Smaller Left Ventricular End-diastolic Dimension Research Articles

Association between epicardial adipose tissue and incident heart failure mediating by alteration of natriuretic peptide and myocardial strain

BackgroundEpicardial adipose tissue (EAT) has been suggested to exert deleterious effects on myocardium and cardiovascular disease (CVD) consequence. We evaluated the associations of EAT thickness with adverse outcomes and its potential mediators in the community.MethodsParticipants without heart failure (HF) who had undergone cardiac magnetic resonance (CMR) to measure EAT thickness over the right ventricular free wall from the Framingham Heart Study were included. The correlation of EAT thickness with 85 circulating biomarkers and cardiometric parameters was assessed in linear regression models. The occurrence of HF, atrial fibrillation, coronary heart disease (CHD), and other adverse events was tracked since CMR was implemented. Their associations with EAT thickness and the mediators were evaluated using Cox regression and causal mediation analysis.ResultsOf 1554 participants, 53.0% were females. Mean age, body mass index, and EAT thickness were 63.3 years, 28.1 kg/m2, and 9.8 mm, respectively. After fully adjusting, EAT thickness positively correlated with CRP, LEP, GDF15, MMP8, MMP9, ORM1, ANGPTL3, and SERPINE1 and negatively correlated with N-terminal pro-B-type natriuretic peptide (NT-proBNP), IGFBP1, IGFBP2, AGER, CNTN1, and MCAM. Increasing EAT thickness was associated with smaller left ventricular end-diastolic dimension, thicker left ventricular wall thickness, and worse global longitudinal strain (GLS). During a median follow-up of 12.7 years, 101 incident HF occurred. Per 1-standard deviation increment of EAT thickness was associated with a higher risk of HF (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.19–1.72, P < 0.001) and the composite outcome consisting of myocardial infarction, ischemic stroke, HF, and death from CVD (adjusted HR [95% CI], 1.23 [1.07–1.40], P = 0.003). Mediation effect in the association between thicker EAT and higher risk of HF was observed with NT-proBNP (HR [95% CI], 0.95 [0.92–0.98], P = 0.011) and GLS (HR [95% CI], 1.04 [1.01–1.07], P = 0.032).ConclusionsEAT thickness was correlated with inflammation and fibrosis-related circulating biomarkers, cardiac concentric change, myocardial strain impairment, incident HF risk, and overall CVD risk. NT-proBNP and GLS might partially mediate the effect of thickened EAT on the risk of HF. EAT could refine the assessment of CVD risk and become a new therapeutic target of cardiometabolic diseases.Trial registrationURL: https://clinicaltrials.gov. Identifier: NCT00005121.

Effects of trehalose on recurrence of remodeling after ventricular reconstruction in rats with ischemic cardiomyopathy.

Recurrence of left ventricular (LV) remodeling after surgical ventricular reconstruction (SVR) for ischemic cardiomyopathy has been reported to be partially attributed to autophagy. We aimed to examine the effects of trehalose, an autophagy inducer, on the recurrence of LV remodeling after SVR. After SVR in rats with ICM, trehalose was orally administered. The changes in LV end-diastolic dimension (LVEDD) and fractional shortening (FS) were evaluated. The activation of myocardial autophagy was also estimated by autophagy markers: microtubule-associated light chain 3 II (LC3-II) and p62; the former usually increases and the latter decreases if autophagy is activated. Significant LV reverse remodeling was observed early after SVR. On the other hand, the 28th postoperative day SVR + trehalose was associated with smaller LVEDD and better FS than SVR alone (LVEDD, P = 0.043; FS, P < 0.01). LC3-II increased comparably in both groups, while p62 was significantly lower in the SVR + trehalose group than in the SVR alone group (P < 0.01). In conclusion, trehalose attenuated the recurrence of LV remodeling and changed autophagy markers after SVR in rats with ICM. Trehalose may be a candidate for adjuvant therapy to retain the effects of SVR.

Physiologic and Clinical Features of the Paralympic Athlete’s Heart

Paralympic medicine is a newly adopted term to describe the varied health care issues associated with athletes in the Paralympics. Scarce scientific data, however, are currently available describing the cardiac remodeling in Paralympic athletes. To investigate the physiological and clinical characteristics of the Paralympic athlete's heart and derive the normative values. This is a single-center study on a relatively large cohort of Paralympic athletes, conducted at the Italian Institute of Sport Medicine and Science. Paralympic athletes free of cardiac or systemic pathologic conditions other than their cause of disability were selected for participation in the Paralympic Games from January 2000 to June 2014. Athletes were arbitrarily classified for disability in 2 groups: those with spinal cord injuries (SCI) and those with non-SCI (NSCI). Data analysis occurred from March 2019 to June 2020. The primary outcome was the difference in cardiac remodeling in Paralympic athletes according to disability type and sports discipline type. Athletes underwent cardiac evaluation, including 12-lead and exercise electrocardiograms, echocardiography, and cardiopulmonary exercise testing. Among 252 consecutive Paralympic athletes (median [interquartile range (IQR)] age, 34 [29-41] years; 188 men [74.6%]), 110 had SCI and 142 had NSCI. Those with SCI showed a higher prevalence of abnormal electrocardiogram findings than those with NSCI (13 of 110 [11.8%] vs 6 of 142 [4.2%]; P = .003), smaller left ventricular end-diastolic dimension (median [IQR], 48 [46-52] vs 51 [48-54] mm; P = .001) and left ventricular mass index (median [IQR], 80.6 [69-94] vs 91.3 [80-108] g/m2; P = .001), and lower peak oxygen uptake (VO2) (median [IQR], 27.1 [2-34] vs 38.5 [30-47] mL/min/kg; P = .001) in comparison with those with NSCI. Regarding sport discipline, endurance athletes had a larger left ventricular cavity (median [IQR], 52 [47-54] vs 49 [47-53] mm; P = .006) and higher peak VO2 (median [IQR], 46 [39-55] vs 30 [25-35] mL/min/kg; P = .001) than athletes in nonendurance sports. Cardiac remodeling in Paralympic athletes differed by disability and sport discipline. Having NSCI lesions and engaging in endurance sports were associated with the largest left ventricular cavity and left ventricular mass and highest VO2 peak. Having SCI lesions and engaging in nonendurance disciplines, on the contrary, were associated with the smallest left ventricular cavity and mass and lowest VO2 peak.

Effects of dexrazoxane on doxorubicin-related cardiotoxicity and second malignant neoplasms in children with osteosarcoma: a report from the Children\u2019s Oncology Group

BackgroundDexrazoxane protects from lower-cumulative-dose doxorubicin cardiotoxicity, but the effect of dexrazoxane in children with sarcoma treated with higher-cumulative-dose doxorubicin is unknown.MethodsWe evaluated children with osteosarcoma (OS) on two Children’s Oncology Group trials with higher dose doxorubicin (375–600 mg/m2) preceded by dexrazoxane (10:1 dexrazoxane:doxorubicin dosing). They were evaluated after the minimum expected treatment time (METT), defined as 28 weeks. Cardiotoxicity was identified by echocardiography and serum N-terminal pro-brain natriuretic peptide (NT-proBNP). Second malignant neoplasm (SMN) data was collected.ResultsAll children had normal left ventricular (LV) systolic function as measured by LV fractional shortening and no heart failure. The end-diastolic septal thickness Z-scores (P < 0.01) and LV mass Z-scores (P < 0.01) were significantly smaller than normal for body-surface area in both sexes. The average LV mass Z-scores were significantly smaller for girls (P < 0.01) and marginally smaller for boys (P = 0.06). Girls had significantly smaller LV end-diastolic dimension Z-scores normalized to BSA (P < 0.01) compared to healthy controls and had significant increases in NT-proBNP. Four children developed SMNs as first events, a rate similar to historical controls.ConclusionsDexrazoxane prevented LV dysfunction and heart failure in children with OS receiving higher dose doxorubicin. However, LV structural changes were not fully prevented, especially in girls. As a result, hearts become abnormally small for body size, resulting in higher LV stress. Dexrazoxane did not increase the risk of SMN. Dexrazoxane should be used in this population, particularly for girls, to mitigate anthracycline-induced cardiotoxicity.Trial registrationsClinicalTrials.gov: NCT00003937 (P9754) registered 1 Nov 1999, and NCT00023998 (AOST0121) registered 13 Sept 2001.

Reply to “Moving Beyond Linear Formulas for Left Ventricular Mass in Aortic Valve Replacement”

We thank Moneghetti and colleagues for acknowledging positively our investigative result related to a potential pitfall of the linear echocardiography method for calculating left ventricular (LV) mass. The Devereux LV mass formula is the most widely used echocardiographic method to estimate LV mass and it has been a reliable predictor of cardiovascular outcomes in various populations. The formula was originally derived from the cube function of the LV end-diastolic dimension, posterior wall thickness, and interventricular septal thickness. The LV mass estimated from this formula was validated against the anatomically measured LV mass in 34 patients. The main point of our paper was to provide an explanation for the paradoxical finding of a greater and faster LV mass reduction in patients with severe aortic stenosis after surgical aortic valve replacement (SAVR) compared to after transcatheter AVR (TAVR) despite better hemodynamics with transcatheter aortic prostheses. In evaluating the echocardiographic parameters used to calculate LV mass in the CoreValve high-risk trial, we found that LV end-diastolic dimension became significantly smaller soon after SAVR, but not after TAVR, while both posterior and ventricular septal wall thickness decreased in both groups over time and to a similar extent. The smaller LV end-diastolic dimension after SAVR was responsible for the paradoxical faster and greater regression of the calculated LV mass. The reduced LV dimension after SAVR appeared to be related to reduced stroke volume after SAVR which did not occur after TAVR. There are several other echocardiographic methods to calculate LV mass. The Area-length method has also been well-validated against LV mass calculated by cardiac magnetic resonance imaging (MRI). The Area-length method uses LV cavity long-axis dimension and short-axis area. However, the Area-length method would also be falsely reduced if stroke volume decreases immediately after SAVR. There are several alternative means to compare LV mass regression after SAVR and TAVR. As suggested by Moneghetti and colleagues, 3D echocardiography or other imaging techniques such as cardiac computed tomography (CT) or cardiac MRI should provide more accurate LV mass calculations without being affected by acute changes in LV dimensions. We are currently conducting a prospective study to compare LV mass after SAVR and TAVR using cardiac CT, and hope to share our data soon. Ana Kadkhodayan has nothing to disclose. Dr. Jae K. Oh has received research support for the echocardiographic core laboratory from Medtronic.

Health-Related Quality of Life and Functional Status Are Associated with Cardiac Status and Clinical Outcome in Children with Cardiomyopathy

To measure the health-related quality of life (HRQOL) and functional status of children with cardiomyopathy and to determine whether they are correlated with sociodemographics, cardiac status, and clinical outcomes. Parents of children in the Pediatric Cardiomyopathy Registry completed the Child Health Questionnaire (CHQ; age ≥ 5 years) and Functional Status II (Revised) (age ≤ 18 years) instruments. Linear and Cox regressions were used to examine hypothesized associations with HRQOL. The 355 children evaluated at ≥ 5 years (median 8.6 years) had lower functioning (CHQ Physical and Psychosocial Summary Scores 41.7 ± 14.4 and 47.8 ± 10.7) than that of healthy historical controls. The most extreme CHQ domain score, Parental Impact-Emotional, was one SD below normal. Younger age at diagnosis and smaller left ventricular end-diastolic dimension z score were associated independently with better physical functioning in children with dilated cardiomyopathy. Greater income/education correlated with better psychosocial functioning in children with hypertrophic and mixed/other types of cardiomyopathy. In the age ≥ 5 year cohort, lower scores on both instruments predicted earlier death/transplant and listing for transplant in children with dilated and mixed/other types of cardiomyopathy (P < .001). Across all ages (n = 565), the Functional Status II (Revised) total score was 87.1 ± 16.4, and a lower score was associated with earlier death/transplant for all cardiomyopathies. HRQOL and functional status in children with cardiomyopathy is on average impaired relative to healthy children. These impairments are associated with older age at diagnosis, lower socioeconomic status, left ventricular size, and increased risk for death and transplant. Identification of families at risk for functional impairment allows for provision of specialized services early in the course of disease. ClinicalTrials.gov: NCT00005391.

Echocardiographic measurement methods for left ventricular linear dimensions in children result in predictable variations in results

Precise quantification of left ventricular (LV) cavity dimensions assumes great importance in clinical cardiology. Pediatric guidelines recommend the left parasternal short axis (PSA) imaging plane for measuring LV cavity dimensions, while measuring from the long axis (PLA) plane is the convention in adult echocardiography. We sought to compare measurements obtained by two-dimensional (2D) and M-mode (MM) techniques in the two imaging planes. Healthy subjects were prospectively recruited for research echocardiography. Complete 2D, spectral and color flow Doppler examinations were performed in a non-sedated state. All subjects had structurally and functionally normal hearts. LV cavity dimensions were obtained in PLA and PSA views using 2D and MM yielding four measurement sets for each subject: PLA direct 2D; PLA 2D-guided MM, PSA direct 2D, PSA 2D-guided MM. A commercially available ultrasound system (Vivid E9, GE) was used and data stored digitally for subsequent analysis (EchoPAC BT11, GE). Acquisition and measurements were made by a single observer from at least three consecutive cardiac cycles, and averaged for each of the four categories. The study cohort consisted of 114 subjects (mean age 9 years, range 1-18; mean BSA 1.1 m(2), range 0.42-2.6). The smallest estimate of LV end-diastolic dimension (LVED) was obtained by PLA 2D, with larger estimates by PLA MM, PSA 2D, and PSA MM. Largest estimates of LV end-systolic dimension (LVES) are by 2D methods, with smaller estimates by both MM techniques. The smallest shortening fraction (SF) was by PLA 2D; other methods yielded larger SF. Temporal resolution is limited in 2D methodology and may account for the smaller LVED, larger LVES and smaller SF observed. Long axis methodology may predispose to off-center or non-perpendicular data acquisition and the potential for dimensional underestimation, particularly in diastole. Consistency in method for assessment of LV dimensions in children is an important factor for serial comparisons.

Preoperative evaluation of children with anomalous origin of left coronary artery from the pulmonary artery and the follow-up after surgery

Objective To retrospectively study 50 children with anomalous origin of the left coronary artery from the pulmonary artery(ALCAPA) and find the simple and practical indexes that may predict myocardial viability and the possible risk factors that may affect the choice of operation and the recovery after surgery. Methods A retrospective study was performed in 50 children with ALCAPA[29 male, 21 female, aged from 4 months to 18 years, average (4.49±4.30) years] between Apr.1999 and Mar. 2013. The preoperative examination included electrocardiogram(ECG), echocardiography, chest X-ray, mutislice spiral computerized tomography(MSCT), angiocardiography et al. Follow-up data were obtained by reviewing the records made in out-patient and recent telephone call. According to myocardial 18F-FDG imaging, the extent of myocardial viability of 15 patients with ALCAPA was classified into 4 grades.0 normal myocardial; 1 viable myocardial; 2 partial viable myocardial; 3 myocardial infarction. Meanwhile, the global clinical scores were calculated and divided into 10 levels according to the deviations of clinical manifestations which included abnormal Q waves, left ventricular ejection fraction(LVEF), left ventricular end-diastolic dimension(LVED), cardiothoracic ratio(CTR), intercoronary collaterals(ICC), mitral regurgitation(MR) and aneurysm. The relationship of the extent of myocardial viability and clinical features were studied. All patients with ALCAPA were classified into groups by the global clinical scores and the preoperative, perioperative and post operative clinical manifestations were compared among groups. Results The extent of myocardial viability was related well to the global clinical scores(r=0.936, P 0.05). The results showed that grade 0-1 equaled scores 0-3, grade 2 equaled scores 3-5, grade 3 equaled scores>5. Children with less viable myocardium had more severe clinical symptoms. Among abnormal Q waves, LVEF 0.65, ICC dysplasia, median to severe MR and the global clinical scores>3, the global clinical scores>3 and LVEF 3) in all patients. More infants and toddlers, abnormal Q waves, ICC dysplasia, RCA/AO<0.2, larger CTR and lower LVEF were found in group B than those in group A. The time of cross-clamp and CPB was not different between the 2 groups, but the postoperative ventilation time and postoperative ICU stay were longer in group B than in group A. Forty-seven patients underwent operation and there were no operative deaths. One infant with scores 9 died while waiting heart transplantation. Follow-ups from 1 to 168 months were conducted in 38 patients(80.9%, 38/47 cases) and 1 patient with ligation of the left coronary artery(LCA) had a sudden death after 8 months of surgery. All patients had gotten smaller LVED after surgery. Nineteen patients had mild MR and 3 patients had mild supravalvular pulmonary stenosis in following-up. Of the 16 patients with LVEF<50%, 14 had a recovery of LVEF, 2 patients still had LVEF<50%. Conclusions In children with ALCAPA, the extent of myocardial viability evaluated by myocardial 18F-FDG imaging is related closely to the preoperative clinical manifestations. The global clinical scores>3 and LVEF<50% have a good predict of myocardial infarction. Even in young children with severely depressed left ventricular function, higher global clinical scores and more myocardial infarction, median and long-term follow-ups showed satisfactory recovery of cardiac function after successful restoration of a dual coronary arterial system. Key words: Anomalous origin of the left coronary artery from the pulmonary artery; Preoperative evaluation; Follow-up; Myocardial viability

Centrifugal Continuous-Flow Left Ventricular Assist Device in Patients With Hypertrophic Cardiomyopathy

Left ventricular assist device (LVAD) therapy has been used primarily in patients with end-stage dilated cardiomyopathy (DCM), and patients with hypertrophic cardiomyopathy (HCM) are generally excluded. We compared outcomes in 3 HCM patients with 36 DCM patients. While HCM patients had smaller left ventricular end-diastolic dimensions, average pump flows for the two groups were similar. All patients had marked improvement in mean pulmonary arterial pressures and cardiac index at 5 months. This analysis shows that patients with end-stage heart failure resulting from HCM do benefit from centrifugal cfLVAD therapy in the short to medium term.

THE EFFECTS OF ENDOTHELIAL PROGENITOR CELL TRANSPLANTATION ON MYOCARDIAL INFARCTION IN MICE

ObjectivesEndothelial progenitor cells (EPC) are thought to be engaged in neovascularisation after myocardial infarction (MI). In most cases, however, autologous EPC seem to be insufficient for recovery. EPC transplantation is...

Small Heart With Low Cardiac Output for Orthostatic Intolerance in Patients With Chronic Fatigue Syndrome

The etiology of chronic fatigue syndrome (CFS) is unknown. Orthostatic intolerance (OI) is common in CFS patients. Recently, small heart with low cardiac output has been postulated to be related to the genesis of both CFS and OI. Small heart is associated with OI in patients with CFS. Study CFS patients were divided into groups of 26 (57%) CFSOI(+) and 20 (43%) CFSOI(-) according to the presence or absence of OI. In addition, 11 OI patients and 27 age- and sex-matched control subjects were studied. Left ventricular (LV) dimensions and function were determined echocardiographically. The mean values of cardiothoracic ratio, systemic systolic and diastolic pressures, LV end-diastolic dimension, LV end-systolic dimension, stroke volume index, cardiac index, and LV mass index were all significantly smaller in CFSOI(+) patients than in CFSOI(-) patients and healthy controls, and also in OI patients than in controls. A smaller LV end-diastolic dimension (<40 mm) was significantly (P<0.05) more prevalently noted in CFSOI(+) (54%) and OI (45%) than in CFSOI(-) (5%) and controls (4%). A lower cardiac index (<2 L/min/mm(2)) was more prevalent in CFSOI(+) (65%) than in CFSOI(-) (5%, P<0.01), OI (27%), and controls (11%, P<0.01). A small size of LV with low cardiac output was noted in OI, and its degree was more pronounced in CFSOI(+). A small heart appears to be related to the genesis of OI and CFS via both cerebral and systemic hypoperfusion. CFSOI(+) seems to constitute a well-defined and predominant subgroup of CFS.

Left Ventricular Assist Device Therapy in Patients With Restrictive and Hypertrophic Cardiomyopathy

Background— Left ventricular assist device (LVAD) is being increasingly used in patients with end-stage dilated and ischemic cardiomyopathy. There have been no clinical trials addressing the use of LVAD therapy in patients with end-stage heart failure caused by restrictive (RCM) or hypertrophic cardiomyopathy (HCM). The purpose of this study was therefore to analyze the outcome of LVAD therapy in these patients. Methods and Results— Eighty-three patients received continuous axial flow LVAD (Heart mate II, Thoratec, Pleasanton, CA) from February 2007 to May 2010 at our institution. We analyzed the baseline characteristics and surgical and long-term impact of LVAD therapy in 8 patients with RCM or HCM and compared their outcomes with the 75 patients with dilated and ischemic cardiomyopathy. Compared with patients with ischemic or dilated cardiomyopathy, patients with RCM and HCM have significantly smaller left ventricular end-diastolic dimensions (52.5±6 mm versus 68.6±8 mm; P &lt;0.0001) and increased thickness of septal (16 [12, 19] mm versus 10[8.5, 11] mm, P =0.0003) and higher left ventricular ejection fraction (21 [20, 36]% versus 17 [15, 22]%; P =0.0009). We found no difference in early mortality (12.5% versus 9.3%, P =0.57) or length of hospital stay (11 [8, 45] days versus 18.5 [12.2, 27.7] days; P =0.51) between the 2 groups. The right atrial pressure was higher (18 [15, 20] mm Hg versus 12 [9, 15] mm Hg, P =0.03), and pump flow was lower (4.3 [3.8, 4.5] L versus 5.2 [4.7, 5.5] L, P =0.001) after LVAD implantation in patients with RCM and HCM. Central venous catheter related infections were more common in patients with RCM and HCM (87.5% versus 44.5%, P =0.006). There was no difference in the total number of blood units transfused. Median (min, max) follow-up duration after LVAD implantation was 166 [1, 1044] days. The 1-year actuarial survival rate was not different between the 2 groups (87.5% [95% confidence interval, 52.9% to 97.8%] versus 73.2 [95% confidence interval, 60% to 85%]; P =0.77). Conclusions— Our preliminary data show that patients with end-stage heart failure caused by RCM or HCM may benefit from continuous axial flow LVAD therapy. This small study suggests that mortality is comparable with those patients who have dilated or ischemic cardiomyopathy, but right heart failure, prolonged inotropic use, and central venous catheter infections are more common in patients with RCM and HCM who were treated with LVAD. Because of the small numbers the differences should be interpreted cautiously, and prospective clinical trials would be required to recommend this therapy for these patients as bridge to transplantation or destination treatment.

Cardiac Myocyte-specific Ablation of Follistatin-like 3 Attenuates Stress-induced Myocardial Hypertrophy

Transforming growth factor-β family cytokines have diverse actions in the maintenance of cardiac homeostasis. Follistatin-like 3 (Fstl3) is an extracellular regulator of certain TGF-β family members, including activin A. The aim of this study was to examine the role of Fstl3 in cardiac hypertrophy. Cardiac myocyte-specific Fstl3 knock-out (KO) mice and control mice were subjected to pressure overload induced by transverse aortic constriction (TAC). Cardiac hypertrophy was assessed by echocardiography and histological and biochemical methods. KO mice showed reduced cardiac hypertrophy, pulmonary congestion, concentric LV wall thickness, LV dilatation, and LV systolic dysfunction after TAC compared with control mice. KO mice displayed attenuated increases in cardiomyocyte cell surface area and interstitial fibrosis following pressure overload. Although activin A was similarly up-regulated in KO and control mice after TAC, a significant increase in Smad2 phosphorylation only occurred in KO mice. Knockdown of Fstl3 in cultured cardiomyocytes inhibited PE-induced cardiac hypertrophy. Conversely, adenovirus-mediated Fstl3 overexpression blocked the inhibitory action of activin A on hypertrophy and Smad2 activation. Transduction with Smad7, a negative regulator of Smad2 signaling, blocked the antihypertrophic actions of activin A stimulation or Fstl3 ablation. These findings identify Fstl3 as a stress-induced regulator of hypertrophy that controls myocyte size via regulation of Smad signaling.

Human Mesenchymal Stem Cells Improve Myocardial Performance in a Splenectomized Rat Model of Chronic Myocardial Infarction

Cellular therapy has been applied to animal studies and clinical trials for acute or subacute myocardial infarction. Little is known about the effect of cell therapy on chronic myocardial infarction. The goal of this study was to investigate myocardial performance after human bone marrow-derived mesenchymal stem cell (hMSCs) transplantation in rats with chronic myocardial infarction. The hMSCs were obtained from adult human bone marrow and expanded in vitro. The purity and characteristics of hMSCs were identified by flow cytometry and immunophenotyping. Splenectomy in male rats was performed to prevent immune reaction. One week after splenectomy, ligation of the left anterior descending coronary artery was performed to induce myocardial infarction. Four weeks after ligation of the coronary artery, culture-expanded hMSCs were injected intramyocardially at the left anterior free wall. Left ventricular function measured by echocardiography, infarct size and immunohistochemical stain were performed to evaluate the effect of the therapy. The engrafted hMSCs were positive for the cardiac marker troponin T. Infarct size (35.4 +/- 3.4% vs. 53.3 +/- 3.0%, p < 0.001) and fibrotic area (2.6 +/- 0.1% vs. 5.9 +/- 0.2%, p < 0.001) were significantly smaller in the hMSC-treated group than in the control group at 28 days after therapy. hMSC transplantation resulted in smaller left ventricular end-diastolic dimension (6.5 +/- 0.1 mm vs. 7.9 +/- 0.7 mm, p < 0.001) and better left ventricular ejection fraction (88.7 +/- 1.2% vs. 65.8 +/- 2.5%, p < 0.001) than in the control group. Capillary density was markedly increased after hMSC transplantation compared with the control group. This study demonstrates that intramyocardial transplantation of hMSCs improves cardiac function after chronic myocardial infarction through enhancement of angiogenesis and myogenesis in the ischemic myocardium. Transplantation of hMSCs for myocardial regeneration may become the future therapy for chronic myocardial infarction.

Residual fibrosis affects a long-term result of left ventricular volume reduction surgery for dilated cardiomyopathy in a rat experimental study?

The aim of this study is to evaluate the relationship between left ventricular (LV) wall property and the results of LV volume reduction surgery (LVR) to treat dilated cardiomyopathy (DCM) in an experimental model. DCM was introduced in 18 Lewis rats by autoimmunization with cardiac myosin. Among them, 12 rats underwent LVR and the rest were served as controls. They were subjected to echocardiography and cardiac catheterization for dimensional and functional measurements. The animals were sacrificed 4 weeks after surgery, and the fraction of myocardial fibrosis was calculated in 4 divided parts of the LV wall. Percent fibrosis varied widely from 4.7 to 45.2%. LV volume reduction surgery improved cardiac function immediately after surgery in all rats (Emax, 0.28+/-0.14 to 0.48+/-0.18 mmHg/microl; LV end-diastolic pressure, 21.0+/-6.1 to 13.3+/-5.1 mmHg, P<0.05, respectively). Four weeks later, 6 hearts remained in good shape with smaller LV end-diastolic dimension (Dd) than baseline values (LV Dd, 9.7+/-0.6mm; fractional area change (FAC), 40.3+/-8.4%) and the other 6 had more redilation in diameter and more deterioration in function than baseline values (LV Dd, 10.9+/-0.6mm; FAC, 25.8+/-6.9%; P<0.05, respectively). Percent fibrosis in the septum differed 11.1+/-3.4 vs. 27.8+/-2.8% between the two groups (P<0.01). There was a significant correlation between the ratio of LV redilatation after surgery and percent fibrosis in the septum (r=0.951, P<0.01). Although the initial benefit of LVR was confirmed, the long-term result was affected by the amount of residual fibrosis. This information suggests that surgical site selection is important to achieve a good result of LV restoration surgery for DCM.

Left ventricular size and function in elite bodybuilders using anabolic steroids.

To investigate the relationship between resistance training, anabolic steroid use, and left ventricular function. Sixteen competitive bodybuilders were recruited for an echocardiography study. University of North Texas Health Science Center (Fort Worth, TX, U.S.A.); the cardiologist and technician were blinded as to subjects' drug status. Eight competitive heavyweight drug-free (DF) bodybuilders and eight competitive heavyweight body-builders on self-directed regimens of anabolic steroids. Average body mass indexes (BMI; kg/m2) for the drug-user (DU) and DF groups were not significantly different (34.1 +/- 2.8 and 32.0 +/- 4.3, respectively). Increases in left ventricular posterior wall and ventricular septal thickness were apparent in the DU group (p < 0.05). The ratio of echocardiographic findings to BMI revealed a significantly smaller left ventricular end-diastolic dimension (LVDEd/BMI; p < 0.05) in the DU group. The smaller LVDEd in DUs is coupled with a significantly disproportionate septal and posterior wall thickness in DUs when indexed to body mass compared to DFs. There was no direct evidence of diastolic dysfunction detected by mitral inflow velocity patterns. Anabolic steroids may potentiate concentric left ventricular hypertrophy with decreasing ventricular compliance without affecting cardiac function.

Impact of chamber geometry and gender on left ventricular systolic function in patients >60 years of age with aortic stenosis

In aortic stenosis, gender and other differences in the adaptive remodeling of the left ventricle have been described, but the influence of left ventricular (LV) geometry on systolic function is not widely appreciated. This study tested the hypothesis that the increased ejection fraction seen in some elderly women with aortic stenosis is due to changes in LV geometry, not increased myocardial mass or enhanced myocardial function. We therefore investigated gender-related differences in LV and myocardial function by analysis of end-systolic circumferential stress versus shortening relations in 65 patients (29 men and 36 women) with aortic stenosis who underwent cardiac catheterization and echocardiography. Despite similar degrees of aortic stenosis, there were significant differences between men and women with regard to LV geometry and function. When compared with men, women had higher peak LV pressures (205 ± 27 vs 188 ± 27 mm Hg, p < 0.01), higher ejection fractions (66 ±14% vs 57 ± 18%, p < 0.05), smaller LV end-diastolic dimensions (43 ± 8 vs 51 ± 6 mm, p < 0.01) and higher relative wall thickness (0.66 ± 0.27 vs 0.50 ± 0.10, p < 0.01). LV mass was similar in the 2 groups. Mean values for stress were lower in women and there was a predominance of women at extremely low levels of stress; this subgroup had very high values for relative wall thickness and endocardial shortening, but overall stress-shortening relations were normal. In contrast to chamber function (i.e., endocardial shortening), myocardial function was depressed compared with age-matched control subjects; the midwall shortening analysis, however, showed no difference in circumferential shortening between men and women. Differences between endocardial and midwall shortening were directly related to differences in relative wall thickness. Thus, exaggerated endocardial fractional shortening and high ejection fraction in elderly women with aortic stenosis is due to alterations in LV geometry, not increased LV mass or enhanced myocardial function.