Publications by authors named "Luís E Rohde"

63 Publications

Effects of a diuretic adjustment algorithm protocol on heart failure admissions: A randomized clinical trial.

J Telemed Telecare 2021 Jun 9;27(5):288-297. Epub 2021 May 9.

School of Nursing, Universidade Federal do Rio Grande do Sul, Brazil.

Introduction: The aim of this study was to evaluate the effectiveness of a diuretic adjustment algorithm (DAA) in maintaining clinical stability and reducing HF readmissions using telemonitoring technologies.

Methods: Randomized clinical trial of patients with an indication for furosemide dose adjustment during routine outpatient visits. In the intervention group (IG), the diuretic dose was adjusted according to the DAA and the patients received telephone calls for 30 days. In the control group (CG), the diuretic dose was adjusted by a physician at baseline only. Co-primary outcomes were hospital readmission and/or emergency department visits due to decompensated HF within 90 days, and a 2-point change in the Clinical Congestion Score and/or a deterioration in New York Heart Association functional class within 30 days.

Results: A total of 206 patients were included. Most patients were male (=119; 58%), with a mean age of 62 (SD 13) years. Four patients (2%) in the IG and 14 (7%) in the CG were hospitalized for HF (odds ratio (OR) 0.31 (0.10-0.91); =0.04). Multivariate analysis showed a reduction of 67% in readmissions and/or emergency department visits due to decompensated HF in the IG compared with the CG (95% CI 0.13-0.88; =0.027). Regarding the combined outcome of HF readmission and/or emergency department visits or clinical instability, the IG had 20% fewer events than the CG within 30 days (IG: =48 (23%), CG: =70 (34%); OR 0.80 (0.63-0.93); =0.03).

Discussion: Using DAA improved the combined outcome in these outpatients, with favorable and significant results that included a reduction in HF admissions and in clinical instability. (NCT02068937).
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http://dx.doi.org/10.1177/1357633X211009640DOI Listing
June 2021

Cardiac and Noncardiac Disease Burden and Treatment Effect of Sacubitril/Valsartan: Insights From a Combined PARAGON-HF and PARADIGM-HF Analysis.

Circ Heart Fail 2021 03 12;14(3):e008052. Epub 2021 Mar 12.

Division of Cardiovascular, Brigham and Women's Hospital, Boston, MA (L.E.R., B.L.C., M.A.P., A.S.D., S.D.S.).

Background: The net clinical benefit of cardiac disease-modifying drugs might be influenced by the interaction of different domains of disease burden. We assessed the relative contribution of cardiac, comorbid, and demographic factors in heart failure (HF) and how their interplay might influence HF prognosis and efficacy of sacubitril/valsartan across the spectrum of left ventricular ejection fraction.

Methods: We combined data from 2 global trials that evaluated the efficacy of sacubitril/valsartan compared with a renin-angiotensin antagonist in symptomatic HF patients (PARADIGM-HF [Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure; n=8399] and PARAGON-HF [Prospective Comparison of Angiotensin-Converting Enzyme Inhibitor With Angiotensin Receptors Blockers Global Outcomes in Heart Failure With Preserved Ejection Fraction; n=4796]). We decomposed the previously validated Meta-Analysis Global Group in Chronic Heart Failure risk score into cardiac (left ventricular ejection fraction, New York Heart Association class, blood pressure, time since HF diagnosis, HF medications), noncardiac comorbid (body mass index, creatinine, diabetes, chronic obstructive pulmonary disease, smoking), and demographic (age, gender) categories. Based on these domains, an index representing the balance of cardiac to noncardiac comorbid burden was created (cardiac-comorbid index). Clinical outcomes were time to first HF hospitalization or cardiovascular deaths and all-cause mortality.

Results: Higher scores of the cardiac domain were observed in PARADIGM-HF (10 [7-13] versus 5 [3-6], <0.001) and higher scores of the demographic domain in PARAGON-HF (10 [8-13] versus 5 [2-9], <0.001). In PARADIGM-HF, the contribution of the cardiac domain to clinical outcomes was greater than the noncardiac domain (<0.001), while in PARAGON-HF the attributable risk of the comorbid and demographic categories predominated. Individual scores from each sub-domain were linearly associated with the risk of clinical outcomes (<0.001). Beneficial effects of sacubitril/valsartan were observed in patients with preponderance of cardiac over noncardiac comorbid burden (cardiac-comorbid index >5 points), suggesting a significant treatment effect modification (interaction <0.05 for both outcomes).

Conclusions: Domains of disease burden are clinically relevant features that influence the prognosis and treatment of patients with HF. The therapeutic benefits of sacubitril/valsartan vary according to the balance of components of disease burden, across different ranges of left ventricular ejection fraction.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.008052DOI Listing
March 2021

Dynamic changes in cardiovascular and systemic parameters prior to sudden cardiac death in heart failure with reduced ejection fraction: a PARADIGM-HF analysis.

Eur J Heart Fail 2021 Feb 9. Epub 2021 Feb 9.

Division of Cardiovascular, Brigham and Women's Hospital, Boston, MA, USA.

Aims: Prognostic models of sudden cardiac death (SCD) typically incorporate data at only a single time-point. We investigated independent predictors of SCD addressing the impact of integrating time-varying covariates to improve prediction assessment.

Methods And Results: We studied 8399 patients enrolled in the PARADIGM-HF trial and identified independent predictors of SCD (n = 561, 36% of total deaths) using time-updated multivariable-adjusted Cox models, classification and regression tree (CART), and logistic regression analysis. Compared with patients who were alive or died from non-sudden cardiovascular deaths, patients who suffered a SCD displayed a distinct temporal profile of New York Heart Association (NYHA) class, heart rate and levels of three biomarkers (albumin, uric acid and total bilirubin), with significant differences observed more than 1 year prior to the event (P  < 0.001). In multivariable models adjusted for baseline covariates, seven time-updated variables independently contributed to SCD risk (incremental likelihood chi-square = 46.2). CART analysis identified that baseline variables (implantable cardioverter-defibrillator use and N-terminal prohormone of B-type natriuretic peptide levels) and time-updated covariates (NYHA class, total bilirubin, and total cholesterol) improved risk stratification. CART-defined subgroup of highest risk had nearly an eightfold increment in SCD hazard (hazard ratio 7.7, 95% confidence interval 3.6-16.5; P < 0.001). Finally, changes over time in heart rate, NYHA class, blood urea nitrogen and albumin levels were associated with differential risk of sudden vs. non-sudden cardiovascular deaths (P < 0.05).

Conclusions: Beyond single time-point assessments, distinct changes in multiple cardiac-specific and systemic variables improved SCD risk prediction and were helpful in differentiating mode of death in chronic heart failure.
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http://dx.doi.org/10.1002/ejhf.2120DOI Listing
February 2021

Revisiting heart failure assessment based on objective measures in NYHA functional classes I and II.

Heart 2020 Dec 23. Epub 2020 Dec 23.

Post-Graduate Program in Cardiology and Cardiovascular Sciences, Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

Objective: New York Heart Association (NYHA) functional class plays a central role in heart failure (HF) assessment but might be unreliable in mild presentations. We compared objective measures of HF functional evaluation between patients classified as NYHA I and II in the (ReBIC)-1 Trial.

Methods: The ReBIC-1 Trial included outpatients with stable HF with reduced ejection fraction. All patients had simultaneous protocol-defined assessment of NYHA class, 6 min walk test (6MWT), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and patient's self-perception of dyspnoea using a Visual Analogue Scale (VAS, range 0-100).

Results: Of 188 included patients with HF, 122 (65%) were classified as NYHA I and 66 (35%) as NYHA II at baseline. Although NYHA class I patients had lower dyspnoea VAS Scores (median 16 (IQR, 4-30) for class I vs 27.5 (11-49) for class II, p=0.001), overlap between classes was substantial (density overlap=60%). A similar profile was observed for NT-proBNP levels (620 pg/mL (248-1333) vs 778 (421-1737), p=0.015; overlap=78%) and for 6MWT distance (400 m (330-466) vs 351 m (286-408), p=0.028; overlap=64%). Among NYHA class I patients, 19%-34% had one marker of HF severity (VAS Score >30 points, 6MWT <300 m or NT-proBNP levels >1000 pg/mL) and 6%-10% had two of them. Temporal change in functional class was not accompanied by variation on dyspnoea VAS (p=0.14).

Conclusions: Most patients classified as NYHA classes I and II had similar self-perception of their limitation, objective physical capabilities and levels of natriuretic peptides. These results suggest the NYHA classification poorly discriminates patients with mild HF.
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http://dx.doi.org/10.1136/heartjnl-2020-317984DOI Listing
December 2020

COVID-19 in Brazil: the headlines should be about science.

Lancet 2020 12 10;396(10265):1803. Epub 2020 Nov 10.

Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, Brazil; Cardiology Division, Hospital Moinhos de Vento, Porto Alegre, Brazil.

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http://dx.doi.org/10.1016/S0140-6736(20)32375-8DOI Listing
December 2020

Why do poor patients have poor outcomes? Shedding light on the neglected facet of poverty and heart failure.

Heart 2021 Feb 2;107(3):178-179. Epub 2020 Nov 2.

Cardiovascular Division, Hospital de Clinicas de Porto Alegre and Departament of Internal Medicine, Medical School, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

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http://dx.doi.org/10.1136/heartjnl-2020-317977DOI Listing
February 2021

Sacubitril/Valsartan and Sudden Cardiac Death According to Implantable Cardioverter-Defibrillator Use and Heart Failure Cause: A PARADIGM-HF Analysis.

JACC Heart Fail 2020 10 9;8(10):844-855. Epub 2020 Sep 9.

Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address:

Objectives: The purpose of this study was to investigate the effect of sacubitril/valsartan therapy on sudden cardiac death (SCD) according to the use of and eligibility for an implantable cardioverter-defibrillator (ICD), stratified by heart failure cause.

Background: SCD still accounts for a significant proportion of overall mortality in heart failure with reduced ejection fraction (HFrEF).

Methods: Patients enrolled in the PARADIGM-HF (Prospective Comparison of ARNI with an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial (n = 8,399) were evaluated to assess patterns of ICD implantation and eligibility according to clinical guidelines. The impact of ICD (adjusted for propensity of ICD implantation) and sacubitril/valsartan therapy on SCD was evaluated by using cause-specific Cox models and competing risk analysis.

Results: At baseline, of the 7,145 patients (85%) eligible for ICD implantation, only 1,243 (15%) had an ICD. Use of ICD varied by region with the highest rates in North America (56%) and lowest in Asia-Pacific (1.7%). In a propensity score-adjusted analysis, use of an ICD was associated with a 56% lower risk of SCD in ICD-eligible patients, in both patients with ischemic (p < 0.001) and nonischemic cardiomyopathy (p = 0.02). Sacubitril/valsartan reduced SCD risk in patients with an ICD (hazard ratio [HR]: 0.49; 95% confidence interval [CI]: 0.25 to 0.99) and in those who were eligible for but did not receive an ICD (HR: 0.81; 95% CI: 0.67 to 0.98). This effect was particularly evident in nonischemic cardiomyopathy (p < 0.05), although interaction with the cause of HF was not significant (p = 0.11 in subjects using an ICD and p = 0.25 in eligible nonusers).

Conclusions: Use of an ICD was associated with lower rates of SCD, regardless of HF cause but was underused in most regions of the world in the PARADIGM-HF study. Sacubitril/valsartan reduced SCD risk regardless of use of an ICD or eligibility, particularly in ICD users and nonischemic cardiomyopathy.
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http://dx.doi.org/10.1016/j.jchf.2020.06.015DOI Listing
October 2020

Identification of environmental and genetic factors that influence warfarin time in therapeutic range.

Genet Mol Biol 2020 10;43(1 suppl 2):e20190025. Epub 2020 Feb 10.

Universidade Federal do Rio Grande do Sul, Departamento de Genética, Porto Alegre, RS, Brazil.

Warfarin is an oral anticoagulant prescribed to prevent and treat thromboembolic disorders. It has a narrow therapeutic window and must have its effect controlled. Prothrombin test, expressed in INR value, is used for dose management. Time in therapeutic range (TTR) is an important outcome of quality control of anticoagulation therapy and is influenced by several factors. The aim of this study was to identify genetic, demographic, and clinical factors that can potentially influence TTR. In total,422 patients using warfarin were investigated. Glibenclamide co-medication and presence of CYP2C9*2 and/or *3 alleles were associated with higher TTR, while amiodarone, acetaminophen and verapamil co-medication were associated with lower TTR. Our data suggest that TTR is influenced by co-medication and genetic factors. Thus, individuals in use of glibenclamide may need a more careful monitoring and genetic testing (CYP2C9*2 and/or *3 alleles) may improve the anticoagulation management. In addition, in order to reach and maintain the INR in the target for a longer period, it is better to discuss dose adjustment in office instead of by telephone assessment. Other studies are needed to confirm these results and to find more variables that could contribute to this important parameter.
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http://dx.doi.org/10.1590/1678-4685-GMB-2019-0025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198020PMC
February 2020

Short-term diuretic withdrawal in stable outpatients with mild heart failure and no fluid retention receiving optimal therapy: a double-blind, multicentre, randomized trial.

Eur Heart J 2019 11;40(44):3605-3612

Hospital de Clínicas de Porto Alegre and Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, CEP, Porto Alegre, RS, Brazil.

Aims: Although loop diuretics are widely used to treat heart failure (HF), there is scarce contemporary data to guide diuretic adjustments in the outpatient setting.

Methods And Results: In a prospective, randomized and double-blind protocol, we tested the safety and tolerability of withdrawing low-dose furosemide in stable HF outpatients at 11 HF clinics in Brazil. The trial had two blindly adjudicated co-primary outcomes: (i) symptoms assessment quantified as the area under the curve (AUC) of a dyspnoea score on a visual-analogue scale evaluated at 4 time-points (baseline, Day 15, Day 45, and Day 90) and (ii) the proportion of patients maintained without diuretic reuse during follow-up. We enrolled 188 patients (25% females; 59 ± 13 years old; left ventricular ejection fraction = 32 ± 8%) that were randomized to furosemide withdrawal (n = 95) or maintenance (n = 93). For the first co-primary endpoint, no significant difference in patients' assessment of dyspnoea was observed in the comparison of furosemide withdrawal with continuous administration [median AUC 1875 (interquartile range, IQR 383-3360) and 1541 (IQR 474-3124), respectively; P = 0.94]. For the second co-primary endpoint, 70 patients (75.3%) in the withdrawal group and 77 patients (83.7%) in the maintenance group were free of furosemide reuse during follow-up (odds ratio for additional furosemide use with withdrawal 1.69, 95% confidence interval 0.82-3.49; P = 0.16). Heart failure-related events (hospitalizations, emergency room visits, and deaths) were infrequent and similar between groups (P = 1.0).

Conclusions: Diuretic withdrawal did not result in neither increased self-perception of dyspnoea nor increased need of furosemide reuse. Diuretic discontinuation may deserve consideration in stable outpatients with no signs of fluid retention receiving optimal medical therapy.

Clinicaltrials.gov Identifier: NCT02689180.
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http://dx.doi.org/10.1093/eurheartj/ehz554DOI Listing
November 2019

The Diuretic Effect of Sacubitril/Valsartan Might Be Clinically Relevant.

Arq Bras Cardiol 2019 07 15;112(6):791-792. Epub 2019 Jul 15.

Serviço de Cardiologia - Hospital de Clínicas de Porto Alegre, Porto Alegre, RS - Brazil.

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http://dx.doi.org/10.5935/abc.20190080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636368PMC
July 2019

Cardiac hypertrophy in mice submitted to a swimming protocol: influence of training volume and intensity on myocardial renin-angiotensin system.

Am J Physiol Regul Integr Comp Physiol 2019 06 1;316(6):R776-R782. Epub 2019 May 1.

Experimental and Molecular Cardiovascular Laboratory and Heart Failure and Cardiac Transplant Unit, Cardiology Division, Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil.

Exercise promotes physiological cardiac hypertrophy and activates the renin-angiotensin system (RAS), which plays an important role in cardiac physiology, both through the classical axis [angiotensin II type 1 receptor (AT1R) activated by angiotensin II (ANG II)] and the alternative axis [proto-oncogene Mas receptor (MASR) activated by angiotensin-(1-7)]. However, very intense exercise could have deleterious effects on the cardiovascular system. We aimed to analyze the cardiac hypertrophy phenotype and the classical and alternative RAS axes in the myocardium of mice submitted to swimming exercises of varying volume and intensity for the development of cardiac hypertrophy. Male mice were divided into three groups, sedentary, swimming twice a day without overload (T2), and swimming three times a day with a 2% body weight overload (T3), totaling 6 wk of training. Both training groups developed similar cardiac hypertrophy, but only T3 mice improved their oxidative capacity. We observed that T2 had increased levels of MASR, which was followed by the activation of its main downstream protein AKT; meanwhile, AT1R and its main downstream protein ERK remained unchanged. Furthermore, no change was observed regarding the levels of angiotensin peptides, in either group. In addition, we observed no change in the ratio of expression of the myosin heavy chain β-isoform to that of the α-isoform. Fibrosis was not observed in any of the groups. In conclusion, our results suggest that increasing exercise volume and intensity did not induce a pathological hypertrophy phenotype, but instead improved the oxidative capacity, and this process might have the participation of the RAS alternative axis.
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http://dx.doi.org/10.1152/ajpregu.00205.2018DOI Listing
June 2019

Rational and design of a randomized, double-blind, multicenter trial to evaluate the safety and tolerability of furosemide withdrawal in stable chronic outpatients with heart failure: The ReBIC-1 trial.

Am Heart J 2017 Dec 24;194:125-131. Epub 2017 Aug 24.

Hospital de Clínicas de Porto Alegre e Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Porto Alegre, (RS), Brazil.

Aims: Furosemide is commonly prescribed for symptom relief in heart failure (HF) patients. Although few data support the continuous use of loop diuretics in apparently euvolemic HF patients with mild symptoms, there is concern about safety of diuretic withdrawal in these patients. The ReBIC-1 trial was designed to evaluate the safety and tolerability of withdrawing furosemide in stable, euvolemic, chronic HF outpatients. This multicenter initiative is part of the Brazilian Research Network in Heart Failure (ReBIC) created to develop clinical studies in HF and composed predominantly by university tertiary care hospitals.

Methods: The ReBIC-1 trial is currently enrolling HF patients in NYHA functional class I-II, left ventricular ejection fraction ≤45%, without a HF-related hospital admission within the last 6 months, receiving a stable dose of furosemide (40 or 80 mg per day) for at least 6 months. Eligible patients will be randomized to maintain or withdraw furosemide in a double-blinded protocol. The trial has two co-primary outcomes: (1) dyspnea assessment using a visual-analogue scale evaluated at 4 time points and (2) the proportion of patients maintained without diuretics during the follow-up period. Total sample size was calculated to be 220 patients. Enrolled patients will be followed up to 90 days after randomization, and diuretic will be restarted if clinical deterioration or signs of congestion are detected. Pre-defined sub-group analysis based on NT-proBNP levels at baseline is planned.

Perspective: Evidence-based strategies aiming to simplify HF pharmacotherapy are needed in clinical practice. The ReBIC-1 trial will determine the safety of withdrawing furosemide in stable chronic HF patients.
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http://dx.doi.org/10.1016/j.ahj.2017.08.012DOI Listing
December 2017

The tip of the iceberg in the sub-Saharan Africa: unraveling the real world in the diagnosis and treatment of heart failure.

Heart 2017 12 5;103(23):1842-1843. Epub 2017 Jun 5.

Advanced Heart Failure Program, Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.

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http://dx.doi.org/10.1136/heartjnl-2017-311558DOI Listing
December 2017

Predictors of serious arrhythmic events in patients with nonischemic heart failure.

J Interv Card Electrophysiol 2017 Mar 10;48(2):131-139. Epub 2016 Dec 10.

Heart Failure and Transplant Group, Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.

Purpose: Risk stratification of serious arrhythmic events in patients with nonischemic heart failure (HF), beyond estimates of left ventricular ejection fraction (LVEF), remains an important clinical challenge. This study aims to determine the clinical value of different noninvasive and invasive tests as predictors of serious arrhythmic events in patients with nonischemic HF.

Methods: A prospective observational study was conducted including 106 nonischemic HF patients who underwent a comprehensive clinical and laboratory evaluation including two-dimensional echocardiography, 24-h Holter monitoring, cardiopulmonary exercise testing (CPX), and an invasive electrophysiological study. The study's primary end-point was either syncope, appropriate therapy by implantable cardioverter-defibrillators, or sudden cardiac death.

Results: During a mean follow-up of 704 ± 320 days, the primary end-point occurred in 15 patients (14.2%). In multivariable analysis, LV end-diastolic diameter >73 mm (hazard ratio [HR] 3.7; p = 0.016), exercise periodic breathing (EPB) on CPX (HR 2.88; p = 0.045), and non-sustained ventricular tachycardia (NSVT) ≥10 beats (HR 8.2; p < 0.01) remained independently associated with serious arrhythmic events. The positive predictive value of the presence of two of these predictors ranged from 44 to 100%. The absence of all three factors (n = 65, 61% of the sample) identified a subset of patients with low risk of future arrhythmic events, with a negative predictive value of 96.9%.

Conclusions: In this cohort study of nonischemic HF patients, LV dimension, EPB, and NSVT ≥10 beats were independent predictors of serious arrhythmic events. The presence or absence of these characteristics identified sub-groups of high and low risk of serious arrhythmic events, respectively.
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http://dx.doi.org/10.1007/s10840-016-0213-7DOI Listing
March 2017

Short-term Effects of High-Dose Caffeine on Cardiac Arrhythmias in Patients With Heart Failure: A Randomized Clinical Trial.

JAMA Intern Med 2016 Dec;176(12):1752-1759

Postgraduate Program in Health Science: Cardiology and Cardiovascular Sciences, Medical School, Federal University of Rio Grande do Sul, Porto Alegre, Brazil3Cardiovascular Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil6Department of Internal Medicine, Medical School, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

Importance: The presumed proarrhythmic action of caffeine is controversial. Few studies have assessed the effect of high doses of caffeine in patients with heart failure due to left ventricular systolic dysfunction at high risk for ventricular arrhythmias.

Objective: To compare the effect of high-dose caffeine or placebo on the frequency of supraventricular and ventricular arrhythmias, both at rest and during a symptom-limited exercise test.

Design, Setting, And Participants: Double-blinded randomized clinical trial with a crossover design conducted at the heart failure and cardiac transplant clinic of a tertiary-care university hospital. The trial included patients with chronic heart failure with moderate-to-severe systolic dysfunction (left ventricular ejection fraction <45%) and New York Heart Association functional class I to III between March 5, 2013, and October 2, 2015.

Interventions: Caffeine (100 mg) or lactose capsules, in addition to 5 doses of 100 mL decaffeinated coffee at 1-hour intervals, for a total of 500 mg of caffeine or placebo during a 5-hour protocol. After a 1-week washout period, the protocol was repeated.

Main Outcomes And Measures: Number and percentage of ventricular and supraventricular premature beats assessed by continuous electrocardiographic monitoring.

Results: We enrolled 51 patients (37 [74%] male; mean [SD] age, 60.6 [10.9] years) with predominantly moderate-to-severe left ventricular systolic dysfunction (mean [SD] left ventricular ejection fraction, 29% [7%]); 31 [61%] had an implantable cardioverter-defibrillator device. No significant differences between the caffeine and placebo groups were observed in the number of ventricular (185 vs 239 beats, respectively; P = .47) and supraventricular premature beats (6 vs 6 beats, respectively; P = .44), as well as in couplets, bigeminal cycles, or nonsustained tachycardia during continuous electrocardiographic monitoring. Exercise test-derived variables, such as ventricular and supraventricular premature beats, duration of exercise, estimated peak oxygen consumption, and heart rate, were not influenced by caffeine ingestion. We observed no increases in ventricular premature beats (91 vs 223 vs 207 beats, respectively) in patients with higher levels of plasma caffeine concentration compared with lower plasma levels (P = .91) or with the placebo group (P = .74).

Conclusions And Relevance: Acute ingestion of high doses of caffeine did not induce arrhythmias in patients with systolic heart failure and at high risk for ventricular arrhythmias.

Trial Registration: clinicaltrials.gov Identifier: NCT02045992.
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http://dx.doi.org/10.1001/jamainternmed.2016.6374DOI Listing
December 2016

Matrix Metalloproteinase-2 Polymorphisms in Chronic Heart Failure: Relationship with Susceptibility and Long-Term Survival.

PLoS One 2016 23;11(8):e0161666. Epub 2016 Aug 23.

Laboratory of Human Molecular Genetics, Universidade Luterana do Brasil, Canoas, RS, Brazil.

Circulating levels of matrix metalloproteinase-2 (MMP-2) predict mortality and hospital admission in heart failure (HF) patients. However, the role of MMP-2 gene polymorphisms in the susceptibility and prognosis of HF remains elusive. In this study, 308 HF outpatients (216 Caucasian- and 92 African-Brazilians) and 333 healthy subjects (256 Caucasian- and 77 African-Brazilians) were genotyped for the -1575G>A (rs243866), -1059G>A (rs17859821), and -790G>T (rs243864) polymorphisms in the MMP-2 gene. Polymorphisms were analyzed individually and in combination (haplotype), and positive associations were adjusted for clinical covariates. Although allele frequencies were similar in HF patients and controls in both ethnic groups, homozygotes for the minor alleles were not found among African-Brazilian patients. After a median follow-up of 5.3 years, 124 patients (40.3%) died (54.8% of them for HF). In Caucasian-Brazilians, the TT genotype of the -790G>T polymorphism was associated with a decreased risk of HF-related death as compared with GT genotype (hazard ratio [HR] = 0.512, 95% confidence interval [CI] 0.285-0.920). However, this association was lost after adjusting for clinical covariates (HR = 0.703, 95% CI 0.365-1.353). Haplotype analysis revealed similar findings, as patients homozygous for the -1575G/-1059G/-790T haplotype had a lower rate of HF-related death than those with any other haplotype combination (12.9% versus 28.5%, respectively; P = 0.010). Again, this association did not remain after adjusting for clinical covariates (HR = 0.521, 95% CI 0.248-1.093). Our study does not exclude the possibility that polymorphisms in MMP-2 gene, particularly the -790G>T polymorphism, might be related to HF prognosis. However, due to the limitations of the study, our findings need to be confirmed in further larger studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161666PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4995023PMC
July 2017

Long-term Cost-Effectiveness of Diagnostic Tests for Assessing Stable Chest Pain: Modeled Analysis of Anatomical and Functional Strategies.

Clin Cardiol 2016 May 15;39(5):249-56. Epub 2016 Apr 15.

Institute of Health Technology Assessment, Porto Alegre, Brazil.

Several tests exist for diagnosing coronary artery disease, with varying accuracy and cost. We sought to provide cost-effectiveness information to aid physicians and decision-makers in selecting the most appropriate testing strategy. We used the state-transitions (Markov) model from the Brazilian public health system perspective with a lifetime horizon. Diagnostic strategies were based on exercise electrocardiography (Ex-ECG), stress echocardiography (ECHO), single-photon emission computed tomography (SPECT), computed tomography coronary angiography (CTA), or stress cardiac magnetic resonance imaging (C-MRI) as the initial test. Systematic review provided input data for test accuracy and long-term prognosis. Cost data were derived from the Brazilian public health system. Diagnostic test strategy had a small but measurable impact in quality-adjusted life-years gained. Switching from Ex-ECG to CTA-based strategies improved outcomes at an incremental cost-effectiveness ratio of 3100 international dollars per quality-adjusted life-year. ECHO-based strategies resulted in cost and effectiveness almost identical to CTA, and SPECT-based strategies were dominated because of their much higher cost. Strategies based on stress C-MRI were most effective, but the incremental cost-effectiveness ratio vs CTA was higher than the proposed willingness-to-pay threshold. Invasive strategies were dominant in the high pretest probability setting. Sensitivity analysis showed that results were sensitive to costs of CTA, ECHO, and C-MRI. Coronary CT is cost-effective for the diagnosis of coronary artery disease and should be included in the Brazilian public health system. Stress ECHO has a similar performance and is an acceptable alternative for most patients, but invasive strategies should be reserved for patients at high risk.
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http://dx.doi.org/10.1002/clc.22532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6490729PMC
May 2016

Effect of caffeine on ventricular arrhythmia: a systematic review and meta-analysis of experimental and clinical studies.

Europace 2016 Feb 5;18(2):257-66. Epub 2015 Oct 5.

Post-Graduate Program in Health Science: Cardiology and Cardiovascular Sciences, Porto Alegre, RS, Brazil Cardiovascular Division of Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2350, room 2061, Porto Alegre, RS 90035-003, Brazil Department of Internal Medicine, Medical School, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil

Aims: The relationship between caffeine consumption and the occurrence of arrhythmias remains controversial. Despite this lack of scientific evidence, counselling to reduce caffeine consumption is still widely advised in clinical practice. We conducted a systematical review and meta-analysis of interventional studies of the caffeine effects on ventricular arrhythmias.

Methods And Results: The search was performed on Pubmed, Embase, and Cochrane database, and terms related to coffee, caffeine, and cardiac arrhythmias were used. Methodological quality was assessed based on The Cochrane Collaboration recommendations and the ARRIVE guidelines. There were 2016 citations retrieved on the initial research. After full-text assessment, seven human and two animal studies were included in the meta-analysis. In animal studies, the main outcome reported was the ventricular fibrillation threshold. We observed a significant mean difference of -2.15 mA (95% CI -3.43 to -0.87; I(2) 0.0%, P for heterogeneity = 0.37). The main outcome evaluated in human studies was the rate of ventricular premature beats (VPBs). The overall relative risk for occurrence of VPBs in 24 h attributed to caffeine exposure was 1.00 (95% CI 0.94-1.06; I(2) 13.5%, P for heterogeneity = 0.32). Sensitivity analysis for caffeine dose, different designs, and subject profile was performed and no major differences were observed.

Conclusion: Our meta-analysis demonstrates that data from human interventional studies do not show a significant effect of caffeine consumption on the occurrence of VBPs. The effects observed in animal studies are most probably the result of very high caffeine doses that are not regularly consumed in a daily basis by humans.
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http://dx.doi.org/10.1093/europace/euv261DOI Listing
February 2016

PPARA gene and phenprocoumon: a new predictor of response variability.

Pharmacogenet Genomics 2015 Feb;25(2):93-5

aDepartment of Genetics, Federal University of Rio Grande do Sul bRio Grande do Sul Cardiology Institute, Cardiology University Foundation cCardiology Division, Porto Alegre Clinics Hospital, Porto Alegre, Rio Grande do Sul, Brazil.

Phenprocoumon is an anticoagulant used for thromboembolic disorder prophylaxis metabolized mainly by CYP3A4. However, polymorphisms in this gene did not explain the observed variability. PPARA (peroxisome proliferator-activated receptor-α) is a nuclear receptor that, among others, influences CYP3A4 gene expression. The aim of this study was to determine whether PPARA gene polymorphisms and the CYP3A4*22 allele are associated with phenprocoumon dose variability. A total of 198 patients on a stable dose of phenprocoumon were included in the study. Genotyping was performed by allele discrimination using standardized TaqMan assays. Differences between the average phenprocoumon dose and genotypes/haplotypes were assessed by analysis of variance and multiple linear regression analyses. Patients with the PPARA rs4253728A allele needed higher phenprocoumon doses. However, the effect size (3%) of this association was small. The CYP3A4*22 allele was not associated with the dose of phenprocoumon. As this is the first report of an association between PPARA gene polymorphisms and phenprocoumon dose, future studies are warranted to confirm these results.
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http://dx.doi.org/10.1097/FPC.0000000000000109DOI Listing
February 2015

Effect of fluid and dietary sodium restriction in the management of patients with heart failure and preserved ejection fraction: study protocol for a randomized controlled trial.

Trials 2014 Sep 4;15:347. Epub 2014 Sep 4.

Graduate Program in Health Sciences, Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 200, 90035-003 Porto Alegre, RS, Brazil.

Background: Although half of all patients with heart failure (HF) have a normal or near-normal ejection fraction and their prognosis differs little from that of patients with a reduced ejection fraction, the pathophysiology of HF with preserved ejection fraction (HF-PEF) is still poorly understood, and its management poorly supported by clinical trials. Sodium and fluid restriction is the most common self-care measure prescribed to HF patients for management of congestive episodes. However, its role in the treatment of HF-PEF remains unclear. This trial seeks to compare the effects of a sodium- and fluid-restricted diet versus an unrestricted diet on weight loss, neurohormonal activation, and clinical stability in patients admitted for decompensated HF-PEF.

Methods/design: This is a randomized, parallel trial with blinded outcome assessment. The sample will include adult patients (aged ≥18 years) with a diagnosis of HF-PEF admitted for HF decompensation. The patients will be randomized to receive a diet with sodium and fluid intake restricted to 0.8 g/day and 800 mL/day respectively (intervention group) or an unrestricted diet, with 4 g/day sodium and unlimited fluid intake (control group), and followed for 7 days or until hospital discharge. The primary outcome shall consist of weight loss at 7 days or discharge. The secondary outcome includes assessment of clinical stability, neurohormonal activation, daily perception of thirst and readmission rate at 30 days.

Discussion: Assessment of the effects of sodium and fluid restriction on neurohormonal activation and clinical course of HF-PEF can promote a deeper understanding of the pathophysiology and progression of this complex syndrome.

Trial Registration Number: ClinicalTrials.gov identifier: NCT01896908 (date of registration: 8 August 2013).
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http://dx.doi.org/10.1186/1745-6215-15-347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162967PMC
September 2014

Heart failure: preventing disease and death worldwide.

ESC Heart Fail 2014 Sep;1(1):4-25

Heart Failure Unit, Department of Cardiology, Attikon University Hospital, University of Athens, Athens, Greece.

Heart failure is a life-threatening disease and addressing it should be considered a global health priority. At present, approximately 26 million people worldwide are living with heart failure. The outlook for such patients is poor, with survival rates worse than those for bowel, breast or prostate cancer. Furthermore, heart failure places great stresses on patients, caregivers and healthcare systems. Demands on healthcare services, in particular, are predicted to increase dramatically over the next decade as patient numbers rise owing to ageing populations, detrimental lifestyle changes and improved survival of those who go on to develop heart failure as the final stage of another disease. It is time to ease the strain on healthcare systems through clear policy initiatives that prioritize heart failure prevention and champion equity of care for all. Despite the burdens that heart failure imposes on society, awareness of the disease is poor. As a result, many premature deaths occur. This is in spite of the fact that most types of heart failure are preventable and that a healthy lifestyle can reduce risk. Even after heart failure has developed, premature deaths could be prevented if people were taught to recognize the symptoms and seek immediate medical attention. Public awareness campaigns focusing on these messages have great potential to improve outcomes for patients with heart failure and ultimately to save lives. Compliance with clinical practice guidelines is also associated with improved outcomes for patients with heart failure. However, in many countries, there is considerable variation in how closely physicians follow guideline recommendations. To promote equity of care, improvements should be encouraged through the use of hospital performance measures and incentives appropriate to the locality. To this end, policies should promote the research required to establish an evidence base for performance measures that reflect improved outcomes for patients. Continuing research is essential if we are to address unmet needs in caring for patients with heart failure. New therapies are required for patients with types of heart failure for which current treatments relieve symptoms but do not address the disease. More affordable therapies are desperately needed in the economically developing world. International collaborative research focusing on the causes and treatment of heart failure worldwide has the potential to benefit tens of millions of people. Change at the policy level has the power to drive improvements in prevention and care that will save lives. It is time to make a difference across the globe by confronting the problem of heart failure.

A Call To Action: POLICY RECOMMENDATIONS: We urge policymakers at local, national and international levels to collaborate and act on the following recommendations.

Promote Heart Failure Prevention: Support the development and implementation of public awareness programmes about heart failure. These should define heart failure in simple and accessible language, explain how to recognize the symptoms and emphasize that most types of heart failure are preventable.Highlight the need for healthcare professionals across all clinical disciplines to identify patients with illnesses that increase the risk of heart failure and to prescribe preventive medications.Prioritize the elimination of infectious diseases in parts of the world where they still cause heart failure.

Improve Heart Failure Awareness Amongst Healthcare Professionals: Encourage the development and use of heart failure education programmes for all appropriate healthcare professionals. These should aim to improve the prevention, diagnosis, treatment and long-term management of heart failure and raise awareness of clinical practice guidelines.

Ensure Equity Of Care For All Patients With Heart Failure: Provide a healthcare system that delivers timely access to diagnostic services and treatment of heart failure, as well as a seamless transition to long-term management.Ensure that the best available and most appropriate care is consistently provided to all patients with heart failure through efficient use of resources.

Support And Empower Patients And Their Caregivers: Provide resources for the education and practical support of patients with heart failure and their families or other caregivers, empowering them to engage proactively in long-term care.

Promote Heart Failure Research: Fund and encourage international collaborative research to improve understanding of the patterns, causes and effects of modern day heart failure and how the disease can be prevented across the globe.Fund and encourage research into new and more affordable therapies and medical devices for all types of heart failure.Fund and encourage research into evidence-based healthcare performance measures that reflect improved clinical outcomes for patients with heart failure.
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http://dx.doi.org/10.1002/ehf2.12005DOI Listing
September 2014

Tumorlike cardiac fungal mycetoma caused by Scedosporium apiospermum presenting as symptomatic ventricular tachycardia.

Circulation 2014 May;129(19):e488-9

From Cardiology, Radiology, and Infectious Divisions, Hospital de Clinicas de Porto Alegre, Internal Medicine Department, Medical School, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.114.009162DOI Listing
May 2014

An analysis of the global expression of microRNAs in an experimental model of physiological left ventricular hypertrophy.

PLoS One 2014 21;9(4):e93271. Epub 2014 Apr 21.

Experimental and Molecular Cardiovascular Laboratory and the Heart Failure and Cardiac Transplant Unit from the Cardiology Division at Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; Post-Graduate Program in Cardiology and Cardiovascular Science, Porto Alegre, RS, Brazil.

Background: MicroRNAs (miRs) are a class of small non-coding RNAs that regulate gene expression. Studies of transgenic mouse models have indicated that deregulation of a single miR can induce pathological cardiac hypertrophy and cardiac failure. The roles of miRs in the genesis of physiological left ventricular hypertrophy (LVH), however, are not well understood.

Objective: To evaluate the global miR expression in an experimental model of exercise-induced LVH.

Methods: Male Balb/c mice were divided into sedentary (SED) and exercise (EXE) groups. Voluntary exercise was performed on an odometer-monitored metal wheels for 35 days. Various tests were performed after 7 and 35 days of training, including a transthoracic echocardiography, a maximal exercise test, a miR microarray (miRBase v.16) and qRT-PCR analysis.

Results: The ratio between the left ventricular weight and body weight was increased by 7% in the EXE group at day 7 (p<0.01) and by 11% at day 35 of training (p<0.001). After 7 days of training, the microarray identified 35 miRs that were differentially expressed between the two groups: 20 were up-regulated and 15 were down-regulated in the EXE group compared with the SED group (p = 0.01). At day 35 of training, 25 miRs were differentially expressed: 15 were up-regulated and 10 were decreased in the EXE animals compared with the SED animals (p<0.01). The qRT-PCR analysis demonstrated an increase in miR-150 levels after 35 days and a decrease in miR-26b, miR-27a and miR-143 after 7 days of voluntary exercise.

Conclusions: We have identified new miRs that can modulate physiological cardiac hypertrophy, particularly miR-26b, -150, -27a and -143. Our data also indicate that previously established regulatory gene pathways involved in pathological LVH are not changed in physiological LVH.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0093271PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994002PMC
January 2015

Transcoronary gradient of plasma microRNA 423-5p in heart failure: evidence of altered myocardial expression.

Biomarkers 2014 Mar 10;19(2):135-41. Epub 2014 Feb 10.

Heart Failure and Cardiac Transplant Group, Cardiovascular Experimental and Molecular Laboratory, Division of Cardiology, Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil and.

Context: Elevated plasmatic microRNAs (miRs) are observed in heart failure (HF). However, the cardiac origin of these miRs remains unclear.

Objective: We calculated transcoronary gradients of miR-29b, miR-133a and miR-423-5p in 17 outpatients with stable systolic HF and in controls without structural cardiac disease.

Materials And Methods: MicroRNAs were measured by quantitative real-time polymerase chain reaction.

Results: Positive transcoronary miR gradients were observed in patients with HF but not in controls (p = 0.03). B-type natriuretic peptide (BNP) moderately correlated with the transcoronary gradients of miR-133a and miR-423-5p.

Discussion And Conclusions: The difference in transcoronary gradients between HF outpatients and controls suggests that miR-423-5p has a cardiac origin. The positive correlation between miR-423-5p and BNP transcoronary gradients supports this hypothesis.
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http://dx.doi.org/10.3109/1354750X.2013.870605DOI Listing
March 2014

QRS widening rates and genetic polymorphisms of matrix metalloproteinases in a cohort of patients with chronic heart failure.

Can J Cardiol 2014 Mar 20;30(3):345-51. Epub 2013 Nov 20.

Experimental and Molecular Cardiovascular Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil; Post-Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address:

Background: QRS duration is considered to be an indicator of adverse outcome in patients with heart failure (HF), and genetic polymorphisms may be involved in this conductivity impairment. We studied the prognostic impact of the QRS widening rate (QRS-WR) on patients with HF and the influence of the matrix metalloproteinases gene polymorphisms on the QRS-WR.

Methods: This prospective cohort study included 184 patients with left ventricular (LV) systolic dysfunction (LV ejection fraction [LVEF] < 45%). The QRS-WR was calculated as the difference between 2 electrocardiogram assessments (in ms) divided by the time elapsed between each evaluation (months). The MMP-1 -1607 1G/2G, MMP-2 -790G/T and -1575G/A, MMP-3 -1171 5A/6A, MMP-9 -1562 C/T and R279Q, and MMP-12 -82A/G polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism.

Results: Patients were predominantly white (68%) men (67%) in New York Heart Association functional classes I and II (77%). Patients with HF with a QRS-WR ≥ 0.5 ms/month had more HF-related deaths and more combined clinical events than those with a QRS-WR < 0.5 ms/month (P = 0.03 and P = 0.01, respectively). After adjusting for other covariates, the QRS-WR remained an independent predictor of combined clinical events (hazard ratio, 1.6; 95% confidence interval, 1.1-2.5; P = 0.02). The MMP-1 2G2G genotype was associated with nearly a 2-fold increase in QRS-WR (P = 0.03). Conversely, patients with the MMP-3 5A5A genotype and a nonischemic cause of HF were protected against QRS enlargement (P = 0.03).

Conclusions: QRS-WR retains prognostic value in patients with chronic HF receiving guideline-based pharmacologic treatment. MMP gene polymorphisms can influence the rate of QRS enlargement over time.
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http://dx.doi.org/10.1016/j.cjca.2013.11.014DOI Listing
March 2014

A new algorithm for weekly phenprocoumon dose variation in a southern Brazilian population: role for CYP2C9, CYP3A4/5 and VKORC1 genes polymorphisms.

Basic Clin Pharmacol Toxicol 2014 Apr 7;114(4):323-9. Epub 2013 Dec 7.

Genetics Department, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

Phenprocoumon is widely used in prophylaxis and treatment of thromboembolic disorders. However, its pharmacokinetics and pharmacodynamics vary according to several genetic and non-genetic factors. Phenprocoumon metabolism is mediated by CYP2C9 and CYP3A enzymes. Moreover, VKORC1 is phenprocoumon target of action. Therefore, the aim of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) in VKORC1, CYP2C9, CYP3A4 and CYP3A5 genes with the variance of weekly phenprocoumon dose as well as to develop an algorithm for dose prediction based on genetic and environmental factors. A total of 198 patients with stable phenprocoumon dose, 81% of European ancestry, were investigated. Genotypes were determined by allelic discrimination with TaqMan assays. Polymorphisms -1639G>A and 1173C>T in VKORC1 and the presence of CYP2C9*2 and/or CYP2C9*3 are associated with lower doses. On the other hand, 3730G>A in VKORC1 gene is associated with higher doses. No association was found between CYP3A4*1B, CYP3A5*3 and CYP3A5*6 polymorphisms. Among non-genetic factors, gender, height, age and use of captopril, omeprazole, simvastatin and β-blockers are associated with dose. Two algorithms were derived: one for the whole sample explained 42% of dose variation and one for patients of European ancestry only which explained 46% of phenprocoumon dose. The mean absolute difference between observed and predicted dose was low in both models (3.92 mg/week and 3.54 mg/week, for models 1 and 2, respectively). However, more studies with other genes and environmental factors are needed to test and to improve the algorithm.
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http://dx.doi.org/10.1111/bcpt.12172DOI Listing
April 2014

Iron therapy in patients with heart failure. A straight shot.

Int J Cardiol 2013 Oct 30;168(5):5071-2. Epub 2013 Jul 30.

Heart Failure and Cardiac Transplant Unit, Cardiology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; Post-Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2013.07.199DOI Listing
October 2013

Influence of VKORC1 gene polymorphisms on the effect of oral vitamin K supplementation in over-anticoagulated patients.

J Thromb Thrombolysis 2014 Apr;37(3):338-44

Post-Graduate Program in Health Science, Cardiology and Cardiovascular Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

Significant inter-individual variability on the effect of vitamin K to reverse overanticoagulation has been identified. Genetic polymorphisms of the vitamin K epoxide reductase complex subunit 1 (VKORC1) gene might explain in part this variability. The objective of this study was to evaluate the influence of VKORC1 -1639G>A and 3730G>A polymorphisms on the effect of oral vitamin K supplementation in overanticoagulated patients. We performed an interventional trial of oral vitamin K supplementation in over-anticoagulated outpatients (international normalized ratio [INR] ≥ 4). Subjects received vitamin K (2.5-5.0 mg) according to baseline INR and were genotyped by real time polymerase chain reaction (PCR). INR values were determined at 3, 6, 24 and 72 h after supplementation. We evaluated 33 outpatients, 61 % were males, with a mean age of 62 ± 12 years old. There was a significant decrease in INR values over time for both polymorphisms after oral vitamin K. At 3 h after supplementation, patients carrying the G allele for the -1639G>A polymorphism had a greater decrease in INR values compared to AA patients (p < 0.05 for difference among groups; p < 0.001 for time variation; p = 0.001 for time × group interaction), with differences of -1.01 for GG versus AA (p = 0.003) and -0.84 for GA versus AA (p = 0.024). Mean INR value at 24 h was 1.9 ± 0.6 and at 72 h was 2.1 ± 0.7, with no differences among genotypes. No significant interaction was identified between the 3730G>A polymorphism and vitamin K supplementation. Our study indicated that the VKORC1 -1639G>A polymorphism plays a role in the response to acute vitamin K supplementation in over-anticoagulated patients, with faster decrease of INR value in patients carrying the G allele.
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http://dx.doi.org/10.1007/s11239-013-0947-3DOI Listing
April 2014

Aggressive fluid and sodium restriction in acute decompensated heart failure: a randomized clinical trial.

JAMA Intern Med 2013 Jun;173(12):1058-64

Postgraduate Program in Cardiovascular Sciences, Cardiology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

Importance: The benefits of fluid and sodium restriction in patients hospitalized with acute decompensated heart failure (ADHF) are unclear.

Objective: To compare the effects of a fluid-restricted (maximum fluid intake, 800 mL/d) and sodium-restricted (maximum dietary intake, 800 mg/d) diet (intervention group [IG]) vs a diet with no such restrictions (control group [CG]) on weight loss and clinical stability during a 3-day period in patients hospitalized with ADHF.

Design: Randomized, parallel-group clinical trial with blinded outcome assessments.

Setting: Emergency room, wards, and intensive care unit.

Participants: Adult inpatients with ADHF, systolic dysfunction, and a length of stay of 36 hours or less.

Intervention: Fluid restriction (maximum fluid intake, 800 mL/d) and additional sodium restriction (maximum dietary intake, 800 mg/d) were carried out until the seventh hospital day or, in patients whose length of stay was less than 7 days, until discharge. The CG received a standard hospital diet, with liberal fluid and sodium intake.

Main Outcomes And Measures: Weight loss and clinical stability at 3-day assessment, daily perception of thirst, and readmissions within 30 days.

Results: Seventy-five patients were enrolled (IG, 38; CG, 37). Most were male; ischemic heart disease was the predominant cause of heart failure (17 patients [23%]), and the mean (SD) left ventricular ejection fraction was 26% (8.7%). The groups were homogeneous in terms of baseline characteristics. Weight loss was similar in both groups (between-group difference in variation of 0.25 kg [95% CI, -1.95 to 2.45]; P = .82) as well as change in clinical congestion score (between-group difference in variation of 0.59 points [95% CI, -2.21 to 1.03]; P = .47) at 3 days. Thirst was significantly worse in the IG (5.1 [2.9]) than the CG (3.44 [2.0]) at the end of the study period (between-group difference, 1.66 points; time × group interaction; P = .01). There were no significant between-group differences in the readmission rate at 30 days (IG, 11 patients [29%]; CG, 7 patients [19%]; P = .41).

Conclusions And Relevance: Aggressive fluid and sodium restriction has no effect on weight loss or clinical stability at 3 days and is associated with a significant increase in perceived thirst. We conclude that sodium and water restriction in patients admitted for ADHF are unnecessary.

Trial Registration: clinicaltrials.gov Identifier: NCT01133236.
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http://dx.doi.org/10.1001/jamainternmed.2013.552DOI Listing
June 2013