Multifaceted Strategy Based on Automated Text Messaging After a Recent Heart Failure Admission: The MESSAGE-HF Randomized Clinical Trial.

Importance: Readmissions after an index heart failure (HF) hospitalization are a major contemporary health care problem. Objective: To evaluate the feasibility and efficacy of an intensive telemonitoring strategy in the vulnerable period after an HF hospitalization. Design, Setting, and Participants: This randomized clinical trial was conducted in 30 HF clinics in Brazil. Patients with left ventricular ejection fraction less than 40% and access to mobile phones were enrolled up to 30 days after an HF admission. Data were collected from July 2019 to July 2022. Intervention: Participants were randomly assigned to a telemonitoring strategy or standard care. The telemonitoring group received 4 daily short message service text messages to optimize self-care, active engagement, and early intervention. Red flags based on feedback messages triggered automatic diuretic adjustment and/or a telephone call from the health care team. Main Outcomes and Measures: The primary end point was change in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to 180 days. A hierarchical win-ratio analysis incorporating blindly adjudicated clinical events (cardiovascular deaths and HF hospitalization) and variation in NT-proBNP was also performed. Results: Of 699 included patients, 460 (65.8%) were male, and the mean (SD) age was 61.2 (14.5) years. A total of 352 patients were randomly assigned to the telemonitoring strategy and 347 to standard care. Satisfaction with the telemonitoring strategy was excellent (net promoting score at 180 days, 78.5). HF self-care increased significantly in the telemonitoring group compared with the standard care group (score difference at 30 days, -2.21; 95% CI, -3.67 to -0.74; P = .001; score difference at 180 days, -2.08; 95% CI, -3.59 to -0.57; P = .004). Variation of NT-proBNP was similar in the telemonitoring group compared with the standard care group (telemonitoring: baseline, 2593 pg/mL; 95% CI, 2314-2923; 180 days, 1313 pg/mL; 95% CI, 1117-1543; standard care: baseline, 2396 pg/mL; 95% CI, 2122-2721; 180 days, 1319 pg/mL; 95% CI, 1114-1564; ratio of change, 0.92; 95% CI, 0.77-1.11; P = .39). Hierarchical analysis of the composite outcome demonstrated a similar number of wins in both groups (telemonitoring, 49 883 of 122 144 comparisons [40.8%]; standard care, 48 034 of 122 144 comparisons [39.3%]; win ratio, 1.04; 95% CI, 0.86-1.26). Conclusions and Relevance: An intensive telemonitoring strategy applied in the vulnerable period after an HF admission was feasible, well-accepted, and increased scores of HF self-care but did not translate to reductions in NT-proBNP levels nor improvement in a composite hierarchical clinical outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT04062461.

Multifaceted strategy based on automated text messaging after a recent heart failure admission: the MESSAGE-HF Randomized Clinical Trial

IMPORTANCE: Readmissions after an index heart failure (HF) hospitalization are a major contemporary health care problem. OBJECTIVE: To evaluate the feasibility and efficacy of an intensive telemonitoring strategy in the vulnerable period after an HF hospitalization. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted in 30 HF clinics in Brazil. Patients with left ventricular ejection fraction less than 40% and access to mobile phones were enrolled up to 30 days after an HF admission. Data were collected from July 2019 to July 2022. INTERVENTION: Participants were randomly assigned to a telemonitoring strategy or standard care. The telemonitoring group received 4 daily short message service text messages to optimize self-care, active engagement, and early intervention. Red flags based on feedback messages triggered automatic diuretic adjustment and/or a telephone call from the health care team. MAIN OUTCOMES AND MEASURES: The primary end point was change in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to 180 days. A hierarchical win-ratio analysis incorporating blindly adjudicated clinical events (cardiovascular deaths and HF hospitalization) and variation in NT-proBNP was also performed. RESULTS: Of 699 included patients, 460 (65.8%) were male, and the mean (SD) age was 61.2 (14.5) years. A total of 352 patients were randomly assigned to the telemonitoring strategy and 347 to standard care. Satisfaction with the telemonitoring strategy was excellent (net promoting score at 180 days, 78.5). HF self-care increased significantly in the telemonitoring group compared with the standard care group (score difference at 30 days, -2.21; 95% CI, -3.67 to -0.74; P = .001; score difference at 180 days, -2.08; 95% CI, -3.59 to -0.57; P = .004). Variation of NT-proBNP was similar in the telemonitoring group compared with the standard care group (telemonitoring: baseline, 2593 pg/mL; 95% CI, 2314-2923; 180 days, 1313 pg/mL; 95% CI, 1117-1543; standard care: baseline, 2396 pg/mL; 95% CI, 2122-2721; 180 days, 1319 pg/mL; 95% CI, 1114-1564; ratio of change, 0.92; 95% CI, 0.77-1.11; P = .39). Hierarchical analysis of the composite outcome demonstrated a similar number of wins in both groups (telemonitoring, 49 883 of 122 144 comparisons [40.8%]; standard care, 48 034 of 122 144 comparisons [39.3%]; win ratio, 1.04; 95% CI, 0.86-1.26). CONCLUSIONS and relevance: An intensive telemonitoring strategy applied in the vulnerable period after an HF admission was feasible, well-accepted, and increased scores of HF self-care but did not translate to reductions in NT-proBNP levels nor improvement in a composite hierarchical clinical outcome.

Design of a multifaceted strategy based on automated text messaging in patients with recent heart failure admission.

AIMS: To evaluate a telemonitoring strategy based on automated text messaging and telephone support after heart failure (HF) hospitalization. METHODS AND RESULTS: The MESSAGE-HF study is a prospective multicentre, randomized, nationwide trial enrolling patients from 30 clinics in all regions of Brazil. HF patients with reduced left ventricular ejection fraction (<40%) and access to mobile phones are eligible after an acute decompensated HF hospitalization. Patients meeting eligibility criteria undergo an initial feasibility text messaging assessment and are randomized to usual care or telemonitoring intervention. All patients receive a HF booklet with basic information and recommendations about self-care. Patients in the intervention group receive four daily short text messages (educational and feedback) during the first 30 days of the protocol to optimize self-care; the feedback text messages from patients could trigger diuretic adjustments or a telephone call from the healthcare team. After 30 days, the frequency of text messages can be adjusted. Patients are followed up after 30, 90, and 180 days, with final status ascertained at 365 days by telephone. Our primary endpoint is the change in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels after 180 days. Secondary endpoints include changes in NT-proBNP after 30 days; health-related quality of life, HF self-care, and knowledge scales after 30 and 180 days; and a composite outcome of HF hospitalization and cardiovascular death, adjudicated by a blinded and independent committee. CONCLUSIONS: The MESSAGE-HF trial is evaluating an educational and self-care promotion strategy involving a simple, intensive, and tailored telemonitoring system. If proven effective, it could be applied to a broader population worldwide.

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

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 Rede Brasileira de Estudos em Insuficiência Cardíaca (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.

Prevalence of metabolic syndrome and its association with risk factors in patients with established atherosclerosis disease.

Risk factors can lead to clinical conditions, like metabolic syndrome, that predisposes the development of cardiovascular diseases. The aim of this study was to describe the prevalence and which risk factors cause more impact in metabolic syndrome in patients with established atherosclerosis disease. A cross-sectional study was performed as a subanalysis of Programa Alimentação Cardioprotetora Brasileira. Weight, height, waist circumference, blood pressure, lipid profile and fasting glucose were collected. Metabolic syndrome was defined according to the harmonized criteria. Linear regression was used to analyze the association between number of components of metabolic syndrome and risk factors. 82 patients were included and the prevalence of metabolic syndrome was 84.1%. Being overweight was associated with an increase by 0.55 point in diagnostic criteria of metabolic syndrome in crude analysis (95%CI 0.09-1.00) and 0.64 in adjusted analysis (95%CI 0.18-1.09), while former/current smoker status was responsible for raising by 0.48 the number of components of metabolic syndrome, only in adjusted analysis (95%CI 0.04-0.92). Overweight and former/current smoker status are associated with MS, increasing the probability of atherosclerotic events. A healthy lifestyle, that includes avoiding tobacco exposure and proper weight control, must be encouraged in this high-risk population.

Implementation of a Brazilian Cardioprotective Nutritional (BALANCE) Program for improvement on quality of diet and secondary prevention of cardiovascular events: A randomized, multicenter trial

Background Complex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk (HBR) may be present, making it unclear whether short- or long-term DAPT should be prioritized. Objectives This study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT [PRE dicting bleeding Complications in patients undergoing stent Implantation and Sub sequent Dual Anti Platelet Therapy] score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting. Methods Complex PCI was defined as ≥3 stents implanted and/or ≥3 lesions treated, bifurcation stenting and/or stent length >60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high (≥25) or non-high (<25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT. Results Among 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference: −3.86%; 95% confidence interval: −7.71 to +0.06) and noncomplex PCI strata (absolute risk difference: −1.14%; 95% confidence interval: −2.26 to −0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity. Conclusions Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT. (AU)

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

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.

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.

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.

Cost-effectiveness of anatomical and functional test strategies for stable chest pain: public health perspective from a middle-income country.

OBJECTIVES: The aim of this research is to evaluate the relative cost-effectiveness of functional and anatomical strategies for diagnosing stable coronary artery disease (CAD), using exercise (Ex)-ECG, stress echocardiogram (ECHO), single-photon emission CT (SPECT), coronary CT angiography (CTA) or stress cardiacmagnetic resonance (C-MRI). SETTING: Decision-analytical model, comparing strategies of sequential tests for evaluating patients with possible stable angina in low, intermediate and high pretest probability of CAD, from the perspective of a developing nation's public healthcare system. PARTICIPANTS: Hypothetical cohort of patients with pretest probability of CAD between 20% and 70%. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is cost per correct diagnosis of CAD. Proportion of false-positive or false-negative tests and number of unnecessary tests performed were also evaluated. RESULTS: Strategies using Ex-ECG as initial test were the least costly alternatives but generated more frequent false-positive initial tests and false-negative final diagnosis. Strategies based on CTA or ECHO as initial test were the most attractive and resulted in similar cost-effectiveness ratios (I$ 286 and I$ 305 per correct diagnosis, respectively). A strategy based on C-MRI was highly effective for diagnosing stable CAD, but its high cost resulted in unfavourable incremental cost-effectiveness (ICER) in moderate-risk and high-risk scenarios. Non-invasive strategies based on SPECT have been dominated. CONCLUSIONS: An anatomical diagnostic strategy based on CTA is a cost-effective option for CAD diagnosis. Functional strategies performed equally well when based on ECHO. C-MRI yielded acceptable ICER only at low pretest probability, and SPECT was not cost-effective in our analysis.

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

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.

Cost-effectiveness of heart failure therapies.

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Management of HF involves accurate diagnosis and implementation of evidence-based treatment strategies. Costs related to the care of patients with HF have increased substantially over the past 2 decades, partly owing to new medications and diagnostic tests, increased rates of hospitalization, implantation of costly novel devices and, as the disease progresses, consideration for heart transplantation, mechanical circulatory support, and end-of-life care. Not surprisingly, HF places a huge burden on health-care systems, and widespread implementation of all potentially beneficial therapies for HF could prove unrealistic for many, if not all, nations. Cost-effectiveness analyses can help to quantify the relationship between clinical outcomes and the economic implications of available therapies. This Review is a critical overview of cost-effectiveness studies on key areas of HF management, involving pharmacological and nonpharmacological clinical therapies, including device-based and surgical therapeutic strategies.

Cost-effectiveness of cardiac resynchronization therapy in patients with heart failure: the perspective of a middle-income country's public health system.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves symptoms and survival in patients with heart failure (HF). However, the devices used to deliver it are costly and can impose a significant burden to the relatively constrained health budgets of middle-income countries such as Brazil. METHODS: A Markov model was constructed, representing the follow-up of a hypothetical cohort of HF patients, with a 20-year time horizon. Input data were based on information from a Brazilian cohort of 316 HF patients, as well as meta-analyses of data on devices' effectiveness and risks. Stochastic and probabilistic sensitivity analyses were performed for all important variables in the model. Costs were expressed as International Dollars (Int$), by application of current purchasing power parity conversion rate. RESULTS: In the base-case analysis, the incremental cost-effectiveness ratio (ICER) of CRT over medical therapy was Int$ 15,723 per quality-adjusted life years (QALYs) gained. For CRT combined with an implantable cardioverter-defibrillator (ICD), ICER was Int$ 36,940/QALY over ICD alone, and Int$ 84,345/QALY over CRT alone. Sensitivity analyses showed that the model was generally robust, though susceptible to the cost of the devices, their impact on HF mortality, and battery longevity. CONCLUSIONS: CRT is cost-effective for HF patients in the Brazilian public health system scenario. In patients eligible for CRT, upgrade to CRT+ICD has an ICER above the World Health Organization willingness-to-pay threshold of three times the nation's Gross Domestic Product per Capita (Int$ 31,689 for Brazil). However, for ICD eligible patients, upgrade to CRT+ICD is marginally cost-effective.