LONG QT SYNDROME , HỘI CHỨNG QT DÀI

Bài giảng dành cho sinh viên y khoa, bác sĩ đa khoa, sau đại học. ĐH Y Dược TP Hồ Chí Minh. Etiology Pathophysiology Manifestations Diagnosis Treatment Prognosis

LONG QT SYNDROME

IN CHILDREN

Vu Minh Phuc MD PhD.

1 ETIOLOGY

 Congenital LQTS

 Acquired LQTS

? 3 2

11p15.5 7q35-36 3p21-24 4q25-27 21q22.2-22.2 21q22.2-22.2

KCNQ1/KVLQT1 KCNH2/HERG SCN5A

AKNB KCNE1/mink KCNE2/MiRP1

Potassium channel (IKs) Potassium channel (IKr) Sodium channel (INa) Na/Ca exchanger (INa-Ca) Potassium channel (IKs) Potassium channel (IKs)

JLN1

JLN2

80 20

11p15.5 21q22.1-22.2

KCNQ1/KVLQT1 KCNE1/mink

Potassium channel (IKs) Potassium channel (IKs)

ATS1 50 17q23 KCNJ2 Inward rectifer potassium

channel (IK1)

TS1 ? 1q42-q43 CACNA1C Cardiac L-type calcium

channel (Ica.L)

Romano-Ward Syndrome (Autosomal Dominant) – with Normal Hearing

Jervel and Lange-Nielsen Syndrome (Autosomal Recessive) – with Deafness

Andersen-Tawil Syndrome (Autosomal Dominant)

Timothy Syndrome (Sporadic)

 Congenital LQTS

Antihistamine : astemizole, terfenadine

Antidepressants : tricyclics: imipramine (Tofranil), amitryptyline (Elavil),

desipramine (Norpramin), and doxepin (Sinequan)

Antipsychotics : haloperidol, risperidone, phenothiazine (Mellaril) and

chlorpromazine (Thorazine)

Antiarrhythmic agents

Class 1A (sodium channel blockers) : quinidine, procainamide, disopyramide Class III (prolong depolarization) : amiodarone (rare), bretylium, dofetilide, N-

acetyl procainamide, sotalol

Lipid-lowering agents : probucol

Antianginals : bepridil

Diuretics (through K loss) : furosemide (Lasix), ethacrynic acid (Edercrin)

Oral hypoglycemic agents : glibenamide, glyburide

Organophosphate insecticides

UNDERLYING MEDICAL CONDITION

Bradycardia : complete AV block, severe bradycardia, sick sinus syndrome

Myocardial function : anthracycline cardiotoxicity, congestive heart failure, myocarditis, cardiac tumors

Endocrinopathy : hyperparathyroidism, hypothyroidism, pheochromocytoma

Neurologic : encephalitis, head trauma, stroke, subarachnoid hemorrhage

Nutritional : alcoholism, anorexia nervosa, starvation

Gene Mutations Changes of channel protein structure Alteration in channel function, in permeability and selectivity

Potassium channel Sodium channel

1 Reduction in K + channel numbers Intermittent reopening of

2 Decreased outward K + current multiple Na + channels

3 Inhibition of channel closure

Abnormal inward K + current Continued and sustained

inward Na + current

Prolonged action potential Prolonged QT interval

Ventricular Arrhythmias

2 PATHOPHYSIOLOGY

 QT interval on ECG : duration of activation and recovery of the

ventricular myocardium

 Prolonged recovery from electrical excitation

→ An increased likelihood of dispersion of refractoriness

→ Some parts of myocardium might be refractory to subsequent depolarization

→ The wave of excitation appears

→ Circus reentry rhythm

→ Ventricular tachycardia

 Arrhythmogenesis

─ Adrenergic stimuli : exercise, emotion, loud noise, swimming

Cathecholamines enhance EADs (early afterdepolarizations) in LQTS

─ Without preceding conditions

3 MANIFESTATIONS

 Clinical manifestations

 Jervell and Lange-Nielsen

 Family history : sudden death

 Congenital deafness, syncopial spells

 Romano-Ward (LQT1- LQT6)

 Family history of LQTS : ±, (-) > (+)

 Normal hearing, syncope

 Cardiac events occur during

3 MANIFESTATIONS

 ECG

 Leads of choice to measure QT interval :

 lead II (no significant U wave, q wave is often present)

 Lead V5 is probably next best

 QTc = QT/√ RR (normal upper limit = 0.44sec)

 QTc > 0.46 sec in LQTS

 Abnormal T wave morphology (bifid,diphasic, notched)

 Considered risk factors of suddent death

 QT interval dipersion

 Bradycardia 20%

 AV block (functional block)

 Multiform PVCs

3 MANIFESTATIONS

 Notices on ECG

1. QTc can be normal in LQTS (rare)

2. QTc > 0.44sec should not be used isolation in diagnosis LQTS

3. Large, notched T waves (“hump”) or T-wave alternans are

suspicious for LQTS, even with normal QTc

- LQT1 : broad-based, prolonged T waves (IKs)

- LQT2 : low-amplitude, delayed T waves (IKr)

- LQT3 : normal duration and amplitude T waves, significant late

in onset (INa)

4. QTc depends on the state of sympathetic or parasympathetic tone

5. QTc varies in different times on Holter ECG

Not to diagnose LQTS by Holter monitor alone

3 MANIFESTATIONS

 Notices on ECG

6. In sinus arrhythmia, consider LQTS when

- QT interval varies by > 0.03 sec

- The longest QTc following the shortest RR interval > 0.46 sec

7. In ventricular conduction disturbance (RBBB, LBBB)

- QT interval may be prolonged because of long QRS duration

- J point is the junction of the S wave and the ST segment

- JTc is used instead of QTc

- normal JTc = 0.32 ± 0.02 sec

3 MANIFESTATIONS

 Treadmill exercise test in LQTS

 Baseline ECG

 QTc 1 minute after exercise

 QTc 2 minutes after exercise

 QT interval does not shorten appropriated with exercise

 Fail to achieve a normal maxium heart rate

 QTc 1 minute after exercise > 0.44 sec

 Ventricular arrhythmias appear during the test (30%)

3 MANIFESTATIONS

 Invasive electrophysiologic study is not useful and unnecessary in diagnosis and prognosis of LQTS

 Echocardiography usually shows

structurally and functionally normal heart

 Genetic study is only done in research

3 MANIFESTATIONS

 LQTS in neonates

transient or may be an early indicator of LQTS

 whether prolonged QT interval represents transient sympathetic imbalance or electrical instability that may occur in the first year

of life and then disappear

 How to manage the patient with the previous symptoms and a prolonged QT interval who complete normalizes by 1 year of age

 Find the causes of acquired LQTS

 ECG for patient and family members

Notched T waves (3 leads)

Low heart rate for age

3 2 1 2 1 1 0.5

Clinical History

Syncope with stress

Syncope without stress

Cogenital deaness

2 1 0.5

Family History

Definite LQTS

Unexplained sudden death in immediate family members, age < 30 years old

1 0.5

 Abnormal exercise test : LQTS

 Risk factors for sudden death

 Bradycardia for age (sinus bradycardia, junctional escape rhythm, second degree AV block)

 QTc interval > 0.55 sec

 Symptoms at presentation (syncope, seizure, cardiac arrest)

 Young age at presentation (< 1 month), and

 Documented torsades de pointes or ventricular fibrillation

 T-wave alternation (major changes in T-wave morphology):

relative risk factor

 Noncompliance with medication:

 Continuous ECG monitoring during infusion

 QTc is prolonged in all patients with LQT subgroups

5 TREATMENT

 General measures

 Patients and family should be aware of

 LQTS

 Medications can cause LQTS

 Physicians should discontinue and avoid prescribing

 QT prolonging medications (obligated)

 Cathecholamine and sympathominetic drugs

 No competitive sports policy applies, especially

swimming

 Patients and family should be educated about the importance of being compliant with their medication

5 TREATMENT

 Acquired LQTS

 hypokalemia

 hypomagnesemia

5 TREATMENT

 Congenital LQTS

 Antiarrhythmic Drugs Classes

Class Channel Effects Repolarization time Drugs

IA Sodium block : ++ Prolongs Quinidine, Disopyramide,

indirect Ca ++ channel block

Unchanged Beta blockers

III Repolarizing K + currents Markedly prolongs Amiodarone, Sotalol,

Ibutilide, Dofetilide

IV AV nodal Ca ++ block Unchanged Verapamil, Diltiazem

5 TREATMENT

 Congenital LQTS

 Definite treatment when:

 LQTS score ≥ 4 regardless of symptoms

 LQTS score = 2-3, no symptoms, associated with

─ Newborns and infants

─ Sensorineuronal hearing loss

─ Affected siblings with LQTS and sudden cardiac death

─ QTc > 0.60sec or T-wave alternans

─ Purpose to prevent the family’s or patient’s anxiety

 Beta blockers

 All beta blockers have similar effectiveness

 Moderate dose is better than large dose

 Large dose can cause bradycardia which is the high risk of sudden death

5 TREATMENT

 Congenital LQTS

 Cardiac pacemaker

 When symptomatic bradycardia related beta- blockers

 Use continuous ventricular or dual chamber pacing

 With pacemaker, beta-blockers’ dose can be maximally used

 Implantable cardioverter-defibrillator (ICD)

 Incidence : high risk patients

5 TREATMENT

 Congenital LQTS

 Left cardiac sympathetic denervation

 Remove the lower part of the stellate ganglion and first 4 thoracic ganglia:

no risk for Homer’s syndrome

 Left cervicothoracic sympathectomy:

─ Provides inadequate cardiac sympathetic denervation

 80% of deaths occur while patients are taking beta-blockers

 With cardiac pacemaker : 16% have cardiac events

 With ICD : prognosis appears better

 With left cardiac sympathetic denervation

 Sudden death : 8%

 5-year survival rate : 94%

Thanks for your attention