Measurement of left ventricular function in anaesthetised horses using transoesophageal doppler echocardiography

Studies were undertaken using transesophageal Doppler echocardiography to monitor left ventricular systolic function in anaesthetised horses. A 3.5 MHz transoesophageal probe was specifically developed in collaboration with Vingmed Sound for equine use. The indices of systolic function investigated were maximum acceleration of aortic blood flow (dv/dt^J, maximum blood flow velocity, (V^J, cardiac output (CO), left ventricular pre-ejection period (PEP) and left ventricular ejection time (ET).The feasibility of the technique was demonstrated in a group of 8 healthy Thoroughbred horses anaesthetised using a standard protocol. It was established that two dimensional transoesophageal echocardiography provided a reference view of the left ventricular outflow tract and aorta that consistently allowed high quality Doppler echocardiographic measurement of aortic blood flow velocity. The flow envelopes obtained were suitable for measurement of indices of left ventricular systolic function. The repeatability of the measured indices was similar to that of the maximum rate of rise of left ventricular pressure (LVdp/dtmax), obtained simultaneously by cardiac catheterisation.Cardiac output estimations made using transoesophageal Doppler echocardiography were compared with those obtained by thermodilution in the same group of horses under general anaesthesia. Cardiac output was altered by infusions of the sympathomimetic amine, dobutamine. Aortic velocity spectra obtained both by high pulse repetition frequency and continuous wave insonation modes were used to obtain the velocity time integral for calculation of cardiac output. The measurements derived from transoesophageal echocardiography agreed well with those obtained by thermodilution. Both correlation coefficients and limits of agreement between the two techniques were better than those obtained from similar studies in standing horses using transthoracic echocardiography.The sensitivity of the Doppler derived indices of left ventricular function to inotropic intervention was assessed in the final sequence of studies. As these indices are derived during the ejection period they are load dependent, so their response to changes in ventricular loading was also assessed and compared with the most commonly used index of myocardial contractility in horses, LVdp/dtmax. Three drugs were administered to the anaesthetised horses in a randomised sequence during three separate anaesthetic episodes. The drugs, dobutamine, dopamine and dopexamine were selected because of their relatively different effects on afterload, preload and contractility. Maximum acceleration of aortic blood flow was as sensitive to the changes in ventricular performance as LVdp/dtmax. Maximum aortic blood velocity showed the same qualitative response to infusion of the drugs but the changes were quantitatively less than in dv/dtmax and LVdp/dtmax. The systolic time intervals, PEP and ET, were also responsive to drug infusion; pre-ejection period shortened with each drug, whilst ET increased after dopamine and dopexamine, but was reduced by dobutamine.These studies have shown that dv/dtmax is as sensitive as the invasive index LVdp/dtmax for detecting changes in left ventricular performance. In addition dv/dtmax and Vmax appear to be no more affected by changes in ventricular loading conditions than the isovolumic index LVdp/dtmax. It is concluded that transoesophageal Doppler echocardiography provides a minimally invasive technique for assessment of left ventricular systolic function in anaesthetised horses

Empagliflozin in Patients with Chronic Kidney Disease

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to < 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of & GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P < 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo

Risk of COVID-19 after natural infection or vaccinationResearch in context

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health