LVEDV) And End-systolic Volume Research Articles

The preferable position for quantifying left ventricular diameter by transthoracic echocardiography.

In quantifying left ventricular (LV) diameter, which position for echocardiographic measurements, mitral valve tip level (MV-tip) or LV mid level (LV-mid), more accurately represents the LV volume is unclear. Furthermore, which factor affects the measurement error also has not been elucidated. We enrolled 150 patients without myocardial infarction and local asynergy who underwent echocardiography and cardiac magnetic resonance imaging (CMRI). Echocardiographic LV diastolic diameter (LVDD) and LV systolic diameter (LVDS) were measured at both MV-tip and LV-mid, and the LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were quantified using CMRI. We quantified the degree of aortic wedging as the angle between the anterior wall of the aorta and the ventricular septal surface (ASA). The average LVDD was smaller and average LVDS larger when measured at the MV-tip than at the LV-mid. In regression analyses, the correlation coefficient between LVDD and LVEDV was larger at LV-mid (R = 0.89) than at MV-tip (R = 0.82), and the correlation coefficient between LVDS and LVESV also larger at LV-mid (R = 0.93) than MV-tip (R = 0.87). ASA, Valsalva diameter, left atrial diameter, patient height, and LV mass significantly affected the echocardiographic measurement error, but no factor affected the measurement error when quantifying LVDD at the LV-mid level. The echocardiographic LV diameter measured at LV-mid has a stronger correlation with LV chamber size derived from CMRI than measurements at MV-tip. The LVDD measured at the LV-mid level is not affected by other factors.

Angiotensin Receptors and Neprilysin Inhibitors on Myocardial Remodeling in Patients with Acute Myocardial Infarction after Percutaneous Coronary Intervention

Heart failure (HF) is a leading cause of late morbidity and mortality after acute myocardial infarction worldwide. Myocardial remodeling is an important mechanism in the development of chronic heart failure. Development of the HF phenotype in these patients arise from a complex, progressive, molecular and cellular transformation called “ventricular remodeling”. In this paper, the research progress of myocardial remodeling is summarized. Left ventricular remodeling is characterized by a progressive increase in both end-diastolic (LVEDV) and end-systolic volumes (LVESV). Cardium remodeling is due to an increased activity of cardiac fibroblasts in response to different soluble fibrogenic mediators. ARNI can inhibit the biological activity of brain natriuretic peptide enzyme, prevent the deactivation of natriuretic peptide and increase its concentration. The inhibition of brain natriuretic peptidase and the increase of natriuretic peptide level by ARNI is an important means to treat heart failure and fight against ventricular remodeling, and the inhibition of RAAS system over activation is also of great significance to delay myocardial remodeling. much of the observed clinical benefit of sacubitril/valsartan therapy in patients with HFrEF, HFpEF and in the post-myocardial infarction setting is likely related to significant reverse cardiac remodeling.

Cardioprotective effects of aerobic training in diabetic rats: Reducing cardiac apoptotic indices and oxidative stress for a healthier heart.

The present study evaluated the effects of aerobic training with variable intensities on apoptotic indices of cardiac tissue in fatty diabetic rats. Twenty-four male Wistar rats were randomly divided into non-diabetic (ND, n=8), trained diabetic (TD, n=8), and control diabetic (CD, n=8) groups. Following a high-fat dietary regimen, type 2 diabetes was induced by streptozotocin, with blood glucose levels above 300 mg/dL considered indicative of diabetes. The TD group underwent aerobic exercise five times a week for six weeks. Subsequently, measurements were taken for left ventricular end-diastolic (LVEDV) and end-systolic volumes (LVESV), ejection fraction (EF%), catalase, caspase-9, P53, glucose, insulin, and HOMA-IR. Aerobic training led to a significant decrease in blood glucose levels (P < 0.01), caspase-9 (P < 0.05), HOMA-IR (P < 0.05), and P53 expression (P < 0.001) compared with the CD group. LVEDV and LVESV decreased significantly (P < 0.05 for both), while LVEF increased significantly (P < 0.05). Catalase activation showed an insignificant increase in the TD group pre- to post-training compared to CD. Incremental aerobic exercise training (6 weeks) may exert a cardioprotective effect in diabetic rats by reducing apoptosis and oxidative stress indices, while simultaneously increasing aerobic fitness and reducing body weight.

Abstract 10915: Microvascular Obstruction Identifies a Subgroup of Patients Who Benefit From Intracoronary Stem Cell Delivery Following ST-Elevation Myocardial Infarction

Aims: Microvascular obstruction (MVO) following ST-elevation myocardial infarction (STEMI) is associated with greater infarct size, adverse left-ventricular (LV) remodeling and reduced ejection fraction. We hypothesized that patients with MVO may constitute a subgroup of patients that would benefit from intracoronary stem cell delivery with bone marrow mononuclear cells (BMCs) given previous findings that BMCs tended to improve LV function only in patients with significant LV dysfunction. Methods and Results: We analyzed the cardiac MRIs of 356 patients (303 M, 53 F) with anterior STEMIs who received autologous BMCs as part of 3 clinical trials that included the Cardiovascular Cell Therapy Research Network (CCTRN) TIME trial and its pilot (n=157), the multi-center French BONAMI trial (n=91) and the SWISS-AMI trial (n=108). All patients received 100 - 150 million intracoronary autologous BMCs or placebo / control 3 - 7 days following primary PCI and stenting. LV function, volumes, infarct size and MVO were assessed prior to infusion of BMCs and 1 year later. Patients with MVO (n=210) had reduced LVEF and much greater infarct size and LV volumes compared to patients without MVO (n=146) (all p &lt; 0.01) (TABLE). At 12 months, patients with MVO who received BMCs had significantly greater recovery of LVEF compared to those patients with MVO who received placebo (absolute difference = 2.7 %; p &lt; 0.05). Similarly, the changes in left-ventricular end-diastolic (LVEDV) and end-systolic volumes (LVESV) were consistent with significantly less adverse remodeling in patients with MVO who received BMCs compared to placebo ( % change; LVEDV = -9.7%; p &lt; 0.05 and LVESVI = -14.7 %; p = 0.006). In contrast, patients without MVO experienced no benefit of BMC administration compared to placebo. Conclusion: The presence of MVO on cardiac MRI following STEMI identifies a subgroup of patients who may benefit from intracoronary stem cell delivery of BMCs.

Three-dimensional echocardiographic assessment of left ventricular volume in different heart diseases using a fully automated quantification software.

BACKGROUNDHeartModel (HM) is a fully automated adaptive quantification software that can quickly quantify left heart volume and left ventricular function. This study used HM to quantify the left ventricular end-diastolic (LVEDV) and end-systolic volumes (LVESV) of patients with dilated cardiomyopathy (DCM), coronary artery heart disease with segmental wall motion abnormality, and hypertrophic cardiomyopathy (HCM) to determine whether there were differences in the feasibility, accuracy, and repeatability of measuring the LVEDV, LVESV, LV ejection fraction (LVEF) and left atrial end-systolic volume (LAESV) and to compare these measurements with those obtained with traditional two-dimensional (2D) and three-dimensional (3D) methods.AIMTo evaluate the application value of HM in quantifying left heart chamber volume and LVEF in clinical patients.METHODSA total of 150 subjects who underwent 2D and 3D echocardiography were divided into 4 groups: (1) 42 patients with normal heart shape and function (control group, Group A); (2) 35 patients with DCM (Group B); (3) 41 patients with LV remodeling after acute myocardial infarction (Group C); and (4) 32 patients with HCM (Group D). The LVEDV, LVESV, LVEF and LAESV obtained by HM with (HM-RE) and without regional endocardial border editing (HM-NE) were compared with those measured by traditional 2D/3D echocardiographic methods to assess the correlation, consistency, and repeatability of all methods.RESULTS(1) The parameters measured by HM were significantly different among the groups (P < 0.05 for all). Compared with Groups A, C, and D, Group B had higher LVEDV and LVESV (P < 0.05 for all) and lower LVEF (P < 0.05 for all); (2) HM-NE overestimated LVEDV, LVESV, and LAESV with wide biases and underestimated LVEF with a small bias; contour adjustment reduced the biases and limits of agreement (bias: LVEDV, 28.17 mL, LVESV, 14.92 mL, LAESV, 8.18 mL, LVEF, -0.04%). The correlations between HM-RE and advanced cardiac 3D quantification (3DQA) (rs = 0.91-0.95, P < 0.05 for all) were higher than those between HM-NE (rs = 0.85-0.93, P < 0.05 for all) and the traditional 2D methods. The correlations between HM-RE and 3DQA were good for Groups A, B, and C but remained weak for Group D (LVEDV and LVESV, rs = 0.48-0.54, P < 0.05 for all); and (3) The intraobserver and interobserver variability for the HM-RE measurements were low.CONCLUSIONHM can be used to quantify the LV volume and LVEF in patients with common heart diseases and sufficient image quality. HM with contour editing is highly reproducible and accurate and may be recommended for clinical practice.

In silico screening method for non-responders to cardiac resynchronization therapy in patients with heart failure: a pilot study

BackgroundCardiac resynchronization therapy (CRT) is an effective treatment option for patients with heart failure (HF) and left ventricular (LV) dyssynchrony. However, the problem of some patients not responding to CRT remains unresolved. This study aimed to propose a novel in silico method for CRT simulation.MethodsThree-dimensional heart geometry was constructed from computed tomography images. The finite element method was used to elucidate the electric wave propagation in the heart. The electric excitation and mechanical contraction were coupled with vascular hemodynamics by the lumped parameter model. The model parameters for three-dimensional (3D) heart and vascular mechanics were estimated by matching computed variables with measured physiological parameters. CRT effects were simulated in a patient with HF and left bundle branch block (LBBB). LV end-diastolic (LVEDV) and end-systolic volumes (LVESV), LV ejection fraction (LVEF), and CRT responsiveness measured from the in silico simulation model were compared with those from clinical observation. A CRT responder was defined as absolute increase in LVEF ≥ 5% or relative increase in LVEF ≥ 15%.ResultsA 68-year-old female with nonischemic HF and LBBB was retrospectively included. The in silico CRT simulation modeling revealed that changes in LVEDV, LVESV, and LVEF by CRT were from 174 to 173 mL, 116 to 104 mL, and 33 to 40%, respectively. Absolute and relative ΔLVEF were 7% and 18%, respectively, signifying a CRT responder. In clinical observation, echocardiography showed that changes in LVEDV, LVESV, and LVEF by CRT were from 162 to 119 mL, 114 to 69 mL, and 29 to 42%, respectively. Absolute and relative ΔLVESV were 13% and 31%, respectively, also signifying a CRT responder. CRT responsiveness from the in silico CRT simulation model was concordant with that in the clinical observation.ConclusionThis in silico CRT simulation method is a feasible technique to screen for CRT non-responders in patients with HF and LBBB.

Increased arterial stiffness during acute myocardial infarction results in adverse cardiac remodelling: a two year follow-up study

Abstract Increased arterial stiffness is associated with adverse cardiac events. However, it not clear whether increased arterial stiffness at the early phase of acute myocardial infraction (AMI) is associated with adverse left ventricular remodelling. Methods We examined 80 patients with STEMI (53±16 years, 80% male, 42% anterior AMI, LVEF=49±15%) after successful revascularisation by echocardiography 48h after admission and 2 years after the index event. We measured a) left-ventricular end-diastolic (LVEDV) and end-systolic volumes (LVESV) using the Simpson Method b) global longitundinal strain (GLS) by speckle tracking imaging c) carotid-femoral pulse wave velocity (PWV, augmentation index and central Aortic pressures by Complior apparatus d) The ratio of PWV/GLS as a marker of ventricular-arterial interaction. Results LVEDV and LVESV were decreased while GLS was improved after the 2-year follow-up period (from 103.3±30 to 89.1±37ml, p=0.004, 58.3±25 to 57.6±25, p=0.05, −16.1±4.7 to 17.5±3.2%, p=0.03 respectively). Baseline PWV, GLS and the ratio PWV/GLS were associated with the percent change of LVESV at 2 years (p=0.033, p=0.04 and p=0.035 respectively) after adjustment for type of MI (anterior vs other location), baseline troponin blood pressure and medication. Patients with PWV &amp;gt;10.6 m/s (upper tercile) had similar baseline LVESV (56.5±18 to 57.2±24 ml, p=0.8) but higher LVESV at 2 years follow-up (74.4±35 to 55.9±24 ml, p=0.03) resulting in a greater percent increase of LVESV compared to patients with baseline PWV &amp;lt;10.6m/s (+26% vs −5% p=0.012). Conclusion Increased arterial stiffness in the early phase of AMI impairs ventricular-arterial coupling resulting in adverse LV remodeling despite successful revascularization. Funding Acknowledgement Type of funding source: None

P898 Role and evolution of the right ventricle in heart failure patients treated with cardiac resynchronization therapy delivered by left ventricle pacing alone

Abstract Funding Acknowledgements This work was supported by CREDO Project - ID: 49182, financed through the SOP IEC -A2-0.2.2.1-2013-1 cofinanced by the ERDF. Background Cardiac resynchronization therapy (CRT) is an effective treatment for patients with heart failure (HF) with reduced ejection fraction. Biventricular pacing is the most common mode of delivering CRT. However, several studies have demonstrated non-inferiority of LV pacing alone. There are several trials about the role and evolution of right ventricle (RV) systolic function in CRT patients delivered by biventricular pacing showing that RV function is an independent predictor of long-term outcome following CRT, and improvement in RV function after CRT. Purpose To examine if RV function and dimensions prior to CRT could have an impact on CRT response and assessment of the evolution of RV function after 1 year follow up in patients with LV pacing alone. Methods 22 patients with a mean age of 63 ± 10.6 years including 9 (40,9%) females and 13 man (59,1%), with HF (EF &amp;lt; 35%, LBBB &amp;gt; 120 ms, or non-LBBB &amp;gt; 150 ms, with NYHA II to IV) were enrolled and underwent CRT implantation LV pacing alone . Each patient benefited from standard two dimensional (2D) echocardiography, tissue Doppler imaging, with assessment of Left ventricular (LV) end-diastolic (LVEDV), and end-systolic volumes (LVESV), ejection fraction, RV maximum basal (RVD basal), TAPSE, fractional area change (FAC), and tricuspid lateral annular systolic velocity (S′) , RV TEI index , RV systolic pressure using Bernoulli equation, at inclusion before CRT and 12 ± 2 months after CRT implantation. Patients presenting with reductions of LVESV of &amp;gt;15% were termed volumetric responders for further statistical analysis and patients with reduction of NYHA class were termed clinical responders. Results 14 patients (63.63 %) cases were volumetric responders and 21 patients were clinical responders showing an improvement in NYHA class at one year. 1 patient died. Among echocardiographic parameters of RV: RVD basal , TAPSE , FAC , TEI index, RV systolic pressure (p &amp;lt; 0.01) were good predictors for volumetric response proving that a dilated RV with poor systolic function may be a predictor for non response to CRT even in patients with LV alone pacing. TAPSE and FAC have the best AUC for prediction of response to CRT therapy.We proposed cutoff values for predicting response versus non response to CRT therapy TAPSE 16.6mm (AUC 0.827, 95% CI, p &amp;lt; 0.05, sensibility 100%, specificity 71.4% ) and FAC 36% (AUC 0.826, 95%CI, p &amp;lt; 0.05, specificity 91%, sensibility 66%) and RVD basal 37,5mm (AUC 0.805, 95%CI, p = 0.03, sensibility 63%, specificty 85%). In volumetric non-responders, RV function improves at one year follow up with an increase in TAPSE (p = 0.008) and a decrease of RV TEI index (p = 0.04). Conclusions LV pacing alone CRT improves RV systolic function and may account for clinical benefit in patients without LV function improvement at one year follow-up. RV systolic function and dimensions before CRT implantation could predict response to LV pacing alone CRT therapy.

P306 Left ventricular volumes during 3D transesophageal echocardiography in comparison to those obtained by 3D transthoracic echocardiogram. A feasibility study

Abstract Background Three dimensional (3D) transthoracic echocardiogram (TTE) has been validated to have good agreement with cardiac magnetic resonance for the assessment of left ventricular ejection fraction (LVEF) with good interobserver reproducibility. Despite the increased use of perioperative transesophageal echocardiogram (TEE), TEE assessment of left ventricular (LV) function and volumes have never been validated against 3D TTE. Objective To evaluate whether 3D TEE measurement of LV function shows better agreement with 3DTTE, compared to 2DBiplane and X-plane TEE. Methods A total of 60 patients were included from a single large volume tertiary center, the mean age of 71.9 years, 40% were female; TTE and TEE studies were performed within one week. LV function parameters including LV EF, LV end-diastolic (LVEDV) and end systolic volumes (LVESV), stroke volumes (SV) were calculated with Qlab version 9, and 3DQ advanced software, with semi-automated endocardial contours for 3D TTE and 3D TEE. LV function parameters for 2D X-plane and Biplane TEE data sets were assessed using AGFA with manual endocardial contours. Mean differences were compared with paired, two-tail T-test, and limits of agreement were determined using the Bland-Altman analysis. Correlation between TTE and TEE values were tested using Pearson’s correlation test. Results 3D transthoracic LV EDV, ESV, SV, and EF respectively were 112± 46 ml, 57 ±32 ml, 55± 55 ml, and 51 ±11%. Comparisons and correlations between TTE and TEE for the four measures were: for EDV bias = 9.94 ml and 95% lower and upper limits of agreements being -68.7 and 88.5 ml, and r= 0.7; for ESV the bias was -0.3 ml with 95% lower and upper limits of agreements being -55 to 55 ml, and r = 0.7: for stroke volume bias= 0.2 with 95% lower and upper limits of agreements being -37 to 67 ml, and r = 0.2; for LVEF the bias was 2.7% with 95% lower and upper limits of agreements being -18.9% to 24.3%, and r= 0.7 (Fig) Conclusion Left ventricular volumetric assessments during 3D transesophageal echocardiography is not only feasible but also comparable to 3D transthoracic echocardiography obtained LV volumes and EF. Data from multicenter studies with a larger number of subjects are needed to corroborate our findings. Abstract P306 Figure. Fig. 3D LV volumes by 3D TEE vs. 3D TTE

Interplay Between RV Function and CRT, Which One Affects the Other?

Background: Cardiac resynchronization therapy (CRT) is an established treatment of heart failure with reduced EF (HFrEF) and wide QRS complex. Nearly 30% of candidates are non-responders. One of the suggested mechanisms of inadequate response is the reduced baseline RV function; also the effect of CRT on right ventricular systolic function has not been well studied. We examined the effect of CRT on right ventricular (RV) dimensions and overall systolic function and whether RV function prior to CRT could have an impact on CRT response. Methods: 30 patients with a mean age of 51.9 ± 9.2 years including 9 (30%) females, with advanced HF (EF 120 ms, or non-LBBB > 150 ms, with NYHA class III or ambulatory class IV) were enrolled and underwent CRT implantation. Standard two dimensional (2D) echocardiography, tissue Doppler imaging, for assessment of Left ventricular (LV) end-diastolic (LVEDV), and end-systolic volumes (LVESV), ejection fraction, RV maximum basal (RVD1 basal), maximum mid (RVD2 mid) transverse, maximum longitudinal (RVD3 long) diameters, TAPSE, fractional area change (FAC), right ventricle index of myocardial performance(RIMP) and tricuspid lateral annular systolic velocity (S’), were done before CRT implantation and at the end of the follow up period (6 months). Patients presenting with reduction of LVESV of >15% were considered responders. Results: 20 (67%) cases were responders. Both groups were similar regarding demographic, clinical, ECG, and echocardiographic criteria at baseline however, the RA volume and RV transverse diameters were smaller and systolic function parameters were significantly better in the responders group prior to CRT compared to non-responders (NR) group. At the end of the follow up, only the responders group had further significant reduction in RV basal, mid and longitudinal diameters together with significant improvement in RV systolic function, in contrast to non-responders group who showed more RV dilatation and more decline of RV systolic function, compared to baseline readings(with P value 40 % has 85% sensitivity and 90 % specificity (P value= 0.004). TAPSE of >20 mm has 85% sensitivity and 80 % specificity (P value=0.002), S' of >10 cm/s % has 85% sensitivity and 70 % specificity (P value=0.001) and RIMP of <0.52 has 85% sensitivity and 70 % specificity (P value=0.003) in predicting CRT response. Conclusions: CRT induces RV reverse remodeling and improves RV systolic function particularly in cardiac volumetric responders. RV systolic dysfunction before CRT implantation could identify patients that might not benefit from CRT thus helping proper patient selection and optimizing CRT response.

Assessment of right ventriclular systolic function prior to cardiac resynchronization therapy: Does it make any difference?

BackgroundCardiac resynchronization therapy (CRT) is an effective treatment for patients with advanced heart failure (HF). Nearly 30% of candidates are inadequate responders. The benefit of patients with right sided heart failure from CRT is still a matter of debate. We examined the effect of CRT on right ventricular (RV) dimensions and overall systolic function and whether RV function prior to CRT could have an impact on CRT response. Methods94 patients with a mean age of 53.7±14.6 years including 19 (20%) females, with advanced HF (EF<35%, LBBB>120ms, or non-LBBB>150ms, with NYHA –III or ambulatory class IV) were enrolled and underwent CRT implantation. Standard two dimensional (2D) echocardiography, tissue Doppler imaging, for assessment of Left ventricular (LV) end-diastolic (LVEDV), and end-systolic volumes (LVESV), ejection fraction, RV maximum basal (RVD basal), maximum mid (RVD mid) transverse, maximum longitudinal (RVD long) diameters, TAPSE, fractional area change (FAC), and tricuspid lateral annular systolic velocity (S′), in addition to RV global longitudinal strain (RVGLS) measured by speckle tracking echocardiography, were done before CRT implantation and at the end of the follow up period (5.9±1.2 months). Patients presenting with reductions of LVESV of >15% were termed volumetric responders for further statistical analysis. Results63 (67%) cases were volumetric responders. Both groups were matched regarding demographic, clinical, ECG, and echocardiographic criteria apart from the RV significantly smaller transverse diameters and significantly better systolic function parameters in the responders group prior to CRT compared to non-responders (NR) group. At the end of the follow up, only the responders group had further significant reduction in RV basal, mid and longitudinal diameters (33.6±7.1 vs 40.7±8.6, 21.4±4.9 vs 27±6.1, 68.3±10.8 vs 81.2±15, respectively), p<0.01, together with significant improvement in RV systolic performance: FAC (47.7±7.3 vs 40.9±6.4), TAPSE (25.2±4.6 vs 22.1±4.9), S′ (15.3±2.3 vs 12.8±2.3), and GLS (26.1±2.1 vs 18.5±1.6), P<0.01, compared to baseline readings. S' and GLS were the only independent predictors of CRT response by multivariate analysis. S′>9cm/s, and GLS >12.45% had 100% sensitivity and 70%, 99.7% specificity, respectively for prediction of response to CRT. ConclusionsCRT induces RV reverse remodeling and improves RV systolic function particularly in cardiac volumetric responders. RV systolic dysfunction before CRT implantation could identify patients that might not benefit from CRT thus helping proper patient selection and optimizing CRT response.

Benefit of cardiopoietic mesenchymal stem cell therapy on left ventricular remodelling: results from the Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) study.

Left ventricular (LV) reverse remodelling is an important marker of improved outcomes in patients with advanced heart failure (HF). We examined the impact of the intramyocardial administration of bone-marrow-derived, lineage-directed, autologous cardiopoietic mesenchymal stem cells (C3BS-CQR-1) on LV remodelling in patients with advanced HF enrolled in the CHART-1 study. Patients (n=351) with symptomatic advanced HF secondary to ischaemic heart disease, and reduced LV ejection fraction (LVEF <35%) were randomized to receive C3BS-CQR-1 or a sham procedure. In a post hoc analysis we examined the effect of C3BS-CQR-1 on LV reverse remodelling within 1 year of the procedure and the influence of C3BS-CQR-1 dosing in the 271 patients treated as randomized. Delivery of C3BS-CQR-1 was associated with a progressive decrease in both LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) within 52 weeks after treatment. At 1 year, the LVEDV and LVESV of treated patients decreased by 17.0 mL and 12.8 mL greater than controls (P=0.006 and P=0.017, respectively). The effect on LVEDV was maintained after multivariable adjustment for baseline age, systolic blood pressure, LVEDV, LVEF and history of myocardial infarction. The largest reverse remodelling was evident in the patients receiving a moderate number of injections (<20). In CHART-1, intramyocardial administration of cardiopoietic stem cells led to reverse remodelling as evidenced by significant progressive decreases in LVEDV and LVESV through the 52 weeks of follow-up. Further studies are needed to explore the dose response with regard to cell number and injected volume, and reverse remodelling.

Safety and efficacy of intracoronary hypoxia-preconditioned bone marrow mononuclear cell administration for acute myocardial infarction patients: The CHINA-AMI randomized controlled trial

BackgroundPre-clinical studies have shown that hypoxia preconditioning can enhance stem cell therapeutic potential for myocardial repair. We sought to investigate the safety and feasibility of intracoronary administration of hypoxia-preconditioned bone marrow mononuclear cells (HP-BMCs) for acute ST segment elevation myocardial infarction (STEMI). MethodsWe randomized 22 patients with acute STEMI to receive intracoronary administration of normoxia bone marrow mononuclear cells (N-BMCs) (n=11) or HP-BMCs (n=11) following successful reperfusion. Another 14 patients receiving standard therapy were recruited as control (n=14). ResultsThere were no differences in the occurrence of major adverse cardiovascular events at 30days and 1year among three groups. There were significant improvement in the change of left ventricular end-diastolic volume (LVEDV) and end-systolic volume (LVESV) in HP-BMC group both at 6 and 12months compared with N-BMCs or control group (P<0.05). No differences were observed in the change of left ventricular ejection fraction (LVEF), or wall motion score index (WMSI) among three groups. Nevertheless, WMSI was improved in HP-BMCs and N-BMC group (P<0.05, within group), but not in control. The ratio of myocardial perfusion defect determined by SPECT was significantly decreased in HP-BMCs and N-BMC groups at 6months compared with baseline (P<0.05, within group), but no significant differences were observed among three groups. ConclusionsOur results provide the first-in-man evidence that intracoronary administration of HP-BMCs following acute MI appears to be safe and feasible. These results provide the basis for future prospective randomized clinical trials in a larger patient cohort.Clinical trial registration information: NCT01234181 (http://clinicaltrials.gov/ct2/show/NCT01234181?term=NCT01234181&rank=1).

Assessment of LV ejection fraction using real-time 3D echocardiography in daily practice: direct comparison of the volumetric and speckle tracking methodologies to CMR.

AimsThis study is the first to directly compare two widely used real-time 3D echocardiography (RT3DE) methods of cardiac magnetic resonance imaging (CMR) and assess their reproducibility in experienced and less experienced observers.MethodsConsecutive patients planned for CMR underwent RT3DE within 8 h of CMR with Philips (volumetric method) and Toshiba Artida (speckle tracking method). Left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were measured using RT3DE, by four trained observers, and compared with CMR values.ResultsThirty-five patients were included (49.7 ± 15.7 years; 55 % male), 30 (85.7 %) volumetric and 27 (77.1 %) speckle tracking datasets could be analysed. CMR derived LVEDV, LVESV and LVEF were 198 ± 58 ml, 106 ± 53 ml and 49 ± 15 %, respectively. LVEF derived from speckle tracking was accurate and reproducible in all observers (all intra-class correlation coefficients (ICC) > 0.86). LVEF derived from the volumetric method correlated well to CMR in experienced observers (ICC 0.85 and 0.86) but only moderately in less experienced observers (ICC 0.58 and 0.77) and was less reproducible in these observers (ICC = 0.55). Volumes were significantly underestimated compared with CMR (p < 0.001).ConclusionThis study demonstrates that both RT3DE methodologies are sufficiently accurate and reproducible for use in daily practice. However, experience importantly influences the accuracy and reproducibility of the volumetric method, which should be considered when introducing this technique into clinical practice.

Age and sex differences in muscle sympathetic nerve activity in relation to haemodynamics, blood volume and left ventricular size

We compared the effect of age- and sex-related differences in haemodynamics, blood volume (BV) and left ventricular (LV) size and mass on resting muscle sympathetic nerve activity (MSNA) in healthy, normotensive adults. Twenty young men (19-47 years old) and 20 young women (21-46 years old) as well as 15 older men (62-80 years old) and 15 older women (60-82 years old) were studied. Cardiac output (acetylene rebreathing), total peripheral resistance, forearm vascular resistance (FVR; venous occlusion plethysmography) and MSNA were measured during supine rest. Blood volume was calculated (CO rebreathing), and LV mass, end-diastolic (LVEDV) and end-systolic volumes (LVESV) were measured using magnetic resonance imaging. Cardiac index (P < 0.001 and P = 0.016), BV (both P < 0.001), LV mass (P < 0.001 and P = 0.002), LVEDV (P < 0.001 and P = 0.002) and LVESV (both P < 0.001) were lower in the older and female groups, respectively. Total peripheral resistance was significantly higher in the older (P < 0.001) and female groups (P = 0.014), but FVR was increased in the female groups (P = 0.048) only (age, P = 0.089). The MSNA was greater in the older groups (P < 0.001) only (sex, P = 0.228). Increased MSNA was shown to correlate with a decrease in BV (P = 0.004) in men only when adjusted for age (women, P = 0.133). There was a positive relation between MSNA and FVR (P = 0.020) in men but not women (P = 0.422). There were no significant relations between MSNA and LV mass, LVEDV or LVESV. The findings suggest that the increase in resting MSNA with age may be related to the decline in BV in men only, but it is unknown whether sex differences in sympathetic adrenergic vasoconstriction occur independently of these changes.

Association between Cystatin C and MRI Measures of Left Ventricular Structure and Function: Multi-Ethnic Study of Atherosclerosis

Introduction. Reduced kidney function, approximated by elevated cystatin C, is associated with diastolic dysfunction, heart failure, and cardiovascular mortality; however, the precise mechanism(s) that account for these relationships remains unclear. Understanding the relationship between cystatin C and subclinical left ventricular (LV) remodeling, across ethnically diverse populations, may help explain the mechanisms underlying the association of kidney dysfunction with heart failure and cardiovascular mortality. Methods. Measures of cystatin C and LV parameters were obtained from the multi-ethnic study of atherosclerosis (MESA) cohort at baseline (N = 4, 970 with complete data on cystatin C and LV parameters). LV parameters; LV end-diastolic (LVEDV) and end-systolic volumes (LVESV), LV mass (LVM), concentricity (LV mass/LV end-diastolic volume), and LV ejection fraction (LVEF) were measured using magnetic resonance imaging. Nested linear models were used to examine the relationship between higher quartiles of cystatin C and LV parameters, with and without adjustment for demographics, height, and weight, and traditional cardiovascular risk factors. Similar analyses were performed stratified by ethnicity and gender. Results. A fully adjusted model demonstrated a linear relationship between higher quartiles of cystatin C and lower LVEDV, (Mean ± SE, 128 ± 0.7, 128 ± 0.7, 126 ± 0.7, 124 ± 0.8 mL; P = 0.0001). Associations were also observed between higher quartiles of cystatin C and lower LVESV (P = 0.04) and concentricity (P = 0.0001). In contrast, no association was detected between cystatin C and LVM or LVEF. In analyses stratified by race and gender, the patterns of association between cystatin C quartiles and LV parameters were qualitatively similar to the overall association. Conclusion. Cystatin C levels were inversely associated with LVEDV and LVESV with a disproportionate decrease in LVEDV compared to LVM in a multi-ethnic population. This morphometric pattern of concentric left ventricular remodeling, may in part explain the process by which kidney dysfunction leads to diastolic dysfunction, heart failure and cardiovascular mortality.

Allogeneic Mesenchymal Precursor Cell Therapy to Limit Remodeling After Myocardial Infarction: The Effect of Cell Dosage

This experiment assessed the dose-dependent effect of a unique allogeneic STRO-3-positive mesenchymal precursor cell (MPC) on postinfarction left ventricular (LV) remodeling. The MPCs were administered in a manner that would simulate an off-the-self, early postinfarction, preventative approach to cardiac cell therapy in a sheep transmural myocardial infarct (MI) model. Allogeneic MPCs were isolated from male crossbred sheep. Forty-six female sheep underwent coronary ligation to produce a transmural LV anteroapical infarction. One hour after infarction, the borderzone myocardium received an injection of 25, 75, 225, or 450 x 10(6) MPCs, or cell medium. Echocardiography was performed at 4 and 8 weeks after MI to quantify LV end-diastolic (LVEDV) and end-systolic volumes (LVESV), ejection fraction (EF), and infarct expansion. CD31 and smooth muscle actin (SMA) immunohistochemical staining was performed on infarct and borderzone specimens to quantify vascular density. Compared with controls, low-dose (25 and 75 x 10(6) cells) MPC treatment significantly attenuated infarct expansion and increases in LVEDV and LVESV. EF was improved at all cell doses. CD31 and SMA immunohistochemical staining demonstrated increased vascular density in the borderzone only at the lower cell doses. There was no evidence of myocardial regeneration within the infarct. Allogeneic STRO-3 positive MPCs attenuate the remodeling response to transmural MI in a clinically relevant large-animal model. This effect is associated with vasculogenesis and arteriogenesis within the borderzone and infarct and is most pronounced at lower cell doses.

Haemodialysis is associated with a pronounced fall in myocardial perfusion

Whereas haemodialysis (HD) is lifesaving by replacement of renal function, there are data to suggest that the HD procedure itself may contribute to the high cardiac risk in dialysis patients. The HD procedure is associated with an increased risk of sudden death, and there is accumulating evidence that HD can elicit myocardial ischaemia. In this study, we evaluated the effect of HD on global and regional myocardial blood flow (MBF) and left ventricular (LV) function in non-diabetic, non-cardiac compromised patients. (13)N-NH(3) positron emission tomography (PET) was used to quantify changes in MBF, LV wall motion, cardiac output (CO), LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) in seven non-diabetic patients with uneventful cardiac histories. PET scans were performed before and at 30 and 220 min of HD. In all patients global MBF fell during HD. At 30 min of HD without ultrafiltration (UF), global MBF had fallen 13.5 +/- 11.5% (P < 0.05) while CO, LVEDV and LVESV were 4.6 +/- 5.3% (NS), 5.6 +/- 4.2% (P < 0.05) and 6.9 +/- 7.2% (P < 0.05) lower, respectively. At 220 min of HD, after UF of 2.5 +/- 0.9 l, global MBF had fallen 26.6 +/- 13.9% (P < 0.05) from baseline while CO, LVEDV and LVESV were 21.0 +/- 19.7%, 31.1 +/- 12.7% and 36.4 +/- 17.5% (all P < 0.05) lower, respectively. In two patients, new LV regional wall motion abnormalities (RWMA) developed at 220 min of HD. MBF was reduced to a greater extent in regions that developed LV RWMA compared to those that did not. Haemodialysis induced a pronounced fall in MBF. Since MBF fell already early during HD not only hypovolaemia but also acute dialysis-associated factors seem to play a role. Haemodialysis-associated reductions in MBF may contribute to the high cardiac event rate of dialysis patients.

The effect of left bundle branch block on left ventricular remodeling, dyssynchrony and deformation of the mitral valve apparatus: an observational cardiovascular magnetic resonance imaging study

The effect of a left bundle branch block (LBBB) on cardiac function and remodeling in patients at different stages of heart failure (HF) is unknown. We used cardiac magnetic resonance imaging (CMR) to evaluate the effect of LBBB on left ventricular (LV) remodeling, mechanical dyssynchrony, functional mitral regurgitation (FMR) and deformation of the mitral valve apparatus (MVA) in LBBB patients at different stages of HF. In 12 LBBB patients with HF, 4 patients with isolated LBBB, and 4 controls, cine CMR was performed to measure LV remodeling, FMR grade and deformation of the MVA. CMR tagging was used to measure septal-to-lateral onset of shortening delay and coefficient of circumferential strain variation (CV) to quantify dyssynchrony. LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were largest in LBBB patients with HF. Patients with isolated LBBB tended to have a larger LVESV and smaller LV ejection fraction compared to controls, (56 +/- 22 ml/m2 versus 45 +/- 9 ml/m2, P = ns, 42 +/- 9% versus 53 +/- 4 %, P = ns). QRS duration and septal-to-lateral-onset-of-shortening delay were comparable between LBBB patients with HF and isolated LBBB patients, CV was larger (98 +/- 45 versus 40 +/- 4, P < 0.05). MVA tenting and FMR were present both in LBBB patients with HF and patients with isolated LBBB and were not observed in controls. The presence of a LBBB in asymptomatic patients is related to mechanical dyssynchrony and deformation of the MVA and may be associated with LV remodeling. If confirmed, close monitoring or even timely initiation of therapy may be warranted in patients with isolated LBBB. This advocates to conduct a longitudinal CMR follow-up study on the clinical course in patients with isolated LBBB.

Cardiac magnetic resonance imaging abnormalities in systemic lupus erythematosus: a preliminary report

The purpose of this prospective, pilot study was to determine whether differences in myocardial T2 relaxivity can be identified among active systemic lupus erythematosus (SLE) patients with clinically suspected SLE myocarditis, other active SLE patients, inactive SLE patients and age and gender matched controls. Eleven consecutive female patients (six with active SLE and five with inactive SLE), and five age, gender and race matched healthy controls underwent imaging with echocardiography and cardiac magnetic resonance imaging (MRI). Echocardiographic measurements included left ventricular end diastolic (LVEDV) and end systolic volumes (LVESV), and mass (LVM) (all indexed to body mass); ejection fraction and cardiac output. The cardiac MRI measurement was the T2 relaxation time (an index of soft tissue signal, with higher levels suggestive of increased tissue water content). Patients with active SLE had significantly higher LVEDV and LVM than inactive SLE patients and healthy controls, and significantly larger LVESV than healthy controls. Myocardial T2 relaxation times were significantly higher in patients with active SLE compared to those with inactive SLE and to healthy controls, and remained higher even after excluding the two active SLE patients who had clinical myocarditis. The four active SLE patients who underwent repeat cardiac imaging studies after clinical improvement showed normalization of these myocardial abnormalities. The conclusion was that active SLE patients demonstrate abnormalities in myocardial structure manifested by high myocardial T2 relaxation times that normalized after clinical improvement in disease activity. These findings suggest that T2 relaxation values are a sensitive indicator of myocardial disease in patients with SLE and that myocardial T2 relaxation abnormality frequently occur in patients with active SLE, even in the absence of myocardial involvement by clinical criteria.