Combined cardiac and lung volume reduction surgery

Coronary artery disease is prevalent in patients who have severe emphysema and who are being considered for lung volume reduction surgery (LVRS). Significant valvular heart diseases may also coexist in these patients. Few thoracic surgeons have performed LVRS in patients who have severe cardiac diseases. Conversely, few cardiac surgeons have been willing to undertake major cardiac surgery in patients who have severe emphysema. This report reviews the evidence regarding combined cardiac surgery and LVRS to determine the optimal management strategy for patients who have severe emphysema and who are suitable for LVRS, but who also have coexisting significant cardiac diseases that are operable.

NO-dependent CaMKII activation during -adrenergic stimulation of cardiac muscle

AIMS:During β-adrenergic receptor (β-AR) stimulation, phosphorylation of cardiomyocyte ryanodine receptors by protein kinases may contribute to an increased diastolic Ca(2+) spark frequency. Regardless of prompt activation of protein kinase A during β-AR stimulation, this appears to rely more on activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), by a not yet identified signalling pathway. The goal of the present study was to identify and characterize the mechanisms which lead to CaMKII activation and elevated Ca(2+) spark frequencies during β-AR stimulation in single cardiomyocytes in diastolic conditions. METHODS AND RESULTS:Confocal imaging revealed that β-AR stimulation increases endogenous NO production in cardiomyocytes, resulting in NO-dependent activation of CaMKII and a subsequent increase in diastolic Ca(2+) spark frequency. These changes of spark frequency could be mimicked by exposure to the NO donor GSNO and were sensitive to the CaMKII inhibitors KN-93 and AIP. In vitro, CaMKII became nitrosated and its activity remained increased independent of Ca(2+) in the presence of GSNO, as assessed with biochemical assays. CONCLUSIONS:β-AR stimulation of cardiomyocytes may activate CaMKII by a novel direct pathway involving NO, without requiring Ca(2+) transients. This crosstalk between two established signalling pathways may contribute to arrhythmogenic diastolic Ca(2+) release and Ca(2+) waves during adrenergic stress, particularly in combination with cardiac diseases. In addition, NO-dependent activation of CaMKII is likely to have repercussions in many cellular signalling systems and cell types.

Sudden cardiac death in forensic medicine – Swiss recommendations for a multidisciplinary approach

Sudden cardiac death (SCD) is by definition unexpected and cardiac in nature. The investigation is almost invariably performed by a forensic pathologist. Under these circumstances the role of the forensic pathologist is twofold: (1.) to determine rapidly and efficiently the cause and manner of death and (2.) to initiate a multidisciplinary process in order to prevent further deaths in existing family members. If the death is determined to be due to "natural" causes the district attorney in charge often refuses further examinations. However, additional examinations, i.e. extensive histopathological investigations and/or molecular genetic analyses, are necessary in many cases to clarify the cause of death. The Swiss Society of Legal Medicine created a multidisciplinary working group together with clinical and molecular geneticists and cardiologists in the hope of harmonising the approach to investigate SCD. The aim of this paper is to close the gap between the Swiss recommendations for routine forensic post-mortem cardiac examination and clinical recommendations for genetic testing of inherited cardiac diseases; this is in order to optimise the diagnostic procedures and preventive measures for living family members. The key points of the recommendations are (1.) the forensic autopsy procedure for all SCD victims under 40 years of age, (2.) the collection and storage of adequate samples for genetic testing, (3.) communication with the families, and (4.) a multidisciplinary approach including cardiogenetic counselling.

Cardiac chymase: pathophysiological role and therapeutic potential of chymase inhibitors

On release from cardiac mast cells, alpha-chymase converts angiotensin I (Ang I) to Ang II. In addition to Ang II formation, alpha-chymase is capable of activating TGF-beta 1 and IL-1 beta, forming endothelins consisting of 31 amino acids, degrading endothelin-1, altering lipid metabolism, and degrading the extracellular matrix. Under physiological conditions the role of chymase in the mast cells of the heart is uncertain. In pathological situations, chymase may be secreted and have important effects on the heart. Thus, in animal models of cardiomyopathy, pressure overload, and myocardial infarction, there are increases in both chymase mRNA levels and chymase activity in the heart. In human diseased heart homogenates, alterations in chymase activity have also been reported. These findings have raised the possibility that inhibition of chymase may have a role in the therapy of cardiac disease. The selective chymase inhibitors developed to date include TY-51076, SUN-C8257, BCEAB, NK320, and TEI-E548. These have yet to be tested in humans, but promising results have been obtained in animal models of myocardial infarction, cardiomyopathy, and tachycardia-induced heart failure. It seems likely that orally active inhibitors of chymase could have a place in the treatment of cardiac diseases where injury-induced mast cell degranulation contributes to the pathology.

Epigenetic Therapy for the Treatment of Hypertension-Induced Cardiac Hypertrophy and Fibrosis

BACKGROUND: The development of heart failure is associated with changes in the size, shape, and structure of the heart that has a negative impact on cardiac function. These pathological changes involve excessive extracellular matrix deposition within the myocardial interstitium and myocyte hypertrophy. Alterations in fibroblast phenotype and myocyte activity are associated with reprogramming of gene transcriptional profiles that likely requires epigenetic alterations in chromatin structure. The aim of our work was to investigate the potential of a currently licensed anticancer epigenetic modifier as a treatment option for cardiac diseases associated with hypertension-induced cardiac hypertrophy and fibrosis.

METHODS AND RESULTS: The effects of DNA methylation inhibition with 5-azacytidine (5-aza) were examined in a human primary fibroblast cell line and in a spontaneously hypertensive rat (SHR) model. The results from this work allude to novel in vivo antifibrotic and antihypertrophic actions of 5-aza. Administration of the DNA methylation inhibitor significantly improved several echocardiographic parameters associated with hypertrophy and diastolic dysfunction. Myocardial collagen levels and myocyte size were reduced in 5-aza-treated SHRs. These findings are supported by beneficial in vitro effects in cardiac fibroblasts. Collagen I, collagen III, and α-smooth muscle actin were reduced in a human ventricular cardiac fibroblast cell line treated with 5-aza.

CONCLUSION: These findings suggest a role for epigenetic modifications in contributing to the profibrotic and hypertrophic changes evident during disease progression. Therapeutic intervention with 5-aza demonstrated favorable effects highlighting the potential use of this epigenetic modifier as a treatment option for cardiac pathologies associated with hypertrophy and fibrosis.

Effect of β3-adrenoceptor on cardiac fibrosis in rat cardiac fibroblast cells and its potential mechanism

Purpose: To investigate the effect of β3-adrenoceptors (β3-AR) up-regulation on fibrosis in cardiac fibroblast cells in rats and its potential mechanism. Methods: Cardiac fibroblast cells (CFB) were isolated and identified from rats’ hearts. The β3-ARupregulated cardiac fibroblast cells were constructed by lentiviral transfection technology. Thereafter, Ang II was used to induce fibrosis in cardiac fibroblast cells, and subsequently, Western blot assay was performed to investigate fibrosis related marker proteins (TGF-β, Smad-2, p-Smad-2, Col-I and Col-III) in cardiac fibroblast cells. Results: β3-AR up-regulated cardiac fibroblast cells were successfully constructed. Furthermore, the results show that up-regulation of β3-AR increased the expressions of TGF-β, p-Smad-2, Col-I and Col- III proteins in Ang II treated cardiac fibroblast cells. Conclusion: The results suggest that up-regulation of β3-AR aggravates fibrosis of cardiac fibroblast cells. In other words, inhibition of β3-AR expressions in cardiac tissues would be beneficial for treating cardiac fibrosis and its related cardiac diseases.

Controle autonomico da frequencia cardiaca de adolescentes em treinamento

Universidade Estadual de Campinas . Faculdade de Educação Física

Aerobic exercise training improves skeletal muscle function and Ca(2+) handling-related protein expression in sympathetic hyperactivity-induced heart failure

Bueno CR Jr, Ferreira JC, Pereira MG, Bacurau AV, Brum PC. Aerobic exercise training improves skeletal muscle function and Ca(2+) handling-related protein expression in sympathetic hyperactivity-induced heart failure. J Appl Physiol 109: 702-709, 2010. First published July 1, 2010; doi: 10.1152/japplphysiol.00281.2010.-The cellular mechanisms of positive effects associated with aerobic exercise training on overall intrinsic skeletal muscle changes in heart failure (HF) remain unclear. We investigated potential Ca(2+) abnormalities in skeletal muscles comprising different fiber compositions and investigated whether aerobic exercise training would improve muscle function in a genetic model of sympathetic hyperactivity-induced HF. A cohort of male 5-mo-old wild-type (WT) and congenic alpha(2A)/alpha(2C) adrenoceptor knockout (ARKO) mice in a C57BL/6J genetic background were randomly assigned into untrained and trained groups. Exercise training consisted of a 8-wk running session of 60 min, 5 days/wk (from 5 to 7 mo of age). After completion of the exercise training protocol, exercise tolerance was determined by graded treadmill exercise test, muscle function test by Rotarod, ambulation and resistance to inclination tests, cardiac function by echocardiography, and Ca(2+) handling-related protein expression by Western blot. alpha(2A)/alpha(2C)ARKO mice displayed decreased ventricular function, exercise intolerance, and muscle weakness paralleled by decreased expression of sarcoplasmic Ca(2+) release-related proteins [alpha(1)-, alpha(2)-, and beta(1)-subunits of dihydropyridine receptor (DHPR) and ryanodine receptor (RyR)] and Ca(2+) reuptake-related proteins [sarco(endo) plasmic reticulum Ca(2+)-ATPase (SERCA) 1/2 and Na(+)/Ca(2+) exchanger (NCX)] in soleus and plantaris. Aerobic exercise training significantly improved exercise tolerance and muscle function and reestablished the expression of proteins involved in sarcoplasmic Ca(2+) handling toward WT levels. We provide evidence that Ca(2+) handling-related protein expression is decreased in this HF model and that exercise training improves skeletal muscle function associated with changes in the net balance of skeletal muscle Ca(2+) handling proteins.

Standard Values for Real-Time Transthoracic Three-Dimensional Echocardiographic Dyssynchrony Indexes in a Normal Population

Background: There is a paucity of information describing the real-time 3-dimensional echocardiography (RT3DE) and dyssynchrony indexes (DIs) of a normal population. We evaluate the RT3DE DIs in a population with normal electrocardiograms and 2- and 3-dimensional echocardiographic analyses. This information is relevant for cardiac resynchronization therapy. Methods: We evaluated 131 healthy volunteers (73 were male, aged 46 +/- 14 years) who were referred for routine echocardiography; who presented normal cardiac structure on electrocardiography, 2-dimensional echocardiography, and RT3DE; and who had no history of cardiac diseases. We analyzed 3-dimensional left ventricular ejection fraction, left ventricle end-diastolic volume, left ventricle end-systolic volume, and left ventricular systolic DI% (6-, 12-, and 16-segment models). RT3DE data were analyzed by quantifying the statistical distribution (mean, median, standard deviation [SD], relative SD, coefficient of skewness, coefficient of kurtosis, Kolmogorov-Smirnov test, D`Agostino-Pearson test, percentiles, and 95% confidence interval). Results: Left ventricular ejection fraction ranged from 50% to 80% (66.1% +/- 7.1%); left ventricle end-diastolic volume ranged from 39.8 to 145 mL (79.1 +/- 24.9 mL); left ventricle end-systolic volume ranged from 12.9 to 66 mL (27 +/- 12.1 mL); 6-segment DI% ranged from 0.20% to 3.80% (1.21% +/- 0.66%), median: 1.06, relative SD: 0.5482, coefficient of skewness: 1.2620 (P < .0001), coefficient of Kurtosis: 1.9956 (P = .0039); percentile 2.5%: 0.2900, percentile 97.5%: 2.8300; 12-segment DI% ranged from 0.22% to 4.01% (1.29% +/- 0.71%), median: 1.14, relative SD: 0.95, coefficient of skewness: 1.1089 (P < .0001), coefficient of Kurtosis: 1.6372 (P = .0100), percentile 2.5%: 0.2850, percentile 97.5%: 3.0700; and 16-segment DI% ranged from 0.29% to 4.88% (1.59 +/- 0.99), median: 1.39, relative SD: 0.56, coefficient of skewness: 1.0792 (P < .0001), coefficient of Kurtosis: 0.9248 (P = .07), percentile 2.5%: 0.3750, percentile 97.5%: 3.750. Conclusion: This study allows for the quantification of RT3DE DIs in normal subjects, providing a comparison for patients with heart failure who may be candidates for cardiac resynchronization therapy. (J Am Soc Echocardiogr 2008; 21: 1229-1235)

Quality of life in dilated cardiomyopathy with refractory chronic heart failure undergoing devices implantation

Heart failure is the final stage of most of cardiac diseases. It is a complex syndrome in which the patients should have the following features: symptoms of heart failure, typically shortness of breath at rest or during exertion, and/or fatigue; signs of fluid retention such as pulmonary congestion or ankle swelling; and objective evidence of an abnormality of the structure or function of the heart at rest. This progressive syndrome as a high incidence and prevalence and poor prognosis: four-year mortality is around 50% with 40% of the patients admitted to hospital dying or readmitted within a year. With ageing, many patients will develop chronic heart failure, which, because of its symptoms, patient’s awareness of their risk of dying, and the effects of therapy, together with frequent hospitalizations, has considerable impact on patient’s health-related quality of life.

Estudo da deformação miocárdica para detecção precoce de disfunção ventricular esquerda em doentes submetidos a quimioterapia com antraciclinas

Mestrado em Tecnologia de Diagnóstico e Intervenção Cardiovascular - Área de especialização: Ultrassonografia cardiovascular

Optimização e Validação da Produção de [13n]-Nh3 para Estudos Clínicos de Tomografia por Emissão de Positrões na Avaliação da Perfusão Miocárdica

A par das patologias oncológicas, as doenças do foro cardíaco, em particular a doença arterial coronária, são uma das principais causas de morte nos países industrializados, devido sobretudo, à grande incidência de enfartes do miocárdio. Uma das formas de diagnóstico e avaliação desta condição passa pela obtenção de imagens de perfusão miocárdica com radionuclídeos, realizada por Tomografia por Emissão de Positrões (PET). As soluções injectáveis de [15O]-H2O, [82Rb] e [13N]-NH3 são as mais utilizadas neste tipo de exame clínico. No Instituto de Ciências Nucleares Aplicadas à Saúde (ICNAS), a existência de um ciclotrão tem permitido a produção de uma variedade de radiofármacos, com aplicações em neurologia, oncologia e cardiologia. Recentemente, surgiu a oportunidade de iniciar exames clínicos com [13N]-NH3 para avaliação da perfusão miocárdica. É neste âmbito que surge a oportunidade do presente trabalho, pois antes da sua utilização clínica é necessário realizar a optimização da produção e a validação de todo o processo segundo as normas de Boas Práticas Radiofarmacêuticas. Após uma fase de optimização do processo, procedeu-se à avaliação dos parâmetros físico-químicos e biológicos da preparação de [13N]-NH3, de acordo com as indicações da Farmacopeia Europeia (Ph. Eur.) 8.2. De acordo com as normas farmacêuticas, foram realizados 3 lotes de produção consecutivos para validação da produção de [13N]-NH3. Os resultados mostraram um produto final límpido e ausente de cor, com valores de pH dentro do limite especificado, isto é, entre 4,5 e 8,5. A pureza química das amostras foi verificada, uma vez que relativamente ao teste colorimétrico, a tonalidade da cor da solução de [13N]-NH3 não era mais intensa que a solução de referência. As preparações foram identificadas como sendo [13N]-NH3, através dos resultados obtidos por cromatografia iónica, espectrometria de radiação gama e tempo de semi-vida. Por examinação do cromatograma obtido com a solução a ser testada, observou-se que o pico principal possuia um tempo de retenção aproximadamente igual ao pico do cromatograma obtido para a solução de referência. Além disso, o espectro de radiação gama mostrou um pico de energia 0,511 MeV e um outro adicional de 1,022 MeV para os fotões gama, característico de radionuclídeos emissores de positrões. O tempo de semi-vida manteve-se dentro do intervalo indicado, entre 9 e 11 minutos. Verificou-se, igualmente, a pureza radioquímica das amostras, correspondendo um mínimo de 99% da radioactividade total ao [13N], bem como a pureza radionuclídica, observando-se uma percentagem de impurezas inferiores a 1%, 2h após o fim da síntese. Os testes realizados para verificação da esterilidade e determinação da presença de endotoxinas bacterianas nas preparações de [13N]-NH3 apresentaram-se negativos.Os resultados obtidos contribuem, assim, para a validação do método para a produção de [13N]-NH3, uma vez que cumprem os requisitos especificados nas normas europeias, indicando a obtenção de um produto seguro e com a qualidade necessária para ser administrado em pacientes para avaliação da perfusão cardíaca por PET.

Diagnóstico cardíaco a partir de dados acústicos e clínicos

Este documento foi redigido no âmbito da dissertação do Mestrado em Engenharia Informática na área de Arquiteturas, Sistemas e Redes, do Departamento de Engenharia Informática, do ISEP, cujo tema é diagnóstico cardíaco a partir de dados acústicos e clínicos. O objetivo deste trabalho é produzir um método que permita diagnosticar automaticamente patologias cardíacas utilizando técnicas de classificação de data mining. Foram utilizados dois tipos de dados: sons cardíacos gravados em ambiente hospitalar e dados clínicos. Numa primeira fase, exploraram-se os sons cardíacos usando uma abordagem baseada em motifs. Numa segunda fase, utilizamos os dados clínicos anotados dos pacientes. Numa terceira fase, avaliamos a combinação das duas abordagens. Na avaliação experimental os modelos baseados em motifs obtiveram melhores resultados do que os construídos a partir dos dados clínicos. A combinação das abordagens mostrou poder ser vantajosa em situações pontuais.

Dynamic three-dimensional reconstruction of the heart by transesophageal echocardiography

OBJECTIVE: To evaluate echocardiography accuracy in performing and obtaining images for dynamical three-dimensional (3D) reconstruction. METHODS: Three-dimensional (3D) image reconstruction was obtained in 20 consecutive patients who underwent transesophageal echocardiography. A multiplanar 5 MHz transducer was used for 3D reconstruction. RESULTS: Twenty patients were studied consecutively. The following cardiac diseases were present: valvar prostheses-6 (2 mitral, 2 aortic and 2 mitral and aortic); mitral valve prolapse- 3; mitral and aortic disease - 2; aortic valve disease- 5; congenital heart disease- 3 (2 atrial septal defect- ASD - and 1 transposition of the great arteries -TGA); arteriovenous fistula- 1. In 7 patients, color Doppler was also obtained and used for 3D flow reconstruction. Twenty five cardiac structures were acquired and 60 reconstructions generated (28 of mitral valves, 14 of aortic valves, 4 of mitral prostheses, 7 of aortic prostheses and 7 of the ASD). Fifty five of 60 (91.6%) reconstructions were considered of good quality by 2 independent observers. The 11 reconstructed mitral valves/prostheses and the 2 reconstructed ASDs provided more anatomical information than two dimensional echocardiography (2DE) alone. CONCLUSION: 3D echocardiography using a transesophageal transducer is a feasible technique, which improves detection of anatomical details of cardiac structures, particularly of the mitral valve and atrial septum.

Nobel Prizes: Contributions to Cardiology

The Nobel Prize was created by Alfred Nobel. The first prize was awarded in 1901 and Emil Adolf von Behring was the first laureate in medicine due to his research in diphtheria serum. Regarding cardiology, Nobel Prize’s history permits a global comprehension of progress in pathophysiology, diagnosis and therapeutics of various cardiac diseases in last 120 years. The objective of this study was to review the major scientific discoveries contemplated by Nobel Prizes that contributed to cardiology. In addition, we also hypothesized why Carlos Chagas, one of our most important scientists, did not win the prize in two occasions. We carried out a non-systematic review of Nobel Prize winners, selecting the main studies relevant to heart diseaseamong the laureates. In the period between 1901 and 2013, 204 researches and 104 prizes were awarded in Nobel Prize, of which 16 (15%) studies were important for cardiovascular area. There were 33 (16%) laureates, and two (6%) were women. Fourteen (42%) were American, 15 (45%) Europeans and four (13%) were from other countries. There was only one winner born in Brazil, Peter Medawar, whose career was all in England. Reviewing the history of the Nobel Prize in physiology or medicine area made possible to identify which researchers and studies had contributed to advances in the diagnosis, prevention and treatment of cardiovascular diseases. Most winners were North Americans and Europeans, and male.