Abstract 12702: A Novel Human S10F-Hsp20 Mutation Induces Lethal Peripartum Cardiomyopathy (Best of Basic Science Abstract)

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Guansheng Liu ◽  
Min Jiang ◽  
Wenfeng Cai ◽  
George Adly ◽  
George Gardner ◽  
...  

Background: Heat shock protein 20 (Hsp20) has emerged as a novel cardioprotector against stress-induced injury. In this study, we investigated the functional significance of a novel human Hsp20 mutation (S10F) in peri-partum cardiomyopathy. Methods and Results: We identified a human S10F-Hsp20 mutant with a frequency of 2.8% in dilated cardiomyopathy patients (470 screened), while we did not find any normal subjects carrying this mutation (282 screened). To determine the functional significance of S10F-Hsp20, transgenic mice with cardiac-specific overexpression of this mutant were generated. We observed that female TGs were fertile, and delivered normal litter sizes, but they invariably died after 2, 3 or 4 pregnancies (Fig. 1a). However, overexpression of WT-Hsp20 to similar levels as S10F was not associated with any deaths following multiple pregnancies. Further histological examination of S10F females revealed significantly dilated hearts and increased heart weight/tibia length after the third delivery, compared to WT (non transgenic) mice. (Fig. 1b,c). Echocardiography assessment showed that this dilation (Fig. 1d) is associated with increased left ventricular end-systolic volume (Fig. 1e), increased left ventricular end-diastolic volume, depressed ejection fraction (Fig. 1f) and decreased fractional shortening. Further studies revealed that cardiomyocyte apoptosis was increased by 4 fold in S10F hearts after the third delivery(Fig. 1g,h). The mechanisms associated with the detrimental remodelling in S10F females included decreased Akt (Fig. 1i) and ERK phosphorylation under both baseline and pregnancy conditions. As a result, the activities of Akt and ERK were reduced, contributing to increased cell death in the S10F hearts of pregnant females. Conclusion: The human S10F mutation may compromise the heart’s coping with pregnancy induced stress conditions mainly through increased apoptosis by reduction of Akt and ERK activities.

Author(s):  
Tiantian Shen ◽  
Lin Xia ◽  
Wenliang Dong ◽  
Jiaxue Wang ◽  
Feng Su ◽  
...  

Background: Preclinical and clinical evidence suggests that mesenchymal stem cells (MSCs) may be beneficial in treating heart failure (HF). However, the effects of stem cell therapy in patients with heart failure is an ongoing debate and the safety and efficacy of MSCs therapy is not well-known. We conducted a systematic review of clinical trials that evaluated the safety and efficacy of MSCs for HF. This study aimed to assess the safety and efficacy of MSCs therapy compared to the placebo in heart failure patients. Methods: We searched PubMed, Embase, Cochrane library systematically, with no language restrictions. Randomized controlled trials(RCTs) assessing the influence of MSCs treatment function controlled with placebo in heart failure were included in this analysis. We included RCTs with data on safety and efficacy in patients with heart failure after mesenchymal stem cell transplantation. Two investigators independently searched the articles, extracted data, and assessed the quality of the included studies. Pooled data was performed using the fixed-effect model or random-effect model when it appropriate by use of Review Manager 5.3. The Cochrane risk of bias tool was used to assess bias of included studies. The primary outcome was safety assessed by death and rehospitalization and the secondary outcome was efficacy which was assessed by six-minute walk distance and left ventricular ejection fraction (LVEF),left ventricular end-systolic volume(LVESV),left ventricular end-diastolic volume(LVEDV) and brain natriuretic peptide(BNP) Results: A total of twelve studies were included, involving 823 patients who underwent MSCs or placebo treatment. The overall rate of death showed a trend of reduction of 27% (RR [CI]=0.73 [0.49, 1.09], p=0.12) in the MSCs treatment group. The incidence of rehospitalization was reduced by 47% (RR [CI]=0.53[0.38, 0.75], p=0.0004). The patients in the MSCs treatment group realised an average of 117.01m (MD [95% CI]=117.01m [94.87, 139.14], p<0.00001) improvement in 6MWT.MSCs transplantation significantly improved left ventricular ejection fraction (LVEF) by 5.66 % (MD [95% CI]=5.66 [4.39, 6.92], p<0.00001), decreased left ventricular end-systolic volume (LVESV) by 14.75 ml (MD [95% CI]=-14.75 [-16.18, -12.83], p<0.00001 ) and left ventricular end-diastolic volume (LVEDV) by 5.78 ml (MD [95% CI]=-5.78[-12.00, 0.43], p=0.07 ) ,in the MSCs group , BNP was decreased by 133.51 pg/ml MD [95% CI]= -133.51 [-228.17,-38.85], p=0.54, I2= 0.0%) than did in the placebo group. Conclusions: Our results suggested that mesenchymal stem cells as a regenerative therapeutic approach for heart failure is safe and effective by virtue of their self-renewal potential, vast differentiation capacity and immune modulating properties. Allogenic MSCs have superior therapeutic effects and intracoronary injection is the optimum delivery approach. In the tissue origin, patients who received treatment with umbilical cord MSCs seem more effective than bone marrow MSCs. As to dosage injected, (1-10)*10^8 cells were of better effect.


1986 ◽  
Vol 251 (6) ◽  
pp. H1101-H1105 ◽  
Author(s):  
G. D. Plotnick ◽  
L. C. Becker ◽  
M. L. Fisher ◽  
G. Gerstenblith ◽  
D. G. Renlund ◽  
...  

To evaluate the extent to which the Frank-Starling mechanism is utilized during successive stages of vigorous upright exercise, absolute left ventricular end-diastolic volume and ejection fraction were determined by gated blood pool scintigraphy at rest and during multilevel maximal upright bicycle exercise in 30 normal males aged 26-50 yr, who were able to exercise to 125 W or greater. Left ventricular end-systolic volume, stroke volume, and cardiac output were calculated at rest and during each successive 3-min stage of exercise [25, 50, 75, 100, and 125–225 W (peak)]. During early exercise (25 W), end-diastolic and stroke volumes increased (+17 +/- 1 and +31 +/- 4%, respectively), with no change in end-systolic volume. With further exercise (50–75 W) end-diastolic volume remained unchanged as end-systolic volume decreased (-12 +/- 4 and -24 + 5%, respectively). At peak exercise end-diastolic volume decreased to resting level, stroke volume remained at a plateau, and end-systolic volume further decreased (-48 +/- 7%). Thus the Frank-Starling mechanism is used early in exercise, perhaps because of a delay in sympathetic mobilization, and does not appear to play a role in the later stages of vigorous exercise.


2021 ◽  
Vol 2114 (1) ◽  
pp. 012006
Author(s):  
M K Mohammed ◽  
S I Essa

Abstract Ischemic heart disease is a major causes of heart failure. Heart failure patients have predominantly left ventricular dysfunction (systolic or diastolic dysfunction, or both). Acute heart failure is most commonly caused by reduced myocardial contractility, and increased LV stiffness. We performed echocardiography and gated SPECT with Tc99m MIBI within 263 patients and 166 normal individuals. Left ventricular end systolic volume (LVESV), left ventricular end diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF) were measured. For all degrees of ischemia, there was a significant difference between ejection fraction values measured by SPECT and echocardiography, and there were no significant differences among end systolic volume and end diastolic volume value calculated by two methods for all cases. The mean value for EDV (ECHO)/EDV (SPECT) was 1.07 ± 0.31 for degree (1, 2); in the degree 3 the mean value was 1.02 ± 0.08, and 1.005 ± 0.07 for degree 4. The mean value for ESV (ECHO)/ESV (SPECT) was 1.08 ± 0.34 for degree (1, 2); while 1.03 ± 0.12, 1.021 ± 0.128 for degree 3 and 4 respectively. This study was showed a good relation between left ventricular size and ejection fraction measured by SPECT with Tc99m, and echocardiography.


1963 ◽  
Vol 204 (3) ◽  
pp. 446-450 ◽  
Author(s):  
Franz J. Hallermann ◽  
G. C. Rastelli ◽  
H. J. C. Swan

In each of 12 mongrel dogs, data for end-diastolic volume, end-systolic volume, and stroke volume of the left ventricle were obtained by two independent methods: the indicator dilution method and a radiographic method. While the values for stroke volume showed good agreement between the two methods, a significant and directionally constant difference was found between values for end-diastolic volume and end-systolic volume calculated by the two different methods. This was observed in dogs with fast heart rates (exceeding 150 beats/min), as well as in dogs with heart rates of about 100 beats/min. The findings strongly suggest that a fundamental error is present in estimations of volume based on the washout of an indicator dye.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Mia Cokljat ◽  
Nicholas Bunce ◽  
Taigang He ◽  
Debasish Banerjee

Abstract Background and Aims Sudden cardiac death rates are higher in patients with CKD and on haemodialysis. Hypotheses include the presence of diffuse myocardial fibrosis secondary to fluid and toxin overload. Native T1, T2 and T2* mapping through cardiac magnetic resonance (CMR) is emerging as a novel technique to quantify myocardial fibrosis. This pilot study aimed to quantify cardiac morphological change using CMR native T1, T2 and T2* mapping and correlate with autonomic provocation testing, in CKD 3b-5 and haemodialysis patients. Method Patients with stable CKD 3b and higher, and patients on haemodialysis (CKD-haemodilaysis) underwent a non-contrast CMR, which included native T1, T2, T2* mapping. Autonomic provocation testing was performed using a dipolar ECG lead, followed by 14-days of recording. Results were compared between patient groups, and T1, T2, T2* maps compared to healthy controls using the student t test and Kruskal-Wallis tests. Results Nine CKD, eight haemodialysis and seven control patients were recruited (Table 1). Of the late-stage CKD patients, three were stage 3b, four were stage 4 and two were stage 5. There were no significant differences between the two patient groups in baseline characteristics (Table 1). There were no significant differences between CKD and CKD-haemodialysis patients in left ventricular end-diastolic volume index, left ventricular end-systolic volume index, right ventricular end-diastolic volume index, right ventricular end-systolic volume index, ejection fraction, and left ventricular mass index (71.1±15.2 vs. 80.51 ±21.9 ml/m2, p=0.316; 24.4±7.09 vs. 34.4±19.4 ml/m2, p=0.171; 67.11 ± 14.9 vs. 75.5±23.4 ml/m2, p=0.386; 22.2±4.87 vs. 23.9±9.93 ml/m2, p=0.663; 65.8±6.34 vs. 59.5±12.4 %, p=0.200; 48.4±8.60 vs. 50.5±11.0 g/m2, p=0.673). T1 and T2 were significantly increased in CKD and CKD-haemodialysis patients compared to healthy controls (1259±57.7 vs. 1204±22.3 ms, p=0.038 and 49.1±4.74 vs. 42.0±2.79 ms, p=0.034). There was no difference in T2* star (32.8±7.59 vs. 28.8±3.77, p=0.291). There was no significant difference in native T1, T2 and T2* times between CKD and CKD-haemodialysis patients (1247±66.7 vs. 1273±45.7, p=0.361; 49.1±5.22 vs. 49.0±4.49, p=0.960; 34.1±7.57 vs. 31.3±7.81, p=0.769). Mean percentage change of HR in CKD patients from lying to sitting to standing was 4.51%±6.66 and 11.5%±11.8 respectively. Mean percentage change of HR in CKD-haemodialysis from lying to sitting to standing was 2.15%±6.30 and 6.0%±4.45 respectively. There were no significant differences in postural HR variability between CKD and CKD-haemodialysis patients (p=0.478 and p=0.237). Conclusion In late stage CKD, cardiac volumes, mass, ejection fraction and native T1, T2 and T2* are comparable to those of patients on long-term haemodialysis. However native T1 and T2 times are significantly elevated in later stage CKD and haemodialysis, compared to healthy controls. Heart rate changes over postural provocation are comparable between CKD and CKD-haemodialysis patients, although autonomic response is reduced compared to previously published data in healthy controls. Processes that drive myocardial fibrosis may start earlier in CKD pathogenesis.


1975 ◽  
Vol 228 (2) ◽  
pp. 536-542 ◽  
Author(s):  
SJ Leshin ◽  
LD Horwitz ◽  
JH Mitchell

The effects of acute severe aortic regurgitation on the left ventricle were investigated in conscious, chronically instrumented dogs. Left ventricular dimensions and volumes were measured from biplane cineradiographs of beads positioned near the endocardium. Data were collected before and after the production of aortic regurgitation by a catheter technique. The aortic regurgitation resulted in increases in mean aortic pulse pressure from 44 to 73 mmHg (P smaller than 0.001), heart rate from 87 to 122 beats/min (P smaller than 0.02), and left ventricular end-diastolic pressure from 11 to 25 mmHg (P smaller than 0.05). Mean end-diastolic volume rose from 61 to 69 cc (P smaller than 0.001), while end-systolic volume remained unchanged at 37 cc. The end-diastolic dilatation following regurgitation was asymmetrical in that the increase in size was due principally to an increase in the septal-lateral axis. The acute volume load of aortic regurgitation was accomplished by an increase in end-diastolic volume, i.e., the Frank-Starling mechanism. The tachycardia probably reflects augmented cardiac sympathetic activity, but the constant end-systolic volume at a similar mean systolic pressure suggests that the net contractile state was unchanged.


1993 ◽  
Vol 21 (3) ◽  
pp. 113-125
Author(s):  
O de Divitiis ◽  
M Galderisi ◽  
A Celentano ◽  
P Tammaro ◽  
M Garofalo ◽  
...  

The antihypertensive and haemodynamic efficacies of ketanserin and ketanserin plus enalapril were compared. The monotherapy phase of the study involved the oral administration of 40 mg ketanserin twice daily or 20 mg enalapril once daily for 12 weeks to 25 hypertensive patients. Systolic and diastolic blood pressures were significantly reduced by both drugs. Left ventricular function both at rest and during effort improved significantly with either drug. This was due to a reduction of end-systolic volume; end-diastolic volume decreased only with the use of enalapril. Combination therapy, involving 16 patients and both drugs given at the original dosage schedule for 12 weeks, resulted in further reductions in systolic and diastolic blood pressures, and an improvement in left ventricular function; indices of diastolic function were not modified. In conclusion, ketanserin and enalapril showed comparable antihypertensive and haemodynamic activities. A combination of ketanserin and enalapril increased the favourable characteristics of both drugs.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jiahui Li ◽  
Lijun Zhang ◽  
Yueli Wang ◽  
Huijuan Zuo ◽  
Rongchong Huang ◽  
...  

Aims: To determine the agreement between two-dimensional transthoracic echocardiography (2DTTE) and cardiovascular magnetic resonance (CMR) in left ventricular (LV) function [including end-systolic volume (LVESV), end-diastolic volume (LVEDV), and ejection fraction (LVEF)] in chronic total occlusion (CTO) patients.Methods: Eighty-eight CTO patients were enrolled in this study. All patients underwent 2DTTE and CMR within 1 week. The correlation and agreement of LVEF, LVESV, and LVEDV as measured by 2DTTE and CMR were assessed using Pearson correlation, Kappa analysis, and Bland–Altman method.Results: The mean age of patients enrolled was 57 ± 10 years. There was a strong correlation (r = 0.71, 0.90, and 0.80, respectively, all P &lt; 0.001) and a moderately strong agreement (Kappa = 0.62, P &lt; 0.001) between the two modalities in measurement of LV function. The agreement in patients with EF ≧50% was better than in those with an EF &lt;50%. CTO patients without echocardiographic wall motion abnormality (WMA) had stronger intermodality correlations (r = 0.84, 0.96, and 0.87, respectively) and smaller biases in LV function measurement.Conclusions: The difference in measurement between 2DTTE and CMR should be noticed in CTO patients with EF &lt;50% or abnormal ventricular motion. CMR should be considered in these conditions.


2018 ◽  
Vol 14 (1) ◽  
pp. 3-8
Author(s):  
Mohammad Ashraf Hossain ◽  
Khurshed Ahmed ◽  
Md Faisal Ibn Kabir ◽  
Md Fakhrul Islam Khaled ◽  
Rakibul H Rashed ◽  
...  

Background: Chronic heart failure (CHF) is the most common and prognostically unfavorable outcome of many diseases of the cardiovascular system. Recent data suggest that beta-blockers are beneficial in patients with CHF. Among β-blocker class of drugs, bisoprolol is a highly selective β1-adrenergic receptor blocker whereas Carvedilol is non-selective. Many large-scale trials have confirmed that both these β-blockers are superior to placebo and other β-blockers. This study was designed to compare the effects of carvedilol and bisoprolol in patients with chronic HF in a single center.Methods: It was a quasi experimental study. A total of 288 cases of heart failure were selected by purposive sampling, from January 2017 to June 2017. Each patient was allocated into either of the two groups, and was continued receiving treatment with either bisoprolol (Group-I) or carvedilol (Group-II). Each patient was evaluated clinically and echocardiographically at the beginning of treatment (baseline) and at the end of 3rd month. Echocardiography was performed to find out change in left ventricular systolic function.Result: After 3 months of treatment, ejection fraction was found higher in the bisoprolol group (42.6 ± 6.5 versus 38.3 ± 4.6%; P < 0.05). Ejection fraction (EF) changes were 8.4% in bisoprolol group and 4.1% in carvedilol group. A significant reduction in left ventricular end-systolic volume (21.9±2.5 in group I versus 14.9±5.7 in group II; P < 0.05) and left ventricular systolic diameter (3.2±0.1 in group I versus 2.3±0.5 in group II; P<0.05) occurred after 3 months of treatment. But no significant differences were observed in left ventricular end-diastolic volume (10.1±3.2 versus 6.1±6.4; P=0.101) and left ventricular diastolic diameter (1.7±0.8 versus 1.3±0.8; P=0.081) between groups. Three months after treatment, heart rate was reduced in the bisoprolol group from 87.7±9 to 74.5±8.1 and carvedilol group from 88.8±9.1 to 80.1±8.7. Differences in heart rate responses between 2 groups were not statistically significant (P=0.113). Assessment of blood pressure three months later of treatment shows, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were improved in both group but difference between two groups were statistically non significant (p>0.05).Conclusion: In this study, bisoprolol was superior to carvedilol in increasing left-ventricular ejection fraction, improving left ventricular end systolic volume and left ventricular end systolic diameter but no significant difference was observed in LV end diastolic volume, LV end diastolic diameter, heart rate and blood pressure.University Heart Journal Vol. 14, No. 1, Jan 2018; 3-8


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