scholarly journals Dexrazoxane preferentially mitigates doxorubicin cardiotoxicity in female children with sarcoma

Open Heart ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. e001025 ◽  
Author(s):  
Hari K Narayan ◽  
Mary E Putt ◽  
Nikitha Kosaraju ◽  
Alejandro Paz ◽  
Shivani Bhatt ◽  
...  
Keyword(s):  
Circumferential Strain ◽  
Wall Stress ◽  
Left Ventricular ◽  
High Dose ◽  
Protective Effects ◽  
Cavity Size ◽  
Linear Regression Models ◽  
Cardioprotective Effects ◽  
And Function

ObjectiveWe sought to determine how sex and dexrazoxane therapy influence cardiac remodelling in children with sarcoma receiving high-dose doxorubicin.MethodsIn a retrospective cohort of 85 children with sarcoma receiving high-dose doxorubicin, echocardiography measures prior to, early after (within 6 months of doxorubicin completion) and 1 – 2 years after doxorubicin completion were quantified. At each follow-up visit, multivariable, propensity-adjusted linear regression models evaluated dexrazoxane’s effects on changes in left ventricular (LV) shortening fraction (SF), structure, strain and wall stress for subgroups divided by sex. Likelihood ratio tests assessed the interaction between sex and dexrazoxane in determining these changes.ResultsEarly after doxorubicin completion, males not treated with dexrazoxane (n = 15) developed increased cavity size and diminished circumferential strain; females (n = 8) developed diminished SF and strain indices, and increased cavity size and wall stress. With dexrazoxane, males (n = 33) demonstrated less deterioration in circumferential strain by 3.4% (95% CI 0.01 to 6.8), and females (n = 29) demonstrated less reduction in SF by 5.7% (95% CI 2.1 to 9.3), and had mitigation of increases in cavity size and wall stress. In interaction analyses, females had greater protection with dexrazoxane with regard to SF (p = 0.019) and cavity size in diastole (p = 0.002) and systole (p ≤ 0.001). These findings largely persisted 1 – 2 years after doxorubicin therapy.ConclusionsEarly, sustained alterations in LV structure and function occur in children with sarcoma after high-dose doxorubicin, with adverse changes and protective effects of dexrazoxane more pronounced in females as compared with males. Dexrazoxane may have sex-specific cardioprotective effects.

Abstract P022: Association of Longitudinal Change in Kidney Function with Left Ventricular Structure and Function as Measured by Cardiac MRI: The Multi-Ethnic Study of Atherosclerosis (MESA)

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Yoshiaki Ohyama ◽  
Bharath Ambale-Venkatesh ◽  
Kihei Yoneyama ◽  
Sirisha Donekal ◽  
Satoru Kishi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Reference Group ◽  
Left Ventricular ◽  
Structure And Function ◽  
Longitudinal Change ◽  
Linear Regression Models ◽  
Cvd Risk ◽  
Lv Mass ◽  
And Function

Background: This study examines the association of change in estimated glomerular filtration rate (eGFR) with change in left ventricular (LV) structure and function over 10 years of follow-up. Method: MESA participants with cardiac magnetic resonance imaging (CMR) measures and eGFR measured at both baseline (2000-2002, year-0) and the 10 year follow-up (2010-2012, year-10) exam were studied. Participants with cardiovascular disease (CVD) were excluded. LV mass and volume indexed to body surface area, LV ejection fraction (LVEF), and LV mass volume ratio (MVR) were determined by CMR. We stratified participants by the presence of eGFR < 60 ml/min/m2 at baseline and at year 10 into 4 groups; eGFR ≥60 at both year-0 and year-10 (reference), ≥60 at year-0 and <60 at year-10, <60 at year-0 and ≥60 at year-10, and <60 at both year-0 and 10. Multiple linear regression models were used to evaluate the association between eGFR groups and change in LV parameters (year-10 - year-0) after adjusting for the demographics, baseline CVD risk factors, change in risk factors, and baseline LV parameters. Results: 2,722 participants (age 59 ± 9 years, 53% women, 42% White, 13% Chinese, 25% African American, 20% Hispanic) were included. Compared to the reference group, the group with eGFR ≥60 at year-0 and <60 at year-10 and the group with eGFR <60 at both year-0 and 10 group showed increasing MVR during 10 year follow-up. No difference in longitudinal change in LV mass or LVEF by eGFR groups were noted (Table). Conclusion: In this multi-ethnic cohort of adults without clinical CVD, reduced eGFR at baseline or during follow-up was associated with the development of concentric remodeling represented by increased MVR.

Abstract 3782: Persistent Prehypertension is a Risk Factor for Left Ventricular Hypertrophy

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Marcello R Markus ◽  
Jan Stritzke ◽  
Björn Mayer ◽  
Wolfgang Lieb ◽  
Andreas Luchner ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Wall Thickness ◽  
Left Ventricular ◽  
Linear Regression Models ◽  
Antihypertensive Medications ◽  
Increased Risk ◽  
Gender And Age ◽  
Blood Pressures ◽  
And Function

BACKGROUND: We aimed to study whether persistent prehypertension has detrimental effects on left ventricular (LV) geometry and function and increases cardiovascular risk. METHODS: Subjects (n=1005, aged 25 to 74 years) from a gender and age stratified random sample of residents of the Augsburg (D) area, were examined by standardized echocardiography at baseline and a second time, at a ten year follow-up. We defined two groups of individuals who persistently had either normal systolic and diastolic blood pressures (nBP, i.e., <120 mm Hg and <80 mm Hg; n=142) or prehypertensive blood pressures (preBP, 120 – 139 mm Hg or 80 – 89 mm Hg; n=119) at both examinations. We prospectively evaluated temporal changes in geometry, mass and function occurring with either persistent normotension or prehypertension using linear regression models adjusting for relevant confounders. Subjects taking antihypertensive medications or having hypertensive blood pressures (≥ 140 mm Hg or ≥ 90 mm Hg) were excluded from this analysis. RESULTS: After ten years of follow-up, individuals with preBP , as compared to nBP, showed larger relative increases in LV wall thickness (WT, 11.9% [95% CI: 9.3 to 14.5] versus 4.7% [2.4 to 7.1]; p<0.001), relative wall thickness (RWT, 12.9% [9.3 to 16.5] versus 4.3% [1 to 7.5]; p=0.001) and LVM indexed to height 2.7 (LVM/height 2.7 , 15.8% [12.4 to 19.3] versus 8.5% [5.4 to 11.6]; p=0.004) and decrease in E/A (early/late diastolic peak transmitral flow velocity, 15.7% [12 to 19.3] versus 7.7% [4.4 to 11]; p=0.003), respectively. Persistent prehypertension was also associated with a markedly elevated incidence of concentric remodeling of the left ventricle (RWT >0.43) with an odds ratio OR =9.38 [2.94 to 29.9] (p<0.001), of LV hypertrophy (LVM/height 2.7 >44 g/m 2.7 in women and >48 g/m 2.7 in men) with OR =5.59 [1.69 to 18.4] (p=0.009) and of diastolic dysfunction (E/A <1 or E/A ≥ 1 and left atrial end-systolic diameter larger than 40 mm for males or 38 mm for females) with OR=2.52 [1.01 to 6.31] (p=0.048). CONCLUSIONS: Persistent prehypertension is associated with an increased risk of concentric remodelling and hypertrophy of the left ventricle and a worse diastolic function suggesting that prehypertension is related to detrimental alterations of the left ventricle.

Impact of rhythm in non-valvular atrial fibrillation on four cardiac chamber deformation imaging

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P Philabout ◽  
L Soulat-Dufour ◽  
I Benhamou-Tarallo ◽  
S Lang ◽  
S Ederhy ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Cardiac Rhythm ◽  
Longitudinal Strain ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Cardiac Chamber ◽  
Deformation Imaging ◽  
And Function

Abstract Background Few studies have assessed the evolution of cardiac chambers deformation imaging in patients with atrial fibrillation (AF) according to cardiac rhythm outcome. Purpose To evaluate cardiac chamber deformation imaging in patients admitted for AF and the evolution at 6-month follow-up (M6). Methods In forty-one consecutive patients hospitalised for AF two-dimensional transthoracic echocardiography was performed at admission (M0) and after six months (M6) of follow up. In addition to the usual parameters of chamber size and function, chamber deformation imaging was obtained including global left atrium (LA) and right atrium (RA) reservoir strain, global left ventricular (LV) and right ventricular (RV) free wall longitudinal strain. Patients were divided into three groups according to their cardiac rhythm at M0 and M6: AF at M0 and sinus rhythm (SR) at M6 (AF-SR) (n=23), AF at M0 and AF at M6 (AF-AF) (n=11), SR at M0 (spontaneous conversion before the first echocardiography exam) and SR in M6 (SR-SR) (n=7) Results In comparison with SR patients (n=7), at M0, AF patients (n=34)) had lower global LA reservoir strain (+5.2 (+0.4 to 12.8) versus +33.2 (+27.0 to +51.5)%; p&lt;0.001), lower global RA reservoir strain (+8.6 (−5.4 to 11.6) versus +24.3 (+12.3 to +44.9)%; p&lt;0.001), lower global LV longitudinal strain (respectively −12.8 (−15.2 to −10.4) versus −19.1 (−21.8 to −18.3)%; p&lt;0.001) and lower global RV longitudinal strain (respectively −14.2 (−17.3 to −10.7) versus −23.8 (−31.1 to −16.2)%; p=0.001). When compared with the AF-SR group at M0 the AF-AF group had no significant differences with regard to global LA and RA reservoir strain, global LV and RV longitudinal strain (Table). Between M0 and M6 there was a significant improvement in global longitudinal strain of the four chambers in the AF-SR group whereas no improvements were noted in the AF-AF and SR-SR group (Figure). Conclusion Initial atrial and ventricular deformations were not associated with rhythm outcome at six-month follow up in AF. The improvement in strain in all four chambers strain suggests global reverse remodelling all cardiac cavities with the restoration of sinus rhythm. Evolution of strain between M0 and M6 Funding Acknowledgement Type of funding source: None

Abstract 15706: Association of Blood Pressure Level With Left Atrial Size and Function in Adolescents (SHIP AHOY)

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Edem Binka ◽  
Cedric Manlhiot ◽  
Elaine M Urbina ◽  
Tarek ALSAIED ◽  
Tammy M Brady
Keyword(s):  
Blood Pressure ◽  
Left Atrial ◽  
Global Longitudinal Strain ◽  
Blood Pressure Level ◽  
Left Ventricular ◽  
Z Score ◽  
Linear Regression Models ◽  
Cvd Risk ◽  
Strain And Strain Rate ◽  
And Function

Introduction: Left atrial (LA) enlargement and dysfunction are risk factors for stroke, atrial fibrillation and death in adults, and are associated with hypertension (HTN). In children, left ventricular hypertrophy is the most common manifestation of cardiac-specific organ damage in those with HTN, but gaps in knowledge remain regarding the association of HTN with LA size and function. Hypothesis: Increasing blood pressure (BP) is associated with increased LA volume and abnormal LA strain in children. Methods: Echocardiographic images of youth, aged 11 to 18 yrs from 5 clinical sites were obtained. LA strain and strain rate were analyzed using 2-D speckle tracking imaging with R-R gating in the apical 4 and 2-chamber views and averages of both views were used. Subjects were grouped by SBP as low-risk (L; <80th %ile), mid-risk (M; 80-<90th %ile), or high-risk, (H;≥90th %ile). Linear regression models were used to determine the association between BP z-score and LA size and function adjusting for age, sex, race and ethnicity. Results: N=347 youth (median age 15.7 yrs) 60% (n=208) male and 40% (n=139) non-white were included. BP groups differed by age (L&H<M) and BMI (L<M&H). BP groups did not differ by LA size and strain but differed by left ventricular mass index (H>L), stroke volume (M&H<L), peak global longitudinal strain (L>H), mitral E/e’ (H>L) and pulse wave velocity (H>L), each indicating worse CVD risk in the H vs. L group (Table). Multivariable analyses revealed DBP z-score to be independently associated with LA conduit strain (beta 0.73, 95% CI 0.01, 1.45, p<0.05). No other LA size or function variables were associated with BP. Conclusions: Greater BP is associated with increased CVD risk among youth as assessed by non-invasive measurements of CV structure and function. DBP is independently associated with LA conduit strain, a finding associated with CV events in adults. Future studies to determine the long-term association of abnormal DBP with LA strain are needed.

Abstract 16018: Impaired Intrinsic Myocardial Shortening in Both Two Directions and Compensatory Mechanism to Maintain Left Ventricular Ejection Fraction in Patients With Hypertensive Heart Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Satoshi Yamada ◽  
Kazunori Okada ◽  
Hisao Nishino ◽  
Hiroyuki Iwano ◽  
Daisuke Murai ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ejection Fraction ◽  
Wall Thickness ◽  
Circumferential Strain ◽  
Hypertensive Heart Disease ◽  
Wall Stress ◽  
Left Ventricular ◽  
Relative Wall Thickness ◽  
Left Ventricular Ejection ◽  
Compensatory Mechanism

Background: Longitudinal myocardial shortening is known to be reduced even if left ventricular (LV) ejection fraction (EF) is preserved in patients with hypertensive heart disease (HHD). However, the compensatory mechanism remains to be elucidated. Thus layer-specific longitudinal and circumferential strain as well as stress-strain relationship was observed in HHD patients. Methods: In 46 HHD patients with preserved EF (>50%) and 29 age-matched control subjects, global longitudinal strain (LS) and layer-specific circumferential strain (CS) were measured from the apical 4-chamber view and mid-ventricular short-axis view, respectively, by using speckle tracking echocardiography. LS was measured at innermost LV wall layer, and CS at innermost, midwall, and outermost layers. Layer-specific end-systolic circumferential wall stress (CWS) according to Mirsky’s formula and endocardial meridional wall stress (MWS) were calculated. Results: Systolic blood pressure (147±20 mm Hg), interventricular septal thickness (13±2 mm), and LV dimension (48±4 mm) were greater in HHD than controls, whereas EF was comparable (66±8 vs 66±5%). LS was smaller in HHD than controls (-13±3 vs -17±3%, p<0.001) in spite of reduced MWS (520±141 vs 637±164 dyn·mm -2 , p<0.01), suggesting impaired longitudinal myocardial function in HHD. Similarly, CS was smaller in HHD than controls at outer layer (-6.8±2.2 vs -8.8±2.2%, p<0.01) and at midwall (-11.3±3.4 vs -13.9±3.2%, p<0.01) in spite of reduced CWS (outer: 238±82 vs 336±110 dyn·mm -2 , p<0.001; mid: 360±107 vs 473±131 dyn·mm -2 , p<0.001). In contrast, at the innermost layer, both CS (-26±5 vs -25±5%, p=0.41) and CWS (979±153 vs 992±139 dyn·mm -2 , p=0.72) were comparable between groups. Furthermore, the difference of CS between inner and outer layers significantly correlated with relative wall thickness (r=-0.33, p<0.01). Finally, CS at inner layer significantly correlated with EF (r=-0.43, p<0.001), whereas LS did not. Conclusions: In patients with HHD, intrinsic myocardial shortening was impaired both longitudinally and circumferentially. Some compensatory mechanism associated with increased relative wall thickness might work to maintain subendocardial CS, resulting in preserved EF.

Abstract 15607: Right Atrial Reservoir Strain Predicts Survival in Patients With Cardiac Amyloidosis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Peter Huntjens ◽  
Kathleen Zhang ◽  
Yuko Soyama ◽  
Maria Karmpalioti ◽  
Daniel Lenihan ◽  
...  
Keyword(s):  
Cardiac Amyloidosis ◽  
Ventricular Hypertrophy ◽  
Cardiac Tissue ◽  
Fold Increase ◽  
Left Ventricular ◽  
Right Atrial ◽  
Chamber View ◽  
All Cause Mortality ◽  
And Function

Introduction: Myofibril deposition in amyloidosis diffusely may affect cardiac structure and function. Right ventricular involvement has been associated with adverse clinical outcome. However, the utility of right atrial (RA) function assessment by echocardiographic strain imaging is unclear. Hypothesis: We hypothesize that right atrial stain has prognostic value in cardiac amyloidosis. Methods: We studied 121 consecutive patients with cardiac amyloidosis: 18% had transthyretin and 79% had light chain amyloidosis. Cardiac amyloidosis was either confirmed by endocardial biopsy (36%) or by a combination of non-cardiac tissue biopsy and proof of left ventricular hypertrophy (64%). Speckle tracking peak RA reservoir strain was assessed based on 6 segments from the apical 4-chamber view. All-cause mortality was tracked over a median of 5 years. Results: Echocardiographic peak longitudinal RA strain was feasible in 109 patients (90%). 60 CA patients died during follow-up period. Peak longitudinal RA strain was reduced in cardiac amyloidosis non-survivors (8.1%) in comparison to survivors (18.3%, p<0.01), showing RA involvement in cardiac amyloidosis. Peak RA strain was significantly associated with survival (using median 12.5%) (p<0.001). Low peak longitudinal RA strain was associated with a 3.3-fold increase in mortality risk (95% confidence interval: 1.83 - 5.96). Conclusions: Reduced peak longitudinal RA strain was significantly associated with survival in patients with cardiac amyloidosis. RA reservoir function assessed by strain appears to be useful as a new means to predict prognosis in cardiac amyloidosis patients and has promise for clinical application.

Dose-dependent effect of ANG II-receptor antagonist on myocyte remodeling in rat cardiac hypertrophy

1997 ◽  
Vol 273 (4) ◽  
pp. H1824-H1831 ◽  
Author(s):  
Masakazu Obayashi ◽  
Masafumi Yano ◽  
Michihiro Kohno ◽  
Shigeki Kobayashi ◽  
Taketo Tanigawa ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Receptor Antagonist ◽  
Pressure Overload ◽  
Wall Stress ◽  
Treated Group ◽  
Left Ventricular ◽  
Abdominal Aortic ◽  
Significant Difference ◽  
And Function ◽  
Vehicle Treated Group

The goal of this study was to examine the effect of an angiotensin II type 1 (AT1)-receptor antagonist (TCV-116) on left ventricular (LV) geometry and function during the development of pressure-overload LV hypertrophy. A low (LD; 0.3 mg ⋅ kg−1 ⋅ day−1) or a high (HD; 3.0 mg ⋅ kg−1 ⋅ day−1) dose of TCV-116 was administered to abdominal aortic-banded rats over 4 wk, and hemodynamics and morphology were then evaluated. In both LD and HD groups, peak LV pressures were decreased to a similar extent compared with the vehicle-treated group but stayed at higher levels than in the sham-operated group. In the LD group, both end-diastolic wall thickness (3.08 ± 0.14 mm) and myocyte width (13.3 ± 0.1 μm) decreased compared with those in the vehicle-treated group (3.67 ± 0.19 mm and 15.3 ± 0.1 μm, respectively; both P < 0.05). In the HD group, myocyte length was further decreased (HD: 82.6 ± 2.6, LD: 94.1 ± 2.9 μm; P < 0.05) in association with a reduction in LV midwall radius (HD: 3.36 ± 0.12, LD: 3.60 ± 0.14 mm; P < 0.05) and peak midwall fiber stress (HD: 69 ± 8, LD: 83 ± 10 × 103dyn/cm2; P < 0.05). There was no significant difference in cardiac output among all groups. The AT1-receptor antagonist TCV-116 induced an inhibition of the development of pressure-overload hypertrophy. Morphologically, not only the width but also the length of myocytes was attenuated with TCV-116, leading to a reduction of midwall radius and hence wall stress, which in turn may contribute to a preservation of cardiac output.

scholarly journals CTRP9 Mediates Protective Effects in Cardiomyocytes via AMPK- and Adiponectin Receptor-Mediated Induction of Anti-Oxidant Response

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1229
Author(s):  
Bernd Niemann ◽  
Ling Li ◽  
Dorothee Siegler ◽  
Benedikt H. Siegler ◽  
Fabienne Knapp ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Direct Interaction ◽  
Left Ventricular ◽  
Cardiac Cells ◽  
Adiponectin Receptor ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Anti Oxidant ◽  
Cardioprotective Effects ◽  
The Right

The C1q/tumor necrosis factor-alpha-related protein 9 (CTRP9) has been reported to exert cardioprotective effects, but its role in the right ventricle (RV) remains unclear. To investigate the role of CTRP9 in RV hypertrophy and failure, we performed pulmonary artery banding in weanling rats to induce compensatory RV hypertrophy seven weeks after surgery and RV failure 22 weeks after surgery. CTRP9 expression, signal transduction and mechanisms involved in protective CTRP9 effects were analyzed in rat and human RV tissue and cardiac cells. We demonstrate that CTRP9 was induced during compensatory RV hypertrophy but almost lost at the stage of RV failure. RV but not left ventricular (LV) cardiomyocytes or RV endothelial cells demonstrated increased intracellular reactive oxygen species (ROS) and apoptosis activation at this stage. Exogenous CTRP9 induced AMP-activated protein kinase (AMPK)-dependent transcriptional activation of the anti-oxidant thioredoxin-1 (Trx1) and superoxide dismutase-2 (SOD2) and reduced phenylephrine-induced ROS. Combined knockdown of adiponectin receptor-1 (AdipoR1) and AdipoR2 or knockdown of calreticulin attenuated CTRP9-mediated anti-oxidant effects. Immunoprecipitation showed an interaction of AdipoR1 with AdipoR2 and the co-receptor T-cadherin, but no direct interaction with calreticulin. Thus, CTRP9 mediates cardioprotective effects through inhibition of ROS production induced by pro-hypertrophic agents via AMPK-mediated activation of anti-oxidant enzymes.

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