Iron Deficiency in Patients with Advanced Heart Failure.

Background and Objectives: Iron deficiency (ID) is a common comorbidity in patients with heart failure. It is associated with reduced physical performance, frequent hospitalisations for heart failure decompensation, and high cardiovascular and overall mortality. The aim was to determine the prevalence of ID in patients with advanced heart failure on the waiting list for heart transplantation. Methods and Materials: We included 52 patients placed on the waiting list for heart transplantation in 2021 at our centre. The cohort included seven patients with LVAD (left ventricle assist device) as a bridge to transplantation implanted before the time of results collection. In addition to standard tests, the parameters of iron metabolism were monitored. ID was defined as a ferritin value <100 µg/L, or 100−299 µg/L if transferrin saturation (T-sat) is <20%. Results: ID was present in 79% of all subjects, but only in 35% of these patients anaemia was expressed. In the group without LVAD, ID was present in 82%, a median (lower−upper quartile) of ferritin level was 95.4 (62.2−152.1) µg/mL and mean T-sat was 0.18 ± 0.09. In LVAD group, ID was present in 57%, ferritin level was 268 (106−368) µg/mL and mean T-sat was 0.14 ± 0.04. Haemoglobin concentration was the same in patients with or without ID (133 ± 16) vs. (133 ± 23). ID was not associated with anaemia defined with regard to patient's gender. In 40.5% of cases, iron deficiency was accompanied by chronic renal insufficiency, compared to 12.5% of the patients without ID. In the patients with LVAD, ID was present in four out of seven patients, but the group was too small for reliable statistical testing due to low statistical power. Conclusions: ID was present in the majority of patients with advanced heart failure and was not always accompanied by anaemia and renal insufficiency. Research on optimal markers for the diagnosis of iron deficiency, especially for specific groups of patients with heart failure, is still ongoing.

Stress pulmonary circulation parameters assessed by a cardiovascular magnetic resonance in patients after a heart transplant.

Rest pulmonary circulation parameters such as pulmonary transit time (PTT), heart rate corrected PTT (PTTc) and pulmonary transit beats (PTB) can be evaluated using several methods, including the first-pass perfusion from cardiovascular magnetic resonance. As previously published, up to 58% of patients after HTx have diastolic dysfunction detectable only in stress conditions. By using adenosine stress perfusion images, stress analogues of the mentioned parameters can be assessed. By dividing stress to rest biomarkers, potential new ratio parameters (PTT ratio and PTTc ratio) can be obtained. The objectives were to (1) provide more evidence about stress pulmonary circulation biomarkers, (2) present stress to rest ratio parameters, and (3) assess these biomarkers in patients with presumed diastolic dysfunction after heart transplant (HTx) and in childhood cancer survivors (CCS) without any signs of diastolic dysfunction. In this retrospective study, 48 patients after HTx, divided into subgroups based on echocardiographic signs of diastolic dysfunction (41 without, 7 with) and 39 CCS were enrolled. PTT was defined as the difference between the onset time of the signal intensity increase in the left and the right ventricle. PTT in rest conditions were without significant differences when comparing the CCS and HTx subgroup without diastolic dysfunction (4.96 ± 0.93 s vs. 5.51 ± 1.14 s, p = 0.063) or with diastolic dysfunction (4.96 ± 0.93 s vs. 6.04 ± 1.13 s, p = 0.13). However, in stress conditions, both PTT and PTTc were significantly lower in the CCS group than in the HTx subgroups, (PTT: 3.76 ± 0.78 s vs. 4.82 ± 1.03 s, p < 0.001; 5.52 ± 1.56 s, p = 0.002). PTT ratio and PTTc ratio were below 1 in all groups. In conclusion, stress pulmonary circulation parameters obtained from CMR showed prolonged PTT and PTTc in HTx groups compared to CCS, which corresponds with the presumption of underlying diastolic dysfunction. The ratio parameters were less than 1.

Identification of a Diagnostic Set of Endomyocardial Biopsy microRNAs for Acute Cellular Rejection Diagnostics in Patients after Heart Transplantation Using Next-Generation Sequencing.

INTRODUCTION: Acute cellular rejection (ACR) of heart allografts represents the most common reason for graft failure. Endomyocardial biopsies (EMB) are still subject to substantial interobserver variability. Novel biomarkers enabling precise ACR diagnostics may decrease interobserver variability. We aimed to identify a specific subset of microRNAs reflecting the presence of ACR. PATIENTS AND METHODS: Monocentric retrospective study. A total of 38 patients with the anamnesis of ACR were identified and for each patient three consecutive samples of EMB (with, prior and after ACR) were collected. Sixteen trios were used for next-generation sequencing (exploratory cohort); the resting 22 trios were used for validation with qRT-PCR (validation cohort). Statistical analysis was performed using R software. RESULTS: The analysis of the exploration cohort provided the total of 11 miRNAs that were altered during ACR, the three of which (miR-144, miR-589 and miR-182) were further validated in the validation cohort. Using the levels of all 11 miRNAs and principal component analysis, an ACR score was created with the specificity of 91% and sensitivity of 68% for detecting the presence of ACR in the EMB sample. CONCLUSION: We identified a set of microRNAs altered in endomyocardial biopsies during ACR and using their relative levels we created a diagnostic score that can be used for ACR diagnosis.

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.

Genetic architecture of recent-onset dilated cardiomyopathy in Moravian region assessed by whole-exome sequencing and its clinical correlates.

AIMS: Recent-onset dilated cardiomyopathy (RODCM) is a disease of heterogeneous aetiology and clinical outcome. In this pilot study, we aimed to assess its genetic architecture and correlate genotype with left ventricular reverse remodelling (LVRR). PATIENTS AND METHODS: In this multi-centre prospective observational study, we enrolled 83 Moravian patients with RODCM and a history of symptoms of less than 6 months, for whole-exome sequencing (WES). All patients underwent 12-month clinical and echocardiographic follow-up. LVRR was defined as an absolute increase in left ventricular ejection fraction > 10% accompanied by a relative decrease of left ventricular end-diastolic diameter > 10% at 12 months. RESULTS: WES identified at least one disease-related variant in 45 patients (54%). LVRR occurred in 28 patients (34%), most often in carriers of isolated titin truncated variants, followed by individuals with a negative, or inconclusive WES and carriers of other disease-related variants (56% vs. 42% vs. 19%, P=0.041). CONCLUSION: A substantial proportion of RODCM cases have a monogenic or oligogenic genetic background. Carriers of non-titin disease-related variants are less likely to reach LVRR at 12- months than other individuals. Genetic testing could contribute to better prognosis prediction and individualized treatment of RODCM.

Renal Functions and Prognosis Stratification in Chronic Heart Failure Patients and the Importance of Neutrophil Gelatinase-Associated Lipocalin.

BACKGROUND/AIMS: The rate of incidence and prevalence of acute kidney injury is increasing due to an increased number of patients with heart failure. Therefore it is very pertinent to early detect the level of renal injuries and to make necessary heart failure predictions. Thus the aim of this study is to determine renal functions and prognosis stratification in chronic heart failure patients and importance of Neutrophil Gelatinase-Associated Lipocalin (NGAL), an early diagnostic marker of acute kidney injury, as well as stratification of cardiovascular risk in heart failure patients. METHODS: Data including age, gender, comorbidities and medical history of outpatients and hospitalized patients from Farmacology and NeuroHumoraL activation (FAR NHL) multicenter prospective registry comprising three Cardiological Centers in the Czech Republic were collected between 1st October 2014 and 30th November 2015. One-year follow-up data were collected in November 2016 in such a way that all patients had at least one-year data from the time of recruitment, but up to two years to the time of follow-up. One-year data were used for the whole set of patients while data up to 24 months were used with Kaplan-Meier's survival curves to analyse the patients' survival data. Blood samples were collected from the patients and basic parameters were evaluated in order to analyse Neutrophil gelatinase-associated lipocalin (NGAL) and plasma levels of N-terminal pro-brain natriuretic peptide (NT-ProBNP) using Lipocalin-2/NGAL Human ELISA kit (Bio Vendor, Czechia) and the Cobas E411 NT-proBNP Immunoassay kit (Roche Diagnostics, Indianapolis, IN, USA) respectively. Statistical analysis was further carried out to explain the level of significance of the evaluated parameters using Spearman Correlation, Mann Whitney or Kruskal-Wallis test and log-rank test. RESULTS: Out of 547 patients from Farmacology and NeuroHumoraL activation (FAR NHL) multicenter prospective registry with available data on hospitalizations, mortality, biomarkers and one-year follow-up that were recorded, there were 439 males (80.3%) with a median age of 66 years. At least one-month stable patients with left ventricle ejection fraction (LV EF) under 50% were recorded. The etiology of heart failure was ischemic heart disease in 54%, dilated cardiomyopathy in 40% and others in 6%. 69% patients were in New York Heart Association functional class II. There were 76 events (13.9%; all-cause mortality, acute heart failure hospitalization, left ventricle assist device implantation and orthotopic heart transplant) in the first 365 days of follow-up. The area under the receiver operating characteristic curve was higher for NT-proBNP (0.77) than the creatinine (0.57), NGAL (0.55) or creatinine clearance (0.54). In multivariable analyses, NT-proBNP (P= 0.001) and NGAL (P = 0.004) were significant predictors of events. Subjects with NT-proBNP and NGAL above the cut off value (NT-proBNP 1,121 pg/ml, NGAL 80 ng/ml) survived without any event in 55.7%, subjects with NT-proBNP and NGAL under the cut off value survived without any event in 90.5%, after two years (P = 0.001). CONCLUSION: The findings of the study showed that NGAL associated with NT-proBNP was a stronger predictor of the primary endpoint than NGAL or NT-proBNP alone. The level of NGAL was rising in hypertension, ischemia, anemia, hypoalbuminemia, diabetes or arrhythmias.

Viral genome changes and the impact of viral genome persistence in myocardium of patients with inflammatory cardiomyopathy.

INTRODUCTION: Viral infections are considered the most frequent cause of myocarditis and dilated cardiomyopathy (DCM). MATERIAL AND METHODS: We investigated the changes in viral presence and the impact of viral genome persistence in the myocardium on echocardiographic parameters, functional status and some laboratory parameters in a 6-month follow-up. Fifty-four patients with recent onset DCM, left ventricular ejection fraction < 40% and biopsy-proven myocarditis (> 14 mononuclear leukocytes/mm2 and/or > 7 T-lymphocytes/mm2) were enrolled. Polymerase chain reaction (PCR) was performed to detect pathogens in the myocardium. Patients were divided according to the administered therapy: standard heart failure medication (46 patients) and immunosuppressive therapy (8 patients). RESULTS: In the standard heart failure medication group viral clearance was observed in 13 patients and viral persistence in 24 patients in the follow-up period. Comparing both groups, there was no statistically significant difference - LVEF improvement of 12.0 ±11.4% vs. 18.3 ±12.6%, decrease in NYHA class of 0.7 ±0.7 vs. 1.0 ±0.7, decline in NT-proBNP of 1335 ±1933 ng/l vs. 1942 ±3242 ng/l and decrease in infiltrating leukocytes of 11.1 ±15.8 vs. 6.7 ±23.0 cells/mm2 and T-lymphocytes of 5.8 ±15.1 vs. 1.8 ±10.9 cells/mm2 (all p = NS). A decrease in PCR positive patients from 37 to 29 was observed. The number of PVB19 positive PCR findings decreased from 5 to 4 in patients with immunosuppressive therapy. CONCLUSIONS: A decrease in the number of positive PCR findings in control endomyocardial biopsy was observed. Viral genome persistence was not associated with worse outcome in short-term follow-up.

[Heart transplantation and follow-up treatment with AL-amyloidosis in 5 patients]. / Transplantace srdce a následující lécba AL-amyloidózy u 5 pacientu.

The prognosis for patients with cardiac impairment due to AL-amyloid deposition and severe cardiac insufficiency is poor, with a survival median in the order of months. The classical treatment of AL-amyloidosis in combination with cardiac insufficiency is very poorly tolerated and the treatment of such patients is associated with considerably higher mortality than among other patients with AL-amyloidosis. If, however, patients with an isolated or another dominating cardiac impairment, without severe damage to other organs and tissues, have a heart transplant performed, their cardiovascular condition will significantly improve as a result, along with their ability to tolerate any kind of treatment for AL-amyloidosis including that using high-dose chemotherapy with a transplant of autologous hematopoietic stem cells. The achievement of complete remission of AL-amyloidosis is a precondition for long-term survival, since when not achieved, amyloid deposition also arises in the transplanted heart. At the Centre for Cardiovascular and Transplantation Surgery, Brno, the first heart transplant due to its impairment by AL-amyloidosis was performed in 2010. By the year 2017 the number of patients with AL-amyloidosis, who had first undergone a heart transplant with subsequent treatment for AL-amyloidosis, increased to 5. The median age at which a heart transplant was performed is 60 (48-65) years. Four patients were men, one was a woman. The median monitoring equals 65 (88-15) months. Complete remission of AL-amyloidosis was achieved in all the patients. There were 5 lines of treatment needed for the first patient to attain it, of that twice high-dose melphalan with autologous stem cell transplantation, for the second patient a second-line treatment, high-dose melphalan and bortezomib-based therapy. No specific therapy was needed for the third patient, as immunosuppressive therapy following the heart transplant containing prednison led to complete remission of AL-amyloidosis. In the fourth case, sustainable complete remission was reached by high-dose melphalan and in the fifth case by one line of bortezomib-based therapy. The aforementioned data illustrate that a heart transplant is the first step which makes the patients with a severe heart failure, not tolerating any efficient therapy of AL-amyloidosis, capable of undergoing intense treatment of AL-amyloidosis. Sometimes one high-dose chemotherapy is sufficient, while at other times multiple treatment lines are needed to reach complete remission of AL-amyloidosis.Key words: AL-amyloidosis - autologous hematopoietic stem cells transplantation - bortezomib - cardiomyopathy - lenalidomide - thalidomide - heart transplantation.

Improvement of left ventricular systolic function in inflammatory cardiomyopathy: What plays a role?

AIMS: To compare the differences between patients with inflammatory cardiomyopathy (ICM) with and without improvement in left ventricular (LV) systolic function and to identify the relevant predictors of LV improvement. PATIENTS AND METHODS: The study included 63 patients with biopsy-proven ICM and heart failure symptoms of at least NYHA II, symptom duration ≤ 6 months, LV ejection fraction (LVEF) ≤ 40% assessed by echocardiography and presence of >14 mononuclear leukocytes (LCA+ cells)/mm2 in biopsy samples. Patients were evaluated at baseline and after 6 months. RESULTS: In the group with LVEF improvement of ≥ 10% (I+ group, n = 41), LVEF increased from 24 ± 7% to 47 ± 8% (P < 0.001). In 22 patients (group I-), there was no or minimal LVEF increase (< 10%). In the I+ group, there were more LCA+ cells/mm2 at baseline (25.1 ± 16.5 vs. 18.5 ± 4.4 cells/mm2; P = 0.032) and a more significant decrease in LCA+ cells in the follow-up (reduction of 13.6 ± 14.3 cells/mm2 vs. 5.0 ± 7.7 cells/mm2 in the I- group; P = 0.009). The univariate logistic regression showed a possible association of number of LCA+ cells, LV end-diastolic diameter and N-terminal fragment of pro-brain natriuretic peptide (NTproBNP) value with LVEF improvement. In the multivariate analysis, only NTproBNP at diagnosis was confirmed as an independent predictor of LVEF improvement (OR=1.2; 1.003 to 1.394; P = 0.046). CONCLUSION: The LV systolic function improvement was observed in 65% of the patients. In these patients, the number of inflammatory cells at baseline was higher and decreased more but the higher baseline NTproBNP value was the only independent predictor of LVEF improvement.

Longitudinal, circumferential and radial systolic left ventricular function in patients with heart failure and preserved ejection fraction.

INTRODUCTION: Heart failure with preserved left ventricular ejection fraction (HFPEF) is an epidemiologically serious disease. Noninvasive diagnosis of HFPEF remains challenging. The current diagnosis is based on evidence of diastolic dysfunction, albeit systolic dysfunction is also present but not included in the diagnostic algorithm. The aim of this study was to analyze the longitudinal (long), circumferential (circ) and radial (rad) component of systolic left ventricular (LV) function in patients with exertional dyspnea of unexplained etiology and normal left ventricular ejection fraction (LVEF). METHODS: One hundred and twenty-two patients with exertional dyspnea of unexplained etiology and normal LVEF and 21 healthy controls, underwent echocardiography examination at rest and at the end of symptom-limited exercise. We analysed the longitudinal, circumferential and radial deformation of myocardium using two dimensional speckle tracking echocardiography in all subjects. RESULTS: Patients with exertional dyspnea and preserved LVEF were divided into group A1 (46 patients meeting the criteria for the diagnosis HFPEF) and group A2 (76 patients without HFPEF). Group A1 had significantly worse longitudinal and circumferential systolic LV function than group A2. Subjects in group A1 compared to group A2 showed significantly different strain rates during atrial contraction (SR A), circ and ratio of peak early trans-mitral flow velocity (E) and strain rate E wave (E / SR E) circ. Multivariate logistic regression analysis showed that the SR parameter A circ is an independent predictor of HFPEF (odds ratio 0.550, 95% confidence interval: 0.370 - 0.817, P value 0.003). CONCLUSION: Longitudinal and circumferential LV deformation was significantly more impaired in patients with HFPEF than in patients with exertional dyspnea without HFPEF. In patients with exertional dyspnea and normal LVEF, the value of SRA circ appears to be a significant and independent predictor of HFPEF. This parameter may, in the future complement the diagnostic algorithm for HFPEF.

Correlations of the changes in bioptic findings with echocardiographic, clinical and laboratory parameters in patients with inflammatory cardiomyopathy.

Patients with myocarditis and left ventricular (LV) dysfunction may improve after standard heart failure therapy. This improvement seems to be related to retreat of myocardial inflammation. The aim of the present study was to assess changes in clinical, echocardiographic and some laboratory parameters and to correlate them with changes in the number of inflammatory infiltrating cells in endomyocardial biopsy (EMB) samples during the 6-month follow-up, and to define predictors of LV function improvement among baseline parameters. Forty patients with biopsy-proven myocarditis and impaired LV function (LV ejection fraction-LVEF <40 %) with heart failure symptoms ≤ 6 months were evaluated. Myocarditis was defined as the presence of >14 mononuclear leukocytes/mm(2) and/or >7 T-lymphocytes/mm(2) in the baseline EMB. The EMB, echocardiography and clinical evaluation were repeated after 6 months of standard heart failure therapy. LVEF improved on average from 25 ± 9 to 42 ± 12 % (p < 0.001); LV end-systolic volume and LV end-diastolic volume (LVEDV) decreased from 158 ± 61 to 111 ± 58 ml and from 211 ± 69 to 178 ± 63 ml (both p < 0.001). NYHA class decreased from 2.6 ± 0.5 to 1.6 ± 0.6 (p < 0.001) and NTproBNP from 2892 ± 3227 to 851 ± 1835 µg/ml (p < 0.001). A decrease in the number of infiltrating leukocytes (CD45+/LCA+) from 23 ± 15 to 13 ± 8 cells/mm(2) and in the number of infiltrating T lymphocytes (CD3+) from 7 ± 5 to 4 ± 3 cells/mm(2) (both p < 0.001) was observed. The decline in the number of infiltrating CD45+ cells significantly correlated with the change in LVEF (R = -0.43; p = 0.006), LVEDV (R = 0.39; p = 0.012), NYHA classification (R = 0.35; p = 0.025), and NTproBNP (R = 0.33; p = 0.045). The decrease in the number of CD3+ cells correlated with the change of systolic and diastolic diameters of the left ventricle (R = -0.33; p = 0.038 and R = -0.45; p = 0.003) and with the change in LVEDV (R = -0.43; p = 0.006). Tricuspid annular plane systolic excursion (TAPSE) (OR 0.61; p = 0.005) and early transmitral diastolic flow velocity (E wave) (OR 0.89; p = 0.002) were identified as predictors of LVEF improvement. Improvements in clinical status, LV function and NTproBNP levels correlated with decrease in the number of infiltrating inflammatory cells. TAPSE and E wave velocity were significant predictors of improvement in multivariate regression. Our observations suggest that contemporary guidelines-based therapy of heart failure is an effective treatment option in patients with recent onset biopsy-proven inflammatory cardiomyopathy.

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.

Variability of post-exercise pulmonary capillary wedge pressure recovery. Implications for noninvasive echocardiographic diagnostics.

AIM: The aim of our study was to assess the course of immediate post-exercise pulmonary capillary wedge pressure (PCWP) changes to identify the optimal time window for the noninvasive diagnostics of exercise-induced PCWP elevation. METHODS AND RESULTS: Seventy-one patients at risk of heart failure with normal left ventricular ejection fraction underwent simultaneous exercise echocardiography and right heart catheterization. The ratio of early left ventricular filling velocity (E) to early diastolic mitral annular velocity (e') was used to predict noninvasively exercise-induced PCWP elevation. Fifty-one patients had exercise-induced PCWP elevation ≥ 8 mmHg and reached peak exercise PCWP ≥ 20 mmHg. Rapid post-exercise recovery of PCWP within 2 min was achieved in 18 (35.3%) patients. Intermediate post-exercise PCWP recovery at 3 and 4 min was found in 16 (31.4%) patients while late post-exercise PCWP recovery (≥ 5 min) was achieved in 17 (33.3%) patients. CONCLUSION: The course of post-exercise PCWP recovery is highly variable, and a significant proportion of patients have only a brief period (≤ 2 min) of exercise-induced PCWP elevation. This fact should be taken into account in noninvasive assessment of exercise-induced PCWP.

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.

Pharmacotherapy of dilated cardiomyopathy.

The pharmacological treatment of dilated cardiomyopathy overlaps with the treatment of heart failure. The primary objective of this treatment is to slow the progression of disease and improve quality and length of life. All patients, including those with asymptomatic dysfunction of the left ventricle, ought to receive angiotensin converting enzyme inhibitors, (in the case of intolerance, angiotensin receptor blockers), and beta blockers. The results of studies involving aliskiren have been, so far, disappointing. In symptomatic heart failure NYHA II-IV diuretics and mineralcorticoid receptor antagonists should be added to treatment. Digoxin is recommended in the event of atrial fibrillation, and otherwise only in the event of NYHA III and IV. Ivabradine is recommended for patients with sinus rhythm and pulse rate of > 70/min. In decompensation of heart failure, dobutamine, phosphodiesterase inhibitors or levosimendan are administered over the short-term. Of the recent treatment options, the vasopressin blocker and adenosine A1 receptor antagonist (rolofylline) were disappointing. One treatment with potential for the future is omecamtiv mecarbil, a heart myosin activator.

[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.

Effects of nebivolol on biomarkers in elderly patients with heart failure.

BACKGROUND: Heart failure activates neurohormones, and elevated levels of brain natriuretic peptide (BNP) are associated with adverse outcomes. The SENIORS trial showed that nebivolol, a highly selective beta-1 antagonist with vasodilating properties, reduced the composite outcome of all cause mortality or cardiovascular hospital admissions in older patients with heart failure. We explored the effects of nebivolol on a range of neurohormones, cytokines and markers of nitric oxide activity in heart failure. METHODS: In a subset of patients in SENIORS we measured N-terminal pro-brain natriuretic peptide (NT-BNP), pro atrial natriuretic peptide (Pro-ANP), endothelin-1 (ET-1), peripheral norepinephrine (PNE), soluble Fas (sFas), soluble Fas-ligand (sFas-L), tumour necrosis factor-alpha (TNF-α), serum uric acid (SUA), symmetrical dimethyl arginine (SDMA), arginine, citrulline and asymmetrical dimethyl arginine (ADMA) at baseline (before study drug), at 6 months and 12 months in a prespecified substudy. RESULTS: One hundred and six patients were enrolled and 75 had a baseline and at least one follow-up sample. There were no significant differences in neurohormone cytokines or nitric oxide markers measured between the two groups at six or twelve months. NT-ProBNP showed a numerical increase in the nebivolol group compared to placebo (P=0.08) and sFas showed a numerical increase in patients on placebo (P=0.08). Mean baseline LVEF was 35% in both groups and at 12 months was 43% on nebivolol group and 34% on placebo group (P=0.01). CONCLUSION: There were trends but no clear changes associated with nebivolol in neurohormones, cytokines or markers of nitric oxide activity in this study of elderly patients with heart failure. Further studies are needed to understand the mechanistic effects of beta blockers on biomarkers in heart failure.

High prevalence of exercise-induced heart failure with normal ejection fraction in post-heart transplant patients.

AIM: Post-heart transplant patients are at increased risk of diastolic dysfunction. The aim of this study was to assess the prevalence of isolated only exercise-induced heart failure with normal ejection fraction (HFNEF) in heart transplant recipients. METHODS AND RESULTS: To determine pulmonary capillary wedge pressure (PCWP) at rest and during exercise, 81 patients after orthotopic heart transplantation with normal left ventricular ejection fraction (LVEF) underwent exercise right heart catheterization with simultaneous exercise echocardiography. Based on PCWP values, the patients were divided into three groups. Twenty-one patients had no evidence of HFNEF (PCWP at rest < 15 mmHg, maximal PCWP during exercise < 25 mmHg, prevalence 26%). Forty-seven subjects were found to have only exercise-induced HFNEF (PCWP at rest < 15 mmHg, maximal PCWP during exercise ≥ 25 mmHg, prevalence 58%). Thirteen patients had HFNEF already at rest (PCWP ≥ 15 mmHg at rest, prevalence 16%). Of the noninvasive parameters obtained at rest, multivariate regression analysis identified LV mass index adjusted for allograft age to be an independent predictor of exercise-induced HFNEF. CONCLUSIONS: In heart transplant recipients with normal LVEF, there is a high prevalence of exercise-induced HFNEF. LV mass index adjusted for allograft age is predictive of exercise-induced HFNEF.

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.

Impact of pulmonary hypertension on early hemodynamics, morbidity and mortality after orthotopic heart transplantation. A single center study.

AIMS: To determine the effect of pre-existing pulmonary hypertension (PHT) on early hemodynamics, morbidity and mortality after heart transplantation (HTx). METHODS: Data were prospectively collected from 149 patients, who underwent HTx between January 2000 and December 2007. The subjects were divided into 3 groups: Group A (n=84) without PTH, group B (n=50) with mild to moderate PTH and group C (n=15) with severe PTH. We studied hemodynamic profile, tricuspid valve regurgitation (TR), incidence of acute cellular rejections (AR), infections, duration of hospitalization, 30-day mortality and a long-term survival. RESULTS: Baseline characteristics were similar in all groups. Using vasodilator treatment PVR was successfully brought down to normal range 2.5 ± 0.6 Wood' units (WU) on the day 1 following the surgery in all groups. Over 80% of patients were treated in Group C, 32% in Group A and 46% in Group B. There was no significant difference in the severity of TR among the 3 groups early after HTx (severe TR was observed in 46%, 54%, 33%, respectively). There was no significant difference in incidence of AR (G ≥ 2 Banff classification) (23%, 23%, 33%, respectively), infections (28%, 32%, 33%, respectively) or duration of hospitalization (30, 30, 28 days, respectively). There was no correlation between pre-transplant PHT and 30-day mortality or a long-term survival. CONCLUSIONS: In our cohort, PHT dropped very quickly after HTx, and was not associated with acute right heart failure following the surgery. Reversible PTH does not have a negative impact on short- or long-term survival after HTx.