Reply to G. Betts's letter referring to "Serum potassium dynamics during acute heart failure hospitalization".

This work was funded by the Instituto de Salud Carlos III (Ministry of Economy, Industry and Competitiveness) and cofunded by the European Regional Development Fund, through the CIBER in cardiovascular diseases (CB16/11/00502).S

Non-Invasive Assessment of Pulmonary Vasculopathy

Right heart catheterization remains necessary for the diagnosis of pulmonary hypertension and, therefore, for the prognostic evaluation of patients with chronic heart failure. The non-invaSive Assessment of Pulmonary vasculoPathy in Heart failure (SAPPHIRE) study was designed to assess the feasibility and prognostic relevance of a non-invasive evaluation of the pulmonary artery vasculature in patients with heart failure and pulmonary hypertension. Patients will undergo a right heart catheterization, cardiac resonance imaging, and a pulmonary function test in order to identify structural and functional parameters allowing the identification of combined pre- and postcapillary pulmonary hypertension, and correlate these findings with the hemodynamic dataThis research was funded by European Regional Development Fund and the Carlos III Research Institute through a grant of the Health Strategy Action (PI17/01569).S

The development of chronic diuretic resistance can be predicted during a heart-failure hospitalization: Results from the REDIHF registry

Introduction: Diuretic resistance (DR) is a common condition during a heart failure (HF) hospitalization, and is related to worse prognosis. Although the risk factors for DR during a HF hospitalization are widely described, we do not know whether the risk of chronic DR could be predicted during admission. Material and methods: We conducted a multicenter, prospective observational study between July 2017 and July 2019. All patients admitted for acute HF with intravenous diuretic treatment and at least one criterion of congestion on admission were invited to participate. Patients on renal replacement therapy, under intravenous diuretic treatment for >72 hours before screening and those who were unable to sign the informed consent were excluded. We monitored decongestion (physical exam, hemoconcentration, NTproBNP change and lung ultrasound) and DR (diuresis and weight loss per unit of 40mg furosemide and fractional excretion of sodium) on the fifth day of admission. Chronic DR was evaluate two months after hospitalization and was defined as persistent signs of congestion despite ≥80 mg furosemide per day. We compared variables from the hospitalization between patients with and without chronic DR. A multivariate logistic regression analysis was conducted to find predictors of chronic DR. Results: A total of 105 patients were included in the study. Mean age was 74.5±12.0 years, 64.8% were male and mean LVEF was 46±17%. In the two months follow-up, five patients have died and one patient has had a heart transplant. Of the 99 remaining patients, 21 patients (21.2%) had chronic DR. The dose of furosemide before admission and the decrease in NT-proBNP ≤30% during admission were predictors of chronic DR in the multivariate analysis. Conclusions: We can predict during a HF hospitalization which patients will develop chronic DR. The dose of furosemide before admission and the change in NT-proBNP are independent predictors of chronic DR

Dose of furosemide before admission predicts diuretic efficiency and long-term prognosis in acute heart failure

Aims: The outpatient diuretic dose is a marker of diuretic resistance and prognosis in chronic heart failure (HF). Still, the impact of the preadmission dose on diuretic efficiency (DE) and prognosis in acute HF is not fully known. Methods and results: we conducted an observational and prospective study. All patients admitted for acute HF treated with intravenous diuretic and at least one criterion of congestion on admission were evaluated. Decongestion [physical examination, hemoconcentration, N-terminal pro-brain natriuretic peptide (NT-proBNP) change, and lung ultrasound], DE (weight loss and urine output per unit of 40 mg furosemide), and urinary sodium were monitored on the fifth day of admission. DE was dichotomized into high-low based on the median value. A multivariate Cox regression analysis was conducted to find predictors of HF readmission or mortality. A total of 105 patients were included between July 2017 and July 2019. Mean age was 74.5 ± 12.0 years, 64.8% were male, 33.3% had de novo HF, and mean left ventricular ejection fraction was 46 ± 17%. Median follow-up was 26 [15-35] months. Low DE based on weight loss was associated with a higher previous dose of furosemide (odds ratio [OR] 1.01 [1.00-1.02]), thiazide treatment before admission (OR 9.37 [2.19-40.14]), and lower diastolic blood pressure (OR 0.95 [0.91-0.98]) in the multivariate regression model. Only previous dose of furosemide (OR 1.01 [1.00-1.02]) and haemoglobin at admission (OR 0.76 [0.58-0.99]) were associated with low DE based on urine output in the multivariate analysis. The correlation between the previous dose of furosemide and DE based on weight loss was poor (r = -0.12; P = 0.209) and with DE based on urine output was weak to moderate (r = -0.33; P 80 mg in ADHF identified patients with particularly poor prognosis (log-rank < 0.001). In ADHF, the preadmission dose of furosemide (hazard ratio [HR] 1.34 [1.08-1.67] per 40 mg) and NT-proBNP at admission (HR 1.03 [1.01-1.06] per 1000 pg/mL) were independently associated with mortality or HF readmission in the multivariate Cox regression analysis. Conclusions: the outpatient dose of furosemide before acute HF admission predicts DE and must be taken into account when deciding on the initial diuretic dose. In ADHF, the outpatient dose of furosemide can predict long-term prognosis better than DE during hospitalization

Frailty is an independent prognostic marker in elderly patients with myocardial infarction.

Acute coronary syndrome (ACS) patients are increasingly older. Conventional prognostic scales include chronological age but do not consider vulnerability. In elderly patients, a frail phenotype represents a better reflection of biological age. This study aims to determine the prevalence of frailty and its influence on patients age ≥75 years with ACS. Patients age ≥75 years admitted due to type 1 myocardial infarction were included in 2 tertiary hospitals, and clinical data were collected prospectively. Frailty was defined at admission using the previously validated Survey of Health Ageing and Retirement in Europe Frailty Index (SHARE-FI) tool. The primary endpoint was the combination of death or nonfatal myocardial reinfarction during a follow-up of 6 months. Major bleeding (hemoglobin decrease ≥3 g/dL or transfusion needed) and readmission rates were also explored. A total of 234 consecutive patients were included. Frail patients (40.2%) had a higher-risk profile, based on higher age and comorbidities. On multivariate analysis, frailty was an independent predictor of the combination of death or nonfatal myocardial reinfarction (adjusted hazard ratio [aHR]: 2.54, 95% confidence interval [CI]: 1.12-5.79), an independent predictor of the combination of death, nonfatal myocardial reinfarction, or major bleeding (aHR: 2.14, 95% CI: 1.13-4.04), and an independent predictor of readmission (aHR: 1.80, 95% CI: 1.00-3.22). Frailty phenotype at admission is common among elderly patients with ACS and is an independent predictor for severe adverse events. It should be considered in future risk-stratification models

MiR-146a Contributes to Thromboinflammation and Recurrence in Young Patients with Acute Myocardial Infarction

Studies on older patients have established notable conceptual changes in the etiopathogenesis of acute coronary syndrome (ACS), but little is known about this disease in young patients (&lt;45 years). Of special interest is thromboinflammation, key at onset, evolution and therapy of cardiovascular pathology. Therefore, we explored whether ACS at an early age is a thromboinflammatory disease by analyzing NETs and rs2431697 of miR-146a (a miRNA considered as a brake of TLR/NF-kB pathway), elements previously related to higher rates of recurrence in atrial fibrillation and sepsis. We included 359 ACS patients (&lt;45 years) and classified them for specific analysis into G1 (collected during the hospitalization of the first event), G2 and G3 (retrospectively collected from patients with or without ACS recurrence, respectively). cfDNA and citH3&ndash;DNA were quantified, and rs2431697 was genotyped. Analysis in the overall cohort showed a moderate but significant correlation between cfDNA and citH3&ndash;DNA and Killip&ndash;Kimball score. In addition, patients with citH3&ndash;DNA &gt; Q4 more frequently had a history of previous stroke (6.1% vs. 1.6%). In turn, rs2431697 did not confer increased risk for the onset of ACS, but T carriers had significantly higher levels of NET markers. By groups, we found that cfDNA levels were similarly higher in all patients, but citH3&ndash;DNA was especially higher in G1, suggesting that in plasma, this marker may be attenuated over time. Finally, patients from G2 with the worst markers (cfDNA and citH3&ndash;DNA &gt; Q2 and T allele) had a two-fold increased risk of a new ischemic event at 2-year follow-up. In conclusion, our data confirm that ACS is younger onset with thromboinflammatory disease. In addition, these data consolidate rs2431697 as a silent proinflammatory factor predisposing to NETosis, and to a higher rate of adverse events in different cardiovascular diseases

Tracking of charged particles with nanosecond lifetimes at LHCb

A method is presented to reconstruct charged particles with lifetimes between 10 ps and 10 ns, which considers a combination of their decay products and the partial tracks created by the initial charged particle. Using the $\Xi^-$ baryon as a benchmark, the method is demonstrated with simulated events and proton-proton collision data at $\sqrt{s}=13$ TeV, corresponding to an integrated luminosity of 2.0 fb${}^{-1}$ collected with the LHCb detector in 2018. Significant improvements in the angular resolution and the signal purity are obtained. The method is implemented as part of the LHCb Run 3 event trigger in a set of requirements to select detached hyperons. This is the first demonstration of the applicability of this approach at the LHC, and the first to show its scaling with instantaneous luminosity

Measurement of D0−D‾0D^0-\overline{D}^0 mixing and search for CPCP violation with D0→K+π−D^0\rightarrow K^+\pi^- decays

International audienceA measurement of the time-dependent ratio of the $D^0\rightarrow K^+\pi^-$ to $\overline{D}^0\rightarrow K^+\pi^-$ decay rates is reported. The analysis uses a sample of proton-proton collisions corresponding to an integrated luminosity of 6 fb$^-1$ recorded by the LHCb experiment from 2015 through 2018 at a center-of-mass energy of 13 TeV. The $D^0$ meson is required to originate from a $D^{*+}\rightarrow D^0\pi^+$ decay, such that its flavor at production is inferred from the charge of the accompanying pion. The measurement is performed simultaneously for the $K^+\pi^-$ and $K^-\pi^+$ final states, allowing both mixing and $CP$-violation parameters to be determined. The value of the ratio of the decay rates at production is determined to be $R_{K\pi} = (343.1 \pm 2.0) \times 10^{-5}$. The mixing parameters are measured to be $c_{K\pi} = (51.4 \pm 3.5) \times 10^{-4}$ and $c_{K\pi}^{\prime} = (13 \pm 4) \times 10^{-6}$, where $\sqrt{R_{K\pi}}c_{K\pi}$ is the linear coefficient of the expansion of the ratio as a function of decay time in units of the $D^0$ lifetime, and $c_{K\pi}^{\prime}$ is the quadratic coefficient, both averaged between the $K^+\pi^-$ and $K^-\pi^+$ final states. The precision is improved relative to the previous best measurement by approximately 60%. No evidence for $CP$ violation is found

Measurement of D0−D‾0D^0-\overline{D}^0 mixing and search for CPCP violation with D0→K+π−D^0\rightarrow K^+\pi^- decays

International audienceA measurement of the time-dependent ratio of the $D^0\rightarrow K^+\pi^-$ to $\overline{D}^0\rightarrow K^+\pi^-$ decay rates is reported. The analysis uses a sample of proton-proton collisions corresponding to an integrated luminosity of 6 fb$^-1$ recorded by the LHCb experiment from 2015 through 2018 at a center-of-mass energy of 13 TeV. The $D^0$ meson is required to originate from a $D^{*+}\rightarrow D^0\pi^+$ decay, such that its flavor at production is inferred from the charge of the accompanying pion. The measurement is performed simultaneously for the $K^+\pi^-$ and $K^-\pi^+$ final states, allowing both mixing and $CP$-violation parameters to be determined. The value of the ratio of the decay rates at production is determined to be $R_{K\pi} = (343.1 \pm 2.0) \times 10^{-5}$. The mixing parameters are measured to be $c_{K\pi} = (51.4 \pm 3.5) \times 10^{-4}$ and $c_{K\pi}^{\prime} = (13 \pm 4) \times 10^{-6}$, where $\sqrt{R_{K\pi}}c_{K\pi}$ is the linear coefficient of the expansion of the ratio as a function of decay time in units of the $D^0$ lifetime, and $c_{K\pi}^{\prime}$ is the quadratic coefficient, both averaged between the $K^+\pi^-$ and $K^-\pi^+$ final states. The precision is improved relative to the previous best measurement by approximately 60%. No evidence for $CP$ violation is found

Measurement of D0−D‾0D^0-\overline{D}^0 mixing and search for CPCP violation with D0→K+π−D^0\rightarrow K^+\pi^- decays

International audienceA measurement of the time-dependent ratio of the $D^0\rightarrow K^+\pi^-$ to $\overline{D}^0\rightarrow K^+\pi^-$ decay rates is reported. The analysis uses a sample of proton-proton collisions corresponding to an integrated luminosity of 6 fb$^-1$ recorded by the LHCb experiment from 2015 through 2018 at a center-of-mass energy of 13 TeV. The $D^0$ meson is required to originate from a $D^{*+}\rightarrow D^0\pi^+$ decay, such that its flavor at production is inferred from the charge of the accompanying pion. The measurement is performed simultaneously for the $K^+\pi^-$ and $K^-\pi^+$ final states, allowing both mixing and $CP$-violation parameters to be determined. The value of the ratio of the decay rates at production is determined to be $R_{K\pi} = (343.1 \pm 2.0) \times 10^{-5}$. The mixing parameters are measured to be $c_{K\pi} = (51.4 \pm 3.5) \times 10^{-4}$ and $c_{K\pi}^{\prime} = (13 \pm 4) \times 10^{-6}$, where $\sqrt{R_{K\pi}}c_{K\pi}$ is the linear coefficient of the expansion of the ratio as a function of decay time in units of the $D^0$ lifetime, and $c_{K\pi}^{\prime}$ is the quadratic coefficient, both averaged between the $K^+\pi^-$ and $K^-\pi^+$ final states. The precision is improved relative to the previous best measurement by approximately 60%. No evidence for $CP$ violation is found