Performance of Different Risk Scores for the Detection of Atrial Fibrillation Among Patients With Cryptogenic Stroke.

BACKGROUND: Atrial fibrillation (AF) is a frequent underlying cause of cryptogenic stroke (CS) and its detection can be increased using implantable cardiac monitoring (ICM). We sought to evaluate different risk scores and assess their diagnostic ability in identifying patients with CS with underlying AF on ICM. METHODS: Patients with CS, being admitted to a single tertiary stroke center between 2017 and 2022 and receiving ICM, were prospectively evaluated. The CHA2DS2-VASc, HAVOC, Brown ESUS-AF, and C2HEST scores were calculated at baseline. The primary outcome of interest was the detection of AF, which was defined as at least 1 AF episode on ICM lasting for 2 consecutive minutes or more. The diagnostic accuracy measures and the net reclassification improvement were calculated for the 4 risk scores. Stroke recurrence was evaluated as a secondary outcome. RESULTS: A total of 250 patients with CS were included, and AF was detected by ICM in 20.4% (n=51) during a median monitoring period of 16 months. Patients with CS with AF detection were older compared with the rest (P=0.045). The median HAVOC, Brown ESUS-AF, and C2HEST scores were higher among the patients with AF compared with the patients without AF (all P<0.05), while the median CHA2DS2-VASc score was similar between the 2 groups. The corresponding C statistics for CHA2DS2-VASc, HAVOC, Brown ESUS-AF, and C2HEST for AF prediction were 0.576 (95% CI, 0.482-0.670), 0.612 (95% CI, 0.523-0.700), 0.666 (95% CI, 0.587-0.746), and 0.770 (95% CI, 0.699-0.839). The C2HEST score presented the highest diagnostic performance based on C statistics (P<0.05 after correction for multiple comparisons) and provided significant improvement in net reclassification for AF detection (>70%) compared with the other risk scores. Finally, stroke recurrence was documented in 5.6% of the study population, with no difference regarding the 4 risk scores between patients with and without recurrent stroke. CONCLUSIONS: The C2HEST score was superior to the CHA2DS2-VASc, HAVOC, and Brown ESUS-AF scores for discriminating patients with CS with underlying AF using ICM.

Association of clinical, laboratory and imaging biomarkers with the occurrence of acute myocardial infarction in patients without standard modifiable risk factors - rationale and design of the "Beyond-SMuRFs Study".

BACKGROUND: Acute myocardial infarction (AMI) remains the leading cause of mortality worldwide. The majority of patients who suffer an AMI have a history of at least one of the standard modifiable risk factors (SMuRFs): smoking, hypertension, dyslipidemia, and diabetes mellitus. However, emerging scientific evidence recognizes a clinically significant and increasing proportion of patients presenting with AMI without any SMuRF (SMuRF-less patients). To date, there are no adequate data to define specific risk factors or biomarkers associated with the development of AMIs in these patients. METHODS: The ''Beyond-SMuRFs Study'' is a prospective, non-interventional cohort trial designed to enroll patients with AMI and no previous coronary intervention history, who undergo coronary angiography in two academic hospitals in Thessaloniki, Greece. The rationale of the study is to investigate potential relations between SMuRF-less AMIs and the clinical, laboratory and imaging profile of patients, by comparing parameters between patients with and without SMuRFs. Complete demographic and comprehensive clinical data will be recorded, Venous blood samples will be collected before coronary angiography and the following parameters will be measured: total blood count, standard biochemistry parameters, coagulation tests, hormone levels, glycosylated hemoglobin, N- terminal pro-B-type natriuretic peptide and high-sensitivity troponin T levels- as well as serum levels of novel atherosclerosis indicators and pro-inflammatory biomarkers. Furthermore, all participants will undergo a complete and comprehensive transthoracic echocardiographic assessment according to a pre-specified protocol within 24 h from admission. Among others, 2D-speckle-tracking echocardiographic analysis of cardiac chambers and non-invasive calculation of myocardial work indices for the left ventricle will be performed. Moreover, all patients will be assessed for angiographic parameters and the complexity of coronary artery disease using the SYNTAX score. Multivariable linear and logistic regression models will be used to phenotypically characterize SMuRF-less patients and investigate independent clinical, laboratory, echocardiographic and angiographic biomarkers-predictors of SMuRF-less status in AMI.The first patient was enrolled in March 2022 and completion of enrollment is expected until December 2023. DISCUSSION: The ''Beyond-SmuRFs'' study is an ongoing prospective trial aiming to investigate potential clinical, laboratory and imaging biomarkers associated with the occurrence of AMIs in SMuRF-less patients. The configuration of these patients' profiles could lead to the development of personalized risk-stratification models predicting the occurrence of cardiovascular events in SΜuRF-less individuals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05535582 / September 10, 2022.

Risk assessment of post-myocardial infarction patients with preserved ejection fraction using 45-min short resting Holter electrocardiographic recordings.

BACKGROUND: Risk stratification for sudden cardiac death in post-myocardial infarction (post-MI) patients remains a challenging task. Several electrocardiographic noninvasive risk factors (NIRFs) have been associated with adverse outcomes and were used to refine risk assessment. This study aimed to evaluate the performance of NIRFs extracted from 45-min short resting Holter ECG recordings (SHR), in predicting ventricular tachycardia inducibility with programmed ventricular stimulation (PVS) in post-MI patients with preserved left ventricular ejection fraction (LVEF). METHODS: We studied 99 post-MI ischemia-free patients (mean age: 60.5 ± 9.5 years, 86.9% men) with LVEF ≥40%, at least 40 days after revascularization. All the patients underwent PVS and a high-resolution SHR. The following parameters were evaluated: mean heart rate, ventricular arrhythmias (premature ventricular complexes, couplets, tachycardias), QTc duration, heart rate variability (HRV), deceleration capacity, heart rate turbulence, late potentials, and T-wave alternans. RESULTS: PVS was positive in 24 patients (24.2%). HRV, assessed by the standard deviation of normal-to-normal R-R intervals (SDNN), was significantly decreased in the positive PVS group (42 ms vs. 51 ms, p = .039). SDNN values <50 ms were also associated with PVS inducibility (OR 3.081, p = .032 in univariate analysis, and 4.588, p = .013 in multivariate analysis). No significant differences were identified for the other NIRFs. The presence of diabetes, history of ST-elevation MI (STEMI) and LVEF <50% were also important predictors of positive PVS. CONCLUSIONS: HRV assessed from SHR, combined with other noninvasive clinical and echocardiographic variables (diabetes, STEMI history, LVEF), can provide an initial, practical, and rapid screening tool for arrhythmic risk assessment in post-MI patients with preserved LVEF.

Different venous approaches for implantation of cardiac electronic devices. A network meta-analysis.

OBJECTIVES: Many of the complications arising from cardiac device implantation are associated to the venous access used for lead placement. Previous analyses reported that cephalic vein cutdown (CVC) is safer but less effective than subclavian vein puncture (SVP). However, comparisons between these techniques and axillary vein puncture (AVP) - guided either by ultrasound or fluoroscopy - are lacking. Thus, we aimed to compare safety and efficacy of these approaches. METHODS: We searched for articles assessing at least two different approaches regarding the incidence of pneumothorax and/or lead failure (LF). When available, bleeding and infectious complications as well as procedural success were analyzed. A frequentist random effects network meta-analysis model was adopted. RESULTS: Thirty-six studies were analyzed. Most articles assessed SVP versus CVC. Compared to SVP, both CVC and AVP were associated with reduced odds of pneumothorax (OR: 0.193, 95%CI: 0.136-0.275 and OR: 0.128, 95%CI: 0.050-0.329; respectively) and LF (OR: 0.63, 95%CI: 0.406-0.976 and OR: 0.425, 95%CI: 0.286-0.632; respectively). No significant differences between AVP and CVC were demonstrated. Limited data suggests no major impact of different approaches on infectious and bleeding complications. Initial CVC approach required significantly more often an alternate/additional venous access for lead placement, compared to both AVP and SVP. No differences between these two were identified. CONCLUSION: Both AVP and CVC seem to decrease incident pneumothorax and LF, compared to SVP. Initial AVP approach seems to decrease the need of alternate venous access, compared to CVC. These results suggest that AVP should be further clinically tested.

Nonlinear Finite Element Analysis of γ-Graphyne Structures under Shearing.

In this study, a nonlinear, spring-based finite element approach is employed in order to predict the nonlinear mechanical response of graphyne structures under shear loading. Based on Morse potential functions, suitable nonlinear spring finite elements are formulated simulating the interatomic interactions of different graphyne types. Specifically, the four well-known types of γ-graphyne, i.e., graphyne-1 also known as graphyne, graphyne-2 also known as graphdiyne, graphyne-3, and graphyne-4 rectangular sheets are numerically investigated applying appropriate boundary conditions representing shear load. The obtained finite element analysis results are employed to calculate the in-plane shear stress-strain behaviour, as well as the corresponding mechanical properties as shear modulus and shear strength. Comparisons of the present graphyne shearing response predictions with other corresponding estimations are performed to validate the present research results.

Implantable Cardiac Monitoring in the Secondary Prevention of Cryptogenic Stroke.

OBJECTIVE: In this study, we sought to evaluate the impact of implantable cardiac monitoring (ICM) in the prevention of stroke recurrence after a cryptogenic ischemic stroke or transient ischemic attack (TIA). METHODS: We evaluated consecutive patients with cryptogenic ischemic stroke or TIA admitted in a comprehensive stroke center during an 8-year period. We compared the baseline characteristics and outcomes between patients receiving conventional cardiac monitoring with repeated 24-hour Holter-monitoring during the first 5 years in the outpatient setting and those receiving continuous cardiac monitoring with ICM during the last 3 years. Associations on the outcomes of interest were further assessed in multivariable regression models adjusting for potential confounders. RESULTS: We identified a total of 373 patients receiving conventional cardiac monitoring and 123 patients receiving ICM. Paroxysmal atrial fibrillation (PAF) detection was higher in the ICM cohort compared to the conventional cardiac monitoring cohort (21.1% vs 7.5%, p < 0.001). ICM was independently associated with an increased likelihood of PAF detection during follow-up (hazard ratio [HR] = 1.94, 95% confidence interval [CI] = 1.16-3.24) in multivariable analyses. Patients receiving ICM were also found to have significantly higher rates of anticoagulation initiation (18.7% vs 6.4%, p < 0.001) and lower risk of stroke recurrence (4.1% vs 11.8%, p = 0.013). ICM was independently associated with a lower risk of stroke recurrence during follow-up (HR = 0.32, 95% CI = 0.11-0.90) in multivariable analyses. INTERPRETATION: ICM appears to be independently associated with a higher likelihood of PAF detection and anticoagulation initiation after a cryptogenic ischemic stroke or TIA. ICM was also independently related to lower risk of stroke recurrence in our cryptogenic stroke / TIA cohort. ANN NEUROL 2020;88:946-955.

Systemic autoimmune diseases, anti-rheumatic therapies, COVID-19 infection risk and patient outcomes.

As of June 10th 2020 about 7.2 million individuals have tested positive for, and more than 410,000 have died due to COVID-19. In this review we outline the pathophysiology that underpins the potential use of anti-rheumatic therapies for severe COVID-19 infection and summarize the current evidence regarding the risk and outcome of COVID-19 in patients with systemic autoimmune diseases. Thus far there is no convincing evidence that any disease-modifying anti-rheumatic drug (conventional synthetic, biologic or targeted synthetic) including hydroxychloroquine, may protect against severe COVID-19 infection; answers about their possible usefulness in the management of the cytokine storm associated with severe COVID-9 infection will only arise from ongoing randomized controlled trials. Evidence on COVID-19 risk and outcome in patients with systemic autoimmune diseases is extremely limited; thus, any conclusions would be unsafe and should be seen with great caution. At present, the risk and severity (hospitalization, intensive care unit admission and death) of COVID-19 infection in people with autoimmune diseases do not appear particularly dissimilar to the general population, with the possible exception of hospitalization in patients exposed to high glucocorticoid doses. At this stage it is impossible to draw any conclusions for differences in COVID-19 risk and outcome between different autoimmune diseases and between the various immunomodulatory therapies used for them. More research in the field is obviously required, including as a minimum careful and systematic epidemiology and appropriately controlled clinical trials.

Effect of cryoballoon and radiofrequency ablation for pulmonary vein isolation on left atrial function in patients with nonvalvular paroxysmal atrial fibrillation: A prospective randomized study (Cryo-LAEF study).

BACKGROUND: Isolation of the pulmonary veins (PVI) has become a mainstay in atrial fibrillation (AFib) therapy. Lesions in left atrial tissue lead to scar formation and this may affect left atrial function. METHODS: Patients with paroxysmal AFib were randomly assigned in a 1:2 allocation scheme to radiofrequency (RF) ablation or cryoballoon. Real-time three-dimensional echocardiography was performed (under sinus rhythm in all cases) before ablation and at 1 and 3 months to evaluate the left atrial functional indices. The primary outcome measure was change in left atrial ejection fraction (LAEF) at 1 month. RESULTS: 120 patients were randomized (80 to cryoballoon, 40 to RF). The absolute change in LAEF at 1 month was 4.0 (Q1-Q3, -0.1to 7.6)% in the cryoballoon group and -0.8 (Q1-Q3, -1.9 to 0.9)% in the RF group (P < 0.001 for the comparison between groups). At 3 months, the corresponding changes were 6.7 (Q1-Q3, 3.4-11.2)% and 0.7 (Q1-Q3, -0.7 to 3.5)%, respectively (P < 0.001). Overall, the rate of patients with lower LAEF at 3 months compared to baseline was 2.5% in the cryoballoon group and 32.5% in the RF group (P < 0.001). AFib recurrence rate at 6 months was higher in patients with decreased LAEF (odds ratio, 6.2; 95% confidence interval, 2.0-19.5; P = 0.002). CONCLUSION: The Cryo-LAEF study prospectively compared the effects of RF and cryoballoon ablation on left atrial function. Both at 1 and 3 months postablation, LAEF was either improved or stable in both ablation groups.

Clinical characteristics and long-term clinical course of patients with Brugada syndrome without previous cardiac arrest: a multiparametric risk stratification approach.

AIMS: Risk stratification in Brugada syndrome (BrS) still represents an unsettled issue. In this multicentre study, we aimed to evaluate the clinical characteristics and the long-term clinical course of patients with BrS. METHODS AND RESULTS: A total of 111 consecutive patients (86 males; aged 45.3 ± 13.3 years) diagnosed with BrS were included and followed-up in a prospective fashion. Thirty-seven patients (33.3%) were symptomatic at enrolment (arrhythmic syncope). An electrophysiological study (EPS) was performed in 59 patients (53.2%), and ventricular arrhythmias were induced in 32 (54.2%). A cardioverter defibrillator was implanted in 34 cases (30.6%). During a mean follow-up period of 4.6 ± 3.5 years, appropriate device therapies occurred in seven patients. Event-free survival analysis (log-rank test) showed that spontaneous type-1 electrocardiogram pattern (P = 0.008), symptoms at presentation (syncope) (P = 0.012), family history of sudden cardiac death (P < 0.001), positive EPS (P = 0.024), fragmented QRS (P = 0.004), and QRS duration in lead V2 > 113 ms (P < 0.001) are predictors of future arrhythmic events. Event rates were 0%, 4%, and 60% among patients with 0-1 risk factor, 2-3 risk factors, and 4-5 risk factors, respectively (P < 0.001). Current multiparametric score models exhibit an excellent negative predictive value and perform well in risk stratification of BrS patients. CONCLUSIONS: Multiparametric models including common risk factors appear to provide better risk stratification of BrS patients than single factors alone.

Statin Pretreatment and Microembolic Signals in Large Artery Atherosclerosis.

OBJECTIVE: Although statin pretreatment (SP) is associated with better outcomes in patients with acute cerebral ischemia after an ischemic stroke/transient ischemic attack, data on the underlying mechanism of this beneficial effect are limited. APPROACH AND RESULTS: We sought to evaluate the potential association between SP and microembolic signal (MES) burden in acute cerebral ischemia because of large artery atherosclerosis (LAA). We prospectively evaluated consecutive patients with first-ever acute cerebral ischemia because of LAA in 3 tertiary stroke centers over a 2-year period. All patients underwent continuous 1-hour transcranial Doppler monitoring of the relevant vessel at baseline (≤24 hours). SP was recorded and dichotomized as high dose or low-to-moderate dose. SP was documented in 43 (41%) of 106 LAA patients (mean age, 65.4±10.3 years; 72% men; low-to-moderate dose, 32%; high dose, 8%). There was a significant (P=0.022) dose-dependent effect between SP and MES prevalence: no SP (37%), SP with low-to-moderate dose (18%), and SP with high dose (0%). Similarly, a significant (P=0.045) dose-dependent effect was documented between SP and MES burden: no SP (1.1±1.8), SP with low-to-moderate dose (0.7±1.6), and SP with high dose (0±0). In multivariable logistic regression analysis adjusting for demographics, vascular risk factors, location of LAA, stroke severity, and other prevention therapies, SP was associated with lower likelihood of MES presence (odds ratio, 0.29; 95% confidence interval, 0.09-0.92; P=0.036). In addition, SP was found also to be independently related to higher odds of functional improvement (common odds ratio, 3.33; 95% confidence interval, 1.07-10.0; P=0.037). CONCLUSIONS: We found that SP in patients with acute LAA is related with reduced MES presence and lower MES burden with an apparently dose-dependent association.

Effect of Postablation Statin Treatment on Arrhythmia Recurrence in Patients With Paroxysmal Atrial Fibrillation.

BACKGROUND: Statins have been proposed as a means to prevent postablation atrial fibrillation (AF) recurrences, mainly on the basis of their pleiotropic effects. The objective of this subanalysis of a prospectively randomized controlled study population of patients undergoing radiofrequency ablation for paroxysmal AF was to test the hypothesis that statin treatment is associated with longer time to recurrence. METHODS AND RESULTS: This is a subanalysis over an extended follow-up period of a prospective randomized study (ClinicalTrials.gov Identifier NCT01791699). Among 291 patients, 2 propensity score-matched subgroups of patients who received or did not receive statins after pulmonary vein isolation were created. In the unmatched cohort, there was no difference in the rate of recurrence between statin-treated and not treated patients, with a 1-year recurrence estimate of 19% and 23%, respectively (Gehan statistic 0.59, P = 0.443). In the propensity-matched cohort (N = 166, 83 per group), recurrence-free survival did not differ significantly between groups (839 days, 95% confidence interval 755-922 days, in the no statin group vs. 904 days, 95% confidence interval 826-983 in the statin group; P = 0.301). The 1-year recurrence rate estimate was 30% in the no statin group versus 27% in the statin group (Gehan statistic 0.56, P = 0.455). CONCLUSION: Statin treatment does not seem to affect AF recurrence in following radiofrequency ablation for paroxysmal AF, over a follow-up time of about 2.5 years.

A meta-analysis on the prognostic significance of inferolateral early repolarization pattern in Brugada syndrome.

Aims: The early repolarization (ER) pattern has been linked to an increased risk for arrhythmic death in various clinical settings. There are limited and conflicting data regarding the prognostic significance of ER pattern in Brugada syndrome (BS). The aim of this meta-analysis was to provide a detailed analysis of the currently available studies regarding the arrhythmic risk in patients with BS and ER pattern. Methods and results: Current databases were searched until May 2015. A random-effect meta-analysis of the effect of ER pattern on the incidence of arrhythmic events in patients with BS was performed. Five studies were included comprising a total of 1375 patients with BS. An ER pattern was reported in 177 patients (12.8%). During follow-up (44.9-93 months), 143 patients (10.4%) suffered an arrhythmic event. Overall, BS patients with ER pattern displayed an increased risk of arrhythmic events compared to patients without ER (OR 3.29, 95% CI: 2.06 to 5.26, P < 0.00001; Heterogeneity: P = 0.11, I2 = 48%). Three studies provided data regarding ER pattern location. Inferior, lateral, or inferolateral ER pattern location was observed in 20.3%, 32.2%, and 48%, respectively. An inferolateral ER location conferred the higher arrhythmic risk (OR 4.87, 95% CI: 2.64 to 9.01, P< 0.00001; Heterogeneity: P = 0.85, I2 = 0%). Conclusion: This meta-analysis suggests that the ER pattern is associated with a high risk of arrhythmic events in patients with BS. In particular, BS patients with inferolateral ER (global ER pattern) displayed the highest arrhythmic risk.

Effect of pulmonary vein isolation on left atrial appendage flow in paroxysmal atrial fibrillation.

BACKGROUND: Left atrial appendage (LAA) functional modification in the context of pulmonary vein isolation has been a focus point of research and LAA emptying flow velocity (LAAEFV) is considered to reflect LAA contractility, stunning, and fibrosis. OBJECTIVE: In the present study, we sought to prospectively evaluate short-term LAAEFV changes after radiofrequency (RF) or cryoballoon ablation in paroxysmal AF. METHODS: This was a prospective substudy of the Effect of Cryoballoon and RF Ablation on Left Atrial Function (CryoLAEF) study (ClinicalTrials.gov Identifier: NCT02611869). Thirty patients, randomly assigned to RF or cryoablation, were prospectively followed. Transesophageal echocardiograms were performed at baseline and at 3 months postablation to measure LAAEFV. RESULTS: All measurements were performed in sinus rhythm. Overall, LAAEFV was 44.2 [38.5-62.8] cm/s at baseline and was increased to 70.8 [64.8-77.6] cm/s at 3 months' postablation (P < 0.001). Baseline LAAEFV was 52.5 [37.7-68.0] cm/s in the RF group and 42.8 [38.7-52.9] cm/s in the CryoBalloon group (P  =  0.653). At 3 months, the corresponding values were 68.5 [61.9-76.6] cm/s and 73.9 [69.2-79.9] cm/s, respectively (P  =  0.081 for the difference between the two groups at 3 months). The median change in LAAEFV was 11.0 [4.7-26.2] cm/s in the RF group versus 29.6 [15.8-37.0] cm/s in the CryoBalloon group (P  =  0.033). CONCLUSION: LAA function is improved after catheter ablation with RF or balloon cryoablation in patients with paroxysmal AF, evaluated while in sinus rhythm both at baseline and on follow-up.

Tuning the modular Paracoccus denitrificans respirome to adapt from aerobic respiration to anaerobic denitrification.

Bacterial denitrification is a respiratory process that is a major source and sink of the potent greenhouse gas nitrous oxide. Many denitrifying bacteria can adjust to life in both oxic and anoxic environments through differential expression of their respiromes in response to environmental signals such as oxygen, nitrate and nitric oxide. We used steady-state oxic and anoxic chemostat cultures to demonstrate that the switch from aerobic to anaerobic metabolism is brought about by changes in the levels of expression of relatively few genes, but this is sufficient to adjust the configuration of the respirome to allow the organism to efficiently respire nitrate without the significant release of intermediates, such as nitrous oxide. The regulation of the denitrification respirome in strains deficient in the transcription factors FnrP, Nnr and NarR was explored and revealed that these have both inducer and repressor activities, possibly due to competitive binding at similar DNA binding sites. This may contribute to the fine tuning of expression of the denitrification respirome and so adds to the understanding of the regulation of nitrous oxide emission by denitrifying bacteria in response to different environmental signals.

Lazaroid U-74389G for cardioplegia-related ischemia-reperfusion injury: an experimental study.

BACKGROUND: The adverse effects of myocardial ischemia and reperfusion during cardiopulmonary bypass (CPB) have been thoroughly described. Lazaroid U-74389G, a 21 aminosteroid, has been shown to attenuate ischemia and reperfusion injury and improve recovery in a variety of experimental models. METHODS: Sixteen male swine were randomly divided in two groups. All animals underwent 45 min of ischemic cardioplegic arrest, with U-74389G addition to the standard cardioplegic solution, whereas controls underwent the same procedure without U-74389G. Creatine kinase-MB isoenzyme (CK-MB) and cardiac troponin T levels were measured immediately before CPB (time point 0), during the ischemic period (time point 1) and 30 (time point 2), 60 (time point 3), and 120 (time point 4) min after reperfusion. Myocardial biopsies were obtained at time points 0 and 4. RESULTS: CK-MB levels (in U/L) at time points 0-4 were 205 (186-235) versus 219 (196-269; P = 0.72), 215 (167-248) versus 253 (193-339; P = 0.23), 234 (198-255) versus 338 (249-441; P = 0.02), 244 (217-272) versus 354 (269-496; P = 0.01), and 285 (230-321) versus 439 (432-530; P < 0.01) in lazaroid-treated animals versus controls, respectively. Cardiac troponin T levels (in ng/L) at time points 0-4 were 58 (26-287) versus 237 (26-395; P = 0.72), 129 (61-405) versus 265 (145-525; P = 0.23), 261 (123-467) versus 474 (427-1604; P = 0.04), 417 (204-750) versus 841 (584-1818; P = 0.11), and 643 (353-1259) versus 1600 (1378-2313; P < 0.01), respectively. Necrosis grades at time point 4 were 0.0 (0.0-1.0) versus 1.5 (1.0-2.0; P < 0.01) in lazaroid-treated animals versus controls, respectively. CONCLUSIONS: The present study, in addition to reconfirming the well-described adverse effects of CPB, demonstrates the efficacy of the newer generation lazaroid U-74389G in alleviating these effects.

Coincidental ganglionated plexus modification during radiofrequency pulmonary vein isolation and post-ablation arrhythmia recurrence.

AIMS: Vagal responses (VR) during left atrial ablation for atrial fibrillation (AF) treatment have been reported to be associated with less recurrences, presumably because they are a sign of ganglionated plexi modification. Our objective was to evaluate whether coincidentally elicited VR during left atrial ablation are associated with lower AF recurrence rates. METHODS AND RESULTS: This is a post hoc analysis of a prospective study of 291 patients with paroxysmal AF undergoing radiofrequency pulmonary vein isolation (PVI). Vagal responses were defined as episodes of heart rate <40 bpm or asystole lasting >5 s elicited during energy application. Sixty-eight patients (23.4%) had a VR during ablation. In Kaplan-Meier analysis, mean recurrence-free survival was 449 days (95% confidence interval 411-488) in patients with VR when compared with 435 days (95% confidence interval 415-455) in those without (P = 0.310). The 12-month recurrence rate estimates were 25 and 27%, respectively. In an unadjusted Cox model, VR was associated with an odds ratio for recurrence of 0.77 (95% confidence interval 0.46-1.28). CONCLUSION: Coincidentally elicited VR during radiofrequency PVI in patients with paroxysmal AF do not appear to be related to lower risk of arrhythmia recurrence. This may mean that, even if a VR is truly a sign of coincidental ablation of a ganglionated plexus, this does not necessarily mean that a therapeutic modification has been effected, at least to a degree associated with clinical benefit.

Circulating Erythrocyte Microparticles and the Biochemical Extent of Myocardial Injury in ST Elevation Myocardial Infarction.

OBJECTIVES: Red blood cell microparticles (RBCm) have potential adverse vascular effects and they have been shown to be elevated in ST elevation myocardial infarction (STEMI). The purpose of this study is to investigate their relationship with biochemical infarct size. METHODS: RBCm were quantified with flow cytometry in blood drawn from 60 STEMI patients after a primary angioplasty. The creatine kinase-myocardial brain fraction (CK-MB) was measured at predefined time points and the area under the curve (AUC) was calculated. RESULTS: RBCm count was correlated with CK-MB AUC (Spearman's ρ = 0.83, p < 0.001). The CK-MB AUC values per RBCm quartile (lower to upper) were: 3,351 (2,452-3,608), 5,005 (4,450-5,424), 5,903 (4,862-10,594), and 8,406 (6,848-12,782) ng × h/ml, respectively. From lower to upper quartiles, the maximal troponin I values were: 42.2 (23.3-49.3), 49.6 (28.8-54.1), 59.2 (41.4-77.3), and 69.1 (48.0-77.5) ng/ml (p = 0.005). In multivariable analysis, RBCm remained a significant predictor of CK-MB AUC (standardized ß = 0.63, adjusted p = 0.001). CONCLUSIONS: Erythrocyte microparticles appear to be related to the total myocardial damage biomarker output. The exact pathophysiologic routes, if any, for this interaction remain to be identified. However, these results suggest that erythrocytes may be a - thus far virtually ignored - player in the pathogenesis of ischemic injury.