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  string(98) "SGLT2 I in heart failure with non-reduced ejection fraction :a systematic review and meta analysis"
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  string(506) "The aim of this study was to assess the impact of SGLT2 inhibitors in non-HFrEF heart failure Background The proportion of HF patients without reduced ejection fraction have a mortality rate similar to that of patients with HF with reduced ejection fraction.  In recent years, some experiments have found that SGLT2i drugs can reduce the mortality and readmission rate of patients with non-HFrEF.  Therefore, we performed a meta-analysis to be able to assess the effect of SGLT2i in patients with non-HFrEF"
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      ["p_pers_f_name"]=>
      string(9) "Chenliang"
      ["p_pers_l_name"]=>
      string(4) "Song"
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      string(2) "MD"
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      string(25) "China Medical  University"
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      string(195) "NCT01032629 - A Randomized, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of JNJ-28431754 on Cardiovascular Outcomes in Adult Subjects With Type 2 Diabetes Mellitus"
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      string(238) "https://dev-yoda.pantheonsite.io/clinical-trial/nct01032629-a-randomized-multicenter-double-blind-parallel-placebo-controlled-study-of-the-effects-of-jnj-28431754-on-cardiovascular-outcomes-in-adult-subjects-with-type-2-diabetes-mellitus/"
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  ["property_scientific_abstract"]=>
  string(1786) "Background?The proportion of HF patients without reduced ejection fraction have a mortality rate similar to that of patients with HF with reduced ejection fraction.  In recent years, some experiments have found that SGLT2i drugs can reduce the mortality and readmission rate of patients with non-HFrEF.  Therefore, we performed a meta-analysis to be able to assess the effect of SGLT2i in patients with non-HFrEF.

Objective?Assess the impact of SGLT2 inhibitors in non-HFrEF heart failure.

Study Design?Three databases, pubmed, Cochrane Library for Central Register of Clinical Trials, and web of sciences, were searched, and the last search date was 16 July 2021. Follow-up included a new study presented at the end-August meeting with a meta-analysis of several outcomes?For the included trials?we will do a meta-analysis.

 Participants?Heart failure with non-reduced ejection fraction.

Main Outcome Measure?A total of 9 studies were included, including 5 RCTs and 4 prospective studies, involving a total of 7891 patients, of which 4264 patients with non-EFF HF were treated with SGLT2 inhibitors, and another 3631 patients were treated with SGLT2 inhibitors.  Incidence of clinical events (OR, 0.74, 95% CI 0.65-0.84, p < 0.00001), NT-PROBNP (MD, -16.85, 95% CI: -23.73 to -9.98, p < 0.00001), E/E`  No difference (MD, -0.56, 95% CI: -1.85-0.74, P=0.40)

Statistical Analysis:Adjusted ORs and MD with 95% CIs were pooled to evaluate prognosis.Data were separated into two distinct groups  for comparisions : SGLT2I and placebo and compared by  fixed-effect distribution tests. The variablity of the results between the studies was considered the same for the two groups? and differences between the groups were  considered statistically significant if p"
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  string(291) "The proportion of HF patients without reduced ejection fraction have a mortality rate similar to that of patients with HF with reduced ejection fraction.  In recent years, some experiments have found that SGLT2i drugs can reduce the mortality and readmission rate of patients with non-HFrEF."
  ["project_specific_aims"]=>
  string(124) "Assess the impact of SGLT2 inhibitors in non-HFrEF heart failure

hypotheses ?SGLT2i is beneficial to non-heart failure"
  ["project_study_design"]=>
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  ["project_purposes"]=>
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      ["value"]=>
      string(32) "Summary-level data meta-analysis"
      ["label"]=>
      string(32) "Summary-level data meta-analysis"
    }
    [1]=>
    array(2) {
      ["value"]=>
      string(69) "Meta-analysis using data from the YODA Project and other data sources"
      ["label"]=>
      string(69) "Meta-analysis using data from the YODA Project and other data sources"
    }
  }
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    ["label"]=>
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  string(447) "Data Source:other articles from pubmed and this article

INCLUSION CRITERIA

1.The trials which  invention method is SGLT2I.

2.The trials which  participants are heart failure patients with a LVEF>40%

3.The trials which outcome can evaluate the improvement of heart failure?

Exclusion Criteria

1.The trials without outcome?

2.The trials which baseline don`t have details of LVEF

3.The summary abstract"
  ["project_main_outcome_measure"]=>
  string(149) "The main  outcome was a composite of adjudicated cardiovascular death or hosipitalizations for heart failure,analyzed as the time to the first event."
  ["project_main_predictor_indep"]=>
  string(74) "Variable is the use of SGLT2I,

It is an invention-to-treat analysis."
  ["project_other_variables_interest"]=>
  string(2) "no"
  ["project_stat_analysis_plan"]=>
  string(398) "Statistical Analysis Adjusted ORs and MD with 95% CIs were pooled to evaluate prognosis.Data were separated into two distinct groups  for comparisions : SGLT2I and placebo and compared by  fixed-effect distribution tests? The variablity of the results between the studies was considered the same for the two groups? and differences between the groups were  considered statistically significant if p"
  ["project_timeline"]=>
  string(123) "If I can achieve the data ,the meta-analysis will be complained in two months,and we will try to publicate it in 3 months ."
  ["project_dissemination_plan"]=>
  string(11) "Circulation"
  ["project_bibliography"]=>
  string(7177) "
[1]	Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370(15):1383-1392.

[2]	Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC [published correction appears in Eur Heart J. 2016 Dec 30;:]. Eur Heart J. 2016;37(27):2129-2200.

[3]	van Riet EE, Hoes AW, Wagenaar KP, Limburg A, Landman MA, Rutten FH. Epidemiology of heart failure: the prevalence of heart failure and ventricular dysfunction in older adults over time. A systematic review. Eur J Heart Fail. 2016;18(3):242-252.

[4]	Groenewegen A, Rutten FH, Mosterd A, Hoes AW. Epidemiology of heart failure. Eur J Heart Fail. 2020;22(8):1342-1356.

[5]	Sakai T, Miura S. Effects of Sodium-Glucose Cotransporter 2 Inhibitor on Vascular Endothelial and Diastolic Function in Heart Failure With Preserved Ejection Fraction?- Novel Prospective Cohort Study. Circ Rep. 2019;1(7):286-295. Published 2019 Jun 3.

[6]	Ye Y, Bajaj M, Yang HC, Perez-Polo JR, Birnbaum Y. SGLT-2 Inhibition with Dapagliflozin Reduces the Activation of the Nlrp3/ASC Inflammasome and Attenuates the Development of Diabetic Cardiomyopathy in Mice with Type 2 Diabetes. Further Augmentation of the Effects with Saxagliptin, a DPP4 Inhibitor. Cardiovasc Drugs Ther. 2017;31(2):119-132.

[7]	Zhang Y, Lin X, Chu Y, et al. Dapagliflozin: a sodium-glucose cotransporter 2 inhibitor, attenuates angiotensin II-induced cardiac fibrotic remodeling by regulating TGF?1/Smad signaling. Cardiovasc Diabetol. 2021;20(1):121. Published 2021 Jun 11.

[8]	Hasan R, Lasker S, Hasan A, et al. Canagliflozin attenuates isoprenaline-induced cardiac oxidative stress by stimulating multiple antioxidant and anti-inflammatory signaling pathways. Sci Rep. 2020;10(1):14459. Published 2020 Sep 2.

[9]	Zannad F, Ferreira JP, Pocock SJ, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet. 2020;396(10254):819-829.

[10]	Bhatt DL, Szarek M, Steg PG et al. SOLOIST-WHF Trial Investigators. Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. N Engl J Med. 2021 Jan 14;384(2):117-128.

[11]	 Ejiri K, Miyoshi T, Kihara H, et al. Effect of Luseogliflozin on Heart Failure With Preserved Ejection Fraction in Patients With Diabetes Mellitus. J Am Heart Assoc. 2020;9(16):e015103.

[12]	Nakagaito M, Joho S, Ushijima R, Nakamura M, Kinugawa K. Comparison of Canagliflozin, Dapagliflozin and Empagliflozin Added to Heart Failure Treatment in Decompensated Heart Failure Patients With Type 2 Diabetes Mellitus. Circ Rep. 2019;1(10):405-413. Published 2019 Sep 27.

[13]	Oka S, Kai T, Hoshino K, et al. Effects of empagliflozin in different phases of diabetes mellitus-related cardiomyopathy: a prospective observational study. BMC Cardiovasc Disord. 2021;21(1):217. Published 2021 Apr 29.

[14]	Sakai T, Miura S. Effects of Sodium-Glucose Cotransporter 2 Inhibitor on Vascular Endothelial and Diastolic Function in Heart Failure With Preserved Ejection Fraction?- Novel Prospective Cohort Study. Circ Rep. 2019;1(7):286-295. Published 2019 Jun 3. ?

[15]	Tanaka A, Hisauchi I, Taguchi I, et al. Effects of canagliflozin in patients with type 2 diabetes and chronic heart failure: a randomized trial (CANDLE). ESC Heart Fail. 2020;7(4):1585-1594.

[16]	Tanaka H, Soga F, Tatsumi K, et al. Positive effect of dapagliflozin on left ventricular longitudinal function for type 2 diabetic mellitus patients with chronic heart failure. Cardiovasc Diabetol. 2020;19(1):6. Published 2020 Jan 7.

+1emperor preserved

+2Sant’Anna LB, Couceiro SLM, Ferreira EA, et al. Vagal Neuromodulation in Chronic Heart Failure With Reduced Ejection Fraction: A Systematic Review and Meta-Analysis. Front Cardiovasc Med. 2021;8:766676.

[17]	Nagueh SF. Heart failure with preserved ejection fraction: insights into diagnosis and pathophysiology. Cardiovasc Res. 2021 Mar 21;117(4):999-1014.

[18]	Cordero-Reyes AM, Youker K, Estep JD, Torre-Amione G, Nagueh SF. Molecular and cellular correlates of cardiac function in end-stage DCM: a study using speckle tracking echocardiography. JACC Cardiovasc Imaging. 2014 May;7(5):441-52.

[19]	Eisner DA, Caldwell JL, Trafford AW, Hutchings DC. The Control of Diastolic Calcium in the Heart: Basic Mechanisms and Functional Implications. Circ Res. 2020 Jan 31;126(3):395-412.

[20]	Wang J, Khoury DS, Yue Y, Torre-Amione G, Nagueh SF. Preserved left ventricular twist and circumferential deformation, but depressed longitudinal and radial deformation in patients with diastolic heart failure. Eur Heart J. 2008;29(10):1283-1289.

[21]	Franssen C, Chen S, Unger A, et al. Myocardial Microvascular Inflammatory Endothelial Activation in Heart Failure With Preserved Ejection Fraction. JACC Heart Fail. 2016;4(4):312-324.

[22]	Schiattarella GG, Altamirano F, Tong D, et al. Nitrosative stress drives heart failure with preserved ejection fraction. Nature. 2019;568(7752):351-356.

[23]	Zelniker TA, Braunwald E. Mechanisms of Cardiorenal Effects of Sodium-Glucose Cotransporter 2 Inhibitors: JACC State-of-the-Art Review [published correction appears in J Am Coll Cardiol. 2020 Sep 22;76(12):1505]. J Am Coll Cardiol. 2020;75(4):422-434.

[24]	Engelhardt S, Hein L, Keller U, Klmbt K, Lohse MJ. Inhibition of Na(+)-H(+) exchange prevents hypertrophy, fibrosis, and heart failure in beta(1)-adrenergic receptor transgenic mice. Circ Res. 2002;90(7):814-819.

[25]	Lee TM, Chang NC, Lin SZ. Dapagliflozin, a selective SGLT2 Inhibitor, attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts. Free Radic Biol Med. 2017;104:298-310.

[26]	Zhang Y, Lin X, Chu Y, et al. Dapagliflozin: a sodium-glucose cotransporter 2 inhibitor, attenuates angiotensin II-induced cardiac fibrotic remodeling by regulating TGF?1/Smad signaling. Cardiovasc Diabetol. 2021;20(1):121.

[27]	Mustroph J, Wagemann O, Lcht CM, et al. Empagliflozin reduces Ca/calmodulin-dependent kinase II activity in isolated ventricular cardiomyocytes. ESC Heart Fail. 2018;5(4):642-648.

[28]	Ye Y, Bajaj M, Yang HC, Perez-Polo JR, Birnbaum Y. SGLT-2 Inhibition with Dapagliflozin Reduces the Activation of the Nlrp3/ASC Inflammasome and Attenuates the Development of Diabetic Cardiomyopathy in Mice with Type 2 Diabetes. Further Augmentation of the Effects with Saxagliptin, a DPP4 Inhibitor. Cardiovasc Drugs Ther. 2017;31(2):119-132.

[29]	El-Daly M, Pulakazhi Venu VK, Saifeddine M, et al. Hyperglycaemic impairment of PAR2-mediated vasodilation: Prevention by inhibition of aortic endothelial sodium-glucose-co-Transporter-2 and minimizing oxidative stress. Vascul Pharmacol. 2018;109:56-71.
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