Jolanta Nowak

Iron deficiency: an ominous sign in patients with systolic chronic heart failure

AIMS Beyond erythropoiesis, iron is involved in numerous biological processes crucial for maintenance of homeostasis. Patients with chronic heart failure (CHF) are prone to develop iron deficiency (ID), and iron supplementation improves their functional status and quality of life. We sought to examine the relationship between ID and survival in patients with systolic CHF. METHODS AND RESULTS In a prospective observational study, we evaluated 546 patients with stable systolic CHF [age: 55 +/- 11 (mean +/- standard deviation) years, males: 88%, left ventricular ejection fraction: 26 +/- 7%, New York Heart Association (NYHA) class (I/II/III/IV): 57/221/226/42]. Iron deficiency was defined as: ferritin <100 microg/L, or 100-300 microg/L with transferrin saturation <20%. The prevalence of ID was 37 +/- 4% [+/-95% confidence intervals (CI)] in the entire CHF population (32 +/- 4 vs. 57 +/- 10%-in subjects without vs. with anaemia defined as haemoglobin level <12 g/dL in women and <13 g/dL in men, P < 0.001). In a multiple logistic model, ID was more prevalent in women, those in the advanced NYHA class, with higher plasma N-terminal pro-type B natriuretic peptide and higher serum high-sensitivity C-reactive protein (all P < 0.05). At the end of follow-up (mean duration: 731 +/- 350 days), there were 153 (28%) deaths and 30 (6%) heart transplantations (HTX). In multivariable models, ID (but not anaemia) was related to an increased risk of death or HTX (adjusted hazard ratio 1.58, 95% CI 1.14-2.17, P < 0.01). CONCLUSION In patients with systolic CHF, ID is common and constitutes a strong, independent predictor of unfavourable outcome. Iron supplementation may be considered as a therapeutic approach in these patients to improve prognosis.

Circulating Estradiol and Mortality in Men With Systolic Chronic Heart Failure

CONTEXT Androgen deficiency is common in men with chronic heart failure (HF) and is associated with increased morbidity and mortality. Estrogens are formed by the aromatization of androgens; therefore, abnormal estrogen metabolism would be anticipated in HF. OBJECTIVE To examine the relationship between serum concentration of estradiol and mortality in men with chronic HF and reduced left ventricular ejection fraction (LVEF). DESIGN, SETTING, AND PARTICIPANTS A prospective observational study at 2 tertiary cardiology centers (Wroclaw and Zabrze, Poland) of 501 men (mean [SD] age, 58 [12] years) with chronic HF, LVEF of 28% (SD, 8%), and New York Heart Association [NYHA] classes 1, 2, 3, and 4 of 52, 231, 181, and 37, respectively, who were recruited between January 1, 2002, and May 31, 2006. Cohort was divided into quintiles of serum estradiol (quintile 1, < 12.90 pg/mL; quintile 2, 12.90-21.79 pg/mL; quintile 3, 21.80-30.11 pg/mL; quintile 4, 30.12-37.39 pg/mL; and quintile 5, > or = 37.40 pg/mL). Quintile 3 was considered prospectively as the reference group. MAIN OUTCOME MEASURES Serum concentrations of estradiol and androgens (total testosterone and dehydroepiandrosterone sulfate [DHEA-S]) were measured using immunoassays. RESULTS Among 501 men with chronic HF, 171 deaths (34%) occurred during the 3-year follow-up. Compared with quintile 3, men in the lowest and highest estradiol quintiles had increased mortality (adjusted hazard ratio [HR], 4.17; 95% confidence interval [CI], 2.33-7.45 and HR, 2.33; 95% CI, 1.30-4.18; respectively; P < .001). These 2 quintiles had different clinical characteristics (quintile 1: increased serum total testosterone, decreased serum DHEA-S, advanced NYHA class, impaired renal function, and decreased total fat tissue mass; and quintile 5: increased serum bilirubin and liver enzymes, and decreased serum sodium; all P < .05 vs quintile 3). For increasing estradiol quintiles, 3-year survival rates adjusted for clinical variables and androgens were 44.6% (95% CI, 24.4%-63.0%), 65.8% (95% CI, 47.3%-79.2%), 82.4% (95% CI, 69.4%-90.2%), 79.0% (95% CI, 65.5%-87.6%), and 63.6% (95% CI, 46.6%-76.5%); respectively (P < .001). CONCLUSION Among men with chronic HF and reduced LVEF, high and low concentrations of estradiol compared with the middle quintile of estradiol are related to an increased mortality.

Higher serum phosphorus is associated with catabolic/anabolic imbalance in heart failure

A higher serum phosphate level is associated with worse outcome. Energy‐demanding intracellular transport of phosphate is needed to secure anion bioavailability. In heart failure (HF), energy starvation may modify intracellular and serum levels of phosphate. We analysed determinants of serum phosphates in HF and assessed if catabolic/anabolic balance (CAB) was associated with elevation of serum phosphate.

Therapeutic Window for Calcium-Channel Blockers in the Management of Dilated Cardiomyopathy: A Prospective, Two-Centre Study on Non-Advanced Disease

Objective: This study aimed to investigate the usefulness of the calcium-channel blocker verapamil in non-advanced dilated cardiomyopathy (DCM). Methods: This was a randomised trial of 70 DCM patients treated with carvedilol (36 patients) and verapamil (instead of β-blocker; 34 patients) for 12 months. The remaining heart failure (HF) therapy was constant in both groups. The primary outcomes were to determine selected echocardiography parameters and functional status of patients. The secondary outcome included death, heart transplantation and re-hospitalisation due to HF progression. Results: Of the primary outcomes, only the mean ratio of early to late transmitral flow velocities increased significantly in the verapamil-treated patients as compared with the carvedilol-based therapy (1.1 ± 0.3 vs. 0.7 ± 0.2; 95% CI –0.6 to –0.1; p = 0.015). Simultaneously, the Minnesota Quality of Life improved significantly in the verapamil group (95% CI 5.2–19.9; p = 0.002). It was accompanied by the favourable effect of verapamil therapy on exercise capacity in the 6-min walk test (95% CI 21.3–110.7; p = 0.005). Conclusion: The addition of verapamil to angiotensin-converting enzyme and aldosterone inhibitors in non-advanced DCM patients has been shown to have a neutral or even positive effect in a few patients.

Albumin-to-globulin ratio as an independent predictor of mortality in chronic heart failure

AIM Albumin-to-globulin ratio (AGR) is emerged as a marker of impaired prognosis. We determined the predictive value of AGR in patients with heart failure with reduced ejection fraction (HFrEF). METHODOLOGY 999 patients with HFrEF were enrolled. Rates of 1-year all-cause mortality were compared between AGR quartiles (Q). Moreover, multivariate survival analysis in Coxs regression model and receiver operating characteristic analyses were performed. RESULTS 90-day and 1-year mortality was the highest in AGR Q1. AGR was an independent predictor of 90-day and 1-year mortality. Receiver operating characteristic analysis revealed moderate diagnostic value in predicting 90-day (AGR cutoff <1.2) and 1-year (AGR cutoff <1.38) mortality. CONCLUSION AGR had a good prognostic value and remained an independent predictor of mortality in HFrEF patients.

Determinants of unfavorable prognosis for out-of-hospital sudden cardiac arrest in Bielsko-Biala district

Introduction The prognosis in out-of-hospital sudden cardiac arrest (OHCA) remains unfavorable and depends on a number of demographic and clinical variables, the reversibility of its causes and its mechanisms. Aim To investigate the risk factors of prehospital death in patients with OHCA in Bielsko County. Material and methods The study analyzed all dispatch cards of the National Emergency Medical Services (EMS) teams in Bielsko-Biala for the year 2013 (n = 23 400). Only the cards related to sudden cardiac arrest in adults were ultimately included in the study (n = 272; 190 men, 82 women; median age: 71 years). Results Sixty-seven victims (45 men, 22 women) were pronounced dead upon the arrival of the EMS team, and cardiopulmonary resuscitation (CPR) was not undertaken. In the remaining group of 205 subjects, CPR was commenced but was ineffective in 141 patients (97 male, 44 female). Although univariate analysis indicated 6 predictors of prehospital death, including OHCA without the presence of witnesses (odds ratio (OR) = 4.2), OHCA occurring in a public place (OR = 3.1), no bystander CPR (OR = 9.7), no bystander cardiac massage (OR = 13.1), initial diagnosis of non-shockable cardiac rhythm (OR = 7.0), and the amount of drugs used for CPR (OR = 0.4), logistic regression confirmed that only the lack of bystander cardiac massage (OR = 6.5) and non-shockable rhythm (OR = 4.6) were independent determinants of prehospital death (area under ROC curve = 0.801). Conclusions Non-shockable rhythm of cardiac arrest and lack of bystander cardiac massage are independent determinants of prehospital death in Bielsko-Biala inhabitants suffering from OHCA.

Utstein-style reporting of out-of-hospital cardiac arrest in the Bielsko-Biała county

Introduction. Out-of-hospital cardiac arrest (OHCA) is one of the most severe medical emergencies, with significantly high both pre- and in-hospital mortality rates. The aim of the study was to assess the quality of reporting OHCA data by the Emergency Medical Service teams (EMS) in the Bielsko-Biala county, using standard ambulance dispatch cards. Material and methods. The study included adult inhabitants of Bielsko-Biala county who suffered from OHCA in 2013. Data were retrieved from standardised PRM forms, and compared to the Utstein style template. The study group comprised 272 patients, 190 (70%) males and 82 (30%) females, with a median age of 71 years (IQR 60–80). The pre-hospital mortality rate was 76.5% (75.3% in men and 79.3% in women). Results. The potential cause of OHCA was least known, with only 22% of forms including any information concerning this issue. Suboptimal reporting on the data enabling patient identification was noted in 12% cases. There was no association between reporting style and time and place of the OHCA. Conclusions. The overall quality of reporting of OHCA by PMR in Bielsko-Biala was good. The greatest concern was inability to identify the potential cause of the event, which can significantly influence application of adequate treatment.

Clinical and laboratory determinants of low serum level of 25-hydroxyvitamin D during escalation of pharmacotherapy in heart failure patients.

Introduction The activation of the renin-angiotensin-aldosterone (RAA) system is a main element of the pathophysiology of chronic heart failure (CHF), determining its symptoms and prognosis. Vitamin D is an RAA inhibitor, and its deficiency frequently accompanies CHF. The factors determining the concentration of 25-hydroxyvitamin D [25(OH)D] in CHF are not well understood, although an association has been suggested between the deficiency and the advancement of CHF. Also unknown is the influence of therapeutic escalation using recommended agents on the serum level of 25(OH)D. The aim of this study was to examine the incidence of abnormal 25(OH)D concentrations in CHF patients and to establish the clinical and laboratory determinants of low activity of this metabolite. Material and methods The retrospective analysis included the data of 412 CHF patients not receiving optimal pharmacological treatment who were initially in NYHA (New York Heart Association) class III or IV. Over the period of 3 months the therapy was escalated until reaching maximum tolerated doses or those recommended by the current guidelines. After optimizing the therapy, the incidence of 25(OH)D deficiency (< 30 ng/ml) and insufficiency (< 20 ng/ml) was established, and clinical and laboratory determinants for these abnormal concentrations were analyzed. Results Normal serum level, insufficiency, and deficiency of 25(OH)D were observed in, respectively, 41.5%, 26.0% and 32.5% of patients. The NYHA class improved by at least 1 class in 63.6% of patients, remained unchanged in 32.8% of patients, and deteriorated in 3.6% of patients. In multivariables analysis, low availability of natural ultraviolet B (UVB) radiation, loss of body mass during the CHF, higher concentrations of phosphates and albumins, and the presence of diabetes increased the risk of 25(OH)D deficiency, while higher concentrations of uric acid reduced this risk. In patients with a positive response to therapy, the concentration of 25(OH)D was borderline significantly higher (p = 0.055), while insufficiency and deficiency were less frequent (p = 0.02) than in patients without a treatment response, but this pertained only to patients with higher exposure to UVB. These differences were not observed in patients with low UVB exposure. Conclusions The concentration of 25(OH)D in CHF patients is not associated with the advancement of the disease, but is strongly determined by the potential availability of UVB radiation. A positive response to therapy increases the concentration of 25(OH)D only in the case of high UVB exposure; other determinants of 25(OH)D level include the patients metabolic profile and the presence of diabetes.

The relationship between late gadolinium enhancement imaging and myocardial biopsy in the evaluation of chronic heart failure patients with suspected myocarditis

Aim The aim of this study was to assess the relationship between late gadolinium-enhanced (LGE) cardiovascular magnetic resonance (CMR) and immunohistochemical markers of inflammation in patients with heart failure and a reduced ejection fraction (HFrEF). Material and methods Endomyocardial biopsy and CMR were performed in 38 consecutive patients (24 males, average age 43.2 ± 6.9 years, New York Heart Association [NYHA] class II) with HFrEF and suspected myocarditis. The immunohistochemical evaluation was done by the En-Vision system using DAKO monoclonal antibodies. The presence of > 14 infiltrating cells together with myocardial damage and ≥ 2 + up-regulation of HLA class II was considered diagnostic for myocarditis. The results of LGE were compared with the immunohistochemical markers of inflammation. All patients underwent coronary angiography. Results Twelve out of 38 (31.6%) patients met the immunohistological criteria for the diagnosis of myocarditis. Late gadolinium enhancement was present in 23 of 38 (60.5%) patients, mostly at the interventricular septum. No correlation was found between LGE and immunohistochemistry results (Kendalls tau; r = 0.21, p = 0.09). Conclusions Our study revealed no significant relationship between LGE cardiovascular magnetic resonance imaging and immunohistochemical markers of inflammation in patients with HFrEF.