In response to the augmented haemodynamic load placed upon the heart by intense and prolonged exercise, various forms of physiological remodelling are elicited. The resultant cardiac structural, functional and electrical adaptations are coined the athlete’s heart. Due to the nature of the remodelling, in some cases these adaptations may however overlap with the diagnostic criteria for varying pathological conditions, often related to sudden cardiac death. Several variables are associated with the athlete’s heart including age, sex, sport, body size, and ethnicity. Ethnicity is of particular importance as athletes of an African/Afro-Caribbean ethnicity demonstrate a greater prevalence of abnormal changes suggestive of pathology. There is however paucity in the literature of the athlete’s heart among other ethnicities. For this reason Study 1 investigated the impact of Arabic ethnicity upon the structure, function and electrophysiology of the heart in male athletes. Study 1 identified that while Arabic athletes had larger hearts than Arabic controls, they had significantly smaller hearts than their Black and Caucasian athletic counterparts. While Black athletes had a significantly greater prevalence of training unrelated/abnormal ECG findings, Arabic and Caucasian both had similar levels of training unrelated/abnormal findings, suggesting the European Society of Cardiology guidelines for ECG interpretation in athletes are applicable for the ethnicity. Study 2 investigated another important facet of the athlete’s heart, which is body size. Study 2 identified that while there was a progressive relationship between body size and cardiac dimensions, the previously identified upper limits of cardiac structural remodelling were applicable even among those with a body surface area (BSA) over 2.3m2. Among the cohort of athletes with a BSA >2.3m2, Black athletes demonstrated significantly greater wall thickness’ than Caucasian and Arabic athletes. The second aspect to the thesis highlighted how the findings of Study 1 and 2 impact upon pre-participation screening. While debate still exists around the most effective methodology to screen for pathological cardiac conditions, several organisations mandate the use of the echocardiography alongside the resting 12-Lead ECG. Study 3 established that should echocardiography be limited to use as a follow up investigation, significant cost benefits could be elicited (47% reduction). The premise of this significant cost reduction was that no pathological case was identified by echocardiography in isolation. While still found to be useful in confirming pathology, significantly, in our study the investigation failed to identify two cases of hypertrophic cardiomyopathy. Study 4 investigated the implications of adopting modified ECG interpretation guidelines in light of the criticism that ECG screening should be avoided due to a high false positive rate. Utilising an ethnically diverse cohort, Study 4 demonstrated that using the ‘Refined’ criteria reduced the false positive rate from 22% when using the 2010 ESC guidelines to 5%. Importantly both criteria achieved 100% sensitivity, highlighting the importance of the ECG in cardiovascular screening.

Made available in DSpace on 2014-06-11T19:23:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-12-07Bitstream added on 2014-06-13T20:29:49Z : No. of bitstreams: 1 braganholi_df_me_araiq_parcial.pdf: 104237 bytes, checksum: e3996c0a9549c5f5ea02263aa29adb8f (MD5) Bitstreams deleted on 2014-10-03T16:24:42Z: braganholi_df_me_araiq_parcial.pdf,Bitstream added on 2014-10-03T16:27:39Z : No. of bitstreams: 2 braganholi_df_me_araiq_parcial.pdf.txt: 24116 bytes, checksum: 4311db628427328ebb1b15b5edcab15d (MD5) 000694394.pdf: 608461 bytes, checksum: dceff09293ceb64124b8735297fa48e3 (MD5) Bitstreams deleted on 2014-10-03T16:33:16Z: 000694394.pdf,Bitstream added on 2014-10-03T16:43:30Z : No. of bitstreams: 2 braganholi_df_me_araiq_parcial.pdf.txt: 24116 bytes, checksum: 4311db628427328ebb1b15b5edcab15d (MD5) 000694394.pdf: 608461 bytes, checksum: dceff09293ceb64124b8735297fa48e3 (MD5) Bitstreams deleted on 2014-10-03T16:48:56Z: 000694394.pdf,Bitstream added on 2014-10-03T16:49:47Z : No. of bitstreams: 1 000694394.pdf: 608461 bytes, checksum: dceff09293ceb64124b8735297fa48e3 (MD5) Bitstreams deleted on 2014-10-27T11:47:10Z: 000694394.pdf,Bitstream added on 2014-10-27T11:48:05Z : No. of bitstreams: 1 000694394.pdf: 608461 bytes, checksum: dceff09293ceb64124b8735297fa48e3 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Morte súbita cardíaca (MSC) é um dos maiores problemas de saúde pública no mundo, afetando cerca de 335 mil pessoas por ano nos EUA e aproximadamente 712 pessoas por dia no Brasil, predominantemente na faixa etária mais produtiva. Principalmente em jovens, as causas são desordens cardíacas com anormalidades estruturais e arritmogênicas de origens genéticas; além disso, alguns medicamentos podem influenciar na susceptibilidade a MSC ou a doenças cardiovasculares. Como a morte pode ocorrer num período máximo de uma hora após o início dos sintomas e não ser decorrente de trauma ou violência, o diagnóstico da causa de morte pode ser dificultado. A análise genética nestes casos é muito útil para ajudar a identificá-la e informar aos parentes próximos sobre um possível fator genético de risco pré-existente. Este trabalho propôs padronizar as reações de PCR e SNaPshot em multiplex para analisar 11 SNPs (single nucleotide polymorphisms) relacionados à MSC (NEWTON-CHEH et al. 2009) em grupos de familiares brasileiros com histórico de insuficiência cardíaca para uma futura utilização na Genética Forense e Médica, entretanto, o multiplex contendo 8 SNPs mostrou ser mais eficiente . Para tanto, amostras foram coletadas de indivíduos com histórico familiar de: coronariopatia, cardiomiopatia hipertrófica ou familiar próximo que sofreu ataque cardíaco e, indivíduos sem este histórico utilizados como controles. As análises não apresentaram diferenças significativas entre o grupo de indivíduos com histórico e controle, mas, os dados são compatíveis com as freqüências conhecidas dos SNPs. Também identificou-se um provável fator hereditário para o SNP rs4725982 em uma das famílias / Sudden cardiac death (SCD) is a major public health problems worldwide, affeting about 335,000 people per year in the U.S. and approximately 712 people per day in Brazil, predominantly in the most productive age group. Especially in young people, the causes are structural abnormalities of cardiac disorders and genetic origins of arrhythmogenic, in addition, some medications may influence susceptibility to SCD or cardiovascular disease. As death can occur whitin a maximum of one hour after onset of symptoms and not be due to trauma or violence, the diagnosis of the cause of the death can be difficult. Genetic analysis in these cases is very useful to help identify them and inform close relatives about a possible genetic risk factor pre-existing. This work proposed to standardize the PCR and SNaPshot multiplex to analyze 11 SNPs (single nucleotide polymorphisms) related to the SCD (NEWTON-CHEH et al. 2009) in Brazilian familial groups with a history of heart failure for future use in Forensic Genetics and Medical. For this, samples were collected from individuals with a family history of heart disease, hypertrophic cardiomyophathy or close relative who suffered a heart attack, and individuals without this history used as controls. The analysis showed no siginificant differences between the group of the individuals with a history and control, but the data are compatible with the frequencies of known SNPs. It also identified a probable hereditary factor for the SNP rs4725982 in one of the studied families

Orientador: Regina Maria Barretto Cicarelli / Banca: Rogério Nogueira de Oliveira / Banca: Greiciane Gaburro Panetto / Resumo: Morte súbita cardíaca (MSC) é um dos maiores problemas de saúde pública no mundo, afetando cerca de 335 mil pessoas por ano nos EUA e aproximadamente 712 pessoas por dia no Brasil, predominantemente na faixa etária mais produtiva. Principalmente em jovens, as causas são desordens cardíacas com anormalidades estruturais e arritmogênicas de origens genéticas; além disso, alguns medicamentos podem influenciar na susceptibilidade a MSC ou a doenças cardiovasculares. Como a morte pode ocorrer num período máximo de uma hora após o início dos sintomas e não ser decorrente de trauma ou violência, o diagnóstico da causa de morte pode ser dificultado. A análise genética nestes casos é muito útil para ajudar a identificá-la e informar aos parentes próximos sobre um possível fator genético de risco pré-existente. Este trabalho propôs padronizar as reações de PCR e SNaPshot em multiplex para analisar 11 SNPs (single nucleotide polymorphisms) relacionados à MSC (NEWTON-CHEH et al. 2009) em grupos de familiares brasileiros com histórico de insuficiência cardíaca para uma futura utilização na Genética Forense e Médica, entretanto, o multiplex contendo 8 SNPs mostrou ser mais eficiente . Para tanto, amostras foram coletadas de indivíduos com histórico familiar de: coronariopatia, cardiomiopatia hipertrófica ou familiar próximo que sofreu ataque cardíaco e, indivíduos sem este histórico utilizados como controles. As análises não apresentaram diferenças significativas entre o grupo de indivíduos com histórico e controle, mas, os dados são compatíveis com as freqüências conhecidas dos SNPs. Também identificou-se um provável fator hereditário para o SNP rs4725982 em uma das famílias / Abstract: Sudden cardiac death (SCD) is a major public health problems worldwide, affeting about 335,000 people per year in the U.S. and approximately 712 people per day in Brazil, predominantly in the most productive age group. Especially in young people, the causes are structural abnormalities of cardiac disorders and genetic origins of arrhythmogenic, in addition, some medications may influence susceptibility to SCD or cardiovascular disease. As death can occur whitin a maximum of one hour after onset of symptoms and not be due to trauma or violence, the diagnosis of the cause of the death can be difficult. Genetic analysis in these cases is very useful to help identify them and inform close relatives about a possible genetic risk factor pre-existing. This work proposed to standardize the PCR and SNaPshot multiplex to analyze 11 SNPs (single nucleotide polymorphisms) related to the SCD (NEWTON-CHEH et al. 2009) in Brazilian familial groups with a history of heart failure for future use in Forensic Genetics and Medical. For this, samples were collected from individuals with a family history of heart disease, hypertrophic cardiomyophathy or close relative who suffered a heart attack, and individuals without this history used as controls. The analysis showed no siginificant differences between the group of the individuals with a history and control, but the data are compatible with the frequencies of known SNPs. It also identified a probable hereditary factor for the SNP rs4725982 in one of the studied families / Mestre

Abstract Short QT syndrome is an inherited arrhythmia disorder characterized by a short QT interval, typical T-wave and ST-segment morphology and an increased risk of sudden cardiac death. The purpose of this thesis was to study the epidemiology and prognosis of the subjects with short QT intervals. Special attention was paid to the ECG changes that could illustrate the prognosis of subjects with short QT interval. The first study comprised a group of patients with short QT syndrome. We report clinical presentation, ECG morphology, the prevalence of genetic mutations and the results of therapies in this group of patients. The second study population consisted of 10 822 randomly selected middle-aged subjects followed up for 29 ± 10 years. QT intervals were measured using three correction methods for the heart rate in order to assess the prevalence and prognosis of those subjects with short QT intervals. The third population consisted of three patients with short QT syndrome and nine controls. Holter recordings were analyzed to compare transmural dispersion of repolarization between patients and controls and also to study their capability to change repolarization indexes from baseline to maximal values. In the fourth study ECGs from 10 patients with short QT syndrome were compared with ECGs of 12 asymptomatic subjects with short QT intervals. The aim was to find ECG abnormalities that would predict the outcome of the patients. We found 62% of patients to be symptomatic, 34% had cardiac arrest. Atrial fibrillation was common. Most of the patients received an ICD or were placed on hydroquinidine. The prevalence of QTc < 320ms was 0.10% and QTc < 340ms was 0.4%, respectively. Mortality or other serious symptoms did not differ between subjects and controls. We also found that the TPE/QT ratio as an index for abnormal transmural dispersion of repolarization was high compared to controls. Short QT syndrome patients had also lesser capacity to change the QT interval, indicating blunted autonomic response in SQTS. Ten SQTS patients had significantly shorter Jpoint–Tpeak interval and higher TPE/QT ratio compared to controls. In conclusion, shorter than normal QT interval might represent a novel short QT syndrome. However, in the general community short QT interval can reflect only the extreme end of the normal Gaussian distribution of QT intervals and these subjects carry a good prognosis. TPE/QT ratio and Jpoint–Tend intervals can be used as risk stratifiers in subjects with short QT intervals.

Marfan's syndrome is a common connective tissue disease with different musculoskeletal, ophthalmic and cardiac manifestations. Marfan's patients carry increased risk for cardiac arrhythmias. Only three cases of atrial flutter in Marfan's patients are described in the literature. We report a fourth case of a young Marfan's patient who presents with typical atrial flutter after motor vehicle accident. After electrical cardioversion, sinus rhythm was restored but he had recurrent atrial flutter on follow up. The patient then underwent electrophysiological study and successful radiofrequency catheter ablation of the flutter circuit. Since discharge, the patient has had no documented arrhythmias on follow up.

No description available.

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An accumulation of sudden unexpected cardiac deaths (SUCD) occurred in young Swedish orienteers, most of whom were elite athletes. From 1979 to 1992 the incidence in 18 to 34 year old male elite orienteers ranked on the national level the same year as death was calculated to 30 (per 100,000), which represents a 20 to 40 fold increase from the expected rate. From 1989 to 1992, the incidence was 50. There were, however, no indications on any similar clusters of SUCD in other sports. A special program to alter behaviour in orienteers was implemented in 1992-1993, after which there have been no more cases of SUCD in orienteers below 35 years of age. A histopathological re-evaluation of 16 cases of SUCD revealed myocarditis in 75% of these cases. In parallel, four of those cases also had changes mimicing arrhythmogenic right ventricular cardiomyopathy (ARVC). The combination of an increased incidence and myocarditis suggested that infection may be a pathogenetic factor. A broad search for different microorganisms in archival sera from five cases and tissues from the autopsies in two of those cases revealed the only common finding that all had antibodies to Chlamydia pneumoniae. DNA from C. pneumoniae was detected in the lung and heart in one of two cases. The intimate contact with nature of orienteers suggested possible zoonotic/vectorborne pathogens. Bartonella is such a pathogen and known to cross-react with C. pneumoniae. The use of PCR to test for DNA from the gltA gene of Bartonella in the two formerly mentioned cases of SUCD, and in three additional cases, gave positive bands from the hearts in four cases and the lung in a fifth case. The PCR products were sequenced and found to be identical to B. henselae in three cases and almost identical to B. quintana in the remaining two cases. Four of the five cases had antibodies to Bartonella when using micro immunofluorescence test with the antigens B. henselae, B. quintana, and B. elizabethae. The total prevalence of antibodies to Bartonella was 31% in 1,136 elite orienteers vs. 6.8% in 322 healthy blood donors (p<0.001), suggesting widespread exposure in the elite. It is hypothesized that subacute or reactivated Bartonella infection has a pathogenetic role in SUCD in orienteers, and may be involved in the development of ARVC-like disease.

Electrical restitution has been shown to inaccurately predict the occurrence of alternans of action potential duration. A new method using the spatial gradient of alternans (SGA) is proposed to predict alternans and cardiac electrical stability. A simulated 1-D strand of tissue was used to compare indexes computed from restitution methods and the SGA method to changes in the amplitude of alternans using different electro-physiological alterations. The SGA method correlated better with changes in the amplitude of alternans than restitution methods for a decrease in the transient outward current (Ito) and conduction velocity. Restitution methods correlated better with changes in the amplitude of alternans than the SGA method when the inward rectifier potassium current (Ik1) and the delayed rectifier potassium current (Ikr) were decreased. Restitution methods and the SGA method correlated well with changes in the amplitude of alternans when the L-type calcium channel current (ICaL) was altered and when Ikr, Ik1, and the sodium/calcium exchange current (INaCa) were increased. The SGA method includes the effect of conduction in tissue and reveals other features that provide advantages in predicting stability over currently used restitution methods.