The paradox of the first cycle of chemotherapy-transient improvement of contractility and diastolic function after the first cycle of anthracycline-based chemotherapy: a prospective clinical trial.

AIMS: Breast cancer is the most common cancer among women, and anthracyclines are the most commonly administered drugs for these patients. Cardiotoxicity is one of the complications, which limits the success of this therapy. Very few studies have evaluated anthracycline toxicities within the first few hours after the first infusion, and the majority of published studies were performed in animal models. The present study aimed to evaluate changes in echocardiographic parameters in women with breast cancer 24 hours after receiving the first dose of an anthracycline. MATERIALS AND METHODS AND RESULTS: The present study included 75 chemotherapy-naive female patients without heart failure, who were diagnosed with breast cancer and were scheduled to undergo anthracycline-based chemotherapy (epirubicin and doxorubicin). During their visits to the Heart Center, the patients underwent detail echocardiographic examination, including assessment of systolic and diastolic function and longitudinal strain. There were no differences in baseline echocardiographic parameters between patients with and those without cardiotoxicity. Cardiotoxicity was observed during follow-up in 14 patients (18.7%). Improvements in left ventricular ejection fraction and global longitudinal strain were observed at 24 hours after administration of the cytotoxic agent in the subgroup of patients without further cardiotoxicity. The changes were transient and the assessment of left ventricular ejection fraction after completion of chemotherapy revealed similar values to those before the treatment. CONCLUSIONS: The findings of our study suggest that transient improvement in contractility and systolic and diastolic function might occur 24 hours after anthracycline administration, especially in patients who do not develop cardiotoxicity.

Effect of Immunosuppressive Therapy on Proteinogram in Rats.

BACKGROUND It has been observed that the use of immunosuppressive drugs in patients after transplantation of vascularized organs may be associated with changes in the concentration of certain fractions of plasma proteins. The concentration of these proteins was correlated with an increased risk of occurrence of stage 3 chronic kidney disease (CKD). This article examines the effect of the most commonly used immunosuppressive drugs on the concentration of plasma proteins in Wistar rats. MATERIAL AND METHODS The study involved 36 rats grouped according to the immunosuppressive regimen used (tacrolimus, mycophenolate mofetil, cyclosporine A, rapamycin, and prednisone). The rats in all study groups were treated with a 3-drug protocol for 6 months. The treatment dose was adjusted based on available data in the literature. No drugs were administered to the control group. The rats were sacrificed and blood samples collected to determine the concentration of plasma proteins using electrophoresis technique. RESULTS Statistically significant differences were observed between protein concentrations within the studied groups. The differences related to the proteins with masses of 195 kDa, 170 kDa, 103 kDa, and 58 kDa. CONCLUSIONS (1) Immunosuppressive drugs caused changes in the proteinogram of plasma proteins. (2) The strongest effect on rat plasma proteins was exerted by a regimen based on rapamycin. Intermediate, weak, and weakest effects were observed in regimens based on cyclosporine A, tacrolimus, and mycophenolate mofetil, respectively.

[The role of biochemical markers with special regard to troponin, CK-MB, NT-proBNP as early biomarkers of cardiotoxicity among women after chemotherapy due to breast cancer].

Introduction: Cardiotoxicity of drugs in oncology is a growing problem which cardiologists and oncologists have to struggle with. So far, researchers have been looking for biochemical markers which could help to extract a group more prone to developing complications after chemotherapy. Authors' reports are inconsistent in this topic. Aim: This study assesses the role of troponin I, CK-MB and NT-proBNP as early predictive markers for later cardiotoxicity among patients with breast cancer treated with chemotherapy. Methods: One hundred five patients with breast cancer, without either heart failure or more than moderate severity of valvular heart diseases were qualified to the study. Results: NT-proBNP concentration significantly increased just after the first cycle of chemotherapy, either in a subgroup which developed cardiotoxicity or without this end point (p<0.001, p=0.004). CK-MB did not change significantly during observation. Troponin I did not change in any of the patients. During observation HDL-cholesterol concentration significantly decreased. A transient increase of the concentration of LDL-cholesterol had been noted, but later it decreased below baseline level. Conclusion: Troponin I has too low sensitivity to be used as a prognostic marker for further cardiotoxicity after chemotherapy. No prognostic values have been noted of NT-proBNP and CK-MB due to the lack of differences in both a subgroup with and without cardiotoxicity.

Ascending aorta aneurysm as a cause of superior vena cava syndrome.

Superior vena cava syndrome (SVCS) is mostly presented in advanced stage of lung cancer. Similar symptoms may misdirect correct diagnosis, especially in nonmalignant cases of SVCS. In the fifties of the 20th century, mediastinitis caused by tuberculosis and syphilis were dominant causes of non-malignant SVCS. Currently, non-cancer causes of SVCS are responsible for 5% to 22% of all SVCS cases. In most cases inner obliteration of the vessel is a result of thrombosis at the site of endothelial injury caused by either intravascular devices (catheters, electrodes). Clinical signs are nonspecific particularly in acute course of syndrome. We present a case of a men with edema of the lower part of the head and neck, as a pseudo allergic acute reaction, where eventually diagnosis of acute superior vena cava syndrome due to ascending aorta aneurysm was established. Based on the case, review of nonmalignant causes of SVCS and treatment options are discussed.

Microvolt T-wave alternans for the risk stratification of dangerous ventricular arrhythmias in patients with previously implanted automatic cardioverter-defibrillator.

BACKGROUND: Sudden cardiac death (SCD) is the main cause of death in patients with reduced left ventricular ejection fraction (LVEF). Implantation of an automatic cardioverter-defibrillator (ICD) significantly reduces mortality of these patients. T-wave alternans (TWA) analysis is a relatively new method of SCD risk stratification. However, it's prognostic role in patients with ICD has not yet been fully established. AIM: To assess the predictive value of TWA in patients with previously implanted ICD. METHODS: The study included 67 patients with properly functioning ICD (54 men and 13 women, aged 62.2 ± 8.4 years). All patients underwent TWA analysis on the treadmill using the Cambridge Heart 2000 system. Results were considered as positive, negative or indeterminate. Each patient had at least 1 clinical control visit with ICD interrogation during the 12 ± ± 6 months of follow-up. The recurrence of sustained ventricular arrhythmias: ventricular tachycardia (VT) or ventricular fibrillation (VF) was analysed. RESULTS: No significant relationship was found between previous infarction (p = 0.810), aetiology (p = 0.768), LVEF (p = 0.413) or age (p = 0.562) and the incidence of arrhythmia during follow-up. The results of TWA were not significantly different between patients with or without VT or VF. The TWA analysis identified patients with arrhythmia recurrences with a sensitivity of 62%, specificity of 49%, negative predictive value of 81%, and positive predictive value of 28%. The TWA performance was better in patients with non-ischaemic than ischaemic cardiomyopathy (negative predictive value: 100%, positive predictive value: 75%). CONCLUSIONS: The TWA alternans was moderately effective for identification of patients with ICD and ventricular arrhythmia recurrences. The test was most useful for identification of patients with non-ischaemic cardiomyopathy who are of low arrhythmic risk.

Inappropriate cardioverter-defibrillator discharge continues to be a major problem in clinical practice.

BACKGROUND: The purpose of this study was to determine the rate and causes of inappropriate rhythm detection, and to compare adequacy of ventricular arrhythmia detection by single-chamber and dual-chamber cardioverter-defibrillators (ICD). METHODS: We evaluated 190 patients (age 57.2 +/- 11.2 years) with ICD. FOLLOW-UP: 34.3 +/- +/- 22 months. Dual-chamber ICD was used in 54 patients. RESULTS: We evaluated 2244 arrhythmia events recognized as of ventricular origin, including ventricular tachycardia and ventricular fibrillation. 431 events (19.2%) were recognized erroneously and resulted in an inappropriate ICD discharge. Most cases of inappropriate therapies (182 events, 42.23%) were due to atrial fibrillation or flutter. Overall, inappropriate arrhythmia detection was found in 64 (33.6%) of 190 patients. In terms of the number of affected patients, the most common cause of inappropriate ICD discharge was sinus tachycardia - 23 (12.1%) patients, followed by atrial fibrillation - 16 (8.4%) patients. Among 54 patients with dual-chamber ICD, inappropriate therapy was noted in 21 (38.8%) patients, (T wave oversensing, sinus tachycardia and atrial fibrillation etc.). No significant difference was seen in the rate of inappropriate therapy due to a rapid supraventricular rhythm between patients with single-chamber versus dual-chamber ICD. In contrast, patients with single-chamber ICD more often experienced inappropriate therapy due to atrial fibrillation (155 vs. 28 patients) and sinus tachycardia (66 vs. 9 patients). CONCLUSIONS: Despite of introduction of new generations of ICDs, the problem of inappropriate ICD discharge could not be eliminated. The major problem is distinction between supraventricular arrhythmia and ventricular tachyarrhythmia.

Association of C34T AMPD1 gene polymorphism with features of metabolic syndrome in patients with coronary artery disease or heart failure.

OBJECTIVE: The common C34T polymorphism in the AMP deaminase-1 (AMPD1) gene results in an inactive enzyme in homozygotes for the mutated T allele. Some studies have shown an association of T allele with longer survival in heart failure (HF) and/or coronary artery disease (CAD). The aim of this study was to assess genotype-phenotype correlations in such patients, with emphasis on components of the metabolic syndrome. METHODS: Ninety-seven patients with CAD without HF (CAD+ HF-) and 104 with HF (HF+) were genotyped by PCR-RFLP. The genetic control group comprised 200 newborns. RESULTS: No significant differences were found in the frequency of AMPD1 genotypes between the groups. In the CAD+ HF- group, the carriers of T allele compared to CC homozygotes had significantly lower values of waist circumference (89.5+/-8.5 versus 97.7+/-11.2 cm; p = 0.00029), waist/hip ratio (p = 0.0059) and BMI (p = 0.045). There was no diabetes or fasting glycaemia > or =126 mg/dL in T carriers, while these features were present in 25% of CC homozygotes (p = 0.0024). In the HF+ group, a tendency towards a lower prevalence of diabetes (20 % versus 41%; p = 0.068) and significantly lower systolic blood pressure (p = 0.048) were observed in T allele carriers. CONCLUSIONS: C34T AMPD1 polymorphism may be associated with reduced frequency of obesity in CAD patients and of hyperglycaemia and diabetes in both CAD and HF patients. Morphometric parameters associated with adipose tissue distribution and parameters of glucose metabolism should be analysed as potential confounders in further studies on the role of polymorphisms of AMPD1 and other genes associated with AMP and adenosine metabolism in cardiovascular disease.

The influence of low dose atorvastatin on inflammatory marker levels in patients with acute coronary syndrome and its potential clinical value.

BACKGROUND: High-dose statins are used in acute coronary syndromes (ACS) to reduce inflammation. The aim of the study was the evaluation of the influence of low-dose atorvastatin (20 mg) on selected inflammatory parameters and clinical outcomes after ACS. METHODS: Seventy eight patients (pts) with ACS were randomly divided into group A (39 pts) taking atorvastatin, and group NA (39 pts) not taking any statin for the following six weeks. C-reactive protein (CRP), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and tumour necrosis factor alpha (TNFa) levels were measured on the first and the fifth days and six weeks after ACS. RESULTS: There was no significant CRP and IL-6 level decrease in group A (CRP--62%; IL-6-73%) or group NA (CRP-44%; IL-6-62%). There was also no significant change in TNFa levels. The MCP-1 level finally reached the level of significant difference (p < 0.04). Cardiovascular events (MACE) and the restenosis rates did not differ between the groups. CONCLUSIONS: Low-dose atorvastatin does not have a significant influence on cooling down inflammation in ACS, and MCP-1 can be used as an early indicator of statin anti-inflammatory activity. Furthermore, it does not reduce MACE or restenosis rates despite its influence on MCP-1 levels.

Insertion/deletion polymorphism of angiotensin I converting enzyme gene and left ventricular hypertrophy in patients with type 2 diabetes mellitus.

INTRODUCTION: Left ventricular hypertrophy (LVH) is a well known risk factor of death from cardiovascular causes. Patients with type 2 diabetes mellitus are at particularly high risk of developing cardiovascular disease, which accounts for 80% of deaths in this group. Type 2 diabetes mellitus is probably related to increased left ventricular mass (LVM). Existing data show that the renin-angiotensin-aldosterone (RAA) system may play a role in the development of LVH. Since the I/D polymorphism of angiotensin-converting enzyme (ACE) gene influences the activity of RAA, it is likely that it could also have an impact on LVH. AIM: To assess the relationship between I/D polymorphism of the ACE gene and the severity of LVH assessed by echocardiography (Echo) in patients with type 2 diabetes mellitus. METHODS: The study group consisted of 103 patients (37 women and 66 men; mean age 60.1+/-9.1 years) suffering from type 2 diabetes mellitus with a mean duration of 9.0+/-6.5 years. BMI, waist-to-hip ratio (WHR), arterial blood pressure, LVM and LVM index (LVM indexed for body surface area [g/m(2)] or height raised to the power 2.7 [g/m(2.7)]) were evaluated. I/D polymorphism of the ACE gene was determined using polymerase chain reaction (PCR). RESULTS: Distribution of I/D polymorphism of the ACE gene in the study group was as follows: genotype II--32.0%, ID--42.7%, DD--25.2% of patients. LVH was diagnosed in 43-71% of patients (depending on criteria used). Distribution of individual genotypes was similar in patients with and without LVH. Genotypes II, ID and DD were observed in 37.3%, 31.4% and 31.4% of patients without LVH (according to the Levy criteria) and in 26.9%, 53.9%, 19.2% in the LVH group, respectively. In persons with DD genotype, when compared to group II, significantly higher values of systolic and diastolic blood pressure were noted (147.7+/-20.2 vs 138.2+/-16.7 mmHg, p=0.03 and 89.4+/-9.7 vs 81.9+/-8.7 mmHg, p=0.004, respectively). CONCLUSIONS: In patients with type 2 diabetes mellitus there is no relationship between I/D polymorphism of the ACE gene and LVH.

[Effect of low dobutamine doses dobutamine on left ventricular diastolic flow parameters in subjects with a low ejection fraction]. / Wplyw niskiej dawki dobutaminy na rozkurczowy przeplyw w lewej komorze u osób z niska frakcja wyrzutowa.

UNLABELLED: A low dobutamine dose (DOB) improves the systolic function of impaired myocardium. There are some data suggesting the improvement of left ventricular (LV) diastolic function as well. The aim of this work was to assess the influence of DOB on some left ventricular diastolic flow parameters: inflow curve profile and early inflow wave propagation velocity (Prop). MATERIAL AND METHODS: 33 persons (7 women and 26 men) aged 35-74, with a mean age of 53 and with an ejection fraction (EF) < 35% were examined. DOB was administered in doses of 5 and 10 micrograms/kg/min every 3 minutes. At the beginning of the examination (D-0) and at the end (D-1), the LV contractility and the following inflow parameters were assessed: E and A waves velocities, E/A-ratio on mitral orifice level (U) and at the half of LV (1/2 LV) and Prop. RESULTS: DOB increased the heart rate from 69.4/min to 74.4/min (p < 0.01) and improved the LV contractility in every case. We observed no significant changes of the E wave velocity influenced by DOB on U (D-O: 0.7 +/- 0.22 m/s; D-1: 0.68 +/- 0.2 m/s) and in 1/2 LV, or no E/A changes (D-O: 1.24 +/- 0.71; D-1 1.21 +/- 1.08 on U and D-O: 1.68 +/- 1.06; D-1: 1.64 +/- 1.16 in 1/2 LV). Statistically significant differences were recorded only between A in D-O and A in D-1 on both levels (p < 0.05): D-O was 0.66 +/- 0.21 m/s and D-1 was 0.71 +/- 0.22 m/s on U and D-O was 0.422 +/- 0.2 m/s and D-1 was 0.47 +/- 0.2 m/s in 1/2 LV. Significant Prop shortening was ascertained: from 39.4 +/- 10.9 cm/s to 45.4 +/- 16.1 cm/s; p < 0.01. The correlation registered at rest between Prop and EF (R = 0.4) and Prop and contractility index (R = -0.52), was recorded at a similar level after DOB as well. No correlation between Prop and heart rate was seen. CONCLUSIONS: 1. Dobutamine in low doses in subjects with impaired LV causes no significant heart rate acceleration and no progression in contractility disorders, improves LV diastolic function, expressed by early diastolic blood flow towards the apex (inflow propagation) acceleration. 2. Dobutamine in low dose increases mitral A wave velocity caused by improvement of LV diastolic function and/or improvement of LA contractility.