2007 rieti, convegno regionale, quale terapia nelle channelopatie
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The document discusses risk stratification and treatment approaches for channelopathies. It describes how risk is stratified based on factors like prior cardiac arrest, spontaneous sustained ventricular tachycardia, syncope with inducible ventricular tachycardia, and reduced left ventricular ejection fraction for conditions like ischemic cardiomyopathy and dilated cardiomyopathy. Emerging indications discussed include hypertrophic cardiomyopathy, Brugada syndrome, arrhythmogenic right ventricular dysplasia, long QT syndrome, and idiopathic ventricular fibrillation or tachycardia. The implantable cardioverter-defibrillator is presented as an effective treatment for preventing sudden cardiac death, though its cost-benefit ratio depends on the underlying disease and risk level.
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2007 rieti, convegno regionale, quale terapia nelle channelopatie
- 1. Quale terapia nelle Channelopatie ?Quale terapia nelle Channelopatie ? quando e come approfondire la diagnosiquando e come approfondire la diagnosi Stefano Nardi MD, PhD AZIENDA OSPEDALIERA SANTA MARIA TERNIAZIENDA OSPEDALIERA SANTA MARIA TERNI DIPARTIMENTO CARDIOTORACOVASCOLAREDIPARTIMENTO CARDIOTORACOVASCOLARE STRUTTURA COMPLESSA DI CARDIOLOGIASTRUTTURA COMPLESSA DI CARDIOLOGIA UNITA’ OPERATIVA DI ARITMOLOGIA CARDIACAUNITA’ OPERATIVA DI ARITMOLOGIA CARDIACA LABORATORIO DI ELETTROFISIOLOGIA ED ELETTROSTIMOLAZIONELABORATORIO DI ELETTROFISIOLOGIA ED ELETTROSTIMOLAZIONE
- 3. T waves flattened, inverted (esp in V1-V3) Precordial QRS prolongation ε waves (small amplitude pot. at start of ST – “intrav. myocardial defect”) SAECG PERCEZIONE del Problema
- 5. sopralsivell punto J ≥ 2 mm con onda T negativa. PERCEZIONE del Problema
- 7. • QTC 470 ms. PERCEZIONE del Problema
- 10. • Until 20% survival • Between 30 - 80% of survivals suffer of Anoxic Encephalopaty Magnitude (annual mortality) • U. S.U. S. →→ 450.000450.000 • EuropeEurope →→ 600.000600.000 • GermanyGermany →→ 80.00080.000 • ItalyItaly →→ 65.00065.000 Incidence in ItalyIncidence in Italy 11 case each 9 minutescase each 9 minutes
- 11. Total DeathTotal Death →→ 557.584 (100%)557.584 (100%) Death for CV diseaseDeath for CV disease →→ 242.248 (43%)242.248 (43%) Sudden DeathSudden Death →→ 57.000 (10.2%)57.000 (10.2%) ISTAT source ‘00ISTAT source ‘00 0 50000 100000 150000 200000 250000 Cancro della Mammella Cancro Colon Retto Cancro Bronchi/Polmoni Ictus Morte Improvvisa Malattie Cardiovascolari Mortiperanno Mortality Distribution
- 12. Magnitude and Etiology of SCD • ion-channel abnormalities, valvular or congenital HD, other causes 80% CAD15% CM 5% Other* SCA4 450,000 #1 Killer in the U.S. 4 Zheng Z. Circulation. ‘01
- 13. • 2 peak age-related in which SCD is more prevalent • Between born and 6 mo (sudden infant death syndrome) • Between 45 and 75 years old Sudden Cardiac DeathSudden Cardiac Death Relationship with Age • 1 case each1 case each 1010 hourshours (UMBRIA)(UMBRIA) • 912/850.000 each years912/850.000 each years • 10 %10 % of all total mortalityof all total mortality • 40 %40 % of all deaths for CARDIAC DISEASEof all deaths for CARDIAC DISEASE
- 14. Cardiopatia Non cardiopatia - I-DCM - H(O)CM - Valvular CM - Congenital HD - Altre forme (ARVD) - Tachicardia monomorfa dal tratto d’efflusso del VDx (RVOT) -Tachicardia ventricolare sinistra idiopatica (ILVT) - Tachicardia Ventricolare monomorfa catecolaminergica - Sindrome del QT lungo - Sindrome del QT breve - Sindrome di Brugada - SUBSTRATO SOTTOSTANTE
- 15. Stratificazione del Rischio • AMPIO spettro di substrati sottostanti • Diverse combinazioni fra TIPO di ARITMIA e SUBSTRATO configura differenti quadri clinici con diversi profili di rischio SUBSTRATOSUBSTRATO • I-DCM - riduzione LVEF - NSVT - Sincope • H(O)CM • ARVD • Brugada syndrome • QTLS • FV Idiopatica • VT Idiopatica
- 16. Condizioni cliniche • Cardiopatia Coronarica • Cardiomiopatia Ipertrofica • Cardiomiopatia Dilatativa • Cardiopatia Valvolare • Sindromi Aritmogene Ereditarie (ARVD, QTLS, BS, VT Polimorfa Catecolam) • Altre (Cuore d’atleta, Cuore normale, ecc.) Stratificazione del Rischio
- 17. Primary Based on Studies and Clinical Research in a large cohort of pts Based on Statistical Analisys but strickly linked with Personal Experiences and common good practise What is Evidence Based Medicine (EBM)? Magnitude of Sudden Cardiac Arrest
- 18. Esiste un modo per stratificare i pazienti? La maggior parete dei soggetti che SPERIMENTA un Arresto Cardiaco non sopravvive per poterlo raccontare
- 19. Morte Improvvisa PATOGENESI BradiaritmiaBradiaritmia 15-20%15-20% VT/VF 75-80%VT/VF 75-80% EMD 5%EMD 5% Ritmo registrato nei pzRitmo registrato nei pz risuscitati ad arrestorisuscitati ad arresto cardiaco extraospedalierocardiaco extraospedaliero o nei pazienti decedutio nei pazienti deceduti improvvisamente duranteimprovvisamente durante registrazione Holterregistrazione Holter Cummins RO, Annals Emerg Med. ‘89 Albert CM. Circulation ‘03 Bayés de Luna A. Am Heart J. ‘89
- 20. Ma quali sono le categorie a rischio ?
- 21. • Dati raccolti sottoposti a revisione sintetica da parte della Task Force della ESC • Da tale revisione sono emerse raccomandazioni (NON LINEE GUIDA !!!) in base alla EBM che coinvolgono la fase diagnostica e terapeutica dell’approccio alla MI Priori S - Eur Heart J ‘01 Premessa Metodologica
- 22. • Considerazioni ESTRAPOLATE dai dati a nostra disposizione NON risultano essere SEMPRE TRASFERIBILI DIRETTAMENTE nei pazienti con condizioni di base DIVERSE, malgrado segni/sintomi di uguale espressione Premessa Metodologica orienta l’investigatore circa la strategia da utilizzare nei singoli casi!
- 23. STRATIFICAZIONE del RISCHIO Alto Rischio Medio Rischio Popolazione Basso Rischio In quale popolazione esiste un REALE BENEFICIO ????
- 24. Sindrome del QT - Lungo TdP = Torsades de Pointes; VF = Fibrillazione Ventricolare; AC = Arresto Cardiaco; JLN = Jervell and Lange Nielsen; Sin = Sindattilia; BAV = Blocco AtrioVentricolare; SCD = Morte Improvvisa; I IIa IIbClasse •QTc > 600ms •Evento Cardiaco nei neonati •Post-partum •Sind + BAV •Alternanza onda T •Sesso Femminile • TdP / VF / AC • Sincope • JLN • LQT3 • Familiarità di SCD ∀↑ Dispersione del QT Stratificazione del Rischio 5 Priori et al. Task Force on Sudden Cardiac Death of the European Society of Cardiology. Eur Heart J 2001; 22:1374-1450. [Full text]
- 25. Sindrome di Brugada VF = Fibrillazione Ventricolare; VT = Tachicardia Ventricolare; SCD = Morte Improvvisa; VT Sost.= Tachicardia Ventricolare Sostenuta I IIa IIb •Sincope •Familiarità di SCD• VF - VT • Inducibilita VT Sost. - VF Classe Stratificazione del Rischio 5 Priori et al. Task Force on Sudden Cardiac Death of the European Society of Cardiology. Eur Heart J 2001; 22:1374-1450. [Full text]
- 26. VT Polimorfa Catecolaminergica VF = Fibrillazione Ventricolare; SCD = Morte Improvvisa; VT Non Sost. = Tachicardia Ventricolare Non Sostenuta I IIa IIb •Familiarità di SCD •VT Non Sost. / sincope nell’età pediatrica • VF • Sincope Classe Stratificazione del Rischio 5 Priori et al. Task Force on Sudden Cardiac Death of the European Society of Cardiology. Eur Heart J 2001; 22:1374-1450. [Full text]
- 27. Stratificazione del rischio Letalità patologia Vantaggio dell’ICD Costo Beneficio Per la serie: le ultime parole famose... Maggiore è il rischio di MORTE ARITMICA Maggiore il beneficio dell’ICD
- 28. Profilassi della Morte Improvvisa Vantaggi Svantaggi Defibrillatore impiantabile • Riconoscimento e trattamento di un’aritmia ventricolare (1-2% MI per anno di FU) • • Costi • Terapia inappropriata • Impatto su QoL sconosciuto • Complicanze precoci e tardive • Consumo batterie ed elettrodi
- 29. • ICD molto efficaci ed affidabili nell’interruzione della VT/VF • FV causa principale della morte improvvisa ICD indispensabile nella lotta contro la morte improvvisa! Premessa Metodologica POSSIBILE IMPLICAZIONE
- 30. Mortalità totale Frazione di eiezione Morte per causa aritmica Diss. E-M Elettrica Infettiva Neoplastica Neurologica Ecc. Considerazioni • L’ impatto di una determinata strategie si basa sulla riduzione di probabilità dell’evento “END POINT”
- 31. – Per dimostrare l’applicabilità clinica dell’ICD è necessaria una PROVA INCONFUTABILE della sua efficacia - Tale prova è spesso vincolata dai filtri a maglie strette della metodologia applicata alla pratica clinica (EBM). Implicazioni
- 32. IndicazioniIndicazioni CONSOLIDATECONSOLIDATE • Sopravvissuti a MI • TV sostenute spontanee • Sincope + TV inducibile ICD Costo Beneficio
- 33. Class I Cardiac arrest due to VF or VT not due to a transient or reversible cause (Level of Evidence: A) Spontaneous sustained VT in association with structural heart disease (Level of Evidence: B) Syncope of undetermined origin with clinically relevant, hemodynamically significant sustained VT or VF induced at EP study when drug therapy is ineffective, not tolerated, or not preferred (Level of Evidence: B) AVID CASH CIDS CIDS AVID Registry AVID Gregoratos G. ACC/AHA/NASPE Circulation ‘02
- 34. L’evidence based è dominata dalla frazione di eiezione (LVEF) (vincolo PREVALENTE) Premessa Metodologica
- 35. SCD RISK ICD efficacy Cost Benefit I-DCM – RISK stratification • Prior CA or S-VT (I)Prior CA or S-VT (I) • Syncope (II a)Syncope (II a) • Ridotta LVEF (II b)Ridotta LVEF (II b) • NSVT (II b)NSVT (II b) HIGH RISK Priori et al. Eur Heart J ‘01Priori et al. Eur Heart J ‘01
- 36. – Quale rapporto COSTO/BENEFICIO ? Considerazioni aggiuntive ICD in soggetti senza aritmie sostenute CAT, DEFINITE, SCD-HeFTCAT, DEFINITE, SCD-HeFT QoL • Impatto psicologico • Terapia inappropriata • Terapia appropriata in stato di coscienza Assenza di dati prospettici!
- 37. END POINT mortalità: è corretto?END POINT mortalità: è corretto? Arresto cardiaco Completo recupero Intervento Invalidità permanenteInvalidità permanente MORTE Basic Life Support T E M P O
- 38. IndicazioniIndicazioni CONSOLIDATECONSOLIDATE • Sopravvissuti a MI • TV sostenute spontanee • Sincope + TV inducibile • I-DCM - Riduzione LVEF - NSVT - Sincope EMERGENTIEMERGENTI • HCM • ARVD • Brugada syndrome • QTLS • FV Idiopatica • VT Idiopatica ICD
- 39. Esiste oggi una terapia che può essere considerata il GOLD STANDARD nelle CARDIOPATIE ARITMOGENE ? Qual è la percezione del PROBLEMA ? Quali sono le INDICAZIONI univocamente ACCETTATE ?
- 40. RISK stratification Alto Rischio Medio Rischio Popolazione Basso Rischio In quale popolazione esiste un REALE BENEFICIO ? Patologie EMERGENTIPatologie EMERGENTI • HCM • Brugada syndrome • ARVD • QTLS
- 41. CLINICAL GOVERNANCE • National Operative Organized System by which is possible to CTR the Standard references of QUALITY and the Continuous Educational System • Merge between Clinical Practice and Health Management • Efficacy and Effectivness of Local Source Big Brother
- 42. CLINICAL GOVERNANCE PerformancePerformance DiseaseDisease ManagementManagement EventoEvento SentinellaSentinella AUDITAUDIT EBMEBM Clinical Governance is a cyclical process GUIDELINESGUIDELINES
- 43. In both aviation and medicine, people depend on technology as the solution…
- 44. SCD RISK ICD efficacy Cost Benefit HCM – RISK stratification • Prior CA or S-VTPrior CA or S-VT • Family history of 1Family history of 1stst degree SCDdegree SCD • LVH wall thickness >3,0cmLVH wall thickness >3,0cm • Syncope (exercional/repetitive)Syncope (exercional/repetitive) • Repetitive/prolonged NSVTRepetitive/prolonged NSVT • BP flat response during STBP flat response during ST HIGH RISK
- 45. HCM – RISK stratification Alto Rischio Medio Rischio Popolazione Basso Rischio • Prior CAPrior CA • Sust. VTSust. VT • VFVF • Family history of SCDFamily history of SCD • SyncopeSyncope • Extreme LVH (>3cm)Extreme LVH (>3cm) • BP flat during STBP flat during ST • NSVT (Holter)NSVT (Holter) • VT/VF at PESVT/VF at PES • LV outflow gradientLV outflow gradient • MRMR • Chest-pain/dispneaChest-pain/dispnea • Paroxismal AFibParoxismal AFib Class I Class II Class III Priori et al. EHJ ‘01Priori et al. EHJ ‘01
- 46. The ‘Swiss cheese’ model of organizational accidents Some holes due To active failures Other holes due to latent conditions Successive layers of defences Hazards Losses It takes an average of 4.5 errors in the system for a medical accident to result Modified from James Reason, 1991.
- 47. 1. FAILURE to use a systematic approach to the assessment of critically ill pts 2. POOR communication 3. LACK of teamwork 4. INSUFFICIENT use of treatment limitation plans. Addictional factors Deficiencies in Acute Care
- 48. Prevenzione Primaria Prevenzione Secondaria I IIa IIbClasse •ICD •ICD •Amiodarone HCMHCM Priori et al. Eur Heart J ‘01Priori et al. Eur Heart J ‘01
- 49. HCMHCM Management of high risk ptsManagement of high risk pts • InIn “PREVENZIONE PRIMARIA” nei pts con ≥2 fattori di rischio (f. annua SCD 3-6%) • Frequenza annua di SCD variabile da un minimo di 1% (community-based population) ad un max di 2-4% (referral centre cohorts) • In questo specifico “sub-set” pts, dati retrospettivi recenti riportano un 5% annuo di DC shock appropriati, con no SCDs
- 50. ARVDARVD Stefano Nardi MD AZIENDA OSPEDALIERA SANTA MARIA TERNIAZIENDA OSPEDALIERA SANTA MARIA TERNI DIPARTIMENTO CARDIOTORACOVASCOLAREDIPARTIMENTO CARDIOTORACOVASCOLARE STRUTTURA COMPLESSA DI CARDIOLOGIASTRUTTURA COMPLESSA DI CARDIOLOGIA UNITA’ OPERATIVA DI ARITMOLOGIA CARDIACAUNITA’ OPERATIVA DI ARITMOLOGIA CARDIACA LABORATORIO DI ELETTROFISIOLOGIA ED ELETTROSTIMOLAZIONELABORATORIO DI ELETTROFISIOLOGIA ED ELETTROSTIMOLAZIONE
- 51. • “ARVC” proposed in 1977 by Fontaine • Occurs in teenagers and young adults (>80% diagnosed by age 40) – Rarely in early childhood • INCIDENCE: unknown (6/10000 ???) • PREVALENCE: unknown • Italian study - 20% of postmortem SD in pts < 35 ys old • Incidence 1:~5,000 Background 1:5000
- 52. Epidemiology - Typical ECG, VTs from RV and structural and functional RV abnormalities represent only one extreme of the disease spectrum. - Clinically silent cases are not recognized because asymptomatic - The first presentation could be SD - Diagnosys could be difficult by conventional non- invasive tools. Task Force of the World Health Organization/International Society and Federation of
- 53. • Degeneration – Myocyte death due to inherited metabolic or ultrastructural defect – “Myocardial dystrophy” • Inflammatory/infectious/myocarditis – Coxsackie-like RNA found in some cases • Apoptosis • Trans-differentiation – From myocardial cells to adipose tissue Etiology
- 54. • ~50% Autosomica Dominante • Espressione Variabile • Penetranza incompleta (30%) • Chromosomi 14, 1, 10 • Patologia della Plakoglobina Genetica • Atrofia muscolare cardiaca • Sostituzione fibro-adiposa • Aritmie ventricolari (RV) • Morte Cardiaca Improvvisa Definizione DESMOPLAKINA PLAKOGLOBINA (Naxos) RIANODINA (MAVD2) STRESS MECCANICO INTERCELLULARE APOPTOSI SOSTITUZIONE FIBROSA ED ADIPOSA
- 55. PRESENTAZIONE CLINICA • PALPITAZIONI (67%) • Sincope (32%) • Cardiac Arrest (7-23%) • Dolore toracico atipico (27%) • Dispnea (11%) • ASINTOMATICI
- 56. • “Concealed” phase - subtle RV changes - minor VTs - rarely SD ( competitive athletics) • “Overt electrical disorder” – overt RV - structural/functional changes - symptomatic RV tachyarrhythmias • “RV failure” – global RV dysfunction with - preserved LV function • ”Biv CHF” – Task Force of the World Health Organization/International Society and Federation of Dynamic and evolutive substrate
- 57. T waves flattened, inverted (esp in V1-V3) Precordial QRS prolongation ε waves (small amplitude pot. at start of ST – “intrav. myocardial defect”) SAECG CLINICAL PRESENTATION
- 58. TV1- APEX
- 61. • The assessment of SD risk is still not well established, • No precise guidelines are available to determine which are the pts who need to be treated • Which is the best management approach? • Therapeutic options include beta blockers, AADs, CA and ICD. • In pts in whom ARVD/C has progressed to severe RV or BIV systolic dysfunction, treatment consists of current therapy for HF including diuretics, ACE- I, and digitalis, as well as ACT. • These pts may become candidates for heart transplantation. THERAPY
- 62. 43 66 47 22 81 45 48 69 11 12 15 JRA Cataracts Syncope 1311 Adopted Lung CA Sudden death Etiology? VSD Asthma Hypothyroid Fibromyalgias Bell’s palsy Hypothyroid 45 51 1468 ARVC Hypothyroid OK OK OK OK OK Palps OK OK * * * ARVD: family tree
- 63. ARVD – RISK stratification Alto Rischio Medio Rischio Popolazione Basso Rischio • Family history ofFamily history of ARVD/SCDARVD/SCD • SyncopeSyncope • Late potential +Late potential + RV dysfRV dysf • VTVT • RVSTIM +RVSTIM + • QTc disp and TWAQTc disp and TWA • PVCsPVCs Class IIa Class IIb Class III Priori et al. EHJ ‘01Priori et al. EHJ ‘01 • VT sostenuteVT sostenute • Diffuse RV dilDiffuse RV dil • LV involvementLV involvement • RV dysf/dilatRV dysf/dilat ++ RVSTIM +RVSTIM + • Previous CA/VFPrevious CA/VF LEVEL of EVIDENCE CLEVEL of EVIDENCE C
- 64. ARVD/RVCARVD/RVC • Il valore PREDITTIVO dei MARKERS non è stato definito in studi prospettici su larga scala • I dati riportati sono basati su PICCOLI STUDI (prevalentemente derivanti da centri terziari nei quali il paziente era giunto per l’aritmia • Il PROFILO di RISCHIO dei pts asimptomatici (albero genialogico) NON E’ STATO sistematicamente VALUTATO
- 65. •VT Sost./ VF •Dilatazione RV •Disfunzione RV + inducibilita’ SATE I IIa IIbClasse •Familiarity SCD •PT+ RV dysfunction •VT •Inducibilita’ SATE Stratificazione del Rischio Priori, Eur Heart J ‘01 • ICD I IIa IIb • ICD •AADs (Sotalol) Prevenzione Primaria Prevenzione Secondaria Classe
- 66. ARVDARVD • ICD I IIa IIb • ICD •AADs (Sotalol) Prevenzione Primaria Prevenzione Secondaria Classe Priori et al. Eur Heart J ‘01Priori et al. Eur Heart J ‘01
- 67. T waves flattened, inverted (esp in V1-V3) Precordial QRS prolongation ε waves (small amplitude pot. at start of ST – “intrav. myocardial defect”) SAECG
- 68. Registro Internazionale • www. arvd.org • www.arvd.net Onda Epsilon (ε)
- 69. Incisura onda S ascendente >55 ms
- 71. • Right ventricular angiography – Dilated, poorly contractile RV free wall and RV outflow tract • RV endomyocardial biopsy – Excessive fatty infiltration – Sporadic, typically involves epicardium first (ie. False negative sampling) ARVD: Cardiac Catheterization
- 72. ANGIOGRAFIA PATRON DE ORO - VD 1.- Aumento trabeculatura a “pila di piatti” 2.- Dilatazione ed Ipocinesia 3.- Alterazione segmentaria della Contrattilita` 4.- Discinesia 5.- Abultamiento e aneurisma localizzato
- 73. ?????? ???? Ouyang et al, 2002 ArrhythmogenicRight Ventricular Dysplasia
- 74. ?????? ???? Ouyang et al, 2002
- 75. ?????? ???? Marchlinski et al, 2000
- 76. • The definitive test? • Requires experienced cardiac imaging specialist • Can distinguish fat from muscle • Cine MRI helps qualitate free wall function ARVD: MRI
- 77. • Restricted activities • Medic Alert bracelet/necklace • Medications – Amiodarone, sotalol, beta-blockers • RF Catheter ablation • ICD ARVD: treatment
- 78. One of the major causes of SCD in pts in pre-CAD age, accounting for approximately 25% of SD in young athletes ARVD/RVCARVD/RVC AADs is often used as primary Rx, however this approach is often “INEFFECTIVE” PREVALENCEPREVALENCE is not well defined (post-mortem features of RVC may be subtle/confined to region of RV wich may not have been routinely examined at autoptic evaluation
- 79. Disease that involve Plakoglobin, an intracellular adhesion molecule involved in the apoptosis process ARVD/RVCARVD/RVC ARVD/RVC manifests with VTs, however the initial presenting symptom may be SINCOPE (29%) or CA (7-23%) Familiar disease with autosomal dominant and incomplete penetrance
- 80. LIMITED INFORMATIONSLIMITED INFORMATIONS are available on risk assessment of SCD Predictive marker have not yet been defined in prospective studies focus on SURVIVAL, therefore data reported here are based on small studies in pts who presented with arrhythmia The RISK PROFILE of asymt. Pts hase not been systematically evaluated ARVD/RVCARVD/RVC
- 81. ARVD/RVCARVD/RVC Management of high risk ptsManagement of high risk pts Data regarding efficacy of various AADs for prevention VTs or SCD relies on retrospective and prospective “non- randomized” studies Sotalol showed higher efficacy, then is recommended as a first choice drug to prevent recurrence of VTs, however in pts with aborted SCD ICD Rx is likely to reduce mortality
- 82. ARVDARVD • ICD I IIa IIb • ICD •AADs (Sotalol) Prevenzione Primaria Prevenzione Secondaria Classe Priori et al. Eur Heart J ‘01Priori et al. Eur Heart J ‘01
- 83. BRUGADA SyndromeBRUGADA Syndrome Stefano Nardi MD AZIENDA OSPEDALIERA SANTA MARIA TERNIAZIENDA OSPEDALIERA SANTA MARIA TERNI DIPARTIMENTO CARDIOTORACOVASCOLAREDIPARTIMENTO CARDIOTORACOVASCOLARE STRUTTURA COMPLESSA DI CARDIOLOGIASTRUTTURA COMPLESSA DI CARDIOLOGIA UNITA’ OPERATIVA DI ARITMOLOGIA CARDIACAUNITA’ OPERATIVA DI ARITMOLOGIA CARDIACA LABORATORIO DI ELETTROFISIOLOGIA ED ELETTROSTIMOLAZIONELABORATORIO DI ELETTROFISIOLOGIA ED ELETTROSTIMOLAZIONE
- 84. • AUTOSOMAL DOMINANT trait and incomplete penetrance with variable expression. BRUGADA SyndromeBRUGADA Syndrome • Genetic defects in the α-subunit of cardiac Na+ channel, (reduction the Na+ channel current) that accentuates the epicardial action potential notch leading to ST-segment elevation. • Abnormal EP activity in the RV epicardium that leads to the development of coupled PVCs that precipitates VT/VF. • Mutations in the cardiac Na+ channel gene SCN5A
- 85. • RBBB and ST-segment elevation in the right precordial leads (V1 to V3 ), w/o evidence of structural HD. • Exclusion of mimic diseases (hypothermia, pericarditis, myocarditis, or ischemic events). • ECG pattern could be intermittent (variable and dynamic) and influenced by many factors (°C, ANS, Drugs) that can affect ion channel function. BRUGADA SyndromeBRUGADA Syndrome
- 86. ST segment elevation in Brugada syndrome • Autonomic tests – Isoproterenol, propranolol, norepinephrine, phentolamine • Antiarrhythmic drugs – Ia (procainamide) Ib (lidocaine) Ca channel blocker (verapamil) • Early repolarization hypothesis
- 87. • PREVALENCE: 0.1% in Europe • DIAGNOSIS: ~ 40 years (2 to 77 years) • MALE/FEMALE: 3:1 • TACHYARRHYTHMIAS at rest or during the night. • RECURRENCE of arrhythmic events is as high as 40%. • Sudden Infant Death Syndrome (SIDS) in the first mo. of life where it may be misdiagnosed as BRUGADA SyndromeBRUGADA Syndrome
- 88. • Provocative test with Na+ channel blockers proposed to unmask the diagnostic ECG pattern. – Ajmaline (1mg/kg IV) or – Flecainide (2mg/kg IV) or – Procainamide (10mg/kg IV) as a bolus over 10 m’. – ST-segment further elevation > 2 mm BRUGADA SyndromeBRUGADA Syndrome
- 90. • The inducibility during the EPS was used to identify the risk of cardiac event, although its accuracy was limited BRUGADA SyndromeBRUGADA Syndrome
- 91. BRUGADA SyndromeBRUGADA Syndrome • α-agonist, neostigmine/edrophonium and Class IA AADs should be avoided because they consistently augmented ST segment elevation in pts with BS • Although the number of pts was small in this study.
- 92. • Indication for ICD – symptomatic Brugada syndrome patients including syncope, cardiac arrest or documented VT – Asymptomatic individuals with a positive ECG and a family history of sudden death and/or inducible during electrophisiological study BRUGADA SyndromeBRUGADA Syndrome
- 93. A sudden syncope in a 35-year old man, with no prior cardiac history. The physical examination was unremarkable, the echo parameters were normal and an head-up test does not reproduced the symptoms. The ECG shown is obtained. At this point you would advise: A.No specific therapy B.Empiric B-blocker C.EP Study with ICD implantation if positive D.ICD implantation
- 97. A clinical and electrocardiographic syndrome - no demonstrable structural HD • - suffering from cardiac arrhythmias • - a very specific ECG • apparent RBBB • ST elevation in leads V1-V3 Description of the syndrome
- 98. • The disease is associated with a mutation in sodium channel (SCN5A). • The early theory was that the syndrome reflected an increase in the Ito channel (governing the potassium current in phase 1 of the ECG). • In fact, the Ito current is only increased relative to the sodium current, because the sodium channel closes prematurely. Ionic basis of disease
- 99. • ECG definition has become more and more strict. • ST elevation of a coved type of at least 2 mm or ST elevation of saddleback type if it becomes coved type under stress with anti-arrhythmics. • Elevation is always present in V2, and either V1 or V3 (usually both). Diagnosing the syndrome
- 100. • Flecainide used now that ajmaline is no longer available. • Given in an IV in Europe, but maybe 200mg orally but patient must be monitored for 8 hours because of the long half-life. • Procainamide is effective in unmasking the syndrome, but the ECGs are much less spectacular. May have less specificity and sensitivity than ajmaline. Drugs for diagnosis
- 101. • In all pts where we had genetic confirmation of the disease, we did not have a single false negative or false positive with ajmaline. • The ajmaline test was consistently reproducible in over 100 pts. • Pts’ hearts are different and the positioning of the leads can play an important role in diagnosis since the syndrome is localized in a specific region of the heart. Sensitivity and specificity
- 102. EP testing • Every single patient that has a classic Brugada ECG gets an EP test. • Asymptomatic patients who have a normal basal ECG have 0% events in follow-up so far. • So we don’t do EP tests in these patients. • Wait and watch because there is no evidence they are at risk.
- 103. Asymptomatics • If the base ECG is abnormal, then we follow with EP testing. • In these pts, 2/3 are non-inducible. • If non-inducible, we do nothing, because the event rate is extremely low. • Events in asymptomatic pts with abnormal basal ECG occurred in pts who were inducible by EP testing.
- 104. • Pt with a father who died of SD – no ECG available. • The pt has abnormal ECG, which becomes classic Brugada after stressing with flecainide. • This pt should get EP study due to family history. • If the study is positive, give them a defibrillator. If negative, do nothing. Clinical decision making
- 105. • Only 60% of SD in families with known Brugada syndrome can be attributed to the syndrome. • ECGs can normalize over time. A completely normal ECG in one moment doesn’t mean it will always be normal. • If the ECG ever becomes abnormal, you then follow up with drug tests and then EP testing. Clinical decision making
- 106. • A 28 year old uncle who died suddenly, no ECG available. My father died suddenly at 46. No autopsy. • The kid has a classic Brugada ECG but is non- inducible to EP testing. • I would suggest a defibrillator due to the strong family history, but there is no evidence that the risk is extremely high. • But with the strong family history and the baseline Brugada ECG, I would be nervous. Clinical decision making
- 107. Definition of Brugada ECG • RBBB in V1-V3 (V2 most important) • Coved ST-segment elevation of > 2mm • If not present at baseline, ECG can be induced by flecainide or procainamide. • ICD is treatment of choice for pts with documented cases of serious arrhythmias • In general if the EP study shows no inducible VT, watch and wait. Review
- 108. Brugada syndrome: RISK stratifiaction Sindrome ereditaria caratt. da un tipico pattern ECG, spesso in presenza di mutazione genetica. 1 Brugada, Circulation ‘98 COVED TYPE: sopralsivellamento punto J ≥ 2 mm con onda T negativa. Tipo 2 e 3 CLINICA Sincope
- 109. Brugada - Circulation ‘05 547 “coved type” 124 Sincope 170 Routine 253 Familiarità 391 Spointanei 156 dopo ajmalina 28±42 mesi Follow Up 45 (8%) eventi Età media 40 aa
- 110. Brugada - Circulation ‘05 ECG spontaneo coved type, % (95% IC) ECG dopo test ajmalina, % (95% IC) Sincope •Inducibilità •Non inducibilità Asintomatici •Inducibilità •Non inducibilità 27.2 (17.3-40.0) 4.1 (1.4-11.7) 4.5 (1.0-17.1) 0.5 (0.1-2.7) 14.0 (8.1-23.0) 1.8 (0.6-5.1) 9.7 (2.3-33.1) 1.2 (0.2-6.6)
- 111. • FU 28±42 mo • 45 FV (8%) • Inducibilità durante PES/ storia di sincope Analisi di REGRESSIONE LOGISTICA: Sincope sufficiente rischio da giustificare un ICD (1.2 % -27.2 %) COVED TYPE: sopralsivell punto J ≥ 2 mm con onda T negativa. BS
- 112. Sindrome di Brugada •Storia di sincope •Un episodio di arresto cardiaco ICD Ma qual è il RISCHIO degli altri pazienti?
- 113. • NON ESISTE una terapia medica di sicura e documentata efficacia. • ICD funziona in pazienti che SVILUPPANO o SVILUPPERANNO una VF • Altrimenti ……….. tutti i rischi dell’impianto e nessun beneficio Sindrome di Brugada CONSIDERAZIONI
- 114. Possibile strategia “insertable LR + ICD esterno” BRUGADA syndrome: stratificazione Alto rischio Rapporto di rischio: 6.4 Rischio intermedio Rapporto di rischio: 2.1 Basso rischio Priori et al - Circulation ‘02 Rischio Sincope e pattern ECG positivo Pattern ECG positivo Pattern ECG negativo con o senza sincope Percentuale popolazione 10 % 41 % 49 % ICD Terapie Ulteriori controlli in caso di sintomi
- 115. Sindrome di Brugada I IIa IIb •Sincope •Familiarità per SCD • VF - VT • Inducibilita VT-S/ VF Classe Priori et al. Eur Heart J ‘01Priori et al. Eur Heart J ‘01 STRATIFICAZSTRATIFICAZ del RISCHIOdel RISCHIO
- 116. I IIa IIb • ICD in Pz. con Sincope / TV •ICD •ICD in pz asintomatici EPS inducibili Prevenzione Primaria Prevenzione Secondaria Classi Priori et al. Eur Heart J ‘01Priori et al. Eur Heart J ‘01 Sindrome di BrugadaSindrome di Brugada
- 117. QTc long syndromeQTc long syndrome Stefano Nardi MD AZIENDA OSPEDALIERA SANTA MARIA TERNIAZIENDA OSPEDALIERA SANTA MARIA TERNI DIPARTIMENTO CARDIOTORACOVASCOLAREDIPARTIMENTO CARDIOTORACOVASCOLARE STRUTTURA COMPLESSA DI CARDIOLOGIASTRUTTURA COMPLESSA DI CARDIOLOGIA UNITA’ OPERATIVA DI ARITMOLOGIA CARDIACAUNITA’ OPERATIVA DI ARITMOLOGIA CARDIACA LABORATORIO DI ELETTROFISIOLOGIA ED ELETTROSTIMOLAZIONELABORATORIO DI ELETTROFISIOLOGIA ED ELETTROSTIMOLAZIONE
- 118. Anestimated prevalence below 5 in 10 000 (0,5% each 1000 inhabitants). Which aspects should be considered before developing recommendations for risk stratification and management of patients? Most of the data available for these conditions derive from large registries No randomized studies are available
- 119. LEVEL of EVIDENCE B for data collected by the registries on LQTS (large nr of pts with a long FU
- 120. Data on the natural history of these diseases are potentially biased by the fact that it is more likely that a highly symptomatic case is referred to a registry Some concepts applied for risk stratification are common to the different inherited arrhythmogenic diseases
- 121. the severity of the ECG phenotype is generally a marker of increased risk of SCD (1) In LQTS, the “severe” phenotype is represented by the presence of a QTc exceeding 500 ms (2) In the Brugada syndrome by the spontaneous presence of ST-segment elevation in the right precordial leads (3) In CPVT by VT induced by exercise stress testing
- 122. Because these diseases are characterized by electrical abnormalities occurring in the structurally intact heart, the use of the ICD is always indicated with a class I indication in the secondary prevention of cardiac arrest (CA). Its use in primary prevention is more debated, considering the young age of patients at diagnosis
- 123. In LQTS and in CPVT, pharmacological therapy with beta blockers is effective in reducing the risk of cardiac events In the Brugada syndrome, no effective pharmacological treatment is known Physical activity is not considered to be the trigger for arrhythmic episodes, such as in patients with Brugada syndrome and LQT3
- 124. • Mutations in 8 genes have been identified: • 7 of them encode cardiac ion channel subunits • 1 encodes an anchoring protein that has been implicated in controlling ion channel targeting specific membrane sites identification of the genetic subtypes A QTc exceeding 500 ms Long QTc syndromeLong QTc syndrome
- 125. • the interplay between (1) genetic defect, (2) QT duration, and (3) gender may provide an algorithm for risk stratification (103) (A) the highest risk of becoming symptomatic are LQT1 and LQT2 patients with a QTc greater than 500 ms and males with LQT3 irrespective of QT interval duration
- 126. GENETIC ARRHYTHMIA SYNDROMES Arrhythmogenic Hereditary Syndromes (LQTcS, BS and CPVT) are inherited arrhythmogenic diseases Share genetically determined susceptibility to VT and SCD in the absence of recognizable structural abnormalities of the heart. General Concepts for Risk Stratification
- 127. • Primary electrical disorder with BROAD SPECTRUM • NO macroscopic EVIDENCE of structural HD • PROLONGED QTc interval • DEFORMATION of T wave/presence of U wave • STRESS MEDIATED life-threatening VTs • One variant AUTOSOMAL RECESSIVE (J-LN) • One prevalent AUTOSOMAL DOMINANT (RW) Long QTc syndromeLong QTc syndrome
- 128. CARDIAC MYOCITE repolarization • IK responsible for repolarization of cell during action potential – IKs helps keep action potential duration at normal levels – Problems with channel longer APD (lengthened because of abnormal repolarization)
- 129. Quantitative Data Age and Sex Prolonged QTc (sec) Reference Range (sec) Children (< 15 y) > .46 < .44 Adult Males > .45 < .43 Adult Females > .46 < .45 -Deformation of T wave -Presence of U wave
- 130. LQTS Type Chromosomal Locus Mutated Gene Ion Current Affected LQT1 11p 15.5 KVLQT1 IKs LQT2 7q 35-36 HERG IKr LQT3 3p 21-24 SCN5A INa LQT4 4q 25-27 ? ? LQT5 21q 22.1-22.2 KCNE1 (heterozygotes) IKs LQT6 21q 22.1-22.2 MiRP1 IKr GENETIC subtypes
- 131. DISEASE statistics • Affects 1 in about 3000-5000 individuals • LQTcS type 1 and LQTcS type 2: Potassium channel mutations (KvLQT1 and HERG) estimated to cause 87% of all Long QTc Syndromes • LQT3 (SCN5A): approximately 8% • LQT5 (KCNE1/minK), LQT6 (MiRP1): 5%
- 132. • LQT1 (IKs) is more susceptible to cardiac events occurring during exercise (particularly swimming) • LQT2 (IKr) is more susceptible to cardiac events occurring during rest or emotion (characteristically acoustic stimuli) • LQT3 carrying mutations in the SCN5A (cardiac Na channel) is susceptible to cardiac events occurring at rest and during sleep
- 133. • LQT2 patients, those with a mutation resulting in a change in the pore region of the protein appear to be at higher risk of cardiac events than are those with mutations in other regions of the gene. • Beta blockers are highly effective in LQT1, whereas they offer incomplete protection in LQT2 and LQT3
- 134. Romano-Ward and JLN • Romano-Ward: autosomal dominant – Characterized by gradual hearing loss • Jervell-Lange-Nielsen (JLN): autosomal recessive – Characterized by congenital deafness
- 135. Chromosome 11 11p15.5 Potassium Channel and Current • affects KvLQT1 gene • Encodes K channel α subunit • Mutation leads to loss of function of K+ channel • Delayed potassium rectifying current (IKs)
- 136. Cardiac related symptoms Abnormal heartbeat (aka Cardiac arrhythmia) - Tachyarrhythmias – fast heart rate (>100 bpm) - Torsades de Pointes • Syncope (Fainting) • Cardiac arrest (heart failure) • Sudden death
- 137. Risk stratification Causa più frequente: mutazioni dei geni relativi al canale del potassio (sito LQT1 o LQT2) o del sodio (sito LQT3) Stratificazione proposta: a seconda del genotipo e di altre variabili quali sesso e lunghezza del QT Probabilità di evento cardiaco prima dei 40 anni e prima della terapia? (sincope, CA, SCD)
- 138. Alto rischio (≥ 50 %) Rischio intermedio (30-49%) Basso rischio (< 29%) S. Priori et al. - NEJM ‘03 Probabilità di evento cardiaco prima dei 40 anni e prima della tx (sincope, CA, SCD) QTc M = sesso maschile F = sesso femminile QTc ≥ 500 ms LQT1 LQT2 M, LQT3 QTc < 500 ms F, LQT2 F, LQT3 M, LQT3 QTc ≥ 500 ms F, LQT3 QTc < 500 ms M, LQT2 LQT1 QTLS: Risk stratification
- 139. Caution! Arrhythmia can be induced by: – Stress/ Exercise • Accelerated heart rate • Superposition of action potentials • β-blockers (suppresses sympathetic nervous system) • Pacemakers (control heart rhythm) • Gene therapy
- 140. A quantification of the actual prevention of SCD withA quantification of the actual prevention of SCD with β- blocker is missing, because we have to rely on retrospective data
- 141. Clinical Implications • IKs gating can be changed with drug therapy or gene therapy – This will alter channels so that values change – Decrease in time constant • Change in gating variables will be suggestive of a change in the voltage-gating properties – Drug will target fourth domain of KvLQT1
- 142. • 41- The ECG shows a prolonged QT interval (QTC 470 ms). The repolarisation abnormality in the chest leads attached in the figure is suggestive for which subtype of the long QT syndrome? • a.- Long QT 1 • b.- Long QT 2 • c.- Long QT 3 • d.- Long QT 4 • e.- Long QT 5
- 143. QTLS TdP = Torsades de Pointes; VF = Fibrillazione Ventricolare; AC = Arresto Cardiaco; JLN = Jervell and Lange Nielsen; Sin = Sindattilia; BAV = Blocco AtrioVentricolare; SCD = Morte Improvvisa; I IIa IIbClasse •QTc > 600ms •Evento Cardiaco nei neonati •Post-partum •Sind + BAV •Alternanza onda T •Sesso Femminile • TdP / VF / AC • Sincope • JLN • LQT3 • Familiarità di SCD ∀↑ Dispersione del QT Stratificazione del Rischio Priori et al. Eur Heart J ‘01Priori et al. Eur Heart J ‘01
- 144. QTLSQTLS I IIa IIb •Stellectomia sx •Pacemaker •Evitare i farmaci che allungano il QT •Evitare Sport •Beta-bloccanti •ICD+ betabloccanti + evitare i farmaci che allungano il QT •Evitare Sport Prevenzione Primaria Prevenzione Secondaria Classi Priori et al. Eur Heart J ‘01Priori et al. Eur Heart J ‘01
- 145. QTLS I IIa IIbClasse •QTc > 600ms •Evento Cardiaco nei neonati •Post-partum •Sind + BAV •Alternanza onda T •Sesso Femminile • TdP / VF / AC • Sincope • JLN • LQT3 • Familiarità di SCD ∀↑ Dispersione del QT Priori et al. Eur Heart J ‘01Priori et al. Eur Heart J ‘01 STRATIF RISCHIO
- 146. QTLSQTLS I IIa IIb •Stellectomia sx •Pacemaker •Evitare i farmaci che allungano il QT •Evitare Sport •Beta-bloccanti •ICD+ betabloccanti + evitare i farmaci che allungano il QT •Evitare Sport Prevenzione Primaria Prevenzione Secondaria Classi Priori et al. Eur Heart J ‘01Priori et al. Eur Heart J ‘01
- 147. • Primary electrical disorder with BROAD spectrum • No macroscopic evidence of structural HD • Prolonged QTc interval • Stress-mediated life-threatening VTs • One variant autosomal recessive (J-LN) • One prevalent variant autosomal dominant (RW) QTc long syndromeQTc long syndrome
- 148. QTLS I IIa IIbClasse •QTc > 600ms •Evento Cardiaco nei neonati •Post-partum •Sind + BAV •Alternanza onda T •Sesso Femminile • TdP / VF / AC • Sincope • JLN • LQT3 • Familiarità di SCD ∀↑ Dispersione del QT Priori et al. Eur Heart J ‘01Priori et al. Eur Heart J ‘01 STRATIF RISCHIO
- 149. Alto rischio (≥ 50 %) Rischio intermedio (30-49%) Basso rischio (< 29%) S. Priori et al. - NEJM ‘03 Probabilità di evento cardiaco prima dei 40 anni e prima della tx (sincope, CA, SCD) QTc M = sesso maschile F = sesso femminile QTc ≥ 500 ms LQT1 LQT2 M, LQT3 QTc < 500 ms F, LQT2 F, LQT3 M, LQT3 QTc ≥ 500 ms F, LQT3 QTc < 500 ms M, LQT2 LQT1 QTLS: Risk stratification
- 150. QTLSQTLS I IIa IIb •Stellectomia sx •Pacemaker •Evitare i farmaci che allungano il QT •Evitare Sport •Beta-bloccanti •ICD+ betabloccanti + evitare i farmaci che allungano il QT •Evitare Sport Prevenzione Primaria Prevenzione Secondaria Classi Priori et al. Eur Heart J ‘01Priori et al. Eur Heart J ‘01
- 151. • Any QTc-interval > 440 msec is considered prolonged • Borderline QT shows a prolongation of QTc, but not prolonged enough to clearly make the diagnosis. • 450 to 470 msec is considered borderline. • The average QTc for someone who has L-QTS is 490 msec • A QTc ≥ 480 msec in females or 470 msec in males, is probably a sign for L-QT S, in the absence of drugs, electrolyte disturbance, or other conditions that might independently lengthen the QT-interval. What is borderline QT ?What is borderline QT ?
- 152. • Frequency is unknown but it appears to be a common cause of SD unexplained in children and young adults. • It is certainly much more common than previously thought. • It may be as frequent as 1 in 5000 to 7000. • This means, one of 5000 to 7000 newborns have the disease. • In USA the presence of L-QT S is estimated to affect about 50.000 people and to cause as many as 3000 deaths each year. How common is inherent L-QT S ?How common is inherent L-QT S ?
- 153. • SYNCOPE or SD, typically occurring during physical activity or emotional upset. • Most commonly in preteen to teenage yrs, but may present from a few days of age to middle age. • Syncopal episodes are often misdiagnosed as the common faint (vasovagal event) or a seizure. Actual seizures are uncommon in L- QT S, but epilepsy is one of the common errors in diagnosis. • Sudden loss of consciousness during physical exertion or during emotional excitement should strongly raise the possibility of the L-QT S. • Family history of unexplained syncope or SD in young people should also raise suspicion. Importantly, about 1/3 of individuals who have the L- QT S never exhibit symptoms, and therefore, the lack of symptoms does not exclude a What are the Symptoms ?What are the Symptoms ?
- 154. • Swimming, running • An alarm clock, a loud horn, a ringing phone • Emotions: anger, crying, test taking or other stressful situations • Sudden death may also occur during sleep What are known triggers in L-QTS ?What are known triggers in L-QTS ?
- 155. • Beta blocker medications are the mainstay of Rx for most pts with the L- QT S • These AADs are effective in about 90 % of affected subjects. • However, a new study (JAMA ‘04) shows that among treated patients with LQT2 and LQT3 genotypes, there still is a high rate of cardiac events. • New information regarding the genetics of the syndrome suggests that a subset of patients might be treated with other drugs, either instead of or in addition to the beta blocker medications. This can be discussed with your physician and it depends upon the gene type which you have. What is the THERAPY ?What is the THERAPY ?
- 156. • In pts who do not respond to medication, the insertion of a PM or the ICD can be utilized. • Another procedure, mainly used in Europe, is the surgical cutting of certain nerves in the neck, called left cardiac sympathetic denervation. • All patients with symptoms should be treated, and because it is not possible to predict which patients are vulnerable to the syncope and sudden death, and sudden death often occurs with the first episode, asymptomatic patients, especially children, should also be treated. What is the THERAPY ?What is the THERAPY ?
- 157. 9. CAN AN AUTOPSY REVEAL LONG QT SYNDROME? There are two ways to make a diagnosis for QT syndrome. The first is to check if the QT-interval on the ECG of a suspected patient is prolonged. Because the heart stopps beating when death occurs, this possbility is out of question - except an ECG of the dead person already exists, of course. The only possibility would be to check body fluids of the dead person - in this case blood - for the known gene mutations that cause QT syndrome.
- 158. • SYMPTOMATIC pts should receive treatment. • It is RECOMMENDED to screen the family members • The BEST TREATMENT should be aimed at the specific gene types of L- QT S. • However, it has not yet been proven that such therapy is effective. Beta -adrenergic blocking agents. Effective in preventing cardiac events in approximately 70% of patients, while cardiac events continue to occur despite beta- blocker therapy in the remaining 30% of pts. ICD: Pts who have experienced CA, particularly if already on drug treatment, or who continue to have syncope in spite of medications, might best be treated with ICD. Management of L-QT S ?Management of L-QT S ?
- 159. Left thoracic sympathectomy. This procedure has mainly been used in Europe, for patients who were not responding to Beta blockers. It now has been largely replaced with permanent pacemaker and cardioverter- defibrillator implantation. Asymptomatic patients. In asymptomatic patients, preventive therapy is required. The reason is that it cannot be predicted with any accuracy which patient will subsequently have symptoms and which one will not. It is important to point out that 30% to 40% of sudden deaths occur at the first event. The treatment option is the long-term use of Beta blockers agent. It is generally recommended to treat all asymptomatic patients younger than 40 years old at the time of. However, on the other hand, some investigators have recommended treating asymptomatic patients only if they have high-risk Management of L-QT S ?Management of L-QT S ?
- 160. • Non esistono evidenze circa l’efficacia, nella prevenzione della mortalità totale e MI, per nessuno degli AADs in nessuna delle residue forme di CP • Storicamente, impiego clinico diffuso non validato per alcune categorie in alcune CP (ß-bloccanti in LQTS, Amiodarone in HCM) Sintesi nelle forme non CAD, non SC Rx Medica della Morte Improvvisa ICD in non-ischaemic CMICD in non-ischaemic CM
- 161. VT Polimorfa Catecolaminergica Blocchi atrioventricolari acquisiti Blocchi atrioventricolari congeniti III° Blocchi cronici bifascicolari o trifascicolari I IIa IIbClasse •BAV III° •BAV II° di tipo II •Sincope •Coesistente Cardiopatia / HF • Sincope • HV≥100 ms o blocco infraissiano • Inducibilita’ alla NIPS • Sincope • Intervallo QT lungo • Cardiopatia congenita • Coesistente Cardiopatia / HF HF = Scompenso Cardiaco; BAV = Blocco Atrioventricolare; NIPS = Stimolazione Programmata Non Invasiva 5 Priorietal.TaskForceonSuddenCardiacDeath oftheEuropeanSocietyofcardiology.EurHeart J2001;22:1374-1450.[Fulltext]
- 162. VT Polimorfa Catecolaminergica VF = Fibrillazione Ventricolare; SCD = Morte Improvvisa; VT Non Sost. = Tachicardia Ventricolare Non Sostenuta I IIa IIb •Familiarità di SCD •VT Non Sost. / sincope nell’età pediatrica • VF • Sincope Classe Stratificazione del Rischio 5 Priori et al. Task Force on Sudden Cardiac Death of the European Society of Cardiology. Eur Heart J 2001; 22:1374-1450. [Full text]
- 163. Described in ’99 by Swan AUTOSOMAL DOMINANT arrhythmic syndrome characterized by exercise induced polymorphic VTs in the absence of detectable structural HD. A similar disorder was clinically described by Coumel in ‘83 and more extensively (21 cases reported) by Lenhardt et al. in ’95. Usually occurs in young, healthy children and young adults and is characterized by stress- or emotion-induced syncope due to the onset of polymorphic VTs. Peculiar ECG pattern of bi-directional VTs and are reproducibly elicited either during exercise or by beta adrenergic stimulation with IPN infusion. At rest no significant ECG abnormalities are present. QT interval is within the normal limits and no ST segment elevation or intraventricular conduction abnormalities suggesting Brugada VT Polimorfa Catecolaminergica
- 164. Implicazioni CLINICHE • Non esistonoNon esistono TRIALS RANDOMIZZATITRIALS RANDOMIZZATI a supporto delle attuali indicazionia supporto delle attuali indicazioni • Le indicazioni proposte son prevalentementeLe indicazioni proposte son prevalentemente basate subasate su STUDI RETROSPETTIVISTUDI RETROSPETTIVI o piccolio piccoli STUDI PROSPETTICISTUDI PROSPETTICI (level B) o sull’opinione(level B) o sull’opinione deglidegli ESPERTIESPERTI (level C)(level C) • I criteri di stratificazione non sono ben definitiI criteri di stratificazione non sono ben definiti
- 165. Se è difficile la corretta stratificazione di patologie ad alta prevalenza nella popolazione generale ... che richiede TEMPO e COLLABORAZIONE Stratificare il rischio in patologie (relativamente ) rare diventa un obiettivo ...
- 166. • La revisione sintetica dei dati raccolti dalla Task Force della ESC ci ha fornito delle raccomandazioni (NON LINEE GUIDA !!!) in base alla EBM che coinvolgono la fase diagnostica e terapeutica dell’approccio alla morte improvvisa …… il PRESENTE …il PRESENTE … orienta l’investigatore circa la strategia da utilizzare nei singoli casi!
- 167. – Vincoli metodologici legati ai filtri a maglie strette della EBM, determinano il fatto che strategie terapeutiche che prevedono l’impiego dell’ICD sono confinate a popolazioni limitate (costo) e selezionate (rischio elevato MI), con conseguente generazione di ipotesi di lavoro forzate …… il PRESENTE …il PRESENTE … CONSEGUENZA: possibile mancanza di verifica legata ai vincoli!
- 168. …… il PRESENTE …il PRESENTE … • Tale condizione rende di DIFFICILE realizzazione una indagine SISTEMATICA circa gli effetti delle strategie profilattiche e terapeutiche nelle specifiche condizioni. • La maggioranza delle considerazioni estrapolate dai dati a nostra disposizione NON sono SEMPRE TRASFERIBILI direttamente a pazienti che malgrado segni e sintomi di uguale espressione, presentano condizioni di base profondamente DIVERSE.
- 169. Necessario il giusto “link” tra RICERCA e PRATICA CLINICA …… ed il FUTURO …ed il FUTURO … Perfezionare ulteriormente le conoscenze sui meccanismi fisiopatologici delle aritmie Migliorare ulteriormente la fase DIAGNOSTICA
- 170. Sudden Death with Normal Left Ventricular Function • Brugada Syndrome – Incompete RBB ST elevation V1V2 – exacerbated by Procainamide and Flecainide – ICD implantation • Right ventricular Dysplasia – Delayed Right Ventricular activation – Epsilon wave , deep precordial Twave inversion – fatty infiltration RV, MRI, RV gram
- 171. Sudden Death with Normal Left Ventricular Function • Hypertrophic Cardiomyopathy – Majority of sudden death in U.S. in young patients without coronary artery disease – Risk factors extreme hypertrophy(>3.0 cm)exertional hypotension, nonsustained VT,syncope, family history sudden death – ICD effective but appropriate selection for primary prevention problematic
Editor's Notes
- 1Myerburg, Robert. Sudden Death due to Cardiac Arrhythmias. NEJM, Vol. 345, No. 20; November 15, 2001. This slide reviews our best understanding of the causes of SCA. According to Dr. Myerburg, CAD is the underlying cause for 80% of SCA events. Either an acute ischemic event and/or a reentry pathway from a previous MI can cause an SCA event. According to this diagram, non-ischemic cardiomyopathy accounts for 10-15% of cases of SCA even though non-ischemics account for about 40% of CHF patients. Given that DEFINITE showed positive results in Class III patients with non-ischemic cardiomyopathy and we do not yet know the results of the non-ischemic arm in SCD-HeFT, our understanding of the etiology of SCA could change in the next several months.
- It is estimated that less than 40% of people in the US who meet Class I ACC/AHA indications receive an ICD. (Ruskin, J et al, J Cardiovasc Electrophysiol. 2002;14:38-43) In other parts of the world, less than 10% of patients with these indications receive an ICD. #2 previously read: Spontaneous sustained VT. This was changed by adding the requirement for structural heart disease. This change reflects the data showing that ICDs are most effective in patients with impaired LV function. VT in normal hearts can usually be treated with drugs or ablation. Refer to indication #5 on the next slide which states that ICDs are indicated in patients with no structural heart disease when other treatments (drugs, ablation) are not an option for the patient.
- Polymorphic ventricular tachyarrythmias is thought to be initiated by early after-depolarizations in the Purkinje system and maintained by reentry in the myocardium. pH gets decreases and results in cascades of events that lead to syncope.