Klára Benešová

Heart rate is a useful marker of adherence to beta-blocker treatment in hypertension

Abstract Objectives: Suboptimal medication adherence is common among patients with hypertension. Measurements of plasma or urinary levels of antihypertensive drugs are useful, but not widely available. The aim of our study was to investigate the relation of patients’ heart rates to their serum beta-blocker levels. Methods: We correlated 220 measurements of serum beta-blocker levels in 106 patients with apparently resistant hypertension to their corresponding office heart rate. A significant proportion, 44.6% of patients, were non-adherent to beta-blocker treatment according to serum level measurement. Non-adherent patients had significantly higher heart rates (80.9 vs. 66.6 bpm, p < .001), systolic (157.4 vs. 147.0 mm Hg, p = .002) and diastolic blood pressure (91.1 vs. 87.2 mm Hg, p = .041) in comparison to adherent patients. Results: Heart rate above 75.5 beats per minute predicted non-adherence to beta-blocker treatment with a sensitivity of 62.5%, specificity 86.8% and AUC ROC 0.802 (p < .001). Higher heart rate cutoff might be applicable for nebivolol but was not determined due to the low number of patients treated with nebivolol. Conclusions: We concluded that heart rate was shown to be a good predictor of non-adherence to beta-blocker treatment, and might become a quick and easy measure to determine patient adherence in hypertensive patients.

Association of the right ventricle impairment with electrocardiographic localization and related artery in patients with ST-elevation myocardial infarction

INTRODUCTION The right ventricular myocardial infarction (RVMI) has traditionally been mainly related to inferior wall ST elevation myocardial infarction (STEMI). This study assessed the RVMI electrocardiographic (ECG-RVMI) signs in relationship to ECG-based STEMI localization and to the infarct related artery in patients treated with primary percutaneous coronary intervention (pPCI). METHODS Three hundred consecutive adult patients (107 females) were referred to catheterization laboratory with the acute STEMI diagnosis. In all patients, both the standard 12-lead ECGs and the right-sided precordial leads (V1R-V6R) were recorded. ECG-RVMI was diagnosed by ST segment elevation above 100μV in V4R. RESULTS ECG signs of RVMI were found in 35 and 31 (23.8% for both) patients with inferior and anterior wall STEMI, respectively. In 32 ECG-RVMI patients, the right coronary artery (RCA) was occluded while in 34 patients, the occlusions were in the left anterior descending (LAD) or the left circumflex artery. No statistically significant differences were found in ECG-RVMI patients when comparing clinical variables between those with anterior and inferior wall STEMI. CONCLUSIONS ECG signs of RVMI during acute STEMI are not uncommon. RCA was the infarction-related artery in only one half of these patients. Anterior wall STEMI and the LAD were associated with a significant proportion of ECG-RVMI cases.

Delayed-Type Hypersensitivity to Metals of Environmental Burden in Patients with Takotsubo Syndrome - Is There a Clinical Relevance?

Objective Takotsubo syndrome (TS) is a heart condition characterised by a sudden transient left ventricular dysfunction; its pathophysiology is probably associated with elevated levels of catecholamines but the exact mechanism is not known as yet. Literature and clinical experience suggest that TS affects persons with various comorbidities. This pilot work aims to evaluate the frequency of comorbidities with potential pathological immune reactivity, and to evaluate the potential association between TS and hypersensitivity to metals assessed by LTT-MELISA®. Methodology, Results A total of 24 patients (23 women, 1 man) with a history of TS attack and 27 healthy controls were evaluated. Hypersensitivity was evaluated by a lymphocyte transformation test (LTT-MELISA®); a questionnaire of environmental burden was used to select evaluated metals. A total of 19 patients (79%) had at least one condition that might potentially be associated with pathological immune reactivity (autoimmune thyroid disease, drug allergy, bronchial asthma, cancer, contact dermatitis, rheumatoid arthritis). Hypersensitivity to metals was identified significantly more frequently in TS patients than in healthy controls (positive reaction to at least one metal was identified in 95.8% of TS patients and in 59.3% of controls; p = 0.003); the difference was statistically significant for mercury (45.8% and 14.8%, respectively; p = 0.029). Conclusion Our work shows that conditions with pathological immune reactivity occur frequently in TS patients, and our data suggest a possible association between TS and hypersensitivity to metals (mercury in particular) evaluated by LTT-MELISA®. We also suggest that apart from the triggering stress factor, potential existence of other serious conditions should be considered when taking medical history of TS patients.

Plasma levels and leucocyte RNA expression of adipokines in young patients with coronary artery disease, in metabolic syndrome and healthy controls

OBJECTIVES Little is known about the role of adipokines in the pathogenesis of coronary artery disease in young patients. The aims of this study were to compare serum levels of adipokines and expression of adipokines in peripheral blood leukocytes in patients with premature coronary artery disease (CAD), metabolic syndrome and healthy individuals. DESIGN AND METHODS Sixty-five patients with premature CAD (men 18-45years old and women 18-55years old) formed the study group. The control groups were 75 patients with metabolic syndrome and 50 healthy individuals. For each group, RNA expression in peripheral blood leukocytes was determined for 24 different adipokines and 11 adipokines were examined in serum. RESULTS In individuals with CAD, serum visfatin levels were significantly higher than in metabolic syndrome and healthy controls (2.3 vs. 1.6 vs. 0.7µg/L, P<0.001) while both omentin-1 (92.9 vs. 587.0 vs. 552.3µg/L, P<0.001) and ZAG2 (45.5 vs. 72.5 vs. 77.1mg/L, P<0.001) levels were lower. The receiver operating curve (ROC) analysis for testing the validity of these adipokines in the diagnosis of CAD compared to control groups provided the following areas under the curve (AUC): omentin-1 AUC 0.97 (cut-off ≤222µg/L), ZAG2 AUC 0.89 (cut-off ≤51.7mg/L) and visfatin AUC 0.74 (cut-off ≥1.0µg/L) (P<0.001 in all cases). Visfatin and omentin-1 serum levels did not differ between the acute phase of myocardial infarction and the chronic phase of CAD. In patients with CAD, we found no significant relation between mRNA expression and adipokine concentration. CONCLUSION Serum omentin-1, visfatin and ZAG2 could serve as biomarkers of premature CAD in young apparently healthy people.

Prognostic Impact of Copeptin and Mid-Regional Pro-Adrenomedullin in Chronic Heart Failure with Regard to Comorbidities

The aim of the study is to evaluate the impact of new humoral substances: copeptin and mid- regional proadrenomedullin (MR-proADM) on one-year survival of patients with stable systolic chronic heart failure (CHF) and to compare them with AHEAD score assessing the comorbidities. The FAR NHL (FARmacology and NeuroHumoraL activation) registry is a database of patients with stable CHF (ejection fraction (EF) <50%) treated in specialized HF departments. AHEAD score is a simple bed-side mortality predictive model based on age and comorbidities. Primary endpoint after 1-year follow-up was: death or hospitalization for decompensation of HF or heart transplantation or LVAD implantation. To whole FAR NHL registry, a total amount of 1088 patients were included, in 552 of them the levels of copeptin and MR-proADM were available. Mean age was 65+12 years, mean EF was 31+9%. Patients without primary endpoint were assigned as group A (469 pts), those with the primary endpoint group B (83 pts). There were statistically significant differences between the groups in the levels of copeptin: group A median 15.9 pmol/l (3.4-50.9) vs group B 23.7 pmol/l(5.0-89.44) (p<0.001), MR-proADM: group A median 0.63 nmol/l(0.32-1.34) vs group B 0.74 nmol/l (0.4-1.94) (p<0.001). Relationship of AHEAD score to primary endpoint in the first year of follow-up was not significant, but within 24th month it reached statistical significance: p= 0.017. Patients with higher AHEAD score (more comorbidities) reached more often the primary end-point. The cutt-off value ≥ 23.7 for copeptin had 50.6% sensitivity and 73.3%. The cut –off value for MR-proADM ≥ 0.58 had higher sensitivity 79.5% and lower specificity 42.0%. For both humoral substances there was statistical significant difference for discrimination of patients with primary endpoint in lower AHEAD score groups. However, in the highest AHEAD score the level of these substances lost their predictive value.

Hypersensitivity to material and environmental burden as a possible cause of late complications of cardiac implantable electronic devices

Abstract Aims To evaluate whether patients with late complications of pacemakers or implantable cardioverter-defibrillators have hypersensitivity reactions to some of the materials used in generators or in electrodes, or to environmental metal burden. Methods and results The cohort consisted of 20 men and 4 women (mean age: 62.3 ± 17.2 years) who had a history of late complications of implanted devices. The control group involved 25 men and 8 women (mean age: 64.6 ± 14.0 years) who had comparable devices, but no history of late complications. Lymphocyte transformation test was used to evaluate hypersensitivity to eight metal pollutants (antimony, manganese, mercury, molybdenum, nickel, platinum, tin, and titanium) selected by results of questionnaires on environmental burden, and by material analysis of generators and electrode surfaces. Exposures to metal pollutants were approximately the same in patients and in controls. Titanium alloy used in generators contained at least 99.32% of titanium and trace levels of other metals; higher levels of tin and platinum were detected in electrode surfaces. Hypersensitivity reactions to mercury and tin were significantly more frequent in patients than in controls (patients and controls: mercury: 68.2 and 31.1%, respectively; P = 0.022; tin: 25.0 and 3.2%, respectively; P = 0.035). In contrast, hypersensitivity to manganese was significantly more frequent in controls than in patients (patients and controls: 13.6 and 50.0%, respectively; P = 0.008). Conclusion Our findings suggest a possible relation between hypersensitivity to metals used in implantable devices or to environmental metal burden and the occurrence of their late complications.

Prediction of major adverse kidney events in critically ill burn patients

OBJECTIVE We aimed at assessing the predictive value of plasmatic Neutrophil Gelatinase Associated Lipocalin (pNGAL) at admission and severity scores to predict major adverse kidney events (MAKE, defined as death and/or need for renal replacement therapy (RRT) and/or non-renal recovery at day 90) in critically ill burn patients. MATERIAL AND METHODS Single-center cohort study in a burn critical care unit in a tertiary center, including all consecutive severely burn patients (total burned body surface >20%) from January 2012 until January 2015 with a pNGAL dosage at admission. Reclassification of patients was assessed by Integrated Discrimination Improvement (IDI). MEASUREMENTS AND RESULTS 87 patients were included. Mean age was 47.7 (IQ 25-75: 33.4-65.2) years; total burn body surface area was 40 (IQ 25-75: 30-55) % and ICU mortality 36%. 39 (44.8%) patients presented a MAKE, 32 (88.9%) patients died at day 90. pNGAL was higher in the MAKE group (423 [IQ 25-75: 327-518]pg/mL vs 184 [IQ 25-75: 147-220]pg/mL, p<0.001). In multivariate analysis, pNGAL and abbreviated burn severity index (ABSI) remained associated with MAKE (OR 1.005 [CI 95% 1.0005-1.009], p=0.03 and OR 1.682 [CI95%1.038-2.726], p=0.035 respectively). Adding pNGAL to abbreviated burn severity index, simplified organ failure assessment and the simplified acute physiology score 2 did outperform clinical scores for the prediction of MAKE and AKI and for most severe forms of AKI and allowed a statistically significant reclassification of patients compared to ABSI for MAKE, RRT, AKI at Day 7 and AKI during hospitalization with a number of patients needed to screen to detect one extra episode of MAKE was 44, 13 for severe AKI and 15 for AKI. CONCLUSIONS pNGAL at admission is associated with the risk of MAKE in this population, and outperform severity scores when associated. Interventional studies are now needed to assess if impact of biomarkers-guided strategies would improve outcome.

Relationship between TRAIL and Left Ventricular Ejection Fraction in Patients with ST-Elevation Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention

Background Apoptosis plays an important role in the myocardial injury after acute myocardial infarction and in the subsequent development of heart failure. Aim To clarify serum kinetics of apoptotic markers TRAIL and sFas and their relation to left ventricular ejection fraction (LVEF) in patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). Methods In 101 patients with STEMI treated with pPCI, levels of TRAIL and sFas were measured in series of serum samples obtained during hospitalization and one month after STEMI. LVEF was assessed at admission and at one month. Major adverse cardiovascular events (MACE, i.e., death, re-MI, and hospitalization for heart failure and stroke) were analysed during a two-year followup. Results Serum level of TRAIL significantly decreased one day after pPCI (50.5pg/mL) compared to admission (56.7pg/mL), subsequently increased on day 2 after pPCI (58.8pg/mL), and reached its highest level at one month (70.3pg/mL). TRAIL levels on days 1 and 2 showed a significant inverse correlation with troponin and a significant positive correlation with LVEF at baseline. Moreover, TRAIL correlated significantly with LVEF one month after STEMI (day 1: r=0.402, p<0.001; day 2: r=0.542, p<0.001). On the contrary, sFas level was significantly lowest at admission (5073pg/mL), increased one day after pPCI (6370pg/mL), and decreased on day 2 (5548pg/mL). Significantly highest sFas level was marked at one month (7024pg/mL). sFas failed to correlate with LVEF at baseline or at one month. Both TRAIL and sFas showed no ability to predict improvement of LVEF one month after STEMI or a 2-year MACE (represented by 3.29%). Conclusion In STEMI treated with pPCI, TRAIL reaches its lowest serum concentration after reperfusion. Low TRAIL level is associated with worse LVEF in the acute phase of STEMI as well as one month after STEMI. Higher TRAIL level appears to be beneficial and thus TRAIL seems to represent a protective mediator of post-AMI injury.

Higher incidence of hypotension episodes in women during the sub-acute phase of ST elevation myocardial infarction and relationship to covariates

Objective The introduction of primary percutaneous coronary intervention (PPCI) has modified the profile of ST elevation myocardial infarction (STEMI) patients. Occurrence and prognostic significance of hypotension episodes are not known in PPCI treated STEMI patients. It is also not known whether and/or how the hypotension episodes correlate with the degree of myocardial damage and whether there are any sex differences. Methods Data of 293 consecutive STEMI patients (189 males) treated by PPCI and without cardiogenic shock were analyzed. Blood pressure was measured noninvasively. A hypotensive episode was defined as a systolic blood pressure below 90 mmHg over a period of at least 30 minutes. Results A hypotensive episode was observed in 92 patients (31.4%). Female sex was the strongest independent predictor of hypotension episodes (p < 0.0001), while there was no relationship to electrocardiographic STEMI localization. Hypotensive patients had significantly higher levels of troponin T and brain natriuretic peptide; hypotensive episodes were particularly frequent in women with increased troponin T. Treatment with angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB) and betablockers was less frequent in hypotensive patients. After a mean 20-month follow-up, all-cause mortality did not differ between hypotensive patients and others. However, mortality in hypotensive patients who did not tolerate ACEI/ARB therapy was significantly higher compared to other hypotensive patients (p = 0.016). Conclusion Hypotension episodes are not uncommon in the sub-acute phase of contemporarily treated STEMI patients with a striking difference between sexes—female sex was the strongest independent predictor of hypotension episodes. Hypotensive episodes may lead to a delay in pharmacotherapy which influences prognosis. Higher incidence of hypotension in women could at least partially explain the sex-related differences in the use of cardiovascular pharmacotherapy which was repeatedly observed in various studies.

Pressure Injuries in Inpatient Care Facilities in the Czech Republic: Analysis of a National Electronic Database

PURPOSE: The purpose of this study was to analyze pressure injury (PI) occurrence upon admission and at any time during the hospital course inpatients care facilities in the Czech Republic. Secondary aims were to evaluate demographic and clinical data of patients with PI and the impact of a PI on length of stay (LOS) in the hospital. DESIGN: Retrospective, cross-sectional analysis. SETTING AND SUBJECTS: The sample comprised data of hospitalized patients entered into the National Register of Hospitalized Patients (NRHOSP) database of the Czech Republic between 2007 and 2014 with a diagnosis L89 (pressure ulcer of unspecified site based on the International Classification of Diseases, Tenth Revision, ICD-10). Electronic records of 17,762,854 hospitalizations were reviewed. METHOD: Data from the NRHOSP from all acute and non–acute care hospitals in the Czech Republic were analyzed. Specifically, we analyzed patients admitted to acute and non–acute care facilities with a primary or secondary diagnosis of PI. RESULTS: The NRHOSP database included 17,762,854 cases, of which 46,224 cases (33,342 cases in acute care hospitals; 12,882 in non–acute care hospitals) had the L89 diagnosis (0.3%). The mean age of patients admitted with a PI was 73.8 ± 15.3 years (mean ± SD), and their average LOS was 33.2 ± 76.9 days. The mean LOS of patients hospitalized with L89 code as a primary diagnosis (n = 6877) was significantly longer compared to those patients for whom L89 code was a secondary diagnosis (25.8 vs 20.2 days, P < .001) in acute care facilities. In contrast, we found no difference in the mean LOS for patients hospitalized in non–acute care facility (58.7 days vs 65.1 days; P = .146) with ICD code L89. CONCLUSION: Pressure injuries were associated with significant LOS in both acute and non–acute care settings in the Czech Republic. Despite the valuable insights we obtained from the analysis of NRHOSP data, we advocate creation of a more valid and reliable electronic reporting system that enables policy makers to evaluate the quality and safety concerning PI and its impact on patients and the healthcare system.