P3476High-resolution respirometry reveals enhanced myocardial mitochondrial ketone oxidation after fasting and ventricular unloading

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Zweck ◽  
V Burkart ◽  
C Wessel ◽  
D Scheiber ◽  
K H M Leung ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Ex Vivo ◽  
Oxidative Capacity ◽  
Left Ventricular ◽  
University Hospital ◽  
Oxygen Flux ◽  
Protective Effects ◽  
Coa Transferase

Abstract Background Impairment of myocardial mitochondrial function is regarded as an established pathomechanism in heart failure. Enhanced oxidation of ketone bodies may potentially exert protective effects on myocardial function. High-resolution respirometry (HRR) resembles a gold-standard methodology to determine myocardial mitochondrial metabolism and oxidative function but has not been validated for ketone substrates yet. Purpose We hypothesized that (1) quantification of ketone body oxidative capacity (OC) in myocardium utilizing ex-vivo HRR is feasible and that (2) ketone-associated OC is elevated after fasting and under conditions of chronic mechanical ventricular unloading. Methods We established new HRR (Oxygraph-2k) protocols, measuring oxygen flux generated by oxidation of the ketone substrates beta-hydroxybutyrate (HBA) and acetoacetate (ACA). Ketone protocols were then applied to twelve C57BL/6 mice' (of which six were fasted for 16h) left ventricular and right liver lobe tissue, as well as to eleven terminal heart failure patients' left ventricular tissue, harvested at heart transplantation. Heart transplant recipients were subdivided into patients with left ventricular assist device prior to transplantation (LVAD group, n=6) or no unloading prior to transplantation (HTX group, n=5). Results In non-fasted rodent hearts, HBA yielded an OC of 25±4 pmol/(s*mg tissue) above basal respiration, when applied as sole substrate (21±11 pmol/(s*mg) in liver). ACA alone did not induce oxygen flux, but ACA+succinate yielded 229% higher oxygen flux than succinate alone in state III (146±32 vs 44±12 pmol/(s*mg); p=0.0003). When titrated after succinate, ACA increased OC by 93±25 pmol/(s*mg) (p=0.0003). In 16h-fasted rodent hearts, HBA-supported OC was 27% higher (41±3 vs 52±9 pmol/(s*mg); p=0.04), while OC with ACA+succinate was unchanged (p=0.60). In rodent liver, no oxygen flux was induced by ACA, reflecting absence of 3-oxoacid CoA-transferase. However, HBA-supported OC was 118% higher in fasted liver (37±13 vs 57±13 pmol/(s*mg); p=0.03). In humans, left ventricular unloading was not associated with altered myocardial OC for fatty acids and glycolytic substrates (standard protocol, p=0.13), but HBA-supported OC was 39% higher in the LVAD group compared to the HTX group (54±12 vs 39±9 pmol/(s*mg), p=0.04). Conclusion Quantification of ketone body OC with HRR is feasible in permeabilized myocardial fibers. Applying this novel method revealed increased HBA-supported myocardial mitochondrial respiration after fasting and chronic left ventricular unloading. These data support a concept of enhanced ketone oxidation following ventricular unloading in myocardial mitochondria. Our findings facilitate new studies on myocardial ketone turnover and the interaction of mitochondrial ketone metabolism with cardiac performance. Acknowledgement/Funding CRC 1116, Research commission of the University Hospital Düsseldorf

scholarly journals Left ventricular systolic function decreases in lamin a/c cardiomyopathy wihout concomitant ventricular dilatation

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
ES Eystein Skjolsvik ◽  
OL Oyvind Haugen Lie ◽  
MC Monica Chivulescu ◽  
MR Margareth Ribe ◽  
AIC Anna Isotta Castrini ◽  
...  
Keyword(s):  
Heart Failure ◽  
Left Ventricular ◽  
University Hospital ◽  
Lv Function ◽  
Lamin A ◽  
Age Related ◽  
End Stage Heart Failure ◽  
Lv Volumes ◽  
End Stage

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This work was supported by the Norwegian Research Council [203489/030] onbehalf Department of Cardiology, Research group for genetic cardiac diseases and sudden cardiac death, Oslo University Hospital, Rikshospitalet, Oslo, Norwa Background Lamin A/C disease is an inheritable cardiomyopathy characterized by conduction abnormalities, ventricular arrhythmias and end stage heart failure with complete age-related penetrance. Purpose To assess left ventricular structural and functional progression in patients with lamin A/C cardiomyopathy. Methods We included and followed consecutive lamin A/C genotype positive patients with clinical examination and echocardiography at every visit. We evaluated progression of left- ventricular size and function by mixed model statistics. Results We included 101 consecutive lamin A/C genotype positive patients (age 44 [29-54] years, 39% probands, 51%female) with 576 echocardiographic exams during 4.9 (IQR 2.5-8.1) years of follow-up. LV ejection fraction (LVEF) declined from 50 ± 12% to 47 ± 13%, p < 0.001 (rate -0.5%/year). LV end diastolic volumes (LVEDV) remained stationary with no significant dilatation in the total population (136 ± 45ml to 138 ± 43ml, p = 0.60), (Figure). In the subgroup of patients >58 years, we observed a decline in LV volumes 148, SE 9 ml to 140, SE 9 ml p < 0.001 (rate -2.7 ml/year) towards end stage heart failure. Conclusions LVEF deteriorated, while LV size remained unchanged during 4.9 years of follow-up in patients with lamin A/C cardiomyopathy. In patients <58 years, we observed a reduction in LV volumes. These findings represent loss of LV function without the necessary compensatory dilation to preserve stroke volume indicating high risk of decompensated end stage heart failure in lamin A/C. Abstract Figure.

Abstract 16485: The Nitroxyl Donor 1-Nitrosocyclohexyl Acetate Limits Cardiac Superoxide Upregulation and Diastolic Dysfunction in a Mouse Model of Diabetic Cardiomyopathy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Rebecca H Ritchie ◽  
Nga Cao ◽  
Yung George Wong ◽  
Sarah Rosli ◽  
Helen Kiriazis ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mouse Model ◽  
Diastolic Dysfunction ◽  
Diabetic Cardiomyopathy ◽  
Ex Vivo ◽  
Systolic Function ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Lv Diastolic Dysfunction ◽  
The Impact

Nitroxyl (HNO), a redox congener of NO•, is a novel regulator of cardiovascular function combining vasodilator and positive inotropic properties. Our previous studies have demonstrated these properties occur concomitantly in the intact heart; HNO moreover also exhibits antihypertrophic and superoxide-suppressing actions. HNO donors may thus offer favorable actions in heart failure. The impact of chronic HNO donor administration has however yet to be reported in this context. We tested the hypothesis that the HNO donor 1-nitrosocyclohexyl acetate (1-NCA) limits cardiomyocyte hypertrophy and left ventricular (LV) diastolic dysfunction in a mouse model of diabetic cardiomyopathy in vivo. Male 6 week-old FVB/N mice received either streptozotocin (55 mg/kg/day i.p. for 5 days, n=17), to induce type 1 diabetes, or citrate vehicle (n=16). After 4 weeks of hyperglycemia, mice were allocated to 1-NCA therapy (83mg/kg/day i.p.) or vehicle, and followed for a further 4 weeks. As shown in the table, blood glucose was unaffected by 1-NCA. LV diastolic dysfunction was evident in diabetic mice, measured as echocardiography-derived A wave velocity, deceleration time and E:A ratio; LV systolic function was preserved. Diabetes-induced diastolic dysfunction was accompanied by increased LV cardiomyocyte size, hypertrophic and pro-fibrotic gene expression, and upregulation of LV superoxide. These characteristics of diabetic cardiomyopathy were largely prevented by 1-NCA treatment. Selectivity of 1-NCA as a donor of HNO versus NO• was demonstrated by the sensitivity of the coronary vasodilation response of 1-NCA to the HNO scavenger L-cysteine (4mM), but not to the NO• scavenger hydroxocobalamin (50μM), in the normal rat heart ex vivo (n=3-7). Collectively, our studies provide the first evidence that HNO donors may represent a promising new strategy for the treatment of diabetic cardiomyopathy, and implies their therapeutic efficacy in settings of chronic heart failure.

scholarly journals Lung Ultrasound B-lines as a Surrogate Marker for High Left Ventricular Diastolic Pressures; a bed-side Diagnostic tool

2021 ◽  
Vol 4 (18) ◽  
pp. 01-11
Author(s):  
Abdulaziz Aboshahba ◽  
Alsayed Ali Abdou Almarghany ◽  
Moaz Atef Elshahat Abdel ati
Keyword(s):  
Heart Failure ◽  
Cost Efficiency ◽  
Lung Ultrasound ◽  
Surrogate Marker ◽  
Left Ventricular ◽  
University Hospital ◽  
Emergency Setting ◽  
Comet Tail ◽  
Chest Ultrasound ◽  
B Lines

Background: We studied the diagnostic accuracy of B-lines (comet-tail sign) on bedside lung US, NT-proBNP, E/e` on ECHO in differentiation of the causes of acute dyspnea in the emergency setting. Major advantages include bedside availability, no radiation, high feasibility and reproducibility, and cost efficiency. Methods: Our prospective study was performed at the alazhar university hospital, Cairo, Egypt, between July 2019 and March 2020. All patients underwent lung ultrasound examinations, along with TTE, laboratory testing, including rapid NT-proBNP testing. Results: The median E/e’ levels in patients with B-profile were 18, compared with a median of 7.4 in the subjects with A-profile (P =< 0.0001 CI = -9.649 to -7.044). It was found that the sensitivity and the specificity of detecting B-profile on ultrasound is high when E/e’ > 15.5 (95.0% and 83.0% consecutively), which concluded the high correlation between finding B profile on U/S chest and elevated left ventricle filling pressure in a patient presenting with picture of suggestive of heart failure Conclusion: Chest ultrasound can be used as screening test for the evaluation of patients with suspicion of heart failure with excellent sensitivity and good specificity.

Abstract 96: Thioredoxin-1 Is Essential for Hydrogen Sulfide-Mediated Cardioprotection in the Setting of Ischemic-Induced Heart Failure

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Chad K Nicholson ◽  
Bridgette F Moody ◽  
Rebecca L Hood ◽  
Junichi Sadoshima ◽  
John W Calvert
Keyword(s):  
Heart Failure ◽  
Hydrogen Sulfide ◽  
Left Ventricular ◽  
Dominant Negative ◽  
Left Ventricular Ejection ◽  
Protective Effects ◽  
Ventricular Ejection Fraction ◽  
Left Ventricular Dimensions ◽  
Thioredoxin 1 ◽  
And Function

Background: Numerous studies have reported the cytoprotective effects of hydrogen sulfide (H2S) in various models of myocardial injury. Here we examined the role that thioredoxin-1 (Trx1) plays in mediating the protective effects of H2S in a model of heart failure. Methods and Results: Mice were subjected to 60 min of left coronary artery ischemia followed by 4 wks of reperfusion (R) at which time left ventricular dimensions and function were assessed. Mice received saline (Veh) or H2S in the form of sodium sulfide (Na2S, 100 μ g/kg) at the time of R followed by daily i.v. injections for the first 7 days of R. Mice treated with Na2S experienced less left ventricular dilatation and hypertrophy, displayed improved left ventricular ejection fraction, and displayed improved contractility and relaxation when compared to Veh-treated mice. Studies aimed at evaluating the underlying cardioprotective mechanisms found that Na2S treatment increased the expression of Trx1. Further analysis revealed that this was accompanied by an increase in phosphorylation of apoptosis signaling kinase-1 (ASK1) at serine residue 966 (inhibitory site), as well as a decrease in the phosphorylation of JNK and p38 (downstream targets of ASK1). We also found that Na2S treatment did not improve cardiac dilatation, cardiac dysfunction, or cardiac hypertrophy in cardiac specific Trx1 dominant negative transgenic (Trx1 dnTg) mice when compared to Veh-treated mice. Conclusion: These findings provide important information that the upregulation of cardiac Trx1 by H2S in the setting of ischemic-induced heart failure sets into motion events, including ASK1 inhibition, which ultimately leads to cardioprotection.

scholarly journals Qiliqiangxin Attenuates Cardiac Remodeling via Inhibition of TGF-β1/Smad3 and NF-κB Signaling Pathways in a Rat Model of Myocardial Infarction

2018 ◽  
Vol 45 (5) ◽  
pp. 1797-1806 ◽  
Author(s):  
Anbang Han ◽  
Yingdong Lu ◽  
Qi Zheng ◽  
Jian Zhang ◽  
YiZhou Zhao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiac Function ◽  
Signaling Pathways ◽  
Rat Model ◽  
Cardiac Remodeling ◽  
Left Ventricular ◽  
Protective Effects ◽  
Tnf Α ◽  
Tgf Β1

Background/Aims: Qiliqiangxin (QL), a traditional Chinese medicine, has been demonstrated to be effective and safe for the treatment of chronic heart failure. Left ventricular (LV) remodeling causes depressed cardiac performance and is an independent determinant of morbidity and mortality after myocardial infarction (MI). Our previous studies have shown that QL exhibits cardiac protective effects against heart failure after MI. The objective of this study was to explore the effects of QL on myocardial fibrosis in rats with MI and to investigate the underlying mechanism of these effects. Methods: A rat model of acute myocardial infarction was induced by ligating the left anterior descending coronary artery. The rats were treated with QL (1.0 g/kg/day) for 4 weeks after surgery. Echocardiography and histology examination were performed to evaluate heart function and fibrosis, respectively. Protein levels of transforming growth factor-β1 (TGF-β1), phosphorylated Smad3 (p-Smad3), phosphorylated Smad7 (p-Smad7), collagen I (Col- I), alpha smooth muscle actin (a-SMA), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), nuclear factor κB (NF-κB), and phosphorylated inhibitor of kappa B alpha (p-IκBα) were measured by western blot analysis. Results: QL treatment ameliorated adverse cardiac remodeling 8 weeks after AMI, including better preservation of cardiac function, decreased inflammation, and reduced fibrosis. In addition, QL treatment reduced Col-I, a-SMA, TGF-β1, and p-Smad3 expression levels but increased p-Smad7 levels in postmyocardial infarct rat hearts. QL administration also reduced the elevated levels of cardiac inflammation mediators, such as TNF-α and IL-6, as well as NF-κB and p-IκBα expression. Conclusions: QL therapy exerted protective effects against cardiac remodeling potentially by inhibiting TGF-β1/Smad3 and NF-κB signaling pathways, thereby preserving cardiac function, as well as reducing myocardial inflammation and fibrosis.

P6209Relationship between skin autofluorescence levels and clinical outcomes in heart failure patients undergoing cardiac rehabilitation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Kunimoto ◽  
K Shimada ◽  
M Yokoyama ◽  
A Honzawa ◽  
M Yamada ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Rehabilitation ◽  
Cox Regression ◽  
Left Ventricular ◽  
University Hospital ◽  
Left Ventricular Ejection ◽  
Skin Autofluorescence ◽  
Ventricular Ejection Fraction ◽  
All Cause Mortality

Abstract Background Advanced glycation end-products, indicated by skin autofluorescence (SAF) levels, could be prognostic predictors of all-cause and cardiovascular mortality in patients with diabetes mellitus (DM) and renal disease. However, the clinical usefulness of SAF levels in patients with heart failure (HF) who underwent cardiac rehabilitation (CR) remains unclear. Purpose The purpose of this study was to investigate the prognostic value of SAF levels in patients with HF who underwent CR. Methods This study enrolled 204 consecutive patients with HF who had undergone CR at our university hospital between November 2015 and October 2017. Clinical characteristics and anthropometric data were collected at the beginning of CR. SAF levels were noninvasively measured with an autofluorescence reader. The major adverse cardiovascular event (MACE) was a composite of all-cause mortality and unplanned hospitalization for HF. Follow-up data concerning primary endpoints were collected until November 2018. Results Patients' mean age was 68.1 years, and 61% were males. Patients were divided into two groups according to the median SAF levels (high and low SAF groups). Patients in the high SAF group were significantly older, had a higher prevalence of chronic kidney disease, and histories of coronary artery bypass surgery; however, there were no significant between-group differences in sex, prevalence of DM, left ventricular ejection fraction, and physical function. During a median follow-up period of 623 days, 25 patients experienced all-cause mortality and 34 were hospitalized for HF. Kaplan–Meier analysis showed that patients in the high SAF group had a higher incidence of MACE (log-rank P<0.05), whereas when patients were divided into two groups according to the median hemoglobin A1c level, no significant between-group difference was observed for the incidence of MACE (Figure). After adjusting for confounding factors, Cox regression multivariate analysis revealed that SAF levels were independently associated with the incidence of MACE (hazard ratio: 1.74, 95% confidence interval: 1.12–2.65, P<0.05). Figure 1 Conclusion SAF levels were significantly associated with the incidence of MACE in patients with HF and may be useful for risk stratification in patients with HF who undergo CR.

scholarly journals Relation between Red Cell Distribution Width and Left Ventricular Function in Children with Heart Failure

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Wegdan Mawlana ◽  
Amr Donia ◽  
Doaa Elamrousy
Keyword(s):  
Heart Failure ◽  
Left Ventricular Function ◽  
Ventricular Function ◽  
Left Ventricular ◽  
Red Cell Distribution Width ◽  
University Hospital ◽  
Red Cell ◽  
Cell Distribution ◽  
Distribution Width ◽  
The Mean

Background. Most of the studies done on adults showed that red cell distribution width (RDW) can be used as a prognostic marker in patients with chronic heart failure. However, RDW has not been tested in children with heart failure. Methods and Results. 31 children with heart failure admitted to Cardiology Unit, Tanta University Hospital, during the period of January 2012 to December 2012 were included in this study, RDW as a component of routine blood count was evaluated and correlated to the echocardiographic parameters of left ventricle. The mean age of our cohort was 16.16 ± 14.97 months, congenital heart disease with left-to-right shunt represented 58.1% of the underlying causes of heart failure while dilated cardiomyopathy made 41.9%. The mean hemoglobin level was 9.14 ± 1.18 gm/dL; RDW level ranged from 10.7% to 27.7% with a mean of 16.01 ± 3.34. Hemoglobin was significantly correlated with RDW at any level. For the echo parameters, at cutoff point of 16.4%, RDW was significantly correlated with fraction shortening (FS), and A, E/A ratio, but it was not correlated with LVEDD, LVESD, and E/É at the same cutoff level. Conclusion. RDW, a simple, available test, can be used as a marker for the left ventricular function in children with heart failure until an echocardiography assessment for the patients is done.

scholarly journals Širdies nepakankamumo gydymas implantuojant dirbtinį skilvelį INCOR

2007 ◽  
Vol 5 (3) ◽  
pp. 0-0
Author(s):  
Kęstutis Ručinskas ◽  
Saulius Miniauskas ◽  
Gintaras Rasimavičius ◽  
Rimantas Bubulis ◽  
Stanislovas Stankevič ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ventricular Assist Device ◽  
Left Ventricular ◽  
University Hospital ◽  
Ventricular Assist Devices ◽  
Assist Device ◽  
Ventricular Assist ◽  
Key Words Heart ◽  
Key Words Heart Failure ◽  
Vilnius University

Kęstutis Ručinskas1, Saulius Miniauskas1, Gintaras Rasimavičius1, Rimantas Bubulis2, Stanislovas Stankevič2, Vaclovas Jurkuvėnas2, Gitana Žemaitytė3, Vytė Valerija Maneikienė3, Vytautas Sirvydis1, Aleksandras Taucevičius41 Vilniaus universiteto Širdies chirurgijos centras, Santariškių g. 2, LT-08661 Vilnius2 Vilniaus universiteto ligoninės Santariškių klinikų Anesteziologijos,intensyviosios terapijos ir skausmo gydymo centras, Santariškių g. 2, LT-08661 Vilnius3 Vilniaus universiteto ligoninės Santariškių klinikų Širdies chirurgijos centras,Santariškių g. 2, LT-08661 Vilnius4 Vilniaus universiteto Širdies ir kraujagyslių ligų klinika, Santariškių g. 2, LT-08661 VilniusEl paštas: [email protected] Dirbtinis implantuojamas pastovios tėkmės kairysis skilvelis INCOR Vilniaus universiteto Širdies chirurgijos centre naudojamas nuo 2003 metų. Pacientams, kuriems nustatytas kraštutinis širdies nepakankamumas, implantuota 14 dirbtinių skilvelių. Po prijungimo 9 pacientai buvo išrašyti į namus, 4 iš jų sulaukė širdies persodinimo operacijos. Šiuo metu ambulatoriškai stebimi 4 pacientai, kuriems implantuotas INCOR skilvelis. Bendras pacientų stebėjimo laikas yra daugiau kaip 8,5 metų. Dirbtinio skilvelio INCOR implantacija yra labai efektyvus atrinktos grupės pacientų širdies nepakankamumo gydymo būdas. Pagrindiniai žodžiai: širdies nepakankamumas, dirbtinis skilvelis, širdies persodinimas Treatment of heart failure by implanting an INCOR left ventricular assist device Kęstutis Ručinskas1, Saulius Miniauskas1, Gintaras Rasimavičius1, Rimantas Bubulis2, Stanislovas Stankevič2, Vaclovas Jurkuvėnas2, Gitana Žemaitytė3, Vytė Valerija Maneikienė3, Vytautas Sirvydis1, Aleksandras Taucevičius41 Cardial Surgery Centre, Vilnius University, Santariškių str. 2, LT-08661 Vilnius, Lithuania2 Vilnius University Hospital „Santariškių klinikos“, Anesthesiology,Intensive Care and Pain Management Center, Santariškių str. 2, LT-08661 Vilnius, Lithuania 3 Cardial Surgery Centre of Vilnius University Hospital „Santariškių klinikos“,Santariškių str. 2, LT-08661 Vilnius, Lithuania4 Vilnius University, Clinic of Cardiovascular Diseases,Santariškių str. 2, LT-08661 Vilnius, LithuaniaE-mail: [email protected] Continuous blood flow ventricular assist devices, INCOR, are used at Vilnius University Cardial Surgery Centre since 2003. Fourteen of them were implanted to terminal heart failure patients. After the procedure, 9 patients were discharged home and 4 received heart transplant. At the present time, four patients with INCOR are being observed at home. The cumulative time of the patients with the INCOR assist device is 8.5 years. Effective treatment for a selected group of patients with heart failure is ventricular assist device INCOR implantation. Key words: heart failure, assist device, heart transplantation

scholarly journals Study protocol for the PURSUIT-HFpEF study: a Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e038294
Author(s):  
Shinichiro Suna ◽  
Shungo Hikoso ◽  
Takahisa Yamada ◽  
Masaaki Uematsu ◽  
Yoshio Yasumura ◽  
...  
Keyword(s):  
Heart Failure ◽  
Observational Study ◽  
Ejection Fraction ◽  
Acute Decompensated Heart Failure ◽  
Left Ventricular ◽  
University Hospital ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction

IntroductionNeither the pathophysiology nor an effective treatment for heart failure with preserved ejection fraction (HFpEF) has been elucidated to date. The purpose of this ongoing study is to elucidate the pathophysiology and prognostic factors for patients with HFpEF admitted to participating institutes. We also aim to obtain insights into the development of new diagnostic and treatment methods by analysing patient background factors, clinical data and follow-up information.Methods and analysisThis study is a prospective, multicentre, observational study of patients aged ≥20 years admitted due to acute decompensated heart failure with preserved left ventricular ejection fraction (≥50%) and elevated N-terminal-pro brain natriuretic peptide (NT-proBNP) (≥400 pg/mL). The study began in June 2016, with the participation of Osaka University Hospital and 31 affiliated facilities. We will collect data on history in detail, accompanying diseases, quality of life, frailty score, medication history, and laboratory and echocardiographic data. We will follow-up each patient for 5 years, and collect outcome data on mortality, cause of death, and the number and cause of hospitalisation. The target number of registered cases is 1500 cases in 5 years.Ethics and disseminationThe protocol was approved by the Institutional Review Board (IRB) of Osaka University Hospital on 24 February 2016 (ID: 15471), and by the IRBs of the all participating facilities. The findings will be disseminated through peer-reviewed publications and conference presentations.

Abstract P490: Vascular Rarefaction And Decreased Angiogenic Potential In The Development Of Left Ventricular Diastolic Dysfunction In Heart Failure With Preserved Ejection Fraction

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Katie Anne Fopiano ◽  
Yanna Tian ◽  
Vadym Buncha ◽  
Liwei Lang ◽  
Zsolt Bagi
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Rat Model ◽  
Ex Vivo ◽  
Diastolic Heart Failure ◽  
Left Ventricular ◽  
Coronary Microvascular Dysfunction ◽  
Preserved Ejection Fraction ◽  
Angiogenic Potential

Coronary microvascular dysfunction (CMD) develops in patients with heart failure with preserved ejection fraction (HFpEF, also known as diastolic heart failure), but the nature of the underlying pathomechanisms behind this prevalent disease remain poorly understood. The hypothesis tested was that coronary microvascular rarefaction contributes to left ventricle (LV) diastolic function in HFpEF. The obese ZSF1 rat model of human HFpEF was employed and using transthoracic echocardiography it was found that 18-week-old male obese ZSF1 rats exhibited a significantly reduced E/A ratio (E=early, A=late mitral inflow peak velocities) and increased DT (E wave deceleration time) with no change in ejection fraction, indicating diastolic dysfunction. Coronary arteriolar and capillary trees were labeled using Tomato Lectin (Lycopersicon esculentum) DyLight®594 and were imaged by fluorescent confocal microscopy to generate image stacks for 3D reconstruction. Unbiased automated tracing of the microvasculature was done using VesselLucida360 software (MBF) followed by a morphometric analysis (VesselLucida Explorer). It was found that total vessel length and the number of vessel’s branching nodes were reduced in the obese ZSF1 rats, whereas the total vessel’s volumes remained consistent, when compared to the lean ZSF1 controls. These changes in the microvasculature were accompanied by decreased angiogenesis in the coronary arteries in the obese ZSF1 rats when compared to the lean ZSF1 rats using an ex vivo endothelial sprouting assay. From these results, it was concluded that vascular rarefaction and decreased angiogenesis both play a role in the development of LV diastolic dysfunction in the obese ZSF1 rat model of human HFpEF.

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