genetic testing in patients with arrhythmia and risk for sudden cardiac death : indications and...
TRANSCRIPT
![Page 1: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/1.jpg)
Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice
Mary Gertrude Ong-Cordovez, M.D.
Cebu City
![Page 2: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/2.jpg)
Inherited Cardiac Arrhythmias
• Channelopathy (ion channel disease)• LQTS• CPVT• Brugada Syndrome
• Primary Structural Heart Disease (cardiomyopathies)• ARVC/D• HOCM• Familial DCM
![Page 3: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/3.jpg)
Epidemiology
• 1:500 (HOCM)• 1:1000 (ARVD)• 1:2000 (LQTS, CPVT, Brugada syndrome)• 1:2500 (DCM)
![Page 4: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/4.jpg)
Ion Channel Diseases
LQTS: KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2 (65%)
Brugada syndrome: SCN5A (25% to 30%)
CPVT: RYR2 (60%), possibly CASQ2
![Page 5: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/5.jpg)
Cardiomyopathies
ARVD: PKP2, DSP, DSG2 (60%)
HOCM: MYH7, MYBPC3, TNNT2 (60%)
DCM: LMNA, MYH7, TNNT2, SCN5A (20% to 30%)
![Page 6: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/6.jpg)
LQTS
![Page 7: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/7.jpg)
Genotype-phenotype correlations in long-QT syndrome.
Tester D J , Ackerman M J Circulation 2011;123:1021-1037
Copyright © American Heart Association
![Page 8: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/8.jpg)
LQTS
• Management• Beta Blockers• Mexilitene, flecainide, propanolol• Treat hypokalemia and hypomagnesemia• ICD• Avoid QT prolonging drugs
![Page 9: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/9.jpg)
QT Prolonging Drugs
• Albuterol epinephrine roxithromycin• Alfuzosin erythromycin salmeterol• Amiodarone famotidine sertraline• Amphetamine flecainide sotalol• Azithromycin gatifloxacin tamoxifen• Ciprofoxacin imipramine terbutaline• Clarythhromycin ketoconazole SXT• Diphenhydramin levofloxacin vardenafil• Dobutamine moxifloxacin• Dopamine ofloxacin
www.qtdrugs.org
![Page 10: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/10.jpg)
Ion Channel Diseases
LQTS: KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2 (65%)
Brugada syndrome: SCN5A (25% to 30%)
CPVT: RYR2 (60%), possibly CASQ2
ARVD: PKP2, DSP, DSG2 (60%)
![Page 11: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/11.jpg)
Recommendations for Genetic Testing
• Cardiac arrest survivor ++• Syncope
• QTc abnormal ++• QTc borderline +/-• QTc normal _
• Asymptomatic • QTc abnormal ++• QTc borderline _
• First degree relative• Proband genotype + ++• Proband genotype _ _
Canadian J of Cardiology 27(2011) 232-248
![Page 12: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/12.jpg)
Brugada Syndrome
![Page 13: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/13.jpg)
Brugada Syndrome
• Management• Beta blocker and amiodarone• Quinidine• Aggressive fever control• Avoid strenuous physical activity• ICD• Avoid sodium channel blocker
![Page 14: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/14.jpg)
Na Channel Blockers
• Anti-arrhythmic drugs• Flecainide, propafenone, ajmalin, procainamide
• Psychotropic Drugs• Amitriptyline, lithium, nortriptyline, trifluoperazine
• Anesthetics/Analgesics• Bupivacaine, procaine, profolol
• Others• Acetylcholine, alcohol, cocaine, ergonovine
![Page 15: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/15.jpg)
Ion Channel Diseases
LQTS: KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2 (65%)
Brugada syndrome: SCN5A (25% to 30%)
CPVT: RYR2 (60%), possibly CASQ2
![Page 16: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/16.jpg)
Recommendations for Genetic Testing (Brugada Syndrome)
• Cardiac arrest survivor• Type I Brugada ECG pattern ++• Type 2 or 3 ECG pattern __
• Syncope• Type I Brugada ECG pattern ++• Type 2 or 3 ECG pattern __
• Asymptomatic• Type I Brugada ECG pattern ++• Type 2 or 3 ECG pattern __
• First Degree Relative• Proband genotype positive ++
• Proband genotype negative ___
![Page 17: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/17.jpg)
CPVT
![Page 18: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/18.jpg)
CPVT
• Management• Beta blockers• Flecainide/cardiac sympathectomy• ICD• Avoid intense physical exercise
![Page 19: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/19.jpg)
Ion Channel Diseases
LQTS: KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2 (65%)
Brugada syndrome: SCN5A (25% to 30%)
CPVT: RYR2 (60%), possibly CASQ2
![Page 20: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/20.jpg)
Recommendations for Genetic Testing (CPVT)
• Clinically suspected CPVT ++
• First degree relative• Proband genotype + ++
![Page 21: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/21.jpg)
ARVD/C
• Task Force Criteria • RV function• Tissue characteristic of the myocardium• ECG repolarization abnormalities• Arrhythmias• Family history• Genetic testing
![Page 22: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/22.jpg)
ARVD
• Management• Avoid competitive sports• ICD
• Documented ventricular arrhythmias
![Page 23: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/23.jpg)
Cardiomyopathies
ARVD: PKP2, DSP, DSG2 (60%-70%)
HOCM: MYH7, MYBPC3, TNNT2 (60%)
DCM: LMNA, MYH7, TNNT2, SCN5A (20% to 30%)
![Page 24: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/24.jpg)
Recommendations for Genetic Testing (ARVD)
• Clinical ARVD ++• Clincal ARVD no ID at risk family members __• Clinically suspected ARVD ++• First degree relative
• Genotype positive ++• Genotype negative __
![Page 25: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/25.jpg)
HOCM
• Echocardiography• MRI
![Page 26: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/26.jpg)
Management
• Asymptomatic• Treat risk factors- HPN, DM, dyslipidemia, obesity
• Beta-blockers• Angina and dyspnea
• verapamil• Septal reduction Rx
• surgical septal myectomy/ alcohol septal ablation• Drug refractory and LVOT obstruction
• ICD
![Page 27: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/27.jpg)
Indications for ICDs in HCM. *SCD risk modifiers include established risk factors and emerging risk modifiers (Section 9.4.2).
et al. Circulation 2011;124:2761-2796
Copyright © American Heart Association
![Page 28: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/28.jpg)
Management
• Asymptomatic• Treat risk factors- HPN, DM, dyslipidemia, obesity
• Beta-blockers• Angina and dyspnea
• verapamil• Septal reduction Rx
• surgical septal myectomy/ alcohol septal ablation• Drug refractory and LVOT obstruction
• ICD• Exercise restriction
![Page 29: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/29.jpg)
HOCM
• Exercise• Permitted
• Bowling, brisk walking, golf, skating, snorkeling, treadmill, biking
• Strongly discouraged• Basketball, body building, rock climbing , sprinting,
soccer, tennis , wind surfing, scuba diving
Circulation 2011;124:2761-2796
![Page 30: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/30.jpg)
Cardiomyopathies
ARVD: PKP2, DSP, DSG2 (60%-70%)
HOCM: MYH7, MYBPC3, TNNT2 (60%)
DCM: LMNA, MYH7, TNNT2, SCN5A (20% to 30%)
![Page 31: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/31.jpg)
Recommendationf for Genetic Testing (HOCM)
• Clinically diagnose HOCM• Family screening ++• Diagnosis __• Risk stratification/Rx decisions __
![Page 32: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/32.jpg)
DCM
• Cardiac imaging studies• Cardiac biopsy- diagnostic tool
• Management• ACEI, B blockers, spironolactone• ICD - EF <35%• Biventricular pacing
![Page 33: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/33.jpg)
Cardiomyopathies
ARVD: PKP2, DSP, DSG2 (60%-70%)
HOCM: MYH7, MYBPC3, TNNT2 (60%)
DCM: LMNA, MYH7, TNNT2, SCN5A (20% to 30%)
![Page 34: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/34.jpg)
Recommendation for Genetic Testing (DCM)
• Clinically Dx DCM __
• Clinically Dx DCM w/ atrial arrhythmias/high grade conduction disease ++
(LMNA, SCNA5)
![Page 35: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/35.jpg)
Future Perspective
• Gene sequencing will be faster and available more cheaply
• Multidisciplinary approach• Gray areas • Gene therapy
![Page 36: Genetic Testing in Patients with Arrhythmia and Risk for Sudden Cardiac Death : Indications and Implications for Practice Mary Gertrude Ong-Cordovez, M.D](https://reader035.vdocuments.us/reader035/viewer/2022062421/56649cf55503460f949c37fc/html5/thumbnails/36.jpg)