Hyperuricemia treatment in acute heart failure patients does not improve their long-term prognosis: A propensity score matched analysis from the AHEAD registry.

BACKGROUND: Hyperuricemia is associated with a poorer prognosis in heart failure (HF) patients. Benefits of hyperuricemia treatment with allopurinol have not yet been confirmed in clinical practice. The aim of our work was to assess the benefit of allopurinol treatment in a large cohort of HF patients. METHODS: The prospective acute heart failure registry (AHEAD) was used to select 3160 hospitalized patients with a known level of uric acid (UA) who were discharged in a stable condition. Hyperuricemia was defined as UA ≥500 µmoL/L and/or allopurinol treatment at admission. The patients were classified into three groups: without hyperuricemia, with treated hyperuricemia, and with untreated hyperuricemia at discharge. Two- and five-year all-cause mortality were defined as endpoints. Patients without hyperuricemia, unlike those with hyperuricemia, had a higher left ventricular ejection fraction, a better renal function, and higher hemoglobin levels, had less frequently diabetes mellitus and atrial fibrillation, and showed better tolerance to treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and/or beta-blockers. RESULTS: In a primary analysis, the patients without hyperuricemia had the highest survival rate. After using the propensity score to set up comparable groups, the patients without hyperuricemia had a similar 5-year survival rate as those with untreated hyperuricemia (42.0% vs 39.7%, P = 0.362) whereas those with treated hyperuricemia had a poorer prognosis (32.4% survival rate, P = 0.006 vs non-hyperuricemia group and P = 0.073 vs untreated group). CONCLUSION: Hyperuricemia was associated with an unfavorable cardiovascular risk profile in HF patients. Treatment with low doses of allopurinol did not improve the prognosis of HF patients.

Cryptosporidium proliferans n. sp. (Apicomplexa: Cryptosporidiidae): Molecular and Biological Evidence of Cryptic Species within Gastric Cryptosporidium of Mammals.

The morphological, biological, and molecular characteristics of Cryptosporidium muris strain TS03 are described, and the species name Cryptosporidium proliferans n. sp. is proposed. Cryptosporidium proliferans obtained from a naturally infected East African mole rat (Tachyoryctes splendens) in Kenya was propagated under laboratory conditions in rodents (SCID mice and southern multimammate mice, Mastomys coucha) and used in experiments to examine oocyst morphology and transmission. DNA from the propagated C. proliferans isolate, and C. proliferans DNA isolated from the feces of an African buffalo (Syncerus caffer) in Central African Republic, a donkey (Equus africanus) in Algeria, and a domestic horse (Equus caballus) in the Czech Republic were used for phylogenetic analyses. Oocysts of C. proliferans are morphologically distinguishable from C. parvum and C. muris HZ206, measuring 6.8-8.8 (mean = 7.7 µm) × 4.8-6.2 µm (mean = 5.3) with a length to width ratio of 1.48 (n = 100). Experimental studies using an isolate originated from T. splendens have shown that the course of C. proliferans infection in rodent hosts differs from that of C. muris and C. andersoni. The prepatent period of 18-21 days post infection (DPI) for C. proliferans in southern multimammate mice (Mastomys coucha) was similar to that of C. andersoni and longer than the 6-8 DPI prepatent period for C. muris RN66 and HZ206 in the same host. Histopatologicaly, stomach glands of southern multimammate mice infected with C. proliferans were markedly dilated and filled with necrotic material, mucus, and numerous Cryptosporidium developmental stages. Epithelial cells of infected glands were atrophic, exhibited cuboidal or squamous metaplasia, and significantly proliferated into the lumen of the stomach, forming papillary structures. The epithelial height and stomach weight were six-fold greater than in non-infected controls. Phylogenetic analyses based on small subunit rRNA, Cryptosporidium oocyst wall protein, thrombospondin-related adhesive protein of Cryptosporidium-1, heat shock protein 70, actin, heat shock protein 90 (MS2), MS1, MS3, and M16 gene sequences revealed that C. proliferans is genetically distinct from C. muris and other previously described Cryptosporidium species.

Positive influence of being overweight/obese on long term survival in patients hospitalised due to acute heart failure.

BACKGROUND: Obesity is clearly associated with increased morbidity and mortality rates. However, in patients with acute heart failure (AHF), an increased BMI could represent a protective marker. Studies evaluating the "obesity paradox" on a large cohort with long-term follow-up are lacking. METHODS: Using the AHEAD database (a Czech multi-centre database of patients hospitalised due to AHF), 5057 patients were evaluated; patients with a BMI <18.5 kg/m2 were excluded. All-cause mortality was compared between groups with a BMI of 18.5-25 kg/m2 and with BMI >25 kg/m2. Data were adjusted by a propensity score for 11 parameters. RESULTS: In the balanced groups, the difference in 30-day mortality was not significant. The long-term mortality of patients with normal weight was higher than for those who were overweight/obese (HR, 1.36; 95% CI, 1.26-1.48; p<0.001)). In the balanced dataset, the pattern was similar (1.22; 1.09-1.39; p<0.001). A similar result was found in the balanced dataset of a subgroup of patients with de novo AHF (1.30; 1.11-1.52; p = 0.001), but only a trend in a balanced dataset of patients with acute decompensated heart failure. CONCLUSION: These data suggest significantly lower long-term mortality in overweight/obese patients with AHF. The results suggest that at present there is no evidence for weight reduction in overweight/obese patients with heart failure, and emphasize the importance of prevention of cardiac cachexia.

Comparison of clinical outcomes and safety of catheter ablation for atrial fibrillation supported by data from CT scan or three-dimensional rotational angiogram of left atrium and pulmonary veins.

BACKGROUND: Catheter ablation in the left atrium has become a common therapeutic strategy in the management of atrial fibrillation (AF). The high degree of success and safety profile of this procedure is dependent on precise knowledge of the true anatomy in the chamber. This information is imported mostly from cardiac computed tomography. A novel method for imaging the left atrial anatomy is three-dimensional rotational angiography (3DRA). METHODS: The aim of our study was to the compare clinical outcome and safety of catheter ablation for atrial fibrillation guided by 3DRA vs. conventional CT scan. One hundred and twenty-five patients referred for AF catheter ablation at St. Anne's University Hospital Brno were included in the retrospective analysis of clinical outcome within the first year after the procedure. RESULTS: There was a close correlation in overall procedural parameters between the groups. The frequency of recurrent episodes of AF (24% in CT-guided group vs. 27% in 3DRA-guided group, P=0.721) as well as the onset of atypical atrial flutter after the procedure (10% vs. 8%, respectively, P=0.731) were similar in both groups. No difference in the number of patients necessitating repeat ablation (5% vs. 5%, P=0.984) was found. Procedural complications of ablations guided by 3DRA were comparable with those guided by CT (2% vs. 3%, respectively, P=0.568). CONCLUSION: 3DRA has proven to be a safe and simple method for imaging the left atrium and guiding catheter ablation for AF. This approach is anticipated to become a new standard in 3D reconstruction of the left atrium.

Prevalence and clinical significance of liver function abnormalities in patients with acute heart failure.

AIMS: Liver pathology caused by cardiac dysfunction is relatively well recognized, however, its clinical importance has not been fully evaluated. The aim of this study was to assess the prevalence of liver function tests (LFTs) abnormalities and to identify associated factors mediating hepatic impairment in patients with acute heart failure (AHF). METHODS: The AHEAD (Acute Heart Failure Database) registry is a database conducted in 9 university hospitals and 5 regional health care facilities in the Czech Republic. From December 2004 to October 2012, the data of 8818 patients were included. The inclusion criteria for the database followed the European guidelines for AHF. Serum activities of all LFTs and total bilirubin were available in 1473 patients at the baseline. RESULTS: In patients with AHF, abnormal LFTs were seen in 76% patients (total bilirubin in 34%, γ-glutamyltransferase in 44%, alkaline phosphatase in 20%, aspartate aminotransferase in 42%, alanine aminotransferase in 35%). Patients with cardiogenic shock were more likely to have LFTs abnormalities compared to mild AHF and pulmonary oedema. LFTs abnormalities were strongly associated with AHF severity (left ventricular ejection fraction and NYHA functional class) and clinical manifestation. While hepatocellular LFTs pattern predominated in left sided forward AHF, cholestatic profile occurred mainly in bilateral and right sided AHF. Additionally, patients with moderate to severe tricuspid regurgitation had significantly higher prevalence of abnormalities in cholestatic LFTs. CONCLUSIONS: Defining the LFTs profile typical for AHF plays an important role in management of AHF patients, since it may avoid redundant hepatic investigations and diagnostic misinterpretations.

[Comparison of American and European (Czech) guidelines for diagnosis and treatment of chronic heart failure]. / Srovnání amerických a evropských (ceských) doporucení pro diagnostiku a lécbu chronického srdecního selhání

The new Czech and European recommendations for diagnosis and treatment of heart failure were published in 2012. The American guidelines ACCF/AHA were published in 2013. Main difference between them is presentation of acute and chronic heart failure in the European guidelines while the American and the Czech guidelines include only chronic heart failure. The American recommendations distinguish heart failure with reduced ejection fraction and with remained ejection fraction. In the beginning, the American guidelines introduce A-D classification which doesn´t figure in the European neither Czech guidelines. Class A patients are ill with risk factors, but without heart failure. In contrast, class D patients are decompensated with symptoms in the rest. Epidemiologic data shows interesting results with prevalence about 0.2% in 60-69 years old subjects and 80% in subjects older than 85 years. 5 year mortality is 50%. The American guidelines start to treat class A which is in fact prevention and treatment of risk factors. There is mentioned inevitably treatment of hypertension, both systolic and diastolic which decrease risk of heart failure up to 50%. There is almost no difference in pharmacotherapy. Noteworthy, the American guidelines introduce also ACE inhibitors - fosinopril and quinapril, on the other hand beta-blockers don´t involve nebivolol. Wide range of diuretics are mentioned, some of them aren´t registered in the Czech Republic. European and Czech guidelines involve ivabradin. Neither nesiritid nor levosimendan for inpatients aren´t involved. There is briefly mentioned surgery and cardiac mechanical support, moreover there are references for guidelines for heart transplantation.

The variable clinical course of peripartum cardiomyopathy.

BACKGROUND: In Europe, peripartum cardiomyopathy (PPCM) is a rare disorder, often difficult to diagnose and it has a variable clinical course. The aim of this report was to describe and discuss the individual variability of this disorder and its management. PATIENTS AND METHODS: Three cases of PPCM manifesting as severe heart failure are compared. Common was the presence of myocardial inflammation detected by endomyocardial biopsy. Different were treatment methods and clinical course. Modern therapeutic concepts such as immunosuppressive therapy and bromocriptin administration are discussed, as well as non-pharmacological approaches. CONCLUSION: In the differential diagnostics of dyspnea associated with pregnancy and childbirth, PPCM should be considered. The potentially severe course of the disease requires hospitalization with the possibility of comprehensive heart failure treatment, including non-pharmacological approaches such as device therapy and heart transplantation.

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.

Gender differences in total cholesterol levels in patients with acute heart failure and its importance for short and long time prognosis.

AIM: The purpose of this study was to evaluate whether there are gender differences in total cholesterol levels in patients with acute heart failure and if there is an association of this parameter with short and long time mortality. METHODS: The AHEAD MAIN registry is a database conducted in 7 university hospitals, all with 24 h cath lab service, in 4 cities in the Czech Republic. The database included 4 153 patients hospitalised for acute heart failure in the period 2006-2009. 2 384 patients had a complete record of their total cholesterol levels. 946 females and 1437 males were included in this analysis. According to the admission total cholesterol levels, patients were divided into 5 groups: < 4.50 mmol/l (group A), 4.50-4.99 mmol/l (group B), 5.0-5.49 mmol/l (group C), 5.50-5.99 mmol/l (group D) and > 6.0 mmol/l (group E). The median total cholesterol levels were 4.24 in males and 4.60 in females (P<0.001). There were differences in the distribution of total cholesterol levels between men and women: group A 57.6 vs 45.0%, group B 13.8 vs 16.3%, group C 9.8 vs 12.5%, group D 7.7 vs 11.4%, group E 11.1 vs 14.8% respectively (all P<0.001). The median age of men was 68.7 vs 77.3 years in women (P<0.001). In all total cholesterol categories women were older than men: group A 77.7 vs 69.5 years, group B 78.6 vs 69.1 years, group C 77.3 vs 68.8 years, group D 76.8 vs 64.2 years, group E 75.6 vs 64.4 years (all P<0.001). For the calculation of long term mortality, the cohort was divided into three groups: total cholesterol levels below 4.50 mmol/l, 4.50-5.49 mmol/l and above 5.50 mmol/l. The log rank test was used for the analysis. RESULTS: There were no differences in hospital mortality between male and female in general (9.2 vs 10.8%, P<0.202), or in total cholesterol levels in subgroups. Total cholesterol levels were associated with in-hospital mortality (P<0.002). In the long-term follow up (78 months) patients with total cholesterol levels below 4.5 mmol/l had the worst prognosis (P<0.001). An independent influence of total cholesterol level on mortality and survival was confirmed in the multivariate model as well. CONCLUSIONS: Women with acute heart failure had higher total cholesterol levels than men in all ages. There was a higher percentage of women with total cholesterol levels above 6 mmol/l and lower percentage in the group below 4.5 mmol/l than in men. In all, total cholesterol categories women were older than men. Total cholesterol levels are important for in- hospital mortality and long term survival of patients admitted for acute heart failure.

Usefulness of left ventricle dyssynchrony assessment before cardiac resynchronization implantation.

BACKGROUND: A number of trials have demonstrated the effect of cardiac resynchronization therapy (CRT) on functional improvement and reversed left ventricle remodeling. Meeting contemporary guidelines approximately 30- 40% of patients do not respond to CRT (non-responders). AIM: To quantify the predictive ability of basal QRS width and basal echocardiographic parameters of left ventricle contraction dyssynchrony in our group of CRT patients. To compare effectiveness of these parameters assessment in patients with ischemic (iCMP) and non-ischemic cardiomyopathy (niCMP) and with sinus rhythm (SR) and atrial fibrillation (AF). PATIENTS AND METHODS: 194 patients after successful introduction of CRT device were evaluated. Evaluation of NYHA function class, QRS width and echocardiographic parameters including parameters of left ventricle contraction dyssynchrony (SPWMD: septal-to-posterior wall motion delay, Ts-sep-lat: time interval between maximum of systolic movement of septum and lateral wall using tissue Doppler imaging, IVMD: interventricular mechanical delay) performed before implantation and 3 months after implantation of CRT device. RESULTS: Responder (improved in NYHA class after CRT) rate was 61%. SR patients showed higher benefit compared to AF patients (responder rate 63% vs. 52%, p<0.05). Narrowing of QRS width after CRT was observed only in responders. SPWMD and Ts-sep-lat decreased after CRT in all subgroups. SPWMD dyssynchrony (SPMWD > or = 130 ms) reduction after CRT was more expressed in niCMP population. Ts-sep-lat dyssynchrony (Ts-sep-lat > or = 65 ms) reduction after CRT was more expressed in SR patients. IVMD (IVMD > or = 60 ms) remained unchanged in average, but significant decrease was observed in responders and significant increase in non-responders. QRS width, SPWMD and Ts-sep-lat showed moderate sensitivity but poor specificity to predict CRT benefit. QRS width > or = 150 ms in niCMP patients showed higher sensitivity to predict CRT effect compared to iCMP patients (91%, 65% respectively). IVMD showed poor sensitivity but good specificity to predict CRT benefit. IVMD in SR patients (compared to AF patients) showed higher specificity to predict CRT effect (90%, 63% respectively). CONCLUSION: None of tested left ventricle contraction dyssynchrony parameters showed good sensitivity and specificity to predict CRT benefit. QRS width as a predictor factor was more beneficial in non-ischemic patients and IVMD in sinus rhythm patients.

Infectivity, pathogenicity, and genetic characteristics of mammalian gastric Cryptosporidium spp. in domestic ruminants.

Farm ruminants were infected experimentally with four mammalian gastric Cryptosporidium, namely Cryptosporidium andersoni LI03 originated from cattle and three isolates of Cryptosporidium muris from brown rat (isolate RN66), Bactrian camel (isolate CB03) and firstly characterized isolate from East African mole rat (isolate TS03). Sequence characterizations of the small-subunit rRNA gene showed that the LI03 isolate was C. andersoni and the other three isolates belonged to C. muris, although the TS03 isolate showed unique sequence variations (one single nucleotide change and four nucleotide insertions). C. andersoni LI03 was infectious for calves only, whereas lambs and kids were susceptible to C. muris CB03. C. muris TS03 and RN66 were not infectious for any farm ruminants. Infection dynamics including prepatent and patent period and infection intensity of the isolates used differed depending on the host species, but no clinical signs of cryptosporidiosis were observed in any of experimentally infected hosts. Cryptosporidium developmental stages were only detected in infected animals in the abomasum region. Histopathological changes were characterized by dilatation and epithelial metaplasia of infected gastric glands with no significant inflammatory responses in the lamina propria.

Neurohumoral changes in chronic heart failure.

BACKGROUND: Humoral systems play an important role in the pathophysiology and development of chronic heart failure (CHF). METHODS: We conducted a search of neurohumoral activation in heart failure and its risk in the development of CHF. RESULTS AND CONCLUSION: Neurohumoral factors may be divided into vasoconstrictive, vasodilative and cytokines. The main vasoconstrictive systems are the renin-angiotensin-aldosterone system (RAAS) and the sympathoadrenal system (SAS). Cytokines include tumour necrosis factor (TNF) alpha and interleukins. The systems of actions are interconnected and they mutually influence their secretion and activities. The possibilities of their detection and assessment for clinical purposes depend on their changes and kinetics in the organism and on the activity of individual metabolites. Apart from their vasoactive effects, the majority of humoral actions also interfere in the process of remodelling, function of the endothelium, blood elements, cardiomyocytes, cells of the smooth muscles, and in immunity as well as inflammatory processes. The rapid development of knowledge on the humoral actions in recent years has made possible their utilisation in diagnostics, treatment and prognosis.

Infectivity and pathogenicity of Cryptosporidium andersoni to a novel host, southern multimammate mouse (Mastomys coucha).

The infectivity and pathogenicity of Cryptosporidium andersoni (bovine isolate) for neonatal and adult southern multimammate mice (Mastomys coucha) was studied using transmission experiments. C. andersoni isolate used in this study was not infective for BALB/c mice, but experimental infection proved susceptibility of neonatal and adult M. coucha to the infection. The prepatent period was 20-24 days, the patent period varied between 46 and 59 days. No signs of clinical illness or macroscopic findings were detected in infected animals. Cryptosporidium developmental stages were detected only in the glandular part of the stomach of M. coucha in histological sections stained with Wolbach's modification of Giemsa and using immunofluorecence. Histopathological changes were characterized by dilatation and epithelial metaplasia of infected gastric glands without inflammatory response in the lamina propria. Neonatal M. coucha were more susceptible to C. andersoni infection than adults. M. coucha seems to be a useful laboratory model for study of C. andersoni infection.

Combined right ventricular systolic and diastolic dysfunction represents a strong determinant of poor prognosis in patients with symptomatic heart failure.

BACKGROUND: The presence of right ventricular systolic dysfunction is known to significantly worsen prognosis of patients with heart failure. However, the prognostic impact of right ventricular diastolic dysfunction and of its combination with right ventricular systolic dysfunction and with other prognostic markers has not yet been systematically studied. The aim of this study was to assess the prognostic impact of combined right ventricular systolic and diastolic dysfunction in patients with symptomatic heart failure due to ischemic or idiopathic dilated cardiomyopathy. METHODS: The study included 177 consecutive patients with symptomatic heart failure (mean left ventricular ejection fraction of 23%). All patients underwent clinical and laboratory examination, standard echocardiography completed by Doppler tissue imaging of the tricuspid annular motion, and right-sided heart catheterization. They were followed up for a mean period of 16 months (range, 1-48 months). RESULTS: During the follow-up, there were 28 cardiac-related deaths and 35 non-fatal cardiac events (31 hospitalizations for heart failure decompensation and 4 hospitalizations for malignant arrhythmias requiring the implantation of a cardioverter-defibrillator). The multivariate stepwise Cox regression modeling revealed the right ventricular systolic (represented by the peak systolic tricuspid annular velocity-Sa) and diastolic (represented by the peak early diastolic tricuspid annular velocity-Ea) function to be the independent predictors of event-free survival or survival (p<0.01). The Sa separated better between patients with and without the risk of cardiac events (p<0.05), while the Ea appeared to further distinguish patients with increased risk (those at risk of late event from those at risk of early non-fatal event and early death). The strongest predictive information was obtained by the combination of Sa and Ea creating the Sa/Ea categories. The Sa/Ea I category of patients (Sa>or=10.8 cm s(-1) and Ea>or=8.9 cm s(-1)) had excellent prognosis. On the other hand, the Sa/Ea IV category (Sa<10.8 cm s(-1) and Ea<8.9 cm s(-1)) was found to be at a very high risk of cardiac events (p<0.001 vs. Sa/Ea I). Imbalanced categories of patients (Sa/Ea II and III) with only one component (Sa or Ea) pathologically decreased were at medium risk when assessing event-free survival. However, a significantly better survival (p<0.05) was found in patients with Ea>or=8.9 cm s(-1) (Sa/Ea I and III categories) as compared with those having Ea<8.9 cm s(-1) (Sa/Ea II and IV categories). Thus, in contrast to event-free survival, the survival pattern was determined mainly by the Ea value with only little additional contribution of Sa. CONCLUSIONS: The assessment of right ventricular systolic and diastolic function provides complementary information with a very high power to stratify prognosis of patients with heart failure. The combination of right ventricular systolic and diastolic dysfunction identifies those with a very poor prognosis.