Search

Hypertrophic cardiomyopathy (HCM) often leads to heart failure. Mutations in sarcomeric proteins are most frequently the cause of HCM but in many patients the gene defect is not known. Here we report on a young man who was diagnosed with HCM shortly after birth. Whole exome sequencing revealed a mutation in the FLNC gene (c.7289C > T; p.Ala2430Val) that was previously shown to cause aggregation of the mutant protein in transfected cells. Myocardial tissue from patients with this mutation has not been analyzed before and thus, the underlying etiology is not well understood. Myocardial tissue of our patient obtained during myectomy at the age of 23 years was analyzed in detail by histochemistry, immunofluorescence staining, electron microscopy and western blot analysis. Cardiac histology showed a pathology typical for myofibrillar myopathy with myofibril disarray and abnormal protein aggregates containing BAG3, desmin, HSPB5 and filamin C. Analysis of sarcomeric and intercalated disc proteins showed focally reduced expression of the gap junction protein connexin43 and Xin-positive sarcomeric lesions in the cardiomyocytes of our patient. In addition, autophagy pathways were altered with upregulation of LC3-II, WIPI1 and HSPB5, 6, 7 and 8. We conclude that the p.Ala2430Val mutation in FLNC most probably is associated with HCM characterized by abnormal intercalated discs, disarray of myofibrils and aggregates containing Z-disc proteins similar to myofibrillar myopathy, which supports the pathological effect of the mutation. [ABSTRACT FROM AUTHOR]

Background: Previous investigations assessing the genetic cause of pediatric hypertrophic cardiomyopathy (HCM) found underlying genetic mutations in 50-60% of cases. The purpose of our study was to analyze whether this number can be augmented by applying next-generation sequencing and directing further diagnostics by discussing unsolved cases in a multidisciplinary board.Methods and results: 42 patients with the diagnoses of HCM made before age 18 years were treated in our center from 2000 to 2016. Genetic analysis was performed in 36 subjects, a genetic defect was detected in 29 (78%) patients. 15 individuals (42%) had pathogenic variants in genes encoding sarcomere proteins, and 5 (14%) in genes coding for components of the RAS/MAPK signaling pathway. 4 subjects (11%) had mutations in the GAA gene (Pompe disease), and 3 (8%) had Frataxin repeat expansions (Friedreich's ataxia). One patient each showed a mutation in BAG3 and LMNA. Discussion of unsolved HCM cases after performing next-generation sequencing (28 genes) in an interdisciplinary board unraveled the genetic cause in 9 subjects (25%).Conclusion: A definite genetic diagnosis can be reached in nearly 80% with HCM of childhood onset. Next-generation sequencing in conjunction with a multidisciplinary cooperation can enhance the diagnostic yield substantially. This may be important for risk stratification, treatment planning and genetic counseling. [ABSTRACT FROM AUTHOR]

While in adults major advances in heart failure therapy in patients with dilated cardiomyopathy were documented in the last two decades, research on the mechanism and therapies of heart failure in children with left ventricular dilated cardiomyopathy has lagged behind. Despite the lack of sufficient randomized prospective studies, ACE inhibitors are first line and ß-receptor antagonists are second-line strategies in children. Following the adult guidelines, without having data concerning the pediatric population, mineral corticoids are also accepted in the treatment of pediatric heart failure, while diuretics should only be used to achieve a euvolemic status. In cases of complete left bundle bunch block or prolonged QRS duration, cardiac resynchronization is an option. If these instruments are exploited, and the child is still listed for heart transplantation as destination, evolving therapies like pulmonary artery banding in cases of preserved right ventricular function and cardiac cell therapy in cases of localized ventricular dysfunction might represent additional treatment options. This review summarizes the actual guidelines and provides an outlook for evolving therapies. [ABSTRACT FROM AUTHOR]

Very young mammals have an impressive cardiac regeneration capacity. In contrast, cardiac regeneration is very limited in adult humans. The hearts of young children have a higher regenerative capacity compared with adults, as, for example, seen after surgical correction of an anomalous left coronary artery arising from the pulmonary artery or in children with univentricular hearts, who present enormous morphological changes after volume unloading. In addition, the enormous regenerative potential of growing children's hearts is reflected in the spontaneous courses of children with severely deteriorated cardiac function (e.g., patients with dilated cardiomyopathy). The extent of this regenerative capacity and its time dependency remain to be elucidated in the future and should be exploited to improve the treatment of children with severe heart insufficiency. [ABSTRACT FROM AUTHOR]

Pulmonary arterial endothelial function is known to be affected in patients with idiopathic pulmonary arterial hypertension (IPAH). Current reports also detected peripheral systemic arterial dysfunction in IPAH patients. The purpose of this study was to assess whether there is a relation between pulmonary arterial and systemic arterial endothelial function. Pulmonary arterial endothelium-dependent relaxation was assessed by changes in pulmonary blood flow in response to acetylcholine which were determined using intravascular Doppler flow measurements. Pulmonary flow reserve (PFR) was calculated as the ratio of pulmonary blood flow velocity in response to acetylcholine relative to baseline values. Systemic arterial endothelial function was assessed by the vascular response to reactive hyperemia, and was recorded non-invasively by peripheral arterial finger tonometry under standardized conditions. Thirteen children and young adults [mean age 16.7 (±5.6) years] with IPAH and 13 age-/gender-matched controls were included in the study. Digital reactive hyperemic index (RHI) of the IPAH patients was 1.54 (±0.69), and of the controls was 1.67 (±0.66) [ p = 0.64]. The mean baseline flow velocity in the segmental pulmonary artery of all patients was 18.5 (±5.5) cm/s, increasing to 27.4 (±12.3) cm/s ( p = 0.003) during acetylcholine infusion. The calculated mean PFR was 1.48 (±0.4). There was no significant correlation between the PFR and RHI ( r = 0.19; p = 0.54). According to our results, systemic arterial endothelial function assessed by peripheral arterial finger tonometry was not significantly impaired in children and young adults with IPAH compared with age-/gender-matched controls. There was no correlation between systemic arterial and pulmonary arterial endothelial function, suggesting that different mechanisms may contribute to their pathogenesis and progression. [ABSTRACT FROM AUTHOR]

Preservation of the pulmonary valve, even at the expense of a mild residual stenosis, is the current surgical policy for the management of patients with tetralogy of Fallot (TOF). This study aimed to assess the long-term effect of a residual right ventricular outflow tract obstruction (RVOTO) on RV dimension and function. This study prospectively assessed 53 children (mean age, 13.4 ± 6.4 years) after repair of TOF using cardiovascular magnetic resonance imaging. Residual RVOTO on echocardiography was defined as a peak systolic RVOT gradient of 25 mmHg or higher. Patients with RVOTO ( n = 29) had significantly less pulmonary regurgitation (25.2 ± 10.6 %) than patients without RVOTO (30.8 ± 9.3 %; p = 0.05) ( n = 24). Compared with patients who had no RVOTO, children with RVOTO had significantly smaller RV end-diastolic volume (94.0 ± 2.6 vs 104.0 ± 20.7 ml/m; p < 0.05) and end-systolic volume (42.9 ± 20.0 vs 48.9 ± 13.2 ml/m; p < 0.05), whereas RV ejection fraction did not differ significantly between the two groups (55.5 ± 8.4 vs 54.0 ± 6.6 %). Restrictive physiology, assessed by late diastolic forward flow in the main pulmonary artery, was equally distributed within the two groups (31 vs 25 %; nonsignificant difference). According to the study data, residual RVOTO after repair of TOF does not affect RV function, whereas RV dimensions and the degree of pulmonary regurgitation are more favorable in the long-term follow-up evaluation of those patients. These results confirm the beneficial effects of the current strategy for repair of TOF. [ABSTRACT FROM AUTHOR]

Recent studies suggest that the mammalian heart possesses some capacity for cardiac regeneration. This regenerative capacity is primarily documented postnatally and after myocardial infarction or pressure overload. Although the cell type that mediates endogenous regeneration is unclear, cardiac stem cells might be considered as potential candidates. To determine the number of c-kit + cardiac resident cells under conditions of pressure overload, we evaluated specimens derived from n = 8 patients with pressure overloaded single right ventricles in comparison to n = 4 explanted hearts from patients with dilated cardiomyopathy and n = 14 biopsies from children after heart transplantation. The age of the patients ranged from 16 days to 19 years. For quantification of cardiac stem cells, c-kit+/mast cell tryptase-/CD45- cells were counted and expressed as percent of the total nuclei. In specimens from patients with dilated cardiomyopathy, 0.13 ± 0.09% c-kit +/mast cell tryptase-/CD45- cells were detected. However, in specimens from patients with pressure overloaded single right ventricles, the numbers of c-kit+/mast cell tryptase-/CD45- cells were significantly higher (0.41 ±0.24%, p < 0.05). Under conditions of pressure overload, the right ventricle shows an approximately three-fold increase in c-kit+/mast cell tryptase-/CD45- cardiac resident cells. Despite the fact that this increased number of c-kit+ cells is not sufficient to prevent the failing heart from congestive heart failure, understanding the mechanism that leads to an increase of presumably cardiac resident stem cells under conditions of pressure overload might help to develop new strategies to enhance endogenous repair. [ABSTRACT FROM AUTHOR]

Extracorporeal shock wave lithotripsy (ESWL) has been used increasingly in clinical practice over the last few years. The aim of this study was to investigate the effects of shock waves on cartilage often unintentionally placed inside the focal volume during ESWL. We investigated whether the physical state of the chondrocytes exposed to shock waves has an influence on cell lethality. Chondrocytes of 12 patients were exposed to shock waves generated by a Piezoson 300. We used 200 shock waves of different energy levels (0.08 and 0.26 mJ/mm2) and the cells were prepared in two physical states: a fluid suspension and a viscous alginate. After ESWL the percentage of dead cells was determined by microscopy. DNA electrophoresis was carried out to detect fragmentation of the DNA. A significant increase of dead cells at higher energy levels in suspension ( P = 0.001) in contrast to alginate medium ( P = 0.263) was detected immediately after ESWL. The long-term survival of chondrocytes was not affected in either substance, as shown in an investigation of the cells three weeks after ESWL. At the molecular level a permeabilisation of the cell membrane was detected. DNA was not affected, even at high-energy levels. Alginate is definitely closer to the real state of cartilage in vivo than suspension. Therefore the negative effects of shock waves which are shown in many investigations that used cells in suspension are not necessarily to be expected in vivo. It can be assumed that side effects will not occur in a clinical setting. [ABSTRACT FROM AUTHOR]

To perform an open-wedge high-tibial osteotomy (HTO), the medial proximal tibia is frequently exposed by partial distal release of the overlying insertion of the medial collateral ligament (MCL). Biomechanically, any release of the MCL can increase knee laxity when valgus stress is applied. Clinically however, post-surgical valgus instability following HTO with partial MCL release is an uncommon complication. It is known that the open-wedge procedure can re-tention an intact MCL by the width of the base of the wedge. However, this re-tentioning effect is uncertain in small wedge sizes, preexisting medial compartment laxity and in the presence of a partially detached MCL. Considering the good clinical results after HTO, we hypothesized that a partial release of the superficial MCL for HTO does not play a crucial role in stabilizing valgus forces in the human knee. We therefore measured the effect of partial versus complete release of the superficial MCL to determine medial knee laxity represented by the amount of medial joint opening (MJO) under valgus stress in this human cadaver study. In ten knee pairs, the superficial and deep MCL were sectioned in sequence with a standardized abduction force of 15 kp with a Scheuba apparatus applied. In group 1 (5 knee pairs), the superficial MCL was completely sectioned whereas in group 2 (5 knee pairs), sectioning of the superficial MCL was restricted to the anterior border to mimic the surgical exposure for an HTO. To account for the interindividual variability of ligamentous laxity, only increments of MJO within knee pairs were statistically evaluated. Stress radiography did not reveal any significant differences in increments of MJO between knee pair specimens with complete versus partial release of the superficial MCL. We disproved our hypothesis and concluded that the anterior fibers of the superficial MCL do play a crucial role in maintaining valgus stability in this biomechanical setting. Therefore, the release of the superficial MCL for open-wedge HTO should be kept to a minimum to decrease the potential of late valgus instability. This is especially important in patients with small wedge sizes and medial compartment laxity since the anterior MCL fibers are the main contributor to medial joint stability and the re-tentioning effect of the remaining MCL fibers is presumably decreased. [ABSTRACT FROM AUTHOR]

Introduction The aim of this study was to investigate the effect of extracorporeal shock wave therapy (ESWT) on the ultrasonographic appearance of chronically painful, proximal plantar fasciitis. Materials and methods Twenty-two patients with a unilateral proximal plantar fasciitis were prospectively enrolled after unsuccessful conservative treatment lasting 6 months. The contralateral plantar fascia was used as the control. ESWT (3·3000 shock waves/session of 0.2 mJ/mm2) was performed at weekly intervals. The thickness of the plantar fascia was measured ultrasonographically about 2 cm distal of the medial calcaneal tuberosity. Pain estimation on a visual analogue scale (VAS) and the comfortable walking time were recorded. No local anaesthesia was applied. Follow-up was done at 6, 12 and 24 weeks. Results Before ESWT, the plantar fasciitis side was ultrasonographically significantly thicker than the control side (p<0.05), whereas 6 months after ESWT, the thickness of the fascia was no longer significantly different. The decrease in thickness of the plantar fasciitis side was significant (p<0.05). Pain during activities of daily living decreased by 79% according to the VAS, and the comfortable walking time increased, both significantly (p<0.01). In patients with little pain (VAS<30), the thickness of the plantar fasciitis side was significantly less (p<0.01) compared with patients who still suffered more pain (VAS>30). Conclusion After ESWT, the thickness of the plantar fascia in patients with plantar fasciitis decreased, pain and walking time improved (all significantly). [ABSTRACT FROM AUTHOR]

Human endothelial progenitor cells (EPCs) can differentiate into cardiomyogenic cells in vitro. We tested the effects of statin therapy on the differentiation rate of EPCs from patients with coronary artery disease (CAD), who may benefit from autologous cell therapy. EPCs from 3 age-matched groups were tested: No CAD (n = 13), CAD patients with (n = 10) or without (n = 16) statin therapy. From 4 CAD patients, EPCs were tested before and after 4 weeks of therapy with 20 mg atorvastatin. After 6 days of co-culture with rat neonatal cardiomyocytes, EPC differentiation was quantified by immunostaining for α-sarcomeric actinin flow cytometry analysis. After 6 days of co-culture, the percentage of -sarcomeric actinin–positive EPCs was significantly (p = 0.014) higher in EPCs from adults without CAD (8.07% ± 1.48% of EPCs) compared to EPCs from CAD patients without statin (3.56% ± 0.72%). Importantly, patients with statin therapy revealed significantly higher numbers of α-sarcomeric actinin-positive EPCs (6.36% ± 0.69%, p = 0.01) compared to CAD patients without statin. In addition, statin therapy resulted in a significant (p = 0.017) increase of EPC differentiation in all 4 CAD patients investigated before and 4 weeks after statin therapy. The survival of EPCs did not differ between the different groups suggesting that the regulation of EPC differentiation is not secondary to altered EPC survival. In vitro, EPC treatment with 0.1 µM atorvastatin did not affect EPC differentiation (116.15% ± 49.11% of control). EPCs from patients with CAD display impaired differentiation into cardiomyogenic cells. This defect can be improved by in vivo, statin therapy. [ABSTRACT FROM AUTHOR]

Aseptic osteonecrosis of the medial femoral condyle has recently been reported as a complication of arthroscopic surgery. The time interval between the onset of symptoms and pathognomonic MRI changes (diagnostic window) is not known for osteonecrosis of the knee. To determine the prevalence of early-stage spontaneous osteonecrosis of the knee (SONK) we prospectively examined 176 patients by MRI between May 1998 and December 1999. In six patients MRI revealed a bone marrow edema pattern and subtle subchondral bone changes in the medial condyle consistent with early-stage SONK (prevalence of 3.4%); in the 53 patients older than 65 years the prevalence was 9.4%. In 10 patients (5.7%) the bone and marrow changes on MRI imaging either resolved on follow-up MRI and were regarded as transient epiphyseal lesions or were considered to be reactive changes due to underlying degenerative articular disease. Including MRI in the preoperative diagnostic procedures could avoid missing the diagnosis of avascular necrosis before planning an operative treatment of suspected meniscal tears in elderly patients. [ABSTRACT FROM AUTHOR]

Unlabelled: The objective of the study was to compare prospectively short-term and mid-term results after ACL reconstruction with special focus on changes in instrumented knee laxity. Methods: The original study group included prospectively 58 patients who underwent arthroscopically assisted ACL reconstruction with BPTB graft in a two-tunnel technique between 1991 and 1993. Seven patients were lost to follow-up, leaving 51 patients for a first follow-up at 6 months and a second follow-up at 3-6 years (mean 4.3 years). Clinical results were evaluated by means of the Lysholm score and the IKDC score. Laxity was assessed using a KT-1000 arthrometer applying an 89 N anterior load in 20 degrees of flexion. Increased laxity was defined as a 3 mm increase in AP translation between the first and the second follow-up. Results: At mid-term follow-up pivot shift was negative in 86% of cases. IKDC score: normal = 28%, nearly normal = 44%, abnormal = 24%, severely abnormal = 4%. KT-1000: < 3 mm = 68%, 3-5 mm = 24%, > 5 mm = 8%. The mean KT-1000 side-to-side difference was 1.08 (0.17) mm at 6 months and 2.01 (0.29) mm at 3-6 years. The difference was statistically significant (P < 0.005). According to the defined criteria, seven patients had increased laxity at the second follow-up, suggesting a malfunction of the graft due to stretch-out or injury. In this subgroup the mean KT-1000 measurements were 0.86 (0.26) mm at the first follow-up and 5.93 (0.54) mm at the second follow-up. In five of these patients, a malposition of the tunnels was identified as a possible cause. In the remaining group, KT-1000 measurements did not differ significantly between the first and the second follow-up [1.12 (0.20) mm versus 1.37 (0.21) mm]. Conclusions: Increase in AP laxity occurred in 14% of our cases between the first and the second follow-up. In most of these cases increased laxity was due to inadequate surgical technique, especially malposition of bony tunnels. If tunnel position was correct, there was no evidence for elongation of grafts over time as a general principle. [ABSTRACT FROM AUTHOR]

Copyright of Arthroskopie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The aim of this study was to evaluate the effect of extracorporal shock wave therapy (ESWT) in tennis elbow and painful heel. Nineteen patients with tennis elbow and 44 patients with painful heel in which conservative treatment had failed underwent ESWT. Both groups received 3000 shock waves of 0.12 mJ/mm2 three times at weekly intervals. After a follow-up of 5 and 6 months respectively, pain measured on a visual analogue scale (VAS) decreased significantly in both groups. The success rate (excellent and good results) was 63% in tennis elbows and 70% in painful heels. ESWT seems to be a useful conservative alternative in the treatment of both conditions. [ABSTRACT FROM AUTHOR]

Copyright of Arthroskopie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)