Right Ventricular Wall Thickness Research Articles

The therapeutic impact of human neonatal BMSC in a right ventricular pressure overload model in mice

ObjectiveTo determine the impact of donor age on the therapeutic effect of bone marrow-derived mesenchymal stem cells (BMSCs) in treating adverse remodeling as the result of right ventricle (RV) pressure overload.MethodsBMSCs were isolated from neonatal (< 1 month), infant (1 month to 1 year), and young children (1 year to 5 years) and were compared in their migration potential, surface marker expression, VEGF secretion, and matrix metalloprotein (MMP) 9 expression. Four-week-old male C57 mice underwent pulmonary artery banding and randomized to treatment and untreated control groups. During the surgery, BMSCs were administered to the mice by intramyocardial injection into the RV free wall. Four weeks later, RV function and tissue were analyzed by echocardiography, histology, and quantitative real-time polymerase chain reaction.ResultsHuman neonatal BMSCs demonstrated the greatest migration capacity and secretion of vascular endothelial growth factor but no difference in expression of surface markers. Neonate BMSCs administration resulted in increasing expression of VEGF, a significant reduction in RV wall thickness, and internal diameter in mice after PA banding. These beneficial effects were probably associated with paracrine secretion as no cardiomyocyte transdifferentiation was observed.ConclusionsHuman BMSCs from different age groups have different characteristics, and the youngest BMSCs may favorably impact the application of stem cell-based therapy to alleviate adverse RV remodeling induced by pressure overload.

P804 Heart complication of chikungunya fever: ecocardiographic evaluation of late effects

Abstract Introduction Chicungunya fever, epidemic caused by Alphavirus (CHIKV) transmitted by mosquitoes of the genus Aedes, is characterized by highly debilitating joint pain and can cause atypical cardiac complications in 10% of patients. CHIKV produces direct damage to myofibrils (inflammation and infiltration) and secondary damage due to hypersensitivity and necrosis. Objective To evaluate, by echocardiography, the chronic cardiac alterations of the CHIKV infection. Methods Thirty-two patients were studied (mean age was 56 ± 14 years, 17 females) with CHIKV-confirmed infection and signs of cardiac involvement between 5 and 25 months of evolution. The dimensions and function of the ventricles were measured by two-dimensional and Doppler echocardiography. The global longitudinal strain (GLS) of the left ventricle (LV) and left atrial longitudinal strain (LALS) were evaluated. Patients were divided into Group A, with duration of CHIKV infection shorter than 12 months (12 patients) and Group B, with disease duration equal to or greater than 12 months (20 patients). Comparative statistical data were considered significant when p &amp;lt;0.05. Results The diameters and volumes of LV, Left atrium (LA), right ventricular (RV) diameter and RV wall thickness were increased in Group B. LV ejection fraction (EF) was lower in Group B patients. The GLS was decreased in both Groups and the regression equation with EF were significant (r = 0.74, r ² = 0.55, p &amp;lt;0.00001). LALS was decreased in Group B. Diastolic dysfunction was predominantly grade 1 in Group A and restrictive in Group B. Segmental alteration (akinesia, dyskinesia) occurred in 7 patients. No patient had a history of precordial pain or coronary disease, nor clear signs of myocardial infarction on the ECG. Seven patients were hypertensive and four were diabetic. Eccentric LV hypertrophy and concentric remodeling of the walls were observed in 14 patients. Two patients had atrial fibrillation. Nine patients presented other types of arrhythmia, mainly ventricular extrasystoles. Conclusion Decreased EF of LV and SLG was observed in most patients with chronic CHIKV infection. In the first 12 months of evolution, the dimensions of the LV were normal, but after one year, most of the patients had dilatation of the cavity. LV concentric remodeling was more frequent in the first year and eccentric hypertrophy after one year of evolution. Segmental changes were observed in almost a quarter of the cases, as well as a high incidence of arrhythmias. All these findings suggest the progressive nature of the disease. Echocardiography plays an important role in the detection of cardiovascular alterations caused by Chicungunya fever and should be used after confirmation of infection, to initiate appropriate treatment already in the acute phase, which will probably minimize the deleterious effects of disease.

The echocardiographic impact of the systemic hypertension on the right ventricular: A Tunisian Cohort

Only few echocardiographic data are available in literature concerning the impact of the systemic hypertension on the right ventricle (RV) comparing to the left ventricle's impact. To describe the echocardiographic parameters concerning the impact of the systemic hypertension on the RV. Prospective and comparative study including 100 patients from June 2016 to June 2017, subdivided into two groups: Group A (50 patients, systemic hypertension) and group B (50 healthy patient, a control group). We compared the echocardiography parameters of the RV identified in both groups. The RV diameter, the RV ejection fraction (RVEF) and the right ventricular fractional area change (RV-FAC) were preserved and comparable in both groups. RV wall thickness was more increased in group A. The tricuspid annular plane systolic excursion (TAPSE) were comparable in both groups. TEI index was significantly higher ( P < 0.01) and the peak of systolic tricuspid annular motion velocity was significantly lower ( P < 0.01) in group A, reflecting the subclinical and asymptomatic RV systolic dysfunction. The RV global longitudinal strain (GLS-RV) was significantly lower in patient with hypertension. Tissue-Doppler and 2Dstrain were more reliable then RVEF, RV-FAC and TAPSE to determine a latent RV systolic dysfunction. The peak of Ea wave was significantly lower in group A and the peak of Aa wave was significantly higher in this group. The Ea/Aa ratio was lower in patient with hypertension ( P = 0.001) suggesting a RV diastolic dysfunction. Our study confirms that the impact of the systemic hypertension includes the RV as is well known about the LV. Therefore, the functional and morphological analysis of the RV must be evaluated during the regular echocardiographic follow-up of patients with hypertension to allow an early identification of subclinical systolic and diastolic RV dysfunction in order to revise the current therapeutic strategy.

Mechanism of the right ventricular reverse remodeling after balloon pulmonary valvuloplasty in patients with congenital pulmonary stenosis: A three-dimensional echocardiographic study.

Background and Objectives:The main effect of pulmonary stenosis is a rise in right ventricular pressure. This pressure overload leads to multiple changes in the shape, dimensions, and volumes of the right ventricle (RV) that are reversed after the relieve of the valve obstruction. We thought to study the changes in the RV in patients undergoing balloon pulmonary valvuloplasty (BPV) using three-dimensional (3D) echocardiography.Subjects and Methods:The study included 50 patients with isolated valvular pulmonary stenosis who underwent BPV at our hospital from December 2016 to August 2017; echocardiography was recorded preprocedural and 3 months after the procedural.Results:The median age of the study group at the time of the procedure was 2.7 years. The indexed RV wall thickness, basal, and mid-right ventricular dimensions decreased significantly after the procedure (P < 0.005), and the longitudinal dimension increased significantly after the procedure (P < 0.005). The end-systolic and the end-diastolic volumes (EDVs) by 3D echocardiography increased insignificantly (P > 0.05), and the right ventricular function increased significantly (P < 0.05), indicating that the changes in the EDVs were more than the changes in the end-systolic volumes.Conclusions:There are several factors that interplay together and result in reverse remodeling of the RV after BPV including regression in the RV hypertrophy; changes in the interventricular septal morphology, bowing, and mobility; and changes in the ventricular geometry and dimensions, rather than changes in the ventricular volumes.

Involvement of miR‐200b–PKCα signalling in pulmonary hypertension in cor pulmonale model

The right ventricle (RV) enlargement and pulmonary fibrosis are involved in cor pulmonale. The role of miR-200b in cor pulmonale is less well understood. This study was designed to evaluate the regulatory roles of miR-200b in cor pulmonale. Cor pulmonary mouse model was built via monocrotaline injection of monocrotaline (MCT). The expression of miR-200b in the lungs, RV and left ventricle (LV) are using real-time polymerase chain reaction. The transthoracic echocardiography was employed to determine the effects of miR-200b mimics and Gö6976 injection on MCT mice. The protein levels of protein kinase C α (PKCα), collagen, and fibronectin in the lung, RV, and LV in the mice with and without miR-200b mimics and Gö6976 injection were evaluated using western blot. The expression of miR-200b decreased in MCT mice, while there was no difference in LV. Both the miR-200b mimics and Gö6976 injection reversed the muscularization in the pulmonary artery, reversed RV hypertrophy, reduced RV systolic pressure, wall thickness and pulmonary fibrosis. The injection of miR-200b can reduce the PKCα expression in the lung, RV, and LV. This study confirmed the down-regulation of miR-200b in cor pulmonale. The reverse effects of miR-200b in the present study may provide a potential tool for cor pulmonary treatment.

Parameters of Right Ventricular Function Reveal Ventricular-Vascular Mismatch as Determined by Right Ventricular Stroke Work versus Pulmonary Vascular Resistance in Children with Pulmonary Hypertension

Right ventricular (RV) failure, a determinant of outcomes in pulmonary hypertension (PH), occurs when the right ventricle cannot compensate for increased afterload. The authors showed that RV stroke work (RVSW) can be estimated in children with PH as the product of stroke volume and RV pressure and is related to adverse outcomes. The aim of this study was to test the hypothesis that ventricular-vascular (VV) mismatch (high afterload and low RVSW) is associated with echocardiographic measures of RV performance and adverse outcomes. Invasive hemodynamic data and concurrent echocardiograms were reviewed. Fifty subjects with PH were included. Four groups were created by dividing the patients using median RVSW and median pulmonary vascular resistance. For each group, tricuspid annular plane systolic excursion, fractional area change, myocardial performance index, and anterior RV wall thickness were determined. Both major (i.e., death) and minor (i.e., worsening World Health Organization class) clinical outcomes were tabulated. Groups were compared using the Kruskal-Wallis or Fisher exact test. Patients in the high pulmonary vascular resistance/low RVSW cohort (VV mismatch) had the worst RV dysfunction: median tricuspid annular plane systolic excursion, 0.8cm (interquartile range, 0.7-0.8cm; P=.0002); median fractional area change, 0.29% (interquartile range, 0.27%-0.30%; P=.004); median myocardial performance index, 0.622 (interquartile range, 0.548-0.789; P=.0004). This group had the highest incidence of adverse outcomes: major events in 40%, minor events in 80%, and syncope in 60%. VV mismatch in pediatric PH can be assessed using RVSW and pulmonary vascular resistance and is associated with RV performance and adverse events. RVSW increases in compensated high-afterload states and falls as the right ventricle fails to meet increased load; thus, VV matching status may be a sensitive predictor of outcomes in pediatric PH.

Echocardiographic assessment of right heart size and function in dogs with pulmonary valve stenosis

Introduction/ObjectivesWe sought to determine the prevalence and clinical significance of right heart remodeling and right ventricular (RV) dysfunction in dogs with pulmonary valve stenosis (PS). We also sought to evaluate repeatability of several measurements of severity of PS, right heart size, and RV function in dogs with PS. Animals, materials and methodsSeveral indices of right atrial (RA) size and RV size and function were prospectively evaluated in 48 dogs with PS. Regression analysis was used to determine if indices of right heart size and function were independently associated with maximum transpulmonary pressure gradient (max PG) and adverse clinical findings (exercise intolerance, syncope, or right heart failure). Eight dogs underwent a second echocardiogram performed by the same operator to assess repeatability of the echocardiographic indices, which was quantified by coefficient of variation (CV) and repeatability coefficient. ResultsIncreased RA size (81%), increased RV wall thickness (83%), and decreased tricuspid annular plane systolic excursion (TAPSE [81%]) were common. Right atrial size, end-diastolic RV area, and RV wall thickness were independently associated with max PG. Decreased TAPSE was independently associated with adverse clinical findings. All indices except RA area (18.6%) and RV systolic velocity (20.7%) had CVs <15%. Repeatability coefficients are available to help distinguish a true change versus measurement variability during serially obtained exams. ConclusionsRight heart remodeling and RV dysfunction are common in dogs with PS and are associated with echocardiographic and clinical severity. Results support the quantitative assessment of right heart size and function in dogs with PS.

Do reverse dippers have the highest risk of right ventricular remodeling?

We aimed to evaluate right ventricular (RV) deformation in recently diagnosed untreated hypertensive patients with different 24-h blood pressure (BP) patterns (dipping, nondipping, extreme dipping and reverse dipping). This cross-sectional study involved 190 untreated hypertensive patients who underwent 24-h ambulatory BP monitoring and a detailed two-dimensional echocardiographic examination, including the assessment of layer-specific strain. We found that 24-h and daytime BP values did not differ between the four groups. Nighttime BP significantly and gradually increased from extreme dippers across dippers and nondippers to reverse dippers. RV structure and systolic and diastolic function did not significantly differ among the four groups. However, RV global and RV free wall longitudinal strains were significantly lower in nondippers and reverse dippers than in dippers and extreme dippers. The endocardial and epicardial RV longitudinal strains of the whole RV and free wall RV were the lowest in reverse dippers and highest in extreme dippers. Multivariate logistic regression analysis demonstrated that only reverse dipping patterns were associated with reduced RV global longitudinal strain [OR 2.9 (95% CI: 1.5-8.2)], independent of age, sex, 24-h systolic BP, LV mass index, RV wall thickness and E/e't. Similarly, the reverse dipping pattern was associated with reduced RV free wall longitudinal strain, independently of the mentioned parameters [OR 3.8 (95% CI: 1.8-8.5)]. In conclusion, in the hypertensive population, the reverse dipping BP pattern had an adverse effect on RV deformation. RV remodeling progressively deteriorated from extreme dippers to reverse dippers, but only the reverse dipping BP pattern was independently associated with the reduction in RV longitudinal strain.

Comparison of fetal echocardiography findings in mothers of gestational diabetes mellitus and control group

Increased metabolic rate of hyperglycemia in gestational diabetes causes macrosomia, which can also affect the Fetus heart. The thickness of the walls of the heart and its function in pregnant mothers of GDM can change over the ages before treatment. Therefore, the aim of this study was to evaluate the thickness of the walls of the heart and its function in the embryos with mothers of gestational diabetes mellitus in comparison with the control group for indirect evaluation of the effects of hyperglycemia on the heart of the fetal.Pregnant women between the ages of 28 to 32 weeks of gestational age who had anomalous scan ultrasonography between 22-22 weeks of normal who were included in the screening of a three hour glucose test for the definition of gestational gestational diabetes (GDM) compared with the control group using M –mode of ultrasound was evaluated for the thickness of the ventricles and the intra ventricular septum(IVS), as well as cardiac function.Of 93 cases, pregnant women with diabetes mellitus and 48 subjects were selected as controls. The mean age of the subjects was 26.33 with a standard deviation of 4.88. There was a significant and direct relationship between right ventricular wall thickness(RVT), left ventricular thickness(LVT) and Intra ventricular septum(IVS), as well as right ventricular fractional shortening (P 0.05).The thickness of the walls of the fetal heart in diabetic mothers is independent of changes in macrosomia and EFW, which can be indicative of increased metabolism and need for oxygenation in the fetus in these patients.

P1248Characteristics and clinical significance of right ventricular involvement in patients with hypertrophic cardiomyopathy

Abstract Background A few studies have demonstrated bi-ventricular hypertrophy in hypertrophic cardiomyopathy (HCM). However, clinical significance of HCM with right ventricular (RV) involvement has not been fully established. Therefore, we aimed to investigate the structural characteristics and clinical significance of RV hypertrophy in patients with HCM. Methods In a single center, large HCM registry, 256 patients with HCM who underwent both cardiac magnetic resonance (CMR) and transthoracic echocardiography within 6 months were retrospectively analyzed. RV involvement was defined as increased RV wall thickness &gt;7 mm on CMR in any segments of RV free wall and apex. Patients who had evidence of significant RV pressure overload (RV systolic pressure &gt;50mmHg) or had undergone septal myectomy were excluded. Cardiovascular outcomes were defined as the composite of cardiovascular death and hospitalization for cardiovascular disease. Results Among 256 patients, 41 (16%) showed RV involvement. During follow-up period (median 1099 days), 32 cardiovascular outcomes (3 cardiovascular death and 29 cardiovascular hospitalization) were occurred. Patients with RV involvement showed a significantly higher left ventricular (LV) thickness (23.8±5.8 vs. 21.2±5.0 mm, p=0.004), more advanced diastolic dysfunction, and larger left atrial volume index (LAVI, 48.5±20.3 vs. 40.2±14.9 mm/m2, p=0.016) compared to those without RV involvement. In multivariate cox regression analysis, presence of RV involvement (HR: 4.21, 95% CI: 1.99–8.90, p&lt;0.001) and LV ejection fraction &lt;50% (HR: 4.29, 95% CI: 1.37–13.43, p=0.012) were independently associated with cardiovascular outcomes. The Kapan-Meier curve showed that there was a significant decrease in probability of cardiovascular outcomes-free survival in patients with RV involvement (p=0.007) after using 1:1 propensity score matching (n=82) to adjust for age, sex, LV ejection fraction, LV maximal wall thickness, LAVI, and RV systolic pressure than patients without RV involvement (Figure 1). Figure 1 Conclusion RV involvement in patients with HCM were not rare (16%). Patients with RV involvement showed more advanced LV structure and dysfunction, suggesting an indicator of severe HCM. RV involvement in HCM has clinical significance related to cardiovascular outcomes.

P4446Cardiopulmonary exercise test in young patients with in early stages of sarcoidosis

Abstract Purpose To assess CPET data in young patients with pulmonary sarcoidosis (grade I-II) respectively corresponding parameters in healthy individuals. Methods 99 people aged 25–44 years were examined: 66 people with pulmonary sarcoidosis (PS) I-II grade formed the main group. The control group included 33 healthy, non-smoking people. In both groups the CPET was performed for assessment functional status of cardiorespiratory system. Results Vital capacity and FEV1 didn't differ in both groups (p=0.6 and 0.19). However, Tiffno's index was significantly higher in the control group (p=0.0002). There were no differences in RVOT1, RVOT2, RA volume index in both groups. A comparative analysis of the RV wall thickness revealed that the values in both groups did not exceed the normal limits, but in the main group it was significantly larger (p=0.01). The basal RV diameter at rest were also larger in patients with sarcoidosis (p=0.007). LV contractility at rest was within normal values in both groups, however, in patients with sarcoidosis EF were statistically less than in the control group. At the peak of exercise EF increased more significantly in the control group (p&lt;0.0001). The EF-2D increase was higher in healthy young's (15% vs 10%). GLS LV both at rest and at the peak of exercise in both groups had no statistically significant differences. RV GLS in patients with sarcoidosis at the peak of exercise didn't increase (p=0.18) in contrast to healthy individuals (p=0.002). PAP at rest in patients with sarcoidosis was slightly higher than in healthy individuals (p=0.03), but didn't exceed the standard values. At the peak of exercise, in the main group PAP increased more than in the control group (p=0.ehz745.084701). In the control group the upper quartile of PAP was 29 mm Hg, at the peak of exercise-38 mm Hg. In the main group these values were much higher: 35 and 62 mm Hg. In control group, the maximum OC was higher (27.07±3.53 ml/min/kg, p=0.014). The duration of exercise was longer in healthy individuals (p=0.04). Thus, at the early stages of pulmonary sarcoidosis in young people there are no significant contractility abnormalities both at rest and at the peak of exercise, whereas the EF increase was lower than in healthy individuals. It is necessary to determine GLS RV, which may indicate RV dysfunction preceding the development of LV dysfunction. In patients with sarcoidosis, it's necessary to determine PAP at the peak of exercise, which increased in 79% of cases more than in healthy individuals. This may be due to secondary heart lesion at presence of pulmonary hypertension. The maximum oxygen consumption at the peak of exercise is higher in healthy individuals than in patients with sarcoidosis. So functional reserve was higher in the control group. Thus, the CPET today is an informative diagnostic tool which should be included in the diagnostic algorithms for patients with sarcoidosis.

Right Ventricular Hypertrophy in Refractory Acute Respiratory Distress Syndrome Treated With Venovenous Extracorporeal Membrane Oxygenation Support

In severe acute respiratory distress syndrome (ARDS) treated with extracorporeal membrane oxygenation (ECMO), right ventricular (RV failure) and dilation have been investigated with the use of echocardiography, whereas RV hypertrophy has not been addressed in the literature. The present study assessed the incidence of RV hypertrophy using echocardiography before ECMO treatment and at intensive care unit (ICU) discharge in severe ARDS patients. Observational, retrospective, single-center study. A single ECMO center. The study comprised 46 consecutive patients with severe ARDS. Echocardiographic evaluation and ECMO support. A dual-lumen cannula was implanted in most patients (38/46 [82.6%]). Before the start of ECMO, RV hypertrophy was present in 28 patients (60.8%) with no significant differences in baseline characteristics between the 2 subgroups. The ICU mortality rate was 30.4% (14/46), with no difference between patients with RV hypertrophy and those without. At ICU discharge, all patients showed RV hypertrophy. In severe ARDS treated with ECMO support, RV hypertrophy is a common finding and patients with normal RV wall thickness developed RV hypertrophy after ECMO support. The latter finding may suggest that during ECMO support, the right ventricle still may be subjected to increased afterload. However, additional research should be performed to elucidate the spectrum of mechanism(s) involved in the genesis of RV hypertrophy.

Pulmonary Obstruction Index in Multidetector Computed Tomographic Imaging for the Risk Assessment of Right Ventricular Dysfunction in Patients with Pulmonary Embolism

Objectives: Rapid and accurate risk assessment is critical in selecting the appropriate treatment strategy in the management of pulmonary embolism. This study was designed to assess the relationship between multidetector computed tomographic (MDCT) imaging and the pulmonary obstruction index, right ventricular dysfunction, and serum D-dimer levels in normotensive patients with pulmonary embolism. Patients and Methods: In 74 patients with suspected pulmonary embolism (38 men, 36 women), two readers in consensus assessed the central clot score and the signs of right ventricular dysfunction using MDCT by quantifying right ventricular diameter (RVD), left ventricular diameter (LVD), the ratio of the right ventricle to left ventricle short-axis diameters (RV/LV), and septal deviation. Results: The patients were divided into three groups. Thirty five patients had negative CT pulmonary angiography (CTPA) and deep vein thrombosis (DVT) findings (group 1), 29 had positive CTPA and negative DVT findings of pulmonary embolism (PE) (group 2), and 10 patients had positive DVT and CTPA findings (group 3). Serum D-dimer levels were statistically higher in group 3 than in the other groups. It was found as 329.2 ± 46.9, 461.3 ± 70.5, and 1726.6 ± 543.5 in groups 1, 2, and 3 (P = 0.0001), respectively. We found a significant positive correlation between the lower extremity clot load score and the pulmonary artery obstruction index, and pulmonary artery clot volumes. The right ventricle (RV)/left ventricle (LV) short-axis ratio, azygos vein diameter, the RV wall thickness (RVW), reflux of contrast medium into the inferior vena cava (IVC), leftward septal bowing, and interventricular septal thickness were statistically different in group 1 compared to groups 2 and 3. Conclusion: Evaluation of the total pulmonary artery clot load and morphologic findings of the right heart obtained using CTPA are extremely important in order to follow up patients with suspected venous thrombosis.

Exercising Skeletal Muscle Blood Flow is Diminished in a Rat Model of Pulmonary Arterial Hypertension

PURPOSE: Skeletal muscle dysfunction including a shift toward glycolytic metabolism has been suggested to contribute to exercise intolerance in pulmonary arterial hypertension (PAH) but an exercise perfusion limitation of skeletal muscle has not been identified. Therefore, we performed novel characterization of skeletal muscle blood flow response to exercise in a rat model of PAH. METHODS: Treadmill running at 50% VO2max was performed by male Sprague-Dawley rats (368±13g) injected with monocrotaline (MCT, 60mg/kg) to elicit a severe PAH phenotype (MCT, n=7), or vehicle control (saline) (CON, n=7). Fluorescent microspheres injected during run and rest bouts were utilized to determine blood flow via photo spectroscopy of harvested skeletal muscles. VO2max was measured prior to terminal blood flow studies to characterize exercise capacity of each rat and determine relative exercise intensity for flow analysis. Echocardiographic determination of right ventricular (RV) morphometry and function was also performed. Values are mean ± SE. RESULTS: As expected, MCT exhibited RV hypertrophy (as elevated ratio of RV to LV+S mass, p=0.002, and RV wall thickness in echocardiography, p=0.004), higher RV systolic pressure (p=0.02) and lower VO2max (p=0.03) vs. CON. During exercise, blood flow (expressed as as ml/min per 100g tissue) of the vastus lateralis, semitendinosus, gastrocnemius and biceps femoris was significantly reduced (p=0.02) in MCT (0.187±0.07) compared to CON (0.662±0.17) concomitant with higher (p=0.008) whole blood lactate in MCT (10.44±1.65 mmol/L) vs. CON (4.33±0.72 mmol/L). Further, exercising blood flow was inversely related to blood lactate at exercise (r=-0.603, p=0.03), and positively related to cardiac output (r=0.61, p<0.05). At rest, there was a tendency for both blood flow reduction (p=0.06) and higher lactates (p=0.09) in MCT (0.053±0.01, 5.98±2.48 mmol/L) vs. CON (0.148±0.04, 1.82±0.19 mmol/L). CONCLUSIONS: Exercising blood flow is reduced in a rat model of PAH and may contribute to metabolic limits to exercise capacity. Future studies will explore ways to augment skeletal muscle exercising blood flow in PAH, with the hope of improving tolerance for exercise in patients. Funding: NIH-NHLBI R-15 (MB Brown)

Focal scar and diffuse myocardial fibrosis are independent imaging markers in repaired tetralogy of Fallot.

AimsTo identify the correlates of focal scar and diffuse fibrosis in patients with history of tetralogy of Fallot (TOF) repair.Methods and resultsConsecutive patients with prior TOF repair underwent electrocardiogram, 24-h Holter, transthoracic echocardiography, exercise testing, and cardiac magnetic resonance (CMR) including cine imaging to assess ventricular volumes and ejection fraction, T1 mapping to assess left ventricular (LV) and right ventricular (RV) diffuse fibrosis, and free-breathing late gadolinium-enhanced imaging to quantify scar area at high spatial resolution. Structural imaging data were related to clinical characteristics and functional imaging markers. Cine and T1 mapping results were compared with 40 age- and sex-matched controls. One hundred and three patients were enrolled (age 28 ± 15 years, 36% women), including 36 with prior pulmonary valve replacement (PVR). Compared with controls, TOF showed lower LV ejection fraction (LVEF) and RV ejection fraction (RVEF), and higher RV volume, RV wall thickness, and native T1 and extracellular volume values on both ventricles. In TOF, scar area related to LVEF and RVEF, while LV and RV native T1 related to RV dilatation. On multivariable analysis, scar area and LV native T1 were independent correlates of ventricular arrhythmia, while RVEF was not. Patients with history of PVR showed larger scars on RV outflow tract but shorter LV and RV native T1.ConclusionFocal scar and biventricular diffuse fibrosis can be characterized on CMR after TOF repair. Scar size relates to systolic dysfunction, and diffuse fibrosis to RV dilatation. Both independently relate to ventricular arrhythmias. The finding of shorter T1 after PVR suggests that diffuse fibrosis may reverse with therapy.

Protection against pressure overload-induced right heart failure by uncoupling protein 2 silencing.

AimsThe role of uncoupling protein 2 (UCP2) in cardiac adaptation to pressure overload remains unclear. In a classical model of left ventricular pressure overload genetic deletion of UCP2 (UCP2−/−) protected against cardiac hypertrophy and failure. However, in UCP2−/− mice increased proliferation of pulmonary arterial smooth muscle cells induces mild pulmonary hypertension, right ventricular (RV) hypertrophy, and reduced cardiac output. This suggests a different role for UCP2 in RV and left ventricular adaptation to pressure overload. To clarify this situation in more detail UCP2−/− and wild-type mice were exposed to pulmonary arterial banding (PAB).Methods and resultsMice were analysed (haemodynamics, morphometry, and echocardiography) 3 weeks after PAB or sham surgery. Myocytes and non-myocytes were isolated and analysed separately. Cell shortening of myocytes and fura-2 loading of cardiomyocytes were used to characterize their function. Brd assay was performed to study fibroblast proliferation. Isolated mitochondria were analysed to investigate the role of UCP2 for reactive oxygen species (ROS) production. UCP2 mRNA was 2.7-fold stronger expressed in RV myocytes than in left ventricular myocytes and stronger expressed in non-myocytes compared with myocytes. Three weeks after PAB, cardiac output was reduced in wild type but preserved in UCP2−/− mice. UCP2−/− had increased RV wall thickness, but lower RV internal diameters and displayed a significant stronger fibrosis. Cardiac fibroblasts from UCP2−/− had reduced proliferation rates but higher collagen-1 expression. Myocytes isolated from mice after PAB banding showed preserved function that was further improved by UCP2−/−. Mitochondrial ROS production and respiration was similar between UCP2−/− or wild-type hearts.ConclusionDespite a mild pulmonary hypertension in UCP2−/− mice, hearts from these mice are well preserved against additional pressure overload (severe pulmonary hypertension). This—at least in part—depends on different behaviour of non-myocytes (fibroblasts).

Doppler-derived echocardiographic evidence of pulmonary hypertension in cats with left-sided congestive heart failure

IntroductionPulmonary hypertension (PH) caused by left-sided congestive heart failure (L-CHF) is common in dogs and contributes to clinical signs and outcome. The aim of this study was to evaluate the prevalence of Doppler echocardiography–derived PH in a population of cats with L-CHF. AnimalsThe study involved 131 cats with L-CHF and 56 control cats. MethodsThe study design is retrospective, observational study. Tricuspid regurgitation velocity, right atrial dimension, right ventricular (RV) dimension and function, RV wall thickness, pulmonary artery (PA) dimension, Doppler-derived systolic time intervals of PA flow, and presence of septal flattening were evaluated. Pulmonary hypertension was considered if tricuspid regurgitation velocity was >2.7 m/s. ResultsTricuspid regurgitation was present in 57/131 (44%) of cats with L-CHF and 24/56 (43%) in control cats based on color flow Doppler. Doppler-derived of PH was identified in 22/131 cats with L-CHF (17%). In 15/22 cats, PH was associated with cardiomyopathy, in 5/22 cases with congenital heart disease, and in 2/22 cases with other causes. Cats with Doppler-derived PH more often had chronic L-CHF, as opposed to acute L-CHF (p<0.05). All cats with Doppler-derived PH had subjectively-assessed right-sided heart enlargement, with larger right atrial and RV diameters (p<0.001), increased RV wall thickness (p<0.05), and higher prevalence of septal flattening (<0.001) and PA enlargement (p<0.05). ConclusionsPulmonary hypertension identified by Doppler echocardiography is not a common finding in cats with L-CHF. Right-sided heart enlargement, more frequently observed, may raise the suspicion of PH in cats with L-CHF.

Multi-Modality Image-Based Modeling Approach for Cardiovascular Disease: Simulation, Assessment, Prediction, and Virtual Surgery

Medical imaging and image-based modeling have made considerable progress in recent years in cardiovascular research, such as identifying atherosclerotic plaque morphological and mechanical risk factors which may be used in developing improved patient screening strategies, and performing virtual heart surgery seeking optimal surgical procedures for best post-surgical outcome. We will report recent progress in using multi-modality image-based models to predict vulnerable plaque progression and vulnerability change. In particular, we will report our recent results using IVUS+OCT data to obtain more accurate stress/strain calculations. Inflammation and cap erosion will affect cap material properties. If OCT image could provide inflammation and erosion information, cap stress/strain calculation can be further improved. Preliminary results using molecular imaging will be presented. Patient-specific ventricle models were constructed to perform virtual surgery for patients with repaired tetralogy of Fallot (TOF) to predict post-surgery outcome, and to seek parameters which could be used to identify patients who could benefit more from pulmonary valve replacement surgery. Cardiac magnetic resonance (CMR) data were obtained from 16 TOF patients (8 male, median age, 42.75) and 6 healthy group (HG) volunteers (1 male, median age, 20.1). CMR-based patient-specific computational RV/LV models were constructed to obtain RV wall thickness (WT), volumes, curvature, and mechanical stress and strain for comparative analysis. It was found that mechanical stress could be a good predictor for surgical outcome.

Focal scar and diffuse myocardial fibrosis in patients with history of repaired tetralogy of Fallot

Left and right ventricular (LV and RV) remodeling in repaired tetralogy of Fallot (TOF) is poorly understood. To identify correlates of focal scar and diffuse fibrosis in patients with history of TOF repair by using cardiac magnetic resonance (CMR). Patients with prior TOF repair underwent CMR including cine imaging to assess ventricular volumes and ejection fraction (EF), T1 mapping to assess LV and RV diffuse fibrosis, and high resolution late gadolinium-enhanced (LGE) imaging to quantify scar size. Structural imaging data were related to clinical characteristics and functional imaging markers. In 40 patients, cine and T1 mapping results were compared to age- and sex-matched controls. In total, 103 patients were enrolled (age 28 ± 15 years, 36% women), including 36 with prior PV replacement. Compared to controls, TOF patients showed lower LV and RVEF and higher RV volume, RV wall thickness, and native T1 and ECV values on both ventricles. Scar size related to LVEF and RVEF while LV and RV native T1 related to RV dilatation. On multivariable analysis, scar size and LV native T1 were independent correlates of ventricular arrhythmia. Patients with history of PV replacement showed larger scar on RV outflow tract but LV and RV native T1 were shorter ( Fig. 1 ). Focal scar and biventricular diffuse fibrosis are detected on CMR after TOF repair. Scar size relates to systolic dysfunction, and diffuse fibrosis to RV dilatation. Both may be implicated in ventricular arrhythmias. The finding of shorter T1 after PV replacement suggests that diffuse fibrosis may reverse with therapy.

B-type Natriuretic Peptide as a Marker of Different Forms of Systemic Sclerosis.

SummaryBackgroundSystemic sclerosis (SSc) is an autoimmune connective tissue disease which affects various tissues and organs, including skin, lungs, kidneys, gastrointestinal tract and cardiovascular system. Cardiac involvement is the most commonly recognized problem and a significant cause of morbidity. The brain natriuretic peptide (BNP) is a previously known marker of elevated cardiovascular risk in SSc, but the levels of BNP in various forms of SSc have not been investigated so far.AimThe aim of our study was to evaluate the influence of SSc on the function of the right ventricle and the right atrium using the echocardiographic parameters. Moreover, we examined the levels of BNP in different forms of SSc as well as the association of disease severity with the plasma concentrations of BNP.MethodsWe included 42 patients with newly diagnosed SSc and patients whose disease had been diagnosed earlier. SSc patients and non-SSc control patients were examined by using echocardiography and the concentrations of BNP were determined.ResultsWe analyzed differences in the parameters of right ventricle (RV) function and right atrium (RA) function between SSc patients and healthy controls. The two groups had similar distribution of gender, but SSc patients were significantly older than controls. RV wall thickness was increased in SSc patients (p<0.001), while right ventricular end-systolic area (RVESA; p=0.408) and right ventricular end-diastolic area (RVEDA; p=0.368) did not differ among the examinees. In contrast, RA minor-axis dimension (p=0.001) and the tricuspid annular plane systolic excursion (TAPSE) (p=0.001) were significantly higher in SSc patients. Also, we analyzed differences in brain natriuretic peptide (BNP) concentrations between diffuse cutaneous systemic sclerosis (DSSc) and limited cutaneous systemic sclerosis (LSSc) patients. DSSc patients had significantly higher concentrations of BNP. We found that levels of BNP were in significant positive correlations with age (p=0.007), disease duration (p=0.023), C reactive protein (CRP) (p=0.032), right ventricle fractional area change (FAC) (p=0.022), pulmonary vascular resistance (PVR) and Rodnan score (p=0.019).ConclusionsGiven the obtained results, the laboratory determination of BNP could be useful in differentiating different forms of systemic sclerosis as well as in predicting the severity of the disease and future cardiovascular complications.