Jiří Pařenica

Uric acid, allopurinol therapy, and mortality in patients with acute heart failure—results of the Acute HEart FAilure Database registry

STUDY OBJECTIVE The aim of this study was to explore the prognostic role of serum uric acid (UA) measurement in the hospital and long-term mortality assessment in subjects with acute heart failure (AHF) from the Acute HEart FAilure Database registry (AHEAD). The AHEAD registry comprised 4153 patients with AHF syndromes hospitalized at the AHEAD participating centers. PATIENTS AND METHODS The study included 1255 patients who were admitted to the AHEAD participating centers with acute decompensated chronic heart failure, de novo heart failure, or cardiogenic shock between September 2006 and October 2009 and who had information about serum UA concentration available at the time of hospital admission. The hospital and long-term mortality was followed using the centralized database of the Ministry of Health, Czech Republic. The mean age of the cohort was 73.4 years, the female population represented 43%, the median hospital stay was 8 days, and the mean hospital mortality was 7.6%. RESULTS The median UA concentration of the patients with AHF was 432 μmol/L (7.26 mg/dL), the median estimated glomerular filtration rate (eGFR) was 49.0 mL/min, and N-terminal pro-brain natriuretic peptide level was 5510 pg/mL. Among other laboratory variables, UA concentration greater than 515 μmol/L (8.67 mg/dL) was associated with increased hospital mortality (P < .001), as well as eGFR less than 30 mL/min (P < .001), Na 135 mmol/L or less, and positive troponin. Uric acid concentration greater than 500 μmol/L (8.41 mg/dL) was associated with increased long-term mortality (P < .001), followed by eGFR less than 30 mL/min (P < .001), Na 135 mmol/L or less, and hemoglobin level lower than 130 g/L (P < .001). The 1-year survival rate of patients discharged from hospital (n = 1159) was 75.6%, and the 2-year rate was 66.8%. Survival of patients treated with allopurinol for hyperuricemia was significantly lower compared with untreated subjects (70.1 vs 77.2 for 1-year survival and 60.3 vs 68.5 for 2-year survival). CONCLUSION In patients with AHF, increased UA levels and documented allopurinol therapy for hyperuricemia were associated with increased hospital and long-term mortality. Allopurinol therapy is not a cause but the identifier of the subjects at risk.

Does previous hypertension affect outcome in acute heart failure

BACKGROUND The effect of previous long-term hypertension on mortality in acute heart failure (HF), regardless of blood pressure values, has not been well studied. METHODS Acute Heart Failure Database (AHEAD) - Czech HF registry enrolled 4153 consecutive patients with acute HF. We excluded severe forms (cardiogenic shock, pulmonary oedema, right HF) and analysed 2421 patients with known presence or absence of previous hypertension. Demographic, clinical and laboratory profile, treatment and mortality rates were assessed and predictors of outcome were identified. RESULTS Patients with previous hypertension (71.5%) were older, more of female gender, with worse pre-hospitalisation NYHA class, increased incidence of co-morbidities and higher left ventricular ejection fraction (LVEF). Although in-hospital mortality was similar in both cohorts (2.6%), survival at 1, 2 and 3-year was worse in the hypertensive group (75.6%, 65.9% and 58.7% vs. 80.7%, 74.2% and 69.8%; P<0.001). Nevertheless, hypertension was not associated with mortality in multivariate analysis and stronger predictors of outcome were identified (P<0.05): new-onset acute HF [hazard ratio (HR) 0.62] and increased body mass index (HR 0.68) proved to have a protective role. Advanced age (HR 1.86), diabetes (HR 1.45), lower LVEF (HR 1.28) and admission blood pressure (HR 1.54), elevated serum creatinine (HR 1.63), hyponatremia (HR 1.77) and anaemia (HR 1.40) were associated with worse survival. CONCLUSION Antecedent hypertension is frequent in patients with acute HF and contributes to organ and vascular impairment. However its presence has no independent influence on short- and medium-term mortality, which is influenced by other related co-morbidities.

Worse prognosis of real-world patients with acute heart failure from the Czech AHEAD registry in comparison to patients from the RELAX-AHF trial

The randomized clinical trial RELAX‐AHF demonstrated a positive effect of vasodilator therapy with serelaxin in the treatment of AHF patients. The aim of our study was to compare clinical characteristics and outcomes of patients from the AHEAD registry who met criteria of the RELAX‐AHF trial (relax‐comparable group) with the same characteristics and outcomes of patients from the AHEAD registry who did not meet those criteria (relax‐non‐comparable group), and finally with characteristics and outcomes of patients from the RELAX‐AHF trial.

ACE2 gene polymorphisms and invasively measured central pulse pressure in cardiac patients indicated for coronarography.

Background and aim: The objective of this research was to determine whether invasively measured central pulse pressure (PP) in patients indicated for coronarography is associated with two common polymorphisms in the ACE2 region (rs4646156 and rs4646174). Methods: A total of 307 patients were enrolled in the study. The genotyping of both SNPs from peripheral blood samples was carried out using 5′exonuclease (Taqman®) chemistry on the ABI Prism® 7000 system (Applied Biosystems, Foster City, CA, USA). Results: In both polymorphisms, the associations with central PP were found to be highly significant when all five possible genotypes in the population had been compared (p = 0.0001). In men, there was a higher incidence of previous myocardial infarction in G0 genotype carriers of rs54646174 (OR ratio = 7; p = 0.005). The AA genotype of rs4646156 had a 7.81× higher risk of severe angina pectoris in women (OR = 7.81, p = 0.05). A significant difference in allelic frequency of ACE2rs4646174 was found between women with and without significant stenoses of the circumflex branch of the left coronary artery. Conclusion: More research into the role of ACE2 genetic variability in PP regulations is necessary for more detailed physiological and pathophysiological comprehension of PP regulation.

Per3 VNTR polymorphism and chronic heart failure

AIMS The aim of this study was to investigate the relationship between gene Period3 (Per3) variable number tandem repeat (VNTR) polymorphism and chronic heart failure (CHF). METHODS The study subjects (372 patients of Caucasian origin with CHF and 332 healthy controls) were genotyped for Per3 VNTR polymorphism using an allele-specific PCR. RESULTS No significant differences in genotype or Per3 VNTR allele frequencies were found between CHF cases and controls (Pg=0.30, Pa=0.52). No significant differences were uncovered either between CHF cases according to etiology (DCMP vs. IHD; Pg=0.87, Pa=0.91). In the multivariate regression modeling, no predictive function of VNTR Per3 polymorphism on ejection fraction or NYHA class, hyperlipidaemia or type II diabetes risk was found. CONCLUSION Per3 VNTR polymorphism is not a major risk factor for chronic heart failure or a factor modulating the severity of the CHF in this population.

Atrial fibrillation as prognostic factor of myocardial infarction and/or acute heart failure

Atrial fibrillation (AF) is a supraventricular tachyarrhythmia characterized by uncoordinated atrial activation with consequence deterioration of atrial mechanical function. It has an incidence of approximately 6 million people in European Union as a result of the aging population and affects about 1 percent of patients younger than 60 years and about 8 percent of patients older than 80 years [2, 10]. AF is also the most common supraventricular arrhythmia in patients with acute myocardial infarction (MI) and/or acute heart failure (AHF), complicating its course with an incidence between 6–21% in hospitalized patients with MI although recent advances in pharmacological treatment of myocardial infarction has probably changed the impact of this arrhythmia and vice versa. These two diseases (AF + MI) are a growing health concern all over the world and when one considers the occurrence of these two diseases simultaneously, the relevance of AF in the course of MI and vice versa cannot be overemphasized in cardiovascular health care and more importantly its treatment and prevention. This article therefore aims to correlate data from controlled studies to summarize the incidence of AF in MI and vice versa and the impact of pharmacotherapy. Data from our registry Brno (3502 patients with MI and/or AHF) show that AF is not a predictor of short-term mortality in patients with myocardial infarction and/or heart failure, but is a strong predictor of long-term mortality.

One year outcome of acute heart failure patients withhypertension as underlying disease

Purpose: Hypertension (HT) and diabetes mellitus are the most common underlying diseases of acute heart failure (AHF). Our aim was to analyse patients with anamnesis of HT hospitalised for AHF and to determine their one year mortality (1YM). Methods: During the years 2005–2007 we hospitalised 1253 patients with AHF. We selected 843 (70,3%) patients with anamnesis of HT (treated, not treated, diagnosed during hospital stay) and analysed their basic epidemiologic data, presentation during hospital stay in relation to one year mortality (1YM). Results: Mean age of HT patients was 72,3 years (patients deceased before 1 year follow up 76,0 years, p < 0,001), 54,1% of patients were male, 52,2% presented as new onset AHF. Main clinical manifestation was AHF with peripheral oedema/congestion (48,6%) with 1YM rate 22,2%, 12,8% of patients presented with cardiogenic shock with very poor one year outcome (89,8% shock patients died). The most common aetiology of AHF were acute coronary syndromes (41,3%) and chronic coronary heart disease (21,5%). Median length of hospital stay was 7 days, overall 1YM was 32,2%. Patients deceased before 1 year follow up presented with lower LV EF (mean value 30,6%, survived 38,8%, p < 0,001), lower entry haemoglobin level (126,9 g/l against 133,8 g/l of survived, p < 0,001), higher creatinine (124,9 ¦Ìmol/l deceased, 99,0 ¦Ìmol/l survived, p < 0,001) and CRP level (died 62,1 mg/l, 26,1 mg/l survived, p < 0,001). The use of ACE inhibitors (76,4%) and ¦Â-blockers (84,4%) after discharge was much higher by survived patients (55,5% and 65,2% respectively by deceased, p < 0,001). 65,8% of survived patients presented with admission systolic BP ≥ 140 mmHg, majority of deceased patients (60,3%) had entry SBP < 140. Conclusions: Hypertension as underlying disease of AHF patients affects their outcome. Especially cardiogenic shock of these patients is associated with very poor prognosis. One third of HT patients die before one year after the hospitalisation for AHF.