Presentación del tema: "Síndrome de QT Prolongado"— Transcripción de la presentación:
1 Síndrome de QT Prolongado Dra. Laura SanzianiHospital Italiano – Sanatorio Los Arroyos
2 SQTL: Historia 1957: 1er reporte SQTL 1963-1964: Síndrome Romano-Ward : 25 casos de SQTL reportados1971: 1er Tto SQTL (Estelectomía izquierda)1979: Comenzó el Registro de SQTL: + 10 genes responsables identificadosJervell and Lange-Nielsen provided the first documented description of this syndrome in They described a family with 4 deaf children with QT prolongation and syncope. 3 of the children died suddenly. The parents, and 2 other children had normal ECGs and normal hearing. This report was critical to the development of current knowledge regarding LQTS.Romano in 1963, and Ward in 1964 separately reported patients who were not deaf, but had an almost identical cardiac disorder. Later called the “Romano-Ward syndrome,” this disorder was realized to be much more common than the “Jervell-Lange-Nielsen syndrome.” The genetic transmission was thought to be autosomal dominant.Between 1958 and 1970, there are only 25 cases of LQTS reported.In 1971, Moss and McDonald performed the first successful therapy for LQTS in a patient who had not responded to any other antiarrhythmic therapy: left cardiac sympathetic denervation to shorten the QT interval.In 1979,Drs. Moss, Schwartz, and Crampton started the International Registry for LQTS, with headquarters in Rochester, NY.Between 1991 and 2001, a total of 6 LQTS genes were identified, 3 of which were reported between March 1995 and January 1996.
5 QT largo Congénito Sme. RW Autosómica dominanteAudición normalMás frecuente de los QTL hereditarios
6 QT Largo Congénito Sme de JLN Autosómico recesivoAsocia sordera neurosensorial1.6 a 6 casos/millón de habitantes
7 QTL Congénito Formas esporádicas 10 al 15 % de los casosAudición normalCarácter hereditario no identificadoPentrancia incompleta???
8 SQTL: Aspectos clínicos Signos y Síntomas:SíncopeConvulsionesMSPalpitaciones o dolor precordialSymptoms include:The presence of palpitations or children may describe as “chest pain”Recurrent syncopeSeizuresSCD can occur if the symptoms are ignoredECG signs include:QTc abnormal or borderlineEvidence of Torsade de pointes is also commonPatients at higher risk are those with deafness, female, syncope, and documented torsades or VF.
9 Sme QT Prolongado Características ECG Intervalo QTMorfología de la onda TAlternancia de la onda TPausas/Bradicardia SinusalT de P
11 SQTL: Patrones en ECG Circ 1992;85[Suppl I]:I140-I144 Although the long QT syndrome often presents as unexplained syncope, the ECG is the definitive factor in differential diagnosis of the syndrome.This slide displays examples of delayed repolarization patterns observed in lead II of the ECG in patients with long QT syndrome. (Reproduced with permission from Moss AJ: Clinical features of idiopathic long QT syndrome. Circulation 1992;85[Suppl I]:I140-I144.)Circ 1992;85[Suppl I]:I140-I144
12 QT Largo: patrones en ECG Additional examples of delayed repolarization patterns observed in lead II of the ECG in patients with long QT syndrome. (Reproduced with permission from Moss AJ: Clinical features of idiopathic long QT syndrome. Circulation 1992;85[Suppl I]:I140-I144.)Circ 1992;85[Suppl I]:I140-I144
14 QT Largo: Diagnóstico No olvidar: * 10% de los portadores asintomáticos tienen QT normal* 15% de la población normal tiene un QT entre 450 y 470 miliseg.
15 Sme QT Prolongado Características ECG Intervalo QTMorfología de la onda TAlternancia de la onda TPausas/Bradicardia Sinusal
16 Morfología de la onda T en los diferentes genotipos de SQTL Moss AJ, et al. Circulation 1995;92:
17 Bases del Sme de QT prolongado Major currents underlying the ventricular action potential. As shown on the lower left, interventions that decrease outward currently (primarily through K+ channels), or increase inward current (through Na+ or Ca2+ channels) during the plateau, delay repolarization at the level of the ECG and individual action potentials, and prolong QT interval (upper left). The generic action potential on the right shows the major currents flowing during the cardiac cycle. The five LQTS genes and the currents they underlie are shown in bold.(Reprinted with permission from the authors and the Journal of Cardiac Electrophysiology. 1999;10: ).JCE 1999;10:
18 TAQUICARCIAS VENTRICULARES POLIMORFAS QT LARGO CONGÉNITOLQT1 cromosoma 11 gen KCNQ1LQT2 cromosoma 7 gen HERGLQT3 cromosoma 3 gen SCN5A
21 LQTS: Consideraciones genotipo-fenotipo 10 genotipos; ~300 mutaciones diferentesDiferencias clínicas entre LQT1, LQT2, & LQT3Variabilidad Clínica dentro de un mismo genotipoVariabilidad Clínica entre miembros de una familia con la misma mutación genética sugiere la presencia de genes moduladoresResearchers have already identified 6 genes that are affected, with more than 200 mutations identified to date. (By analogy, contrast this to cystic fibrosis, in which only 1 gene is thought to be responsible, with more than 800 different mutations).Many more mutations could still be unidentified.Even individuals in the same family, with the same gene and the same mutation, can have significant variations in severity. This provides support to the theory that there are modifying factors, which as of yet are undefined.
22 Gatillos para síncope o MSC 3 factores principales que contribuyen a síncope o MSCEjercicio (LQT1), especialmente nataciónEmociones, stress emocional,estímulos acústicos (LQT2)Evento durante el sueño o reposo, (LQT2 o LQT3)Exercise is a source of physical stress, that induces an increase in heart rate and a release of catecholamines.Research has shown that swimming is a gene-specific trigger for cardiac events in LQTS.Emotional stress can include fear, anger, stressful events or arousals during normal daily activities, or arousal due to a noise or startling during sleep.Events during sleep are difficult to document. Events here would not include those triggered by arousal (startling or noise). These are most likely related to a decrease in heart rate.Exercise is the most common triggering event in LQT1. Emotions or emotional stress are the most common trigger in LQT2, and events occurring during sleep are more common in LQT2 or LQT3.Circ 2001;103:89-95 Mayo Clin Proc. 1999;74:
23 Relación gen : gatillo específico PorcentajeThis study identified patients of a known genotype, who had experienced significant cardiac events. Triggers for cardiac events according to 3 genotypes: percentage of patients in each genotype, and the pattern of triggers within each genotype.(Schwartz, et al. Circulation. 2001;103:89-95).In the LQT1 variant, exercise is a trigger for >60%, while barely 3% are triggered while at rest.In the LQT2 variant, a significant number of events occur due to emotional stress or while at rest, while exercise is a trigger in only 13%.In LQT3, the majority of events appear to occur during sleep or at rest.LQT1 is the only variant that has a high percentage of events occurring during exercise, and thus is very different from LQT2 or LQT3. LQT1 patients would be advised not to participate in competitive athletic activities.Circ 2001;103:89-95
24 SQTL: Criterios diagnósticos Hallazgos ECG: QTc, TdP, muescas en onda T, baja FC para la edad.HC: Síncope, convulsiones, PC abortado.Historia familiar: miembros con QT largo, MS inexplicada en familiares directos a una edad < 55 años.The 3 major components of information needed are:A detailed ECGA thorough clinical history, including onset, frequency and predisposing factors of the syncopal episodesA thorough family historyCirc 1993;88:
26 Intervalo QTc y riesgoThe risk increases significantly with increased QTc above 440ms.
27 Intervalo QTc y riesgo Risk for Cardiac Event QTc AJC 1993;72:21B The risk increases significantly with increased QTc above 440ms.QTcAJC 1993;72:21B
28 Probabilidad de eventos cardíacos Note that the peak incidence for cardiac events is from birth through adolescence for LQT1 and LQT2, with the peak incidence occurring later in LQT3. In all 3 genotypes, males are at risk primarily through age 25, and females have a persistent risk up to age 40.No. de ptes.LQTLQTLQTNEJM 1998;339:
29 QTL: criterios de alto riesgo Sordera congénitaSíncope recurrente por TVAF de MS o PC resuscitadoQT > 0.50 seg/0.60 seg.QTL 3
30 LQTS: quién está en riesgo de MS? PC abortadoHistoria familiar de MS inexplicadaSíncopeTorsade de pointesAlternancia de la onda TQTc prolongadoHighest risk patients are those who have already experienced a SCD event, those with recurrent syncope, those with ECG evidence of torsade de pointes, alternation of the T-wave, and those with significantly prolonged QT.Family history may include unexplained car accident, drowning, or other sudden death.
39 SQT largo: Tto. preventivo Prohibición de deporte competitivoEvitar drogas que prolonguen el QTBloqueantes BetaMPDResección ganglionar simpática (Estelectomía izquierda: ocasionalmente utilizada en niños y pacientes refractarios a otras formas de terapia).CDIQT 3???...Drogas Clase I?...BB?...
40 Probabilidad de eventos cardíacos Estimated cumulative probability of experiencing syncope, aborted cardiac arrest, or LQTS-related death on prescribed ß-blockers in LQTS patients who were asymptomatic (dotted line) or symptomatic (solid line) before starting ß-blockers.LQTS patients who were symptomatic prior to ß-blocker therapy have a much higher probability of experiencing another cardiac event. More than 30% of patients who were symptomatic prior to ß-blocker therapy will have another cardiac event within 5 years.Circ 2000;101:
41 Uso de BB: probabilidad acumulativa de MS relacionada con SQTL Estimated cumulative probability of experiencing aborted cardiac arrest or death on ß-blocker therapy in LQTS patients who were asymptomatic (dotted line), experienced syncope only (dashed line), or had a prior aborted cardiac arrest (solid line) before ß-blockers. Vertical lines are 95% Confidence Intervals.Risk curves are for LQTS patients started on ß-blockers at >10 years of age; the risk curves are higher for those started at a younger age. Time periods off therapy for more than 2 days are excluded.Patients with a prior aborted SCD should receive an ICD, as they have a higher probability of experiencing another cardiac arrest or LQTS-related death.Circ 2000;101:
42 SQTL: Eventos cardíacos antes y después de BB Probandos MFA†(n=581) (n=288)Riesgo(pre- y post- B)Pre-B Post- B Pre- B Post BPts con eventos * *Numero eventos * *Eventos/pt * *Eventos/pt/año * *This slide outlines 869 patients from the International LQTS Registry who were treated with beta-blockers.The goal of this study was to evaluate the effectiveness of beta-blockers in LQTS patients. It also looked at specific risk factors for syncope and SCD for patients who were already on beta-blocker therapy.Both the number of patients with events and the number of events decreased significantly after the initiation of ß-blocker therapy. In addition this reduction in events was seen in both probands and affected family members.Circ 2000;101: * P<0.01 vs. pre--blocker
43 CONGÉNITO TRATAMIENTO QT LARGOCONGÉNITO TRATAMIENTOLQT1 19% recurrencia Paro o MS %LQT2 31 % recurrencia Paro o MS %LQT3 50% recurrencia Paro o MS %NADOLOL o PROPANOLOL (*)b-Bloqueantes
44 Limitaciones de los BB en SQTL MSC puede ocurrir a pesar de TTO con BBEs problemático el cumplimiento de una terapia diaria a largo plazoEfectos indeseables conocidos de los BBAlthough -blockers reduce the number of cardiac events, syncopal events and SCD can still occur.The challenge is to have the patient continue to take the drugs, even if they are feeling well. In addition, in young, active, healthy patients, the side effects can hamper their activity tolerance.In standard doses, up to 15% of patients will not tolerate beta-blockers due to side effects. Common side effects include asthma, fatigue, sleep disturbances.
45 SQTL: Experiencia con MPD Reduce la frecuencia de síncope en pacientes con eventos gatillados por bradicardiaSu mayor utilidad se demuestra al combinarse con terapia BBNo previene la MSC en terapia a largo plazoPareciera más útil en pacientes con LQT3 y bradicardiaA retrospective study followed 37 patients with idiopathic LQTS who received both -blocker and pacing therapy, to determine the efficacy of combined therapy.After an average of years, 28 of 37 patients remained without symptoms on combined therapy. Recurrent pacemaker malfunction causing symptoms was experienced in 3 patients, 3 patients died, and 3 patients had resuscitated cardiac arrest. An additional patient died of unrelated causes. The overall incidence of sudden death and aborted sudden death was 24% in all patients and 17% in compliant patients.Conclusion: Even with combined therapy, these patients remained at significant risk for sudden death.Circ. 1999;100:Hoy perdiendo terreno…
46 SQTL: Experiencia con CDI CDI indicado en todo SQTL que presentó FV o PC abortadoPreviene MSC en ptes. con eventos cardíacos previosProvee un back-up para pacientes en TTO con BB quienes continúan sintomáticosPublished beta-blocker and pacemaker studies document continued cardiac events with single or combination therapy.ICDs can treat breakthrough tachyarrhythmias to prevent sudden cardiac death.
47 Manejo segun genotipo LQT1 y LQT2 se benefician ppalmente. Con BB El beneficio de BB en LQT3 es menos claro.CDI indicado (IIa-B)Si el paciente se presenta como sobreviviente de MSC o PC abortadoSi los BB fallaron en prevenir eventos cardíacos: síncope, TV, MSC.Because the sympathetic nervous system plays a role in LQT1 and LQT2, these 2 genotypes benefit the most from ß-blocker therapy.The role of ß-blocker therapy in LQT3 is less well-defined, as no clear benefit has been documented in these patients.Since LQT3 involves a Na+ channel defect, exercise provides the benefit of shortening the QTc interval.
48 SQTL: Presente y futuro LQTS Registry: identificación de factores de riesgoIdentificación de nuevos genesTest de esfuerzo para Dx y estratificación de riesgoGenes moduladoresTerapia específica para cada mutaciónThe Long QT Registry continues to evaluate specific risk factors for LQTS-related cardiac events.There is potential to identify additional genes, gene mutations, and modifier genes due to the great variability in current presentation of the disease. The goal is to continue to try to develop gene- and mutation-specific therapy.
53 Paciente con QT largo y síncope: Registro Holter
54 Torsión de Puntas: Tto agudo CVEAumento de la FC* Estimulación* Isoproterenol* AtropinaSulfato de Magnesio (50%)Corrección de anormalidades MTBSupresión de drogas responsables
55 SQTL: Información en la WEB Cardiac Arrhythmias Research and Education (CARE) Foundation:Cardiac Arrest Survivors Network (CASN):International Registry for Drug-Induced Arrhythmias, including drugs to use with caution or avoid in Long QT patients: