Heat stress compromises blood pressure (BP) control during a simulated hemorrhagic challenge, while acute volume loading attenuates this response. This study tested the hypothesis that the mechanism ...of preserved BP control during heat stress + volume loading is, in part, through preservation of left ventricular end diastolic volume (LVEDV). LVEDV was measured in nine subjects during normothermia (NT), after an increase in pulmonary artery blood temperature of 1.3 ± 0.2 °C (HS; P < 0.05), and after volume infusion (HS + Inf). In each condition, supine LVEDV was assessed via echocardiography, by the Simpson biplane method, prior to and during simulated hemorrhage, evoked via 30 mmHg lower body negative pressure (LBNP). LVEDV was reduced by HS (NT: 148 ± 26 ml, HS: 126 ± 31 ml; P < 0.05), however, this fall was attenuated by HS + Inf (HS + Inf: 133 ± 25 ml; P > 0.05 relative to NT and HS). During simulated hemorrhage, the reductions in LVEDV were similar between NT (45 ± 20 ml) and HS (52± 20 ml), whereas the reduction in LVEDV after volume infusion (22 ± 22 ml) was attenuated relative to NT and HS (P < 0.05). Importantly, infusion resulted in an LVEDV during LBNP that was significantly elevated (111 ± 26 ml) relative to HS alone (74 ± 25 ml). Improved control of BP following volume infusion during HS occurs in part by attenuating the reduction in LVEDV to a simulated hemorrhagic challenge.
Supported by NIH Grant NIH‐HL61388 & HL84072
Early mobilization after surgery is crucial for an enhanced recovery and can reduce complications associated with immobility. Symptoms such as nausea, vomiting, blurred vision and dizziness are ...however known to impede early mobilization. Together these symptoms comprise orthostatic intolerance (OI), in which the ultimate manifestation is syncope. In reference to find preventive and relevant treatment for OI studies with a multimodal approach have shown promising results, though the pathophysiology behind OI is not fully understood.
Blood transfusions are frequently given to patients with septic shock. However, the benefits and harms of different hemoglobin thresholds for transfusion have not been established.
In this ...multicenter, parallel-group trial, we randomly assigned patients in the intensive care unit (ICU) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less (lower threshold) or when the level was 9 g per deciliter or less (higher threshold) during the ICU stay. The primary outcome measure was death by 90 days after randomization.
We analyzed data from 998 of 1005 patients (99.3%) who underwent randomization. The two intervention groups had similar baseline characteristics. In the ICU, the lower-threshold group received a median of 1 unit of blood (interquartile range, 0 to 3) and the higher-threshold group received a median of 4 units (interquartile range, 2 to 7). At 90 days after randomization, 216 of 502 patients (43.0%) assigned to the lower-threshold group, as compared with 223 of 496 (45.0%) assigned to the higher-threshold group, had died (relative risk, 0.94; 95% confidence interval, 0.78 to 1.09; P=0.44). The results were similar in analyses adjusted for risk factors at baseline and in analyses of the per-protocol populations. The numbers of patients who had ischemic events, who had severe adverse reactions, and who required life support were similar in the two intervention groups.
Among patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion at a lower threshold; the latter group received fewer transfusions. (Funded by the Danish Strategic Research Council and others; TRISS ClinicalTrials.gov number, NCT01485315.).
Brexpiprazole (OPC-34712, 7-{4-4-(1-benzothiophen-4-yl)piperazin-1-ylbutoxy}quinolin-2(1H)-one) is a novel drug candidate in clinical development for psychiatric disorders with high affinity for ...serotonin, dopamine, and noradrenaline receptors. In particular, it bound with high affinity (Ki < 1 nM) to human serotonin 1A (h5-HT1A)-, h5-HT2A-, long form of human D2 (hD2L)-, hα1B-, and hα2C-adrenergic receptors. It displayed partial agonism at h5-HT1A and hD2 receptors in cloned receptor systems and potent antagonism of h5-HT2A receptors and hα1B/2C-adrenoceptors. Brexpiprazole also had affinity (Ki < 5 nM) for hD3-, h5-HT2B-, h5-HT7-, hα1A-, and hα1D-adrenergic receptors, moderate affinity for hH1 (Ki = 19 nM), and low affinity for hM1 receptors (Ki > 1000 nM). Brexpiprazole potently bound to rat 5-HT2A and D2 receptors in vivo, and ex vivo binding studies further confirmed high 5-HT1A receptor binding potency. Brexpiprazole inhibited DOI (2,5-dimethoxy-4-iodoamphetamine)-induced head twitches in rats, suggestive of 5-HT2A antagonism. Furthermore, in vivo D2 partial agonist activity of brexpiprazole was confirmed by its inhibitory effect on reserpine-induced DOPA accumulation in rats. In rat microdialysis studies, brexpiprazole slightly reduced extracellular dopamine in nucleus accumbens but not in prefrontal cortex, whereas moderate increases of the dopamine metabolites, homovanillic acid and DOPAC (3,4-dihydroxy-phenyl-acetic acid), in these areas also suggested in vivo D2 partial agonist activity. In particular, based on a lower intrinsic activity at D2 receptors and higher binding affinities for 5-HT1A/2A receptors than aripiprazole, brexpiprazole would have a favorable antipsychotic potential without D2 receptor agonist- and antagonist-related adverse effects. In conclusion, brexpiprazole is a serotonin-dopamine activity modulator with a unique pharmacology, which may offer novel treatment options across a broad spectrum of central nervous system disorders.
The first cases of alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy (HCM) were published two decades ago. Although the outcomes of single-centre and national ASA registries ...have been published, the long-term survival and clinical outcome of the procedure are still debated.
We report long-term outcomes from the as yet largest multinational ASA registry (the Euro-ASA registry). A total of 1275 (58 ± 14 years, median follow-up 5.7 years) highly symptomatic patients treated with ASA were included. The 30-day post-ASA mortality was 1%. Overall, 171 (13%) patients died during follow-up, corresponding to a post-ASA all-cause mortality rate of 2.42 deaths per 100 patient-years. Survival rates at 1, 5, and 10 years after ASA were 98% (95% CI 96-98%), 89% (95% CI 87-91%), and 77% (95% CI 73-80%), respectively. In multivariable analysis, independent predictors of all-cause mortality were age at ASA (P < 0.01), septum thickness before ASA (P < 0.01), NYHA class before ASA (P = 0.047), and the left ventricular (LV) outflow tract gradient at the last clinical check-up (P = 0.048). Alcohol septal ablation reduced the LV outflow tract gradient from 67 ± 36 to 16 ± 21 mmHg (P < 0.01) and NYHA class from 2.9 ± 0.5 to 1.6 ± 0.7 (P < 0.01). At the last check-up, 89% of patients reported dyspnoea of NYHA class ≤2, which was independently associated with LV outflow tract gradient (P < 0.01).
The Euro-ASA registry demonstrated low peri-procedural and long-term mortality after ASA. This intervention provided durable relief of symptoms and a reduction of LV outflow tract obstruction in selected and highly symptomatic patients with obstructive HCM. As the post-procedural obstruction seems to be associated with both worse functional status and prognosis, optimal therapy should be focused on the elimination of LV outflow tract gradient.
Aims
The present study had two aims: (i) compare echocardiographic parameters in COVID‐19 patients with matched controls and (2) assess the prognostic value of measures of left (LV) and right ...ventricular (RV) function in relation to COVID‐19 related death.
Methods and results
In this prospective multicentre cohort study, 214 consecutive hospitalized COVID‐19 patients underwent an echocardiographic examination (by pre‐determined research protocol). All participants were successfully matched 1:1 with controls from the general population on age, sex, and hypertension. Mean age of the study sample was 69 years, and 55% were male participants. LV and RV systolic function was significantly reduced in COVID‐19 cases as assessed by global longitudinal strain (GLS) (16.4% ± 4.3 vs. 18.5% ± 3.0, P < 0.001), tricuspid annular plane systolic excursion (TAPSE) (2.0 ± 0.4 vs. 2.6 ± 0.5, P < 0.001), and RV strain (19.8 ± 5.9 vs. 24.2 ± 6.5, P = 0.004). All parameters remained significantly reduced after adjusting for important cardiac risk factors. During follow‐up (median: 40 days), 25 COVID‐19 cases died. In multivariable Cox regression reduced TAPSE hazard ratio (HR) = 1.18, 95% confidence interval (CI) 1.07–1.31, P = 0.002, per 1 mm decrease, RV strain (HR = 1.64, 95%CI1.02;2.66, P = 0.043, per 1% decrease) and GLS (HR = 1.20, 95%CI1.07–1.35, P = 0.002, per 1% decrease) were significantly associated with COVID‐19‐related death. TAPSE and GLS remained significantly associated with the outcome after restricting the analysis to patients without prevalent heart disease.
Conclusions
RV and LV function are significantly impaired in hospitalized COVID‐19 patients compared with matched controls. Furthermore, reduced TAPSE and GLS are independently associated with COVID‐19‐related death.
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