Velocity Of Circumferential Fiber Shortening Research Articles

Effects of conditioning on the left ventricular function of young purebred Arabian horses.

The effects of conditioning on cardiac function in young horses is still unknown. For this reason, this study evaluated the left ventricular (LV) function of young horses by echocardiography after six weeks of conditioning. Fourteen untrained young purebred Arabian horses were evaluated at rest and after a stress test (ST) before and after a six-week conditioning program. There was an increase in V4 (p < 0.001) after conditioning, as well as a reduction in both heart rate (HR) at rest and peak HR during the ST (p < 0.001). There was also a reduction in internal diameter, along with an increase in interventricular septal, free wall and mean thicknesses and LV mass (p < 0.05). After the ST, the conditioned animals showed higher values of velocity time integral, stroke volume, systolic and cardiac indices, ejection (ET) and deceleration times (DT), end-diastolic volume, time to onset of radial myocardial velocity during early diastole and time to peak of transmitral flow velocity, in addition to reduced pre-ejection period (PEP), PEP/ET ratio and mean velocity of circumferential fiber shortening (p < 0.05). The conditioning protocol promoted physiological adaptations that indicate an improvement in the animals' aerobic capacity associated with an enhanced left ventricular function.

Artificial intelligence technology applied to an unoccluded catheter for recognition of hemodynamic changes

This study seeks to provide a reliable means for physicians to diagnose hemorrhagic complications associated with patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. We employ the YOLOv4 algorithm to analyze cardiac parameters from the echocardiography device's ultrasonic wave, such as left ventricular ejection time (LVET), left ventricular internal dimension-diastole (LVIDd), left ventricular internal dimension-systole (LVIDs), posterior wall thickness at end-systole (HES), and RR interval. The proposed model has achieved an impressive average detection accuracy of 89.4% for these five parameters. Additionally, the further evaluation of cardiac function can be done by deriving the end-systolic wall stress (ESWS) and left ventricle rate-corrected mean velocity of circumferential fiber shortening (mVcFc) values from these parameters. As a result, it indicates that the accuracy of ESWS and mVcFc values is 88.7% and 90.3%, respectively. With this deep learning-based approach, physicians can confidently evaluate the cardiac function of ELBW infants and diagnose PDA-related hemorrhagic complications.

The Effect of Glycemic Control on Left Ventricular Function in Clinical and Experimental Diabetes

BackgroundGlycemic control in diabetes mellitus (DM) has not improved cardiovascular outcomes with normal left ventricular (LV) function. We assessed the effect on LV dysfunction using a canine model of LV dysfunction and DM, and in patients with DM and LV dysfunction. MethodsChronic LV dysfunction was produced by coronary microsphere embolization in 34 canines (15-25 kg). Following 8 weeks of stabilization, DM was induced in 24 canines and randomized to good or poor glycemic control for 3 months. Ten canines without DM were controls. Hemodynamic and Doppler echocardiographic data were obtained prior to and following pressure loading. We reviewed the Doppler-echocardiography at baseline and follow-up in 207 patients with DM with reduced ejection fraction (EF; median follow-up = 612 days) and 60 age- and sex-matched non-DM patients with normal EF. Laboratory results, medications, and incident adverse events from medical records were obtained. ResultsEF = 43.8% ± 11.2% for all canines at 8 weeks. Canines with poor glycemic control (hemoglobin [Hb]A1c = 8.05% ± 3.02%) demonstrated reduced LV mass and rate-corrected velocity of circumferential fiber shortening, compared to those with LV dysfunction (1.36 ± 0.73 vs 0.88 ± 0.13 circumference per second, P < 0.01). Good glycemic control (HbA1c = 3.88% ± 0.89%) demonstrated similar LV parameters, compared to controls (HbA1c = 2.99% ± 0.44%). EF was similar among groups. Patients with vs without DM were followed for up to 3 years. Patients with DM and poor glycemic control had reduced EF, lower rate-corrected velocity of circumferential fiber shortening = 0.93 ± 0.26 vs 1.11 ± 0.26, P < 0.001), and greater incidence of heart failure. ConclusionsPoor glycemic control had an adverse effect on preexisting LV dysfunction experimentally and in patients with type 2 diabetes.

Myocardial perfusion and function dichotomy in growth restricted preterm infants.

Compared to preterm appropriate for gestational age (AGA) fetuses, fetuses with fetal growth restriction (FGR) have earlier visualisation of coronary artery blood flow (CABF) but impaired cardiac function. This dichotomy remains uncharacterised during postnatal life. This study compared CABF and cardiac function in preterm FGR infants, against AGA infants during the postnatal period. FGR was defined as birthweight < 10th centile for gestation and sex with absent/reversed antenatal umbilical artery Doppler. Diastolic CABF was measured in the left anterior descending coronary artery. Twenty-eight FGR infants were compared with 26 AGA infants (gestation and birthweight, 29.7 ± 1.3 vs 29.9 ± 1 weeks, P = 0.6 and 918 ± 174 vs 1398 ± 263g, P < 0.001, respectively). Echocardiography was performed in the second week of life. FGR infants had higher CABF (velocity time integral, 2.4 ± 0.9 vs 1.6 ± 0.8 cm, P = 0.002). Diastolic function was impaired (↑ trans-mitral E/A ratio in FGR infants; 0.84 ± 0.05 vs 0.79 ± 0.03, P = 0.0002) while the systolic function was also affected (mean velocity of circumferential fibre shortening [mVCFc], 1.9 ± 0.3 vs 2.7 ± 0.5 circ/s, P < 0.001). Indexing CABF to cardiac function noted significant differences between the groups (CABF: E/A [FGR vs AGA], 2.9 ± 1.1 vs 2.1 ± 1, P = 0.01 and CABF: mVCFc [FGR vs AGA], 1.3 ± 0.5 vs 0.6 ± 0.3, P < 0.001). Diastolic blood pressure (BP) was significantly higher, and CABF to diastolic BP ratio trended higher in FGR infants (30 ± 2 vs 25 ± 3 mmHg, P < 0.001 and 0.08 ± 0.03 vs 0.06 ± 0.03, P = 0.059, respectively). Greater CABF in FGR infants did not translate into better cardiac function. This dichotomy may be a persistent response to fetal hypoxaemia (fetal programming) and/or reflection of altered cardiac architecture.

Аналіз застосування Мексикору у хворих із гострим коронарним синдромом

Матеріали та методи. Під спостереженням знаходилися дві групи хворих із гострим коронарним синдромом. Перша група включала 48 хворих із нестабільною стенокардією (НС) віком 58,5 ± 3,8 року. Діагноз НС верифікований на підставі скарг хворих і змін на електрокардіограмі — підйому або депресії інтервалу на 1 мм тривалістю не більше 3 діб, відсутності зон гіпокінезії при УЗД серця, негативного тропонінового тесту. Другу групу становили 45 хворих із гострим інфарктом міокарда. Діагноз верифіковано за допомогою тропонінового тесту і змін на ЕКГ. У цю групу включалися хворі з Q-позитивним гострим інфарктом міокарда (ГІМ). Чоловіки — 83,2 %, жінки — 16,8 %. Середній вік хворих становив 60,3 ± 1,2 року. Задньобазальна локалізація виявлена у 40,2 %, передня — у 59,8 %. В анамнезі у 70 % хворих гіпертонічна хвороба ІІ ст. «Стаж» ішемічної хвороби серця становив у середньому 10,8 ± 4,5 року. 80 % хворих цієї групи неодноразово лікувалися в кардіологічних стаціонарах із приводу загострень ішемічної хвороби серця. У 38,5 % хворих на момент надходження відзначені надшлуночкові і шлуночкові (екстрасистолія) порушення ритму. Результати. Застосування Мексикору у хворих із ГІМ значно покращувало систолічну функцію серця, що проявлялося у вірогідній різниці основних показників, що її відображають (фракція викиду, швидкість циркуляторного скорочення волокон, серцевого викиду), і відповідних показників у хворих контрольної групи. Подібні сприятливі зміни були виявлені і при вивченні в динаміці показників діастолічної функції серця, що визначаються за швидкістю трансмітрального потоку. Обговорення. Зазначені зміни ми пов’язуємо з відновленням або поліпшенням скоротливості ішемізованого міокарда та функціонального стану так званих інтактних відділів серця, що компенсують своєю діяльністю втрату скоротливості некротизованих ділянок. Це підтверджується динамікою стану зон акінезії і дискінезії у хворих на ІМ, де відстежується відновлення скоротливості окремих ділянок серця на фоні застосування Мексикору (перехід граничних із зонами інфаркту сегментів зі стану акінезії в гіпокінез, гіпокинезу — в нормокінез), і практично зворотною динамікою у хворих контрольної групи. Мексикор сприяв поліпшенню клінічного перебігу ІМ, що проявлялося в обмеженні величини вогнища некрозу і стимуляції репаративних процесів, поліпшенні скорочувальної функції серця і газообміну, зменшенні частоти пролонгованого і рецидивного перебігу, ймовірності розвитку аневризми серця і випадків серцевої недостатності, порушень ритму і провідності, недостатності кровообігу і в кінцевому підсумку летальності. За результатами холтерівського моніторування у хворих на НС Мексикор прискорював стабілізацію стенокардії і зменшував, порівняно з контрольною групою, добову частоту і тривалість періодів ішемії міокарда, епізодів порушень ритму, сприятливо впливав на зміну інтеграла зміщення ST і співвідношення больових/безбольових періодів ішемії. Висновки. Включення Мексикору в традиційну терапію гострого коронарного синдрому вже на догоспітальному етапі дозволяє істотно зменшити прояви окислювального стресу, сприяє нормалізації діяльності серцево-судинної системи і покращує клінічний перебіг захворювань.

СОВРЕМЕННЫЕ ПОДХОДЫ К МЕДИЦИНСКОЙ ПРОФИЛАКТИКЕ КАРДИОТОКСИЧЕСКИХ ЭФФЕКТОВ КОМПЛЕКСНОГО ЛЕЧЕНИЯ РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ

Objectives. To study the effect of complex treatment of breast cancer (BC) on the parameters of the structural and functional state of the cardiovascular system. To develop a model for predicting the ejection fraction (EF) of the left ventricle (LV) measured by the Simpson method after the end of antitumor therapy on the basis of initial laboratory and instrumental data. Methods. The cardiovascular system was examined in 100 women who received complex treatment of BC. The groups were formed depending on the presence of arterial hypertension (AH) and on the cardiotropic therapy (CT) received: the BC group, the BC+ CT group, the BC+ AH+CT group. Results. The research showed a decrease in LVEF measured by the Simpson method from 66,0 (62,0; 71,0)% to 60,0 (57,0-66,0)%, an increase in LV end systolic diameter from 27,0 (24,0–29,0) mm to 27,0 (25,0–31,0) mm, LV end systolic volume from 27,0 (22,0; 32,0) ml to 28,0 (24,0; 37,0) ml; a decrease in the mitral ratio of peaks early to late diastolic filling velocity from 1,4 (1,1; 1,8) to 1,2 (1,1; 1,5), in the ratio of early to late diastolic mitral annular velocity from 1,4 (1,2; 1,7) to 1,2 (1,0; 1,6); in the of early to late diastolic tricuspid annular velocity from 1,4 (1,2; 1,7) to 1,0 (0,8; 1,1), reduction of the increase in the diameter (d) of the brachial artery (BA) after performing a post-occlusion test from 12,5 (11,0; 16,0)% to 9,0 (6,0; 12,0)%, the reduction of heart rate variability: standard deviation of NN intervals from 57,7 (44,9; 72,9) ms to 54,1 (44,0; 63,3) ms, root mean square of successive RR interval differences from 29,6 (17,5; 43,3) ms to 20,0 (15,2; 28,0) ms, total power of the spectrum from 1326,3 (996,4; 2061,7) to 1132,4 (824,3; 1649,8) ms2/ Hz; power of the high-frequency (HF) from 647,3 (416,8; 921,4) to 443,7 (315,9; 669,0) ms2/ Hz; an increase in ratio of low-frequency to HF from 0,8 (0,7; 1,0) to 1,05 (0,8; 1,2). A Simpson-based EF prognostic model after the end of BC treatment has been developed. It includes the total dose of doxorubicin calculated for the body surface area, the peak early diastolic filling velocity of transtricuspid flow, the diameter of the pulmonary artery, the velocity of circumferential fiber shortening, the intima-medial thickness of the left common carotid artery, HF, % increase of the d of the BA. The developed model has a high prognostic ability. Conclusions. Breast cancer treatment negatively affects the structural and functional state of the cardiovascular system. The administration of a combination of valsartan and carvedilol prevents the development of adverse changes. The developed EF prognostic model allows to identify patients for the preventive administration of cardiotropic therapy.

Abstract 11855: Disruption of β-arrestin-2 Signaling Resulted in Impaired Systolic and Diastolic Function During Aging

Introduction: Angiotensin II (ang II) signaling at ang II receptor type 1 (AT1R), which is a G-protein coupled receptor (GPCR), promotes both G-protein signaling as well as β-arrestin-2 signaling. β-arrestin-2 participates in GPCR desensitization, internalization, but also acts a scaffold for adaptive signal transduction that may occur independently or in parallel to G-protein signaling. Hypothesis: We tested the hypothesis that β-arrestin-2 is an important element in the preservation of cardiac function during aging. Methods: We tested this hypothesis by aging β-arrestin-2 knock-out (KO) mice, and wild-type equivalent (WT) to 12-16 months. We performed echocardiography studies, and Western blot analysis. Results: By echocardiography we found that compared to controls aged KO mice exhibited enlarged left atria (2.2±0.1 vs 2.5±0.1 mm) and left ventricular diameters (4.2±0.2 vs 4.5 ±0.1mm) as well as depressed contractility parameters such as s’ (23.2±1.4 vs 21.4±0.8 mm/s) and decreased circumferential fiber shortening velocity (5.5±0.4 vs 4.5±0.2) with preserved ejection fraction (EF&gt;50%). Aged KO also exhibited depressed relaxation parameters such as e’ (29.2±1.4 vs 21.4±0,6 mm/s) and E/e’ (27.4±1.6 vs 35.6±2.0) when compared to WT controls at the same age. Cardiac dysfunction in aged KO mice was correlated with decreased phosphorylation of RLC and increased phosphorylation of cMyBP-C at Ser302. Among other kinases, cMyBP-C phosphorylation at Ser302 is a PKCε target which activation is negatively regulated by β-arrestin-2 signaling. To determine the direct effects of PKCε over-activation on cMyBP-C phosphorylation, we used mice that over-expresses constitutively active PKC ε in the heart. We found that similarly to our aged KO mice, PKCε overexpression model exhibited significantly higher levels of cMyBP-C phosphorylation at Ser302, when aged to 12 - 15 months. Conclusions: Deletion of β-arrestin-2 signaling in KO mice affected aged mice, resulting in changes in the phosphorylation of myofilament proteins consisting of decreased phosphorylation of RLC and increased phosphorylation of cMyBP-C at Ser302 through the unrestricted activity of PKCε. These changes negatively affected systolic and diastolic function in aged KO mice.

Echocardiography in the bovine animal

Echocardiograms were obtrained from 15 standing clinically normal cows using an ultrasonic recording device. The echo beam penetrated the right thoracic wall in the area of the fourth intercostal space with a frequency of 2.25 MH3. Left ventricular wall thickness measured 2.00 +/- .19 cm while the septal dimension was slightly higher at 2.24 +/- .26 cm. Velocity of circumferential fiber shortening (Vcf), and index of contractility, was .87 +/- .4 m/s and minor axis shortening fraction (% delta D), and indicator of pump frunction, was 43.5 +/- 5.8%.

Electronic cigarettes cause alteration in cardiac structure and function in diet-induced obese mice.

In spite of the widespread use of electronic cigarettes, also known as e-cigarettes, and the proposed adverse cardiac effects of nicotine, the detrimental effects of e-cigarettes on the heart are not well known. This study examines the detrimental effects of e-cigarettes with nicotine at doses that yield circulating nicotine and cotinine in the ranges similar to the levels found in habitual smokers, and a high fat diet (HFD) on cardiac structure and function in a commonly used model of diet-induced obesity (DIO). C57BL/6J mice on an HFD were exposed to e-cigarette in the presence (2.4% nicotine) or absence (0% nicotine) of nicotine and saline aerosol for 12 weeks. Echocardiographic data demonstrated a decrease in left ventricular (LV) fractional shortening, LV ejection fraction, and velocity of circumferential fiber shortening (VCF) in mice treated with e-cigarette (2.4% nicotine) compared to e-cigarette (0% nicotine) or saline exposed mice. Cardiomyocytes (CMs) of mice treated with e-cigarette (2.4% nicotine) exhibited LV abnormalities, including lipid accumulation (ventricular steatosis), myofibrillar derangement and destruction, and mitochondrial hypertrophy, as revealed by transmission electron microscopy. The detrimental effects of e-cigarettes (2.4% nicotine) on cardiac structure and function was accompanied by increased oxidative stress, plasma free fatty acid levels, CM apoptosis, and inactivation of AMP-activated protein kinase and activation of its downstream target, acetyl-CoA-carboxylase. Our results indicate profound adverse effects of e-cigarettes (2.4% nicotine) on the heart in obese mice and raise questions about the safety of the nicotine e-cigarettes use.

Gene therapy targeting cardiac phosphoinositide 3-kinase (p110α) attenuates cardiac remodeling in type 2 diabetes.

Diabetic cardiomyopathy is a distinct form of heart disease that represents a major cause of death and disability in diabetic patients, particularly, the more prevalent type 2 diabetes patient population. In the current study, we investigated whether administration of recombinant adeno-associated viral vectors carrying a constitutively active phosphoinositide 3-kinase (PI3K)(p110α) construct (rAAV6-caPI3K) at a clinically relevant time point attenuates diabetic cardiomyopathy in a preclinical type 2 diabetes (T2D) model. T2D was induced by a combination of a high-fat diet (42% energy intake from lipid) and low-dose streptozotocin (three consecutive intraperitoneal injections of 55 mg/kg body wt), and confirmed by increased body weight, mild hyperglycemia, and impaired glucose tolerance (all P < 0.05 vs. nondiabetic mice). After 18 wk of untreated diabetes, impaired left ventricular (LV) systolic dysfunction was evident, as confirmed by reduced fractional shortening and velocity of circumferential fiber shortening (Vcfc, all P < 0.01 vs. baseline measurement). A single tail vein injection of rAAV6-caPI3K gene therapy (2×1011vector genomes) was then administered. Mice were followed for an additional 8 wk before end point. A single injection of cardiac targeted rAAV6-caPI3K attenuated diabetes-induced cardiac remodeling by limiting cardiac fibrosis (reduced interstitial and perivascular collagen deposition, P < 0.01 vs. T2D mice) and cardiomyocyte hypertrophy (reduced cardiomyocyte size and Nppa gene expression, P < 0.001 and P < 0.05 vs. T2D mice, respectively). The diabetes-induced LV systolic dysfunction was reversed with rAAV6-caPI3K, as demonstrated by improved fractional shortening and velocity of circumferential fiber shortening (all P < 0.05 vs pre-AAV measurement). This cardioprotection occurred in combination with reduced LV reactive oxygen species (P < 0.05 vs. T2D mice) and an associated decrease in markers of endoplasmic reticulum stress (reduced Grp94 and Chop, all P < 0.05 vs. T2D mice). Together, our findings demonstrate that a cardiac-selective increase in PI3K(p110α), via rAAV6-caPI3K, attenuates T2D-induced diabetic cardiomyopathy, providing proof of concept for potential translation to the clinic.NEW & NOTEWORTHY Diabetes remains a major cause of death and disability worldwide (and its resultant heart failure burden), despite current care. The lack of existing management of heart failure in the context of the poorer prognosis of concomitant diabetes represents an unmet clinical need. In the present study, we now demonstrate that delayed intervention with PI3K gene therapy (rAAV6-caPI3K), administered as a single dose in mice with preexisting type 2 diabetes, attenuates several characteristics of diabetic cardiomyopathy, including diabetes-induced impairments in cardiac remodeling, oxidative stress, and function. Our discovery here contributes to the previous body of work, suggesting the cardioprotective effects of PI3K(p110α) could be a novel therapeutic approach to reduce the progression to heart failure and death in diabetes-affected patients.

Urocortin 2 Gene Transfer Reduces the Adverse Effects of a Western Diet on Cardiac Function in Mice.

Diabetes mellitus is associated with increased risk of heart failure. It has been previously demonstrated in mice that a single injection of adeno-associated virus 8 encoding urocortin 2 (AAV8.UCn2) increases glucose disposal in models of insulin resistance and improves the function of the failing heart. The present study tested the hypothesis that UCn2 gene transfer would reduce diabetes-related left ventricular (LV) dysfunction. Eight-week-old C57BL6 male mice were fed a Western diet (WD; 45% fat, 35% carbohydrate) for 40 weeks. At week 30, they received saline or AAV8.UCn2 (2 × 1013 genome copies/kg) via intravenous injection. Ten weeks after gene transfer, fasting blood glucose, glucose tolerance, and cardiac function were measured via echocardiography and in vivo measurement of LV contractile function, and the results were compared to those of mice fed normal chow (NC; 10% fat; 70% carbohydrate). The contents of key LV signaling proteins were also measured to probe mechanisms. WD increased 12 h fasting glucose (WD: 190 ± 11 mg/dL, n = 8; NC: 105 ± 12 mg/dL, n = 7; p = 0.0004). WD tended to reduce LV peak +dP/dt (p = 0.08) and LV peak -dP/dt (p = 0.05). LV ejection fraction was unchanged. Among WD-fed mice, UCn2 gene transfer reduced 12 h fasting glucose (WD-UCn2: 149 ± 6 mg/dL, n = 8; WD-Saline: 190 ± 11 mg/dL, n = 8; p = 0.012), increased LV peak +dP/dt (p < 0.001) and LV peak -dP/dt (p = 0.013), and reduced Tau (p < 0.02), indicating beneficial effects on systolic and diastolic LV function. In addition, among WD-fed mice, UCn2 gene transfer increased LV ejection fraction (p < 0.005) and the velocity of circumferential fiber shortening (p = 0.0005). Finally, a reduction was seen in fatty infiltration of the liver in WD-fed mice that had received UCn2 gene transfer. LV samples from WD-UCn2 mice showed increased phosphorylation of the protein kinase A catalytic domain (p = 0.03). In conclusion, UCn2 gene transfer increased LV systolic and diastolic function and reduced blood glucose in mice with diabetes-related LV dysfunction, indicating that UCn2 gene transfer may be of potential therapeutic benefit.

Echocardiographic Assessment of Ventricular Function During Exercise in Adolescent Female Patients With Anorexia Nervosa

Patients with anorexia nervosa (AN) have altered physiologic responses to exercise. The aim of this study was to investigate exercise capacity and ventricular function during exercise in adolescent patients with AN. Sixty-six adolescent female patients with AN and 21 adolescent female control subjects who exercised to volitional fatigue on a semisupine ergometer, using an incremental step protocol of 20W every 3min, were retrospectively studied. Heart rate, blood pressure, and echocardiographic Doppler indices were measured at rest and during each stage of exercise. Fractional shortening, rate-corrected mean velocity of circumferential fiber shortening, stress at peak systole, cardiac output, and cardiac index were calculated. Minute ventilation, oxygen consumption, carbon dioxide production, and respiratory exchange ratio were measured using open-circuit spirometry. Patients with AN had significantly lower body mass index (16.7 vs 19.7kg/m2, P<.001), total work (1,126 vs 1,914J/kg, P<.001), and test duration (13.8 vs 20.8min, P<.001) compared with control subjects. Peak minute ventilation, oxygen consumption, and carbon dioxide production were significantly decreased in patients with AN. Heart rate, systolic blood pressure, cardiac index, fractional shortening, and rate-corrected mean velocity of circumferential fiber shortening demonstrated similar patterns of increase with progressive exercise between groups but were decreased at peak exercise in patients with AN. Body mass index percentile, age, peak oxygen consumption, and peak cardiac output were independently associated with exercise duration. Adolescent patients with AN have reduced exercise capacity and peak cardiovascular indices compared with control subjects but normal patterns of cardiovascular response during progressive exercise. Systolic ventricular function is maintained during exercise in adolescents with AN.

Abstract 16670: Urocortin 2 Gene Transfer Reduces the Adverse Effects of Western Diet on Cardiac Function in Mice

Diabetes mellitus increases the risk of heart failure. We previously showed that injection of adeno-associated virus 8 encoding urocortin 2 (AAV8.UCn2) increases glucose disposal in insulin resistance and improves function of the failing heart in mice. In the present study, we tested the hypothesis that UCn2 gene transfer would have beneficial effects in diabetic cardiomyopathy. Eight-week-old C57Bl/6J male mice were fed normal chow (NC) or a Western diet (WD, 35% kcal carbohydrate and 45% fat) for 30w, and then received saline or AAV8.UCn2 (1.9x10 13 genome copy/kg) via intravenous injection. Before and 10w after gene transfer, we measured fasting blood glucose, glucose tolerance, and cardiac function via echocardiography and rates of LV pressure development (+dP/dt) and decline (-dP/dt) using micromanometers. We also measured key signaling proteins in the left ventricle (LV). Western diet increased 12h fasting glucose levels compared to normal chow (81% increase; p&lt;.0002). WD vs normal chow reduced LV peak +dP/dt (p=.042) and LV peak -dP/dt (p=.027), although LV ejection fraction (EF) was unchanged. Thus WD induced diabetes and cardiomyopathy with normal EF. Among mice fed WD, UCn2 gene transfer reduced fasting glucose (WD+Saline: 190±11 mg/dL, n=8; WD+UCn2: 149±6 mg/dL, n=8; p=.006), increased LV peak +dP/dt (p=.005; Fig A ), LV peak -dP/dt (p=.007; Fig B ), and reduced Tau (p=.016; Fig C ). In addition, among WD-fed mice, UCn2 gene transfer increased LV EF (p=.005) and the velocity of circumferential fiber shortening (p=.0005). LV samples from WD+UCn2 mice showed increased phosphorylation of PKA catalytic domain (WD+Saline: .2±.04, n=5; WD+UCn2: .3±.02, n=5; p=.03). In conclusion, UCn2 gene transfer increased LV systolic and diastolic function and reduced blood glucose in mice with diabetic cardiomyopathy.

A3516 The effects of the change of arterial stiffness on left ventricular remodeling in asymptotic women

Objectives: To determine the longitudinal effect of arterial stiffness and cardiac remodeling in asymptotic women. Methods: 355 women subjects (mean age 60.43 ± 8.73 years) were enrolled who underwent aortic PWV determination and echocardiography, from which the mean velocity of circumferential fiber shortening was calculated as a measure of the velocity of myocardial shortening, and relative wall thickness was taken as a measure of left ventricular concentric remodeling. Results: During the 4-years follow-up, there is significant increase in PWV (0.38 m/s, P < 0.001), LVMI (5.60, P < 0.001) and RWT (0.03, P < 0.001) respectively. No significant change has been found in LVSD or LVDD and blood pressure remained normal due to antihypertensive treatment. In the cross-sectional analysis at age 64 years, PWV was positively associated with RWT (coefficient = 0.01, P < 0.001); but not with LVMI after adjusted for age, BMI, map, heritability, medication, hypertension and smoking status. The increase of PWV but not baseline PWV was associated with the rise of RWT (coefficient = 0.01, P < 0.001) in the fully adjusted mixed effect model. Conclusion: Increased PWV as an indicator of elevated afterload, may accelerate ventricular remodeling despite of blood pressure level.

ACE inhibition for severe bronchopulmonary dysplasia - an approach based on physiology.

Premature infants have a high incidence of bronchopulmonary dysplasia (BPD). Systemic hypertension, arterial thickness and stiffness, and increased systemic afterload may all contribute to BPD pathophysiology by altering left ventricular (LV) function and increasing pulmonary venous congestion by lowering end‐diastolic compliance. This case series studied the usefulness of angiotensin‐converting enzyme (ACE) inhibition by measuring clinical and echocardiographic improvements in six consecutive infants with “severe” BPD unresponsive to conventional therapy. The range of gestation and birthweight were 23–29 weeks and 505–814 g, respectively. All required mechanical ventilation (including high‐frequency oscillation) and all but one were administered postnatal corticosteroids. Other treatments including sildenafil and diuretics made no clinical improvements. Captopril was started for systemic hypertension after cardiac and vascular ultrasounds which were repeated 5 weeks later. A significant reduction in oxygen (55 ± 25 to 29 ± 3%, two‐tailed P = 0.03) and ventilator requirements, and improved cardiovascular parameters were noted. This included a trend toward reduction in aorta intima media thickness [840 ± 94 to 740 ± 83 μm, P = 0.07] and an increased pulsatile diameter [36 ± 14 to 63 ± 25 μm, P = 0.04]). Improvements were observed for both systolic (increased LV output, 188 ± 13 to 208 ± 13 mL/kg/min, P = 0.046 and mean velocity of circumferential fiber shortening, 1.6 ± 0.2 to 2.5 ± 0.3 [circ/sec], P = 0.0004) and diastolic (decreased isovolumic relaxation time, 69.6 ± 8.2 to 59.4 ± 5 msec, P = 0.044) function which was accompanied by increased pulmonary vein flow. Right ventricular output increased accompanied by a significant lowering of pulmonary vascular resistance. These findings suggest that improving respiratory and cardiac indices (especially diastolic function) warrants further exploration of ACE inhibition in BPD infants unresponsive to conventional therapy.

Normal Values and Growth-Related Changes of Left Ventricular Volumes, Stress, and Strain in Healthy Children Measured by 3-Dimensional Echocardiography

Normal pediatric values of three-dimensional (3D) left ventricular (LV) volumes and strain are not well established; moreover, no reports exist of the stress-strain relation and the heart rate-corrected velocity of circumferential fiber shortening (VCFc) based upon 3D imaging in children. Three-dimensional LV datasets were obtained in pediatric patients (≤18 years of age) with structurally normal hearts. Ventricular volumes and strain components (longitudinal, GLS; circumferential, GCS; and 3D strain, 3DS) were analyzed using a commercial 3D speckle-tracking analysis package. LV mid-wall global average end-systolic fiber stress was calculated from 3D LV volumes. A total of 238 patients were included in the analysis with a median age of 13.1 years (range 0.4 to 17.9 years). Regression equations were derived for 3D volume parameters, permitting body surface area-based Z score calculation. Overall, 3DS values were more negative than GLS and GCS (mean ± SD = -33.8 ± 2.8; -27.8 ± 2.9; and -21.7 ± 3.1, respectively); only GLS varied significantly with age (r = 0.22; p <0.001). Both global average end-systolic fiber stress and 3D VCFc increased significantly with age (p <0.001 for both). Stress-adjusted 3DS and VCFc both varied with age (p <0.001 for both), consistent with increased contractility. In conclusion, 3D echocardiography may be used to calculate LV stress, strain, and volumes in pediatric patients with strong reproducibility. Among strain parameters, significant age-related changes were seen only in GLS. Both indexes of contractility investigated (3DS and VCFc indexed to wall stress) improved with age. Future studies of the 3D echocardiography stress-strain relation may yield new insights into maturational changes in myocardial contractility.

Myocardial strain/stress changes identified by echocardiography may reveal early sepsis-induced myocardial dysfunction.

ObjectiveTo perform early assessment of sepsis-induced myocardial dysfunction (SIMD) using strain/stress echocardiography.MethodsA canine model of SIMD was established using intravenous injection of lipopolysaccharide (LPS, 2 mg/kg). Thirteen dogs were included, comprising an LPS-treated SIMD group (n = 7) and saline control group (n = 6). SIMD was assessed at various time-points using cardiac measurements including haemodynamics and echocardiography.ResultsSystolic and radial ventricular wall stress and circular ventricular wall stress (WSsc) were significantly lower in the sepsis group versus the control group at all time-points. Logistic regression analysis revealed an inverse correlation between stress rate of the front-posterior and bottom wall and left ventricle systolic wall strength. In contrast, a positive correlation was found between the mean velocity of circumferential fibre shortening (mVCF) or heart rate-adjusted mVCF (RVCF) and WSsc. Using regression equations, predicted values for mVCF and RVCF in animals with sepsis were significantly higher than measured values at 4- 5- and 6-h time-points.ConclusionsThese findings will further the understanding of pathophysiological alterations in SIMD at the early stage of sepsis, and suggest that strain rate may reflect the nature of myocardial contractility.

Echocardiographic and electrocardiographic parameters during the normal postpartum period in toy breeds of dogs

The aim of this study was to evaluate echocardiographic and electrocardiographic parameters during the normal canine postpartum period. Twenty clinically healthy pregnant bitches of toy breeds (11 Miniature poodles, five Yorkshire terriers, two Maltese terriers and two Bichons Frises) were evaluated on days −3, 3, 10, 17, 24, 38, 52 and 80 relative to parturition (day 0). During the first postpartum week, the width of the interventricular septum in systole, the shortening fraction and the left atrium size decreased, while the left ventricle internal diameter in systole and end systolic stress increased. There were progressive decreases in the velocity of circumferential fibre shortening, stroke volume, cardiac output, and mitral E and A wave values. Systolic blood pressure increased markedly during the first postpartum week to gradually increase thereafter. Heart rate and corrected QT interval progressively decreased, while P wave amplitude increased. QRS complex amplitude decreased in the second week after parturition and then increased during the following weeks. In conclusion, there were changes in systolic function and some structural adaptive changes in the bitch during the first 80days postpartum. In addition, maternal heart rate and corrected QT interval decreased, while P wave and QRS amplitudes increased.

Cardiac Morphology and Function in Preterm Growth Restricted Infants: Relevance for Clinical Sequelae

To assess cardiac morphology and function in preterm infants with fetal growth restriction (FGR) compared with an appropriate for gestational age cohort, and to ascertain clinical correlation with neonatal sequelae. With informed consent, 20 infants born between 28 and 32 weeks of gestational age and birthweight (BW) <10th percentile were compared using conventional and tissue Doppler echocardiography with 20 preterm appropriate for gestational age infants. Total duration of respiratory support was recorded. The gestational age and BW of the infants with FGR and appropriate for gestational age infants were 29.8 ± 1.3 weeks vs 30 ± 0.9 weeks (P = .78) and 923.4 ± 168 g vs 1403 ± 237 g (P < .001), respectively. Preterm infants with FGR had significantly greater interventricular septal hypertrophy, greater free wall thickening, and lower sphericity indices (1.53 ± 0.15 vs 1.88 ± 0.2; P < .001), signifying globular and hypertrophied hearts. The transmitral E/A ratio and isovolumic relaxation time, markers of diastolic function, were significantly increased in the FGR cohort (0.84 ± 0.05 vs 0.78 ± 0.03 [P < .001] and 61.4 ± 4.1 ms vs 53.2 ± 3.2 ms [P < .001], respectively). Ejection fraction, as measured by the rate corrected mean velocity of circumferential fiber shortening was reduced (1.93 ± 0.4 circ/second vs 2.77 ± 0.5 circ/second; P < .001) in the FGR cohort. On follow-up, the total duration of respiratory support was significantly longer in the FGR cohort, and correlated with tissue Doppler E/E' (r = 0.65; P = .001), mean velocity of circumferential fiber shortening (r = -0.64; P = .001) and mitral annular peak systolic excursion (r = -0.57; P = .008). Preterm infants with FGR have altered cardiac function evident within days after birth, which is associated with respiratory sequelae.

A Doppler Echocardiographic Study of the Myocardial Inotropic Response to Peak Semisupine Exercise in Healthy Children: Development of a Simplified Index of Myocardial Reserve

Stress echocardiography has been advocated for the detection of abnormal myocardial function and unmasking diminished myocardial reserve in pediatric patients. The aim of this study was to create a simplified index of myocardial reserve, derived from the myocardial inotropic response to peak semisupine exercise in healthy children, and illustrate its applicability in a sample of pediatric oncology patients. In this prospective analysis, children (7-18years of age) with normal cardiac structure and function performed semisupine stress echocardiography to volitional fatigue. The quotient of wall stress at peak systole and heart rate-corrected velocity of circumferential fiber shortening were calculated at baseline and at peak exercise, the difference of which was termed the index of myocardial reserve (IMR). The IMR was also calculated in a retrospective sample of pediatric oncology patients with normal resting left ventricular function who had received anthracycline treatment and had performed the same exercise protocolto illustrate utility. Fifty healthy subjects (mean age, 13.2±2.6years) and 33 oncology patients (mean age, 12.7±4.0years) were assessed. In the healthy children at peak exercise, heart rate-corrected velocity of circumferential fiber shortening significantly increased (from 1.17±0.17 to 1.58±0.24circ·sec-1, P<.001), while the quotient of wall stress at peak systole significantly decreased (from 75.3±17.1 to 55.3±13.8g·cm-2, P<.001), shifting the plot of the relationship between the two parameters upward and to the left. The mean IMR was -30.8±17.8, and the normal distribution ranged from -4.7 (fifth percentile) to -67.3 (95th percentile). The IMR was abnormal in 10 oncology patients who were treated with anthracyclines. The authors have developed a novel IMR. Relative to the normal distribution of this IMR in healthy subjects, it is possible to identify patients with abnormal myocardial reserve. Thus, this study demonstrates the application of the IMR to aid in clinical decision making in individual patients.