Φαρμακεσηική αγωγή ζηις ιδιοπαθείς κοιλιακές αρρσθμίες. Άννα Κωζηοπούλοσ Επιμελήηρια Α Ωνάζειο Καρδιοτειροσργικό Κένηρο

Transcription

1 Φαρμακεσηική αγωγή ζηις ιδιοπαθείς κοιλιακές αρρσθμίες Άννα Κωζηοπούλοσ Επιμελήηρια Α Ωνάζειο Καρδιοτειροσργικό Κένηρο

2 Όλες οι κοιλιακές αρρσθμίες δεν είναι ίδιες Υπάρτοσν διαθορές ζηον πληθυσμό, ηον μηχανισμό και ηο υπόστρωμα.

3 Ventricular tachycardia A) underlying heart disease ischemic dilated cardiomyopathy HOCM B) anatomically normal hearts i) Non life threatening- idiopathic II) life threatening brugada long short QT, polymorphic VT, idiopathic VFib

4 Idiopathic ventricular tachycardia 10-20% of VTs Younger pts with normal hearts Typically monomorphic Good prognosis

5 Classifications Anatomical Outflow tract VTs- RVOT LVOT Ao cusps PA LVVTs Mechanism Response to medication adenosine, verapamil propranolol, sensitive Morphological: bundle branch pattern QRS width- RBBB LBBB

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7 Διαζπορά επαναπόλωζης καθορίζει ζηαθερόηηηαεπικινδσνόηηηα

8 Outflow RVOT/ LVOT

9 Outflow tract tachycardias 3-5 th decade RVOT LVOT Ao cusps, rare PA RVOT more frequent, in women- Equal genders in LVOT Stress induced-iso- adenosine sensitive repetitive monomorphic non sustained or PVCs good prognosis Spontaneous resolution in 20%

10 Substrate RVOT LVOT Similar embryogenesis and mechanism The distal part of the outflow tracts looses its myocardial phenotype and becomes the proximal part of the Asc AO and the pulmonary trunk. It has slow propagation poor coupling. Myocardial regression continues until after birth when incomplete a myocardial sleeve may remain in PA and Ao sinuses connected to the ventricles. Anatomic study has shown myocardial extension in PA in humans. Iwai et al J Cardiovasc Electrophysiol 2006 Yamayake et al J Cardiovasc Electrophysiol 2007

11 OT VT Mechanisms: Triggered activity: camp-increased intracellular Ca- DADs- induced by exercise and isoproterenol- responds to b bl and adenosine Reentry Abnormal automaticity Impaired catecholamine- Sympathovagal imbalance- G protein mutations

12 Triggered activity and automaticity EAD phase 2 and phase 3 - different mechanism- 2 caused by inward Ca current or Na (QT)- phase 3: late Na/Ca exchange DADs catecholamines/ digitalis through camp result of increase intracs Caabnormal Na/Ca exchange -through phosphorylation of ryanodine receptorfurther increase in Ca in Na/Ca exchanger- increase in inward Na If increased over a threshold new AP (triggered arrhythmia) Phase 4 automaticity acute ischemia reperfusion catecholamines increase in V automaticity which is usually overdrived

13 Why are idiopathic VTs more stable? Triggered DADs from the epicardium increase dispersion of repolarization polymorphic VT of VT The endocardium DAD cause more stable VT

14 Idiopathic LVVT originates in fascicules Zipes et al AM J Cardiol1979 Belhassen et al Br Heart J years men Most at rest may be induced by exercise and emotional stress Good prognosis- syncope Sudden death cardiomyopathy rare 3 ECG types left posterior fascicular VT RBBB superior axis (common) Left anterior fascicular VT RBBB RAD (uncommon) Upper septal fascicular narrow QRS normal axis (rare) mechanism heterogeneity Verapamil sensitive reentry Adenosine sensitive behaves like RVOT originated deep within IVS -CAMP mediated exits on left side of IVS (triggered) there are induced by iso and terminated with adenosine Propranolol sensitive automaticity

15 Verapamil sensitive is the most frequent reentry within Purkinje false tendon has been found in anatomic studies site of slow conduction A component may be partially sodium dependent Tsuchiya et al JACC 2001

16 Therapy depends on mechanism

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18 C AMP mediated delayed aftredepolarizations-otvt Lerman et al Circulation Yamawake et al J Cardiovasc Electrophysiol 2007 Twai et al J Cardiovasc Electrophysiol 2005 camp mediated triggered activity stops with adenosine- Adenosine through A1 receptor activates inhibitory G1 protein and antagonizes increased camp by b adrenergic stimulation. ATP acts similarly to Adenosine Vagal maneuvers may act through G1 protein via cardiac muscarinic receptors M2 that suppress increased camp by catecholamines 2007

19 OT VT Acute: vagal, Valsava, carotid sinus massage, IV adenosine, IV verapamil No treatment required OT VT respond to all antiarrhythmics B blockers first choice- response 25-50% Ca bl Verapamil and diltiazem equally effective- synergistic to bbl IA IB Quinidine- Prolongation of AP increase DADs- lidocaine decreases AP DADS decrease IC 25-50% III sotalol amiodarone more effective

20 Adenosine Adenosine has no direct effect on the myocardium and Purkinje it only reverses the effect of catecholmine induced increase of camp. If no c AMP stimulation there is no effect on the myocardial ions. Adenosine terminates trigged activity temporarily affects catecholamine- induced automaticity but it doesn t stop it No effect on structural VT even if catecholamine- mediated Sung et al J clin Invest 1987

21 LVVT Belhassen et al Br Heart J 1981 Tsuchiya et al JACC 2001 San Jou et al JACC 1997 Yamada et al J Cardiovasc Electrophysiol 2009 Allen et al Pediatr Cardiology 2011 Reentry: is Calcium dependent responds to Ca bl, oral or IV, verapamil or diltiazem A component of the reentry may be responsive to sodium blockers - lidocaine report in infant unresponsive to amiodarone and bbl Adenosine and Valsava typically ineffective Adenosine sensitive in subtype exercise related which acts like RVOT - deep from IVS Focal LVVT from papillary muscles- no involvement of Purkinje- abnormal automaticity- refractory to Ca and Na blockers responsive to Bbl

22 Nicoradil Potassium Channel opener It can suppress ATP and Calcium sensitive VTs Potassium blockers inhibit reentry because they prolong refractoriness in the reentry circuit They can also suppress exercise indused VT- by reducing APD and DADs Kombayashu et al JACC 1998

23 Abnormal Automaticity B bl slow the upstroke of AP and suppresses abnormal automaticity Verapamil direclty blocks Ca channels and is also a competitive b- bl receptor antagonist.

24 In conclusion