LONG Q-T SYNDROME – A PRACTICAL INSIGHTLONG Q-T SYNDROME – A PRACTICAL INSIGHTVERCO P.J.W.VERCO P.J.W.

B.D.S., B.Sc.Dent.(Hons), M.D.S., F.A.A.P.D., F.P.F.A., M.R.A.C.D.S.,F.I.C.D.B.D.S., B.Sc.Dent.(Hons), M.D.S., F.A.A.P.D., F.P.F.A., M.R.A.C.D.S.,F.I.C.D.NORTH ADELAIDE MEDICAL CENTRE NORTH ADELAIDE MEDICAL CENTRE

SOUTH AUSTRALIA 5006 SOUTH AUSTRALIA 5006 AUSTRALIAAUSTRALIA

EAPD JUNE 2008, DUBROVNIC, CROATIA.EAPD JUNE 2008, DUBROVNIC, CROATIA.PTPI SEPTEMBER 2008, PRETORIA, SOUTH AFRICAPTPI SEPTEMBER 2008, PRETORIA, SOUTH AFRICA

AmAPD MAY 2009 HONOLULU, HAWAI’I U.S.AAmAPD MAY 2009 HONOLULU, HAWAI’I U.S.AEAPD JUNE 2010, HARROGATE, UNITED KINGDOM.EAPD JUNE 2010, HARROGATE, UNITED KINGDOM.

ANZSPD AUGUST 2011, ULURU, AUSTRALIA.ANZSPD AUGUST 2011, ULURU, AUSTRALIA.EAPD JUNE 2014, SOPOT, POLAND.EAPD JUNE 2014, SOPOT, POLAND.

AusAPD AUGUST 2016, BRISBANE, AUSTRALIA AusAPD AUGUST 2016, BRISBANE, AUSTRALIA

AUSTRALIAN INVENTIONSAUSTRALIAN INVENTIONS1926 ELECTRONIC HEART PACEMAKER1928 ROYAL FLYING DOCTOR SERVICE1940-50 BEGG OTHODONTICS1945 LATEX GLOVES (1964 FOR SURGERY)1950 SCHOOL OF THE AIR1968 POLYVALENT SNAKE ANTI VENOM1969 RELAYED MOON LANDING TO WORLD1979 BIONIC EAR1984 IN VITRO FERTILIZATION1992 MULTI FOCAL CONTACT LENS 1999 DAY / NIGHT CONTACT LENS1996 Wi-Fi

NOBEL LAUREATES (AUS 11) (SA 5) INCLUDING:

1915 SIR WILLIAM BRAGG, and LAWRENCE BRAGG ( age 25 yrs )1945 LORD FLOREY - PENICILLIN2005 PROF ROBIN WARREN / BARRY MARSHALL HELICOBACTER PYLORI

ALSO BLACK BOX FLIGHT RECORDER / ILS / OVER HORIZON RADAR (JINDALEE PROJECT)

LONG Q-T SYNDROMELONG Q-T SYNDROME

Variable AETIOLOGY includes:Variable AETIOLOGY includes:• CONGENITAL (cLQTS): disorder of variable penetrance and gene CONGENITAL (cLQTS): disorder of variable penetrance and gene

location location • ACQUIRED (aLQTS):Prescription medications e.g. Antibiotics, ACQUIRED (aLQTS):Prescription medications e.g. Antibiotics,

ADHD drugs,ADHD drugs, decongestants ,general anaesthetic agents.decongestants ,general anaesthetic agents.• “Triggers” of EXERCISE/STRESS /SOUND /LIGHTTriggers” of EXERCISE/STRESS /SOUND /LIGHT

The Long Q-T Syndrome (LQTS) is a congenital electrical malfunction of The Long Q-T Syndrome (LQTS) is a congenital electrical malfunction of an otherwise normal functioning heart.an otherwise normal functioning heart.30 – 40% of deaths are at the first event in “asymptomatic patients”.30 – 40% of deaths are at the first event in “asymptomatic patients”.3000 to 4000 sudden deaths in USA per annum.3000 to 4000 sudden deaths in USA per annum.60 sudden deaths – Australia per annum, attributable to Long Q-T60 sudden deaths – Australia per annum, attributable to Long Q-T

HISTORY OF LONG Q-T HISTORY OF LONG Q-T SYNDROMESYNDROME

• 1856 Meissner – Collapse and death of deaf-mute schoolgirl. Two brothers in the same family also died.died.

Taubstummheit and Taubstummenbildung, Leipzig and Heidelberg

• 1957 “Jervell and Lange-Nielson Syndrome” LQTS with congenital deaf–mutism. Inherited autosomal recessiveautosomal recessive trait. Rare< 100 worldwide. (5% Aug 2011)

(Am.Heart J. 1957 Jul; 54(1):59-69).[Now 2 mutations on opposite Chromosomes LTQ1 LTQ5]

• 1963/4 “Romano–Ward Syndrome” LQTS not associated with deafness Genetic transmission autosomal dominantautosomal dominant.4genes

1980 Schwarz – LQTS could include patients with 1980 Schwarz – LQTS could include patients with normal Q-Tnormal Q-T..

1992 “Brugada Syndrome” patients with right bundle branch block, and S-T elevation.1992 “Brugada Syndrome” patients with right bundle branch block, and S-T elevation. Idiopathic polymorphic ventricular tachycardia. (M>F)Idiopathic polymorphic ventricular tachycardia. (M>F)

1998 Schwarz-ECG’S 34,442 neonates: 34 deaths, 1998 Schwarz-ECG’S 34,442 neonates: 34 deaths, 24 SIDS with LQTS

2003 Fukushige et al found prevalence 1:1100–3000 in developed countries.2003 Fukushige et al found prevalence 1:1100–3000 in developed countries.

OTHER CORRELATIONSOTHER CORRELATIONS• Andersen-Tawil Syndrome (ATS) – Long QT7 • Caused by mutations of gene KCNJ2. It is a disorder of cellular repolarisation. Micrognathia,clinodactyly,scoliosis.

• Timothy Syndrome (TS) - Long QT8 Cardiac arrhythmias, webbing of fingers and toes, cognitive abnormalities and autism.

• Sudden Infant Death Syndrome(SIDS) – ? LQT Now asphyxia amyloid precursor protein found (16 April 2014) • Incidence in infants 1-12 months old is 1-2:1000.

• 9.4% of SIDS had a genetic variant. (Schwarz 2007)

CLINICAL PARAMETERSCLINICAL PARAMETERSPenetrance of different ethnic groups not clarified.Penetrance of different ethnic groups not clarified.Range 1:1000 to 1:7000 (Vincent 2000)Range 1:1000 to 1:7000 (Vincent 2000)Now considered 1:2500 (Crotti 2005)Now considered 1:2500 (Crotti 2005)Distribution LQTI (41%), LQT2 (45%), LQT3 (7%)Distribution LQTI (41%), LQT2 (45%), LQT3 (7%)

LQTS associated with 6 different genetic mutations on:LQTS associated with 6 different genetic mutations on:11 (LQT1), 7 (LQT2), 3 (LQT3), 21 (LQT5) 11 (LQT1), 7 (LQT2), 3 (LQT3), 21 (LQT5) 4 (LQT4) – gene not yet identified.4 (LQT4) – gene not yet identified.Mutations in 8 different Sarcolemmal ion channel subunit Mutations in 8 different Sarcolemmal ion channel subunit genes have been identifiedgenes have been identified(Bezzina 2005(Bezzina 2005))About 300 different genetic mutations have now been found.About 300 different genetic mutations have now been found.

Q-T Interval varies with Q-T Interval varies with HEART RATE HEART RATE and is and is CORRECTEDCORRECTED for heart rate (QTc) for heart rate (QTc) AGEAGE GENDERGENDERUpper limits QTc interval is males > 430ms, females >450ms, children>440ms.Upper limits QTc interval is males > 430ms, females >450ms, children>440ms.Formula QTc = Formula QTc = Observed Q-T (QTo)Observed Q-T (QTo) (In milliseconds) (In milliseconds)

√ √R - RR - R

PREVALENCEPREVALENCE

GENETIC STUDIES GENETIC STUDIES

MEASUREMENTMEASUREMENT

CLINICAL PARAMETERSCLINICAL PARAMETERS

Potent stimuli include laryngoscopy, intubation,Potent stimuli include laryngoscopy, intubation,extubation, pack removal.extubation, pack removal.

Hypothermia prolongs the Q-T interval.Hypothermia prolongs the Q-T interval.

QTc is prolonged by:QTc is prolonged by:

Inhalation agents:Inhalation agents:- Sevoflurane- Sevoflurane- Isoflurane - Isoflurane - Enflurane- Enflurane

IV Agents:IV Agents:- Thiopental (but decreased with Propofol)- Thiopental (but decreased with Propofol)- Midazolam is safe - Midazolam is safe Neuromuscular blocking drugsNeuromuscular blocking drugs- Succinylcholine - Succinylcholine

Anticholinesterases- Atropine and glycopyrrolateAnticholinesterases- Atropine and glycopyrrolate Antireflux - CisaprideAntireflux - Cisapride

Long Q-T and ANAESTHESIALong Q-T and ANAESTHESIA

Dr Alistair MILLER RFDSDr Alistair MILLER RFDS

CLINICAL PARAMETERSCLINICAL PARAMETERS

Examples of those which may prolong Q-T:Examples of those which may prolong Q-T:

• Some sports drinks containing caffeine, even grapefruit juiceSome sports drinks containing caffeine, even grapefruit juice

• Meridia – appetite suppressantMeridia – appetite suppressant

• Sudafed – decongestant / asthmaSudafed – decongestant / asthma

• Ritalin – CNS Stimulant / ADHDRitalin – CNS Stimulant / ADHD

• Ventolin – bronchodilator / asthmaVentolin – bronchodilator / asthma

• Erythromycin, azithromycin, metronidazole – antibioticErythromycin, azithromycin, metronidazole – antibiotic

• Sotalol – anti arrhythmicSotalol – anti arrhythmic

Others include anticancer drugs, migraine medications, antivirals, Others include anticancer drugs, migraine medications, antivirals, antihistamines, antidepressants, antimalarials.antihistamines, antidepressants, antimalarials.

Long Q-T and PRESCRIPTION DRUGSLong Q-T and PRESCRIPTION DRUGS

LONG QTc AGE GENDERLONG QTc AGE GENDER

QTc, AGE, GENDER 1-15yrs Adult Male Adult FemaleNormal <0.44 <0.43 <0.45Borderline <0.44-0.46 0.43- 0.45 0.45 - 0.47Prolonged >0.47 >0.46 >0.48

LONG QTc AND GENETICSLONG QTc AND GENETICS

LQT1 LQT2 LQT3 Gene Chromosome

KvLQT 11p15.5

HERG 7q35-q36

SCN5A 3p21

Current IKs IKr INa

Events <40yrs Age 1st event

63% 9yr

46% 12yr

18% 16yr

T pattern Broad, tall Late T-U Late

Heart rate High High Low

Trigger Exercise Mixed Rest

E C GE C GNormal QTNormal QT

QT with T-wave AberrationsQT with T-wave AberrationsChromosome AbnormalitiesChromosome Abnormalities

Corrected ECG Corrected ECG LQTcLQTcLong QT 530ms QTc 507ms

CHROMOSOME 11 CHROMOSOME 7 CHROMOSOME 3CHROMOSOME 11 CHROMOSOME 7 CHROMOSOME 3

E C GE C G

GENETIC INHERITANCEGENETIC INHERITANCE

INHERITED LQTINHERITED LQTApril 2008April 2008

Died at Died at 21y 21 21y 21 daysdays

Of Of meningitismeningitis

SCD at 12ySCD at 12yOn 1/2/08On 1/2/08

LBBBLBBBDCMPDCMP

?SCD at ?SCD at 21y21y

?SIDS at ?SIDS at 2y2y

I DegreeI DegreeA-V blockA-V blockdied at died at age 9yage 9y

All died before age 1yAll died before age 1yCause—not knownCause—not known

PROBABILITY – BASE CRITERIAPROBABILITY – BASE CRITERIAClinical & ECG (Schwarz)Clinical & ECG (Schwarz)

ECGECG

(Without medications or disorders known to effect ECG features)(Without medications or disorders known to effect ECG features)

QTc > 480ms QTc > 480ms (3 Points)(3 Points)QTc 460-470ms QTc 460-470ms (2 Points)(2 Points)QTc 450ms QTc 450ms (1 Point)(1 Point)Torsade de pointes (mutually exclusive)Torsade de pointes (mutually exclusive) (2 Points)(2 Points)T wave alternans T wave alternans (1 Point)(1 Point)Notched T Wave in 3 leads Notched T Wave in 3 leads (1 Point)(1 Point)Low Resting heart rate for ageLow Resting heart rate for age (0.5 Point)(0.5 Point)

CLINICALCLINICAL Syncope with stressSyncope with stress (2 Points)(2 Points)Syncope without stressSyncope without stress (1 Point)(1 Point)Clinical deafnessClinical deafness (0.5 Point)(0.5 Point)

FAMILY FAMILY HISTORYHISTORY

Family member with LQTSFamily member with LQTS (1 Point)(1 Point)Unexplained cardiac death in familyUnexplained cardiac death in family (0.5 Point)(0.5 Point)

Maximum is 9 : Score of >3 = High Probability of LTQSMaximum is 9 : Score of >3 = High Probability of LTQS

DENTAL APPLICATIONDENTAL APPLICATIONMorbidity associated with a failure to recognise and refer symptomatic patients before dental treatment Morbidity associated with a failure to recognise and refer symptomatic patients before dental treatment cannot be over emphasized. cannot be over emphasized. However, with 30% - 40% of LQTS expressing normal phenotype (Vincent 2005) the first fatal arrhythmic However, with 30% - 40% of LQTS expressing normal phenotype (Vincent 2005) the first fatal arrhythmic episode in the 21st century would appear soul-destroying to any family.episode in the 21st century would appear soul-destroying to any family.

LQTS accounts for 19% of deaths in 1-13 year old children. LQTS accounts for 19% of deaths in 1-13 year old children. And 30% of deaths in 14-21 year old children (And 30% of deaths in 14-21 year old children (AntzelevitchAntzelevitch 2001) 2001)

•Family history fainting/sudden deathsFamily history fainting/sudden deaths

•Family history of heart diseaseFamily history of heart disease

•Previous history: Fainting,dizziness, palpitations, Previous history: Fainting,dizziness, palpitations, chest painchest pain

•Congenital deafnessCongenital deafness

•Medications causing metabolic imbalanceMedications causing metabolic imbalance

-Eating disorder…anorexia nervosa,low K+Eating disorder…anorexia nervosa,low K+

-VomitingVomiting

-DiarrhoeaDiarrhoea

-HIV / HepatitisHIV / Hepatitis•Medications include methadone (Medications include methadone (LipskiLipski et al 1973) et al 1973)•Drugs cocaine, ecstasy, alcoholDrugs cocaine, ecstasy, alcohol

HISTORYHISTORY

DENTAL APPLICATIONDENTAL APPLICATION

Does this patient have LQTS:Does this patient have LQTS:•If LQTS is it If LQTS is it acquiredacquired or or congenitalcongenitalHow should it be assessed:How should it be assessed:•ECG 12 lead/EEG/genetic testing/ K+ ECG 12 lead/EEG/genetic testing/ K+ supplement/fish oil.supplement/fish oil.•Non exercise stress test..epinehrine.Non exercise stress test..epinehrine.•Risks of life and life-style.Risks of life and life-style.•How is patient managed.How is patient managed.•How is family advised.How is family advised.

Stress, exams, even sleep.

Noise e.g. bells, horn, alarm clock, anger & crying.

Exercise: hockey, rowing & football...

Undiagnosed syncope.

Faint before, during or after stress.

CLINICAL ASSESSMENTCLINICAL ASSESSMENT SIGNSSIGNS

EVENTS TRIGGERING LQTSEVENTS TRIGGERING LQTS

PATIENT PROFILESPATIENT PROFILES

Child, male aged 9 years presented from Millicent (3.5 hours from Adelaide) for aChild, male aged 9 years presented from Millicent (3.5 hours from Adelaide) for aconsultation with a view to dental treatment the following day at Calvary Hospital Adelaide,consultation with a view to dental treatment the following day at Calvary Hospital Adelaide,12th March 2007.12th March 2007.At the time of treatment, under general anaesthesia, a Long Q-T was recognised on the ECG monitor. At the time of treatment, under general anaesthesia, a Long Q-T was recognised on the ECG monitor. The dental treatment and anaesthetic procedure fortunately did not ‘trigger’ an unpredictableThe dental treatment and anaesthetic procedure fortunately did not ‘trigger’ an unpredictableeventful situation.eventful situation.The patient was referred back to their local medical General Practitioner for further investigationThe patient was referred back to their local medical General Practitioner for further investigationwhich they attended on 19th March 2007.which they attended on 19th March 2007.

The patient was not referred further to a Cardiologist. Fortunately the child is still alive. (April 2009) The patient was not referred further to a Cardiologist. Fortunately the child is still alive. (April 2009)

Comment THE BLACK SWANComment THE BLACK SWAN1.The child should have gone to a Cardiologist for assessment of LQTc.1.The child should have gone to a Cardiologist for assessment of LQTc.2.Unless LQTc is assessed with heart rate, LTQ can look normal.2.Unless LQTc is assessed with heart rate, LTQ can look normal.3.There may be denial that a problem exists by doctor or patient, 3.There may be denial that a problem exists by doctor or patient, or bothor both

Note: Note: www.cairdtechnology.comwww.cairdtechnology.comfor Nomogram for measured Q-T and heart rate.for Nomogram for measured Q-T and heart rate.

CASE 1CASE 1

PATIENT PROFILESPATIENT PROFILES

Adult male aged 62 died while rowing a 1000 metre Masters’ Race in Adelaide. Adult male aged 62 died while rowing a 1000 metre Masters’ Race in Adelaide. Being an ‘old oarsman’ he consumed a good lunch of pizza and a bottle of wine before the race.Being an ‘old oarsman’ he consumed a good lunch of pizza and a bottle of wine before the race.Upon a few minutes of exhaustive exercise ‘he failed to proceed’ over the finish line.Upon a few minutes of exhaustive exercise ‘he failed to proceed’ over the finish line.

CommentCommentThe family had a history of cardiac disease. The family had a history of cardiac disease. Denial was assessed - ‘If I don’t find out whether I have a problem, then I haven’t got a problem’Denial was assessed - ‘If I don’t find out whether I have a problem, then I haven’t got a problem’ Or Or ‘If it’s not broke(n) don’t fix it’ (Australian expression) (Australian expression)

“Outback Australia”

Past-President International Federation

of Dental Health Educators

Emeritus Prof.Johann deVries

CASE 2CASE 2

PATIENT PROFILESPATIENT PROFILES

Child, male, age 14, was at rowing training in the under 15 year ‘fours’, 1500m.Child, male, age 14, was at rowing training in the under 15 year ‘fours’, 1500m.This child was an adoptee from Thailand, so little of his medical history was known, and certainly notThis child was an adoptee from Thailand, so little of his medical history was known, and certainly notthat of his extended family.that of his extended family.

This boy always rowed ‘bow’ in the boat and it was customary for him to slump backwards at the endThis boy always rowed ‘bow’ in the boat and it was customary for him to slump backwards at the endof a race and let others row back to the bank of the river. of a race and let others row back to the bank of the river. (Or was this a series of ‘recovered’ events) On his final row, he did not recover his colleagues felt he(Or was this a series of ‘recovered’ events) On his final row, he did not recover his colleagues felt hehad ‘cried wolf’ once too often.had ‘cried wolf’ once too often.

Coroners diagnosis was cardiomyopathy but later confirmed as Long Q-T.Coroners diagnosis was cardiomyopathy but later confirmed as Long Q-T.

CommentComment1.Should sportsmen of extreme sports be ECG Tested as a matter of course.1.Should sportsmen of extreme sports be ECG Tested as a matter of course.2.Combination of exercise, stress, heat and electrolyte depletion can exacerbate a ‘normal’ existence.2.Combination of exercise, stress, heat and electrolyte depletion can exacerbate a ‘normal’ existence.

CASE 3

PATIENT PROFILESPATIENT PROFILES

Female born 1 October 1998. QT not particularly long, does not shorten with exercise,Female born 1 October 1998. QT not particularly long, does not shorten with exercise,echocardiogram normal. Holter monitor showed higher degree of A-V only for shortechocardiogram normal. Holter monitor showed higher degree of A-V only for shortperiods of time. (Patients can develop second degree A-V block during sleep). periods of time. (Patients can develop second degree A-V block during sleep).

Family tree see above.Family tree see above.There is a need to find out There is a need to find out mode of death of seven other family membersmode of death of seven other family members and investigate and investigateappropriately whether she is at risk form bradycardia or tachycardia.appropriately whether she is at risk form bradycardia or tachycardia.There is evidence of some abnormality in the Q-T interval with an abnormal responseThere is evidence of some abnormality in the Q-T interval with an abnormal responseto exercise and most of these patients who have syncopal episodes will have rapidto exercise and most of these patients who have syncopal episodes will have rapidventricular tachycardia going onto ventricular fibrillation and death. So obviously theventricular tachycardia going onto ventricular fibrillation and death. So obviously themost appropriate treatment in that setting would be the insertion of a defibrillator,most appropriate treatment in that setting would be the insertion of a defibrillator,quite a different procedure to that of an A-V block where the primary diagnosisquite a different procedure to that of an A-V block where the primary diagnosisprophylactic pacing may be a considered option. prophylactic pacing may be a considered option.

CASE 4CASE 4

CASE 5CASE 5Male 28 years old ,no previous medical history ,died in his sleep.Male 28 years old ,no previous medical history ,died in his sleep.

PATIENT PROFILE PATIENT PROFILE Case 6Case 6

LONG QTc and GENETICS and THE LAWLONG QTc and GENETICS and THE LAWCost of Genetic testingCost of Genetic testing Not from Federal Funds but genetic service budget! LTQS $3500 LTQS $3500

(A/ Prof Julie McGoughran Mar 2011).

2003 6yrs old 2003 6yrs old ““Man-of-the-match”, felt ill / pale Man-of-the-match”, felt ill / pale →→hospital. . No arrhythmia ECG LQTc 530msECG LQTc 530ms.

Brother 3yrs old in 1989Brother 3yrs old in 1989 Collapsed while running, child died, police alleged child abuse. Family engaged QC – allegation inconclusive.

MotherMother ““Funny feelings”, anxiety, stress and drug reactions over years.Funny feelings”, anxiety, stress and drug reactions over years.- Her ECG with son in hospital – prolonged - Her ECG with son in hospital – prolonged QTQT then back to normal. then back to normal. - Her exercise test and IV isoprenalone prolonged QT again - - Her exercise test and IV isoprenalone prolonged QT again - LQTc600ms.LQTc600ms.

AuntAunt - Had child die of SIDS 15months , age 20yrs ago.- Had child die of SIDS 15months , age 20yrs ago. - She had blackouts with car accident.- She had blackouts with car accident. - Also - Also blackout at the dentistblackout at the dentist… misdiagnosed with … misdiagnosed with epilepsy.epilepsy.

Maternal Cousin Maternal Cousin -10 yr. old boy, dived into pool & blacked out.-10 yr. old boy, dived into pool & blacked out.- Resuscitated in hospital, history of blackouts at the movies. - Resuscitated in hospital, history of blackouts at the movies. - Treated for - Treated for epilepsyepilepsy for 3yrs. for 3yrs.

Cousin Cousin Now has baby daughter – reacted badly to Cisapride Now has baby daughter – reacted badly to Cisapride ECG – LQTc ECG – LQTc (A/Prof Dorothy Radford Mar 2011)(A/Prof Dorothy Radford Mar 2011)

TREATMENTTREATMENTThe aim of treatment is to achieve longevity of patients and professional awareness of LTQS.The aim of treatment is to achieve longevity of patients and professional awareness of LTQS.Familial traits and tendencies, and an understanding of genetic mutations is required also.Familial traits and tendencies, and an understanding of genetic mutations is required also.

•Paediatric Cardiologist •Geneticist•Psychologist / Psychiatrist•Social Worker

•An understanding of dizziness, weakness or blurring vision should be signs of a problem.

•The wearing of a ‘Medic Alert’ bracelet may be helpful.

•Automated external defibrillator ( Phillips HeartStart Home Defibrillator)

•Family members should be aware of CPR to assist. (ABCD) (now DRABC)

•Avoid - household loud noises eg door bells, phones, alarm clocks, buzzers - public loud noises eg concerts

•Never swim alone, surf or water-ski.

•Be aware of medicinals which prolong Q-T. www.qtdrugs.org The University of Arizona, College of Pharmacy

SELF HELPSELF HELP

COUNSELINGCOUNSELING

TREATMENTTREATMENT•Eliminate drug–induced LQTS•Beta blockers prevent dangerously fast heart beats (>130bpm) 95% of LQTS is suppressed by the use of BETA BLOCKERS. Compliance is critical. Stopping suddenly can result in an adrenergic rebound arrhythmia. •Potassium supplementation may be helpful in shortening some LQTs.•Electrolyte imbalance:

HypokalemiaHypocalcaemiaHypomagnesemia

•Medical devices:Artificial pacemakerAutomated Intracardiac Cardioverter – defibrillator (AICD)Left cervical sympathectomy

•Restriction of water sports: no swimming, scuba diving or water-skiing,wind-surfing.•Restriction of competitive sports e.g. rowing, tennis, basketball, squash, football. (Aussie Rules!)….even cricket!

SUPPORT GROUPSSUPPORT GROUPSSUPPORT GROUPSSUPPORT GROUPS

Sites include :Sites include :

www.heartkids.org.auwww.heartkids.org.auRoyal Children’s Hospital Royal Children’s Hospital Melbourne, AustraliaMelbourne, Australia

www.qtsyndrome.chwww.qtsyndrome.chThe European LQTS Information CentreThe European LQTS Information Centre

The Web provides us with a ‘Flat Earth’, emails and the electronic sharingThe Web provides us with a ‘Flat Earth’, emails and the electronic sharingof information through Blogs, You Tube etc. of information through Blogs, You Tube etc. To wait for the printed journals by the profession seems short-sighted inTo wait for the printed journals by the profession seems short-sighted intoday’s fast moving environment.today’s fast moving environment.

www.qtdrugs.orgCollege of PharmacyThe University of Arizonawww.c-r-y.org.ukwww.c-r-y.org.ukCardiac Risk in the YoungCardiac Risk in the Youngwww.sads.org.au www.sads.org.au Sudden Arrhythmic Death Syndrome Sudden Arrhythmic Death Syndrome (SADS)(SADS)

CONCLUSIONCONCLUSION

To date some 300 genetic variants of LQTS have been documented. To date some 300 genetic variants of LQTS have been documented. 30% to 40% of cases are asymptomatic. 30% to 40% of cases are asymptomatic. There is now an International Q-T Registry (36th Anniversary) of 1200There is now an International Q-T Registry (36th Anniversary) of 1200families and 7000 family members.families and 7000 family members.

In researching the literature there is a more bizarre In researching the literature there is a more bizarre Short QT (1999)Short QT (1999) of ofwhich sofar, some 20 cases have been reported. which sofar, some 20 cases have been reported. Rarely fatal.Rarely fatal.

Paediatric Dental Care should have an holistic approach. The aim of thisPaediatric Dental Care should have an holistic approach. The aim of thispaper has been to bring to the attention of the profession LQTS.paper has been to bring to the attention of the profession LQTS.

It is probable that we have not been informed as our learned teachers inIt is probable that we have not been informed as our learned teachers inthe profession have not come across such cases.the profession have not come across such cases.

POLITICAL ADVANCEMENTPOLITICAL ADVANCEMENT

In 2009 Dentistry is 2In 2009 Dentistry is 2ndnd only to McDonalds in getting repeat business ( BRW ) only to McDonalds in getting repeat business ( BRW )Could we be LEADERS and have an holistic approach to DENTISTRY and promoteCould we be LEADERS and have an holistic approach to DENTISTRY and promote

EARLY CARDIAC SCREENING OF NEONATESEARLY CARDIAC SCREENING OF NEONATES

The The United States of America United States of America has a “Head Start” Programme launched in 1965has a “Head Start” Programme launched in 1965for children aged birth to 5 years, including pregnant women and their families. for children aged birth to 5 years, including pregnant women and their families. ““Early Head Start” was launched in USA 1994.Early Head Start” was launched in USA 1994.

In the In the UKUK Children’s care has been improved with the “Sure Safe” Programme Children’s care has been improved with the “Sure Safe” Programmesince 1999 for infants and children (0-3 years).since 1999 for infants and children (0-3 years).

2014 Australia, Child Dental Benefit Scheme ( Means tested)2014 Australia, Child Dental Benefit Scheme ( Means tested)

2016 CDBS - ?Dead in Bed2016 CDBS - ?Dead in Bed

DENTAL APPLICATIONDENTAL APPLICATION LQTS – 19% of deaths in children 1-13y.o LQTS – 19% of deaths in children 1-13y.o

and 30% of deaths in children 14-21y.o (Autzelevitch 2001)and 30% of deaths in children 14-21y.o (Autzelevitch 2001)AETIOGOLYAETIOGOLY • GENETIC disorder of variable penetrance and gene location.GENETIC disorder of variable penetrance and gene location.

•ACQUIRED eg Antibiotics / antifungals/ antivirals/ antimalarials/ anaesthetics/ ACQUIRED eg Antibiotics / antifungals/ antivirals/ antimalarials/ anaesthetics/ antiarrhythmics/ antidepressants/ ADHD drugs/ antihistamines/decongestants.antiarrhythmics/ antidepressants/ ADHD drugs/ antihistamines/decongestants.

•““TRIGGERS” of stress ,sound,light.TRIGGERS” of stress ,sound,light.

TREATMENTTREATMENT •Beta Blockers – 95% LTQS suppressedBeta Blockers – 95% LTQS suppressed

•PacemakerPacemaker

•Automated Intracardiac Cardioverter – defibrillator (AICD)Automated Intracardiac Cardioverter – defibrillator (AICD)

CASE ICASE I Male 9 years, LQ-T under General Anaesthesia, uneventful. Med. GP would not refer for Male 9 years, LQ-T under General Anaesthesia, uneventful. Med. GP would not refer for further tests.further tests.

CASE IICASE II Adult Male 62 yrs, family history cardiac disease. 1000m Masters Rowing. Died.Adult Male 62 yrs, family history cardiac disease. 1000m Masters Rowing. Died.

CASE IIICASE III Male 15 years, 1500m rowing. Repeated events of fainting. Died.Male 15 years, 1500m rowing. Repeated events of fainting. Died.

CASE IVCASE IV Female with Cardiac HISTORY, 11 children: 2 lived, 7 died before 1yr LQT? 2 died of Female with Cardiac HISTORY, 11 children: 2 lived, 7 died before 1yr LQT? 2 died of other problems (meningitis and A-V Block).other problems (meningitis and A-V Block).

CASE VCASE V Male 28 years, died in sleep.Male 28 years, died in sleep.

CASE VICASE VI Long Q-T Genetics and Legal Complications….child abuse ! Long Q-T Genetics and Legal Complications….child abuse !

VERCO P.J.W.VERCO P.J.W.B.D.S.,B.Sc.Dent.(Hons),M.D.S.,F.A.A.P.D.,F.P.F.A.,M.R.A.C.D.S.,F.I.C.DB.D.S.,B.Sc.Dent.(Hons),M.D.S.,F.A.A.P.D.,F.P.F.A.,M.R.A.C.D.S.,F.I.C.D..

NORTH ADELAIDE MEDICAL CENTRE NORTH ADELAIDE MEDICAL CENTRE SOUTH AUSTRALIA 5006 SOUTH AUSTRALIA 5006

AUSTRALIAAUSTRALIAjoeverco@verco.com.au

is a congenital electrical malfunction of an otherwise normal is a congenital electrical malfunction of an otherwise normal functioning heart.functioning heart.

LONG Q-T SYNDROMELONG Q-T SYNDROME

HISTORYHISTORY

THE LONG Q-T SYNDROME – A PRACTICAL INSIGHTTHE LONG Q-T SYNDROME – A PRACTICAL INSIGHT

1856 Meissner – Collapse and death of deaf-mute schoolgirl.1856 Meissner – Collapse and death of deaf-mute schoolgirl.1957 “Jervell and Lange-Nielson Syndrome” LQTS/ deaf mutism /autosomal recessive. 1957 “Jervell and Lange-Nielson Syndrome” LQTS/ deaf mutism /autosomal recessive. 1963/4 “Romano–Ward Syndrome” LQTS / no deafness / autosomal dominant.1963/4 “Romano–Ward Syndrome” LQTS / no deafness / autosomal dominant.

PREVALENCEPREVALENCE 1:2500 (Crotti 2005) , Aust 1:1060 (Atherton 2011)1:2500 (Crotti 2005) , Aust 1:1060 (Atherton 2011)

GENETIC STUDIESGENETIC STUDIES MUTATIONS on 6 Genes: 3 (LQT3), 7(LQ-T2), 11(LQT1), 21(LQT5) MUTATIONS on 6 Genes: 3 (LQT3), 7(LQ-T2), 11(LQT1), 21(LQT5) 300 plus, different mutations.300 plus, different mutations.

MEASUREMENTMEASUREMENT Q-T Varies with heart rate and is CORRECTED (QTc) Q-T Varies with heart rate and is CORRECTED (QTc)

FORMULA QTc = observed FORMULA QTc = observed Q-T(LQTo)Q-T(LQTo) in milliseconds. in milliseconds. √ R-R√ R-R

MEDICAL HEALTH SCIENCE MEDICAL HEALTH SCIENCE BUILDING ADELAIDE 2016BUILDING ADELAIDE 2016