Decreased Left Ventricular Torsion and Untwisting in Children with Dilated Cardiomyopathy

The purpose of this study was to analyze left ventricular (LV) torsion and untwisting, and to evaluate the correlation between torsion and other components of LV contraction in children with dilated cardiomyopathy (DCM). Segmental and global rotation, rotational rate (Vrot) were measured at three levels of LV using the two-dimensional (2D) speckle tracking imaging (STI) method in 10 DCM patients (range 0.6-15 yr, median 6.5 yr, 3 females) and 17 age- and sex-matched normal controls. Global torsion was decreased in DCM (peak global torsion; 10.9±4.6° vs. 0.3±2.1°, p<0.001). Loss of LV torsion occurred mainly by the diminution of counterclockwise apical rotation and was augmented by somewhat less reduction in clockwise basal rotation. In DCM, the normal counterclockwise apical rotation was not observed, and the apical rotation about the central axis was clockwise or slightly counterclockwise (peak apical rotation; 5.9±4.1° vs. -0.9±3.1°, p<0.001). Systolic counterclockwise Vrot and early diastolic clockwise Vrot at the apical level were decreased or abolished. In DCM, decreased systolic torsion and loss of early diastolic recoil contribute to LV systolic and diastolic dysfunction. The STI method may facilitate the serial evaluation of the LV torsional behavior in clinical settings and give new biomechanical concepts for better management of patients with DCM

Dyssynchronous Left Ventricular Activation is Insufficient for the Breakdown of Wringing Rotation

Cardiac resynchronization therapy is a valuable tool to restore left ventricular function in patients experiencing dyssynchronous ventricular activation. However, the non-responder rate is still as high as 40%. Recent studies suggest that left ventricular torsion or specifically the lack thereof might be a good predictor for the response of cardiac resynchronization therapy. Since left ventricular torsion is governed by the muscle fiber orientation and the heterogeneous electromechanical activation of the myocardium, understanding the relation between these components and the ability to measure them is vital. To analyze if locally altered electromechanical activation in heart failure patients affects left ventricular torsion, we conducted a simulation study on 27 personalized left ventricular models. Electroanatomical maps and late gadolinium enhanced magnetic resonance imaging data informed our in-silico model cohort. The angle of rotation was evaluated in every material point of the model and averaged values were used to classify the rotation as clockwise or counterclockwise in each segment and sector of the left ventricle. 88% of the patient models (n = 24) were classified as a wringing rotation and 12% (n = 3) as a rigid-body-type rotation. Comparison to classification based on in vivo rotational NOGA XP maps showed no correlation. Thus, isolated changes of the electromechanical activation sequence in the left ventricle are not sufficient to reproduce the rotation pattern changes observed in vivo and suggest that further patho-mechanisms are involved

Modifying and Measuring the Stiffness of a Regenerative Cardiac Scaffold In Vitro

The stiffness of scaffolds used in surgical ventricular restoration may play an important role in the degree to which they facilitate regeneration of functional cardiac tissue. The stiffness of the scaffold influences the phenotype of cells which are present in it as well as their ability to deform the scaffold. The goal of this study was to evaluate in vitro methods to characterize and alter the stiffness of new scaffold materials. Membrane inflation testing, an in vitro mechanical testing method, was evaluated in this study because of its ease of use and the similar mode of loading which it shares with scaffolds implanted in vivo. The structural stiffness of two scaffold materials, urinary bladder matrix and Dacron, were determined in vivo and using membrane inflation testing. Despite higher tensions and lower area stretch ratios for scaffolds tested using membrane testing, similar changes in structural stiffness between the two materials were found for both methods (5.6 ± 3.3 fold in vivo, 5.0 ± 1.0 in vitro). This finding demonstrated that membrane inflation testing is a useful in vitro method for measuring changes in structural stiffness between scaffold materials with a level of sensitivity similar to that which is measured in vivo. Membrane inflation testing was used to assess the effectiveness of altering scaffold stiffness through exposure to various cell culture conditions. Incubation of a biological membrane in cell culture media resulted in a drastic decrease in the elastic modulus from its initial value (3.55 ± 0.52 MPa) after 2 weeks (1.79 ± 0.30 MPa), 4 weeks (1.04 ± 0.09 MPa), and 10 weeks (0.014 ± 0.01 MPa). When fibroblasts were cultured on the scaffolds for 10 weeks an increase in elastic modulus (0.134 ± 0.05 MPa) over scaffolds incubated in culture media for the same amount of time was observed. The increase in elastic modulus due to the presence of fibroblasts was accompanied by an increase in the percentage of collagen in the samples (54.1 ± 5.1 % without fibroblasts, 83.2 ± 5.1 % with fibroblasts). Contrary to expectation, addition of ascorbic acid to the media to increase production of collagen by the fibroblasts resulted in a decrease in elastic modulus (0.030 ± 0.01 MPa) compared to scaffolds cultured with fibroblasts in standard media and a decrease in the amount of enzymatically degraded collagen (40.8 ± 4.7 % without ascorbic acid, 21.1 ± 3.3 % with ascorbic acid). Regeneration of cardiac tissue after a myocardial infarction is a complicated process which is influenced by a myriad of different factors. Future studies investigating the exact role which substrate stiffness has on regeneration will be essential to the development of improved cardiac scaffolds. Characterization of the stiffness of these scaffolds by membrane inflation and manipulation through exposure to cell culture conditions are powerful approaches to facilitate future studies

Front Lines of Thoracic Surgery

Front Lines of Thoracic Surgery collects up-to-date contributions on some of the most debated topics in today's clinical practice of cardiac, aortic, and general thoracic surgery,and anesthesia as viewed by authors personally involved in their evolution. The strong and genuine enthusiasm of the authors was clearly perceptible in all their contributions and I'm sure that will further stimulate the reader to understand their messages. Moreover, the strict adhesion of the authors' original observations and findings to the evidence base proves that facts are the best guarantee of scientific value. This is not a standard textbook where the whole discipline is organically presented, but authors' contributions are simply listed in their pertaining subclasses of Thoracic Surgery. I'm sure that this original and very promising editorial format which has and free availability at its core further increases this book's value and it will be of interest to healthcare professionals and scientists dedicated to this field

MRI Evaluation of Injectable Hyaluronic Acid Hydrogel Therapy to Attenuate Myocardial Infarct Remodeling

Left ventricular (LV) remodeling following myocardial infarction (MI) leads to maladaptive processes that often progress to heart failure. Injectable biomaterials can alter the mechanical signaling post-MI to limit this progression. To design optimal therapies, noninvasive techniques are needed to elucidate the reciprocal interaction between the injected material and the surrounding myocardial tissue. Towards this goal, the general hypothesis of this dissertation was that magnetic resonance imaging (MRI) can be used to characterize the properties of injectable materials once delivered to the myocardium and evaluate the temporal effects of injectable materials on myocardial tissue properties post-MI. To test this hypothesis, injectable hyaluronic acid (HA) hydrogels were developed with a range of gelation, degradation and mechanical properties by altering the initiator concentration, macromer modification, and macromer concentration, respectively. Non-contrast MRI was then used to characterize the properties (e.g., distribution, chemical composition) of injectable HA hydrogels in myocardial explants. Altering hydrogel gelation led to differences in distribution in myocardial tissue, as quantified by T2-weighted MRI. As an alternative to conventional (i.e.T2-weighted) MRI where contrast depends on differences in MR properties and thus, is non-specific for the material, chemical exchange saturation transfer (CEST) MRI was used to specifically image hydrogels based on their functional (i.e. exchangeable proton) groups. CEST contrast correlated with changes in material properties, specifically macromer concentration. Furthermore, CEST MRI was shown to simultaneously visualize and discriminate between different injectable materials based on their unique chemistry. Finally, the effect of injectable HA hydrogels on myocardial tissue properties was temporally evaluated in a porcine infarct model up to 12 weeks post-MI. Outcome assessment using MRI (e.g. cine, late-gadolinium enhancement, and spatial modulation of magnetization MRI) and finite element (FE) modeling demonstrated that hydrogel therapy led to improved global LV structure and function, increased wall thickness, preserved borderzone contractility, and increased infarct stiffness, respectively. This work demonstrates that MRI can be used to simultaneously study hydrogel properties after injection into the myocardium and evaluate the ability of injectable hydrogels to alter myocardial tissue properties to ultimately improve cardiac outcomes and enable future optimization of biomaterial therapies to attenuate adverse remodeling post-MI

Myoblast transplantation and adenoviral VEGF-C transfer in porcine model of coronary artery disease

Heart failure is a common and highly challenging medical disorder. The progressive increase of elderly population is expected to further reflect in heart failure incidence. Recent progress in cell transplantation therapy has provided a conceptual alternative for treatment of heart failure. Despite improved medical treatment and operative possibilities, end-stage coronary artery disease present a great medical challenge. It has been estimated that therapeutic angiogenesis would be the next major advance in the treatment of ischaemic heart disease. Gene transfer to augment neovascularization could be beneficial for such patients. We employed a porcine model to evaluate the angiogenic effect of vascular endothelial growth factor (VEGF)-C gene transfer. Ameroid-generated myocardial ischemia was produced and adenovirus encoding (ad)VEGF-C or β-galactosidase (LacZ) gene therapy was given intramyocardially during progressive coronary stenosis. Angiography, positron emission tomography (PET), single photon emission computed tomography (SPECT) and histology evidenced beneficial affects of the adVEGF-C gene transfer compared to adLacZ. The myocardial deterioration during progressive coronary stenosis seen in the control group was restrained in the treatment group. We observed an uneven occlusion rate of the coronary vessels with Ameroid constrictor. We developed a simple methodological improvement of Ameroid model by ligating of the Ameroid–stenosed coronary vessel. Improvement of the model was seen by a more reliable occlusion rate of the vessel concerned and a formation of a rather constant myocardial infarction. We assessed the spontaneous healing of the left ventricle (LV) in this new model by SPECT, PET, MRI, and angiography. Significant spontaneous improvement of myocardial perfusion and function was seen as well as diminishment of scar volume. Histologically more microvessels were seen in the border area of the lesion. Double staining of the myocytes in mitosis indicated more cardiomyocyte regeneration at the remote area of the lesion. The potential of autologous myoblast transplantation after ischaemia and infarction of porcine heart was evaluated. After ligation of stenosed coronary artery, autologous myoblast transplantation or control medium was directly injected into the myocardium at the lesion area. Assessed by MRI, improvement of diastolic function was seen in the myoblast-transplanted animals, but not in the control animals. Systolic function remained unchanged in both groups.Pitkälle edennyt sydämen vajaatoiminta on hyvin vaikeahoitoinen tauti. Vanhuusväestön suhteellinen lisääntyminen lisää taudin merkittävyyttä ja sydänlihaksen solusiirtoja on ehdotettu uudeksi vaihtoehtoiseksi hoitomuodoksi. Huolimatta parantuneesta lääkehoidosta ja kehittyneistä pallolaajennus- ja leikkausmenetelmistä, loppuvaiheen sepelvaltimotauti on lääketieteellinen haaste. On arvioitu, että geenihoito olisi seuraava merkittävä hoitomenetelmä vaikeassa sepelvaltimotaudissa. Kokeilimme koe-eläimellä adenoviruksella siirretyn VEGF-C-kasvutekijän vaikutusta uudissuonten kehittymiseen. Sialle asetettiin hitaasti elimistössä turpoava rengastin sepelvaltimon tyveen. Kolme viikkoa rengastimen asettamisesta sioille siirrettiin VEGF-C-hoitogeeni tai kontrolligeeni hapenpuutetta kärsivälle sydänlihaksen alueelle. Sydänlihaksen verenkierto tutkittiin verisuonten varjoainekuvauksilla, sekä PET- ja SPECT kuvauksin. Lopuksi tutkittiin kudosnäytteet. Hoitoryhmällä havaittiin merkittävästi enemmän uudissuonia ja rengastimen aiheuttama sydänlihaksen toiminnanvajaus ei edennyt, toisin kuin kontrolligeeniä saaneilla eläimillä. Kyseinen rengastin on käytetyin laite sepelvaltimotaudin mallintamisessa isoeläimellä. Havaitsimme kuitenkin ahtautuma-asteen vaihtelevan yksilöiden välillä. Kehitimme yksinkertaisen menetelmän, jossa kiristimen asetuksen yhteydessä jätettiin suonen ympärille sulkulanka. Langalla varmistetaan suonen tukkeutuminen kolmen viikon kohdalla, kun luontainen uudissuonimuodostus on kehittynyt sydämen suojaksi. Menetelmä osoittautui toimivaksi ja kuvasimme uuden mallin luontaisen paranemistaipumuksen magneetti- SPECT ja PET- kuvauksin sekä verisuonten varjoainekuvauksilla. Kudostutkimuksissa havaitsimme immunohistokemiallisin kaksoisvärjäyksin sydänlihassolujen tumien jakautumista luontaisen paranemisen merkkinä. Aiemmin on uskottu, että sydänlihassolujen jakaantumista ei tapahdu enää hyvin varhaisen lapsuuden jälkeen. Myoblastit ovat luurankolihassolujen esiasteita, joista voi kehittyä uusia lihassoluja. Kokeilimme eläimestä itsestään kerättyjen myoblastien vaikutusta sydänlihaskuolion ja -hapenpuutteen hoidossa. Sioille luotiin pienet sydäninfarktit ja hapenpuutteesta kärsivä alue. Jokaisesta eläimestä kerättiin lihasnäytteet, joista myoblastit eristettiin ja solujen lukumäärää lisättiin miljooniin laboratoriossa kasvattamalla. Siat saivat sokkoutetusti joko myoblasti-solusiirron tai kontrolliliuosta sydämen vaurioalueelle. Sydänlihaksen toiminta ja -hapensaanti arvioitiin magneetti- ja sepelvaltimoiden varjoainekuvauksin. Myoblasteja saaneilla eläimillä sydämen diastolinen toiminta oli parempi kuin kontrolliryhmällä. Tämä tutkimussarja tukee sydämen solu- ja geenihoitojen vaikuttavuutta sydäntautien hoidossa

Non-pharmacological heart failure therapies : evaluation by ventricular pressure-volume loops

In this thesis, we evaluated the acute and chronic hemodynamic effects of non-pharmacological heart failure therapies. In particular, the effects of surgical treatment and biventricular pacing therapy were investigated by left ventricular pressure-volume loop analyses. We demonstrated that restrictive mitral annuloplasty effectively restored mitral leaflet coaptation without inducing significant acute changes in ventricular function. This indicates that this procedure can be safely applied in patients with heart failure. Surgical ventricular restoration was shown to achieve acute normalisation of left ventricular volumes, improved systolic function, and decreased left ventricular wall stress and mechanical dyssynchrony. At the expense of a higher diastolic pressure resulting from altered diastolic properties, stroke work and cardiac output were not importantly altered, but mechanical efficiency was significantly improved. Chronically, surgical therapy resulted in improved clinical status evidenced by improved NYHA class, quality of life score, and 6-min walking distance. Left ventricular function and dyssynchrony remained significantly improved at 6 months follow-up. In addition, we observed a decrease in pulmonary artery pressure, right ventricular reverse remodeling and reduced tricuspid regurgitation. Acute and chronic hemodynamic effects of cardiac resynchronization therapy (biventricular pacing) were demonstrated by pressure-volume loop analysis. Hemodynamic improvements, previously only shown in acute studies, were shown to be maintained at 6 months follow-up. In addition, ventricular-arterial coupling, mechanical efficiency, and chronotropic responses were improved. In conclusion, the acute and chronic hemodynamic effects of these non-pharmacological heart failure therapies were demonstrated by ventricular pressure-volume analysis. These findings provide insight in the underlying mechanisms and help to explain improved functional status achieved with these therapies.UBL - phd migration 201

Cardiac assist devices: Cognitive and behavioral factors among patients awaiting cardiac transplantation

Cognitive functioning and quality of life are salient factors in predicting mortality and morbidity in end-stage heart failure patients receiving cardiac assist devices while awaiting cardiac transplantation. This study focused on cognitive functioning and selfreported quality of life, neurological impairment, and depressive symptoms. Of 103 candidates for cardiac assist devices (HeartMate ThermoCardiosystems, Inc. [TCI] Left Ventricular Devices [LVAD] or Abiomed Biventricular Assist System [Abiomed]) as a bridge to cardiac transplantation at Hahnemann University Hospital, a total of 53 patients completed neuropsychological evaluations. Cognitive factors included visual-spatial andverbal memories, motor speed, grip strength, and cognitive processing speed. Inaddition, a total of 298 end-stage heart failure (ESHF) inpatients completed the same cognitive measures over the past decade. Overall, cognitive functioning for both groups was within the normal range. Not surprisingly, a series of t-tests revealed that ESHF inpatients performed better than MCAD candidates on most cognitive measures. However, MCAD candidates performed better than ESHF inpatients on the Mental Status Exam, Visual Reproduction Immediate subtest of the Wechsler Memory Scale, and grip strength task with the nondominant hand.A total of 23 cardiac assist device candidates completed self-report measures ofgeneral and disease-specific quality of life, depressive symptoms, memory, and selfreported neuropsychological symptoms. Results did not support the hypothesis that depression would mediate the relationship between cognitive functioning and quality of life. There were significant differences in quality of life between the three groups: ESHF, MCAD, and OHT warranting a discussion of the implications of various definitions of quality of life. There were no significant gender differences. Major behavioral findings were 1) these patients are resilient in comparison to the general population; their cognitive functioning was not impaired and they were not depressed and 2) there was a strong relationship between self-report depressive symptoms and self-reportedneurological impairment.Ph.D., Clinical Psychology -- Drexel University, 200

The pathology of equine laryngeal hemiplegia

Abstract Not Provided