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SPATIAL QRS-T ANGLE IS ASSOCIATED WITH MORTALITY IN INCIDENT HEMODIALYSIS PATIENTS
CLINICAL SCIENCE ABSTRACTS FUNCTIONAL ANALYSIS ON A NOVEL KCNH2 MUTATION IDENTIFIED IN FAMILIAL SHORT QT SYNDROME Q. Wang, S. Ohno, W. Ding, J. Bai, T. Makiyama, H. Matsuura, M. Horie Shiga University of Medical Science, Otsu, Japan. Background: Short QT syndrome (SQTS) is an inherited disease characterized by abbreviated QTc intervals and ventricular fibrillation (VF). Although 3 genes have been reported responsible for SQTS, only 2 mutations, N588K and T618I, were reported in KCNH2. We aimed to screen gene mutations in SQTS and perform functional analysis of the mutations. Methods: For 7 SQTS patients, we performed genetic analysis in genes responsible for SQTS. We also analyzed a novel KCNH2 mutation using the patch-clamp method. Results: We identified a KCNH2-H70Y in a 25-year-old man who suffered cardiac arrest. VF was recorded in the ambulance, and the patient was successfully resuscitated by AED. His QTc interval after cardioversion was 287 ms. There was no family history; however, QTc intervals of his mother and 2 brothers were 293, 307, and 323 ms, respectively. They carried the same KCNH2 mutation. Regarding codon H70 located in the N-terminus, H70R was previously reported as a mutation associated with long QT syndrome (LQTS). Electrophysiologic study showed that cells expressing H70Y had significantly larger IKr densities than WT. In contrast, those expressing H70R had smaller IKr densities than WT (Figure). Gating kinetics of both mutant channels showed no difference compared to WT. These results were greatly different from those of previously reported KCNH2 mutations. Conclusions: The novel SQTS-related mutation H70Y increased IKr densities without altering the gating kinetics, and H70R resulted in a simple IKr reduction. Thus, codon 70 appeared to be an important site for membrane expression of the IKr channel, causing SQTS by H70Y and LQTS by H70R.
LONG QT SYNDROME COMPLICATING ATRIOVENTRICULAR BLOCK: ARRHYTHMOGENIC EFFECTS OF CARDIAC MEMORY S. Viskin,1 A. Adler,1 B. Strasberg,1 M. Guevara-Valdivia,2 A. Baranchuk,3 R. Rosso,1 1 Tel Aviv Medical Center Tel Aviv, Israel, 2UMAE Hospital de Especialidades Dr. Antonio Fraga Mouret, CMN La Raza IMSS, Mexico, Mexico, 3 Kingston General Hospital and Queen’s University, Ontario, ON, Canada. Background: The magnitude of QT prolongation in response to bradycardia, rather than the bradycardia per se, determines the risk for torsades de pointes (TdP) during atrioventricular (AV) block. However, we do not know why some patients develop more QT prolongation than others despite similar degrees of bradycardia. We hypothesized that in patients who develop significant QRS vector changes during AV block, the ensuing cardiac memory leads to excessive QT prolongation. Methods and Results: We studied 91 patients who presented with 2:1 (18 patients) or high-degree/complete AV block (73 patients) and who also had an ECG predating the bradyarrhythmia for comparison. We correlated the changes in QRS morphology and axis taking place during AV block with the degree of bradycardia-induced QT prolongation. Patients with and without QRS morphology changes at the time of AV block were of similar age and gender. Moreover, despite similar R-R interval during AV block, cases involving a QRS morphology change had significantly longer QT (648 ⫾ 84 vs 561 ⫾ 84, Po.001) than cases with no QRS morphology change. Patients who developed a change in QRS morphology at the time of AV block had a 6-fold higher risk of developing long QT. This risk doubled when the change in QRS morphology was accompanied by a change in QRS axis. Conclusions: Cardiac memory resulting from a change in QRS morphology and/or QRS axis during AV block is independently associated with QT prolongation and may be proarrhythmic during AV block.
SPATIAL QRS-T ANGLE IS ASSOCIATED WITH MORTALITY IN INCIDENT HEMODIALYSIS PATIENTS L. Tereshchenko,1 A. Oehler,1 L. Meoni,2 S. Sur,3 T. Rami,2 M. Maly,2 B. Jaar,2 S. Sozio,2 M. Estrella,2 R. Parekh,2 1 Oregon Health and Science University Portland, OR, 2 Johns Hopkins University SOM, Baltimore, MD, 3 Johns Hopkins University, Baltimore, MD. Background: Mortality in end-stage renal disease (ESRD) patients on dialysis is extremely high, and the single largest cause of death is linked to ventricular arrhythmias. However, risk stratification strategy in ESRD has not been developed. We examined whether spatial QRS-T angle is associated with mortality in incident hemodialysis patients.
1547-5271/$-see front matter B 2014 Published by Elsevier Inc. on behalf of Heart Rhythm Society.
2139 Methods: Orthogonal ECG was recorded during 5 minutes at rest in participants of the Predictors of Arrhythmia and Cardiovascular Events Study, a prospective cohort of incident hemodialysis patients. Data from 338 participants (mean age 54.4 ⫾ 13.4 years, 58% male, 73% black; mean left ventricular ejection fraction [LVEF] 65.3% ⫾ 11.8%) were analyzed. Spatial “peak” QRST angle was measured as an angle between spatial QRS and T vectors averaged across a 3-minute period. Patients were followed prospectively. All-cause mortality served as a primary outcome. Results: During 2.4 ⫾ 1.2 years of follow-up, 64 patients (19%) died. QRS-T angle was wider in men than in women (111.1 ⫾ 43.71 vs 98.1 ⫾ 43.41, P ¼ .007). In univariable survival analysis men with baseline QRS-T angle 490º had higher mortality compared to those with narrower angles (Figure). In multivariable Cox regression, after adjustment for age, race, prevalent coronary heart disease, LVEF, and averaged 90-day albumin, QRS-T angle 490º was associated with higher mortality risk in men (HR 4.7, 95%CI 1.3–16.9, P ¼ .018). In contrast, no association was observed between QRS-T angle and mortality among women (adjusted HR 0.8, 95%CI 0.3–2.1, P ¼ .713). Conclusion: Spatial QRS-T angle was strongly and independently associated with mortality after hemodialysis initiation in men but not women.
Background: Rapid organized activity (ROA) in atrial fibrillation (AF) has been observed during epicardial mapping as well as catheter ablation. Lately, localized sources termed “rotors” or “drivers” have been characterized as maintaining AF. Their supposedly small size and surrounding fibrillatory environment has prevented detailed evaluation with conventional mapping techniques. Methods: Using a multispline catheter with 10 electrode pairs (EP) covering an area of 3.5-cm diameter, we systematically mapped the left atrium (LA) to detect areas of ROA. 603 ⫾ 64 points per patient (pt) were recorded in 15 pts undergoing catheter ablation for persistent AF. Areas of ROA were further evaluated by their length-scale properties and response to entrainment and adenosine. Adenosine dosage was 12 mgm. Results: Mapping revealed 3–7 areas of ROA per pt. The cycle length (CL) of ROA tended to be similar, ie, unique for a patient, in different areas of LA. Some areas of ROA demonstrated stable activation pattern consistent with a recurring wavefront (WF). In areas showing WF the pre-adenosine CL was 196 ⫾ 57 ms, and the post-adenosine CL was 188 ⫾ 61 ms (Po.03). Mean conduction velocity (CV) in WF areas was 0.6 ⫾ .21 m/s. Mean circuit length (CVCL) for recurring WF was 110 ⫾ 34 mm or a diameter of 3.5 ⫾ 1.1 cm. The areas of WF-like activation were resistant to entrainment with overdrive pacing. Conclusions: The organized atrial activity in persistent AF appears to be part of circuits that are larger than previously suspected. Our measured circuit lengths are in range of formerly reported human LA tissue wavelength. The inability to entrain, as well as the response to adenosine, suggests reentry without an excitable gap.
ACTIVATION DELAY IS ALREADY PRESENT IN THE EARLY CONCEALED STAGE OF ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA/ CARDIOMYOPATHY T.P. Mast, A.J. Teske, A.S. Te Riele, J.A. Groeneweg, J.F. van der Heijden, B.K. Velthuis, P. Loh, P.A. Doevendans, D. Dooijes, M.J. Cramer, R.N. Hauer UMC Utrecht, Utrecht, Netherlands.
AREAS OF REENTRANT WAVEFRONT-LIKE ACTIVATION CHARACTERIZE PERSISTENT ATRIAL FIBRILLATION R. Mahmud, D. Lee, N. Ahmed, P. Kamaraju, S. Raza, T. Ahmed, B. Janer McLaren Bay Region, Bay City, MI.
Background: Sudden death may be the first manifestation in the concealed stage of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). However, particularly at this stage, disease detection is hampered by absence of criteria. Activation delay (AD) is a hallmark of arrhythmogenesis in ARVD/C. Echocardiographic deformation imaging may unmask AD in the absence of established electrocardiographic (ECG) and structural abnormalities. Methods: Three groups were compared: (1) symptomatic ARVD/C patients with a mutation in the Plakophilin-2 (PKP2) gene (n ¼ 37); (2) asymptomatic PKP2 mutation carriers (n ¼ 20); and (3) healthy controls (n ¼ 30). All groups underwent echocardiography, including deformation imaging of the right ventricle (RV) and ECG recording according to Task Force criteria (TFC). As surrogate for AD, the electromechanical interval (EMI) was measured, defined as time between first electrical deflection and local onset of mechanical shortening. Results: Mean EMI was prolonged in all RV segments in ARVD/C patients. In asymptomatic mutation carriers, prolonged EMI was detected in the subtricuspid area in 9 of 20 subjects (45%), whereas ECG abnormalities and structural alteration were only seen in 6 of 20 (30%) and 2 of 20 (10%), respectively. Isolated prolonged EMI occurred in 7 of 20 (35%) asymptomatic mutation carriers (Figure). Conclusions: Deformation imaging reveals AD in both patient groups. In asymptomatic mutation carriers, prolonged EMI in the subtricuspid region is often detected without any abnormalities on ECG and imaging. EMI is a new noninvasive parameter unmasking AD in concealed ARVD/C stage and may contribute to risk stratification.
LONG QT SYNDROME COMPLICATING ATRIOVENTRICULAR BLOCK: ARRHYTHMOGENIC EFFECTS OF CARDIAC MEMORY S. Viskin,1 A. Adler,1 B. Strasberg,1 M. Guevara-Valdivia,2 A. Baranchuk,3 R. Rosso,1 1 Tel Aviv Medical Center Tel Aviv, Israel, 2UMAE Hospital de Especialidades Dr. Antonio Fraga Mouret, CMN La Raza IMSS, Mexico, Mexico, 3 Kingston General Hospital and Queen’s University, Ontario, ON, Canada. Background: The magnitude of QT prolongation in response to bradycardia, rather than the bradycardia per se, determines the risk for torsades de pointes (TdP) during atrioventricular (AV) block. However, we do not know why some patients develop more QT prolongation than others despite similar degrees of bradycardia. We hypothesized that in patients who develop significant QRS vector changes during AV block, the ensuing cardiac memory leads to excessive QT prolongation. Methods and Results: We studied 91 patients who presented with 2:1 (18 patients) or high-degree/complete AV block (73 patients) and who also had an ECG predating the bradyarrhythmia for comparison. We correlated the changes in QRS morphology and axis taking place during AV block with the degree of bradycardia-induced QT prolongation. Patients with and without QRS morphology changes at the time of AV block were of similar age and gender. Moreover, despite similar R-R interval during AV block, cases involving a QRS morphology change had significantly longer QT (648 ⫾ 84 vs 561 ⫾ 84, Po.001) than cases with no QRS morphology change. Patients who developed a change in QRS morphology at the time of AV block had a 6-fold higher risk of developing long QT. This risk doubled when the change in QRS morphology was accompanied by a change in QRS axis. Conclusions: Cardiac memory resulting from a change in QRS morphology and/or QRS axis during AV block is independently associated with QT prolongation and may be proarrhythmic during AV block.
SPATIAL QRS-T ANGLE IS ASSOCIATED WITH MORTALITY IN INCIDENT HEMODIALYSIS PATIENTS L. Tereshchenko,1 A. Oehler,1 L. Meoni,2 S. Sur,3 T. Rami,2 M. Maly,2 B. Jaar,2 S. Sozio,2 M. Estrella,2 R. Parekh,2 1 Oregon Health and Science University Portland, OR, 2 Johns Hopkins University SOM, Baltimore, MD, 3 Johns Hopkins University, Baltimore, MD. Background: Mortality in end-stage renal disease (ESRD) patients on dialysis is extremely high, and the single largest cause of death is linked to ventricular arrhythmias. However, risk stratification strategy in ESRD has not been developed. We examined whether spatial QRS-T angle is associated with mortality in incident hemodialysis patients.
1547-5271/$-see front matter B 2014 Published by Elsevier Inc. on behalf of Heart Rhythm Society.
2139 Methods: Orthogonal ECG was recorded during 5 minutes at rest in participants of the Predictors of Arrhythmia and Cardiovascular Events Study, a prospective cohort of incident hemodialysis patients. Data from 338 participants (mean age 54.4 ⫾ 13.4 years, 58% male, 73% black; mean left ventricular ejection fraction [LVEF] 65.3% ⫾ 11.8%) were analyzed. Spatial “peak” QRST angle was measured as an angle between spatial QRS and T vectors averaged across a 3-minute period. Patients were followed prospectively. All-cause mortality served as a primary outcome. Results: During 2.4 ⫾ 1.2 years of follow-up, 64 patients (19%) died. QRS-T angle was wider in men than in women (111.1 ⫾ 43.71 vs 98.1 ⫾ 43.41, P ¼ .007). In univariable survival analysis men with baseline QRS-T angle 490º had higher mortality compared to those with narrower angles (Figure). In multivariable Cox regression, after adjustment for age, race, prevalent coronary heart disease, LVEF, and averaged 90-day albumin, QRS-T angle 490º was associated with higher mortality risk in men (HR 4.7, 95%CI 1.3–16.9, P ¼ .018). In contrast, no association was observed between QRS-T angle and mortality among women (adjusted HR 0.8, 95%CI 0.3–2.1, P ¼ .713). Conclusion: Spatial QRS-T angle was strongly and independently associated with mortality after hemodialysis initiation in men but not women.
Background: Rapid organized activity (ROA) in atrial fibrillation (AF) has been observed during epicardial mapping as well as catheter ablation. Lately, localized sources termed “rotors” or “drivers” have been characterized as maintaining AF. Their supposedly small size and surrounding fibrillatory environment has prevented detailed evaluation with conventional mapping techniques. Methods: Using a multispline catheter with 10 electrode pairs (EP) covering an area of 3.5-cm diameter, we systematically mapped the left atrium (LA) to detect areas of ROA. 603 ⫾ 64 points per patient (pt) were recorded in 15 pts undergoing catheter ablation for persistent AF. Areas of ROA were further evaluated by their length-scale properties and response to entrainment and adenosine. Adenosine dosage was 12 mgm. Results: Mapping revealed 3–7 areas of ROA per pt. The cycle length (CL) of ROA tended to be similar, ie, unique for a patient, in different areas of LA. Some areas of ROA demonstrated stable activation pattern consistent with a recurring wavefront (WF). In areas showing WF the pre-adenosine CL was 196 ⫾ 57 ms, and the post-adenosine CL was 188 ⫾ 61 ms (Po.03). Mean conduction velocity (CV) in WF areas was 0.6 ⫾ .21 m/s. Mean circuit length (CVCL) for recurring WF was 110 ⫾ 34 mm or a diameter of 3.5 ⫾ 1.1 cm. The areas of WF-like activation were resistant to entrainment with overdrive pacing. Conclusions: The organized atrial activity in persistent AF appears to be part of circuits that are larger than previously suspected. Our measured circuit lengths are in range of formerly reported human LA tissue wavelength. The inability to entrain, as well as the response to adenosine, suggests reentry without an excitable gap.
ACTIVATION DELAY IS ALREADY PRESENT IN THE EARLY CONCEALED STAGE OF ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA/ CARDIOMYOPATHY T.P. Mast, A.J. Teske, A.S. Te Riele, J.A. Groeneweg, J.F. van der Heijden, B.K. Velthuis, P. Loh, P.A. Doevendans, D. Dooijes, M.J. Cramer, R.N. Hauer UMC Utrecht, Utrecht, Netherlands.
AREAS OF REENTRANT WAVEFRONT-LIKE ACTIVATION CHARACTERIZE PERSISTENT ATRIAL FIBRILLATION R. Mahmud, D. Lee, N. Ahmed, P. Kamaraju, S. Raza, T. Ahmed, B. Janer McLaren Bay Region, Bay City, MI.
Background: Sudden death may be the first manifestation in the concealed stage of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). However, particularly at this stage, disease detection is hampered by absence of criteria. Activation delay (AD) is a hallmark of arrhythmogenesis in ARVD/C. Echocardiographic deformation imaging may unmask AD in the absence of established electrocardiographic (ECG) and structural abnormalities. Methods: Three groups were compared: (1) symptomatic ARVD/C patients with a mutation in the Plakophilin-2 (PKP2) gene (n ¼ 37); (2) asymptomatic PKP2 mutation carriers (n ¼ 20); and (3) healthy controls (n ¼ 30). All groups underwent echocardiography, including deformation imaging of the right ventricle (RV) and ECG recording according to Task Force criteria (TFC). As surrogate for AD, the electromechanical interval (EMI) was measured, defined as time between first electrical deflection and local onset of mechanical shortening. Results: Mean EMI was prolonged in all RV segments in ARVD/C patients. In asymptomatic mutation carriers, prolonged EMI was detected in the subtricuspid area in 9 of 20 subjects (45%), whereas ECG abnormalities and structural alteration were only seen in 6 of 20 (30%) and 2 of 20 (10%), respectively. Isolated prolonged EMI occurred in 7 of 20 (35%) asymptomatic mutation carriers (Figure). Conclusions: Deformation imaging reveals AD in both patient groups. In asymptomatic mutation carriers, prolonged EMI in the subtricuspid region is often detected without any abnormalities on ECG and imaging. EMI is a new noninvasive parameter unmasking AD in concealed ARVD/C stage and may contribute to risk stratification.