Vassiliki Bistola

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.

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.

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.

Clinical and Prognostic Value of Duke's Activity Status Index Along With Plasma B-Type Natriuretic Peptide Levels in Chronic Heart Failure Secondary to Ischemic or Idiopathic Dilated Cardiomyopathy

The Duke Activity Status Index (DASI) provides an accurate estimate of functional capacity in patients with chronic heart failure (HF). The aim of this study was to evaluate the prognostic value of the DASI against well-established prognostic factors in 130 consecutive patients hospitalized for worsening HF symptoms (mean age 64 +/- 12 years, mean left ventricular ejection fraction 26 +/- 7%), followed for 9 months for major cardiovascular events, defined as death or hospitalization for HF decompensation. During follow-up, 77 of 130 patients (59%) experienced major cardiovascular events after a median time of 60 days (range 5 to 220). Patients with eventful courses were in higher New York Heart Association functional classes (p = 0.001) and had shorter 6-minute walking distances (p = 0.041), lower ejection fractions (p <0.001), higher plasma B-type natriuretic peptide (BNP) levels at hospital admission and discharge (both p <0.001), and lower DASI scores (16 +/- 12 vs 25 +/- 17, p = 0.003). In multivariate Cox regression analysis including all these variables, only BNP level at discharge (p = 0.006) and DASI score (p = 0.047) were independently associated with event-free survival. A BNP cutoff of 697 pg/ml predicted future events with 59% sensitivity and 86% specificity, while a DASI score cutoff of 8 had 76% sensitivity and 25% specificity. The combination of the 2 cutoffs predicted events with 33% sensitivity and 95% specificity. Event-free survival was significantly lower in patients with the 2 markers positive (BNP >697 pg/ml and DASI score <8) compared with those with with 2 markers negative (63 +/- 27 vs 183 +/- 15 days, log-rank p <0.0001). In conclusion, functional status assessment by the DASI bears prognostic value, and its combination with plasma BNP may provide quite specific risk stratification in patients with chronic HF.

Plasma B-type natriuretic peptide and anti-inflammatory cytokine interleukin-10 levels predict adverse clinical outcome in chronic heart failure patients with depressive symptoms: a 1-year follow-up study.

To assess the prognostic value of a wide spectrum of neurohormonal and inflammatory markers along with functional status and exercise capacity, in hospitalized chronic heart failure (CHF) patients with depressive symptoms.

Novel biologic mechanisms of levosimendan and its effect on the failing heart

Background: Calcium sensitizers belong to a new class of cardiac enhancers that stimulate cardiac contractility without causing intracellular calcium overload or increasing myocardial oxygen demand. Levosimendan, the most well-studied calcium sensitizer in the real clinical practice, produces greater hemodynamic and symptomatic improvement in patients with acute heart failure than traditional inotropes. Objective: To review the recent experimental and clinical evidence on novel biologic mechanisms explaining the pleiotropic effects of levosimendan on the failing heart. Methods: A systematic search of peer-reviewed publications was performed on Medline and EMBASE from January 1995 to December 2007. The results of unpublished trials were obtained from presentations at national and international meetings. Results: Levosimendan has a unique dual mechanism of action by enhancing cardiac contractility and causing peripheral vasodilatation. Immunomodulatory and antiapoptotic properties of levosimendan may be an additional biologic mechanism that prevents further cytotoxic and hemodynamic consequences of abnormal immune and neurohormonal responses in acute heart failure, leads to cardioprotection, and beneficially intervenes in the progression of syndrome. Experimental data show that levosimendan exerts its cardioprotective effects through its antioxidant properties and seems to be a potent inhibitor of H2O2-induced cardiomyocyte apoptotic cell death. Clinical data demonstrate that levosimendan does not increase markers of oxidative and nitrosative stress, in contrast to placebo treatment, in advanced chronic heart failure patients. Levosimendan has also been shown to activate mitoKATP channels which are important mediators of ischemic preconditioning. Pharmacological modulation of KATP channels may prove beneficial in patients at risk of myocardial ischemia, particularly those requiring inotropic support. Conclusion: Pleiotropic effects of levosimendan appear to have important clinical and prognostic implications in acute heart failure syndromes and ischemic heart disease.

Temporal trends in epidemiology, clinical presentation and management of acute heart failure: results from the Greek cohorts of the Acute Heart Failure Global Registry of Standard Treatment and the European Society of Cardiology-Heart Failure pilot survey

AIM Temporal trends of epidemiological data on acute heart failure (AHF) are limited. We sought to assess changes in epidemiology, clinical presentation and management of AHF in Greece using data from two international registries conducted three years apart. METHODS AND RESULTS The Acute Heart Failure Global Registry of Standard Treatment (ALARM-HF) and the European Society of Cardiology-Heart Failure (ESC-HF) pilot survey were conducted during 2006-2007 and 2009-2010, respectively. A total of 432 AHF patients were recruited by Greek sites in the two registries (255 in ALARM-HF and 177 in ESC-HF pilot survey). About 60% of patients in both registries presented with acutely decompensated chronic HF and 40% with de novo AHF. The use of life-prolonging, guideline-recommended medications increased over time (pre-admission use of angiotensin-converting enzyme (ACE) inhibitors/ angiotensin receptor blockers (ARBs) from 47% to 60%, beta-blockers from 31% to 65%, aldosterone antagonists from 18% to 45%). Those therapies also increased during hospitalisation in both registries. Patients were treated by cardiologists in >90% of cases during hospitalisation; the main intravenous therapies in both registries were diuretics (94% and 97%), followed by vasodilators (47% and 22%) and inotropes (31% and 20%). The length of hospitalisation remained similar (6-7 days in both registries), while in-hospital mortality dropped from 8.5% in the ALARM-HF to 4.5% in the ESC-HF pilot survey. CONCLUSIONS A temporal increase in the use of life-prolonging therapies along with an improvement of in-hospital mortality was observed. Clinical profiles, in-hospital management and outcome of AHF patients in Greece were similar to other European countries, despite regional differences in healthcare systems.

Clinical and neurohormonal correlates and prognostic value of serum prolactin levels in patients with chronic heart failure.

Hypothalamic axis deregulation is associated with clinical severity and depression in chronic heart failure (CHF). We investigated the relationship of serum prolactin, an indicator of hypothalamic axis function, to neurohomonal/immune activation and depressive symptoms in CHF as well as its prognostic value.

Practical considerations on the introduction of sacubitril/valsartan in clinical practice: Current evidence and early experience

The combination of neprilysin inhibitor sacubitril with the angiotensin II receptor 1 blocker valsartan is the first agent from the angiotensin receptor neprilysin inhibitors (ARNI) class authorized for clinical use in heart failure (HF) patients with reduced ejection fraction (HFrEF). Sacubitril/valsartan resulted in 20% reduction in the incidence rate of death or HF hospitalization compared to enalapril in symptomatic HFrEF patients in the seminal PARADIGM-HF trial. As a result, the recently updated European and American HF guidelines granted this agent a class IB indication for the treatment of ambulatory/chronic symptomatic HFrEF patients. However, translating the positive results of trials into true clinical benefit is often challenging. This is particularly true in the case of sacubitril/valsartan, as HF is a heterogeneous syndrome including many severely ill patients who are prone to decompensation, while this new agent comes to replace a cornerstone of current evidence-based HF therapy. In the present paper, we address a number of practical issues regarding the introduction of sacubitril/valsartan and propose an algorithm based on available evidence and early clinical experience.

Usefulness of Dobutamine-Induced Changes of the Two-Dimensional Longitudinal Deformation Predict Clinical and Neurohumoral Improvement in Men After Levosimendan Treatment in Acutely Decompensated Chronic Heart Failure

Levosimendan reduces symptoms and improves hemodynamics in patients with acutely decompensated chronic heart failure (ADCHF). The aim of this study was to investigate (1) the association of changes induced by low-dose dobutamine stress echocardiography in 2-dimensional strain parameters with the corresponding changes in the left ventricular (LV) ejection fraction (EF) and LV outflow tract velocity time integral (VTI) in patients with ADCHF and (2) whether LV contractile reserve assessed by conventional and speckle-tracking echocardiography is associated with clinical and neurohumoral improvement after levosimendan treatment. Twenty-eight consecutive patients with ADCHF (mean age 65 +/- 10 years, mean New York Heart Association class 3.6 +/- 0.3, mean EF 22 +/- 6%) were studied using dobutamine stress echocardiography before 24-hour infusion of levosimendan. The LV EF, VTI, and mean longitudinal, circumferential, and radial strain and strain rate using speckle-tracking imaging were measured. Twenty-one patients (75%) had evidence of contractile reserve (LV EF increase >10% and VTI increase >20% after peak dobutamine dose). Patients with versus without contractile reserve demonstrated greater improvements in New York Heart Association class (mean change -1.0 +/- 0.5 vs -0.5 +/- 0.3, p = 0.01) and reductions in B-type natriuretic peptide levels (-34 +/- 30% vs +4 +/- 31%, p <0.01) 48 hours after treatment. On multivariate analysis, mean longitudinal systolic strain rate reserve (peak longitudinal strain rate minus longitudinal strain rate at rest) was the best predictor of improvement in New York Heart Association class (p = 0.039) and B-type natriuretic peptide level (p = 0.042) after levosimendan among the reserve of LV fractional shortening, the EF, VTI, and longitudinal, circumferential, and radial strain and strain rate. In conclusion, dobutamine-induced changes in longitudinal systolic strain rate are associated with clinical and neurohumoral improvement after levosimendan treatment in patients with ADCHF.