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.

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.

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.

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.

The use of 24-h ambulatory blood pressure monitoring (ABPM) during the first cycle of sunitinib improves the diagnostic accuracy and management of hypertension in patients with advanced renal cancer.

AIM: Hypertension (HT) complicates treatment with antiangiogenic agents, including the tyrosine kinase inhibitor (TKI) sunitinib. To prospectively evaluate the prevalence and management of HT in patients with advanced renal cell carcinoma (RCC) receiving sunitinib we used 24-h ABPM and we treated HT according to guidelines of the Joint National Committee on Prevention, Detection and Evaluation and the Treatment of High Blood Pressure (JNC7). PATIENTS AND METHODS: Normal 24-h ABPM at the baseline and at 2, 4 and 6 weeks of the first cycle was ensured with the successive use of hydrochlorothiazide+irbesartan, nebivolol and amlodipine. Office BP measurements were used in subsequent cycles to monitor HT. Sunitinib dose was modified only if BP was not controlled with four anti-hypertensive agents. RESULTS: Forty patients were included in this analysis. Twenty-one patients (53%) had baseline HT, while 12 of 14 (84%) normotensive patients required anti-HT treatment during the 1st cycle of sunitinib. HT was infrequent in subsequent cycles and increase of anti-HT medication was required in only 2 cases. Two patients permanently discontinued sunitinib due to HT. The remaining 34 (94%) required no dose modifications for HT. One cardiac event (2.8%) was observed. There was no correlation of HT with sunitinib efficacy. CONCLUSION: Sunitinib-associated HT is more frequent than previously reported. The use of 24-h ABPM for diagnosis and tailoring of HT according to JNC7 guidelines may achieve uninterrupted, full dose therapy in most patients. The substitution of such protocols for currently used Toxicity Criteria may be warranted.

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.

Diagnosis and management of hypertension in advanced renal cell carcinoma: prospective evaluation of an algorithm in patients treated with sunitinib.

Hypertension may complicate treatment with antiangiogenic agents, leading to dose reductions and treatment delays. To prospectively evaluate the frequency and management of hypertension in 10 patients with advanced kidney cancer receiving sunitinib, we used 24-h blood pressure monitoring (BPM) and home BPM and homogenously treated hypertension according to guidelines of the european Society of Hypertension. Normal BP was ensured prior to sunitinib initiation with the successive use of hydrochlorothiazide + irbesartan, nebivolol, amlodipine. During treatment, additional antihypertensive therapy was introduced, if necessary. Sunitinib dose was modified only if BP was not controlled with four anti-hypertensive agents. four patients had baseline hypertension, while 5 of 6 normotensive patients required antihypertensive treatment during sunitinib administration. One patient permanently discontinued sunitinib due to hypertensive crisis but 9 patients received full dose. Sunitinib-associated hypertension is more frequent than previously reported. Aggressive BP monitoring and treatment of hypertension may achieve uninterrupted, full-dose therapy in most patients treated with sunitinib. The application of such protocols instead of commonly used toxicity criteria should be further validated.

Statin therapy after first stroke reduces 10-year stroke recurrence and improves survival.

OBJECTIVE: To determine whether statin therapy after hospital discharge affects ischemic stroke recurrence and long-term mortality in patients admitted for a first-ever occurrence of ischemic stroke. METHODS: This was a retrospective observational study involving linked hospitalization and death records. The cohort comprised a series of 794 consecutive, first-ever acute ischemic stroke patients from the Athenian Stroke Registry, admitted to the acute stroke unit and the general medicine and neurology ward of our institutions since January 1997 for whom there was available information covering a 10-year follow-up period. Cox proportional hazards model was used to identify risk factors for stroke recurrence and death. RESULTS: The recurrence rate was 16.3% among stroke patients not receiving a statin after hospital discharge compared with 7.5% among those who received statin therapy (p = 0.002). Cox regression analyses revealed only statin therapy postdischarge to be a significant independent predictor of stroke recurrence (adjusted hazard ratio [HR], 0.65, 95% confidence interval [CI] 0.39 to 0.97, p < 0.01). Similarly, patients receiving a statin had a significantly lower mortality during the 10-year period after the acute cerebrovascular event (adjusted HR, 0.43; 95% CI 0.29 to 0.61, p < 0.01). CONCLUSIONS: Prescribing statin therapy upon hospital discharge to patients with first-ever acute stroke lowers the risk of 10-year stroke recurrence and improves survival.

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.

The role of the post-cardioversion time course of hs-CRP levels in clarifying the relationship between inflammation and persistence of atrial fibrillation.

OBJECTIVES: Although recent studies suggest that inflammation is involved in the pathogenesis of atrial fibrillation (AF), it remains controversial whether it is a consequence or a cause of the arrhythmia. DESIGN: Prospective study. SETTING: Tertiary referral centre. PATIENTS AND INTERVENTIONS: In 52 patients with persistent AF lasting >3 months, high-sensitivity C-reactive protein (hs-CRP) was measured before and after electrical cardioversion. MEASUREMENTS AND RESULTS: All patients were successfully cardioverted to sinus rhythm (SR), but the recurrence rate was 23% at 1 month. Baseline hs-CRP was higher in patients with AF recurrence than in those who remained in SR (0.5 (SD 0.18) mg/dl vs 0.29 (SD 0.13) mg/dl, respectively, p<0.001). Similarly, arrhythmia recurrence was associated with greater left atrial diameters (45.4 (SD 3.3) mm vs 40.7 (SD 3.1) mm, respectively, p<0.001). However, logistic regression analysis showed that hs-CRP was the only independent predictor for AF recurrence (p<0.001). Additionally, patients who were in SR on final evaluation had significantly lower hs-CRP levels than at baseline (0.10 (SD 0.06) mg/dl vs 0.29 (SD 0.13) mg/dl, respectively, p<0.001), while those who experienced AF recurrence had similar values on final and on initial evaluation (0.56 (SD 0.24) mg/dl vs 0.50 (SD 0.18) mg/dl, respectively, p = 0.42). CONCLUSION: High levels of hs-CRP are associated with an increased risk of AF recurrence after cardioversion. The restoration and maintenance of SR result in a gradual decrease of hs-CRP while AF recurrence has a different effect, suggesting that inflammation is a consequence, rather than a cause, of AF.

Occupational exposure in the electrophysiology laboratory: quantifying and minimizing radiation burden.

Fluoroscopically guided procedures in the electrophysiology room, such as radiofrequency catheter ablation and implantation of cardiac resynchronization devices, may result in high radiation exposure of electrophysiologists and assisting staff. Our aim was to provide accurate and applicable data on occupational doses to the electrophysiology laboratory personnel. We exposed fluoroscopically an anthropomorphic phantom at three projections common in electrophysiology studies. For each exposure, scattered radiation was measured at 182 sites of the cardiology room at four body levels. Effective dose values, eye lens, skin and gonadal doses to the laboratory staff were calculated. Our study has shown that a procedure requiring 40 min of fluoroscopy yields a maximum effective dose of 129 microSv and a maximum value of gonadal dose of 56.8 microSv to staff using a 0.35 mm lead-equivalent apron. A conservative estimate of the electrophysiologist's annual maximum permissible workload is 155 procedures. Staff effective dose values vary by a factor of 40 due to positioning during fluoroscopy and by a factor of 11 due to radiation protection equipment. Undercouch protective shields may reduce gonadal doses up to 98% and effective dose up to 25%. Consequently, radiation levels in the electrophysiology room are not negligible. Mitigation of occupational exposure is feasible through good fluoroscopy and working practices.

Twenty four hour pulse pressure predicts long term recurrence in acute stroke patients.

OBJECTIVES: The impact of different blood pressure (BP) components during the acute stage of stroke on the risk of recurrent stroke is controversial. The present study aimed to investigate by 24 hour BP monitoring a possible association between acute BP values and long term recurrence. METHODS: A total of 339 consecutive patients with first ever acute stroke underwent 24 hour BP monitoring within 24 hours of ictus. Known stroke risk factors and clinical findings on admission were documented. Patients given antihypertensive medication during BP monitoring were excluded. The outcome of interest during the one year follow up was recurrent stroke. The Cox proportional hazard model was used to analyse association of casual and 24 hour BP recordings with one year recurrence after adjusting for stroke risk factors, baseline clinical characteristics, and secondary prevention therapies. RESULTS: The cumulative one year recurrence rate was 9.2% (95% CI 5.9% to 12.3%). Multivariate Cox regression analyses revealed age, diabetes mellitus, and 24 hour pulse pressure (PP) as the only significant predictors for stroke recurrence. The relative risk for one year recurrence associated with every 10 mm Hg increase in 24 hour PP was 1.323 (95% CI 1.019 to 1.718, p = 0.036). Higher casual PP levels were significantly related to an increased risk of one year recurrence on univariate analysis, but not in the multivariate Cox regression model. CONCLUSIONS: Elevated 24 hour PP levels in patients with acute stroke are independently associated with higher risk of long term recurrence. Further research is required to investigate whether the risk of recurrent stroke can be reduced to a greater extent by decreasing the pulsatile component of BP in patients with acute stroke.

[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.

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.

U-shaped relationship between mortality and admission blood pressure in patients with acute stroke.

OBJECTIVE: To evaluate the relationship between systolic blood pressure (SBP) or diastolic blood pressure (DBP) on admission and early or late mortality in patients with acute stroke. DESIGN: Prospective study of hospitalized first-ever stroke patients over 8 years. SETTING: Stroke unit and medical wards in a University hospital. SUBJECTS: A total of 1121 patients admitted within 24 h from stroke onset and followed up for 12 months. MAIN OUTCOME MEASURES: Mortality at 1 and 12 months after stroke in relation to admission SBP and DBP. RESULTS: Early and late mortality in patients with acute ischaemic or haemorrhagic stroke in relation to admission SBP and DBP followed a 'U-curve pattern'. After adjusting for known outcome predictors, the relative risk of 1-month and 1-year mortality associated with a 10-mmHg SBP increase above 130 mmHg (U-point of the curve) increased by 10.2% (95% CI: 4.2-16.6%) and 7.2% (95% CI: 2.2-12.3%), respectively. For every 10 mmHg SBP decrease, below the U-point, the relative risk of 1-month and 1-year mortality rose by 28.2% (95% CI: 8.6-51.3%) and 17.5% (95% CI: 3.1-34.0%), respectively. Low admission SBP-values were associated with heart failure (P < 0.001) and coronary artery disease (P = 0.006), whilst high values were associated with history of hypertension (P < 0.001) and lacunar stroke (P < 0.001). Death due to cerebral oedema was significantly (P = 0.005) more frequent in patients with high admission SBP-values, whereas death due to cardiovascular disease was more frequent (P = 0.004) in patients with low admission SBP-values. CONCLUSION: Acute ischaemic or haemorrhagic stroke patients with high and low admission BP-values have a higher early and late mortality. Coincidence of heart disease is associated with low initial BP-values. Death due to neurological damage from brain oedema is associated with high initial BP-values.

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.

Atrial defibrillation threshold in humans minutes after atrial fibrillation induction; "A stitch in time saves nine".

AIMS: To assess the effects of atrial fibrillation duration on the defibrillation threshold in atrial fibrillation patients seconds or minutes after initiation of the arrhythmia. METHODS AND RESULTS: Nineteen patients with recurrent symptomatic atrial fibrillation were evaluated. After programmed induction of atrial fibrillation, the defibrillation threshold was assessed after two sequential periods of arrhythmia in the same patient: an "ultrashort" period of 30 s duration and a "short" period, which lasted 10 min. After the specified period, internal cardioversion was attempted using a balloon-guided catheter that allows the delivery of biphasic shocks between one electrode array placed in the left pulmonary artery and a proximal electrode array on the lateral right atrial wall. The defibrillation threshold was assessed with energy steps of 0.5 J with a starting level of 0.5 J. Mean time from induction to successful defibrillation was 92+/-30 s after the "ultrashort" period of atrial fibrillation and 910+/-86 s after the short period. The defibrillation threshold was significantly greater after 10 min of atrial fibrillation than after 30 s of arrhythmia (2.32+/-0.61 J vs 1.31+/-0.66 J, P<0.001). Clinical data were not found to affect the defibrillation threshold. CONCLUSIONS: Prolongation of atrial fibrillation over minutes in patients with paroxysmal arrhythmia increases the energy requirements for successful defibrillation.