Walter Knirsch

Sarcomere Gene Mutations in Isolated Left Ventricular Noncompaction Cardiomyopathy Do Not Predict Clinical Phenotype

Background— Left ventricular noncompaction of the myocardium (LVNC) has been recognized as a cardiomyopathy with a genetic etiology. Mutations in genes encoding sarcomere proteins were shown to be associated with LVNC. We evaluated the potential clinical impact of genetic analysis of sarcomere genes in patients with LVNC. Methods and Results— We identified 5 mutations in cardiac myosin-binding protein C (MYBPC3) and 2 mutations in &agr;-tropomyosin (TPM1) in a cohort of unrelated adult probands with isolated LVNC. The mutations in MYBPC3 and TPM1 and in 6 other previously reported sarcomere genes in this cohort resulted in a total of 18 (29%) heterozygous mutations in 63 probands. &bgr;-myosin heavy chain (MYH7) was the most prevalent disease gene and accounts for 13% of cases, followed by MYBPC3 (8%). Comparing sarcomere mutation-positive and mutation-negative LVNC probands showed no significant differences in terms of average age, myocardial function, and presence of heart failure or tachyarrhythmias at initial presentation or at follow-up. Familial disease was found in 16 probands of whom 8 were sarcomere mutation positive. Nonpenetrance was detected in 2 of 8 mutation-positive families with LVNC. Conclusions— Mutations in sarcomere genes account for a significant (29%) proportion of cases of isolated LVNC in this cohort. The distribution of disease genes confirms genetic heterogeneity and opens new perspectives in genetic testing in patients with LVNC and their relatives at high risk of inheriting the cardiomyopathy. The presence or absence of a sarcomere gene mutation in LVNC cannot be related to the clinical phenotype.

Infective endocarditis in congenital heart disease.

Congenital heart disease (CHD) has become the leading risk factor for pediatric infective endocarditis (IE) in developed countries after the decline of rheumatic heart disease. Advances in catheter- and surgery-based cardiac interventions have rendered almost all types of CHD amenable to complete correction or at least palliation. Patient survival has increased, and a new patient population, referred to as adult CHD (ACHD) patients, has emerged. Implanted prosthetic material paves the way for cardiovascular device-related infections, but studies on the management of CHD-associated IE in the era of cardiovascular devices are scarce. The types of heart malformation (unrepaired, repaired, palliated) substantially differ in their lifetime risks for IE. Streptococci and staphylococci are the predominant pathogens. Right-sided IE is more frequently seen in patients with CHD. Relevant comorbidity caused by cardiac and extracardiac episode-related complications is high. Transesophageal echocardiography is recommended for more precise visualization of vegetations, especially in complex type of CHD in ACHD patients. Antimicrobial therapy and surgical management of IE remain challenging, but outcome of CHD-associated IE from the neonate to the adult is better than in other forms of IE. Conclusion: Primary prevention of IE is vital and includes good dental health and skin hygiene; antibiotic prophylaxis is indicated only in high-risk patients undergoing oral mucosal procedures.

Brain volumes predict neurodevelopment in adolescents after surgery for congenital heart disease

Patients with complex congenital heart disease are at risk for neurodevelopmental impairments. Evidence suggests that brain maturation can be delayed and pre- and postoperative brain injury may occur, and there is limited information on the long-term effect of congenital heart disease on brain development and function in adolescent patients. At a mean age of 13.8 years, 39 adolescent survivors of childhood cardiopulmonary bypass surgery with no structural brain lesions evident through conventional cerebral magnetic resonance imaging and 32 healthy control subjects underwent extensive neurodevelopmental assessment and cerebral magnetic resonance imaging. Cerebral scans were analysed quantitatively using surface-based and voxel-based morphometry. Compared with control subjects, patients had lower total brain (P = 0.003), white matter (P = 0.004) and cortical grey matter (P = 0.005) volumes, whereas cerebrospinal fluid volumes were not different. Regional brain volume reduction ranged from 5.3% (cortical grey matter) to 11% (corpus callosum). Adolescents with cyanotic heart disease showed more brain volume loss than those with acyanotic heart disease, particularly in the white matter, thalami, hippocampi and corpus callosum (all P-values < 0.05). Brain volume reduction correlated significantly with cognitive, motor and executive functions (grey matter: P < 0.05, white matter: P < 0.01). Our findings suggest that there are long-lasting cerebral changes in adolescent survivors of cardiopulmonary bypass surgery for congenital heart disease and that these changes are associated with functional outcome.

Adverse effects of Wolff-Parkinson-White syndrome with right septal or posteroseptal accessory pathways on cardiac function

AIMS Wolff-Parkinson-White syndrome with right septal or posteroseptal accessory pathways causes eccentric septal mechanical activation and may provoke left ventricular (LV) dyssynchrony and dysfunction. The aim of the study was to evaluate the effect of radiofrequency catheter ablation (RFA) of the accessory pathways on LV function. METHODS AND RESULTS Retrospectively, transthoracic echocardiography and electrocardiogram recordings were analysed in 34 patients (age: 14.2 +/- 2.5 years) with right septal or posteroseptal accessory pathways prior and after (median: 1 day) successful RFA. Results prior to RFA, LV ejection fraction was decreased (<55%) in 19/34 patients (56%). After RFA, QRS duration was normalized (129 +/- 23 vs. 90 +/- 11, P < 0.0001), LV function improved (ejection fraction: 50 +/- 10 vs. 56 +/- 4%, P = 0.0005) and septal-to-posterior wall motion delay as a global measure for LV dyssynchrony decreased (110 +/- 94 vs. 66 +/- 53, P = 0.012). Longitudinal two-dimensional strain evaluated in five patients demonstrated a decrease of left intraventricular mechanical delay from 292 +/- 125 to 118 +/- 37 ms after RFA. CONCLUSION Wolff-Parkinson-White syndrome with right septal or posteroseptal accessory pathways may cause LV dyssynchrony and jeopardize global LV function. Radiofrequency catheter ablation resulted in normalized QRS duration, mechanical resynchronization, and improved LV function. Even in the absence of arrhythmias, RFA of right septal or posteroseptal pathways may be considered in patients with significantly decreased LV function.

Longitudinal stent fracture 11 months after implantation in the left pulmonary artery and successful management by a stent-in-stent maneuver.

Fracture of a 12 mm Palmaz stent after implantation in the left pulmonary artery for palliation of postoperative stenosis in a 9‐year‐old child is described. Successful management by implantation of a second Palmaz stent revealed immediate stabilization and no signs of significant restenosis during 1‐year follow‐up. Cathet Cardiovasc Intervent 2003;58:116–118.

Cardiac output measurement in children: comparison of Aesculon® cardiac output monitor and thermodilution

BACKGROUND We compared cardiac output (CO) measurements by the non-invasive electrical velocimetry (Aesculon) monitor with the pulmonary artery catheter (PAC) thermodilution method in children. METHODS CO values using the Aesculon monitor and PAC thermodilution were simultaneously recorded during cardiac catheterization in children. Measurements were performed under general anaesthesia. To compare, three consecutive measurements for each patient within 3 min were obtained. The means of the three values were compared using simple regression and Bland-Altman analysis. Data were presented as mean (sd). A mean percentage of <30% was defined to indicate clinical useful reliability of the Aesculon monitor. RESULTS A total of 50 patients with a median (range) age of 7.5 (0.5-16.5) yr were enrolled in the study. Mean CO values were 3.7 (1.5) litre min(-1) (PAC thermodilution) and 3.1 (1.7) litre min(-1) (Aesculon) monitor). Analysis for CO measurement showed a good correlation between the two methods (r=0.894; P<0.0001). The bias between the two methods was 0.66 litre min(-1) with a precision of 1.49 litre min(-1). The mean percentage error for CO measurements was 48.9% for the Aesculon monitor when compared with PAC thermodilution. CONCLUSIONS Electrical velocimetry using the Aesculon monitor did not provide reliable CO values when compared with PAC thermodilution. Whether the Aesculon monitor can be used as a CO trend monitor has to be assessed by further investigations in patients with changing haemodynamics.

Neurodevelopmental outcome, psychological adjustment, and quality of life in adolescents with congenital heart disease.

The aim of this study was to examine neurodevelopment, psychological adjustment, and health‐related quality of life (HRQoL) in adolescents after bypass surgery for congenital heart disease (CHD) during early childhood.

Modified Blalock Taussig shunt: a not-so-simple palliative procedure

OBJECTIVES Thirty-two consecutive isolated modified Blalock Taussig (BT) shunts performed in infancy since 2004 were reviewed and analysed to identify the risk factors for shunt intervention and mortality. METHODS Sternotomy was the only approach used. Median age and weight were 10.5 (range 1-74) days and 2.9 (1.9-4.4) kg, respectively. Shunt palliation was performed for biventricular hearts (Tetralogy of Fallot/double outlet right ventricle/transposition of great arteries_ventricular septal defect_pulmonary stenosis/pulmonary atresia_ventricular septal defect/others) in 21, and univentricular hearts in 11, patients. Hypoplastic left heart syndrome patients were excluded. Two procedures required cardiopulmonary bypass. Median shunt size was 3.5 (3-4) mm and median shunt size/kg body weight was 1.2 (0.9-1.7) mm/kg. Reduction in shunt size was necessary in 5 of 32 (16%) patients. RESULTS Three of 32 (9%) patients died after 3 (1-15) days due to cardiorespiratory decompensation. Lower body weight (P = 0.04) and bigger shunt size/kg of body weight (P = 0.004) were significant risk factors for mortality. Acute shunt thrombosis was observed in 3 of 32 (9%), none leading to death. Need for cardiac decongestive therapy was associated with univentricular hearts (P < 0.001), bigger shunt size (P = 0.054) and longer hospital stay (P = 0.005). Twenty-eight patients have undergone a successful shunt takedown at a median age of 5.5 (0.5-11.9) months, without late mortality. CONCLUSIONS Palliation with a modified BT shunt continues to be indicated despite increased thrust on primary corrective surgery. Though seemingly simple, it is associated with significant morbidity and mortality. Effective over-shunting and acute shunt thrombosis are the lingering problems of shunt therapy.

Mortality and neurodevelopmental outcome at 1 year of age comparing hybrid and Norwood procedures

OBJECTIVES Neonates with hypoplastic left heart syndrome (HLHS) are at risk of high mortality and neurodevelopmental morbidity. As an alternative to Norwood-type stage I palliation, the hybrid procedure has been developed. It consists of bilateral pulmonary artery banding, catheter-based stenting of the arterial duct and balloon atrioseptostomy and delays open-heart surgery. Thus, it may be associated with a better outcome. The aim of this study was to determine the mortality and neurodevelopmental outcome in patients with HLHS and other univentricular heart (UVH) defects treated with hybrid or Norwood procedures. METHODS Thirty-one children (18 males) with HLHS and other UVH defects undergoing Norwood or hybrid procedure between 2004 and 2008 were consecutively enrolled. Mortality and neurodevelopmental outcome at 1 year of age were determined. RESULTS One-year mortality was 36% (31% in the hybrid vs. 39% in the Norwood group, P=0.71). Predictors of mortality were lower birth weight (P=0.02), older age at first procedure (P=0.02) and smaller size of ascending aorta (P=0.05). Overall, median psychomotor development index (PDI) and mental development index (MDI) of the Bayley Scales of Infant Development II were lower than the norm of 100 [PDI 57 (49-99), P<0.001; MDI 91 (65-109), P=0.002]. No effect of surgical treatment on neurodevelopmental outcome was found. Predictors of impaired motor outcome were length of hospital stay (LOHS) (P=0.01), lower body weight at second procedure (P=0.004) and female sex (P=0.01). Predictors of impaired cognitive outcome were longer mechanical ventilation time (P=0.03), intensive care unit stay (P=0.04) and LOHS (P<0.001), respectively. CONCLUSIONS Mortality at 1 year of age is comparable between patients undergoing hybrid and Norwood procedures. Early neurodevelopmental outcome is significantly impaired in patients with both HLHS and other UVH defects. Multicentre randomized studies are needed to determine the long-term neurodevelopmental outcome of children treated with the hybrid procedure.

Successful management of a resistant renal artery stenosis in a child using a 4 mm cutting balloon catheter

Percutaneous transluminal renal angioplasty (PTRA) is a well‐established method to treat renal artery stenosis (RAS) in children and adults. However, a significant number of stenoses might not be treated by interventional techniques due to the inability to dilate the RAS. Conventional balloon angioplasty with a high‐pressure coronary angioplasty balloon at 20 atm was unable to dilate a significant RAS in a 12‐year‐old child with severe renovascular hypertension (RR 195/125 mm Hg). After using a 4 mm cutting balloon, we achieved wide patency of the renal artery and an instant normalization of blood pressure without further need of antihypertensive therapy. PTRA using the cutting balloon technique may offer an additional therapeutic option for selected patients in whom conventional balloon angioplasty was not able to dilate RAS. Cathet Cardiovasc Intervent 2002;56:227–231.