Data-driven machine-learning analysis of potential embolic sources in embolic stroke of undetermined source.

BACKGROUND AND PURPOSE: Hierarchical clustering, a common 'unsupervised' machine-learning algorithm, is advantageous for exploring potential underlying aetiology in particularly heterogeneous diseases. We investigated potential embolic sources in embolic stroke of undetermined source (ESUS) using a data-driven machine-learning method, and explored variation in stroke recurrence between clusters. METHODS: We used a hierarchical k-means clustering algorithm on patients' baseline data, which assigned each individual into a unique clustering group, using a minimum-variance method to calculate the similarity between ESUS patients based on all baseline features. Potential embolic sources were categorised into atrial cardiopathy, atrial fibrillation, arterial disease, left ventricular disease, cardiac valvulopathy, patent foramen ovale (PFO) and cancer. RESULTS: Among 800 consecutive ESUS patients (43.3% women, median age 67 years), the optimal number of clusters was four. Left ventricular disease was most prevalent in cluster 1 (present in all patients) and perfectly associated with cluster 1. PFO was most prevalent in cluster 2 (38.9% of patients) and associated significantly with increased likelihood of cluster 2 [adjusted odds ratio: 2.69, 95% confidence interval (CI): 1.64-4.41]. Arterial disease was most prevalent in cluster 3 (57.7%) and associated with increased likelihood of cluster 3 (adjusted odds ratio: 2.21, 95% CI: 1.43-3.13). Atrial cardiopathy was most prevalent in cluster 4 (100%) and perfectly associated with cluster 4. Cluster 3 was the largest cluster involving 53.7% of patients. Atrial fibrillation was not significantly associated with any cluster. CONCLUSIONS: This data-driven machine-learning analysis identified four clusters of ESUS that were strongly associated with arterial disease, atrial cardiopathy, PFO and left ventricular disease, respectively. More than half of the patients were assigned to the cluster associated with arterial disease.

Glucose and arterial blood pressure variability in Obstructive Sleep Apnea Syndrome.

INTRODUCTION: Current evidence supports an association between Obstructive Sleep Apnea Syndrome (OSAS), insulin resistance, type 2 diabetes mellitus (DM) and cardiovascular disorders. The relationship is complex and still remains poorly understood. AIM: The aim of this study was to examine the potential correlation of sleep characteristics with glucose and arterial pressure values variability in non - diabetic, non-hypertensive patients with OSAS. SUBJECTS AND METHODS: We examined 22 subjects, 11 men and 11 women (mean age 54 ± 14,5 years), recently diagnosed with OSAS (Apnea - Hypopnea Index (AHI) ≥ 5 apneas/hypopneas per hour of sleep) by full night polysomnography (PSG). Fasting and postprandial after a 2 hour oral glucose tolerance test (OGTT) glucose and insulin levels were measured, and homeostatic model assessment of insulin resistance (HOMA(IR)) index profile as well as Matsuda insulin sensitivity index (ISI) were calculated. A 24 hour glucose monitoring with subcutaneous measurements every 5 minutes and a 24-hour arterial blood pressure (ABP) monitoring (Holter monitoring) were evaluated. RESULTS: AHI, a widely accepted marker of the severity of OSAS, was correlated with HOMA and Matsuda index (p = 0.016 and p = 0.022, respectively), Standard Deviation (SD) of glucose measurements (p = 0.05) and mean diastolic blood pressure (p = 0.007). Percentage of sleep time with saturation of hemoglobin with oxygen, as measured by pulse oximetry, (SpO2) < 90% was also correlated with HOMA and Matsuda index (p = 0.014 and p = 0.012, respectively), coefficient of variation (CV) of glucose measurements (p = 0.009) and SD of 24-hour systolic blood pressure. Moreover, minimum SpO2 was correlated with glucose levels (p = 0.018), Matsuda index (p = 0.30) and SD of 24-hour diastolic and systolic blood pressure (p = 0.005 and p = 0.022, respectively). CONCLUSIONS: Glucose and arterial pressure variability were associated with markers of OSAS severity (AHI, % sleep time with SpO2 < 90%, min SpO2), among nondiabetic patients. Thus, glucose and arterial pressure variability in OSAS may be an additional marker of cardiovascular risk as well as of future diabetes in these subjects. Nevertheless, the clinical significance of our observations remains to be confirmed by prospective studies.

Defected red blood cell membranes and direct correlation with the uraemic milieu: the connection with the decreased red blood cell lifespan observed in haemodialysis patients.

Together with impaired production of erythropoietin and iron deficiency, the decreased lifespan of red blood cells (RBCs) is a main factor contributing to the chronic anaemia observed in haemodialysis (HD) patients. Atomic force microscopy is employed in this work to thoroughly survey the membrane of intact RBCs (iRBCs) of HD patients in comparison to those of healthy donors, aiming to obtain direct information on the structural status of RBCs that can be related to their decreased lifespan. We observed that the iRBC membrane of the HD patients is overpopulated with extended circular defects, termed 'orifices', that have typical dimension ranging between 0.2 and 1.0 µm. The 'orifice' index-that is, the mean population of 'orifices' per top membrane surface-exhibits a pronounced relative increase of order 54 ± 12% for the HD patients as compared to healthy donors. Interestingly, for the HD patients, the 'orifice' index, which relates to the structural status of the RBC membrane, correlates strongly with urea concentration, which is a basic index of the uraemic milieu. Thus, these results indicate that the uraemic milieu downgrades the structural status of the RBC membrane, possibly triggering biochemical processes that result in their premature elimination from the circulation. This process could decrease the lifespan of RBCs, as observed in HD patients.

On the biocompatibility of Fe3O4 ferromagnetic nanoparticles with human blood cells.

Magnetic particles are currently applied to special biomedical and environmental applications owing to their unique magnetic, morphological and substance-carrying capabilities. Very recently we introduced Magnetically Assisted Hemodialysis (MAHD), an innovative therapeutic application of Ferromagnetic Nanoparticles (FNs) for the treatment of End-Stage Renal Disease (ESRD). MAHD can be employed for the selective and efficient removal of toxins that, although of high biological importance, they cannot be handled by current Hemodialysis strategies. This work is focused on evaluating the biocompatibility of Fe3O4 FNs with cells of donated human blood, namely red blood cells (RBCs), white blood cells (WBCs) and platelets (Plts). To that end, optical microscopy and atomic force microscopy were employed for the morphological examination of blood cells that were maturated under the presence of Fe3O4 FNs by means of mild incubation up to 120 min at T=20 degrees C. As a conclusion we have not detected noticeable interference between RBCs, WBCs and Pits with FNs for the maturation conditions and the extreme FNs concentrations examined in this work.

Bare and protein-conjugated Fe(3)O(4) ferromagnetic nanoparticles for utilization in magnetically assisted hemodialysis: biocompatibility with human blood cells.

Magnetically assisted hemodialysis is a development of conventional hemodialysis and is based on the circulation of ferromagnetic nanoparticle-targeted binding substance conjugates (FN-TBS Cs) in the bloodstream of the patient and their eventual removal by means of a 'magnetic dialyzer'. Presented here is an in vitro investigation on the biocompatibility of bare Fe(3)O(4) FNs and Fe(3)O(4)-bovine serum albumin Cs with blood cells, namely red blood cells (RBCs), white blood cells (WBCs) and platelets (Plts). Atomic force microscopy (AFM) and optical microscopy (OM) enabled the examination of blood cells at the nanometer and micrometer level, respectively. The observations made on FN- and C-maturated blood samples are contrasted to those obtained on FN- and C-free reference blood samples subjected to exactly the same maturation procedure. Qualitatively, both AFM and OM revealed no changes in the overall shape of RBCs, WBCs and Plts. Incidents where bare FNs or Cs were bound onto the surface of RBCs or internalized by WBCs were very rare. Detailed examination by means of OM proved that impaired coagulation of Plts is not initiated/promoted either by FNs or Cs. Quantitatively, the statistical analysis of the obtained AFM images from RBC surfaces clearly revealed that the mean surface roughness of RBCs maturated with bare FNs or Cs was identical to the one of reference RBCs.

Addition of cyclophosphamide and higher doses of dexamethasone do not improve outcomes of patients with AL amyloidosis treated with bortezomib.

Bortezomib, in combination with dexamethasone (VD) or with the addition of cyclophosphamide (VCD), is highly effective in patients with amyloid light-chain (AL) amyloidosis. Currently, VCD is considered as a primary regimen for patients with AL, but it is not clear whether the addition of cyclophosphamide to VD further and significantly improves efficacy, given the substantial activity of bortezomib itself. We retrospectively compared the outcomes of 101 patients with AL amyloidosis who received VD (n=59) or VCD (n=42) in two consecutive periods. Early mortality after adjustment for Mayo stage was similar. On intent to treat, a hematologic response rate was 68% for patients treated with VD and 78% for VCD (P=0.26), while complete response+very good partial response (CR+VGPR) rate was 47.5% and 35%, respectively. Higher doses of dexamethasone or twice-weekly bortezomib were not associated with significantly higher CR+VGPR rates. Organ responses occurred in similar rates between the two groups. Median survival was similar (33 vs 36 months, P=0.45) even after adjustment for Mayo stage and dose and schedule of bortezomib and dexamethasone. In conclusion, bortezomib even with low doses of dexamethasone is effective for the treatment of AL amyloidosis; higher doses of dexamethasone and addition of cyclophosphamide do not seem to have a profound effect on efficacy and survival.

Accurate assessment of patient effective radiation dose and associated detriment risk from radiofrequency catheter ablation procedures.

BACKGROUND: Radiofrequency (RF) cardiac catheter ablation procedures may require extended fluoroscopic exposure resulting in elevated radiation risk. The aim of the present study was to accurately establish RF ablation radiation risk levels and to provide means for accurate patient risk estimation from studies performed in any electrophysiology laboratory. METHODS AND RESULTS: Fluoroscopy required during cardiac ablation was classified into 4 types identified by beam orientation and irradiated tissue: (1) posteroanterior exposure during catheter advancing from the groin to the heart, (2) posteroanterior heart exposure, (3) left anterior oblique heart exposure, and (4) right anterior oblique heart exposure. The duration of each exposure was monitored in 24 patients undergoing RF cardiac ablation. Dose per minute of fluoroscopy was measured at 15 organs/tissues for each projection with the use of anthropomorphic phantom and thermoluminescence dosimetry. The effective dose rate was 219, 144, 136, and 112 mu/min for groin-to-heart posteroanterior, posteroanterior, left anterior oblique, and right anterior oblique exposure, respectively. A typical ablation procedure results in a total effective dose of 8.3 mSv per hour of fluoroscopy. The average excess of fatal cancers was estimated to be 650 and 480 per million patients undergoing RF ablation requiring 1 hour of fluoroscopy for US and UK populations, respectively. The average risk for genetic defects was determined to be 1 per million births. CONCLUSIONS: Radiation risk from RF cardiac ablation is moderate compared with other complications, but it may highly exceed radiation risk from common radiological procedures. Efforts should be made toward minimization of patient radiation risk from RF ablation procedures.

Conceptus radiation dose and risk from cardiac catheter ablation procedures.

BACKGROUND: The aim of the current study was to estimate the conceptus radiation dose and risk associated with fluoroscopic imaging during a catheter ablation procedure for supraventricular tachycardia performed on the expectant mother. METHODS AND RESULTS: Exposure parameters and fluoroscopy times for each projection of the cardiac ablation procedure performed in 20 female patients of childbearing age were recorded. Radiation doses for a potential conceptus were estimated by using dose data obtained in anthropomorphic phantoms simulating pregnancy at the first, second, and third trimesters. Dose measurements were carried out using thermoluminescent dosimeters. For a typical examination, the average radiation dose to the conceptus was <1 mGy in all periods of gestation. Average excess fatal cancer was 14.5/10(6) unborn children irradiated during the first postconception weeks. Corresponding values for the second and third trimesters were 30 and 55.7/10(6), respectively. The risk for hereditary effects in future generations was 1.5/10(6) cases for conceptus irradiation during the first postconception weeks. Corresponding values for the second and third trimesters were 3.0 and 5.6/10(6), respectively. Formulas and dose data are presented for estimating the conceptus risk from any technique and x-ray system used for catheter ablation procedures. CONCLUSIONS: A typical catheter ablation procedure results in a very small increase in risk of harmful effects to the conceptus. However, estimation of conceptus dose from catheter ablation procedures is always needed to assess the risk to the individual developing in utero.

[Factors influencing secondary preventive blood pressure control in hypertensive stroke patients]. / Einflussfaktoren auf die effektive Blutdruckeinstellung im Rahmen der sekundären Schlaganfallprophylaxe.

BACKGROUND: More than half of patients with documented hypertension surviving cerebrovascular events do not have their blood pressure (BP) controlled, despite the use of antihypertensive medication. Data on the possible reasons for poor BP control in stroke survivors are limited. METHODS: We evaluated prospectively parameters influencing the effectiveness of BP control in hypertensive stroke survivors who were followed up. RESULTS: At 3 months after stroke BP was effectively controlled in only 38.8% of patients. Diabetes mellitus had a negative influence on the effectiveness of antihypertensive medication by reducing significantly the chance of achieving a significant BP reduction, while patients suffering from coronary artery disease had an increased chance of getting their BP under control within 3 months after stroke onset. Diuretic medication was found to be an independent positive predictor for effective antihypertensive control. Combined therapy including diuretics was significantly more effective than antihypertensive monotherapy. CONCLUSIONS: Arterial pressure control in stroke survivors is poor. Risk factor profile, manifest heart disease, and the chosen antihypertensive medication are factors of prognostic relevance for effective BP control.

Changes in atrial electrical properties following cardioversion of chronic atrial fibrillation: relation with recurrence.

OBJECTIVE: To study the reversibility of atrial electrical remodeling and its relation with recurrence in post-conversion chronic atrial fibrillation (CAF) patients. METHODS: In 28 drug-free CAF patients (mean AF duration 41+/-39 months) electrically converted to sinus rhythm effective refractory period (ERP) at 500 ms, monophasic action potential at 90% of repolarization (MAPd90) at five cycle lengths (CL, 350, 400, 450, 500, 600 ms), and P wave duration were measured three times: within the interval 5-20 min post-conversion, 24 h and 1 month later. Fifteen subjects with no history of AF and normal atrial structure served as a control group. Patients were followed up for recurrence for 1 month; 12 relapsed. RESULTS: ERP changed from 205+/-20 to 243+/-31 to 241+/-24 ms (P<0. 001), attaining a level comparable to that of the controls (238+/-21 ms) within 24 h. MAPd90 significantly (P<0.001) increased (from 175+/-11 to 190+/-19 to 191+/-10 ms at CL 350 ms and 201+/-12 to 234+/-20 and 233+/-23 ms at CL 600 ms) also reaching control levels within 24 h. MAPd90 exhibited an abnormal adaptation to rate only in the first evaluation. P wave duration was prolonged (137+/-33 ms) and exhibited a slower course of shortening (130+/-32 to 123+/-27 ms, P<0.001), reaching control levels within 1 month. Patients with higher values of MAPd90 at CL 350 in the immediate post-conversion period were more likely to relapse (P<0.005). CONCLUSIONS: ERP and repolarization shortening as a result of CAF are reversed within 24 h after conversion, while P wave duration reduces more slowly. Post-conversion MAPd90 values contain prognostic information for recurrence.

Relation of autonomic modulation to recurrence of atrial fibrillation following cardioversion.

The aim of this study was to investigate the time course of changes in autonomic nervous system activity in patients with long-standing atrial fibrillation (AF) following internal electrical conversion to sinus rhythm and to look for differences between patients who do and do not relapse. Time-domain indexes of heart rate variability were calculated from 24-hour Holter recordings on the day of conversion and 1 day and 1 month afterward for 22 patients with chronic (> 3 months) AF. Ten healthy subjects served as a control group. During the day of cardioversion the mean RR interval and its circadian variation differed significantly between controls and patients. The mean values of successive RR intervals that deviated by > 50% from the prior RR interval and the root-mean-square of successive RR interval differences--indexes of vagal modulation--were initially significantly higher in patients than in controls but showed a decrease (p < 0.05) by the second day (from 12.4 +/- 7% to 8.1 +/- 5% to 7.3 +/- 5% and from 49 +/- 9 to 39 +/- 12 to 41 +/- 11 ms, respectively) to levels similar to those of the controls (7.6 +/- 5% and 40 +/- 17 ms, respectively). Only these 2 indexes contained significant prognostic information about relapse: patients who later relapsed had higher initial values than those who did not, and these values remained high during the 2 days after conversion. In conclusion, this study provides data confirming that spontaneous chronic AF in humans results in a significant increase in vagal tone that is reversed with time after restoration of sinus rhythm. Persistently higher values of vagal tone are observed in patients who relapse, and are probably a predictor for recurrence.

Effect of pericardial pressure on human coronary circulation.

A 52-year-old patient underwent percutaneous balloon pericardiotomy because of rapid fluid accumulation. During the procedure, we calculated the amount of blood flow to the nondiseased left anterior descending coronary artery while pericardial pressure was gradually increased by the infusion of warmed normal saline solution. Coronary vasodilator reserve was assessed by intracoronary adenosine. With increasing pericardial pressure, there was a continuous decline in coronary blood flow, due to an increase in coronary vascular resistance, and an unaffected hyperemic response throughout. The maximal hyperemic flow was far less under increased pericardial pressure than at normal pressure, which implies an augmented susceptibility to myocardial ischemia.

Twenty four hour variation in plasma atrial natriuretic factor during VVI and DDD pacing.

OBJECTIVE: To investigate whether plasma atrial natriuretic factor (ANF) follows a pattern of circadian variation similar to that of other hormones in patients paced under VVI and DDD pacing modes and to determine if the known effect of pacing mode on ANF secretion is maintained throughout the 24 hour period. PATIENTS AND DESIGN: 20 patients were studied. They had complete atrioventricular block and had been paced for 17 (SD 3.5) months with a dual chamber multiprogrammable pacemaker. They were divided into two groups according to the duration of pacing in either VVI or DDD mode before the measurements: group A, n = 11 (8 men, 3 women, aged 65 (7) years), each paced for 24 h under each of VVI and DDD modes in random order; group B, n = 9 (7 men, 2 women, aged 63 (8) years), each paced for 60 d under each pacing mode before the measurements. Blood samples were taken and ANF concentrations measured every 4 h over a 24 h period, starting at 09.00. Measurements were also made of plasma cortisol, which has a known circadian pattern, so that the 24 h curve could be compared with that of ANF. RESULTS: In contrast to cortisol, ANF values indicated a pulsatile pattern of secretion throughout the 24 h period, with no clear circadian variation. In group B, ANF concentrations were significantly higher during VVI than during DDD pacing throughout the 24 h period, whereas in group A this difference was statistically significant only at certain times of day. CONCLUSIONS: ANF does not show the circadian pattern of variation shown by cortisol and other hormones. Dual chamber pacing contributes to an improvement not only in cardiac haemodynamics but also in the neuroendocrine system, especially in the long term.

Factors influencing acute blood pressure values in stroke subtypes.

The aim of this prospective observational study was to determine the association of acute blood pressure values with independent factors (demographic, clinical characteristics, early complications) in stroke subgroups of different aetiology. We evaluated data of 346 first-ever acute (<24 h) stroke patients treated in our stroke unit. Casual and 24-h blood pressure (BP) values were measured. Stroke risk factors and stroke severity on admission were documented. Strokes were divided into subgroups of different aetiopathogenic mechanism. Patients were imaged with CT-scan on admission and 5 days later to determine the presence of brain oedema and haemorrhagic transformation. The relationship of different factors to 24-h BP values (24-h BP) was evaluated separately in each stroke subgroup. In large artery atherosclerotic stroke (n=59), history of hypertension and stroke severity correlated with higher 24-h BP respectively. In cardioembolic stroke (n=87), history of hypertension, stroke severity, haemorrhagic transformation and brain oedema were associated with higher 24-h BP, while heart failure with lower 24-h BP. History of hypertension and coronary artery disease was related to higher and lower 24-h BP, respectively, in lacunar stroke (n=75). In patients with infarct of undetermined (n=57) cause 24-h BP were mainly influenced by stroke severity and history of hypertension. An independent association between higher 24-h BP and history of hypertension and cerebral oedema was documented in intracerebral haemorrhage (n=68). In conclusion, different factors influence acute BP values in stroke subtypes of different aetiology. If the clinical significance of these observations is verified, a differentiated approach in acute BP management based on stroke aetiology may be considered.

Impact of atrioventricular delay on heart rate variability of paced patients with and without heart failure.

The aim of the study was to investigate whether the optimisation of atrioventricular (AV) delay in patients with complete AV block, with or without heart failure, paced under VDD mode, has an effect on heart rate variability and consequently on the autonomic nervous system in these patients. We studied 10 patients (Group I: 7 men, aged 68 +/- 9 years) with normal left ventricular function and 9 patients (Group II: 6 men, aged 70 +/- 6 years) with systolic left ventricular dysfunction (NYHA heart failure Class II or III). Each patient was paced for 24 h with the optimal and 24 h with the worst AV delay in random order and ambulatory electrocardiograms (ECGs) (Marquette) were recorded. Spectral heart rate variability was analysed for each 24-h period on a Holter analysis system (Marquette Series 8000). The optimal and worst AV delay were determined by echo-Doppler as those which produced the greatest and least cardiac output, respectively. For the patients in Group I, there was no difference between the two AV delays as regards indices of heart rate variability. In contrast, for Group II the total frequency (TF) was significantly higher and the low frequency (LF) and LF/high frequency (HF) ratio were significantly lower when the patients were paced with optimum AV delay. Furthermore, this AV delay resulted in significantly higher mean NN and SD. In conclusion, in patients with normal left ventricular function, changes in AV delay do not appear to affect the activity of the autonomic nervous system in the heart. In patients with mild to moderate heart failure, optimisation of the AV delay causes a significant drop in sympathetic nervous tone.

Evaluation of the reliability of ST segment monitoring by transtelephonic electrocardiogram transmission.

INTRODUCTION: Transtelephonic electrocardiographic transmission is a diagnostic technique which has been systematically applied in recent years, mainly for the detection of arrhythmias or pacemaker malfunction. The purpose of this study was to assess the efficacy of this method in the recording and transmission of ST segment and T wave changes. METHOD: A Bruce protocol exercise stress test was carried out in 47 consecutive patients (39 males, eight females, age 53.1 +/- 11.5 years) with suspected coronary artery disease (CAD). At the same time, a transtelephonic ECG system, with a 2-min memory and the capability for 16.5 days continuous recording, was used to transmit the ECG (modified leads II and V5). RESULTS: A positive ST segment shift was observed in 19 patients (40.4%) during the exercise test. The transtelephonic system recorded this change in 18 of these patients but missed the anteroseptal ST segment depression (V2-V4) in one patient (sensitivity 94.7%). All of the 23 patients with no ST segment changes during the exercise test had a negative transtelephonic ECG transmission (specificity 100%). The width of the ST depression recorded from modified lead II on the transtelephonic recording was not significantly different from that of the 12-lead ECG. The same was true for modified lead V5. CONCLUSION: Transtelephonic ECG transmission in patients with suspected CAD can significantly contribute to the investigation of this problem, since the method has high sensitivity and specificity. The capacity for continuous recording and the memory of the device make possible the monitoring of high risk patients for a good length of time.

Radiofrequency ablation of atrioventricular node reentrant tachycardia: experience in 302 patients.

Radiofrequency catheter ablation was performed in 302 consecutive patients with drug refractory atrioventricular (AV) node reentrant tachycardia. Fast pathway ablation was attempted in 167 patients and was successful in 161 patients (96.4%). At a mean follow-up of 24 +/- 12 months, there were 21 tachycardia recurrences (12.5%). A second fast pathway ablation was attempted in 17 patients and was successful in all but 1 patient. Permanent complete AV block occurred in 12 patients (7.2%). Among the latter, late AV block was noted in 5 patients. Final success without pacemaker implantation was accomplished in 151 patients (90.4%). Slow pathway was attempted in 135 patients and was successful in 130 patients (96.3%). Three patients in whom slow pathway ablation failed underwent successful fast pathway ablation during the same session. At a mean follow-up of 14 +/- 11 months, there were 16 tachycardia recurrences (11.8%). A second slow pathway ablation was attempted in 16 patients and was successful in all but 1 patient. Permanent complete AV block occurred in 3 patients (2.2%). An additional patient developed 2 : 1 AV block during exercise, 3 months after ablation. Final success without pacemaker implantation was achieved in 129 patients (95.5%). Fast and slow pathway ablation had similar success and recurrence rates, procedure and fluoroscopy times, and number of radiofrequency pulses. However, the incidence of permanent complete AV block was higher following fast pathway ablation (p = 0.049). Although equally effective, slow pathway ablation is safer than fast pathway ablation, therefore, should be the first choice approach for treatment of AV node reentrant tachycardia.

Statin treatment is associated with improved prognosis in patients with AF-related stroke.

BACKGROUND/OBJECTIVES: The most recent ACC/AHA guidelines recommend high-intensity statin therapy in ischemic stroke patients of presumably atherosclerotic origin. On the contrary, there is no specific recommendation for the use of statin in patients with non-atherosclerotic stroke, e.g. strokes related to atrial fibrillation (AF). We investigated whether statin treatment in patients with AF-related stroke is associated with improved survival and reduced risk for stroke recurrence and future cardiovascular events. METHODS: All consecutive patients registered in the Athens Stroke Registry with AF-related stroke and no history of coronary artery disease nor clinically manifest peripheral artery disease were included in the analysis and categorized in two groups depending on whether statin was prescribed at discharge. The primary outcome was overall mortality; the secondary outcomes were stroke recurrence and a composite cardiovascular endpoint comprising of recurrent stroke, myocardial infarction, aortic aneurysm rupture or sudden cardiac death during the 5-year follow-up. RESULTS: Among 1602 stroke patients, 404 (25.2%) with AF-related stroke were included in the analysis, of whom 102 (25.2%) were discharged on statin. On multivariate Cox-proportional-hazards model, statin treatment was independently associated with a lower mortality (hazard-ratio (HR): 0.49, 95%CI:0.26-0.92) and lower risk for the composite cardiovascular endpoint during the median 22 months follow-up (HR: 0.44, 95%CI:0.22-0.88), but not with stroke recurrence (HR: 0.47, 95%CI:0.22-1.01, p: 0.053). CONCLUSIONS: In this long-term registry of patients with AF-related stroke, statin treatment was associated with improved survival and reduced risk for future cardiovascular events.

Pleiotropic effects of the acute and chronic inhibition of the renin-angiotensin system in hypertensives.

Renin-angiotensin system (RAS) inhibition may exert beneficiary pleiotropic effects on heart hemodynamics in hypertensive patients. We aimed to assess these effects on coronary flow reserve (CFR) and left ventricular (LV) filling pressure after acute and long-term treatment. Thirty-nine patients (48.4±6.8 years) with newly diagnosed, never-treated essential arterial hypertension were consecutively recruited from an outpatient hypertension clinic. CFR in the left anterior descending artery and the ratio of mitral inflow E wave to the averaged mitral annulus tissue velocity of the E waves (E/e' ratio), as an estimate of LV filling pressure, were assessed by Doppler echocardiography. In the acute phase of the study, consecutive eligible patients were assigned to receive po Quinapril (Q) 20 mg (n=15) or Losartan (L) 100 mg (n=14) or no treatment (n=10) and were reexamined 2 h post treatment. In the chronic phase of the study, the patients were reevaluated after 1 month on the assigned treatment. During the acute phase, CFR (P=0.005) was significantly improved in the RAS inhibition as compared with the control group, independently of blood pressure (BP) changes. The E/e' ratio was also marginally improved (P=0.053), but this effect was more pronounced in patients with E/e' ratio>8 (P=0.005). CFR and E/e' ratio were also improved after 1 month of treatment, particularly in responders after the acute phase. In hypertensive patients, RAS inhibition acutely improved CFR and E/e' ratio independently of BP changes. An acute positive response in these parameters was closely related to sustained improvement after 1 month of single-drug treatment.

VTD consolidation, without bisphosphonates, reduces bone resorption and is associated with a very low incidence of skeletal-related events in myeloma patients post ASCT.

We prospectively evaluated the effect of bortezomib, thalidomide and dexamethasone (VTD) consolidation on bone metabolism of 42 myeloma patients who underwent an autologous stem cell transplantation (ASCT). VTD started on day 100 post ASCT; patients received four cycles of VTD (first block), were followed without treatment for 100 days and then received another four VTD cycles (second block). During this 12-month period, bisphosphonates were not administered. Best response included stringent complete remission (sCR) in 15 (35.7%) patients, complete response (CR) in 13 (30.9%), vgPR in 7 (16.6%), PR in 4 (9.5%), while 3 (7.1%) patients developed a progressive disease (PD). Importantly, 33.3% and 47.6% of patients improved their status of response after the first and second VTD block, respectively. VTD consolidation resulted in a significant reduction of circulating C-terminal cross-linking telopeptide of collagen type I (CTX), soluble receptor activator of the nuclear factor-kappa B ligand (sRANKL) and osteocalcin (OC), whereas bone-specific alkaline phosphatase (bALP) remained stable compared with pre-VTD values. During the study period, only one patient with a PD developed a skeletal-related event (that is, radiation to bone). The median time to progression (TTP) after ASCT was 34 months and the median time of next treatment was 40 months. We conclude that VTD consolidation post ASCT reduces bone resorption and is associated with a very low incidence of skeletal-related events (SREs) despite the absence of bisphosphonates; the later do not appear to be necessary in this context.