Sudden Cardiac DeathDR ABDULPGY3MEM

DefinitionThe natural death from cardiac causes, heralded by abrupt loss of consciousness within 1 hour of the onset of an acute change in cardiovascular status.

is an unexpecteddeathdue tocardiaccauses that occurs in a short time period (generally within 1 hour of symptom onset) in a person with known or unknowncardiacdisease.*

Epidemiology 300,000 cases per year1-2/1000Bimodal distribution

*Highest risk between birth and 6months or 45yrs to 75yrs

CausesLong QT SyndromeBrugada SyndromeHypertrophic Cardiomyopathy Arrhythmogenic Right Ventricular Dysplasia Commotio Cordis Coronary Anomaly

K chanellopathyNa chanellopathyMuscle mass thicknessDeposition of muscle with fatSudden force over precordium leading to vt*

Long QT SyndromeAutosomal Dominate- Romano-WardAutosomal Recessive- Jervell and Lange-NielsenAcquired1/10,000

*Aprox 1 in 2500 to 1 in 10,000 w/ genetic LGTs. JLN-occurrs in around 3-3.5% of kids w/ congenital neuronal deafness-has a more malignant course

As much as 15% of pt w/ acguired L QT have and underlying mutationACQUIRED:A:DRUGS:1.AMPHETAMINE:COCAINE,EPHEDRINE,2.ANTICHOLERNERGICS:ATROPINE,AMITRIPTYLINE,DIPHENIREHYDRAMINE,ALPRAX,CITRIZINE,3.MACROLIDS:AZITHRO,ERYTHRO,CLARITHROMYCIN B>ELECTROLYTEDISTURBANCE C.HYPOTHERMIAAutosomal dominat:1 copy of gene sufficient to cause disease,autosomal recessive :2copy of genes necessary to disese develope

*Phase 0- rapid depolarization phase- fast sodium channels open-rapid influx of positively charges ion. Phase 1-closure of fast Na channels O and 1=R and S wavePhase 2-platue phase-balance between inward mvt of Cal and outward mvt of K,very slow k effulux ..thus channels remain open for prolonged time ..qt prolongationPhase 3-repolarization phase outward flow of K-T wavePhase 4-resting membrane potential

blocking/slowing Na influx or K eflux causes a prolongation of the qt interval (Duration of activation and recovery of ventricular myocardium), if prolongation is long enough can get a second excitation phase from myocardium (early after-depolarization) leads to loose of synchronization and arrhythemia--ankyirin-thought to effect Na channels

*FIGure---R-W: Romano-Ward syndrome; J-L-N: Jervell and Lange-Nielsen syndrome with deafness; NR: not reported; HPP: hypokalemia periodic paralysis.* KCNE1 is also referred to as minK; KCNE2 is also referred to as MiRP1 (minK related protein 1). The KvLQT1 gene encodes the alpha-subunit protein of the IKs channel, with the KCNE1 gene encoding the beta- subunit protein of this same channel. The alpha- and beta-subunit proteins combine together to form a cardiac potassium channel expressing the IKs (slowly activating component of delayed rectifier potassium current); Ikr is the rapidly activating component of delayed rectifier potassium current.Amended with permission from Schwartz, PJ, Priori, SG, Napolitano C. Long QT syndrome in Zipes, DP, Jalife, J (Eds.) Cardiac Electrophysiology: From Cell to Bedside. Orlando, Fla: WB Saunders. 1999.

LQT1-account for 40-55% of cases

LQT2- 35-45%

LQT3-8-10%

Others 2-5% each

PresentationPalpitations, Presyncope, Syncope, Seizures, or Cardiac arrestAsymptomatic prolonged QTcReferred by family membersHas a predilection for younger patient

*Pressentation can depend on genetics LGT1-exercise-related events, LQT2-auditory-allarm clocks or phones, LQT3-events at rest or sleep

Seems to afeect younger pt, syncope and SCD unusual in pt older then 40

1 small box =.04sec,1 large box =.2sec,5 large box =1sec*

*LGT1-broad T waveLGT2-low-amplitude-bifid T waveLQT3-long isoelectric segment followed by a narrow tall Twave

http://www.torsades.org/

*10-15% of pts w/ acquired LGT have underlying genetics

Diagnosis: Schwartz score

*-provacation with epinephrine for LGT1-give epi and qt increaseTo make a definitive diagnosis score of greater than 4 is needed

TherapyNEJM 2008; 358:169-175

*Long acting BB

Brugada SyndromeAutosomal dominate defect in cardiac Na channels- variable expression0.4% US populationMale predominanceAverage age of Dx=41

*Incidence increases in asian populations, first described in asiansAprox 18% of pt w/ syndrome have gene, variable penetranceRarely dx in children

Texas Heart Inst J 2007;34:67-75

In a normal condition :there is almost simultaneous excitation of endo & epicardium due to N functioning NA channels but in case of brugada action potential is delayed due to slow opening or block in NA channels .leading to a lag b/w endocardium & epicardium aka phase 2 reentry,PHASE 2 WILL BE SHORTNEDEpicardium has shortest AP{high conc. Of ions},endocardium has longest AP

Loss-of-function mutations in this gene lead to a loss of the action potential dome of some epicardial areas of the right ventricle. This results in transmural andepicardialdispersion ofrepolarizatio*

PresentationFunny looking ECGSCD/Syncope TriggersFeverSleepGlucose/insulinCocaine/ETOHElectrolytes

*SCD-initial pressentation in aprox 30%, -Three distinct types of ST segment elevation have been described. In type 1, the ST segment gradually descends to an inverted T wave. In type 2, the T wave is positive or biphasic, and the terminal portion of the ST segment is elevated 1 mm. In type 3, the T wave is positive, and the terminal portion of the ST segment is elevated

Unmasking AgentsNa channel blockers-ajmalineCalcium Channel blockersBeta blockersNitratesTricyclicsSSRI

Prognosis & TREATMENTSCD or VF/VTSyncope

*Pts w/ SCD / VF have aprox 25% chance of a second event w/in 2 yrs Pts pressenting w/ syncope have a six fold increase in SCD above asymptomatic ptPt w/ spontaneous type I pattern were three times more likely up to 15% in 2 yrs follow up

TREATMENT IS AICD PLACEMENT OR MEDICALLY BY QUINIDINE CLASS 1 ANTIARYTHIMIC {BLOCKE FAST NA CHANNELS}

Hypertrophic Cardiomyopathy defect in the myocardial contractile proteins

HCM is a familial disease

hallmark : myocardial hypertrophy that is inappropriate, often asymmetrical, and occurs in the absence of an obvious inciting hypertrophy stimulus.

*Prt affected: cardiac troponin T, cardiac troponin I, myosin regulatory chain, myosin essential light chain, cardiac myosin binding protein-C, alpha and beta-cardiac myosin heavy chain, cardiac alpha actin, alpha tropomyosin, and titin. -more common in men and AA

HCM involves changes in connective tissue elements as well as sarcomere proteins l

disorganized myocyte architecture, including with bizarre-shaped nuclei, widespread interstitial fibrosis . *

*387 high school age/college age in minnasoata

PresentationSCDDOESyncopeHeart failureChest PainPalpitationAsymptomatic

*No good correlation bettwen degree of obstruction and severity of symptoms-DOE most common syptom >90 of symptomatic pts, 2/2 to diastolic dysfunction, MR, empaired LV emptying-syncope occurs in 15-25% of pt w/ at least one episode 2/2 to inadequate cardiac out put or ischemia or ventricular barofeflex w/ inappropriate vasodialtionsmall chamber size is risk factor

Physical ExamSystolic Crescendo-decrescendo murmur LLSB/apexDecreases w/ squatting, hand dripIncrease w/ standingBifid pulsesEKG-LVH

*

DiagnosisECHO

*LV wall thickness >=15, with out other causes HTN, AS, differientiate from athlete heart

TreatmentPharmocologicVerapamilBeta blockers

ICDClass I- h/o sustained VT/VFOne or more major risk factor Ablation/Surgery

*--Verapamil/bb slow HR and prolong diastoling allowing more filling, decrease 02 demand--Beatblokcer--Disopyramide-antiarrythmic and negative iontrop****use w/ caution vasodilator-nefidipine NTG, ACE, decrease PVR inc gradient-diuretics decrease preload andless LV fillling smaller change greater out flow obstruction===ICD need to be on apropriate medical management and have life exspectancy of a year+++ETOH septal ablation or surgical myomectomies in pt w/ severe obstruction >50mmhg/ refractory symptoms

Arrhythmogenic Right Ventricular DysplasiaDefective DesmosomeFibrofatty replacement of the RV myocardium1:1000Autosomal dominant -mcf

*fibrofatty replacement of the RV myocardium initially produces typical regional wall motion abnormalities that later become global, producing RV dilation. The tissue replacement can also involve area of the left ventricle (LV) with relative sparing of the septum -dispite the name in can occur in the LV as well, infact these proteens a poorer prognosis w/ higher incidence of arryhtmia and CHF--an autosomal dominant form, which is most common, and an autosomal recessive form called Naxos disease, in which ARVD is part of a syndrome including hyperkeratosis of the palms and soles and woolly hair.

--)

*. Panel A:Four chamber view cut of the heart specimen showing the trans mural fatty replacement of the right ventricular free wall and the translucent infundibulum. Panel B: Panoramic histologic view of the same heart confirming that the replacement of the myocardium by fat is largely confined to the right ventricle (arrow) and substantially spares the interventricular septum as well as the left ventricular free wall (trichrome Heidenhain x 3).

PresentationAsymptomaticPalpitation, syncope, atypical chest pain, dyspneaArrhythmiasSCDExercise associated

*Palpitations 67 percent Syncope 32 percent Atypical chest pain 27 percent Dyspnea 11 percent Signs of Right heart failure are rare, clinical pressentation is usualy arrthymia (50%)/SCD or incidental finding mean age fo dx is 30 10-30--most common arythemia is monomorphic VT from the RV

*

Diagnosis- Arrhythmogenic RV dysplasia1. Epsilon wave: just after the QRS complex 2. T inversion in v 1 to v33. Positive QRS in v1 (the classical RBBB pattern is not present in this ecg)

AIVR w/ LBBB morphologyRight sided VT-ARVD vs. Idiopathic Right Ventricular Arrhythmia (IRVA) vs Right Ventricular Outflow Tract (RVOT) tachycardia (70-90%)--As many as 40 to 50 percent of patients have a normal ECG at presentation [8,31]. However, by six years, virtually all patients with ARVD have one or more of the following findings on ECG during normal sinus rhythm [31]:The QRS duration is frequently prolonged; this is seen more often in lead V1 than in lead I or V6. This prolongation is consistent with delayed right ventricular activation. A QRS duration greater than 110 msec (0.110 sec) in lead V1 has a sensitivity of only about 50 percent but a very high specificity in patients suspected of having ARVD based upon the above historical features. There may be a pattern of incomplete or complete right bundle branch block. Epicardial mapping suggests that these patterns are usually due to parietal block (conduction delay in the terminal Purkinje system), rather than to disease of the bundle branch [32]. (See "General principles of asynchronous activation and preexcitation", section on Intraventricular and intramural block). Thirty percent of patients with ARVD have an epsilon wave that has the appearance of a distinct wave just beyond the QRS complex, particularly in V1 (show ECG 2). This finding represents low amplitude potentials caused by delayed activation of some portion of the RV. Inversion of T waves in the right precordial leads occurs in one-half of cases presenting with VT (show ECG 3). The extent of T-wave inversion has been correlated with the degree of RV enlargement [33]. Increased QT dispersion, ie, interlead variability of QT intervals, may be seen. (See "QT dispersion: Measurement and interpretation"). A prolonged S wave upstroke has been described. This finding (interval from the nadir of the S wave to the isoelectric baseline 55 msec) has been noted in 91 to 95 percent of ARVD patients who did not have RBBB [7,34].

Diagnosis

2major or 1major + 2minor or 4minor

*

TreatmentICD: Class I: History of sustained VT/VFClass IIa: extensive disease, LV involvement, family members w/ SCD, syncopeAmiodarone or Sotalol-Class IIAAblation-Class IIA

*

Commotio Cordis SCD due to low-impact precordial traumaMale predominance, young ageHigh mortalityProbability related to speed, time, hardness of object and location of impact

*According to CC registry only 15% survival

Ventricular fibrillation can be triggered by chest wall impact immediately over the heart and occurs most frequently with impact over the center of the left ventricle

Commotio cordisTreatmentCPRShockPreventionSafety baseballsChest protectorsFollow upEKGHolterEcho

*--the impact is thought to cause a premature ventricular depolarization at a vulnerable time period

Congenital Coronary Artery AnomaliesVariation in the take off the Coronary ArteriesIncidence 5.60.17%Deaths related to exertion

*Rca: arises from right cusp of the aortic valve & travels into right arterioventricular grooveLca:above theleft cuspof theaortic valve

--Incidence of any coronary anomaly(variation that occurs in

PathophysiologyCompression between the pulmonary artery and aortaAcute angle take offMyocardial necrosis

*The subsequent course between the aorta and pulmonary artery to the left ventricle may result in compression of the vessel, myocardial ischemia, and sudden death in both adults and teenagers [3,4]. These complications commonly occur during or immediately after exercise. Exercise leads to expansion of the aortic root and pulmonary trunk, which, in addition to external coronary artery expression, may increase the preexisting angulation of the coronary artery takeoff, reducing the luminal diameter in the proximal portion of the coronary artery [3].

--transient ischemia overtime can lead to myocardial necrosis-fibrosis-foci for arrhytmias

PresentationAnginaAtypical chest painSyncopePalpitationDizzinessSCD

*In a small case series of 27pt (italian/US) about 1/3 of pt w/ SCD 2/2 anomolous arteris had-CP, syncope palpitation. Of these about a third had normal stess test/ekg-no abnormal stress test, the symptoms came for anomolouse LCA

DiagnosisECHOCardiac MRICT angiographyCardiac Cath

*Echo is between 80-95% sensitiveCardiac MRI Sen 88- Spec-100%

Military Significance

*All non traumatic SCD in the AF, army, marines or navy between 77-01, occuring during basic training 6.3million soldiers--- found 126 non traumatic, 44 idopathic and 18 non-cardiacAbout half of the patients with iditifiable cardiac causes had prodromal, syncope, CP, DOE, palpitaions

TreatmentBeta BlockersSurgeryCoronary StentsAvoid strenuous activities

*BB control HRSurgery to CABG or unroof intramural portions of vesselsCardic stent have been use in stonoti origins.

0/1-not advisable, 2/3 intermediate risk, 4/5-permitted

*

thanks

is an unexpecteddeathdue tocardiaccauses that occurs in a short time period (generally within 1 hour of symptom onset) in a person with known or unknowncardiacdisease.**Highest risk between birth and 6months or 45yrs to 75yrsK chanellopathyNa chanellopathyMuscle mass thicknessDeposition of muscle with fatSudden force over precordium leading to vt**Aprox 1 in 2500 to 1 in 10,000 w/ genetic LGTs. JLN-occurrs in around 3-3.5% of kids w/ congenital neuronal deafness-has a more malignant course

As much as 15% of pt w/ acguired L QT have and underlying mutationACQUIRED:A:DRUGS:1.AMPHETAMINE:COCAINE,EPHEDRINE,2.ANTICHOLERNERGICS:ATROPINE,AMITRIPTYLINE,DIPHENIREHYDRAMINE,ALPRAX,CITRIZINE,3.MACROLIDS:AZITHRO,ERYTHRO,CLARITHROMYCIN B>ELECTROLYTEDISTURBANCE C.HYPOTHERMIAAutosomal dominat:1 copy of gene sufficient to cause disease,autosomal recessive :2copy of genes necessary to disese develope*Phase 0- rapid depolarization phase- fast sodium channels open-rapid influx of positively charges ion. Phase 1-closure of fast Na channels O and 1=R and S wavePhase 2-platue phase-balance between inward mvt of Cal and outward mvt of K,very slow k effulux ..thus channels remain open for prolonged time ..qt prolongationPhase 3-repolarization phase outward flow of K-T wavePhase 4-resting membrane potential

blocking/slowing Na influx or K eflux causes a prolongation of the qt interval (Duration of activation and recovery of ventricular myocardium), if prolongation is long enough can get a second excitation phase from myocardium (early after-depolarization) leads to loose of synchronization and arrhythemia--ankyirin-thought to effect Na channels*FIGure---R-W: Romano-Ward syndrome; J-L-N: Jervell and Lange-Nielsen syndrome with deafness; NR: not reported; HPP: hypokalemia periodic paralysis.* KCNE1 is also referred to as minK; KCNE2 is also referred to as MiRP1 (minK related protein 1). The KvLQT1 gene encodes the alpha-subunit protein of the IKs channel, with the KCNE1 gene encoding the beta- subunit protein of this same channel. The alpha- and beta-subunit proteins combine together to form a cardiac potassium channel expressing the IKs (slowly activating component of delayed rectifier potassium current); Ikr is the rapidly activating component of delayed rectifier potassium current.Amended with permission from Schwartz, PJ, Priori, SG, Napolitano C. Long QT syndrome in Zipes, DP, Jalife, J (Eds.) Cardiac Electrophysiology: From Cell to Bedside. Orlando, Fla: WB Saunders. 1999.

LQT1-account for 40-55% of cases

LQT2- 35-45%

LQT3-8-10%

Others 2-5% each*Pressentation can depend on genetics LGT1-exercise-related events, LQT2-auditory-allarm clocks or phones, LQT3-events at rest or sleep

Seems to afeect younger pt, syncope and SCD unusual in pt older then 401 small box =.04sec,1 large box =.2sec,5 large box =1sec**LGT1-broad T waveLGT2-low-amplitude-bifid T waveLQT3-long isoelectric segment followed by a narrow tall Twave*10-15% of pts w/ acquired LGT have underlying genetics*-provacation with epinephrine for LGT1-give epi and qt increaseTo make a definitive diagnosis score of greater than 4 is needed *Long acting BB*Incidence increases in asian populations, first described in asiansAprox 18% of pt w/ syndrome have gene, variable penetranceRarely dx in childrenIn a normal condition :there is almost simultaneous excitation of endo & epicardium due to N functioning NA channels but in case of brugada action potential is delayed due to slow opening or block in NA channels .leading to a lag b/w endocardium & epicardium aka phase 2 reentry,PHASE 2 WILL BE SHORTNEDEpicardium has shortest AP{high conc. Of ions},endocardium has longest AP

Loss-of-function mutations in this gene lead to a loss of the action potential dome of some epicardial areas of the right ventricle. This results in transmural andepicardialdispersion ofrepolarizatio**SCD-initial pressentation in aprox 30%, -Three distinct types of ST segment elevation have been described. In type 1, the ST segment gradually descends to an inverted T wave. In type 2, the T wave is positive or biphasic, and the terminal portion of the ST segment is elevated 1 mm. In type 3, the T wave is positive, and the terminal portion of the ST segment is elevated 90 of symptomatic pts, 2/2 to diastolic dysfunction, MR, empaired LV emptying-syncope occurs in 15-25% of pt w/ at least one episode 2/2 to inadequate cardiac out put or ischemia or ventricular barofeflex w/ inappropriate vasodialtionsmall chamber size is risk factor*

*LV wall thickness >=15, with out other causes HTN, AS, differientiate from athlete heart

*--Verapamil/bb slow HR and prolong diastoling allowing more filling, decrease 02 demand--Beatblokcer--Disopyramide-antiarrythmic and negative iontrop****use w/ caution vasodilator-nefidipine NTG, ACE, decrease PVR inc gradient-diuretics decrease preload andless LV fillling smaller change greater out flow obstruction===ICD need to be on apropriate medical management and have life exspectancy of a year+++ETOH septal ablation or surgical myomectomies in pt w/ severe obstruction >50mmhg/ refractory symptoms*fibrofatty replacement of the RV myocardium initially produces typical regional wall motion abnormalities that later become global, producing RV dilation. The tissue replacement can also involve area of the left ventricle (LV) with relative sparing of the septum -dispite the name in can occur in the LV as well, infact these proteens a poorer prognosis w/ higher incidence of arryhtmia and CHF--an autosomal dominant form, which is most common, and an autosomal recessive form called Naxos disease, in which ARVD is part of a syndrome including hyperkeratosis of the palms and soles and woolly hair.

--) *. Panel A:Four chamber view cut of the heart specimen showing the trans mural fatty replacement of the right ventricular free wall and the translucent infundibulum. Panel B: Panoramic histologic view of the same heart confirming that the replacement of the myocardium by fat is largely confined to the right ventricle (arrow) and substantially spares the interventricular septum as well as the left ventricular free wall (trichrome Heidenhain x 3). *Palpitations 67 percent Syncope 32 percent Atypical chest pain 27 percent Dyspnea 11 percent Signs of Right heart failure are rare, clinical pressentation is usualy arrthymia (50%)/SCD or incidental finding mean age fo dx is 30 10-30--most common arythemia is monomorphic VT from the RV*

Diagnosis- Arrhythmogenic RV dysplasia1. Epsilon wave: just after the QRS complex 2. T inversion in v 1 to v33. Positive QRS in v1 (the classical RBBB pattern is not present in this ecg)

AIVR w/ LBBB morphologyRight sided VT-ARVD vs. Idiopathic Right Ventricular Arrhythmia (IRVA) vs Right Ventricular Outflow Tract (RVOT) tachycardia (70-90%)--As many as 40 to 50 percent of patients have a normal ECG at presentation [8,31]. However, by six years, virtually all patients with ARVD have one or more of the following findings on ECG during normal sinus rhythm [31]:The QRS duration is frequently prolonged; this is seen more often in lead V1 than in lead I or V6. This prolongation is consistent with delayed right ventricular activation. A QRS duration greater than 110 msec (0.110 sec) in lead V1 has a sensitivity of only about 50 percent but a very high specificity in patients suspected of having ARVD based upon the above historical features. There may be a pattern of incomplete or complete right bundle branch block. Epicardial mapping suggests that these patterns are usually due to parietal block (conduction delay in the terminal Purkinje system), rather than to disease of the bundle branch [32]. (See "General principles of asynchronous activation and preexcitation", section on Intraventricular and intramural block). Thirty percent of patients with ARVD have an epsilon wave that has the appearance of a distinct wave just beyond the QRS complex, particularly in V1 (show ECG 2). This finding represents low amplitude potentials caused by delayed activation of some portion of the RV. Inversion of T waves in the right precordial leads occurs in one-half of cases presenting with VT (show ECG 3). The extent of T-wave inversion has been correlated with the degree of RV enlargement [33]. Increased QT dispersion, ie, interlead variability of QT intervals, may be seen. (See "QT dispersion: Measurement and interpretation"). A prolonged S wave upstroke has been described. This finding (interval from the nadir of the S wave to the isoelectric baseline 55 msec) has been noted in 91 to 95 percent of ARVD patients who did not have RBBB [7,34].

*

*

*According to CC registry only 15% survival

Ventricular fibrillation can be triggered by chest wall impact immediately over the heart and occurs most frequently with impact over the center of the left ventricle*--the impact is thought to cause a premature ventricular depolarization at a vulnerable time period*Rca: arises from right cusp of the aortic valve & travels into right arterioventricular grooveLca:above theleft cuspof theaortic valve

--Incidence of any coronary anomaly(variation that occurs in