Presentation on theme: "Sudden Cardiac Death in Structurally Normal Heart"— Presentation transcript:
1 Sudden Cardiac Death in Structurally Normal Heart Brian D. Le, MDPresbyterian HospitalCIVA
2 Gaita et al. Circulation. 2003; 108 PresentationHPI-35 yo WM s PMH presents with exertional syncopeh/o PAF since 18 yrs of ageHolter- monomorphic isolated PVC’sEcho- structurally normal heartMeds- no OTC or herbalSocial- occ. Etoh, no IVDAFamily HistorySister (31) - dizziness and palpitationsSister’s son (6) - cardiac arrest at 8 mo old after a loud noise with successful DCCVGaita et al. Circulation. 2003; 108
3 A- 35 yo WM c syncopeB- 31 yo sister, dizziness and palpitationsC- 6 yo son, SCD
4 Sudden Cardiac Death“Unexpected death from cardiac cause within a short time (~1 hour of sx) in a person without prior conditions that would appear fatal.”,000 deaths annually (U.S.).VT/VF account for 80%.20% have structurally normal hearts.Wever E, et al. JACC. Vol 43, 2004.
5 Sudden Cardiac Death Normal hearts, < 40 years old < 30% successful resuscitation reaching hospitalRisk of life-threatening events in cardiac arrest survivors is 25-40% at two yearsWever E, et al. JACC. Vol 43, 2004.
10 A- 35 yo WM c syncopeB- 31 yo sister, dizziness and palpitationsC- 6 yo son, SCD
11 Evaluation Physical Exam Serial ECG’s Holter Heart rate variability QT dispersionSignal-averaged ECGEchocardiogramCardiac MRIElectrophysiological Study
12 QT Interval Represents ventricular repolarization. Normal QTc upper limit: 440ms.Bazett’s formula: QTc = QT/ RRRautaharju formula (14,379 pts):QTp (ms)= 656/ (1+HR/100)QT/QTp x 100% = % QTpredicted.88% of QTp = 2 SD below meanLower limit of nl QT int. = 88% of QTpRautaharju: <88% QTp (2.5% of patients studied); <80% QTp (0.03% of patients studied).
13 QT Interval and SCD Algra et al. Br.Ht.J. 1993;70:43-8. Nested cohort 6693 consecutive pts w/24 ECG.F/U 2.5 years in 99.5% of pts.End point: QTc correlation w/SCD (104 pts).Results:QTc >= 440ms 2.3 RR of SCD.QTc < 400ms 2.4 RR of SCD.
14 Familial Short QT Gussak et al. Cardiology 2000;94:99-102. 3 members of one family; age yo.Palpitations, sx PAF, syncopeSCDAll w/ structurally normal hearts.All w/ S-QT ( ms); QT interval <80% predicted by Rautaharju method.
15 Factors That Shorten QT Increase in heart rateHyperthermiaHypercalcemiaHyperkalemiaAcidosisChanges in autonomic tone
16 Genetic Basis of Short QT Brugada, Antzelevitch, et al. Circ. 2004;109:30-5.Different missense mutations in same residue codon 588 of KCNH2 (HERG [IKr]).Mutations only seen in sQT, and not in normal relatives.Patch clamp modelsScreened: HERG (KCNH2), KCNE2, KCNQ1, KCNE1, SCN5A, KCNJ2, Kv4.3, Kv4.2,Kv1.5, KCHiP2, KCHAP, KCHiP1, KCNJ3, KCNJ6, SUR1, KCNJ11, ANKB, CHRM1,4,&5.N=asparagine588=codon #K=Lysine
17 Heterogeneity of Short QT Genetic Studies- KCNQ1 gene mutation G for C, subs. valine for leucine (IKs)Mutations negative in 200 unrelated controlled individualsLoss of function leadsLQT1Bellocq et al. Circulation. 109; 2004
18 KCNJ2, encoding for inwardly rectifying K channel Kir2.1 Rapid repolarizationSQT3Loss of function results in LQT7 (Anderson’s disease)Priori et al. Circ. Res ; 96
19 Ion Channel Mutations Loss of Function Gain of Function SCN5A BrugadaIKs LQT1IKr LQT2Gain of FunctionSCN5A LQT3IKs Fam. A. Fib., Short QTIKr Short QT4123NaCa > NaIKr & IKs
20 Short QT Syndrome Rx Gaita et al. JACC. 2004;43:1494-9. 6 pts. from 2 different families.Drugs: Flecainide (IV or oral), Sotalol, Ibutilide, and Hydroquinidine.Steady-state: >5 t1/2 of drug.Flecainide (Class 1c)dose: IV 2mg/kg in 10 mins; oral 100mg po BID.Sotalol (class 3): IV 50mg and oral til max tolerated (which was 80mg po BID).Ibutilide (class 3): 1mg IV in 10mins.Hydroquinidine (class 1a): 250mg po TID or 500mg po BID.
21 Short QT Rx ResultsFlecainide: slight inc. QT due to QRS prolongation.Ibutilide & Sotalol: no change in QTHydroquinidine:5/6 pts- QTc normalized (290405ms)EPS 5/5 pts- inc. VERP, no VF/VTF/U 11 mos- 4/6 on hydroquinidine w/o sx or arrhythmias detected by ICD.
23 Figure 1. Twelve-lead electrocardiographic (ECG) recordings of Patient 1, while treated with different antiarrhythmic drugs. From left to right: basal ECG; during oral flecainide administration, oral sotalol, ibutilide, and hydroquinidine. During hydroquinidine administration: QT prolongation and ST-T changes: appearance of ST-segment, T-wave increases in duration.
24 Quinidine VW Class: Ia (sodium channel blocker) Blocks: INa, IKr, IKs, Ito, L-type Ca2+, IK1(in.rect.), & IKATP QT increase.Adverse effects: diarrhea, SLE, thrombocytopenia, hepatitis, cinchonism (tinnitus/HA), TdP, many drug interactions 2/2 block of CYP2D6.
25 ICDFirst line therapyRisk of inappropriate shock delivery- Tw oversensing (Schimpf et al. JCE. 14: Dec 2003)