Lech Poloński

Randomized, Placebo-Controlled Study for Immunosuppressive Treatment of Inflammatory Dilated Cardiomyopathy Two-Year Follow-Up Results

Background—Previous studies have shown disappointing results for immunosuppressive treatment in patients with dilated cardiomyopathy. Therefore, we studied the effectiveness of such therapy in patients with HLA upregulation on biopsy. Methods and Results—Of 202 patients with dilated cardiomyopathy, 84 patients with increased HLA expression were randomized to receive either immunosuppression or placebo for 3 months; they were then followed for 2 years. After 2 years, there were no significant differences in the primary end point (a composite of death, heart transplantation, and hospital readmission) between the 2 study groups (22.8% for the immunosuppression group and 20.5% for the placebo). The secondary efficacy end point included changes in ejection fraction, end-diastolic diameter, end-diastolic volume, end-systolic volume and NYHA class; left ventricular ejection fraction increased significantly in the immunosuppression group compared with the placebo group (95% CI, 4.20 to 13.12;P <0.001) after 3 months of follow-up. The early favorable effects of immunosuppressive therapy on left ventricular volume, left ventricular diastolic dimension, and New York Heart Association class were also present. This improvement was maintained in the immunosuppression group at 2 years (ejection fraction: 95% CI, 6.94 to 19.04;P <0.001). In addition, on the basis of the protocol-specified definition of improvement, 71.8% patients in the immunosuppression group versus 20.9% patients in the placebo group met the criteria of improvement after 3 months (P <0.001). At the end of the follow-up period, 71.4% patients from the immunosuppression group versus 30.8% patients from the placebo group were improved (P =0.001). Conclusions—These data demonstrate a long-term benefit of immunosuppressive therapy in patients with dilated cardiomyopathy and HLA upregulation on biopsy specimens. Thus, restoration of immunosuppressive therapy for such patients should be considered.

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.

Iron deficiency in chronic heart failure: An international pooled analysis

BACKGROUND Iron deficiency (ID) is an emerging problem in patients with chronic heart failure (HF) and can be a potential therapeutic target. However, not much is known about the prevalence, predictors, and prognosis of ID in patients with chronic HF. METHODS In an international pooled cohort comprising 1,506 patients with chronic HF, we studied the clinical associates of ID and its prognostic consequences. RESULTS Iron deficiency (defined as a ferritin level <100 μg/L or ferritin 100-299 μg/L with a transferrin saturation <20%) was present in 753 patients (50%). Anemic patients were more often iron deficient than nonanemic patients (61.2% vs 45.6%, P < .001). Other independent predictors of ID were higher New York Heart Association class, higher N-terminal pro-brain-type natriuretic peptide levels, lower mean corpuscular volume levels, and female sex (all P < .05). During follow-up (median 1.92 years, interquartile range 1.18-3.26 years), 440 patients died (29.2%). Kaplan-Meier survival analysis revealed ID as a strong predictor for mortality (log rank χ(2) 10.2, P = .001). In multivariable hazard models, ID (but not anemia) remained a strong and independent predictor of mortality (hazard ratio 1.42, 95% confidence interval 1.14-1.77, P = .002). Finally, the presence of ID significantly enhanced risk classification and integrated discrimination improvement when added to a prediction model with established risk factors. CONCLUSIONS Iron deficiency is common in patients with chronic HF, relates to disease severity, and is a strong and independent predictor of outcome. In this study, ID appears to have greater predictive power than anemia.

Perindopril for elderly people with chronic heart failure: the PEP-CHF study

The prevalence of chronic heart failure (CHF) rises with increasing age, from <1% in those below 65 years of age to > 5% in those over 65 years of age and is a major cause of morbidity and mortality in older people. Recent European guidelines point to a major deficiency in our knowledge of how to treat diastolic chronic heart failure, and a lack of information on treatment for heart failure in the elderly in general.

A double-blind randomized multicentre clinical trial to evaluate the efficacy and safety of two doses of etomoxir in comparison with placebo in patients with moderate congestive heart failure: the ERGO (etomoxir for the recovery of glucose oxidation) study

Etomoxir is an inhibitor of mitochondrial CPT1 (carnitine palmitoyltransferase 1) and thereby switches energy metabolism from fatty acids to glucose oxidation. Such a metabolic change may be beneficial in CHF (congestive heart failure). The ERGO (etomoxir for the recovery of glucose oxidation) study was designed in which etomoxir was tested at a dose of 80 and 40 mg compared with placebo for a period of 6 months in patients with CHF. As the principle measure of efficacy, a maximal exercise tolerance test and a submaximal 6-min corridor walk test were used. Secondary end points were echocardiographical dimensions and quality-of-life assessment scores. A total of 350 patients were planned to be screened, with the expectation that end point data would be available from approx. 260 patients. However, the study had to be stopped prematurely, because unacceptably high liver transaminase levels were detected in four patients taking etomoxir. At the termination of the study, 121 patients were randomized to placebo, 118 to 40 mg of etomoxir and 108 to 80 mg of etomoxir. At that time, 21 patients in the placebo group, 16 in the 40 mg of etomoxir group and 14 patients in the 80 mg of etomoxir group had completed the study. The mean increases in exercise time were 3.3, 10.2 and 19.4 s for the placebo, 40 mg of etomoxir and 80 mg of etomoxir groups respectively (P value was not significant). No changes were obvious in the 6-min corridor walk test or in echocardiographical parameters from baseline. The number of patients that completed the study was too small to demonstrate significant effects on exercise time, although there was a tendency towards an increase in exercise time. Therefore, before rejecting the hypothesis that inhibition of fatty acid oxidation might be beneficial in CHF, similar studies have to be performed using different inhibitors of fatty acid oxidation targeting CPT1 and other enzymes in this metabolic pathway.

Four-Year Follow-Up of TYPHOON (Trial to Assess the Use of the CYPHer Sirolimus-Eluting Coronary Stent in Acute Myocardial Infarction Treated With BallOON Angioplasty)

OBJECTIVES The aim of this study was to assess the long-term safety and efficacy of the CYPHER (Cordis, Johnson and Johnson, Bridgewater, New Jersey) sirolimus-eluting coronary stent (SES) in percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). BACKGROUND Concern over the safety of drug-eluting stents implanted during PCI for STEMI remains, and long-term follow-up from randomized trials are necessary. TYPHOON (Trial to assess the use of the cYPHer sirolimus-eluting stent in acute myocardial infarction treated with ballOON angioplasty) randomized 712 patients with STEMI treated by primary PCI to receive either SES (n = 355) or bare-metal stents (BMS) (n = 357). The primary end point, target vessel failure at 1 year, was significantly lower in the SES group than in the BMS group (7.3% vs. 14.3%, p = 0.004) with no increase in adverse events. METHODS A 4-year follow-up was performed. Complete data were available in 501 patients (70%), and the survival status is known in 580 patients (81%). RESULTS Freedom from target lesion revascularization (TLR) at 4 years was significantly better in the SES group (92.4% vs. 85.1%; p = 0.002); there were no significant differences in freedom from cardiac death (97.6% and 95.9%; p = 0.37) or freedom from repeat myocardial infarction (94.8% and 95.6%; p = 0.85) between the SES and BMS groups. No difference in definite/probable stent thrombosis was noted at 4 years (SES: 4.4%, BMS: 4.8%, p = 0.83). In the 580 patients with known survival status at 4 years, the all-cause death rate was 5.8% in the SES and 7.0% in the BMS group (p = 0.61). CONCLUSIONS In the 70% of patients with complete follow-up at 4 years, SES demonstrated sustained efficacy to reduce TLR with no difference in death, repeat myocardial infarction or stent thrombosis. (The Study to Assess AMI Treated With Balloon Angioplasty [TYPHOON]; NCT00232830).

Reperfusion strategy in Europe: temporal trends in performance measures for reperfusion therapy in ST-elevation myocardial infarction

AIMS The rate and type of reperfusion, as well as time delays to reperfusion are directly associated with mortality and are established as performance measures (PMs) in the treatment of ST elevation myocardial infarction (STEMI). To date, little information exists about PMs for reperfusion in clinical practice in Europe and their temporal changes. METHODS AND RESULTS Using the Euro Heart Survey ACS-III data set (2 years of inclusions between 2006 and 2008, 138 centres in 21 countries), we selected patients with STEMI eligible for reperfusion therapy. Recorded variables corresponded to the CARDS data set. The rate and type of reperfusion, as well as door to needle and door to artery times were assessed and compared between periods. Timely reperfusion was defined as a door to needle time < 30 min, or a door to artery time < 90 min. We assessed changes in PMs for reperfusion over the 2 years of recruitment. Among 19 205 patients included in the registry, 7655 had STEMI, and 6481 were admitted within the first 12 h and eligible for reperfusion. The rate of patients who underwent reperfusion increased from 77.2 to 81.3%, with an increase in the use of primary percutaneous coronary intervention (P-PCI). The door to needle and door to artery times decreased significantly during the study period, from 20 to 15 min (P = 0.0011) and from 60 to 45 min (P < 0.0001) respectively. As a result, the number of eligible patients receiving reperfusion therapy in a timely manner increased from 53.1 to 63.5% (P < 0.0001). In parallel, over the 2-year period, in-hospital mortality decreased from 8.1 to 6.6% (P = 0.047). CONCLUSION In centres participating in the Euro Heart Survey ACS III, PMs for reperfusion in STEMI improved significantly between 2006 and 2008, with greater use of PCI. Similarly, the rate of patients reperfused in a timely manner also increased, with a significant reduction in door to needle and door to artery times.

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.

Gender-related differences in mortality after ST-segment elevation myocardial infarction: a large multicentre national registry.

AIMS Clinical outcomes in the treatment of acute ST-segment elevation myocardial infarction (STEMI) differ between men and women. The aim of the study was to compare results of STEMI management in a large multicentre national registry. METHODS AND RESULTS A total of 456 hospitals (including 58 interventional centres) participated in the registry during one year. The study group consisted of 8,989 (34.5%) females and 17,046 (65.5%) males. Women were older (69.7 ± 11 vs. 62 ± 12 years; p<0.0001) and had more risk factors. Percutaneous coronary intervention was performed significantly less in women (47.8% vs. 57.4%; p<0.0001). There was a longer time delay in women at each stage of treatment. The incidence of in-hospital complications was higher in women. In-hospital (11.9% vs. 6.9%; p<0.0001) and 12-months (22% vs. 14.1%; p<0.0001) mortality was significantly higher in women. In multivariate analysis pulmonary oedema, cardiogenic shock, cardiac arrest, age, diabetes and anterior infarction significantly increased both in-hospital and long-term mortality. The in-hospital mortality was higher in the female group. CONCLUSIONS Despite poor clinical characteristics, less than satisfactory management and a worse prognosis of STEMI in women, being a women itself is not a risk factor for increased long-term mortality, however, other well known risk factors affecting the prognosis relate frequently to the female gender.

A comparison of ST elevation versus non-ST elevation myocardial infarction outcomes in a large registry database: are non-ST myocardial infarctions associated with worse long-term prognoses?

BACKGROUND Prognoses in STEMI and NSTEMI beyond one year from onset remain unclear. We aimed to compare the treatments and the two-year outcomes in patients with myocardial infarction (MI) enrolled at the Polish Registry of Acute Coronary Syndromes (PL-ACS). METHODS A total of 13,441 patients with MI (8250 with STEMI, and 5191 with NSTEMI) underwent medical care between October 2003 and June 2005 in the Silesia region (4.8 million inhabitants). The events analyzed were death, MI, stroke and percutaneous (PCI) or surgical (CABG) revascularization. RESULTS After two years, NSTEMI was associated with a higher incidence of death (hazard ratio (HR) of 1.09 (95% confidence interval (CI) 1.02-1.17, p<0.0001)); a higher incidence of reinfarction, stroke, CABG and a lower rate of PCI. Adjustments for baseline characteristics and treatment strategy (invasive vs. non-invasive) reversed the HR for mortality and eliminated the difference in MI and stroke. The adjusted HR for mortality was 0.76 (95% CI, 0.71-0.83, p<0.0001). STEMI and NSTEMI patients treated non-invasively were older and showed higher incidences of diabetes, obesity, pulmonary edema and cardiogenic shock than their invasively treated counterparts. Invasively treated patients received aspirin, beta-blockers, ACE inhibitors and statins more often during hospitalization and at discharge. CONCLUSIONS The unadjusted long-term prognosis was worse in NSTEMI. After adjustment for the baseline characteristics and treatment strategy, the long-term prognosis was worse in STEMI. Patients with MI treated invasively showed more favorable clinical characteristics and received guideline-recommended therapy more often than patients who did not undergo invasive treatment.