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To compare intraosseous access with peripheral venous access on adults out-of-hospital cardiac arrest (OHCA) patients’ clinical outcomes. A national retrospective multicentre study was conducted based on the French National Cardiac Arrest Registry. Comparison of patients (intraosseous vs. peripheral venous access) was conducted before and after a matching using a propensity score. The propensity score included confounding factors: age, time between the call (T0) to epinephrine (to take account of how quickly vascular access was achieved), the aetiology of OHCA, the shock and the patient initial rhythm at MMT arrival. A total of 1576 patients received intraosseous access, and 27,280 received peripheral intravenous access. Before matching, OHCA patients with intraosseous access were less likely to survive at all stages (return of spontaneous circulation (ROSC), 0-day survival and 30-day survival). No significant difference in neurological outcome was observed. After propensity score matching, no significant differences in 30-day survival rates (OR = 0.763 [0.473;1.231]) and neurological outcome (OR = 1.296 [0.973;1.726]) were observed. However, intraosseous patients still showed lower likelihood of short-term survival (ROSC and 0-day survival) even after propensity score matching was implemented. The populations we investigated were similar to those of other studies suggesting that intraosseous access is associated with reduced survival and poorer neurological outcome. Our findings suggest that intraosseous access is a comparably effective alternative to peripheral intravenous access for treating OHCA patients on matched populations.

Diuretics in low doses have the greatest support among current available antihypertensives in that they have been shown to reduce total mortality, coronary mortality, stroke, and congestive heart failure in an important meta-analysis by Psaty. Recently, Messerli has linked long-term diuretic use to renal cell carcinoma in women. In some patients, diuretic use leads to increasing blood cholesterol and blood sugar levels. Impotence is a recognized side effect, with rates rising about twofold with low-dose chlorthalidone and fourfold with a higher dose. Certain population groups such as younger (<60 years) white males often do not respond to low-dose diuretic therapy with an adequate blood pressure fall. In females of a similar age group, Messerli calculates that prolonged diuretic therapy will prevent only one stroke and no coronary events nor any deaths for every renal cell carcinoma that is provoked. Despite these evident problems, the outcome data on hard endpoints in trials with initial low-dose diuretic therapy remain valid and convincing. Thus, it is argued, low- but not high-dose diuretics retain their primacy in the ranking of antihypertensive therapy.

We report the results of a two center study on the use of the HMG Co A reductase inhibitor, simvastatin, in 44 patients suffering from familial hypercholesterolemia or from primary hypercholesterolemia of unknown etiology. The study included two separate phases: Phase I was part of a multicenter, 4-week, placebo-controlled trial; phase II was a 6-month, open extension trial, the object of which was to reduce low density lipoprotein (LDL) cholesterol levels to below the 50th percentile by increasing the dose of simvastatin, by the use of additional lipid-lowering medication, or both. Our phase I results were commensurate with those reported for the entire international cohort of 272 patients, indicating a clear dose-response relationship, with approximately 75% of the maximum reduction in LDL-C levels being achieved with 20 mg/day and over 90% of the maximum being achieved with 40 mg of simvastatin per day. In the open extension trial, the results from the 2 centers were essentially similar. Total cholesterol fell by 29% on the 20 mg/day dose and by 34% on the full dose of 40 mg/day. LDL-C levels were reduced by 40% on the 40 mg/day schedule, and triglycerides also fell to between 20% and 40% below baseline values. HDL-C concentration rose by 14% and 17.6%. The effects of simvastatin were uniform, both within and between the two cohorts. The addition of cholestyramine caused a further substantial reduction in LDL-cholesterol to below 55% of the initial value in four patients, whereas bezafibrate further enhanced the fall in triglycerides and the increase in high-density lipoprotein cholesterol, but had only a slight effect on LDL-C levels. Adverse reactions included asymptomatic increases in plasma creatine kinase activity, generally associated with previous physical exertion, and transient rises in transaminase levels. In one patient with a history of alcoholic excess, transaminase levels were persistently greater than normal. These results indicate that the HMG Co A reductase inhibitor, simvastatin, is a powerful therapeutic agent for the lowering of plasma cholesterol levels in patients with genetic hypercholesterolemia.

The persistent existence of pathological cardiac remodeling, resulting from aortic stenosis, is related to poor clinical prognosis after successful transcatheter aortic valve replacement (TAVR). Sacubitril/valsartan (Sac/Val), comprising an angiotensin receptor blocker and a neprilysin inhibitor, has been demonstrated to have a beneficial effect against pathological cardiac remodeling, including cardiac fibrosis and inflammation in heart failure. The aim of this study was to determine whether Sac/Val exerts a cardioprotective effect after pressure unloading in mice. Male C57BL/6 J mice were subjected to debanding (DB) surgery after 8 weeks (wk) of aortic banding (AB). Cardiac function was assessed by echocardiography, which indicated a protective effect of Sac/Val after DB. After treatment with Sac/Val post DB, decreased heart weight and myocardial cell size were observed in mouse hearts. In addition, histological analysis, immunofluorescence, and western blot results showed that Sac/Val attenuated cardiac fibrosis and inflammation after DB. Finally, our data indicated that Sac/Val treatment could significantly suppress NF-κB signaling and NLRP3 inflammasome activation in mice after relief of pressure overload. Sac/Val exerted its beneficial effects to prevent maladaptive cardiac fibrosis and dysfunction in mice following pressure unloading, which was at least partly due to the inhibition of NLRP3 inflammasome activation.

In congestive heart failure, in addition to a compensatory increase in neurohumoral activation, there is an increase in the endothelial-derived vasoconstrictive and positive inotropic substance, endothelin. Whether downregulation of the cardiac inotropic effects of this endothelial-derived substance occurs, as has been shown to occur with neurohumoral beta- and alpha-adrenergic agonists, remains unknown. In this study we investigated the effects of endothelin-1 [dose-response curve (10-11 to 10-7 M)] on the contractile characteristics of isolated papillary muscles from normal dogs and from dogs with heart failure induced by pacing overdrive, with or without removing endocardial endothelium from the papillary muscles. Endothelin-1 caused a similar absolute increase in myocardial contractile indices in all four groups, except for shortening, which increased more in muscles with heart failure without endocardial endothelium. However, in muscles with an intact endocardial endothelium, the relative increase was greater in muscles from pacing overdrive dogs (failing) as compared with normal dogs (tension increase of 110% vs. 53%, p<0.01 and shortening increase of 127% vs. 24%, p<0.01). Also, failing muscles with intact endocardial endothelium began responding to endothelin-1 at lower endothelin-1 concentrations (10-10 vs. 10-9 M) than normal muscles with intact endocardial endothelium. Endocardial endothelial removal increased the contractile effects of endothelin-1, whether this was done in normal or failing myocardium. This study thus indicates that, in contrast to other positive inotropic substances, in this model of heart failure there is an increase in sensitivity and relative response to endothelin-1. It also indicates that although endocardial endothelial removal increases the relative effects of endothelin-1 in both normal and failing myocardium, the increased responsiveness of failing myocardium is not endocardial endothelial dependent.

Background: Extracellular matrix metabolism (ECM) has an important role in left ventricular (LV) remodeling in chronic heart failure (CHF). Matrix metalloproteinases (MMPs) are involved in the regulation of extracellular matrix (ECM) metabolism. We investigated the effect of levosimendan, a novel calcium sensitizer, on serum levels of MMP-2. Methods: Our study population consisted of 60 consecutive patients with advanced heart failure who were admitted to hospital with an acute decompensation of their CHF. Patients were randomized to levosimendan (n = 30; 18 men, aged 65 ± 3 years) or placebo (n = 30; 15 men, aged 67 ± 4 years). Serum MMP-2 levels were assessed before and after treatment with levosimendan or placebo, using a commercially available ELISA. Results: Serum levels of MMP-2 were reduced from 427 ng/ml 95%CI 372–484 to 371 ng/ml 95%CI 329–413 in the levosimendan treated group and from 433 ng/ml 95%CI 422–444 to 425 ng/ml 95%CI 414–436 in the placebo group. Repeated measurements ANOVA showed that treatment with levosimendan significantly affected levels of MMP-2 (p = 0.019). Conclusions: The present study showed that levosimendan may beneficially affect ECM remodeling in patients with acutely decompensated CHF. Whether these effects translate into added clinical benefits, as suggested by an improved ejection fraction in the levosimendan group, deserves further investigation.

Direct oral anticoagulants (DOACs) are not recommended in adult Fontan patients (Level of Evidence C). We hypothesized that DOACs are comparable to warfarin and do not increase thrombotic and embolic complications (TEs) or clinically significant bleeds. We reviewed the medical records of adult Fontan patients on DOACs or warfarin at three major medical centers. We identified 130 patients: 48 on DOACs and 107 on warfarin. In total, they were treated for 810 months on DOACs and 5637 months on warfarin. The incidence of TEs in patients on DOACs compared to those on warfarin was not increased in a statistically significant way (hazard ratio [HR] 1.7 and p value 0.431). Similarly, the incidence of nonmajor and major bleeds in patients on DOACs compared to those on warfarin was also not increased in a statistically significant way (HR for nonmajor bleeds in DOAC patients was 2.8 with a p value of 0.167 and the HR for major bleeds was 2.0 with a p value 0.267). In multivariate analysis, congestive heart failure (CHF) was a risk factor for TEs across both groups (odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.3–17.6) and bleed history was a risk factor for clinically significant bleeds (OR = 6.8, 95% CI = 2.7–17.2). In this small, retrospective multicenter study, the use of DOACs did not increase the risk of TEs or clinically significant bleeds compared to warfarin in a statistically significant way.

An adequate matching for race, sex, stage of the menstrual cycle, family history of hypertension, and the amount of sodium and other electrolytes in the diet should be a prerequisite for valid conclusions when interpreting the erythrocyte concentration and fluxes of sodium in essential hypertensive patients in comparison with normal subjects. Alterations in intracellular sodium concentration and transmembrane sodium transport systems as causes of essential hypertension are postulated. This review article describes how this abnormal sodium and calcium metabolism translates into increased systemic vascular resistance through altered vasoactive responses and/or vasculature structural changes.