Transcript Sudden Cardiac Death BRUGADA SYNDROME
Sudden Cardiac Arrest BRUGADA SYNDROME
Carlo Francisco S. Gochuico, M.D.
August 14, 2008
OBJECTIVES
• To present a case of sudden cardiac arrest in a young male • To discuss the approach and management of Brugada syndrome
General Data
• J.D.
• 28 year old • Male • Filipino Chief Complaint Loss of consciousness
History of Present Illness
One hour PTA Found unconscious Seen with upward rolling of eyeballs, stiffening of extremities, and salivary pooling Lasted 3 to 5 minutes Regained full consciousness with no recollection of the incident Was able to drink, sit on a chair, and talk with parents No slurring of speech, no extremity weakness, no chest pain
History of Present Illness
Five minutes after Recurrence of stiffening of extremities and upward rolling of eyeballs Rushed to MMC ER During transit, he remained unconscious
Events at ER
Quicklook showed cyanosis BP 0 HR 0 GCS 3 E1V1M1 Initial tracing at ER at 1:42 AM Chest compressions and bag mask ventilation Defibrillation at 200 joules Epinephrine 1mg IV Intubated and advised ICU admission
12 L EKG 8-1-08 2:16 AM post defibrillation CRBBB PR interval 0.16 sec QT interval 0.36 sec
Events at ER
2:33 AM at ER Systolic BP170 Pulse 80s regular Post CP arrest
Events at ER
2:47 AM Episode of stiffening of extremities chest compression and defibrillation at 200 joules
Events at ER
2:52 AM Post defibrillation BP 120/80 Pulse 80s Amiodarone drip started
Referred to neurology Admitted to ICU
Review of Systems
General: no fever , fatigue, weight loss Skin: no rashes, jaundice, ecchymoses, petechiae Head: no recent head injury, headache, dizziness Eyes: no blurring of vision, redness, pain Ears: no tinnitus, vertigo, earache, discharge
Review of Systems
Nose: no colds, nasal congestion, discharge Mouth: no sore throat, hoarseness Neck: no pain, lumps, mass, stiffness Respiratory: no cough, dyspnea, wheezing, hemoptysis Cardiac: no chest pain, palpitations, orthopnea, PND, edema, recent chest trauma
Review of Systems
Gastrointestinal: no nausea, vomiting, regurgitation, dysphagia, hematemesis, abdominal pain, change in frequency and characteristic of stools Urinary: no hematuria, dysuria, oliguria, polyuria, urgency, hesitancy Vascular: no claudication, varicose veins, leg cramps Musculoskeletal: no myalgia, arthralgia, and swelling
Review of Systems
Hematologic: no anemia, pallor, easy bruising or bleeding Endocrine: no heat or cold intolerance, no excessive thirst or hunger Psychiatric: no depression, nervousness
Past Medical History
No history of HPN, DM, and BA PTB, treated for 6 months
No previous seizure disorder, no known neurologic and cardiac problems Had a history of syncope during early childhood and another one a year ago, no work-ups were done
Family History
(+) HPN in paternal side
(-) DM, BA, stroke, cancer
No seizure disorder
Personal and Social History
Occasional smoker Occasional alcoholic beverage drinker
Denies illicit drug use
PHYSICAL EXAMINATION
Conscious, restless, intubated BP 120/80 HR 80 regular RR 20 assisted afebrile Warm moist skin, no active dermatoses, no jaundice Anicteric sclerae, pink palpebral conjunctivae, pupils 2-3 mm ERTL OU No visible anterior neck mass, no neck vein distention, no carotid bruit No cervical lymphadenopathies
PHYSICAL EXAMINATION
Equal chest expansion, no retractions, no rales, wheezes, crackles Adynamic precordium, AB at 5th LICS MCL, regular rhythm, S1>S2 at base, S2>S1 at apex, no extra heart sounds, no murmurs Abdomen flabby, normoactive bowel sounds, soft, no guarding, no direct and rebound tenderness, no hepatosplenomegaly No costovertebral angle tenderness No pedal edema Pulses full and equal
PHYSICAL EXAMINATION
GCS 11 E4V1 (intubated) M6 No papilledema Full and equal EOM No facial asymmetry Intact doll’s eye movement, gag and corneal reflexes Direct tendon reflexes normal Motor and Sensory: intact Localizes to pain and temperature No babinski, kernig’s, and brudzinski
Salient Features
28 M Filipino Loss of consciouness at night during sleep 2 episodes of stiffening of extremities Post CP arrest 2x (VFib) No fever, headache, chest pain, weakness History of syncope 2x Positive family history of cardiac disease No illicit drug use
Differential Diagnosis
Loss of consciousness Neurologic Cardiac Seizure Disorder Cerebrovascular Accident Structural Primary physiologic abnormality
Differential Diagnosis
Neurologic Seizure No previous history
glucose toxicology liver and renal function test
Cerebrovascular accident
Loss of consciousness Neurologic Cardiac Seizure Disorder Cerebrovascular Accident Structural Primary physiologic abnormality
Differential Diagnosis
Cardiac
Structural heart disease Non-structural heart disease
Differential Diagnosis
Structural heart diseases – Ischemic heart disease – Non-ischemic cardiomyopathies – Valvular heart diseases – Arrhythmogenic right ventricular dysplasia Primary electrophysiologic abnormalities – Long QT syndrome – Brugada syndrome
Ischemia
Cardiac arrest due to ventricular arrhythmias may be due to chronic
. A chronic infarct scar can serve as the focus for reentrant ventricular tachyarrhythmias
Non-ischemic cardiomyopathies
represent the second largest group of patients who experience SCD Dilated cardiomyopathy is usually characterized by ventricular dilatation, initially usually of the left ventricle (LV), with myocyte hypertrophy and diminished systolic function
Hypertrophic cardiomyopathy (HCM)
an autosomal-dominant, incompletely penetrant genetic disorder resulting from a mutation in one of the many (>45) genes encoding proteins of the cardiac muscle sarcomere
Echo of HCM
Small LV cavity due to marked hypertrophy of the myocardium and encroachment into the LV cavity Reduced septal motion and thickening during systole, particularly of the upper septum, due to the disarray of the myofibrillar architecture and abnormal contractile function Reduced rate of closure of the mitral valve in mid diastole due to a decrease in LV compliance Left atrial enlargement
Cardiac
Structural heart disease Non-structural heart disease Primary physiologic abnormality
Course in the Ward
1 st Hospital day in the ICU (1230 PM)
– Rsr’ pattern – ST elevation in lead V1-V3 2D echo – N LVD EF69% Normal LA and RA dimensions Normal MV, TV, AV, PV Mild MR, TR Normal left ventricular diastolic function indices FIo2 adjusted to 0.35
Course in the Ward
ICU at 1500H T-piece placed and
Referred to cardiology EPS
requested Quinidine bisulfate started
Course in the Ward
ICU at 1750 H Patient extubated 4 th Hospital day Transferred to regular room Quinidine 200mg/tab adjusted to 1 ½ tablets in the morning and evening, and 1 tablet at lunchtime
Course in the Ward
5 th hospital day
– Normal
on 6 th hospital day Follow-up after 1 week
Aug 1, 2008 • Lungs are clear • Heart is magnified • ET in place with tip at carina
Scan Aug 1, 08 • Normal non contrast CT of the brain
• Normal
ECHOCARDIOGRAPHY August 1, 2008
Normal left ventricular dimension with normal wall motion and contractility.
Computed LV EF 69% Normal left and right atrial dimensions Normal mitral, aortic, tricuspid, and pulmonic valves Mild MR, TR Normal left ventricular diastolic function indices
Repeat 12 L EKG 8-1-08 12:30 PM
PR interval 0.16 sec QT interval 0.40 sec
Laboratory Results and Ancillary Procedures
Na 137 K 2.7
Hgb 16.7
Hct 49 Glucose (random) 245 mg/dL
Hgb 16.8
Hct 50.2
WBC 14.21
– seg54 – lymph36 – eos4 – mono5 – Baso1 Platelet 204000
Laboratory Results and Ancillary Procedures
CK total 165 U/L CPK MB 1.4 ng/mL
I 0 ng/mL
PTT
patient 27.3
control 27.6
PT
patient 11.1
control 11.7
activity 115.6% INR 0.94
Laboratory Results and Ancillary Procedures
Na 137 K 3.6 Cl 103 calcium 9.78 BUN 13 creatinine 1.1
HDL 46 trig 119 LDL 166 cholesterol 245 glucose 120 CPK 506 LDH 262 ALT 185 AST 82 alkaline phosphatase 148
Laboratory Results and Ancillary Procedures
Routine urinalysis
Yellow hazy PH 6 spgr 1.020 +3 protein trace sugar negative ketones, nitrites, leucocyte esterase +1 blood rbc 2/hpf wbc 2/hpf epith 10/hpf Bact 15/hpf
TSH Function Test
0.037
(0.27-3.75)
FT3 FT4
4.419 (4.2-12) 17.815 (8.8-33)
Laboratory Results and Ancillary Procedures
ABG
PO2 426.2 PH 7.34 PCO2 41 HCO3 O2 sat 22.1 99.8 AC mode 100% FiO2 VT 420
Laboratory Results and Ancillary Procedures
ABG
PO2 169.1 PH 7.39 PCO2 37.3 HCO3 O2 sat 22.5 99.1 inline neb via T piece 35% FiO2
Repeat 12 L EKG 8-6-08 9:54 AM Normal
PR interval 0.20 sec QT interval 0.44 sec
DISCUSSION
Sudden cardiac death (SCD) is an unexpected death due to cardiac causes, heralded by loss of consciousness occurring in a short time period (generally within 1 hour of symptom onset) Most cases are due to cardiac arrhythmias such as VF or VT which is responsible for 50-80% of cases
Sudden Cardiac Death
Most cases of SCD occur in patients with structural abnormalities in the heart, related to either a prior MI, coronary artery disease, cardiomyopathies Valvular diseases such as aortic stenosis are associated with increased risk of SCD Acute inflammatory and infiltrative disorders, such as myocarditis, provide a sustained risk of SCD
Sudden Cardiac Death
Less commonly, SCD happens in patients who may not have apparent structural disease These conditions are usually inherited arrhythmia syndromes or primary electrophysiologic abnormalities
Primary Electrophysiologic Abnormalities
This generally represents a group of abnormalities in which patients have no apparent structural heart disease but have a primary electrophysiologic abnormality that predisposes them to VF or VT Brugada syndrome, Long QT syndrome
Brugada Syndrome
A cardiac disease caused by an inherited ion channelopathy associated with a propensity to develop ventricular fibrillation (VF) Reported as early as 1953 but was first described as a distinct clinical entity associated with a high risk of sudden cardiac death in 1992
Brugada Syndrome
In the 1980s, the Centers for Disease Control and Prevention reported a high incidence of sudden death in young immigrants from Southeast Asia.
For natives, it is known as during sleep) in Thailand,
lai tai
(death
bangungut (
sudden death during sleep) in the Philippines, and
pokkuri
(unexpected sudden death at night) in Japan
Brugada Syndrome
Familial disease with an autosomal dominant mode of transmission, with incomplete penetrance and an incidence ranging between 5 and 66 per 10 000 In Southeast Asia where it is endemic, it is distinguished by a male predominance (8:1 male:female ratio) and the appearance of arrhythmic events at an average age of 40 years (range: 1 to 77 years)
Brugada Syndrome
The syndrome typically manifests during adulthood, with a mean age of sudden death of 41 +/- 15 years. The youngest patient clinically diagnosed with the syndrome is 2 days old and the oldest is 84 years old
Brugada Syndrome: Report of the Second Consensus
Conference Circulation 2005
Brugada Syndrome
It is thought that it may cause 4 to 10 sudden deaths per 10,000 inhabitants in Southeast Asia annually, making it the second most common cause of natural death in men aged younger than 40 years In endemic countries, it has been estimated to cause at least 4% of all sudden deaths and at least 20% of all sudden cardiac deaths in patients with structurally normal hearts.
Orphanet Journal of Rare Diseases
2006
Brugada Syndrome
The prevalence of BrS in the general population is unknown. The suggested prevalence ranges from 5/1,000 (Caucasians) to 14/1,000 (Japanese) In Laos, it causes an estimated 1 sudden death per 1000 inhabitants per year, and in Thailand, unexpected sudden death is the most common cause of natural death in young people
Brugada Syndrome
It has been linked to a genetic mutation located on the SCN5A gene on chromosome 3 p21-23, which codes for the α subunit of the cardiomyocyte sodium ion channels This mutation leads to either complete loss of channel function or an accelerated recovery from activation This can generate heterogeneity of repolarization and increase the chance of intramyocardial re-entry circuits, which may induce ventricular tachyarrhythmias
Genetic mutations detected so far in the Brugada syndrome result in defective myocardial sodium channels that reduce sodium inflow currents, resulting in shorter than-normal action potentials
Brugada Syndrome
It can also present atrial fibrillation, which is present in 10% to 20% of cases Potential clinical manifestations dizziness, palpitations, syncope, and sudden cardiac death ECG abnormalities constitute the hallmark of Brugada syndrome
Circadian pattern
VF and sudden death in Brugada syndrome usually occur at rest and at night
Modulating and precipitating factors
The ECG manifestations of congenital Brugada syndrome are often concealed but can be unmasked or modulated by: Sodium channel blockers, a febrile state, vagotonic agents, alpha and beta adrenergic agonists, tricyclic or tetracyclic antidepressants, a combination of glucose and insulin, hyperkalemia, hypokalemia, hypercalcemia, and alcohol and cocaine toxicity
Brugada Syndrome
Electrocardiographic Characteristics The J wave is a deflection that appears in the ECG as a late delta wave following the QRS or as a small secondary R wave (R'). Also referred to as the Osborn wave
Brugada Syndrome
Electrocardiographic Characteristics
Type1 is characterized by a prominent coved ST-segment elevation displaying J wave amplitude or ST segment elevation 2 mm or 0.2 mV at its peak followed by a negative T-wave, with little or no isoelectric separation
Proposed Diagnostic Criteria for the Brugada Syndrome: Consensus
Report Circulation 2002
Brugada Syndrome
Brugada Syndrome
Electrocardiographic Characteristics Type 2 also has a high take-off STsegment elevation, but in this case, J wave amplitude (2 mm) gives rise to a gradually descending ST-segment elevation (remaining 1 mm above the baseline), followed by a positive or biphasic T-wave that results in a saddle back configuration
Proposed Diagnostic Criteria for the Brugada Syndrome: Consensus Report
Circulation
2002
Brugada Syndrome
Electrocardiographic Characteristics Type 3 is a right precordial ST segment elevation of 1 mm of saddle back type, coved type, or both
Proposed Diagnostic Criteria for the Brugada Syndrome: Consensus Report
Circulation
2002
Brugada Syndrome
Proposed Diagnostic Criteria for the Brugada Syndrome: Consensus Report
Circulation
2002
Brugada Syndrome: Report of the Second Consensus Conference
Circulation 2002
It can be established in the presence of: ST-segment elevation (type 1) in more than one right precordial lead (V1 to V3), and one of the following: Documented ventricular fibrillation; self terminating polymorphic ventricular tachycardia; a family history of sudden cardiac death (<45 years); coved type ECGs in family members; electrophysiological inducibility; syncope There should be no other factors that can account for the ECG abnormality
Brugada Syndrome: Report of the Second Consensus Conference
Appearance of type 2 ST-segment elevation ("saddleback type") in more than one right precordial lead upon challenge with a sodium channel blocker. A drug-induced ST-segment elevation to a value >2 mm should raise the possibility of Brugada syndrome when one or more clinical criteria are present
Brugada Syndrome: Report of the Second Consensus Conference
Appearance of type 3 ST segment elevation in more than one lead under baseline conditions with conversion to type 1 after challenge with a sodium channel blocker is considered equivalent to case 1 above Drug-induced conversion of type 3 to type 2 is not considered diagnostic Characteristic EKG morphologies recorded within the first few hours after resuscitation cannot be taken as diagnostic
Drug Challenge
Drug challenge should be performed while the patient is continuously monitored and with defibrillator and advanced coronary life support facilities close at hand Drug administration should be stopped when the test is positive and/or when ventricular arrhythmias, including ventricular premature complexes, are evident, or when significant QRS widening (30%) is observed Type 2 and type 3 ECGs, the test is recommended to clarify the diagnosis. Conversion of a type 2 or 3 ECG to a type 1 is considered positive
Proposed Diagnostic Criteria for the Brugada Syndrome: Consensus Report Circulation 2002
Differential Diagnosis
Acute myocardial ischemia Acute myocarditis Tricyclic antidepressant overdose Cocaine intoxication Arrhythmogenic right ventricular dysplasia Long QT syndrome
Arrhythmogenic right ventricular dysplasia
Discrimination between BrS and ARVC may be particularly difficult because ARVC may at times mimic BrS Before the diagnosis Brugada syndrome is made, a serious attempt should be taken to exclude ARVC.
Drug challenge with sodium channel blockers may be useful in discriminating between these 2 disease
Proposed Diagnostic Criteria for the Brugada Syndrome: Consensus Report Circulation 2002
Long QT syndrome
There is an alteration in the function of a myocellular channel protein that regulates the potassium flux during electrical repolarization Clinical course is variable, some remain aymptomatic and some develop syncope and sudden death Risk is impacted by factors such as hypokalemia, emotional extremes, and vigorous physical activity
Long QT syndrome
involve an abnormal repolarization of the heart causes differences in the "refractoriness" of the myocytes leading to re-entrant ventricular arrhythmias
Long QT syndrome
A commonly used criterion to diagnose LQTS is the LQTS "diagnostic score“. Its based on several criteria giving points to each. With 4 or more points the probability is high for LQTS, and with 1 or less point the probability is low. Two or 3 points indicates intermediate probability.
Long QT syndrome
QTc (Defined as QT interval / square root of RR interval) – >= 480 msec - 3 points – 460-470 msec - 2 points – 450 msec and male gender - 1 point Torsade de Pointes ventricular tachycardia - 2 points T wave alternans - 1 point Notched T wave in at least 3 leads - 1 point Low heart rate for age (children) - 0.5 points Syncope (one cannot receive points both for syncope and Torsades de pointes) – With stress - 2 points – Without stress - 1 point Congenital deafness - 0.5 points Family history (the same family member cannot be counted for LQTS and sudden death) – Other family members with definite LQTS - 1 point – Sudden death in immediate family (members before the age 30) - 0.5 points
Long QT syndrome
Long QT syndrome
Beta blockers are the first choice in treating Long QT syndrome The only effective form of arrhythmia termination in individuals with LQTS is placement of an implantable cardioverter-defibrillator (ICD). ICD are commonly used in patients with syncopes despite beta blocker therapy, and in patients who have experienced a cardiac arrest.
Brugada: Risk stratification
Brugada et al found that patients initially presenting with aborted sudden death are at the highest risk for a recurrence (69%) Those presenting with syncope and a spontaneously appearing type 1 ECG have a recurrence rate of 19% Men had a 5.5-fold higher risk of sudden death than did women
Brugada Syndrome
Indication for ICD implantation Brugada Syndrome Report of the Second Consensus Conference
Endorsed by the Heart Rhythm Society and the European Heart Rhythm Association
Brugada Syndrome
Indication for ICD implantation Brugada Syndrome Report of the Second Consensus Conference
Endorsed by the Heart Rhythm Society and the European Heart Rhythm Association
Outcome After Implantation of a Cardioverter Defibrillator in Patients With Brugada Syndrome A Multicenter Study Circulation 2006 In this large Brugada syndrome population, a low incidence of arrhythmic events was found, with an annual event rate of 2.6% during a follow-up of 3 years Device-related complications (8.9%/year). Inappropriate shocks were 2.5 times more frequent than appropriate ones
Efficacy of Quinidine in High-Risk Patients With Brugada Syndrome
Bernard Belhassen, MD; Aharon Glick, MD; Sami Viskin, MD Circulation 2004 Quinidine depresses an important role in the arrhythmogenesis of this disease I to current, which may play It prevented VF induction in 22 of the 25 patients (88%) The effective quinidine serum blood levels rangedfrom 1.29 to 5.2 mg/L (meanSD, 2.650.99 mg/L)
Quinidine
May exert its beneficial effects in Brugada syndrome by inhibiting electrical homogeneity I to, thereby restoring In addition, quinidine prolongs ventricular refractoriness Finally, the anticholinergic effect of quinidine might contribute to its antiarrhythmic efficacy in the Brugada syndrome Despite these hypotheses, the basis for quinidine efficacy in this setting remains to be elucidated
Study shows the following: First, quinidine is highly effective (88% success rate) for preventing VF induction in patients with inducible VF Second, it also appears to be effective in preventing spontaneous VF, with no arrhythmic events observed during a mean SD follow-up of 56-67 months
Third, the drug could be chronically tolerated with therapeutic effectiveness in 16 study patients (64%) Fourth, no proarrhythmic event occurred in any treated patient despite QT prolongation. Finally, although quinidine related side effects (thrombocytopenia, diarrhea, esophagitis, allergic reaction, aggravation of sinus node dysfunction) were common, they were always transient and invariably resolved after drug discontinuation