Maria Nikolaou

Inhibition of Interleukin-1 by Anakinra Improves Vascular and Left Ventricular Function in Patients With Rheumatoid Arthritis

Background— Interleukin-1 increases nitrooxidative stress. We investigated the effects of a human recombinant interleukin-1a receptor antagonist (anakinra) on nitrooxidative stress and vascular and left ventricular function. Methods and Results— In an acute, double-blind trial, 23 patients with rheumatoid arthritis were randomized to receive a single injection of anakinra (150 mg SC) or placebo and, after 48 hours, the alternative treatment. At baseline and 3 hours after the injection, we assessed (1) coronary flow reserve, aortic distensibility, systolic and diastolic (Em) velocity of the mitral annulus, and E to Em ratio (E/Em) using echocardiography; (2) flow-mediated, endothelium-dependent dilation of the brachial artery; and (3) malondialdehyde, nitrotyrosine, interleukin-6, endothelin-1, and C-reactive protein. In a chronic, nonrandomized trial, 23 patients received anakinra and 19 received prednisolone for 30 days, after which all indices were reassessed. Compared with baseline, there was a greater reduction in malondialdehyde, nitrotyrosine, interleukin-6, and endothelin-1 and a greater increase in flow-mediated dilation, coronary flow reserve, aortic distensibility, systolic velocity of mitral annulus, and E/Em after anakinra than after placebo (malondialdehyde −25% versus 9%; nitrotyrosine −38% versus −11%; interleukin-6 −29% versus 0.9%; endothelin-1 −36% versus −11%; flow-mediated dilation 45% versus −9%; coronary flow reserve 29% versus 4%; and aortic distensibility 45% versus 2%; P<0.05 for all comparisons). After 30 days of treatment, the improvement in biomarkers and in vascular and left ventricular function was greater in the anakinra group than in the prednisolone group (P<0.05). Conclusions— Interleukin-1 inhibition improves vascular and left ventricular function and is associated with reduction of nitrooxidative stress and endothelin.

Liver function abnormalities, clinical profile, and outcome in acute decompensated heart failure

AIMS The aim of this study was to assess the prevalence of abnormal liver function tests (LFTs) and the associated clinical profile and outcome(s) in acute decompensated heart failure (ADHF) patients. Alteration in LFTs is a recognized feature of ADHF, but prevalence and outcomes data from a broad contemporary cohort of ADHF are scarce and the mechanism(s) of ADHF-induced cholestasis is unknown. METHODS AND RESULTS We conducted a post hoc analysis of SURVIVE, a large clinical trial including ADHF patients treated with levosimendan or dobutamine. All LFTs were available in 1134 patients at baseline. Abnormal LFTs were seen in 46% of ADHF patients: isolated abnormal alkaline phosphatase (AP) was noted in 11%, isolated abnormal transaminases in 26%, and a combination of abnormal AP and transaminases in 9%. Abnormal AP was associated with marked signs of systemic congestion and elevated right-sided filling pressure. Abnormal AP had no relationship with 31-day mortality but was associated with worse 180-day mortality (23.5 vs. 34.9%, P = 0.001 vs. patients with normal AP). Abnormal transaminases were associated with clinical signs of hypoperfusion and with greater 31-day and 180-day mortality compared with normal transaminase profiles (17.6 vs. 8.4% and 31.6 vs. 22.4%, respectively; both P < 0.001). There was no additive value of abnormal AP plus abnormal transaminase on a long-term outcome. CONCLUSION Abnormal LFTs were present in about a half of patients presenting with ADHF treated with inotropes. Abnormal AP and abnormal transaminases were associated with specific clinical, biological, and prognostic features, including a short-term overmortality with increased transaminases but not with biological signs of cholestasis, in ADHF patients.

Trends in death attributed to heart failure over the past two decades in Europe

Little is known regarding temporal trends in mortality attributed to heart failure (HF) from a population perspective. The aim of this study was to assess the mortality related to HF as an underlying cause during the last 20 years in seven European countries.

Clinical and prognostic implications of self-rating depression scales and plasma B-type natriuretic peptide in hospitalised patients with chronic heart failure

Background: Depression is common among patients with chronic heart failure (CHF) and has been independently associated with a poorer prognosis. Purpose: This study evaluated the clinical and prognostic value of depression scales (Beck Depression Inventory (BDI), Zung Self-rating Depression Scale (Zung SDS)) along with plasma B-type natriuretic peptide (BNP) in CHF. Methods: 155 hospitalised CHF patients (ejection fraction 26.9% (SD 6.4%)) were studied by depression (BDI, Zung SDS) and functional questionnaires (Kansas City Cardiomyopathy Questionnaire (KCCQ), Duke Activity Status Index (DASI)), BNP and 6-minute walk test (6MWT). Patients were followed for 6 months for cardiovascular events, including death from any cause or rehospitalisation for CHF decompensation. Results: Seventy-six (49%) patients with depressive symptoms, as estimated by both scales, had significantly lower DASI and KCCQ scores (13.2 (SD 9.9) vs 23.6 (SD 13.0) and 26.6 (SD 15.0) vs 45.0 (SD 17.0), respectively; p<0.001), higher BNP (921 (SD 889) vs 439 (SD 267) pg/ml, p = 0.001) and reduced 6MWT (270 (SD 130) vs 337 (SD 133); p<0.001). According to logistic regression analysis, Zung SDS and BNP were independently associated with adverse clinical outcomes; values of Zung SDS ⩾40 and of BNP ⩾290 pg/ml predicted future events with a sensitivity of 82% and 94% and a specificity of 45% and 46%, respectively. The combination of Zung SDS plus BNP had an additive prognostic value, predicting events with a sensitivity of 77% and a specificity of 70% (event-free survival: Zung <40 and BNP <290 pg/ml; 170 (SD 9) days; Zung ⩾40 and BNP <290 pg/ml, 159 (SD 14) days; Zung <40 and BNP ⩾290 pg/ml, 118 (SD 15) days; Zung ⩾40 and BNP ⩾290 pg/ml, 73 (SD 8) days, p<0.001). Conclusions: CHF patients with depressive symptoms have impaired physical activity, associated with excessive neurohormonal activation. Among the studied scales, Zung SDS seemed to independently predict clinical outcome, especially in patients with increased plasma BNP concentration. Hence, the combination of those two modalities provides a practical means for risk stratification in CHF.

Impact of diuretic dosing on mortality in acute heart failure using a propensity‐matched analysis

Loop diuretics are recommended to treat congestion in heart failure (HF), despite limited quality evidence. High‐dose (HD) loop diuretics seem to worsen outcomes in chronic HF, though; data for acute HF are scarce, with equivocal results.

Acute pulmonary oedema: clinical characteristics, prognostic factors, and in‐hospital management

Acute pulmonary oedema (APE) is the second, after acutely decompensated chronic heart failure (ADHF), most frequent form of acute heart failure (AHF). This subanalysis examines the clinical profile, prognostic factors, and management of APE patients (n = 1820, 36.7%) included in the Acute Heart Failure Global Survey of Standard Treatment (ALARM‐HF).

Self‐assessment of health status is associated with inflammatory activation and predicts long‐term outcomes in chronic heart failure

Clinicians lack a generally accepted means for health status assessment in chronic heart failure (CHF). We investigated the correlation between health status and inflammation burden as well as its long‐term prognostic value in CHF outpatients.

Lowering interleukin-1 activity with anakinra improves myocardial deformation in rheumatoid arthritis.

Objective: Inhibition of interleukin-1 activity improves nitro-oxidative stress, endothelial and coronary function. The authors investigated (a) the association of nitro-oxidative stress and endothelial function with myocardial deformation, (b) the effects of anakinra, an interleukin-1a receptor antagonist on myocardial deformation in patients with rheumatoid arthritis (RA). Methods: The authors compared 46 RA patients to 23 normal controls. 23 patients received anakinra (150 mg subcutaneously once daily) and 23 patients a 5-mg increase of prednisolone dose for 30 days. At baseline and post-treatment this study assessed (a) the left ventricular (LV) longitudinal, circumferential and radial strain and strain rate, using speckle tracking echocardiography, (b) the coronary flow reserve (CFR), (c) the flow-mediated endothelial-dependent dilation of the brachial artery (FMD) and (d) nitrotyrosine (NT) and malondialdehyde blood levels. Results: Patients had impaired baseline myocardial deformation indices compared to controls (p<0.05). CFR and NT levels were related to longitudinal strain, systolic and diastolic strain rate, circumferential strain and systolic strain rate (p<0.05). FMD was related to longitudinal and circumferential diastolic strain rate (p<0.01). Compared to baseline, anakinra-treated patients increased the longitudinal strain (−17.8% (3.7%) vs −22.1% (3.5%)), systolic (−1.02 (0.23) l/s vs −1.25 (0.23) l/s) and diastolic (0.96 (0.37) l/s vs 1.20 (0.39) l/s) longitudinal strain rate, circumferential strain and strain rate (p<0.05 for all comparisons). No significant changes were observed among prednisolone-treated patients Conclusions: Myocardial deformation is impaired in RA patients and is related to nitro-oxidative stress and endothelial dysfunction. Chronic inhibition of IL-1 improves LV deformation in parallel with endothelial function and nitro-oxidative stress.

Acute heart failure in patients with diabetes mellitus: clinical characteristics and predictors of in-hospital mortality.

OBJECTIVE/METHODS ALARM-HF was an in-hospital observational survey that included 4953 patients admitted for acute heart failure (AHF) in six European countries, Mexico and Australia. This article is a secondary analysis of the survey which evaluates differences in clinical phenotype, treatment regimens and in-hospital outcomes in AHF patients with diabetes mellitus (DM) compared to non-diabetics. The data were collected retrospectively by the investigators, and the diagnosis of AHF (reported at discharge) was based on the definition and classification of ESC guidelines, while the diagnosis of DM was based on medical record (past medical and medication history). RESULTS This sub-analysis demonstrates substantial differences regarding both baseline features and in-hospital outcome among diabetic and non-diabetic AHF patients. Diabetic patients (n=2229, 45%) presented more frequently with acute pulmonary edema (p<0.001) than non-diabetics, had more often acute coronary syndrome (p<0.001) as precipitating factors of AHF, and multiple comorbidities such as renal dysfunction (p<0.001), arterial hypertension (p<0.001), anemia (p<0.001) and peripheral vascular disease (p<0.001). All-cause in-hospital mortality of diabetics was higher compared to non-diabetics (11.7% vs 9.8%, p=0.01). The multivariate analysis revealed that older age (p=0.032), systolic blood pressure <100mm Hg (p<0.001), acute coronary syndrome and non compliance as precipitating factors (p=0.05 and p=0.005, respectively), history of arterial hypertension (p=0.022), LVEF<50% (p<0.001), serum creatinine >1.5mg/dl (p=0.029), absence of life saving therapies such as ACE inhibitors/ARBs (p<0.001) and beta-blockers (p=0.014) at admission, as well as absence of interventional treatment by PCI (p<0.001), were independently associated with adverse in-hospital outcome. CONCLUSION Diabetics with AHF have higher in-hospital mortality than non-diabetics despite their intensive treatment regimens (regarding care for HF and ACS), possibly due to underlying ischemic heart disease and the presence of multiple comorbidities.

Association of left ventricular diastolic dysfunction with elevated NT-pro-BNP in general intensive care unit patients with preserved ejection fraction: a complementary role of tissue Doppler imaging parameters and NT-pro-BNP levels for adverse outcome.

The mechanisms of the N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) release in intensive care unit (ICU) patients with preserved ejection fraction (EF) are unclear. We investigated whether left ventricular (LV) dysfunction, as assessed by tissue Doppler imaging (TDI), is related to NT-pro-BNP levels in ICU patients with preserved EF and has a complementary value to NT-pro-BNP in the determination of in-hospital mortality. We examined 58 mechanically ventilated patients with no history of heart failure (age, 60 ± 18 years; EF, 63% ± 7%). The systolic (S) and early diastolic (E&vprime;) velocity of the mitral annulus by TDI and the E/E&vprime; as well as NT-pro-BNP, troponin, lactate acid, blood oxygen (PO2/FiO2), sepsis, and ICU mortality were assessed. Systolic, E&vprime;, and E/E&vprime; correlated with age, PO2/FiO2, lactate acid, NT-pro-BNP, troponin, history of arterial hypertension, and diabetes (P < 0.05). By multivariate analysis, the determinants of NT-pro-BNP were S (P = 0.024), E/E&vprime; (P = 0.017), and sepsis (P = 0.015). An NT-pro-BNP greater than 941 pg/mL was a reliable predictor of LV diastolic dysfunction defined as a composite of E&vprime; less than or equal to 8 cm/s and/or mean E/E greater than or equal to 13 (area under the curve, 75%; P = 0.03). Patients with combined NT-pro-BNP greater than 941 pg/mL and abnormal TDI markers had increased creatinine levels and a lower MAP, PO2/FiO2, and survival rate than those with abnormal TDI or NT-pro-BNP alone or patients with normal TDI markers and NT-pro-BNP (25%, 60%, 70%, and 84%, respectively; P < 0.05). The addition of abnormal TDI in a model including NT-pro-BNP and sepsis increased the models value for in-hospital mortality (P for change = 0.01). In ICU patients with preserved EF, LV diastolic dysfunction and sepsis determine NT-pro-BNP levels. Tissue Doppler imaging markers and NT-pro-BNP have a complementary value for in-hospital mortality.