nÃo hà / Sistemas automÃticos de auxÃlio ao diagnÃstico visam à extraÃÃo de mÃtricas especÃficas, podendo ser por algoritmos computacionais, de forma a subsidiar a anÃlise por parte do especialista de condiÃÃes orgÃnicas e fisiolÃgicas do paciente. No contexto da cardiologia, referidos sistemas sÃo particularmente importantes quando aplicados no processamento de sinais de longa duraÃÃo, como o eletrocardiograma (ECG) de 24 horas. As tÃcnicas para segmentaÃÃo e extraÃÃo automÃtica de parÃmetros do sinal ECG propostas nesta tese abrangem diversos campos de pesquisa. Inicialmente, o sistema realiza a detecÃÃo e a segmentaÃÃo do complexo QRS, relacionado à despolarizaÃÃo ventricular. Como metodologia, utiliza-se a combinaÃÃo das tÃcnicas do limiar adaptativo, das transformadas de Hilbert e Wavelet e do filtro derivativo com uma nova abordagem de reduÃÃo de prÃ-processamento e de seleÃÃo do fator de escala da Wavelet. Ao final desta etapa, obtÃm-se a sÃrie de intervalos RR, a sÃrie de duraÃÃes de cada complexo QRS e de suas amplitudes. No segundo momento, tem-se a detecÃÃo e a segmentaÃÃo da onda T, relacionada à repolarizaÃÃo ventricular. PropÃe-se um novo modelo matemÃtico do comportamento morfolÃgico da onda T baseado na funÃÃo Gaussiana, modificada por um procedimento matemÃtico de inserÃÃo de assimetria. Uma vez obtidos os parÃmetros de modelagem para uma dada morfologia predominante de onda T, a funÃÃo de correlaÃÃo cruzada à utilizada para a detecÃÃo do pico e uma tÃcnica baseada no cÃlculo da Ãrea de trapÃzios à utilizada para a localizaÃÃo do final da forma de onda. Dentre as mÃtricas derivadas das informaÃÃes extraÃdas, destaca-se a sÃrie de intervalos QT, segmento que vai do inÃcio de cada complexo QRS ao final de cada onda T. Finalizado o processo de segmentaÃÃo, dois estudos de caso sÃo realizados: subtraÃÃo da atividade ventricular em sinais eletrogramas atriais de pacientes com fibrilaÃÃo atrial (FA) e anÃlise de sÃries de variabilidade da frequÃncia cardÃaca (VFC) de um conjunto de pacientes idosos selecionados pelo AmbulatÃrio de Geriatria do Hospital UniversitÃrio WÃlter CantÃdio. A partir de experimentos de validaÃÃo em bases de dados diversas com anotaÃÃes manuais dos batimentos, obtÃm-se as seguintes taxas de detecÃÃo e erros de delineamento para o complexo QRS: sensibilidade de 99,51%, preditividade positiva de 99,44%, erro mÃdio de inÃcio (QRS onset) de 2,85  9,90 ms e erro mÃdio de final (QRS offset) de 2,83  12,26 ms. Com relaÃÃo à detecÃÃo e segmentaÃÃo da onda T, obtÃm-se os seguintes resultados: sensibilidade de 99,48%, preditividade positiva de 99,53%, erro mÃdio de localizaÃÃo de pico de 0,51  8,06 ms e erro mÃdio de localizaÃÃo de final da forma de onda de 0,11  11,73 ms. Quanto ao primeiro estudo de caso de uso dos pontos fiduciais detectados, a potÃncia mÃdia dos sinais eletrogramas atriais, apÃs a subtraÃÃo da atividade ventricular, à significativamente reduzida para frequÃncias acima de 10 Hz, predominantemente associadas ao complexo QRS, bem como para frequÃncias na faixa de 3 a 5 Hz, relacionadas à atividade elÃtrica de repolarizaÃÃo ventricular. Para o segundo estudo, a anÃlise do comportamento de mÃtricas no domÃnio da frequÃncia associadas à atividade do sistema nervoso simpÃtico permite o reconhecimento de tendÃncias prÃprias e caracterÃsticas, no que tange a aspectos de funcionamento/disautonomia do sistema nervoso autonÃmico, de cada classe prÃ-determinada de idosos segundo os conceitos de fenÃtipo de fragilidade: idosos frÃgeis, prÃ-frÃgeis e robustos. Os resultados obtidos sugerem que o conjunto de metodologias desenvolvidas para a segmentaÃÃo do sinal ECG apresenta altas taxas de precisÃo, repetibilidade e robustez a uma ampla gama de morfologias, podendo ser aplicado em diversos contextos de auxÃlio ao diagnÃstico. Dadas as mÃtricas e sÃries temporais que podem ser extraÃdas, os referidos mÃtodos tambÃm podem dar suporte a processos de investigaÃÃo clÃnica e desenvolvimento de marcadores/indicadores de eventos cardiovasculares adversos.

No description available.

Proteomic studies aim to identify, quantify and characterise the full complement of proteins in a cell or organism under a defined set of conditions, and are important to our understanding of cellular mechanisms. However, such studies represent a major analytical challenge. A typical proteome analysis involves enzyme-mediated digestion of complex protein mixtures to yield an even more complex mixture of peptides. Combined reverse-phase liquid chromatography and tandem mass spectrometry is then traditionally utilised to ascertain sequence information from the characteristic peptide sequences. Analytical data derived for the peptides are employed as search terms in database searching of protein sequences derived from gene sequences. The extreme complexity of the peptide mixtures analysed means that additional novel approaches are required to fully interrogate the vast number of tandem mass spectra generated, assigning peptide identity and thereby helping to address demanding biological questions. The research reported here aims to further our understanding of both gas phase peptide/peptide fragment ion structure and peptide fragmentation behaviour using a combination of tandem mass spectrometry and ion mobility measurement.To facilitate the determination of peptide ion collision cross section, a novel standard, QCAL-IM, produced using the QconCAT strategy, has been developed to enable calibration of drift time in Travelling Wave Ion Mobility instruments. The standard facilitates empirical determination of the rotationally averaged collision cross section of any peptide/peptide fragment ion that lies within the calibration range encompassed. QCAL-IM was subsequently utilised to determine the collision cross section of a range of peptide ions produced by Lys-C and Lys-N proteolysis of ‘standard’ proteins. Data produced allowed the effect upon gas phase ion conformation through changing the location of the basic residue lysine within a peptide sequence to be assessed.The fragmentation behaviour of peptide ions produced by a variety of digestion regimes during both collision-induced dissociation (CID) and electron transfer dissociation (ETD) has also been extensively studied. The proteases trypsin and Lys-C are those typically utilised during proteomic studies and peptides produced by each have either the basic residues arginine or lysine at their carboxy-terminus. Secondary enzymatic treatment with the exoprotease carboxypeptidase B cleaves these basic residues from the C-terminus. Tandem mass spectrometric analysis of both tryptic/Lys-C peptides and their CBPB truncated analogue highlights that the dominant fragment ion series observed during both CID and ETD is determined, at least in part, by the location of such basic residues.Finally, studies were undertaken to investigate the factors which may promote/inhibit scrambling of peptide fragment ion sequence, which has recently been shown to take place during CID. The effect of modifying the gas phase basicity of the N-terminal amino acid residue is studied through a combination of derivatisation and synthesis of alternative peptide sequences. Increasing the gas phase basicity is shown to inhibit the observed sequence scrambling while promoting concomitant rearrangement/retention of a carboxyl oxygen at the C-terminus to give enhanced formation of bn+H2O product ion species.

Objectives: The inverse relationship between QT interval variability (QTV) and T wave amplitude potentially confounds QT variability assessment. We quantified the influence of the T wave amplitude on QTV in a comprehensive dataset and devised a correction formula. Methods: Three ECG datasets of healthy subjects were analyzed to model the relationship between T wave amplitude and QTV. To derive a generally valid correction formula, linear regression analysis was used. The proposed correction formula was applied to patients enrolled in the Evaluation of Defibrillator in Non-Ischemic Cardiomyopathy Treatment Evaluation trial (DEFINITE) to assess the prognostic significance of QTV for all-cause mortality in patients with non-ischemic dilated cardiomyopathy. Results: A strong inverse relationship between T wave amplitude and QTV was demonstrated, both in healthy subjects (R2 = 0.68, p < 0.001) and DEFINITE patients (R2 = 0.20, p < 0.001). Applying the T wave amplitude correction to QTV achieved 2.5-times better group discrimination between patients enrolled in the DEFINITE study and healthy subjects. Kaplan-Meier estimator analysis showed that T wave amplitude corrected QTVi is inversely related to survival (p < 0.01) and a significant predictor of all-cause mortality. Conclusion: We have proposed a simple correction formula for improved QTV assessment. Using this correction, predictive value of QTV for all-cause mortality in patients with non-ischemic cardiomyopathy has been demonstrated.

Automatic detection and delineation of ECG characteristic points is a basic procedure of any analyze of ECG using computer. This detection is a necessary step to simplify the work of cardiologists to evaluate long ECG records. In this thesis is proposed and evaluate a method of detection and delineation in a single-lead ECG using dyadic wavelet transform followed by correction in pseudo-orthogonal lead system taken from standard 12-lead system. The method uses information about position of positive maximum – negative minimum pair to detect ECG characteristic waves. At first the QRS complex is detected and than its morphology (waves Q and S) and the onset and end of the complex. After that the T-wave is detected and delineated within a searching window dependent on QRS position. And last the P-wave is detected and delineated. There are used two types of wavelets in developed method, “haar” and “quadratic spline”. The developed method was evaluated on CSE database. When haar wavelet was used the QRS detector sensitivity was 99.14%. In the work is also evaluated the accuracy of delineation characteristic points. As the P-wave and QRS complex delineation produced quite good results the T-wave end delineator produced relatively big deviations. All deviations are presented in histograms.

The thesis deals with possibilities of using wavelet transform in the field of surface electrocardiogram (ECG) signals denoising and ECG signals measuring. Several algorithms have been used to detect and estimate T-wave alternans (TWA), such as spectral method (SM), Poincaré Mapping (PM) or correlation method (CM). T-wave alternans, also called repolarization alternans, is a phenomenon appearing in the electrocardiogram as a consistent fluctuation in the repolarization morphology on every-other-beat basis. Electrical TWA has been recognized as a marker of electrical instability, and has been shown to be related with patients at increased risk for ventricular arrhytmias. Presence of TWA has been reported in a wide range of clinical and experimental situations including long QT syndrome, myocardial infarction, angina pectoris, acute ischemia, etc. Projected methods of detection TWA are realized in Matlab software, and they are experimentally verified on real ECG signals from the European ST-T Database.

The thesis completes the current programming equipment for experimental measurement of isolated animal heart signals. It adds a block providing the pre-processing of the signals. The signals measured are the elektrogram (EG) and the action potential (AP). The origin of individual signals, the measuring method and the possibilities of noise elimination are dealt with in the theoretical part of the thesis. The practical part describes the pre-processing block securing the noise elimination during the AP. It uses accumulative methods of averaging the corresponding time periods of the AP. Based on the results of measuring the signal to noise ratio, the thesis suggests the most appropriate accumulative methods and their variables. In order for the chosen accumulative methods to work well, it is important to divide the AP process into sectors of corresponding shape (repeats). The connection between the EG and AP processes is used to determine the beginning and end of the sectors. These points are identified by the detection of R and T wave peaks in the EG. To detect the R and T waves, the thesis uses methods based on wavelet transform. The efficiency and accuracy of detection methods is verified by test EG signals with hand-marked R and T wave peaks.

No description available.

Abstract Sudden cardiac death (SCD) is a major medical and public health concern responsible for 50% of cardiovascular deaths and as much as 15% to 20% of overall mortality. Coronary heart disease is the underlying cause of most of these deaths, and in 50% of such cases, SCD is the first manifestation of the disease. Researchers have investigated numerous noninvasive methods to more accurately identify individuals at high risk of SCD, but most such studies have focused on patients with specific heart disease. The standard 12-lead electrocardiogram (ECG) is a widely available tool to analyze the electrical activity of the heart, but few epidemiological studies have successfully identified specific electrocardiographic risk markers of SCD at the population level. This thesis aims to clarify the prognostic implications of several ECG patterns in the general population. We evaluated the 12-lead ECGs of 10899 middle-aged Finnish subjects (52% male) recorded between 1966 and 1972, and followed the subjects for 30&#160;± &#160;11 years. The prevalence of a prolonged QRS duration ≥ 110 ms and nonspecific intraventricular conduction delay (IVCD; defined as QRS ≥ 110 ms with no partial or complete bundle branch block) in the population was 1.3% and 0.6%, respectively. Both were significantly associated with an elevated risk of all-cause mortality and cardiovascular mortality. QRS duration ≥ 110&#160;ms doubled the risk of SCD, and IVCD was associated with a three-fold higher risk of SCD. Two percent of the subjects presented with wide frontal QRS-T angle ≥ 100° (the angle between the QRS axis and the T-wave axis in the frontal plane). A wide QRS-T angle was associated with higher overall mortality and more than doubled the risk of SCD, which was mainly due to an abnormal T-wave axis. Inverted T-waves in the right precordial leads (V1–V3) or beyond were present in 0.5% of the population. No increase in mortality or SCD was associated with right precordial T-wave inversions. In contrast, inverted T-waves in other leads than V1–V3 were associated with higher risk of cardiovascular mortality and SCD. Altogether 2.1% of the study participants presented with a prolonged PR interval > 200 ms. No rise in overall mortality, SCD, or hospitalizations due to heart failure, atrial fibrillation, or stroke was observed among these subjects during the follow-up period. In conclusion, of the electrocardiographic parameters studied, prolonged QRS duration, IVCD, and wide QRS-T angle are associated with SCD in the general population, and such changes in an ECG should therefore alert the physician to more closely evaluate and follow the patient. On the other hand, a prolonged PR interval and right precordial T-wave inversions seem to have no prognostic implications in the absence of other features suggestive of underlying heart disease. / Tiivistelmä Sydänperäinen äkkikuolema on yleisin kuolinsyy länsimaissa, missä puolet sydänkuolemista ja 15–20&#160;% kokonaiskuolleisuudesta johtuu äkillisestä sydänpysähdyksestä. Sepelvaltimotauti on yleisin taustalla oleva syy, ja jopa puolessa sepelvaltimotautikuolemista äkkikuolema on taudin ensimmäinen oire. Jo pitkään on yritetty kehittää menetelmiä, joilla voitaisiin tunnistaa suurimmassa äkkikuoleman vaarassa olevat. 12-kanavainen EKG on laajalti käytössä oleva tutkimus, jolla tutkitaan sydämen sähköistä toimintaa, mutta sydänperäistä äkkikuolemaa spesifisti väestössä ennustavia EKG-poikkeavuuksia ei ole juuri pystytty osoittamaan. Tämän väitöskirjatyön tarkoituksena oli tutkia, miten EKG:ssä nähtävät ilmiöt kuten QRS kompleksin kesto, QRS-kompleksin ja T-aallon välinen kulma, kääntyneet T-aallot sekä PR-aika korreloivat ennusteeseen väestötasolla. Tutkimme 10899 suomalaisen keski-ikäisen henkilön (52&#160;% miehiä) EKG:t, jotka oli rekisteröity 1966–1972, ja seurasimme tutkittavia keskimäärin 30 (± 11) vuotta. Leventynyt QRS kompleksi ≥ 110 ms löytyi 1.3&#160;%:lta ja epäspesifi kammionsisäinen johtumishäiriö eli IVCD (QRS&#160;≥&#160;110&#160;ms ilman osittaista tai täydellistä haarakatkosta) 0.6&#160;%:lta tutkituista. Molemmat muutokset liittyivät lisääntyneeseen kokonaiskuolleisuuteen sekä sydänkuoleman riskiin. QRS kompleksin kesto ≥ 110 ms assosioitui lisäksi kaksinkertaiseen ja IVCD kolminkertaiseen äkkikuolemariskiin. 2&#160;%:lla tutkituista sydänlihaksen depolarisaation suuntaa kuvaavan QRS-kompleksin akselin ja repolarisaatiota kuvaavan T-aallon akselin välinen frontaalitason QRS-T kulma oli leveä&#160;≥&#160;100°. Näillä henkilöillä kokonaiskuolleisuus oli lisääntynyt, ja sydänperäisen äkkikuoleman riski oli yli kaksinkertainen verrattuna henkilöihin jolla QRS-T kulma oli&#160; &#60;&#160;100°. Oikeanpuoleisissa rintakytkennöissä V1–V3 todettiin negatiiviset T-aallot 0.5&#160;%:lla tutkituista, mutta näillä ei ollut vaikutusta kuolleisuuteen. Sen sijaan henkilöillä, joilla todettiin negatiiviset T-aallot muissa kytkennöissä, oli yli kaksinkertainen sydänkuoleman ja äkillisen sydänpysähdyksen vaara muihin tutkittuihin verrattuna. Osallistujista 2.1&#160;%:lla todettiin pidentynyt PR-aika &#62; 200 ms. Tämä ei kuitenkaan vaikuttanut henkilöiden kuolleisuuteen eikä sydämen vajaatoiminnasta, eteisvärinästä tai aivoverenkiertohäiriöistä johtuvien sairaalahoitojen määrään. Tutkituista EKG:n poikkeavuuksista siis pidentynyt QRS-kompleksin kesto, IVCD ja leveä QRS-T kulma liittyvät selvästi lisääntyneeseen äkillisen sydänpysähdyksen riskiin. Sen sijaan pidentynyt PR-aika tai T-inversiot oikeanpuoleisissa rintakytkennöissä ilman muuta viitettä sydänsairaudesta eivät vaikuta ennusteeseen keski-ikäisessä väestössä.

No description available.