Cause of death based on systematic post-mortem studies in patients with positive SARS-CoV-2 tissue PCR during the COVID-19 pandemic.

IMPORTANCE: Assessment of the causative association between the COVID-19 and cause of death has been hampered by limited availability of systematically performed autopsies. We aimed to present autopsy-confirmed causes of death in patients who died with COVID-19 and to assess the association between thrombosis and diffuse alveolar damage consistent with COVID-19 (DAD). METHODS: Consecutive forensic (n = 60) and clinical (n = 42) autopsies with positive post-mortem SARS-CoV-2 PCR in lungs (age 73 ± 14 years, 50% men) were included. The cause of death analysis was based on a review of medical records and histological reports. Thrombotic phenomena in lungs were defined as pulmonary thromboembolism (PE), thrombosis in pulmonary artery branches or microangiopathy in capillary vessels. RESULTS: COVID-19 caused or contributed to death in 71% of clinical and 83% of forensic autopsies, in whom significant DAD was observed. Of the patients with COVID-19 as the primary cause of death, only 19% had no thrombotic phenomena in the lungs, as opposed to 38% amongst those with COVID-19 as a contributing cause of death and 54% amongst patients whose death was not related to COVID-19 (p = 0.002). PE was observed in 5 patients. Two patients fulfilled the criteria for lymphocyte myocarditis. CONCLUSIONS: Vast majority of all PCR-positive fatalities, including out-of-hospital deaths, during the SARS-CoV-2 pandemic were related to DAD caused by COVID-19. Pulmonary artery thrombosis and microangiopathy in pulmonary tissue were common and associated with the presence of DAD, whilst venous PE was rarely observed. Histology-confirmed lymphocyte myocarditis was a rare finding.

Relationship between atrial fibrillatory rate based on analysis of a modified base-apex surface electrocardiogram analysis and the results of transvenous electrical cardioversion in horses with spontaneous atrial fibrillation.

OBJECTIVES: To compare the atrial fibrillatory rate (AFR) derived from a local right atrial intracardiac recording (RA-FR) and from a single-lead surface electrocardiogram (ECG) during atrial fibrillation (AF) and to evaluate the correlation with transvenous electrical cardioversion (TVEC) threshold (in Joules), number of shocks and cardioversion success rate in horses. ANIMALS: ECGs and clinical records of horses with AF treated by TVEC. Horses were included if a simultaneous recording of the right atrial intracardiac electrogram and a modified base-apex ECG were available. MATERIALS AND METHODS: Clinical records of horses with AF treated by TVEC were reviewed. Three-minute long episodes of simultaneous electrograms and surface ECG during AF were selected for analysis and compared using Bland-Altman analysis. The mean RA-FR was measured from the deflections on the intracardiac electrogram, while the AFR was extracted from the surface ECG using spatiotemporal QRS and T-wave cancellation. RESULTS: Seventy-three horses satisfied the inclusion criteria. The mean difference between RA-FR and AFR was -13 fibrillations per minute (fpm), the 95% limits of agreement were between -66 and 40 fpm, and there was a moderate (ρ = 0.65) correlation between RA-FR and AFR (p < 0.001). Neither RA-FR nor AFR appeared to influence the TVEC cardioversion threshold or the number of TVEC shocks applied. CONCLUSIONS: The AFR may allow non-invasive long-term monitoring of AF dynamics. Neither RA-FR nor AFR could be used to predict the minimal defibrillation threshold for TVEC.

Optimal measuring point for ST deviation in chest pain patients with possible acute coronary syndrome.

INTRODUCTION: In the ECG, significant ST elevation or depression according to specific amplitude criteria can be indicative of acute coronary syndrome (ACS). Guidelines state that the ST amplitude should be measured at the J point, but data to support that this is the optimal measuring point for ACS detection is lacking. We evaluated the impact of different measuring points for ST deviation on the diagnostic accuracy for ACS in unselected emergency department (ED) chest pain patients. MATERIAL AND METHODS: We included 14,148 adult patients with acute chest pain and an ECG recorded at a Swedish ED between 2010 and 2014. ST deviation was measured at the J point (STJ) and at 20, 40, 60 and 80 ms after the J point. A discharge diagnosis of ACS or not at the index visit was noted in all patients. RESULTS: In total, 1489 (10.5%) patients had ACS. ST amplitude criteria at STJ had a sensitivity of 28% and a specificity of 92% for ACS. With these criteria, the highest positive and negative predictive values for ACS were obtained near the J point, but the optimal point varied with ST deviation, age group and sex. The overall best measuring points were STJ and ST20. CONCLUSIONS: This study indicates that the diagnostic accuracy of the ECG criteria for ACS is very low in ED chest pain patients, and that the optimal measuring point for the ST amplitude in the detection of ACS differs between ST elevation and depression, and between patient subgroups.

Idiopathic ventricular fibrillation - Long term prognosis in relation to clinical findings and ECG patterns in a Swedish cohort.

BACKGROUND: Idiopathic ventricular fibrillation (IVF) is a rare cause of sudden cardiac arrest which may pose therapeutic and prognostic challenges. To date, the only effective treatment for survivors of cardiac arrest is the insertion of an implantable cardioverter-defibrillator (ICD). We sought to review the long-term outcome of a Swedish cohort with IVF. METHODS AND RESULTS: Fifty patients with IVF diagnosis between 1988 and 2016 (mean age at index 34.3, 56% male), were followed for a median 13.8 years in this retrospective multicenter observational study. No cardiac mortality was reported. 32% (n = 16) of patients had recurrence of ventricular fibrillation or sustained ventricular tachycardia, requiring ICD therapy, at a median time of 1.9 years (range 0.1-20.3) from the index event. Annual incidence rate of ventricular tachyarrhythmia was 3.1%. Abnormal ECG at baseline did not predict appropriate ICD therapy (p = 0.56). During the follow-up period, 14% (n = 7) patients received a cardiac diagnosis. Follow-up genetic testing was low (26%), however did confirm pathogenic mutations in three cases. CONCLUSION: Idiopathic VF is a rare diagnosis with a relatively good prognosis provided ICD therapy is initiated. Routine clinical follow-up is recommended due to potential late emerging cardiac pathology. ECG changes are common, but have no prognostic value in determining the risk of ventricular arrhythmias recurrence. Screening for genetic diseases has previously been low, and this calls for improvement, especially since cheaper and more comprehensive genetic panels are now readily available.

Interatrial block in prediction of all-cause mortality after first-ever ischemic stroke.

BACKGROUND: Interatrial block (IAB) is an ECG indicator of atrial fibrosis related to atrial remodeling and thrombus formation thus leading to embolic stroke and increasing mortality. We aimed to assess weather IAB predicted all-cause mortality during 10 years after ischemic stroke. METHODS: The study sample comprised 235 patients (median age 74 (interquartile range 25-75% 65-81) years, 95 female) included in the Lund Stroke Register in 2001-2002, who had sinus rhythm ECGs at stroke admission. IAB was defined as a P-wave duration ≥120 ms without = partial IAB (n = 56) or with = advanced IAB (n = 41) biphasic morphology (±) in the inferior ECG leads. All-cause mortality was assessed via linkage with the Swedish Causes of Death Register. RESULTS: During follow-up 126 patients died (54%). Advanced IAB, but not partial, was associated with all-cause mortality in univariate Cox regression analysis (hazard ratio (HR) 1.98, 95% CI 1.27-3.09, p = 0.003). After adjustment for age, gender, severity of stroke measured by NIHSS scale and smoking status in patients without additional comorbidities advanced IAB independently predicted all-cause mortality (HR 7.89, 95% CI 2.01-30.98, p = 0.003), while in patients with comorbidities it did not (HR 1.01 95% CI 0.59-1.72, p = 0.966). CONCLUSION: Advanced IAB predicted all-cause mortality after ischemic stroke, but mostly in patients without additional cardiovascular comorbidities.

Prolonged Tpeak-Tend interval is associated with ventricular fibrillation during reperfusion in ST-elevation myocardial infarction.

AIM: Ventricular fibrillation (VF) during reperfusion in ST-elevation myocardial infarction (STEMI) is associated with increased in-hospital mortality. Dispersion of ventricular repolarization contributes to ventricular vulnerability during ischemia. Tpeak-Tend interval was proposed as a ventricular repolarization dispersion marker, however its value for prediction of reperfusion VF remains uncertain. We aimed to assess whether Tpeak-Tend before PCI in STEMI is associated with reperfusion VF. METHODS: STEMI patients admitted for primary PCI were retrospectively assessed for VF during reperfusion. Pre-PCI ECGs recorded in 40 patients with reperfusion VF (rVF group; age 65 ±â€¯13 years, 80% male) were compared with 374 consecutive patients without reperfusion arrhythmias (No-rVF group; age 67 ±â€¯12 years; 68% male). Digital ECGs were automatically processed and Tpeak-Tend interval computed on a per-lead basis. The global Tpeak-Tend was calculated between the earliest Tpeak and the latest Tend in any lead, and tested for association with reperfusion VF using logistic regression analysis. RESULTS: The leftward shift of Tpeak toward QRS complex in ischemic leads resulted in Tpeak-Tend prolongation. Global Tpeak-Tend in rVF group was higher than in No-rVF group (142 ±â€¯24 vs 130 ±â€¯27 ms; p = 0.007). Global Tpeak-Tend ≥ 131 ms predicted reperfusion VF (OR = 3.41; 95% CI 1.66-7.04; p = 0.001) and remained a significant predictor of reperfusion VF in multivariable analysis. CONCLUSION: Tpeak-Tend interval before PCI in STEMI was an independent predictor of reperfusion VF. Our findings warrants further research aimed at prospective validation of Tpeak-Tend as a marker of periprocedural arrhythmic risk.

Semi-automated QRS score as a predictor of survival in CRT treated patients with strict left bundle branch block.

BACKGROUND: Cardiac Resynchronization Therapy (CRT) is widely used for treating selected heart failure patients, but patients with myocardial scar respond worse to treatment. The Selvester QRS scoring system estimates myocardial scar burden using 12-lead ECG. This study's objective was to investigate the scores correlation to mortality in a CRT population. METHODS AND RESULTS: Data on consecutive CRT patients was collected. 401 patients with LBBB and available ECG data were included in the study. QuAReSS software was used to perform Selvester scoring. Mean Selvester score was 6.4, corresponding to 19% scar burden. The endpoint was death or heart transplant; outcome was analyzed using Cox proportional hazards models. A Selvester score >8 was significantly associated with higher risk of the combined endpoint (HR 1.59, p=.014, CI 1.09-2.3). CONCLUSION: Higher Selvester scores correlate to mortality in CRT patients with strict LBBB and might be of value in prognosticating survival.

MYBPC3 hypertrophic cardiomyopathy can be detected by using advanced ECG in children and young adults.

INTRODUCTION: The conventional ECG is commonly used to screen for hypertrophic cardiomyopathy (HCM), but up to 25% of adults and possibly larger percentages of children with HCM have no distinctive abnormalities on the conventional ECG, whereas 5 to 15% of healthy young athletes do. Recently, a 5-min resting advanced 12-lead ECG test ("A-ECG score") showed superiority to pooled criteria from the strictly conventional ECG in correctly identifying adult HCM. The purpose of this study was to evaluate whether in children and young adults, A-ECG scoring could detect echocardiographic HCM associated with the MYBPC3 genetic mutation with greater sensitivity than conventional ECG criteria and distinguish healthy young controls and athletes from persons with MYBPC3 HCM with greater specificity. METHODS: Five-minute 12-lead ECGs were obtained from 15 young patients (mean age 13.2years, range 0-30years) with MYBPC3 mutation and phenotypic HCM. The conventional and A-ECG results of these patients were compared to those of 198 healthy children and young adults (mean age 13.2, range 1month-30years) with unremarkable echocardiograms, and to those of 36 young endurance-trained athletes, 20 of whom had athletic (physiologic) left ventricular hypertrophy. RESULTS: Compared with commonly used, age-specific pooled criteria from the conventional ECG, a retrospectively generated A-ECG score incorporating results from just 2 derived vectorcardiographic parameters (spatial QRS-T angle and the change in the vectorcardiographic QRS azimuth angle from the second to the third eighth of the QRS interval) increased the sensitivity of ECG for identifying MYBPC3 HCM from 46% to 87% (p<0.05). Use of the same score also demonstrated superior specificity in a set of 198 healthy controls (94% vs. 87% for conventional ECG criteria; p<0.01) including in a subset of 36 healthy, young endurance-trained athletes (100% vs. 69% for conventional ECG criteria, p<0.001). CONCLUSIONS: In children and young adults, a 2-parameter 12-lead A-ECG score is retrospectively significantly more sensitive and specific than pooled, age-specific conventional ECG criteria for detecting MYBPC3-HCM and in distinguishing such patients from healthy controls, including endurance-trained athletes.

Current controversies in determining the main mechanisms of atrial fibrillation.

Despite considerable basic research into the mechanisms of atrial fibrillation (AF), not much progress has been made in the prognosis of patients with AF. With the exception of anticoagulant therapy, current treatments for AF still do not improve major cardiovascular outcomes. This may be due partly to the diverse aetiology of AF with increasingly more factors found to contribute to the arrhythmia. In addition, a strong increase has been seen in the technological complexity of the methods used to quantify the main pathophysiological alterations underlying the initiation and progression of AF. Because of the lack of standardization of the technological approaches currently used, the perception of basic mechanisms of AF varies widely in the scientific community. Areas of debate include the role of Ca(2+) -handling alterations associated with AF, the contribution and noninvasive assessment of the degree of atrial fibrosis, and the best techniques to identify electrophysiological drivers of AF. In this review, we will summarize the state of the art of these controversial topics and describe the diverse approaches to investigating and the scientific opinions on leading AF mechanisms. Finally, we will highlight the need for transparency in scientific reporting and standardization of terminology, assumptions, algorithms and experimental conditions used for the development of better AF therapies.

Efficacy of primary preventive ICD therapy in an unselected population of patients with reduced left ventricular ejection fraction.

AIMS: International guidelines advocate an implantable cardioverter and defibrillator (ICD) in patients with reduced left ventricular ejection fraction (LVEF) to prevent sudden death (SCD). Previous data suggest that the benefit of ICD therapy in real life may be lower than expected from the results of controlled studies and side-effects are not negligible. It is also unclear whether women benefit from treatment to the same extent as men. The aim of this study was to investigate the balance between benefits and complications of ICD therapy in a real-life population of patients with heart failure. METHODS AND RESULTS: We studied 865 consecutive patients with reduced LVEF treated with ICDs for primary prevention of SCD in 2006-11 in four tertiary care hospitals in Sweden (age 64 ± 11 years, 82% men, 62% ischaemic). The patients' medical records were scrutinized as regards appropriate therapies, complications related to the defibrillator, all-cause mortality, and gender differences. Mean follow-up was 35 ± 18 months. During follow-up 155 patients (18%) received appropriate ICD therapy, 61 patients (7%) had inappropriate shocks, 110 patients (13%) had at least one complication that required reoperation and 213 patients (25%) died. Men were twice as likely to receive ICD treatment compared with women (20 vs. 9%, P < 0.01), but neither total mortality nor complication rates differed. CONCLUSIONS: Ventricular arrhythmias necessitating ICD therapy are common (6% annually). Women are less likely to have correct ICD treatment, but have the same degree of treatment complications, thus reducing the net benefit of their treatment.

[Electrocardiogram in acute period of myocardial infarction: from ischemia severity and size of myocardial injury to clinical outcome].

Electrocardiogram (ECG) registered in acute period of myocardial infarction (MI) can be used not only for diagnostic purposes, but also for prediction of extent of myocardial injury and assessment of prognosis. This review covers assessment of acute ischemia in MI using Sclarovsky-Birnbaum classification and Anderson-Wilkins score, prediction of myocardial injury and necrosis size using changes of repolarization and depolarization and relation of these characteristics to clinical outcome. The importance of ECG-assessment during reperfusion, particularly using continuous ECG-monitoring, is also discussed.

Documentation of atrial fibrillation prior to first-ever ischemic stroke.

OBJECTIVES: We assessed the prevalence of atrial fibrillation (AF) prior to first-ever ischemic stroke by examining a comprehensive electronic ECG archive. METHODS: The study sample comprised 336 consecutive stroke patients (median age 76 (IQ16) y, 200 men) enrolled in Lund Stroke Register from March 2001 to February 2002 and 336 age- and gender-matched controls without stroke history. AF prior to admission was studied using the regional electronic ECG database and record linkage with the National Swedish Hospital Discharge Register (SHDR). Medical records were reviewed for AF documentation and CHA2 DS2-VASc risk score. RESULTS: Atrial fibrillation before or at stroke onset was detected in 109 (32.4%) stroke patients and 44 (13.1%) controls, P<0.001. Twenty-five of 109 stroke patients had AF detected only on previous ECG (n=14) or through the SHDR (n=11). The most prevalent type of AF in stroke group was non-permanent AF (59.6%). AF prevalence among patients admitted with sinus rhythm at hospital admission (n=266) was higher in those with CHA2 DS2 -VASc score≥6 (28.6%) than with CHA2 DS2-VASc score<6 (13.0%), P=0.043. CONCLUSION: Comprehensive approach for AF screening allows detecting AF in one-third of patients admitted with first-ever ischemic stroke. Patients with high cardiovascular risk are more likely to have non-permanent AF.

Novel mutation in the KCNJ2 gene is associated with a malignant arrhythmic phenotype of Andersen-Tawil syndrome.

BACKGROUND: Andersen-Tawil syndrome (ATS) is a rare inherited multisystem disorder associated with mutations in KCNJ2 and low prevalence of life-threatening ventricular arrhythmias. Our aim was to describe the clinical course of ATS in a family, in which the proband survived aborted cardiac arrest (ACA) and genetic screening revealed a previously unknown mutation (c.271_282del12[p.Ala91_Leu94del]) in the KCNJ2 gene. METHODS: A cascade family screening was performed in a 5-generation family after identification of the KCNJ2 mutation in the proband. Subsequently, 10 of 21 screened individuals appeared to be mutation carriers (median age 38 [range 10-75] years, 3 female). Mutation carriers underwent clinical examination including biochemistry panel, cardiac ultrasound, Holter ECG, and exercise stress test. RESULTS: (1) At baseline, 2 patients had survived ACA, 3 had syncope or presyncopal attacks, and 2 reported palpitations. Exercise-induced nonsustained bidirectional ventricular tachycardia was documented in 4 patients, 2 received implantable cardioverter-defibrillators (ICD) for primary prevention and 2 for secondary prevention. (2) During follow-up, 1 primary prevention and 1 secondary prevention patient received in total 4 adequate ICD shocks. Life-threatening ventricular arrhythmias were documented during childhood in 5 of 10 mutation carriers. (3) All mutation carriers presented with characteristic mild dysmorphic features. Only 1 patient suffered from periodic paralysis. All had normal serum potassium level at repeated assessments and none had any other extracardiac disease manifestation. CONCLUSION: Our findings suggest that the novel KCNJ2 mutation is associated with a predominantly cardiac phenotype of Andersen-Tawil syndrome with high propensity to life-threatening ventricular arrhythmias presenting from childhood and young adulthood.

Genetic polymorphisms for estimating risk of atrial fibrillation: a literature-based meta-analysis.

BACKGROUND: Genetic polymorphisms associated with common aetiologically complex diseases have recently been identified through genome-wide association studies. Direct-to-consumer genetic testing for such polymorphisms, with provision of absolute genetic risk estimates, is marketed by several commercial companies. Polymorphisms associated with atrial fibrillation (AF) have shown relatively large risk estimates, but the robustness of such estimates across populations and study designs has not been investigated. DESIGN: A systematic literature review with meta-analysis and assessment of between-study heterogeneity was carried out for single-nucleotide polymorphisms (SNPs) in the six genetic regions associated with AF in genome-wide or candidate gene studies. RESULTS: Data were identified from 18 samples of European ancestry (n=12,100 cases, 115,702 controls) for the single-nucleotide polymorphisms (SNP) on chromosome 4q25 (rs220733), from 16 samples (n=12,694 cases, 132,602 controls) for the SNP on 16q22 (rs2106261) and from four samples (n=5272 cases, 59,725 controls) for the SNP in KCNH2 (rs1805123). Only the publications in which the associations were initially reported were identified for SNPs on 1q21 and in GJA5 and IL6R, why meta-analyses were not performed for those SNPs. In overall random-effects meta-analyses, association with AF was observed for both SNPs on chromosomes 4q25 [odds ratio (OR), 1.67; 95% CI, 1.50-1.86, P=2×10(-21)] and 16q22 (OR, 1.21; 95% CI, 1.13-1.29, P=1×10(-8)) from genome-wide studies, but not the SNP in KCNH2 from candidate gene studies (P=0.15). There was substantial effect heterogeneity across case-control and cross-sectional studies for both polymorphisms (I(2)=0.50-0.78, P<0.05), but not across prospective cohort studies (I(2)=0.39, P=0.15). Both polymorphisms were robustly associated with AF for each study design individually (P<0.05). CONCLUSIONS: In meta-analyses including up to 150,000 individuals, polymorphisms in two genetic regions were robustly associated with AF across all study designs but with substantial context-dependency of risk estimates.

Atrial myocardial pathoelectrophysiology in adults with a secundum atrial septal defect is unaffected by closure of the defect. A study using high resolution signal-averaged orthogonal P-wave technique.

BACKGROUND: In patients with atrial septal defect (ASD) the P-wave is prolonged as a marker of delayed atrial conduction which is associated with atrial fibrillation. The study aim was to analyse the impact of ASD closure in adults on P-wave duration and morphology by means of signal-averaged P-waves (PSA-ECG) and to investigate potential mechano-electrical interactions. METHODS: PSA-ECG was obtained before and 8+/-6 months after ASD closure in 35 adult patients (age 53+/-15 years). Heart chamber sizes and pulmonary artery pressure levels were assessed by echoDopplercardiography. RESULTS: P-wave duration and morphology did not change after ASD closure (148+/-16 vs 144+/-16 ms, P=0.07). P-wave duration did not relate to age at repair, preclosure atrial sizes or pulmonary artery pressure. Pre- or postclosure atrial fibrillation propensity was associated with longer P-wave duration both before and after ASD closure. CONCLUSION: Atrial conduction disturbances in middle-aged patients with ASD, manifested as a prolonged P-wave duration, do not change after ASD closure and are not related to the dilatation of the right and left atria. It is suggestive that atrial conduction disturbance associated with ASD develop early and early intervention is required to prevent the development of late atrial fibrillation.

[Morphological characteristic of the interatrial septum and the conducting system of the heart].

Layer-by-layer preparations of interatrial septum, atrium walls and the histological study of its transverse serial sections in 84 human heart specimens revealed 6 kinds of interatrial muscle fascicles: posterior horizontal, posterior oblique-horizontal, superior horizontal, anterior horizontal (Bachmann's), Z-shaped superior (above the oval fossa) and inferior (below the oval fossa). In the oval fossa and its valve, a particular structure consisting of the transitional T-cells of the heart conducting system was detected, which contacted the muffs of the entries of all pulmonary veins by means of working myocardium muscle fascicles.

Sinus rhythm maintenance following DC cardioversion of atrial fibrillation is not improved by temporary precardioversion treatment with oral verapamil.

OBJECTIVE: To evaluate prospectively the effects of pretreatment with verapamil on the maintenance of sinus rhythm after direct current (DC) cardioversion. DESIGN: Randomised, active control, open label, parallel group comparison of verapamil versus digoxin. SETTINGS: Multicentre study in three teaching and three non-teaching hospitals in Sweden. PATIENTS: 100 consecutive patients with atrial fibrillation (AF) of at least four weeks' duration and indications for cardioversion were assigned randomly to two groups, one treated with verapamil (verapamil group) and the other with digoxin (digoxin group) before cardioversion. Fifty patients were assigned randomly to each treatment arm. After dropout of four patients from the digoxin group and seven patients from the verapamil group, data obtained from 89 patients were analysed. INTERVENTIONS: After randomly assigned pretreatment with either verapamil or digoxin for four weeks, DC cardioversion was performed. If sinus rhythm was restored then verapamil treatment was discontinued. MAIN OUTCOME MEASURES: The rate of AF recurrence was assessed one, four, eight, and 12 weeks after cardioversion. RESULTS: 6 patients in the verapamil treated group and none in the digoxin treated group reverted to sinus rhythm spontaneously (p < 0.05). DC cardioversion restored sinus rhythm in 24 of 37 (65%) patients in the verapamil group and 41 of 46 patients (89%) in the digoxin group (p < 0.05). After 12 weeks' follow up 28% (13 of 46) of digoxin pretreated patients versus 9% (four of 43) of verapamil pretreated patients remained in sinus rhythm (p < 0.05). CONCLUSION: Pretreatment with verapamil alone does not improve maintenance of sinus rhythm after DC cardioversion in patients with AF. The rate of spontaneous cardioversion may be improved by verapamil.

Changes in tissue optical properties due to radio-frequency ablation of myocardium.

The optical properties of pig heart tissue were measured after in vivo ablation therapy had been performed during open-heart surgery. In vitro samples of normal and ablated tissue were subjected to measurements with an optically integrating sphere set-up in the region 470-900 nm. Three independent measurements were made: total transmittance, total reflectance and collimated transmittance, which made it possible to extract the absorption and scattering coefficients and the scattering anisotropy factor g, using an inverse Monte Carlo model. Between 470 and 700 nm, only the reduced scattering coefficient and absorption could be evaluated. The absorption spectra were fitted to known tissue chromophore spectra, so that the concentrations of haemoglobin and myoglobin could be estimated. The reduced scattering coefficient was compared with Mie computations to provide Mie equivalent average radii. Most of the absorption was from myoglobin, whereas haemoglobin absorption was negligible. Metmyoglobin was formed in the ablated tissue, which could yield a spectral signature to distinguish the ablated tissue with a simple optical probe to monitor the ablation therapy. The reduced scattering coefficient increased by, on average, 50% in the ablated tissue, which corresponded to a slight decrease in the Mie equivalent radius.

Clinical trials in Russia and Eastern Europe: recruitment and quality.

OBJECTIVE: To review the current situation of clinical trials in Russia and Eastern Europe. FINDINGS: The volume of clinical trials in these territories is increasing. The quality of the data obtained, ethical care and compliance with Good Clinical Practice guidelines is at least as good as anywhere else. United States Food and Drug Administration inspection data indicate that sites in these countries are often superior to those elsewhere. Large-scale clinical trials conducted in these territories have been subsequently published in mainstream journals. Territory-specific attention must be paid to communications' equipment and language. However, this is countered, for example, by the fact that most clinical research associates in Russia hold degrees in medicine, that patients with previously untreated disease are more easily found than in North America or Western Europe, and the participation of large, purpose-built, healthcare institutions. CONCLUSION: Eastern Europe and Russia are well-established locales for clinical trials. These territories offer a solution to the competition for patients among clinical trials in North America or Western Europe.