Abstract
Aims
The Routine vs. Aggressive risk factor driven upstream rhythm Control for prevention of Early persistent atrial fibrillation (AF) in heart failure (HF) (RACE 3) trial demonstrated that ...targeted therapy of underlying conditions improved sinus rhythm maintenance at 1 year. We now explored the effects of targeted therapy on the additional co-primary endpoints; sinus rhythm maintenance and cardiovascular outcome at 5 years.
Methods and results
Patients with early persistent AF and mild-to-moderate stable HF were randomized to targeted or conventional therapy. Both groups received rhythm control therapy according to guidelines. The targeted group additionally received four therapies: angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers (ARBs), statins, mineralocorticoid receptor antagonists (MRAs), and cardiac rehabilitation. The presence of sinus rhythm and cardiovascular morbidity and mortality at 5-year follow-up were assessed. Two hundred and sixteen patients consented for long-term follow-up, 107 were randomized to targeted and 109 to conventional therapy. At 5 years, MRAs 76 (74%) vs. 10 (9%) patients, P < 0.001 and statins 81 (79%) vs. 59 (55%), P < 0.001 were used more in the targeted than conventional group. Angiotensin-converting enzyme inhibitors/ARBs and physical activity were not different between groups. Sinus rhythm was present in 49 (46%) targeted vs. 43 (39%) conventional group patients at 5 years (odds ratio 1.297, lower limit of 95% confidence interval 0.756, P = 0.346). Cardiovascular mortality and morbidity occurred in 20 (19%) in the targeted and 15 (14%) conventional group patients, P = 0.353.
Conclusion
In patients with early persistent AF and HF superiority of targeted therapy in sinus rhythm maintenance could not be preserved at 5-year follow-up. Cardiovascular outcome was not different between groups.
Trial registration number
Clinicaltrials.gov NCT00877643.
Tomographic imaging based on ambient seismic noise measurements has shown to be a powerful tool, especially in areas like Iceland, where the microseism illumination is excellent. In this paper, we ...produce a 3D S-wave tomographic image over the western Reykjanes Peninsula high-enthalpy geothermal fields and evaluate the reliability of the tomographic results for different resolutions through simulated and real data. We use 30 broadband stations operating for approximately one-and-a-half year and apply ambient noise seismic interferometry for each station-pair. This results in empirical Green's functions in which especially the ballistic surface waves (BSW) are well resolved. The retrieved BSW exhibit a high signal-to-noise ratio between 0.1 and 0.5 Hz, and the beamforming analysis indicates an apparent surface-wave velocity of 3 km/s over a broad azimuthal range. For the tomographic inversion, we invert the estimated phase velocities between all station pairs to frequency-dependent phase velocity maps in four different resolutions (1, 2, 3, and 4 km) using a Tikhonov regularisation. With the estimated regularisation parameter per frequency per resolution, we invert simulated data for checkerboard sensitivity tests per frequency for different combinations of velocity anomaly sizes and resolutions.
Finally, after the inversion to depth, we detect S-wave velocity anomalies with variations between −15% and 15% with reference to an estimated average velocity using 1 km and 3 km of lateral resolutions and 1 km of vertical resolution. This study shows the potential of ambient noise tomography as complementary seismological tool for reservoir characterization.
A cataclasm due to spasm Denham, R. N.; Appelman, Y. E.; Verdel, G. J. E.
Netherlands heart journal,
01/2013, Letnik:
21, Številka:
1
Journal Article
Odprti dostop
We describe a 59-year-old patient presenting with ST-elevation acute coronary syndrome. Coronary angiography with intravascular ultrasound (IVUS) showed an important nonsignificant atherosclerotic ...lesion in the proximal left anterior descending artery (LAD) and presence of bridging in the mid-LAD. Our hypothesis was that focal spasm at this site was the cause of transmural ischaemia; therefore, treatment was given by performing a percutaneous coronary intervention (PCI) of the lesion. The patient remained symptom-free which confirmed our conclusion. The myocardial bridging had no clinical implications at this moment.
A recent large, randomized trial suggested that statins may increase the risk of intracerebral hemorrhage. Accordingly, we systematically reviewed the association of statins with intracerebral ...hemorrhage in randomized and observational data.
We screened 17 electronic bibliographic databases to identify eligible studies and consulted with experts in the field. We used DerSimonian-Laird random-effects models to compute summary risk ratios with 95% confidence intervals. Randomized trials, cohort studies, and case-control studies were analyzed separately. Only adjusted risk estimates were used for pooling observational data. We included published and unpublished data from 23 randomized trials and 19 observational studies. The complete data set comprised 248 391 patients and 14 784 intracerebral hemorrhages. Statins were not associated with an increased risk of intracerebral hemorrhage in randomized trials (risk ratio, 1.10; 95% confidence interval, 0.86-1.41), cohort studies (risk ratio, 0.94; 95% confidence interval, 0.81-1.10), or case-control studies (risk ratio, 0.60; 95% confidence interval, 0.41-0.88). Substantial statistical heterogeneity was evident for the case-control studies (I(2)=66%, P=0.01), but not for the cohort studies (I(2)=0%, P=0.48) or randomized trials (I(2)=30%, P=0.09). Sensitivity analyses by study design features, patient characteristics, or magnitude of cholesterol lowering did not materially alter the results.
We found no evidence that statins were associated with intracerebral hemorrhage; if such a risk is present, its absolute magnitude is likely to be small and outweighed by the other cardiovascular benefits of these drugs.
Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce progression of chronic kidney disease and the risk of cardiovascular morbidity and mortality in a wide range of patients. However, their ...effects on kidney disease progression in some patients with chronic kidney disease are unclear because few clinical kidney outcomes occurred among such patients in the completed trials. In particular, some guidelines stratify their level of recommendation about who should be treated with SGLT2 inhibitors based on diabetes status and albuminuria. We aimed to assess the effects of empagliflozin on progression of chronic kidney disease both overall and among specific types of participants in the EMPA-KIDNEY trial.
EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA), and included individuals aged 18 years or older with an estimated glomerular filtration rate (eGFR) of 20 to less than 45 mL/min per 1·73 m
, or with an eGFR of 45 to less than 90 mL/min per 1·73 m
with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher. We explored the effects of 10 mg oral empagliflozin once daily versus placebo on the annualised rate of change in estimated glomerular filtration rate (eGFR slope), a tertiary outcome. We studied the acute slope (from randomisation to 2 months) and chronic slope (from 2 months onwards) separately, using shared parameter models to estimate the latter. Analyses were done in all randomly assigned participants by intention to treat. EMPA-KIDNEY is registered at ClinicalTrials.gov, NCT03594110.
Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and then followed up for a median of 2·0 years (IQR 1·5-2·4). Prespecified subgroups of eGFR included 2282 (34·5%) participants with an eGFR of less than 30 mL/min per 1·73 m
, 2928 (44·3%) with an eGFR of 30 to less than 45 mL/min per 1·73 m
, and 1399 (21·2%) with an eGFR 45 mL/min per 1·73 m
or higher. Prespecified subgroups of uACR included 1328 (20·1%) with a uACR of less than 30 mg/g, 1864 (28·2%) with a uACR of 30 to 300 mg/g, and 3417 (51·7%) with a uACR of more than 300 mg/g. Overall, allocation to empagliflozin caused an acute 2·12 mL/min per 1·73 m
(95% CI 1·83-2·41) reduction in eGFR, equivalent to a 6% (5-6) dip in the first 2 months. After this, it halved the chronic slope from -2·75 to -1·37 mL/min per 1·73 m
per year (relative difference 50%, 95% CI 42-58). The absolute and relative benefits of empagliflozin on the magnitude of the chronic slope varied significantly depending on diabetes status and baseline levels of eGFR and uACR. In particular, the absolute difference in chronic slopes was lower in patients with lower baseline uACR, but because this group progressed more slowly than those with higher uACR, this translated to a larger relative difference in chronic slopes in this group (86% 36-136 reduction in the chronic slope among those with baseline uACR <30 mg/g compared with a 29% 19-38 reduction for those with baseline uACR ≥2000 mg/g; p
<0·0001).
Empagliflozin slowed the rate of progression of chronic kidney disease among all types of participant in the EMPA-KIDNEY trial, including those with little albuminuria. Albuminuria alone should not be used to determine whether to treat with an SGLT2 inhibitor.
Boehringer Ingelheim and Eli Lilly.
The EMPA-KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly ...through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population.
EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m
, or 45 to less than 90 mL/min per 1·73 m
with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m
, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110.
Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5-2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 95% CI 0·62-0·81), with no evidence that the relative effect size varied significantly by primary kidney disease (p
=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m
per year (95% CI 1·16-1·59), representing a 50% (42-58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1).
In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease.
Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council.
Hatchery‐reared fish and their eggs are commonly afflicted with saprolegniasis, a fungal disease that can cause significant losses in production. Fish culturists need safe and effective fungicides to ...minimize losses and meet production demands. The efficacy of hydrogen peroxide was evaluated for preventing or controlling mortality associated with saprolegniasis in channel catfish Ictalurus punctatus. Saprolegniasis was systematically induced in channel catfish so various therapies could be evaluated in a controlled laboratory environment. Both prophylactic and therapeutic hydrogen peroxide bath treatments of 50, 100, and 150 μL/L for 1 h were administered every other day for seven total treatments. All untreated positive control fish died of saprolegniasis during the prophylactic and therapeutic tests. Hydrogen peroxide treatments of 150 μL/L were harmful (relative to lower concentrations) to test fish and resulted in 73–95% mortality. Mortality was attributed to a combination of abrasion, temperature, chemical treatment, and disease stressors. Treatments of 100 μL/L were less harmful (relatively) but also appeared to contribute to mortality (60–79%). These treatments, however, significantly reduced the incidence of mortality and infection compared with those observed for fish of the positive control or 150‐μL/L treatment groups. Overall, treatments of 50 μL/L were found to be the most safe and effective of those tested. Mortality with this concentration ranged from 16% in therapeutic tests to 41% in prophylactic tests. The statistical model employed estimated that the optimum treatment concentration for preventing or controlling mortality, reducing the incidence of infections, and enhancing the recovery of infected fish was 75 μL H2O2/L.
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