REPOLARIZATION SYNDROMESDr Ramachandra/Dr AN Patnaik

REPOLARIZATION SYNDROME

Ventricular repolarisation is defined by the interval from the end of the QRS complex to the end of the T wave on surface ECG= J waves+ T +U waves+ ST segment. This phase of the cardiac cycle is subject to intrinsic and extrinsic influences; thereby, alterations noted in this phase can have Ventricular arrhythmias =repolarisation syndrome.

REPOLARIZATION SYNDROMES

1. ST-segment elevation a. Early repolarisation(elevated J point) b.Brugada syndrome 2. QT-interval abnormalities a. Short QT syndromes b. Long QT syndromes

EARLY REPOLARIZATION SYNDROME

J waves are found at the junction of the QRS complex and beginning of ST segment

Early repolarisation syndrome is an ECG finding consistent with J-point elevation(0.1-Mv) and prominent T waves usually associated with ST-segment elevation in 2 contiguous leads

It is not “normal variant” but linked to SCD and 2-5% general incidence.

Causes a.Extracardiac:Osborn waves,hypercalcemia,

hypervagotonia, spinal cord injuries. b.Cardiac :Prinzmetal angina, acute transmural

ischemia, and Brugada syndrome.

INCIDENCE

Incidence =2%-5%, most commonly seen in young, athletic, male and with stringent criterion (0.2-mV J-point elevation in 2 contiguous leads) drops the prevalence in the general population to 0.3%-0.8%.

ERP - increased risk of SCD is associated with J-point and ST-segment elevations limited to inferior and lateral leads on surface ECG

31% of patients with idiopathic VF More at night in patients with VF, consistent

with increased night-time vagal tone Increased transmural dispersion of

refractoriness in Phase 1-2 of the APD

INCIDENCE CONTD....

Inferior vs lateral leads/magnitude of J-point elevation (0.2 mV) are associated with a high risk of SCD(RR=2.98;95% CI=1.85-4.92; P 0.001)

EPS is unclear in risk stratification of such patients given low sensitivity (40%) and rate of VF inducibility.

GENETICS OF EARLY REPOLARIZATION SYNDROME

Phase 2 reentry likely mechanism of VF = increase in the activity of ITO, IKATP(KCNJ8), and IKACh

16% of ERPS and idiopathic VF had F/H of SCD

DIFFERENTIAL DIAGNOSIS

CONDITIONS FEATURES

Reversible causes of early repolarization pattern on ECG must be excluded, namely acute schemia, hypothermia, hypercalcemia, and irreversible spinal cord injuries and sympathetic nerve damage

Vasospastic angina Mostly normal CAG

Brugada syndrome limited to V1-V3 leads,

Early repolarization pattern INF/Lateral leads and Ajmaline injection attenuates ERP.

CLASSIFICATION HAS BEEN PROPOSED FOR STRATIFYING ARRHYTHMIC RISKIN INDIVIDUALS OF ERP PATTERN

Type 1: The ERP only in the lateral leads= benign outcome=young, healthy men.

Type 2: ERP = inferior or inferolateral leads and is associated with moderate risk of Arrhythmic SCD, especially in individuals with syncope and personal or F/H of SCD.

Type 3: ERP = globally =inferior+ lateral+Rt precordial leads /highest risk of malignant ventricular arrhythmias, VT/VF storms, and sudden death.

TREATMENT

Pharmacologic:Quinidine, Intravenous Isoproterenol are useful.amiodarone, -blockers, and flecainide,are ineffective

ICD:Usuful for both for primary and secondary prevention of SCD along with Quinidine as adjuvant.

SUMMARY OF EARLY REPOLARIZATION SYNDROME

ERP pattern on ECG is not always a “benign variant,” Careful assessment and close follow-up of

H/O syncope/ERPS pattern. A F/H of SCD is high risk. Not a sensitive phenotypical marker for SCD,

per se, but indicates a genetic predisposition toward the development of the same

Notched QRS complexes as markers of SCD.

NOTCHED QRS IS FATAL

BRUGADA SYNDROME

RBBB, ST-segment elevation and T inversion. mutations in at least 8 separate genes encoding

the sodium, potassium, and calcium channels involved in the generation of cardiac myocyte action potential

sudden cardiac death in up to 20% (12/10,000) in Southeast Asia and less frequent

cases (5/10,000) in the Western hemisphere bangungut in Philippines, lai tai in Thailand,

most common cause of SCD in young males in night

3 DISTINCT ECG PATTERNS (V1-V3)

Type 1 pattern is characterized by J-point or coved ST-segment elevation 2 mm followed by a negative T wave.

Type 2 pattern is characterized by J-point or saddle-shaped St segment elevation 2 mm followed by positive or biphasic T wave.

Type 3 pattern is characterized by coved or saddle-shaped ST-segment elevation 1 mm.

BRUGADA ECG

I J↑ >2mm

T INV

II J ↑2mm

T Biphasic

III J↑ 1mm

T Biphasic

POSITIVE RESPONSE

A positive response to a sodium channel blocker is characterized by the following:

1. Type 1 coving ST-segment elevation in leadsV1-V2 or V3 (Fig 6).

2. Conversion of type 2 or type 3 to type 1 pattern.

GENETICS OF BRUGADA SYNDROME

autosomal-dominant, heterogeneous genetic disorder ,variable penetrance

MALE Mutation(300 mutations) at the alpha-subunit

of the sodium channel (SCNA5),K-channel(ITO),Ca channel seen.

loss of function of the sodium channel, is the most common genetic abnormality observed in up to 20% patients with BS

Spontaneous and inducible AF is noted in up to 20% of with biphasic P waves.

MECHANISMS OF BRUGADA SYNDROME

Hallmark -heterogeneous shortening of the APD in the RV epicardium

A decrease in the inward Na and Ca currents coupled with a strong outward K current (ITO) toward the end of the phase 1 action potential results in the accentuation of the action potential notch and loss of action potential dome in some of the epicardium cells

Brugada ECG phenotype is a direct mmanifestation of the imbalance in ion currents during the latter portion of Phase 1 and prolonged phase 2 causing long APD.

CONTI..

electrical heterogeneity = electrical gradient Phase 2 reentry =of VT/VF

Predominance ITO in the epicardium, t repolarization in the epicardial cells recedes that in the M-cells (midmyocardial) and the endocardial cells, is responsible for the ST-segment elevation observed in the right Precordial leads in BS

The shortening of the APD secondary to enhanced vagal activity in association with Phase 3 afterdepolarizations may be responsible for the development of VF, a clinical scenario consistent with nocturnal deaths.

CLINICAL FEATURES

2 following groups: 1. Asymptomatic with Brugada ECG. 2. Symptomatic with Brugada ECG ECG remains the cornerstone The proposed clinical criteria for the

diagnosis 1. Syncope with or without warning. 2. Seizures.

3. Nocturnal agonal respiration.4. Family history of sudden cardiac death 40 years.5. Brugada type 1 ECG in family member.6. Documented VT/VF.

PHARMACOLOGIC DRUG CHALLENGE

Na channel-blocking - diagnostic /prognostic to reveal a concealed form of BS or convert type 2 or type 3 patterns to Brugada type 1 ECG.

Ajmaline, Procainamide, Flecainide, and Propafenone- challenge should be considered positive only when a type 1 ECG pattern (coved ST-segment elevation 2 mm with T-wave inversion in V1-V2 or V3)=8% event rate (ventricular arrhythmias, lethal and nonlethal) at 33 39 months of follow-up (hazard ratio 2.5)

PROGRAMMED ELECTRICAL STIMULATION

abnormal PES (inducible VT/VF) has a positive predictive value of 50% and a negative predictive value of 46% and is associated with increased risk of sudden cardiac death

Asymptomatic individuals with provoked type 1 ECG post-drug challenge with a negative electrical study (PES) have a good prognosis

ALGORITHM FOR RISK STRATIFICATION

RX

ICD remains the most effective treatment 20%-35% of inappropriate ICD shocks—most

likely secondary to SVT(ST/ AF) Drugs that modify the outward Na current in

phase like Quinidine, an ITO blocker, is effective in ECG pattern normalization as well as in suppression of spontaneous and inducible VT/VF or Ca channel function promoter like Isoproteronal is useful.

RFA is used less frequent Atrial fibrillation is treated with

BB,Disopyramide and Quinidine.

SHORT QT SYNDROME

First description in 2000 Five genes encoding the potassium and

calcium channels involved in generation of myocardial cell action potential= Gain of function

The gold standard for diagnosis remains a short QT interval on surface ECG

Only 27% of the patients with confirmed SQTS who underwent testing could be genetically classified.

The prevalence of SQTS (QTc 340 ms) in the general population is about 0.5%, making it a rare condition

.

DX; hypercalcemia, hyperthermia, and digitalis toxicity

CAUTION The classic ECG: QTc interval of 360 ms, short ST

segment, and tall T waves. It is extremely crucial to record the heart rate at the

time of QTc calculation, as the overcorrection of QTc and T-wave amplitude during bradycardia is well-known, the latter of which also increases at slower heart rates.

confirmed SQTS have a flat QTc/R-R interval relationship, whereby the QTc interval fails to prolong at slower heart rates and remains in the low range (ie, 360 ms at heart rates greater than 80 bpm).

Recording ECG at different heart rates with varying QTc intervals is helpful in separating a patient with “true SQTS” from a flat QTc/R-R interval response to a

“normal short QTc” during bradycardia.

GOLLOB MH, REDPATH CJ, ROBERTS JD. THE SHORT QT SYNDROME: PROPOSED DIAGNOSTIC CRITERIA. J AM COLL CARDIOL 2011;57:802-12

GENETICS OF SHORT QT SYNDROME

genetically heterogenous mutations in 5 different genes encoding the

potassium and calcium channels, gain of function involving the potassium channels is the major abnormality in the first 3 gene mutations

SQTS1-KCNH2 (hERG),=gain in function Ikr= ↓ APD and ↓ affinity to IKr blockers.

SQTS2 -KCNQ1= gain in function IKs= clinically associated with AF with SVR and SCD.

SQTS3-KCNI2,= gain in Iki. CACNA1C and CACNB2b mutation for SQTS4 and

SQTS5 only 27% confirmed SQTS genetically classified

RISK STRATIFICATION

D/D-hypercalcemia, hyperkalemia, Hypervagotonia, digitalis toxicity, hyperthermia

Ambulatory ECG recording is helpful not only to demonstrate a flat QTc/R-R,VT/VF/AF

Electrophysiologic study-short refractory periods (140-200 ms) in the atrium and ventricles during programmed stimulation helps confirm the underlying diagnosis and vulnerability of such patients toward spontaneous polymorphic VT/VF and AF.

PMVT/VF /AF is inducible in 60% in confirmed SQTS. sensitivity of inducing VF with hx of SCD 40% ,hence EPS is not final for Rx decision.

CLINICAL FEATURESTo date, the largest database of patients in the world with confirmedSQTS comprises less than 60 patients.93 The most common first

presentationis cardiac arrest, noted in 33% of the patients, with more than 60%having symptomatic history at the time of initial diagnosis. The initial

ageof presentation varies, ranging from 8 months to 70 years, with 80%

ofpatients having a personal or family history of sudden cardiac death.

Thesecond most common presentation is syncope, noted in about 13%

ofpatients, with the presumptive diagnosis of self-terminating VT

episodesas the most likely cause of syncopal episodes. Isolated episodes of

AF oratrial flutter, especially in young patients, are noted in about 17% ofpatients.

THERAPY OPTIONS

Therapy options include ICD implant. Use of hydroquinidine is recommended to suppress recurrent VT/VF and also in patients deemed unsuitable for or who refuse an ICD implant

LONG QT SYNDROME

polymorphic VT gold standard for DX= ECG Exclude severe hypocalcemia/ hypokalemia,

hypothermia/acute ischemia/CNS events, and drug effects

Prevalence=1:3000

GENETIC MUTATION WITH LONG QT

ELECTROCARDIOGRAPHY

12-lead ECG -the gold standard Bazett’s formula- most commonly used Up to 460ms in women, 440ms in men –normal An average of at least 5 cardiac cycles, in II,

V5, and V6, and the longest QT any of these leads

Biphasic /notched/variations in amplitude and polarity (T-wave alternans)- is most commonly

observed during exercise or emotional or physical stress and is a precursor to the development of polymorphic VT - regarded as a risk factor for sudden cardiac arrest and malignant VT.

ELECTROCARDIOGRAPHIC PATTERNS IN 3 TYPES OF LONG QT SYNDROME.

MEASURE QTC

RISK STRATIFICATION

RX

Pharmacology BB, mexiletine ICD

Cardiac arrest survivors. On -blockers with recurrent syncope. Age 5 years with syncope. High-risk asymptomatic patients (J-LNS, marked QTc

prolongation [550 ms], men with LQTS3, patients with 2 mutations who remain symptomatic despite -blocker therapy)

Combined=BB+ICD for daryprevention Surgical -Left cardiac sympathetic denervation

=removal of the first 4 thoracic ganglia

CONCLUSION

Many have a molecular basis known & many will be discovered