scholarly journals A Randomized Controlled Trial to Study the Effect of Yoga Therapy on Cardiac Function and N Terminal Pro BNP in Heart Failure

2014 ◽  
Vol 9 ◽  
pp. IMI.S13939 ◽  
Author(s):  
Bandi Hari Krishna ◽  
Pravati Pal ◽  
G. K. Pal ◽  
J. Balachander ◽  
E. Jayasettiaseelon ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Medical Therapy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Tei Index ◽  
Ventricular Ejection Fraction ◽  
Yoga Therapy ◽  
Standard Medical Therapy

Aims The purpose of this study was to evaluate whether yoga training in addition to standard medical therapy can improve cardiac function and reduce N terminal pro B-type natriuretic peptide (NT pro BNP) in heart failure (HF). Methods 130 patients were recruited and randomized into two groups: Control Group (CG) ( n = 65), Yoga Group (YG). In YG, 44 patients and in CG, 48 patients completed the study. Cardiac function using left ventricular ejection fraction (LVEF), myocardial performance index (Tei index), and NT pro BNP, a biomarker of HF, was assessed at baseline and after 12 weeks. Result Improvement in LVEF, Tei index, and NT pro BNP were statistically significant in both the groups. Furthermore, when the changes in before and after 12 weeks were in percentage, LVEF increased 36.88% in the YG and 16.9% in the CG, Tei index was reduced 27.87% in the YG and 2.79% in the CG, NT pro BNP was reduced 63.75% in the YG and 10.77% in the CG. The between group comparisons from pre to post 12 weeks were significant for YG improvements (LVEF, P < 0.01, Tei index, P < 0.01, NT pro BNP, P < 0.01). Conclusion These results indicate that the addition of yoga therapy to standard medical therapy for HF patients has a markedly better effect on cardiac function and reduced myocardial stress measured using NT pro BNP in patients with stable HF.

scholarly journals Effect of Traditional Chinese Medicine Poge Heart-Saving Decoction on Cardiac Function in Heart Failure Rat Model

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Lei Liu ◽  
Yanfei Mo ◽  
Bingying Wu ◽  
Zongliang Yu ◽  
Bugao Sun
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiac Function ◽  
Sham Group ◽  
Test Group ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Blank Control Group ◽  
Ventricular Ejection Fraction

Background. Poge heart-saving decoction (PHSD) has been used as a medicine treating heart failure in China for many years. The study aimed to explore the effect of PHSD on cardiac function in heart failure conditions and its underlying mechanism. Methods. Adriamycin was used to induce the model of heart failure (HF) in rats. Sixty rats were randomly divided into six groups: blank control group, sham group, 9.33 g/kg group (low-PHSD, test group), 13.995 g/kg group (moderate-PHSD, test group), 18.66 g/kg group (high-PHSD, test group), and fosinopril group (4.67 mg/kg, comparison test group). Cardiac ultrasound was used to evaluate the cardiac function of the rats, and radioimmunoassay was used to measure aldosterone (ALD) and angiotensin II (AngII) levels in the serum. Results. Compared with the blank control group, the left ventricular end-diastolic dimension (LVEDd) and left ventricular end-systolic dimension (LVEDs) in the sham group were increased (1.04 ± 0.12 vs. 0.67 ± 0.13 cm; 0.75 ± 0.13 vs. 0.28 ± 0.10 cm; P < 0.05 ), and the left ventricular ejection fraction was decreased (36.65 ± 5.74 vs. 76.09 ± 4.23%; P < 0.05 ). The ejection fraction of HF rats was increased in 9.33 g/kg group, 13.995 g/kg group, and 18.66 g/kg group compared with those of the sham group (57.13 ± 1.63, 58.43 ± 1.98, and 59.21 ± 1.37 vs. 36.65 ± 5.74%; P < 0.05 ). PHSD also improved cardiac function by reducing the LVEDd and LVEDs (0.88 ± 0.11, 0.75 ± 0.13, and 0.72 ± 0.18 vs. 1.04 ± 0.12 cm; 0.62 ± 0.10, 0.63 ± 0.17, and 0.45 ± 0.11 vs. 0.75 ± 0.13 cm; P < 0.05 ). The levels of ALD and AngII in the serum of rats in the sham group were significantly higher than those in the blank control group (371.58 ± 39.25 vs. 237.12 ± 17.35 μg/L; 232.18 ± 16.33 vs. 159.44 ± 18.42 pg/L; P < 0.05 ). The ALD and AngII of the rats in all of the three PHSD groups and the fosinopril group were decreased (276.81 ± 25.63, 277.18 ± 21.35, 268.19 ± 19.28, and 271.47 ± 28.96 vs. 371.58 ± 39.25 μg/L; 169.41 ± 27.53, 168.81 ± 19.78, 164.23 ± 21.34, and 174.27 ± 22.84 vs. 232.18 ± 16.33 pg/L; P < 0.05 ). The histopathological changes of the myocardium in the sham group showed the disorganized fiber, shaded staining, fracture, and zonation. The fracture of the myocardium was relieved in all groups except the sham group and the blank control group. Conclusion. Therefore, PHSD could shorten LVEDd and LVEDs of rats and reverse ventricular remodeling. The mechanism might be related to the inhibition of the activation level of renin-angiotensin-aldosterone system (especially ALD and AngII) and decreasing the postload of the heart.

Effect of Diltiazem Hydrochloride on Cardiac Function and Prognosis in Patients with Atrial Fibrillation–Mediated Cardiomyopathy

2021 ◽  
Author(s):  
yongrong liu ◽  
Dan Wang
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Ejection Fraction ◽  
Cardiac Function ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Diltiazem Hydrochloride ◽  
Ventricular Ejection Fraction ◽  
Experimental Group

Abstract BackgroundIn previous studies, faster heart rates in patients with atrial fibrillation combined with heart failure have been associated with poor long-term patient prognosis. However, the classical pharmacological regimen of beta-blockers has not reduced mortality in patients with atrial fibrillation combined with heart failure. Therefore, in patients with atrial fibrillation combined with heart failure with an ejection fraction >40%, we further screened patients with a diagnosis of atrial fibrillation cardiomyopathy and compared the combination of diltiazem with standard anti-heart failure drug therapy.Objective:To observe the effect of diltiazem hydrochloride on cardiac function and prognosis in patients with Atrial Fibrillation–Mediated Cardiomyopathy.Methods: A total of 186 patients diagnosed with atrial fibrillation–mediated cardiomyopathy who were admitted to the First Affiliated Hospital of Zhengzhou University from August 2018 to June 2020 were randomly divided into two groups: 93 cases in the experimental group and 93 cases in the control group, both groups were given standardized pharmacological treatment for heart failure (diuretics, digoxin, β-blockers, perindopril), and the experimental group was given diltiazem 30 mg on the basis of standardized treatment, 3 times a day. The patients were followed up for 30 days to observe the target heart rate <110 beats/min, left ventricular ejection fraction, proBNP, the rate of decrease in activity tolerance during the treatment period, and readmission rate within 30 days.Results:After the addition of diltiazem, the attainment rate of target heart rate was significantly higher in the experimental group than in the control group (p<0.05) . The improvement of left ventricular ejection fraction and proBNP was more significant in the experimental group than in the control group (p<0.05). The incidence of decreased activity tolerance during the follow-up period was higher in the experimental group than in the control group, but the difference was not statistically significant (p>0.05). The readmission rate for heart failure within 30 days was significantly lower in the experimental group than in the control group (p < 0.05).Conclusion：Diltiazem hydrochloride is effective in improving cardiac function and prognosis in patients with atrial fibrillation–mediated cardiomyopathy, and is a safe and effective method.

Abstract 1213: Cardiac Overexpression of Epac1 in Transgenic Mice Protects Heart from Lipopolysaccharide-induced Cardiac Dysfunction and Inhibits JAK-STAT Pathway

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Satoshi Okumura ◽  
Yunzhe Bai ◽  
Meihua Jin ◽  
Sayaka Suzuki ◽  
Akiko Kuwae ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cyclic Amp ◽  
Transgenic Mice ◽  
Cardiac Function ◽  
Proinflammatory Cytokines ◽  
Cardiac Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Stat Pathway

The sympathetic nervous system and proinflammatory cytokines are believed to play independent roles in the pathophysiology of heart failure. However, the recent identification of Epac (exchange protein activated by cyclic AMP), a new cyclic AMP-binding protein that directly activates Rap1, have implicated that there may be a potential cross talk between the sympathetic and cytokine signals. In order to examine the role of Epac in cytokine signal to regulate cardiac function, we have generated transgenic mice expressing the human Epac1 gene under the control of alpha-cardiac myosin heavy chain promoter (Epac1-TG), and examined their response in lipopolysaccharide (LPS)-induced cardiac dysfunction, a well established model for sepsis-induced cardiac dysfunction. Sepsis-induced cardiac dysfunction results from the production of proinflammatory cytokines. At baseline, left ventricular ejection fraction (LVEF) was similar (TG vs. NTG, 67±1.7 vs. 69±2.1%, n =7–9). The degree of cardiac hypertrophy (LV(mg)/tibia(mm)) was also similar at 3 months old (TG vs. NTG 4.0±0.1 vs. 4.2±0.1, n =5–6), but it became slightly but significantly greater in Epac1-TG at 5 month old (TG vs. NTG 4.9±0.1 vs. 4.4±0.1, p< 0.05, n =5–7). LPS (5mg/kg) elicited a significant and robust reduction of LVEF in both Epac1-TG and NTG, but the magnitude of this decrease was much less in Epac1-TG at 6 hr after injection (TG vs. NTG 48±2.4 vs. 57±1.8%, p< 0.01, n =6–9). At 24 hr after injection, cardiac function was restored to the baseline in both Epac1-TG and NTG. We also examined the activation of JAK-STAT pathway at 24 hr after injection. The tyrosine phosphorylation of STAT1 (Tyr701) and STAT3 (Tyr705) in LV, which is an indicator of STAT activation, was reduced to a greater degree in Epac1-TG by 31±8.8% ( p< 0.05, n =4) and 29±5.9% ( p< 0.05, n =7), respectively, relative to that in NTG. Taken together, Epac1 protects the heart from the cytokine-induced cardiac dysfunction, at least in part, through the inhibition of the JAK-STAT pathway, suggesting the beneficial role played by sympathetic signal to antagonize proinflammatory cytokine signal in heart failure.

Abstract 3791: Improved Ventricular-Arterial Coupling After 4 Weeks of Exercise Training in Patients with Chronic Heart Failure

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Marcus Sandri ◽  
Stephan Gielen ◽  
Norman Mangner ◽  
Volker Adams ◽  
Sandra Erbs ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Exercise Training ◽  
Endothelial Function ◽  
Training Group ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Lv Function ◽  
Ventricular Ejection Fraction

Background: The concept of ventricular-arterial coupling implies that LV-function is determined by the three factors left ventricular diastolic, left ventricular systolic and arterial elastance. We have previously documented an improvement in endothelial function and systolic LV-function in patients with chronic heart failure (CHF) after 6 months of exercise training (ET). It remains, however, unclear, how shorter ET periods may affect endothelial, systolic and diastolic ventricular function as echocardiographic parameters related to ventricular arterial coupling in patients with CHF. METHODS: In this ongoing study we randomised 43 patients with stable CHF (age 60.3 ± 2.9 years, EF 27.4 ± 1.7%, VO 2 max 14.7 ± 4.3ml/kg*min) to a training or a control group (C). Patients in the training group exercised 4 times daily at 70% of the individual heart rate reserve for 4 weeks under supervision. At baseline and after 4 weeks the E/A ratio and septal/lateral E’/A’ velocities were determined by echocardiography with tissue Doppler. Exercise capacity was measured by ergospirometry and flow-mediated dilatation (FMD) was assessed by high-resolution radial ultrasound. RESULTS: After only 4 weeks of ET oxygen uptake at peak exercise increased from 14.9 ± 3.3 to 18.1 ± 4.7 ml/min/kg, (p<0.01 vs. C) in training subjects. Left ventricular ejection fraction improved from 26.8 ± 4.6 to 33.1 ± 5.5% (p<0.05 vs. C) in patients of the training group while it remained unchanged in the control group. E/A-ratio mended from 0.63 ± 0.12 to 0.81 ± 0.22 (p<0.01 vs. C) in training patients. Septal E’ velocities increased from 5.5 ± 0.5 to 7.8 ± 1.4 cm/s in training patients (p<0.05 vs. C). FMD of the radial artery improved from 8.2 ± 2.1 to 15.2 ± 3.8% (p<0.01 vs. C) as a result of ET. CONCLUSIONS: Only 4 weeks of endurance training are highly effective with significantly improved FMD accompanied by an emended systolic and diastolic LV-function. We hypothesise that the improvement in LV-EF in training patients may be caused by a corrected ventricular-arterial coupling: ventricular diastolic relaxation and effective endothelial function are ameliorated resulting in an augmentation of stroke volume.

scholarly journals Prognostic algorithms for the progression of chronic heart failure depending on the clinical phenotype

2019 ◽  
Vol 18 (3) ◽  
pp. 41-47
Author(s):  
E. A. Polunina ◽  
L. P. Voronina ◽  
E. A. Popov ◽  
I. S. Belyakova ◽  
O. S. Polunina ◽  
...  
Keyword(s):  
Heart Failure ◽  
Logistic Regression ◽  
Chronic Heart Failure ◽  
Clinical Phenotype ◽  
Left Ventricular ◽  
Regression Method ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Ventricular Ejection Fraction ◽  
Logistic Regression Method

Aim. To develop a mathematical equation (algorithm) to predict the development of chronic heart failure (CHF) for three years, depending on the clinical phenotype.Material and methods. Three hundred forty five patients with CHF with a different left ventricular ejection fraction (preserved, mean, low) were examined. The control group included somatically healthy individuals (n=60). In all patients, 48 parameters that most widely characterize the pathogenesis of CHF (gender-anamnestic, clinical, instrumental, biochemical) were analyzed. To isolate phenotypes, dispersive and cluster analysis was used: the hierarchical classification method and the k-means method. In the development of algorithms we used binary logistic regression method. We used ROC curve to assess the quality of the obtained algorithms.Results. We identified four phenotypes in patients with CHF: fibro-rigid, fibro-inflammatory, inflammatory-destructive, dilated-maladaptive. For the first three phenotypes, a mathematical logistic regression method was used to develop mathematical models for predicting the progression of CHF for three years, with the release of predictors for each phenotype. Belonging to the dilatedmaladaptive phenotype according to the results of the analysis is already an indicator of an unfavorable prognosis in patients with CHF.Conclusion. The developed algorithms based on the selected phenotypes have high diagnostic sensitivity and specificity and can be recommended for use in clinical practice.

scholarly journals CORRELATION BETWEEN VAS OPRESSIN CONCENTRATION AND CHRONIC HEART FAILURE SEVE RITY: CHARAC TERISTICS OF PA TIENTS WITH TERMINAL AND DECOMPE NSA TED HEART FAILURE

The Clinician ◽  
2018 ◽  
Vol 12 (1) ◽  
pp. 36-42
Author(s):  
E. S. Trofimov ◽  
A. S. Poskrebysheva ◽  
N. А. Shostak
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Clinical Symptoms ◽  
Left Ventricular ◽  
Stage Iii ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Ventricular Ejection Fraction ◽  
Significant Difference ◽  
Functional Classes

Objective: to evaluate vasopressin (VP) concentration in patients with varying severity of chronic heart failure (CHF), intensity of clinical symptoms, and decreased level of left ventricular ejection fraction (LVEF). Materials and methods. In total, 120 patients (44 males, 76 females) with CHF of varying genesis (mean age 72.12 ± 10.18 years) and 30 clinically healthy individuals (18 males, 12 females) as a control group (mean age 33.4 ± 6.23 years) were examined. All patients underwent comprehensive clinical and instrumental examination in accordance with the standards for patients with CHF. The VP level was determined using ELISA. Statistical analysis was performed using the IBM SPSS Statistics v. 23 software.Results. The patients with CHF had significantly higher blood VP levels compared to the control group (72.91 ± 53.9 pg/ml versus 6.6 ± 3.2 pg/ml respectively; p <0.01). At the same time, patients with stage III CHF had significantly lower VP levels than patients with stages IIВ and IIА (35.61 ± 21.53 pg/ml versus 71.67 ± 48.31 pg/ml and 86.73 ± 59.78 pg/ml respectively; p<0.01). A similar picture was observed for the functional classes (FC). For instance, for CHF FC II and III, the VP level was 91.93 ± 67.13 pg/ml and 77.95 ± 54.01 pg/ml respectively, while for FC IV it decreased to 50.49 ± 28.18 pg/ml (p <0.01). The VP concentration in patients who subsequently perished was significantly lower than in patients who survived (48.79 ± 26.30 pg/ml versus 79.72 ± 57.73 pg/ml; p = 0.012). Moreover, in patients with LVEF <50 %, the VP level was significantly lower than in patients with LVEF >50 % (59.43 ± 42.51 pg/ml versus 86.43 ± 62.46 pg/ml respectively; p <0.05).Conclusion. The observed significant differences in VP in patients with stage III and IV CFH can indicate depletion of neurohumoral mediators in this patient category. However, a correlation between the VP level and the level of LVEF decrease can indicate a significant difference in the role of VP in CHF pathogenesis in patients with preserved and decreased LVEF. This observation requires further research.

scholarly journals P971 The echocardiographic phenotype in patients with cardiac amyloidosis and heart failure with preserved ejection fraction

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
M D M Perez Gil ◽  
V Mora Llabata ◽  
A Saad ◽  
A Sorribes Alonso ◽  
V Faga ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiac Amyloidosis ◽  
Nyha Class ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Ventricular Ejection Fraction ◽  
Apical Rotation ◽  
Dynamic Torsion

Abstract BACKGROUND New echocardiographic phenotypes of heart failure (HF) are focused on myocardial systolic involvement of the left ventricle (LV), either endocardial and/or transmural. PURPOSE. To study the pattern of myocardial involvement in patients (p) with HF with preserved left ventricular ejection fraction (pLVEF) and cardiac amyloidosis (CA). METHODS. Comparative study of 16 p with CA and HF with pLVEF, considering as cut point LVEF &gt; 50%, in NYHA class ≥ II / IV, and a control group of 16 healthy people. Longitudinal Strain (LS) and Circumferential Strain (CS) were calculated using 2D speckle-tracking echocardiography, along with Mitral Annulus Plane Systolic Excursion (MAPSE) and Base-Apex distance (B-A). Also, the following indexes were calculated: Twist (apical rotation + basal rotation, º); Classic Torsion (TorC): (twist/B-A, º/cm); Torsion Index (Tor.I): (twist/MAPSE, º/cm) and Deformation Index (Def.I): (twist/LS, º). We suggest the introduction of these dynamic torsion indexes as Tor.I and Def.I that include twist per unit of longitudinal systolic shortening of the LV instead of using TorC which is the normalisation of twist to the end-diastolic longitudinal diameter of the LV. RESULTS There were no differences of age between the groups (68.2 ± 11.5 vs 63.7 ± 2.8 years, p = 0.14). Global values of LS and CS were lower in p with CA indicating endocardial and transmural deterioration during systole, while TorC and Twist of the LV remained conserved in p with CA. However, there is an increase of dynamic torsion parameters such as Tor.I and Def.I that show an increased Twist per unit of longitudinal shortening of the LV in the CA group (Table). CONCLUSIONS In p with CA and HF with pLVEF, the impairment of LS and CS indicates endocardial and transmural systolic dysfunction. In these conditions, LVEF would be preserved at the expense of a greater dynamic torsion of the LV. Table LS (%) CS (%) Twist (º) TorC (º/cm) Tor.I (º/cm) Def.I (º/%) CA pLVEF (n = 16) -11.7 ± 4.2 17.2 ± 4.8 19.8 ± 8.3 2.5 ± 1.1 27.7 ± 13.5 -1.8 ± 0.9 Control Group (n = 15) -20.6 ± 2.5 22.7 ± 4.9 21.7 ± 6.1 2.7 ± 0.8 16.4 ± 4.7 -1.0 ± 0.3 p &lt; 0.001 &lt; 0.01 0.46 0.46 &lt; 0.01 &lt; 0.01 Dynamic Torsion Indexes and Classic Torion Parameters in pLVEF CA patients vs Control group.

scholarly journals Implantable cardioverter defibrillator - powerful weapon in primary and secondary prevention of sudden cardiac death

2019 ◽  
Vol 76 (10) ◽  
pp. 1007-1013
Author(s):  
Tomislav Kostic ◽  
Dragana Stanojevic ◽  
Ognjen Gudelj ◽  
Dragan Milic ◽  
Svetozar Putnik ◽  
...  
Keyword(s):  
Drug Therapy ◽  
Sudden Cardiac Death ◽  
Medical Therapy ◽  
Cardiac Death ◽  
Left Ventricular ◽  
Cardiac Insufficiency ◽  
Cardiac Resynchronization ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Ventricular Ejection Fraction

Bacgraund/Aim. Sudden cardiac death (SCD) is one of the biggest problems of the contemporary medicine. Large studies showed that anti-arrhythmics, including amiodarone, are not effective in prevention of SCD in the patients with cardiac diseases who were on drug treatment. Those patients who received implantable cardioverter defibrillators (ICD) had better survival. The aim of this paper was to determine whether the patients receiving the ICD in the primary and secondary SCD prevention have longer survival than the patients treated exclusively with drug therapy. Methods. We included 1,260 patients with cardiac insufficiency and reduced left ventricular ejection fraction (LVEF < 35%) who were at high risk for malignant ventricular arrhythmias and SCD. Five hundred forty patients received ICD therapy. The cardiac resynchronization therapy ? CRT/ICD group (n = 270) comprised the patients with cardiac insufficiency and CRT/ICD pacemaker at an optimal medical therapy. In the control group (n = 450), there were the patients with cardiac insufficiency (NYHA functional class 3?4, LVEF ? 35%, QRS duration ? 130 ms), at optimum drug therapy. Results. In the ICD group, there was a statistically significant increase in end-systolic volume (ESV) from 92.68 mL to 99.05 mL. In the group of patients with cardiac insufficiency who were on drug therapy, there was a significant decrease in LVEF (33.15% vs. 30.2%; p = 0.017), 6-minute walk distance (6 MWT distance) (216.55 m vs. 203.27 m, p = 0.003). In the same group, there was an increase in the values of ESV (90.19 mL vs. 95.41 mL; p = 0.011). An increase in the mortality rate in the group of patients with drug therapy compared to the CRT/ICD and ICD groups was statistically significant (p < 0.05). Conclusions. An ICD pacemaker implantation significantly reduces mortality compared to medical therapy only. In addition, the patients who have CRT in addition to ICD pacemaker, have a significantly better quality of life and increase in LVEF.

scholarly journals Novel antisense therapy targeting microRNA-132 in patients with heart failure

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
J Taubel ◽  
W Hauke ◽  
S Rump ◽  
J Viereck ◽  
S Batkai ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Fibrosis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Private Company ◽  
Ventricular Ejection Fraction ◽  
Pharmacodynamic Effects ◽  
Amino Terminal ◽  
Patients With Heart Failure

Abstract Background Cardiac microRNA-132-3p (miR-132) levels are increased in patients with heart failure (HF) and mechanistically drive cardiac remodelling processes. CDR132L, a specific antisense oligonucleotide, is a first-in-class miR-132 inhibitor that attenuates and even reverses HF in preclinical models. Purpose The aim of the current clinical Phase 1b study was to assess safety, pharmacokinetics, target engagement, and exploratory pharmacodynamic effects of CDR132L in patients on standard-of-care therapy for chronic ischaemic HF in a randomized, placebo-controlled, double-blind, dose-escalation study. Methods Patients had left ventricular ejection fraction between ≥30% and &lt;50% or amino terminal fragment of pro-brain natriuretic peptide (NT-proBNP) &gt;125 ng/L at screening. Twenty-eight patients were randomized to receive CDR132L (0.32, 1, 3, and 10 mg/kg body weight) or placebo (0.9% saline) in two intravenous infusions, 4 weeks apart in four cohorts of seven (five verum and two placebo) patients each. Results CDR132L was safe and well tolerated, without apparent dose-limiting toxicity. A pharmacokinetic/pharmacodynamic dose modelling approach suggested an effective dose level at ≥1 mg/kg CDR132L. CDR132L treatment resulted in a dose-dependent, sustained miR-132 reduction in plasma. Patients given CDR132L ≥1 mg/kg displayed median 23.3% NT-proBNP reduction, vs. 0.9% median increase in the control group. CDR132L treatment induced significant QRS narrowing and positive trends for cardiac fibrosis biomarkers. Conclusions This study is the first clinical trial of an antisense drug in HF patients. CDR132L was safe and well tolerated, confirmed linear plasma pharmacokinetics with no signs of accumulation, and suggests cardiac functional improvements. The indicative efficacy of this drug is very encouraging justifying additional clinical studies to confirm the beneficial CDR132L pharmacodynamic effects for the treatment of HF. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Cardior Pharmaceuticals GmbH

scholarly journals Xinmailong Injection for Improvement of Cardiac Function in Patients with Heart Failure: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Yuan-long Sun ◽  
Yi-ping Li ◽  
Ting-ting Qiang ◽  
Xiao-fen Ruan ◽  
Xiao-long Wang
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Periplaneta Americana ◽  
Meta Analysis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cochrane Library ◽  
Ventricular Ejection Fraction ◽  
Patients With Heart Failure ◽  
Potential Factor

Background. Insect drugs have great potential for treating cardiovascular diseases. Xinmailong (XML) injection, a bioactive composite extracted from Periplaneta americana (a species of cockroach), was wildly used in treating heart failure in China. This meta-analysis aimed to assess the efficacy and safety of XML injection for the improvement of cardiac function in HF. Materials and Methods. Online literature search for relevant studies was performed using databases including PubMed, EMBASE, Cochrane Library, CNKI, and Wanfang. Left ventricular ejection fraction (LVEF), six-minute walk test (6MWT), and brain natriuretic peptide (BNP) were selected as target outcomes. The analysis was performed using Stata 12.0, and sources of heterogeneity were explored by subgroup analysis and metaregression. Results. 32 studies were included in this meta-analysis after meeting the inclusion/exclusion criteria. The results demonstrated that additional use of XML improved LVEF (WMD = 5.82, 95% CI: 5.52–7.13, P < 0.00001 ) and 6MWT (WMD = 51.48, 95% CI: 35.83–67.13, P < 0.00001 ) and reduced BNP (WMD = −172.84, 95% CI: −205.79 to −139.89, P < 0.00001 ). The results of subgroup analyses and metaregression suggested that XML injection has more cardiac function improvement for middle-aged HF patients than youth, and greater LVEF and 6MWT improvement were associated with higher average age. Conclusions. XML plus conventional treatment demonstrated a significant effect in reducing cardiac dysfunction in HF patients, and age is a potential factor of higher efficacy. Given the heterogeneity and bias of the included RCTs, large, prospective, rigorous trials are still needed.

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