The power of zero calcium in 82-Rubidium PET irrespective of sex and age.

BACKGROUND: Despite clinical suspicion, many non-invasive tests for coronary artery disease (CAD) are normal. Coronary artery calcification score (CACS) is a well-validated method to detect and risk stratify CAD. Patients with zero calcium score (ZCS) rarely have abnormal tests. Therefore, aims were to evaluate CACS as a gatekeeper to further functional downstream testing for CAD and estimate potential radiation and cost savings. METHODS: Consecutive patients with suspected CAD referred for PET were included (n = 2640). Prevalence and test characteristics of ZCS were calculated in different groups. Summed stress score ≥ 4 was considered abnormal and summed difference score ≥ 7 equivalent to ≥ 10% ischemia. To estimate potential radiation/cost reduction, PET scans were hypothetically omitted in ZCS patients. RESULTS: Mean age was 65 ± 11 years, 46% were female. 21% scans were abnormal and 26% of patients had ZCS. CACS was higher in abnormal PET (median 561 vs 27, P < 0.001). Abnormal PET was significantly less frequent in ZCS patients (2.6% vs 27.6%, P < 0.001). Sensitivity/negative predictive value (NPV) of ZCS to detect/exclude abnormal PET and ≥ 10% ischemia were 96.8% (95%-CI 95.0%-97.9%)/97.4% (95.9%-98.3%) and 98.9% (96.7%-99.6%)/99.6% (98.7%-99.9%), respectively. Radiation and cost reduction were estimated to be 23% and 22%, respectively. CONCLUSIONS: ZCS is frequent, and most often consistent with normal PET scans. ZCS offers an excellent NPV to exclude an abnormal PET and ≥ 10% ischemia across different gender and age groups. CACS is a suitable gatekeeper before advanced cardiac imaging, and potential radiation/cost savings are substantial. However, further studies including safety endpoints are needed.

Lipophilic oligopeptides for chemo- and enantioselective acyl transfer reactions onto alcohols.

Inspired by the extraordinary selectivities of acylases, we envisioned the use of lipophilic oligopeptidic organocatalysts for the acylative kinetic resolution/desymmetrization of rac- and meso-cycloalkane-1,2-diols. Here we describe in a full account the discovery and development process from the theoretical concept to the final catalyst, including scope and limitations. Competition experiments with various alcohols and electrophiles show the full potential of the employed oligopeptides. Additionally, we utilized NMR and IR-spectroscopic methods as well as computations to shed light on the factors responsible for the selectivity. The catalyst system can be readily modified to a multicatalyst by adding other catalytically active amino acids to the peptide backbone, enabling the stereoselective one-pot synthesis of complex molecules from simple starting materials.

Silicon-(thio)urea Lewis acid catalysis.

We present a new class of catalysts based on the combination of N,N'-diaryl(thio)ureas and weak silicon Lewis acids (e.g., SiCl(4)). Such silicon-(thio)urea catalysts effectively catalyze the stereospecific rearrangement of epoxides to quaternary carbaldehydes.

Organocatalytic enantioselective acyl transfer onto racemic as well as meso alcohols, amines, and thiols.

Acyl transfer is at the heart of functional-group transfers utilized both in nature and in the chemical laboratory. Acylations are part of the natural assembly machinery for the generation of complex molecules and for energy transport in biological systems. The recognition of covalent acyl-enzyme intermediates led to both mechanistic studies as well as the development of biomimetic approaches. Consequently, chemists first used the tools of nature in the form of enzymes and naturally occurring alkaloids as catalysts, before eventually developing a large variety of synthetic small molecules for selective acyl transfer. In contrast to nature, chemists utilize acylation reactions as a practical way for stereoselection and functional-group protection. Indeed, the number of studies concerning acyl transfer has significantly increased over the last 15 years. This Review examines and highlights these recent developments with the focus as given in the title.

Synergistic Impact of Systolic Blood Pressure and Perfusion Status on Mortality in Acute Heart Failure.

BACKGROUND: Physical examination remains the cornerstone in the assessment of acute heart failure. There is a lack of adequately powered studies assessing the combined impact of both systolic blood pressure (SBP) and hypoperfusion on short-term mortality. METHODS: Patients with acute heart failure from 41 Spanish emergency departments were recruited consecutively in 3 time periods between 2011 and 2016. Logistic regression models were used to assess the association of 30-day mortality with SBP (<90, 90-109, 110-129, and ≥130 mm Hg) and with manifestations of hypoperfusion (cold skin, cutaneous pallor, delayed capillary refill, livedo reticularis, and mental confusion) at admission. RESULTS: Among 10 979 patients, 1143 died within the first 30 days (10.2%). There was an inverse association between 30-day mortality and initial SBP (35.4%, 18.9%, 12.4%, and 7.5% for SBP<90, SBP 90-109, SBP 110-129, and SBP≥130 mm Hg, respectively; P<0.001) and a positive association with hypoperfusion (8.0%, 14.8%, and 27.6% for those with none, 1, ≥2 signs/symptoms of hypoperfusion, respectively; P<0.001). After adjustment for 11 risk factors, the prognostic impact of hypoperfusion on 30-day mortality varied across SBP categories: SBP≥130 mm Hg (odds ratio [OR]=1.03 [95% CI, 0.77-1.36] and OR=1.18 [95% CI, 0.86-1.62] for 1 and ≥2 compared with 0 manifestations of hypoperfusion), SBP 110 to 129 mm Hg (OR=1.23 [95% CI, 0.86-1.77] and OR=2.18 [95% CI, 1.44-3.31], respectively), SBP 90 to 109 mm Hg (OR=1.29 [95% CI, 0.79-2.10] and OR=2.24 [95% CI, 1.36-3.66], respectively), and SBP<90 mm Hg (OR=1.34 [95% CI, 0.45-4.01] and OR=3.22 [95% CI, 1.30-7.97], respectively); P-for-interaction =0.043. CONCLUSIONS: Hypoperfusion confers an incremental risk of 30-day all-cause mortality not only in patients with low SBP but also in normotensive patients. On admission, physical examination plays a major role in determining prognosis in patients with acute heart failure.

Editor's Choice- Impact of identifying precipitating factors on 30-day mortality in acute heart failure patients.

BACKGROUND: The aim of this study was to describe the prevalence and prognostic value of the most common triggering factors in acute heart failure. METHODS: Patients with acute heart failure from 41 Spanish emergency departments were recruited consecutively in three time periods between 2011 and 2016. Precipitating factors were classified as: (a) unrecognized; (b) infection; (c) atrial fibrillation; (d) anaemia; (e) hypertension; (f) acute coronary syndrome; (g) non-adherence; and (h) two or more precipitant factors. Unadjusted and adjusted logistic regression models were used to assess the association between 30-day mortality and each precipitant factor. The risk of dying was further evaluated by week intervals over the 30-day follow-up to assess the period of higher vulnerability for each precipitant factor. RESULTS: Approximately 69% of our 9999 patients presented with a triggering factor and 1002 died within the first 30 days (10.0%). The most prevalent factors were infection and atrial fibrillation. After adjusting for 11 known predictors, acute coronary syndrome was associated with higher 30-day mortality (odds ratio (OR) 1.87; 95% confidence interval (CI) 1.02-3.42), whereas atrial fibrillation (OR 0.75; 95% CI 0.56-0.94) and hypertension (OR 0.34; 95% CI 0.21-0.55) were significantly associated with better outcomes when compared to patients without precipitant. Patients with infection, anaemia and non-compliance were not at higher risk of dying within 30 days. These findings were consistent across gender and age groups. The 30-day mortality time pattern varied between and within precipitant factors. CONCLUSIONS: Precipitant factors in acute heart failure patients are prevalent and have a prognostic value regardless of the patient's gender and age. They can be managed with specific treatments and can sometimes be prevented.

Departments involved during the first episode of acute heart failure and subsequent emergency department revisits and rehospitalisations: an outlook through the NOVICA cohort.

OBJECTIVES: We investigated the natural history of patients after a first episode of acute heart failure (FEAHF) requiring emergency department (ED) consultation, focusing on: the frequency of ED visits and hospitalisations, departments admitting patients during the first and subsequent hospitalisations, and factors associated with difficult disease control. METHODS AND RESULTS: We included consecutive patients diagnosed with FEAHF (either with or without previous heart failure diagnosis) in four EDs during 5 months in three different time periods (2009, 2011, 2014). Diagnosis was adjudicated by local principal investigators. The clinical characteristics of the index event were prospectively recorded, and all post-discharge ED visits and hospitalisations [related/unrelated to acute heart failure (AHF)], as well as departments involved in subsequent hospitalisations were retrospectively ascertained. 'Uncontrolled disease' during the first year after FEAHF was considered if patients were attended at ED (≥ 3 times) or hospitalised (≥ 2 times) for AHF or died. Overall, 505 patients with FEAHF were included and followed for a mean of 2.4 years. In-hospital mortality was 7.5%. Among 467 patients discharged alive, 288 died [median survival 3.9 years, 95% confidence interval (CI) 3.5-4.4], 421 (90%) revisited the ED (2342 ED visits; 42.4% requiring hospitalisation, 34.0% AHF-related) and 357 (77%) were hospitalised (1054 hospitalisations; 94.1% through ED, 51.4% AHF-related). AHF-related hospitalisations were mainly in internal medicine (28.0%), short-stay unit (26.3%), cardiology (20.8%), and geriatrics (14.1%). Only 47.4% of AHF-related hospitalisations were in the same department as the FEAHF, and internal medicine involvement significantly increased with subsequent hospitalisations (P = 0.01). Uncontrolled disease was observed in 31% of patients, which was independently related to age > 80 years [odds ratio (OR) 1.80, 95% CI 1.17-2.77], systolic blood pressure < 110 mmHg at ED arrival (OR 2.61, 95% CI 1.26-5.38) and anaemia (OR 2.39, 95% CI 1.51-3.78). CONCLUSION: In the present aged cohort of AHF patients from Barcelona, Spain, the natural history after FEAHF showed different patterns of hospital department involvement. Advanced age, low systolic blood pressure and anaemia were factors related to uncontrolled disease during the year after debut.

Time trends in characteristics, clinical course, and outcomes of 13,791 patients with acute heart failure.

OBJECTIVES: To analyse time trends in patient characteristics, clinical course, hospitalisation rate, and outcomes in acute heart failure along a 10-year period (2007-2016). METHODS: The EAHFE registry has prospectively collected 13,971 consecutive AHF patients diagnosed in 41 Spanish emergency departments (EDs) at five different time points (2007/2009/2011/2014/2016). Eighty patient-related variables and outcomes were described and statistically significant changes along time were evaluated. We also compared our data with large ED- and hospital-based registries. RESULTS: Compared to other large registries, our patients were older [80 (10) years], more frequently women (55.5%), and had a higher prevalence of hypertension (83.5%) and a lower prevalence of ischaemic cardiomyopathy (29.4%). De novo AHF was observed in 39.6%. 63.6% showed some degree of functional dependence and 56.1% had preserved left ventricular ejection fraction (LVEF). 56.8% of the patients arrived at the ED by ambulance, 4.5% arrived hypotensive, and 21.3% hypertensive. Direct discharge from the ED home was seen in 24.9%, and internal medicine (32.5%) and cardiology (15.8%) were the main hospital destinations. Triggers for decompensation were identified in 75.4%, the most being frequent infection (35.2%) and rapid atrial fibrillation (14.7%). The AHF phenotypes were: warm/wet 82.0%, warm/dry 6.2%, cold/wet 11.1%, and cold/dry 0.7%. The length of hospitalisation was 9.3 (8.6) days, and in-hospital, 30-day, and 1-year all-cause mortality were 7.8, 10.2 and 30.3%, respectively; and 30-day re-hospitalisation and ED revisit due to AHF were 16.9 and 24.8%, respectively. Thirty-nine of the eighty characteristics studied showed significant changes over time, while all outcomes remained unchanged along the 10-year period. CONCLUSIONS: The EAHFE Registry is the first European ED-based registry describing the characteristics, clinical course, and outcomes of a cohort resembling the universe of patients with AHF. Significant changes were observed over time in some aspects of AHF characteristics and management, but not in outcomes.

Enantiomerically enriched trans-diols from alkenes in one pot: a multicatalyst approach.

Multicatalysts consisting of non-natural oligopeptides with distinctly different catalytic moieties create molecular complexity in a multistep one-pot sequence starting from simple alkenes yielding highly enantiomerically enriched trans-diols.

Kinetic resolution of trans-cycloalkane-1,2-diols via Steglich esterification.

We describe the efficient and highly enantioselective kinetic resolution of trans-cycloalkane-1,2-diols utilizing an enantioselective Steglich reaction with a variety of carboxylic acids that form the corresponding anhydrides in situ.