emery - dreifuss muscular dystrophy ( edmd )  first described by emery and dreifuss in 1966  is a hereditary muscle disorder characterized by slowly progressive muscle wasting and weakness , with humero - peroneal distribution in the early stages , early contractures of the elbows , achilles tendons and post - cervical muscles , and cardiomyopathy . edmd can be inherited either as an x - linked recessive disorder , caused by mutations in the sta gene that encodes the nuclear protein emerin on chomosome xq28 , or as an autosomal dominant trait caused by mutations in the gene encoding the nuclear protein lamin a / c ( lmna ) on chromosome 1q21.2 . cardiomyopathy is the most serious and life - threatening clinical manifestation of the disease , and usually appears later compared with muscle impairment . rhythm abnormalities commonly noted in the all forms of muscular dystrophies , especially in edmd , include sinus node dysfunction , atrial flutter , atrial fibrillation , heart block , ventricular tachycardia , and ventricular fibrillation . sudden cardiac death ( scd ) is common in patients with edmd , and is attributed to the development of life - threatening arrhythmias which occur in the presence of normal left ventricular systolic function . thus , electrical abnormalities may be the earliest manifestation of the histopathological process conducive to the development of cardiomyopathy . the gene therapy , unfortunately , has not yet given the desired results up to this moment , so prevention of arrhythmic risk plays an important role in the current treatment of this rare form of muscular dystrophy . assessment of the individual risk for sudden death in patients with emery - dreifuss muscular dystrophy remains a clinical challenge . scd in edmd patients has not received sufficient recognition in the literature , and its mechanism is potentially of great interest . qtc dispersion ( qtc- d ) and jtc dispersion ( jtc- d ) have been proposed as noninvasive methods to measure the heterogeneity of ventricular repolarization . increased dispersion of ventricular repolarization is considered to provide an electrophysiological substrate for life - threatening ventricular arrhythmias   in several clinical conditions [ 1116 ] . the aim of our study was to evaluate the heterogeneity of ventricular repolarization in edmd by examining qtc - d and jtc - d , electrocardiographic parameters of spatial heterogeneity of ventricular repolarization , in edmd patients with preserved systolic and diastolic function . the study enrolled 36 edmd subjects ( 26 men ; age 2012 years ) recruited from the cardiomyology and medical genetics section of the 2 university of naples . thirty - six age- and sex - matched non - edmd healthy subjects were also recruited as controls . exclusion criteria were : history of hypertension ( systolic and diastolic blood pressure > 140/90 mmhg ) , obesity , previous atrial fibrillation , electrolyte imbalance , valvular heart disease , diabetes mellitus or impaired glucose tolerance , chronic renal disease , thyroid disorders , chronic obstructive pulmonary disease , cardiomyopathy , connective tissue disorders , heart failure , left bundle branch block or atrioventricular conduction abnormalities on electrocardiogram ( ecg ) , congenital heart disease , congestive heart failure , pericarditis , pulmonary embolism , sick sinus syndrome , and preexcitation syndromes . all patients were in sinus rhythm , and none of them was taking medications known to affect electrocardiographic intervals . medical history , physical examination , anthropometric evaluation , 12-lead surface ecg , 2d color doppler echocardiogram and ecg holter monitoring were performed in the study population . the patients were rested for at least 15 min before cardiovascular assessments , including electrocardiography and echocardiography . all subjects underwent a routine standard 12-lead body surface ecg , recorded at a paper speed of 50 mm / s and gain of 10 mm / mv in the supine position , and were breathing freely but not allowed to speak during the ecg recording . to avoid diurnal variations , we generally performed the ecg recordings at the same time ( 9:00 a.m. to 10:00 a.m. ) . ecgs were transferred to a personal computer by an optical scanner and then magnified 400 times by adobe photoshop software ( adobe systems inc . qrs duration , qt interval and jt interval were evaluated with the use of computer software ( configurable measurement system ) using digitizer 34180 ( calcomp , anaheim , ca , usa ) . the standard correlation was 95% ( 95% ci 25.63 to 6.31 ) . in each electrocardiogram lead , leads were excluded from analysis when the end of the t - wave was not clearly distinguishable , or the signal quality was too poor for analysis . the qrs interval was measured from the start of the q wave , or , in the absence of the q wave , from the start of r wave to the end of s ( to its return to the isoelectric line ) . the qt interval was measured from the initial deflection of the qrs complex to the end of the t wave ( to the point where the t wave returned to the isoelectric line ) . when u wave was present , the qt was measured to the nadir of the curve between the t and u waves . if the end of the t wave could not be reliably determined , or if the t waves were isoelectric or of very low amplitude , measurements were not done and these leads were excluded from analysis . qtd was the difference between the maximal and the minimal qt value in all leads . the difference between the maximal and the minimal jt value in all leads was defined as jtd . all measurements were corrected for heart rate using bazett s formula ( qtc = qt/rr ; jtc = jt/rr ) . images were gathered with a standard ultrasound machine with a 3.5-mhz phased - array probe ( m3s ) . all the echocardiographic studies were digitally stored , and all the measurements were performed off - line by 2 independent observers who were blinded to the clinical status of the subjects . selected parameters were measured according to the american society of echocardiography recommendations   in m - mode from parasternal long - axis view : left ventricular end - diastolic diameter ( lvedd ) , left ventricular end - systolic diameter ( lvesd ) , interventricular septum thickness ( ivst ) , left ventricular posterior wall thickness ( lvpt ) . lv mass ( lvm ) was calculated by using devereux s formula , and was indexed for body surface area and height . pulsed - wave doppler examination was performed to obtain the following indexes of lv diastolic function : peak mitral inflow velocities at early ( e ) and late ( a ) diastole and e / a ratio . average values of these indexes obtained from 5 consecutive cardiac cycles were used for analysis . the study enrolled 36 edmd subjects ( 26 men ; age 2012 years ) recruited from the cardiomyology and medical genetics section of the 2 university of naples . thirty - six age- and sex - matched non - edmd healthy subjects were also recruited as controls . exclusion criteria were : history of hypertension ( systolic and diastolic blood pressure > 140/90 mmhg ) , obesity , previous atrial fibrillation , electrolyte imbalance , valvular heart disease , diabetes mellitus or impaired glucose tolerance , chronic renal disease , thyroid disorders , chronic obstructive pulmonary disease , cardiomyopathy , connective tissue disorders , heart failure , left bundle branch block or atrioventricular conduction abnormalities on electrocardiogram ( ecg ) , congenital heart disease , congestive heart failure , pericarditis , pulmonary embolism , sick sinus syndrome , and preexcitation syndromes . all patients were in sinus rhythm , and none of them was taking medications known to affect electrocardiographic intervals . medical history , physical examination , anthropometric evaluation , 12-lead surface ecg , 2d color doppler echocardiogram and ecg holter monitoring were performed in the study population . the patients were rested for at least 15 min before cardiovascular assessments , including electrocardiography and echocardiography . all subjects underwent a routine standard 12-lead body surface ecg , recorded at a paper speed of 50 mm / s and gain of 10 mm / mv in the supine position , and were breathing freely but not allowed to speak during the ecg recording . to avoid diurnal variations , we generally performed the ecg recordings at the same time ( 9:00 a.m. to 10:00 a.m. ) . ecgs were transferred to a personal computer by an optical scanner and then magnified 400 times by adobe photoshop software ( adobe systems inc . qrs duration , qt interval and jt interval were evaluated with the use of computer software ( configurable measurement system ) using digitizer 34180 ( calcomp , anaheim , ca , usa ) . the standard correlation was 95% ( 95% ci 25.63 to 6.31 ) . in each electrocardiogram lead , leads were excluded from analysis when the end of the t - wave was not clearly distinguishable , or the signal quality was too poor for analysis . the qrs interval was measured from the start of the q wave , or , in the absence of the q wave , from the start of r wave to the end of s ( to its return to the isoelectric line ) . the qt interval was measured from the initial deflection of the qrs complex to the end of the t wave ( to the point where the t wave returned to the isoelectric line ) . when u wave was present , the qt was measured to the nadir of the curve between the t and u waves . if the end of the t wave could not be reliably determined , or if the t waves were isoelectric or of very low amplitude , measurements were not done and these leads were excluded from analysis . qtd was the difference between the maximal and the minimal qt value in all leads . the difference between the maximal and the minimal jt value in all leads was defined as jtd . all measurements were corrected for heart rate using bazett s formula ( qtc = qt/rr ; jtc = jt/rr ) . images were gathered with a standard ultrasound machine with a 3.5-mhz phased - array probe ( m3s ) . all the echocardiographic studies were digitally stored , and all the measurements were performed off - line by 2 independent observers who were blinded to the clinical status of the subjects . selected parameters were measured according to the american society of echocardiography recommendations   in m - mode from parasternal long - axis view : left ventricular end - diastolic diameter ( lvedd ) , left ventricular end - systolic diameter ( lvesd ) , interventricular septum thickness ( ivst ) , left ventricular posterior wall thickness ( lvpt ) . lv mass ( lvm ) was calculated by using devereux s formula , and was indexed for body surface area and height . pulsed - wave doppler examination was performed to obtain the following indexes of lv diastolic function : peak mitral inflow velocities at early ( e ) and late ( a ) diastole and e / a ratio . average values of these indexes obtained from 5 consecutive cardiac cycles were used for analysis . the healthy control group did not significantly differ from edmd group in bmi , heart rate and blood pressure ( bp ) . no significant differences in lvpwedt ( 7.20.8 vs. 5.91.2 mm , p=0.3 ) , ivsedt ( 7.51.2 vs. 6.30.8 mm , p=0.4 ) , lvedd ( 49.45.1 vs. 43.44.5 mm , p=0.3 ) , lvesd ( 34.45.7 vs. 32.24.8 mm , p=0.4 ) , lvm / h ( 35.710 vs. 32.59 g / m 2.7 , p=0.3 ) , left ventricle fractional shortening ( fs ; 34.84.1 vs. 32.34.2% , p=0.2 ) and ejection fraction ( ef 64.65.1 vs. 63.48.1% , p=0.1 ) between the 2 groups were observed . these data indicate compensated normal systolic function in the edmd group . compared with controls , the edmd group did not show significant e wave ( 82.316.5 vs. 92.410.8 cm / s ; p=0.2 ) , a wave ( 57.912.5 vs. 52.039.72 cm / s ; p=0.3 ) and e / a ratio ( 1.50.4 vs. 1.80.38 ; p=0.3 ) variations . compared to the healthy control group , the edmd group presented increased values of qtc - d ( 82.744.2 vs. 53.113.7 ; p=0.003 ) and jtc - d ( 73.632.3 vs. 60.411.1 ms ; p=0.001 ) ( figure 1 ) . absolute value of intraobserver variability of qtc and jtc dispersion measurement was 74 ms and 42 ms , respectively . no statistically significant correlation between qtc - d , jtc - d , bmi ( p=0.2 ) , lvm ( p=0.3 ) and ejection fraction ( p=0.1 ) was found . no statistically significant differences in qtc - d ( 92.539.3 vs. 70.648.7 ms , p=0.4 ) and jtc - d ( 61.7316.46 vs. 64.7214,12 ms , p=0.4 ) between the laminopathy edmd subgroup and the emerinopathy edmd subgroup were found . the healthy control group did not significantly differ from edmd group in bmi , heart rate and blood pressure ( bp ) . no significant differences in lvpwedt ( 7.20.8 vs. 5.91.2 mm , p=0.3 ) , ivsedt ( 7.51.2 vs. 6.30.8 mm , p=0.4 ) , lvedd ( 49.45.1 vs. 43.44.5 mm , p=0.3 ) , lvesd ( 34.45.7 vs. 32.24.8 mm , p=0.4 ) , lvm / h ( 35.710 vs. 32.59 g / m 2.7 , p=0.3 ) , left ventricle fractional shortening ( fs ; 34.84.1 vs. 32.34.2% , p=0.2 ) and ejection fraction ( ef 64.65.1 vs. 63.48.1% , p=0.1 ) between the 2 groups were observed . these data indicate compensated normal systolic function in the edmd group . compared with controls , the edmd group did not show significant e wave ( 82.316.5 vs. 92.410.8 cm / s ; p=0.2 ) , a wave ( 57.912.5 vs. 52.039.72 cm / s ; p=0.3 ) and e / a ratio ( 1.50.4 vs. 1.80.38 ; p=0.3 ) variations . electrocardiographic characteristics of the study population are shown in table 2 . compared to the healthy control group , the edmd group presented increased values of qtc - d ( 82.744.2 vs. 53.113.7 ; p=0.003 ) and jtc - d ( 73.632.3 vs. 60.411.1 ms ; p=0.001 ) ( figure 1 ) . absolute value of intraobserver variability of qtc and jtc dispersion measurement was 74 ms and 42 ms , respectively . no statistically significant correlation between qtc - d , jtc - d , bmi ( p=0.2 ) , lvm ( p=0.3 ) and ejection fraction ( p=0.1 ) was found . no statistically significant differences in qtc - d ( 92.539.3 vs. 70.648.7 ms , p=0.4 ) and jtc - d ( 61.7316.46 vs. 64.7214,12 ms , p=0.4 ) between the laminopathy edmd subgroup and the emerinopathy edmd subgroup were found . in our study we evaluated the qtc dispersion and jtc dispersion , electrocardiographic markers of ventricular repolarization heterogeneity , in emery - dreifuss muscular dystrophy patients with preserved systolic and diastolic function . qtd and jtd are expressions of regional differences in cellular action potential duration and in ventricular recovery time . increase in qtd and jtd increases the risk of development of malignant ventricular arrhythmias , probably via 2 mechanisms . first , it facilitates transmural early afterdepolarization propagation ; second , it could cause intramural functional conduction blocks that predispose to re - entrant polymorphic ventricular tachyarrhythmias . an increase in qt dispersion is a possible substrate for ventricular arrhythmias and sudden cardiac death in patients with chronic heart failure , left ventricular hypertrophy , diabetes mellitus , prolonged qt interval , obesity   and in subjects who are 55 years of age or older . several studies suggested that jtc - d is clinically useful in assessing arrhythmia risk   because it is a parameter that is less dependent on ventricular depolarization and reflects the ventricular repolarization heterogeneities better than qtc - d in patients with intra - ventricular conduction abnormalities . less is known about the heterogeneity of ventricular repolarization in emery - dreifuss muscular dystrophy patients with preserved systolic and diastolic function . previous experimental studies have shown a slight decrease of heart rates , with significant prolongations of pq , qrs and qt intervals compared with control recordings in conscious , restrained lmna mice ecg recordings . these ecg changes resemble some aspects of the ecg records from humans with edmd ( 28 ) . to our knowledge , no information is present in literature about qtc and jtc dispersion in edmd patients with normal systolic and diastolic function . it is known that sudden cardiac death has a high incidence in patients carrying sta and lamin a / c gene mutations . scd is attributed to the development of life - threatening arrhythmias , probably related to the specific histopathological pattern characterized by diffuse fibrosis and fatty acid infiltration . studying the qtc - d and jtc - d in edmd patients without systolic or diastolic dysfunction , and without other clinically appreciable diseases , might have offered the unique clinical opportunity to exclude the influence of possible comorbidities on the evaluation of heterogeneity of ventricular repolarization in this population . our data showed that the electrocardiographic parameters , proposed to estimate the ventricular repolarization heterogeneity ( qtc - d , jtc - d ) , were significantly increased in edmd patients when compared with age and sex - matched healthy controls . the significant increase in heterogeneity of ventricular repolarization parameters in edmd patients suggests that cardiac diffuse fibrosis and fatty acid infiltration per se influences regional dispersion of repolarization , even when systolic and diastolic cardiac function are preserved . the small number of patients included is certainly a limitation , and a more extensive study is needed to confirm these findings . qt interval and jt interval were made on 12-lead ecgs , with the use of computer software and digitizer by an experienced cardiologist observer . however , there remains an absence of indisputable , generally accepted criteria for the definition of the end of t interval , implying some degree of possible error in the measurements . the 12-lead surface ecg , compared with body surface mapping or vector cardiography , gives an incomplete picture of cardiac electric activity , so qtd could not be a true manifestation of local heterogeneity of repolarization . previous experimental studies have shown a slight decrease of heart rates , with significant prolongations of pq , qrs and qt intervals compared with control recordings in conscious , restrained lmna mice ecg recordings . these ecg changes resemble some aspects of the ecg records from humans with edmd ( 28 ) . to our knowledge , no information is present in literature about qtc and jtc dispersion in edmd patients with normal systolic and diastolic function . it is known that sudden cardiac death has a high incidence in patients carrying sta and lamin a / c gene mutations . scd is attributed to the development of life - threatening arrhythmias , probably related to the specific histopathological pattern characterized by diffuse fibrosis and fatty acid infiltration . studying the qtc - d and jtc - d in edmd patients without systolic or diastolic dysfunction , and without other clinically appreciable diseases , might have offered the unique clinical opportunity to exclude the influence of possible comorbidities on the evaluation of heterogeneity of ventricular repolarization in this population . our data showed that the electrocardiographic parameters , proposed to estimate the ventricular repolarization heterogeneity ( qtc - d , jtc - d ) , were significantly increased in edmd patients when compared with age and sex - matched healthy controls . the significant increase in heterogeneity of ventricular repolarization parameters in edmd patients suggests that cardiac diffuse fibrosis and fatty acid infiltration per se influences regional dispersion of repolarization , even when systolic and diastolic cardiac function are preserved . the small number of patients included is certainly a limitation , and a more extensive study is needed to confirm these findings . qt interval and jt interval were made on 12-lead ecgs , with the use of computer software and digitizer by an experienced cardiologist observer . however , there remains an absence of indisputable , generally accepted criteria for the definition of the end of t interval , implying some degree of possible error in the measurements . the 12-lead surface ecg , compared with body surface mapping or vector cardiography , gives an incomplete picture of cardiac electric activity , so qtd could not be a true manifestation of local heterogeneity of repolarization . our study showed a significant increase of qtc - d and jtc - d , electrocardiographic parameters considered to reflect the heterogeneity of the ventricular repolarization , in edmd patients with normal systolic and diastolic function . our results suggest the hypothesis that diffuse fibrosis and fatty acid infiltration , in the absence of systolic and diastolic dysfunction , may increase ventricular electrical instability and produce the electrophysiological substrate for ventricular malignant tachyarrhythmias and sudden cardiac death . further studies are necessary to assess the effective relationship between qtc and jtc dispersion and sudden death in edmd patients .
summarybackgroundsudden cardiac death ( scd ) is common in patients with emery - dreifuss muscular dystrophy ( edmd ) and is attributed to the development of life - threatening arrhythmias that occur in the presence of normal left ventricular systolic function . 
 heterogeneity of ventricular repolarization is considered to provide an electrophysiological substrate for malignant arrhythmias . 
 qtc dispersion ( qtc - d ) and jtc dispersion ( jtc - d ) are electrocardiographic parameters indicative of heterogeneity of ventricular repolarization . 
 the aim of our study was to evaluate the heterogeneity of ventricular repolarization in patients with emery - dreifuss muscular dystrophy with preserved systolic and diastolic cardiac functionmaterial / methodsthe study involved 36 edmd patients ( age 2012 , 26 m ) and 36 healthy subjects used as controls , matched for age and sex . 
 heart rate , qrs duration , maximum and minimum qt and jt interval , qtc - d and jtc - d measurements were performed.resultscompared to the healthy control group , the edmd group presented increased values of qtc - d ( 82.744.2 vs. 53.113.7 ; p=0,003 ) and jtc - d ( 73.632.3 vs. 60.411.1 ms ; p=0.001 ) . 
 no correlation between qtc dispersion and ejection fraction ( r=0.2 , p=0.3 ) was found.conclusionsour study showed a significant increase of qtc - d and jtc - d in emery - dreifuss muscular dystrophy patients with preserved systolic and diastolic cardiac function .