Background: Hyperthyroidism has substantial effects on the circulatory system. The cardiac biomarkers NT-proBNP and troponin I (cTNI) have proven useful in identifying cats with myocardial disease but have not been as extensively investigated in hyperthyroidism. Hypothesis: Plasma NT-proBNP and cTNI concentrations are higher in cats with primary cardiac disease than in cats with hyperthyroidism and higher in cats with hyperthyroidism than in healthy control cats. Animals: Twenty-three hyperthyroid cats, 19 cats with HCM without congestive heart failure, and 19 euthyroid, normotensive healthy cats eight years of age or older. Fourteen of the hyperthyroid cats were re-evaluated three months after administration of 131I. Methods: A complete history, physical examination, complete blood count, serum biochemistries, urinalysis, blood pressure measurement, serum T4 concentration, plasma concentrations of NT-proBNP and cTNI, and echocardiogram was prospectively obtained from each cat. Results: Hyperthyroid and HCM cats had plasma NT-proBNP and cTNI concentrations that were significantly greater than healthy older cats, but there was no significant difference between hyperthyroid and HCM cats with respect to concentration of either biomarker. In hyperthyroid cats that were re-evaluated three months after 131I treatment, plasma NT-proBNP and cTNI concentrations as well as ventricular wall thickness decreased. Conclusions and Clinical Relevance: Although there may be a role for NT-proBNP in monitoring the cardiac response to treatment of hyperthyroidism, neither NT-proBNP nor cTNI can be used to distinguish hyperthyroid cats from cats with HCM. Therefore, the thyroid status of older cats should be ascertained prior to interpreting results of cardiac biomarker testing. / Master of Science

名古屋大学博士学位論文 学位の種類:博士(医療技術学) (課程) 学位授与年月日:平成20年3月25日

国立情報学研究所で電子化したコンテンツを使用している。

Com o objetivo de avaliar se o exercício físico prolongado causa alterações miocárdicas em eqüinos de enduro e se estas alterações cardíacas têm influência no desempenho dos animais durante as provas, avaliaram-se 30 cavalos, divididos em três grupos de dez animais cada, sendo G1 composto por animais que percorreram distâncias acima de 100 km, G2 por animais que percorreram distâncias menores de 100 km e G3 por animais desqualificados por alterações metabólicas. Os animais foram avaliados em três momentos distintos, T0 (pré-exercício, em repouso), T1 (entre 30 e 60 minutos após o exercício) e T2 (entre 90 e 120 minutos pós-exercício). Realizaram-se o exame físico e o exame ecocardiográfico, além de colheita de amostras de sangue para determinação de troponina I cardíaca sérica e outras provas bioquímicas. Não houve diferença nos valores de troponina I cardíaca entre os diversos grupos nem nos diferentes tempos. Observou-se diminuição dos valores do diâmetro interno do ventrículo esquerdo em diástole e aumento de espessura de septo interventricular pós-exercício. Não houve diferença nos índices funcionais cardíacos e houve manutenção do débito cardíaco por aumento da freqüência cardíaca. Estas alterações ecocardiográficas de pequena magnitude foram mais evidentes nos animais desqualificados por alterações metabólicas e não parecem estar relacionadas a injúria miocárdica e sim secundárias a outras condições orgânicas. Conclui-se que o exercício físico prolongado não leva a injúrias cardíacas severas em cavalos de enduro. / With the purpose of evaluating myocardial alterations caused by prolonged physical exercise and whether these alterations influence the endurance horses\' performance during the races, 30 horses were evaluated, divided into three groups of ten horses each, being G1 composed by animals that performed distances of more than 100 km, G2 by animals that performed distances of less than 100 km and G3 by animals disqualified by metabolic alterations. The horses were evaluated in three distinct moments, T0 (pre-exercise, at rest), T1 (between 30 and 60 minutes post-exercise) and T2 (between 90 and 120 minutes post-exercise). Physical and echocardiographic examinations and else blood sample collection for the determination of cardiac troponin I and other biochemical tests were done. There was no difference in cardiac troponin I values neither between the various groups, nor between the moments. There was a decrease in the post-exercise values of the diastolic left ventricle internal diameter and an increase in the post-exercise values of the interventricular septal thickness. There was no difference in the cardiac functional indexes and the cardiac output was maintainded by augmentation of the heart rate. These minor echocardiographic alterations were more evident in the animals that were disqualified by metabolic alterations, and they don\'t seem to be related to myocardial injury, but secondary to other organic conditions. Based on these results, prolonged physical exercise doesn\'t seem to cause severe cardiac injuries in endurance horses.

Com o objetivo de avaliar se o exercício físico prolongado causa alterações miocárdicas em eqüinos de enduro e se estas alterações cardíacas têm influência no desempenho dos animais durante as provas, avaliaram-se 30 cavalos, divididos em três grupos de dez animais cada, sendo G1 composto por animais que percorreram distâncias acima de 100 km, G2 por animais que percorreram distâncias menores de 100 km e G3 por animais desqualificados por alterações metabólicas. Os animais foram avaliados em três momentos distintos, T0 (pré-exercício, em repouso), T1 (entre 30 e 60 minutos após o exercício) e T2 (entre 90 e 120 minutos pós-exercício). Realizaram-se o exame físico e o exame ecocardiográfico, além de colheita de amostras de sangue para determinação de troponina I cardíaca sérica e outras provas bioquímicas. Não houve diferença nos valores de troponina I cardíaca entre os diversos grupos nem nos diferentes tempos. Observou-se diminuição dos valores do diâmetro interno do ventrículo esquerdo em diástole e aumento de espessura de septo interventricular pós-exercício. Não houve diferença nos índices funcionais cardíacos e houve manutenção do débito cardíaco por aumento da freqüência cardíaca. Estas alterações ecocardiográficas de pequena magnitude foram mais evidentes nos animais desqualificados por alterações metabólicas e não parecem estar relacionadas a injúria miocárdica e sim secundárias a outras condições orgânicas. Conclui-se que o exercício físico prolongado não leva a injúrias cardíacas severas em cavalos de enduro. / With the purpose of evaluating myocardial alterations caused by prolonged physical exercise and whether these alterations influence the endurance horses\' performance during the races, 30 horses were evaluated, divided into three groups of ten horses each, being G1 composed by animals that performed distances of more than 100 km, G2 by animals that performed distances of less than 100 km and G3 by animals disqualified by metabolic alterations. The horses were evaluated in three distinct moments, T0 (pre-exercise, at rest), T1 (between 30 and 60 minutes post-exercise) and T2 (between 90 and 120 minutes post-exercise). Physical and echocardiographic examinations and else blood sample collection for the determination of cardiac troponin I and other biochemical tests were done. There was no difference in cardiac troponin I values neither between the various groups, nor between the moments. There was a decrease in the post-exercise values of the diastolic left ventricle internal diameter and an increase in the post-exercise values of the interventricular septal thickness. There was no difference in the cardiac functional indexes and the cardiac output was maintainded by augmentation of the heart rate. These minor echocardiographic alterations were more evident in the animals that were disqualified by metabolic alterations, and they don\'t seem to be related to myocardial injury, but secondary to other organic conditions. Based on these results, prolonged physical exercise doesn\'t seem to cause severe cardiac injuries in endurance horses.

This dissertation focuses on the effect of breeding on the myocardium of stallions using cardiac troponin I (cTnI) as the preferred blood biomarker for detection of myocardial cell injury. Haematological, echocardiographic and heart rate (HR) parameters are also reported. Fourteen clinically healthy phantom-trained stallions were assessed. Cardiac troponin I concentration was determined pre-semen collection and at 4, 6, 12 and 24 hours following semen collection. Predictors that were measured included mean HR during each stage of semen collection, maximum HR, area under the curve for HR and fractional shortening (FS). Pre-semen collection cTnI concentrations were within reported reference ranges for all stallions. Following semen collection, cTnI concentration was significantly increased at 4 and 6 hours post-semen collection. Results also suggest that the HR of stallions peak during mounting of the phantom. Five stallions failed to show an expected increase in FS immediately post-semen collection. No association was identified between the measured predictors and increased cTnI concentration. This study concluded that cTnI concentration may increase in stallions following semen collection although the clinical significance of this observed increase in healthy stallions is unclear without histopathological evaluation of the myocardium. No conclusion regarding FS immediately post-semen collection could be drawn from results in this study. The research reported in this dissertation can serve as a reference for future studies investigating cTnI concentrations in stallions. / Dissertation (MSc)--University of Pretoria, 2010. / Companion Animal Clinical Studies / unrestricted

No description available.

A degeneração valvar crônica mitral (DVCM) é uma cardiopatia de alta prevalência na clínica médica de pequenos animais e acomete principalmente cães idosos de raças de pequeno porte. A fim de se acompanhar a evolução da insuficiência cardíaca (IC), a galectina-3 (Gal-3) vem sendo utilizada como um biomarcador na identificação de doenças cardíacas pré-clínicas, progressão e descompensação em pacientes humanos. O objetivo deste estudo clínico foi estabelecer intervalos de referência da Gal-3 na população canina estudada e determinar a utilidade desse novo biomarcador sérico, isoladamente ou em associação com o pró-peptídeo natriurético tipo B (NT-proBNP) e a troponina cardíaca I (cTnI), para estimativa de prognóstico em curto prazo em cães com IC decorrente de DVCM. O delineamento fundamentou-se em um estudo clínico observacional transversal prospectivo com braço longitudinal. A amostra foi composta por 139 cães distribuídos em cinco grupos criteriosamente selecionados de acordo com o estadiamento da DVCM (Grupo controle: estágio A- composto por 60 cães hígidos de raças de pequeno porte com predisposição à DVCM, 28 cães em estágio B1, 20 cães em B2, 20 cães em estágio C e 11 cães em estágio D), advindos da rotina do Serviço de Cardiologia do VCM, Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo. Os grupos B1, B2, C e D foram avaliados em um segundo momento, aos 60 dias. Foram dosados Gal-3 humana e canina, NTproBNP e cTnI. Os valores de referência mensurados no grupo A para Gal-3 humana foram de 7,548 ng/mL (P25%-75%=8,933-10,960). A recuperação da concentração de Gal-3 em cães clinicamente saudáveis, obtida com kit canino, foi significativamente mais baixa, com baixa repetibilidade e reprodutibilidade, em comparação com o kit humano, sugerindo assim menor sensibilidade do kit canino utilizado. Ainda, a magnitude e a variação nas concentrações de Gal-3 humana e canina não permitiram a detecção de diferenças entre os estágios da DVCM e também não foram capazes de identificar pacientes em IC. Conclui-se, portanto, que diferentemente dos demais marcadores avaliados, NT-proBNP e cTnI, já consagrados na IC para a espécie canina, a Gal-3 não se constitui em um biomarcador adequado para avaliar a IC secundária à DVCM em cães / Chronic mitral valve degeneration (CMVD) is a highly prevalent heart disease in small animal internal medicine seen mainly in older small breed dogs. In order to follow the progression of heart failure (HF), galectin-3 (Gal-3) has been applied as a biomarker to identify pre-clinical cardiac diseases, progression and decompensation in human patients. This study aimed to establish reference intervals for Gal-3 in a canine population, and to determine the utility of this new biomarker, isolated or in association with Type B natriuretic pro-peptide (NT-proBNP) and cardiac troponin I to estimate short term prognosis in dogs with HF caused by CMVD. It was designed as an observational prospective cross-sectional clinical study with a longitudinal arm. One hundred thirty nine dogs were distributed among five groups with rigorous selection criteria, according to ACVIM CMVD staging (Control group: stage A- 60 healthy small breed dogs, predisposed to CMVD; 28 dogs in stage B1, 20 dogs in stage B2, 20 dogs in stage C and 11 dogs in stage D), recruited from the Cardiology Service from the Veterinary Teaching Hospital, School of Veterinary Medicine, University of São Paulo. Groups B1, B2, C and D had a second blood sampling at day 60. Measurements were obtained for human and canine Gal-3, NT-proBNP and cTnI. Reference values obtained for group A for human Gal-3 were 7.548 ng/mL (P25%-75%=8.933-10.960). Gal-3 concentration recovery for healthy dogs obtained with canine kit was significantly lower, with low repeatability and reproducibility, compared to the human kit, suggesting lower sensitivity of the canine Gal-3 kit used. We concluded that the magnitude and variation observed in human and canine Gal-3 did not allow for detection of differences between stages of CMVD nor were capable of identifying patients in HF, compared to the other measured biomarkers, NT-proBNP and cTnI, already established for canine HF evaluation

Myocardial infarction is a leading cause of morbidity and mortality worldwide. The purpose of this thesis was to develop strategies for the assessment of patients with suspected myocardial infarction using a high-sensitivity cardiac troponin I assay, and to evaluate the relationship between the aetiology of myocardial infarction and long term clinical outcomes to identify opportunities to modify outcomes. In the United Kingdom, approximately 1 million patients present to hospital with chest pain each year and are assessed for suspected myocardial infarction, yet fewer than 20% of patients receive this diagnosis. Prior clinical standards mandated the admission of patients for serial cardiac troponin testing to identify myocardial necrosis and determine if myocardial infarction had occurred. However, new high-sensitivity assays offer a magnitude improvement in diagnostic precision, and as such provide a novel approach to diagnose or exclude myocardial infarction at an earlier stage. In our first study, I evaluate the performance of a high-sensitivity cardiac troponin I assay as a risk stratification tool in patients with suspected acute coronary syndrome. A systematic review and individual patient-level data meta-analysis was performed, including prospective studies measuring high-sensitivity cardiac troponin I in patients with suspected acute coronary syndrome, where the diagnosis was adjudicated according to the universal definition of myocardial infarction. The primary outcome was myocardial infarction or cardiac death during the index hospitalization or at 30 days. Meta-estimates for primary and secondary outcomes were derived using a binomial-normal random effects model. Performance was evaluated in subgroups and across a range of troponin concentrations (2-16 ng/L) using individual patient data. A total of 22,457 patients were included in the meta-analysis (age 62 [15.5] years; n=9,329 (41.5%) women), of whom 2,786 (12.4%) experienced myocardial infarction or cardiac death at 30 days. Cardiac troponin I concentrations were < 5 ng/L at presentation in 11,012 (49%) patients, with a negative predictive value of 99.5% (95% confidence interval [CI] 99.3-99.6) for myocardial infarction or cardiac death at 30 days. Lower thresholds did not improve safety, but did significantly reduce the proportion identified as low risk. This threshold of 5 ng/L formed the basis for the development of a diagnostic pathway for patients with suspected acute coronary syndrome. In a cohort study of 1,218 patients with suspected acute coronary syndrome who underwent high-sensitivity cardiac troponin I measurement at presentation, 3 and 6 or 12 hours, I derived and validated a novel pathway (rule out myocardial infarction if < 5 ng/L at presentation, or change < 3 ng/L and < 99th centile at 3 hours), and compared this with the established European Society of Cardiology 3-hour pathway (rule out myocardial infarction if < 99th centile at presentation, or at 3 hours if symptoms < 6 hours). The primary outcome was a comparison of the negative predictive value (NPV) of both pathways for myocardial infarction or cardiac death at 30 days. The primary outcome was evaluated in pre-specified subgroups stratified by age, gender, time of symptom onset and known ischaemic heart disease. In those < 99th centile at presentation, the ESC pathway ruled out myocardial infarction in 28.1% (342/1,218) and 78.9% (961/1,218) at presentation and 3 hours respectively, missing 18 index and two 30-day events (NPV 97.9%, 95% confidence intervals [CI] 96.9-98.7%). The novel pathway ruled out 40.7% (496/1,218) and 74.2% (904/1,218) at presentation and 3 hours, missing two index and two 30-day events (NPV 99.5%, 95% CI 99.0-99.9%; P < 0.001 for comparison). The NPV of the novel pathway was greater than the ESC pathway overall (P < 0.001), and in all subgroups including those presenting early or known to have ischaemic heart disease. There are a number of additional approaches for the rule out of myocardial infarction. Clinical risk scores apply conventional risk factors to estimate the probability of myocardial infarction. The most widely implemented scores, HEART, EDACS, GRACE and TIMI, have been extensively validated when used alongside contemporary troponin assays, however, their impact on pathways applying high-sensitivity cardiac troponin testing is less clear. In 1,935 patients with suspected acute coronary syndrome, I evaluated the safety and efficacy of our novel pathway or the European Society of Cardiology 3-hour pathway alone, or in conjunction with low-risk TIMI (0 or 1), GRACE (≤108), EDACS (< 16) or HEART (≤3) scores. Myocardial infarction or cardiac death at 30-days occurred in 14.3% (276/1,935). The ESC pathway ruled out 70% with 27 missed events giving a negative predictive value (NPV) of 97.9% (95% confidence interval [CI], 97.1 to 98.6%). Addition of a HEART score ≤3 reduced the proportion ruled out by the ESC pathway to 25%, but improved the NPV to 99.7% (95%CI 99.0 to 100%, P < 0.001). The novel pathway ruled out 65% with three missed events for a NPV of 99.7% (95%CI 99.4 to 99.9%). No risk score improved the NPV, but all reduced the proportion ruled out (24-47%, P < 0.001 for all). Whilst myocardial infarction due to atherosclerotic plaque rupture and thrombosis (type 1) is well described, the natural disease course of myocardial infarction due to oxygen supply-demand imbalance without atherothrombosis (type 2) is poorly understood. I aimed to define long-term outcomes and explore risk stratification in patients with type 2 myocardial infarction and myocardial injury. Consecutive patients (n=2,122) with elevated cardiac troponin I concentrations (≥0.05 μg/L) were identified at a tertiary cardiac centre. All diagnoses were adjudicated as per the Universal Definition of Myocardial Infarction. The primary outcome was all-cause death. Secondary outcomes included major adverse cardiovascular events (MACE; non-fatal myocardial infarction or cardiovascular death) and non-cardiovascular death. To explore competing risks, cause-specific hazard ratios were obtained using Cox regression models. The adjudicated index diagnosis was type 1 or type 2 myocardial infarction or myocardial injury in 1,171 (55.2%), 429 (20.2%) and 522 (24.6%) patients, respectively. At five years, all-cause death rates were higher in those with type 2 myocardial infarction (62.5%) or myocardial injury (72.4%) compared with type 1 myocardial infarction (36.7%). The majority of excess deaths in those with type 2 myocardial infarction or myocardial injury were due to non-cardiovascular causes (HR 2.32, 95%CI 1.92-2.81, versus type 1 myocardial infarction). Despite this, the observed crude MACE rates were similar between groups (30.6% versus 32.6%), with differences apparent after adjustment for co-variates (HR 0.82, 95%CI 0.69-0.96). Coronary heart disease was an independent predictor of MACE in those with type 2 myocardial infarction or myocardial injury (HR 1.71, 95%CI 1.31-2.24). Patients with type 2 myocardial infarction were less likely to receive secondary prevention therapy, suggesting a treatment gap may exist and there may be potential to modify clinical outcomes. A risk stratification threshold has been defined using high-sensitivity cardiac troponin I which identifies patients at very low risk of myocardial infarction or cardiac death. A diagnostic pathway incorporating this risk stratification threshold appears safer than established guidelines which apply the 99th centile alone. The use of clinical risk scores does not appear to improve the safety of this approach, however, does significantly reduce efficacy. Overall, these findings demonstrate the potential of high-sensitivity cardiac troponin testing to improve the efficiency of the assessment of patients with suspected acute coronary syndrome without compromising patient safety. The observations in those with myocardial injury and infarction have identified a phenotype of patients with type 2 myocardial infarction and coronary artery disease who are at increased cardiovascular risk, and who may benefit from targeted secondary prevention. The studies presented will inform the design of future clinical trials, and may inform international guidelines for the assessment of patients with suspected acute coronary syndrome.

Yes / The development of androgenetic alopecia is associated with a risk of developing cardiovascular diseases, but the association of alopecia areata with cardiovascular diseases in humans is largely unexplored. We measured the plasma level of two common cardiovascular disease markers, cardiac troponin I and Creactive protein, in alopecia areata and androgenetic alopecia-affected subjects. Also, we investigated the possible presence of pro-apoptotic factors in the plasma of hair loss subjects. The mean plasma cardiac troponin I level was highest in alopecia areata subjects, moderately higher in androgenetic alopecia subjects, and lowest in subjects without hair loss (p < 0.05). Alopecia areata subjects not receiving treatments had highest levels of cardiac troponin I (p < 0.05). Alopecia areata plasma samples with high cardiac troponin I levels also induced significantly higher rates of cardiomyocyte apoptosis in cell culture assays. The results suggest the potential for increased heart remodelling. Close monitoring of cardiovascular health in alopecia areata subjects, as well as subsets of androgenetic alopecia patients, may be appropriate. / Canadian Institutes of Health Research (CIHR; MOP-82927). EW is the recipient of a Banting Postdoctoral Fellowship (SAC-92845).