- Email: [email protected]
THE EFFECT OF GENDER ON SURVIVAL FROM SUDDEN CARDIAC DEATH IN THE YOUNG
Abstracts
interquartile ranges were significantly shorter in patients during their febrile presentation, as compared to their alternate, afebrile presentation [QT ¼ 388.7ms, (371.5-407.5) vs 406.7ms, (386.7-434.4); p <0.001]. This difference was observed in both sexes. Males were found to be more likely to experience medication induced QTc prolongation as compared with females [OR 5.35, 95% CI ¼ 1.46 e 19.68, P < 0.05]. Serum phosphorus, total calcium and magnesium levels correlated poorly with QTc values during both afebrile and febrile states (R2 ¼ 0.1321, 0.0086; 0.0077, 0.0185; 0.0462, 0.0001 respectively). One patient developed Torsades des pointes, a male receiving multiple QT prolonging medications (QTc ¼ 454.7ms). CONCLUSIONS: In a general patient population, fever shortens the QTc independent of sex. Prolongation of the QT interval during fever should thus increase clinical suspicion of congenital or acquired long QT syndrome. McLaughlin Summer Studentship
255 IS DILATED CARDIOMYOPATHY A PRIMARY FEATURE OF ANDERSEN-TAWIL SYNDROME? CHARACTERIZATION OF A NOVEL KCNJ2 MUTATION S Rezazadeh, H Duff, B Gerull Calgary, Alberta BACKGROUND:
Andersen-Tawil syndrome (ATS) is a rare autosomal dominant multisystem disorder characterized by cardiac arrhythmias, periodic paralysis, and dysmorphic features. Mutations in the KCNJ2, the gene encoding the human inward rectifier potassium channel Kir2.1 (IK1) have been linked to ATS. Currently, it remains unclear whether dilated cardiomyopathy is a primary feature of ATS. METHODS: Our proband featured recurrent ventricular arrhythmias, periodic muscle weakness, in addition to dilated cardiomyopathy with moderate-severe left ventricular dysfunction. A broad next generation sequencing panel assessing for 151 genes associated with familial arrhythmias and cardiomyopathies was performed, leading to identification of a novel missense variant in KCNJ2. Functional properties of the identified variant were studied in transiently transfected HEK-293 cells using whole cell patch clamp technique. RESULTS: A novel missense mutation c.665T>C (p.L222S) was identified in the carboxyl-terminus of Kir2.1. Biophysical assessments revealed p.L222S suppressed IK1 completely. Treatment of this patient with beta blocking agents, suppressed ventricular arrhythmias. With this, serial assessment of left ventricular function revealed normalization of size and function. CONCLUSION: We report a novel KCNJ2 mutation associated with phenotypic features of ATS. The L222S mutation resulted in reduction in IK1 current. Furthermore, treatment of ventricular arrhythmia resulted in normalization of left
S213
ventricular size and systolic function, suggesting dilated cardiomyopathy is a secondary phenotype in ATS due to high tachyarrhythmia burden. Alberta Innovates Health Solutions, Canadian Institutes of Health Research
256 THE EFFECT OF GENDER ON SURVIVAL FROM SUDDEN CARDIAC DEATH IN THE YOUNG KS Allan, LJ Morrison, JV Tu, A Pinter, T Aves, M McGillion, P Dorian Hamilton, Ontario BACKGROUND:
Studies of sudden cardiac death (SCD) have shown contradictory results concerning the effect of gender on survival, possibly due to incomplete analyses of all clinical factors. We hypothesized that both intra-arrest and cardiac risk factors for SCD would influence the effect of gender on survival to discharge in a young SCD cohort. METHODS: We utilized a prospectively collected, populationbased registry of out-of-hospital cardiac arrests (OHCAs) in the Greater Toronto Area, to identify patients from 20092012. Cases with presumed cardiac etiology, ages 18-45, who were treated, died or survived (aborted SCDs) were included. Past medical history, prescribed medications and intra-arrest variables were recorded from ambulance/fire call reports, inhospital charts, police reports, coroner investigative statements, autopsy and toxicology reports. We reviewed all available data for each case to adjudicate an etiology, cardiac or non-cardiac. The final cohort included only adjudicated cases of cardiac etiology (both SCDs and aborted SCDs), further divided by gender. Chi square tests and unadjusted and adjusted logistic regression models were used to examine the association between gender and survival to hospital discharge. RESULTS: We identified 450 treated SCDs and aborted SCDs (75.6% male; 24.4% female). Females survived to hospital discharge more often than males (33.6% vs. 22.4%; p¼0.02). The unadjusted OR for survival was 1.76 (95%CI: 1.10, 2.81; p¼0.02); after adjustment for both intra-arrest and cardiac risk factors, females were almost 3 times as likely to survive to hospital discharge compared to males (OR: 2.92; 95%CI: 1.44, 5.91; p¼0.003) (Table 1). There were no differences between genders with the proportion of structural (non-coronary) heart disease (32.0% females vs. 27.0% males; p¼0.21), however, males had significantly higher proportions of coronary heart disease than females (44.0% males vs. 32.0% females; p¼0.01). Proportions with hypertension (27.9% vs. 19.0%; p¼0.02) and diabetes (19.4% vs. 12.1%; p¼0.03) were significantly higher in females than males, while rates of mental illnesses such as depression, were similar (12.4% females vs. 7.3% males; p¼0.11). Over a third of males and females were prescribed cardiac medications. Males were more often prescribed antipsychotics (8.2% males vs. 0% females; p¼0.006) but not opioids (9.4% males vs. 14.9%
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females; p¼0.15) or antidepressants (7.0% males vs. 11.5% females; p¼0.19). CONCLUSION: Males and females significantly differed in their cardiac risk factors and prescribed medications. Despite having more SCD risk factors, young females were almost three times as likely as males to survive to hospital discharge after cardiac arrest. Table 1: Adjusted regression estimates for assessing the effect of gender and survival to discharge Odds Ratio (95% P Value Variable CI) Age (years)
0.96 (0.91, 0.99)
0.03
Women
2.92 (1.44, 5.91)
0.003
Initial Rhythm VF
8.64 (3.80, 19.67) <0.0001
Bystander Witnessed
2.78 (1.30, 5.98)
0.009
Bystander CPR
1.05 (0.55, 2.01)
0.88
Public Location
0.80 (0.40, 1.62)
0.54
Non-Smoker
4.19 (1.33, 13.19) 0.01
Hypertension
1.43 (0.63, 3.26)
0.39
Diabetes
0.49 (0.17, 1.40)
0.18
257 ABSENCE OF A J-WAVE MAY BE PREDICTIVE OF WORSE OUTCOMES DURING THERAPEUTIC HYPOTHERMIA IN POST CARDIAC ARREST PATIENTS M Alshehri, L Semeniuk, D Exner, A Mardell, D Zygun, R Sheldon, S Wagel, G Schnell, H Duff Calgary, Alberta BACKGROUND:
The presence of Osborn or J-waves during hypothermia may be associated with increased propensity of arrhythmias, However, J-waves may be a normal physiologic response to hypothermia, since the activity of many cardiac ion channels is altered by temperature. OBJECTIVE: We sought to investigate if the absence of J-waves during hypothermia was associated with clinical outcome among cardiac arrest survivors and accidental hypothermic patients. METHODS: Cardiac arrest survivors undergoing mild therapeutic hypothermia and accidental hypothermic patients were evaluated for the presence or absence of J-waves during hypothermia (28-33 C) using standard 12-lead electrocardiograms (ECGs). ECGs were assessed blinded to clinical outcome and using standard criteria. Subjects were followed an average of 6-years. The primary outcome was total mortality. In-hospital ventricular tachycardia or ventricular fibrillation were secondary outcomes. RESULTS: J-waves were present in 9 of the 44 (20%) cardiac arrest survivors and in all 10 of the accidental hypothermia patients. Cardiac arrest survivors without J-waves had a higher rate of death (56%) as compared to cardiac arrest survivors with J-waves (34%) or accidental hypothermic patients (30%). Differences were largely related to in-hospital death. Survival among the groups remained significant, when
stratified by clinically important variables including the presence of left ventricular dysfunction, prolonged down-time and the initial rhythm at the time of initial resuscitation; Log-rank p¼0.05. Rates of in-hospital ventricular tachycardia or ventricular fibrillation were similar among the three groups. CONCLUSION: The absence of J-waves during therapeutic hypothermia is associated with increased risk of death among cardiac arrest survivors.
258 ECG MARKERS OF REPOLARIZATION IN EATING DISORDERS: A CASE CONTROL STUDY M Janzen, P Lam, K Gibbs, C Steinberg, C Cheung, G Mellor, G Padfield, A Krahn Vancouver, British Columbia BACKGROUND:
Eating disorders (ED) affect 1-2% of the general population, with a concentrated prevalence of 3% among adolescent females. Sudden unexpected death (SUD) is a leading cause of death in ED, specifically Anorexia Nervosa (AN) and EDNOS (ED Not Otherwise Specified). ECG changes during acute ED may be able to predict the risk of SUD by drawing parallels to other well-studied arrhythmia conditions. In addition, up to 80% of ED are associated with mood disorders; these patients may be prescribed psychotropic medications, such as anxiolytics and/or antidepressants, which may have a compound effect on the ECG. We sought to characterize HR, QT interval, and T-wave changes observed in AN and EDNOS. METHODS/RESULTS: A retrospective cohort study of adolescent females treated at the British Columbia Specialized Eating Disorders Clinic between 2010-2014 was performed. Available resting ECGs were analyzed and compared to ageand sex-matched healthy controls. ECGs were read with assessment of the HR, QT interval, and T-wave morphology. Comparisons were made between patients and controls, and patients with or without medication. A total of 45 ECGs from 23 females (age 14.91.4, BMI 15.61.8) with a diagnosis of either AN (n¼16, 70%) or EDNOS (n¼7, 30%) were reviewed and compared to ECGs from 45 age- and sexmatched healthy controls (BMI 19.82.8). There were no differences in ECG parameters between ED diagnoses. ED patients showed lower HR compared to controls (5811 vs. 7511 bpm, p<0.01). There was no difference in absolute QT interval (p¼0.89), but patients had shorter corrected QT intervals (QTc, 383ms vs. 426 ms, p<0.01). Only a minority of patients (n¼6) had T-wave abnormalities without difference between patients and controls (p¼0.95). In the patient group, a significant correlation was not seen between BMI and HR (R2 ¼ -0.02, p¼0.82) or QTc (R2¼-0.02, p¼0.96). Eleven patients received psychotropic medications; ECGs recorded in the presence of psychotropic medications trended toward longer QTc intervals compared to those without, but this was not significant (39128 vs 38228 ms, p¼0.37). There was also no difference in HR or T-wave morphology
interquartile ranges were significantly shorter in patients during their febrile presentation, as compared to their alternate, afebrile presentation [QT ¼ 388.7ms, (371.5-407.5) vs 406.7ms, (386.7-434.4); p <0.001]. This difference was observed in both sexes. Males were found to be more likely to experience medication induced QTc prolongation as compared with females [OR 5.35, 95% CI ¼ 1.46 e 19.68, P < 0.05]. Serum phosphorus, total calcium and magnesium levels correlated poorly with QTc values during both afebrile and febrile states (R2 ¼ 0.1321, 0.0086; 0.0077, 0.0185; 0.0462, 0.0001 respectively). One patient developed Torsades des pointes, a male receiving multiple QT prolonging medications (QTc ¼ 454.7ms). CONCLUSIONS: In a general patient population, fever shortens the QTc independent of sex. Prolongation of the QT interval during fever should thus increase clinical suspicion of congenital or acquired long QT syndrome. McLaughlin Summer Studentship
255 IS DILATED CARDIOMYOPATHY A PRIMARY FEATURE OF ANDERSEN-TAWIL SYNDROME? CHARACTERIZATION OF A NOVEL KCNJ2 MUTATION S Rezazadeh, H Duff, B Gerull Calgary, Alberta BACKGROUND:
Andersen-Tawil syndrome (ATS) is a rare autosomal dominant multisystem disorder characterized by cardiac arrhythmias, periodic paralysis, and dysmorphic features. Mutations in the KCNJ2, the gene encoding the human inward rectifier potassium channel Kir2.1 (IK1) have been linked to ATS. Currently, it remains unclear whether dilated cardiomyopathy is a primary feature of ATS. METHODS: Our proband featured recurrent ventricular arrhythmias, periodic muscle weakness, in addition to dilated cardiomyopathy with moderate-severe left ventricular dysfunction. A broad next generation sequencing panel assessing for 151 genes associated with familial arrhythmias and cardiomyopathies was performed, leading to identification of a novel missense variant in KCNJ2. Functional properties of the identified variant were studied in transiently transfected HEK-293 cells using whole cell patch clamp technique. RESULTS: A novel missense mutation c.665T>C (p.L222S) was identified in the carboxyl-terminus of Kir2.1. Biophysical assessments revealed p.L222S suppressed IK1 completely. Treatment of this patient with beta blocking agents, suppressed ventricular arrhythmias. With this, serial assessment of left ventricular function revealed normalization of size and function. CONCLUSION: We report a novel KCNJ2 mutation associated with phenotypic features of ATS. The L222S mutation resulted in reduction in IK1 current. Furthermore, treatment of ventricular arrhythmia resulted in normalization of left
S213
ventricular size and systolic function, suggesting dilated cardiomyopathy is a secondary phenotype in ATS due to high tachyarrhythmia burden. Alberta Innovates Health Solutions, Canadian Institutes of Health Research
256 THE EFFECT OF GENDER ON SURVIVAL FROM SUDDEN CARDIAC DEATH IN THE YOUNG KS Allan, LJ Morrison, JV Tu, A Pinter, T Aves, M McGillion, P Dorian Hamilton, Ontario BACKGROUND:
Studies of sudden cardiac death (SCD) have shown contradictory results concerning the effect of gender on survival, possibly due to incomplete analyses of all clinical factors. We hypothesized that both intra-arrest and cardiac risk factors for SCD would influence the effect of gender on survival to discharge in a young SCD cohort. METHODS: We utilized a prospectively collected, populationbased registry of out-of-hospital cardiac arrests (OHCAs) in the Greater Toronto Area, to identify patients from 20092012. Cases with presumed cardiac etiology, ages 18-45, who were treated, died or survived (aborted SCDs) were included. Past medical history, prescribed medications and intra-arrest variables were recorded from ambulance/fire call reports, inhospital charts, police reports, coroner investigative statements, autopsy and toxicology reports. We reviewed all available data for each case to adjudicate an etiology, cardiac or non-cardiac. The final cohort included only adjudicated cases of cardiac etiology (both SCDs and aborted SCDs), further divided by gender. Chi square tests and unadjusted and adjusted logistic regression models were used to examine the association between gender and survival to hospital discharge. RESULTS: We identified 450 treated SCDs and aborted SCDs (75.6% male; 24.4% female). Females survived to hospital discharge more often than males (33.6% vs. 22.4%; p¼0.02). The unadjusted OR for survival was 1.76 (95%CI: 1.10, 2.81; p¼0.02); after adjustment for both intra-arrest and cardiac risk factors, females were almost 3 times as likely to survive to hospital discharge compared to males (OR: 2.92; 95%CI: 1.44, 5.91; p¼0.003) (Table 1). There were no differences between genders with the proportion of structural (non-coronary) heart disease (32.0% females vs. 27.0% males; p¼0.21), however, males had significantly higher proportions of coronary heart disease than females (44.0% males vs. 32.0% females; p¼0.01). Proportions with hypertension (27.9% vs. 19.0%; p¼0.02) and diabetes (19.4% vs. 12.1%; p¼0.03) were significantly higher in females than males, while rates of mental illnesses such as depression, were similar (12.4% females vs. 7.3% males; p¼0.11). Over a third of males and females were prescribed cardiac medications. Males were more often prescribed antipsychotics (8.2% males vs. 0% females; p¼0.006) but not opioids (9.4% males vs. 14.9%
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Canadian Journal of Cardiology Volume 32 2016
females; p¼0.15) or antidepressants (7.0% males vs. 11.5% females; p¼0.19). CONCLUSION: Males and females significantly differed in their cardiac risk factors and prescribed medications. Despite having more SCD risk factors, young females were almost three times as likely as males to survive to hospital discharge after cardiac arrest. Table 1: Adjusted regression estimates for assessing the effect of gender and survival to discharge Odds Ratio (95% P Value Variable CI) Age (years)
0.96 (0.91, 0.99)
0.03
Women
2.92 (1.44, 5.91)
0.003
Initial Rhythm VF
8.64 (3.80, 19.67) <0.0001
Bystander Witnessed
2.78 (1.30, 5.98)
0.009
Bystander CPR
1.05 (0.55, 2.01)
0.88
Public Location
0.80 (0.40, 1.62)
0.54
Non-Smoker
4.19 (1.33, 13.19) 0.01
Hypertension
1.43 (0.63, 3.26)
0.39
Diabetes
0.49 (0.17, 1.40)
0.18
257 ABSENCE OF A J-WAVE MAY BE PREDICTIVE OF WORSE OUTCOMES DURING THERAPEUTIC HYPOTHERMIA IN POST CARDIAC ARREST PATIENTS M Alshehri, L Semeniuk, D Exner, A Mardell, D Zygun, R Sheldon, S Wagel, G Schnell, H Duff Calgary, Alberta BACKGROUND:
The presence of Osborn or J-waves during hypothermia may be associated with increased propensity of arrhythmias, However, J-waves may be a normal physiologic response to hypothermia, since the activity of many cardiac ion channels is altered by temperature. OBJECTIVE: We sought to investigate if the absence of J-waves during hypothermia was associated with clinical outcome among cardiac arrest survivors and accidental hypothermic patients. METHODS: Cardiac arrest survivors undergoing mild therapeutic hypothermia and accidental hypothermic patients were evaluated for the presence or absence of J-waves during hypothermia (28-33 C) using standard 12-lead electrocardiograms (ECGs). ECGs were assessed blinded to clinical outcome and using standard criteria. Subjects were followed an average of 6-years. The primary outcome was total mortality. In-hospital ventricular tachycardia or ventricular fibrillation were secondary outcomes. RESULTS: J-waves were present in 9 of the 44 (20%) cardiac arrest survivors and in all 10 of the accidental hypothermia patients. Cardiac arrest survivors without J-waves had a higher rate of death (56%) as compared to cardiac arrest survivors with J-waves (34%) or accidental hypothermic patients (30%). Differences were largely related to in-hospital death. Survival among the groups remained significant, when
stratified by clinically important variables including the presence of left ventricular dysfunction, prolonged down-time and the initial rhythm at the time of initial resuscitation; Log-rank p¼0.05. Rates of in-hospital ventricular tachycardia or ventricular fibrillation were similar among the three groups. CONCLUSION: The absence of J-waves during therapeutic hypothermia is associated with increased risk of death among cardiac arrest survivors.
258 ECG MARKERS OF REPOLARIZATION IN EATING DISORDERS: A CASE CONTROL STUDY M Janzen, P Lam, K Gibbs, C Steinberg, C Cheung, G Mellor, G Padfield, A Krahn Vancouver, British Columbia BACKGROUND:
Eating disorders (ED) affect 1-2% of the general population, with a concentrated prevalence of 3% among adolescent females. Sudden unexpected death (SUD) is a leading cause of death in ED, specifically Anorexia Nervosa (AN) and EDNOS (ED Not Otherwise Specified). ECG changes during acute ED may be able to predict the risk of SUD by drawing parallels to other well-studied arrhythmia conditions. In addition, up to 80% of ED are associated with mood disorders; these patients may be prescribed psychotropic medications, such as anxiolytics and/or antidepressants, which may have a compound effect on the ECG. We sought to characterize HR, QT interval, and T-wave changes observed in AN and EDNOS. METHODS/RESULTS: A retrospective cohort study of adolescent females treated at the British Columbia Specialized Eating Disorders Clinic between 2010-2014 was performed. Available resting ECGs were analyzed and compared to ageand sex-matched healthy controls. ECGs were read with assessment of the HR, QT interval, and T-wave morphology. Comparisons were made between patients and controls, and patients with or without medication. A total of 45 ECGs from 23 females (age 14.91.4, BMI 15.61.8) with a diagnosis of either AN (n¼16, 70%) or EDNOS (n¼7, 30%) were reviewed and compared to ECGs from 45 age- and sexmatched healthy controls (BMI 19.82.8). There were no differences in ECG parameters between ED diagnoses. ED patients showed lower HR compared to controls (5811 vs. 7511 bpm, p<0.01). There was no difference in absolute QT interval (p¼0.89), but patients had shorter corrected QT intervals (QTc, 383ms vs. 426 ms, p<0.01). Only a minority of patients (n¼6) had T-wave abnormalities without difference between patients and controls (p¼0.95). In the patient group, a significant correlation was not seen between BMI and HR (R2 ¼ -0.02, p¼0.82) or QTc (R2¼-0.02, p¼0.96). Eleven patients received psychotropic medications; ECGs recorded in the presence of psychotropic medications trended toward longer QTc intervals compared to those without, but this was not significant (39128 vs 38228 ms, p¼0.37). There was also no difference in HR or T-wave morphology