Cardiomyopathy of Duchenne muscular dystrophy

Summary A total of 18 male patients with Duchenne muscular dystrophy (DMD), aged 8–29 years (mean, 15.7 years), were prospectively studied to assess the cardiomyopathy associated with DMD, using clinical parameters and noninvasive cardiovascular investigations: electrocardiogram (ECG), Holter monitoring, and echocardiography. In addition, five clinical tests of cardiovascular autonomic function were used to assess the role of the autonomic nervous system in the pathogenesis of dysrhythmias.The majority of subjects were asymptomatic, but four had abnormal physical findings. All had abnormal ECG, the commonest abnormality (in 16) being tall R waves or increased R/S ratios in the right precordial leads; 14 had abnormal findings on echocardiography, including three with poor left ventricular function and five with mitral valve prolapse (MVP). Labile abrupt sinus tachycardia was present in 11, and four had high-grade ventricular ectopy. None had definite clinical evidence of autonomic dysfunction.The cardiomyopathy of DMD appears to be unrelated to disease severity. However, abnormal Q waves or Q/R ratios in ECG leads I, a V_L, and V₅–V₆ are significantly related to young age (p<0.05), and high-grade ventricular ectopy occurred significantly more frequently (p<0.05) in older subjects (>15 years). Dysrhythmias were not related to the presence of MVP, poor left ventricular function, or autonomic dysfunction.     

Electrocardiographic Standard for the Diagnosis of Right Ventricular Hypertrophy in Complete Right Bundle Branch Block

It is generally considered that in complete right bundle branch block, the electrocardiographic standard for the diagnosis of right ventricular hypertrophy is not applicable. According to Cohen's criteria, right ventricular overload exists if thallium-201 myocardial perfusion demonstrates the right ventricular wall, and in this light we attempted to reassess the validity of the electrocardiographic standard for right ventricular hypertrophy. Twenty-three children with complete right bundle branch block (abbreviated as CRBBB) were evaluated. The agreement and disagreement ratios of the electrocardiographic standard with Cohen's criteria was 20/23 and 3/23 respectively. Even in patients without intracardiac anomalies, right ventricular overload was suspected by Cohen's criteria. The electrocardiographic standard was in agreement with Cohen's criteria in most of these patients.     

Body surface isopotential T map for assessment of right ventricular volume and pressure overloads in secundum atrial septal defect

The body surface isopotential T map was analyzed to detect right ventricular volume and pressure overloads in 25 patients with secundum atrial septal defect. Three patterns were distinguished: a T map resembling normal (type A,n=9); that with an isolated negative area in a positive area (type B,n=11); and that with rightward movement of maximum (type C,n=5). Right ventricular end-diastolic volumes in types B (161±19% of normal; %N) and C (175±40%N) were significantly (p<0.01) greater than those in controls (100±9%N) and type A (113±18%N). Right ventricular systolic pressure in type C (48±11 mmHg) was significantly (p<0.01) higher than those in the controls (30±5 mmHg), type A (31±4 mmHg), or type B (34±5 mmHg). These results suggest that the patients with type B have right ventricular volume overload and those with type C have both volume and pressure overloads.     

Amino-Terminal Fragment of Pro-Brain Natriuretic Hormone Identifies Functional Impairment and Right Ventricular Overload in Operated Tetralogy of Fallot Patients

To evaluate the relationship between plasma concentration of amino-terminal fragment of pro-brain natriuretic peptide (NT-proBNP), functional capacity, and right ventricular overload in survivors of tetralogy of Fallot (TOF) repair, we prospectively studied 70 operated TOF patients (44 males, 21 ± 1 years old; mean ± SEM) who underwent, during the same day, echocardiography, cardiac magnetic resonance imaging, neurohormonal characterization (plasma NT-proBNP, catecholamines, plasma renin activity, and aldosterone assay), and cardiopulmonary exercise testing. Forty-eight age- and sex-matched healthy volunteers served as the control group. Compared to controls, maximal workload and peak oxygen consumption (VO₂/kg) were lower in operated TOF patients (p < 0.001), whereas NT-proBNP concentration was elevated (p < 0.001). No difference was found among the other neurohormones. In operated TOF patients, NT-proBNP showed a significant positive correlation with right ventricular (RV) end systolic and end diastolic volumes and RV systolic pressure, and it showed a negative correlation with peak VO₂/kg and RV ejection fraction. From multivariable analysis, NT-proBNP concentration was found to be an independent predictor of peak VO₂/kg, RV end systolic volume, and RV systolic pressure. These results show an association among RV overload, decrease in functional capacity, and cardiac natriuretic peptide expression in operated TOF patients. NT-proBNP plasma assay may be a useful tool for diagnostic purposes and for decision making in this setting.     

Comparative Study of the Electrocardiograms of Healthy Fullterm and Premature Newborns

ABSTRACT. The electrocardiograms of 421 healthy fullterm and premature newborns, recorded on the fifth day of life, were evaluated for possible systematic differences related to gestational age. All newborns were appropriate for gestational age and were divided into four groups according to birthweight. As birthweight increased, we noted: ( a ) a progressive rightward shifting of the QRS axis in the frontal plane; ( b ) an increase in the amplitude mainly of the precordial R and S waves reflecting the right ventricle and both ventricles combined, whereas a less significant increase or even a decrease was noted in the R and S waves reflecting the left ventricle; ( c ) a more frequent occurrence of diphasic and positive T waves in the right precordial leads; and ( d ) a prolongation in the duration of the P wave and the QRS complex. These findings reflect both an increase in total myocardial mass as well as a progressive right ventricular predominance, as birthweight or gestational age increases. Practical implications for electrocardiographic identification of cardiac hypertrophy in newborns of different gestational age are discussed.     

Comparative study of the electrocardiograms of healthy fullterm and premature newborns

The electrocardiograms of 421 healthy fullterm and premature newborns, recorded on the fifth day of life, were evaluated for possible systematic differences related to gestational age. All newborns were appropriate for gestational age and were divided into four groups according to birthweight. As birthweight increased, we noted: (a) a progressive rightward shifting of the QRS axis in the frontal plane; (b) an increase in the amplitude mainly of the precordial R and S waves reflecting the right ventricle and both ventricles combined, whereas a less significant increase or even a decrease was noted in the R and S waves reflecting the left ventricle; (c) a more frequent occurrence of diphasic and positive T waves in the right precordial leads; and (d) a prolongation in the duration of the P wave and the QRS complex. These findings reflect both an increase in total myocardial mass as well as a progressive right ventricular predominance, as birthweight or gestational age increases. Practical implications for electrocardiographic identification of cardiac hypertrophy in newborns of different gestational age are discussed.     

Evaluation of the North Star Ambulatory Assessment scale and cardiac abnormalities in ambulant boys with Duchenne muscular dystrophy

Aim We evaluated ambulatory patients with Duchenne muscular dystrophy from the cardiovascular standpoint and studied the correlation between the results of electrocardiographic (ECG) findings, left ventricular ejection fraction (LVEF), troponin T and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels and patients' North Star Ambulatory Assessment scores. Methods: Fifty patients of ages 6–12 (8.9 ± 2.8) were enrolled in this cross‐sectional study. Cardiac evaluation included electrocardiography, echocardiography and cardiac enzyme tests. Results North Star scores ranged from 6/34 to 34/34. Twenty‐eight patients (56%) had ECG changes. The most frequently seen ECG abnormalities were short PR interval (14%, n= 7), right ventricular hypertrophy (16%, n= 8), prolonged QTc interval (10%, n= 5), prominent Q wave (10%, n= 5) and T wave inversion (44%, n= 22). In 10 patients (20%), LVEF was below 55%, troponin T and NT‐proBNP levels were significantly elevated (P= 0.003 and P < 0.001, respectively). When North Star scores were compared to patients' age, enzyme levels, ECG and echocardiographic results, we discovered negative correlation with age (P < 0.001) and troponin T levels (P= 0.02) and positive correlation with LVEF (P= 0.02). Conclusion Patients with North Star scores of ≤16 are more at risk of developing cardiomyopathies. Troponin T is a cardiac index that can be used for evaluating myopathic patients and it seems to be correlated with the proBNP levels and LVEF values.     

The SCN5A Mutation A1180V is Associated With Electrocardiographic Features of LQT3

Mutations of the SCN5A gene are associated with several arrhythmic syndromes including the Brugada syndrome, conduction disease, long QT syndrome type 3 (LQT3), atrial fibrillation, and dilated cardiomyopathy. We report LQT3 associated with an A1180V cardiac sodium channel mutation, previously associated with cardiac conduction block, and dilated cardiomyopathy in three generations of a Chinese family. Clinical, electrocardiographic (ECG), and echocardiographic examination was followed by direct sequencing of SCN5A and HERG to screen genomic DNA from blood samples. The proband presented with multiple syncopes from the age of 7 years and was found to share a mutation with two other members of his family. Continuous ECG monitoring after presentation showed prolonged QTc and biphasic T waves, multiple episodes of ventricular tachycardia and torsades de pointes. The other two mutation carriers showed ECG features of LQT3 without clinical symptoms. Transthoracic echocardiography showed normal cardiac structure in all three mutation carriers. This study shows LQT3 features associated with an A1180V cardiac sodium channel mutation, expanding the spectrum of phenotypes resulting from this mutation in which biophysical study has shown a persistent late Na⁺ current.     

Tricuspid atresia with special emphasis on cases with increased pulmonary blood flow

Summary Though an average case of tricuspid atresia offers no diagnostic challenge, the clinical picture of the relatively less common form of tricuspid atresia with increased pulmonary blood flow is not properly defined. The problem of suitable surgery for this type of lesion has not been given serious consideration. On the basis of clinical, radiological and electrocardiographic findings in twenty-six proven cases of tricuspid atresia (six of whom had increased pulmonary blood flow) we feel that a child with mild cyanosis, biatrial hypertrophy, left ventricular hypertrophy and/or absent normal right ventricular potentials in the precordial leads and the clinical picture of a large left to right shunt is likely to have tricuspid atresia with increased pulmonary blood flow. The presence of counter clock wise loop and electrical axis around +90° in the frontal plane is of further help. In the present state of our knowledge pulmonary artery banding seems to be a useful palliative procedure for these children.     

Tei指数和三尖瓣血流频谱评价左向右分流型先天性心脏病患儿右心功能的价值

目的探讨Tei指数和三尖瓣血流频谱评价左向右分流型先天性心脏病(CHD)患儿右心功能的价值。方法根据心室负荷将47例左向右分流型CHD患儿分为左心型组(30例)和右心型组(17例),应用三尖瓣血流频谱及Tei指数评价右心室功能,并与50例正常儿童进行对比研究。结果与正常组比较,CHD患儿42例三尖瓣血流频谱呈双峰型,均为舒张早期最大流速(EV)/舒张晚期最大流速(AV)>1;左心型组AV、A波流速积分(AVI)升高,右心型组EV、AV、E波流速积分(EVI)、AVI、E波减速时间(EDT)增大;左心型组右室等容舒张时间(IRT)和等容收缩时间(ICT) IRT延长;右心型组ICTI、RT和ICT IRT延长,右室射血时间(RVET)降低;两组CHD患儿右室Tei指数均增大;Tei指数与ICTI、RTI、CT IRT间呈显著性正相关(r=0.642,0.734,0.862 P均<0.01),与RVET间呈负相关(r=-0.481 P<0.01)。结论Tei指数能更简便、敏感、准确、综合评价右心室整体功能,与三尖瓣血流频谱结合可更全面了解CHD患儿右心功能。     

Dependence of canine right coronary arterial flow upon heart rate and right ventricular pressure

There is a paucity of knowledge regarding right coronary pulsatile hemodynamics when the right ventricle is under hemodynamic overload as is often the case in pediatric patients with congenital cardiac anomalies. To elucidate the exact mechanisms for the right coronary artery (RCA) to cope with the overload, we studied nine open-chest adult Beagles and analyzed the flow signals of the RCA in relation to independently varied heart rate (pacing) and right ventricular pressure (pulmonary artery banding). Both increased heart rate and right ventricular pressure increased the total volume flow of the RCA. The diastolic over total flow ratio (D/T), however, enlarged on increasing right ventricular pressures while it declined on increasing heart rates. Our data confirmed, as well, that increased flow of RCA on rising heart rate was provided mainly by an increase in systolic phase, while the increase on augmented right ventricular pressure was provided by the increase in diastolic phase. The RCA manages to deliver blood to the right ventricular musculature in two different ways in response to increasing heart rate and right ventricular pressure.     

Plasma Concentrations of Atrial and Brain Natriuretic Peptides and Cyclic Guanosine Monophosphate in Response to Dobutamine Infusion in Patients with Surgically Repaired Tetralogy of Fallot

We examined the plasma concentrations of atrial and brain natriuretic peptides (ANP and BNP) and cyclic guanosine monophosphate (cGMP) during dobutamine infusion and their relationship with hemodynamic parameters in 14 patients with surgically repaired tetralogy of Fallot (TOF). Dobutamine was infused at an initial dose of 5 μg/kg/min and increased by 5 μg/kg/min up to 20 μg/kg/min. The plasma ANP, BNP, and cGMP concentrations were determined before infusion, at the end of each stage, and 15 minutes after discontinuing dobutamine infusion. The plasma concentrations of ANP, BNP, and cGMP were elevated in all patients before dobutamine infusion. The ANP, BNP, and cGMP concentrations decreased in 11 of the 14 patients during dobutamine infusion. In contrast, the plasma ANP and BNP concentrations increased in the remaining 3 patients without a change in the cGMP concentration. The right ventricular pressure and volume were significantly elevated in these patients. The plasma cGMP concentration correlated with the ANP concentration (r= 0.62, p < 0.01) but not the BNP concentration. The plasma ANP concentration during dobutamine infusion correlated with right ventricular systolic pressure (r= 0.71, p < 0.05), mean right atrial pressure (r= 0.29, p < 0.05), and mean pulmonary capillary wedge pressure (r= 0.32, p < 0.05). The BNP concentration correlated with right ventricular volume (r= 0.61, p < 0.05) and systolic pressure (r= 0.46, p < 0.05). In conclusion, rapid changes in ANP, BNP, and cGMP concentrations during dobutamine infusion reflect the changes in atrial and ventricle pressure and volume overload. In surgically repaired TOF, the ANP concentration is affected by right ventricular systolic pressure, right atrial pressure, and pulmonary capillary pressure. Furthermore, the BNP concentration reflects right ventricular pressure and volume overload.     

不明原因胸闷痛静息期儿童卧位与立位心电图T波及ST段振幅变化的临床意义

目的 探讨不明原因胸闷痛儿童静息期卧位与立位心电图T波及ST段振幅变化的临床意义。方法 选取以不明原因胸闷痛(静息期)为主诉的6~14岁儿童122例行直立倾斜试验(HUTT),分HUTT阳性组(n=61)和HUTT阴性组(n=61)。测量卧位与立位12导联心电图的心率及Ⅱ、Ⅲ、aVF、V5导联T波和ST段振幅。结果 (1)HUTT阴性组:立位较卧位心率增快(P<0.05),Ⅱ、Ⅲ、aVF、V5导联T波振幅降低(P<0.05);Ⅱ、aVF、V5导联ST段振幅增加(P<0.05)。(2)HUTT阳性组:立位较卧位心率增加(P<0.05),Ⅱ、Ⅲ、aVF、V5导联T波振幅降低(P<0.05);V5导联ST段振幅增加(P<0.05)。(3)T波振幅及ST段振幅变化:立位与卧位心电图Ⅱ、Ⅲ、aVF、V5导联T波及ST段振幅在HUTT阳性组、HUTT阴性组之间差异无统计学意义(P>0.05)。(4)卧位与立位心电图T波和ST段振幅差比较:HUTT阳性组卧位与立位心电图Ⅱ、Ⅲ、aVF、V5导联T波振幅差及心率差较HUTT阴性组增加(P<0.05)。结论 不明原因胸闷痛静息期儿童HUTT阳性组卧位与立位心电图T波振幅差及心率差较HUTT阴性组增加,表明卧位与立位心电图T波振幅变化对提示自主神经功能紊乱具有临床价值。     

Assessment of Progressive Changes in Exercise Performance in Patients with a Systemic Right Ventricle Following the Atrial Switch Repair

There is a high prevalence of right ventricular dysfunction and reduced exercise performance in survivors of atrial switch repair for transposition of the great arteries. However, it is not known whether the impairment in exercise performance is progressive. We performed paired comparison of exercise performance in 28 patients who underwent two serial incremental exercise tests at an interval of 5.0 ± 1.4 years between the two tests (age 11.5 ± 3.7 years at first test, 16.4 ± 3.6 years at second test). There was no change in the chronotropic response between the two tests. However, there was a reduction in both the peak VO₂ (32.5 ± 8.3 vs 29.6 ± 5.7 ml/kg/min, p= 0.05) and anerobic threshold (22.1 ± 5.1 vs 18.3 ± 4.2 ml/kg/min, p < 0.01) with time. Furthermore, there was a decline in the O₂ pulse (oxygen uptake/beat) at anaerobic threshold (% predicted value 95 ± 23% vs 82 ± 23%, p= .02), O₂ pulse at a heart rate of 140 (% predicted value 100 ± 30% vs 85 ± 19%, p= 0.02), and the maximum O₂ pulse (z value −0.27 ± 1.31 vs −1.27 ± 1.16, p < 0.01) when compared to growth-related normal values. We conclude that there is a progressive reduction in aerobic response to exercise in patients with a systemic right ventricle. The maintenance of chronotropic response suggests that the stroke volume response of the systemic right ventricle during exercise does not increase commensurate with somatic growth.     

Assessment of cor pulmonale in cystic fibrosis by echocardiography.

Thirty-one patients with cystic fibrosis of varying severity were examined by echocardiography. Right ventricular dimension (RVD) was above upper normal limit in 14 patients and right ventricular dimension index (RVD index) was higher than the upper normal limit in 11 patients. Furthermore, there was a significant relationship between increasing RVD index and 1) decreasing forced vital capacity (FVC) both actual test results and average 6 months values; and 2) decreasing peak-expiratory flow rate (PEFR) both actual test results and average 6 months values. This observation suggests a persistent heart involvement. Five patients had either heart failure and/or electrocardiographic evidence of right ventricular abnormality. These patients had increased RVD index and one patient with the highest RVD index died 8 weeks after the examination. The present study has shown the usefulness of echocardiographic measurement of right ventricular dimension and of septal motion in assessing cor pulmonale, before development of electrocardiographic abnormalities and right heart failure.     

Chronically Transfused Pediatric Sickle Cell Patients are Protected from Cardiac Iron Overload

Iron overload is a major toxicity of chronic transfusions. Myocardial iron overload is associated with cardiac dysfunction. Cardiac and liver magnetic resonance imaging (MRI) was performed on 14 chronically transfused sickle cell disease (SCD) and non-sickle cell disease (non-SCD) patients seen at Vanderbilt Children's Hospital from 1 January 2000 to 10 March 2010. Retrospective review was conducted to assess cardiac T2*, liver T2*, ventricular dimensions and function, echocardiogram, length of transfusion, hemoglobin, and ferritin measurements. Ten patients had SCD and 4 had non-SCD, including α-thalassemia, β-thalassemia, and Diamond-Blackfan anemia. Cardiac T2* was normal in all SCD patients (mean 39 ± 12 ms), but abnormal in 3 of 4 non-SCD patients (mean 11.8 ± 2.4 ms). Liver T2* was similar between SCD (mean 6.2 ± 1.6 ms) and non-SCD patients (mean 5.9 ± 1.9 ms), and did not correlate with serum ferritin. Comparing SCD and non-SCD patients with similar transfusion duration, SCD patients had normal cardiac T2* and non-SCD patients had abnormal cardiac T2*. No patients had cardiomyopathy, but ventricular dilatation was common among SCD patients. Chronically transfused pediatric SCD patients are relatively spared of myocardial iron overload, which is unlikely to be due to lower total body iron burden in SCD patients than non-SCD patients.     

Duplex versus Unguided Pulsed Doppler Measurements of Right Ventricular Output in Newborn Infants

ABSTRACT. Noninvasive measurement of pulmonary artery blood flow has widespread implications for management of newborn infants requiring intensive care. Using a precordial, unguided, single Doppler technique, we evaluated right ventricular output in 26 preterm and 16 term infants without cardiopulmonary problems and compared it with right ventricular output obtained by duplex Doppler scanning and left ventricular output measured by a suprasternal single Doppler approach. Weights ranged from 1120 to 3960 g and postconceptional ages from 29 to 42 weeks. Unguided measurements of left and right ventricular output and guided and unguided measurements of right ventricular output were highly correlated (r=+0.92 and +0.95 respectively, p<0.001). The precordial single Doppler technique offers a reliable noninvasive estimate of right ventricular output in preterm and term newborn infants.     

Echocardiography of intracardiac filling defects in infants and children

Summary Intracardiac masses are rare in infants and children. Early detection is essential to their successful management. We present seven patients in whom echocardiography established the diagnosis and was crucial in the management. Three of the masses were primary cardiac tumors and four were thrombi.Patient 1: an infant with a calcified left ventricular fibroma.Patient 2: a neonate who presented with cyanosis due to obstruction of the right ventricular inflow tract by a fibroblastic tumor.Patient 3: an infant with a right atrial myxoma presenting as sepsis.Patient 4: a child who had a pulmonary embolus after a pulmonary valvotomy and was found to have a right ventricular thrombus.Patient 5: a child with a right atrial thrombus following a Fontan procedure for univentricular atrioventricular connection.Patient 6: a child with a left ventricular thrombus due to a dilated cardiomyopathy in association with epidermolysis bullosa.Patient 7: An infant with bilateral lobar emphysema, an aorticopulmonary window with left ventricular fibroelastosis, who developed a left ventricular thrombus.     

Doppler echocardiographic evaluation of left ventricular diastolic function after surgical correction of atrial septal defect during childhood

Summary Transmitral flow was studied using Doppler echocardiography with the A/E ratio as a parameter of left ventricular diastolic function in 21 patients (ages 2.5–30.0 years) who had undergone early surgical correction of an isolated secundum type atrial septal defect (ASD) compared to a healthy cohort of 21 subjects. Pre- and postoperative M-mode recordings were compared in 12 of the 21 patients to evaluate the effect of operation on interventricular septal motion (IVS) and left ventricular (LV) and right ventricular (RV) end-diastolic diameter ratio (LVDD/RVDD) as parameters of right ventricular volume overload. No significant difference in A/E ratio was found between the patient and control groups. IVS was shown to normalize in 11 of 12 patients postoperatively and to improve from paradox to flattened in 1 of 12. LVDD/RVDD increased from 1.26±0.31 to 2.10±0.51 (p=0.0008), with no significant difference remaining between the control and patient groups postoperatively. These findings support the conclusion that an intrinsic abnormality of the left ventricle is not responsible for its diastolic dysfunction in patients with ASD who develop left ventricular failure, thereby implicating an acquired abnormality. Mechanical sequelae of right ventricular volume overload were shown to normalize in all patients subsequent to operation in the present study, and therefore cannot be excluded as a cause of left ventricular failure in ASD.     

ASSESSMENT OF COR PULMONALE IN CYSTIC FIBROSIS BY ECHOCARDIOGRAPHY

Abstract. Thirty-one patients with cystic fibrosis of varying severity were examined by echocardiography. Right ventricular dimension (RVD) was above upper normal limit in 14 patients and right ventricular dimension index (RVD index) was higher than the upper normal limit in 11 patients. Furthermore, there was a significant relationship between increasing RVD index and 1) decreasing forced vital capacity (FVC) both actual test results and average 6 months values; and 2) decreasing peak-expiratory flow rate (PEFR) both actual test results and average 6 months values. This observation suggests a persistent heart involvement. Five patients had either heart failure and/or electrocardiographic evidence of right ventricular abnormality. These patients had increased RVD index and one patient with the highest RVD index died 8 weeks after the examination. The present study has shown the usefulness of echocardiographic measurement of right ventricular dimension and of septal motion in assessing cor pulmonale, before development of electrocardiographic abnormalities and right heart failure.