Kambiz Norozi

High-resolution in vivo imaging of the cross-sectional deformations of contracting embryonic heart loops using optical coherence tomography

The embryonic heart tube consists of an outer myocardial tube, a middle layer of cardiac jelly, and an inner endocardial tube. It is said that tubular hearts pump the blood by peristaltoid contractions. The traditional concept of cardiac peristalsis sees the cyclic deformations of pulsating heart tubes as concentric narrowing and widening of tubes of circular cross‐section. We have visualized the cross‐sectional deformations of contracting embryonic hearts in chick embryos (HH‐stages 9–17) using real‐time high‐resolution optical coherence tomography. Cardiac contractions are detected from HH‐stage 10 onward. During the cardiac cycle, the myocardial tube undergoes concentric narrowing and widening while the endocardial tube undergoes eccentric narrowing and widening, having an elliptic cross‐section at end‐diastole and a slit‐shaped cross‐section at end‐systole. The eccentric deformation of the endocardial tube is the consequence of an uneven distribution of the cardiac jelly. Our data show that the cyclic deformations of pulsating embryonic heart tubes run other than originally thought. There is evidence that heart tubes of elliptic cross‐section might pump blood with a higher mechanical efficiency than those of circular‐cross section. The uneven distribution of cardiac jelly seems to prefigure the future AV and cono‐truncal endocardial cushions. Developmental Dynamics 237:953–961, 2008.

A prospective, randomized, double-blind, placebo controlled trial of beta-blockade in patients who have undergone surgical correction of tetralogy of Fallot

AIMS Our purpose was to evaluate the effect of a treatment over six months with bisoprolol on the surrogate parameters of N-Terminal-pro brain natriuretic peptide, subsequently to be described as brain natriuretic peptide, peak uptake of oxygen, and ventricular function assessed by magnetic resonance imaging in grown ups and adults who had undergone surgical correction of tetralogy of Fallot. METHODS AND RESULTS We designed a prospective, randomized, double-blind, placebo controlled trial. We enrolled 33 patients, aged 30.9 plus or minus 9.5 years in either class 1 or 2 of the grading of the New York Heart Association class with both levels of brain natriuretic peptide greater than 100 pg/ml and a reduced peak uptake of oxygen less than 25 ml/kg/min. During treatment with Bisoprolol, the levels of brain natriuretic peptide increased significantly from 206 plus or minus 95 to 341 plus or minus 250 pg/ml (p< 0.05), and those of atrial natriuretic peptide from 4117 plus or minus 1837 to 5340 plus or minus 2102 fmol/ml (p = 0.0005). These measures remained unchanged in the group of patients receiving the placebo. Peak uptake of oxygen did not differ significantly in either group, nor did treatment have any significant effect on right and left ventricular volumes and ejection fractions as determined by magnetic resonance imaging. The clinical state as judged within the grading system of the New York Heart Association was also unchanged by beta-blockade. CONCLUSION Beta blockade with Bisoprolol seems to have no beneficial effect on asymptomatic or mildly symptomatic patients with right ventricular dysfunction secondary to repaired tetralogy of Fallot with residual pulmonary regurgitation and/or stenosis.

In vivo imaging of the cyclic changes in cross‐sectional shape of the ventricular segment of pulsating embryonic chick hearts at stages 14 to 17: A contribution to the understanding of the ontogenesis of cardiac pumping function

The cardiac cycle‐related deformations of tubular embryonic hearts were traditionally described as concentric narrowing and widening of a tube of circular cross‐section. Using optical coherence tomography (OCT), we have recently shown that, during the cardiac cycle, only the myocardial tube undergoes concentric narrowing and widening while the endocardial tube undergoes eccentric narrowing and widening, having an elliptic cross‐section at end‐diastole and a slit‐shaped cross‐section at end‐systole. Due to technical limitations, these analyses were confined to early stages of ventricular development (chick embryos, stages 10–13). Using a modified OCT‐system, we now document, for the first time, the cyclic changes in cross‐sectional shape of beating embryonic ventricles at stages 14 to 17. We show that during these stages (1) a large area of diminished cardiac jelly appears at the outer curvature of the ventricular region associated with formation of endocardial pouches; (2) the ventricular endocardial lumen acquires a bell‐shaped cross‐section at end‐diastole and becomes compressed like a fireplace bellows during systole; (3) the contracting portions of the embryonic ventricles display stretching along its baso‐apical axis at end‐systole. The functional significance of our data is discussed with respect to early cardiac pumping function. Developmental Dynamics 238:3273–3284, 2009.

Chances of employment in women and men after surgery of congenital heart disease: comparisons between patients and the general population.

OBJECTIVE It was examined whether women and men (17-45 years) with operated congenital heart disease differ with respect to chances of employment. Patients were compared with the general population. DESIGN Patients (n = 314) were classified by type of surgery (curative, reparative, palliative) as indicator of initial severity of disease. The second classification was performed according to a system proposed by the New York Heart Association in order to take reported impairments into account. Controls (n = 1165) consisted of a 10% random sample drawn from the German Socio-Economic Panel. RESULTS Chances of full-time employment decreased as disease severity increased. Chances of part-time and minor employment were higher in patients than among controls. These general effects were because of male patients, while the employment patterns of women did not differ from the control group. Independent of patient status, women were more likely to have lower rates of full-time employment, and the rates of part-time and minor employment were higher. CONCLUSION Long-term adaptation to impairments as a result of congenital heart disease differs between women and men with respect to employment status. While female patients do not differ from the general population, males may lower their engagement in paid work.

Is the Ability index superior to the NYHA classification for assessing heart failure?: comparison of two classification scales in adolescents and adults with operated congenital heart defects.

BackgroundHeart failure (HF) is a major problem in the long-term follow-up of adolescents and adults with congenital heart disease (ACHD) after cardiac surgery. The functional status of ACHD may be assessed in terms of the NYHA classification or the Ability index (ABILITY).ObjectiveThe purpose of our study was to examine which of the two classification systems is more closely related to objectively defined HF.MethodsNT-pro brain natriuretic peptide (N-BNP) and maximal oxygen uptake (VO2max) were measured in 360 consecutive ACHD patients. HF was defined as an elevated N-BNP level ≥100 pg/ml combined with a reduced VO2max ≤25 ml/kg/min.ResultsThere were no significant differences between the NYHA and ABILITY in grading HF in these patients. In both classifications, the risk of HF increases continuously over the classes and grades from odds ratio (OR) 1 in NYHA I/ABILITY 1 to an OR=3.4 in NYHA II/ ABILITY 2 up to 11.6 or 5.4 (ns) in NYHA III/ABILITY 3. Thus in the highest scores HF is found in 70–77% of the patients. The fact that in NYHA class I and ABILITY grade 1, 15% and 19% of the patients exhibited HF according to the measured indices underscores the discrepancy between subjective and objective assessment of the individual patients condition.ConclusionThe NYHA classification and the Ability index take different approaches to the patients with congenital heart defects but are equally suitable for the judgement of HF in post surgical ACHD.

Pacemaker implantation as a risk factor for heart failure in young adults with congenital heart disease.

Aim: Complete postoperative heart block following open‐heart surgery and sinus node dysfunction are indications for permanent cardiac pacing in children with congenital heart defects. The purpose of our study was to evaluate if cardiac pacing is a risk factor of heart failure during longtime follow‐up of grown ups with congenital heart disease (GUCH).

Psychological symptoms in patients after surgery for congenital cardiac disease.

AIMS We studied a population of patients with surgically corrected congenital cardiac disease to determine whether limitations in activity, impaired cardiac performance, and perception of body image have effects on psychological symptoms. METHODS We undertook medical examinations, and carried out standardized interviews, in 361 patients aged between 14 and 45 years with surgically corrected congenital cardiac disease. From this data, findings from 343 patients were suitable for analysis. Subjectively reported limitations in activity were classified according to the system proposed by the New York Heart Association, while cardiopulmonary capacity was used as the indicator of cardiac performance. The Brief Symptom Inventory was used for assessing psychological symptoms, such as somatization, obsession-compulsion, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism. The Body Image Questionnaire was used to depict attitudes towards body image, which is assessed on the two subscales of rejection of the body and vitality. Multivariate regression analyses were conducted separately for females and males, taking into account age and socio-economic position. RESULTS Impairments of everyday activities had only a few substantial associations with psychological symptoms. No significant effects of cardiac functional capacity as a standardized physiological measure emerged. Psychological symptoms were strongly influenced by perceptions of body image, particularly if they rejected it, this holding particularly for males. There were no gender differences in terms of psychological symptoms. CONCLUSIONS Limitations of activity, and impaired cardiac performance, have only minor effects on psychological symptoms in patients with surgically corrected congenital cardiac disease. The perception of body image was the strongest predictor, especially if patients rejected their body as a result of disfigurement or perceived deficiency.

Growth differentiation factor 15: an additional diagnostic tool for the risk stratification of developing heart failure in patients with operated congenital heart defects?

BACKGROUND Many young adults who have congenital heart defects develop heart failure despite corrective surgeries. Growth differentiation factor 15 (GDF-15) has an established role as a marker for risk stratification and mortality both in patients after acute myocardial infarction and in patients with heart failure. Our aim was to establish a role for GDF-15 for monitoring heart failure in operated congenital heart defects (ACHD). This potential biomarker was validated through comparison with maximal oxygen uptake (VO(2max)) and to another biomarker, N-terminal pro-brain natriuretic peptide (NT-proBNP). METHODS A total of 317 ACHD patients (129 females) with an average age of 26.5 ± 8.5 years (mean ± SD) enrolled in the study. We studied the relation between GDF-15 and NT-proBNP and VO(2max%) (percent predicted for age and gender). The cutoffs for the groups were as follows: NT-proBNP <100, 100 to 300, and >300 pg/mL; VO(2max%) <65%, 65% to 85%, and >85% of predicted normal. RESULTS Significant differences in mean GDF-15 levels were found between the NT-proBNP <100 and NT-proBNP >300 groups, as well as between the 100 to 300 and the >300 groups. For VO(2max%), significant differences were found in GDF-15 levels between <65% and >85% and between <65% and 65% to 85%, respectively. The lowest mean GDF-15 was found in groups with NT-proBNP <100 pg/mL and VO(2max%) >85%. The highest mean GDF-15 was found in the groups with NT-proBNP >300 pg/mL and VO(2max%) <65%. A subgroup analysis, including 82 patients with operated tetralogy of Fallot, showed that patients in the New York Heart Association I class have significantly lower NT-proBNP and GDF-15 level and markedly higher VO(2max) compared with the patients in higher New York Heart Association class. CONCLUSION Growth differentiation factor 15 might be used as a surrogate marker for latent heart failure and could help to identify patients with ACHD who are at risk for developing heart failure, even if they are clinically asymptomatic.

How to Predict the Impact of Methylphenidate on Cardiovascular Risk in Children with Attention Deficit Disorder: Methylphenidate Improves Autonomic Dysfunction in Children with ADHD

Background. Although stimulants have long been touted as treatments for attention deficit disorder with or without hyperactivity (ADHD), in recent years, increasing concerns have been raised about the cardiovascular safety of these medications. We aimed to prove if measurements of autonomic function with time domain analysis of heart rate variability (HRV) in 24-hour Holter ECG are useful to predict the risk of sudden cardiac death in ADHD children and adolescents. Methods. We analysed HRV obtained from children with the diagnosis of ADHD prior to (N = 12) or during medical therapy (N = 19) with methylphenidate (MPH), aged 10.8 ± 2.0 years (mean ± SD), who were referred to our outpatient Paediatric Cardiology Clinic to rule out heart defect. As a control group, we compared the HRV data of 19 age-matched healthy children without heart defect. Results. Average HRV parameters from 24-hour ECG in the ADHD children prior to MPH showed significant lower values compared to healthy children with respect to rMSSD (26 ± 4 ms versus 44 ± 10 ms, P ≤ 0.0001) and pNN50 (6.5 ± 2.7% versus 21.5 ± 9.0%, P ≤ 0.0001). These values improved in MPH-treated children with ADHD (RMSSD: 36 ± 8 ms; pNN50: 14.2 ± 6.9%). Conclusion. Children who suffer from ADHD show significant changes in HRV that predominantly reflects diminished vagal tone, a well-known risk factor of sudden cardiac death in adults. In our pilot study, MPH treatment improved HRV.

Life chances after surgery of congenital heart disease: the influence of cardiac surgery on intergenerational social mobility. A comparison between patients and general population data

Background To examine whether operated congenital heart disease (CHD) is setting preconditions for an active life by comparing intergenerational social mobility in patients with a population sample. Design and methods The patient sample consisted of 314 females (42.1%) and males who underwent surgery for CHD (mean age at surgery 7.3 years, SD 7.8). According to the type of surgery, patients were classified as curative, reparative, or palliative. Consequently, the three groups reflect increasing severities of the initial heart defect. The mean age at examination was 26.9 years (7.6). Controls consisted of individuals who participated in the 2002 survey of the German Socio-Economic Panel. All individuals with complete sociodemographic information were included, and the final sample consisted of 4864 women (46.1%) and men (mean age 32.5 years, SD 7.2). Results Once having entered the labour market, intergenerational social mobility between patients and controls did not differ. For upward mobility respondents’ social background was the key determinant; the respective standardized regression effect was β = 0.66. After dividing the study population, the social background turned out to having a slightly stronger effect in patients (β = 0.73) than in controls (β = 0.65). For downward mobility effects of the social background were smaller than for upward mobility (β = 0.19 in patients and β = 0.21 in controls). In economically active patients CHD severity did not determine social mobility. Discussion We conclude that a large proportion of patients could not or did not enter the labour market. Those who did experienced social mobility rates that are comparable with the general population. Eur J Cardiovasc Prev Rehabil 14: 128-134