One-year follow-up of the effects of sildenafil on pulmonary arterial hypertension and veno-occlusive disease

We hypothesized that chronic oral administration of the phosphodiesterase-5 inhibitor sildenafil could improve the exercise capacity and pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH) on the basis of previous short-term studies. We tested this hypothesis in 14 subjects with PAH, including seven patients with the idiopathic form and seven patients with atrial septal defects, but no other congenital heart abnormalities. Patients were subjected to a 6-min walk test and dyspnea was graded according to the Borg scale. Pulmonary flow and pressures were measured by Doppler echocardiography. Patients were given sildenafil, 75 mg orally three times a day, and followed up for 1 year. Sildenafil therapy resulted in the following changes: increase in the 6-min walk distance from a median value of 387 m (range 0 to 484 m) to 462 m (range 408 to 588 m; P < 0.01), improvement of the Borg dyspnea score from 4.0 (median value) to 3.0 (P < 0.01), and increased pulmonary flow (velocity-time integral) from a median value of 0.12 (range 0.08 to 0.25) to 0.23 (range 0.11 to 0.40; P < 0.01) with no changes in pulmonary pressures. In one patient with pulmonary veno-occlusive disease diagnosed by a lung biopsy, sildenafil had a better effect on the pulmonary wedge pressure than inhaled nitric oxide (15 and 29 mmHg, respectively, acute test). He walked 112 m at baseline and 408 m at one year. One patient died at 11 months of treatment. No other relevant events occurred. Thus, chronic administration of sildenafil improves the physical capacity of PAH patients and may be beneficial in selected cases of veno-occlusive disease.

Possible risk factors for vertical transmission of Chagas' disease

The author emphasizes the importance of the congenital transmission of Chagas' disease and discusses the possible risk factors for transmission such as age, origin, obstetrical history and maternal form of disease. Exacerbation of infection during pregnancy is also considered as a possible risk factor for transmission. Besides, a relationship between the frequency of transmission and gestational age is presented. Concerning breast-feeding, the risk of transmission is directly related to the acute phase of maternal disease and bleeding nipples. The deleterious effects of chagasic infection on the fetus and newborn are also considered.

Diversity of Trypanosoma cruzi stocks and clones derived from Chagas disease patients: I-Behavioral characterization in vitro

In this study, we isolated Trypanosoma cruzi from chronic Chagas heart disease and from megaesophagus patients. The parasite stock hSLU239 (heart disease) yielded clones h1 and h2, whereas stock mSLU142 (megaesophagus) yielded clones m1, m2, m3 and m4. The parasite growth kinetics, doubling time and differentiation in axenic liquid medium showed broad behavioral diversity. It was shown that a particular pattern of behavior for a parental stock could not necessarily be assigned for subsequent clones. This study indicates that i) each Chagas disease patient is infected with several T. cruzi populations; ii) clonal lines derived from patient samples may have different biological characteristics from the original isolate; and that iii) additional behavioral and/or molecular markers are required for further characterization of Trypanosoma cruzi stocks and clones derived from Chagas disease patients in order to identify correlations with pathology.

Differing phagocytic function of monocytes and neutrophils in Chagas' cardiopathy according to the presence or absence of congestive heart failure

We evaluated the in vitro phagocytic function and the production of microbicidal oxygen radicals by monocytes and neutrophils of 9 Chagas' heart disease subjects with heart failure and 9 without the syndrome in comparison with 11 healthy subjects, by assessing phagocytosis of Saccharomyces cerevisiae and NBT reduction by peripheral blood phagocytes. Phagocytic index of monocytes of chagasics without heart failure was significantly 6.7 and 10.6 times lower than those of controls and chagasics with the congestive syndrome, respectively, due to a lesser engagement in phagocytosis and to an inability of these cells to ingest particles. Neutrophils also show in chagasics without heart failure PI 11.2 and 19.8 times lower than that of controls and chagasics with heart failure, respectively. The percent of NBT reduction was normal and similar for the three groups. Balanced opposite effects of cardiovascular and immune disturbances may be acting in Chagas' disease subjects with heart failure paradoxically recovering the altered phagocytic function.

Chagas disease as a mechanistic model for testing a novel hypothesis

The association between depression and cardiovascular disease is well documented. Nevertheless, the process through which they are linked remains unknown, as does the direction of this relationship. Studies have suggested both that depression is a risk factor for heart disease and that heart disease is a risk factor for depression. A number of studies have established that a relationship exists between depression and inflammation, with alterations in the levels of inflammatory markers (IL-1, IL-6, TNF-alpha and others). Depressive symptoms have also been identified in many diseases characterized by inflammatory processes e.g. rheumatoid arthritis, bronchial asthma, diabetes, tuberculosis and cardiovascular diseases. In this brief viewpoint, we explain and propose how to use Chagas disease, a disorder characterized by inflammatory processes and leading to cardiovascular and autonomic problems, as a model for studying the directionality of the relationship between heart disease and depression.

Insights into the clinical and functional significance of cardiac autonomic dysfunction in Chagas disease

INTRODUCTION: Exclusive or associated lesions in various structures of the autonomic nervous system occur in the chronic forms of Chagas disease. In the indeterminate form, the lesions are absent or mild, whereas in the exclusive or combined heart and digestive disease forms, they are often more pronounced. Depending on their severity these lesions can result mainly in cardiac parasympathetic dysfunction but also in sympathetic dysfunction of variable degrees. Despite the key autonomic effect on cardiovascular functioning, the pathophysiological and clinical significance of the cardiac autonomic dysfunction in Chagas disease remains unknown. METHODS: Review of data on the cardiac autonomic dysfunction in Chagas disease and their potential consequences, and considerations supporting the possible relationship between this disturbance and general or cardiovascular clinical and functional adverse outcomes. RESULTS: We hypothesise that possible consequences that cardiac dysautonomia might variably occasion or predispose in Chagas disease include: transient or sustained arrhythmias, sudden cardiac death, adverse overall and cardiovascular prognosis with enhanced morbidity and mortality, an inability of the cardiovascular system to adjust to functional demands and/or respond to internal or external stimuli by adjusting heart rate and other hemodynamic variables, and immunomodulatory and cognitive disturbances. CONCLUSIONS: Impaired cardiac autonomic modulation in Chagas disease might not be a mere epiphenomenon without significance. Indirect evidences point for a likely important role of this alteration as a primary predisposing or triggering cause or mediator favouring the development of subtle or evident secondary cardiovascular functional disturbances and clinical consequences, and influencing adverse outcomes.

Multiple causes of death related to Chagas' disease in Brazil, 1999 to 2007

INTRODUCTION: Chagas' disease is a major public health problem in Brazil and needs extensive and reliable information to support consistent prevention and control actions. This study describes the most common causes of death associated with deaths related to Chagas' disease (underlying or associated cause of death). METHODS: Mortality data were obtained from the Mortality Information System of the Ministry of Health (approximately 9 million deaths). We analyzed all deaths that occurred in Brazil between 1999 and 2007, where Chagas' disease was mentioned on the death certificate as underlying or associated cause (multiple causes of death). RESULTS: There was a total of 53,930 deaths related to Chagas' disease, 44,543 (82.6%) as underlying cause and 9,387 (17.4%) as associated cause. The main diseases and conditions associated with death by Chagas' disease as underlying cause included direct complications of cardiac involvement, such as conduction disorders/arrhythmias (41.4%) and heart failure (37.7%). Cerebrovascular disease (13.2%), ischemic heart disease (13.2%) and hypertensive diseases (9.3%) were the main underlying causes of deaths in which Chagas' disease was identified as an associated cause. CONCLUSIONS: Cardiovascular diseases were often associated with deaths related to Chagas' disease. Information from multiple causes of death recorded on death certificates allows reconstruction of the natural history of Chagas' disease and suggests preventive and therapeutic potential measures more adequate and specifics.

Ventricular arrhythmias in Chagas disease

Sudden death is one of the most characteristic phenomena of Chagas disease, and approximately one-third of infected patients develop life-threatening heart disease, including malignant ventricular arrhythmias. Fibrotic lesions secondary to chronic cardiomyopathy produce arrhythmogenic substrates that lead to the appearance and maintenance of ventricular arrhythmias. The objective of this study is to discuss the main clinical and epidemiological aspects of ventricular arrhythmias in Chagas disease, the specific workups and treatments for these abnormalities, and the breakthroughs needed to determine a more effective approach to these arrhythmias. A literature review was performed via a search of the PubMed database from 1965 to May 31, 2014 for studies of patients with Chagas disease. Clinical management of patients with chronic Chagas disease begins with proper clinical stratification and the identification of individuals at a higher risk of sudden cardiac death. Once a patient develops malignant ventricular arrhythmia, the therapeutic approach aims to prevent the recurrence of arrhythmias and sudden cardiac death by the use of implantable cardioverter defibrillators, antiarrhythmic drugs, or both. In select cases, invasive ablation of the reentrant circuit causing tachycardia may be useful. Ventricular arrhythmias are important manifestations of Chagas cardiomyopathy. This review highlights the absence of high-quality evidence regarding the treatment of ventricular arrhythmias in Chagas disease. Recognizing high-risk patients who require specific therapies, especially invasive procedures such as the implantation of cardioverter defibrillators and ablative approaches, is a major challenge in clinical practice.

Exercise-induced ventricular arrhythmias and vagal dysfunction in Chagas disease patients with no apparent cardiac involvement

INTRODUCTION : Exercise-induced ventricular arrhythmia (EIVA) and autonomic imbalance are considered as early markers of heart disease in Chagas disease (ChD) patients. The objective of the present study was to verify the differences in the occurrence of EIVA and autonomic maneuver indexes between healthy individuals and ChD patients with no apparent cardiac involvement. METHODS : A total of 75 ChD patients with no apparent cardiac involvement, aged 44.7 (8.5) years, and 38 healthy individuals, aged 44.0 (9.2) years, were evaluated using echocardiography, symptom-limited treadmill exercise testing and autonomic function tests. RESULTS : The occurrence of EIVA was higher in the chagasic group (48%) than in the control group (23.7%) during both the effort and the recovery phases. Frequent ventricular contractions occurred only in the patient group. Additionally, the respiratory sinus arrhythmia index was significantly lower in the chagasic individuals compared with the control group. CONCLUSIONS : ChD patients with no apparent cardiac involvement had a higher frequency of EIVA as well as more vagal dysfunction by respiratory sinus arrhythmia. These results suggest that even when asymptomatic, ChD patients possess important arrhythmogenic substrates and subclinical disease.

Pediatric cardiac postoperative care

The Heart Institute of the University of São Paulo, Medical School is a referral center for the treatment of congenital heart diseases of neonates and infants. In the recent years, the excellent surgical results obtained in our institution may be in part due to modern anesthetic care and to postoperative care based on well-structured protocols. The purpose of this article is to review unique aspects of neonate cardiovascular physiology, the impact of extracorporeal circulation on postoperative evolution, and the prescription for pharmacological support of acute cardiac dysfunction based on our cardiac unit protocols. The main causes of low cardiac output after surgical correction of heart congenital disease are reviewed, and methods of treatment and support are proposed as derived from the relevant literature and our protocols.

Heart transplantation in neonates and children. Intermediate-term results

OBJECTIVE: To assess intermediate-term outcome in children who have undergone orthotopic heart transplantation. METHODS: We carried out a longitudinal and prospective study between October '92 and June '99 comprising 20 patients with ages ranging from 12 days to 7 years (mean of 2.8 years). We employed a double immunosuppression protocol with cyclosporine and azathioprine and induction therapy with polyclonal antithymocyte serum. Survival and complications resulting from the immunosuppression protocol were analyzed. RESULTS:The double immunosuppression protocol and the induction therapy with polyclonal antithymocyte serum resulted in an actuarial survival curve of 90% and 78.2% at 1 and 6 years, respectively, with a mean follow-up period of 3.6 years. One patient died due to acute rejection 40 days after transplantation; another patient died 2 years after transplantation due to lymphoproliferative disorder; a third patient died because of primary failure of the graft; and a fourth patient died due to bronchopneumonia. The major complications were as follows: acute rejection, infection, nephrotoxicity, and systemic hypertension. The means of rejection and infection episodes per patient were 2.9 and 3.4, respectively. After one year of transplantation, a slight reduction in the creatinine clearance and systemic hypertension were observed in 7 (38.9%) patients. CONCLUSION: Heart transplantation made life possible for those patients with complex congenital heart diseases and cardiomyopathies in refractory congestive heart failure constituting a therapeutical option for this group of patients in the terminal phase.

Mortality due to cardiovascular disease in women during the reproductive age (15 to 49 years), in the State of São Paulo, Brazil, from 1991 to 1995

OBJECTIVE: To describe mortality due to cardiovascular diseases in women during the reproductive age (15 to 49 years) in the state of São Paulo, Brazil, from 1991 to 1995. METHODS: A list of all deaths and their underlying causes, coded according to the International Classification of Diseases, 9th revision, multiple causes of death, and estimates of the female population according to age groups were provided by the SEADE Foundation. Specific coefficients for 100 thousand women for each year as well as the medians of these coefficients related to 5 years, and the percentage of death by subgroups were calculated. RESULTS: Cerebrovascular diseases have the highest coefficients (14.24 for 100 thousand females), followed by ischemic heart disease (7.37), other heart diseases (6.39), hypertensive disease (3.03), chronic rheumatic heart disease (1.58), pulmonary vascular diseases (1.29), and active rheumatic fever (0.05). Systemic arterial hypertension, as an associated cause, occurred in 55.3% to 57.8% of all the deaths due to intracerebral hemorrhage and in 30.4% to 30.8% due to subarachnoid hemorrhage. CONCLUSION: The significance of cerebrovascular diseases, coronary artery disease, and systemic arterial hypertension as causes of mortality suggests the need to emphasize preventive actions for young women who have the potential to reproduce to avoid possible complications in future pregnancies, and premature mortality.

Catecholaminergic polymorphic ventricular tachycardia. An important diagnosis in children with syncope and normal heart

Syncope in children is primarily related to vagal hyperreactivity, but ventricular tachycardia (VT) way rarely be seen. Catecholaminergic polymorphic VT is a rare entity that can occur in children without heart disease and with a normal QT interval, which may cause syncope and sudden cardiac death. In this report, we describe the clinical features, treatment, and clinical follow-up of three children with syncope associated with physical effort or emotion and cathecolaminergic polymorphic VT. Symptoms were controlled with beta-blockers, but one patient died suddenly in the fourth year of follow-up. Despite the rare occurrence, catecholaminergic polymorphic VT is an important cause of syncope and sudden death in children with no identified heart disease and normal QT interval.

Lipid profile of nutrition students and its association with cardiovascular disease risk factors

OBJECTIVE: To describe the lipid profile and to verify its relationship with cardiovascular disease risk factors in students at a public university in São Paulo. METHODS: After obtaining clinical, anthropomorphic, and lipid profile data from 118 students, variables of the lipid profile were related to other risk factors. RESULTS: The mean age of the students was 20.3 years (SD=1.5). The risk of cardiovascular disease was characterized by a positive family history of ischemic heart disease in 38.9%; sedentariness in 35.6%; limiting and increased total and LDL-C cholesterol levels in 17.7% and 10.2%, respectively; decreased HDL-C levels in 11.1%; increased triglyceride levels in 11.1%; body mass index >25 in 8.5%, and smoking in 6.7% of the subjects. Students' diet was found to be inadequate regarding protein, total fat, saturated fat, sodium, and fiber contents. A statistically significant association between cholesterol and contraceptive use, between HDL-C and contraceptive use, age and percent body fat, and triglycerides and percent lean weight was observed. CONCLUSION: A high prevalence of some risk factors of cardiovascular disease as well as the association between these factors with altered lipid profiles was observed in the young population studied.

Prevalencia das Doencas Cardiacas Ilustrada em 60 Anos dos Arquivos Brasileiros de Cardiologia

Considerando a relevância histórica e acadêmica dos Arquivos Brasileiros de Cardiologia, posto que sua indexação no MEDLINE iniciou-se em 1950, assumiu-se como hipótese que a análise das publicações de 60 anos poderia refletir as tendências evolutivas das doenças cardíacas no Brasil. Os dados do trabalho foram coletados com um programa desenvolvido para a finalidade, tornando possível a extração automática das informações do banco de dados MEDLINE. As informações do trabalho foram coletadas pesquisando-se "Arquivos Brasileiros de Cardiologia AND parâmetro selecionado em inglês". Foram arbitrados quatro grupos observacionais: (1) principais grupos de doenças do coração (doença arterial coronariana, valvulopatia cardíaca, cardiopatias congênitas e cardiomiopatias); (2) doenças relevantes na prática clínica (arritmias cardíacas, Cor Pulmonale, infarto do miocárdio e insuficiência cardíaca congestiva); (3) fatores de risco cardiovascular (hipertensão arterial, diabete, dislipidemia e aterosclerose), e; (4) grupo arbitrado em função da evolução crescente das publicações sobre insuficiência cardíaca congestiva constadas nos grupos anteriores (insuficiência cardíaca congestiva, infarto do miocárdio, cardiopatia reumática e cardiopatia chagásica). Foram descritas todas as publicações dentro dos grupos estabelecidos, ressaltando-se o crescente aumento da insuficiência cardíaca e do diabete como fatores de risco. Foi possível um levantamento relativamente fácil, com auxílio do programa de computação desenvolvido para a pesquisa bibliográfica de seis décadas. Ressaltando-se as limitações do estudo, sugere-se a existência de um elo epidemiológico entre as doenças cardiológicas prevalentes no Brasil e as publicações dos Arquivos Brasileiros de Cardiologia.