Alterations In Diastolic Function Research Articles

TCTAP A-092 Non-invasive Evaluation of Global and Territorial Coronary Vascular Function: Association with Diastolic Function

There is emerging interest in the assessment of coronary vascular flow by SPECT myocardial perfusion imaging (MPI). Coronary flow may be influenced by underlying alterations in diastolic function. To advance understanding of coronary vascular flow measures obtained by SPECT, we investigated the

Assessment of Function of the Left Heart Myocardium by Tissue Doppler Imaging and Speckle Tracking Echocardiography in Patients with Chronic Heart Failure with Preserved Left Ventricular Ejection Fraction

to study myocardial function in patients with chronic heart failure (CHF) with preserved left ventricular ejection fraction (PEF) by speckle tracking echocardiography and tissue doppler imaging. We examined 80 patients aged 50-70 years with verified NYHA class I-IIa CHF and PEF due to arterial hypertension and ischemic heart disease, and 35 healthy persons. Examination included echocardiography, and speckle-tracking echocardiography. According to 6-min walk test 26.9 % of patients had functional class (FC) I CHF, 48.3 % - FC II CHF, and 24.8 - FC III CHF. The mean left ventricular ejection fraction (Simpson's method) was 62.3±5.35 %, mean end systolic left atrial volume index - 45±8.1 ml / m2. All patients had left ventricular diastolic dysfunction: 60 patients - abnormal relaxation pattern, 20 patients - pseudonormal pattern. Other findings were reduced global longitudinal strain (GLS, -16.56±2.61 %) and GLS rate (GLSR, -0.75±0.11 s-1) of the left ventricle and reduced segmental strain and strain rate in basal anteroseptal (-13.62±3.44 % and -0.77±0.04 s-1, respectively) and basal anterolateral (-14.17±3.31 % and -0.81±0.11 s-1, respectively) segments. Lowering of global circular left ventricular strain and strain rate (-15.63±4.8% and -1.4±0.23 s-1, respectively) was found to be smaller than that of GLS (p<0.05). There was positive correlation between left ventricular systolic GLS and left atrial volume (r=0.601, р<0.01). In patients with CHF and PEF we revealed alterations of diastolic function (abnormal relaxation and pseudonormal patterns), reductions of global and segmental strain and strain rate of the left ventricle. More pronounced lowering of segmental strain and strain rate was registered in left ventricular basal anteroseptal and basal anterolateral segments. Circular strain was found to be slightly reduced, while radial strain was unchanged.

The influence of LV geometry on the occurrence of abnormal exercise tests in athletes

BackgroundPrevious studies revealed a high rate of abnormal exercise test (ET) results in the absence of obstructive coronary artery disease (CAD) in asymptomatic athletes. The physiological background of this phenomenon is not well established. In particular, it is unclear whether sports-induced morphological cardiac adaptations are determinants of abnormal ET results. The main objective of this study was to investigate if healthy asymptomatic recreational and competitive athletes with abnormal ET results without obstructive CAD have a higher LV mass when compared with athletes with normal ET results.MethodsSeventy-three athletes with abnormal ET results without presence of obstructive CAD underwent echocardiographic assessment of LV mass, systolic and diastolic measurements. These data were compared with data from 73 athletes with normal ET results, matched for gender, age, body composition, sports characteristics and exercise capacity.ResultsNo significant increase in LV mass (161.9 ± 39 g vs. 166.9 ± 42.1 g, p = 0.461) was found between groups. Athletes with abnormal ET results had a significant thicker IVSd (9.7 ± 1.8 mm vs. 9.0 ± 1.7 mm, p = 0.014), higher IVSd/PWTd ratio (1.08 ± 0.20 vs. 1.00 ± 0.12, p = 0.011) and deceleration time (DT) was prolonged ((225.14 ± 55.08 vs. 199.96 ± 34.65, p = 0.003).ConclusionAthletes with abnormal ET result did not show a higher in LV mass when compared to athletes with a normal ET result. However, a pattern of asymmetric cardiac remodeling, together with altered diastolic function is present. Due to small differences, cardiac remodeling only plays a limited role in the occurrence of positive ET results in athletes.

Left Atrial 2D Speckle Tracking Echocardiography as a Prognostic Marker in Patients With Chronic Kidney Disease

Background: Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular events that is underestimated by traditional risk stratification algorithms. We evaluated clinical and echocardiographic parameters that would determine long-term adverse outcomes in CKD patients. Methods: Patients with Stage 3/4 CKD without previous cardiac disease were prospectively recruited. Participants underwent a comprehensive transthoracic echocardiogram with detailed assessment of left ventricular (LV) and left atrial (LA) size and function including strain analysis; a stress echocardiogram was additionally performed to rule out latent ischaemia. Participants were followed annually for 5 years for adverse events, corroborated with hospital records and registry data. The primary end point was a composite of all-cause death and major adverse cardiovascular events (MACE). Results: A total of 243 patients (male 63%; mean age 59.23 ± 14.44 years) were followed for a median of 46.90 ± 32.56 months. 69 patients met the composite endpoints of death and MACE; these patients were older with history of DM. On Kaplan Meier analysis, age (p < 0.01), DM (p < 0.01), LV mass (p < 0.01), LV GLS (p < 0.01), LAVI (p < 0.01) and LA GLS (p < 0.01) were independent predictors for death and MACE. On multiple Cox proportional hazards analysis, LA GLS (p < 0.01) was the only significant predictor for death and MACE in a model accounting for the effect of age, DM, LV mass, LV GLS, E/e’ and LAVI. Conclusions: LA GLS is an independent predictor of death and adverse cardiovascular events in patients with CKD. LA GLS is a potential prognostic biomarker, possibly reflecting alterations in diastolic function with CKD.

Diagnosis of Cardiac Amyloidosis: Clinical and Echocardiographic Features

This review is geared to address the various forms of amyloidosis which have cardiac involvement and discuss the echocardiographic findings that may be present in patients with cardiac amyloidosis. The use of echocardiography has revolutionized the diagnosis of cardiac amyloidosis. The diagnosis is often first suspected due to characteristic echocardiographic findings. Although no single finding is pathognomonic, there are a constellation of features that point to the diagnosis including increased left and right ventricular wall thickness, thickened cardiac valves and atrial walls, and a pericardial effusion. Alterations in diastolic function with evidence of elevated filling pressures are common. The use of myocardial strain imaging has allowed for earlier detection of cardiac amyloidosis and has revealed a distinctive pattern, sometimes suggesting the diagnosis when more classic findings are subtle or absent. Multiple echocardiographic findings have been found to be prognostic in cardiac amyloid. Using current techniques, functional measures such as myocardial strain and stroke volume index are more powerful predictors of outcome than myocardial thickness. While other imaging modalities are complementary including cardiac magnetic resonance imaging and nuclear medicine scintigraphy techniques using bone tracers, echocardiography remains a mainstay in the diagnosis and follow-up of patients with cardiac amyloidosis. Echocardiography is a critical tool in the evaluation of the patient with heart failure, as well as those with unexplained chest pain and arrhythmias. Key findings on an echocardiogram can help alert the clinician to the presence of cardiac amyloidosis. The degree of cardiac dysfunction in a patient with systemic amyloidosis correlates with prognosis. Recognition of subtle echocardiographic findings may allow for earlier and more aggressive treatment to improve overall mortality in patients with cardiac amyloidosis.

Inhibition of Lysyl Oxidase Activity Prevents Volume Overload Diastolic and Systolic Dysfunction

The cardiac extracellular matrix (ECM) is a structural framework which bridges cardiomyocytes to the cystoskeletal myofibril, preserving alignment, while providing tensile strength to the myocardium. Abnormalities in the architectural scaffolding of the ECM have been noted during various cardiac pathologies. The major structural components of the cardiac ECM are collagens, which are produced by fibroblasts. The relative expression of collagens and the degree of cross‐linking dictate the passive mechanical properties of the heart. Lysyl oxidase (LOX) is a copper‐dependent amine oxidase that plays a critical role in covalently cross‐linking fibrillar collagens, which determines the insolubility, stiffness and resistance to degradation of the resulting collagen fibrils. In our previous studies we have shown marked increases in LOX expression and activity in failing hearts relative to compensated and unstressed hearts. Our goal of this study was to determine whether LOX inhibition, initiated during the early stages of cardiac remodeling, could attenuate fibrosis and cardiac dysfunction.We used the aortocaval fistula (ACF) surgical model on Sprague‐Dawley rats to induce biventricular volume overload (VO). Two weeks after surgery, both sham‐operated and VO rats were treated with the LOX inhibitor, beta‐aminoproprionitrile (BAPN; 100 mg/kg/d), for 12 weeks. BAPN was administered via an osmotic pump surgically inserted into the abdominal cavity. After a total of 14 weeks of VO, left ventricular (LV) pressure‐volume catheterization was used to assess alterations in cardiac function. Western blot protein analyses were performed to assess alterations in LOX, collagens I and III, matrix metalloproteinases (MMPs), and their inhibitors (TIMPs). Further, LV strain and stiffness were calculated to determine alterations in diastolic function.Our data demonstrate that chronic VO caused a significant increase in LV wall stress at both diastole and systole, and produced significant LV hypertrophy (183%, 60%, and 92% increase, respectively vs. control; p&lt;0.05). Further, VO induced significant increases in LV strain and stiffness (126% and 77% increase, respectively vs. control), as well as significant increases in the expression of fibrotic proteins including LOX, collagen I, collagen III, MMP2, and TIMP1 (135%, 58.4%, 26.7%, 39%, and 63% increase, respectively vs. control; p&lt;0.05). Finally, VO also caused systolic dysfunction, as evident by decreases in cardiac contractility and ejection fraction (51% and 26% decrease, respectively vs. control; p&lt;0.05). Further, our data highlight the cardioprotective role of LOX inhibition against adverse cardiac remodeling due to VO. LOX inhibition completely prevented VO‐induced increases in LV wall stress and ventricular hypertrophy. Further, LOX inhibition prevented VO‐induced fibrosis and diastolic dysfunction, as evident by normalized levels of collagens, LOX, MMPs, TIMPs, and LV stiffness. Finally, LOX inhibition prevented the VO‐induced decline in cardiac contractility. Overall, our data indicate that LOX inhibition prevented adverse ECM remodeling and cardiac dysfunction in the volume overloaded heart.Support or Funding InformationSupport for this project provided by the American Heart Association Southeast Affiliate and the NIH Heart, Lung and Blood Institute: Grant‐in‐Aid (#16GRNT30440008‐JDG), AHA Predoctoral Fellowship (# 16PRE29150010‐EEH), and F31 (#1F31HL134263‐ 01A1‐EEH).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Role of Doppler Diastolic Parameters in Differentiating Physiological Left Ventricular Hypertrophy from Hypertrophic Cardiomyopathy

The association between athletic participation and alteration in diastolic function is not well established. The aims of this study were to determine the spectrum of Doppler parameters of left ventricular (LV) diastolic function in a large cohort of healthy athletes and to quantify the overlap between physiologic LV hypertrophy and hypertrophic cardiomyopathy (HCM). A retrospective analysis of indices of LV diastolic function was performed in 1,510 healthy athletes (mean age, 22±5years; range, 13-33years; 72% men). The results were compared with those from 58 young patients with HCM. Septal E' < 7cm/sec and lateral E' < 10cm/sec were found in five (0.3%) and eight (0.5%) athletes, respectively. Septal E' was >14.6cm/sec in 170 (11%) and lateral E' was >19.9cm/sec in 430 (28%) athletes. Athletes aged >25years showed lower E' velocities compared with younger athletes (mean septal E', 11.8±6.1 vs 12.9±5.9cm/sec [P<.001]; mean lateral E', 17.1±3.6 vs 19.3±4.1cm/sec [P<.001]). Athletes with high indexed LV end-diastolic diameters (>32mm/m2) exhibited lower septal E' compared with athletes with normal indexed LV end-diastolic diameters (mean septal E', 11.9±6 vs 12.7±6cm/sec; P=.002). Septal E' < 10cm/sec and lateral E' < 12cm/sec showed the best accuracy in differentiating between HCM and athlete's heart. Reduced septal and lateral E' are rarely observed in young elite athletes. Tissue Doppler velocities tend to decrease with increasing age and LV size, and values representative of supernormal diastolic function are found in less than one-third of young athletes. Cutoff thresholds for Doppler parameters of diastolic function should be corrected for multiple demographic and clinical variables to differentiate cardiac adaptation to exercise from HCM in young individuals.

Echocardiographic left atrial remodelling in the early phase of high blood pressure and its correlation with microalbuminuria: A case control study in sub-Saharan Africans

Left atrial remodelling (LAR) is a common finding in patients with chronic hypertension and increases the risk of adverse cardiovascular events. However, early changes in the left atrial size and association microalbuminuria are poorly elucidated. To assess early left atrial structural remodelling in hypertensive patients and determine its correlation with microalbuminuria. Fifty-two patients diagnosed with hypertension for less than a year were matched for age sex to forty healthy controls. Patients with pre-existing, cardiovascular disease, kidney disease and diabetes were excluded. The left atrial endocardial border was traced to get atrial length, transverse diameter, surface area and volume while the anteroposterior diameter was obtained on the parasternal long axis by M-Mode echocardiography. Early morning urine was analysed for microalbuminuria. The hypertensive patients and controls were comparable for age and sex, but had significantly higher body mass indices, Left ventricular mass (LVM) and an altered diastolic function. Hypertensive patients had significant increase in the left atrial longitudinal diameter (50.0 mm versus 47.4 mm, P = 0.045 mm), surface area (17.9 cm 2 versus 15.5 cm 2 , P = 0.003) and volume (52.4 ml versus 43.8 ml, P = 0.002). Fourteen hypertensive patients (26.9%) had left atrial enlargement compared to 1 (2.5%) in the control group ( P = 0.001). Diastolic dysfunction ( P = 0.008) was the only independent predictor of LA size and LAE. There was a no correlation between microalbumin and left atrial size. Changes in the left atrial size in the early phase of hypertension characterised increase left atrial length, surface area and volume. Left atrial remodelling in hypertension is an evidence of the chronicity of diastolic dysfunction. Microalbuminuria does not predict left atrial remodelling.

Echocardiographic left atrial remodelling in the early phase of high blood pressure and its correlation with microalbuminuria: A case control study in sub Saharan Africans

Left atrial remodelling (LAR) is a common finding in patients with chronic hypertension and increases the risk of adverse cardiovascular events. However, early changes in the left atrial size and association microalbuminuria are poorly elucidated. To assess early left atrial structural remodelling in hypertensive patients and determine its correlation with microalbuminuria. Fifty-two patients diagnosed with hypertension for less than a year were matched for age sex to forty healthy controls. Patients with pre-existing, cardiovascular disease, kidney disease and diabetes were excluded. The left atrial endocardial border was traced to get atrial length, transverse diameter, surface area and volume while the anteroposterior diameter was obtained on the parasternal long axis by M-Mode echocardiography. Early morning urine was analysed for microalbuminuria. The hypertensive patients and controls were comparable for age and sex, but had significantly higher body mass indices, Left ventricular mass (LVM) and an altered diastolic function. Hypertensive patients had significant increase in the left atrial longitudinal diameter (50.0 mm versus 47.4, = 0.045 mm), surface area (17.9 cm 2 versus 15.5 cm 2 , P = 0.003) and volume (52.4 mL versus 43.8 mL, P = 0.002). Fourteen hypertensive patients (26.9%) had left atrial enlargement compared to 1(2.5%) in the control group. Diastolic dysfunction ( P = 0.008) was the only independent predictor of LA size and LAE. There was a no correlation between microalbumin and left atrial size. Changes in the left atrial size in the early phase of hypertension are characterised by an increase in the left atrial length, surface area and volume. Left atrial remodelling in hypertension is an evidence of the chronicity of diastolic dysfunction. Microalbuminuria does not predict left atrial remodelling.

B-type natriuretic peptide and echocardiography reflect volume changes during pregnancy.

To evaluate B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac structure and function in normal women through pregnancy and the postpartum. In this prospective observational study, we obtained serial transthoracic echocardiograms, BNP, and NT-proBNP at seven intervals from 6 weeks' gestation through 12 months postpartum. Women with hypertension or cardiac disease were excluded. Using 6-12 months postpartum as reference for non-pregnant levels, echocardiogram measurements and BNP/NT-proBNP were compared over time using linear mixed models with Tukey-Kramer adjustment for multiple comparisons. Of 116 patients, data was available for 78-114 healthy pregnant or postpartum women within each time interval, and 102 patients provided data for ≥4 intervals. Compared to 6-12 months postpartum, BNP and NT-proBNP remained stable through pregnancy and delivery, increased within 48 h postpartum (P<0.0001), then returned to baseline. Left ventricular volume increased within 48 h postpartum (P=0.021) while left atrial volume increased at 18-24 weeks (P=0.0002), 30-36 weeks (P<0.0001) and within 48 h postpartum (P=0.002). The transmitral early/late diastolic velocity (E/A) ratio, transmitral early/peak mitral annulus diastolic velocity (E/E') ratio, isovolumic relaxation times, and mitral valve deceleration times were similar within 48 h and 6-12 months postpartum. In normal women, BNP/NT-proBNP, left atrial, and left ventricular volumes increase within 48 h postpartum without indications of altered diastolic function.

Abstract P285: Diastolic Dysfunction After Estrogen Loss is Linked to Cardiac Chymase in WKY but Not SHR Rats

Left ventricular diastolic dysfunction (LVDD) develops in response to hypertension and estrogen (E2) loss and is consequent to heart failure in women. To understand the mechanisms underlying the development of LVDD as a result of the interaction between E2 loss and the cardiac RAS, we compared the relationships of LV tissue RAS components and E/e′ between adult SHR (n=13) and WKY (n=9) female rats after ovariectomy (OVX) or sham surgery (intact). In intact rats, E/e′ was higher in SHR vs. WKY rats (P&lt;0.05 strain effect) and after OVX, the diastolic phenotype of WKY’s mimicked that of intact SHR counterparts (Figure). While relationships between RAS enzymatic activities and E/e′ were not significant in SHRs with respect to estrogen status (data not shown), OVX-induced increases in E/e′ were significantly linked to increases in chymase gene expression and enzymatic activity in the WKY strain (Figure). These data indicate that 1) the altered diastolic function in SHR is relatively insensitive to loss of estrogen while the opposite is true in WKY rats, and 2) OVX-induced LVDD in WKY is directly related to increases in cardiac chymase activity. Further elucidation of the interplay between an activated cardiac chymase-mediated RAS metabolism and LVDD following estrogen loss in normotensive subjects is warranted.

0363 : Epidemiological, clinical, paraclinical and therapeutical features of Chronic Heart Failure (CHF) among hypertensive patients

Hypertension is the most common cause for developing chronic heart failure. However, few studies has investigated the consequences of hypertension among patients followed for chronic heart failure. The aim of our study is to investigate the epidemiological, clinical, paraclinical and therapeutic features of patients followed for Chronic Heart Failure and hypertension by comparing them to non-hypertensive patients. Retrospective study of all CHF patients registered in the therapeutic Unit of Chronic Heart failure over a period of 8 years, between June 2006 and March 2015.During this period 3000 cases of CHF were collected and divided into two groups: hypertensive's patients (40.1%) and non-hypertensive's patients (59.9%). Within the sample studied, 537 patients (17.9%) had a balanced hypertension, and 667 patients (22.2%) had an unbalanced hypertension. The mean age was higher in the hypertensive group 84 +/– 2 years vs 53 years with a male predominance in both groups. The etiology of HF (Heart Failure) in the hypentensive and non hypertensive groups was respectively: ischemic heart disease (51.1% vs 65.8), valvular disease (29% vs 19.8%), toxic (2.1% vs 2.2), idiopathic (6.4% vs 9.5%) and others (5% vs 2.6%). Clinically, the study has shown that the hypertensive group was less supportive than non hypertensive. The alteration in diastolic function in echocardiography was more frequent in the hypertension group (25.1%) vs non-hypertension group (18.4%). The proportion of the AF in the hypertensive and non hypertensive groups was respectively 11.9% and 10%. Blood pressure did not influence the risk of re-hospitalization (16.5% in the hypertensive group vs 18.2% in the non-hypertensive group). Hypertension is more associated with supraventricular rhythm disorders, renal failure and diastolic LV dysfunction but has no influence on the occurrence of cardiac decompensation and hospitalization in our contexte. The author hereby declares no conflict of interest

PP.24.07

Objective: Alteration of diastolic function including left atrial volume (LAV), left ventricular mass (LVM) and E/E’ considered a sensitive means for detecting changes in the normal cardiac adaptation to pregnancy. However, only a few study have assessed the influence of dipping pattern of nocturnal blood pressure on diastolic function in pregnancy. The aim of this study is to know the association between dipping pattern of nocturnal blood pressure and diastolic function in pregnancy. Design and method: We analyzed the results of 24 hour ambulatory blood pressure monitoring (ABPM) and echocardiography of 125 women with pregnancy. All of the tests were done in late third trimester of pregnancy. We exclude the pregnant patients with antihypertensive medication or past history of hypertension. Degree of night BP reduction was calculated as (1- (Mean SBP in night time/Mean SBP in day time) x 100. Results: The mean gestational age at the time of test was 29 ± 3 weeks. Mean blood pressure of 24 hour ABPM was 123.4 ± 16.5 / 84.5 ± 11.2 mmHg (day time mean: 126.3 ± 18.3/84.1 ± 9.8 mmHg, night time mean: 117.5 ± 15.7/75.6 ± 7.9 mmHg). Mean degree of night time blood pressure reduction was 8.8 ± 6.1. In echocardiography, mean left ventricular ejection fraction and E/E’ was 61.8 ± 10.1% and 8.9 ± 3.9, respectively. In addition, mean LAV index and LVM index were 29.3 ± 10.1 mL/m2 and 114.9 ± 22.5 g/ m2. Mean deceleration time (DT) was 192.4 ± 31.2 ms. Regarding to the relation between nocturnal blood pressure and diastolic function, LVM index was not correlated with degree of nocturnal blood pressure reduction, However, E/E’ was negatively correlated with degree of nocturnal blood pressure reduction(r = -0.257, p = 0.004). In addition, LAV index showed negative correlation with degree of nocturnal blood pressure reduction (r = -0.637, p < 0.001). Conclusions: In late third trimester of pregnancy, abnormal dipping pattern of nocturnal blood pressure might be associated with enlargement of LAV

Treatment of Brain-Dead Donor Rats with Dimethyloxalylglycine Improves Both Donor and Graft Left-Ventricular Function after Heart Transplantation

Introduction: Cardiac transplantation is the most effective treatment of end-stage heart failure. Brain dead (BD) donors are currently the only reliable source for cardiac grafts. However, hemodynamic instability and cardiac dysfunction have been demonstrated in BD donors and this could therefore also affect posttransplant graft function. Hypothesis: Based upon the protective effect of Prolyl-Hydroxylase (PHD)-Hypoxia Inducible Factor (HIF)-1 pathway against ischemia/reperfusion injury (IRI), we tested the hypothesis that treatment of BD donor rats with the non-selective PHD inhibitor dimethyloxalylglycine (DMOG) results in a better graft heart condition in recipients after heterotopic transplantation. Methods: Lewis rats were injected with one shot DMOG (30 mg/kg i.v.) (n = 7) or equal volume of physiological saline (n = 7) and maintained BD for 5h by a subdurally placed and inflated balloon catheter. Controls were sham-operated (n = 11). Then, hearts were explanted, stored in cold preservation solution, heterotopically transplanted and after 1.5h reperfusion left-ventricular (LV) graft function was evaluated in vivo. Myocardial histological and molecular biological analyses were performed. Results: BD was associated with decreased LV function. DMOG treatment of BD animals resulted in better load-independent contractility and end-diastolic stiffness parameters (ESPVR E´max (mmHg/µl): BD+DMOG: 3.7 ± 0.6 vs BD: 3.1 ± 0.5; EDPVR (mmHg/µl): BD+DMOG: 0.13 ± 0.03 vs BD: 0.31 ± 0.06 p < 0.05). Following transplantation, DMOG treatment of BD donors significantly improved the altered LV systolic and diastolic function (at 80µL volume dP/dtmax (mmHg/s): BD+DMOG: 2284 ± 213 vs BD: 1854 ± 124 p < 0.05; dP/dtmin (mmHg/s): BD+DMOG: 1586 ± 183 vs BD: 1154 ± 74, p < 0.05; Tau-W (ms): BD+DMOG: 33 ± 4 vs BD: 43 ± 9 p < 0.05). Significantly lower myocardial inflammatory cell infiltration and necrosis were detected along with, significantly lower DNA-strand breakage in the DMOG treated BD group compared with BD group. Conclusions: Pre-treatment of BD heart donors with DMOG resulted in a significantly better LV graft function after transplantation. These results support the view that preconditioning of BD donors through the activation of HIF-1 pathway has a protective role against myocardial IRI after transplantation.

Evolution of Left Ventricular Function in the Preterm Infant

The aim of this study was to evaluate left ventricular function in preterm infants from 28 days to near term using echocardiography. Thirty clinically stable preterm infants delivered at <30 weeks' gestational age were prospectively enrolled. At 28 days, conventional, tissue Doppler, and speckle-tracking echocardiography evaluations of left ventricular function were performed, with comparison made to findings in 30 healthy term infants of similar postnatal age. Sixteen preterm infants underwent repeat examinations near term. Compared with controls, preterm infants at 28 days had decreased peak mitral valve (MV) E-wave velocities (P < .01), E/A ratios (P < .0001), annular e' velocities (P < .0001), and e'/a' ratios (P < .0001); increased MV E/e' ratios (P < .01); and lower basal circumferential early diastolic and higher late diastolic strain rates. No significant differences were found in fractional shortening, ejection fraction, and longitudinal or circumferential strain and strain rate between preterm infants and controls. Although preterm infants at 28 days had higher heart rates compared with controls (161 ± 15 vs 142 ± 16 beats/min), no significant correlations existed between heart rate and MV E, E/A ratio, e', e'/a' ratio, and E/e' ratio. Near term, the differences in diastolic function persisted, including decreased MV e'/a' ratio (P < .05), increased E/e' ratio (P < .01), and increased late diastolic strain rate. Clinically stable preterm infants have normal left ventricular systolic function but altered diastolic function, with greater dependence on atrial contraction, the latter of which persists despite nearing term. These findings may be relevant to the management of preterm infants and may relate to the longer term myocardial dysfunction observed in affected adults.

Brain Natriuretic Hormone Predicts Stress-Induced Alterations in Diastolic Function

BackgroundMental stress (MS) reduces diastolic function (DF) and may lead to congestive heart failure with preserved systolic function. Whether brain natriuretic hormone (brain natriuretic peptide [BNP]) mediates the relationship of MS with DF is unknown. MethodsOne hundred sixty individuals aged 30 to 50 years underwent 2-hour protocol of 40-minute rest, videogame stressor and recovery. Hemodynamics, pro-BNP samples and DF indices were obtained throughout the protocol. Separate regression analyses were conducted using rest and stress E/A, E′ and E/E′ as dependent variables. Predictor variables were entered into the stepwise regression models in a hierarchical fashion. At the first level, age, sex, race, height, body mass index, pro-BNP and left ventricular mass (LvM) were permitted to enter the models. The second level consisted of systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR). The final level contained cross-product terms of race by SBP, DBP and HR. ResultsE/A ratio was lower during stress compared to rest and recovery (P < 0.01). Resting E/A ratio was predicted by a regression model of age (−0.31), pro-BNP (0.16), HR (−0.40) and DBP (−0.23) with an R2 = 0.33. Stress E/A ratio was predicted by age (−0.24), pro-BNP (0.08), HR (−0.38) and SBP (−0.21) with total R2 = 0.22. Resting E′ model consisted of age (−0.22), pro-BNP (0.26), DBP (−0.27) and LVM (−0.15) with an R2 = 0.29. Stress E′ was predicted by age (−0.18), pro-BNP (0.35) and LVM (−0.18) with an R2 = 0.18. Resting E/E′ was predicted by race (0.17, B > W) and DBP (0.24) with an R2 = 0.10. Stress E/E′ consisted of pro-BNP (−0.36), height (−0.26) and HR (−0.21) with an R2 = 0.15. Conclusionspro-BNP predicts both resting and stress DF, suggesting that lower BNP during MS may be a marker of diastolic dysfunction in apparently healthy individuals.

Characterization of dystrophin deficient rats: a new model for Duchenne muscular dystrophy.

A few animal models of Duchenne muscular dystrophy (DMD) are available, large ones such as pigs or dogs being expensive and difficult to handle. Mdx (X-linked muscular dystrophy) mice only partially mimic the human disease, with limited chronic muscular lesions and muscle weakness. Their small size also imposes limitations on analyses. A rat model could represent a useful alternative since rats are small animals but 10 times bigger than mice and could better reflect the lesions and functional abnormalities observed in DMD patients. Two lines of Dmd mutated-rats (Dmdmdx) were generated using TALENs targeting exon 23. Muscles of animals of both lines showed undetectable levels of dystrophin by western blot and less than 5% of dystrophin positive fibers by immunohistochemistry. At 3 months, limb and diaphragm muscles from Dmdmdx rats displayed severe necrosis and regeneration. At 7 months, these muscles also showed severe fibrosis and some adipose tissue infiltration. Dmdmdx rats showed significant reduction in muscle strength and a decrease in spontaneous motor activity. Furthermore, heart morphology was indicative of dilated cardiomyopathy associated histologically with necrotic and fibrotic changes. Echocardiography showed significant concentric remodeling and alteration of diastolic function. In conclusion, Dmdmdx rats represent a new faithful small animal model of DMD.

Hypertrophic cardiomyopathy associated Lys104Glu mutation in the myosin regulatory light chain causes diastolic disturbance in mice

We have examined, for the first time, the effects of the familial hypertrophic cardiomyopathy (HCM)-associated Lys104Glu mutation in the myosin regulatory light chain (RLC). Transgenic mice expressing the Lys104Glu substitution (Tg-MUT) were generated and the results were compared to Tg-WT (wild-type human ventricular RLC) mice. Echocardiography with pulse wave Doppler in 6month-old Tg-MUT showed early signs of diastolic disturbance with significantly reduced E/A transmitral velocities ratio. Invasive hemodynamics in 6month-old Tg-MUT mice also demonstrated a borderline significant prolonged isovolumic relaxation time (Tau) and a tendency for slower rate of pressure decline, suggesting alterations in diastolic function in Tg-MUT. Six month-old mutant animals had no LV hypertrophy; however, at >13months they displayed significant hypertrophy and fibrosis. In skinned papillary muscles from 5 to 6month-old mice a mutation induced reduction in maximal tension and slower muscle relaxation rates were observed. Mutated cross-bridges showed increased rates of binding to the thin filaments and a faster rate of the power stroke. In addition, ~2-fold lower level of RLC phosphorylation was observed in the mutant compared to Tg-WT. In line with the higher mitochondrial content seen in Tg-MUT hearts, the MUT-myosin ATPase activity was significantly higher than WT-myosin, indicating increased energy consumption. In the in vitro motility assay, MUT-myosin produced higher actin sliding velocity under zero load, but the velocity drastically decreased with applied load in the MUT vs. WT myosin. Our results suggest that diastolic disturbance (impaired muscle relaxation, lower E/A) and inefficiency of energy use (reduced contractile force and faster ATP consumption) may underlie the Lys104Glu-mediated HCM phenotype.

Long-term obesity promotes alterations in diastolic function induced by reduction of phospholamban phosphorylation at serine-16 without affecting calcium handling.

Few studies have evaluated the relationship between the duration of obesity, cardiac function, and the proteins involved in myocardial calcium (Ca(2+)) handling. We hypothesized that long-term obesity promotes cardiac dysfunction due to a reduction of expression and/or phosphorylation of myocardial Ca(2+)-handling proteins. Thirty-day-old male Wistar rats were distributed into two groups (n = 10 each): control (C; standard diet) and obese (Ob; high-fat diet) for 30 wk. Morphological and histological analyses were assessed. Left ventricular cardiac function was assessed in vivo by echocardiographic evaluation and in vitro by papillary muscle. Cardiac protein expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a), calsequestrin, L-type Ca(2+) channel, and phospholamban (PLB), as well as PLB serine-16 phosphorylation (pPLB Ser(16)) and PLB threonine-17 phosphorylation (pPLB Thr(17)) were determined by Western blot. The adiposity index was higher (82%) in Ob rats than in C rats. Obesity promoted cardiac hypertrophy without alterations in interstitial collagen levels. Ob rats had increased endocardial and midwall fractional shortening, posterior wall shortening velocity, and A-wave compared with C rats. Cardiac index, early-to-late diastolic mitral inflow ratio, and isovolumetric relaxation time were lower in Ob than in C. The Ob muscles developed similar baseline data and myocardial responsiveness to increased extracellular Ca(2+). Obesity caused a reduction in cardiac pPLB Ser(16) and the pPLB Ser(16)/PLB ratio in Ob rats. Long-term obesity promotes alterations in diastolic function, most likely due to the reduction of pPLB Ser(16), but does not impair the myocardial Ca(2+) entry and recapture to SR.

Dexamethasone and recombinant human activated protein C improve myocardial function and efficiency during experimental septic shock.

Corticosteroids have been shown to reduce short-term mortality during septic shock and therefore recommended in the most severe patients as adjuvant therapy. Until recently, recombinant human activated protein C (APC) was also considered in the management of more severe cases. As myocardial depression has long been recognized as a manifestation of organ dysfunction during septic shock, we examined whether corticosteroids (dexamethasone, 150 µg/kg per hour) and/or APC (33 µg/kg per hour) treatments improve sepsis-induced cardiac dysfunction during cecal ligature and puncture-induced septic shock in Wistar rats. All rats received intravenous saline resuscitation (10 mL/kg per hour) and antibiotics. Eighteen hours after surgery, anesthesia was performed (isoflurane), and myocardial function was assessed using a conductance catheter introduced into the left ventricle. Rats were then killed; blood and heart were harvested for biological analysis, including radical oxygen species determination. Cecal ligature and puncture induced hypotension, depression of myocardial systolic performance (demonstrated by significant decreases in dP/dtmax [first derivative of maximal developed pressure during isovolumetric contraction], end-systolic pressure-volume relationship, and preload recruitable stroke work) and alteration of diastolic function (dP/dtmin [first derivative of minimal developed pressure during isovolumetric relaxation]), whereas dexamethasone, APC, and their combination thereof allowed correction of hemodynamic disorders and improved myocardial mechanical efficiency. Cecal ligature and puncture was associated with higher levels of nitric oxide and superoxide anion (O2) in heart (electron paramagnetic resonance studies) and consequently peroxynitrite. Dexamethasone and APC also improved cardiac dysfunction by downregulating the inducible nitric oxide synthase pathway and reducing myocardial oxidative stress.