pinecone/core-2020-05-10-deduplication huggingface dataset:
Baseline characteristics and treatment of patients in Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF)

AIM: To describe the baseline characteristics and treatment of the patients randomized in the PARADIGM-HF (Prospective comparison of ARNi with ACEi to Determine Impact on Global Mortality and morbidity in Heart Failure) trial, testing the hypothesis that the strategy of simultaneously blocking the renin-angiotensin-aldosterone system and augmenting natriuretic peptides with LCZ696 200 mg b.i.d. is superior to enalapril 10 mg b.i.d. in reducing mortality and morbidity in patients with heart failure and reduced ejection fraction. METHODS: Key demographic, clinical and laboratory findings, along with baseline treatment, are reported and compared with those of patients in the treatment arm of the Studies Of Left Ventricular Dysfunction (SOLVD-T) and more contemporary drug and device trials in heart failure and reduced ejection fraction. RESULTS: The mean age of the 8442 patients in PARADIGM-HF is 64 (SD 11) years and 78% are male, which is similar to SOLVD-T and more recent trials. Despite extensive background therapy with beta-blockers (93% patients) and mineralocorticoid receptor antagonists (60%), patients in PARADIGM-HF have persisting symptoms and signs, reduced health related quality of life, a low LVEF (mean 29 ± SD 6%) and elevated N-terminal-proB type-natriuretic peptide levels (median 1608 inter-quartile range 886-3221 pg/mL). CONCLUSION: PARADIGM-HF will determine whether LCZ696 is more beneficial than enalapril when added to other disease-modifying therapies and if further augmentation of endogenous natriuretic peptides will reduce morbidity and mortality in heart failure and reduced ejection fraction
Type 2 diabetes mellitus and heart failure: a position statement from the Heart Failure Association of the European Society of Cardiology

The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent (30-40% of patients) and associated with a higher risk of HF hospitalization, all-cause and cardiovascular (CV) mortality. The most important causes of HF in T2DM are coronary artery disease, arterial hypertension and a direct detrimental effect of T2DM on the myocardium. T2DM is often unrecognized in HF patients, and vice versa, which emphasizes the importance of an active search for both disorders in the clinical practice. There are no specific limitations to HF treatment in T2DM. Subanalyses of trials addressing HF treatment in the general population have shown that all HF therapies are similarly effective regardless of T2DM. Concerning T2DM treatment in HF patients, most guidelines currently recommend metformin as the first-line choice. Sulphonylureas and insulin have been the traditional second- and third-line therapies although their safety in HF is equivocal. Neither glucagon-like preptide-1 (GLP-1) receptor agonists, nor dipeptidyl peptidase-4 (DPP4) inhibitors reduce the risk for HF hospitalization. Indeed, a DPP4 inhibitor, saxagliptin, has been associated with a higher risk of HF hospitalization. Thiazolidinediones (pioglitazone and rosiglitazone) are contraindicated in patients with (or at risk of) HF. In recent trials, sodium-glucose co-transporter-2 (SGLT2) inhibitors, empagliflozin and canagliflozin, have both shown a significant reduction in HF hospitalization in patients with established CV disease or at risk of CV disease. Several ongoing trials should provide an insight into the effectiveness of SGLT2 inhibitors in patients with HFrEF and HFpEF in the absence of T2DM
Sex‐ and age‐based differences in the natural history and outcome of dilated cardiomyopathy

Aim: To evaluate the relationship between sex, age and outcome in dilated cardiomyopathy (DCM). Methods and results: We used proportional hazard modelling to examine the association between sex, age and all‐cause mortality in consecutive patients with DCM. Overall, 881 patients (290 women, median age 52 years) were followed for a median of 4.9 years. Women were more likely to present with heart failure (64.0% vs. 54.5%; P = 0.007) and had more severe symptoms (P < 0.0001) compared to men. Women had smaller left ventricular end‐diastolic volume (125 mL/m2 vs. 135 mL/m2; P < 0.001), higher left ventricular ejection fraction (40.2% vs. 37.9%; P = 0.019) and were less likely to have mid‐wall late gadolinium enhancement (23.0% vs. 38.9%; P < 0.0001). During follow‐up, 149 (16.9%) patients died, including 41 (4.7%) who died suddenly. After adjustment, all‐cause mortality [hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.41–0.92; P = 0.018] was lower in women, with similar trends for cardiovascular (HR 0.60, 95% CI 0.35–1.05; P = 0.07), non‐sudden (HR 0.63, 95% CI 0.39–1.02; P = 0.06) and sudden death (HR 0.70, 95% CI 0.30–1.63; P = 0.41). All‐cause mortality (per 10 years: HR 1.36, 95% CI 1.20–1.55; P < 0.0001) and non‐sudden death (per 10 years: HR 1.51, 95% CI 1.26–1.82; P < 0.00001) increased with age. Cumulative incidence curves confirmed favourable outcomes, particularly in women and those <60 years. Increased all‐cause mortality in patients >60 years of age was driven by non‐sudden death. Conclusion: Women with DCM have better survival compared to men, which may partly be due to less severe left ventricular dysfunction and a smaller scar burden. There is increased mortality driven by non‐sudden death in patients >60 years of age that is less marked in women. Outcomes with contemporary treatment were favourable, with a low incidence of sudden death
Renal denervation in heart failure with preserved ejection fraction (RDT-PEF): a randomized controlled trial

Aim: Heart failure with preserved ejection fraction (HFpEF) is associated with increased sympathetic nervous system (SNS) tone. Attenuating the SNS with renal denervation (RDT) might be helpful and there are no data currently in humans with HFpEF. Methods and results: In this single-centre, randomized, open-controlled study we included 25 patients with HFpEF [preserved left ventricular (LV) ejection fraction, left atrial (LA) dilatation or LV hypertrophy and raised B-type natriuretic peptide (BNP) or echocardiographic assessment of filling pressures]. Patients were randomized (2:1) to RDT with the Symplicity™ catheter or continuing medical therapy. The primary success criterion was not met in that there were no differences between groups at 12 months for Minnesota Living with Heart Failure Questionnaire score, peak oxygen uptake (VO2) on exercise, BNP, E/e′, LA volume index or LV mass index. A greater proportion of patients improved at 3 months in the RDT group with respect to VO2 peak (56% vs. 13%, P = 0.025) and E/e′ (31% vs. 13%, P = 0.04). Change in estimated glomerular filtration rate was comparable between groups. Two patients required plain balloon angioplasty during the RDT procedure to treat renal artery wall oedema. Conclusion: This study was terminated early because of difficulties in recruitment and was underpowered to detect whether RD improved the endpoints of quality of life, exercise function, biomarkers, and left heart remodelling. The procedure was safe in patients with HFpEF, although two patients did require intraprocedure renal artery dilatation
The impact of intravenous ferric carboxymaltose on renal function: An analysis of the FAIR-HF study

<p>Aims</p>

<p>Anaemia and iron deficiency are constituents of the cardio-renal syndrome in chronic heart failure (CHF). We investigated the effects of i.v. iron in iron-deficient CHF patients on renal function, and the efficacy and safety of this therapy in patients with renal dysfunction.</p>

<p>Methods and results</p>

<p>The FAIR-HF trial randomized 459 CHF patients with iron deficiency (ferritin &lt;100 &mu;g/L, or between 100 and 299 &mu;g/L if transferrin saturation was &lt;20%): 304 to i.v. ferric carboxymaltose (FCM) and 155 to placebo, and followed-up for 24 weeks. Renal function was assessed at baseline and at weeks 4, 12, and 24, using the estimated glomerular filtration rate (eGFR, mL/min/1.73m2), calculated from the Chronic Kidney Disease Epidemiology Collaboration (CKD&ndash;EPI) formula. At baseline, renal function was similar between groups (62.4&plusmn;20.6 vs. 62.9&plusmn;23.4 mL/min/1.73m2, FCM vs. placebo). Compared with placebo, treatment with FCM was associated with an increase in eGFR [treatment effect: week 4, 2.11&plusmn;1.21 (P = 0.082); week 12, 2.41&plusmn;1.33 (P = 0.070); and week 24, 2.98&plusmn;1.44 mL/min/1.73m2 (P = 0.039)]. This effect was seen in all pre-specified subgroups (P &gt; 0.20 for interactions). No interaction between the favourable effects of FCM and baseline renal function was seen for the primary endpoints [improvement in Patient Global Assessment (P = 0.43) and NYHA class (P = 0.37) at 24 weeks]. Safety and adverse event profiles were similar in patients with baseline eGFR &lt;60 and &ge;60 mL/min/1.73m2.</p>

<p>Conclusions</p>

<p>Treatment of iron deficiency in CHF patients with i.v. FCM was associated with an improvement in renal function. FCM therapy was effective and safe in CHF patients with renal dysfunction.</p
MicroRNA signatures differentiate preserved from reduced ejection fraction heart failure

Aims Differentiation of heart failure with reduced (HFrEF) or preserved (HFpEF) ejection fraction independent of echocardiography is challenging in the community. Diagnostic strategies based on monitoring circulating microRNA (miRNA) levels may prove to be of clinical value in the near future. The aim of this study was to identify a novel miRNA signature that could be a useful HF diagnostic tool and provide valuable clinical information on whether a patient has HFrEF or HFpEF. Methods and results MiRNA biomarker discovery was carried out on three patient cohorts, no heart failure (no-HF), HFrEF, and HFpEF, using Taqman miRNA arrays. The top five miRNA candidates were selected based on differential expression in HFpEF and HFrEF (miR-30c, −146a, −221, −328, and −375), and their expression levels were also different between HF and no-HF. These selected miRNAs were further verified and validated in an independent cohort consisting of 225 patients. The discriminative value of BNP as a HF diagnostic could be improved by use in combination with any of the miRNA candidates alone or in a panel. Combinations of two or more miRNA candidates with BNP had the ability to improve significantly predictive models to distinguish HFpEF from HFrEF compared with using BNP alone (area under the receiver operating characteristic curve >0.82). Conclusion This study has shown for the first time that various miRNA combinations are useful biomarkers for HF, and also in the differentiation of HFpEF from HFrEF. The utility of these biomarker combinations can be altered by inclusion of natriuretic peptide. MiRNA biomarkers may support diagnostic strategies in subpopulations of patients with HF
Validation of a simple risk stratification tool for patients implanted with Cardiac Resynchronization Therapy: the VALID-CRT risk score

AIMS  Mortality after cardiac resynchronization therapy (CRT) is difficult to predict. We sought to design and validate a simple prognostic score for patients implanted with CRT, based on readily available clinical variables, including age, gender, left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) class, presence/absence of atrial fibrillation, presence/absence of atrioventricular junction ablation, coronary heart disease, diabetes, and implantation of a CRT device with defibrillation.  METHODS  For predictive modelling, 5153 consecutive patients enrolled in 72 European centres (79% male; LVEF 25.9 ± 6.85%; NYHA class III-IV 77.5%; QRS 158.4 ± 32.3 ms) were randomly split into derivation (70%) and validation (30%) samples. The primary endpoint was total mortality and the secondary endpoint was cardiovascular mortality. The final predictive model fit was assessed by plotting observed vs. predicted survival.  RESULTS  In the entire cohort, 1004 deaths occurred over a follow-up of 14 409 person years. Total mortality ranged from 3.1% to 28.2% at 2 years in the first and fifth quintile of the risk score, respectively. At 5 years, total mortality was 10.3%, 18.6%, 27.6%, 36.1%, and 58.8%, from the first to the fifth quintile. Compared with the lowest quintile (Q), total mortality was significantly higher in the other four quintiles [Q2 hazard ratio (HR) = 1.71; Q3 HR = 2.20; Q4 HR = 4.03; Q5 HR = 8.03; all P < 0.001). The final model, which was based on the entire cohort using the above variables, showed a good discrimination (Harrell's c = 0.70) and high explained variation (0.26). The mean predicted survival fitted well with the observed survival for up to 6 years of follow-up.  CONCLUSIONS  The VALID-CRT risk score, which is based on routine, readily available clinical variables, reliably predicted the long-term total and cardiovascular mortality in patients undergoing CRT. While this score cannot be used to predict the benefit of CRT, it may be useful for predicting survival after CRT. This may have useful implications for follow-up
A simple validated method for predicting the risk of hospitalization for worsening of heart failure in ambulatory patients : the Redin‐SCORE

Prevention of hospital readmissions is one of the main objectives in the management of patients with heart failure (). Most of the models predicting readmissions are based on data extracted from hospitalized patients rather than from outpatients. Our objective was to develop a validated score predicting 1‐month and 1‐year risk of readmission for worsening of in ambulatory patients. A cohort of 2507 ambulatory patients with chronic was prospectively followed for a median of 3.3 years. Clinical, echocardiographic, , and biochemical variables were used in a competing risk regression analysis to construct a risk score for readmissions due to worsening of . Thereafter, the score was externally validated using a different cohort of 992 patients with chronic ( registry). Predictors of 1‐month readmission were the presence of elevated natriuretic peptides, left ventricular (LV) HF signs, and estimated glomerular filtration rate () <60 /min/m 2. Predictors of 1‐year readmission were elevated natriuretic peptides, anaemia, left atrial size >26 mm/m 2, heart rate >70 b.p.m., signs, and <60 /min/m 2. The C‐statistics for the models were 0.72 and 0.66, respectively. The cumulative incidence function distinguished low‐risk (<1% event rate) and high‐risk groups (>5% event rate) for 1‐month readmission. Likewise, low‐risk (7.8%), intermediate‐risk (15.6%) and high‐risk groups (26.1%) were identified for 1‐year readmission risk. The C‐statistics remained consistent after the external validation (<5% loss of discrimination). The Redin‐ predicts early and late readmission for worsening of using proven prognostic variables that are routinely collected in outpatient management of chronic
Current state of knowledge on Takotsubo syndrome: a Position Statement from the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology

Takotsubo syndrome is an acute reversible heart failure syndrome that is increasingly recognized in modern cardiology practice. This Position Statement from the European Society of Cardiology Heart Failure Association provides a comprehensive review of the various clinical and pathophysiological facets of Takotsubo syndrome, including nomenclature, definition, and diagnosis, primary and secondary clinical subtypes, anatomical variants, triggers, epidemiology, pathophysiology, clinical presentation, complications, prognosis, clinical investigations, and treatment approaches. Novel structured approaches to diagnosis, risk stratification, and management are presented, with new algorithms to aid decision-making by practising clinicians. These also cover more complex areas (e.g. uncertain diagnosis and delayed presentation) and the management of complex cases with ongoing symptoms after recovery, recurrent episodes, or spontaneous presentation. The unmet needs and future directions for research in this syndrome are also discussed
Plasma growth hormone is a strong predictor of risk at 1 year in acute heart failure

The file associated with this record is under a 12-month embargo from publication in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.AIMS: We sought to compare the prognostic utility of growth hormone (GH) with NT-proBNP) and the ADHERE score in a large cohort of acute heart failure (HF) patients, subcategorized into HF with reduced EF <50% (HFrEF) and preserved EF ≥50% (HFpEF). METHODS AND RESULTS: GH and NTproBNP levels were measured in 537 patients (HFrEF n = 415; HFpEF n = 122) with acute HF recruited into this prospective cohort study. The main outcome measure was death or HF readmission at 1 year. GH levels were higher in both HFrEF [1.26 (0.54-2.62) vs. 0.8 (0.26-1.94) ng/mL, P < 0.001] and HFpEF [1.04 (0.48-2.92) vs. 0.53 (0.18-1.94) ng/mL, P = 0.020] patients with the outcome compared with event-free survivors. GH levels were independently predictive for the outcome at 1 year in the entire cohort [HR 1.47, 95% confidence interval (CI) 1.16-1.86, P = 0.001] and those with HFrEF (HR 1.54, 95% CI 1.19-1.99, P = 0.001) in multivariate Cox hazard analysis. GH improved risk classification as measured by continuous net reclassification improvement (NRI) when added to the ADHERE multivariate logistic model of age, sex, urea, heart rate, and systolic blood pressure, for all patients [NRI 29.6 (12.1-47.1), P = 0.001] and HFrEF NRI 21.7 (1.9-41.6), P = 0.034] patients, as well as in addition to the ADHERE model combined with NT-proBNP for all patients [NRI 25.4 (7.8-43.1), P = 0.005]. CONCLUSION: GH offers incremental prognostic information over the ADHERE score clinical predictors and NT-proBNP for risk stratification of acute HF patients.Peer-reviewedPost-prin
Significance of myocardial tenascin-C expression in left ventricular remodelling and long-term outcome in patients with dilated cardiomyopathy

Aim Dilated cardiomyopathy (DCM) has a variety of causes, and no useful approach to predict left ventricular (LV) remodelling and long-term outcome has yet been established. Myocardial tenascin-C (TNC) is known to appear under pathological conditions, possibly to regulate cardiac remodelling. The aim of this study was to clarify the significance of myocardial TNC expression in LV remodelling and the long-term outcome in DCM. Methods and results One hundred and twenty-three consecutive DCM patients who underwent endomyocardial biopsy for initial diagnosis were studied. Expression of TNC in biopsy sections was analysed immunohistochemically to quantify the ratio of the TNC-positive area to the whole myocardial tissue area (TNC area). Clinical parameters associated with TNC area were investigated. The patients were divided into two groups based on receiver operating characteristic analysis of TNC area to predict death: high TNC group with TNC area ≥2.3% (22 patients) and low TNC group with TNC area <2.3% (101 patients). High TNC was associated with diabetes mellitus. Comparing echocardiographic findings between before and 9 months after endomyocardial biopsy, the low TNC group was associated with decreased LV end-diastolic diameter and increased LV ejection fraction, whereas the high TNC group was not. Survival analysis revealed a worse outcome in the high TNC group than in the low TNC group (P < 0.001). Multivariable Cox regression analysis revealed that TNC area was independently associated with poor outcome (HR = 1.347, P = 0.032). Conclusions Increased myocardial TNC expression was associated with worse LV remodeling and long-term outcome in DCM
Prognostic significance of endogenous erythropoietin in long-term outcome of patients with acute decompensated heart failure

Aims Although previous reports suggest that an elevated endogenous erythropoietin (EPO) level is associated with worse clinical outcomes in chronic heart failure (HF) patients, the prognostic implication of EPO in patients with acute decompensated HF (ADHF) and underlying mechanisms of the high EPO level in severe HF patients who have a poor prognosis remain unclear. Methods and results We examined 539 consecutive ADHF patients with EPO measurement on admission from our registry. During a median follow-up period of 329 days, a higher EPO level on admission was independently associated with worse clinical outcomes [hazard ratio (HR) 1.25, 95% confidence interval (CI) 1.06–1.48, P = 0.008], and haemoglobin level was the strongest determinant of EPO level (P < 0.001), whereas estimated glomerular filtration rate (eGFR) was not significant in multivariate regression analysis. In the anaemic subgroup of 318 patients, a higher EPO level than expected on the basis of their haemoglobin level was related to increased adverse events (HR 1.63, 95% CI 1.05–2.49, P = 0.028). Moreover, estimated plasma volume excess rate was positively associated with EPO level (P = 0.003), and anaemic patients with a higher than expected EPO level tended to have a higher estimated plasma volume excess rate and plasma lactate level, and lower systemic oxygen saturation level with the preservation of the reticulocyte production index than those with a lower than expected EPO level. Conclusion A high EPO level predicts long-term worse clinical outcomes in ADHF patients, independent of anaemia and impaired renal function. Anaemia and hypoxia due to severe congestion may synergistically contribute to a high EPO level in high-risk HF patients
Traditional and new composite endpoints in heart failure clinical trials: facilitating comprehensive efficacy assessments and improving trial efficiency

Composite endpoints are commonly used as the primary measure of efficacy in heart failure clinical trials to assess the overall treatment effect and to increase the efficiency of trials. Clinical trials still must enrol large numbers of patients to accrue a sufficient number of outcome events and have adequate power to draw conclusions about the efficacy and safety of new treatments for heart failure. Additionally, the societal and health system perspectives on heart failure have raised interest in ascertaining the effects of therapy on outcomes such as repeat hospitalization and the patient's burden of disease. Thus, novel methods for using composite endpoints in clinical trials (e.g. clinical status composite endpoints, recurrent event analyses) are being applied in current and planned trials. Endpoints that measure functional status or reflect the patient experience are important but used cautiously because heart failure treatments may improve function yet have adverse effects on mortality. This paper discusses the use of traditional and new composite endpoints, identifies qualities of robust composites, and outlines opportunities for future research