Aortic valve replacement versus conservative treatment in asymptomatic severe aortic stenosis: long-term follow-up of the AVATAR trial.

BACKGROUND AND AIMS: The question of when and how to treat truly asymptomatic patients with severe aortic stenosis (AS) and normal left ventricular (LV) systolic function is still subject to debate and ongoing research. Here, the results of extended follow-up of the AVATAR trial are reported (NCT02436655, clinical trials.gov). METHODS: The AVATAR trial randomly assigned patients with severe, asymptomatic AS and LV ejection fraction ≥50% to undergo either early surgical aortic valve replacement (AVR) or conservative treatment with watchful waiting strategy. All patients had negative exercise stress testing. The primary hypothesis was that early AVR will reduce a primary composite endpoint comprising all-cause death, acute myocardial infarction, stroke or unplanned hospitalization for heart failure (HF), as compared to conservative treatment strategy. RESULTS: A total of 157 low-risk patients (mean age 67 years, 57% men, mean Society of Thoracic Surgeons score 1.7%) were randomly allocated to either early AVR group (n=78) or conservative treatment group (n=79). In an intention-to-treat analysis, after a median follow-up of 63 months, the primary composite endpoint outcome event occurred in 18/78 patients (23.1%) in the early surgery group and in 37/79 patients (46.8%) in the conservative treatment group (hazard ratio [HR] early surgery vs. conservative treatment 0.42; 95% confidence interval [CI] 0.24-0.73, p=0.002). The Kaplan-Meier estimates for individual endpoints of all-cause death and HF hospitalization were significantly lower in the early surgery compared with the conservative group (HR 0.44; 95% CI 0.23-0.85, p=0.012 for all-cause death, and HR 0.21; 95% CI 0.06-0.73, p=0.007 for HF hospitalizations). CONCLUSIONS: The extended follow-up of the AVATAR trial demonstrates better clinical outcomes with early surgical AVR in truly asymptomatic patients with severe AS and normal LV ejection fraction compared with patients treated with conservative management on watchful waiting. TRIAL REGISTRATION NUMBER: NCT02436655 (ClinicalTrials.gov).

Prognostic Value of Mitral Regurgitation in Patients with Primary Hypertrophic Cardiomyopathy.

Background and Objectives: Mitral valve pathology and mitral regurgitation (MR) are very common in patients with hypertrophic cardiomyopathy (HCM), and the evaluation of mitral valve anatomy and degree of MR is important in patients with HCM. The aim of our study was to examine the potential influence of moderate or moderately severe MR on the prognosis, clinical presentation, and structural characteristics of HCM patients. Materials and Methods: A prospective study examined 176 patients diagnosed with primary asymmetric HCM. According to the severity of the MR, the patients were divided into two groups: Group 1 (n = 116) with no/trace or mild MR and Group 2 (n = 60) with moderate or moderately severe MR. All patients had clinical and echocardiographic examinations, as well as a 24 h Holter ECG. Results: Group 2 had significantly more often the presence of the obstructive type of HCM (p < 0.001), syncope (p = 0.030), NYHA II class (p < 0.001), and atrial fibrillation (p = 0.023). Also, Group 2 had an enlarged left atrial dimension (p < 0.001), left atrial volume index (p < 0.001), and indirectly measured systolic pressure in the right ventricle (p < 0.001). Patients with a higher grade of MR had a significantly higher E/e' (p < 0.001) and, as a result, higher values of Nt pro BNP values (p < 0.001) compared to Group 1. Kaplan-Meier analysis demonstrated that the event-free survival rate during a median follow-up of 88 (IQR 40-112) months was significantly higher in Group 1 compared to Group 2 (84% vs. 45% at 8 years; log-rank 20.4, p < 0.001). After adjustment for relevant confounders, the presence of moderate or moderately severe MR remained as an independent predictor of adverse outcomes (HR 2.788; 95% CI 1.221-6.364, p = 0.015). Conclusions: The presence of moderate or moderately severe MR was associated with unfavorable long-term outcomes in HCM patients.

Role of different echocardiographic modalities in the assessment of microvascular function in women with ischemia and no obstructive coronary arteries.

This review summarizes current knowledge about echocardiographic modalities used to assess microvascular function and left ventricular (LV) systolic function in women with ischemia and no obstructive coronary arteries (INOCA). Although the entire pathophysiological background of this clinical entity still remains elusive, it is primarily linked to microvascular dysfunction which can be assessed by coronary flow velocity reserve. Subtle impairments of LV systolic function in women with INOCA are difficult to assess by interpretation of wall motion abnormalities. LV longitudinal function impairment is considered to be an early marker of subclinical systolic dysfunction and can be assessed by global longitudinal strain quantification.

Prompt and consistent improvement of coronary flow velocity reserve following successful recanalization of the coronary chronic total occlusion in patients with viable myocardium.

BACKGROUND: Coronary chronic total occlusion (CTO) is characterized by the presence of collateral blood vessels which can provide additional blood supply to CTO-artery dependent myocardium. Successful CTO recanalization is followed by significant decrease in collateral donor artery blood flow and collateral derecruitment, but data on coronary hemodynamic changes in relation to myocardial function are limited. We assessed changes in coronary flow velocity reserve (CFVR) by echocardiography in collateral donor and recanalized artery following successful opening of coronary CTO. METHODS: Our study enrolled 31 patients (60 ± 9 years; 22 male) with CTO and viable myocardium by SPECT scheduled for percutaneous coronary intervention (PCI). Non-invasive CFVR was measured in collateral donor artery before PCI, 24 h and 6 months post-PCI, and 24 h and 6 months in recanalized artery following successful PCI of CTO. RESULTS: Collateral donor artery showed significant increase in CFVR 24 h after CTO recanalization compared to pre-PCI values (2.30 ± 0.49 vs. 2.71 ± 0.45, p = 0.005), which remained unchanged after 6-months (2.68 ± 0.24). Baseline blood flow velocity of the collateral donor artery significantly decreased 24 h post-PCI compared to pre-PCI (0.28 ± 0.06 vs. 0.24 ± 0.04 m/s), and remained similar after 6 months, with no significant difference in maximum hyperemic blood flow velocity pre-PCI, 24 h and 6 months post-PCI. CFVR of the recanalized coronary artery 24 h post-PCI was 2.55 ± 0.35, and remained similar 6 months later (2.62 ± 0.26, p = NS). CONCLUSIONS: In patients with viable myocardium, prompt and significant CFVR increase in both recanalized and collateral donor artery, was observed within 24 h after successful recanalization of CTO artery, which maintained constant during the 6 months. TRIAL REGISTRATION: ClinicalTrials.gov (Number NCT04060615 ).

Improved Propensity-Score Matched Long-Term Clinical Outcomes in Patients with Successful Percutaneous Coronary Interventions of Coronary Chronic Total Occlusion.

The objective of the study was to evaluate major adverse cardiovascular events (MACE) after successful versus failed percutaneous coronary intervention for chronic total occlusion (PCI-CTO).Limited data are available on long-term clinical follow-up in the treatment of chronic total occlusion (CTO).Between January 2009 and December 2010 PCI-CTO was attempted in 283 consecutive patients with 289 CTO lesions. Procedural success was 62.3% and clinical follow-up covered 83% (235/283) of the study population with a median follow-up of 66 months (range, 59-74).The total incidence of MACE was 57/235 (24.3%), and was significantly higher in the procedural failure group than in the procedural success group (33/87 (37.9%) versus 24/148 (16.2%), P < 0.001). All-cause mortality was significantly lower in patients with successful PCI-CTO compared to failed PCI-CTO (10.8% versus 20.7%, P < 0.05). Also, the rate of cardiovascular death in the procedural failure group (14.9%) was slightly higher than that in the procedural success group (7.4%, P = 0.066). The rate of TVR was statistically higher in the procedural failure group (P < 0.009). Propensity score-adjusted Cox regression showed that procedural success remained a significant predictor of MACE (adjusted HR 0.402; 95% CI 0.196-0.824; P = 0.013).Our study emphasizes the importance of CTO recanalization in improving long-term outcome including all-cause mortality with a borderline effect on cardiovascular mortality.

Optimal parameters for the efficient microwave ablation of liver tumor from the 3D-IRCADb-01 database.

Purpose: Microwave ablation is a minimally invasive thermal modality for cancer treatment with high survival and low recurrence rates. Despite the unquestionable benefits of microwave ablation, the interaction between the medical instruments and the tissue may cause damage to the healthy tissue around the tumor. Such damages can be removed by clarifying the conditions for their development. In addition to clinical methods, computer simulations have become very effective tools for optimizing microwave ablation performance. Methods: The study was focused on the determination of the optimal input power for complete microwave tumor ablation with an ade-quate safety margin avoiding injury to the surrounding healthy tissue. In three-dimensional simulations, the liver tumor model was based on a real tumor (1.74 cm × 2.40 cm × 1.43 cm) from the 3D-IRCADb-01 database. Calculations were performed for a 10-slot antenna proven to achieve a higher degree of ablation zone localization than a standard single-slot antenna. The temperature-dependent dielectric and thermal properties of healthy and tumoral liver tissue, blood perfusion, and water content were included in the model. Results: The obtained simulation results revealed that the proper choice of input power ensures that necrotic tissue is mainly located in the tumor with minimal damage to the surrounding healthy tissue. Conclusions: This study may represent a step forward in the planning of individual microwave ablation treatment for each patient.

Noninvasive evaluation of dynamic microvascular dysfunction in ischemia and no obstructive coronary artery disease patients with suspected vasospasm.

INTRODUCTION: In patients with ischemia and no obstructive coronary artery disease (INOCA), a dynamic coronary microvascular dysfunction (CMD) is frequent but difficult to capture by noninvasive means.The aim of our study was to assess dynamic CMD in INOCA patients with stress echocardiography after vasoconstrictive and vasodilator stimuli. METHODS: In this prospective single-center study, we have enrolled 40 INOCA patients (age 56.3 ±â€Š13 years, 32 women). All participants underwent stress echocardiography with hyperventilation (HYP), followed by supine bicycle exercise (HYP+EXE) and adenosine (ADO). Stress echocardiography included an assessment of regional wall motion abnormality (RWMA) and coronary flow velocity (CFV) in the distal left anterior descending (LAD) coronary artery. RESULTS: HYP induced a 30% increase in rate pressure product (rest = 10 244 ±â€Š2353 vs. HYP = 13 214 ±â€Š3266 mmHg x bpm, P  < 0.001) accompanied by a paradoxical reduction in CFV (HYP< rest) in 21 patients (52%). HYP alone was less effective than HYP+EXE in inducing anginal pain (6/40, 15% vs. 10/40, 25%, P  = 0.046), ST segment changes (6/40, 15% vs. 24/40, 60%, P  < 0.001), and RWMA (6/40, 15% vs. 13/40, 32.5%, P  = 0.008). ADO-induced vasodilation was preserved (≥2.0) in all patients. CONCLUSION: In patients with INOCA, a coronary vasoconstriction after HYP is common, in absence of structural CMD detectable with ADO. HYP+EXE test represents a more powerful ischemia inducer than HYP alone. Stress echocardiography with LAD-CFV may allow the noninvasive assessment of dynamic and structural coronary microcirculation during stress.

Optimizing Newborn Outcomes in Cesarean Sections: A Comparative Analysis of Stress Indicators under General and Spinal Anesthesia.

BACKGROUND AND OBJECTIVES: The moment of birth represents a complex physiological process that is followed by adaptive changes in the vital systems of the newborn. Such reactions have their positive but also negative effects. The aim of this research was to determine the difference in laboratory values of stress indicators in newborn children delivered by cesarean section (CS) with general and spinal anesthesia. We attempted to make a recommendation about the optimal type of anesthesia based on our results. MATERIALS AND METHODS: The study was performed on 150 healthy term newborns delivered by urgent or planned CS. Samples for adrenocorticotropic hormone (ACTH), cortisol, triglycerides, and interleukin-6 (IL-6) were analyzed. RESULTS: Leukocyte numbers, triglycerides, and blood sugar values were normal for the newborns' age, with statistically significantly lower values of blood sugar and triglycerides in newborns delivered by CS in spinal anesthesia (p < 0.005) compared to general anesthesia. There were no significant differences in ACTH, cortisol, and IL-6 levels between those newborns delivered via CS after spinal or general anesthesia. CONCLUSIONS: In cases where vaginal delivery is not possible, when CS is indicated, the use of well-controlled spinal anesthesia is followed by lower degrees of metabolic, inflammatory, and stress responses and better vitality of the baby upon birth.

Molnupiravir's real-world effectiveness in COVID-19 outpatients at high risk of severe disease: a single-center study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic started in March 2020. Since then, there has been an urgent need for effective therapeutic methods to manage the disease. We aimed to assess the effectiveness of molnupiravir in reducing the need for hospitalization in at-risk, non-hospitalized COVID-19 patients. METHODOLOGY: This was a single-center, non-randomized, observational retrospective study of non-hospitalized patients with confirmed COVID-19, treated at the Clinic for Infectious and Tropical Diseases, University Clinical Center in Belgrade, Serbia. RESULTS: The study was conducted between 15 December 2021 and 15 February 2022 and included 320 patients. Of these, 165 (51.6%) received treatment with molnupiravir. The study and control groups were similar in gender and age distribution. The study group had a higher proportion of vaccination (75.2% vs. 51%, p < 0.001). There was no statistically significant difference in presence of comorbidity within the groups. Majority of the patients who received molnupiravir did not require hospitalization; and this was statistically significant in comparison to control group (92.7 vs. 24.5%, p < 0.001). Oxygen supplementation was less frequently required in the study group compared to the control group (0.6% vs. 31%, p < 0.001). During the follow-up period of 12.12 ± 3.5 days, significantly less patients from the study group were admitted to the intensive care unit (p < 0.001). Molnupiravir significantly reduced the risk of hospitalization by 97.9% (HR 0.021; 95% CI 0.005-0.089; p < 0.001). CONCLUSIONS: Molnupiravir is an effective therapy in preventing the development of severe forms of COVID-19 and hospitalization.

Does Atrial Fibrillation at Diagnosis Change Prognosis in Patients with Aortic Stenosis?

Background: Aortic stenosis (AS) is a common valve disease and atrial fibrillation (AF) is the most common cardiac arrhythmia, frequently associated with AS. This study aimed to evaluate the impact of AF on mortality in patients with moderate and severe AS. Methods: We retrospectively analyzed 1070 consecutive moderate and severe AS patients (57% were male, age was 69 ± 10, severe AS 22.5%), who underwent transthoracic echocardiography from March 2018 to November 2021. AS severity was defined by specific threshold values with severe AS being defined by a peak velocity > 4 m/s, an MPG > 40 mmHg, and an AVA < 1 cm2 and moderated by a peak velocity of 3-4 m/s, an MPG 20-40 mmHg and an AVA 1-1.5 cm. Patients with AF were defined as those having a history of AF when AS was found on the index echocardiography. The follow-up assessment in December 2023 ascertained vital status and data on aortic valve replacement (AVR). Results: 790 (73.8%) patients were with sinus rhythm (SR) and 280 (26.2%) patients with AF. Mortality was higher in patients with AF than in those with SR (46% vs. 36.2% HR 1.424, 95% CI 1.121-1.809, p = 0.004). After adjusting for clinical confounders, mortality risk in AF relative to SR remained significant (HR 1.284, 95% CI 1.03-1.643, p = 0.047). Patients with AF demonstrated high mortality risk in the moderate aortic stenosis stratum (HR 1.376, 95% CI 1.059-1.788, p = 0.017), with even greater risk in the severe AS stratum (HR 1.644, 95% CI 1.038-2.603, p = 0.034) with significant interaction (p = 0.007). In patients with AF AVR demonstrated a protective effect on survival (HR 0.365, 95% CI 0.202-0.627, p < 0.001), but to a lesser degree than in patients with sinus rhythm (HR 0.376, 95% CI 0.250-0.561, p < 0.001) without significant interaction (p = 0.278). In patients with AF mortality risk was high in the conservative treatment stratum (HR 1.361, 95% CI 1.066-1.739, p = 0.014), in the AVR stratum mortality risk was higher but did not reach statistical significance (HR 1.823, 95% CI 0.973-3.414, p = 0.061). However, when corrected for echocardiographic variables strongly correlated with AF, AF was no longer independently associated with all-cause mortality. (HR 0.97 95% CI 0.709-1.323, p = 0.84). Conclusions: Patients with moderate and severe AS and AF have worse prognosis than patients with SR which can be explained by cardiac damage. AVR improves survival in patients with AF and with SR.

Correlation of Non-Invasive Transthoracic Doppler Echocardiography with Invasive Doppler Wire-Derived Coronary Flow Reserve and Their Impact on Infarct Size in Patients with ST-Segment Elevation Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention.

Background: Coronary microvascular dysfunction is associated with adverse prognosis after ST-segment elevation myocardial infarction (STEMI). We aimed to compare the invasive, Doppler wire-based coronary flow reserve (CFR) with the non-invasive transthoracic Doppler echocardiography (TTDE)-derived CFR, and their ability to predict infarct size. Methods: We included 36 patients with invasive Doppler wire assessment on days 3-7 after STEMI treated with primary percutaneous coronary intervention (PCI), of which TTDE-derived CFR was measured in 47 vessels (29 patients) within 6 h of the invasive Doppler. Infarct size was assessed by cardiac magnetic resonance at a median of 8 months. Results: The correlation between invasive and non-invasive CFR was modest in the overall cohort (rho 0.400, p = 0.005). It improved when only measurements in the LAD artery were considered (rho 0.554, p = 0.002), with no significant correlation in the RCA artery (rho -0.190, p = 0.435). Both invasive (AUC 0.888) and non-invasive (AUC 0.868) CFR, measured in the recanalized culprit artery, showed a good ability to predict infarct sizes ≥18% of the left ventricular mass, with the optimal cut off values of 1.85 and 1.80, respectively. Conclusions: In patients with STEMI, TTDE- and Doppler wire-derived CFR exhibit significant correlation, when measured in the LAD artery, and both have a similarly strong association with the final infarct size.

Predictors of diastolic deceleration time of coronary flow velocity of infarct related and reference coronary artery assessed by transthoracic Doppler echocardiography in the chronic phase of successfully reperfused anterior myocardial infarction: relation to infarct size.

Introduction: High-frequency transthoracic Doppler echocardiography (TDE) enables the assessment of flow velocity and velocity pattern in different coronary arteries, including the assessment of diastolic deceleration time (DDT) of coronary flow velocity. Short DDT of infarct related artery (IRA) (<600 msec) in the acute phase of anterior myocardial infarction (MI) is the predictor of adverse left ventricular (LV) remodeling and prognosis. The significance of DDT of coronary flow velocity assessment in the chronic phase of anterior MI is not well established. Our study aimed to establish the predictors of DDT of the coronary flow velocity of infarct related (left anterior descendent-DDT of LAD) and reference coronary artery, evaluated by TDE, and to assess their relation to infarct size in the chronic phase of successfully reperfused first anterior MI. Methods: Our study included 40 consecutive patients (34 men, mean age 52 ± 12 years) one month after the first anterior STEMI and single vessel disease successfully treated with primary PCI. All patients underwent SPECT MPI for the assessment of LV volumes, ejection fraction, and percentage of the myocardium with fixed perfusion abnormalities and echocardiographic examination including the evaluation of DDT of IRA and reference coronary artery TDE. Results: DDT of LAD correlated significantly to the WMSI (r = -0.467, p = 0.002), LV end-systolic volume (r = -0.412, p = 0.008), LV ejection fraction (r = 0.427, p = 0.006), while the strongest correlation was observed between DDT of LAD and the extent of fixed perfusion abnormality (r = -0.627, p < 0.0001), Multivariate analysis revealed percentage of fixed perfusion abnormalities along with DDT of reference coronary artery as the independent predictors of DDT of IRA. DDT of IRA shorter than 886 msec predicts large fixed perfusion abnormalities (>20%) with a sensitivity of 89% and specificity of 62% (AUC 0.842). Conclusion: DDT of LAD assessed by TDE in the chronic phase of successfully reperfused first anterior MI is a usefull variable for the assessment of microcirculatory function that exclusively reflects the extent of microvascular damage and relates to infarct size.

Heart Rate Recovery as a Predictor of Long-Term Adverse Events after Negative Exercise Testing in Patients with Chest Pain and Pre-Test Probability of Coronary Artery Disease from 15% to 65.

BACKGROUND: The prognosis of patients with chest pain after a negative exercise test is good, but some adverse events occur in this low-risk group. The aim of our study was to identify predictors of long-term adverse events after a negative exercise test in patients with chest pain and a lower intermediate (15-65%) pre-test probability of coronary artery disease (CAD) and to assess the prognostic value of exercise electrocardiography and exercise stress echocardiography in this group of patients. METHODS: We identified from our stress test laboratory database 862 patients with chest pain without previously known CAD and with a pre-test probability of CAD ranging from 15 to 65% (mean 41 ± 14%) who underwent exercise testing. Patients were followed for the occurrence of death, non-fatal myocardial infarction (MI) and clinically guided revascularization. RESULTS: During the median follow-up of 94 months, 87 patients (10.1%) had an adverse event (AE). A total of 30 patients died (3.5%), 23 patients suffered non-fatal MI (2.7%) and 34 patients (3.9%) had clinically guided revascularization (20 patients percutaneous and 14 patients surgical revascularizations). Male gender, age, the presence of diabetes and a slow heart rate recovery (HRR) in the first minute after exercise were independently related to the occurrence of AEs. Adverse events occurred in 10.3% of patients who were tested by exercise stress echocardiography and in 10.0% of those who underwent stress electrocardiography (p = 0.888). CONCLUSION: The risk of AEs after negative exercise testing in patients with a pre-test probability of CAD of 15-65% is low. Male patients with a history of diabetes and slow HRR in the first minute after exercise have an increased risk of an adverse outcome.

Computational Modeling of Microwave Tumor Ablation.

Microwave ablation is recognized as a minimally invasive, fast-recovery treatment for destroying cancer cells using the heat generated by microwave energy. Despite the unquestionable benefits of microwave ablation, the interaction of the microwave applicator with the tissue may result in localized heating and damage to the surrounding tissue. The majority of the tissue damage can be removed by clarifying the conditions for their development. In addition to experimental methods, computer modeling has proven to be an effective tool for optimizing the performance of microwave ablation. Furthermore, because the thermal spread in biological tissue is difficult to measure, developing a predictive model from procedural planning to execution may have a substantial influence on patient care. The comprehension of heat transport in biological tissues plays a significant role in gaining insight into the mechanisms underlying microwave ablation. Numerical methods that enable ablation size control are required to guarantee tumor destruction and minimize damage to healthy tissues. Various values of input power and ablation time correspond to different tumor shapes ensuring the preservation of healthy tissues. The optimal conditions can be estimated by performing full three-dimensional simulations. This topical review recapitulates numerous computational studies on microwave tumor ablation. Novel areas emerging in treatment planning that exploit the advantages of numerical methods are also discussed. As an illustration, the results of the three-dimensional simulations of real liver tumors in the 3D-IRCADb-01 database are presented and analyzed. The simulation results confirm that numerical methods are very useful tools for modeling microwave tumor ablation with minimal invasiveness and collateral damage.

An Analysis of Microwave Ablation Parameters for Treatment of Liver Tumors from the 3D-IRCADb-01 Database.

Simulation techniques are powerful tools for determining the optimal conditions necessary for microwave ablation to be efficient and safe for treating liver tumors. Owing to the complexity and computational resource consumption, most of the existing numerical models are two-dimensional axisymmetric models that emulate actual three-dimensional cancers and the surrounding tissue, which is often far from reality. Different tumor shapes and sizes require different input powers and ablation times to ensure the preservation of healthy tissues that can be determined only by the full three-dimensional simulations. This study aimed to tailor microwave ablation therapeutic conditions for complete tumor ablation with an adequate safety margin, while avoiding injury to the surrounding healthy tissue. Three-dimensional simulations were performed for a multi-slot microwave antenna immersed in two tumors obtained from the 3D-IRCADb-01 liver tumors database. The temperature dependence of the dielectric and thermal properties of healthy and tumoral liver tissues, blood perfusion, and water content are crucial for calculating the correct ablation time and, thereby, the correct ablation process. The developed three-dimensional simulation model may help practitioners in planning patient-individual procedures by determining the optimal input power and duration of the ablation process for the actual shape of the tumor. With proper input power, necrotic tissue is placed mainly in the tumor, and only a small amount of surrounding tissue is damaged.

Effects of biochar on the fate of conazole fungicides in soils and their bioavailability to earthworms and plants.

The study showed novel findings about changes in the fate and bioavailability of conazole fungicides (CFs) after biochar (BC) addition to soil. Two contrasting soils (low- and high-sorbing of CF; L soils, H soils) were amended by three BCs (low-, moderate-, and high-sorbing of CF; L-BC, M-BC, H-BC) at 0.2% and 2% doses. Epoxiconazole (EPC) and tebuconazole (TBC) were then added to the soil-BC mixtures, and their degradation, bioaccumulation in earthworms (Eisenia andrei), and bioconcentration in lettuce (Lactuca sativa) were studied for three months. Also, stir bar sorptive extraction (SBSE) was performed to determine CF (bio)accessibility. The EPC and TBC degradation in the soil-BC mixtures followed usually the first-order decay kinetics. The BC addition prevalently decreased the pesticides degradation in the L soil mixtures but often increased it in the H soil mixtures. In general, EPC degraded less than TBC. BC type and dose roles in the pesticides degradation were unclear. The BC addition significantly reduced pesticide uptake to the earthworms in the L soil mixtures (by 37-96%) and in the H soil mixtures (by 6-89%) with 2% BC. The BC addition reduced pesticide uptake to the lettuce roots and leaves significantly-up to two orders of magnitude, and this reduction was strong in H soil mixtures at 2% of BC. The BC addition reduced the CF (bio)accessibility measured by SBSE in all L soil mixtures and some H soil mixtures with 2% BC. Although not significant, it also seems that the pesticide bioaccumulation, bioconcentration, and (bio)accessibility were decreasing according to the BC type (L-BC > M-BC > H-BC). The pesticide concentrations in the earthworms and lettuce correlated significantly to the SBSE results, which indicates this technique as a possible predictor of biotic uptake. Our results showed that the interactions were hard to predict in the complex soil-BC-pesticide system.

Feasibility and value of two-dimensional volumetric stress echocardiography.

BACKGROUND: Stroke volume response during stress is a major determinant of functional status in heart failure and can be measured by two-dimensional (2-D) volumetric stress echocardiography (SE). The present study hypothesis is that SE may identify mechanisms underlying the change in stroke volume by measuring preload reserve through end-diastolic volume (EDV) and left ventricular contractile reserve (LVCR) with systolic blood pressure and end-systolic volume (ESV). METHODS: We enrolled 4735 patients (age 63.6±11.3 years, 2800 male) referred to SE for known or suspected coronary artery disease (CAD) and/or heart failure (HF) in 21 SE laboratories in 8 countries. In addition to regional wall motion abnormalities (RWMA), force was measured at rest and peak stress as the ratio of systolic blood pressure by cuff sphygmomanometer/ESV by 2D with Simpson's or linear method. Abnormal values of LVCR (peak/rest) based on force were ≤1.10 for dipyridamole (N.=1992 patients) and adenosine (N.=18); ≤2.0 for exercise (N.=2087) or dobutamine (N.=638). RESULTS: Force-based LVCR was obtained in all 4735 patients. Lack of stroke volume increase during stress was due to either abnormal LVCR and/or blunted preload reserve, and 57% of patients with abnormal LVCR nevertheless showed increase in stroke volume. CONCLUSIONS: Volumetric SE is highly feasible with all stresses, and more frequently impaired in presence of ischemic RWMA, absence of viability and reduced coronary flow velocity reserve. It identifies an altered stroke volume response due to reduced preload and/or contractile reserve.

The Value of Stress Echocardiography Imaging and Functional Parameters in Patients with aVR Lead ST-Segment Elevation during an Exercise Stress Test to Detect Significant Left Main Stenosis.

OBJECTIVE: To evaluate the role of functional and imaging parameters during exercise stress echocardiography (SE) in the presence of ST-segment elevation (ST-E) in aVR leads to predict significant left main/left main equivalent/or ostial left anterior descending (LAD) stenosis (LM+). METHODS: The study population included 548 patients with ECG and echo markers of myocardial ischemia, in whom diagnostic coronary angiography was performed. We analyzed the patients' clinical characteristics, ECG changes, wall motion score index (WMSI) by stress echocardiography (SE), as well as functional capacity during exercise (METs) and Duke treadmill score. RESULTS: aVR ST-segment elevation was found in 60/548 (11%) patients, whereas aVR ST-E was found in 23/57 patients with left main LM stenosis (Sn 40%, Sp 92%, PPV 38%, NPV 93%). When aVR ST-E was combined with other functional/imaging parameters, patients with aVR ST-E and LM+ had significantly worse functional capacity in METs (5.0±2.2 vs. 6.7±2.3, P=0.005), lower Duke score (-6.8±6.8 vs. -3.6±4.1, P=0.049), and higher deterioration of WMSI (0.51±0.24 vs. 0.39±0.24, P=0.046). Significant multivariable predictors of the left main (LM) stenosis were aVR ST-E and positive SE in LAD territory in the whole group of patients, and Delta WMSI, Duke score and METs achieved in patients presented with aVR ST-E during exercise. CONCLUSION: The aVR ST-segment alone has intermediate sensitivity in detecting significant LM stenosis in patients referred to SE testing for chest pain. When combined with other functional and imaging parameters, including poor exercise functional capacity in METs, lower Duke score or greater WMA in the territory of LAD, its diagnostic power to detect LM significantly increases.

Conazole fungicides epoxiconazole and tebuconazole in biochar amended soils: Degradation and bioaccumulation in earthworms.

Biochar usage in agriculture becomes increasingly important for the improvement of soil properties. However, from the perspective of pesticides, biochar can influence exposure to pesticides of both target and non-target organisms and also pesticides' fate in soil. Our study investigated degradation and bioaccumulation (in the Eisenia andrei earthworm) of two conazole fungicides, epoxiconazole and tebuconazole, added to high- and low-sorbing soils (by means of fungicides' sorption measured beforehand) amended with low-, moderate- and high-sorbing biochars at 0.2% and 2% doses. We aimed to investigate the effects of contrasting soil and biochar properties, different doses of biochar in soil-biochar mixtures, and different compounds on the degradation and bioaccumulation. We also wanted to explore if the beforehand determined sorption of fungicides on individual soils and biochars is manifested somehow in their degradation and/or bioaccumulation in soil-biochar mixtures. The biochars' presence in the soils promoted the degradation of fungicides with a clear effect of dose and soil, but less clear effect of biochar or compound. The bioaccumulation factors were higher in low-sorbing soil variants and also decreased with increasing biochar dose. For low-sorbing soil variants, the bioaccumulation was also influenced by the type of biochar corresponding to its sorbing potential and the possible effect on the bioavailability of the fungicides. Our results show that mixing of biochars with soils changes the fate and bioaccumulation of the conazole fungicides. However, the sorption results from original materials are not straightforwardly manifested in the more complex soil-biota system.

Coronary Flow Velocity Reserve Using Dobutamine Test for Noninvasive Functional Assessment of Myocardial Bridging.

BACKGROUND: It has been shown that coronary flow velocity reserve (CFVR) measurement by transthoracic Doppler echocardiography (TTDE) during dobutamine (DOB) provocation provides a more accurate functional evaluation of myocardial bridging (MB) compared to adenosine. However; the cut-off value of CFVR during DOB for identification of MB associated with myocardial ischemia has not been fully clarified. PURPOSE: This prospective study aimed to determine the cut-off value of TTDE-CFVR during DOB in patients with isolated-MB, as compared with stress-induced wall motion abnormalities (VMA) during exercise stress-echocardiography (SE) as reference. METHODS: Eighty-one symptomatic patients (55 males [68%], mean age 56 ± 10 years; range: 27-74 years) with the existence of isolated-MB on the left anterior descending artery (LAD) and systolic MB-compression ≥50% diameter stenosis (DS) were eligible to participate in the study. Each patient underwent treadmill exercise-SE, invasive coronary angiography, and TTDE-CFVR measurements in the distal segment of LAD during DOB infusion (DOB: 10-40 µg/kg/min). Using quantitative coronary angiography, both minimal luminal diameter (MLD) and percent DS at MB-site at end-systole and end-diastole were determined. RESULTS: Stress-induced myocardial ischemia with the occurrence of WMA was found in 23 patients (28%). CFVR during peak DOB was significantly lower in the SE-positive group compared with the SE-negative group (1.94 ± 0.16 vs. 2.78 ± 0.53; p < 0.001). ROC analyses identified the optimal CFVR cut-off value ≤ 2.1 obtained during high-dose dobutamine (>20 µg/kg/min) for the identification of MB associated with stress-induced WMA, with a sensitivity, specificity, positive and negative predictive value of 96%, 95%, 88%, and 98%, respectively (AUC 0.986; 95% CI: 0.967-1.000; p < 0.001). Multivariate logistic regression analysis revealed that MLD and percent DS, both at end-diastole, were the only independent predictors of ischemic CFVR values ≤2.1 (OR: 0.023; 95% CI: 0.001-0.534; p = 0.019; OR: 1.147; 95% CI: 1.042-1.263; p = 0.005; respectively). CONCLUSIONS: Noninvasive CFVR during dobutamine provocation appears to be an additional and important noninvasive tool to determine the functional severity of isolated-MB. A transthoracic CFVR cut-off ≤2.1 measured at a high-dobutamine dose may be adequate for detecting myocardial ischemia in patients with isolated-MB.