ABSTRACT
Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Subject(s)
Male , Female , Humans , Aged , Natriuretic Peptide, Brain , Simendan/therapeutic use , Non-ST Elevated Myocardial Infarction , Heart Failure/drug therapy , Peptide Fragments , Arrhythmias, Cardiac , Biomarkers , PrognosisABSTRACT
<p><b>Background</b>Treatment of myoclonic seizures in myoclonic epilepsy with ragged-red fibers (MERRFs) has been empirical and ineffective. Guideline on this disease is not available. Additional trials must be conducted to find more suitable treatments for it. In this study, the antimyoclonic effects of monotherapies, including levetiracetam (LEV), clonazepam (CZP), valproic acid (VPA), and topiramate (TPM) compared to combination therapy group with LEV and CZP on MERRF, were evaluated to find a more advantageous approach on the treatment of myoclonic seizures.</p><p><b>Methods</b>Treatments of myoclonic seizures with VPA, LEV, CZP, and TPM were reported as monotherapies in 17 MERRF patients from Qilu Hospital between 2003 and 2016, who were diagnosed through clinical data and genetic testing. After 1-4 months of follow-up (mean: 82.9 ± 28.1 days), 12 patients that exhibited poor responses to monotherapy were given a combined treatment consisting of LEV and CZP subsequently. The follow-up period was 4-144 months (mean: 66.3 ± 45.3 months), the effective rates of monotherapy group (17 patients) and combination therapy group (12 patients) were analyzed by Chi-square test.</p><p><b>Results</b>The m.8344 A>G mutation was detected in all patients. There were four patients with partial response (4/17, two in the CZP group and two in the LEV group), ten patients with stable disease (10/17, six in the CZP group, three in the LEV group, and one in the TPM group), and three patients with progressive disease (3/18, two in the VPA group and one in the TPM group). Twelve of the patients with LEV combined with CZP showed a positive effect and good tolerance (12/12), eight of them demonstrated improved cognition and coordination. There was a significant difference between the monotherapy group and combination therapy group in the efficacy of antimyoclonic seizures (χ = 13.7, P < 0.001).</p><p><b>Conclusions</b>LEV in combination with CZP is an efficient and safe treatment for myoclonic seizures in patients with this disease exhibiting the m.8344A>G mutation.</p>
ABSTRACT
Objective To investigate clinical symptoms,pathophysiology and brain imaging features of Chinese familial cerebral cavernous angiomas.Methods Head MRI examination,clinical and pathophysiological examination were performed in a Chinese family with one proband of cerebral cavernous malformation.The disease atlas of the family was drawn.The patients indicative of a surgery underwent resection of hemangioma whose pathophysiology and microstructure were observed.Results Nine familial cerebral cavernous angiomas patients were found to have multiple intracranial lesion in the 18 family members,the penetrance being 50%,conforming to the feature of autosomal incomplete dominance inheritance.Four patients with skin cavernous hemangioma had familial cerebral cavernous angiomas.MRI was the most sensitive modality for the diagnosis of cavernous angioma.With T_2-Weighted sequences,the lesion was typically characterized by an area of mixed signal intensity,with a central reticulated core and a peripheral rim of decreased signal intensity related to deposition of hemosiderin.Gradient-echo(GRE)MRI could find microcavernous hemangiomas that would not be found in other sequences.Cavernous angiomas were typically discrete multilobulated berrylike lesions that contained hemorrhage in various stages of evolution.Histological homogeneity and overlap with other vascular malformations such as capillary telangictasia was common.Cavernous angiomas were composed of endothelial-linked sinusoidal spaces not separated by significant amounts of neural tissue.Hemorrhagic residua were common.Clots at different stages of evolution within the lesion were seen.The basic membranes of sinus became thick and soft.Parts of it were layered.Conclusions Familial cerebral cavernous angiomas is an autosomal incomplete dominance inheritance disease.Cavernous angiomas are composed of endothelial-linked sinusoidal spaces not separated by significant amounts of neural tissue.There are more than one focus in every patients and the skin cavernous angiomas is the foundation of diagnosing familial cerebral cavernous angiomas.Gradient-echo imagine sequence MRI(3.0 T)could be the"golden standard".