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1.
Eur J Heart Fail ; 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31584231

RESUMO

Drugs that inhibit the sodium-glucose co-transporter 2 (SGLT2) have been shown to reduce the risk of hospitalizations for heart failure in patients with type 2 diabetes. In populations that largely did not have heart failure at the time of enrolment, empagliflozin, canagliflozin and dapagliflozin decreased the risk of serious new-onset heart failure events by ≈30%. In addition, in the EMPA-REG OUTCOME trial, empagliflozin reduced the risk of both pump failure and sudden deaths, the two most common modes of death among patients with heart failure. In none of the three trials could the benefits of SGLT2 inhibitors on heart failure be explained by the actions of these drugs as diuretics or anti-hyperglycaemic agents. These observations raise the possibility that SGLT2 inhibitors could reduce morbidity and mortality in patients with established heart failure, including those without diabetes. The EMPEROR-Reduced trial is enrolling ≈3600 patients with heart failure and a reduced left ventricular ejection fraction (≤ 40%), half of whom are expected not to have diabetes. Patients are being randomized to placebo or empagliflozin 10 mg daily, which is added to all appropriate treatment with inhibitors of the renin-angiotensin system and neprilysin, beta-blockers and mineralocorticoid receptor antagonists. The primary endpoint is the time-to-first event analysis of the combined risk of cardiovascular death and hospitalization for heart failure, but the trial will also evaluate the effects of empagliflozin on renal function, cardiovascular death, all-cause mortality, and recurrent hospitalization events. By adjusting eligibility based on natriuretic peptide levels to the baseline ejection fraction, the trial will preferentially enrol high-risk patients. A large proportion of the participants is expected to have an ejection fraction < 30%, and the estimated annual event rate is expected to be at least 15%. The EMPEROR-Reduced trial is well-positioned to determine if the addition of empagliflozin can add meaningfully to current approaches that have established benefits in the treatment of chronic heart failure with left ventricular systolic dysfunction.

2.
Eur J Heart Fail ; 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31523904

RESUMO

BACKGROUND: The principal biological processes that characterize heart failure with a preserved ejection fraction (HFpEF) are systemic inflammation, epicardial adipose tissue accumulation, coronary microcirculatory rarefaction, myocardial fibrosis and vascular stiffness; the resulting impairment of left ventricular and aortic distensibility (especially when accompanied by impaired glomerular function and sodium retention) causes increases in cardiac filling pressures and exertional dyspnoea despite the relative preservation of left ventricular ejection fraction. Independently of their actions on blood glucose, sodium-glucose co-transporter 2 (SGLT2) inhibitors exert a broad range of biological effects (including actions to inhibit cardiac inflammation and fibrosis, antagonize sodium retention and improve glomerular function) that can ameliorate the pathophysiological derangements in HFpEF. Such SGLT2 inhibitors exert favourable effects in experimental models of HFpEF and have been found in large-scale trials to reduce the risk for serious heart failure events in patients with type 2 diabetes, many of whom were retrospectively identified as having HFpEF. STUDY DESIGN: The EMPEROR-Preserved Trial is enrolling ≈5750 patients with HFpEF (ejection fraction >40%), with and without type 2 diabetes, who are randomized to receive placebo or empagliflozin 10 mg/day, which is added to all appropriate treatments for HFpEF and co-morbidities. STUDY AIMS: The primary endpoint is the time-to-first-event analysis of the combined risk for cardiovascular death or hospitalization for heart failure. The trial will also evaluate the effects of empagliflozin on renal function, cardiovascular death, all-cause mortality and recurrent hospitalization events, and will assess a wide range of biomarkers that reflect important pathophysiological mechanisms that may drive the evolution of HFpEF. The EMPEROR-Preserved Trial is well positioned to determine if empagliflozin can have a meaningful impact on the course of HFpEF, a disorder for which there are currently few therapeutic options.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31523937

RESUMO

The term sarcopenia was introduced in 1988. The original definition was a "muscle loss" of the appendicular muscle mass in the older people as measured by dual energy x-ray absorptiometry (DXA). In 2010, the definition was altered to be low muscle mass together with low muscle function and this was agreed upon as reported in a number of consensus papers. The Society of Sarcopenia, Cachexia and Wasting Disorders supports the recommendations of more recent consensus conferences, i.e. that rapid screening, such as with the SARC-F questionnaire, should be utilized with a formal diagnosis being made by measuring grip strength or chair stand together with DXA estimation of appendicular muscle mass (indexed for height2). Assessments of the utility of ultrasound and creatine dilution techniques are ongoing. Use of ultrasound may not be easily reproducible. Primary sarcopenia is aging associated (mediated) loss of muscle mass. Secondary sarcopenia (or disease-related sarcopenia) has predominantly focused on loss of muscle mass without the emphasis on muscle function. Diseases that can cause muscle wasting (i.e. secondary sarcopenia) include malignant cancer, COPD, heart failure, and renal failure and others. Management of sarcopenia should consist of resistance exercise in combination with a protein intake of 1 to 1.5 g/kg/day. There is insufficient evidence that vitamin D and anabolic steroids are beneficial. These recommendations apply to both primary (age-related) sarcopenia and secondary (disease related) sarcopenia. Secondary sarcopenia also needs appropriate treatment of the underlying disease. It is important that primary care health professionals become aware of and make the diagnosis of age-related and disease-related sarcopenia. It is important to address the risk factors for sarcopenia, particularly low physical activity and sedentary behavior in the general population, using a life-long approach. There is a need for more clinical research into the appropriate measurement for muscle mass and the management of sarcopenia. Accordingly, this position statement provides recommendations on the management of sarcopenia and how to progress the knowledge and recognition of sarcopenia.

4.
Eur Heart J ; 2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31504452

RESUMO

Making a firm diagnosis of chronic heart failure with preserved ejection fraction (HFpEF) remains a challenge. We recommend a new stepwise diagnostic process, the 'HFA-PEFF diagnostic algorithm'. Step 1 (P=Pre-test assessment) is typically performed in the ambulatory setting and includes assessment for HF symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes mellitus, elderly, atrial fibrillation), and diagnostic laboratory tests, electrocardiogram, and echocardiography. In the absence of overt non-cardiac causes of breathlessness, HFpEF can be suspected if there is a normal left ventricular ejection fraction, no significant heart valve disease or cardiac ischaemia, and at least one typical risk factor. Elevated natriuretic peptides support, but normal levels do not exclude a diagnosis of HFpEF. The second step (E: Echocardiography and Natriuretic Peptide Score) requires comprehensive echocardiography and is typically performed by a cardiologist. Measures include mitral annular early diastolic velocity (e'), left ventricular (LV) filling pressure estimated using E/e', left atrial volume index, LV mass index, LV relative wall thickness, tricuspid regurgitation velocity, LV global longitudinal systolic strain, and serum natriuretic peptide levels. Major (2 points) and Minor (1 point) criteria were defined from these measures. A score ≥5 points implies definite HFpEF; ≤1 point makes HFpEF unlikely. An intermediate score (2-4 points) implies diagnostic uncertainty, in which case Step 3 (F1: Functional testing) is recommended with echocardiographic or invasive haemodynamic exercise stress tests. Step 4 (F2: Final aetiology) is recommended to establish a possible specific cause of HFpEF or alternative explanations. Further research is needed for a better classification of HFpEF.

6.
Eur Heart J ; 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31556953

RESUMO

AIMS: Iron deficiency (ID) is common in heart failure (HF) patients and negatively impacts symptoms and prognosis. The aetiology of ID in HF is largely unknown. We studied determinants and the biomarker profile of ID in a large international HF cohort. METHODS AND RESULTS: We studied 2357 worsening HF patients from the BIOSTAT-CHF cohort. ID was defined as transferrin saturation <20%. Univariable and multivariable logistic regression models were constructed to identify determinants for ID. We measured 92 cardiovascular markers (Olink Cardiovascular III) to establish a biomarker profile of ID. The primary endpoint was the composite of all-cause mortality and first HF rehospitalization. Mean age (±standard deviation) of all patients was 69 ± 12.0 years, 26.1% were female and median N-terminal pro B-type natriuretic peptide levels (+interquartile range) were 4305 (2360-8329) ng/L. Iron deficiency was present in 1453 patients (61.6%), with highest prevalence in females (71.1% vs. 58.3%; P < 0.001). Independent determinants of ID were female sex, lower estimated protein intake, higher heart rate, presence of peripheral oedema and orthopnoea, chronic kidney disease, lower haemoglobin, higher C-reactive protein levels, lower serum albumin levels, and P2Y12 inhibitor use (all P < 0.05). None of these determinants were sex-specific. The biomarker profile of ID largely consisted of pro-inflammatory markers, including paraoxonase 3 (PON3) and tartrate-resistant acid phosphatase type 5. In multivariable Cox proportional hazard regression analyses, ID was associated to worse outcome, independently of predictors of ID (hazard ratio 1.25, 95% confidence interval 1.06-1.46; P = 0.007). CONCLUSION: Our data suggest that the aetiology of ID in worsening HF is complex, multifactorial and seems to consist of a combination of reduced iron uptake (malnutrition, fluid overload), impaired iron storage (inflammation, chronic kidney disease), and iron loss (antiplatelets).

7.
Eur Heart J ; 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31461239

RESUMO

Aims: Stroke is often a devastating event among patients with heart failure with reduced ejection (HFrEF). In COMMANDER HF, rivaroxaban 2.5 mg b.i.d. did not reduce the composite of first occurrence of death, stroke, or myocardial infarction compared with placebo in patients with HFrEF, coronary artery disease (CAD), and sinus rhythm. We now examine the incidence, timing, type, severity, and predictors of stroke or a transient ischaemic attack (TIA), and seek to establish the net clinical benefit of treatment with low-dose rivaroxaban. Methods and results: In this double-blind, randomized trial, 5022 patients who had HFrEF(≤40%), elevated natriuretic peptides, CAD, and who were in sinus rhythm were treated with rivaroxaban 2.5 mg b.i.d. or placebo in addition to antiplatelet therapy, after an episode of worsening HF. The primary neurological outcome for this post hoc analysis was time to first event of any stroke or TIA. Over a median follow-up of 20.5 (25th­75th percentiles 20.0­20.9) months, 150 all-cause stroke (127) or TIA (23) events occurred (ischaemic stroke in 82% and haemorrhagic stroke in 11% of stroke events). Overall, 47.5% of first-time strokes were either disabling (16.5%) or fatal (31%). Prior stroke, low body mass index, geographic region, and the CHA2DS2-VASc score were predictors of stroke/TIA. Rivaroxaban significantly reduced the primary neurological endpoint of all-cause stroke or TIA compared with placebo by 32% (1.29 events vs. 1.90 events per 100 patient-years), adjusted for the time from index HF event to randomization and stratified by geographic region (adjusted hazard ratio 0.68, 95% confidence interval 0.49­0.94), with a number needed to treat of 164 patients per year to prevent one stroke/TIA event. The principal safety endpoint of fatal bleeding or bleeding into a critical space, occurred at a similar rate on rivaroxaban and placebo (0.44 events vs. 0.55 events per 100 patient-years). Conclusion: Patients with HFrEF and CAD are at risk for stroke or TIA in the period following an episode of worsening heart failure in the absence of atrial fibrillation. Most strokes are of ischaemic origin and nearly half are either disabling or fatal. Rivaroxaban at a dose of 2.5 mg b.i.d. reduced rates of stroke or TIA compared with placebo in this population. Trial Registration: COMMANDER HF (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure); ClinicalTrials.gov NCT01877915.

8.
N Engl J Med ; 381(8): 716-726, 2019 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-31433919

RESUMO

BACKGROUND: Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. METHODS: In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 µg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. RESULTS: A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P = 0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P = 0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. CONCLUSIONS: In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.).


Assuntos
Doenças Cardiovasculares/mortalidade , Insuficiência Cardíaca/tratamento farmacológico , Relaxina/uso terapêutico , Vasodilatadores/uso terapêutico , Doença Aguda , Idoso , Pressão Sanguínea/efeitos dos fármacos , Progressão da Doença , Método Duplo-Cego , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Hospitalização , Humanos , Incidência , Infusões Intravenosas , Masculino , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Relaxina/efeitos adversos , Relaxina/farmacologia , Falha de Tratamento , Vasodilatadores/efeitos adversos
10.
Lancet ; 394(10205): 1254-1263, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31447116

RESUMO

BACKGROUND: Guideline-recommended doses of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), and ß blockers are similar for men and women with heart failure with reduced ejection fraction (HFrEF), even though there are known sex differences in pharmacokinetics of these drugs. We hypothesised that there might be sex differences in the optimal dose of ACE inhibitors or ARBs and ß blockers in patients with HFrEF. METHODS: We did a post-hoc analysis of BIOSTAT-CHF, a prospective study in 11 European countries of patients with heart failure in whom initiation and up-titration of ACE inhibitors or ARBs and ß blockers was encouraged by protocol. We included only patients with left ventricular ejection fraction less than 40%, and excluded those who died within the first 3 months. Primary outcome was a composite of time to all-cause mortality or hospitalisation for heart failure. Findings were validated in ASIAN-HF, an independent cohort of 3539 men and 961 women with HFrEF. FINDINGS: Among 1308 men and 402 women with HFrEF from BIOSTAT-CHF, women were older (74 [12] years vs 70 [12] years, p<0·0001) and had lower bodyweights (72 [16] kg vs 85 [18] kg, p<0·0001) and heights (162 [7] cm vs 174 [8] cm, p<0·0001) than did men, although body-mass index did not differ significantly. A similar number of men and women reached guideline-recommended target doses of ACE inhibitors or ARBs (99 [25%] vs 304 [23%], p=0·61) and ß blockers (57 [14%] vs 168 [13%], p=0·54). In men, the lowest hazards of death or hospitalisation for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and ß blockers, but women showed approximately 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels. These sex differences were still present after adjusting for clinical covariates, including age and body surface area. In the ASIAN-HF registry, similar patterns were observed for both ACE inhibitors or ARBs and ß blockers, with women having approximately 30% lower risk at 50% of the recommended doses, with no further benefit at higher dose levels. INTERPRETATION: This study suggests that women with HFrEF might need lower doses of ACE inhibitors or ARBs and ß blockers than men, and brings into question what the true optimal medical therapy is for women versus men. FUNDING: European Commission.

12.
Clin Res Cardiol ; 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31263996

RESUMO

BACKGROUND: In heart failure (HF), levels of NT-proBNP are influenced by the presence of concomitant atrial fibrillation (AF), making it difficult to distinguish between HF versus AF in patients with raised NT-proBNP. It is unknown whether levels of GDF-15 are also influenced by AF in patients with HF. In this study we compared the plasma levels of NT-proBNP versus GDF-15 in patients with HF in AF versus sinus rhythm (SR). METHODS: In a post hoc analysis of the index cohort of BIOSTAT-CHF (n = 2516), we studied patients with HF categorized into three groups: (1) AF at baseline (n = 733), (2) SR at baseline with a history of AF (n = 183), and (3) SR at baseline and no history of AF (n = 1025). The findings were validated in the validation cohort of BIOSTAT-CHF (n = 1738). RESULTS: Plasma NT-proBNP levels of patients who had AF at baseline were higher than those of patients in SR (both with and without a history of AF), even after multivariable adjustment (3417 [25th-75th percentile 1897-6486] versus 1788 [682-3870], adjusted p < 0.001, versus 2231 pg/mL [902-5270], adjusted p < 0.001). In contrast, after adjusting for clinical confounders, the levels of GDF-15 were comparable between the three groups (3179 [2062-5253] versus 2545 [1686-4337], adjusted p = 0.36, versus 2294 [1471-3855] pg/mL, adjusted p = 0.08). Similar patterns of both NT-proBNP and GDF-15 were found in the validation cohort. CONCLUSION: These data show that in patients with HF, NT-proBNP is significantly influenced by underlying AF at time of measurement and not by previous episodes of AF, whereas the levels of GDF-15 are not influenced by the presence of AF. Therefore, GDF-15 might have additive value combined with NT-proBNP in the assessment of patients with HF and concomitant AF.

13.
ESC Heart Fail ; 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31347289

RESUMO

AIMS: Epidemiological heart failure (HF) data in the era of natriuretic peptides and echocardiography are scarce. The primary aim of this study is to evaluate the HF prevalence in the general population. We will also investigate natriuretic peptide cut-off for diagnosis of HF. Finally, we will be able to identify left ventricular function phenotypes and study relations between cardiac function, clinical presentation, and health-related quality of life. METHODS AND RESULTS: Screening Of adult urBan pOpulation To diAgnose Heart Failure (SOBOTA-HF) is a cross-sectional prevalence study in a representative sample of Murska Sobota residents aged 55 years or more. Individuals will be invited to attend screening visit with point-of-care N-terminal pro-b-type natriuretic peptide (NT-proBNP) testing. All subjects with NT-proBNP ≥ 125 pg/mL will be invited for a diagnostic visit that will include history and physical examination, electrocardiogram, echocardiography, blood and urine sampling, ankle brachial index, pulmonary function tests, body composition measurement, physical performance tests, and questionnaires. To validate the screening procedure, a control group (NT-proBNP < 125 pg/mL) will undergo the same diagnostic evaluation. An external centre will validate echocardiography results, and the HF diagnosis will be adjudicated within an international HF expert panel. Overall and age-specific HF prevalence will be calculated in individuals ≥ 55 years and extrapolated to the whole population. CONCLUSIONS: The SOBOTA-HF study will test the latest HF guideline diagnostic criteria in the general population sample. Next to HF prevalence, it will provide insight into left ventricular function and general patient phenotype; we will also extend current understanding of natriuretic peptides for HF screening.

14.
Eur J Heart Fail ; 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31209992

RESUMO

BACKGROUND: Diagnosing non-acute heart failure (HF) remains challenging, notably in the early stages of the syndrome. The diagnostic value of mid-regional pro-atrial natriuretic peptide (MR-proANP) has been proven in acute onset HF, but its role in early non-acute HF is unknown. We aimed to determine the diagnostic value of MR-proANP in suspected non-acute HF. METHODS AND RESULTS: In total, 721 people suspected of non-acute HF in primary care underwent standardised diagnostic work-up including chest X-ray, electrocardiogram, N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement and echocardiography. Of these, 245 people underwent additional MR-proANP measurements. The outcome of HF was assessed by an expert panel comprised of two cardiologists and one expert physician, who used all available diagnostic information including echocardiography, but were blinded to biomarker results. Of the 245 people (mean age 71.0 years, 62.9% female), 72 (29.4%) were diagnosed with HF. The c-statistics of MR-proANP and NT-proBNP as single diagnostic test were 0.77 [95% confidence interval (CI) 0.70-0.84] and 0.79 (95% CI 0.73-0.86), respectively. The cut-point with the highest accuracy for MR-proANP was 120 pmol/L [sensitivity/specificity/positive predictive value (PPV)/negative predictive value (NPV) 0.72, 0.69, 0.46, and 0.86, respectively], and the best exclusionary cut-point was 40 pmol/L (sensitivity/specificity/PPV/NPV 0.99, 0.06, 0.30, and 0.92, respectively). After addition of MR-proANP on top of a previously validated clinical model, the c-statistic rose from 0.82 (95% CI 0.76-0.88) to 0.86 (95% CI 0.80-0.92), and with the addition of NT-proBNP to 0.87 (95% CI 0.81-0.92). No sex interactions between the biomarkers and HF were found in the multivariable models. CONCLUSION: MR-proANP provides added diagnostic value in suspected non-acute HF, similar to NT-proBNP.

15.
ESC Heart Fail ; 6(4): 621-628, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31148411

RESUMO

AIMS: Iron deficiency worsens symptoms, quality of life, and exercise capacity in chronic heart failure (CHF) and might do so by promoting fluid retention. We assessed whether iron repletion improved congestion in CHF and appraised the prognostic utility of calculated plasma volume status (PVS), a novel index of congestion, in the FAIR-HF data set. METHODS AND RESULTS: In FAIR-HF, 459 iron deficient CHF patients were randomized to intravenous ferric carboxymaltose (FCM) or saline and assessed at 4, 12, and 24 weeks. Using weight and haematocrit, we calculated PVS in 436 patients. At baseline, PVS and weight were -5.5 ± 7.7% and 76.9 ± 14.3 kg, with peripheral oedema evident in 35% of subjects. Higher PVS values correlated to other congestion surrogates such as lower serum albumin. At 4 weeks, FCM was associated with greater reductions in weight (0.02) and PVS (P < 0.0001), and a trend for improved peripheral oedema at 24 weeks (0.07). Irrespective of treatment allocation, patients with a decrease in PVS from baseline to week 24 had higher increments in 6 min walking distance (61.4 m vs. 43.5 m, 0.02) and were more likely to improve their NYHA class (33.3% vs. 15.5%, 0.001). A PVS > -4% at baseline predicted worse outcomes even after adjustment for treatment assignment (hazard ratio 1.88, 95% confidence interval 1.01-3.51, 0.046). CONCLUSIONS: Intravenous iron therapy with FCM is associated with early reductions in PVS and weight, implying that decongestion might be one mechanism via which iron repletion aids CHF patients. Calculated PVS is of prognostic utility in this cohort.

16.
JAMA Cardiol ; 4(7): 696-701, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31188392

RESUMO

Importance: Iron deficiency is present in half of patients with heart failure (HF) and is associated with increased morbidity and an impaired prognosis. Iron deficiency due to low iron storage (LIS) and defective iron utilization (DIU) are not entirely the same clinical problem, although they generally receive the same treatment. Objective: To define and describe similarities and differences between LIS and DIU in patients with HF. Design, Setting, and Participants: This analysis included data from 2 prospective observational studies: the Definition of Iron Deficiency in Chronic Heart Failure (DEFINE-HF) study, a single-center study conducted from 2013 to 2015 including 42 patients with a reduced left ventricular ejection fraction of 45% or less scheduled for coronary artery bypass graft surgery, and the A Systems Biology Study to Tailored Treatment in Chronic Heart Failure (BIOSTAT-CHF) study, a multinational study conducted from 2010 to 2014 including 2357 patients with worsening HF from 69 centers in 11 countries. The median (interquartile range) follow-up time was 1.8 (1.3-2.3) years. Data were analyzed from January 2018 to January 2019. Main Outcomes and Measures: The DEFINE-HF cohort was set up to derive a definition for different etiologies of iron deficiency using bone marrow iron staining as the criterion standard. This definition was applied to the BIOSTAT-CHF cohort to assess its association with clinical profile, biomarkers, and the primary composite end point of all-cause mortality or HF hospitalizations. Results: Among the 42 patients in the DEFINE-HF study, 10 (24%) were women, and the mean (SD) age was 68.0 (9.5) years. Low iron storage was defined as a bone marrow-validated combination of transferrin saturation less than 20% and a serum ferritin concentration of 128 ng/mL or less; DIU was defined as transferrin saturation less than 20% and a serum ferritin concentration greater than 128 ng/mL. These criteria were applied to 2356 patients with worsening HF in the BIOSTAT-CHF study; 1074 (45.6%) were women, and the mean (SD) age was 68.9 (12.0) years. A total of 1453 patients with worsening HF (61.6%) had iron deficiency, of whom 960 (66.1%) had LIS and 493 (33.9%) had DIU. Low iron storage was characterized by a higher proportion of anemia and a poorer quality of life, while DIU was characterized by higher levels of various inflammatory markers. Both LIS and DIU were associated with an impaired 6-minute walking test. Low iron storage was independently associated with the composite end point of all-cause mortality or HF hospitalizations (hazard ratio, 1.47; 95% CI, 1.26-1.71; P < .001), while DIU was not (hazard ratio, 1.05; 95% CI, 0.87-1.26; P = .64). Conclusions and Relevance: In this study, both LIS and DIU were prevalent in patients with HF and had a distinct clinical profile. Only LIS was independently associated with increased rates of morality and HF hospitalizations, while DIU was not.

17.
Eur J Heart Fail ; 21(7): 932-942, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31218819

RESUMO

AIMS: Heart failure (HF) is associated with considerable symptom burden and impairment in physical functioning and quality of life. The sodium-glucose co-transporter 2 inhibitor empagliflozin reduced the risk of HF hospitalisation and cardiovascular death in patients with type 2 diabetes and established cardiovascular disease in the EMPA-REG OUTCOME trial, and could potentially improve congestion symptoms and exercise capacity in patients with HF. We describe the designs of the EMPERIAL-Preserved and EMPERIAL-Reduced trials of empagliflozin in patients with chronic stable HF, with or without type 2 diabetes. METHODS: EMPERIAL-Preserved and EMPERIAL-Reduced are randomised, placebo-controlled trials designed to investigate the effects of empagliflozin on exercise capacity and patient-reported outcomes in patients with chronic stable HF with preserved ejection fraction [HFpEF; left ventricular ejection fraction (LVEF) > 40%] and HF with reduced ejection fraction (HFrEF; LVEF ≤ 40%), respectively. In each trial, approximately 300 patients will be randomised 1:1 to receive empagliflozin 10 mg or placebo once daily for 12 weeks. In both trials, the primary endpoint is the change from baseline in 6-min walk test distance at week 12. Key secondary endpoints are the change from baseline in Kansas City Cardiomyopathy Questionnaire total symptom score and change from baseline in dyspnoea score of the Chronic Heart Failure Questionnaire at week 12. CONCLUSION: The EMPERIAL-Preserved and EMPERIAL-Reduced trials will determine the effects of empagliflozin on exercise capacity and patient-reported outcomes in patients with HFpEF and HFrEF, respectively, and provide insight into the potential of empagliflozin in the treatment of patients with HF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03448406 (EMPERIAL-Preserved), NCT03448419 (EMPERIAL-Reduced).

18.
Eur J Heart Fail ; 21(7): 827-843, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31243866

RESUMO

Peripartum cardiomyopathy (PPCM) is a potentially life-threatening condition typically presenting as heart failure with reduced ejection fraction (HFrEF) in the last month of pregnancy or in the months following delivery in women without another known cause of heart failure. This updated position statement summarizes the knowledge about pathophysiological mechanisms, risk factors, clinical presentation, diagnosis and management of PPCM. As shortness of breath, fatigue and leg oedema are common in the peripartum period, a high index of suspicion is required to not miss the diagnosis. Measurement of natriuretic peptides, electrocardiography and echocardiography are recommended to promptly diagnose or exclude heart failure/PPCM. Important differential diagnoses include pulmonary embolism, myocardial infarction, hypertensive heart disease during pregnancy, and pre-existing heart disease. A genetic contribution is present in up to 20% of PPCM, in particular titin truncating variant. PPCM is associated with high morbidity and mortality, but also with a high probability of partial and often full recovery. Use of guideline-directed pharmacological therapy for HFrEF is recommended in all patients respecting contraindications during pregnancy/lactation. The oxidative stress-mediated cleavage of the hormone prolactin into a cardiotoxic fragment has been identified as a driver of PPCM pathophysiology. Pharmacological blockade of prolactin release using bromocriptine as a disease-specific therapy in addition to standard therapy for heart failure treatment has shown promising results in two clinical trials. Thresholds for devices (implantable cardioverter-defibrillators, cardiac resynchronization therapy and implanted long-term ventricular assist devices) are higher in PPCM than in other conditions because of the high rate of recovery. The important role of education and counselling around contraception and future pregnancies is emphasised.

19.
Arq. bras. cardiol ; 112(6): 739-746, Jun. 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-1011203

RESUMO

Abstract Background: Resting sympathetic hyperactivity and impaired parasympathetic reactivation after exercise have been described in patients with heart failure (HF). However, the association of these autonomic changes in patients with HF and sarcopenia is unknown. Objective: The aim of this study was to evaluate the impact of autonomic modulation on sarcopenia in male patients with HF. Methods: We enrolled 116 male patients with HF and left ventricular ejection fraction < 40%. All patients underwent a maximal cardiopulmonary exercise testing. Maximal heart rate was recorded and delta heart rate recovery (∆HRR) was assessed at 1st and 2nd minutes after exercise. Muscle sympathetic nerve activity (MSNA) was recorded by microneurography. Dual-energy X-ray absorptiometry was used to measure body composition and sarcopenia was defined by the sum of appendicular lean muscle mass (ALM) divided by height in meters squared and handgrip strength. Results: Sarcopenia was identified in 33 patients (28%). Patients with sarcopenia had higher MSNA than those without (47 [41-52] vs. 40 [34-48] bursts/min, p = 0.028). Sarcopenic patients showed lower ∆HRR at 1st (15 [10-21] vs. 22 [16-30] beats/min, p < 0.001) and 2nd min (25 [19-39] vs. 35 [24-48] beats/min, p = 0.017) than non-sarcopenic. There was a positive correlation between ALM and ∆HRR at 1st (r = 0.26, p = 0.008) and 2nd min (r = 0.25, p = 0.012). We observed a negative correlation between ALM and MSNA (r = -0.29, p = 0.003). Conclusion: Sympatho-vagal imbalance seems to be associated with sarcopenia in male patients with HF. These results highlight the importance of a therapeutic approach in patients with muscle wasting and increased peripheral sympathetic outflow.


Resumo Fundamento: Hiperatividade simpática de repouso e uma reativação parassimpática diminuída pós-exercício têm sido descritas em pacientes com insuficiência cardíaca (IC). No entanto, a associação dessas alterações autonômicas em pacientes com IC sarcopênicos ainda não são conhecidas. Objetivo: O objetivo deste estudo foi avaliar o impacto da modulação autonômica sobre sarcopenia em pacientes com IC do sexo masculino. Métodos: Foram estudados 116 pacientes com IC e fração de ejeção ventricular esquerda inferior a 40%. Todos os pacientes foram submetidos ao teste de exercício cardiopulmonar máximo. A frequência cardíaca máxima foi registrada, e o delta de recuperação da frequência cardíaca (∆RFC) foi avaliado no primeiro e no segundo minuto após o exercício. A atividade nervosa simpática muscular (ANSM) foi registrada por microneurografia. A Absorciometria Radiológica de Dupla Energia foi usada para medir composição cpororal, e a sarcopenia definida como a soma da massa muscular apendicular (MMA) dividida pela altura em metros ao quadrado e força da mão. Resultados: A sarcopenia foi identificada em 33 pacientes (28%). Os pacientes com sarcopenia apresentaram maior ANSM que aqueles sem sarcopenia - 47 (41-52) vs. 40 (34-48) impulsos (bursts)/min, p = 0,028). Pacientes sarcopênicos apresentaram ∆RFC mais baixo no primeiro [15 (10-21) vs. 22 (16-30) batimentos/min, p < 0,001) e no segundo [25 (19-39) vs. 35 (24-48) batimentos/min, p = 0,017) minuto que pacientes não sarcopênicos. Observou-se uma correlação positiva entre a MMA e a ANSM (r = -0,29; p = 0,003). Conclusão: Um desequilíbrio simpático-vagal parece estar associado com sarcopenia em pacientes com IC do sexo masculino. Esses resultados destacam a importância de uma abordagem terapêutica em pacientes com perda muscular e fluxo simpático periférico aumentado.

20.
Circ Heart Fail ; 12(5): e005544, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31091993

RESUMO

BACKGROUND: PENK (proenkephalin) is a stable surrogate for enkephalins, endogenous opioid peptides, which exert cardiodepressive effects and improve renal function. PENK has been associated with heart failure (HF) severity and renal dysfunction. We therefore hypothesized that PENK could be associated with deterioration of kidney function and could have a role as a novel renal marker in HF. METHODS AND RESULTS: In 2180 patients with HF of a large multicenter cohort (BIOSTAT-CHF [A Systems Biology Study to Tailored Treatment in Chronic Heart Failure]), the relationship between PENK and clinical variables, plasma and urinary biomarkers, and clinical end points was established. Data were validated in a separate cohort of 1703 patients with HF. PENK was elevated (>80 pmol/L, 99th percentile) in 1245 (57%) patients. Higher PENK was associated with more advanced HF and glomerular and tubular dysfunction. The strongest independent predictor of PENK was estimated glomerular filtration rate. Others were plasma NGAL (neutrophil gelatinase-associated lipocalin) and NT-proBNP (N-terminal pro-B-type natriuretic peptide; all P<0.001). Using correlation heatmaps and hierarchical cluster analyses, PENK clustered with estimated glomerular filtration rate, creatinine, NGAL, galectin-3, and urea. Higher PENK was independently associated with increased risk of deterioration of kidney function between baseline and 9 months (odds ratio, 1.29 [1.02-1.65] per PENK doubling; P=0.038; defined as >25% decrease in estimated glomerular filtration rate) and mortality (hazard ratio, 1.23 [1.07-1.43] per doubling; P=0.004). Analyses in the validation cohort yielded comparable findings. CONCLUSIONS: Higher PENK levels are associated with more severe HF, with glomerular and tubular renal dysfunction, with incidence of a deterioration of kidney function, and with mortality. These findings suggest that the opioid system might be involved in deteriorating kidney function in HF.

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