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1.
Circ Heart Fail ; 13(5): e006597, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32354280

RESUMO

BACKGROUND: Loop diuretics are used for congestion relief, and dose adaptations are usually a consequence of the clinicians' clinical judgement about the congestive status of the patient. In EPHESUS (Eplerenone in Patients With Systolic Dysfunction After Myocardial Infarction), many patients required diuretics for congestion relief. We thus hypothesized that blinded allocation to eplerenone would lead clinicians to reduce loop diuretics, as a consequence of the improvement in patients' status. METHODS: Cox and mixed-effects models were used over a median follow-up of 1.3 years in 6632 patients. RESULTS: A total of 6632 patients were included; at baseline, 3352 (50.5%) did not have diuretics, 2195 (33.1%) had diuretic doses between 1 and 40 mg/day, and 1085 (16.4%) had diuretic doses >40 mg/day. Patients with higher furosemide equivalent doses had a worse clinical status. Both baseline and follow-up incremental loop diuretic doses were associated with worse prognosis. Eplerenone treatment was associated with lower prescribed loop diuretic doses throughout the follow-up; lower doses were observed at 90 days and decreased further at 180 days and beyond. Eplerenone treatment led to a mean furosemide equivalent dose reduction of -2.2 mg/day (-2.9 to -1.6) throughout the follow-up. Eplerenone was effective in reducing morbidity and mortality regardless of the baseline loop diuretic dose used: hazard ratio for the outcome of cardiovascular death or heart failure hospitalization was 0.83 ([95% CI, 0.75-0.92]; P for interaction, 0.54). CONCLUSIONS: Eplerenone treatment led to a loop diuretic dose reduction during follow-up without evidence of treatment effect modification by loop diuretics. These findings suggest that eplerenone reduces congestive signs and symptoms, which enables clinicians to reduce loop diuretic doses.

2.
Scand Cardiovasc J ; : 1-6, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32292074

RESUMO

Background. Liraglutide, a glucagon-like peptide-1 agonist, is used for treatment of type 2 diabetes and has beneficial cardiovascular properties. However, treatment increases heart rate (HR) and possibly the risk of cardiovascular events in chronic heart failure (CHF) patients. We investigated potential associations between HR changes and clinical, laboratory and echocardiographic parameters and clinical events in liraglutide treated CHF patients. Methods. This was a sub-study of the LIVE study. CHF patients (N = 241) with a left ventricular ejection fraction ≤45% were randomised to 1.8 mg liraglutide daily or placebo for 24 weeks. Electrocardiograms (N = 117) and readouts from cardiac implanted electronic devices (N = 20) were analysed for HR and arrhythmias. Results. In patients with sinus rhythm (SR), liraglutide increased HR by 8 ± 9 bpm (pulse measurements), 9 ± 9 bpm (ECG measurements) and 9 ± 6 bpm (device readouts) versus placebo (all p<.005). Increases in HR correlated with liraglutide dose (p=.01). HR remained unchanged in patients without SR. Serious cardiac adverse events were not associated with HR changes. Conclusions. During 6 months of treatment, HR increased substantially in CHF patients with SR treated with liraglutide but was not associated with adverse events. The long-term clinical significance of increased HR in liraglutide treated CHF patients needs to be determined.

3.
Eur J Heart Fail ; 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32227556

RESUMO

AIM: To examine the rates of all-cause mortality and heart failure (HF) readmission in patients hospitalized with decompensated HF according to HF duration - new-onset HF and worsening of chronic HF. METHODS AND RESULTS: In this nationwide observational cohort study, 17 176 patients were included at first hospital admission for HF in the period 2013-2015 using data from Danish nationwide registries. In total, 8860 (51.6%) patients were admitted with new-onset HF and 8316 (48.4%) with worsening of chronic HF. Patients with worsening of chronic HF were characterized by a greater comorbidity burden compared with patients with new-onset HF. The rates of outcomes were examined by multivariable Cox regression models, adjusted for age, sex, and comorbidity. Worsening of chronic HF was associated with a higher rate of the composite endpoint of all-cause mortality or HF readmission [hazard ratio (HR) 1.37, 95% confidence interval (CI) 1.31-1.43], all-cause mortality (HR 1.22, 95% CI 1.16-1.28), and HF readmission (HR 1.81, 95% CI 1.69-1.93) compared with new-onset HF. There was an interaction between atrial fibrillation (AF), HF duration, and outcome: in worsening of chronic HF, the rate of the composite endpoint was higher in patients with AF compared with those without (HR 1.12, 95% CI 1.07-1.19), whereas in new-onset HF, the rate of the composite endpoint was lower in patients with AF compared with those without (HR 0.91, 95% CI 0.85-0.96) (P-value for interaction <0.001). CONCLUSIONS: Among patients hospitalized with decompensated HF, worsening of chronic HF was associated with poorer outcomes compared with new-onset HF.

4.
Eur J Heart Fail ; 2020 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-32246806

RESUMO

AIMS: To evaluate the risk of heart failure (HF) in patients with type 2 diabetes (T2D) complicated by development of intercurrent ischaemic heart disease (IHD), end-stage renal disease (ESRD), or both, compared to patients with T2D and no IHD and ESRD. METHODS AND RESULTS: From Danish nationwide registries, we identified all patients with new-onset T2D with no history of HF between 1998 and 2015. Landmark analyses were used to estimate the 5-year absolute risk of HF at several follow-up times, and accounted for the occurrence of IHD and ESRD, identified before HF. The Aalen-Johansen estimator was used to account for censoring and the competing risk of death. A total of 285 024 patients with new-onset T2D were included. During follow-up, 19 960 developed incident HF. Among patients with T2D free of HF 5 years after T2D diagnosis, patients without IHD and ESRD had the lowest 5-year risk of HF [4.02%; 95% confidence interval (CI) 3.90-4.15), those with T2D complicated by IHD [11.51%; relative risk (RR) 2.86; 95% CI 2.72-3.02; P < 0.001] or ESRD (8.11%; RR 2.02; 95% CI 1.39-2.93; P < 0.001) an intermediate risk, and those with both IHD and ESRD (19.76%; RR 4.92; 95% CI 3.43-7.05; P < 0.001) the highest risk. CONCLUSION: Patients with T2D complicated by development of intercurrent IHD, ESRD, or both, showed a significantly higher risk of HF compared to those who did not develop IHD and ESRD. An effective way to delay or prevent the development of HF in patients with T2D may be to prevent IHD and ESRD.

5.
Biomarkers ; 25(3): 248-259, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32126847

RESUMO

Background: Amino-terminal-pro-B-type-natriuretic-peptide (NT-proBNP) is a diagnostic biomarker for heart failure (HF), but plasma concentrations are influenced by numerous factors. Mid-regional-pro-atrial-natriuretic-peptide (MR-proANP) have comparable diagnostic value in acute HF. However, data are lacking in the non-acute setting. This study sought to assess the diagnostic utility of MR-proANP in outpatients with a high risk of HF.Methods: This prospective study included 399 outpatients. Inclusion criteria were: age ≥ 60 years, ≥1 risk factor for HF (diabetes, chronic kidney disease, vascular disease, atrial fibrillation, hypertension), without known or suspected HF. Unrecognized HF was diagnosed based on clinical signs, patient-reported symptoms and echocardiography. Plasma concentrations of MR-proANP and NT-proBNP were analysed.Results: In total, 65 patients were diagnosed with HF or asymptomatic left ventricular systolic dysfunction (N = 12 LVEF ≤ 40%, N = 7 LVEF > 40% to ≤50%, N = 46 LVEF > 50%). Both MR-proANP (odds-ratio: 1.77; 95% CI:1.16-2.72; p = 0.009) and NT-proBNP (odds-ratio: 1.49; 95% CI:1.22-1.82; p < 0.001) were associated with HF. Area under receiver-operator characteristics curve (AUC) for the diagnosis of HF or asymptomatic left ventricular systolic dysfunction was higher for MR-proANP (AUC = 0.886; p < 0.001) and NT-proBNP (AUC = 0.910; p < 0.001) compared to patient-reported symptoms of HF (AUC = 0.830), but NT-proBNP added more diagnostic information compared to MR-proANP (p = 0.022).Conclusions: Both NT-proBNP and MR-proANP are useful biomarkers in the diagnosis of HF or asymptomatic left ventricular systolic dysfunction in a non-acute setting. However, NT-proBNP added more diagnostic information compared to MR-proANP.

6.
JAMA ; 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32219386

RESUMO

Importance: Additional treatments are needed for heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 (SGLT2) inhibitors may be an effective treatment for patients with HFrEF, even those without diabetes. Objective: To evaluate the effects of dapagliflozin in patients with HFrEF with and without diabetes. Design, Setting, and Participants: Exploratory analysis of a phase 3 randomized trial conducted at 410 sites in 20 countries. Patients with New York Heart Association classification II to IV with an ejection fraction less than or equal to 40% and elevated plasma N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. Interventions: Addition of once-daily 10 mg of dapagliflozin or placebo to recommended therapy. Main Outcomes and Measures: The primary outcome was the composite of an episode of worsening heart failure or cardiovascular death. This outcome was analyzed by baseline diabetes status and, in patients without diabetes, by glycated hemoglobin level less than 5.7% vs greater than or equal to 5.7%. Results: Among 4744 patients randomized (mean age, 66 years; 1109 [23%] women; 2605 [55%] without diabetes), 4742 completed the trial. Among participants without diabetes, the primary outcome occurred in 171 of 1298 (13.2%) in the dapagliflozin group and 231 of 1307 (17.7%) in the placebo group (hazard ratio, 0.73 [95% CI, 0.60-0.88]). In patients with diabetes, the primary outcome occurred in 215 of 1075 (20.0%) in the dapagliflozin group and 271 of 1064 (25.5%) in the placebo group (hazard ratio, 0.75 [95% CI, 0.63-0.90]) (P value for interaction = .80). Among patients without diabetes and a glycated hemoglobin level less than 5.7%, the primary outcome occurred in 53 of 438 patients (12.1%) in the dapagliflozin group and 71 of 419 (16.9%) in the placebo group (hazard ratio, 0.67 [95% CI, 0.47-0.96]). In patients with a glycated hemoglobin of at least 5.7%, the primary outcome occurred in 118 of 860 patients (13.7%) in the dapagliflozin group and 160 of 888 (18.0%) in the placebo group (hazard ratio, 0.74 [95% CI, 0.59-0.94]) (P value for interaction = .72). Volume depletion was reported as an adverse event in 7.3% of patients in the dapagliflozin group and 6.1% in the placebo group among patients without diabetes and in 7.8% of patients in the dapagliflozin group and 7.8% in the placebo group among patients with diabetes. A kidney adverse event was reported in 4.8% of patients in the dapagliflozin group and 6.0% in the placebo group among patients without diabetes and in 8.5% of patients in the dapagliflozin group and 8.7% in the placebo group among patients with diabetes. Conclusions and Relevance: In this exploratory analysis of a randomized trial of patients with HFrEF, dapagliflozin compared with placebo, when added to recommended therapy, significantly reduced the risk of worsening heart failure or cardiovascular death independently of diabetes status. Trial Registration: ClinicalTrials.gov Identifier: NCT03036124.

7.
Eur Heart J ; 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32221582

RESUMO

AIMS: In the DAPA-HF trial, the SGLT2 inhibitor dapagliflozin reduced the risk of worsening heart failure (HF) and death in patients with HF and reduced ejection fraction. We examined whether this benefit was consistent in relation to background HF therapy. METHODS AND RESULTS: In this post hoc analysis, we examined the effect of study treatment in the following yes/no subgroups: diuretic, digoxin, mineralocorticoid receptor antagonist (MRA), sacubitril/valsartan, ivabradine, implanted cardioverter-defibrillating (ICD) device, and cardiac resynchronization therapy. We also examined the effect of study drug according to angiotensin-converting enzyme inhibitor/angiotensin receptor blocker dose, beta-blocker (BB) dose, and MRA (≥50% and <50% of target dose). We analysed the primary composite endpoint of cardiovascular death or a worsening HF event. Most randomized patients (n = 4744) were treated with a diuretic (84%), renin-angiotensin system (RAS) blocker (94%), and BB (96%); 52% of those taking a BB and 38% taking a RAS blocker were treated with ≥50% of the recommended dose. Overall, the dapagliflozin vs. placebo hazard ratio (HR) was 0.74 [95% confidence interval (CI) 0.65-0.85] for the primary composite endpoint (P < 0.0001). The effect of dapagliflozin was consistent across all subgroups examined: the HR ranged from 0.57 to 0.86 for primary endpoint, with no significant randomized treatment-by-subgroup interaction. For example, the HR in patients taking a RAS blocker, BB, and MRA at baseline was 0.72 (95% CI 0.61-0.86) compared with 0.77 (95% CI 0.63-0.94) in those not on all three of these treatments (P-interaction 0.64). CONCLUSION: The benefit of dapagliflozin was consistent regardless of background therapy for HF.

8.
Int J Cardiol ; 305: 106-112, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32005452

RESUMO

BACKGROUND: Heart failure (HF) is widely associated with a median survival of 5 years. However, population level data on survival and HF progression has been limited for key subgroups. We assessed survival and HF progression, defined as hospitalization or outpatient diuretic intensification in patients ≤70 years without severe comorbidity, who received relevant medical therapy. METHODS: From administrative registers, we identified all Danish patients ≤70 years diagnosed with HF 2000-2012 without severe comorbidity, survived for 120 days to receive angiotensin converting enzyme inhibitors (ACE-I)/angiotensin receptor blocker (ARB) and beta blocker. Risk of death or progression of HF was assessed with Kaplan-Meier and Aalen Johansen estimators, respectively. Cox regression models were used to identify factors associated with risk of death. RESULTS: We included 19,985 patients, median age 61, 25% women - 1/3 of all HF patients ≤70 years. We excluded 237 patients who died within 120 days and 21,065 due to severe comorbidity. Five-year cumulative incidence of all-cause death was 14% (95%-confidence interval [CI]:13-14). Risk of death was increased for patients first diagnosed in hospital compared to outpatient clinics (hazard ratio: 1.51, 95%-CI:1.38-1.65, p < 0.001). Five-year cumulative incidence of HF hospitalization: 18% (95%-CI, 18-19) and intensification of diuretic therapy: 14% (95%-CI, 14-15). CONCLUSIONS: In patients ≤70 years without severe comorbidity, five-year mortality was only 14% and almost 2/3 were alive after 5 years without evident HF progression. Discussion of prognosis should be tailored to age and health status to provide realistic expectations for patients newly diagnosed and treated with recommended therapies for HF.

9.
Acta Oncol ; 59(4): 475-483, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31931649

RESUMO

Background: Fluoropyrimidines are mainstay chemotherapeutics in the treatment of gastrointestinal cancers and are also used to treat breast cancer and head and neck cancers. However, 5-flourouracil (5-FU) and capecitabine may induce cardiotoxicity that mostly presents as acute coronary syndromes. We compared the incidence of cardiotoxicity induced by 5-FU and capecitabine in patients with colorectal cancer and sought to identify risk markers for cardiotoxicity.Methods: We reviewed all consecutive patients with colorectal cancer who received 5-FU or capecitabine at one institution in the neoadjuvant (2007-2016), adjuvant (2000-2016) or metastatic setting (2007-2016).Results: Totally, 995 patients received 5-FU and 1241 received capecitabine. The incidence of cardiotoxicity induced by 5-FU was 5.2% [95% confidence interval (CI): 3.8-6.6%] and 4.1% (95% CI: 3.0-5.2%) induced by capecitabine (p = .21). The most common events were angina without ischemia (5-FU: 1.6%, capecitabine: 1.3%, p = .53), angina with ischemia on ECG (5-FU: 0.9%, capecitabine: 0.8%, p = .53), unspecified chest pain (5-FU: 0.9%, capecitabine: 0.6%, p = .34), ST-elevation myocardial infarction (5-FU: 0.5%; capecitabine: 0.4%, p = .76) and non-ST-elevation myocardial infarction (5-FU: 0.7%, capecitabine: 0.5%, p = .50). Cardiac arrest or sudden death occurred in 0.5 and 0.4%, respectively (p = 1). No risk markers for cardiotoxicity induced by 5-FU were identified. In the capecitabine group, ischemic heart disease was a risk marker (odds ratio: 2.9, 95% CI: 1.2-7.0, p = .016).Conclusions: Five percent of patients treated with 5-FU developed cardiotoxicity and 4% treated with capecitabine. Ischemic heart disease was a risk marker for cardiotoxicity induced by capecitabine.

10.
Europace ; 22(1): 74-83, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31595294

RESUMO

AIMS: Catheter ablation for atrial fibrillation (CAF) improves symptoms, but whether CAF improves outcome is less clear. The purpose of this study was to investigate whether CAF is associated with improved outcome in atrial fibrillation (AF) patients with previous direct current (DC) cardioversion. METHODS AND RESULTS: We performed a nationwide cohort study including all patients who underwent their 1st direct current cardioversion for AF in the period 2003-15 (N = 25 439). End points were all-cause death, cardiovascular death, stroke/thromboembolism, and incident heart failure (HF). Catheter ablation for AF was treated as a time-varying covariate and the association with outcome was assessed using Cox regression. We also constructed a propensity-matched cohort and assessed the association between CAF and outcome. Median follow-up was 5.3 years (inter-quartile range 3.0-8.7 years). A total of 3509 patients (13.8%) underwent CAF during the study period. Following adjustment for age, gender, comorbidities, medications, educational level, household income, and CHA2DS2VASc score, CAF was associated with reduced risks of all-cause death, cardiovascular death, and incident HF [all-cause death: hazard ratio (HR) 0.69, P < 0.001; cardiovascular death: HR 0.68, P = 0.003; incident HF: HR 0.76, P = 0.011]. Catheter ablation for AF was not associated with a reduced risk of stroke/thromboembolism. These results were replicated in a propensity-matched cohort. CONCLUSION: In AF patients with a prior DC cardioversion, CAF was associated with a reduced risk of all-cause and cardiovascular death. This may be due to a reduced risk of HF.

11.
Eur J Prev Cardiol ; 27(1): 79-88, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31349771

RESUMO

AIMS: We sought to determine whether socioeconomic position affects the survival of patients with heart failure treated in a national healthcare system. METHODS: We linked national Danish registers, identified 145,690 patients with new-onset heart failure between 2000 and 2015, and obtained information on education and income levels. We analysed differences in survival by income quartile and educational level using multiple Cox regression, stratified by sex. We standardised one-year mortality risks according to income level by age, year of diagnosis, cohabitation status, educational level, comorbidities and medical treatment of all patients. We standardised one-year mortality risk according to educational level by age and year of diagnosis. RESULTS: One-year mortality was inversely related to income. In women the standardised average one-year mortality risk was 28.0% in the lowest income quartile and 24.3% in the highest income quartile, a risk difference of -3.8% (95% confidence interval (CI) -4.9% to -2.6%). In men the standardised one-year mortality risk was 26.1% in the lowest income quartile and 20.2% in the highest income quartile, a risk difference of -5.8% (95% CI -6.8% to -4.9%). Similar gradients in standardised mortality were present between the highest and lowest educational levels: -6.6% (95% CI -9.6% to -3.5%) among women and -5.0% (95% CI -6.3% to -3.7%) among men. CONCLUSIONS: Income and educational level affect the survival of patients with heart failure, even in a national health system. Research is needed to investigate how socioeconomic differences affect survival.

12.
Eur J Heart Fail ; 22(2): 267-275, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31833168

RESUMO

AIM: To determine whether initiation of antibiotic therapy (ABX) by procalcitonin (PCT) within 8 h of admission in patients presenting to the emergency department with symptoms and signs of acute heart failure (AHF) and elevated natriuretic peptides would improve clinical outcomes. METHODS AND RESULTS: The study was a randomized multicentre clinical trial conducted at 16 sites in Europe. Patients were randomized to either a PCT-guided strategy or standard care. Patients with PCT-guided strategy (n = 370) had ABX initiated if PCT was > 0.2 µg/L. Patients with standard care (n = 372) had AHF care in accordance with published guidelines without PCT. The primary endpoint was 90-day all-cause mortality. Pre-specified secondary endpoints included 30-day all-cause mortality and readmission and rate of pneumonia. The Data Safety and Review Committee recommended stopping the study for futility when 762 of the planned 792 patients had been enrolled. A total of 742 patients could be analysed. Patients were elderly (median age: 77 years), 38% were women, and had typical signs and symptoms of AHF. All-cause mortality at 90 days was 10.3% in the PCT-guided group vs. 8.2% in standard care (P = 0.316). Thirty-day readmission was significantly higher in the PCT-guided group vs. standard care but the difference vanished until day 90. The rate of pneumonia was overall low (7.5%) and not different between groups. CONCLUSIONS: In patients with AHF, a strategy of PCT-guided initiation of ABX was not more effective than a standard care strategy in improving clinical outcomes.

13.
Eur Heart J ; 41(13): 1346-1353, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31860067

RESUMO

AIMS: To investigate whether diabetes confers higher relative rates of cardiovascular events in women compared with men using contemporary data, and whether these sex-differences depend on age. METHODS AND RESULTS: All Danish residents aged 40-89 years without a history major adverse cardiovascular events, including heart failure, as of 1 January 2012 until 31 December 2016 were categorized by diabetes-status and characterized by individual-level linkage of Danish nationwide administrative registers. We used Poisson regression to calculate overall and age-dependent incidence rates, incidence rate ratios, and women-to-men ratios for myocardial infarction, heart failure, ischaemic stroke, or cardiovascular death (MACE-HF). Among 218 549 (46% women) individuals with diabetes, the absolute rate of MACE-HF was higher in men than in women (24.9 vs. 19.9 per 1000 person-years). Corresponding absolute rates in men and women without diabetes were 10.1 vs. 7.0 per 1000 person-years. Comparing individuals with and without diabetes, women had higher relative rates of MACE-HF than men [2.8 (confidence interval, CI 2.9-2.9) in women vs. 2.5 (CI 2.4-2.5) in men] with a women-to-men ratio of 1.15 (CI 1.11-1.19, P < 0.001). The relative rates of MACE-HF were highest in the youngest and decreased with advancing age for both men and women, but the relative rates were higher in women across all ages, with the highest women-to-men ratio between age 50 and 60 years. CONCLUSION: Although men have higher absolute rates of cardiovascular complications, the relative rates of cardiovascular complications associated with diabetes are higher in women than in men across all ages in the modern era.

14.
ESC Heart Fail ; 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31814331

RESUMO

AIMS: We hypothesized that grading of diastolic dysfunction (DDF) according to two DDF grading algorithms and strain imaging yields prognostic information on all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: We enrolled ambulatory HFrEF (left ventricular ejection fraction < 45%; N = 1 065) patients who underwent echocardiography and speckle tracking assessment of global longitudinal strain (GLS). Patients were stratified according to DDF grades (Grades I-III) according to two contemporary DDF grading algorithms. Prognostic performance was assessed by C-statistics. Of the originally 1 065 enrolled patients, a total of 645 (61%) patients (age: 67 ± 11 years, male: 72%, ejection fraction: 27 ± 9%) were classified according to both DDF grading algorithms. Concordance between the algorithms was moderate (kappa = 0.48) and the reclassification rate was 33%. During a median follow-up of 3.3 years (1.9, 4.7 years), 101 (16%) died from all causes. When comparing DDF Grade I vs. Grade III, both algorithms provided prognostic information [Nagueh: (hazard ratio) HR 2.09, 95% confidence interval (CI),1.32-3.31, P = 0.002; Johansen: HR 2.47, 95% CI, 1.57-3.87, P < 0.001]. However, when comparing DDF Grade II vs. Grade III, only the Johansen algorithm yielded prognostic information (Nagueh: HR 1.04, 95% CI, 0.60-1.77, P = 0.90; Johansen: HR 2.26, 95% CI, 1.35-3.77, P = 0.002). We found no difference in prognostic performance between the two algorithms (C-statistics: 0.604 vs. 0.623, P = 0.24). Assessed by C-statistics, the most powerful predictors of the endpoint from the two algorithms were E/e'-ratio (C-statistics: 0.644), tricuspid regurgitation velocity (C-statistics: 0.625) and E/A-ratio (C-statistics: 0.602). When adding GLS to a combination of these predictors, the prognostic performance increased significantly (C-statistics: 0.705 vs. C-statistics: 0.634, P = 0.028). CONCLUSIONS: Evaluation of DDF in patients with HFrEF yields prognostic information on all-cause mortality. Furthermore, adding GLS to contemporary algorithms of DDF adds novel prognostic information.

16.
BMJ Open ; 9(11): e029098, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31780586

RESUMO

INTRODUCTION: A diagnosis of type 2 diabetes (T2D) more than doubles the risk of cardiovascular disease (CVD), with heart failure (HF) being one of the most common complications with a severe prognosis. The landmark Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Paitients (EMPA-REG OUTCOME) study demonstrated that treatment with the sodium glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin rapidly and significantly reduces CVD mortality and admission rates for HF. However, the mechanisms behind this reduction in clinical events are unknown.This study was designed to investigate the effects of the SGLT-2 inhibitor empagliflozin on myocardial perfusion and function in patients with T2D and high CVD risk. METHODS AND ANALYSIS: In this investigator-initiated, randomised, double-blind controlled clinical trial, 92 patients with T2D and established CVD or high CVD risk will be randomised to treatment with empagliflozin 25 mg or a matching placebo for 13 weeks. The primary outcome measure is change in myocardial flow reserve measured quantitatively by Rubidium-82 position emission tomography. In a substudy, invasive haemodynamics at rest and during exercise will be measured at baseline and following the intervention, using right heart catheterisation. ETHICS AND DISSEMINATION: The study protocol (v7, 02/08/2018) has been approved by the Ethics Committee of the Capital Region, Danish Data Protection Board and the Danish Medicines Agency, and it will be monitored according to the Good Clinical Practice regulations from the International Conference on Harmonization. The results be submitted to international peer-reviewed journals and be presented at conferences. The data will be made available to the public via EudraCT and www.clinicaltrials.gov. TRIAL REGISTRATION NUMBER: NCT03151343.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31764984

RESUMO

BACKGROUND: The formation of calciprotein particles (CPPs) may be an important component of the humoral defences against ectopic calcification. Although magnesium (Mg) has been shown to delay the transition of amorphous calcium-/phosphate-containing primary CPP (CPP-1) to crystalline apatite-containing secondary CPP (CPP-2) ex vivo, effects on the endogenous CPP pool are unknown. METHODS: We used post hoc analyses from a randomized double-blind parallel-group controlled clinical trial of 28 days treatment with high dialysate Mg of 2.0 mEq/L versus standard dialysate Mg of 1.0 mEq/L in 57 subjects undergoing maintenance hemodialysis for end-stage kidney disease. CPP load, markers of systemic inflammation and bone turnover were measured at baseline and follow-up. RESULTS: After 28 days of treatment with high dialysate Mg, serum total CPP (-52%), CPP-1 (-42%) and CPP-2 (-68%) were lower in the high Mg group (all P < 0.001) but were unchanged in the standard dialysate Mg group. Tumour necrosis factor-α (-20%) and interleukin-6 (-22%) were also reduced with high dialysate Mg treatment (both P < 0.01). High dialysate Mg resulted in higher levels of bone-specific alkaline phosphatase (a marker of bone formation) (+17%) but lower levels of tartrate-resistant acid phosphatase 5 b (a marker of bone resorption; -33%) (both P < 0.01). Inflammatory cytokines and bone turnover markers were unchanged in the standard dialysate Mg group over the same period. CONCLUSIONS: In this exploratory analysis, increasing dialysate Mg was associated with reduced CPP load and systemic inflammation and divergent changes in markers of bone formation and resorption.

18.
Open Heart ; 6(2): e001074, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31673386

RESUMO

Objective: Coronary artery disease (CAD) is frequent in patients with newly diagnosed heart failure (HF). Multislice CT (MSCT) is a non-invasive alternative to coronary angiography (CAG) suggested for patients with a low-to-intermediate risk of CAD. No established definition of such patients exists. Our purpose was to develop a simple score to identify as large a group as possible with a suitable pretest risk of CAD. Methods: Retrospective study of patients in Denmark undergoing CAG due to newly diagnosed HF from 2010 to 2014. All Danish patients were registered in two databases according to geographical location. We used data from one registry and multiple logistic regression with backwards elimination to find predictors of CAD and used the derived OR to develop a clinical risk score called the CT-HF score, which was subsequently validated in the other database. Results: The main cohort consisted of 2171 patients and the validation cohort consisted of 2795 patients with 24% and 27% of patients having significant CAD, respectively. Among significant predictor, the strongest was extracardiac arteriopathy (OR 2.84). Other significant factors were male sex, smoking, hyperlipidaemia, diabetes mellitus, angina and age. A proposed cut-off of 9 points identified 61% of patients with a 15% risk of having CAD, resulting in an estimated savings of 15% of the cost and 21% of the radiation. Conclusions: A simple score based on clinical risk factors could identify HF patients with a low risk of CAD; these patients may have benefitted from MSCT as a gatekeeper for CAG.

19.
BMC Cancer ; 19(1): 1105, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31726997

RESUMO

BACKGROUND: The prevalence of both atrial fibrillation (AF) and malignancies are increasing in the elderly, but incidences of new onset AF in different cancer subtypes are not well described.The objectives of this study were therefore to determine the incidence of AF in different cancer subtypes and to examine the association of cancer and future AF. METHODS: Using national databases, the Danish general population was followed from 2000 until 2012. Every individual aged > 18 years and with no history of cancer or AF prior to study start was included. Incidence rates of new onset AF were identified and incidence rate ratios (IRRs) of AF in cancer patients were calculated in an adjusted Poisson regression model. RESULTS: A total of 4,324,545 individuals were included in the study. Cancer was diagnosed in 316,040 patients. The median age of the cancer population was 67.0 year and 51.5% were females. Incidences of AF were increased in all subtypes of cancer. For overall cancer, the incidence was 17.4 per 1000 person years (PY) vs 3.7 per 1000 PY in the general population and the difference increased with age. The covariate adjusted IRR for AF in overall cancer was 1.46 (95% confidence interval (CI) 1.44-1.48). The strength of the association declined with time from cancer diagnosis (IRR0-90days = 3.41 (3.29-3.54), (IRR-180 days-1 year = 1.57 (CI 1.50-1.64) and (IRR2-5 years = 1.12 (CI 1.09-1.15). CONCLUSIONS: In this nationwide cohort study we observed that all major cancer subtypes were associated with an increased incidence of AF. Further, cancer and AF might be independently associated.

20.
Tidsskr Nor Laegeforen ; 139(13)2019 Sep 24.
Artigo em Norueguês, Inglês | MEDLINE | ID: mdl-31556524

RESUMO

BACKGROUND: Norwegian national guidelines recommend that clozapine be offered to patients with schizophrenia after two failed attempts with other antipsychotic drugs. One of the main objectives for the introduction of clinical pathways in mental health care is to provide an equal service to patients irrespective of where in the country they live. We wished to investigate the prescribing level of clozapine in various Norwegian counties. MATERIAL AND METHOD: We retrieved aggregated data from the Norwegian Prescription Database, the Norwegian Patient Registry and Statistics Norway on prescribing of clozapine, number of patients in contact with the specialist health service with the diagnosis schizophrenia, and population figures for 2016. RESULTS: Nationwide in 2016, there were 50 users of clozapine per 100 000 inhabitants (95 % confidence interval (CI) 48-52). The number of users was highest in Troms county (76 (95 % CI 63-89) per 100 000 inhabitants) and lowest in Akershus county (38 (95 % CI 33-43) per 100 000 inhabitants). We found no significant correlation between the prescribing rate for clozapine and the proportion of the population in the county who were undergoing treatment for schizophrenia in the specialist health service. INTERPRETATION: Prescribing of clozapine varies among Norwegian counties and is not correlated with the proportion of the population who are undergoing treatment for schizophrenia in the specialist health service. Different levels of implementation of the national guidelines constitute a possible explanation for the geographic differences.


Assuntos
Antipsicóticos/administração & dosagem , Clozapina/administração & dosagem , Prescrições de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Esquizofrenia/tratamento farmacológico , Adulto , Idoso , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Bases de Dados Factuais , Feminino , Fidelidade a Diretrizes , Humanos , Masculino , Pessoa de Meia-Idade , Noruega , Guias de Prática Clínica como Assunto , Sistema de Registros , Adulto Jovem
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