Cholesteryl ester transfer protein (CETP), HDL capacity of receiving cholesterol and status of inflammatory cytokines in patients with severe heart failure.

BACKGROUND: Heart failure (HF) courses with chronic inflammatory process and alterations in lipid metabolism may aggravate the disease. The aim was to test whether the severity of HF, using brain natriuretic peptide (BNP) as a marker, is associated with alterations in functional aspects of HDL, such as lipid transfer, cholesterol ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT) concentration. METHODS: Twenty-five HF patients in NYHA class I/II and 23 in class III/IV were enrolled. Plasma lipids, apolipoproteins, CETP, LCAT, oxidized-LDL (oxLDL) and paraoxonase-1 (PON-1) activity were determined. Lipid transfer from a donor artificial nanoparticle to HDL was measured by in vitro assay. RESULTS: Total cholesterol (p = 0.049), LDL-C (p = 0.023), non-HDL-C (p = 0.029) and CETP, that promotes lipid transfer among lipoproteins (p = 0.013), were lower in III/IV than in I/II group. Triglycerides, HDL-C, apo A-I, apo B, oxLDL, LCAT, enzyme that catalyzes serum cholesterol esterification, PON-1 activity, and in vitro transfers of cholesterol, triglycerides and phospholipids to HDL, important steps in HDL metabolism, were equal. IL-8 was higher in III/IV (p = 0.025), but TNFα, IL-1ß, IL-6 and MCP-1 were equal. BNP was negatively correlated with CETP (r = - 0.294; p = 0.042) and positively correlated with IL-8 (r = 0.299; p = 0.039). CONCLUSIONS: Our results disclosed the relationship between CETP levels and HF severity, by comparing two HF groups and by correlation analysis. Lower CETP levels may be a marker of HF aggravation and possibly of worse prognosis. Practical applications of this initial finding, as the issue whether CETP could be protective against HF aggravation, should be explored in larger experimental and clinical studies.

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.

The use of peripherally inserted central catheter reduced the incidence of phlebitis in heart failure patients: A randomized trial.

BACKGROUND: During decompensated heart failure, the use of intravenous inotropes can be necessary. With peripheral venous access, prolonged inotrope infusion can cause phlebitis. However, traditional central venous catheters have possible complications. Peripherally inserted central catheters (PICCs) may be an alternative to traditional catheters. AIM: Our objective was to compare the incidence of phlebitis between patients with PICC and those with peripheral venous access catheter indwelling. METHODS: In a randomized clinical trial, the patients were randomized to PICC and control groups, with 40 patients in each group. The inclusion criteria were hospitalized patients with advanced heart failure, ejection fraction of <0.45, and platelet count of >50,000/mm3 and current use of continuous intravenous infusion of dobutamine. The patients were randomly assigned to receive a PICC or keep their peripheral venous access. The primary end point was the occurrence of phlebitis. RESULTS: The PICC and control groups included 40 patients each. The median age was 61.5 years; ejection fraction, 0.24; and dobutamine dose, 7.73 µg/(kg min). Phlebitis occurred in 1 patient (2.5%) in the PICC group and in 38 patients (95.0%) in the control group, with an odds ratio of 0.10% (95% confidence interval: 0.01%-1.60%, p < 0.001). CONCLUSION: In conclusion, in severe heart failure patients who received intravenous dobutamine, PICC use reduced the incidence of phlebitis when compared to patients with peripheral venous access. Therefore, the PICC use should considered over peripheral venous access for prolonged intravenous therapy in heart failure patients.

Sex Differences in Prognosis of Heart Failure Due to Ischemic and Nonischemic Cardiomyopathy.

BACKGROUND: Limited research has explored sex-specific differences in death predictors of HF patients with ischemic (iCMP) and nonischemic (niCMP) cardiomyopathy. This study assessed sex differences in niCMP and iCMP prognosis. METHODS: We studied 7487 patients with HF between February 2017 and September 2020. Clinical features and echocardiographic findings were collected. We used Kaplan-Meier, Cox proportional hazard models, and chi-square scores of Cox regression to determine death predictors in women and men. RESULTS: The mean age was 64.3 ± 14.2 years, with 4417 (59%) males. Women with iCMP and niCMP exhibited a significantly higher mean age, higher mean left ventricular ejection fraction, and smaller left ventricular diastolic diameter than men. Over 2.26 years of follow-up, 325 (14.7%) women and 420 (15.7%) men, and 211 women (24.5%) and 519 men (29.8%) with niCMP (p = NS) and iCMP (p = 0.004), respectively, died. The cumulative incidence of death was higher in men with iCMP (log-rank p < 0.0001) but similar with niCMP. Cox regression showed chronic kidney disease, diabetes, stroke, atrial fibrillation, age, and myocardial infarction as the main predictors of death for iCMP in women and men. CONCLUSIONS: Women exhibited a better prognosis than men with iCMP, but similar for niCMP. Nevertheless, sex was not an independent predictor of death for both CMP.

Sex Differences in Cardiovascular Disease Mortality in Brazil between 1996 and 2019.

BACKGROUND: cardiovascular diseases (CVD) are Brazil's leading causes of death in women and men. This study analyzed age-adjusted death rate (DRaj) trends from all causes of death (ACD), CVD, ischemic heart disease (IHD), and stroke in women and men aged 35 to 74 years from 1996 to 2019. METHODS: We analyzed DRaj trends for all causes of death (ACD), CVD, IHD, and stroke. Data were from the Ministry of Health mortality database. Joinpoint Regression Program™ performed trend analysis and adjustments in death rates. Average annual percentage change (AAPC) determined the intensity of changes. RESULTS: In women, DRaj reduced for ACD (AAPC = -1.6%); CVD (AAPC = -2.6%); IHD (AAPC = -1.9%); and stroke (AAPC = -4.6%) (p < 0.001 for all). In men, ACD reduced from 1996 to 2004 (AAPC = -0.9%; p < 0.001), from 2012 to 2019 (AAPC = -1.9%; p < 0.001), and unchanged from 2004 to 2012; CVD (AAPC = -2.1%); IHD (AAPC = -1.5%); stroke (AAPC = -4.9%) (p < 0.001 for all) reduced from 1996 to 2019. From 1996 to 2019, the male/female ratio for ACD remained unchanged. CVD increased from 1.58 to 1.83, IHD from 1.99 to 2.30, and stroke from 1.52 to 1.83. CONCLUSION: ACD, CVD, IHD, and stroke were reduced more significantly in women, and the ratio of CVD, IHD, and CVD in men and women increased more in men. Future studies will be needed to determine the main factors responsible for a better outcome in women.

Sex Differences in Heart Failure Mortality with Preserved, Mildly Reduced and Reduced Ejection Fraction: A Retrospective, Single-Center, Large-Cohort Study.

BACKGROUND: Heart failure (HF) is one of the leading causes of death worldwide. Studies show that women have better survival rates than men despite higher hospitalizations. However, little is known about differences in mortality and predictors of death in women and men with HF with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF). METHODS: From February 2017 to September 2020, mortality and predictors of death were analyzed in women and men with HF. Baseline data included clinical characteristics and echocardiographic findings. RESULTS: A total of 11,282 patients, 63.9 ± 14.4 years, including 6256 (55.4%) males, were studied. Females were older, had a higher baseline mean left ventricular ejection fraction (LVEF) and lower left ventricular diastolic diameter. During follow-ups, 1375 (22%) men and 925 (18.4%) women died. Cumulative incidence of death was higher in men with HFrEF but similar for HFmrEF and HFpEF. Cox regression for death showed renal dysfunction, stroke, diabetes, atrial fibrillation, age, LVEF, valve disease, MI, and hypertensive CMP as independent death predictors for all HF patients. CONCLUSIONS: Women had a better prognosis than men in HFrEF and similar mortality for HFmrEF and HFpEF, but sex was not an independent predictor of death for all HF subtypes.

Implications for Clinical Practice from a Multicenter Survey of Heart Failure Management Centers.

OBJECTIVES: This observational, cross-sectional study based aimed to test whether heart failure (HF)-disease management program (DMP) components are influencing care and clinical decision-making in Brazil. METHODS: The survey respondents were cardiologists recommended by experts in the field and invited to participate in the survey via printed form or email. The survey consisted of 29 questions addressing site demographics, public versus private infrastructure, HF baseline data of patients, clinical management of HF, performance indicators, and perceptions about HF treatment. RESULTS: Data were obtained from 98 centers (58% public and 42% private practice) distributed across Brazil. Public HF-DMPs compared to private HF-DMP were associated with a higher percentage of HF-DMP-dedicated services (79% vs 24%; OR: 12, 95% CI: 94-34), multidisciplinary HF (MHF)-DMP [84% vs 65%; OR: 3; 95% CI: 1-8), HF educational programs (49% vs 18%; OR: 4; 95% CI: 1-2), written instructions before hospital discharge (83% vs 76%; OR: 1; 95% CI: 0-5), rehabilitation (69% vs 39%; OR: 3; 95% CI: 1-9), monitoring (44% vs 29%; OR: 2; 95% CI: 1-5), guideline-directed medical therapy-HF use (94% vs 85%; OR: 3; 95% CI: 0-15), and less B-type natriuretic peptide (BNP) dosage (73% vs 88%; OR: 3; 95% CI: 1-9), and key performance indicators (37% vs 60%; OR: 3; 95% CI: 1-7). In comparison to non- MHF-DMP, MHF-DMP was associated with more educational initiatives (42% vs 6%; OR: 12; 95% CI: 1-97), written instructions (83% vs 68%; OR: 2: 95% CI: 1-7), rehabilitation (69% vs 17%; OR: 11; 95% CI: 3-44), monitoring (47% vs 6%; OR: 14; 95% CI: 2-115), GDMT-HF (92% vs 83%; OR: 3; 95% CI: 0-15). In addition, there were less use of BNP as a biomarker (70% vs 84%; OR: 2; 95% CI: 1-8) and key performance indicators (35% vs 51%; OR: 2; 95% CI: 91,6) in the non-MHF group. Physicians considered changing or introducing new medications mostly when patients were hospitalized or when observing worsening disease and/or symptoms. Adherence to drug treatment and non-drug treatment factors were the greatest medical problems associated with HF treatment. CONCLUSION: HF-DMPs are highly heterogeneous. New strategies for HF care should consider the present study highlights and clinical decision-making processes to improve HF patient care.

Was the Enalapril Dose Too Low in the PARADIGM-HF Trial?

Heart failure (HF) is a common clinical syndrome associated with significant morbidity and mortality, and there remains a clear need for innovative therapies that can modify disease progression. Sacubitril/valsartan (LCZ696) is a novel complex that combines simultaneous neprilysin inhibition and angiotensin II receptor blockade, that has demonstrated significant cardiovascular death or HF hospitalization reduction in the Prospective Comparison of Angiotensin Receptor/Neprilysin Inhibitor (ARNI) With Angiotensin-Converting Enzyme (ACE) Inhibitors to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial when compared with evidence-based doses of the gold standard ACE inhibitor enalapril. In this comprehensive review, the authors discuss historical trials that have investigated clinical outcomes utilizing variable dosing levels of ACE inhibitors or angiotensin receptor blockers in patients with HF with reduced ejection fraction. A critical analysis of the highlighted studies is proposed in the context of current HF management guidelines and HF clinical practice. In conclusion, based on current evidence, it is unclear whether a maximum recommended enalapril dose would promote improved patient outcomes compared with an intermediate dose. However, no prospective study to date comparing ACE inhibitor doses has documented that higher doses result in significant mortality reduction, although the data suggest that there may be a decrease in HF hospitalizations when compared with lower doses.

Rationale and design of the IRON-HF study: a randomized trial to assess the effects of iron supplementation in heart failure patients with anemia.

BACKGROUND: Anemia is a common finding in heart failure (HF) patients and has been associated with increased morbidity and mortality. It is generally denominated as anemia of chronic disease (ACD), but the association with true ferropenic anemia is common. Many studies have investigated the effects of treating anemia in HF patients with either erythropoietin alone or combination of erythropoietin and intravenous iron. However, the effect of iron supplementation alone in HF patients with ACD, ferropenic anemia, or both is unknown. METHODS AND RESULTS: IRON-HF study is a multicenter, investigator initiated, randomized, double-blind, placebo controlled trial that will enroll anemic HF patients with relatively preserved renal function, low transferrin saturation, low iron levels, and low to moderately elevated ferritin levels. Interventions are iron sucrose intravenously 200 mg once per week for 5 weeks, ferrous sulfate 200 mg by mouth 3 times per day for 8 weeks, or placebo. The primary objective is to assess the impact of iron supplementation (intravenously or by mouth) compared with placebo in HF patients with anemia from deficient iron availability. The primary end point is variation of peak oxygen consumption assessed by ergospirometry over 3-month follow-up. Secondary end points include functional class, brain natriuretic peptide levels, quality of life scores, left ventricular ejection fraction, adverse events, HF hospitalization, and death. CONCLUSIONS: The results of IRON-HF should help to clarify the potential clinical impact of mild to moderate anemia correction in HF patients.

The Medical Burden of Heart Failure: A Comparative Delineation with Cancer in Brazil

Abstract Background: Due to its poor prognosis and mortality rates, heart failure (HF) has been recognized as a malignant condition, comparable to some cancers in developed countries. Objectives: To compare mortality from HF and prevalent cancers using data from a nationwide database in Brazil. Methods: This was a descriptive, cross-sectional study using secondary data obtained from Brazilian administrative databases of death records and hospitalization claims maintained by the Ministry of Health. Data were analyzed according to main diagnosis, year of occurrence (2005-2015), sex and age group. Descriptive analyses of absolute number of events, hospitalization rate, mortality rate, and in-hospital mortality rate were performed. Results: The selected cancers accounted for higher mortality, lower hospitalization and higher in-hospital mortality rates than HF. In a group analysis, HF showed mortality rates of 100-150 per 100,000 inhabitants over the period, lower than the selected cancers. However, HF had a higher mortality rate than each type of cancer, even when compared to the most prevalent and deadly ones. Regarding hospitalization rates, HF was associated with a higher risk of hospitalization when compared to cancer-related conditions as a group. Conclusions: Our findings indicate that HF has an important impact on mortality, hospitalization and in-hospital mortality, comparable to or even worse than some types of cancer, representing a potential burden to the healthcare system.

[Serum NT-proBNP levels are a prognostic predictor in patients with advanced heart failure]. / O nível sérico de NT-proBNP é um preditor prognóstico em pacientes com insuficiência cardíaca avançada.

OBJECTIVE: To verify if the determination of NT-proBNP values would help predict the prognosis in advanced heart failure (HF) patients. METHODS: One hundred and five subjects with average age of 52.4 years were evaluated, 66.6% of them males. Thirty-three (32.0%) subjects were outpatients and 70 (67.9%) were inpatients (functional class III/IV) admitted to the hospital for cardiac compensation. All patients had left ventricular systolic dysfunction and a mean ejection fraction of 0.29. The NT-proBNP levels were measured in all patients and they were followed-up over a period from 2 to 90 days (average 77 days). A ROC curve was drawn to determine the best cut-off point, as well as the corresponding Kaplan-Meyer survival curves. RESULTS: During the follow-up period, 22 patients died. The average NT-proBNP value of the patients who remained alive was 6,443.67+/-6,071.62 pg/ml, whereas that of those who died was 14,609.66+/-12,165.15 pg/ml (p=0.001). The ROC curve identified a cut-off point at 6,000 pg/ml with 77.3% sensitivity (area under the curve: 0.74). The survival curve for values below and above 6,000 pg/ml was significantly different (p=0.002): patients with values below 6,000 pg/ml had a 90.2% 90-day survival, and those patients with values above, a 66% survival. CONCLUSION: Patients with advanced HF, especially those admitted to the hospital for cardiac compensation, had much higher NT-proBNP values, with a two-fold increase among those who died during the follow-up period. Values above 6,000 pg/ml identify the patients most likely to die within 90 days after hospital discharge.

[Score for nutritional status evaluation: the role played in the prognostic stratification of dilated cardiomyopathy and advanced heart failure patients]. / Escore para avaliação do estado nutricional: seu valor na estratificação prognóstica de portadores de cardiomiopatia dilatada e insuficiência cardíaca avançada.

OBJECTIVE: Develop a method for the evaluation of patients nutritional status through a score that expresses universal nutritional status, as well as investigate if that score would be efficient for the prognostic stratification of advanced heart failure (HF) pts. METHODS: The score was reached by the selection of evaluation methods that would quantify nutritional status: ideal body weight percentage, thickness of tricipital skinfold, percentiles for arm muscular mass circumference, albumin serum level, lymphocyte total count. In order to be validated, the score was applied to a group of 95 pts. Pts were under 65 years old no evidence of consumptive diseases. The score was analyzed to confirm whether it would keep correlation with HF clinical data and whether it would stratify its prognostic. RESULTS: Nutritional status suggesting moderate or severe malnutrition could be observed in 31/95 (32.6%). No correlation was found between nutritional score values and the duration of symptoms, or the level of ventricular dysfunction. Pts with high nutritional score showed a trend towards higher mortality rate (p=0.0606). CONCLUSION: Those data suggest malnutrition is reported by 1/3 of pts with advanced HF. A score comprising 5 parameters for nutritional status showed good correlation with the clinical, global evaluation of pts with HF. A score over 8 identified pts with higher probability of death as outcome, confirming that pts under higher malnutrition exhibit worse evolution.

[Economy class syndrome after long duration bus travel]. / Síndrome da classe econômica após longas viagens de ônibus.

A 65 year-old man with heart failure due to hypertensive and ischemic heart disease was admitted to the hospital with dyspnea, bloody sputum and pleuritic chest pain after a 52-hour bus trip. Clinical and laboratory evaluation included chest helical tomography that demonstrated a filling defect of the right main branch of the pulmonary artery and a regular peripheral opacity of triangular shape in the inferior lobe of the lower lung. The diagnosis of pulmonary thromboembolism was made and therapy with heparin, followed by warfarin was introduced. The patient was discharged from the hospital. The diagnosis of pulmonary embolism should be considered in patients with complaints like this patient after long-distance bus travel.

Addressing Major Unmet Needs in Patients with Systolic Heart Failure: The Role of Ivabradine.

We reviewed clinical evidence for the use of ivabradine in systolic heart failure (HF), in which it appears to improve symptoms, improve quality of life, prevent hospitalization, and prolong survival, thereby addressing unmet needs in the management of HF. Ivabradine provides symptomatic benefits in HF on top of standard therapies, in terms of functional parameters and exercise capacity, and there is some evidence that this leads to improvements in quality of life in symptomatic HF patients, who may have dyspnea, altered exercise capacity, and fatigue. The SHIFT trial demonstrated that ivabradine has significant beneficial effects on major outcomes in HF. Ivabradine had a significant effect on pump failure death, which was reduced by 26 % (p = 0.014), with no effect on sudden cardiac death. This is an important result since pump failure death is currently the main cause of death in HF, and also because the reductions in mortality obtained with beta-blockers and spironolactone in the last 20 years appear to be mainly due to reduction in sudden death rather than reduction in pump failure death. Ivabradine also has a beneficial effect on hospital admissions (-26 %, p < 0.0001), which is clinically relevant since a quarter of HF patients can expect to be readmitted to hospital for HF within 1 month of discharge. Ivabradine-treated patients are also at significantly lower risk of experiencing a second or third hospitalization for worsening HF. Ivabradine clearly has a key role to play in the management of HF by covering the main therapeutic objectives of symptoms, quality of life, and outcomes.

Implications for clinical practice from a multicenter survey of heart failure management centers

OBJECTIVES: This observational, cross-sectional study based aimed to test whether heart failure (HF)-disease management program (DMP) components are influencing care and clinical decision-making in Brazil. METHODS: The survey respondents were cardiologists recommended by experts in the field and invited to participate in the survey via printed form or email. The survey consisted of 29 questions addressing site demographics, public versus private infrastructure, HF baseline data of patients, clinical management of HF, performance indicators, and perceptions about HF treatment. RESULTS: Data were obtained from 98 centers (58% public and 42% private practice) distributed across Brazil. Public HF-DMPs compared to private HF-DMP were associated with a higher percentage of HF-DMP-dedicated services (79% vs 24%; OR: 12, 95% CI: 94-34), multidisciplinary HF (MHF)-DMP [84% vs 65%; OR: 3; 95% CI: 1-8), HF educational programs (49% vs 18%; OR: 4; 95% CI: 1-2), written instructions before hospital discharge (83% vs 76%; OR: 1; 95% CI: 0-5), rehabilitation (69% vs 39%; OR: 3; 95% CI: 1-9), monitoring (44% vs 29%; OR: 2; 95% CI: 1-5), guideline-directed medical therapy-HF use (94% vs 85%; OR: 3; 95% CI: 0-15), and less B-type natriuretic peptide (BNP) dosage (73% vs 88%; OR: 3; 95% CI: 1-9), and key performance indicators (37% vs 60%; OR: 3; 95% CI: 1-7). In comparison to non- MHF-DMP, MHF-DMP was associated with more educational initiatives (42% vs 6%; OR: 12; 95% CI: 1-97), written instructions (83% vs 68%; OR: 2: 95% CI: 1-7), rehabilitation (69% vs 17%; OR: 11; 95% CI: 3-44), monitoring (47% vs 6%; OR: 14; 95% CI: 2-115), GDMT-HF (92% vs 83%; OR: 3; 95% CI: 0-15). In addition, there were less use of BNP as a biomarker (70% vs 84%; OR: 2; 95% CI: 1-8) and key performance indicators (35% vs 51%; OR: 2; 95% CI: 91,6) in the non-MHF group. Physicians considered changing or introducing new medications mostly when patients were hospitalized or when observing worsening disease and/or symptoms. Adherence to drug treatment and non-drug treatment factors were the greatest medical problems associated with HF treatment. CONCLUSION: HF-DMPs are highly heterogeneous. New strategies for HF care should consider the present study highlights and clinical decision-making processes to improve HF patient care.

Cardiac and Hemodynamic Benefits: Mode of Action of Ivabradine in Heart Failure.

Heart failure has seen a number of therapeutic advances in recent years. Despite this, heart failure is still related to increasing rates of morbidity, repeated hospitalizations, and mortality. Ivabradine is a recent treatment option for heart failure. It has a mode of action that includes reduction in heart rate, and leads to improvement in outcomes related to heart failure mortality and morbidity, as demonstrated by the results of the SHIFT trial in patients with systolic heart failure, functional classes II and III on the New York Heart Association classification, and left ventricular ejection fraction ≤ 35%. These results are intriguing since many heart failure drugs reduce heart rate without such benefits, or with quite different effects, making it more difficult to understand the novelty of ivabradine in this setting. Many of the drugs used in heart failure modify heart rate, but most have other pathophysiological effects beyond their chronotropic action, which affect their efficacy in preventing morbidity and mortality outcomes. For instance, heart rate reduction at rest or exercise with ivabradine prolongs diastolic perfusion time, improves coronary blood flow, and increases exercise capacity. Another major difference is the increase in stroke volume observed with ivabradine, which may underlie its beneficial cardiac effects. Finally, there is mounting evidence from both preclinical and clinical studies that ivabradine has an anti-remodeling effect, improving left ventricular structures and functions. All together, these mechanisms have a positive impact on the prognosis of ivabradine-treated patients with heart failure, making a compelling argument for use of ivabradine in combination with other treatments.

Most Heart Failure Patients Die from Pump Failure: Implications for Therapy.

Careful review of the literature of the last 20 years since the appearance of the first positive trials in heart failure indicates an evolution in the mode of death moving from sudden death to a predominance of pump failure death (i.e., death due to progression of heart failure). Pump failure is becoming a leading cause of mortality in a range of patient profiles, including patients with newly diagnosed or severe heart failure, patients with devices, and patients with heart failure associated with Chagas' disease. Indeed, the evidence suggests that modern management strategies, such as beta-blockers and devices, are successful in preventing sudden death. However, this means that optimally treated patients are at greater risk for the consequences of pump failure (death, hospitalization, and reduced quality of life). This highlights a new important unmet need in heart failure, and a priority for current research should be therapies that reduce pump failure death and hospitalization for more cost-effective management of the disease. Insofar as one-third of heart failure patients do not survive more than 3 years after diagnosis, properly addressing pump failure is an essential target in heart failure.

Reverse Cardiac Remodeling: A Marker of Better Prognosis in Heart Failure.

In heart failure syndrome, myocardial dysfunction causes an increase in neurohormonal activity, which is an adaptive and compensatory mechanism in response to the reduction in cardiac output. Neurohormonal activity is initially stimulated in an attempt to maintain compensation; however, when it remains increased, it contributes to the intensification of clinical manifestations and myocardial damage. Cardiac remodeling comprises changes in ventricular volume as well as the thickness and shape of the myocardial wall. With optimized treatment, such remodeling can be reversed, causing gradual improvement in cardiac function and consequently improved prognosis.

ProBNP for stratifying patients with heart failure.

OBJECTIVE: To verify whether the serum levels of N-Terminal ProBNP fraction (ProBNP) allow us to identify with accuracy the clinical functional status of patients with heart failure (HF), because the clinical diagnosis of this syndrome is based basically on clinical data when the complementary tests have lower specificity. METHODS: Sixty-nine patients with a history of HF were studied. Their mean age of was 53.5 years and 78.3% were males. All underwent clinical and echocardiographic evaluations and a test to determine the serum dosage of ProBNP. According to clinical manifestation, patients were in the following functional classes (FC), 14% FC I, 40.6% FC II, 28.1% FC III, and 23.4% FC IV. The mean ejection fraction (EF) was 0.28. RESULTS: ProBNP did not differ according to age, sex, and cause of cardiopathy. No correlation existed between EF and the ProBNP serum level. ProBNP levels were significantly lower in patients in FC I than those in FC II (42 vs 326.7 pmol/L; P=0.0001), and in FC II than those in FC III (P=0.01). ProBNP levels did not differ statically between FC III and IV patients (888.1 vs 1082.8 pmol/L; P=0.25). ProBNP values greater than 100 pmol/L identify patients with decompensated HF with a sensitivity of 98%. CONCLUSION: ProBNP values over 100 pmol/L were indicative of HF, and patients with advanced HF had values over 270 pmol/L. A ProBNP dosage test was an excellent auxiliary in the clinical characterization of patients with HF.