Differential methylation of lncRNA KCNQ1OT1 promoter polymorphism was associated with symptomatic cardiac long QT.

AIM: To investigate whether the differential methylation of KCNQ1OT1 was associated with the risk of symptomatic long QTc. PATIENTS & METHODS: We investigated the methylation status of KCNQ1OT1 in a cohort of patients (n = 131) with a symptomatic prolonged QTc. All the patients were genotyped for a common promoter polymorphism (rs11023840). They were also genotyped for DNA digested with the methylation-sensitive HpaII restriction enzyme. RESULTS: We found a significant higher frequency of AA genotype (p = 0.02) in the patients compared with healthy controls (n = 240). In the HpaII-digested samples there was a higher frequency of the A-allele among the patients compared with the controls (p = 0.02). CONCLUSION: Our findings supported a role for the differential methylation/imprinting of KCNQ1OT1 in the risk for symptomatic prolonged QTc.

Momento del implante de un marcapasos tras el recambio valvular aórtico percutáneo / Timing of pacemaker implantation after percutaneous aortic valve replacement

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Time-dependent responses to provocative testing with flecainide in the diagnosis of Brugada syndrome.

BACKGROUND: Time-dependent variability of electrocardiogram (ECG) in patients with Brugada syndrome could affect the interpretation of provocative testing. OBJECTIVE: The aim of this study was to characterize ECG changes during and after flecainide infusion. METHODS: We studied 59 consecutive patients. The ECG was continuously analyzed during the first 30 minutes of provocative testing, and a single ECG was recorded 60 minutes later. We analyzed CYP2D6 and CYP3A5 variants affecting flecainide metabolism and performed blinded measurements at lead II. RESULTS: At baseline, ECG patterns were classified as follows: type II in 31 patients (53%), type III in 15 (25%), and normal ECG in 13 (22%). Because of induction of type I ECG, the percentage of responders progressively increased with longer recording time periods (6.8% in 10 minutes vs 11.9% in 20-30 minutes vs 18.6% in 90 minutes; P < .01). Four patients displayed a late response, which was evidenced 90 minutes after the initiation of provocative testing. QRS width differentially increased between responders and nonresponders (P < .01), with a maximum QRS width of 110 ms during the first 30 minutes being effective for identifying possible late responders (sensitivity 100%; specificity 85.6%; positive predictive value 88%; negative predictive value 100%). The incidence of CYP2D6 variants was lower in late responders than in early or delayed responders (0% vs 75% vs 100%; P = .04), while a homogeneous distribution of CYP3A5*3/*3 was observed in our population. CONCLUSION: Response to flecainide exhibits time-dependent variability of ECG patterns and intervals. Longer periods of ECG recording increase the recognition probability of type I ECG.

Atrioventricular conduction disturbance characterization in transcatheter aortic valve implantation with the CoreValve prosthesis.

BACKGROUND: Atrioventricular (AV) block is one of the most frequent complications of CoreValve transcatheter aortic valve implantation (TAVI). The aim of this study was to analyze the effects of CoreValve implantation on AV conduction. METHODS AND RESULTS: Electrophysiological study was performed immediately before and after CoreValve implantation in 18 consecutive, permanent pacemaker-free patients. An electrode was placed on the His bundle during valve implantation, and data were continuously recorded during the procedure. With surface ECG, a median (first, third quartile) QRS width of 96 (84, 116) to 150 (121, 164) ms (P=0.001) and PR interval of 180 (159, 216) to 210 (190, 240) ms (P=0.008) were significantly prolonged, and QRS axis was left deviated 30° (-32°, 46°) to -20° (-60°, 2°) (P=0.005). With intracardiac electrograms, the AH (97 [70, 123] to 115 [96, 135] ms, P=0.021) and HV (52 [42, 55] to 60 [50, 70] ms, P=0.002) intervals were increased. At the end of the procedure, we observed significant ECG- or electrophysiological study-persistent conduction disturbances in 14 (78%) patients. Five patients experienced transient changes (2 AV blocks and 3 left bundle branch blocks). CONCLUSIONS: CoreValve implantation worsens AV conduction in most patients, either transiently or permanently. This worsening is the result of direct damage either on the His bundle or on the AV node.

The spectrum of SCN5A gene mutations in Spanish Brugada syndrome patients.

Brugada syndrome is characterized by right bundle branch block and ST-segment elevation in the right precordial ECG leads. Familial transmission is frequent and approximately 25% of cases exhibit mutations in the SCN5A gene. We analyzed the sequence of this gene in 25 Spanish patients with Brugada syndrome. In 4 (16%), we found mutations that had not previously been described: three were amino acid changes (i.e. Ala2>Thr, Ala735>Thr and Val1340>Ile) and one was an intron mutation that affected messenger RNA processing (i.e. IVS18-1G>A). These four patients had relatives who were also mutation carriers, several of whom had normal ECGs, even on flecainide challenge. Our study suggests that genetic analysis could be helpful in the presymptomatic diagnosis of Brugada syndrome, but may be less useful for stratifying the risk of adverse events.

Espectro mutacional del gen SCN5A en pacientes españoles con síndrome de Brugada / The spectrum of SCN5A gene mutations in spanish Brugada syndrome patients

El síndrome de Brugada se caracteriza por un bloqueo de la rama derecha y elevación del segmento ST en las derivaciones precordiales derechas del electrocardiograma. Con frecuencia se observa una transmisión familiar, y en aproximadamente el 25% de los casos se han hallado mutaciones en el gen SCN5A. Hemos analizado la secuencia de este gen en 25 pacientes españoles con síndrome de Brugada. En 4 de ellos (16%) hallamos mutaciones que no habían sido descritas previamente: 3 eran cambios de aminoácidos (Ala2>Tre, Ala735>Tre y Val1340>Ile) y 1 era intrónica y afectaría al procesamiento del ARNm (intrón 18 IVS18-1G>A). En los 4 había familiares portadores, y varios de ellos tenían electrocardiogramas normales, incluso tras inducción con flecainida. Nuestro estudio indica que el análisis genético sería útil para el diagnóstico presintomático, pero de utilidad limitada para estratificar el riesgo de eventos adversos (AU)

Brugada syndrome is characterized by right bundle branch block and ST-segment elevation in the right precordial ECG leads. Familial transmission is frequent and approximately 25% of cases exhibit mutations in the SCN5A gene. We analyzed the sequence of this gene in 25 Spanish patients with Brugada syndrome. In 4 (16%), we found mutations that had not previously been described: three were amino acid changes (i.e. Ala2>Thr, Ala735>Thr and Val1340>Ile) and one was an intron mutation that affected messenger RNA processing (i.e. IVS18-1G>A). These four patients had relatives who were also mutation carriers, several of whom had normal ECGs, even on flecainide challenge. Our study suggests that genetic analysis could be helpful in the presymptomatic diagnosis of Brugada syndrome, but may be less useful for stratifying the risk of adverse events (AU)