QT meting en QTc. monogenetische afw. deel 2

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1 QT meting en monogenetische afw. deel 2 Dieter Nuyens Cardiologie Deel 1: QT meting en QTc Monogenetische afw: LQTS SQTS BrS Deel 2: Andere aritmogene monogenet. afw: (HCM) ARVC CPVT Holter en QT dynamiek Drug testen Drug interacties 1

2 Bazett QTc grenzen QTc bovengrens (ms) Rating 1-15yrs Adult male Adult female Normal <440 <430 <450 Borderline Prolonged >460 >450 >470 QTc ondergrens (ms) normaal > 340 ms verkort < 320ms (SQTS cut-off) ARVC 1/5000 5% SCD<35y Variabele penetrantie Inspanning aritmie/scd Mutaties in desmosomale prot. Plakoglobin (JUP) Plakophylin (PKP2) Desmoplakin (DSP) Desmoglein (DSG2) Desmocollin-2 (DSC2) TGFB3 TMEM43! 2

3 ARVC Fatty infiltration, dunne RV wand, interstitiele fibrose, vacuolisatie ARVC - ECG Epsilon golf Negatieve T s precordiaal S-slurring rechts precordiaal 3

4 ARVC - ECG ARVC Global and/or regional dysfunction and structural alterations MAJOR severe dilatation and reduction of RV EF with no or only mild LV impairment localized RV aneurysms severe segmental dilatation of the RV MINOR mild global RV dilatation and/or EF reduction with normal LV mild segmental dilatation of the RV regional RV hypokinesis Tissue characterization of walls MAJOR fibrofatty replacement of myocardium on endomyocardial biopsy Mc Kenna et al. Br Heart J 1994; 71:

5 ARVC Repolarization abnormalities MINOR inverted T waves in V 2-3 (> 12y; absence of RBBB) Depolarization/conduction abnormalities MAJOR epsilon waves localized prolongation (>110 ms) in V 1-3 MINOR late potentials on SAECG Arrhythmias MINOR LBBB ns or svt on ECG, Holter or Exercise testing frequent VES (>1000/24h) on Holter Mc Kenna et al. Br Heart J 1994; 71: ARVC Family Hx MAJOR familial disease confirmed at necropsy or surgery MINOR familial Hx of premature SCD (<35 y) due to suspected ARVC familial Hx of ARVC (Dx based on present criteria) 2 major criteria or 1 major plus 2 minor criteria or 4 minor criteria Mc Kenna et al. Br Heart J 1994; 71:

6 ARVC therapie Hoog risico: symptomatisch aritmie ICD Beta blockers (Sotalol-Amiodarone) Laag risico: asymptomatisch geen aritmieen Sport restrictie Beta blockers Familiale screening (CEH) ARVC casus 6

7 ARVC casus TTE dilated RV with mild hypokinesis normal LV chamber size and overall function MRI mildly dilated RV with global diminished contractility normal LV ARVC casus 7

8 ARVC casus average rate 71 (range ) VES/24h 64 runs of VES, longest 4 beats ARVC casus 1 major criterion? ECG: prolonged QRS > 110 ms in V1-3 3 minor criteria TTE and MRI ECG: inverted T-wave V2-3 Holter 8

9 CPVT Zeldzaam (incidentie?), doch! ZEER pathogeen: 30% SCD < 30j Inspannings- stressgebonden VT/syncope/SCD Structureel nl. Hart Typische bidirectionelevt Mutaties: Ryanodine receptor (RyR2) Calsequestrin (CASQ2) CPVT ECG Prominente U (zonder QT-verlenging) Macro U-wave alternans Inspanningsgebonden VT Bidirectionele VT 9

10 Macro U-wave alternans CPVT ECG CPVT Typische bidirectionelevt (" Torsade de Pointes) 10

11 CPVT ECG CPVT ECG 11

12 CPVT ECG (cyclo) CPVT therapie Beta-blockers (cavé: therapieonderbreking) Flecainide (stabilisatie RyR-mediated Ca++ release) ICD (kinderen!) Familiale screening 12

13 Single lead QT meting QT meting Multiple lead QT meting QT meting 13

14 Multiple lead QT meting QT meting QT dymaniek 14

15 QT dynamiek Ritme Geslacht (vrijwel afwezige postpuberale QTc verkorting bij vrouwen) Leeftijd Dag/nacht Autonome tonus Medicatie Ionenstoornissen (hemodialyse) Ischemie LQTS! QT dymaniek 13jarige Pte. Plots overleden ECG moeder: nl? 15

16 QT dymaniek 13jarige Pte. Plots overleden ECG zus 9j: QT 440ms (75bpm), QTc 492ms QT dynamiek 13jarige Pte. Plots overleden ECG moeder: na inspanning onvoldoende QT verkorting 16

17 QT dynamiek 13jarige Pte. Plots overleden LQT1 diagnose QT meting op holter ECG complex averaging : Qtapex - end 17

18 QT meting op holter ECG complex averaging : 24u RR QTapex - QTend QT meting op holter ECG complex averaging : QTapex Qtend Lineaire regressie: QT/RR relatie -> slope 18

19 QT meting op holter ECG complex averaging : QTapex Qtend Lineaire regressie: QT/RR relatie -> slope QT- rate adaptatie in LQTS QT meting op holter 19

20 QT- rate adaptatie in ICMP QT meting op holter QT- rate adaptatie in ICMP QT meting op holter 20

21 Verworven LQTS Belangrijke QT verlenging met typische pause dependente TdP, met volledige resolutie na stoppen medicatie Risico factoren (multi-hit hypothese): hypok, hypomg Bradycardie LVH Recente cardioversie Vrouw Polymedicatie (interactie) Overdosage / nierfalen forme fruste LQTS versus polymorphysme? Verworven LQTS Stop QT-verlengende medicatie zo belangrijke QT verlenging (QTc>500ms OF toename >60ms) 21

22 TdP aritmogenese Verworven LQTS Pause dependente TdP Verworven LQTS 22

23 Verworven LQTS Pause dependente TdP Locati EH et al, JACC 1992 LQTS en QT-verlengende medicatie Antiaritmica: procainamide, quinidine, amiodarone, sotalol Antihistaminica: astemizole, terfenadine Antimicrobial/antifungal: thiomethoprim, erythromycin, ketoconazole Psychotropica: haloperidol, risperidone, thioridazine, tricyclics Andere: diuretics, cisapride, bepridil, ketanserin

24 Drug-testen Adenosine 12mg IV (bolus) Pre-excitatie? SVT discriminatie? ICD standby Cave: dipyridamole (theophylline) VKF inductie Drug-testen FBI en adenosine: 24

25 Drug-testen Ajmaline 1mg/kg 10mg/2min Brugada Syndroom? Inductie type 1? Continu ECG monitoring ICD standby Stop infusie zo: Belangrijke conductievertraging (AVB) Type 1 VT Drug-testen Sotalol Start 80mg 2x/d Tollerantie? Stop zo QTc >490ms of verlenging >60ms 25

26 Drug-testen Sotalol Drug-testen Adrenaline Continu infuus 0,1-0,3#g/kg/min Bidirectionele VT inductie (CPVT)? QTc-verkorting (LQT3) QTc-verlenging (LQT1) Alternatief: cyloergometrie (veiliger) 26

27 Drug-testen Isoproterenol Continu infuus 0,5-3#g/min Bidirectionele VT inductie (CPVT)? QTc-verkorting (LQT3) QTc-verlenging (LQT1) Alternatief: cyloergometrie (veiliger) Drug-testen Isoproterenol - CPVT Int Heart J 2006; 47: