Computer Vision Techniques for Transcatheter Intervention

Minimally invasive transcatheter technologies have demonstrated substantial promise for the diagnosis and treatment of cardiovascular diseases. For example, TAVI is an alternative to AVR for the treatment of severe aortic stenosis and TAFA is widely used for the treatment and cure of atrial fibrillation. In addition, catheter-based IVUS and OCT imaging of coronary arteries provides important information about the coronary lumen, wall and plaque characteristics. Qualitative and quantitative analysis of these cross-sectional image data will be beneficial for the evaluation and treatment of coronary artery diseases such as atherosclerosis. In all the phases (preoperative, intraoperative, and postoperative) during the transcatheter intervention procedure, computer vision techniques (e.g., image segmentation, motion tracking) have been largely applied in the field to accomplish tasks like annulus measurement, valve selection, catheter placement control, and vessel centerline extraction. This provides beneficial guidance for the clinicians in surgical planning, disease diagnosis, and treatment assessment. In this paper, we present a systematical review on these state-of-the-art methods.We aim to give a comprehensive overview for researchers in the area of computer vision on the subject of transcatheter intervention. Research in medical computing is multi-disciplinary due to its nature, and hence it is important to understand the application domain, clinical background, and imaging modality so that methods and quantitative measurements derived from analyzing the imaging data are appropriate and meaningful. We thus provide an overview on background information of transcatheter intervention procedures, as well as a review of the computer vision techniques and methodologies applied in this area

Current Issues and Recent Advances in Pacemaker Therapy

Patients with implanted pacemakers or defibrillators are frequently encountered in various healthcare settings. As these devices may be responsible for, or contribute to a variety of clinically significant issues, familiarity with their function and potential complications facilitates patient management. This book reviews several clinically relevant issues and recent advances of pacemaker therapy: implantation, device follow-up and management of complications. Innovations and research on the frontiers of this technology are also discussed as they may have wider utilization in the future. The book should provide useful information for clinicians involved in the management of patients with implanted antiarrhythmia devices and researchers working in the field of cardiac implants

Video Kinematic Evaluation: new insights on the cardiac mechanical function

The cardiac mechanical function plays a critical role in governing and regulating its performance under both normal and pathological conditions. The left ventricle has historically received more attention in both congenital and acquired heart diseases and was considered as the mainstay of normal hemodynamics. However, over the past few decades, there has been increasing recognition of the pivotal role of the right ventricle in determining functional performance status and prognosis in multiple conditions. Nonetheless, the ventricles should not be considered separately as they share the septum, are encircled with common myocardial fibers and are surrounded by the pericardium. Thus, changes in the filling of one ventricle may alter the mechanical function of its counterpart. This ventricular interdependence remains even after the removal of the pericardium because of constrictive pericarditis or during open chest surgery. Interestingly, during open chest surgery, only the right ventricle mechanical activity is visually checked by the surgeon and cardiologist due to the absence of an intraoperative imaging technique able to evaluate its complex function. Noteworthy, most of the imaging techniques available to clinicians are established for the assessment of the left ventricle, with the ejection fraction being the most used parameter. However, this value is a measure of global systolic function which comes short in identifying regional myocardial impairment and the mechanical contraction. Therefore, new approaches are needed to deeply investigate the mechanics of both ventricles and correctly assess the cardiac mechanical performance. In this thesis, I studied the mechanical function of the left ventricle through different modalities of cardiac magnetic resonance and employed an innovative imaging technique for the assessment of the right ventricle mechanical function during open chest surgery

Age- and gender-specific reference values for cardiac chamber geometry and function using three-dimensional echocardiography

Background. Three-dimensional echocardiography (3DE) enables a comprehensive, accurate and reproducible quantification of cardiac chamber size and function without any geometric assumption about their shape. Superior accuracy and reproducibility of 3DE over stabdard two-dimensional (2DE) approach for cardiac chamber volume measurements in comparison to cardiac magnetic resonance (CMR) has been well documented in a number of studies. Both the European Association of Cardiovascular Imaging and the American Society of Echocardiography recommend 3DE, rather than 2DE, for routine clinical assessment of cardiac chamber volumes. However, both Societes also acknowledge that the application of 3DE into routine clinical practice has been hindered by the limited availability of reference values, and particularly the lack of gender- and anthropometric-based analysis. Therefore, identification of reference values for cardiac chamber size, geometry and function has become a prerequisite for the routine clinical application of quantitative 3DE. Research Project Single-centre, prospective, observational cohort study aimed to: (i). comprehensively analyze the four cardiac chamber geometry and function using state-of-the-art 3DE equipment in a large cohort of healthy volunteers; (ii). assess the effects of age, body size and gender on these parameters; and (iii). compare the values measured using 3DE with those obtained by conventional echocardiography in the same subjects and with other cohorts of healthy subjects from published 3DE studies. Methods. 263 healthy volunteers (43±14 years, range 18-75; 58% women) whose data sets have been acquired from October 2011 to July 2013 using a commercially available 3D echo scanner (Vivid E9, GE Vingmed, Horten, NO) equipped with 4V matrix array probe. Data sets were analyzed with different commercially available (EchoPac BT 12, GEVingmed Horten, NO; 4D RV function, TomTec Imaging system, Unterschleissheim, D ) and prototype (EchoPac BT 13, GEVingmed Horten, NO; 4D LA Tomtec Imaging systems, Unterschleissheim, D) analysis softwares. The study was approved by the University of Padua Ethics Committee (protocol # 2380 P approved on 06/10/2011) and signed informed consent has been obtained in all volunteers before the screening for eligibility in the study. Results Study #1: Analysis of left ventricular (LV) size, geometry and function. In 226 consecutive healthy volunteers (125 women, aged 18-76 years), we performed a comprehensive 3DE analysis of LV parameters and compared them with values obtained by conventional echocardiography. Upper reference values (mean+2 standard deviatons) for 3D LV end-diastolic (EDV) and end-systolic (ESV) volumes were 85 ml/m2 and 34 ml/m2 in men, and 72 ml/m2 and 28 ml/m2 in women, respectively. Indexing LV volumes by body surface area did not eliminate gender differences. Lower reference values (mean-2 standard deviations) for ejection fraction (EF) were 54% in men and 57% in women, while for stroke volume (SV) were 25 ml/m2 and 24 ml/m2, respectively. Upper reference values for LV mass were 97 g/m2 in men and 90 g/m2 in women, while for end-diastolic sphericity index were 0.49 and 0.48, respectively. Significant age-dependency of LV parameters was identified and reported across age groups. 3DE LV volumes were larger, EF was similar, SV and mass were significantly smaller in comparison with the corresponding values obtained by conventional echocardiography. Study #2: Analysis of right ventricular (RV) size and function. RV volumes, SV and EF were measured by 3DE in 540 healthy adult volunteers, prospectively enrolled, evenly distributed across age and gender. The relation of age, gender and body size parameters with RV volumes and EF were investigated using bivariate and multiple linear regressions. Analysis was feasible in 507 (94%) subjects (260 women, age 45±16 years, range 18-90). Age, gender, height and weight significantly influenced RV volumes and EF. Gender effect was significant (p<0.01), with RV volumes larger and EF smaller in men than in women. Older age was associated with smaller volumes (EDV, -5 ml/decade; ESV, -3 ml/decade; SV, -2 ml/decade), and higher EF (+1%/decade). Inclusion of body size parameters in the statistical models resulted in improved overall explained variance for volumes (EDV, R2=0.43; ESV, R2=0.35; SV, R2=0.30), while EF was unaffected. Ratiometric and allometric indexing for age, gender and body size resulted in no significant residual correlation between RV geometry measures and height or weight. Study #3: Analysis left atrial size and function. 244 healthy volunteers (43±14 years, range 18-75; 58% women) underwent 3DE and 2DE to measure maximal (Vmax), minimal (Vmin) and preA (VpreA) LA volumes to calculate total, passive and active LA emptying volumes (TotEV, PassEV, ActEV) and fractions (TotEmptFr, PassEmptFr, ActEemptFr). Feasibility of 3DE and 2DE LA volumes was 91% and 96% (p=0.59 ). 3DE LA volumes were larger than 2DE ones (Vmax: 48±11 ml vs. 43±11 ml; Vmin: 18±5 vs. 14±6, respectively, p<0.001). LA TotEmptFr (61±6% vs. 68±9%) and ActEmptFr (30±7% vs. 47±10%) were lower by 3DE than 2DE (p<0.001), whereas PassEmptFr (44±10% vs. 41±11%) was higher by 3DE than 2DE (p= 0.002). 3DE LA volumes indexed by body surface area were similar in both genders and increased with ageing (p=0.002). Study #4: Analysis of right atrial (RA) size and function. 200 healthy volunteers (43±15 years; 44% men) underwent 2DE and 3DE to measure maximal (Vmax), minimal (Vmin) and preA (VpreA) volumes to derive total (TotEV), passive (PassEV) and true (TrueEV) emptying volumes and emptying fractions (TotEmptFr, PassEmptFr, TrueEmptFr). 3DE volumes (Vmax, 52±15 ml vs 41±14 ml, p<0.0001), EVs (TotSV, 33±10 ml vs. 24±9 ml, p<0.0001) and EmptFrs (TotEmptFr, 63±9% vs. 58±9%, p<0.0001) were larger than 2DE ones. Indexed 3D RA volumes were significantly larger in men than in women. Aging was associated with a significant decrease in passive RA function (PassEV, r= -0.26; PassEmptFr, r= -0.38; all p<0.0001) and an increase in active RA function (TrueEV, r= 0.25; p<0.0001; and TrueEmptFr, r= 0.15; p= 0.035) in order to maintain TotEV (r= -0.14, p= 0.05). Conclusions The present research project provides a comprehensive quantitative analysis of the four cardiac chamber geometry and function using 3DE in a relatively large cohort of Caucasian healthy volunteers with a wide age range. The main results can be summarized as follows: (i). Cardiac chamber quantification with 3DE is feasible and reproducible; (ii) Reference values for cardiac chamber size and function by 3DE were found to be significantly different from those obtained with conventional echocardiography, highlighting the importance of applying method-specific reference values for a reliable identification of remodeling and/or dysfunction of cardiac chambers; (iii). Cardiac chamber parameters measured by 3DE showed excellent reproducibility, and were more robust than 2DE indices at repeated measurements; (iii). Most parameters describing cardiac chamber size should be defined according to age and gender, since indexing them only for BSA does not account for all the physiologic variations in geometry and function. Availability of reference values and age- and gender-specific cut-off values should facilitate the implementation of 3DE to identify cardiac chamber remodelling and dysfunction in both clinical routine and research

Estudo da remodelagem reversa miocárdica através da análise proteómica do miocárdio e do líquido pericárdico

Valve replacement remains as the standard therapeutic option for aortic stenosis patients, aiming at abolishing pressure overload and triggering myocardial reverse remodeling. However, despite the instant hemodynamic benefit, not all patients show complete regression of myocardial hypertrophy, being at higher risk for adverse outcomes, such as heart failure. The current comprehension of the biological mechanisms underlying an incomplete reverse remodeling is far from complete. Furthermore, definitive prognostic tools and ancillary therapies to improve the outcome of the patients undergoing valve replacement are missing. To help abridge these gaps, a combined myocardial (phospho)proteomics and pericardial fluid proteomics approach was followed, taking advantage of human biopsies and pericardial fluid collected during surgery and whose origin anticipated a wealth of molecular information contained therein. From over 1800 and 750 proteins identified, respectively, in the myocardium and in the pericardial fluid of aortic stenosis patients, a total of 90 dysregulated proteins were detected. Gene annotation and pathway enrichment analyses, together with discriminant analysis, are compatible with a scenario of increased pro-hypertrophic gene expression and protein synthesis, defective ubiquitinproteasome system activity, proclivity to cell death (potentially fed by complement activity and other extrinsic factors, such as death receptor activators), acute-phase response, immune system activation and fibrosis. Specific validation of some targets through immunoblot techniques and correlation with clinical data pointed to complement C3 β chain, Muscle Ring Finger protein 1 (MuRF1) and the dual-specificity Tyr-phosphorylation regulated kinase 1A (DYRK1A) as potential markers of an incomplete response. In addition, kinase prediction from phosphoproteome data suggests that the modulation of casein kinase 2, the family of IκB kinases, glycogen synthase kinase 3 and DYRK1A may help improve the outcome of patients undergoing valve replacement. Particularly, functional studies with DYRK1A+/- cardiomyocytes show that this kinase may be an important target to treat cardiac dysfunction, provided that mutant cells presented a different response to stretch and reduced ability to develop force (active tension). This study opens many avenues in post-aortic valve replacement reverse remodeling research. In the future, gain-of-function and/or loss-of-function studies with isolated cardiomyocytes or with animal models of aortic bandingdebanding will help disclose the efficacy of targeting the surrogate therapeutic targets. Besides, clinical studies in larger cohorts will bring definitive proof of complement C3, MuRF1 and DYRK1A prognostic value.A substituição da válvula aórtica continua a ser a opção terapêutica de referência para doentes com estenose aórtica e visa a eliminação da sobrecarga de pressão, desencadeando a remodelagem reversa miocárdica. Contudo, apesar do benefício hemodinâmico imediato, nem todos os pacientes apresentam regressão completa da hipertrofia do miocárdio, ficando com maior risco de eventos adversos, como a insuficiência cardíaca. Atualmente, os mecanismos biológicos subjacentes a uma remodelagem reversa incompleta ainda não são claros. Além disso, não dispomos de ferramentas de prognóstico definitivos nem de terapias auxiliares para melhorar a condição dos pacientes indicados para substituição da válvula. Para ajudar a resolver estas lacunas, uma abordagem combinada de (fosfo)proteómica e proteómica para a caracterização, respetivamente, do miocárdio e do líquido pericárdico foi seguida, tomando partido de biópsias e líquidos pericárdicos recolhidos em ambiente cirúrgico. Das mais de 1800 e 750 proteínas identificadas, respetivamente, no miocárdio e no líquido pericárdico dos pacientes com estenose aórtica, um total de 90 proteínas desreguladas foram detetadas. As análises de anotação de genes, de enriquecimento de vias celulares e discriminativa corroboram um cenário de aumento da expressão de genes pro-hipertróficos e de síntese proteica, um sistema ubiquitina-proteassoma ineficiente, uma tendência para morte celular (potencialmente acelerada pela atividade do complemento e por outros fatores extrínsecos que ativam death receptors), com ativação da resposta de fase aguda e do sistema imune, assim como da fibrose. A validação de alguns alvos específicos através de immunoblot e correlação com dados clínicos apontou para a cadeia β do complemento C3, a Muscle Ring Finger protein 1 (MuRF1) e a dual-specificity Tyr-phosphoylation regulated kinase 1A (DYRK1A) como potenciais marcadores de uma resposta incompleta. Por outro lado, a predição de cinases a partir do fosfoproteoma, sugere que a modulação da caseína cinase 2, a família de cinases do IκB, a glicogénio sintase cinase 3 e da DYRK1A pode ajudar a melhorar a condição dos pacientes indicados para intervenção. Em particular, a avaliação funcional de cardiomiócitos DYRK1A+/- mostraram que esta cinase pode ser um alvo importante para tratar a disfunção cardíaca, uma vez que os miócitos mutantes responderam de forma diferente ao estiramento e mostraram uma menor capacidade para desenvolver força (tensão ativa). Este estudo levanta várias hipóteses na investigação da remodelagem reversa. No futuro, estudos de ganho e/ou perda de função realizados em cardiomiócitos isolados ou em modelos animais de banding-debanding da aorta ajudarão a testar a eficácia de modular os potenciais alvos terapêuticos encontrados. Além disso, estudos clínicos em coortes de maior dimensão trarão conclusões definitivas quanto ao valor de prognóstico do complemento C3, MuRF1 e DYRK1A.Programa Doutoral em Biomedicin

Alternative site for the placement of totally implantable vascular access device (TIVAD). A case report of two successful TIVAD implantations in the thigh after femoral vein catheterization

Background: Totally implantable venous access devices (TIVADs) have improved the quality of life for seriously ill and cancer patients. These devices represent a convenient option when long-term venous access is indicated. The Subclavian and Internal Jugular Veins are the vessels of choice for catheterization [1]. However, if it is not possible to catheterize them, an alternative vein should be sought for [2]. Femoral vein can be used in such cases [3].Clinical problem: In 2 cases, it was not possible to catheterise any vein ending in the Superior Vena Cava and implant a TIVAD in the chest wall, although this was very necessary for them. Femoral vein was chosen despite higher risk of complications.Case 1: A 47 years old female with a metastatic breast cancer and infected ulcerations of the anterior chest wall. Veins in both arms were occluded. Her implanted TIVAD could not be used. Case 2: A 44 years old female who had a newly diagnosed lung cancer and Superior Vena Cava Syndrome. She was treated by a high-dose anti-coagulants.Surgical intervention: The catheter was inserted in the left femoral vein using ultrasound-guided percutaneous technique. After making a small incision, PORT-A-CATH® II POWER P.A.C. single-lumen standard port was implanted subcutaneously in the anterior surface of the left thigh. Verification of the catheter’s tip intra-operatively was difficult in Case 1 due to fluoroscopy problems. Prior consideration of the required instruments prevented the occurrence of a similar problem in Case 2. We performed these operations in the University Hospital of Norrland in Sweden in 2013.Follow-up: Apart from later adjustment of the catheter positioning in Case 1, we did not get any complications or problems with the use of the TIVAD. Frequent flushing of the device was recommended. Patients’ and staff’s satisfaction were good. Conclusion: Placement of TIVAD in the thigh is to be considered when the veins of the neck and upper arm are not accessible or the area on the chest wall is not appropriate for implanting the device. Experience improves with more cases.References: 1- Di Carlo I, Toro A. Choice of venous sites. Surgical Implant/technique. Springer-Verlag, Italia, 2011;43-54. 2- Toro A, Mannino M, Cappello G et al. Totally implanted venous access devices implanted in saphenous vein. Relation between the reservoir site and comfort/discomfort of the patient. Ann Vasc Surg 2012;26(8):1127.e9-1127.e13. 3- Chen SY, Lin CH, Chang HM, Hsu HM, Yu JC. A safe and effective method to implant a totally implantable access port in patients with synchronous bilateral mastectomies: modified femoral vein approach. J Surg Oncol 2008;98(3):197-199

Avaliação por tomografia computadorizada da aurícula esquerda e veias pulmonares — contexto anátomo-­‐clínico

RESUMO: A Aurícula Esquerda é uma câmara cardíaca com origem embriológica complexa que apresenta contributo prognóstico independente em diversas situações clínicas. É nela que tem origem a arritmia cardíaca crónica mais prevalente, a Fibrilhação Auricular, que afeta 2,5% dos portugueses com mais de 40 anos. A fibrilhação auricular apresenta relevante morbi-mortalidade per se e pela frequente associação a terapêutica anti-agregante ou anti-coagulante. A Ablação Percutânea da fibrilhação auricular é um tratamento com crescente aplicabilidade, seguro, com bons resultados globais, mas com taxas de recidiva a longo prazo relativamente altas. É habitualmente precedido da realização de exame de tomografia computorizada cardíaca para avaliação anatómica e, por vezes, com intuito de excluir trombo intra-cavitário. A informação contida no exame de TC quer anatómica quer funcional poderá ter relevância prognóstica e ajudar a uma escolha otimizada dos doentes que irão beneficiar mais do tratamento, potenciando o binómio custo-benefício. A TC cardíaca para avaliação coronária tem assistido a um enorme aumento de utilização apropriada, sendo considerada por algumas sociedades o exame de primeira linha para avaliação do doente com dor torácica estável de possível etiologia cardíaca. Estima-se que a aplicação destas guidelines condicione um crescimento de cerca de 600% no número destes exames. A evolução tecnológica que acompanhou o desenvolvimento destas técnicas de TC cardíaca permite, hoje, a avaliação das coronárias na grande maioria dos casos com informação obtida apenas em fase médio- -diastólica (cerca de 70% do intervalo entre onda R (RR)). A ausência de informação telesistólica e telediastólica não permite a avaliação funcional cardíaca. A avaliação 18 | AVALIAÇÃO POR TOMOGRAFIA COMPUTADORIZADA DA AURÍCULA ESQUERDA E VEIAS PULMONARES dimensional das câmaras cardíacas fica igualmente condicionada pela inexistência de normogramas para essa fase do ciclo cardíaco (70% do RR). Neste contexto, foi possível desenvolver um normograma do volume da aurícula esquerda em fase médio-diastólica. Confirmámos uma boa correlação entre os volumes obtidos a 70% do intervalo RR e os volumes máximos, e criámos uma regressão para obter o volume máximo da aurícula esquerda com base no diâmetro axial máximo e altura máxima em plano sagital avaliado a 70% do intervalo RR. Esta regressão permite, de forma eficiente e sem necessidade de software dedicado, fazer a avaliação quantitativa da aurícula esquerda na maioria dos exames de coronariografia por TC, inclusive naqueles que, por utilizarem tecnologia mais recente, adquirem informação apenas na fase medio-diastólica. A aplicabilidade deste normograma a doentes com FA foi testada, tendo permitido identificar todos os doentes com FA que tinham dilatação da AEsq. Descobrimos um marcador anatómico (o padrão de drenagem das veias pulmonares à direita) com relevância significativa e independente na taxa de recidiva após ablação percutânea da fibrilhação auricular. Identificámos fatores identificáveis na TC cardíaca, efetuada em contexto prévio à ablação de FA, que se correlacionam com o score de risco de eventos embólicos CHA2DS2VASc, lançando assim os fundamentos para um eventual score incluindo parâmetros clínicos e imagiológicos. Por fim, analisámos a otimização do protocolo e a qualidade de imagem dos exames de TC cardíaca realizados num contexto pré-ablação e foi possível descrever um protocolo, com doses de radiação submilisivert e sem condicionar a qualidade de imagem