Kai Thorsten Laser

Myocardial fibrosis severity on cardiac magnetic resonance imaging predicts sustained arrhythmic events in hypertrophic cardiomyopathy.

BACKGROUND The purpose of our study was to correlate the incidence of adequate implantable cardioverter-defibrillator (ICD) interventions in hypertrophic cardiomyopathy (HCM) patients with risk markers (RMs) for sudden cardiac death (SCD) plus myocardial fibrosis as detected by late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) imaging. METHODS In all, 87 patients with HCM underwent LGE-CMR imaging prior to ICD implantation, performed for secondary (n = 2; 2%) or primary SCD prophylaxis (n = 85; 98%). Fibrosis was graded with a 17-segment left ventricular model (0 = absent, 1 = point-shaped, 2 = limited to 1 left ventricular segment, 3 = involving ≥ 2 segments). During follow-up, ICD memories were read out by a physician blinded to the individual patient data. RESULTS The number of RMs per patient was 1.9 ± 0.8. Myocardial fibrosis was present in 78 patients (90%); 26 (30%) had a fibrosis score of 3. During follow-up (3.5 ± 2.6 [range, 0.2-11.4 years]), 15 patients had 50 appropriate ICD interventions. Episodes of atrial fibrillation were found in 28 patients. Fibrosis severity correlated with occurrence of ventricular tachycardia (Cramérs V, or φc = 0.4, P < 0.001) and atrial fibrillation (φc = 0.6, P < 0.001). On multivariate regression analysis, an independent association between myocardial fibrosis (ß = 0.6, P < 0.01) and sustained ventricular tachycardia was found. CONCLUSIONS In HCM patients treated with ICD implantation because of a high SCD risk by traditional RM assessment, a high rate of arrhythmic events was observed during long-term follow-up. In a cohort of patients with clinical markers for high risk of SCD, severity of myocardial fibrosis as detected by an easy LGE-CMR scoring system was associated with future arrhythmic events and appropriate ICD therapies.

Coronary anomalies assessed by whole-heart isotropic 3D magnetic resonance imaging for cardiac morphology in congenital heart disease.

To determine the value of whole‐heart three‐dimensional magnetic resonance imaging (MRI) for coronary artery imaging in children/adolescents with congenital heart disease (CHD).

Is Torsion a Suitable Echocardiographic Parameter to Detect Acute Changes in Left Ventricular Afterload in Children

BACKGROUND Congenital heart defects such as coarctation or valvular aortic stenosis are followed by changes in left ventricular myocardial deformation mechanics induced by pressure overload. METHODS Echocardiography was performed in 37 patients (aged 0-27 years, 15 female) with coarctation (27) or valvular aortic stenosis (10) before and after interventional catheterization and compared with 37 body surface area/age-matched healthy children. Deformation was calculated by 2-dimensional strain speckle tracking. RESULTS Stress gradients under provocation with orciprenaline in coarctation decreased from 51.8 +/- 20.0 mm Hg to 6.0 +/- 12.0 mm Hg (P < .0001), and resting gradients in aortic stenoses decreased from 57.5 +/- 18.8 mm Hg to 25.5 +/- 14.0 mm Hg (P < .0001) after intervention. Patients had an increased maximal torsion (tor(max): 16.7 +/- 6.7 deg vs 11.0 +/- 4.7 deg (controls; P < .0001), which decreased significantly after therapy (11.8 +/- 4.9 deg, P < .0001). CONCLUSION Compensatory elevation of left ventricular tor(max) in children with moderate left ventricular pressure load changes rapidly after successful interventional treatment. tor(max) may be a valuable tool to assess cardiac unloading or indicate the need for interventional treatment.

Left ventricular volumetry in healthy children and adolescents: comparison of two different real-time three-dimensional matrix transducers with cardiovascular magnetic resonance

AIMS To assess the accuracy of different hardware and software settings for left ventricular (LV) volume quantification in children using real-time three-dimensional echocardiography (RT3DE). METHODS AND RESULTS The impact of different matrix transducers (IE 33, X3-1 and VIVID 7, V3) and quantification software settings [TOMTEC; contour-finding activity (tCFA) values ranging from 30 to 70 U] on the accuracy of LV indices was tested in 24 healthy children/adolescents (median = 12.6 years) and 25 paediatric patients with Tetralogy-of-Fallot (TOF) (median = 7.3 years) with abnormally shaped ventricles. RT3DE was compared with cardiovascular magnetic resonance (CMR) volumetry as reference. Best agreement (Bland-Altman analysis) was achieved using a tCFA value of 30 U. Applying the V3 device, end-diastolic volume (EDV) and end-systolic volume (ESV) were underestimated by 14.8 +/- 10.6% (mean +/- SD) and 11.2 +/- 16.3%, respectively (r = 9.42, P < 0.001 and r = 0.937, P = 0.003); with the X3-1 system 24.2 +/- 11.0 and 14.6 +/- 15.2%, respectively (r = 0.951, P < 0.001 and r = 0.912, P = 0.001). Negligible differences <1% (P = n.s.) between both transducers were detected applying a tCFA value of 70 U but with significant underestimation (EDV: approximately 35%, P < 0.001; ESV: approximately 26%, P < 0.001) compared with CMR. EDV and ESV of TOF patients were underestimated by 3.2 +/- 15.4 and 8.1 +/- 22.6%, respectively. Intra- and interobserver variability was <4%. CONCLUSION In contrast to recommendations of the manufacturer, data sets from both RT3DE transducers showed acceptable agreement to CMR for volumetric parameters only for low tCFA. Fine-tuning of software settings is mandatory to improve accuracy.

The TMEM43 Newfoundland mutation p.S358L causing ARVC-5 was imported from Europe and increases the stiffness of the cell nucleus

AIMS Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetic condition caused predominantly by mutations within desmosomal genes. The mutation leading to ARVC-5 was recently identified on the island of Newfoundland and caused by the fully penetrant missense mutation p.S358L in TMEM43. Although TMEM43-p.S358L mutation carriers were also found in the USA, Germany, and Denmark, the genetic relationship between North American and European patients and the disease mechanism of this mutation remained to be clarified. METHODS AND RESULTS We screened 22 unrelated ARVC patients without mutations in desmosomal genes and identified the TMEM43-p.S358L mutation in a German ARVC family. We excluded TMEM43-p.S358L in 22 unrelated patients with dilated cardiomyopathy. The German family shares a common haplotype with those from Newfoundland, USA, and Denmark, suggesting that the mutation originated from a common founder. Examination of 40 control chromosomes revealed an estimated age of 1300-1500 years for the mutation, which proves the European origin of the Newfoundland mutation. Skin fibroblasts from a female and two male mutation carriers were analysed in cell culture using atomic force microscopy and revealed that the cell nuclei exhibit an increased stiffness compared with TMEM43 wild-type controls. CONCLUSION The German family is not affected by a de novo TMEM43 mutation. It is therefore expected that an unknown number of European families may be affected by the TMEM43-p.S358L founder mutation. Due to its deleterious clinical phenotype, this mutation should be checked in any case of ARVC-related genotyping. It appears that the increased stiffness of the cell nucleus might be related to the massive loss of cardiomyocytes, which is typically found in ventricles of ARVC hearts.

Substantial radiation reduction in pediatric and adult congenital heart disease interventions with a novel X-ray imaging technology

Background Pediatric catheterization exposes patients to varying radiation doses. Concerns over the effects of X-ray radiation dose on the patient population have increased in recent years. This study aims at quantifying the patient radiation dose reduction after the introduction of an X-ray imaging technology using advanced real time image noise reduction algorithms and optimized acquisition chain for fluoroscopy and exposure in a pediatric and adult population with congenital heart disease. Methods Patient and radiation dose data was retrospectively collected (July 2012–February 2013) for 338 consecutive patients treated with a system using state of the art image processing and reference acquisition chain (referred as “reference system”). The same data was collected (March–October 2013) for 329 consecutive patients treated with the new imaging technology (Philips AlluraClarity, referred as “new system”). Patients were divided into three weight groups: A) below 10 kg, B) 10–40 kg, and C) over 40 kg. Radiation dose was quantified using dose area product (DAP), while procedure complexity using fluoroscopy time, procedure duration and volume of contrast medium. Results The new system provides significant patient dose reduction compared to the reference system. Median DAP values were reduced in group A) from 140.6 cGy·cm2 to 60.7 cGy·cm2, in group B) from 700.0 cGy·cm2 to 202.2 cGy·cm2 and in group C) from 4490.4 cGy·cm2 to 1979.8 cGy·cm2 with reduction of 57%, 71% and 56% respectively (p < 0.0001 for all groups). Conclusions Despite no other changes in procedural approach, the novel X-ray imaging technology provided substantial radiation dose reduction of 56% or higher.

Impact of respiration on stroke volumes in paediatric controls and in patients after Fontan procedure assessed by MR real-time phase-velocity mapping

AIMS Blood flow rate quantification using two-dimensional phase-contrast MRI (PC-MRI) results in averaging of flow information due to long acquisition times precluding the examination of short-term effects. The aim of this study was to determine respiration-related flow rate variations by non-electrocardiographic triggered real-time phase-contrast MRI (PC-MRI). METHODS AND RESULTS Real-time PC-MRI was applied to study respiration-driven blood flow fluctuations in the ascending aorta (AAo), superior vena cava (SVC), and inferior vena cava (IVC) under normal and forced breathing in 33 healthy children and 10 Fontan patients. Respiration-dependent flow rates were virtually generated by dividing the respiration curve into four segments: expiration, end-expiration, inspiration, and end-inspiration. Whereas in volunteers aortic flow rate was elevated during end-expiration (5.6 ± 3.0%) and decreased during end-inspiration (-5.8 ± 3.5%) in relation to mean blood flow (P < 0.05), highest flow was detected during inspiration in SVC (10.5 ± 14.1%) and IVC (22.5 ± 12.1%) and lowest flow during expiration (-11.6 ± 13.5%, -13.2 ± 14.1%, P < 0.05). Differences were increased under forced breathing in AAo (10.4 ± 5.5%, -7.4 ± 6.5%, P < 0.05) and SVC (40.0 ± 30.3%, -30.0 ± 19.2%, P < 0.05), whereas were unchanged in IVC (16.5 ± 23.6%, -13.7 ± 21.6%, P = n.s.). Regarding patients, respiratory-dependent flow rate variability was increased and had to be related to the patients individual quality of Fontan circulation. CONCLUSION Real-time PC-MRI allows a physiological assessment of respiratory-related flow rate fluctuations in healthy subjects as well as in Fontan patients. Its capability for detection of short-term effects in clinical routine was demonstrated.

Single center experience: Implantation failures, early, and late complications after implantation of a partially biodegradable ASD/PFO-device (BioStar®)

In the search for a biodegradable device that leaves nothing but the tissue of the patient after complete endotheliazation and absorption, the BioSTAR® device was introduced in 2007 (CE Mark in European community and HPB in Canada) for ASD and PFO closure. It consists of a metal framework covered by a biodegradable membrane generated from a layer of porcine collagen that is broken down and absorbed over time. In a sheep model, the results were promising, showing complete closure of the defect with degradation of approximately 90% of the implanted membrane material after two years.

Bovine Jugular Veins versus Homografts in the Pulmonary Position: An Analysis across Two Centers and 711 Patients-Conventional Comparisons and Time Status Graphs as a New Approach.

BACKGROUND Various diseases and diversity in implantation ages, together with evolving diagnostic and therapeutic options, hinder comparative evaluations of long-term outcomes for valved conduits used for reconstruction of the right ventricular outflow tract (RVOT). We combined two common evaluation methods to optimally use information obtained by pooling the raw data from two high volume centers, each with very regular follow-up procedures, with the aim of analyzing durability differences between conventional homografts and bovine jugular veins. PATIENTS AND METHODS In the period 1985 to 2012, a total of 444 bovine jugular veins and 267 homografts were implanted, and 6,738 postoperative examinations took place. Evaluations included age-stratified Kaplan-Meier analyses, Cox regression models, and time status graphs, the third showing age-group stratified, time-related frequencies of intact, insufficient, stenotic, both insufficient and stenotic, and postinterventional conduits below the freedom from explantation curve. They take into account interventions, explantations, and the nonterminal character of echocardiographic findings. RESULTS The durability of intact bovine jugular veins in children and young adults is not inferior to that of homografts. Averaged over the first 12 years after implantation, the age groups < 25 years in fact showed advantages for bovine jugular vein recipients. The average fraction of patients younger than 25 years whose conduits were not explanted, postinterventional, stenotic, insufficient, or stenotic and insufficient was at least 10% higher in recipients of bovine jugular veins than in homograft recipients. CONCLUSION According to the time status graphs, the use of bovine jugular veins for RVOT in patients younger than 25 years appears to lead to superior results when compared with cryopreserved homografts.

Calculation of pediatric left ventricular mass: validation and reference values using real-time three-dimensional echocardiography.

BACKGROUND Reference values for left ventricular mass (LVM) are important echocardiographic tools for the follow-up of pediatric patients with cardiac disease. Cardiac magnetic resonance (CMR) imaging is currently regarded as the gold standard. The aims of this study were to validate LVM calculated using real-time three-dimensional echocardiography (RT3DE) and to establish pediatric reference values. METHODS For validation, 40 subjects (20 patients) consecutively underwent CMR (3-T TX Achieva, 25 cardiac phases/slice) and RT3DE (iE33 or Vivid E9, four subvolumes) in a single-center approach. The quantification of CMR data by the disk summation method as standard (mean LVM, 84.2 ± 53 g; range, 17.7-231.7 g) was compared with RT3DE. In a multicenter prospective design, 434 healthy children were investigated using standard software (LV-Analysis version 3.1). RESULTS In comparison with CMR, RT3DE provided a slight overestimation of LVM of only 2.5 ± 11.3% (r = 0.990, intraclass correlation coefficient = 0.995), and there was low intraobserver (mean, 0.9 ± 7.1%; scatter, 13.2% to -15.0%; r = 0.996; intraclass correlation coefficient = 0.998) and interobserver (mean, 1.5 ± 9.3%; scatter, 17.2% to -20.1%; r = 0.993; intraclass correlation coefficient = 0.996) variability. Feasibility of the multicenter approach was 76%, resulting in 332 healthy children (median age, 10.0 years; range, 0-18 years; group I range, 0-6 years; group II range, 7-18 years) with data sets providing adequate image quality. LVM was correlated with sex (group II), age (r = 0.901), height (r = 0.881), weight (r = 0.876), and body surface area (r = 0.898). Unisex percentiles for 0 to 6 years of age and separated according to gender from 7 to 18 years of age were established. Mean calculation time for RT3DE was <3 min. CONCLUSIONS In children, LVM calculation presuming excellent real-time three-dimensional echocardiographic data sets is accurate, quick, and reproducible. The percentiles provided are based on a large sample size and may be useful for clinical practice.