Comparison of burst versus ramp antitachycardia pacing therapy for ventricular tachycardia: A meta-analysis.

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.

Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension and diabetes mellitus: results from the PREVER-treatment randomized controlled trial.

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.

Heart rate variability as predictor of mortality in sepsis: A systematic review.

BACKGROUND: Autonomic dysregulation is one of the recognized pathophysiological mechanisms in sepsis, generating the hypothesis that heart rate variability (HRV) can be used to predict mortality in sepsis. METHODS: This was a systematic review of studies evaluating HRV as a predictor of death in patients with sepsis. The search was performed by independent researchers in PubMed, LILACS and Cochrane, including papers in English, Portuguese or Spanish, indexed until August 20th, 2017 with at least 10 patients. Study quality was assessed by Newcastle-Ottawa Scale. To analyze the results, we divided the articles between those who measured HRV for short-term recordings (≤ 1 hour), and those who did long-term recordings (≥ 24 hours). RESULTS: Nine studies were included with a total of 536 patients. All of them were observational studies. Studies quality varied from 4 to 7 stars in Newcastle-Ottawa Scale. The mortality rate in the studies ranged from 8 to 61%. Seven studies performed HRV analysis in short-term recordings. With the exception of one study that did not explain which group had the lowest results, all other studies showed reduction of several HRV parameters in the non-survivors in relation to the surviving septic patients. SDNN (Standard deviation of the Normal to Normal interval), TP (Total Power), VLF (Very Low Frequency Power), LF (Low Frequency Power), LF/HF (Low Frequency Power / High Frequency Power), nLF (Normalized Low Frequency Power), α1/α2 (short-term and long-term fractal scaling coefficients from DFA) and r-MSSD (Square root of the squared mean of the difference of successive NN-intervals) of the non-survivor group were reduced in relation to the survivors in at least one study. Two studies found that SDNN is associated with mortality in sepsis, even after adjusting for possible confounding factors. Three studies performed HRV analysis using long-term recordings. Only one of these studies found difference between surviving and non-surviving groups, and even so, in only one HRV parameter: LogHF. CONCLUSIONS: Several HRV parameters are reduced in nonsurviving septic patients in short-term recording. Two studies have found that SDNN is associated with mortality in sepsis, even after adjusting for possible confounding factors.

Implantable cardioverter-defibrillator in Chagas heart disease: A systematic review and meta-analysis of observational studies.

BACKGROUND: In patients with Chagas cardiomyopathy (ChCM), sudden cardiac death (SCD) is the leading cause of mortality. Implantable cardioverter-defibrillator (ICD) is a well-established therapy for secondary prevention in patients with structural heart disease, but there are conflicting opinions regarding its efficacy and safety in patients with ChCM. The aim of this meta-analysis was to assess the efficacy of the ICD for secondary prevention in patients with ChCM, comparing mortality as the primary outcome of patients treated with ICD with those treated with amiodarone. METHODS: We systematically searched five databases for studies assessing mortality outcomes in patients with ChCM and sustained ventricular tachycardia (VT) treated with ICD implantation or with amiodarone. The results of studies were pooled using random-effects modeling. RESULTS: There was no randomized clinical trial comparing efficacy of ICD versus medical treatment in patients with ChCM. Six observational studies were included, totalizing 115 patients in amiodarone group and 483 patients in ICD group. The mortality outcome in the ICD population was 9.7 per 100 patient-years of follow-up (95%CI 5.7-13.7) and 9.6 per 100 patient-years in the amiodarone group (95%CI 6.7-12.4) (p = 0.95). Meta-regression did not show any association with LV ejection fraction (p = 0.32), age (p = 0.44), beta-blocker (p = 0.33) or angiotensin-converting enzyme inhibitors (p = 0.096) usage. CONCLUSION: The best available evidence derived from small observational studies suggests that ICD therapy in secondary prevention of sudden death (VT or resuscitated SCD) is not associated with lower rate of all-cause mortality in patients with ChCM. Randomized controlled trials are needed to answer this question.

Effectiveness of low-dose diuretics for blood pressure reduction to optimal values in prehypertension: a randomized clinical trial.

BACKGROUND: To determine the effectiveness of low-dose diuretic therapy to achieve an optimal level of blood pressure (BP) in adults with prehypertension. METHODS: 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. RESULTS: 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 compared with placebo was 2.8 mmHg (95% CI 1.1 to 4.5) and 1.1 mmHg (95% CI -0.09 to 2.4), respectively. Most participants in the active treatment group (74.5%) and in the placebo group (80.7%) continued to have BP in the prehypertension range or progressed to hypertension. CONCLUSION: Low-dose diuretic therapy increased the probability of individuals with prehypertension to achieve optimal BP but most of those treated continued to have a BP in the prehypertension range or progressed to having overt hypertension.

Heart rate variability as predictor of mortality in sepsis: A prospective cohort study.

BACKGROUND: Sepsis is a serious medical condition with increasing prevalence and high mortality. The role of the autonomic nervous system in pathophysiology of sepsis has been increasingly researched. The objective of this study is to evaluate the Heart rate variability (HRV) as a predictor of mortality in septic patients. METHODS: This was a prospective cohort of patients diagnosed with sepsis. Patient recruitment was carried out at ICU in tertiary university hospital between March 2012 and February 2014. Clinical data and laboratory exams were collected at admission. Each patient underwent a 20-minute Holter and a 24-hour Holter on the first day of enrollment. The primary outcome was the 28-day all-cause mortality. RESULTS: A total of 63 patients were included. Patients were categorized into nonsurvivor group (n = 16) or survivor group (n = 47) depending on this endpoint. Survivors were younger (48.6 years vs. 63.0 years), had better renal function and lower values in severity scores (APACHE II and SOFA) compared to nonsurvivors. In the 20-minute Holter, SDNN, Total Power, VLF Power, LF Power and LF/HF of nonsurvivors were significantly lower than those of survivors (p = <0.001, p = 0.003, p = 0.002, p = 0.006, p = 0.009 respectively). ROC curve of SDNN was built, showing area under the curve of 0.772 (0.638-0.906) for mortality. The value of 17ms was chosen as best SDNN cutoff to discriminate survivors and nonsurvivors. In the Cox proportional regression, adjusted for SOFA score and for APACHE II, a SDNN ≤ 17ms was associated with a greater risk of death, with hazard ratios of 6.3 (1.4-28.0; p = 0.015) and 5.5 (1,2-24,8; p = 0.027), respectively. The addition of the dichotomized SDNN to the SOFA model reduced AIC and increased the concordance statistic and the R2, indicating that predictive power of the SDNN + SOFA model is better than predictive power of SOFA only. CONCLUSIONS: Several HRV parameters are reduced in nonsurviving septic patients. SDNN ≤17 is a risk factor for death in septic patients, even after adjusting for severity scores.

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.

Effectiveness of chlorthalidone/amiloride versus losartan in patients with stage I hypertension: results from the PREVER-treatment randomized trial.

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 = 333) or 50 mg of losartan (N = 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 ±â€Š40.4 versus 16.2 ±â€Š26.7 mg, P = 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.

Leishmania-HIV co-infection: clinical presentation and outcomes in an urban area in Brazil.

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 HIV-infected 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/mm3 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.

Diagnostic accuracy of intravascular ultrasound-derived minimal lumen area compared with fractional flow reserve--meta-analysis: pooled accuracy of IVUS luminal area versus FFR.

INTRODUCTION: Although intravascular ultrasound minimal luminal area (IVUS-MLA) is one of many anatomic determinants of lesion severity, it has been proposed as an alternative to fractional flow reserve (FFR) to assess severity of coronary artery disease. OBJECTIVE: Pool the diagnostic performance of IVUS-MLA and determine its overall accuracy to predict the functional significance of coronary disease using FFR (0.75 or 0.80) as the gold standard. METHODS: Studies comparing IVUS and FFR to establish the best MLA cutoff value that correlates with significant coronary stenosis were reviewed from a Medline search using the terms "fractional flow reserve" and "ultrasound." DerSimonian Laird method was applied to obtain pooled accuracy. RESULTS: Eleven clinical trials, including two left main (LM) trials (total N = 1,759 patients, 1,953 lesions) were included. The weighted overall mean MLA cutoff was 2.61 mm(2) in non-LM trials and 5.35 mm(2) in LM trials. For non-LM lesions, the pooled sensitivity of MLA was 0.79 (95% CI = 0.76-0.83) and specificity was 0.65 (95% CI = 0.62-0.67). Positive likelihood ratio (LR) was 2.26 (95% CI = 1.98-2.57) and LR- was 0.32 (95% CI = 0.24-0.44). Area under the summary receiver operator curve for all trials was 0.848. Pooled LM trials had better accuracy: sensitivity = 0.90, specificity = 0.90, LR+ = 8.79, and LR- = 0.120. CONCLUSION: Given its limited pooled accuracy, IVUS-MLA's impact on clinical decision in this scenario is low and may lead to misclassification in up to 20% of the lesions. Pooled analysis points toward lower MLA cutoffs than the ones used in current practice.

Efficacy of anti-leishmania therapy in visceral leishmaniasis among HIV infected patients: a systematic review with indirect comparison.

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.

Predictors of visceral leishmaniasis relapse in HIV-infected patients: a systematic review.

BACKGROUND AND OBJECTIVES: Visceral leishmaniasis (VL) is a common complication in AIDS patients living in Leishmania-endemic 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.

Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial.

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 population-based 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. DISCUSSION: The early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil. TRIAL REGISTRATION: Clinical Trials NCT00970931.

A comparison between diuretics and angiotensin-receptor blocker agents in patients with stage I hypertension (PREVER-treatment trial): study protocol for a randomized double-blind controlled trial.

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. CLINICAL TRIALS REGISTRATION NUMBER: ClinicalTrials.gov: NCT00971165.

The Valsalva maneuver in Chagas disease patients without cardiopathy.

OBJECTIVES: To perform a meta-analysis of studies using the Valsalva ratio (VR) in Chagas disease (ChD) patients without cardiopathy in comparison to control subjects in order to determine if vagal heart modulation is impaired in early forms of ChD. METHODS: The medical literature was systematically searched and reviewed for cross-sectional studies in humans in which the Valsalva maneuver was used to evaluate the autonomic modulation of the heart in ChD patients without cardiopathy. The Hedges g statistic (software Medcalc v.9.4.0.0) was used to combine the results of all studies through the calculation of the summary standardized mean difference (SMD): the mean VR in controls minus the mean VR in ChD patients, divided by the pooled and adjusted standard deviation. The sample size necessary to detect this SMD with 80% of power was calculated using the G*Power software v.3.0. RESULTS: The meta-analysis included 396 patients in 7 studies. Summary mean VRs were 1.87 +/- 0.39 ms in controls versus 1.74 +/- 0.40 ms in ChD without cardiopathy, leading to a statistically significant summary SMD of -0.310 (95% CI -0.513 to -0.106). Considering the summary SMD of -0.31, an alpha error of 0.05 and a 1:1 ratio of ChD and control patients, the estimated total sample size for a study with 80% power was 330 patients. INTERPRETATION: ChD patients without cardiopathy have reduced VR values compared to healthy controls, indicating early vagal dysfunction. Most previous studies could not detect this impairment due to small study samples and insufficient statistical power.

Standard Deviation of normal interbeat intervals as a risk marker in patients with left ventricular systolic dysfunction: a meta-analysis.

Our aim was to evaluate the Standard Deviation of Normal-Normal (SDNN) interbeat interval as a risk marker in left ventricular systolic dysfunction (LVSD) patients through a meta-analysis. We searched PubMed for studies that evaluated SDNN as a predictor of all-cause-death, cardiac death, transplantation, and progressive clinical deterioration using a search strategy validated for MEDLINE. Mean values and SD for SDNN in sixteen studies included were 115+/-48 ms in survivors versus 87+/-40 ms in non-survivors, resulting in a statistically significant standardized mean difference (0.594, 95%CI 0.385 to 0.803). In conclusion, SDNN may be a useful prognostic marker in LVSD. Additional studies must evaluate if SDNN may be used to subsidize therapeutic decisions.

Non-sustained ventricular tachycardia as a predictor of sudden cardiac death in patients with left ventricular dysfunction: a meta-analysis.

BACKGROUND: Identifying patients at risk of sudden cardiac death (SCD) remains a challenge. AIM: To evaluate the performance of non-sustained ventricular tachycardia (NSVT) from 24 hour ambulatory electrocardiography as a predictor of SCD in patients with heart failure or non-ischaemic dilated cardiomyopathy with left ventricular systolic dysfunction (LVSD). METHODS AND RESULTS: Study search and selection were performed by independent reviewers using a validated strategy. Eleven prognostic studies with >100 patients with good quality data and multivariate analysis of predictors of SCD were included. Publication bias was evaluated by funnel plot with Kendall's tau b test. A summary ROC (sROC) curve was built to evaluate predictive performance of NSVT. There was threshold effect (Spearman's correlation between sensitivity and specificity=-0.818, p<0.01) which indicates that combining sensitivity and specificity was not appropriate. The area of 0.68+/-0.02 under the sROC curve indicates a statistically significant contribution of NSVT in the prediction of SCD. The true negative rate varied from 89 to 97%. Multivariate analysis and meta-regression suggested that the contribution of NSVT to risk stratification is independent of ejection fraction. CONCLUSIONS: Absence of NSVT indicated a low probability of SCD in patients with LVSD. A risk score including NSVT should be evaluated in prospective studies.