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Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC): Genotype and Phenotype Analysis of a Cohort of Probands
Abstracts
was assessed against the ESC guidelines in the following ways: 1) Overall treatment accuracy. 2) Treatment of valvular vs non-valvular AF. 3) Treatment of low vs high risk AF. 4) Anticoagulant choice. 5) Documentation of CHA2DS2VASC/HAS-BLED scores. Results: 70% of all AF patients were treated as recommended by ESC. 79.2% of high risk patients were treated as per ESC, compared to 33.3% in low-risk patients. 83.3% of valvular AF patients were treated according to ESC, compared to 68.5% in non-valvular AF patients. Patients needing anticoagulation received the following therapies: Vitamin K antagonist (VKA) – 35%, NOAC – 42.5%, Antiplatelet therapy – 17.5%, no treatment - 5%. CHA2DS2VASC scores were documented 21.7% of time and HAS-BLED scores were not recorded. Conclusions: This study illustrates a gap in the utilisation of evidence based guidelines and a need for clearer protocols. We recommend a period of education and re-development of local guidelines that incorporate the recommendations of the ESC 2012 guidelines. We intend to repeat this audit once the above changes have been initiated. http://dx.doi.org/10.1016/j.hlc.2016.06.657 656 Valve Thrombosis in Surgical Bioprosthetic Aortic Valve Replacement (SAVR) and Transcatheter Aortic Valve Replacement (TAVR) K. Balakrishnan ∗ , V. Gupta, U. Hayat, A. Mahmud, B. Herman, G. Koshy Launceston General Hospital, Launceston, Australia Valve thrombosis (VT) is an under-recognised complication in bioprosthetic valves with reported incidence of 0.74 to 4.8%. Here we describe two cases of possible VT involving SAVR and TAVR. The first case is a 79-year-old-male with SAVR performed in 2009 who was found to have a mean transvalvular-gradient of 49 mmHg (compared to 12 mmHg 23 months prior). Transoesophageal echocardiogram (TOE) revealed marked restriction of the prosthetic leaflets and heterogeneous thickening on its downstream aspect. The second case is a 72-year-old male with TAVR in 2014 who presented with Streptococcal bacteraemia. No valvular vegetations were seen on TOE but the transprosthetic gradients had risen significantly within 3 months (from 12 to 31 mmHg). Marked thickening of the aortic leaflets on the downstream aspect with restricted mobility was noted. In both cases, the rapidity of progression in the prosthetic gradients combined with morphologic features of leaflets were highly suggestive of a thrombotic aetiology. Systemic anticoagulation was initiated with planned echocardiographic follow-up to monitor interval change in valve gradients. Thrombosis of bioprosthetic valves is an uncommon phenomenon but there is increasing reporting in the literature. Echocardiographic features to suggest VT include a rise in the gradient of >50% in 5 years, increased cusp thickness and abnormal leaflet mobility. High risk predictive features
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include co-existence of AF, lack of anticoagulation (which were present in both of our cases), smaller prostheses and “valve-in-valve” procedures. There is emerging evidence to support the use of anticoagulation in high risk patients with bio-prosthetic aortic valves. http://dx.doi.org/10.1016/j.hlc.2016.06.658 Cardiovascular Genetics (657–669) 657 Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC): Genotype and Phenotype Analysis of a Cohort of Probands D. Blusztein ∗ , P. Jayadeva, T. Thompson, D. Zentner, A. Trainer, P. James, I. Winship, J. Kalman, J. Vohra Royal Melbourne Hospital, Melbourne, Australia Background: ARVC may be difficult to diagnose. We describe the presentation, cardiac status and genetic test results in a cohort of ARVC patients. Methods: All ARVC proband cases diagnosed at a cardiac genetic clinic (2007-2015) were identified. Demographics, clinical presentation, genetic results and extent of cardiac involvement at initial cardiac assessment (MRI, echocardiography or post-mortem) were analysed. Results: Genetics
No. of Patients
Desmoplakin (DSP)
5
Plakophilin-2 (PKP2)
8
Desmocollin-2 (DSC2)
1
Other
1
VUS
11
No Mutation
6
No test
6
.............................................
74% of the cases were male. The majority were diagnosed after a sudden death (SCD) (n=14) or an aborted cardiac arrest (ACA) (n=6). Symptomatic VT (n=12) and syncope (n=3) accounted for the remainder. Cardiac assessment (n=37) demonstrated LV involvement in 16 (43%), 11 of those at postmortem (79%). Genetic testing (n=32) revealed a pathogenic mutation in a known ARVC gene in 15 probands. 11 probands had a variant of unknown significance (VUS). Plakophillin2 (PKP2) was the commonest gene mutation, (n=8). Of those with a pathogenic mutation, 43% (7/15) had LV involvement. Conclusion: In our clinic experience, probands with ARVC most commonly presented with SCD and ACA. LV involvement was common, particularly in those where the diagnosis was at PM (79%). Genetic testing identified a pathogenic mutation in 47% of cases, allowing family screening. No particular genotype predicted LV involvement.
Abstracts
S282
Conclusion: In our clinic experience, probands with ARVC most commonly presented with SCD and ACA. LV involvement was common, particularly in those where the diagnosis was at PM (79%). Genetic testing identified a pathogenic mutation in 47% of cases, allowing family screening. No particular genotype predicted LV involvement. http://dx.doi.org/10.1016/j.hlc.2016.06.659 658 Can ‘High Risk’ Selection Criteria Improve the Identification of Mutation Positive Individuals in the Cardiacgenetics Clinic? D. Zentner 1,2,∗ , T. Thompson 2 , J. Taylor 2 , M. Bogwitz 2 , I. Macciocca 2 , A. Trainer 2 , I. Winship 2 , J. Vohra 1,2 , P. James 2 1 Cardiology
Department, Royal Melbourne Hospital, Melbourne, Australia 2 Adult Genetics, Royal Melbourne Hospital, Melbourne, Australia Background: Greatest value in cardiac genetic testing comes from identifying families carrying a pathogenic mutation. In these families the mutation result can confirm the diagnosis, guide risk management and facilitate predictive testing for relatives. In practice, although detection rates vary, most index case testing will not identify a mutation. We sought to capture features of the clinical history identifying a higher chance of positive mutation detection and measure their performance as clinical checklist. Methods: A checklist of features associated with a higher risk of a gene mutation was created and applied retrospectively to all cases undergoing next generation sequencing (NGS) mutation detection through a single cardiacgenetics clinic. 126 cases were identified, including familial arrhythmia, cardiomyopathy and aortopathy, with a positive mutation detection rate of 36.5%. Clinical histories were reviewed by 2 clinicians in a de-identified manner and a checklist score assigned, using only information available at the time of testing. Result: A cutoff score ≥3 on the clinical checklist was reached for 35/46 (76%) mutation and 39/78 (50%) mutation negative cases, giving a 47% positive predictive value and 78% negative predictive value. The likelihood ratio for positive mutation detection at this threshold was 1.59. Conclusion: Clinical features can be utilised in a simple checklist to standardise selection of cases for mutation testing and increase the probability of mutation detection. Further refinement of the criteria may be able to improve their performance. http://dx.doi.org/10.1016/j.hlc.2016.06.660 659 Cardiac Genetics in Queensland: A Snapshot W. Peverill ∗ , J. Atherton Royal Brisbane and Women’s Hospital, Brisbane, Australia
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Introduction: Genetic testing is an increasingly recognised method of risk stratification in patients with a family history of cardiac disease. As our knowledge around this topic increases so does our ability to accurately screen and manage patients at high risk of future cardiovascular disease. Aim: To review five years of clinical cardiac genetics testing from 2010 – 2014, in order to examine the prevalence and sensitivity of genetic cardiac diseases with our current panels. Methods: The author examined all referrals to a cardiac genetics clinic from January 2010 until January 2015. Each patient referred was then searched in the Queensland pathology database Auslab. The genetic tests performed on those patients were then entered into a database which was analysed for the purpose of this project. Results: A total of 735 patients were referred. After clinical history and genetic counselling 341 patients went on to genetic screening. 112 patients were screened for Hypertrophic Obstructive Cardiomyopathy, 58 of which were positive, MYPBC3 was the most common gene detected. 105 were screened for Long QT Syndrome, 41 were positive, with KCNQ2 the most common. Twenty patients were screened for Arrhythmogenic right ventricular dysplasia, 20 for Catecholaminergic polymorphic ventricular tachycardia and 15 for Dilated Cardiomyopathy. The remaining conditions included Marfan’s Syndrome, pulmonary artery hypertension, left ventricular non-compaction and sudden cardiac death. 47 results from are still pending. http://dx.doi.org/10.1016/j.hlc.2016.06.661 660 Community Pharmacy Records Demonstrate Suboptimal Adherence to Beta Blockade in Familial Long QT Syndrome K. Waddell-Smith 1,∗ , J. Li 1 , W. Smith 2 , J. Crawford 1 , J. Skinner 1 1 Green Lane Paediatric and Congenital Cardiac Services, Starship Children’s Hospital, Auckland, New Zealand 2 Green Lane Cardiovascular Services, Auckland City Hospital, Auckland, New Zealand
Aim: Risk reduction in familial long QT syndrome (LQTS) relies on long-term regular beta blockade. Adherence data is scarce in this population, retrospectively reported only on day of cardiac arrest. Our aim was to document level of beta blocker adherence in patients with LQTS types 1 and 2 and determine factors associated with adherence. Method: Pharmacy dispensing data and electronic health records for 90 Auckland patients with LQTS types 1 and 2 were reviewed over a 34-month period. The medication possession ratio (MPR: proportion of follow-up days patients were dispensed beta blocker) was calculated for each patient. Adequate adherence was demonstrated by an MPR≥0.8 and ideal as MPR=1.0. Demographic and clinical features were assessed to determine if they predicted adherence.
was assessed against the ESC guidelines in the following ways: 1) Overall treatment accuracy. 2) Treatment of valvular vs non-valvular AF. 3) Treatment of low vs high risk AF. 4) Anticoagulant choice. 5) Documentation of CHA2DS2VASC/HAS-BLED scores. Results: 70% of all AF patients were treated as recommended by ESC. 79.2% of high risk patients were treated as per ESC, compared to 33.3% in low-risk patients. 83.3% of valvular AF patients were treated according to ESC, compared to 68.5% in non-valvular AF patients. Patients needing anticoagulation received the following therapies: Vitamin K antagonist (VKA) – 35%, NOAC – 42.5%, Antiplatelet therapy – 17.5%, no treatment - 5%. CHA2DS2VASC scores were documented 21.7% of time and HAS-BLED scores were not recorded. Conclusions: This study illustrates a gap in the utilisation of evidence based guidelines and a need for clearer protocols. We recommend a period of education and re-development of local guidelines that incorporate the recommendations of the ESC 2012 guidelines. We intend to repeat this audit once the above changes have been initiated. http://dx.doi.org/10.1016/j.hlc.2016.06.657 656 Valve Thrombosis in Surgical Bioprosthetic Aortic Valve Replacement (SAVR) and Transcatheter Aortic Valve Replacement (TAVR) K. Balakrishnan ∗ , V. Gupta, U. Hayat, A. Mahmud, B. Herman, G. Koshy Launceston General Hospital, Launceston, Australia Valve thrombosis (VT) is an under-recognised complication in bioprosthetic valves with reported incidence of 0.74 to 4.8%. Here we describe two cases of possible VT involving SAVR and TAVR. The first case is a 79-year-old-male with SAVR performed in 2009 who was found to have a mean transvalvular-gradient of 49 mmHg (compared to 12 mmHg 23 months prior). Transoesophageal echocardiogram (TOE) revealed marked restriction of the prosthetic leaflets and heterogeneous thickening on its downstream aspect. The second case is a 72-year-old male with TAVR in 2014 who presented with Streptococcal bacteraemia. No valvular vegetations were seen on TOE but the transprosthetic gradients had risen significantly within 3 months (from 12 to 31 mmHg). Marked thickening of the aortic leaflets on the downstream aspect with restricted mobility was noted. In both cases, the rapidity of progression in the prosthetic gradients combined with morphologic features of leaflets were highly suggestive of a thrombotic aetiology. Systemic anticoagulation was initiated with planned echocardiographic follow-up to monitor interval change in valve gradients. Thrombosis of bioprosthetic valves is an uncommon phenomenon but there is increasing reporting in the literature. Echocardiographic features to suggest VT include a rise in the gradient of >50% in 5 years, increased cusp thickness and abnormal leaflet mobility. High risk predictive features
S281
.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. ..
include co-existence of AF, lack of anticoagulation (which were present in both of our cases), smaller prostheses and “valve-in-valve” procedures. There is emerging evidence to support the use of anticoagulation in high risk patients with bio-prosthetic aortic valves. http://dx.doi.org/10.1016/j.hlc.2016.06.658 Cardiovascular Genetics (657–669) 657 Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC): Genotype and Phenotype Analysis of a Cohort of Probands D. Blusztein ∗ , P. Jayadeva, T. Thompson, D. Zentner, A. Trainer, P. James, I. Winship, J. Kalman, J. Vohra Royal Melbourne Hospital, Melbourne, Australia Background: ARVC may be difficult to diagnose. We describe the presentation, cardiac status and genetic test results in a cohort of ARVC patients. Methods: All ARVC proband cases diagnosed at a cardiac genetic clinic (2007-2015) were identified. Demographics, clinical presentation, genetic results and extent of cardiac involvement at initial cardiac assessment (MRI, echocardiography or post-mortem) were analysed. Results: Genetics
No. of Patients
Desmoplakin (DSP)
5
Plakophilin-2 (PKP2)
8
Desmocollin-2 (DSC2)
1
Other
1
VUS
11
No Mutation
6
No test
6
.............................................
74% of the cases were male. The majority were diagnosed after a sudden death (SCD) (n=14) or an aborted cardiac arrest (ACA) (n=6). Symptomatic VT (n=12) and syncope (n=3) accounted for the remainder. Cardiac assessment (n=37) demonstrated LV involvement in 16 (43%), 11 of those at postmortem (79%). Genetic testing (n=32) revealed a pathogenic mutation in a known ARVC gene in 15 probands. 11 probands had a variant of unknown significance (VUS). Plakophillin2 (PKP2) was the commonest gene mutation, (n=8). Of those with a pathogenic mutation, 43% (7/15) had LV involvement. Conclusion: In our clinic experience, probands with ARVC most commonly presented with SCD and ACA. LV involvement was common, particularly in those where the diagnosis was at PM (79%). Genetic testing identified a pathogenic mutation in 47% of cases, allowing family screening. No particular genotype predicted LV involvement.
Abstracts
S282
Conclusion: In our clinic experience, probands with ARVC most commonly presented with SCD and ACA. LV involvement was common, particularly in those where the diagnosis was at PM (79%). Genetic testing identified a pathogenic mutation in 47% of cases, allowing family screening. No particular genotype predicted LV involvement. http://dx.doi.org/10.1016/j.hlc.2016.06.659 658 Can ‘High Risk’ Selection Criteria Improve the Identification of Mutation Positive Individuals in the Cardiacgenetics Clinic? D. Zentner 1,2,∗ , T. Thompson 2 , J. Taylor 2 , M. Bogwitz 2 , I. Macciocca 2 , A. Trainer 2 , I. Winship 2 , J. Vohra 1,2 , P. James 2 1 Cardiology
Department, Royal Melbourne Hospital, Melbourne, Australia 2 Adult Genetics, Royal Melbourne Hospital, Melbourne, Australia Background: Greatest value in cardiac genetic testing comes from identifying families carrying a pathogenic mutation. In these families the mutation result can confirm the diagnosis, guide risk management and facilitate predictive testing for relatives. In practice, although detection rates vary, most index case testing will not identify a mutation. We sought to capture features of the clinical history identifying a higher chance of positive mutation detection and measure their performance as clinical checklist. Methods: A checklist of features associated with a higher risk of a gene mutation was created and applied retrospectively to all cases undergoing next generation sequencing (NGS) mutation detection through a single cardiacgenetics clinic. 126 cases were identified, including familial arrhythmia, cardiomyopathy and aortopathy, with a positive mutation detection rate of 36.5%. Clinical histories were reviewed by 2 clinicians in a de-identified manner and a checklist score assigned, using only information available at the time of testing. Result: A cutoff score ≥3 on the clinical checklist was reached for 35/46 (76%) mutation and 39/78 (50%) mutation negative cases, giving a 47% positive predictive value and 78% negative predictive value. The likelihood ratio for positive mutation detection at this threshold was 1.59. Conclusion: Clinical features can be utilised in a simple checklist to standardise selection of cases for mutation testing and increase the probability of mutation detection. Further refinement of the criteria may be able to improve their performance. http://dx.doi.org/10.1016/j.hlc.2016.06.660 659 Cardiac Genetics in Queensland: A Snapshot W. Peverill ∗ , J. Atherton Royal Brisbane and Women’s Hospital, Brisbane, Australia
.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. ..
Introduction: Genetic testing is an increasingly recognised method of risk stratification in patients with a family history of cardiac disease. As our knowledge around this topic increases so does our ability to accurately screen and manage patients at high risk of future cardiovascular disease. Aim: To review five years of clinical cardiac genetics testing from 2010 – 2014, in order to examine the prevalence and sensitivity of genetic cardiac diseases with our current panels. Methods: The author examined all referrals to a cardiac genetics clinic from January 2010 until January 2015. Each patient referred was then searched in the Queensland pathology database Auslab. The genetic tests performed on those patients were then entered into a database which was analysed for the purpose of this project. Results: A total of 735 patients were referred. After clinical history and genetic counselling 341 patients went on to genetic screening. 112 patients were screened for Hypertrophic Obstructive Cardiomyopathy, 58 of which were positive, MYPBC3 was the most common gene detected. 105 were screened for Long QT Syndrome, 41 were positive, with KCNQ2 the most common. Twenty patients were screened for Arrhythmogenic right ventricular dysplasia, 20 for Catecholaminergic polymorphic ventricular tachycardia and 15 for Dilated Cardiomyopathy. The remaining conditions included Marfan’s Syndrome, pulmonary artery hypertension, left ventricular non-compaction and sudden cardiac death. 47 results from are still pending. http://dx.doi.org/10.1016/j.hlc.2016.06.661 660 Community Pharmacy Records Demonstrate Suboptimal Adherence to Beta Blockade in Familial Long QT Syndrome K. Waddell-Smith 1,∗ , J. Li 1 , W. Smith 2 , J. Crawford 1 , J. Skinner 1 1 Green Lane Paediatric and Congenital Cardiac Services, Starship Children’s Hospital, Auckland, New Zealand 2 Green Lane Cardiovascular Services, Auckland City Hospital, Auckland, New Zealand
Aim: Risk reduction in familial long QT syndrome (LQTS) relies on long-term regular beta blockade. Adherence data is scarce in this population, retrospectively reported only on day of cardiac arrest. Our aim was to document level of beta blocker adherence in patients with LQTS types 1 and 2 and determine factors associated with adherence. Method: Pharmacy dispensing data and electronic health records for 90 Auckland patients with LQTS types 1 and 2 were reviewed over a 34-month period. The medication possession ratio (MPR: proportion of follow-up days patients were dispensed beta blocker) was calculated for each patient. Adequate adherence was demonstrated by an MPR≥0.8 and ideal as MPR=1.0. Demographic and clinical features were assessed to determine if they predicted adherence.