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Biomedical subjects

J Spinar

Publications and source records attributed to J Spinar.

At least 19 recordsLinked to original sources
PubMed2006

[Pharmacogenetics of chronic heart failure--beta blockers].

BACKGROUND: Activation of the renin-angiotensin (RAS) cascade and sympathetic nervous systems adversely affect heart failure progression. ACE deletion allele (ACE D) of insertion/deletion polymorphism in the gene coding for angiotensin-1 converting enzyme is associated with increased renin-angiotensin activation. The aim of the study was to test pharmacogenetic associations of I/D ACE genotype with beta blockers therapy in patients with chronic heart failure. METHODS AND RESULTS: A total of 241 patients were included in the study, 63% with betablocker therapy and 37% without it. Using polymerase chain reaction (PCR) method, I/D genotype was detected in 2% agarose electrophoretic gel in UV light. Patients with chronic heart failure and with the II genotype of polymorphism I/D ACE were younger, with more frequent administration of betablockers and diuretics, with less regular administration of aspirin and with lower glycemia and plasma TNFalpha level. A significant difference in genotype distribution and allele frequency between patients with recommended dose and patients without betablockers therapy was proved, when a decrease of the D allele in patients with betablockers had been observed. Contemporary evaluating of AC inhibitor and betablocker therapy, a decrease of ID+DD genotypes in patients with lower than 50% recommended dose compared with the others was found. CONCLUSIONS: In this study, we proved statistically significant interactions between genotypes in I/D ACE polymorphism, betablocker administration, its dosing and pharmacogenetic interaction with ACE inhibitors in patients with chronic heart failure.

Adrenergic beta-Antagonists↗
PubMed2006

[Does G8002A polymorphism in endothelin gene have a meaning for other risks at the patients with heart failure?].

UNLABELLED: Objective of the work is to determine the relation of G8002 polymorhism in endothelin 1 gene to the incidence of diabetes mellitus (DM), ischemic disease of lower limbs (ID LL) and myocardial infarction (MI) at the patients with heart failure. METHODICS: There were observed 224 patients, 176 males, 48 females, average age 55 +/- 12 years, NYHA II/III/IV 82/131/11, average EF LK 25 +/- 7 %, diagnosis ischemic heart disease (IHD) 133, dilatation cardiomyopathy (DCMP) 91. RESULTS: Patients with IHD had higher incidence of hypertension (p < 0.0007), diabetes mellitus (p < 0.00007) and hyperlipoproteinemy (p < 0.0006) than patients with DCMP. Patients with IHD who experienced MI had a difference in the distribution of G8002A genotypes for endothelin 1 gene: G 0.718 and A 0.282 alleles vs ischemic patients without MI G 0.882 and A 0.118 (p < 0.05) alleles. Ischemic patients with DM had G allele in 0.67 and A 0.33 unlike ischemic patients without DM G allele 0.791 and A 0.209 (p < 0.03). Ischemic patients with synchronous ID LL had G allele in 0.718 and A 0.282 vs ischemic patients without ID LL G allele 0.882 and A 0.118 (p < 0.0004). At the patients with DCMP there was not found a difference in G8002A genotype and the presence of DM or ID LL. RESULTS: At the patients with heart failure on the basis of ischemic heart disease there was found a difference in endothelin G8002A genotype distribution depending on other accessory diseases. There was more frequently present an A allele and less present G allele in the ischemic patients with DM, who had experienced MI or ID LL than in the ischemic patients without these diseases. Genotype with A allele is connected with higher risk of all accessory diseases.

Alleles↗
PubMed2006

[Is the left ventricle enddiastolic pressure pathological in the older population?].

INTRODUCTION: The percentage of older population has significantly increased in the recent decades. Morphologic and functional changes of the cardiovascular system go together with ageing. The aim of the study should show the correlation between the age and left ventricular enddiastolic pressure (LVDEP) value. METHODS: 106 patients of the age from 23 to 79 years without an organic heart disease and the history of hypertension underwent elective coronary angiography including left ventricle angiography between 1999 and 2002. LVEDP was obtained as an average value from 8 consecutive beats without extrasystoles. According to the relation between increased relative frequency of LVEDP and age patients were divided into two groups: 50 years and older (80 patients) and younger than 50 years (26 patients). RESULTS: An average LVEDP value in older population versus younger population was 12.1 +/- 5.0 mm Hg vs 8.9 +/- 3.4 mm Hg, p < 0.05. Increased LVEDP in yonger population was found in only 11.5 % vs 46.2 % in older group, p < 0.01 and the LVEDP was age dependent, p < 0.05. CONCLUSIONS: In compliance with about mentioned results we suppose that the age is a factor with impact to LVEDP value. LVEDP values > 12 mm Hg in older population may not be pathological and probably are due to the left ventricle diastolic dysfunction in consequence with ageing.

Adult↗
PubMed2006

[Mutational analysis of LQT genes in individuals with drug induced QT interval prolongation].

BACKGROUND: In a long list of non-cardiovascular drugs a risk of QT interval prolongation and thus an increased risk of malignant arrhythmias has been described. The precise mechanism remains unclear. Many of these drugs are potent blockers of cardiac ion channels. Thus, prolongation of repolarization could be caused by latent ion channel genes mutations which are revealed under stress conditions. GROUP OF PATIENTS AND METHODS: Patients were recruited in screening of antipsychotic drugs with proarrhythmic potential, another sporadic cases were reffered from regional hospitals. In 13 individuals pathologic values of corrected QT interval (> 0.44 s in males, > 0.46 s in females) were observed. Eleven patients gave their consent to mutational analysis of KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2 and KCNJ2 genes (associated with congenital long QT syndrome). RESULTS: At present complete results of mutational analysis are available in 8 patients. In 5 individuals changes in DNA sequence were found which are considered normal variants according to the literature (nucleotide and aminoacid polymorphisms, intronic variants). In 1 male a KCNQ1 gene mutation A590T was identified (yet not reported in literature). CONCLUSION: Mechanisms of drug-induced QT interval prolongation is complex and it cannot be explained simply by ion channel disorders.

DNA Mutational Analysis↗
PubMed2006

[Extension of QT interval as a consequence of risk factor accumulation--case study].

BACKGROUND: Many non-cardiovascular drugs have a potential for QT interval prolongation. This phenomenon can be related to occurence of ventricular tachycardia torsades de pointes, syncopi and even sudden death. DESCRIPTION OF THE CASE: A female patient treated with antracycline cytostatics developed a depression of left ventricle ejection fraction. At the same time she was administered 2 common drugs with proarrhythmic potential--terfenadine and itraconazole. In this patient hypokalemia also occured. Combination of the above mentioned risk factors led to QT interval prolongation and frequent ventricular tachycardias torsades de pointes degenerating in ventricular fibrillations with need of repeated defibrillations. Both drugs were withdrawn and dysiontaemia corrected. Then arrhythmias disappeared and QT interval completely normalized. In this patient the congenital long QT syndrome was not proved. DISCUSSION AND CONCLUSIONS: In proarrhythmic effect of non-cardiovascular drugs the following factors play role: predisposition of a particular individual, "repolarization reserve", interindividual differences in drug metabolism. The risk factors are age, sex, dysiontaemia, heart disease and drug interactions. By different choice of medication and attention to risk factors teh life threat to the described patient could have been avoided.

Adult↗
PubMed2006

[Comparison of plasmatic levels of B-natriuretic peptide with echocardiographic indicators of left ventricle function after doxorubicin therapy].

THE STUDY OBJECTIVE: The aim of the study was to find out the relationship between plasmatic levels of brain natriuretic peptide (BNP) and echocardiographic indicators of left ventricle (LV) function in patients who were in a long-term remission after the therapy of hematological malignity and examined in order to diagnose the late cardiotoxicity of doxorubicin. METHODS AND PATIENT SAMPLE: We enrolled 55 patients (31 men/24 women) aged 43 +/- 16 (median 41; 21-79) who were treated for historically diagnosed malignant lymphoma. At the time of examination, all patients were in a long-term remission and, at the same time, they completed their initial therapy 6.2 +/- 1.5 (median 5; 5-10) years ago. Patients were examined via resting echocardiography before and after the therapy and during the follow-up examination. We determined the left ventricle ejection fraction (LV EF), parameters of diastolic function and the Doppler parameters of systolic and diastolic function (MPI-Tei index). During the follow-up examination, we measured plasmatic levels of BNP (standard levels were between 0 and 29 pmol/1). RESULTS: Follow-up examination showed that EF of five patients (9 %) decreased below 50% and three patients had symptoms of heart failure. Although EF of another eleven patients (20%) was in the physiological range, it decreased by more than 10% as compared with their pre-treatment EF values. Seventeen patients (30 %) showed higher MPI > 0.55 and twenty patients (36%) demonstrated diastolic dysfunction (impaired relaxation). BNP > 29 pmol/l was observed only in patients with EF < 50% and heart failure symptoms. BNP values significantly correlated only with endsystolic (r = 0.82; p < 0.0001) and enddiastolic (r = 0.72; p < 0.0001) volume of LV. On the other hand, BNP of 11.4 pmol/l showed negative predictive value for the following parameters: 80% for decrease of EF by more than 10%; 72% for detection of MPI > 0.55; and 70% for detection of relaxation disorder, i.e. the diagnostics of subclinical cardiotoxicity. CONCLUSIONS: The present study highlights the practical importance of measuring BNP levels when diagnosing the late changes of LV functions after doxorubicin chemotherapy. Standard cut-off BNP (29 pmol/1) used in diagnostics of heart failures identifies patients with pathological EF and heart failure symptoms. Cut-off BNP of 11.4 pmol/l has sufficient negative predictive value to exclude subclinical damage to the myocardium.

Antibiotics, Antineoplastic↗
PubMed2005

MORE--MOexipril and REgression of left ventricle hypertrophy in combination therapy A multicentric open label clinical trial.

AIM: To evaluate the effect of ACE inhibitor moexipril if added to combination therapy in patient with poorly controlled hypertension. PATIENTS: Four hundred twenty patients with hypertension treated with monotherapy or two dug combination without an ACE inhibitor or AII antagonist and with blood pressure >/=140/90 mm Hg. DESIGN: Single-blind, multicenter, open, with a double-blind echocardiographic examination. METHODS: Basic cardiological examination including echocardiography was performed before including into the study. If the patient fulfilled inclusion criteria, ACE inhibitor moexipril was added to the therapy and uptitrated according to BP values. BP measuring, clinical examination, and basic laboratory were performed every month, echocardiography was repeated after 6 months. RESULTS: Sitting BP decreased from 161.43+/-12.84/96.72+/-7.74 mm Hg to 135.87+/-9.98/82.36+/-5.83 mm Hg (p<0.0001), heart rate from 73.08+/-9.87 to 69.80+/-7.91 (p<0.0001). Three hundred forty patients (81%) had BPd <90 mm Hg after 6 months. Left ventricle mass decreased from 263.24+/-94.69 to 246.71+/-89.08 g (p<0.0001), left atrium decreased from 39.78+/-5.40 to 38.89+/-4.98 mm (p<0.0001), and E/A ratio increased from 0.91+/-0.28 to 0.94+/-0.27 (p<0.0005). Plasma cholesterol level decreased from 5.67+/-0.87 to 5.44+/-0.68 mmol/l (p<0.0001) and plasma triglycerides decreased from 1.92+/-1.07 to 1.78+/-0.80 mmol/l (p<0.001). A greater effect on blood pressure reduction was observed in combination ACE-I+diuretics than in combination ACE-I+betablocker or ACE-I+Ca blocker (statistically borderline). A statistically greater effect on left ventricle mass was observed if moexipril was added to a diuretic than to Ca blocker (p=0.02) or betablocker (p=0.04). SUMMARY: ACE inhibitor moexipril added to combination therapy of hypertension had similar effect on blood pressure reduction and left ventricle mass as in monotherapy trials. The most effective combination is ACE ihibitor+thiazide diuretic. A very small number of adverse events was observed; cough was reported in 2.14% of patients. Decreased heart rate and improvement in lipid parameters were observed in the whole group.

Adrenergic beta-Antagonists↗
PubMed2005

[Comparison of the prevalence of non-invasive risk markers of the sudden cardiac death in patients treated by thrombolysis and by percutaneous transluminal coronary angioplasty].

BACKGROUND: Myocardial infarction survivors may develop a higher risk of sudden cardiac death. The risk markers: left ventricular ejection fraction, ventricular premature beats, late potentials on averaged ECG, baroreflex sensitivity and heart rate variability are used as non-invasive stratification markers. METHODS AND RESULTS: Occurrence of the autonomic and morphologic dysfunction risk markers in the myocardial infarction patients treated by thrombolysis and by primary percutaneous transluminal coronary angioplasty (PTCA) is compared. We studied a cohort of 48 acute myocardial infarction survivors treated by primary PTCA and 96 patients treated by thrombolysis. CONCLUSIONS: Patients treated by primary PTCA had significantly lower occurrence of premature ventricular beats and pathological parameters of the heart rate variability.

Angioplasty, Balloon, Coronary↗
PubMed2004

Big endothelin in chronic heart failure: marker of disease severity or genetic determination?

The first objective of the study was to compare the levels of big endothelin and endothelin-1 and other noninvasive parameters used for evaluation of disease severity in patients with stable chronic heart failure (CHF). Endothelin-1 and big endothelin plasma concentrations were measured in 124 chronic heart failure patients. The second objective of the study was to prove an association between endothelin-1 and big endothelin plasma levels and two frequent polymorphisms in the endothelin-1 coding gene (6p21-23) -3A/-4A and G (8002) A in patients with chronic heart failure. Thirdly, we tried to associate other noninvasive parameters of CHF, especially cardiothoracic index (CTI), NYHA classification, signs of pulmonary congestion (PC) and ejection fraction (EF) with determined genotypes of the two ET-1 polymorphic variants. There were significant differences between big endothelin levels in NYHA II versus IV (P<0.001) and NYHA III versus IV (P<0.001) and endothelin-1 in NYHA II versus IV (P<0.001) and NYHA III versus IV (P<0.001). No associations between plasma levels of endothelin-1 and big endothelin and polymorphisms G (8002) A and -3A/-4A in gene coding endothelin-1 were found. In patients with CHF with CTI above 60% the number of carriers of genotypes with ET-1 8002A (AA and AG genotypes) increases. Concerning on the -3A/-4A ET-1 polymorphism, we observed a significant difference in genotype distribution as well as in allelic frequency in the group of patients with CTI above 60% between patients without and with pulmonary congestion. The allelic frequency of 3A allele is twice elevated in the patients with pulmonary congestion (37.8 vs. 78.1%, respectively).

Analysis of Variance↗
PubMed2004

[Specific complications in the treatment with implantable cardioverter-defibrillators].

BACKGROUND: Using implantable cardioverter-defibrillators in treatment of malignant ventricular arrhythmias revealed new complications specific to this therapy. Inappropriate therapy, arrhythmic storm and device related proarrhythmia belong to the most significant complications. The authors describe specific complications in a group of ICD patients, analyze their etiology and prognostic value. There are some recommendations for the management of specific complications. METHODS AND RESULTS: 138 consecutive patients underwent ICD implantation between 1994-2001. Median follow-up was 47,35 months. Average left ventricular ejection fraction was 38 +/- 14% and 71% of patients suffered from coronary artery disease. From the total of 2490 arrhythmic episodes 1490 were evaluated in detail. 253 episodes (17%) were classified as inappropriate therapy. The most common etiology of inappropriate therapy was atrial fibrillation with rapid ventricular response (68%), atrial flutter (13%) and sinus tachycardia (11%). After the therapeutic intervention, 65% of them remained free of inappropriate therapy. There were 38 arrhythmic storms in 19 patients as another serious complication. CONCLUSIONS: All the observed arrhythmic episodes were ventricular tachycardias (p<0.04). Patients with arrhythmic storm in history had significantly lower survival (p<0.05). The risk factors of cardiac nonsudden death were: age >66 years, left ventricular ejection fraction <35% and arrhythmic storm history. The authors present recommendations for the treatment of the most common specific ICD complications.

Adult↗
PubMed2003

Acute and 3-month treatment effects of candesartan cilexetil on hemodynamics, neurohormones, and clinical symptoms in patients with congestive heart failure.

BACKGROUND: This study evaluated the short-term and long-term effects of the angiotensin II type 1 receptor antagonist candesartan cilexetil on hemodynamics, neurohormones, and clinical symptoms in patients with congestive heart failure (CHF). METHODS: In this multicenter, double-blind, parallel-group study, 218 patients with CHF (New York Heart Association class II or III) with impaired left ventricular function (ejection fraction < or =40%) and pulmonary capillary wedge pressure > or =13 mm Hg were randomly assigned to 12 weeks of treatment with placebo (n = 44) or candesartan cilexetil (2 mg [n = 45], 4 mg [n = 46], 8 mg [n = 39], or 16 mg [n = 44]) once daily after a 2-week placebo run-in period. Hemodynamic measurements were performed by right heart catheterization over a 24-hour period after single (day 1) and repeated (3-month) treatment with the study drug. RESULTS: On regression analysis of the time-response curves, single and multiple doses of candesartan cilexetil produced sustained, significant, and dose-dependent reductions in pulmonary capillary wedge pressure (short-term effect P =.036, long-term effect P =.035) and mean pulmonary arterial pressure (short-term effect P =.031, long-term effect P =.042). Systemic vascular resistance showed a trend toward decreasing with dose on short-term and long-term treatments. No consistent changes were seen in cardiac index. Compensatory increases in plasma renin activity and angiotensin II levels with decreases in aldosterone and atrial natriuretic peptide were dose-dependent and significant. Candesartan cilexetil improved clinical symptoms, stabilized patient New York Heart Association status compared with placebo, and was judged to be an efficacious treatment by the investigators. More patients receiving placebo stopped the trial prematurely because of an adverse event than in any candesartan cilexetil group, and there was no excess of deaths in any treatment group. Candesartan was safe and well tolerated at all dosages. CONCLUSIONS: Candesartan cilexetil demonstrated significant short-term and long-term improvements in hemodynamic, neurohormonal, and symptomatic status and was well tolerated in patients with CHF.

Adolescent↗
PubMed2003

[Atrial fibrillation].

Atrial fibrilation is the most frequent arrhythmia, the occurrence increasing with age and associated diseases. The incidence at the age below 60 years is markedly lower than one per cent, whereas in persons above 80 years of age it exceeds six per cent. The occurrence in patients with heart failure is from 10% (NYHA II) up to 50% (NYHA IV). Atrial fibrillation is classified into that observed for the first time and permanent, respectively, while transient forms include paroxyzmal and persistent atrial fibrillation. The diagnosis is based on ECG recording, while echocardiography is most significant. The therapy includes two basic questions--anticoagulant or anti-aggregation treatment and the control of rhythm or frequency. The anticoagulant therapy should be introduced in all patients, where contraindications are not present, being necessary before every cardioversion, provided atrial fibrillation lasts more than two days. In patients without any heart disease and with a physiological echocardiogram it is possible to administer only anti-aggregation treatment. Cardioversion (the control of rhythm) is recommended to all symptomatic patients, in other cases and especially in older persons the control of frequency is safer and of more advantage. Electrical cardioversion is more effective that a pharmacological treatment, the sinus rhythm is preferably controlled by dofetilid, ibutilid, propafenon and amiodaron. For the control of heart rate beta-blockers, diltiazem, verapamil and digitalis are recommended.

Atrial Fibrillation↗
PubMed2003

[Diabetes mellitus and chronic heart failure].

Diabetes mellitus is one of the significant risk factors for many cardiovascular diseases. Diabetes mellitus is 3-4 times more frequent in patients with heart failure compared to patients without heart failure. Prognosis of patients with heart failure and diabetes mellitus is worse than prognosis of non-diabetic patients with the same left ventricular dysfunction. The term diabetic cardiomyopathy refers to a relation between diabetes mellitus and heart disease, but it probably isn't a separate morphology unit. In treatment of patients with diabetes mellitus general rules apply to heart failure management. The effect of ACE inhibitors was in majority of studies stronger in diabetics than in non-diabetics, the effect of beta blockers was comparable or smaller. Treatment is based on good compensation of metabolic parameters, blood pressure, titration of ACE inhibitors into recommended doses, and an optimal dose of a beta blocker. Type II diabetics with heart failure will, due to decreased resorption and metabolism, need insulin more often than diabetics without heart failure.

Cardiomyopathies↗