Clinical implementation of cardiac resynchronization therapy-regional disparities across selected ESC member countries.

BACKGROUND: The present analysis aimed to estimate the penetration of cardiac resynchronization therapy (CRT) on the basis of the prevalence and incidence of eligible patients in selected European countries and in Israel. METHODS AND RESULTS: The following countries were considered: Italy, Slovakia, Greece, Israel, Slovenia, Serbia, the Czech Republic, Poland, Romania, Hungary, Ukraine, and the Russian Federation. CRT penetration was defined as the number of patients treated with CRT (CRT patients) divided by the prevalence of patients eligible for CRT. The number of CRT patients was estimated as the sum of CRT implantations in the last 5 years, the European Heart Rhythm Association (EHRA) White Book being used as the source. The prevalence of CRT indications was derived from the literature by applying three epidemiologic models, a synthesis of which indicates that 10% of heart failure (HF) patients are candidates for CRT. HF prevalence was considered to range from 1% to 2% of the general population, resulting in an estimated range of prevalence of CRT indication between 1000 and 2000 patients per million inhabitants. Similarly, the annual incidence of CRT indication, representing the potential target population once CRT has fully penetrated, was estimated as between 100 and 200 individuals per million. The results showed the best CRT penetration in Italy (47-93%), while in some countries it was less than 5% (Romania, Russian Federation, and Ukraine). CONCLUSION: CRT penetration differs markedly among the countries analyzed. The main barriers are the lack of reimbursement for the procedure and insufficient awareness of guidelines by the referring physicians.

Ecological quality status of the Adriatic coastal waters evaluated by the organotin pollution biomonitoring.

The aim of this study was to evaluate the post-legislation change in tributyltin (TBT) pollution at Croatian Adriatic coast. Gastropod Hexaplex trunculus and sediments were collected, nearly 10years after TBT based antifouling paints were banned, at 12 locations along the coast where a previous study was conducted in 2005. The study showed a decline of TBT levels over the investigated period, although all gastropods populations were highly affected by imposex meaning that prohibition did not result in the recovery of populations. The further aim was to propose the Ecological Quality Ratio (EQR) boundaries for potential use of H. trunculus as a principal bioindicator in the assessment of the ecological status of the Mediterranean regarding TBT pollution, under the Water Framework Directive (WFD). According to the proposed EQR classes, the WFD target for achieving the Good ecological status of the marine environment by 2015 was not reached.

Treatment and outcome of 2904 CML patients from the EUTOS population-based registry.

The European Treatment and Outcome Study (EUTOS) population-based registry includes data of all adult patients newly diagnosed with Philadelphia chromosome-positive and/or BCR-ABL1+ chronic myeloid leukemia (CML) in 20 predefined countries and regions of Europe. Registration time ranged from 12 to 60 months between January 2008 and December 2013. Median age was 55 years and median observation time was 29 months. Eighty percent of patients were treated first line with imatinib, and 17% with a second-generation tyrosine kinase inhibitor, mostly according to European LeukemiaNet recommendations. After 12 months, complete cytogenetic remission (CCyR) and major molecular response (MMR) were achieved in 57% and 41% of patients, respectively. Patients with high EUTOS risk scores achieved CCyR and MMR significantly later than patients with low EUTOS risk. Probabilities of overall survival (OS) and progression-free survival for all patients at 12, 24 and 30 months was 97%, 94% and 92%, and 95%, 92% and 90%, respectively. The new EUTOS long-term survival score was validated: the OS of patients differed significantly between the three risk groups. The probability of dying in remission was 1% after 24 months. The current management of patients with tyrosine kinase inhibitors resulted in responses and outcomes in the range reported from clinical trials. These data from a large population-based, patient sample provide a solid benchmark for the evaluation of new treatment policies.

Noninvasive monitoring of rejection therapy based on intramyocardial electrograms after orthotopic heart transplantation. Initial experience with 14 cases.

Despite the use of increasingly specific immunosuppressive therapy, rejection remains the leading cause of death in cardiac transplant patients. Endomyocardial biopsy (EMB) is the gold standard for early detection and monitoring of cardiac transplant rejection. However, this approach is invasive and not suitable for routine use. A noninvasive alternative for monitoring cardiac transplant patients uses the analysis of the ventricular evoked response (VER) obtained by programmed electrical stimulation. Rejection-sensitive parameters (RSP) and infection-specific parameters (ISP) are extracted from changes in the slope of the T-wave and from the duration of repolarization, respectively. For the analysis of intramyocardial electrograms, separate left and right ventricular pacing at a rate of 100 beats/min and lasting 60 s is required, following the same protocol. From year 2000, telemetric pacemakers were implanted in 14 patients undergoing heart transplantation at this institution. A total of 95 endomyocardial biopsies and 275 ventricular evoked response measurements were carried out. Five out of 6 cases with significant rejection were correctly identified by RSP values below a threshold of 98% (sensitivity=80%, specificity=50%, negative predictive value=97%, positive predictive value=11%; P<0.002). Of the EMBs, 45% could have been saved if the diagnosis model had been used to indicate need for EMB. Noninvasive cardiac graft monitoring can reduce the need for surveillance biopsies and may offer a tool to optimize immunosupressive therapy after heart transplantation. Rejection grade 2 or higher can safely be detected.

The EUTOS population-based registry: incidence and clinical characteristics of 2904 CML patients in 20 European Countries.

This population-based registry was designed to provide robust and updated information on the characteristics and the epidemiology of chronic myeloid leukemia (CML). All cases of newly diagnosed Philadelphia positive, BCR-ABL1+ CML that occurred in a sample of 92.5 million adults living in 20 European countries, were registered over a median period of 39 months. 94.3% of the 2904 CML patients were diagnosed in chronic phase (CP). Median age was 56 years. 55.5% of patients had comorbidities, mainly cardiovascular (41.9%). High-risk patients were 24.7% by Sokal, 10.8% by EURO, and 11.8% by EUTOS risk scores. The raw incidence increased with age from 0.39/100,000/year in people 20-29 years old to 1.52 in those >70 years old, and showed a maximum of 1.39 in Italy and a minimum of 0.69 in Poland (all countries together: 0.99). The proportion of Sokal and Euro score high-risk patients seen in many countries indicates that trial patients were not a positive selection. Thus from a clinical point of view the results of most trials can be generalized to most countries. The incidences observed among European countries did not differ substantially. The estimated number of new CML cases per year in Europe is about 6370.

Complete cure after a seemingly unsuccessful operation for Wolff-Parkinson-White syndrome.

A 48-year-old man with Wolff-Parkinson-White syndrome and poorly tolerated atrial fibrillation underwent surgical dissection of an accessory pathway. After operation electrocardiogram revealed a very unfavorable outcome: sinus rhythm with persistence of delta waves alternated with sequences of complete atrioventricular block. Therefore, an early reoperation was planned. Fortunately, in the next days conduction through the accessory pathway and signs of atrioventricular block disappeared. Complete cure was observed during long-term follow-up.

Tachycardia induced cardiomyopathy in dogs; relation between chronic supraventricular and chronic ventricular tachycardia.

Long-standing ventricular tachycardia (VT) and supraventricular tachycardia (SVT) can produce a reversible left ventricular dysfunction. The onset of cardiomyopathy and the severity of posttachycardic changes depend at least on three parameters of tachycardia, including its type (VT or SVT), rate and duration. Ten dogs (beagles) were paced at 180 beats/min for 3 weeks. Two pacing modalities, supraventricular and ventricular, were used in each dog. In half of them, the study was started by ventricular, and in the other half by supraventricular high-rate pacing. The alternate pacing modality was applied after complete recovery of left ventricular function. Ventricular function and morphology were evaluated by radionuclide ventriculography, echocardiography and Swan-Ganz catheterisation. Posttachycardic changes were studied in sinus rhythm after cessation of pacing. Left ventricular ejection fraction (LVEF) fell significantly after either type of tachycardia (SVT: 53 +/- 5%, VT: 48 +/- 7%, P < 0.05) compared with baseline values (69.5 +/- 2.3%). Significant increases (P < 0.05) in end-systolic (SVT: 2.1 +/- 0.3 cm, VT: 2.4 +/- 0.2 cm vs. 1.6 +/- 0.3 cm) and end-diastolic dimensions (SVT: 3.0 +/- 0.3 cm, VT: 3.3 +/- 0.4 cm vs. 2.7 +/- 0.3 cm) indicated ventricular dilation in paced animals. Left ventricular pulmonary capillary wedge pressure increased significantly after either type of tachycardia as compared with baseline values (SVT: 7.5 +/- 1.2 mmHg, VT: 8.4 +/- 1.1 mmHg vs. 1.9 +/- 1.5 mmHg, P < 0.05); the difference between tachycardias was not significant. The present study demonstrates that chronic SVT and VT result in left ventricular dysfunction in a relatively short time, even if the heart rate is not very high. Deterioration of left ventricular ejection fraction and dilation of the left ventricle are more marked in chronic VT than in chronic SVT.

Spontaneous shifts in the sinus node pacemaker complex.

Shifts in sinus node pacemaker complex may occur spontaneously, but occurrence of clinically relevant shifts is very rare. In this report, three patients (2 are siblings) with a history of palpitations and nearly permanent shifts in sinus node pacemaker complex are presented. Often, but not always, the pacemaker shifts followed spontaneous sinoatrial exit blocks. The shifts were probably related to varying vagal tone, since they were eliminated by atropine and exercise. The experience with these patients suggests that sinus pacemaker shifts can be a cause of symptomatic nonrespiratory sinus arrhythmia. A 4-year follow-up period showed no changes in symptoms or in heart rhythm; therefore, a benign course of the disease can be expected.

Left atrial systolic function in relation to electrical and mechanical remodeling in a canine model.

Rapid atrial activation causes electrical remodeling that promotes the occurrence and maintenance of atrial fibrillation. The aim of this research was to compare the relationship between mechanical remodeling and atrial electrophysiology. Eight dogs (beagles) were subjected to rapid atrial pacing (AP) at 400 beats/min for 16 days. After a complete recovery of electrical variables and left ventricular function evaluated by echocardiography, they underwent high-rate ventricular pacing (VP) at 240 beats/min of equal duration. In half of them, the study was started by VP and in the other half by AP. Left atrial systolic function was assessed by transesophageal echocardiography. Atrial effective refractory period (AERP) at a basic cycle length of 400 ms decreased significantly after either type of pacing (AP: 115 +/- 17 ms, VP: 136 +/- 22 ms) compared with baseline values (153 +/- 23 ms); the difference between tachycardias was significant too (p < 0.02). Significant increases (p < 0.05) in left atrial dimensions (LA-A) (AP: 2.41 +/- 0.23 cm ,VP: 2. 43 +/- 0. 34 cm vs. basal: 2. 16 +/- 0. 21 cm) indicated atrial dilatation after either type of pacing, the differences between two groups being insignificant. Atrial reversal pulmonary venous flow (AR velocity) decreased in AP (-0.13 +/- 0. 02 m/s) and VP (-0. 17 +/- 0. 04 m/s). The difference was highly significant as compared to basal values (-0.25 +/- 0.05 m/s) and also with respect to both tachycardias (p < 0.01). In both groups, atrial remodeling occurred in a relatively short period of time. The echocardiographic findings suggested that left atrial systolic function was significantly more disturbed in the AP group than in the VP group. Mechanical changes are an important substrate of electrical remodeling, yet the deterioration of electrical variables was more pronounced in AP than in VP.

Sinus node dysfunction and impairment of global atrial conduction time after high rate atrial and ventricular pacing in dogs.

It has been shown in animals and humans that AF shortens the atrial refractory period and impairs its rate adaptation. The aim of the study was to evaluate the effects of high rate pacing on sinus node function and intraatrial conduction. Eight dogs were subjected to rapid atrial pacing (AP) at a rate of 400 beats/min for 16 days. After a complete recovery of left ventricular function, they underwent rapid ventricular pacing (VP) at 240 beats/min of equal duration. Sinus node recovery time (SNRT) was measured after pacing at 150, 160, and 170 beats/min. P wave duration was measured on a surface ECG recorded at a paper speed of 200 mm/s. Measurements were performed at baseline, immediately after AP or VP, and four weeks after termination of AP or VP. SNRT immediately after AP and VP was significantly prolonged at all three pacing rates (P < 0.03). P wave duration increased significantly after either type of pacing (AP: 74.3 +/- 6.4 ms, VP: 70.0 +/- 3.8 ms) compared with baseline values (60.6 +/- 6.2 ms, P < 0.05). Rapid AP and VP induces sinus node dysfunction and prolongs intraatrial conduction time. The effects of sustained AP and VP on sinus node function and atrial myocardium returned toward control values 4 weeks after cessation of pacing. The authors hypothesize that reversible electrical remodeling occurs both in the sinus node and in the atrial myocardium.

Double vessel extension of spontaneous left main coronary artery dissection in young women treated with thrombolytics.

Spontaneous coronary artery dissection is an extremely rare cause of myocardial infarction. The prognosis and treatment of coronary artery dissection have not yet been defined. We report on a 42-year-old woman who was admitted to the emergency unit of a regional hospital with central chest pain and electrocardiographic signs of extensive acute anterior myocardial infarction (MI). She was treated with thrombolytics, yet her condition deteriorated rapidly, resulting in cardiogenic shock. An angiogram revealed dissection of the left main coronary artery that extended into the anterior descending (LAD) and circumflex arteries (LCX). At autopsy a recent anterolateral MI of the left ventricle was found. Dissection of the left coronary artery system was confirmed. Extension of the dissection may have been due to thrombolytic treatment.

Cardiac involvement in Emery-Dreifuss muscular dystrophy: role of a diagnostic pacemaker.

Emery-Dreifuss muscular dystrophy is an X-linked recessive myopathy. Its progression is slow, and it rarely leads to cessation of walking; therefore, it has often been called "benign." On the other hand, cardiac involvement is often severe and sudden death is not uncommon. We describe a family with four affected males, two of whom died suddenly. The case of an affected man with first-degree AV block, incomplete right bundle branch block, and left anterior fascicular block is described in detail. The prophylactic insertion of a diagnostic pacemaker enabled us to follow the progress of conduction disturbances without leaving the patient unprotected. While AV and intraventricular conduction defects were more prominent before pacemaker implantation, sinus node dysfunction became more important during the follow-up.

Reticulocyte analysis using light microscopy and two different flow cytometric procedures.

The reticulocyte count is a clinically important indirect indicator of erythropoietic activity of the bone marrow. Reticulocyte enumeration by light microscopy is rather inaccurate and has poor reproducibility. Automation of the reticulocyte count by means of flow cytometry has considerably improved the quality of this investigation. In our study, we compared three methods of establishing the blood reticulocyte number: the microscopic brilliant cresyl blue method and two flow cytometric procedures using thiazole orange (TO), namely FACSort (Becton-Dickinson) and EPICS Profile (Coulter). The aims of the study were (1) to select the most suitable TO concentration to be used with the EPICS Profile cytometer, (2) to determine the correlation between the microscopic method and the two flow cytometric procedures, and (3) to appraise the suitability of flow cytometry for reticulocyte analysis in routine clinical work. According to our results, the most appropriate TO concentration for the EPICS Profile counter is 0.1 mg/L. We observed a good correlation between the three methods tested; the correlation coefficients ranged from 0.82 to 0.87. The mean intra-assay coefficients of variation for the microscopic method and the EPICS Profile and FACSort procedures were 27.5%, 8.4% and 6.3%, respectively.

Effects of molgramostim, filgrastim and lenograstim in the treatment of myelokathexis.

Myelokathexis is a very rare form of chronic hereditary neutropenia resulting from impaired neutrophil releasing mechanism in the bone marrow. The recombinant human granulocyte-macrophage (molgramostim) and granulocyte (filgrastim, lenograstim) colony stimulating factors release the mature granulocytes from the bone marrow. We describe a 43-year-old woman suffering from myelokathexis, with the absolute neutrophil count ranging between 0.03 and 1.35 x 10(9)/L. In the period before the introduction of cytokines, the patient had more than 80 major infectious episodes. Since 1991, infections in this patient have been treated with cytokines, given in conjunction with antibiotics. Initially, she received molgramostim in a daily dose of 5 microg/kg subcutaneously, which stimulated the release of granulocytes from her bone marrow, thereby allowing successful treatment of infection. After the development of hypersensitivity, molgramostim was substituted with filgrastim. Finally, lenograstim was given a trial. With all three cytokines, the patient's neutrophil count always attained normal values already 4 hours after subcutaneous application of the drug in a dose of 5 microg/kg, the highest neutrophil levels were measured at 24 hours post-injection, and the neutrophil count was again close to the baseline value 72 hours after the treatment. A slight neutropenia was present 48 hours after the application of filgrastim. We believe that all three cytokines are equally effective in increasing the neutrophil count in venous blood of patients with myelokathexis.

Serum thrombopoietin levels in acute myeloid leukaemia.

To improve our understanding of the regulation of circulating platelet counts (PC) by thrombopoietin (TPO), we studied serum TPO levels and PC before and after myelosuppressive chemotherapy in 12 patients with acute myeloid leukaemia (AML). Serum TPO levels were measured by the quantitative sandwich enzyme-linked immunosorbent assay (Quantikine, RD Systems). At the start of the induction chemotherapy, the patients had a median serum TPO level of 199 pg/ml (range 120-2,150 pg/ml), while 10 to 12 days after the end of chemotherapy, their TPO levels were substantially increased, the median value being 1,907 pg/ml (range 1,049-4,194 pg/ml). The correlation between PC and TPO was statistically significant prior to chemotherapy (p < 0.03) and insignificant after chemotherapy. As a result of chemotherapy, the patients developed aplasia; after the administration of platelet transfusions, their median PC increased to 21 x 10(9)/l (range 5-55 x 10(9)/l), while the median TPO value decreased by 300 pg/ml (range 11-1,125 pg/ml). Our results suggest that platelet mass directly regulates serum TPO levels in acute leukaemia patients prior to chemotherapy and after the administration of platelet transfusions. Serum TPO levels may also be influenced by the cytokine response during complicating infections in patients with chemotherapy-induced cytopenia.

Indices of iron status in patients treated by chronic haemodialysis.

Iron deficiency in patients with end stage renal disease (ESRD) treated by haemodialysis (HD) is difficult to diagnose. The reticulocyte hemoglobin content (CHr) and the percentage of hypochromic red cells (%hypo) are sensitive novel assays for the detection of functional iron deficiency in patients treated with erithropoietin (EPO). In our study thirty-nine chronically hemodialyzed patients were evaluated to determine the value of these two parameters in comparison to the conventional biochemical indicators of iron metabolism. There were significant correlations between CHr and transferrin saturation, CHr and weekly dosage of EPO, and also between %hypo and weekly dosage of EPO. Our data represent superior value of %hypo and CHr to the transferrin saturation and ferritin concentration in detecteng of iron deficiency in HD patients.