Małgorzata Lelonek

Pregnancy in Women With a Mechanical Heart Valve Data of the European Society of Cardiology Registry of Pregnancy and Cardiac Disease (ROPAC)

Background— Pregnant women with a mechanical heart valve (MHV) are at a heightened risk of a thrombotic event, and their absolute need for adequate anticoagulation puts them at considerable risk of bleeding and, with some anticoagulants, fetotoxicity. Methods and Results— Within the prospective, observational, contemporary, worldwide Registry of Pregnancy and Cardiac disease (ROPAC), we describe the pregnancy outcome of 212 patients with an MHV. We compare them with 134 patients with a tissue heart valve and 2620 other patients without a prosthetic valve. Maternal mortality occurred in 1.4% of the patients with an MHV, in 1.5% of patients with a tissue heart valve (P=1.000), and in 0.2% of patients without a prosthetic valve (P=0.025). Mechanical valve thrombosis complicated pregnancy in 10 patients with an MHV (4.7%). In 5 of these patients, the valve thrombosis occurred in the first trimester, and all 5 patients had been switched to some form of heparin. Hemorrhagic events occurred in 23.1% of patients with an MHV, in 5.1% of patients with a tissue heart valve (P<0.001), and in 4.9% of patients without a prosthetic valve (P<0.001). Only 58% of the patients with an MHV had a pregnancy free of serious adverse events compared with 79% of patients with a tissue heart valve (P<0.001) and 78% of patients without a prosthetic valve (P<0.001). Vitamin K antagonist use in the first trimester compared with heparin was associated with a higher rate of miscarriage (28.6% versus 9.2%; P<0.001) and late fetal death (7.1% versus 0.7%; P=0.016). Conclusions— Women with an MHV have only a 58% chance of experiencing an uncomplicated pregnancy with a live birth. The markedly increased mortality and morbidity warrant extensive prepregnancy counseling and centralization of care.Background— Pregnant women with a mechanical heart valve (MHV) are at a heightened risk of a thrombotic event, and their absolute need for adequate anticoagulation puts them at considerable risk of bleeding and, with some anticoagulants, fetotoxicity. Methods and Results— Within the prospective, observational, contemporary, worldwide Registry of Pregnancy and Cardiac disease (ROPAC), we describe the pregnancy outcome of 212 patients with an MHV. We compare them with 134 patients with a tissue heart valve and 2620 other patients without a prosthetic valve. Maternal mortality occurred in 1.4% of the patients with an MHV, in 1.5% of patients with a tissue heart valve ( P =1.000), and in 0.2% of patients without a prosthetic valve ( P =0.025). Mechanical valve thrombosis complicated pregnancy in 10 patients with an MHV (4.7%). In 5 of these patients, the valve thrombosis occurred in the first trimester, and all 5 patients had been switched to some form of heparin. Hemorrhagic events occurred in 23.1% of patients with an MHV, in 5.1% of patients with a tissue heart valve ( P <0.001), and in 4.9% of patients without a prosthetic valve ( P <0.001). Only 58% of the patients with an MHV had a pregnancy free of serious adverse events compared with 79% of patients with a tissue heart valve ( P <0.001) and 78% of patients without a prosthetic valve ( P <0.001). Vitamin K antagonist use in the first trimester compared with heparin was associated with a higher rate of miscarriage (28.6% versus 9.2%; P <0.001) and late fetal death (7.1% versus 0.7%; P =0.016). Conclusions— Women with an MHV have only a 58% chance of experiencing an uncomplicated pregnancy with a live birth. The markedly increased mortality and morbidity warrant extensive prepregnancy counseling and centralization of care. # CLINICAL PERSPECTIVE {#article-title-24}

Detection of infectious agents by polymerase chain reaction in human aortic wall

INTRODUCTION Several studies have been suggested that infectious agents may induce or progress the process of atherosclerosis in humans. In the present study, the samples of visually healthy human aortic wall were examined for the presence of Chlamydia pneumoniae, Mycoplasma pneumoniae, Helicobacter pylori, herpes simplex virus (HSV), and cytomegalovirus (CMV). METHODS Bacterial DNA of C. pneumoniae, M. pneumoniae, and H. pylori and viral DNA of HSV and CMV were analyzed by polymerase chain reaction. The specimens were obtained from 40 patients with atherosclerotic three-vessel stable coronary artery disease referred to surgical revascularization (coronary group) and 20 controls referred to aortic valve replacement (valve group). RESULTS C. pneumoniae was detected in 11 of 40 samples of aorta in coronary group (27.5%) and 5 of 20 in valve group (25%). M. pneumoniae was found in 6 of 40 (15%) and 5 of 20 (25%) samples, and CMV was found in 22 of 40 (55%) and 10 of 20 (50%) samples. The most frequent detected pathogens were H. pylori and HSV. H. pylori was found in 32 of 40 samples of aortic wall in coronary group (80%) and 17 of 20 samples in valve group (85%), whereas HSV was found in 27 of 40 (67.5%) and 17 of 20 (85%) aortic wall specimens. CONCLUSION Results demonstrate that C. pneumoniae, M. pneumoniae, H. pylori, CMV, and HSV can be detected in macroscopically healthy aortic wall of coronary and valve patients in similar frequency, which do not support hypothesis concerning the role of microorganisms in atherosclerosis etiology.

Genetic variability and the risk of myocardial infarction in Poles under 45 years of age

Introduction Myocardial infarction is caused by the obstruction of an artery in places of atherosclerosis plaque rupture. Endothelial cells during their activation express chemoattractant and adhesion molecules whereas infiltrating inflammatory cells produce enzymes, predisposing a lesion to rupture. Material and methods We investigated the correlation between polymorphisms in the human genes E-selectin (Ser128Arg), ICAM1 (K469E), OLR1 (K167N), MMP1 (1G/2G) and MMP3 (−1612 5A/6A) and the risk of MI in young Poles under 45 years. There was no significant difference in the frequency of single nucleotide polymorphism (SNP) of the studied genes E-selectin (Ser128Arg), ICAM1 (K469E), OLR1 (K167N) and MMP3 (−1612 5A/6A) between patients with MI and controls. Results The analysis of the association of the 1G2G polymorphism with the risk of myocardial infarction indicated an odds ratio (OR) of 5.68 (95% confidence interval [95% CI] 2.60 to 12.36). Other factors associated with myocardial infarction were: smoking (OR 4.12; 95% CI 1.63–10.44), male sex (OR 16.02; 95% CI 5.90–43.46), hypercholesterolaemia (OR 2.74; 95% CI 1.29–5.83) and arterial hypertension (OR 4.56; 95% CI 1.66–14.47). Conclusions We found that only MMP1 1G/2G polymorphism is associated with myocardial infarction in the Polish population of individuals younger than 45 years. Clinical factors seemed to play a greater role in the analysed group.

A novel approach to syncopal patients: association analysis of polymorphisms in G-protein genes and tilt outcome.

AIMS G-proteins signal transduction pathways play a basic role in cardiovascular reflexes. We hypothesized that the predisposition to reflex-mediated syncope may be associated with genetic variations in G-protein genes. The aim of this study was to evaluate the effect of three single-nucleotide polymorphisms in G-protein genes on tilting outcome in syncopal patients. METHODS AND RESULTS A total of 217 syncopal patients free from any other disease were genotyped and examined related to tilting results. Genotyping was performed by polymerase chain reaction followed by restriction fragment length polymorphism in gene encoding the Gs-protein alpha-subunit (polymorphism C393T), the G-protein beta 3 subunit--GNB3 (polymorphism C825T)--and for the cardiac regulator of G-protein signalling RGS2 (polymorphism C1114G). In multivariate logistic regression analysis, the homozygotes 825TT GNB3 (OR 0.37; 95% CI 0.14-0.97; P < 0.05) and body mass index (OR 0.87; 95% CI 0.78-0.97; P = 0.005) were independently associated with a lower chance of positive tilting results. No relationship was found between Vasovagal Syncope International Study type of syncope and the studied genotypes or the carriage of the polymorphic alleles. CONCLUSIONS An association between tilting results and C825T GNB3 polymorphism in syncopal patients was found. The syncopal homozygotes 825TT GNB3 had a significantly lower chance of syncope during tilt testing.

Soluble ST2 protein in chronic heart failure is independent of traditional factors.

Introduction ST2 protein is the interleukin 33 (IL-33) receptor, whose serum level depends on the biomechanical strain of cardiac myocytes. The aim of this study was to analyse the relationship between soluble ST2 (sST2) level and traditional factors in patients with chronic heart failure. Material and methods Sixty-six patients (mean age 62 years, 75% males) in stable NYHA class I-III with left ventricular ejection fraction < 45% were included in the study. Clinical, biochemical, electrocardiographic, echocardiographic and angiographic data were analysed. Patients were divided into groups depending on sST2 median: > 0.28 ng/ml (n = 31) vs. ≤ 0.28 ng/ml (n = 35). sST2 was measured using a quantitative ELISA kit. In order to define factors associated with sST2 levels uni- and multivariate regression analysis was performed. Results There was no relationship between sST2 levels and age (p = 0.67), body mass index (p = 0.19), hsTnT (p = 0.7) or other analysed parameters (all p > 0.05), except for N-terminal prohormone B-type natriuretic peptide (NT-proBNP). A significant positive correlation between sST2 and NT-proBNP was found (p = 0.013, R = 0.395). Multivariate analysis revealed that the stage of coronary artery disease and NT-proBNP were independent factors associated with sST2 concentration (p = 0.04). Intriguing is the fact that the fewer the sclerotic changes present in arteries, the higher was the sST2 level (β = –0.381, p = 0.04). Conclusions sST2 protein is independent of traditional factors which usually affect levels of NT-proBNP. In chronic heart failure, sST2 protein may be of greater importance in idiopathic dilated cardiomyopathy than in ischaemic aetiology, which seems to be associated with the molecular mechanism (biomechanical strain) related to sST2.

Prospective evaluation of diagnostic work-up in syncope patients: results of the PL-US registry

AIMS Syncope is a common problem. Demographic and clinical characteristics of patients admitted to different types of centres may vary, physicians adherence to the guidelines has been examined only in a few studies, and the requirements for implantable loop recorders (ILR) have not been well defined. The aim of this study was to (i) compare demographic and clinical characteristics of patients with syncope diagnosed and treated in tertiary electrophysiology cardiac centres and those attending syncope units or general hospitals, (ii) assess how physicians adhere to the published guidelines, and (iii) calculate the requirement for ILR insertion. METHODS AND RESULTS In total, 669 consecutive patients with syncope, admitted to 18 electrophysiological cardiac tertiary centres over a mean of 3 months (range 1-10 months), entered a special Internet database called the PL-US (Polish patients with Unexplained Syncope) registry. Detailed demographic and clinical characteristics of the patients, including the results of all diagnostic tests performed, were analysed. Adherence to the guidelines was assessed, based on the published recommendations. The ILR implantation was indicated when (i) all other tests were inconclusive (unexplained syncope) and (ii) syncope associated with injury or presence of organic heart disease or past medical history and ECG suggesting arrhythmic syncope. Syncope of cardiac/arrhythmic origin was the most frequent diagnosis (53%), followed by reflex syncope (33%). Adherence to the guidelines was less than satisfactory-measurement of blood pressure in an upright position, carotid sinus massage, exercise testing, and electrophysiological study were underused, whereas prolonged ECG monitoring and neurological consultations were overused. Unexplained syncope had 58 (9%) patients, and 42 (72%) of them had indication for ILR which accounts for 6% of the whole study population. The calculated need for ILR was 222 implants/million inhabitants/year. CONCLUSION Patients with syncope admitted to the tertiary electrophysiology cardiac centres are a highly selected group of patients with syncope and differ in their characteristics as well as underlying diseases to those managed at general hospitals, outpatient clinics, or special syncope units. In Poland, the adherence to the published guidelines is far from satisfactory. At least 6% of all consecutive patients with syncope are candidates for ILR insertion.

Polymorphism C1114G of gene encoding the cardiac regulator of G-protein signaling 2 may be associated with number of episodes of neurally mediated syncope.

BACKGROUND AND AIMS The cardiac regulator of G-protein signaling 2 (RGS2) negatively regulates G-protein-coupled receptor signaling. The C1114G polymorphism reduces RGS2 gene expression. This molecular disorder may be one of the important factors influencing progress of neurally mediated syncope. The aim of the study was to evaluate the association between C1114G RGS2 polymorphism and tilting results and number of syncope episodes in patients with no other diseases. METHODS Of 214 tilted patients (39% males, 39.7 +/- 17.1 years of age), genomic DNA was extracted from cellular blood components. C1114G RGS2 polymorphism was diagnosed by designed primers. Clinical variables and genetic traits were introduced into multivariate stepwise regression. Analysis was performed as follows: positive tilting n = 145 vs. negative n = 69, positive passive n = 49 vs. nitroglycerin (NTG)-positive n = 96, dominant vasodepressive n = 111 vs. cardioinhibition n = 34; and in number of syncope groups with cut-off >or=10 vs. <10. RESULTS No relationship was found between the studied polymorphism and outcome of tilting (p >0.05). In multivariate regression model, homozygosity G/G 1114 RGS2 was the only variable associated with a reduced number of episodes of syncope (95% CI 2.3-10.9; p = 0.04). CONCLUSIONS Our preliminary results suggest the association of G/G 1114 RGS2 genotype with the number of episodes of neurally mediated syncope. Detailed molecular mechanism of the influence of the studied polymorphism on syncopal number is probably associated with the reduced expression of RGS2 gene.

Soluble ST2 protein in the short-term prognosis after hospitalisation in chronic systolic heart failure

BACKGROUND The prognosis in patients with chronic heart failure (CHF) is poor. ST2 protein is a promising prognostic biomarker for CHF. ST2 belongs to the cardioprotective signalling pathway involving interleukin-33 and its concentration in the serum depends on the biomechanical stress of cardiomyocytes (biomechanical strain). AIM To determine the prognostic value of ST2 in short term follow-up after hospitalisation among patients with CHF. METHODS The study included 167 patients (mean age 62 years, 83% men) in stable NYHA class I-III with left ventricular ejection fraction (LVEF) of ≤ 45% (average 29.65%, ranges 13-45%). We analysed 58 variables including: demographics, co-morbidities, resting ECG, echocardiographic and coronary arteriography data, basic laboratory tests including N-terminal prohormone B-type natriuretic peptide (NT-proBNP), serum concentration of soluble form of ST2 (sST2) using quantitative ELISA test ST2 Kit (Medical and Biological Laboratories; Japan) and adverse cardiovascular events during a one year observation. In the study, the primary endpoint (death) and the composite endpoint (hospitalisation for HF worsening, worsening in NYHA functional class, the need to increase the dose of diuretics, and/or death in a one year observation) were determined. RESULTS Patients who died (n = 24; 14.55%) were in more advanced NYHA class, had prolonged QRS duration, higher levels of sST2, NT-proBNP, and lower estimated glomerular filtration rate. From multivariate analysis, the independent variable for the primary endpoint was NT-proBNP (OR = 1.00012; 95% CI 1.00002-1.00022; p = 0.018). 93 (56%) patients reached the composite endpoint. Multivariate analysis revealed that fasting glucose (OR = 1.343; 95% CI 1.041-1.732; p = 0.023) and sST2 (OR = 3.593; 95% CI 1.427-9.05; p = 0.007) independently enhanced the risk of composite endpoint occurrence in a one year observation. CONCLUSIONS In patients with CHF with LVEF ≤ 45%, the prognostic value of sST2 protein in a short-term observation of one year was confirmed. sST2 protein was an independent variable for the composite endpoint, which consisted of worsening NYHA functional class, hospitalisation for worsening of HF, the need to increase the dose of diuretics, and/or death.

Early Repolarization Variant in Syncopal Patients Referred to Tilt Testing

Early repolarization variant (ERV) was recently described as an electrocardiogram (ECG) pattern associated with increased risk of sudden cardiac death (SCD) in some populations. We decided to establish the significance of ERV in syncopal patients referred to tilt testing due to suspected reflex syncope.

C825T G-protein β3 subunit gene polymorphism, tilt test results and point score in syncopal patients

We evaluated C825T polymorphism of the G-protein β3 subunit gene in syncopal patients in regard to tilting results and the diagnostic point score (PS). In a multivariate analysis, only PS ≥ −2 was associated with positive passive tilting (P < 0.05). The relationship between tilting results and this polymorphism needs further study.