Increase In Left Ventricular Size Research Articles

Mandatory role of endoplasmic reticulum and its pentose phosphate shunt in the myocardial defense mechanisms against the redox stress induced by anthracyclines

AbstractAnthracyclines’ cardiotoxicity involves an accelerated generation of reactive oxygen species. This oxidative damage has been found to accelerate the expression of hexose-6P-dehydrogenase (H6PD), that channels glucose-6-phosphate (G6P) through the pentose phosphate pathway (PPP) confined within the endoplasmic/sarcoplasmic reticulum (SR). To verify the role of SR-PPP in the defense mechanisms activated by doxorubicin (DXR) in cardiomyocytes, we tested the effect of this drug in H6PD knockout mice (H6PD−/−). Twenty-eight wildtype (WT) and 32 H6PD−/− mice were divided into four groups to be treated with intraperitoneal administration of saline (untreated) or DXR (8 mg/Kg once a week for 3 weeks). One week thereafter, survivors underwent imaging of 18F-deoxyglucose (FDG) uptake and were sacrificed to evaluate the levels of H6PD, glucose-6P-dehydrogenase (G6PD), G6P transporter (G6PT), and malondialdehyde. The mRNA levels of SR Ca2+-ATPase 2 (Serca2) and ryanodine receptors 2 (RyR2) were evaluated and complemented with Hematoxylin/Eosin staining and transmission electron microscopy. During the treatment period, 1/14 DXR-WT and 12/18 DXR-H6PD−/− died. At microPET, DXR-H6PD−/− survivors displayed an increase in left ventricular size (p < 0.001) coupled with a decreased urinary output, suggesting a severe hemodynamic impairment. At ex vivo analysis, H6PD−/− condition was associated with an oxidative damage independent of treatment type. DXR increased H6PD expression only in WT mice, while G6PT abundance increased in both groups, mismatching a generalized decrease of G6PD levels. Switching-off SR-PPP impaired reticular accumulation of Ca2+ decelerating Serca2 expression and upregulating RyR2 mRNA level. It thus altered mitochondrial ultrastructure eventually resulting in a cardiomyocyte loss. The recognized vulnerability of SR to the anthracycline oxidative damage is counterbalanced by an acceleration of G6P flux through a PPP confined within the reticular lumen. The interplay of SR-PPP with the intracellular Ca2+ exchanges regulators in cardiomyocytes configure the reticular PPP as a potential new target for strategies aimed to decrease anthracycline toxicity.

Marked improvements in cardiac function in postmenopausal women exposed to blood withdrawal plus endurance training

ABSTRACT The cardiac phenotype of a substantial fraction of the population, i.e., mature women, is mainly unresponsive to endurance training (ET), the most effective intervention to improve cardiorespiratory fitness. This study assessed whether a novel intervention comprising additional haemodynamic stimuli may overcome the generalized limitations to modify the cardiac phenotype of middle-aged and older women. Fifteen healthy postmenopausal women (52–75 yr) were recruited. Transthoracic echocardiography and central haemodynamics were assessed during incremental cycle ergometry (i) in baseline conditions, (ii) after standard (10%) blood withdrawal and (iii) subsequent 8-week ET. Main outcomes such as left ventricular (LV) function and structure and blood volume (BV) were determined. Phlebotomy induced a 0.5 ± 0.1 l reduction of BV, which was re-established after ET. Decrements in LV end-systolic volume (−27%) and increments in LV ejection fraction (+8%) during exercise as well as improved E/A ratio were detected after ET compared with baseline. In parallel, ET induced a 10% increment in LV mass without a concomitant increase in LV size. In conclusion, postmenopausal women exhibit large improvements in cardiac systolic and diastolic functions along with LV concentric remodelling in response to the sequenced combination of blood withdrawal and ET.

Echocardiographic assessment of ventricular function in chronic HCV patients receiving direct antiviral therapy

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Hepatitis C virus (HCV) infection is still a major public health burden in many parts of the world (1). Globally, an estimated 58 million people have chronic hepatitis C virus infection, with about 1.5 million new infections occurring per year (2). Treatment for chronic HCV infection has evolved from interferon (IFN)-based therapy to direct-acting antivirals (DAAs) (3,4). With the development of DAA, treatment of HCV became better-tolerated and highly effective (5,6). Several studies have attempted to explore their cardiac side effects, especially their impact of left ventricular (LV) function; however, these studies were limited by their design and the methods of assessment (7-10). Aim In this prospective study we aimed at evaluating the short effects of DAAs on left ventricular functions using 3D Echocardiography. Methods Patients with HCV infection planned to receive combination therapy of Sofosbuvir 400 mg daily plus Daclatasvir 60 mg daily for 12 weeks were assessed by echocardiography before starting and after 3 months after completion of treatment. Patients with other systemic or cardiac conditions or structural heart disease were excluded. Assessment of LV volume and EF was performed by 3D quantification and global longitudinal strain (GLS). Right ventricle size was assessed by 2D and systolic function was evaluated by TAPSE, S` and FAC. Results In 102 patients who were followed up at 3 months after DAA therapy, We found an increase in increase in both LV end diastolic dimensions and volumes (p∼0.02 & p∼0.045 respectively) as well as end systolic volumes (p∼0.005). There was no significant difference in neither LV systolic function as assessed by EF and GLS (62.25 ± 5.15 vs. 62.35 ± 5.77, p∼0.850, -22.97 ± 2.93 vs. -22.83 ± 2.59, p∼0.546 respectively), nor in diastolic function (p∼0.546). However, subgroup analyses revealed a significant negative correlation between age and GLS (P∼0.022) as well as the number of cardiovascular risk factors (P∼0.039). Hypertension was found to be the only predictor of the decrease in GLS in the regression analysis of risk factors (p∼0.001). There was no significant change in RV size and systolic function at follow up. Conclusions There was no significant change in LV systolic or diastolic function before and after DAA therapy as measured by EF and GLS. Nonetheless, subgroup analysis suggests a drop in GLS in older patients and those with more cardiovascular risk factors. An increase in LV size was also noted while no significant effect was noted with regards to RV size and function.

THE RELATIONSHIPS OF IRS-1 POLYMORPHISM WITH HEMODYNAMIC DISORDERS IN HYPERTENSIVE PATIENTS DEPENDING ON BODY WEIGHT AND METABOLIC COMORBIDITY.

The aim: The aim was to study the relationships of IRS-1 gene polymorphism with indicators of the structural and functional state of the heart and blood vessels in patients with arterial hypertension under conditions of different metabolic comorbidity and body weight. Materials and methods: We examined 340 patients with arterial hypertension with different body weight and different types of metabolic comorbidity and 30 healthy individuals aged 45-55. Anthropometric, Biochemical, Molecular genetic methods, Instrumental, Statistical methods were used. Results: The presence of G/R + R/R genotypes in hypertensive patients with normal body weight was associated with an increase in intima-media thickness (CIMT), pulse wave velocity of carotid artery (cPWV) and lower endothelium-dependent vasodilatation (EDVD) compared with G/G genotype carriers. Hypertensive patients with obesity, carriers of G/R and R/R genotypes displayed more pronounced similar changes in vascular remodeling (higher CIMT, cPWV and lower EDVD) and as well as cardiac remodeling (larger sizes and left ventricular mass (LVM)) compared with G/G genotype carriers. Overweight carriers of the G/R + R/R genotypes were characterized by enlargement of LVM and its sizes, a higher CIMT indicator, but this effect was less than in the comorbidity of hypertension and obesity. In hypertensive patients with hypertension, obesity and type 2 diabetes mellitus, the presence of G/R + R/R genotypes was associated with an increase in left ventricular size, left ventricular mass index (LVMI) and CIMT. Conclusions: The relationships of IRS-1 polymorphism with indicators of cardiovascular remodeling in hypertensive patients depending on body weight and the presence of various metabolic comorbidity have been established.

THE RELATIONSHIPS OF IRS-1 POLYMORPHISM WITH HEMODYNAMIC DISORDERS IN HYPERTENSIVE PATIENTS DEPENDING ON BODY WEIGHT AND METABOLIC COMORBIDITY

The aim: The aim was to study the relationships of IRS-1 gene polymorphism with indicators of the structural and functional state of the heart and blood vessels in patients with arterial hypertension under conditions of different metabolic comorbidity and body weight. Materials and methods: We examined 340 patients with arterial hypertension with different body weight and different types of metabolic comorbidity and 30 healthy individuals aged 45-55. Anthropometric, Biochemical, Molecular genetic methods, Instrumental, Statistical methods were used. Results: The presence of G/R + R/R genotypes in hypertensive patients with normal body weight was associated with an increase in intima-media thickness (CIMT), pulse wave velocity of carotid artery (cPWV) and lower endothelium-dependent vasodilatation (EDVD) compared with G/G genotype carriers. Hypertensive patients with obesity, carriers of G/R and R/R genotypes displayed more pronounced similar changes in vascular remodeling (higher CIMT, cPWV and lower EDVD) and as well as cardiac remodeling (larger sizes and left ventricular mass (LVM)) compared with G/G genotype carriers. Overweight carriers of the G/R + R/R genotypes were characterized by enlargement of LVM and its sizes, a higher CIMT indicator, but this effect was less than in the comorbidity of hypertension and obesity. In hypertensive patients with hypertension, obesity and type 2 diabetes mellitus, the presence of G/R + R/R genotypes was associated with an increase in left ventricular size, left ventricular mass index (LVMI) and CIMT. Conclusions: The relationships of IRS-1 polymorphism with indicators of cardiovascular remodeling in hypertensive patients depending on body weight and the presence of various metabolic comorbidity have been established.

Missing Link between Molecular Aspects of Ventricular Arrhythmias and QRS Complex Morphology in Left Ventricular Hypertrophy.

The aim of this opinion paper is to point out the knowledge gap between evidence on the molecular level and clinical diagnostic possibilities in left ventricular hypertrophy (LVH) regarding the prediction of ventricular arrhythmias and monitoring the effect of therapy. LVH is defined as an increase in left ventricular size and is associated with increased occurrence of ventricular arrhythmia. Hypertrophic rebuilding of myocardium comprises interrelated processes on molecular, subcellular, cellular, tissue, and organ levels affecting electrogenesis, creating a substrate for triggering and maintaining arrhythmias. The knowledge of these processes serves as a basis for developing targeted therapy to prevent and treat arrhythmias. In the clinical practice, the method for recording electrical phenomena of the heart is electrocardiography. The recognized clinical electrocardiogram (ECG) predictors of ventricular arrhythmias are related to alterations in electrical impulse propagation, such as QRS complex duration, QT interval, early repolarization, late potentials, and fragmented QRS, and they are not specific for LVH. However, the simulation studies have shown that the QRS complex patterns documented in patients with LVH are also conditioned remarkably by the alterations in impulse propagation. These QRS complex patterns in LVH could be potentially recognized for predicting ventricular arrhythmia and for monitoring the effect of therapy.

Гендерные особенности изменений состояния сердечно-сосудистой системы при алкгольной кардиомиопатии. Экспериментальное исследование

Цель исследования - изучение гендерных различий в сердечно-сосудистой системе у крыс c алкогольной кардиомиопатией. Методика. Алкогольную кардиомиопатию у крыс воспроизводили, предоставляя им в качестве единственного источника питья 10%-ный водный раствор этилового спирта в течение 24 нед. Для оценки размеров левого желудочка сердца и его инотропной функции использовали эхокардиографию. С помощью полимеразной цепной реакции «в реальном времени» определяли экспрессию ряда рецепторов и регуляторных белков в миокарде левого желудочка и грудной аорте. Результаты. Сравнительный анализ показал, что у интактных самок по сравнению с самцами размеры левого желудочка сердца значительно меньше, в то время как фракции укорочения и выброса выше. Принудительная алголизация в течение 24-х нед как у самцов, так и у самок вызывает развитие алкогольной кардиомиопатии, эхокардиографически проявляющейся увеличением размеров левого желудочка сердца и угнетением его сократительной функции. Однако у самок увеличение размеров левого желудочка выражено в значительно большей степени. В биоптатах левого желудочка сердца животных обоего пола изменения уровня экспрессии мРНК рецепторов эндогенных трансмиттеров: катехоламинов (β1- и β2-AR), ангиотензина II (AT1A-R), эндотелина-1 (ETA-R) и регуляторных белков (Eрас1, Ерас2 и CaM) при алкогольной кардиомиопатии носит однонаправленный характер. В аорте самок повышается экспрессия мРНК ключевых вазоконстрикторных рецепторов (α1-R, ETA-R, VIA-R, AT1A-R), тогда как в аорте самцов, напротив снижается. Заключение. Таким образом, как у самок, так и самцов крыс 24-недельное систематическое потребление алкоголя приводит к формированию алкогольной кардиомиопатии, однако у самок выявленные патологические изменения прогностически более неблагоприятны. Aim. To study sex-related differences of changes in the cardiovascular system in rats with alcoholic cardiomyopathy (AСMP). Methods. Alcoholic cardiomyopathy was induced in rats by offering them a 10% aqueous solution of ethyl alcohol as the only source of fluid for 24 weeks. Echocardiography was used to assess the size and inotropic function of the left ventricle. Expression of receptors and regulatory proteins in the left ventricular myocardium and thoracic aorta was determined using real-time polymerase chain reaction. Results. Comparative analysis showed that the left ventricle was much smaller in intact females than in males whereas shortening and ejection fractions of the female left ventricle were greater. Forced alcoholization for 24 weeks induced ACMP in both males and females, which was evident on echocardiogram as enlargement of the left ventricle and depression of its contractility. However, the increase in left ventricular size was considerably more pronounced in females. In biopsy samples of the left ventricle, the expression of mRNA of genes for endogenous transmitter receptors [catecholamines (β1 and β2-AR), angiotensin II (AT1-R), endothelin-1 (ETA-R) and regulatory proteins (Epac1, Epac2 and CaM) changed in the same direction in both males and females. The mRNA expression of key vasoconstrictor receptor genes (α1-R, VIA-R, ATIA-R) was increased in the female aorta but reduced in the male aorta. Conclusion. In both female and male rats, the 24-week alcohol consumption on a regular basis resulted in ACMP; however, in females, pathological changes were prognostically more adverse.

Prognostic significance of NT-proBNP, 3D LA volume and LV dyssynchrony in patients with acute STEMI undergoing primary percutaneous intervention

ObjectivesThe aim of the present study was to assess the short term prognostic significance of N-terminal pro BNP (NT-proBNP), 3D left atrial volume (LAV) and left ventricular (LV) dyssynchrony in patients of acute ST-elevation myocardial infarction (STEMI) who underwent primary Percutaneous intervention (PCI). BackgroundNT-proBNP, LV dyssynchrony and LAV in patients with acute coronary syndrome have been associated with PCI outcomes and predict the short and long-term prognosis. MethodsThis study consisted of 142 patients with a first STEMI who underwent primary PCI. Baseline echocardiographic data was collected at admission and at 6 months follow up. Left ventricular dyssynchrony was measured by tissue Doppler imaging and LAV by real time 3D-echocardiography, plasma NT-proBNP levels were estimated between 72 and 96 h of admission. ResultsDuring study period 3 patients expired and 4 developed congestive heart failure (CHF). Baseline NT-proBNP and LV dyssynchrony correlated with LV size and LV ejection fraction (LVEF) at baseline and during follow up. Patients with higher NT-proBNP levels and higher LV dyssynchrony showed significant increase in LV size with decrease in LVEF during follow-up. Baseline Left atrial volume index (LAVI) showed significant correlation with LV size but no association with LVEF at baseline and during follow-up. ConclusionsHigher levels of NT-proBNP and higher LV dyssynchrony can predict patients with increase in LV size, worsening of LV systolic and diastolic function during follow-up. Patients with higher NT-proBNP levels at baseline developed CHF during follow-up.

Predictors and prevention of diabetic cardiomyopathy

Despite our cognizance that diabetes can enhance the chances of heart failure, causes multiorgan failure,and contributes to morbidity and mortality, it is rapidly increasing menace worldwide. Less attention has been paid to alert prediabetics through determining the comprehensive predictors of diabetic cardiomyopathy (DCM) and ameliorating DCM using novel approaches. DCM is recognized as asymptomatic progressing structural and functional remodeling in the heart of diabetics, in the absence of coronary atherosclerosis and hypertension. The three major stages of DCM are: (1) early stage, where cellular and metabolic changes occur without obvious systolic dysfunction; (2) middle stage, which is characterized by increased apoptosis, a slight increase in left ventricular size, and diastolic dysfunction and where ejection fraction (EF) is <50%; and (3) late stage, which is characterized by alteration in microvasculature compliance, an increase in left ventricular size, and a decrease in cardiac performance leading to heart failure. Recent investigations have revealed that DCM is multifactorial in nature and cellular, molecular, and metabolic perturbations predisposed and contributed to DCM. Differential expression of microRNA (miRNA), signaling molecules involved in glucose metabolism, hyperlipidemia, advanced glycogen end products, cardiac extracellular matrix remodeling, and alteration in survival and differentiation of resident cardiac stem cells are manifested in DCM. A sedentary lifestyle and high fat diet causes obesity and this leads to type 2 diabetes and DCM. However, exercise training improves insulin sensitivity, contractility of cardiomyocytes, and cardiac performance in type 2 diabetes. These findings provide new clues to diagnose and mitigate DCM. This review embodies developments in the field of DCM with the aim of elucidating the future perspectives of predictors and prevention of DCM.

Myocardial dysfunction in the periinfarct and remote regions following anterior infarction in rats quantified by 2D radial strain echocardiography: An observational cohort study

BackgroundHeart failure from adverse ventricular remodeling follows myocardial infarction, but the contribution of periinfarct and remote myocardium to the development of cardiomyopathy remains poorly defined. 2D strain echocardiography (2DSE) is a novel and sensitive tool to measure regional myocardial mechanics. The aim is to quantify radial strain in infarcted (I), periinfarct (PI) and remote (R) myocardial regions acutely and chronically following anterior infarction in rats.MethodsThe left anterior coronary artery of male Sprague-Dawley rats (270–370 g) were occluded for 20–30 minutes and 2DSE was performed in the acute setting (n = 10; baseline and 60 minutes post-reperfusion) and in the chronic setting (n = 14; baseline, 1, 3 and 6 weeks). Using software, radial strain was measured in the mid-ventricle in short axis view. The ventricle was divided into 3 regions: I (anteroseptum, anterior and anterolateral), PI – (inferoseptum and inferolateral) and R – (inferior). Infarct size was measured using triphenyl tetrazolium chloride in the acute group.ResultsFollowing infarct, adverse remodeling occurred with progressive increase in left ventricular size, mass and reduced fractional shortening within 6 weeks. Radial strain decreased not only in the infarct but also in the periinfarct and remote regions acutely and chronically (I, PI, R, change vs. baseline, 60 minutes -32.7 ± 8.7, -17.4 ± 9.4, -13.5 ± 11.6%; 6 weeks -24.4 ± 8.2, -17.7 ± 8.3, -15.2 ± 8.4% respectively, all p < 0.05). Reduced radial strain in periinfarct and remote regions occurred despite minimal or absent necrosis (area of necrosis I, PI, R: 48.8 ± 23, 5.1 ± 6.6, 0 ± 0%, p < 0.001 vs. I).ConclusionFollowing left anterior coronary occlusion, radial strain decreased at 60 minutes and up to 6 weeks in the periinfarct and remote regions, similar to the reduction in the infarct region. This demonstrates early and chronic myopathic process in periinfarct and remote regions following myocardial infarction that may be an under recognized but important contributor to adverse left ventricular remodeling and progression to ischemic cardiomyopathy.

Myocardial Contrast Echocardiographic Estimates of Infarct Size Predict Likelihood of Left Ventricular Remodeling After Acute Anterior Wall Myocardial Infarction

We sought to determine the utility of myocardial contrast echocardiography (MCE) in predicting left ventricular (LV) remodeling (LVR) in patients with a recent anterior wall myocardial infarction and residual regional LV akinesis. Although recent studies have shown that MCE predicts recovery of regional and global LV systolic function after myocardial infarction, the relationship between myocardial perfusion patterns and likelihood of subsequent LVR has not been extensively studied. In all, 50 patients (mean age 62 years) underwent contrast-enhanced echocardiography for determination of LV volumes and ejection fraction, and MCE, 2 days after admission, with follow-up contrast-enhanced echocardiography 6 months later. LVR was defined as greater than 15% increase in LV end-diastolic volume index at follow-up. LVR occurred in 19 patients (38%) (group 1), with stable LV volumes in 31 patients (62%) (group 2). Routine clinical and angiographic variables did not differ between groups 1 and 2. Both transmural extent of infarction and number of abnormally perfused myocardial segments (assessed by MCE) predicted LVR. LVR occurred in 55% of patients with transmural perfusion defects, and was less common in those with subendocardial perfusion defects or normal perfusion (31% and 21%, respectively). The mean percent increase in LV size was significantly greater for transmural infarcts (15 +/- 7%) versus subendocardial infarcts or normal perfusion (-1 +/- 8 and 8 +/- 8, respectively). When more than 5 myocardial segments were abnormally perfused, remodeling always occurred and was extensive. MCE markers of infarct size are useful in predicting subsequent risk of LVR after myocardial infarction. Routine performance of MCE studies in select patients early after infarction may be helpful in further refining risk stratification.

Comparison of cardiac function in children after surgical and Amplatzer occluder closure of secundum atrial septal defects

The aim of the retrospective study was to examine the changes in the left and right ventricular size as well as the systolic and diastolic function of the left ventricle after surgical and transcatheter treatment of atrial septal defects with Amplatzer atrial septal defect occluder (ASDO). Two groups of patients were examined using transthoracic cross-sectional echocardiography before and after the treatment of atrial septal defect: Group A--Amplatzer ASD occluder--38 children and Group S treated surgically--20 children. The following parameters were assessed: left and right ventricular end-diastolic diameter indexes, ejection fraction, mitral E wave to A wave velocity ratio, deceleration time (DCT), isovolumetric relaxation time (IVRT) and heart rate. There was a significant decrease in right ventricular and an increase in left ventricular size in both groups during the follow-up observation. The long-term ECHO examination revealed smaller right ventricle (RV) (Group A: RVEDI=1.00+/-0.20 vs Group S RVEDI: 1.18+/-0.20 (p=0.001)) and bigger left ventricle (Group A: LVEDI=1.04+/-0.08 vs Group S: LVEDI=0.99+/-0.07 (p=0.022)) in Group A in comparison to Group S. Children undergoing operation had significantly shorter IVRT (Group A: IVRT=50.00+/- 9.65 vs Group S: IVRT=42.5+/- 8.95 (p=0.02)) than patients after ASDO device application. (1) During the follow-up period, the diastolic function of the left ventricle is better in children with device closure of ASD compared with those patients treated surgically. (2) Postoperative changes of the left and right ventricular size indexes are more favourable in patients after the device closure of ASD compared with children undergoing the surgical procedure.

Association of fat-free mass and training status with left ventricular size and mass in endurance-trained athletes

We sought to study the relationship between left ventricular (LV) size and body composition in male endurance athletes and age-matched control subjects. Endurance training is associated with increases in both left ventricular mass (LVM) and left ventricular end-diastolic dimension (LVEDD) in athletes. In other populations, LVM is independently predicted by fat-free mass (FFM). We hypothesized that the increase in LV size and mass observed with training may be a normal response to increased FFM. Twelve young and 18 older male endurance athletes and 10 young and 18 older untrained men underwent exercise testing, echocardiography, and dual-photon x-ray absorptiometry body composition analysis. Univariate correlates (Spearman) and multivariate determinants of LVM and LVEDD were sought from: height, height(1.4), height(2.7), height(3.0), body surface area (BSA), FFM, weight, and body mass index. Un-indexed and indexed LVM and LVEDD were then compared. Athletes were of a similar age, weight, and height, but had higher FFM and maximum oxygen uptake than untrained men. Both LVM and LVEDD were correlated with body size, including FFM, BSA, weight, and height (all p < 0.05). On multivariate analysis, FFM was the only independent predictor of both LVM (R(2) = 0.36, p < 0.001) and LVEDD (R(2) = 0.35, p < 0.001). Furthermore, LVM and LVEDD (un-indexed and indexed to BSA and height) were different between athletes and non-athletes, but not when indexed to height(2.7) or FFM. Both LVM and LVEDD are predicted by FFM in endurance athletes, and when indexed to FFM, no training-related differences were observed. Thus, the extent of LV remodeling (athletic heart) in trained individuals may reflect a normal physiologic response to increased FFM induced by training.

Effects of the oral endothelin-receptorantagonist bosentan on echocardiographicand doppler measures in patients with pulmonary arterial hypertension

ObjectivesThe purpose of this study was to investigate the effects of bosentan (125 or 250 mg twice daily) on echocardiographic and Doppler variables in 85 patients with World Health Organization class III or IV pulmonary arterial hypertension (PAH). BackgroundBosentan, an orally active dual endothelin-receptor antagonist, improves symptoms, exercise capacity, and hemodynamics in patients with PAH. MethodsPatients had primary pulmonary hypertension (84%) or PAH associated with connective tissue disease. Of these, 29 patients received placebo and 56 received bosentan (1:2 randomization). Six-minute walk tests and echocardiograms were performed at baseline and after 16 weeks of treatment. ResultsBaseline characteristics were similar in the placebo and bosentan groups, and echocardiographic and Doppler findings were consistent with marked abnormalities of right ventricular (RV) and left ventricular (LV) structure and function that were due to PAH. The treatment effect on 6-min walking distance was 37 m in favor of bosentan (p = 0.036). Treatment effects of bosentan compared with placebo on other parameters were as follows: Doppler-derived cardiac index = +0.4 l/min/m2(p = 0.007), LV early diastolic filling velocity = +10.5 cm/s (p = 0.003), LV end-diastolic area = +4.2 cm2(p = 0.003), LV systolic eccentricity index = −0.12 (p = 0.047), RV end-systolic area = −2.3 cm2(p = 0.057), RV:LV diastolic areas ratio = −0.64 (p = 0.007), Doppler RV index = −0.06 (p = 0.03), and percentage of patients with an improvement in pericardial effusion score = 17% (p = 0.05). ConclusionsBosentan improves RV systolic function and LV early diastolic filling and leads to a decrease in RV dilation and an increase in LV size in patients with PAH.

Effect of aerobic training and detraining on left ventricular dimensions and diastolic function in prepubertal boys and girls.

The purpose of this study was to determine the effect of an aerobic training program on the left ventricular (LV) cardiac morphology and function of prepubertal children. Twenty-nine 10-11 year old boys and girls (TG) participated in a 13-week running program (3 x 1 h/week, intensity: > 80% HRmax), 26, of the same age, served as a control group (CG). M-mode, 2-dimensional and pulsed-wave Doppler analyses were performed, during resting conditions, before and after the training period (T) as well as, for TG only, after 2 months of detraining (D). LV internal chamber dimension increased (+ 4.6 %, p < 0.01) while wall thicknesses concomitantly decreased (-10.7%, p < 0.05) as a result of T. All cardiac morphological parameters returned to pretraining values after D. Doppler-derived measurements of LV diastolic filling performance were also significantly altered by Tand D. A significant enhancement in the early diastolic passive LV filling with a concomitant reduction in the late diastolic active LV filling were in fact obtained after T. The training-induced bradycardia (-7 beats x min(-1), p < 0.01) was probably responsible for the changes in the late characteristics of the diastolic active filling. All diastolic filling indexes returned to pretraining values after D. Systolic function indexes were not modified after either T or D. No changes were obtained for the overall LV morphological and functional variables after 13 weeks of normal life for CG. These findings indicate that cardiac morphological adaptations can occur in prepubertal children after several months of aerobic training. These alterations differ however, in some areas, to those classically reported in adults following endurance training programs where both an increase in LV size and mass exist. Our data likewise demonstrate that endurance training is able to induce favourable LV diastolic filling modifications, directed principally towards an enhancement in the early rapid filling inflow and a corresponding reduction in the atrial contribution to the total diastolic inflow.

Right ventricular size is acutely decreased by inhaled nitric oxide in newborns with pulmonary hypertension.

The pressure and volume demands of the right and left ventricles may dramatically change following selective pulmonary vasodilation in newborns with pulmonary hypertension. Thus, ventricular planimetry was performed by two-dimensional echocardiography in 35 newborns with lung disease and increased pulmonary vascular resistance who were treated with inhaled nitric oxide to determine the influence of therapy on right and left ventricular size and function. The end-diastolic and end-systolic areas of each ventricle were measured from apical 4-chamber images before, and 30 to 60 minutes after, the onset of 20 parts per million inhaled nitric oxide. Estimates of ventricular function were determined by the systolic decrease in ventricular area, (diastolic area - systolic area) x 100/diastolic area. Heart rate, systemic blood pressure, and left ventricular areas did not change. However, the oxygenation index, the proportion of right-to-left ductal shunt (nonrestrictive ductus arteriosus, n = 22), the systolic pulmonary arterial pressure (closed or restrictive ductus arteriosus, n = 13), and the right ventricular diastolic and systolic areas were decreased after nitric oxide inhalation. The baseline systolic decrease in left ventricular area was lower in a subgroup of patients who developed an increase in left ventricular diastolic area following nitric oxide inhalation. Thus, nitric oxide improves pulmonary hemodynamics and decreases right ventricular size in newborns with lung disease and pulmonary hypertension. However, newborns may develop an increase in left ventricular size if left ventricular function is decreased prior to therapy.

Right and Left Ventricular Planimetry in Newborns Treated with Inhaled Nitric Oxide † 1639

Planimetry was performed by two-dimensional echocardiography in 33 newborns with lung disease and pulmonary hypertension who were treated with inhaled nitric oxide to determine the influence of therapy on right and left ventricular size and function. The area of each ventricle was measured during diastole and systole from apical 4-chamber images before and after (30-60 minutes) the onset of 20 parts per million inhaled nitric oxide. Areas were indexed according to patient weight. Ventricular function was determined by(diastolic area-systolic area)/diastolic area. The severity of pulmonary hypertension was evaluated by Doppler echocardiography. Values are expressed as mean ± standard error, * p <0.05. Results: There were no changes in heart rate, systemic blood pressure, and right or left ventricular function. However, nitric oxide acutely decreased the oxygenation index (53± 5 vs. 30 ± 3*), the proportion of right to left ductal shunt(nonrestrictive ductus arteriosus, n=22; 0.60 ± 0.06 vs. 0.31 ± 0.06*), the systolic pulmonary arterial pressure (closed or restrictive ductus arteriosus, n=11; 71 ± 8 vs. 50 ± 7, mmHg*), and the indexed right ventricular diastolic (0.84 ± 0.04 vs 0.75 ± 0.03, cm2/kg*) and systolic (0.62 ± 0.04 vs 0.55 ± 0.03, cm2/kg*) areas. Baseline heart rate, blood pressure, blood gases, and Doppl. Baseline left ventricular function (0.28 ± 0.03, n=8 vs. 0.39± 0.02, n=25*) was less in patients who developed an increase in left ventricular diastolic area following nitric oxide inhalation. Conclusions and speculation: Oxygenation and pulmonary hemodynamics improve after nitric oxide inhalation in newborns with lung disease and pulmonary hypertension. This results in a decrease in right ventricular size; however, patients may develop an increase in left ventricular size if left ventricular function is decreased.

Quantitative echocardiography in left ventricular remodeling after myocardial infarction.

Two-dimensional transthoracic echocardiography has been used to study patients during and after myocardial infarction. Quantitative studies have revealed that progressive increase in left ventricular size is associated with a poor prognosis. When pre-defined echocardiographic criteria were used to stratify infarction patients for adverse cardiovascular outcome, the efficacy of combined thrombolysis and angiotensin-converting enzyme inhibitor therapy could be shown in those who developed left ventricular enlargement. Other descriptors of left ventricular architecture and function, such as cavity shape and the ratio of short-axis left ventricular muscle to cavity area, may predict cardiovascular death and severe heart failure.

Maternal left ventricular performance during bicycle exercise

Over the last few years, more women are exercising during pregnancy. Although many studies have examined left ventricular (LV) function during exercise in nonpregnant subjects, to date there is minimal data available on the LV response in the pregnant patient exercising at a high level of intensity during the second half of pregnancy. Pregnancy has been compared to a state of volume overload resulting in an increase in LV size without significant hypertrophy of the LV walls. 1 This increase in radius-to-wall thickness ratio may be viewed as detrimental to LV emptying, because wall stress is directly proportional to this ratio. 2 To offset this change in LV shape, vascular resistance and mean arterial blood pressure are significantly reduced during pregnancy. 2 We hypothesized that strenuous exercise during the second half of pregnancy could result in an afterload mismatch. This study examines LV size and function during vigorous stationary bicycle exercise performed in an erect position in 16 fit, pregnant women using 2-dimensional M-mode echocardiography.

Changes in left ventricular output from fetal to early neonatal life

Using pulsed Doppler and two-dimensionally directed M-mode echocardiographic techniques, we measured left ventricular (LV) output, stroke volume, heart rate, LV end-diastolic dimension (LVEDD), LV end-systolic dimension, and LV percent fractional shortening (%FS) in 34 normal term infants 12 to 24 hours before parturition and thereafter serially 1, 24, and 96 hours after birth. Stroke volume was calculated as the product of the aortic flow velocity integral and aortic valve area. There was a twofold increase in LV output 1 hour after birth (fetal 170 +/- 46 ml/min/kg vs 1 hour 327 +/- 66 ml/min/kg; p less than 0.01) which was associated with significant increases in stroke volume, %FS, and LVEDD (stroke volume 1.21 +/- 0.33 ml/kg vs 2.25 +/- 0.37 ml/kg; %FS 34.3% +/- 5.8% vs 37.7% +/- 5.4%; LVEDD 15.4 +/- 1.1 mm vs 17.7 +/- 1.4 mm). Heart rate did not change 1 hour after birth. During the subsequent hours after birth, LV output decreased significantly to a value of 245 +/- 56 ml/min/kg (p less than 0.01) at 24 hours, which did not change 96 hours after birth. There were significant declines in stroke volume, LVEDD, and heart rate 24 hours after birth (stroke volume 2.02 +/- 0.42 ml/kg; LVEDD 17.0 +/- 1.1 mm; heart rate 121 +/- 11 beats/min). The %FS remained unchanged within the first 96 hours of age. These results indicate that the major regulator of LV output immediately after birth is stroke volume and not heart rate. The increase in stroke volume is related to an increase in LV size and LV myocardial contractility. Our data provide a useful basis for the interpretation of abnormal LV function in the early neonatal period.