Echocardiographic changes after cardiac resynchronisation therapy.

BACKGROUND AND AIM: The aim of this prospective study was to evaluate echocardiographic changes in clinical responders and nonresponders after 3 and 15 months of cardiac resynchronisation therapy (CRT). METHODS: Fifty eight patients in whom a biventricular system was implanted between 2005 and 2008 were followed up at 3 and at 15 months. Clinical and echocardiography parameters including intra- and interventricular dyssynchrony were assessed at baseline and after 3 and 15 months of CRT. Every patient in whom quality of life, New York Heart Association (NYHA) class and/or 6-minute walk test (6MWT) improved (improvement of ≥ 1 NYHA class, 6MWT by more than 10%), and who was neither in hospital for heart failure nor died for cardiac reasons, was categorised as a clinical responder. RESULTS: In the responders' group, we found a significant improvement of right ventricular systolic function and a decrease in the size of the right ventricle (RV) only after 15 months (tricuspid annular plane systolic excursion [TAPSE] 17.8 ± 4.0 mm to 19.4 ± 3.7 mm, p 〈 0.05, RV diameter 29.3 ± 5.0 mm to 27.8 ± 4.2 mm, p 〈 0.05). Significant improvement of other monitored parameters occurred 3 months after CRT implantation: left ventricle (LV) end-diastolic diameter 70.5 ± 7.8 mm to 66.1 ± 8.3 mm, p 〈 0.001, LV ejection fraction 22.0 ± 5.4% to 27.1 ± 9.8%, p 〈 0.05, pulmonary artery pressure (peak gradient of tricuspid regurgitation) 37.1 ± 14.8 mm Hg to 27.6 ± 8.9 mm Hg, p 〈 0.001, tricuspid regurgitation (grade) 1.9 ± 0.9 to 1.5 ± 0.6, p 〈 0.05, mitral regurgitation (grade) 2.6 ± 0.9 to 2.2 ± 0.9, p 〈 0.001, LV dP/dt max (peak positive rate of pressure rise [slope of mitral regurgitant jet]) 482.4 ± 155.4 mm Hg/s to 981.2 ± 654.5 mm Hg/s, p 〈 0.001, velocity time integral (VTI) in LV outflow tract (LVOT) 14.1 ± 4.3 cm to 16.7 ± 4.1 cm, p 〈 0.001. In the group of nonresponders, only 2 parameters improved significantly: LV dP/dt max 561.2 ± 347.9 mm Hg/s to 1024.5 ± 745.3 mm Hg/s, p 〈 0.001, and LVOT VTI 14.5 ± 3.0 cm to 16.3 ± 2.9 cm, p 〈 0.001. Other echocardiographic parameters did not show any important changes, and no changes occurred between 3 and 15 months. On the contrary, after 15 months we saw significant progression of tricuspid regurgitation in nonresponders. In multivariate analysis, combination of baseline delay between time to peak systolic velocity in ejection phase at basal septal and basal lateral segments (Ts-lateral-septal delay) and serum creatinine was a strong predictor of clinical CRT response (area under curve was 0.80, percentage of correct decision was 82%). CONCLUSIONS: In the group of responders, significant changes of most monitored echocardiographic parameters were observed 3 months after CRT implantation. The only parameters which changed significantly after 15 months, but not previously, were the systolic function of the RV and the decrease in the RV size. In the group of nonresponders, these changes were not observed.

Cardiac resynchronization therapy in clinical responders: right ventricular echocardiographic changes at mid-term follow-up.

OBJECTIVE: The objective of this study was to assess the mid-term effects of cardiac resynchronization therapy on systolic function and remodelling of the right ventricle in clinical responders and non-responders. METHODS: A biventricular system was implanted between July 2005 and May 2008 in 58 patients with heart failure NYHA class II-IV. At baseline, three and 15 months after implantation, the following parameters were determined: NYHA class, quality of life, six-minute walk test, echocardiography including assessment of right ventricular systolic function by tricuspid annular plane systolic excursion and by pulsed tissue Doppler imaging (myocardial peak systolic velocity was measured at the tricuspid annulus). We also assessed the presence of ventricular dyssynchrony. RESULTS: There were no significant changes after three months of cardiac resynchronization therapy on right ventricular systolic function and remodelling in responders and non-responders. Among responders, we found a statistically significant improvement of right ventricular systolic function and also a significant decrease in the size of the right ventricle after 15 months of therapy (systolic excursion before therapy 17.8 +/- 4.0 mm vs. 19.4 +/- 3.7 mm, P < 0.05, after therapy; peak systolic velocity initially 11.9 +/- 2.9 cm/s vs 12.7 +/- 3.2 cm/s; right ventricle size before therapy 29.3 +/- 5.0 mm vs. 27.8 +/- 4.2 mm, P < 0.05, after therapy. These changes were not observed in non-responders. CONCLUSIONS: Fifteen months after cardiac resynchronization therapy, we found a statistically significant improvement of right ventricular systolic function and a significant reduction of right ventricular size in responders to cardiac resynchronization therapy.

Sensitivity of porcine peripheral blood leukocytes to gamma irradiation in vivo, in vitro and ex vivo.

PURPOSE: The large white pig is a useful experimental model to compare in vivo, in vitro and ex vivo sensitivity of peripheral blood leukocytes to ionising radiation. Such studies are impossible to perform in humans and laboratory rodents due to ethical reasons and body size, respectively. We analysed dose- and time-dependent changes of lymphocyte and granulocyte absolute numbers in porcine peripheral blood after either whole-body irradiation (in vivo and ex vivo experiments) or exposure of porcine whole blood to γ-irradiation (in vitro experiments). MATERIALS AND METHODS: CytoCount™ absolute counting beads and light scatter analysis using a flow cytometer were used to determine major leukocyte subpopulation numbers in blood samples after red cell removal. RESULTS: Similar to other species, lymphocyte numbers significantly decreased in pigs both in vivo and in vitro in a dose-dependent manner. Most importantly, our data clearly show that reduction of lymphocyte numbers after irradiation in vivo proceeds much faster than after irradiation in vitro and that granulocyte changes depend only on the time of analysis after irradiation. CONCLUSIONS: All three tested experimental arrangements demonstrated the radiosensitivity of lymphocytes and the radioresistance of peripheral blood granulocytes. These in vivo and in vitro approaches, as well as the newly introduced ex vivo observations, appear to be relevant to biodosimetry.

Tabun-inhibited rat tissue and blood cholinesterases and their reactivation with the combination of trimedoxime and HI-6 in vivo.

Up to now, intensive attempts to synthesize a universal reactivator able to reactivate cholinesterases inhibited by all types of nerve agents/organophosphates were not successful. Therefore, another approach using a combination of two reactivators differently reactivating enzyme was used: in rats poisoned with tabun and treated with combination of atropine (fixed dose) and different doses of trimedoxime and HI-6, changes of acetylcholinesterase activities (blood, diaphragm and different parts of the brain) were studied. An increase of AChE activity was observed following trimedoxime treatment depending on its dose; HI-6 had very low effect. Combination of both oximes showed potentiation of their reactivation efficacy; this potentiation was expressed for peripheral AChE (blood, diaphragm) and some parts of the brain (pontomedullar area, frontal cortex); AChE in the basal ganglia was relatively resistant. These observations suggest that the action of combination of oximes in vivo is different from that observed in vitro.

Plasma interleukin-6 level is associated with NT-proBNP level and predicts short- and long-term mortality in patients with acute heart failure.

OBJECTIVES: Interleukin 6 plays an important role in chronic heart failure (HF), but little is known about its involvement in acute decompensated heart failure (ADHF). The aim of our study is to evaluate the prognostic role of interleukin 6 (IL-6) in the patients with ADHF. METHODS: Plasma levels of interleukin IL-6, N-terminal pro brain natriuretic peptide levels, and clinical covariates were measured in 92 patients with ADHF. Survival was followed up to 12 months, and prognostic factors were evaluated. RESULTS: Elevated plasma IL-6 levels were increased in nonsurvivors and were associated with 1-year mortality (p < 0.01). Plasma IL-6 levels were associated with plasma NT-proBNP levels. In multivariate analysis, increased plasma IL-6 and NT-proBNP levels remained strong independent predictors of 1-year mortality. CONCLUSIONS: Plasma IL-6 levels provide important prognostic information in the patients with ADHF. Measurement combining plasma IL-6 and NT-proBNP should serve as a powerful prognostic tool of multimarker strategy in patients with acute decompensated heart failure.

Monotherapy with low-dose thalidomide for relapsed or refractory multiple myeloma: better response rate with earlier treatment.

BACKGROUND: Thalidomide is an immunomodulatory drug used in the treatment of relapsed or refractory multiple myeloma (MM). The optimal dosing regimen of thalidomide is not known. PATIENTS AND METHODS: We retrospectively analysed the overall response rate and response duration of 53 patients with relapsed MM who received thalidomide in a median dose of 100 mg daily. The aim of the study was to compare the response rates of thalidomide given as the second-line treatment to those of thalidomide given as the third-line therapy. RESULTS: Of 33 patients receiving thalidomide as second line, 13 (39%) had overall treatment response. Of 20 patients treated with thalidomide monotherapy as the third-line treatment, there were three treatment responses (15%) (P = 0.039). The median duration of treatment response in the second-line thalidomide group (12 months, range 6-60 months) was twice as long as that in the third-line thalidomide group (6 months, range 3-57 months), although the difference was not statistically significant, probably due to low number of patients. Only 6% of patients (3/53) had to stop the treatment because of toxicity. CONCLUSIONS: Monotherapy with low-dose thalidomide results in treatment responses in approximately 30% of patients with advanced MM. The response rate appears to be higher if thalidomide treatment is started after the first relapse or progression in comparison with the second relapse or progression. Treatment toxicity is acceptable even with prolonged exposure to the drug.

NT-proBNP and echocardiographic parameters in patients with acute heart failure.

AIM: The aim of this study was to analyse the relation between clinical, haemodynamic and X-ray parameters and plasma NT-proBNP level in pts with symptoms of left ventricular dysfunction. METHODS: The plasma NT-proBNP levels, chest x-ray, transthoracic 2-d and Doppler echocardiography were performed at the time of admission in a group of 96 consecutive patients (mean age 68 +/- 11 years) with symptoms of acute heart failure. NT-proBNP levels were assessed with the use of commercial tests (Roche Diagnostics). RESULTS: All patients have significant increase in NT-proBNP (8000 +/- 9000 pg/mL vs. controls 90 +/- 80 pg/mL, p < 0.001). The group of all patients has shown a significant increase in cardiothoracic ratio (CTR, 0.6 +/- 0.1, vs. 0.4 +/- 0.1, p < 0.001), left atrium diameter (LAD, 4.4 +/- 0.8 cm, vs.3.5 +/- 0.4 cm, p < 0.01). Left ventricular ejection fraction (LVEF) was decreased (37 +/- 15%, vs. 64 +/- 5%, p < 0.001). In patients with acute heart failure, NT-proBNP significantly correlated with end-systolic and end-diastolic left ventricle diameters, ejection fraction, vena cava inferior diameter and plasma creatinine levels. CONCLUSION: Increased plasma NT-proBNP level is influenced by the clinical severity of acute heart failure and correlates with LVEF and IVCD. NT-proBNP can serve as a marker for the clinical severity of the disease.

Changes of cholinesterase activities in the plasma and some tissues following administration of L-carnitine and galanthamine to rats.

Changes of acetylcholinesterase (AChE) activities in the hypophysis and brain (frontal cortex, hippocampus, medial septum and basal ganglia), and butyrylcholinesterase in plasma and liver following galanthamine (GAL) administration were studied in rats pretreated with L-carnitine (CAR). Following only GAL administration (10 mg/kg, i.m.), both cholinesterases (without clinical symptoms of GAL overdosage) were significantly inhibited. Pretreatment with CAR (3 consecutive days, 250 mg/kg, p.o.) followed by GAL administration showed higher AChE inhibition in comparison with single GAL administration. However, a statistically significant difference was observed for AChE in the hippocampus only. The activity of peripheral cholinesterases was not influenced by CAR pretreatment. Thus, pretreatment with CAR enhanced AChE inhibition in some brain parts of the rat following GAL administration.

Changes of acetylcholinesterase activity in different rat brain areas following intoxication with nerve agents: biochemical and histochemical study.

Acetylcholinesterase activity in defined brain regions was determined using biochemical and histochemical methods 30 min after treating rats with sarin, soman or VX (0.5 x LD(50)). Enzyme inhibition was high in the pontomedullar area and frontal cortex, but was low in the basal ganglia. Histochemical and biochemical results correlated well. Determination of the activity in defined brain structures was a more sensitive parameter than determination in whole brain homogenate where the activity was a "mean" of the activities in different structures. The pontomedullar area controls respiration, so that the special sensitivity of acetylcholinesterase to inhibition by nerve agents in this area is important for understanding the mechanism of death caused by nerve agents. Thus, acetylcholinesterase activity is the main parameter investigated in studies searching for target sites following nerve agent poisoning.