Marcos R Sousa | UFMG (original) (raw)

Papers by Marcos R Sousa

ISRN Cardiology, 2014

Objectives. Assess the impact of associating thrombolytics, anticoagulants, antiplatelets, and pr... more Objectives. Assess the impact of associating thrombolytics, anticoagulants, antiplatelets, and primary angioplasty (PA) on death, reinfarction (AMI), and major bleeding (MB) in STEMI therapy.Methods. Medline search was performed to identify randomized trials comparing these classes in STEMI treatment, at least 500 patients, providing death, AMI, and MB rates. Similar arms were grouped. Correlation between number of drugs and PA and the outcomes was evaluated, as well as correlation between the year of the study and the outcomes.Results. Fifty-nine papers remained after exclusions. 404.556 patients were divided into 35 groups of arms. There was correlation between the number of drugs and rates of death (r=-0.466,P=0.005) and MB (r=0.403,P=0.016), confirmed by multivariate regression. This model also showed that PA is associated with lower mortality and increased MB. Year and period of publication correlated with the outcomes: death (r=-0.380,P<0.001), MB (r=0.212,P=0.014), and AMI...

Systematic Reviews, 2012

Background: The role of intravascular ultrasound (IVUS) in percutaneous coronary interventions (P... more Background: The role of intravascular ultrasound (IVUS) in percutaneous coronary interventions (PCI) is still controversial despite several previously published meta-analyses. A meta-analysis to evaluate the controversial role of IVUS-guided PCI with bare-metal stenting was performed and a previous published meta-analysis was re-evaluated in order to clarify the discrepancy between results of these studies. Methods: A systematic review was performed by an electronic search of the PubMed, Embase and Web of Knowledge databases and by a manual search of reference lists for randomized controlled trials published until April 2011, with clinical outcomes and, at least, six months of clinical follow-up. A meta-analysis based on the intention to treat was performed with the selected studies. Results: Five studies and 1,754 patients were included. There were no differences in death (OR = 1.86; 95% CI = 0.88-3.95; p = 0.10), non-fatal myocardial infarction (OR = 0.65; 95% CI = 0.27-1.58; p = 0.35) and major adverse cardiac events (OR = 0.74; 95% CI = 0.49-1.13; p = 0.16). An analysis of the previous published meta-analysis strongly suggested the presence of publication bias. Conclusions: There is no evidence to recommend routine IVUS-guided PCI with bare-metal stent implantation. This may be explained by the paucity and heterogeneity of the studies published so far.

Journal of Thrombosis and Haemostasis, 2014

Arquivos Brasileiros de Cardiologia, 2012

We would like to congratulate the authors of the study: "Intracoronary ultrasound-guided stenting... more We would like to congratulate the authors of the study: "Intracoronary ultrasound-guided stenting improves outcomes: a meta-analysis of randomized trials" 1 and make the following comments:

Arquivos Brasileiros de Cardiologia, 2011

I Diretriz da Sociedade Brasileira de Cardiologia sobre Processos e Competências para a Formação ... more I Diretriz da Sociedade Brasileira de Cardiologia sobre Processos e Competências para a Formação em Cardiologia no Brasil Realização Sociedade Brasileira de Cardiologia, com a participação dos Departamentos Científicos e da Comissão Julgadora do Título de Especialista (CJTEC) CooRdenadoR de noRmatizações e diRetRizes da sBC

The American Journal of Cardiology, 2002

Beta slope is a nonlinear index derived from the powerlaw analysis of 24-hour heart rate variabil... more Beta slope is a nonlinear index derived from the powerlaw analysis of 24-hour heart rate variability (HRV); in healthy subjects, the ␤ index is typically near ؊1, suggesting a fractal behavior of HRV. There is scarce data on HRV in Chagas' disease. This transversal study intends to describe power-law and linear HRV patterns in different forms of Chagas' disease. Patients and healthy controls (n ‫؍‬ 26) without other diseases were submitted to a standardized protocol, including electrocardiography, echocardiography, and 24-hour Holter monitoring. Patients with Chagas' disease were divided into groups according to their left ventricular (LV) systolic function: normal (group 1, n ‫؍‬ 85), segmental abnormalities (group 2, n ‫؍‬ 49), and reduced ejection fraction (group 3, n ‫؍‬ 26). The temporal series were carefully processed to obtain the HRV indexes and ␤ slope. Despite the differences in the LV systolic function, the 3 groups were comparable in terms of long-term HRV index values. After adjustment for covariates, short-term HRV index values were consistently reduced in the Chagas' disease groups. The ␤-index values were also diminished in Chagas' disease groups (group 1: ؊1.09 ؎ 0.03, group 2: ؊1.11 ؎ 0.06; group 3: ؊1.14 ؎ 0.03; and controls: 0.95 ؎ 0.03, p <0.001). This breakdown of fractal long-range correlation of RR interval dynamics, a strong predictor of mortality in other cardiomyopathies, may reflect cardiac dysautonomia that may have gone undetected in long-term time-domain analysis. This abnormality may explain the increased risk for arrhythmic sudden death found in Chagas' disease even in the absence of signs of LV dysfunction. ᮊ2002 by Excerpta Medica, Inc.

The American Journal of Tropical Medicine and Hygiene, 2013

The aim of this study was to evaluate the accuracy of invasive and non-invasive tests for diagnos... more The aim of this study was to evaluate the accuracy of invasive and non-invasive tests for diagnosis of visceral leishmaniasis (VL) in a large series of human immunodeficiency virus (HIV)-infected patients. In this delayedtype cross-sectional study, 113 HIV-infected symptomatic patients were evaluated by an adjudication committee after clinical follow-up to establish the presence or absence of VL as the target condition (reference test). The index tests were recombinant K39 antigen-based immunochromatographic test (rK39), indirect fluorescent antibody test (IFAT), prototype kit of direct agglutination test (DAT-LPC), and real-time polymerase chain reaction (qPCR) in peripheral blood. Compared with parasitological test and adjudication committee diagnosis or latent class model analyses, IFAT and rk39 dipstick test presented the lowest sensitivity. DAT-LPC exhibited good overall performance, and there was no statistical difference between DAT-LPC and qPCR diagnosis accuracy. Real-time PCR emerges as a less invasive alternative to parasitological examination for confirmation of cases not identified by DAT.

Journal of Cardiovascular Electrophysiology, 2021

Current guidelines recommend at least one attempt of defibrillator antitachycardia pacing (ATP) t... more Current guidelines recommend at least one attempt of defibrillator antitachycardia pacing (ATP) therapy, showing preference for burst therapy. The objective of this study is to compare ramp versus burst ATP therapy proportion of success and acceleration in treating spontaneous or induced ventricular tachycardia (VT). The review protocol was previously published in PROSPERO. Data synthesis and measures of heterogeneity (I2) was performed by CMA® software v.3 comparing proportions in both groups. Sensitivity analysis was performed as subgroup or meta‐regression according to quality, clinical characteristics, and differences in design. Thirteen studies including 30,117 VT episodes in 1672 patients were analyzed. There was no significant difference in the proportion of success between burst and ramp therapy in spontaneous VT (odds ratio = 1.116; 95% confidence interval [CI] = 0.788–1.579; I2 = 89%). There was no significant difference in the proportion of success between burst and ramp therapy in induced VT (odds ratio = 0.820; 95% CI = 0.468–1.437; I2 = 93%). No significant difference was found in the proportion of acceleration between burst and ramp in spontaneous VT (odds ratio = 0.792; 95% CI = 0.476–1.317; I2 = 83%). No significant difference was found in the proportion of acceleration between burst and ramp in induced VT (odds ratio = 1.234; 95% CI = 0.802–1.898; I2 = 55%). Sensitivity analysis did not change main results. There is no difference in success or in acceleration proportion between burst or ramp ATP therapy irrespective if the VT was spontaneous or induced. Future implantable cardioverter defibrillator programming guidelines should offer both ATP therapies without preference in one of them.

A correction to this paper has been published: https://doi.org/10.1007/s00592-021-01689-8.

Acta Diabetologica, 2020

Aims To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combinati... more Aims To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of JNC 7 Stage I hypertension in patients with type 2 diabetes mellitus. Methods In an a priori subgroup analysis of a randomized, double-blind, controlled trial, volunteers aged 30–70 years, with stage I hypertension and diabetes mellitus , were randomized to 12.5/2.5 mg of chlorthalidone/amiloride ( N = 47) or 50 mg of losartan ( N = 50), and followed for 18 months in 21 clinical centers. If BP remained uncontrolled after three months, study medication dose was doubled, and if uncontrolled after six months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg BID) were added as open label drugs in a progressive fashion. Results Systolic BP decreased to a greater extent in participants allocated to diuretics compared to losartan ( P < 0.001). After 18 months of follow-up, systolic BP was 128.4 ± 10.3 mmHg in the diuretic group versus 133.5 ± 8.0 in the losartan group ( P < 0.01). In the diuretic group, 36 out of 43 participants (83.7%) had a JNC 7 normal BP, compared to 31/47 (66%) in the losartan group ( P = 0.089). Serum cholesterol was higher in the diuretic arm at the end of the trial. Other biochemical parameters and reports of adverse events did not differ by treatment. Conclusions Treatment of hypertension based on a combination of chlorthalidone and amiloride is more effective for BP lowering compared to losartan in patients with diabetes mellitus and hypertension. Trial registration Clinical trials registration number: NCT00971165

Journal of hypertension, Jan 7, 2017

To determine the effectiveness of low-dose diuretic therapy to achieve an optimal level of blood ... more To determine the effectiveness of low-dose diuretic therapy to achieve an optimal level of blood pressure (BP) in adults with prehypertension. The PREVER-prevention trial was a randomized, parallel, double-blinded, placebo-controlled trial, with 18 months of follow-up, conducted at 21 academic medical centers in Brazil. Of 1772 individuals evaluated for eligibility, 730 volunteers with prehypertension who were aged 30-70 years, and who did not reach optimal blood pressure after 3 months of lifestyle intervention, were randomized to a fixed association of chlorthalidone 12.5 mg and amiloride 2.5 mg or placebo once a day. The main outcomes were the percentage of participants who achieved an optimal level of BP. A total of 372 participants were randomly allocated to diuretics and 358 to placebo. After 18 months of treatment, optimal BP was noted in 25.6% of the diuretic group and 19.3% in the placebo group (P < 0.05). The mean net reduction in SBP and DBP for the diuretic group comp...

Journal of the American Heart Association, Dec 13, 2016

Prehypertension is associated with higher cardiovascular risk, target organ damage, and incidence... more 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. 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...

Journal of Hypertension, 2016

Objectives: To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride co... more Objectives: To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of stage I hypertension. Methods: In a randomized, double-blind, controlled trial, 655 participants were followed for 18 months in 21 Brazilian academic centers. Trial participants were adult volunteers aged 30-70 years with stage I hypertension (BP 140-159 or 90-99 mmHg) following 3 months of a lifestyle intervention. Participants were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (N ¼ 333) or 50 mg of losartan (N ¼ 322). If BP remained uncontrolled after 3 months, study medication dose was doubled, and if uncontrolled after 6 months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg twice daily) were added as open-label drugs in a progressive fashion. At the end of follow-up, 609 (93%) participants were evaluated. Results: The difference in SBP during 18 months of follow-up was 2.3 (95% confidence interval: 1.2 to 3.3) mmHg favoring chlorthalidone/amiloride. Compared with those randomized to diuretic, more participants allocated to losartan had their initial dose doubled and more of them used add-on antihypertensive medication. Levels of blood glucose, glycosilated hemoglobin, and incidence of diabetes were no different between the two treatment groups. Serum potassium was lower and serum cholesterol was higher in the diuretic arm. Microalbuminuria tended to be higher in patients with diabetes allocated to losartan (28.5 AE 40.4 versus 16.2 AE 26.7 mg, P ¼ 0.09). Conclusion: Treatment with a combination of chlorthalidone and amiloride compared with losartan yielded a greater reduction in BP. Clinical trials registration number: NCT00971165.

Trials, 2011

Background: Cardiovascular disease is the leading cause of death in Brazil, and hypertension is i... more Background: Cardiovascular disease is the leading cause of death in Brazil, and hypertension is its major risk factor. The benefit of its drug treatment to prevent major cardiovascular events was consistently demonstrated. Angiotensin-receptor blockers (ARB) have been the preferential drugs in the management of hypertension worldwide, despite the absence of any consistent evidence of advantage over older agents, and the concern that they may be associated with lower renal protection and risk for cancer. Diuretics are as efficacious as other agents, are well tolerated, have longer duration of action and low cost, but have been scarcely compared with ARBs. A study comparing diuretic and ARB is therefore warranted. Methods/design: This is a randomized, double-blind, clinical trial, comparing the association of chlorthalidone and amiloride with losartan as first drug option in patients aged 30 to 70 years, with stage I hypertension. The primary outcomes will be variation of blood pressure by time, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new subclinical atherosclerosis and sudden death. The study will last 18 months. The sample size will be of 1200 participants for group in order to confer enough power to test for all primary outcomes. The project was approved by the Ethics committee of each participating institution. Discussion: The putative pleiotropic effects of ARB agents, particularly renal protection, have been disputed, and they have been scarcely compared with diuretics in large clinical trials, despite that they have been at least as efficacious as newer agents in managing hypertension. Even if the null hypothesis is not rejected, the information will be useful for health care policy to treat hypertension in Brazil.

Trials, 2011

Background: Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk... more Background: Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a populationbased intervention to prevent the incidence of hypertension and the development of target-organ damage. Methods: This is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution.

PLoS Neglected Tropical Diseases, 2011

Background and Objectives: Visceral leishmaniasis (VL) is a common complication in AIDS patients ... more Background and Objectives: Visceral leishmaniasis (VL) is a common complication in AIDS patients living in Leishmaniaendemic areas. Although antiretroviral therapy has changed the clinical course of HIV infection and its associated illnesses, the prevention of VL relapses remains a challenge for the care of HIV and Leishmania co-infected patients. This work is a systematic review of previous studies that have described predictors of VL relapse in HIV-infected patients. Review Methods: We searched the electronic databases of MEDLINE, LILACS, and the Cochrane Central Register of Controlled Trials. Studies were selected if they included HIV-infected individuals with a VL diagnosis and patient follow-up after the leishmaniasis treatment with an analysis of the clearly defined outcome of prediction of relapse. Results: Eighteen out 178 studies satisfied the specified inclusion criteria. Most patients were males between 30 and 40 years of age, and HIV transmission was primarily via intravenous drug use. Previous VL episodes were identified as risk factors for relapse in 3 studies. Two studies found that baseline CD4+ T cell count above 100 cells/mL was associated with a decreased relapse rate. The observation of an increase in CD4+ T cells at patient follow-up was associated with protection from relapse in 5 of 7 studies. Meta-analysis of all studies assessing secondary prophylaxis showed significant reduction of VL relapse rate following prophylaxis. None of the five observational studies evaluating the impact of highly active antiretroviral therapy use found a reduction in the risk of VL relapse upon patient follow-up. Conclusion: Some predictors of VL relapse could be identified: a) the absence of an increase in CD4+ cells at follow-up; b) lack of secondary prophylaxis; and c) previous history of VL relapse. CD4+ counts below 100 cells/mL at the time of primary VL diagnosis may also be a predictive factor for VL relapse.

PLoS Neglected Tropical Diseases, 2012

Background: Human visceral leishmaniasis (VL), a potentially fatal disease, has emerged as an imp... more Background: Human visceral leishmaniasis (VL), a potentially fatal disease, has emerged as an important opportunistic condition in HIV infected patients. In immunocompromised patients, serological investigation is considered not an accurate diagnostic method for VL diagnosis and molecular techniques seem especially promising. Objective: This work is a comprehensive systematic review and meta-analysis to evaluate the accuracy of serologic and molecular tests for VL diagnosis specifically in HIV-infected patients. Methods: Two independent reviewers searched PubMed and LILACS databases. The quality of studies was assessed by QUADAS score. Sensitivity and specificity were pooled separately and compared with overall accuracy measures: diagnostic odds ratio (DOR) and symmetric summary receiver operating characteristic (sROC). Results: Thirty three studies recruiting 1,489 patients were included. The following tests were evaluated: Immunofluorescence Antibody Test (IFAT), Enzyme linked immunosorbent assay (ELISA), immunoblotting (Blot), direct agglutination test (DAT) and polimerase chain reaction (PCR) in whole blood and bone marrow. Most studies were carried out in Europe. Serological tests varied widely in performance, but with overall limited sensitivity. IFAT had poor sensitivity ranging from 11% to 82%. DOR (95% confidence interval) was higher for DAT 36.01 (9.95-130.29) and Blot 27.51 (9.27-81.66) than for IFAT 7.43 (3.08-1791) and ELISA 3.06 (0.71-13.10). PCR in whole blood had the highest DOR: 400.35 (58.47-2741.42). The accuracy of PCR based on Q-point was 0.95; 95%CI 0.92-0.97, which means good overall performance. Conclusion: Based mainly on evidence gained by infection with Leishmania infantum chagasi, serological tests should not be used to rule out a diagnosis of VL among the HIV-infected, but a positive test at even low titers has diagnostic value when combined with the clinical case definition. Considering the available evidence, tests based on DNA detection are highly sensitive and may contribute to a diagnostic workup.

PLoS Neglected Tropical Diseases, 2014

Background: Visceral leishmaniasis (VL) is an emerging condition affecting HIV-infected patients ... more Background: Visceral leishmaniasis (VL) is an emerging condition affecting HIV-infected patients living in Latin America, particularly in Brazil. Leishmania-HIV coinfection represents a challenging diagnosis because the clinical picture of VL is similar to that of other disseminated opportunistic diseases. Additionally, coinfection is related to treatment failure, relapse and high mortality. Objective: To assess the clinical-laboratory profile and outcomes of VL-HIV-coinfected patients using a group of non HIVinfected patients diagnosed with VL during the same period as a comparator. Methods: The study was conducted at a reference center for infectious diseases in Brazil. All patients with suspected VL were evaluated in an ongoing cohort study. Confirmed cases were divided into two groups: with and without HIV coinfection. Patients were treated according to the current guidelines of the Ministry of Health of Brazil, which considers antimony as the first-choice therapy for non HIV-infected patients and recommends amphotericin B for HIV-infected patients. After treatment, all patients with CD4 counts below 350 cells/mm 3 received secondary prophylaxis with amphotericin B. Results: Between 2011 and 2013, 168 patients with suspected VL were evaluated, of whom 90 were confirmed to have VL. In total, 51% were HIV coinfected patients (46 patients). HIV-infected patients had a lower rate of fever and splenomegaly compared with immunocompetent patients. The VL relapse rate in 6 months was 37% among HIV-infected patients, despite receiving secondary prophylaxis. The overall case-fatality rate was 6.6% (4 deaths in the HIV-infected group versus 2 deaths in the non HIV-infected group). The main risk factors for a poor outcome at 6 months after the end of treatment were HIV infection, bleeding and a previous VL episode. Conclusion: Although VL mortality rates among HIV-infected individuals are close to those observed among immunocompetent patients treated with amphotericin B, HIV coinfection is related to a low clinical response and high relapse rates within 6 months.

PLoS Neglected Tropical Diseases, 2013

Objective: We conducted a systematic literature review with indirect comparison of studies evalua... more Objective: We conducted a systematic literature review with indirect comparison of studies evaluating therapeutic efficacy and toxicity associated to visceral leishmaniasis (VL) therapy among HIV infected individuals. Main outcome measurements: The outcomes of interest were clinical and parasitological cure, mortality, and adverse events. Methods: PRISMA guidelines for systematic reviews and Cochrane manual were followed. Sources were MEDLINE, LILACS, EMBASE, Web of Knowledge databases and manual search of references from evaluated studies. We included all studies reporting outcomes after VL treatment, regardless of their design. Study quality was evaluated systematically by using the Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Comprehensive Meta-Analysis software v.2.2.048 was used to perform one-group meta-analysis of study arms with the same drug to estimate global rates of success and adverse events with each drug. These estimates were used, when possible, to indirectly compare treatment options, adjusted for CD4 count. Direct comparison was pooled when available. Results: Seventeen studies reporting five treatment regimens and outcome of 920 VL episodes occurring in HIV infected individuals were included. The main outstanding difference in outcome among the treatment regimens was observed in mortality rate: it was around 3 times higher with high-dose antimony use (18.4%, CI 95% 13.3-25%), indirectly compared to lipid formulations of amphotericin B treatment (6.1%, CI 95% 3.9-9.4%). It was observed, also by indirect comparison, higher rates of clinical improvement in study arms using amphotericin B than in study arms using pentavalent antimonial therapy (Sb v). The parasitological cure, an outcome that presented some degree of risk of selection and verification bias, had rates that varied widely within the same treatment arm, with high heterogeneity, hampering any formal comparison among drugs. One direct comparison of amphotericin and antimoniate was possible combining results of two studies and confirming the superiority of amphotericin. Conclusions: Available evidence suggests that amphotericin is superior to antimony treatment. Death rate using antimoniate high dose is unacceptably high. Randomized controlled trials are necessary to compare different formulations and doses of amphotericin, alternative therapies and drug combinations.

ISRN Cardiology, 2014

Objectives. Assess the impact of associating thrombolytics, anticoagulants, antiplatelets, and pr... more Objectives. Assess the impact of associating thrombolytics, anticoagulants, antiplatelets, and primary angioplasty (PA) on death, reinfarction (AMI), and major bleeding (MB) in STEMI therapy.Methods. Medline search was performed to identify randomized trials comparing these classes in STEMI treatment, at least 500 patients, providing death, AMI, and MB rates. Similar arms were grouped. Correlation between number of drugs and PA and the outcomes was evaluated, as well as correlation between the year of the study and the outcomes.Results. Fifty-nine papers remained after exclusions. 404.556 patients were divided into 35 groups of arms. There was correlation between the number of drugs and rates of death (r=-0.466,P=0.005) and MB (r=0.403,P=0.016), confirmed by multivariate regression. This model also showed that PA is associated with lower mortality and increased MB. Year and period of publication correlated with the outcomes: death (r=-0.380,P<0.001), MB (r=0.212,P=0.014), and AMI...

Systematic Reviews, 2012

Background: The role of intravascular ultrasound (IVUS) in percutaneous coronary interventions (P... more Background: The role of intravascular ultrasound (IVUS) in percutaneous coronary interventions (PCI) is still controversial despite several previously published meta-analyses. A meta-analysis to evaluate the controversial role of IVUS-guided PCI with bare-metal stenting was performed and a previous published meta-analysis was re-evaluated in order to clarify the discrepancy between results of these studies. Methods: A systematic review was performed by an electronic search of the PubMed, Embase and Web of Knowledge databases and by a manual search of reference lists for randomized controlled trials published until April 2011, with clinical outcomes and, at least, six months of clinical follow-up. A meta-analysis based on the intention to treat was performed with the selected studies. Results: Five studies and 1,754 patients were included. There were no differences in death (OR = 1.86; 95% CI = 0.88-3.95; p = 0.10), non-fatal myocardial infarction (OR = 0.65; 95% CI = 0.27-1.58; p = 0.35) and major adverse cardiac events (OR = 0.74; 95% CI = 0.49-1.13; p = 0.16). An analysis of the previous published meta-analysis strongly suggested the presence of publication bias. Conclusions: There is no evidence to recommend routine IVUS-guided PCI with bare-metal stent implantation. This may be explained by the paucity and heterogeneity of the studies published so far.

Journal of Thrombosis and Haemostasis, 2014

Arquivos Brasileiros de Cardiologia, 2012

We would like to congratulate the authors of the study: "Intracoronary ultrasound-guided stenting... more We would like to congratulate the authors of the study: "Intracoronary ultrasound-guided stenting improves outcomes: a meta-analysis of randomized trials" 1 and make the following comments:

Arquivos Brasileiros de Cardiologia, 2011

I Diretriz da Sociedade Brasileira de Cardiologia sobre Processos e Competências para a Formação ... more I Diretriz da Sociedade Brasileira de Cardiologia sobre Processos e Competências para a Formação em Cardiologia no Brasil Realização Sociedade Brasileira de Cardiologia, com a participação dos Departamentos Científicos e da Comissão Julgadora do Título de Especialista (CJTEC) CooRdenadoR de noRmatizações e diRetRizes da sBC

The American Journal of Cardiology, 2002

Beta slope is a nonlinear index derived from the powerlaw analysis of 24-hour heart rate variabil... more Beta slope is a nonlinear index derived from the powerlaw analysis of 24-hour heart rate variability (HRV); in healthy subjects, the ␤ index is typically near ؊1, suggesting a fractal behavior of HRV. There is scarce data on HRV in Chagas' disease. This transversal study intends to describe power-law and linear HRV patterns in different forms of Chagas' disease. Patients and healthy controls (n ‫؍‬ 26) without other diseases were submitted to a standardized protocol, including electrocardiography, echocardiography, and 24-hour Holter monitoring. Patients with Chagas' disease were divided into groups according to their left ventricular (LV) systolic function: normal (group 1, n ‫؍‬ 85), segmental abnormalities (group 2, n ‫؍‬ 49), and reduced ejection fraction (group 3, n ‫؍‬ 26). The temporal series were carefully processed to obtain the HRV indexes and ␤ slope. Despite the differences in the LV systolic function, the 3 groups were comparable in terms of long-term HRV index values. After adjustment for covariates, short-term HRV index values were consistently reduced in the Chagas' disease groups. The ␤-index values were also diminished in Chagas' disease groups (group 1: ؊1.09 ؎ 0.03, group 2: ؊1.11 ؎ 0.06; group 3: ؊1.14 ؎ 0.03; and controls: 0.95 ؎ 0.03, p <0.001). This breakdown of fractal long-range correlation of RR interval dynamics, a strong predictor of mortality in other cardiomyopathies, may reflect cardiac dysautonomia that may have gone undetected in long-term time-domain analysis. This abnormality may explain the increased risk for arrhythmic sudden death found in Chagas' disease even in the absence of signs of LV dysfunction. ᮊ2002 by Excerpta Medica, Inc.

The American Journal of Tropical Medicine and Hygiene, 2013

The aim of this study was to evaluate the accuracy of invasive and non-invasive tests for diagnos... more The aim of this study was to evaluate the accuracy of invasive and non-invasive tests for diagnosis of visceral leishmaniasis (VL) in a large series of human immunodeficiency virus (HIV)-infected patients. In this delayedtype cross-sectional study, 113 HIV-infected symptomatic patients were evaluated by an adjudication committee after clinical follow-up to establish the presence or absence of VL as the target condition (reference test). The index tests were recombinant K39 antigen-based immunochromatographic test (rK39), indirect fluorescent antibody test (IFAT), prototype kit of direct agglutination test (DAT-LPC), and real-time polymerase chain reaction (qPCR) in peripheral blood. Compared with parasitological test and adjudication committee diagnosis or latent class model analyses, IFAT and rk39 dipstick test presented the lowest sensitivity. DAT-LPC exhibited good overall performance, and there was no statistical difference between DAT-LPC and qPCR diagnosis accuracy. Real-time PCR emerges as a less invasive alternative to parasitological examination for confirmation of cases not identified by DAT.

Journal of Cardiovascular Electrophysiology, 2021

Current guidelines recommend at least one attempt of defibrillator antitachycardia pacing (ATP) t... more Current guidelines recommend at least one attempt of defibrillator antitachycardia pacing (ATP) therapy, showing preference for burst therapy. The objective of this study is to compare ramp versus burst ATP therapy proportion of success and acceleration in treating spontaneous or induced ventricular tachycardia (VT). The review protocol was previously published in PROSPERO. Data synthesis and measures of heterogeneity (I2) was performed by CMA® software v.3 comparing proportions in both groups. Sensitivity analysis was performed as subgroup or meta‐regression according to quality, clinical characteristics, and differences in design. Thirteen studies including 30,117 VT episodes in 1672 patients were analyzed. There was no significant difference in the proportion of success between burst and ramp therapy in spontaneous VT (odds ratio = 1.116; 95% confidence interval [CI] = 0.788–1.579; I2 = 89%). There was no significant difference in the proportion of success between burst and ramp therapy in induced VT (odds ratio = 0.820; 95% CI = 0.468–1.437; I2 = 93%). No significant difference was found in the proportion of acceleration between burst and ramp in spontaneous VT (odds ratio = 0.792; 95% CI = 0.476–1.317; I2 = 83%). No significant difference was found in the proportion of acceleration between burst and ramp in induced VT (odds ratio = 1.234; 95% CI = 0.802–1.898; I2 = 55%). Sensitivity analysis did not change main results. There is no difference in success or in acceleration proportion between burst or ramp ATP therapy irrespective if the VT was spontaneous or induced. Future implantable cardioverter defibrillator programming guidelines should offer both ATP therapies without preference in one of them.

A correction to this paper has been published: https://doi.org/10.1007/s00592-021-01689-8.

Acta Diabetologica, 2020

Aims To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combinati... more Aims To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of JNC 7 Stage I hypertension in patients with type 2 diabetes mellitus. Methods In an a priori subgroup analysis of a randomized, double-blind, controlled trial, volunteers aged 30–70 years, with stage I hypertension and diabetes mellitus , were randomized to 12.5/2.5 mg of chlorthalidone/amiloride ( N = 47) or 50 mg of losartan ( N = 50), and followed for 18 months in 21 clinical centers. If BP remained uncontrolled after three months, study medication dose was doubled, and if uncontrolled after six months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg BID) were added as open label drugs in a progressive fashion. Results Systolic BP decreased to a greater extent in participants allocated to diuretics compared to losartan ( P < 0.001). After 18 months of follow-up, systolic BP was 128.4 ± 10.3 mmHg in the diuretic group versus 133.5 ± 8.0 in the losartan group ( P < 0.01). In the diuretic group, 36 out of 43 participants (83.7%) had a JNC 7 normal BP, compared to 31/47 (66%) in the losartan group ( P = 0.089). Serum cholesterol was higher in the diuretic arm at the end of the trial. Other biochemical parameters and reports of adverse events did not differ by treatment. Conclusions Treatment of hypertension based on a combination of chlorthalidone and amiloride is more effective for BP lowering compared to losartan in patients with diabetes mellitus and hypertension. Trial registration Clinical trials registration number: NCT00971165

Journal of hypertension, Jan 7, 2017

To determine the effectiveness of low-dose diuretic therapy to achieve an optimal level of blood ... more To determine the effectiveness of low-dose diuretic therapy to achieve an optimal level of blood pressure (BP) in adults with prehypertension. The PREVER-prevention trial was a randomized, parallel, double-blinded, placebo-controlled trial, with 18 months of follow-up, conducted at 21 academic medical centers in Brazil. Of 1772 individuals evaluated for eligibility, 730 volunteers with prehypertension who were aged 30-70 years, and who did not reach optimal blood pressure after 3 months of lifestyle intervention, were randomized to a fixed association of chlorthalidone 12.5 mg and amiloride 2.5 mg or placebo once a day. The main outcomes were the percentage of participants who achieved an optimal level of BP. A total of 372 participants were randomly allocated to diuretics and 358 to placebo. After 18 months of treatment, optimal BP was noted in 25.6% of the diuretic group and 19.3% in the placebo group (P < 0.05). The mean net reduction in SBP and DBP for the diuretic group comp...

Journal of the American Heart Association, Dec 13, 2016

Prehypertension is associated with higher cardiovascular risk, target organ damage, and incidence... more 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. 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...

Journal of Hypertension, 2016

Objectives: To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride co... more Objectives: To compare the blood pressure (BP)-lowering efficacy of a chlorthalidone/amiloride combination pill with losartan, during initial management of stage I hypertension. Methods: In a randomized, double-blind, controlled trial, 655 participants were followed for 18 months in 21 Brazilian academic centers. Trial participants were adult volunteers aged 30-70 years with stage I hypertension (BP 140-159 or 90-99 mmHg) following 3 months of a lifestyle intervention. Participants were randomized to 12.5/2.5 mg of chlorthalidone/amiloride (N ¼ 333) or 50 mg of losartan (N ¼ 322). If BP remained uncontrolled after 3 months, study medication dose was doubled, and if uncontrolled after 6 months, amlodipine (5 and 10 mg) and propranolol (40 and 80 mg twice daily) were added as open-label drugs in a progressive fashion. At the end of follow-up, 609 (93%) participants were evaluated. Results: The difference in SBP during 18 months of follow-up was 2.3 (95% confidence interval: 1.2 to 3.3) mmHg favoring chlorthalidone/amiloride. Compared with those randomized to diuretic, more participants allocated to losartan had their initial dose doubled and more of them used add-on antihypertensive medication. Levels of blood glucose, glycosilated hemoglobin, and incidence of diabetes were no different between the two treatment groups. Serum potassium was lower and serum cholesterol was higher in the diuretic arm. Microalbuminuria tended to be higher in patients with diabetes allocated to losartan (28.5 AE 40.4 versus 16.2 AE 26.7 mg, P ¼ 0.09). Conclusion: Treatment with a combination of chlorthalidone and amiloride compared with losartan yielded a greater reduction in BP. Clinical trials registration number: NCT00971165.

Trials, 2011

Background: Cardiovascular disease is the leading cause of death in Brazil, and hypertension is i... more Background: Cardiovascular disease is the leading cause of death in Brazil, and hypertension is its major risk factor. The benefit of its drug treatment to prevent major cardiovascular events was consistently demonstrated. Angiotensin-receptor blockers (ARB) have been the preferential drugs in the management of hypertension worldwide, despite the absence of any consistent evidence of advantage over older agents, and the concern that they may be associated with lower renal protection and risk for cancer. Diuretics are as efficacious as other agents, are well tolerated, have longer duration of action and low cost, but have been scarcely compared with ARBs. A study comparing diuretic and ARB is therefore warranted. Methods/design: This is a randomized, double-blind, clinical trial, comparing the association of chlorthalidone and amiloride with losartan as first drug option in patients aged 30 to 70 years, with stage I hypertension. The primary outcomes will be variation of blood pressure by time, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new subclinical atherosclerosis and sudden death. The study will last 18 months. The sample size will be of 1200 participants for group in order to confer enough power to test for all primary outcomes. The project was approved by the Ethics committee of each participating institution. Discussion: The putative pleiotropic effects of ARB agents, particularly renal protection, have been disputed, and they have been scarcely compared with diuretics in large clinical trials, despite that they have been at least as efficacious as newer agents in managing hypertension. Even if the null hypothesis is not rejected, the information will be useful for health care policy to treat hypertension in Brazil.

Trials, 2011

Background: Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk... more Background: Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a populationbased intervention to prevent the incidence of hypertension and the development of target-organ damage. Methods: This is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution.

PLoS Neglected Tropical Diseases, 2011

Background and Objectives: Visceral leishmaniasis (VL) is a common complication in AIDS patients ... more Background and Objectives: Visceral leishmaniasis (VL) is a common complication in AIDS patients living in Leishmaniaendemic areas. Although antiretroviral therapy has changed the clinical course of HIV infection and its associated illnesses, the prevention of VL relapses remains a challenge for the care of HIV and Leishmania co-infected patients. This work is a systematic review of previous studies that have described predictors of VL relapse in HIV-infected patients. Review Methods: We searched the electronic databases of MEDLINE, LILACS, and the Cochrane Central Register of Controlled Trials. Studies were selected if they included HIV-infected individuals with a VL diagnosis and patient follow-up after the leishmaniasis treatment with an analysis of the clearly defined outcome of prediction of relapse. Results: Eighteen out 178 studies satisfied the specified inclusion criteria. Most patients were males between 30 and 40 years of age, and HIV transmission was primarily via intravenous drug use. Previous VL episodes were identified as risk factors for relapse in 3 studies. Two studies found that baseline CD4+ T cell count above 100 cells/mL was associated with a decreased relapse rate. The observation of an increase in CD4+ T cells at patient follow-up was associated with protection from relapse in 5 of 7 studies. Meta-analysis of all studies assessing secondary prophylaxis showed significant reduction of VL relapse rate following prophylaxis. None of the five observational studies evaluating the impact of highly active antiretroviral therapy use found a reduction in the risk of VL relapse upon patient follow-up. Conclusion: Some predictors of VL relapse could be identified: a) the absence of an increase in CD4+ cells at follow-up; b) lack of secondary prophylaxis; and c) previous history of VL relapse. CD4+ counts below 100 cells/mL at the time of primary VL diagnosis may also be a predictive factor for VL relapse.

PLoS Neglected Tropical Diseases, 2012

Background: Human visceral leishmaniasis (VL), a potentially fatal disease, has emerged as an imp... more Background: Human visceral leishmaniasis (VL), a potentially fatal disease, has emerged as an important opportunistic condition in HIV infected patients. In immunocompromised patients, serological investigation is considered not an accurate diagnostic method for VL diagnosis and molecular techniques seem especially promising. Objective: This work is a comprehensive systematic review and meta-analysis to evaluate the accuracy of serologic and molecular tests for VL diagnosis specifically in HIV-infected patients. Methods: Two independent reviewers searched PubMed and LILACS databases. The quality of studies was assessed by QUADAS score. Sensitivity and specificity were pooled separately and compared with overall accuracy measures: diagnostic odds ratio (DOR) and symmetric summary receiver operating characteristic (sROC). Results: Thirty three studies recruiting 1,489 patients were included. The following tests were evaluated: Immunofluorescence Antibody Test (IFAT), Enzyme linked immunosorbent assay (ELISA), immunoblotting (Blot), direct agglutination test (DAT) and polimerase chain reaction (PCR) in whole blood and bone marrow. Most studies were carried out in Europe. Serological tests varied widely in performance, but with overall limited sensitivity. IFAT had poor sensitivity ranging from 11% to 82%. DOR (95% confidence interval) was higher for DAT 36.01 (9.95-130.29) and Blot 27.51 (9.27-81.66) than for IFAT 7.43 (3.08-1791) and ELISA 3.06 (0.71-13.10). PCR in whole blood had the highest DOR: 400.35 (58.47-2741.42). The accuracy of PCR based on Q-point was 0.95; 95%CI 0.92-0.97, which means good overall performance. Conclusion: Based mainly on evidence gained by infection with Leishmania infantum chagasi, serological tests should not be used to rule out a diagnosis of VL among the HIV-infected, but a positive test at even low titers has diagnostic value when combined with the clinical case definition. Considering the available evidence, tests based on DNA detection are highly sensitive and may contribute to a diagnostic workup.

PLoS Neglected Tropical Diseases, 2014

Background: Visceral leishmaniasis (VL) is an emerging condition affecting HIV-infected patients ... more Background: Visceral leishmaniasis (VL) is an emerging condition affecting HIV-infected patients living in Latin America, particularly in Brazil. Leishmania-HIV coinfection represents a challenging diagnosis because the clinical picture of VL is similar to that of other disseminated opportunistic diseases. Additionally, coinfection is related to treatment failure, relapse and high mortality. Objective: To assess the clinical-laboratory profile and outcomes of VL-HIV-coinfected patients using a group of non HIVinfected patients diagnosed with VL during the same period as a comparator. Methods: The study was conducted at a reference center for infectious diseases in Brazil. All patients with suspected VL were evaluated in an ongoing cohort study. Confirmed cases were divided into two groups: with and without HIV coinfection. Patients were treated according to the current guidelines of the Ministry of Health of Brazil, which considers antimony as the first-choice therapy for non HIV-infected patients and recommends amphotericin B for HIV-infected patients. After treatment, all patients with CD4 counts below 350 cells/mm 3 received secondary prophylaxis with amphotericin B. Results: Between 2011 and 2013, 168 patients with suspected VL were evaluated, of whom 90 were confirmed to have VL. In total, 51% were HIV coinfected patients (46 patients). HIV-infected patients had a lower rate of fever and splenomegaly compared with immunocompetent patients. The VL relapse rate in 6 months was 37% among HIV-infected patients, despite receiving secondary prophylaxis. The overall case-fatality rate was 6.6% (4 deaths in the HIV-infected group versus 2 deaths in the non HIV-infected group). The main risk factors for a poor outcome at 6 months after the end of treatment were HIV infection, bleeding and a previous VL episode. Conclusion: Although VL mortality rates among HIV-infected individuals are close to those observed among immunocompetent patients treated with amphotericin B, HIV coinfection is related to a low clinical response and high relapse rates within 6 months.

PLoS Neglected Tropical Diseases, 2013

Objective: We conducted a systematic literature review with indirect comparison of studies evalua... more Objective: We conducted a systematic literature review with indirect comparison of studies evaluating therapeutic efficacy and toxicity associated to visceral leishmaniasis (VL) therapy among HIV infected individuals. Main outcome measurements: The outcomes of interest were clinical and parasitological cure, mortality, and adverse events. Methods: PRISMA guidelines for systematic reviews and Cochrane manual were followed. Sources were MEDLINE, LILACS, EMBASE, Web of Knowledge databases and manual search of references from evaluated studies. We included all studies reporting outcomes after VL treatment, regardless of their design. Study quality was evaluated systematically by using the Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Comprehensive Meta-Analysis software v.2.2.048 was used to perform one-group meta-analysis of study arms with the same drug to estimate global rates of success and adverse events with each drug. These estimates were used, when possible, to indirectly compare treatment options, adjusted for CD4 count. Direct comparison was pooled when available. Results: Seventeen studies reporting five treatment regimens and outcome of 920 VL episodes occurring in HIV infected individuals were included. The main outstanding difference in outcome among the treatment regimens was observed in mortality rate: it was around 3 times higher with high-dose antimony use (18.4%, CI 95% 13.3-25%), indirectly compared to lipid formulations of amphotericin B treatment (6.1%, CI 95% 3.9-9.4%). It was observed, also by indirect comparison, higher rates of clinical improvement in study arms using amphotericin B than in study arms using pentavalent antimonial therapy (Sb v). The parasitological cure, an outcome that presented some degree of risk of selection and verification bias, had rates that varied widely within the same treatment arm, with high heterogeneity, hampering any formal comparison among drugs. One direct comparison of amphotericin and antimoniate was possible combining results of two studies and confirming the superiority of amphotericin. Conclusions: Available evidence suggests that amphotericin is superior to antimony treatment. Death rate using antimoniate high dose is unacceptably high. Randomized controlled trials are necessary to compare different formulations and doses of amphotericin, alternative therapies and drug combinations.