Iran Castro

Effects of therapeutic angiogenesis with plasmid VEGF165 on ventricular function in a canine model of chronic myocardial infarction

OBJECTIVE Therapeutic angiogenesis is currently under investigation in ischemic heart disease. We examined the effect on left ventricular function induced by therapeutic angiogenesis by intramyocardial injection of plasmid VEGF(165), in a canine model of chronic myocardial infarction. METHODS Left thoracotomy was performed in 10 mongrel dogs, and myocardial infarction induced by ligation of the major diagonal coronary artery. At 7 postoperative (p.o.) day (pre-treatment), left ventricular ejection fraction was assessed by echocardiogram, and a second procedure was done: saline or plasmid VEGF(165) at 200 mg/mL was injected over 10 points of the ischemic areas of control or treated groups, respectively. Fourteen days later (post-treatment, day 21) a control echocardiogram was performed, the animals were sacrificed and histological examination was performed. RESULTS Ejection fraction was maintained in the treated group: 52.45 +/- 15.1% on day 7 and 48.53 +/-11.74% on day 21 (P=0.59), and tended to decrease in the control group, from 59.3 +/- 4% to 39.37 +/- 19.43% (P=0.04), although absolute values did not differ significantly between groups. Histological examination revealed a non significant increase in capillary vessels number in all areas in treated group. Paradoxically, arterioles were significantly less in number in all areas of treated dogs. CONCLUSION Intramyocardial injection of plasmid VEGF(165), in this canine model of chronic myocardial infarction, resulted in preservation of left ventricular ejection fraction, contrary to the control group where left ventricular ejection fraction showed continuous decline during the experiment. Histological examination, however, was unable to explain completely these results.

Effectiveness of Chlorthalidone Plus Amiloride for the Prevention of Hypertension: The PREVER‐Prevention Randomized Clinical Trial

Background Prehypertension is associated with higher cardiovascular risk, target organ damage, and incidence of hypertension. The Prevention of Hypertension in Patients with PreHypertension (PREVER‐Prevention) trial aimed to evaluate the efficacy and safety of a low‐dose diuretic for the prevention of hypertension and end‐organ damage. Methods and Results This randomized, parallel, double‐blind, placebo‐controlled trial was conducted in 21 Brazilian academic medical centers. Participants with prehypertension who were aged 30 to 70 years and who did not reach optimal blood pressure after 3 months of lifestyle intervention were randomized to a chlorthalidone/amiloride combination pill or placebo and were evaluated every 3 months during 18 months of treatment. The primary outcome was incidence of hypertension. Development or worsening of microalbuminuria, new‐onset diabetes mellitus, and reduction of left ventricular mass were secondary outcomes. Participant characteristics were evenly distributed by trial arms. The incidence of hypertension was significantly lower in 372 study participants allocated to diuretics compared with 358 allocated to placebo (hazard ratio 0.56, 95% CI 0.38–0.82), resulting in a cumulative incidence of 11.7% in the diuretic arm versus 19.5% in the placebo arm (P=0.004). Adverse events; levels of blood glucose, glycosylated hemoglobin, creatinine, and microalbuminuria; and incidence of diabetes mellitus were no different between the 2 arms. Left ventricular mass assessed through Sokolow‐Lyon voltage and voltage‐duration product decreased to a greater extent in participants allocated to diuretic therapy compared with placebo (P=0.02). Conclusions A combination of low‐dose chlorthalidone and amiloride effectively reduces the risk of incident hypertension and beneficially affects left ventricular mass in patients with prehypertension. Clinical Trial Registration URL: http://www.ClinicalTrials.gov, www.ensaiosclinicos.gov. Unique identifiers: NCT00970931, RBR‐74rr6s.

Short- and long- term results of percutaneous balloon valvuloplasty in pulmonary valve stenosis

OBJECTIVE To assess the long-term results of percutaneous balloon valvuloplasty at a single institution. METHODS This study comprised 189 patients with pulmonary valve stenosis undergoing percutaneous balloon valvuloplasty from 1984 to 1996, whose mean age was 7.97+/-9.25 years. The procedure was classified as successful when the RV-PA gradient was reduced to levels < 36 mmHg; restenosis was indicated by RV-PA gradients > 36 mmHg after an effective procedure. RESULTS After the procedure, the peak-to-peak transvalvular gradient decreased from 70.12+/-30.06 to 25.11 +/-20.23 mmHg (P<0.001). Immediate success was obtained in 148 (78.72%) patients. A later reduction in the gradient to values < 36 mmHg was obtained in 24 other patients previously categorized as unsuccessful. Therefore, percutaneous balloon valvuloplasty was considered effective in 172 (91.01%) patients. Effectiveness increased to 93.53% (159/170) in the cases of typical morphology. Follow-up ranged from 4.39+/-3 years to 13.01 years. Restenosis was observed in 24 (13.95%) patients. Pulmonary regurgitation was detected in 95.1% of the patients, being more intense than mild in 29.5% of the patients. The probability of maintaining an appropriate result, at any time point, with no restenosis was 92.29% in 2 years, 87.38% in 5 years, 82.46% in 8 years, and 64.48% in 10 years. CONCLUSION Percutaneous balloon valvuloplasty was effective and safe for the treatment of pulmonary valve stenosis with excellent short- and long-term results.OBJETIVO: Determinar os resultados em longo prazo da valvoplastia percutânea por balao em uma instituicao isolada. METODOS: Estudados 189 pacientes com estenose valvar pulmonar submetidos a valvoplastia percutânea por balao, entre 1984-1996, com idade media de 7,97±9,25 anos, classificando-se como bem sucedida, a reducao do gradiente VD-AP em niveis 36mmHg apos procedimento eficaz. RESULTADOS: Apos o termino do procedimento, o gradiente pico a pico transvalvar reduziu-se de 70,12±30,06 para 25,11±20,23 mmHg (p<0,001). Obtiveram sucesso imediato 148 (78,72%) pacientes. Houve reducao posterior do gradiente para valores < 36mmHg em outros 24 pacientes categorizados sem sucesso no grupo. Assim a valvoplastia percutânea por balao foi considerada efetiva em 172 (91,01%) pacientes. A efetividade aumentou para 93,53% (159/170) nos casos de morfologia tipica. O tempo de seguimento foi de 4,39±3anos ate o periodo maximo de 13,01 anos. Observou-se reestenose em 24 (13,95%). A presenca de regurgitacao pulmonar foi detectada em 95,1% dos pacientes, sendo que em 29,5% com grau maior do que leve. A probabilidade de se manter um resultado adequado, ate qualquer ponto no tempo, sem a ocorrencia de reestenose, foi de 92,29% em 2 anos, de 87,38 % em 5 anos, de 82,46% em 8 anos e de 64,48% em 10 anos. CONCLUSAO: A valvoplastia percutânea por balao foi efetiva e segura no tratamento da estenose valvar pulmonar com excelentes resultados imediatos e a longo prazo.

Association between coronary artery atherosclerosis and the intima-media thickness of the common carotid artery measured on ultrasonography

OBJECTIVE To assess whether the intima-media thickness of the common carotid artery of patients with coronary artery disease is greater than that of individuals without that disease. METHODS Case-control prospective study of prevalence assessing the thickness of the intima and media layers of 29 patients with coronary artery disease and 29 individuals without that disease by using ultrasonography of the carotid arteries. Diabetic patients and those with peripheral artery and cerebral vasculopathies were excluded from the study. RESULTS The mean age was 51 +/- 7.5 years. Fifty-five per cent of the patients were males. Acute myocardial infarction was present in 62%; cardiac catheterization in 72%; saphenous bypass in 5%; and coronary angioplasty in 24%. The intima-media thickness of the common carotid artery in case patients and in control patients was, respectively, 0.81 +/- 0.25 mm and 0.62 +/- 0.18 mm (P=0.001). CONCLUSION Intima-media thickness of the common carotid artery was significantly greater in patients with coronary artery disease.

II DIRETRIZ BRASILEIRA DE CARDIOPATIA GRAVE

NTRODUCAOInumeras pesquisas tem demonstrado que, se, por um lado, a expectativa de vida do brasileiro cresceu nos ultimos dez anos, ha, por outro, um indice muito maior de doencas cardiovasculares. Verifi cou-se, entre essas, o incremento de situacoes graves, que impedem o retorno de muitos pacientes ao trabalho. Tornou-se, entao, fundamental conceituar Cardiopatia Grave, para a orientacao tanto do cardiologista como de colegas de outras especialidades. Com essa intencao, a Sociedade Brasileira de Cardiologia propos esta Diretriz.O termo Cardiopatia Grave aparece pela primeira vez na legislacao brasileira com a Lei n.o 1711 (item III, do Artigo 178) do Estatuto dos Funcionarios Civis da Uniao, sancionada em 28 de outubro de 1952, que visava benefi ciar os pacientes acometidos de molestia profi ssional, acidente em servico, tuberculose ativa, alienacao mental, neoplasia maligna, cegueira, lepra, paralisia irreversivel e incapacitante, cardiopatia grave e estados avancados da doenca de Paget (osteite deformante). Esta lei foi reeditada em outras ocasioes, sem modifi cacoes signifi cativas. A partir de 1.o de janeiro de 1989, passou a vigorar como a Lei 7713/88, incluindo, entao, a sindrome de imunodefi ciencia adquirida (SIDA/AIDS) e benefi ciando os pacientes acometidos pelas mesmas doencas listadas na lei anterior, mesmo que tenham sido contraidas depois da aposentadoria ou reforma (Artigos 6.o, XVI e 57.o). Em 30 de dezembro de 2004, foi publicada, no Diario Ofi cial da Uniao, a inclusao das hepatopatias graves, nefropatias graves, doencas causadas por radiacao ionizante e a doenca de Parkinson, como merecedoras do mesmo beneficio. Em 1952, uma comissao multidisciplinar de medicos enunciou o conceito de Cardiopatia Grave como doenca que leva, em carater temporario ou permanente, a reducao da capacidade funcional do coracao, a ponto de acarretar risco a vida ou impedir o servidor de exercer as suas atividades. A incapacitacao laboral deve ser avaliada por pericia medica. Nesse procedimento, o segurado ou paciente, vitima de uma doenca ou acidente de trabalho, e examinado por um profi ssional especializado (medico-perito), que avalia as condicoes de saude e a capacidade laborativa, decidindo sobre a conveniencia do afastamento ou o retorno as atividades laborativas habituais, de acordo com as normatizacoes contidas nos Estatutos do Funcionalismo Publico Civil ou Militar dos municipios, estados e federacao (Manual do Medico Perito, 1980; Pericia Medica, 1990).O medico-perito, diferentemente do medico-cardiologista-clinico, nao exerce a medicina clinica, pois nao cuida de enfermos. Utiliza os conhecimentos medicos apenas para estabelecer o diagnostico e o prognostico clinico, para julgar a capacidade laborativa e sua imputabilidade. Assim, a atividade e o conhecimento pericial sugerem uma especialidade de cunho medico-judicial, na qual, alem dos conhecimentos profundos de clinica, existe a necessidade de uma postura, raciocinio e julgamento, como fi m. A adaptacao do conhecimento medico as exigencias das normas legais realiza-se com criterios e principios diferentes dos que regem a apreciacao dos problemas clinicos. As exigencias da medicina clinica sao diferentes da pericial, que se ve envolvida com a legislacao, que devem sustentar o parecer pericial.A medicina pericial exercida atualmente em muito difere da praticada ha 30 ou 40 anos. Mais do que nunca, passou-se a exigir a comprovacao diagnostica por meio de uma rigorosa avaliacao clinica e comprovacao laboratorial (metodos complementares nao-invasivos e invasivos), evitando-se as conclusoes baseadas em impressoes subjetivas ou alegacoes emanadas dos pacientes, sem o corroborativo laboratorial, tao sujeitas a erros ou interpretacoes enganosas.

Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant Hypertension: The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment)

The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5–50 mg QD) or clonidine (0.1–0.3 mg BID). The primary end point was BP control during office (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring. Secondary end points included BP control from each method and absolute BP reduction. From 1597 patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension criteria. Compared with the spironolactone group (n=95), the clonidine group (n=92) presented similar rates of achieving the primary end point (20.5% versus 20.8%, respectively; relative risk, 1.01 [0.55–1.88]; P=1.00). Secondary end point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP monitoring (44% versus 46.2%) control for spironolactone and clonidine, respectively. However, spironolactone promoted greater decrease in 24-h systolic and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol analysis (limited to patients with ≥80% adherence to spironolactone/clonidine treatment) showed similar results regarding the primary end point. In conclusion, clonidine was not superior to spironolactone in true resistant hypertensive patients, but the overall BP control was low (≈21%). Considering easier posology and greater decrease in secondary end points, spironolactone is preferable for the fourth-drug therapy. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01643434.

Variações de parâmetros da função diastólica do ventrículo esquerdo de acordo com a idade através da ecocardiografia com Doppler tissular

OBJETIVO: Determinar a correlacao entre as velocidades diastolicas do Doppler tissular com a idade em amostra de adultos saudaveis, e correlacionar a idade com as velocidades do fluxo transmitral e de veias pulmonares. METODOS: Estudados, atraves da ecocardiografia, 51 individuos saudaveis, com idades entre 21 e 69 anos e registradas as velocidades miocardicas diastolicas ao Doppler tissular e determinadas as velocidades dos fluxos transmitral e venoso pulmonar. RESULTADOS: As velocidades miocardicas diastolicas iniciais septal basal e lateral basal apresentaram correlacao inversa com a idade, com r = - 0,40 (p = 0,004) e r = - 0,60 (p = 0,0001) respectivamente. As velocidades atriogenicas do Doppler tissular foram diretamente correlacionadas com a idade, sendo no segmento septal basal r = 0,56 (p = 0,0001) e no segmento lateral basal r = 0,50 (p = 0,0001). As velocidades do fluxo transmitral e do fluxo venoso pulmonar tambem mostraram correlacao com a idade. CONCLUSAO: Existe correlacao entre a idade e as velocidades miocardicas diastolicas do Doppler tissular e com as velocidades do fluxo transmitral e fluxo venoso pulmonar, demonstrando em individuos saudaveis uma variacao de parâmetros da funcao diastolica do ventriculo esquerdo com a evolucao natural da idade.

Effect of red wine associated with physical exercise in the cardiovascular system of spontaneously hipertensive rats.

FUNDAMENTO: Pratica de exercicio fisico (EF) e eficiente no tratamento e na prevencao da hipertensao, associada a melhora do perfil lipidico e da funcao contratil cardiaca. Consumo moderado e regular de bebidas alcoolicas, como vinho tinto, desempenha efeito cardiovascular protetor. Polifenois da bebida apresentam propriedades antioxidantes, beneficiando vasos sanguineos. Ha poucas evidencias sobre o consumo de vinho tinto associado ao EF e as influencias no sistema cardiovascular. OBJETIVO: Investigar o efeito da interacao entre o EF e o consumo moderado de vinho tinto na pressao arterial sistolica (PAS), lipoproteina de alta densidade (HDL), desempenho fisico e fracao de ejecao do ventriculo esquerdo (FEVE) de ratos espontaneamente hipertensos (SHR). METODOS: Amostra de 32 SHR distribuidos em quatro grupos: grupo vinho e exercicio (GVE), grupo vinho (GV), grupo exercicio (GE) e grupo controle (GC). Doses de vinho tinto, equivalentes ao consumo moderado em humanos, foram administradas por gavagem, durante dez semanas, simultâneas ao periodo de EF, realizado em esteira. Os SHR receberam 3,715 ml/kg/dia de vinho. O desempenho fisico foi analisado por teste de esforco (TE), e a FEVE foi obtida por medidas ecocardiograficas. A afericao da PAS ocorreu antes e apos o protocolo do EF. RESULTADOS: Demonstrou-se reducao significativa da PAS nos grupos de intervencao, comparados ao GC. Ao final do protocolo, o GVE apresentou a maior reducao. Assim como na PAS, o GVE apresentou melhor resultado nos niveis de HDL. Nao houve diferenca significativa no desempenho fisico e na FEVE entre os grupos. CONCLUSAO: O EF associado a ingesta moderada de vinho tinto exerce efeito cardioprotetor na PAS e na HDL de SHR. O desempenho fisico e a FEVE nao sao alterados.BACKGROUND Physical exercise (PE) is effective in the treatment and prevention of hypertension associated with improved lipid profile and cardiac contractile function. Regular and moderate consumption of alcoholic beverages such as red wine brings a cardiovascular protective effect. Beverage-derived polyphenols have antioxidant properties benefiting blood vessels. There is little evidence on the consumption of red wine associated with PE and the influences on the cardiovascular system. OBJECTIVE To investigate the effect of physical exercise (PE) and moderate red wine intake interaction on systolic blood pressure (SBP), high density lipoprotein (HDL) levels, physical performance (PP) and left ventricular ejection fraction (LVEF) in spontaneously hypertensive rats (SHR). METHODS Sample of 32 SHRs divided into four groups: wine and exercise group (WEG), wine group (WG), exercise group (EG) and control group (CG). Red wine doses were given by intra-gastric gavage, during ten weeks, coincident with PE period, performed on treadmills. The SHRs received red wine doses of 3.715 ml/kg/day. Physical performance was analyzed by maximal exercise test (MET) and LVEF by echocardiographic measures. SBP measurement was made before and after the PE protocol. RESULTS Demonstrated that the three groups which suffered intervention presented significant SBP reduction compared to CG. At the end of the protocol, WEG showed the largest reduction. Like in SBP results, WEG showed the best outcome on HDL levels at the experiment end. There was no significant difference of physical performance and LVEF between groups. CONCLUSION PE associated with moderate red wine intake has cardioprotective effects on SBP and HDL levels in SHR. Their physical performance and LVEF are not modified.

Prognóstico da esclerose valvar aórtica na mortalidade cardíaca de pacientes atendidos no instituto de cardiologia do Rio Grande do Sul

OBJECTIVE To evaluate the prognostic effect of aortic valve sclerosis on all-cause and cardiovascular mortality of patients seen at the Cardiology Institute of the Brazilian state of Rio Grande do Sul from 1996 to 2000. METHODS A historical cohort study using information from both the database of the Echocardiography Laboratory of the Cardiology Hospital and the Death Registry of Rio Grande do Sul Health Department. The evaluation was carried out from 1996 to 2000. Study endpoints were all-cause and cardiovascular mortality. RESULTS A total of 8585 patients were analyzed, 2154 (25%) of whom had aortic valve sclerosis. Mean follow-up was 41+/-6 months, and all-cause and cardiovascular deaths were 299 (3.5%) and 95 (1.1%), respectively. The group of patients with aortic valve sclerosis had more segmental cardiomyopathy, ventricular dysfunction, ventricular enlargement, and ventricular hypertrophy; yet, they did not show higher risk for all-cause or cardiovascular mortality in the multivariate analysis. CONCLUSION The presence of aortic valve sclerosis was not associated with increased risk for all-cause and cardiovascular mortality in the population studied.

Direct intramyocardial transthoracic transplantation of bone marrow mononuclear cells for non-ischemic dilated cardiomyopathy: INTRACELL, a prospective randomized controlled trial

Objective We tested the hypothesis that direct intramyocardial injection of bone marrow mononuclear cells in patients with non-ischemic dilated cardiomyopathy can improve left ventricular function and physical capacity. Methods Thirty non-ischemic dilated cardiomyopathy patients with left ventricular ejection fraction <35% were randomized at a 1:2 ratio into two groups, control and treated. The bone marrow mononuclear cells group received 1.06±108 bone marrow mononuclear cells through mini-thoracotomy. There was no intervention in the control group. Assessment was carried out through clinical evaluations as well as a 6-min walk test, nuclear magnectic resonance imaging and echocardiogram. Results The bone marrow mononuclear cells group showed a trend toward left ventricular ejection fraction improvement, with magnectic resonance imaging - at 3 months, showing an increase from 27.80±6.86% to 30.13±9.06% (P=0.08) and returning to baseline at 9 months (28.78%, P=0.77). Magnectic resonance imaging showed no changes in left ventricular ejection fraction during follow-up of the control group (28.00±4.32%, 27.42±7.41%, and 29.57±4.50%). Echocardiogram showed left ventricular ejection fraction improved in the bone marrow mononuclear cells group at 3 months, 25.09±3.98 to 30.94±9.16 (P=0.01), and one year, 30.07±7.25% (P=0.001). The control group showed no change (26.1±4.4 vs 26.5±4.7 and 30.2±7.39%, P=0.25 and 0.10, respectively). Bone marrow mononuclear cells group showed improvement in New York Heart Association functional class, from 3.40±0.50 to 2.41±0.79 (P=0.002); patients in the control group showed no change (3.37±0.51 to 2.71±0.95; P=0.17). Six-minute walk test improved in the bone marrow mononuclear cells group (348.00±93.51m at baseline to 370.41±91.56m at 12 months, P=0.66) and there was a non-significant decline in the control group (361.25±90.78m to 330.00±123.42m after 12 months, P=0.66). Group comparisons were non-significant. Conclusion The trend of intragroup functional and subjective improvement was not confirmed when compared to the control group. Direct intramyocardial application of bone marrow mononuclear cells in non-ischemic dilated cardiomyopathy was not associated with significant changes in left ventricular function. Differences observed within the bone marrow mononuclear cells group could be due to placebo effect or low statistical power.