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Aims A retrospective nationwide observational analysis of diagnoses, procedures, and treatment reported to the Czech National Registry of Reimbursed Health Services between 2012 and 2018. Methods and results Prevalence of heart failure (HF) patients increased from 176 496 (1679.4 per 100 000 population) in 2012 to 285 745 (2689.0 per 100 000 population) patients in 2018 (mean age 74.4 ± 12.8 years). In the last years, a stable incidence of HF patients was observed (544 per 100 000 population in 2016 vs. 551 per 100 000 population in 2018; P = 0.310). Mortality rate decreased from 20.55% in 2012 to 15.89% in 2018. The number of hospitalized patients remained similar (318.2 per 100 000 population in 2012 vs. 311.8 per 100 000 population in 2018; P = 0.479). The most used drugs were diuretics (173 295; 60.6%) and beta‐blockers (178 823; 62.6%), followed by angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers (angiotensin‐converting enzyme inhibitors 120.581; 42.2%; angiotensin II receptor blockers 47 216; 16.5%). Even though the whole number of implanted devices in HF patients increased steadily (from 25 205 in 2012 to 45 363 in 2018), the prevalence of all devices (pacemakers and defibrillators) in the HF patients remained about the same (14.3% in 2012; 15.9% in 2018). Conclusions The study included all patients with HF in the Czech Republic. These are the first nationwide data of HF epidemiology in the Eastern bloc. The incidence of HF remains stable in the last years. Due to aging of the population, the prevalence of HF significantly increased in the last 6 years. Despite a continuous increase in the prevalence of HF and a suboptimal utilization of its pharmacological therapy, mortality decreased, and the number of hospitalized patients remained the same.

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 mu moL/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.

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. Methods and results A total of 5856 patients from the AHEAD registry (Czech registry of AHF) were divided into two groups according to RELAX-AHF criteria: relax-comparable (n = 1361) and relax-non-comparable (n = 4495). As compared with the relax-non-comparable group, patients in the relax-comparable group were older, had higher levels of systolic and diastolic blood pressure, lower creatinine clearance, and a higher number of comorbidities. Relax-comparable patients also had significantly lower short-term as well as long-term mortality rates in comparison to relax-non-comparable patients, but a significantly higher mortality rate in comparison to the placebo group of patients from the RELAX-AHF trial. Using AHEAD score, we have identified higher-risk patients from relax-comparable group who might potentially benefit from new therapeutic approaches in the future. Conclusions Only about one in five of all evaluated patients met criteria for the potential treatment with the new vasodilator serelaxin. AHF patients from the real clinical practice had a higher mortality when compared with patients from the randomized clinical trial.

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.

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%, gama-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.

Aims. The primary questions asked by the MEDINA (MEtabolic parameters, DIabetes mellitus and NephropAthy) study are: 1) Do angiotensin converting enzyme inhibitors (ACE-I) have any advantages over angiotensin receptor blockers (ARB)? 2) Should the other drug for combination be a diuretic or a calcium-channel blocker (CCB)? 3) How are the risks reduced by the co administration of a statin? Methods. A total of 439 hypertensive patients with metabolic syndrome and/or diabetes mellitus were randomized to 2 groups: group 1 - ramipril (ACE-I) or perindopril and group 2 - losartan (ARB). Hydrochlorothiazide (diuretic) or amlodipine (CCB) were added to both groups. As a third step, a statin was added. Results. Blood pressure decreased 24.1/13.3 mmHg in the ACE inhibitor group and 25.9/13.5 in the losartan group. The difference was insignificant. Adding either hydrochlorothiazide or amlodipin was equally effective. There were no significant differences on metabolic parameters in the trial arms. Cholesterol level decreased by 0.95 mmol/L in the ACE-I group and 1.02 mmol/L in the ARB group (ns). Conclusion. MEDINA has so far confirmed the equivalence of ACE-I and ARB in hypertension treatment. Adding either diuretic or CCB was equally effective. Our data support the current recommendations on adding a statin to reduce cardiovascular risk.

The purposes of this study are to identify the strongest clinical parameters in relation to in-hospital mortality, which are available in the earliest phase of the hospitalization of patients, and to create an easy tool for the early identification of patients at risk.The classification and regression tree analysis was applied to data from the Acute Heart Failure Database-Main registry comprising patients admitted to specialized cardiology centers with all syndromes of acute heart failure. The classification model was built on derivation cohort (n = 2543) and evaluated on validation cohort (n = 1387).The classification tree stratifies patients according to the presence of cardiogenic shock (CS), the level of creatinine, and the systolic blood pressure (SBP) at admission into the 5 risk groups with in-hospital mortality ranging from 2.8% to 66.2%. Patients without CS and creatinine level of 155 μmol/L or less were classified into very-low-risk group; patients without CS, creatinine level greater than 155 μmol/L, and SBP greater than 103 mm Hg, into low-risk group, whereas patients without CS, creatinine level greater than 155 μmol/L, and SBP of 103 mm Hg or lower, into intermediate-risk group. The high-risk group patients had CS and creatinine of 140 μmol/L or less; patients with CS and creatinine level greater than 140 μmol/L belong to very-high-risk group. The area under receiver operating characteristic curve was 0.823 and 0.832, and the value of Brier's score was estimated on level 0.091 and 0.084, for the derivation and the validation cohort, respectively.The presented classification model effectively stratified patients with all syndromes of acute heart failure into in-hospital mortality risk groups and might be of advantage for clinical practice.

Neuromuscular electrical stimulation (NMES) of leg muscles has been introduced in clinical practice as a rehabilitation (RHB) method in patients with chronic heart failure (CHF); however, the role of NMES on the reduction of arterial stiffness and autonomic disbalance in these patients has not yet been studied. Sixty-one patients with stable CHF (mean age 58.9 [2.1] years; mean ejection fraction 31 [4.2]%, New York Heart Association IIIII) were randomly assigned into two groups. Patients in (i) exercise training group (ET; n = 30) underwent 12 weeks of bicycle ET (3 x 40 min/week); (ii) group NMES (n = 31) performed 12 weeks of NMES of quadriceps and calf muscles (frequency 10 Hz, mode 20 s on20 s off, intensity 60 mA), 2 x 60 min/day. Noninvasive assessment of arterial stiffness was done using the cardio-ankle vascular index (CAVI). CAVI and heart rate variability (HRV) and were evaluated before and after RHB program. Both types of RHB reduced significantly CAVI (ET from 9.6 [0.2] to 8.9 [0.2], P < 0.012; NMES from 9.3 [0.2] to 8.7 [0.2], P < 0.013), increased high frequency (HF) component of HRV (+65.6%; P = 0.001) and decreased ratio of low frequency (LF) component with HF component (LF/HF ratio) in group ET (-39.8%; P < 0.001). Changes of HRV parameters in group NMES were not significant; however, a marked tendency to autonomic stabilization was present. Both types of RHB led also to significant increase of (ET from 18.7 [0.7] to 20.8 [0.7] mL/kg/min, P < 0.004; NMES from 17.3 [0.7] to 19.0 [0.7] mL/kg/min, P < 0.001). ET or NMES has been shown to improve significantly arterial stiffness and to stabilize autonomic balance.

Retinoic X receptor alpha (RXRA), a member of nuclear receptor superfamily, plays a key role in development, metabolism, glucose homeostasis, and intestinal cholesterol balance. The aim of this study was to examine an association of RXR alpha introne 5 A(39526)AA polymorphism and ABO blood groups with chronic heart failure (CHF) in the Czech population. A total of 238 patients with chronic heart failure and a control group of 246 subjects were included in the study. The RXR alpha gene polymorphism and ABO blood groups were detected by PCR and RFLP methods. Significant differences in distributions of RXRA A(39526)AA alleles and genotypes between CHF patients and controls were observed (Pg=0.03, Pa=0.02). The RXRA gene polymorphism differences of within blood group A between CHF patients and controls were highly significant in genotype distributions (Pg=0.002) and in allele frequency comparisons (Pa=0.0001). The prevalence of AA allele in CHF patients with A blood group was four-fold lower than in controls with the same blood group (OR=0.24; Pcorr=0.0001). A highly significant association of RXRA introne single-nucleotide insertion polymorphism and A blood group in chronic heart failure was observed. Our results suggest close linkage between RXRA A(39526)AA polymorphism and ABO blood groups.

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 3040% 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

Background: The role of co-morbidities in the prognosis of patients hospitalized for AHFwas examined using the AHEAD (A — atrial fibrillation, H — haemoglobin b 130 g/l for men and 120 g/l for women (anaemia), E — elderly (age N 70 years), A — abnormal renal parameters (creatinine N 130 micromol/l), D — diabetes mellitus) scoring system. Methods: AHEAD — multicentre prospective Czech registry of AHF patients; GREAT registry — international cohort of AHF patients. Data from 5846 consecutive patients hospitalized for AHF (AHEAD registry; derivation cohort) were analysed to build the AHEAD score. Each risk factor of the AHEAD score was counted as 1 point. The model was validated externally using an international cohort of similar patients in the GREAT registry (6315). Results:Main outcome was one year all-cause mortality. The mean age of patientswas 72±12 years,with 61.6% of patients aged N70 years; 43.4% were women. Atrial fibrillation was present in 30.7%, anaemia in 38.2%, creatinine N130mmol/l (abnormal renal parameters) in 30.1%, and diabetes mellitus in 44.0%. The mean AHEAD score was 2.1. In patients with AHEAD scores of 0–5, the one-year mortality rates were 13.6%, 23.4%, 32.0%, 41.1%, 47.7%, and 58.2%, respectively (p b 0.001), and the 90 month mortality rates were 35.1%, 57.3%, 73.5%, 84.8%, 88.0%, and 91.7%, respectively (p b 0.001). Conclusion: The AHEAD is a simple scoring system based on the analysis of co-morbidities for the estimation of the short and long term prognosis of patients hospitalized for AHF.

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 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

Background: First-dose hypotension refers to an observed reduction in blood pressure after the administration of the first dose of ACE inhibitors in patients with congestive heart failure. Aim: To compare the first-dose responses of low-dose enalapril and perindopril in patients with stable symptomatic chronic heart failure. Methods: Single blind, randomised, multicenter, parallel, prospective study. Patients (N = 298) with chronic heart failure due to ischemic heart disease or dilated cardiomyopathy, NYHA II–IV, ejection fraction 18 years, naive to ACE inhibitors or ATI-receptor blocker, were randomised to receive a single dose of 2.5 mg enalapril or 2.0 mg perindopril. Baseline laboratory and clinical examinations were performed before entry into the study. Ambulatory blood pressure monitoring started 2 h before the study medication was given, and continued for at least 10 h after the medication. Results: The maximum drop in blood pressure appeared approximately 4 h after dose administration in both groups, and was more pronounced in the enalapril group. Patients in the enalapril group had a significantly higher incidence of asymptomatic hypotension. No symptomatic hypotension requiring a change in medication or a prolongation of hospitalisation was observed. Conclusion: A low dose of perindopril is well-tolerated at initiation of ACE inhibitor therapy in patients with chronic heart failure and causes less first-dose hypotension than a low dose of enalapril.

BACKGROUND: Metoprolol can improve haemodynamics in chronic heart failure, but survival benefit has not been proven. We investigated whether metoprolol controlled release/extended release (CR/XL) once daily, in addition to standard therapy, would lower mortality in patients with decreased ejection fraction and symptoms of heart failure. METHODS: We enrolled 3991 patients with chronic heart failure in New York Heart Association (NYHA) functional class II-IV and with ejection fraction of 0.40 or less, stabilised with optimum standard therapy, in a double-blind randomised controlled study. Randomisation was preceded by a 2-week single-blind placebo run-in period. 1990 patients were randomly assigned metoprolol CR/XL 12.5 mg (NYHA III-IV) or 25.0 mg once daily (NYHA II) and 2001 were assigned placebo. The target dose was 200 mg once daily and doses were up-titrated over 8 weeks. Our primary endpoint was all-cause mortality, analysed by intention to treat. FINDINGS: The study was stopped early on the recommendation of the independent safety committee. Mean follow-up time was 1 year. All-cause mortality was lower in the metoprolol CR/XL group than in the placebo group (145 [7.2%, per patient-year of follow-up]) vs 217 deaths [11.0%], relative risk 0.66 [95% CI 0.53-0.81]; p=0.00009 or adjusted for interim analyses p=0.0062). There were fewer sudden deaths in the metoprolol CR/XL group than in the placebo group (79 vs 132, 0.59 [0.45-0.78]; p=0.0002) and deaths from worsening heart failure (30 vs 58, 0.51 [0.33-0.79]; p=0.0023). INTERPRETATION: Metoprolol CR/XL once daily in addition to optimum standard therapy improved survival. The drug was well tolerated.

Excessive neurohumoral activity remains a major burden to the circulation of patients with advanced heart failure. Prostaglandin E1 (PGE1), a balanced i.v. vasodilator, was shown to elicit favorable hemodynamic and clinical effects in this cohort. A prospective randomized parallel group trial was performed to evaluate acute, intermediate and chronic changes in hemodynamic, neurohumoral and renal variables in response to PGE1, dobutamine and placebo. Thirty patients with class III and IV heart failure and low cardiac index (mean 1.9 l/min/m2) two hours after oral drugs including high dose enalapril were included. A 7-day-infusion of PGE1 (16.5 +/- 5 ng/kg/min, range 10 to 20 ng/kg/min, group A n = 10), dobutamine (4.5 +/- 1 micrograms/kg/min, range 2.5 to 5 micrograms/kg/min, group B n = 10) or placebo (saline, group C n = 10) was administered via a central venous access line after stepwise titration until intolerable side effects developed with PGE1 or a 20% increase in cardiac index occurred with dobutamine, which was continued on this dose throughout while PGE1 was maintained on 50% peak dose. Hemodynamic data were collected at baseline, at peak dosages, after 12 hours and after 7 days. Of neurohumoral variables plasma norepinephrine, big endothelin (Big ET) and atrial natriuretic peptide (ANP) were simultaneously evaluated using RIA methods. Renal plasma flow (by paraaminohippurate clearance) and glomerular filtration rate (by iothalamate clearance) was measured prior to and during the infusions (after 12 hours and after 7 days). At peak dose and at 12 hours significant drops from baseline of mean pulmonary artery pressure, pulmonary capillary wedge pressure and systemic vascular resistance were observed which were accompanied by a rise in cardiac output with both PGE1 and dobutamine. These changes were maintained through 7 days when pulmonary vascular resistance levels also fell with both active drugs. Blood pressure did not change throughout, but PGE1 increased heart rate slightly at 12 hrs. Both PGE1 and dobutamine enhanced renal plasma flow after 7 days, but only PGE1 decreased glomerular filtration fraction significantly. Glomerular filtration rate did not change with either drug. PGE1 decreased ANP levels at 12 hrs, and dobutamine increased big ET levels at peak, but decreased big ET at 7 days. Norepinephrine levels were unaffected throughout. Except a slight decrease in right atrial pressure after 7 days placebo did not change any measured variable significantly. Taken together, these data suggest that treatment with PGE1 is as efficacious as low-dose dobutamine in improving cardiac performance and renal perfusion in advanced heart failure. Of importance, no deleterious neurohumoral counterregulation was observed with PGE1.

The prognosis and clinical findings related to prognosis were examined in 300 patients with congestive heart failure in a prospective study. The diagnosis was based on case history data (NYHA class II or III), depressed ejection fraction (or = 40%) and/or increased cardiothoracic ratio (or = 50%). Forty-eight (16%) patients died within 1 year after the entry examination. Non-invasive baseline parameters of survivors and non-survivors were compared. All necessary medication was allowed. At the entry of the study three parameters independently predicted an increased mortality on a high significance level (P0.01): cardiothoracic ratio, signs of lung congestion on the chest X-ray (four grade classification), and plasma urea level; other three parameters did so on a lower significance level (P0.05): plasma natrium, creatinine value and endsystolic volume. Other parameters such as age, ejection fraction, NYHA class or exercise tolerance duration were not statistically different in survivors and non-survivors. Our modification (a four grade classification) of the signs of lung changes on the chest X-ray enables a more accurate determination of the prognosis in patients with chronic heart failure.

Neuromuscular electrical stimulation (NMES) of leg muscles has been introduced in clinical practice as a rehabilitation (RHB) method in patients with chronic heart failure (CHF); however, the role of NMES on the reduction of arterial stiffness and autonomic disbalance in these patients has not yet been studied. Sixty-one patients with stable CHF (mean age 58.9 [2.1] years; mean ejection fraction 31 [4.2]%, New York Heart Association II-III) were randomly assigned into two groups. Patients in (i) exercise training group (ET; n = 30) underwent 12 weeks of bicycle ET (3 × 40 min/week); (ii) group NMES (n = 31) performed 12 weeks of NMES of quadriceps and calf muscles (frequency 10 Hz, mode "20 s on-20 s off," intensity 60 mA), 2 × 60 min/day. Noninvasive assessment of arterial stiffness was done using the cardio-ankle vascular index (CAVI). CAVI and heart rate variability (HRV) and ·VO(2peak) were evaluated before and after RHB program. Both types of RHB reduced significantly CAVI (ET from 9.6 [0.2] to 8.9 [0.2], P0.012; NMES from 9.3 [0.2] to 8.7 [0.2], P0.013), increased high frequency (HF) component of HRV (+65.6%; P = 0.001) and decreased ratio of low frequency (LF) component with HF component (LF/HF ratio) in group ET (-39.8%; P0.001). Changes of HRV parameters in group NMES were not significant; however, a marked tendency to autonomic stabilization was present. Both types of RHB led also to significant increase of ·VO(2peak) (ET from 18.7 [0.7] to 20.8 [0.7] mL/kg/min, P0.004; NMES from 17.3 [0.7] to 19.0 [0.7] mL/kg/min, P0.001). ET or NMES has been shown to improve significantly arterial stiffness and to stabilize autonomic balance.

Aims. The impact of ApoE polymorphism on angiographic parameters was assessed in patients referred for coronary angiography. Methods. Elective coronary angiography was performed in 671 subjects (525 men, 146 women, mean age 60±10 years) with symptoms of ischemic heart disease. The patients were divided into: no CAD group (smooth coronary vessels, n=83), one-vessel (n=155), two-vessel (n=170) and three-vessel disease (n=196). Patients with stenoses 0-50% were excluded. Within patients with CAD, we evaluated overall extent of CAD measured by the number of stenotic segments according to AHA (1 segment vs. 2–3 vs. ≥4), and the severity of the most serious stenosis (in percent). ApoE genotype was determined using real-time PCR. Results. The frequency of e2/e3 genotype (n=56) was lower in the three-vessel disease group compared to one-vessel disease (OR=0.25, P=0.0019), two-vessel disease (OR=0.31, P=0.0114) or no CAD group (OR=0.24, P=0.0057). Frequency of e2/e3 decreased with the number of affected segments (1 vs. ≥4: OR=0.35, P=0.0143). The e3/e4+e4/e4 genotypes (n=123) were more frequent in CAD patients altogether compared with no CAD group (OR=2.30, P=0.019), while no impact of the e4 allele on angiographic parameters within the CAD patients was detected. In e2/e3 carriers with CAD, lower LDL-cholesterol, total cholesterol and lower use of lipid-lowering drugs were observed. Conclusions. The results show predominantly focal form of CAD in patients with e2/e3 genotype. Lower LDL-cholesterol and total cholesterol may play the key role, although other contributing factors are discussed.

article i nfo Background: The in-hospital mortality of patients with acute heart failure (AHF) is reported to be 12.7% and mortality on day 30 after admission 17.2%. Less information is known about the long-term prognosis of those patients discharged after hospitalization. As such, the aim of this study was to investigate long-term survival in a cohort of patients who had been hospitalized for AHF and then discharged. Methods: The AHEAD Main registry includes 4153 patients hospitalized for AHF in 7 different medical centers, each with its own cathlab, in the Czech Republic. Patient survival rates were evaluated in 3438 patients who had survived to day 30 after admission, and were used as a measurement of long-term survival. Results: The most common etiologies were acute coronary syndrome (32.3%) and chronic ischemic heart disease (20.1%). The survival rate after day 30 following admission was 79.7% after 1 year and 64.5% after 3 years. No statistically significant difference in syndromes was found in survival after day 30. Independent predictors of a worse prognosis were defined as follows: age>70 years, comorbidities, severe left ventricular systolic dysfunction, valvular disease or ACS as an etiology of AHF. A better prognosis was defined for de-novo AHF patients, and those who were taking ACE inhibitors at the time of discharge. In a sub- analysis, high levels of natriuretic peptides were the most powerful predictors of high-risk, long-term mortality. Conclusion: The AHEAD Main registry provides up-to-date information on the long-term prognosis of patients hospitalized with AHF. The 3-year survival of patients following day 30 of admission was 64.5%. Higher age, LV dysfunction, comorbidities and high levels of natriuretic peptides were the most powerful predictors of worse prognosis in long-term survival.

Introduction The prognosis of patients hospitalized with acute heart failure (AHF) is poor and risk stratification may help clinicians guide care. The objectives of the Acute Heart Failure Database (AHEAD) registry are to assess patient characteristics, etiology, treatment and outcome of AHF. Methods The AHEAD main registry includes patients hospitalized for AHF in seven centers with a Catheterization Laboratory Service in the Czech Republic. The data were collected from September 2006 to October 2009. The inclusion criteria for the database adhere to the European guidelines for AHF (2005) and patients were systematically classified according to the basic syndromes, type and etiology of AHF. Results Of 4,153 patients, 12.7% died during hospitalization. The median length of hospitalization was 7.1 days. Mean age of patients was 71.5 ± 12.4 years; men were younger (68.6 ± 12.4 years) compared to women (75.5 ± 11.5 years) (P < 0.001). De-novo heart failure was seen in 58.3% of the patients. According to the classification of heart failure syndromes, acute decompensated heart failure (ADHF) was reported in 55.3%, hypertensive AHF in 4.4%, pulmonary edema in 18.4%, cardiogenic shock in 14.7%, high output failure in 3.3%, and right heart failure in 3.8%. The mortality of cardiogenic shock was 62.7%, of right AHF 16.7%, of pulmonary edema 7.1%, of high output HF 6.1%, whereas the mortality of hypertensive AHF or ADHF was < 2.5%. According to multivariate analyses, low systolic blood pressure, low cholesterol level, hyponatremia, hyperkalemia, the use of inotropic agents and norepinephrine were predictive parameters for in-hospital mortality in patients without cardiogenic shock. Severe left ventricular dysfunction and renal insufficiency were predictive parameters for mortality in patients with cardiogenic shock. Invasive ventilation and age over 70 years were the most important predictive factors for mortality in both genders with or without cardiogenic shock. Conclusions The AHEAD Main registry provides up-to-date information on the etiology, treatment and hospital outcomes of patients hospitalized with AHF. The results highlight the highest risk patients.

Aim. To evaluate the therapeutic effect of resynchronization in patients with chronic heart failure who are symptomatic despite adequate pharmacological medication. Sample and methodology. 118 patients with chronic heart failure, mostly dilated cardiomyopathy and ischaemic heart disease, with depressed systolic function, decreased left ventricular ejection fraction (LVEF) and left bundle branch block wide QRS complex, underwent implantation of the biventricular system between the years 2000–2006. We assessed changes in the NYHA functional class, hemodynamic parameters acquired during right heart catheterization, the maximum oxygen consumption during stress spiroergometric examination, as well as echocardiographic parameters. Results. A statistically significant improvement was found in the NYHA functional class (from 2.8 ± 0.4 to 2.3 ± 0.5 after 3m, p < 0,001 and to 2.5 ± 0.6 after 12m, p < 0,01 respectively), as well as an increase in the maximum oxygen consumption during spiroergometric examination (VO2 max from 14.1 ± 3.1ml/kg/min to 15.3 ± 3.1 ml/kg/ min, p < 0,001 and to 15.3 ± 2.5 ml/kg/min, p = NS respectively). In regard to hemodynamic parameters, there were increases in cardiac output and cardiac index after three months. After 12 months the change was not statistically significant (CO from 3.9 ± 1 l/min to 4.2 ± 0.9 l/min, p < 0,05, and to 4.1 ± 0.9 l/min, p = NS, CI from 2 ± 0.5l/kg/min to 2.2 ± 0.4l/kg/min, p < 0,05, and to 2.1 ± 0.4 l/kg/min, p = NS). Mean pulmonary artery pressure, as well as pulmonary capillary wedge pressure was reduced after 3, as well as after 12 months to a statistically significant degree (MPA from 29.1 ± 11.5 mm Hg to 23.9 ± 10.3 mm Hg, p< 0,001, and to 24.9 ± 11.8 mm Hg, p < 0,01 respectively, and PCWP from 19.9 ± 9.5 mm Hg to 15.2 ± 9.2 mm Hg, p < 0,01, and to 15.6 ± 9 mm Hg, p < 0,01 respectively). In regard to echocardiographic parameters, there was an increase in LVEF, a reduction in the end-diastolic diameter of the left ventricle, as well as a statistically significant reduction in severity of mitral regurgitation after 3, as well as 12 months (LVEF from 20.5 ± 5.3%, to 23 ± 6.5%, p < 0,001, and to 24.5 ± 8%, p < 0,001, LVEDD from 69 ± 9 mm to 68 ± 9 mm, p < 0.01 and to 65 ± 12 mm, p< 0.01 respectively, mitral regurgitation from 2.2 ± 0.8 to 1.9 ± 0.8, p< 0.001, and to 2 ± 0.8, p < 0.001. Conclusions. In patients with chronic heart failure, resynchronization therapy leads to reduced symptoms, reduction in dyspnea and to improvements in cardiac performance due to increase in the systolic function of the left ventricle and hemodynamic changes.

We evaluated the short-term effect of cardiac resynchronization therapy (CRT) on sleep apnea in patients with systolic heart failure.Sleep-disordered breathing is common in patients with left ventricular systolic dysfunction.Twelve patients (mean [+/-SE] age, 59.6+/-7.8 years; mean left ventricular ejection fraction, 28.0+/-2.8%) with an implanted atrial-synchronized biventricular pacemaker for the treatment of left ventricular systolic dysfunction were selected and studied. Each subject underwent polysomnography on 3 consecutive nights with CRT on the first night, CRT off the second night, and CRT on the third night. Echocardiography was performed prior to each polysomnogram.The central sleep event index (ie, the number of central sleep apneas [CSAs] and hypopneas per hour of sleep) score was lower with CRT compared to that without CRT (mean central sleep event index score with CRT on, 6.9+/-1.7 events per hour of sleep; mean central sleep event index score with CRT off, 14.3+/-2.9 events per hour of sleep; mean central sleep event index score with CRT on, 8.1+/-1.5 events per hour of sleep; p0.001). Similarly, the cumulative duration of central sleep events (the number of minutes per hour of sleep during CRT) was one half that observed without CRT (CRT on, 2.8+/-0.7 min per hour of sleep; CRT OFF 6.2+/-1.2 min per hour of sleep; CRT ON 3.1+/-0.7 min per hour of sleep; p0.001). There was a significant correlation between mitral regurgitant volume and central sleep event index on all three nights (ror=0.77; p0.01).CRT reduces CSA severity in the short term. This reduction correlated significantly with the CRT-mediated reduction of mitral regurgitation.

Background: Humoral systems play an important role in the patophysiology 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.

Background The objective of the current study was to examine the efficacy and tolerability of the β-blocker metoprolol succinate controlled release/extended release (CR/XL) in patients with diabetes in the Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF). Methods The Cox proportional hazards model was used to calculate hazard ratios (HR) for convenience expressed as relative risks (risk reduction = 1-HR), and 95% confidence intervals (CI). Results The risk of hospitalization for heart failure was 76% higher in diabetics compared to non-diabetics (95% CI 38% to 123%). Metoprolol CR/XL was well tolerated and reduced the risk of hospitalization for heart failure by 37% in the diabetic group (95% CI 53% to 15%), and by 35% in the non-diabetic group (95% CI 48% to 19%). Pooling of mortality data from the Cardiac Insufficiency Bisoprolol Study II (CIBIS II), MERIT-HF, and the Carvedilol Prospective Randomized Cumulative Survival Study (COPERNICUS) showed similar survival benefits in patients with diabetes (25%; 95% CI 40% to 4%) and without diabetes (36%; 95% CI 44% to 27%); test of diabetes by treatment interaction was non-significant. Adverse events were reported more often on placebo than on metoprolol CR/XL. Conclusions Patients with heart failure and diabetes have a much higher risk of hospitalization than patients without diabetes. Regardless of diabetic status, a highly significant reduction in hospitalizations for heart failure was observed with metoprolol CR/XL therapy, which was very well tolerated also by patients with diabetes. Furthermore, the pooled data showed a statistically significant survival benefit in patients with diabetes.

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

Background — β-Blockade improves survival when administered over a long period of time to patients with heart failure. However, the time course of any possible deterioration during the titration phase has not been reported. Methods and Results — We looked at evidence of clinical deterioration in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF) by analyzing events and symptoms during the first 90 days. During titration, the Kaplan-Meier curves for the combined end point of all-cause mortality/all-cause hospitalization were similar in all patients randomized, with no significant difference in favor of placebo at any visit or in any of the analyzed subgroups (New York Heart Association class II, III/IV, or III/IV with ejection fraction P =0.037 unadjusted, P =NS adjusted); corresponding figures in those with New York Heart Association class III/IV and ejection fraction P =NS). From day 90 until the end of the study, more patients in the placebo group discontinued study medicine in all subgroups. There was no change in diuretic or ACE inhibitor dosing with β-blocker titration. Most patients reported no change in symptoms of breathlessness or fatigue during the titration phase. Conclusions — When carefully titrated, metoprolol CR/XL can be given safely to the overwhelming majority of patients with stable mild to moderate heart failure, with minimal side effects or deterioration.

Jaromir Hradec, Jiri Vitovec, Jindrich Spinar 3rd Department of Medicine, First Faculty of Medicine and Faculty General Hospital, Charles University Prague, Czech Republic Internal Department of Cardiology and Angiology, Faculty of Medicine and Faculty St. Ann’s Hospital, Masaryk University Brno, Czech Republic Internal-Cardiology Department, Faculty of Medicine and Faculty Hospital Brno, Czech Republic