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The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5-50 mg QD) or clonidine (0.1-0.3 mg BID). The primary end point was BP control during office (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring. Secondary end points included BP control from each method and absolute BP reduction. From 1597 patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension criteria. Compared with the spironolactone group (n=95), the clonidine group (n=92) presented similar rates of achieving the primary end point (20.5% versus 20.8%, respectively; relative risk, 1.01 [0.55-1.88]; P =1.00). Secondary end point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP monitoring (44% versus 46.2%) control for spironolactone and clonidine, respectively. However, spironolactone promoted greater decrease in 24-h systolic and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol analysis (limited to patients with ≥80% adherence to spironolactone/clonidine treatment) showed similar results regarding the primary end point. In conclusion, clonidine was not superior to spironolactone in true resistant hypertensive patients, but the overall BP control was low (≈21%). Considering easier posology and greater decrease in secondary end points, spironolactone is preferable for the fourth-drug therapy., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01643434., (© 2018 American Heart Association, Inc.)

Background: The outcome of Chagas disease patients after receiving implantable cardioverter defibrillator (ICD) is still controversial., Objective: To compare clinical outcomes after ICD implantation in patients with chronic Chagas cardiomyopathy (CCC) and ischemic heart disease (IHD)., Methods: Prospective study of a population of 153 patients receiving ICD (65 with CCC and 88 with IHD). The devices were implanted between 2003 and 2011. Survival rates and event-free survival were compared., Results: The groups were similar regarding sex, functional class and ejection fraction. Ischemic patients were, on average, 10 years older than CCC patients (p < 0.05). Patients with CCC had lower schooling and monthly income than IHD patients (p < 0.05). The number of appropriate therapies was 2.07 higher in CCC patients, who had a greater incidence of appropriate shock (p < 0.05). Annual mortality rate and electrical storm incidence were similar in both groups. There was no sudden death in CCC patients, and only one in IHD patients. Neither survival time (p = 0.720) nor event-free survival (p = 0.143) significantly differed between the groups., Conclusion: CCC doubles the risk of receiving appropriate therapies as compared to IHD, showing the greater complexity of arrhythmias in Chagas patients., Competing Interests: Potential Conflict of Interest No potential conflict of interest relevant to this article was reported.

Background: Cardiac resynchronization therapy (CRT) is the recommended treatment by leading global guidelines. However, 30%-40% of selected patients are non-responders., Objective: To develop an echocardiographic model to predict cardiac death or transplantation (Tx) 1 year after CRT., Method: Observational, prospective study, with the inclusion of 116 patients, aged 64.89 ± 11.18 years, 69.8% male, 68,1% in NYHA FC III and 31,9% in FC IV, 71.55% with left bundle-branch block, and median ejection fraction (EF) of 29%. Evaluations were made in the pre‑implantation period and 6-12 months after that, and correlated with cardiac mortality/Tx at the end of follow-up. Cox and logistic regression analyses were performed with ROC and Kaplan-Meier curves. The model was internally validated by bootstrapping., Results: There were 29 (25%) deaths/Tx during follow-up of 34.09 ± 17.9 months. Cardiac mortality/Tx was 16.3%. In the multivariate Cox model, EF < 30%, grade III/IV diastolic dysfunction and grade III mitral regurgitation at 6‑12 months were independently related to increased cardiac mortality or Tx, with hazard ratios of 3.1, 4.63 and 7.11, respectively. The area under the ROC curve was 0.78., Conclusion: EF lower than 30%, severe diastolic dysfunction and severe mitral regurgitation indicate poor prognosis 1 year after CRT. The combination of two of those variables indicate the need for other treatment options.

Background: 30-40% of cardiac resynchronization therapy cases do not achieve favorable outcomes., Objective: This study aimed to develop predictive models for the combined endpoint of cardiac death and transplantation (Tx) at different stages of cardiac resynchronization therapy (CRT)., Methods: Prospective observational study of 116 patients aged 64.8 ± 11.1 years, 68.1% of whom had functional class (FC) III and 31.9% had ambulatory class IV. Clinical, electrocardiographic and echocardiographic variables were assessed by using Cox regression and Kaplan-Meier curves., Results: The cardiac mortality/Tx rate was 16.3% during the follow-up period of 34.0 ± 17.9 months. Prior to implantation, right ventricular dysfunction (RVD), ejection fraction < 25% and use of high doses of diuretics (HDD) increased the risk of cardiac death and Tx by 3.9-, 4.8-, and 5.9-fold, respectively. In the first year after CRT, RVD, HDD and hospitalization due to congestive heart failure increased the risk of death at hazard ratios of 3.5, 5.3, and 12.5, respectively. In the second year after CRT, RVD and FC III/IV were significant risk factors of mortality in the multivariate Cox model. The accuracy rates of the models were 84.6% at preimplantation, 93% in the first year after CRT, and 90.5% in the second year after CRT. The models were validated by bootstrapping., Conclusion: We developed predictive models of cardiac death and Tx at different stages of CRT based on the analysis of simple and easily obtainable clinical and echocardiographic variables. The models showed good accuracy and adjustment, were validated internally, and are useful in the selection, monitoring and counseling of patients indicated for CRT.

The pathophysiological mechanisms of arterial hypertension during hemodialysis (HD) in patients with end-stage renal disease (ESRD) are still poorly understood. The aim of this study is to investigate physiological, cardiovascular and neuroendocrine changes in patients with ESRD and its correlation with changes in blood pressure (BP) during the HD session. The present study included 21 patients with ESRD undergoing chronic HD treatment. Group A (study) consisted of patients who had BP increase and group B (control) consisted of those who had BP reduction during HD session. Echocardiograms were performed during the HD session to evaluate cardiac output (CO) and systemic vascular resistance (SVR). Before and after the HD session, blood samples were collected to measure brain natriuretic peptide (BNP), catecholamines, endothelin-1 (ET-1), nitric oxide (NO), electrolytes, hematocrit, albumin and nitrogen substances. The mean age of the studied patients was 43 ± 4.9 years, and 54.6% were males. SVR significantly increased in group A (P<0.001). There were no differences in the values of BNP, NO, adrenalin, dopamin and noradrenalin, before and after dialysis, between the two groups. The mean value of ET-1, post HD, was 25.9 pg ml(-1) in group A and 13.3 pg ml(-1) in group B (P = < 0.001). Patients with ESRD showed different hemodynamic patterns during the HD session, with significant BP increase in group A, caused by an increase in SVR possibly due to endothelial dysfunction, evidenced by an increase in serum ET-1 levels.

Background: The normal 24-hour albumin excretion rate is of 20 mg. A persistent rate of 30 to 300 mg/day is called microalbuminuria and is related to a higher prevalence of cardiovascular disease., Objective: 1) To determine the prevalence of microalbuminuria in a group of hypertensive patients and in a group of patients with coronary artery disease; 2) To determine the relationship between the presence of microalbuminuria and hypertension, diabetes mellitus, dyslipidemia, smoking and obesity., Methods: The presence of microalbuminuria in a group of hypertensive patients (73 individuals) and in a group of patients with coronary artery disease (39 individuals) was determined and compared with a control group (43 individuals). Microalbuminuria was defined as an albumin/creatinine ratio higher than 30 and lower than 300 in a spot morning urine sample. The chi-square test and the Fishers exact test were used in the statistical analysis., Results: Microalbuminuria was present in 9.5% of the hypertensive individuals and in 33% of the patients with coronary artery disease, and was absent in individuals of the control group. When the occurrence of microalbuminuria was analyzed according to the different clinical parameters, regardless of the group involved, a statistically significant correlation was found with age, diabetes and dyslipidemia., Conclusion: 1) The prevalence of microalbuminuria in hypertensive individuals is high, and is even higher in patients with coronary artery disease; 2) There is a correlation of the presence of microalbuminuria with age, diabetes and dyslipidemia.

The first minutes of the time course of cardiopulmonary reflex control evoked by lower body negative pressure (LBNP) in patients with hypertensive cardiomyopathy have not been investigated in detail. We studied 15 hypertensive patients with left ventricular dysfunction (LVD) and 15 matched normal controls to observe the time course response of the forearm vascular resistance (FVR) during 3 min of LBNP at -10, -15, and -40 mmHg in unloading the cardiopulmonary receptors. Analysis of the average of 3-min intervals of FVR showed a blunted response of the LVD patients at -10 mmHg (P = 0.03), but a similar response in both groups at -15 and -40 mmHg. However, using a minute-to-minute analysis of the FVR at -15 and -40 mmHg, we observed a similar response in both groups at the 1st min, but a marked decrease of FVR in the LVD group at the 3rd min of LBNP at -15 mmHg (P = 0.017), and -40 mmHg (P = 0.004). Plasma norepinephrine levels were analyzed as another neurohumoral measurement of cardiopulmonary receptor response to LBNP, and showed a blunted response in the LVD group at -10 (P = 0.013), -15 (P = 0.032) and -40 mmHg (P = 0.004). We concluded that the cardiopulmonary reflex response in patients with hypertensive cardiomyopathy is blunted at lower levels of LBNP. However, at higher levels, the cardiopulmonary reflex has a normal initial response that decreases progressively with time. As a consequence of the time-dependent response, the cardiopulmonary reflex response should be measured over small intervals of time in clinical studies.

Etofibrate is a hybrid drug which combines niacin with clofibrate. After contact with plasma hydrolases, both constituents are gradually released in a controlled-release manner. In this study, we compared the effects of etofibrate and controlled-release niacin on lipid profile and plasma lipoprotein (a) (Lp(a)) levels of patients with triglyceride levels of 200 to 400 mg/dl, total cholesterol above 240 mg/dl and Lp(a) above 40 mg/dl. These patients were randomly assigned to a double-blind 16-week treatment period with etofibrate (500 mg twice daily, N = 14) or niacin (500 mg twice daily, N = 11). In both treatment groups total cholesterol, VLDL cholesterol and triglycerides were equally reduced and high-density lipoprotein cholesterol was increased. Etofibrate, but not niacin, reduced Lp(a) by 26% and low-density lipoprotein (LDL) cholesterol by 23%. The hybrid compound etofibrate produced a more effective reduction in plasma LDL cholesterol and Lp(a) levels than controlled-release niacin in type IIb dyslipidemic subjects.

It has been reported that growth hormone may benefit selected patients with congestive heart failure. A 63-year-old man with refractory congestive heart failure waiting for heart transplantation, depending on intravenous drugs (dobutamine) and presenting with progressive worsening of the clinical status and cachexia, despite standard treatment, received growth hormone replacement (8 units per day) for optimization of congestive heart failure management. Increase in both serum growth hormone levels (from 0.3 to 0.8 microg/l) and serum IGF-1 levels (from 130 to 300ng/ml) was noted, in association with clinical status improvement, better optimization of heart failure treatment and discontinuation of dobutamine infusion. Left ventricular ejection fraction (by MUGA) increased from 13 % to 18 % and to 28 % later, in association with reduction of pulmonary pressures and increase in exercise capacity (rise in peak VO2 to 13.4 and to 16.2ml/kg/min later). The patient was "de-listed" for heart transplantation. Growth hormone may benefit selected patients with refractory heart failure.