scholarly journals The Effect of Adiposity on Cardiovascular Function and Myocardial Fibrosis in Patients With Duchenne Muscular Dystrophy

2021 ◽  
Vol 10 (19) ◽  
Author(s):  
Sarah E. Henson ◽  
Sean M. Lang ◽  
Philip R. Khoury ◽  
Cuixia Tian ◽  
Meilan M. Rutter ◽  
...  

Background Patients with Duchenne muscular dystrophy (DMD) develop cardiomyopathy because of a dystrophin deficiency causing fibrofatty replacement of the myocardium. Corticosteroid use and mobility limitations place these patients at risk for increased adiposity. We sought to determine the association of adiposity with cardiovascular dysfunction in patients with DMD. Methods and Results This was a retrospective review of patients with DMD who underwent both cardiac magnetic resonance imaging and dual‐energy x‐ray absorptiometry within 1 year. The cardiac magnetic resonance imaging parameters included left ventricular ejection fraction and the presence of late gadolinium enhancement (LGE positive [LGE+]). The adiposity indices, measured by dual‐energy x‐ray absorptiometry, included percentage of body fat, whole body fat mass indexed to height, and body mass index. A total of 324 patients were identified. Fifty‐two percent had LGE+, and 36% had cardiac dysfunction (left ventricular ejection fraction <55%). Patients with cardiac dysfunction had higher whole body fat mass indexed to height and body mass index on univariate analysis (mean difference between patients with and without cardiac dysfunction: +2.9 kg/m, P =0.001; and +1.5 kg/m 2 , P =0.03, respectively). whole body fat mass indexed to height remained independently associated with cardiac dysfunction on multivariable analysis after adjusting for age, LGE+, and corticosteroid duration. High whole body fat mass indexed to height and percentage of body fat were associated with LGE+ on univariate analysis (mean difference between patients with and without LGE+: +2.0 kg/m, P =0.02; and +2.4%, P =0.02, respectively). Using multivariable analysis, including age and cardiac dysfunction, high percentage of body fat remained independently associated with LGE+. Conclusions This study demonstrates an independent association of adiposity with cardiac dysfunction and LGE+ in patients with DMD. Preventing adiposity may mitigate the later development of ventricular dysfunction in DMD.

2007 ◽  
Vol 25 (25) ◽  
pp. 3859-3865 ◽  
Author(s):  
Thomas M. Suter ◽  
Marion Procter ◽  
Dirk J. van Veldhuisen ◽  
Michael Muscholl ◽  
Jonas Bergh ◽  
...  

Purpose The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy. Patients and Methods The Herceptin Adjuvant (HERA) trial is a three-group, multicenter, open-label randomized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2–positive breast cancer. Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction (LVEF ≥ 55%) were eligible. A repeat LVEF assessment was performed in case of cardiac dysfunction. Results Data were available for 1,693 patients randomly assigned to 1 year trastuzumab and 1,693 patients randomly assigned to observation. The incidence of trastuzumab discontinuation due to cardiac disorders was low (4.3%). The incidence of cardiac end points was higher in the trastuzumab group compared with observation (severe congestive heart failure [CHF], 0.60% v 0.00%; symptomatic CHF, 2.15% v 0.12%; confirmed significant LVEF drops, 3.04% v 0.53%). Most patients with cardiac dysfunction recovered in fewer than 6 months. Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin (287 mg/m2 v 257 mg/m2) or epirubicin (480 mg/m2 v 422 mg/m2) and had a lower screening LVEF and a higher body mass index. Conclusion Given the clear benefit in disease-free survival, the low incidence of cardiac adverse events, and the suggestion that cardiac dysfunction might be reversible, adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Satoshi Okumura ◽  
Yunzhe Bai ◽  
Meihua Jin ◽  
Sayaka Suzuki ◽  
Akiko Kuwae ◽  
...  

The sympathetic nervous system and proinflammatory cytokines are believed to play independent roles in the pathophysiology of heart failure. However, the recent identification of Epac (exchange protein activated by cyclic AMP), a new cyclic AMP-binding protein that directly activates Rap1, have implicated that there may be a potential cross talk between the sympathetic and cytokine signals. In order to examine the role of Epac in cytokine signal to regulate cardiac function, we have generated transgenic mice expressing the human Epac1 gene under the control of alpha-cardiac myosin heavy chain promoter (Epac1-TG), and examined their response in lipopolysaccharide (LPS)-induced cardiac dysfunction, a well established model for sepsis-induced cardiac dysfunction. Sepsis-induced cardiac dysfunction results from the production of proinflammatory cytokines. At baseline, left ventricular ejection fraction (LVEF) was similar (TG vs. NTG, 67±1.7 vs. 69±2.1%, n =7–9). The degree of cardiac hypertrophy (LV(mg)/tibia(mm)) was also similar at 3 months old (TG vs. NTG 4.0±0.1 vs. 4.2±0.1, n =5–6), but it became slightly but significantly greater in Epac1-TG at 5 month old (TG vs. NTG 4.9±0.1 vs. 4.4±0.1, p< 0.05, n =5–7). LPS (5mg/kg) elicited a significant and robust reduction of LVEF in both Epac1-TG and NTG, but the magnitude of this decrease was much less in Epac1-TG at 6 hr after injection (TG vs. NTG 48±2.4 vs. 57±1.8%, p< 0.01, n =6–9). At 24 hr after injection, cardiac function was restored to the baseline in both Epac1-TG and NTG. We also examined the activation of JAK-STAT pathway at 24 hr after injection. The tyrosine phosphorylation of STAT1 (Tyr701) and STAT3 (Tyr705) in LV, which is an indicator of STAT activation, was reduced to a greater degree in Epac1-TG by 31±8.8% ( p< 0.05, n =4) and 29±5.9% ( p< 0.05, n =7), respectively, relative to that in NTG. Taken together, Epac1 protects the heart from the cytokine-induced cardiac dysfunction, at least in part, through the inhibition of the JAK-STAT pathway, suggesting the beneficial role played by sympathetic signal to antagonize proinflammatory cytokine signal in heart failure.


2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Makiko Miyata ◽  
Satoshi Suzuki ◽  
Tomofumi Misaka ◽  
Shu-ichi Saitoh ◽  
Yasuchika Takeishi

Background: Senescence marker protein 30 (SMP30) was originally identified as an aging marker protein in the rat liver. The expression of SMP30 decreases with aging androgen-independently. Doxorubicin (DOX) has been used as a potent anticancer agent, but serious cardiotoxicity precludes its use in a wide range of patients. SMP30 may have anti-oxidative and anti-apoptosis functions in several organs, but functional role of SMP30 has not been rigorously examined in the heart. We hypothesized that SMP30 has cardio-protective function by anti-aging and anti-oxidant effects on DOX-induced cardiac dysfunction. Method and Results: Male SMP30 knockout (SMP30KO) and age-matched littermate male wild-type (WT) mice at 12-14 weeks of age were given intraperitoneal injections of DOX (20 mg/kg) or saline. Seven days after DOX injection, echocardiography revealed that left ventricular ejection fraction in DOX-treated SMP30KO mice was more severely reduced than in DOX-treated WT mice (40.9 ± 3.1% vs. 46.9 ± 4.9%, P<0.01). Morphological examination of myocardial sections showed fibrotic change in DOX-treated SMP30KO mice significantly increased compared to DOX-treated WT mice (3.2 ± 0.5% vs. 1.3 ± 0.2%, P<0.01). Generation of reactive oxygen species assessed by dihydroethidium staining was greater in DOX-treated SMP30KO mice than DOX-treated WT mice (166.9 ± 8.6% vs. 131.6 ± 5.8%, P<0.01). Moreover, apoptotic signaling pathways such as caspase-3 activity (1.8 ± 0.1% vs. 1.1 ± 0.2%, P<0.01), bax/bcl-2 ratio (2.4 ± 0.3% vs.1.6 ± 0.2%, P<0.05) and phosphorylation activity of c-Jun N-terminal kinase (1.6 ± 0.3 vs. 1.0 ± 0.1, P<0.05) were significantly elevated in the SMP30KO mice compared with WT mice after DOX injection. The numbers of TUNEL-positive nuclei in the myocardium were higher in DOX-treated SMPKO mice than in DOX-treated WT mice (0.15 ± 0.02% vs. 0.08 ± 0.01%, P<0.01). Conclusions: The results of this study demonstrated that DOX-induced cardiotoxicity is aggravated in SMP30KO mice by exacerbating of superoxide generation, leading to enhanced apoptosis of cardiomyocytes. SMP30 has a cardio-protective role by anti-apoptotic and anti-oxidative effects in DOX-induced cardiotoxicity.


2010 ◽  
Vol 28 (25) ◽  
pp. 3910-3916 ◽  
Author(s):  
Daniela Cardinale ◽  
Alessandro Colombo ◽  
Rosalba Torrisi ◽  
Maria T. Sandri ◽  
Maurizio Civelli ◽  
...  

Purpose Treatment of breast cancer with trastuzumab is complicated by cardiotoxicity in up to 34% of the patients. In most patients, trastuzumab-induced cardiotoxicity (TIC) is reversible: left ventricular ejection fraction (LVEF) improves after trastuzumab withdrawal and with, or sometimes without, initiation of heart failure (HF) therapy. The reversibility of TIC, however, is not foreseeable, and identification of patients at risk and of those who will not recover from cardiac dysfunction is crucial. The usefulness of troponin I (TNI) in the identification of patients at risk for TIC and in the prediction of LVEF recovery has never been investigated. Patients and Methods In total, 251 women were enrolled. TNI was measured before and after each trastuzumab cycle. LVEF was evaluated at baseline, every 3 months during trastuzumab therapy, and every 6 months afterward. In case of TIC, trastuzumab was discontinued, and HF treatment with enalapril and carvedilol was initiated. TIC was defined as LVEF decrease of > 10 units and below 50%. Recovery from TIC was defined as LVEF increase above 50%. Results TIC occurred in 42 patients (17%) and was more frequent in patients with TNI elevation (TNI+; 62% v 5%; P < .001). Twenty-five patients (60%) recovered from TIC. LVEF recovery occurred less frequently in TNI+ patients (35% v 100%; P < .001). At multivariate analysis, TNI+ was the only independent predictor of TIC (hazard ratio [HR], 22.9; 95% CI, 11.6 to 45.5; P < .001) and of lack of LVEF recovery (HR, 2.88; 95% CI,1.78 to 4.65; P < .001). Conclusion TNI+ identifies trastuzumab-treated patients who are at risk for cardiotoxicity and are unlikely to recover from cardiac dysfunction despite HF therapy.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Hak Joo Choi ◽  
Hwa Young Kim ◽  
Kyoung Sik Park

A variety of natural products have been explored for their antiobesity potential and widely used to develop dietary supplements for the prevention of weight gain from excess body fat. In an attempt to find a natural antiobesity agent, this study was designed to evaluate the antiobesity activity of a novel herbal formulation LI85008F composed of extracts from three medicinal plants in high-fat diet- (HFD-) induced obese mice. After the thirteen-week oral administration of the test materials to mice, the body weight gain, whole-body fat mass, adipose tissue weight, and the expression levels of obesity-related proteins were measured. Our results indicated that LI85008F can suppress body weight gain and lower whole-body fat mass in HFD-induced obese mice. Significant decreases in epididymal and retroperitoneal fat mass were observed in LI85008F-treated groups compared with the HFD-fed control group ( p < 0.05 ). Furthermore, the oral administration of LI85008F caused significant decreases in the expression level of adipogenic (C/EBPα and PPARγ) and lipogenic (ACC) markers and notable increases in the production level of thermogenetic (AMPKα, PGC1α and UCP1) and lipolytic (HSL) proteins. These findings suggest that LI85008F holds great promise for a novel herbal formulation with antiobesity activities, preventing body fat accumulation and altering lipid metabolism.


2018 ◽  
Vol 47 (5) ◽  
pp. 361-371 ◽  
Author(s):  
Qing Kuang ◽  
Ning Xue ◽  
Jing Chen ◽  
Ziyan Shen ◽  
Xiaomeng Cui ◽  
...  

Background: Chronic kidney disease (CKD) has been proposed to associate with decreased hydrogen sulfide (H2S) level. Nevertheless, the role of H2S in the pathogenesis of CKD has not been fully investigated. Our study aimed to investigate the plasma level of endogenous H2S in patients with different stages of CKD, and to identify the role of H2S in the progression of CKD and its relationship with cardiovascular diseases. Methods: A total of 157 non-dialysis CKD patients were recruited in our study, with 37 age- and sex-matched healthy individuals as control. Plasma concentration of H2S was measured with spectrophotometry. Sulfhemoglobin, the integration of H2S and hemoglobin, was characterized and measured by dual wavelength spectrophotometry. Serum levels of homocysteine (Hcy), cardiac troponin T (cTnT), and N-terminal pro B type natriuretic peptide were measured using automated analyzers. Conventional transthoracic echocardiography was performed and left ventricular ejection fraction (LVEF) was analyzed as a sensitive parameter of cardiac dysfunction. Results: The plasma H2S level (μmol/L) in CKD patients was significantly lower than those in healthy controls (7.32 ± 4.02 vs. 14.11 ± 5.24 μmol/L, p < 0.01). Plasma H2S level was positively associated with estimated glomerular filtration rate (eGFR; ρ = 0.577, p < 0.01) and negatively associated with plasma indoxyl sulfate concentration (ρ = –0.554, p < 0.01). The mRNA levels of cystathionine β-synthase and cystathionine γ-lyase, 2 catalytic enzymes of H2S formation, were significantly lower in blood mononuclear cells of CKD patients with respect to controls; however, the mRNA level of 3-mercaptopyruvate sulfurtransferase, as another H2S-producing enzyme, was significantly higher in CKD patients. The serum concentration of Hcy, acting as the substrate of H2S synthetase, was higher in the CKD group (p < 0.01). Specifically, the content of serum Hcy in CKD stages 3–5 patients was significantly higher than that in CKD stages 1–2, indicating an increasing trend of serum Hcy with the decline of renal function. Examination of ultrasonic cardiogram revealed a negative ­correlation between plasma H2S level and LVEF (ρ = –0.204, p < 0.05) in CKD patients. The H2S level also correlated negatively with cTnT concentration (ρ = –0.249, p < 0.01). Conclusions: Plasma H2S level decreased with the decline of eGFR, which may contribute to the cardiac dysfunction in CKD ­patients.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Masayoshi Oikawa ◽  
Daiki Yaegashi ◽  
Tetsuro Yokokawa ◽  
Tomofumi Misaka ◽  
Takamasa Sato ◽  
...  

Background: D-dimer is a sensitive biomarker for cancer-associated thrombosis, but little is known about its significance on cancer therapeutics-related cardiac dysfunction (CTRCD). Methods and Results: Consequtive 202 patients planned for cardiotoxic chemotherapy (anthracyclines, monoclonal antibodies, tyrosine kinase inhibitors, and proteasome inhibitors) were enrolled and followed up for 12 months. Cancer types were as follows: breast cancer (n=112), lymphoma (n=37), ovarian or uterine cancer (n=18), leukemia (n=13), multiple myeloma (n=6), bone cancer (n=4), and others (n=12). All patients underwent echocardiography and blood test at baseline, 3-month, 6-month, and 12-month. The patients were divided into 2 groups based on the value of D-dimer (>1.5 μg/ml or ≦1.5 μg/ml) at baseline before chemotherapy: High D-dimer group (n=52) and Low D-dimer group (n=150). At baseline, left ventricular ejection fraction (LVEF), left ventricular end-systolic volume index, and B-type natriuretic peptide levels were similar between two groups. Time-dependent decrease in LVEF was observed after chemotherapy in high D-dimer group (baseline, 66±5%; 3-month, 63±7%; 6-month, 62±7%; 12-month 62±6%; P=0.005, figure), but not in low D-dimer group. Time-dependent increase in troponin I was similarly observed after chemotherapy in both groups. The occurrence of CTRCD was higher in high D-dimer group than in low D-dimer group (11.5% vs. 4.0%, P=0.048). When we set the cut-off value of baseline D-dimer at 1.65 μg/ml from ROC analysis, sensitivity, specificity, and area under the curve to predict CTRCD were 50%, 77%, and 0.679, respectively. Multivariable logistic analysis revealed that baseline D-dimer was an independent factor to predict the decrease in LVEF more than 10% after cardiotoxic chemotherapy (odds ratio 1.210, 95% confidence interval [1.020-1.440], P=0.025). Conclusion: Baseline D-dimer is a pivotal parameter to predict CTRCD.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Michelle Madden ◽  
Rory Gallen ◽  
Lisa LeMond ◽  
D Eric Steidley ◽  
Mira Keddis

Introduction: End stage renal disease (ESRD) patients with concomitant heart failure (HF) are often denied kidney transplantation (KTx). The aims of this study were to explore factors predictive of suitability for KTx and to assess cardiovascular (CV) outcomes in patients with impaired left ventricular ejection fraction (LVEF) presenting for KTx evaluation. Methods: We evaluated 109 consecutive adults with LVEF≤40% at the time of initial KTx evaluation between 2013 and 2018. Post-transplant CV outcomes were defined as non-fatal MI, admission for HF, CV death and all-cause mortality. Results: Mean age was 58.2 years (SD11.9), 78% were male, 58% had diabetes, 70% had history of CV events and 42% had ischemic cardiomyopathy. Mean LVEF was 31.5% (SD 6.47). Eighty patients had nuclear stress imaging; 10% were positive for reversible ischemia and 43% for prior infarct. Mean VO2max was 14.4(SD 5.71)ml/kg/min (31 patients). A cardiologist evaluated 93% of patients and was present at 58% of selection committee meetings. Twenty-four patients (22%) were denied by a cardiologist for KTx and 59 (54%) were denied by the selection committee, of whom 43 were due to CV risk. On univariate analysis, the variables associated with denial for KTx were: cardiologist denial, denial due to CV risk, Native American race (6% of cohort), higher NT-pro-BNP, prior MI, coronary intervention, positive stress study, anemia, lower EF and lower VO2max (all p<0.05). On multivariate analysis, cardiologist denial was the only significant predictor of denial for KTx (OR: 29.4, p=0.0007). At median follow-up of 15 months, 5 (5%) suffered non-fatal MI, 13 (12%) were hospitalized for HF exacerbation and 17 (16%) died. Only 22 (20%) underwent KTx. Post-KTx, there was one death, one non-fatal MI and 3 hospitalizations for HF. Mean LVEF improvement was 16% (SD12.9). Conclusions: Only 38% of ESRD patients with LVEF≤40% presenting for KTx evaluation were approved and of those, only 52% received KTx. Cardiologist approval was the primary predictor of suitability for KTx. Despite careful selection, prevalence of CV events and mortality after KTx was 23%. There is need for a consistent multidisciplinary approach during KTx evaluation, including cardiologist input, to improve CV outcomes.


2019 ◽  
Vol 92 (1103) ◽  
pp. 20190300
Author(s):  
Andrew D. Weedall ◽  
Adrian J. Wilson ◽  
Sarah C. Wayte

Objective: To validate MRI fat measurement protocols using purpose built test objects and by comparison with air-displacement plethysmography (ADP) whole-body fat measurements in non-obese subjects. Methods: Test objects of known fat concentration were used to quantify the accuracy of the MRI measurements. 10 participants with a body mass index in the range 18–30 underwent whole-body MRI using two different Dixon-based sequences (LAVA Flex and IDEAL IQ) to obtain an estimate of their whole-body fat mass. The MRI determined fat mass was compared to the fat mass determined by ADP. Results: MRI test object measurements showed a high correlation to expected fat percentage (r > 0.98). The participant MRI and ADP results were highly correlated (r = 0.99) but on average (mean ± standard deviation) MRI determined a higher fat mass than ADP (3.8 ± 3.1 kg for LAVA Flex and 1.9 ± 3.2 kg for IDEAL IQ). There was no trend in the difference between MRI and ADP with total fat mass. Conclusion: The good agreement between MRI and ADP shows that Dixon-based MRI can be used effectively as a tool in physiological research for non-obese adults. Advances in knowledge: This work found that for ten non-obese subjects body mass index had no effect on the MRI determination of whole-body fat mass.


2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
A M Chitroceanu ◽  
R C Rimbas ◽  
S I Visoiu ◽  
A E Balinisteanu ◽  
M L Luchian ◽  
...  

Abstract Funding Acknowledgements This work was supported by a grant of Ministery of Research and Innovation, CNCS-UEFISCDI, project number PN-III-P1-1-TE-2016-0669, within PNCDI III Background Cirrhotic cardiomyopathy (CCM) is defined as systolic and/or diastolic cardiac dysfunction, associated with high preload and low afterload. Thus, assessment of cardiac dysfunction in these circumstances is still debatable. Left ventricular (LV) deformation is still load-dependent, and does not reflect directly myocardial energy consumption. Since myocardial work (MW)incorporates both deformation and afterload, it might be a better alternative for the assessment of LV function in CCM. Methods 80 subjects were assessed by 2D conventional and speckle tracking echocardiography (STE): 40 patients with liver cirrhosis (LC) (58 ± 8 years, 23 males), free of any cardiovascular disease or diabetes, and 40 age and gender matched normal, control subjects. Left ventricular ejection fraction (LVEF) and systolic/diastolic blood pressure (SBP/DBP) were measured. A new approach was used to evaluate myocardial work by 2DSTE: global constructive work (GCW), as the "positive" work of the heart; global wasted work (GWW), as the "negative" work of the heart; global work efficiency (GWE), as the GCW/(GCW + GWW) in %; and global work index (GWI), as the GCW added to GWW. E/E’ ratio, left atrial volume index (LAVi), and systolic pulmonary arterial pressure (sPAP) were also assessed. Results Patients with LC had significantly lower SBP/DBP than controls, with similar LVEF (Table). GCW and GWI were decreased in patients with LC, probably due to decrease in afterload, which shifts LV work to a lower level of energy. GWE and GWW were similar to controls. By segmental analysis (18 segments model), apical and mid antero-lateral segments were the first affected in terms of myocardial work, with higher WW, low WE, but without a compensatory increase in CW in other segments, suggesting a regional myocardial dysfunction. All patients with LC presented significantly elevated E/E’ ratio, LAVi, and sPAP, compared to controls (Table). Conclusion Myocardial global constructive work and global work index decrease in LC patients, compared to normal individuals, probably due to augmented peripheral vasodilatation. Apical and mid antero-lateral segments are the first affected. Assessment of global and regional MW might be a potential new tool to assess CCM, and to understand the relationship between LV remodeling and increased filling pressure under different loading conditions. Comparative myocardial work indices group SBP (mmHg) DBP LVEF (%) E/E’ LAVI sPAP GWI GWE (% ) GCW (mmHg % ) GWW (mmHg %) LC (40) 111 ±14 69 ± 12 59 ± 7 8.5 ± 2.5 45.9 ± 14.5 26 ± 9 1927 ± 379 95 ± 2 2068 ± 386 90.1 ± 49 Controls (40) 126 ± 14 76 ± 8 61 ± 7 7.5 ± 2.2 31.8 ± 6.8 21 ± 8 2123 ± 353 95± 2 2302 ± 335 94.4 ± 49 P value 0.001 0.004 0.3 0.05 0.001 0.009 0.01 0.9 0.005 0.7 Abstract P1513 Figure. Myocardial Work Cirrhotic Cardiomyopathy


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