Do Pediatric Sickle Cell Disease Patients Develop Diastolic Dysfunction?.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3195-3195
Author(s):  
Mark V. Zilberman ◽  
Wei Du ◽  
Wanda J. Whitten-Surney ◽  
Sharada A. Sarnaik
Keyword(s):  
Mitral Valve ◽  
Sickle Cell Disease ◽  
Tissue Doppler ◽  
Left Ventricular ◽  
Volume Index ◽  
Cell Disease ◽  
Mitral Inflow ◽  
Lv Mass ◽  
Z Scores ◽  
Mass Volume

Abstract Sickle cell disease (SCD) is a known cause of chronic volume overload. Although systolic dysfunction is rare, as many as 80% of adult patients with SCD have an echocardiographic mitral valve inflow pattern suggestive of abnormal left ventricular (LV) diastolic function (DF). DF has not been studied in pediatric SCD patients. Therefore, the objective of this study was to evaluate DF in pediatric SCD patients using echocardiographic velocities of mitral inflow and tissue Doppler (TDI) indices. Echocardiograms were performed in 79 SCD patients (ages 2 – 18 years), and 84 controls matched for age and race. LV and left atrial (LA) volumes, LV mass, early (E) and late (A) mitral inflow velocities, and TDI velocities at the septal and lateral aspects of the mitral valve were obtained. LV dilatation was defined as LV end-diastolic dimension more then 2 standard deviations above the median (z-value >2). LV hypertrophy was defined as LV mass/volume index>1.15 g/ml. For SCD patients, average hemoglobin (Hb) levels for the year prior to the study were recorded. Data were analyzed using t-test and Spearman correlation analysis. Of 79 SCD subjects, 32 (43%) had LV dilatation, 11(14.9%) had LV hypertrophy and 3 had both. LV z-scores were inversely related to Hb (r −0.62, p<0.0001) but unrelated to age. The early mitral inflow velocities E were negatively correlated with Hb levels(r − 0.34, p<0.04) and were positively correlated with LV z-scores (r 0.41, p<0.04) reflecting pre-load dependency of mitral inflow indices. DTI diastolic velocities were unrelated to Hg or LV size reflecting pre-load independent nature of these indices. DTI systolic velocities S’ correlated positively with LV mass/volume index (r 0.28, p<0.02). SCD patients had significantly larger LV and LA volumes than controls (p<0.01). The early E and late A mitral inflow velocities were higher in the SCD group than the control, although the differences were not statistically significant. DTI indices did not differ between SCD patients and the control. Conclusion: Despite high incidence of left ventricular dilatation, pediatric SCD patients don’t demonstrate diastolic dysfunction when evaluated using pre-load independent echocardiographic tissue Doppler indices.

scholarly journals GBT440 Increases Hematocrit and Improves Biventricular Function in Berkeley Sickle Cell Disease Mice

2020 ◽  
Vol 143 (3) ◽  
Author(s):  
Ryan Gassner ◽  
David Schreier ◽  
Timothy Hacker ◽  
Diana M. Tabima ◽  
Naomi Chesler
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Stroke Volume Index ◽  
Left Ventricular ◽  
Volume Index ◽  
Left Ventricular Ejection ◽  
Cell Disease ◽  
Ventricular Ejection Fraction ◽  
Blood Disorder ◽  
Biventricular Function

Abstract Sickle cell disease (SCD) is a hereditary blood disorder affecting millions of people in which red blood cells (RBCs) become sickled and lyse easily driven by polymerization of hemoglobin. Chronically, SCD causes anemia and biventricular dysfunction. GBT440 is an experimental treatment for SCD that prevents hemoglobin polymerization. We hypothesized that 17-month-old Berkeley SCD mice treated with GBT440 would have increased hematocrit (Hct) and better biventricular function compared to vehicle treated SCD mice. Our results demonstrate that 3 weeks of GBT440 treatment eliminated chronic anemia, increased left ventricular ejection fraction (LVEF) and stroke volume index, and improved right ventricular function. Overall, our findings support a therapeutic effect of GBT440 in vivo in a small animal model of SCD. Next steps in investigating mechanisms of improved cardiac function are warranted.

Abstract 15324: Mavacamten Favorably Impacts Key Pathophysiologic Processes in Obstructive Hypertrophic Cardiomyopathy: Results From the EXPLORER-HCM Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sheila M Hegde ◽  
Theodore P Abraham ◽  
Daniel Jacoby ◽  
Andrew Wang ◽  
Carolyn Ho ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Mitral Valve ◽  
Left Ventricular ◽  
Volume Index ◽  
Phase 3 ◽  
Double Blind ◽  
Beneficial Effects ◽  
Lv Mass ◽  
Obstructive Hypertrophic Cardiomyopathy ◽  
And Function

Introduction: Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by dynamic LV outflow tract (LVOT) obstruction resulting from ventricular hypertrophy and mitral valve systolic anterior motion (SAM), and by elevated left ventricular (LV) filling pressures, all of which result in a significant morbidity despite medical therapy. Mavacamten (Mava) is a novel inhibitor of cardiac myosin that significantly reduces LVOT gradients in oHCM, noted initially in the phase 2 PIONEER and more recently in the phase 3 EXPLORER-HCM studies. Additional echocardiographic analyses were performed to investigate the effect of Mava on focused measures of cardiac structure and function in oHCM. Methods: EXPLORER-HCM (NCT03470545) was a multicenter, double-blind, placebo-controlled, phase 3 study that randomized symptomatic oHCM patients (LV ejection fraction ≥55% and resting and/or provoked LVOT gradient ≥50 mmHg) 1:1 to Mava vs placebo for 30 weeks. Echocardiograms were performed serially every 2-4 weeks over 30 weeks. Results: In total, 251 patients with oHCM were enrolled and 244 patients completed the study (mean age 58.5; 40.6% female). Compared to placebo, 30-week treatment with Mava led to significant reductions in LA volume index (-7.5 ml/m 2 , p<0.0001), lateral E/e’ (-3.8, p<0.0001), septal E/e’ (-3.4, p<0.0001), and LV mass index (-15.5 g/m 2 , p<0.0001) ( Table ). Significantly more Mava-treated patients achieved resolution of mitral valve SAM compared to placebo (80.9% vs 34.0% of patients; difference of 46.8%; p<0.0001) and mitral regurgitation (MR) (9.0% vs 0.0% of patients; difference of 9.0%; p=0.0006). Conclusions: Treatment with Mava for 30 weeks led to improvement in LV hypertrophy and markers of left-sided filling pressures (LA volume and E/e’). Furthermore, Mava treatment was associated with reduction of SAM and MR. These findings suggest that Mava has beneficial effects on several adverse pathophysiologic processes that are hallmarks of oHCM.

scholarly journals Differential left ventricular and left atrial remodelling in heart failure with preserved ejection fraction patients with and without diabetes

2019 ◽  
Vol 10 ◽  
pp. 204201881986159 ◽  
Author(s):  
Gaurav S. Gulsin ◽  
Prathap Kanagala ◽  
Daniel C. S. Chan ◽  
Adrian S. H. Cheng ◽  
Lavanya Athithan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Left Atrial ◽  
Left Ventricular ◽  
Volume Index ◽  
Preserved Ejection Fraction ◽  
Cox Regression Analysis ◽  
Markers Of Inflammation ◽  
Lv Mass ◽  
Mass Volume

Background: Attempts to characterize cardiac structure in heart failure with preserved ejection fraction (HFpEF) in people with type 2 diabetes (T2D) have yielded inconsistent findings. We aimed to determine whether patients with HFpEF and T2D have a distinct pattern of cardiac remodelling compared with those without diabetes and whether remodelling was related to circulating markers of inflammation and fibrosis and clinical outcomes. Methods: We recruited 140 patients with HFpEF (75 with T2D and 65 without). Participants underwent comprehensive cardiovascular phenotyping, including echocardiography, cardiac magnetic resonance imaging and plasma biomarker profiling. Results: Patients with T2D were younger (age 70 ± 9 versus 75 ± 9y, p = 0.002), with evidence of more left ventricular (LV) concentric remodelling (LV mass/volume ratio 0.72 ± 0.15 versus 0.62 ± 0.16, p = 0.024) and smaller indexed left atrial (LA) volumes (maximal LA volume index 48 ± 20 versus 59 ± 29 ml/m2, p = 0.004) than those without diabetes. Plasma biomarkers of inflammation and extracellular matrix remodelling were elevated in those with T2D. Overall, there were 45 hospitalizations for HF and 22 deaths over a median follow-up period of 47 months [interquartile range (IQR) 38–54]. There was no difference in the primary composite endpoint of hospitalization for HF and mortality between groups. On multivariable Cox regression analysis, age, prior HF hospitalization, history of pulmonary disease and LV mass/volume were independent predictors of the primary endpoint. Conclusions: Patients with HFpEF and T2D have increased concentric LV remodelling, smaller LA volumes and evidence of increased systemic inflammation compared with those without diabetes. This suggests the underlying pathophysiology for the development of HFpEF is different in patients with and without T2D. ClinicalTrials.gov identifier: NCT03050593.

scholarly journals Left ventricular hypertrophy and diastolic dysfunction in children with sickle cell disease are related to asleep and waking oxygen desaturation

Blood ◽  
2010 ◽  
Vol 116 (1) ◽  
pp. 16-21 ◽  
Author(s):  
Mark C. Johnson ◽  
Fenella J. Kirkham ◽  
Susan Redline ◽  
Carol L. Rosen ◽  
Yan Yan ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Oxygen Saturation ◽  
Diastolic Dysfunction ◽  
Sickle Cell ◽  
Left Ventricular ◽  
Multivariable Logistic Regression Analysis ◽  
Cell Disease ◽  
Low Oxygen ◽  
Cardiac Abnormalities ◽  
Lv Mass

Abstract Premature death and cardiac abnormalities are described in individuals with sickle cell disease (SCD), but the mechanisms are not well characterized. We tested the hypothesis that cardiac abnormalities in children with SCD are related to sleep-disordered breathing. We enrolled 44 children with SCD (mean age, 10.1 years; range, 4-18 years) in an observational study. Standard and tissue Doppler echocardiography, waking oxygen saturation averaged over 5 minutes, and overnight polysomnography were obtained in participants, each within 7 days. Eccentric left ventricular (LV) hypertrophy was present in 46% of our cohort. After multivariable adjustment, LV mass index was inversely related to average asleep and waking oxygen saturation. For every 1% drop in the average asleep oxygen saturation, there was a 2.1 g/m2.7 increase in LV mass index. LV diastolic dysfunction, as measured by the E/E′ ratio, was present in our subjects and was also associated with low oxygen saturation (sleep or waking). Elevated tricuspid regurgitant velocity (≥ 2.5 m/sec), a measure of pulmonary hypertension, was not predicted by either oxygen saturation or sleep variables with multivariable logistic regression analysis. These data provide evidence that low asleep and waking oxygen saturations are associated with LV abnormalities in children with SCD.

Abstract 13767: Cardiac MRI Predictors of Good Long-term Outcomes in Patients With Repaired TOF

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Amara Majeed ◽  
Tal Geva ◽  
Julia Graf ◽  
Minmin Lu ◽  
Sonya Babu-Narayan ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Clinical Course ◽  
Systolic Function ◽  
Volume Ratio ◽  
Left Ventricular ◽  
Volume Index ◽  
Good Outcome ◽  
Intermediate Outcomes ◽  
Lv Mass ◽  
Mass Volume

Introduction: Good outcomes in adults with repaired tetralogy of Fallot (rTOF) are not well explored. Identifying markers of a benign clinical course late after TOF repair can guide resource utilization in this growing population. Methods: Clinical and CMR data were analyzed from the International Multicenter TOF Registry (INDICATOR). The clinical outcome was a composite of death, aborted sudden death, sustained ventricular and atrial arrhythmia, non-sustained ventricular tachycardia, and New York Heart Association functional class>II. Multinomial regression explored predictors of the 3-category outcome-Good and intermediate outcomes; defined as freedom from clinical outcome at 50 and <50 years respectively; and bad outcome; defined as having an adverse event at <50 years. Results: The cohort had 1088 patients-good outcome, n=96; intermediate, n=747; bad, n=245 with median age at last CMR 44 (40, 47); 21 (15, 28); 31 (20, 39) years respectively. Median follow-up was 8 (5, 11) years after CMR in event-free patients. Right ventricular (RV) parameters associated with a good outcome were smaller RV end-systolic volume index, higher RV ejection fraction (EF), lower RV mass index, and lower RV mass/volume ratio. Left ventricular (LV) parameters associated with a good outcome were lower LV mass index and LV mass/volume ratio. Multivariable models showed RV EF (OR 1.56 per 10% increase, p=.009) and RV mass index (OR 1.51, per 10 g/m 2 decrease, p=.002) as independently associated with good outcome after adjusting for age at CMR. Important thresholds identified in older patients (age ≥37 years) were RVEF ≥42% and RV mass index <39 g/m 2 . Combined, this subgroup had a 56% likelihood of a good outcome. Conclusions: Adults with rTOF and CMR findings of adequate RV systolic function and no significant ventricular hypertrophy are likely to have a benign clinical course by age 50 years. Frequency of cardiac testing in such patients may be lower than in those not fulfilling these criteria.

Genetic Influence on Left Ventricular Structure and Function: A Korean Twin and Family Study

2015 ◽  
Vol 18 (3) ◽  
pp. 281-289 ◽  
Author(s):  
Hye-Mi Noh ◽  
Sang Cheol Lee ◽  
Seung Woo Park ◽  
Joohon Sung ◽  
Yun-Mi Song
Keyword(s):  
Left Atrial Volume ◽  
Left Ventricular ◽  
Structure And Function ◽  
Volume Index ◽  
Atrial Volume ◽  
Left Atrial Volume Index ◽  
Mitral Inflow ◽  
Diastolic Velocity ◽  
Lv Mass ◽  
And Function

Genetic factors have been suggested to be one of the determinants of the variation of left ventricular (LV) structure and function. However, the heritability range of LV structure varies across studies and the influence of genetics on LV function is not well established, especially in Asian populations. Study subjects were 1,642 healthy Korean adults from 426 families, consisting of 298 pairs of monozygotic twins, 62 pairs of dizygotic twins, one set of triplets, 567 siblings, and 354 parents. LV structure and function were measured by M-mode and 2D echocardiography, and conventional and tissue Doppler imaging (TDI). Pairwise intra-class correlations for various familial relationships and heritability were estimated for LV structure and function. The heritability of LV mass, LV ejection fraction (LVEF), left atrial volume index, the ratio between early and late diastolic velocity of mitral inflow (E/A ratio), and the ratio between early diastolic velocity of mitral inflow and early diastolic mitral annular velocities (E/Ea ratio) was 0.44, 0.27, 0.44, 0.25, and 0.33, respectively. Bivariate genetic analysis showed that LV structural and functional traits had significant genetic correlations with cardiovascular risk factors. Additive genetic correlation (ρG) of LV mass with body mass index, systolic blood pressure, and high density lipoprotein cholesterol were 0.49, 0.42, and -0.15 respectively. LVEF (ρG = 0.33) and left atrial volume index (ρG = 0.24) also had a significant genetic correlation with systolic blood pressure. These findings support the theory that genetic factors have significant influence on these traits and necessitate further work to identify the specific genes involved.

scholarly journals Echocardiographic phenotypes of patients with sickle cell disease. An unsupervised analysis based on etendard cohort

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
T D"humieres ◽  
J Inamo ◽  
S Deswarte ◽  
T Damy ◽  
G Loko ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
Cardiac Output ◽  
Sickle Cell Disease ◽  
Diastolic Function ◽  
Sickle Cell ◽  
Left Ventricular ◽  
Integrative Approach ◽  
Cell Disease ◽  
Clinical Profiles ◽  
Cluster 2

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): PHRC Backgroung Echocardiography is the cornerstone in the diagnosis of cardiopulmonary involvement in sickle cell disease (SCD). However, given the unique pathophysiology of SCD associating high cardiac output, and various degrees of peripheral vasculopathy, differentiate the pathological from the physiological using echocardiography can be particularly challenging. Purpose This study sought to link cardiac phenotypes in homozygous SCD patients with clinical profiles and outcomes using cluster analysis. Methods We analyzed data of 379 patients with a sufficient echographic dataset included in the French Etendard Cohort, a prospective cohort initially designed to assess the prevalence of pulmonary hypertension. A cluster analysis was performed on echocardiographic variables, and the association between clusters and clinical profiles and outcomes was assessed. Results Three clusters were identified. Cluster 1 (N = 122) patients had the lowest cardiac output, only mild left cavities remodeling, diastolic dysfunction, and high tricuspid regurgitation velocity (TRV). They were predominantly female, as old as cluster 2, and displayed the most severe functional limitation. Cluster 2 (N = 103) patients had the highest cardiac output, left ventricular mass and a severely dilated left atrium. Diastolic function and TRV were similar to cluster 1. These patients had a higher blood pressure and a severe hemolytic anemia. Cluster 3 (N = 154) patients had mild left cavities remodeling, the best diastolic function and the lowest TRV. They were younger patients with the highest hemoglobin and lowest hemolytic markers. Right heart catheterization was performed in 94 patients. Cluster 1 gathered the majority of precapillary PH while cluster 2 gathered postcapillary PH and no PH was found in cluster 3. After a follow-up of 9.9 years (IQR: 9.3 to 10.5 years) death occurred in 38 patients (10%). Clusters 2 had the worst prognosis with 18% mortality rate vs. 12% in cluster 2 and 5% in cluster 1 (P log-rank = 0,02). Results are summarized in the central illustration. Conclusions Cluster analysis of echocardiographic variables identified 3 phenotypes among SCD patients, each associated with different clinical features and outcome. These findings underlines the necessity to rethink echocardiographic evaluation of SCD patients, with an integrative approach based on simultaneous evaluation of TRV along with left cavities remodeling and diastolic parameters. Abstract Figure.

Left ventricular remodeling after transcatheter mitral valve replacement with Tendyne

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Fukui ◽  
P Sorajja ◽  
M Goessl ◽  
R Bae ◽  
B Sun ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Valve Replacement ◽  
Mitral Valve Replacement ◽  
Ventricular Remodeling ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Reverse Remodeling ◽  
Functional Changes ◽  
Transcatheter Mitral Valve Replacement ◽  
Lv Mass

Abstract Background Data on changes in left atrial (LA) and left ventricular (LV) volumes after transcatheter mitral valve replacement (TMVR) are limited. Purpose This study sought to describe the anatomical and functional changes in left-sided cardiac chambers by computed tomography angiography (CTA) from baseline to 1-month after TMVR with Tendyne prosthesis. Methods We analyzed patients who underwent TMVR with Tendyne prosthesis (Abbott Structural, Menlo Park, CA) between 2015 and 2018. Changes in LV end-diastolic volume (LVEDV), ejection fraction (LVEF), mass (LV mass), LA volume and global longitudinal strain (GLS) were assessed at baseline and at 1-month after TMVR with CTA. Specific Tendyne implant characteristics were identified and correlated with remodeling changes. Results A total of 36 patients (mean age 73±8 years, 78% men, 86% secondary MR) were studied. There were significant decreases in LVEDV (268±68 vs. 240±66ml, p&lt;0.001), LVEF (38±10 vs. 32±11%, p&lt;0.001), LV mass (126±37 vs. 117±32g, p&lt;0.001), LA volume (181±74 vs. 174±70 ml, p=0.027) and GLS (−12.6±5.1 vs. −9.5±4.0%, p&lt;0.001) from baseline to 1-month follow-up. Favorable LVEDV reverse-remodeling occurred in the majority (30 of 36 patients, or 83%). Closer proximity of the Tendyne apical pad to the true apex was predictive of favorable remodeling (pad distance: 25.0±7.7 vs. 33.5±8.8mm, p=0.02 for those with and without favorable remodeling). Conclusions TMVR with Tendyne results in favorable left-sided chamber remodeling in the majority of patients treated, as detected on CTA at 1-month after implantation. CTA identifies the favorable post-TMVR changes, which could be related to specific characteristics of the device implantation. Funding Acknowledgement Type of funding source: None

scholarly journals Empagliflozin does not change cardiac index nor systemic vascular resistance but rapidly improves left ventricular filling pressure in patients with type 2 diabetes: a randomized controlled study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Matthias Rau ◽  
Kirsten Thiele ◽  
Niels-Ulrik Korbinian Hartmann ◽  
Alexander Schuh ◽  
Ertunc Altiok ◽  
...  
Keyword(s):  
Cardiac Index ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Resistance Index ◽  
Stroke Volume Index ◽  
Left Ventricular ◽  
Volume Index ◽  
Hemodynamic Parameters ◽  
Mitral Inflow ◽  
Ventricular Filling Pressure

Abstract Background In the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial) treatment with the sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin significantly reduced heart failure hospitalization (HHF) in patients with type 2 diabetes mellitus (T2D) and established cardiovascular disease. The early separation of the HHF event curves within the first 3 months of the trial suggest that immediate hemodynamic effects may play a role. However, hitherto no data exist on early effects of SGLT2 inhibitors on hemodynamic parameters and cardiac function. Thus, this study examined early and delayed effects of empagliflozin treatment on hemodynamic parameters including systemic vascular resistance index, cardiac index, and stroke volume index, as well as echocardiographic measures of cardiac function. Methods In this placebo-controlled, randomized, double blind, exploratory study patients with T2D were randomized to empagliflozin 10 mg or placebo for a period of 3 months. Hemodynamic and echocardiographic parameters were assessed after 1 day, 3 days and 3 months of treatment. Results Baseline characteristics were not different in the empagliflozin (n = 22) and placebo (n = 20) group. Empagliflozin led to a significant increase in urinary glucose excretion (baseline: 7.3 ± 22.7 g/24 h; day 1: 48.4 ± 34.7 g/24 h; p < 0.001) as well as urinary volume (1740 ± 601 mL/24 h to 2112 ± 837 mL/24 h; p = 0.011) already after one day compared to placebo. Treatment with empagliflozin had no effect on the primary endpoint of systemic vascular resistance index, nor on cardiac index, stroke volume index or pulse rate at any time point. In addition, echocardiography showed no difference in left ventricular systolic function as assessed by left ventricular ejections fraction and strain analysis. However, empagliflozin significantly improved left ventricular filling pressure as assessed by a reduction of early mitral inflow velocity relative to early diastolic left ventricular relaxation (E/eʹ) which became significant at day 1 of treatment (baseline: 9.2 ± 2.6; day 1: 8.5 ± 2.2; p = 0.005) and remained apparent throughout the study. This was primarily attributable to reduced early mitral inflow velocity E (baseline: 0.8 ± 0.2 m/s; day 1: 0.73 ± 0.2 m/sec; p = 0.003). Conclusions Empagliflozin treatment of patients with T2D has no significant effect on hemodynamic parameters after 1 or 3 days, nor after 3 months, but leads to rapid and sustained significant improvement of diastolic function. Trial registration EudraCT Number: 2016-000172-19; date of registration: 2017-02-20 (clinicaltrialregister.eu)

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