). RESULTS: Upon presentation, five patients had suffered aborted sudden death, five syncope, and two presyncope. Eleven patients with the ECG pattern of BS had a prolonged (>460 ms) QTc in V2 but usually not in inferior or left leads. No patient had abnormally prolonged QT dispersion. Programmed electrical stimulation induced ventricular tachycardia/fibrillation in 5 out of 26 patients. Inducibility did not predict recurrence of events. Cardioverter-defibrillators were implanted in 14 patients (all symptomatic and two asymptomatic). During follow-up, nine symptomatic patients experienced recurrences. Previous cardiac events and a QTc >460 ms in V2 were significant risk factors (p = 0.00002 and p = 0.03, respectively). Tp-e and Tp-e dispersion were significantly prolonged in patients with recurrences versus patients without events (104.4 and 35.6 ms vs. 87.4 and 23.2 ms; p = 0.006 and p = 0.03, respectively) or controls (90.7 and 17.9 ms; p = 0.02 and p = 0.001, respectively). CONCLUSIONS: Our study demonstrates significant correlation between previous events, QTc >460 ms in V2, Tp-e, and Tp-e dispersion and occurrence of life-threatening arrhythmic events, suggesting that these parameters may be useful in risk stratification of patients with the Brugada syndrome.     

Electrocardiographic predictors of Brugada type response during Na channel blockade challenge.

AIM: To identify ECG predictors of Brugada type response during Na channel blockade challenge. METHODS: We studied prospectively 103 patients (M = 76, 45 +/- 13 years) in whom ECGs were collected during ajmaline challenge. ECG recordings included the high right precordial leads (-2V(1) and -2V(2)). A positive response was defined by a >0.2 mV J point or ST segment elevation and a down-sloping pattern of the ST segment in at least one right precordial lead. RESULTS: Ajmaline challenge was positive in 48 (47%) of the 103 cases. Baseline J wave elevation was greater in -2V(1) (0.077 +/- 0.078 mV vs. 0.038 +/- 0.046 mV, P = 0.003) and -2V(2) (0.149 +/- 0.103 mV vs. 0.043 +/- 0.088 mV, P < 0.001) in cases with a subsequent positive response. In contrast, ST segment elevation and T wave amplitudes were reduced in V(1), V(2) and V(3). Logistic regression showed that J wave elevation in -2V(2) and decreased T wave amplitude in V(3) at baseline were independent predictors of a positive response. Baseline J wave elevation >0.16 mV in -2V(2) had a specificity of 100%, a sensitivity of 40%, a positive predictive value of 100% and a negative predictive value of 28%. CONCLUSION: J wave elevation >0.16 mV in -2V(2) was the strongest predictor of a Brugada type response to Na channel blockade challenge when Brugada syndrome was suspected on a baseline ECG.     

Body surface potential mapping in patients with Brugada syndrome: right precordial ST segment variations and reverse changes in left precordial leads

OBJECTIVE: The aim of this study was to perform quantitative signal analysis of high-resolution body surface potential mapping (BSPM) recordings to assess its usefulness for the electrocardiographic characterization of patients with Brugada syndrome. The diagnostic value of the QRS integral and of the gradient of the ST segment have not been elucidated in Brugada syndrome. METHODS: In 27 subjects (16 with Brugada syndrome and 11 healthy subjects), 120-lead BSPMs were recorded at baseline and after pharmacological provocation with intravenous administration of ajmaline (1 mg/kg). The recordings were analyzed for two regions outside the positions of the standard ECG leads: the right precordial leads (RPL) on the second and third intercostal space (high RPL) and the left precordial leads (LPL) between the fifth and seventh intercostal space (low LPL). RESULTS: At baseline, in high RPL regions, patients with Brugada syndrome showed more positive QRS integrals (-5+/-8 vs. -16+/-8 mV ms) and a steeper negative ST segment gradient (-0.62+/-0.41 vs. -0.29+/-0.40 mV/s) compared to healthy subjects, P<0.001. In contrast, in low LPL regions, reduced QRS integrals and positive ST segment gradients were observed. These ECG signs were even more pronounced after intravenous ajmaline and showed a better discrimination for patients with Brugada syndrome than differences in RPL or LPL during baseline, respectively. CONCLUSIONS: In the left precordial leads, patients with Brugada syndrome showed ECG changes which were reversed in relation to the ECG changes observed in right precordial leads. BSPM measurement is a useful tool to improve the understanding of the electrocardiographic changes in the Brugada syndrome.     

Intravenous drug challenge using flecainide and ajmaline in patients with Brugada syndrome

OBJECTIVES: The purpose of this study was to compare the effect of intravenous flecainide and ajmaline with respect to their ability to induce or accentuate the typical ECG pattern of Brugada syndrome. BACKGROUND: Brugada syndrome is associated with a high incidence of sudden cardiac death. The typical ECG pattern of ST-segment elevation in the right precordial leads often is concealed, but it can be unmasked with sodium channel blockers such as flecainide and ajmaline. Little is known about the relative effectiveness of these provocative agents in unmasking Brugada syndrome. METHODS: Intravenous pharmacologic challenge with flecainide and ajmaline was performed. Whole-cell patch clamp techniques were used to assess the relative potency of ajmaline and flecainide to inhibit the transient outward current (I(to)). RESULTS: A coved-type ST-segment elevation in the right precordial leads was induced or enhanced in 22 of 22 patients following ajmaline administration. Among the 22 patients, only 15 patients showed positive response to flecainide, resulting in a positive concordance of 68%. Both drugs produced equivalent changes in QRS and PQ intervals, suggesting similar effects on sodium channel current. Whole-cell patch clamp experiments revealed a reduction of the total charge provided by I(to) with an IC(50) of 216 and 15.2 microM for ajmaline and flecainide, respectively. CONCLUSIONS: Our data demonstrate disparate response of Brugada patients to flecainide and ajmaline, with a failure of flecainide in 7 of 22 cases (32%). Greater inhibition of I(to) by flecainide may render it less effective. These observations have important implication for identification of patients at risk for sudden death.     

QT interval greater than 460 ms in multiple electrocardiograms during follow-up in patients with Brugada syndrome: What does it contribute?

IntroductionCorrected QT interval (QTc) >460 ms in the right precordial leads has been described as a predictor of malignant ventricular arrhythmias (MVA) in patients with Brugada syndrome (BrS).ObjectiveTo assess the presence of QTc>460 ms in multiple electrocardiograms (ECGs) during follow-up as a predictor of recurrence of MVA in patients with BrS.MethodsThe study group included 43 patients with BrS and an implantable cardioverter-defibrillator. ECGs were performed serially between June 2000 and January 2017. QT interval was measured and QTc was obtained by Bazett's formula. The sample was divided into three groups: Group 1 (patients with no ECGs with QTc>460 ms); Group 2 (patients with only one ECG with QTc>460 ms); and Group 3 (patients with two or more ECGs with QTc>460 ms).ResultsThe following variables were more frequently observed in Group 3: family history of sudden death (p=0.023), previous history of cardiorespiratory arrest (p=0.032), syncope (p=0.039), documented MVA (p=0.002), and proportion of ECGs with coved-type ST interval during follow-up (p=0.002). In Group 3, 67% of BrS patients had events during follow-up, as opposed to only 22% of Group 1 and 14% of Group 2 (Group 1 vs. Group 2, p=0.33015; Group 1 vs. Group 3, p=0.04295; and Group 2 vs. Group 3, p=0.04155).ConclusionsQTc>460 ms in more than one ECG during follow-up increases the risk of MVA events in patients with BrS.     

Effect of sodium channel blockers on ST segment, QRS duration, and corrected QT interval in patients with Brugada syndrome

INTRODUCTION: Brugada syndrome is characterized by an ST segment elevation in leads V1-V3 and a high incidence of ventricular fibrillation (VF). A mutation in a cardiac Na+ channel gene, SCN5A, has been linked to Brugada syndrome, and sodium channel blockers have been shown to be effective in unmasking the syndrome when concealed. The aim of this study was to examine the effects of Na+ channel blockers on ST segment elevation, QRS, corrected QT (QTc) interval, and ventricular arrhythmias in patients with Brugada syndrome. METHODS AND RESULTS: We examined the effects of three different Na+ channel blockers (flecainide, disopyramide, and mexiletine) on the amplitude of the ST segment 20 msec after the end of QRS (ST20), QRS duration, QTc interval measured from 12-lead ECG, and ventricular arrhythmias in 12 Brugada and 10 control patients. Maximum ST20 observed in the V2 or V3 leads under baseline conditions was greater in the Brugada patients than in control patients, whereas QRS duration and maximum QTc interval were no different between the two groups. Flecainide and disopyramide, but not mexiletine, significantly increased maximum ST20 and QRS duration in both groups, although these effects were much more pronounced in the Brugada patients. The increases in ST20 and QRS duration with flecainide were significantly larger than those with disopyramide. An increase of 0.15 mV in ST20 with flecainide separated the two groups without overlap. Ventricular premature complexes developed only with flecainide in Brugada patients (3/12) displaying a marked ST elevation but not widening of QRS. CONCLUSION: Our findings suggest that Na+ channel blockers amplify existing I(Na) and possibly other ion channel defects, with a potency inversely proportional to the rate of dissociation of the drug from the Na+ channel, thus causing a prominent elevation of the ST segment and, in some cases, prolongation of QRS duration in patients with Brugada syndrome.     

Paradoxical effect of ajmaline in a patient with Brugada syndrome.

AIMS: The typical Brugada ECG pattern consists of a prominent J-wave associated with ST-segment elevation localized in the right precordial leads V1-V3. In many patients, the ECG presents periods of transient normalization and the Brugada-phenotype can be unmasked by the administration of class-I antiarrhythmics. Reports have documented the heterogeneity of the Brugada syndrome ECG-phenotype characterized by unusual localization of the ECG abnormalities in the inferior leads. Case report A 51-year-old man, without detectable structural heart disease, was referred to us because of a history of syncope, dizziness, and palpitations. The ECG showed a J-wave and ST-segment elevation in the right precordial leads, suggesting Brugada syndrome. As other causes of the ECG abnormalities were excluded, the patient underwent an electrophysiological study that documented easy induction of ventricular fibrillation. During infusion of ajmaline, new prominent J-waves and ST-segment elevation appeared in the inferior leads, whereas the basal ECG abnormalities in the right precordial leads normalized. After infusion of isoprenaline, the ECG-pattern resumed the typical Brugada pattern. An implantable cardioverter-defibrillator was recommended. CONCLUSION: In our patient, the double localization of the typical Brugada-pattern and the paradoxical effect of ajmaline on the ECG abnormalities confirmed the possibility of a phenotype heterogeneity in the Brugada syndrome.     

Das Oberflächen-EKG in der Diagnostik von Arrhythmien

The surface electrocardiogram (ECG) is a simple noninvasive method to assess the electrical activity of the heart and provides important information to identify patients with cardiac arrhythmias and increased arrhythmic risk. This brief review highlights cardiac conditions in which the right precordial leads recorded on the surface ECG during sinus rhythm or tachycardia are of important diagnostic and prognostic value. Epsilon waves seen in the right precordial ST segments are the electrocardiographic hallmark of arrhythmogenic right ventricular cardiomyopathy. The diagnosis of Brugada syndrome and risk stratification of affected patients are based on a coved-type >or=2 mm ST-segment elevation in the right precordial leads. This typical ECG pattern may be present persistently, intermittently or only after administration of sodium-channel blockers. The early repolarization syndrome, most commonly seen in healthy young individuals, is characterized by a ST-segment elevation of 1 to 4 mm in the mid-precordial leads with a notched and elevated J point in lead V4. The precordial ECG T-wave repolarization pattern may be helpful in identifying the genotype in patients with suspected long QT syndrome. In patients with overt preexcitation, the surface leads V1 and V2 play a key role in localizing the site of bypass-tract insertion. Finally, the right precordial lead V1 is often crucial in the diagnosis of narrow and broad QRS-complex tachycardias.     

Body surface distribution and response to drugs of ST segment elevation in Brugada syndrome: clinical implication of eighty-seven-lead body surface potential mapping and its application to twelve-lead electrocardiograms

INTRODUCTION: Body surface distribution and magnitude of ST segment elevation and their reflection in 12-lead ECGs have not been clarified in Brugada syndrome. METHODS AND RESULTS: Eighty-seven-lead body surface potential mapping and 12-lead ECGs were recorded simultaneously in 25 patients with Brugada syndrome and 40 control patients. The amplitude of the ST segment 20 msec after the end of QRS (ST20) was measured from all 87 leads, and an ST isopotential map was constructed. The maximum ST elevation (maxST20) was distributed in an area of the right ventricular outflow tract in all Brugada patients, and it was larger than that in control patients (0.37 +/- 0.13 vs 0.12 +/- 0.04 mV; P < 0.0005). The maximum was observed on the level of the parasternal fourth intercostal space, on which the V1 and V2 leads of the standard 12-lead ECG were located, in 18 of the 25 Brugada patients in whom typical coved- or saddleback-type ST elevation was seen in leads V1 and V2. The maximum was located on the second intercostal space in the remaining seven Brugada patients in whom only a mild saddleback-type ST elevation was seen in leads V1 and V2 of the 12-lead ECG. Typical ST segment elevation was recognized in leads V1 and V2, which were recorded on the second or third intercostal space. ST elevation in Brugada patients was dramatically normalized by isoproterenol, a beta-adrenergic agonist (maxST20 = 0.17 +/- 0.08 mV; P < 0.0005 vs control conditions), and accentuated by disopyramide, an Na+ channel blocker (maxST20 = 0.50 +/- 0.15 mV; P < 0.0005 vs control conditions), without any change in the location of the maxST20. CONCLUSION: Our data indicate that recordings of leads V1-V3 of the 12-lead ECG on the parasternal second or third intercostal space would be helpful in diagnosing suspected patients with Brugada syndrome. The data suggest that Na+ channel blockers are capable of accentuating ST elevation in leads V1-V3.     

ST segment elevation in the right precordial leads following administration of class Ic antiarrhythmic drugs

Electrocardiographic changes were evaluated retrospectively in five patients without previous episodes of syncope or ventricular fibrillation who developed abnormal ST segment elevation mimicking the Brugada syndrome in leads V1-V3 after the administration of class Ic antiarrhythmic drugs. Pilsicainide (four patients) or flecainide (one patient) were administered orally for the treatment of symptomatic paroxysmal atrial fibrillation or premature atrial contractions. The QRS duration, QTc, and JT intervals on 12 lead surface ECG before administration of these drugs were all within normal range. After administration of the drugs, coved-type ST segment elevation in the right precordial leads was observed with mild QRS prolongation, but there were no apparent changes in JT intervals. No serious arrhythmias were observed during the follow up periods. Since ST segment elevation with mild QRS prolongation was observed with both pilsicainide and flecainide, strong sodium channel blocking effects in the depolarisation may have been the main factors responsible for the ECG changes. As the relation between ST segment elevation and the incidence of serious arrhythmias has not yet been sufficiently clarified, electrocardiographic changes should be closely monitored whenever class Ic drugs are given.     

Three-Lead Measurement of QTc Dispersion

QTc Dispersion. Introduction: QTc dispersion has traditionally been calculated from all 12 leads of a standard electrocardiogram (ECG). It is possible that alternative, quicker methods using fewer than 12 leads could be used to provide the same information. Methods and Results: We have previously shown a difference in QTc dispersion from ECGs recorded at least 1 month after myocardial infarction between patients who subsequently died and long-term survivors. In the current study, we recalculated QTc dispersion in these ECGs using different methods to determine if the observed difference in QTc dispersion measurements between the two groups, as calculated from 12-lead ECGs, persisted when using smaller sets of leads. QTc dispersion was recalculated by four methods: (1) with the two extreme QTc intervals excluded: (2) from the six precordial leads; (3) from the three leads most likely to contribute to QTc dispersion (aVF, V₁V₄); and (4) from the three quasi-orthogonal leads (aVF, I, V). For each of the 270 12-lead ECGs examined, a mean of 9.9 leads (SD 1.5 leads) had a QT interval analyzed; the QT interval could not be accurately measured in the remaining leads. Using the standard 12-lead measurement of QTc dispersion, there was a difference in the fall in QTc dispersion from early to late ECG between the groups: 9.1 (SD 60.8) msec for deaths versus 34.4 (55.2) msec for survivors (P = 0.016). This difference in QTc dispersion between early and late ECGs was maintained using either three-lead method (quasi-orthogonal leads: -2.6 [56.2] msec for deaths vs 26.9 [54.3] msec for survivors [P = 0.003]; “likeliest” leads: 8.6 [64.9] msec vs 29.5 [50.2] msec [P = 0.05]), but not when using the other two methods (precordial leads: 19.1 [55.5] msec vs 22 [50.8] msec [P = 0.76]; extreme leads removed: 9.2 [50.1] msec vs 21.8 [42] msec [P = 0.13]). Conclusion: QTc dispersion calculated from three leads may be as useful a measurement as QTc dispersion calculated from all leads of a standard ECG. Its advantages over the standard measurement are its simplicity and the lack of problems with lead adjustment.     

Electrocardiographic risk stratification in families with congenital long QT syndrome.

AIMS: The QT interval in the surface ECG is one of the most often used risk stratifiers in families with congenital long QT syndrome (LQTS). The best ECG lead for clinical management of LQTS families remains unclear. METHODS AND RESULTS: The predictive power of the QTc interval in all ECG leads was studied in 200 consecutive genotyped LQTS family members to identify mutation carriers (n = 103; age: 35+/-19 years) and high-risk LQTS patients (n = 16 with survived sudden cardiac arrest) using receiver operating curve (ROC) analysis (ROC = area under curve). Additionally, the risk for events (syncope and sudden cardiac arrest) was calculated for QTc decile in all individuals. The predictive power was highest in lead II and lead V5 for identifying carriers in LQTS families. These ECG leads were optimal for risk stratification (ROC range 0.83-0.87). In these leads, positive predictive value (PPV) and negative predictive value (NPV) were highest for suggested QTc cut-offs (440 and 500 ms) for identification of LQTS mutation carriers and high-risk patients (PPV between 78-81 and 73-80%, respectively). The risk for events in QTc deciles increased exponentially from 10 to 80% and was 40% for QTc > 500 ms. CONCLUSION: On the basis of these data, QTc is the best diagnostic and prognostic ECG parameter in LQTS families. A single measurement should be obtained in lead II if measurable and then in left precordial leads (preferably V5) as a second choice.     

Syncope with QT-interval prolongation and T-wave inversion in anterior and inferior leads: Foreboder of a life-threatening condition?

Even though patients with pulmonary embolism usually present with respiratory distress and tachycardia, the patient presented with syncope only. Typical ECG changes associated with PE include right axis deviation, right bundle-branch block, S1Q3T3 pattern, arrhythmia, nonspecific ST-segment changes, QR pattern in lead V1, Brugada ECG pattern, and T-wave inversions in the precordial leads. However, his electrocardiogram showed QT-interval prolongation and simultaneous T-wave inversions in the inferior and anterior leads. This ECG pattern is crucial for diagnosing PE. The patient underwent computed tomography-pulmonary angiography, which revealed pulmonary embolism. At the same time, these ECG changes should be differentiated from those of long QT syndrome, myocardial ischemia, Takotsubo cardiomyopathy, post-pacing T-wave memory, hypertrophic cardiomyopathy, and subarachnoid hemorrhage.     

Concurrent long QT and Brugada syndrome in a single patient]

We present a 61-year-old patient with previous cardiac arrest and frequent syncopal spells. ECG showed a typical Brugada pattern and a QTc interval of 425 ms. During programmed ventricular stimulation a self-limited syncopal polymorphic ventricular tachycardia was induced. On diagnosis of the Brugada syndrome an implantable cardioverter defibrillator was implanted. Two days later two episodes of polimorphic ventricular arrhythmia were converted by the device. The ECG at this time showed a prolonged QTc of 500 ms in addition to a typical Brugada pattern. Atenolol was started and after a 36-month follow-up the patient has remained asymptomatic without arrhythmic events. In conclusion, this patient has the Brugada syndrome and also fulfills the clinical and ECG characteristics of the Long QT syndrome. These findings suggest a genetic link between the two syndromes.     

A prospective study on spontaneous fluctuations between diagnostic and non-diagnostic ECGs in Brugada syndrome: implications for correct phenotyping and risk stratification.

AIMS: Fluctuations between the diagnostic ECG pattern and non-diagnostic ECGs in patients with Brugada syndrome are known, but systematic studies are lacking. The purpose of this study was to prospectively evaluate the spontaneous ECG changes between diagnostic and non-diagnostic ECG patterns in patients diagnosed with Brugada syndrome. METHODS AND RESULTS: In 43 patients with Brugada syndrome (27 males; mean age 45+/-11 years), 310 resting ECGs were obtained during a median follow-up of 17.7 months. The ECGs were analysed for the presence of coved type, saddle-back type or no, respectively unspecific, changes. A coved-type ECG pattern with more than 2 mm ST-segment elevation in at least two right precordial leads was defined as diagnostic. The patients were compared for different clinical characteristics with respect to the pattern of fluctuations. Out of a total of 310 ECGs, 102 (33%) revealed a coved type, 91 (29%) a saddle-back type, and 117 (38%) a normal ECG. Fifteen patients (35%) initially presented with a diagnostic coved-type ECG. Fourteen patients (33%) with an initially coved-type ECG exhibited intermittently non-diagnostic ECGs during follow-up. Only one patient (2%) presented constantly with a coved-type ECG. Out of 28 patients (65%) with an initially non-diagnostic ECG, eight (19%) patients developed a diagnostic coved-type ECG during follow-up. Twenty patients (47%) revealed a coved-type ECG during ajmaline challenge, but never had a baseline coved-type ECG recorded. No significant differences were found in gender and clinical characteristics among patients with or without fluctuations between diagnostic and non-diagnostic basal ECGs. The rate of inducible ventricular fibrillation was significantly higher in patients with more than 50% coved-type ECGs than in patients with less than 50% diagnostic ECGs. CONCLUSION: The prevalence of fluctuations between diagnostic and non-diagnostic ECGs in patients with Brugada syndrome is high and may have an implication on the correct phenotyping and on the risk stratification in patients with Brugada syndrome without aborted sudden cardiac death. For correct phenotyping and risk stratification, repetitive ECG recordings seem to be mandatory.     

A newly characterized SCN5A mutation underlying Brugada syndrome unmasked by hyperthermia

Febrile illness has been rarely reported to modulate ST segment elevation in right precordial leads on ECG or even precipitate ventricular fibrillation in patients with Brugada syndrome. We report the case of a patient whose Brugada ECG pattern was unmasked by hyperthermia secondary to acute cholangitis. Serial ECGs showed progressive attenuation of ST segment elevation as body temperature gradually returned to normal. Structural heart disease was ruled out. Intravenous flecainide injection reproduced a less remarkable ST segment elevation. Genetic screening demonstrated a single amino acid substitution (H681P) in the SCN5A gene, thus confirming the diagnosis of Brugada syndrome. In vitro expression of this newly characterized genetic defect revealed novel biophysical abnormalities consisting of a shift in both steady-state activation and inactivation, resulting in a 60% reduction of sodium window current. Thus, SCN5A-H681P mutation induces a significant loss of transmembrane current and is clinically associated with a pathologic phenotype that is elicited by hyperthermia. Overall the observed clinical features are in agreement with previous observations and strongly suggest that fever may be an environmental modifier among Brugada syndrome patients with a detrimental (and possibly arrhythmogenic) effect on cardiac repolarization.     

The shortage of short QT intervals

BACKGROUND: Syncope or sudden death has been associated with a short QT interval (QTc, < 300 ms), the so-called short QT syndrome. The current prevalence of this syndrome is unknown. The aim of this study was to evaluate the prevalence of short QT intervals (ie, QTc, < 300 ms) in a general hospital population. METHODS: We retrospectively queried 479,120 consecutive ECGs that had been archived (Marquette MAC 5000 Resting ECG System; GE Healthcare; Boston, MA) over a 16-year period. We examined the distribution of QT intervals in our population from 150 randomly selected ECGs with normal findings, excluding patients who had been receiving medications known to prolong the QT interval. RESULTS: From 1988 to 2004, 479,120 ECGs from 106,432 patients were analyzed, which reported 215 tracings with a QTc of < 300 ms. Each ECG was then measured manually, and no QTc of < 300 ms was validated (67% were found to be in error because of a pacemaker artifact, 17% showed supraventricular tachycardia with inaccurate detection of the T-wave offset, and 16% were found to have an error in the cycle length calculation). Therefore, not one of the 106,432 patients was found to have a QTc of < 300 ms. The mean QTc (+/- SD) was 430 +/- 19 ms (95% confidence interval, 392 to 468 ms). The QTc of < 300 ms would then reflect > 5 SDs shorter than the mean QTc. CONCLUSIONS: The short QTc reported by an ECG computer was inaccurate and required manual correction. Short QT syndrome, defined as a QTc of < or = 300 ms, is rare. We were unable to find one patient among a population > 100,000 patients with a true QTc of < 300 ms.     

Genetic susceptibility to acquired long QT syndrome: pharmacologic challenge in first-degree relatives.

OBJECTIVES: The purpose of this study was to test for a genetic component to risk for acquired long QT syndrome (LQTS). BACKGROUND: Many drugs prolong the QT interval, and some patients develop excessive QT prolongation and occasionally torsades de pointes-the acquired LQTS. Similarities between the acquired and congenital forms of the long QT syndrome suggest genetic factors modulate susceptibility. METHODS: Intravenous quinidine was administered to 14 relatives of patients who safely tolerated chronic therapy with a QT-prolonging drug (control relatives) and 12 relatives of patients who developed acquired LQTS, and ECG intervals between groups were compared. RESULTS: Baseline QT and heart-rate corrected QT (QTc) were similar (QT/QTc: 394 +/- 28/410 +/- 20 ms vs 395 +/- 24/418 +/- 20 ms; control vs acquired LQTS) and prolonged equally in the two groups. The interval from the peak to the end of the T wave, an index of transmural dispersion of repolarization, prolonged significantly with quinidine in acquired LQTS relatives (63 +/- 17 to 83 +/- 18 ms, P = .017) but not in control relatives (66 +/- 19 to 71 +/- 18 ms, P = 0.648). In addition, the baseline peak to end of the T wave as a fraction of the QT interval was similar in both groups but was longer in acquired LQTS relatives after quinidine (16.3 +/- 3.5% and 19.5 +/- 3.9% in control and acquired LQTS relatives, respectively, P = .042). CONCLUSIONS: First-degree relatives of patients with acquired long QT syndrome have greater drug-induced prolongation of terminal repolarization compared to control relatives, supporting a genetic predisposition to acquired long QT syndrome.