Biventricular Cardiac Function Research Articles

Morphological and functional cardiac alterations in children with congenital Zika syndrome and severe neurological deficits.

Zika virus infection during pregnancy causes fetal microcephaly and brain damage. Congenital Zika syndrome (CZS) is characterized by systemic involvement with diffuse muscle impairment, a high frequency of arthrogryposis, and microphthalmia. Cardiac impairment in CZS has rarely been evaluated. Our study assessed morphology and biventricular cardiac function in children with CZS and advanced neurological dysfunction. This cross-sectional study was conducted on 52 children with CZS (Zika group; ZG) and 25 healthy children (control group; CG) in Paraiba, Brazil. Clinical evaluation, electrocardiogram (EKG), and transthoracic echocardiogram (TTE) were performed on all children. Additionally, troponin I and natriuretic peptide type B (BNP) levels, the degree of cerebral palsy, and neuroimaging findings were assessed in the ZG group. The median age of the study population was 5 years in both groups, and 40.4% (ZG) and 60% (CG) were female. The most prevalent electrocardiographic alteration was sinus arrhythmia in both the ZG (n = 9, 17.3%) and CG (n = 4, 16%). The morphological parameters adjusted for Z score were as follows: left ventricular (LV) end-diastolic diameter in ZG: -2.36 [-5.10, 2.63] vs. CG: -1.07 [-3.43, 0.61], p<0.001); ascending aorta (ZG: -0.09 [-2.08, 1.60] vs. CG: 0.43 [-1.47, 2.2], p = 0.021); basal diameter of the right ventricle (RV) (ZG: -2.34 [-4.90, 0.97] vs. CG: -0.96 [-2.21, 0.40], p<0.01); and pulmonary artery dimension (ZG: -2.13 [-5.99, 0.98] vs. CG: -0.24 [-2.53, 0.59], p<0.01). The ejection fractions (%) were 65.7 and 65.6 in the ZG and CG, respectively (p = 0.968). The left atrium volume indices (mL/m2) in the ZG and CG were 13.15 [6.80, 18.00] and 18.80 [5.90, 25.30] (p<0.01), respectively, and the right atrium volume indices (mL/m2) were 10.10 [4.90, 15.30] and 15.80 [4.10, 24.80] (p<0.01). The functional findings adjusted for Z score were as follows: lateral systolic excursion of the mitral annular plane (MAPSE) (ZG: 0.36 [-2.79, 4.71] vs. CG: 1.79 [-0.93, 4.5], p = 0.001); tricuspid annular plane systolic excursion (TAPSE) (ZG: -2.43 [-5.47, 5.09] vs. CG: 0.07 [-1.98, 3.64], p<0.001); and the S' of the RV (ZG: 1.20 [3.35, 2.90] vs. CG: -0.20 [-2.15, 1.50], p = 0.0121). No differences in biventricular strain measurements were observed between the groups. Troponin I and BNP levels were normal in in the ZG. Grade V cerebral palsy and subcortical calcification were found in 88.6% and 97.22% of children in the ZG group, respectively. A reduction in cardiac dimensions and functional changes were found in CZS patients, based on the TAPSE, S' of the RV, and MAPSE, suggesting the importance of cardiac evaluation and follow-up in this group of patients.

Evaluation of morphology and biventricular cardiac function in children with congenital zika syndrome

Abstract Introduction The infection caused by the Zika virus during pregnancy causes microcephaly and brain damage in fetus, and the systemic involvement with diffuse muscle impairment, high frequency of arthrogryposis and microphthalmia, characterizes congenital Zika syndrome (CZS). The cardiac impairment in CZS was rarely evaluated. Purpose To evaluate the morphology and biventricular cardiac function in children affected by CZS, using electrocardiogram (EKG), echocardiogram and biomarkers dosage. Methods This is a cross-sectional study conducted with 52 children with CZS (GZ) compared with 25 healthy children (CG). Clinical evaluation, EKG, and echocardiogram were performed in all of them. Also, troponin I and natriuretic peptide type B (BNP) dosages were performed in GZ. Results The median age of the studied population was 5 years in groups, GZ (3 to 6 years), CG (3 to 8 years), 40.4% (GZ) and 60% (CG) of female gender. The most prevalent electrocardiographic alteration was sinus arrhythmia, GZ: 9 (17.3%) and CG: 4 (16%). The echocardiographic evaluation showed the morphological parameters adjusted for the Z score: left ventricular (LV) end-diastolic diameter in GZ: −2.36 [−5.10, 2.63] vs CG: −1.07 [−3.43, 0.61], p&amp;lt;0.001; LV end-systolic diameter in GZ: −1.02 [−4.49, 0.62] vs CG: −0.06 [−1.98, 2.28], p&amp;lt;0.01; ascending aorta in GZ: −0.09 [−2.08, 1.60] vs CG: 0.43 [−1.47, 2.2], p: 0.021; basal diameter of the right ventricle (RV) in GZ: −2.34 [−4.90, 0.97] vs CG: −0.96 [−2.21, 0.40], p&amp;lt;0.01; pulmonary artery dimension in GZ: −2.13 [−5.99, 0.98] vs CG: −0.24 [−2.53, 0.59], p&amp;lt;0.01. The left atrium volume index (ml/m2) was in GZ: 13.15 [6.80, 18.00] vs CG: 18.80 [5.90, 25.30], p&amp;lt;0.01; right atrium volume index (ml/m2) in GZ: 10.10 [4.90, 15.30] vs CG: 15.80 [4.10, 24.80], p&amp;lt;0.01. The septum systolic excursion of the mitral annular plane (MAPSE, cm) was in GZ: 0.98 [0.78, 1.66] vs CG: 1.25 [1.07, 1.56], p&amp;lt;0.01; and lateral annulus: 1.25 [0.81, 1.86] vs CG: 1.46 [1.07, 1.83], p&amp;lt;0.001; tricuspid annular plane systolic excursion (cm) in GZ: 1.52 [1.13, 2.34] vs CG: 1.90 [1.62, 2.35], p&amp;lt;0.01; S' of the RV (cm/s) was in GZ: 10.60 [6.49, 21.00] vs CG: 12.80 [9.19, 16.20], p&amp;lt;0.01. The peak of late mitral inflow (A wave, cm/s) was in GZ: 64 [24, 134] vs CG: 52 [26, 94], p=0.02; peak of late diastolic mitral annular wave (e') of septum (cm/s) was GZ: 15 [7, 23] vs CG: 17 [12, 27], p&amp;lt;0.01; peak of e' lateral (cm/s) was in GZ: 11 [7, 19], CG: 12 [9, 15], p&amp;lt;0,016; E/e' ratio was GZ: 7.52 [4.57, 10.78] vs CG: 6.41 [4.75, 12.64], p&amp;lt;0.01. The LV longitudinal and circumferential and RV longitudinal strain measurements showed no difference between the groups. Conclusion A reduction in cardiac dimensions and biventricular dysfunction was found in CZS, showing an early cardiac impairment, which will enable to establishment early therapies, avoiding severe heart failure. Funding Acknowledgement Type of funding sources: None.

C76 A PARTICULAR CASE OF MULTIORGAN FAILURE

Abstract We reported a case of a 42–year–old man with no major pathologies, symptomatic for a few days for headache, fever and dysuria. For worsening dyspnea and tachycardia the patient was admitted to emergency room. He was markedly hypoxic with severe left ventricular dysfunction, therefore in the suspicion of myocarditis, the patient was centralized in our ICCU. The patient appeared tachycardic (sinus tachycardia 160 bpm), normotensive but hypoperfused (svO2 40%, lac 5 mmol/l, oliguric) and severely hypoxemic despite mechanical ventilation. In the first hours the condition of severe hypoxia persisted (P/F &amp;lt;100), despite optimization of ventilation and curarization, associated with bilateral interstitial edema, marked leukocytosis and PCT&amp;gt; 100. For this reason cultural exams were performed and large spectrum antibiotic therapy started. After about 4 hours the patient was still hypotensive and hypoperfused, despite support with IABP and vasopressors, therefore femoro–femoral VA–ECMO was implanted. There was a rapid improvement of hemodynamic status, peripheral perfusion and reduction of pulmonary congestion but a marked leukocytosis and PCT&amp;gt; 100 persisted with negative cultures. On the 4th day, during ECMO weaning we assisted to wide and rapid pressure fluctuations (SBP from 250 to 60 mmHg in a few minutes). Therefore total body CT was performed in the suspected pheochromocytoma and this showed a necrotized left adrenal mass of about 9 cm and multiple right cerebral hemorrhagic lesions. Therapy with IV alfa–blockers was promptly started and for the marked hemodynamic instability, in the presence of cerebral hemorrhage, left adrenalectomy was performed with removal of the mass approximately 10 hours after diagnosis. In the post–operative phase there was a stabilization of the pressure profile with complete recovery of the biventricular cardiac function, a rapid reduction in inflammation indices and recovery of renal function. The patient gradually recovered to a state of consciousness with residual hemiplegia. Histological examination confirmed the diagnosis of pheochromocytoma. Conclusions The present case represents an example of a catecholaminergic crisis, with fulminant onset and multiorgan dysfunction that initially made diagnosis difficult. Emergency adrenalectomy has conflicting evidence in the literature but in this case it was necessary for pressure instability in the context of cerebral hemorrhage.

Using 7.0 T cardiac magnetic resonance to investigate the effect of estradiol on biventricular structure and function of ovariectomized rats exposed to chronic hypobaric hypoxia at high altitude

BackgroundDespite that estradiol can reduce the risk of cardiovascular diseases in ovariectomized animals in the plains, its effect on animals at high altitude has seldom been reported. We hypothesize that estradiol can ameliorate cardiac damage to ovariectomized rats induced by chronic exposure to hypobaric hypoxia at high altitude. PurposeThis study was intended to investigate whether cardiovascular magnetic resonance (CMR) imaging could reveal cardioprotective effect of estradiol on ovariectomized rats under chronic exposure to hypobaric hypoxia at high altitude. MethodsThirty-two rats were randomized into the Control group (Plain), HH + Sham group (Hypobaric Hypoxia + Sham), HH + OVX group (Hypobaric Hypoxia + Bilateral Ovariectomy) and HH-OVX + E2 group (Hypobaric Hypoxia + Bilateral Ovariectomy + Estradiol, 50 μg/kg, 3 times a week, for 6 weeks) (n = 8 per group). Except the Control group (altitude: 500 m), rats in other groups were subcutaneously injected with 17β -estradiol or vehicle and exposed to chronic hypobaric hypoxia in Qinghai-Tibet Plateau (altitude: 4250 m), China, for 6 weeks. Biventricular cardiac function and global strain of the rats were measured by CMR and analyzed using the cine tissue tracking techniques. Biochemical tests, histopathology and electronic microscopy were used to evaluate the protective effect of estradiol on the heart tissue of ovariectomized rats exposed to a high-altitude environment. ResultsThe biventricular ejection fraction and global strains decreased in the HH + OVX group compared with that in the Control group (all p < 0.05). All the aforementioned changes in the HH + OVX group ameliorated in the HH-OVX + E2 group (all p < 0.05). Estradiol also alleviated the right ventricular dilatation and hypertrophy in the HH + OVX group (all p < 0.05). In addition, histological and biochemical analyses also supported these in vivo results. ConclusionsEstradiol ameliorated the biventricular structural and functional damage in ovariectomized rats exposed to chronic hypobaric hypoxia at high altitude.

Biventricular Myocardial Strain Analysis in Patients with Pulmonary Arterial Hypertension Using Cardiac Magnetic Resonance Tissue-Tracking Technology.

: ObjectivesTo evaluate both left and right ventricular (LV and RV) function in patients with pulmonary arterial hypertension (PAH) using cardiac magnetic resonance tissue-tracking (CMR-TT) technology and explore its clinical value. Methods: A total of 79 participants (including 47 patients with PAH and 32 healthy controls) underwent cardiac magnetic resonance imaging (CMRI) with a short-axis balanced steady-state free precession (SSFP) sequence. The biventricular cardiac function parameters and strain parameters were obtained by postprocessing with CVI42 software. A comparative analysis was performed between the LV and RV strain parameters in all PAH patients and in PAH patients with reduced or preserved cardiac function. Results: The results showed preferable repeatability of CMR-TT in analyzing the global radial strain (GRS), circumferential strain (GCS), and longitudinal strain (GLS) of the left and right ventricles in the PAH group. The GRS, GCS, and GLS of the left and right ventricles except for LV GRS (LVGRS) of PAH patients were significantly lower than those of healthy controls (p < 0.05 for all). The GRS and GCS of the left and right ventricles showed a moderate correlation in the PAH group (r = 0.323, p = 0.02; r = 0.301, p = 0.04, respectively). PAH patients with preserved RV function (n = 9) showed significantly decreased global and segmental RS, CS, and LS of the right ventricles than healthy controls (p < 0.05 for all), except for basal RVGCS (RVGCS-b, p = 0.996). Only the LVGLS was significantly different between the PAH patients with preserved LV function (n = 32) and the healthy controls (−14.23 ± 3.01% vs. −16.79 ± 2.86%, p < 0.01). Conclusions: As a nonradioactive and noninvasive technique, CMR-TT has preferable feasibility and repeatability in quantitatively evaluating LV and RV strain parameters in PAH patients and can be used to effectively detect early biventricular myocardial damage in patients with PAH.

Abstract 8963: Mitochondrial Dysfunction in Peripheral Blood Mononuclear Cells is Associated With Heart Failure in Patients With Single Ventricle Congenital Heart Disease

Introduction: Heart failure (HF) remains a leading cause of death and indication for heart transplant in children with single ventricle congenital heart disease (SV). The purpose of this study was to evaluate mitochondrial function in circulating peripheral blood mononuclear cells (PBMCs) from failing pediatric SV patients compared to age-matched nonfailing controls (NF). Prior data obtained at the time of cardiac transplant shows associations between SV PBMC mitochondrial function and ex-vivo high-resolution respirometry analysis conducted on permeabilized myocardial fibers, suggesting that PBMCs may be surrogates for myocardial mitochondrial function. Hypothesis: SV patients will have impaired mitochondrial respiratory capacity in circulating PBMCs. Methods: Subjects were recruited from Children’s Hospital Colorado. SV patients ages 0-18 years were included. Healthy children 0-18 years of age with normal biventricular cardiac function were included as a control group. PBMCs were isolated from whole blood (EDTA) using density gradient centrifugation in Histopaque Accuspin tubes. Oxygen consumption rates (OCR) of intact PBMCs were measured using the Seahorse XFe Bioanalyzer (Agilent). OCR is measured under 4 different conditions (Figure 1): baseline, after addition of oligomycin, after addition of carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone, and after addition of antimycin A and rotenone. Results: Baseline respiratory capacity, coupling efficiency, and mitochondrial oxygen flux were decreased in failing SV PBMCs relative to NF controls (Figure 2). Conclusions: Our results demonstrate impaired mitochondrial respiratory capacity in circulating PBMCs of pediatric SV patients relative to healthy age-matched controls. Combined with our ex vivo data showing decreased mitochondrial function in failing SV myocardium, our findings suggests PBMCs may serve as a viable non-invasive biomarker of myocardial respiratory capacity.

Cardiac maladaptation in obese pregnant women at term.

Obesity is an increasing problem worldwide, with well recognized detrimental effects on cardiovascular health; however, very little is known about the effect of obesity on cardiovascular adaptation to pregnancy. The aim of the present study was to compare biventricular cardiac function at term between obese pregnant women and pregnant women with normal body weight, utilizing conventional echocardiography and speckle-tracking assessment. This was a prospective case-control study of 40 obese, but otherwise healthy, pregnant women with a body mass index (BMI) of ≥ 35 kg/m2 and 40 healthy pregnant women with a BMI of ≤ 30 kg/m2 . All women underwent a comprehensive echocardiographic examination and speckle-tracking assessment at term. Obese pregnant women, compared with controls, had significantly higher systolic blood pressure (117 vs 109 mmHg; P = 0.002), cardiac output (6.73 vs 4.90 L/min; P < 0.001), left ventricular (LV) mass index (74vs64 g/m2 ;P < 0.001)andrelativewall thickness (0.43 vs 0.37; P < 0.001). Diastolic dysfunction was present in five (12.5%) controls and 16 (40%) obese women (P = 0.004). In obese women, compared with controls, LV global longitudinal strain (-15.59 vs -17.61%; P < 0.001), LV endocardial (-17.30 vs -19.84%; P < 0.001) and epicardial (-13.10 vs -15.73%; P < 0.001) global longitudinal strain as well as LV early diastolic strain rate (1.05 vs 1.24 /s; P = 0.006) were all significantly reduced. No differences were observed in the degree of LV twist and torsion between the two groups. Morbidly obese, but otherwise healthy, pregnant women at term had significant LV hypertrophy with evidence of diastolic dysfunction and impaired deformation indices compared with pregnant women of normal weight. These findings are likely to represent a maladaptive response of the heart to volume overload in obese pregnancy. The impact of theses changes on pregnancy outcome and long-term maternal outcome is unclear. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Improvement in Biventricular Cardiac Function After Ambulatory Counterpulsation

The NupulseCV intravascular ventricular assist system (iVAS), which consists of a durable pump placed through the subclavian artery, provides extended-duration ambulatory counterpulsation. This study investigated the effect of iVAS on biventricular cardiac function. We reviewed all heart failure patients who received iVAS implantation as a bridge to transplantation or a bridge to candidacy since April 2016 as part of the iVAS first-in-humans and subsequent feasibility study. We compared data of transthoracic echocardiography performed just before implantation (without iVAS support) and again at 30 days or just before explantation (on iVAS support). Eighteen patients (58.8 ± 7.4 years old and 15 male) received iVAS support for 53 ± 43 days. Fourteen patients were bridged to cardiac replacement therapy after 35 ± 19 days and the remaining 4 patients had been supported for 118 ± 41 days. There were no deaths during iVAS support. At 30 days, there was a significant improvement in left ventricular ejection fraction (16.5% ± 11.9% vs 24.4% ± 12.8%; P = .007) and marked reduction in left atrial size (62.7 ± 35.7 mL/m2 vs 33.8 ± 17.2 mL/m2; P < .001). Right ventricular fractional area change improved dramatically (25.4% ± 12.9% vs 42.1% ± 12.4%; P < .001). All other right ventricular and right atrial parameters improved significantly as well (size, tricuspid annular plane systolic excursion, and velocity of tricuspid annular systolic motion). Improvement in biventricular cardiac function was observed after 30 days of iVAS support. Further studies should examine the use of this technology as a bridge to recovery.

INFERIOR VENA CAVA DILATATION PREDICTS GLOBAL CARDIAC DYSFUNCTION IN ARDS: A STRAIN ECHOCARDIOGRAPHIC STUDY

SESSION TITLE: Cardiovascular Disease SESSION TYPE: Original Investigations PRESENTED ON: 10/09/2018 02:30 PM - 03:30 PM PURPOSE: The evaluation of the inferior vena cava (IVC) with ultrasound is frequently utilized to gauge intravascular volume in critically ill patients. The reliability of this technique has been questioned on mechanically ventilated patients, and specific data about its use in acute respiratory distress syndrome (ARDS) is practically nonexistent. We examined the utility of IVC diameter in the evaluation of cardiac and hemodynamic performances in patients with ARDS. METHODS: At a quaternary academic center, we did a retrospective cross-sectional analysis of Doppler Echocardiograms of ventilated patients with moderate-severe ARDS. Right ventricular(RV) fractional area change(RVFAC), tricuspid annular plane systolic excursion(TAPSE) and velocity(S'), and IVC diameter were estimated according to the American Society of Echocardiography guidelines. Using speckle tracking echocardiography, RV free wall(RVFWS), RV septal(RVSS) and RV Global longitudinal(RVGLS) strain were calculated. Left ventricular(LV) ejection fraction(LVEF) and LV diastolic function variables were also measured. Pertinent hemodynamic, ventilatory and laboratory data were collected. RESULTS: Fifty-one patients were included. A bimodal IVC classification method created two groups (IVC<2.1cm and IVC≥2.1cm). An IVC≥2.1cm was associated with lower systolic blood pressure (105±15 vs 124±8 mmHg, p:0.002), higher creatinine (1.4±0.6 vs 0.9±0.4 mg/dL, p:0.004), increased lactate (3.2±1.5 vs 1.8±1.2 mmol/L, p:0.002), higher incidence of shock (62% vs 30%, p:0.02), higher central venous pressure(CVP) (16±4 vs 10±4 mmHg, p:0.0001) and higher systolic pulmonary pressure. RVFAC, TAPSE, S', RVFWS and RVGLS (but not RVSS), were also depressed in this group. An IVC≥2.1cm was also associated with lower LVEF (55±12 vs 67±10%, p:0.01) and abnormal LV diastolic function. Positive correlations of RVFAC, TAPSE, S', RVFWS, RVSS and RVGLS with LVEF were observed. CVP and IVC negatively correlated with LVEF. Regression analysis demonstrated that the best predictor of IVC diameter was CVP (R2:0.35, p:0.001) and that the association RVSS+IVC diameter was a strong independent predictor of LVEF (R2:0.25, p:0.002). No significant differences in ventilatory parameters were observed. CONCLUSIONS: In patients with ARDS, an IVC≥2.1cm was independently associated with worse biventricular cardiac function and more abnormal hemodynamic performance. The biventricular interaction of a functionally impaired RV with the LV only partially explained our observations. The role of systemic negative inotropic factors (i.e., inflammatory response mediators) should be considered. CLINICAL IMPLICATIONS: The hemodynamic management of ARDS patients is extremely challenging. Our study suggests that in moderate-severe ARDS, an IVC≥2.1cm is strongly associated with poor global hemodynamic performance and should signal intensivists the potential necessity for a better hemodynamic optimization. DISCLOSURES: No relevant relationships by Romel Garcia-Montilla, source=Web Response No relevant relationships by Stephen Heitner, source=Web Response No relevant relationships by Faryal Imam, source=Web Response Study PI relationship with United Therapeutics Please note: $20001 - $100000 Added 11/29/2017 by Akram Khan, source=Web Response, value=Grant/Research Support study PI relationship with AstraZeneca Please note: $20001 - $100000 Added 11/29/2017 by Akram Khan, source=Web Response, value=Grant/Research Support Study PI relationship with Glaxo SmithKline Please note: $20001 - $100000 Added 11/29/2017 by Akram Khan, source=Web Response, value=Grant/Research Support Study PI relationship with Actelion pharmaceuticals Please note: $20001 - $100000 Added 11/29/2017 by Akram Khan, source=Web Response, value=Grant/Research Support Study PI relationship with National Institute of Health Please note: >$100000 Added 11/29/2017 by Akram Khan, source=Web Response, value=Grant/Research Support Removed 11/29/2017 by Akram Khan, source=Web Response Study PI relationship with Intermune Please note: $20001 - $100000 Added 11/29/2017 by Akram Khan, source=Web Response, value=Grant/Research Support Study PI relationship with Lung LLC Please note: $20001 - $100000 Added 11/29/2017 by Akram Khan, source=Web Response, value=Grant/Research Support Research Grant relationship with Actelion pharmaceuticals Please note: $20001 - $100000 Added 03/02/2018 by Akram Khan, source=Web Response, value=Grant/Research Support Research Grant relationship with AstraZeneca Please note: $20001 - $100000 Added 03/02/2018 by Akram Khan, source=Web Response, value=Grant/Research Support Research Grant relationship with Bristol-Myers Squibb Please note: $5001 - $20000 Added 03/02/2018 by Akram Khan, source=Web Response, value=Grant/Research Support Research Grant relationship with EMD Serono Please note: $5001 - $20000 Added 03/02/2018 by Akram Khan, source=Web Response, value=Grant/Research Support Research Grant relationship with Genentech Please note: $5001 - $20000 Added 03/02/2018 by Akram Khan, source=Web Response, value=Grant/Research Support Research Grant relationship with Glaxo SmithKline Please note: $20001 - $100000 Added 03/02/2018 by Akram Khan, source=Web Response, value=Grant/Research Support Research Grant relationship with Intermune Please note: $20001 - $100000 Added 03/02/2018 by Akram Khan, source=Web Response, value=Grant/Research Support Research Grant relationship with United Therapeutics Please note: >$100000 Added 03/02/2018 by Akram Khan, source=Web Response, value=Grant/Research Support No relevant relationships by Mi Miao, source=Web Response No relevant relationships by Srini Mukundan, source=Web Response No relevant relationships by Kathryn Stinson, source=Web Response

Ageing changes in biventricular cardiac function in male and female baboons (Papio spp.).

Life course changes in cardiovascular function in a non-human primate have been comprehensively characterized. Age-related declines in normalized left ventricular stroke volume and cardiac output were found with corresponding decreases in biventricular ejection fractions and filling rates. There were age-related decreases in male and female baboon normalized left ventricular myocardial mass index, which declined at similar rates. Systolic functional declines in right ventricular function were observed with age, similar to the left ventricle. Sex differences were found in the rates and directions of right ventricular volume changes along with decreased end-systolic right ventricular sphericity. The results validate the baboon as an appropriate model for translational studies of cardiovascular functional decline with ageing. Previous studies reported cardiac function declines with ageing. This study determined changes in biventricular cardiac function in a well-characterized baboon model. Cardiac magnetic resonance imaging measured key biventricular parameters in 47 baboons (22 female, age 4-23years). ANCOVA assessed sex and age changes with P< 0.05 deemed significant. Stroke volume, cardiac output and other cardiac functional parameters were normalized to body surface area. There were similar, age-related rates of decrease in male (M) and female (F) normalized left ventricular (LV) myocardial mass index (M: -1.2gm-2 year-1 , F: -0.9gm-2 year-1 ). LV ejection fraction declined at -0.96%year-1 (r= -0.43, P= 0.002) and right ventricular (RV) ejection fraction decreased at -1.2%year-1 (r= -0.58, P< 0.001). Normalized LV stroke volume fell at -1.1mlm-2 year-1 (r= -0.47, P= 0.001), normalized LV ejection rate at -3.8mls-1 m-2 year-1 (r= -0.43, P< 0.005) and normalized LV filling rate at -4.1mls-1 m-2 year-1 (r= -0.44, P< 0.005). Also, RV wall thickening fraction decreased with age (slope= -1%year-1 , P= 0.008). RV ejection rate decreased at -3.6mls-1 m-2 year-1 (P= 0.002) and the normalized average RV filling rate dropped at -3.7mls-1 m-2 year-1 (P< 0.0001). End-systolic RV sphericity index also dropped with age (r= -0.33, P= 0.02). Many observed changes parallel previously reported data in human and animal studies. These measured biventricular functional declines in hearts with ageing from the closest experimental primate species to man underscore the utility of the baboon model for investigating mechanisms related to heart ageing.

A model of cardiac contraction based on novel measurements of tension development in human cardiomyocytes

Experimental data from human cardiac myocytes at body temperature is crucial for a quantitative understanding of clinically relevant cardiac function and development of whole-organ computational models. However, such experimental data is currently very limited. Specifically, important measurements to characterize changes in tension development in human cardiomyocytes that occur with perturbations in cell length are not available. To address this deficiency, in this study we present an experimental data set collected from skinned human cardiac myocytes, including the passive and viscoelastic properties of isolated myocytes, the steady-state force calcium relationship at different sarcomere lengths, and changes in tension following a rapid increase or decrease in length, and after constant velocity shortening. This data set is, to our knowledge, the first characterization of length and velocity-dependence of tension generation in human skinned cardiac myocytes at body temperature.We use this data to develop a computational model of contraction and passive viscoelasticity in human myocytes. Our model includes troponin C kinetics, tropomyosin kinetics, a three-state crossbridge model that accounts for the distortion of crossbridges, and the cellular viscoelastic response. Each component is parametrized using our experimental data collected in human cardiomyocytes at body temperature. Furthermore we are able to confirm that properties of length-dependent activation at 37°C are similar to other species, with a shift in calcium sensitivity and increase in maximum tension. We revise our model of tension generation in the skinned isolated myocyte to replicate reported tension traces generated in intact muscle during isometric tension, to provide a model of human tension generation for multi-scale simulations. This process requires changes to calcium sensitivity, cooperativity, and crossbridge transition rates. We apply this model within multi-scale simulations of biventricular cardiac function and further refine the parametrization within the whole organ context, based on obtaining a healthy ejection fraction. This process reveals that crossbridge cycling rates differ between skinned myocytes and intact myocytes.

Utility of Functional Hemodynamics and Echocardiography to Aid Diagnosis and Management of Shock.

The utility of functional hemodynamics and bedside ultrasonography is increasingly recognized as advantageous for both improved diagnosis and management of shock states. In contrast to conventional "static" measures, "dynamic" hemodynamic measures and bedside imaging modalities enhance pathophysiology-based comprehensive understanding of shock states and the response to therapy. The current editions of major textbooks in the primary specialties--in which clinicians routinely encounter patients in shock--including surgery, anesthesia, emergency medicine, and internal medicine continue to incorporate traditional (conventional) descriptions of shock that use well-described (but potentially misleading) intravascular pressures to classify shock states. Reliance on such intravascular pressure measurements is not as helpful as newer "dynamic" functional measures including ultrasonography to both better assess volume responsiveness and biventricular cardiac function. This review thus emphasizes the application of current functional hemodynamics and ultrasonography to the diagnosis and management of shock as a contrast to conventional "static" pressure-based measures.

Integrin-linked kinase mediates force transduction in cardiomyocytes by modulating SERCA2a/PLN function.

Human dilated cardiomyopathy (DCM) manifests as a profound reduction in biventricular cardiac function that typically progresses to death or cardiac transplantation. There is no effective mechanism-based therapy currently available for DCM, in part because the transduction of mechanical load into dynamic changes in cardiac contractility (termed mechanotransduction) remains an incompletely understood process during both normal cardiac function and in disease states. Here we show that the mechanoreceptor protein integrin-linked kinase (ILK) mediates cardiomyocyte force transduction through regulation of the key calcium regulatory protein sarcoplasmic/endoplasmic reticulum Ca(2+)ATPase isoform 2a (SERCA-2a) and phosphorylation of phospholamban (PLN) in the human heart. A non-oncogenic ILK mutation with a synthetic point mutation in the pleckstrin homology-like domain (ILK(R211A)) is shown to enhance global cardiac function through SERCA-2a/PLN. Thus, ILK serves to link mechanoreception to the dynamic modulation of cardiac contractility through a previously undiscovered interaction with the functional SERCA-2a/PLN module that can be exploited to rescue impaired mechanotransduction in DCM.

What is the future of acute respiratory distress syndrome after the Berlin definition?

To analyze recently published articles in the medical literature that studied distinct aspects of adult patients with acute respiratory distress syndrome (ARDS) after the new Berlin definition introduced in 2012. The degree of ARDS severity according to this new classification correlated well with extravascular lung water index, pulmonary vascular permeability index and the finding of diffuse alveolar damage on autopsy. The new possibility of bedside echocardiographic evaluation of biventricular cardiac function is indicating the necessity of including a subgroup of severity of patients with right ventricular dysfunction. High-resolution CT evaluation showed that signs of pulmonary fibroproliferation in early ARDS predict increased ventilator dependency, multiple organ failure and mortality. The median development of ARDS 1 or 2 days after hospital admission emphasizes the need for ARDS intrahospital prevention, especially protective ventilation in non-ARDS patients. The better outcome with the use of prone position in patients with PaO2/FIO2 below 150 recently observed questioned the Berlin definition thresholds to decide the future best treatment strategies according to the proposed degree of severity of the syndrome. The impact of the Berlin definition of ARDS on the incidence, better treatment stratification and mortality ratio of ARDS is still to be determined.

The effects of exercise at high altitude on high-sensitivity cardiac troponin release and associated biventricular cardiac function

It has been consistently shown that heavy exercise leads to cardiac troponin (cTn) release and variable changes in post exercise cardiac function. This relationship has not been explored at increasing or significant high altitude (HA). This study assessed the effects of exercise at progressively increasing HA on high-sensitivity (hs)-cTnT levels and their relationship to biventricular cardiac function and severity of acute mountain sickness (AMS). Transthoracic echocardiograms, hs-cTnT levels and AMS scores were measured at rest at 1,300m then repeated post exercise and 12h later after progressive trekking to 3,440, 4,270m and at 5,150m (after trekking to 5,643m) on 19 healthy subjects (age 35.4±years, 52.6% males). There was a detectable increase (>5ng/L) in post exercise hs-cTnT with exercise at HA which became significant at 5,150m (5.84% at 3,440m, 5.2% at 4,270m and 56.3% at 5,150m; p=0.0005). Compared with baseline, HA to 5,150m led to a significant rise in post exercise Lake Louis AMS scores (p<0.001) pulmonary artery systolic pressure (PASP) (23.7±3.8 vs 37.9±11.7mmHg: p<0.001), cardiac output (5.2±1.2 vs 7.5±1.3l/min; p<0.001) and a fall in SpO2 (96.1±vs 77.4±12.0%; p<0.001). There was no change in stroke volume (p=0.10) or estimated filling pressures (E/E') of the left (p=0.50) and right ventricles (p=0.4). On multivariate analysis increasing cardiac output (p=0.02) and PASP (p=0.04) and decreasing SpO2 (p=0.01) were the only independent predictors of increasing cTnT levels (overall R (2)=0.23, p<0.0001). Moderate intensity exercise at significant HA influences the post exercise increase in hs-cTnT without overt deleterious effects on cardiac function.

Cardiac Dysfunction in Pneumovirus-Induced Lung Injury in Mice

To determine biventricular cardiac function in pneumovirus-induced acute lung injury in spontaneously breathing mice. Experimental animal study. Animal laboratory. C57Bl/6 mice. Mice were inoculated with the rodent pneumovirus, pneumonia virus of mice. Pneumonia virus of mice-infected mice were studied for right and left ventricular function variables by high-field strength (7 Tesla) cardiac MRI at specific time points during the course of disease compared with baseline. One day before and at peak disease severity, pneumonia virus of mice-infected mice showed significant right and left ventricular systolic and diastolic volume changes, with a progressive decrease in stroke volume and ejection fraction. No evidence for viral myocarditis or viral presence in heart tissue was found. These findings show adverse pulmonary-cardiac interaction in pneumovirus-induced acute lung injury, unrelated to direct virus-mediated effects on the heart.

Validation of MRI quantification of biventricular cardiac function in term and preterm neonates

Background Accurate measurement of neonatal cardiac function remains a key goal to improve understanding of circulatory pathophysiology in prematurity. Cardiac MRI has been shown to be viable in this population, but robust validation is crucial. Our aim was to assess the accuracy of cardiac functional measures derived from MRI ventricular stack segmentation against phase contrast measures in term and preterm neonates. Methods Cardiac MRI scans were performed on a 3T Philips Achieva scanner (Best, Netherlands) in 40 infants (gestational age 24+3-40+2weeks/ weight at scan 750-3120g). Left ventricular stacks were segmented for epicardial and endocardial contours at end systole and end diastole using Segment software (http://segment.heiberg.se) with manual correction of segmentation where necessary. Correction for long axis motion was performed using the mean of three measures of atrio-ventricular valve descent from a 4 chamber view. Right ventricular stacks were segmented for endocardial contours on 20 infants (gestational age 24+3-40+2weeks/ weight at scan 7903120g) using the same technique. Cardiac output (CO) was measured by semi-automatic segmentation (View Forum,Philips) of phase contrast(PC) images of the left ventricular outflow tract. The two techniques were compared using a Bland Altman plot. Infants with known patent ductus arteriosus were excluded. Results Bland Altman analysis of left ventricular output by stack and PC showed a mean bias of 14.2 ml/min, with limits of agreement of -54.8 to 83.2 ml/min,, corresponding to a repeatability index (RI, limits of agreement/mean of population) of 16.6%. Bland Altman analysis of right ventricular output by stack and left ventricular output by PC showed a mean bias of 39.7 ml/min, with limits of agreement of -36.9 to 116.5 ml/min corresponding to a repeatability index (RI) of 17.3%. For comparison Bland Altman of neonatal heart rate during by stack and PC imaging showed a mean bias of -2.12 beats/min, with limits of agreement of -19.21 to 14.96 beats/min, corresponding to a repeatability index (RI) of 11.92%. Conclusions Given the wide variability of heart rates and potential for motion in preterm neonatal scanning, our findings suggest stack segmentation at our improved resolution can give relatively accurate measures of preterm cardiac function.

Study of Renal Iron Overload by T2* MRI in a Large Cohort of Thalassemia Major Patients

AbstractAbstract 5177 Background.Renal dysfunction has been reported in adult subjects with thalassemia major (TM) since 1975. One of the main cause is the iron overload consequent to regular transfusions. Multiecho T2* MRI is a well-established technique for cardiac and hepatic iron overload assessment, but there very few report concerning the kidneys.The aims of this study were to describe the T2* values of the kidneys in patients with TM, to investigate the correlation between renal and myocardial or hepatic siderosis and biventricular cardiac function. Methods.119 TM patients (58 men, 30. 7 ± 8. 2 years) enrolled in the Myocardial Iron Overload (MIOT) networks underwent MRI. For the measurement of iron overload, multiecho T2* sequences were used. The left ventricle was segmented into a 16-segments standardized model and the T2* value on each segment was calculated as well as the global value. In the liver, the T2* value was assessed in a single region of interest (ROI) in a homogeneous area of the parenchyma. For each kidney, T2* values were calculated in three different ROIs and were averaged to obtain a representative value for the kidney. The mean T2* value over the kidneys was also calculated. Cine images were obtained to quantify biventricular morphological and functional parameters in a standard way. Results.T2* values in the right kidney were significant lower than in the left kidney (40. 3±11. 9 ms vs 44. 1±12. 7 ms, P<0. 0001). The mean T2* value over the kidneys was 42. 2±11. 9 ms and 40 patients (33. 6%) had a pathological value (T2*<36 ms, lower limit of normal evaluated on 20 healthy subjects). The mean T2* value did not show a significant difference amongst men ad women (43. 2±11. 7 ms versus 41. 3±12. 1 ms, P=0. 378). The mean T2* values increased with age in a significant manner (r=0. 321, P<0. 0001). There was a significant negative correlation between serum ferritin levels and mean renal T2* values (r=-0. 446, P<0. 0001). Significant positive correlations of the mean T2* values were demonstrated for liver (r=0. 511, P<0. 0001) and global heart (r=0. 262, P=0. 004) T2* values (Figure 1). No correlation was found between renal iron overload and bi-ventricular function parameters. Conclusions.Systemic T2* differences between left and right kidneys were found, with significant lower values in the right one. Mean T2* value increased with age. We confirmed that kidney iron deposition was not very common in TM, but it was correlated with iron deposition in liver and heart. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Bethesda conference: conference for the design of clinical trials to study circulatory support devices for chronic heart failure

James M. Anderson, MD Eugene H. Blackstone, MD Harvey S. Boroevetz, PhD Arthur Ciarkowski, MD Jack G. Copeland III, MD Maria Rosa Costanzo-Nordin, MD Kurt Daase, MD Mary Amanda Dew, PhD Michael J. Domanski, MD Benjamin H. Eidleman, MD Roger W. Evans, PhD David J. Farrar, PhD O. H. Frazier, MD Bartley P. Griffith, MD Charles-Julien Hahn, MD J. Donald Hill, MD Sharon Hunt, MD Kay Kendell, RN Robert L. Kormos, MD Howard R. Levin, MD Donna M. Mancini, MD Patrick M. McCarthy, MD Dennis McNamara, MD Fr Kevin O’Rourke, PhD Lisa Parker, PhD D. Glenn Pennington, MD Victor L. Poirier, PhD Peer M. Portner, PhD Eric A. Rose, MD Wolf Sapirstein, MD Eleanor Schron, MD Rhona Shanker, MD Ramiah Subramanian, MD John Wallwork, MD Lynne Warner Stevenson, MD