Heart failure with preserved ejection fraction: key stumbling blocks for experimental drugs in clinical trials

References

• Maeder MT, Kaye DM. Heart failure with normal left ventricular ejection fraction. J Am Coll Cardiol. 2009 Mar 17; 53 (11): 905–918.
   PubMed Web of Science ®Google Scholar
• Berry C, Doughty R N, Granger C et al. The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis. Eur Heart J. 2012 Jul;33(14):1750–1757.
   PubMed Web of Science ®Google Scholar
• Ho JE, Enserro D, Brouwers FP, et al. Predicting heart failure with preserved and reduced ejection fraction: the international collaboration on heart failure subtypes. Circ Heart Fail. 2016 Jun;9(6). https://doi.org/10.1161/CIRCHEARTFAILURE.115.003116.
   Google Scholar
• Vasan RS, Xanthakis V, Lyass A, et al. Epidemiology of left ventricular systolic dysfunction and heart failure in the framingham study: an echocardiographic study over 3 decades. JACC Cardiovasc Imaging. 2018 Jan;11(1):1–11.
   PubMed Web of Science ®Google Scholar
• North BJ, Sinclair DA. The intersection between aging and cardiovascular disease. Circ Res. 2012 Apr 13; 110(8):1097–1108.
   PubMed Web of Science ®Google Scholar
• Wood P, Piran S, Liu PP. Diastolic heart failure: progress, treatment challenges, and prevention. Can J Cardiol. 2011 May-Jun;27(3):302–310.
   PubMed Web of Science ®Google Scholar
• Zile MR, Baicu CF, Ikonomidis JS, et al. Myocardial stiffness in patients with heart failure and a preserved ejection fraction: contributions of collagen and titin. Circulation. 2015 Apr 7 131(14):1247–1259.
   PubMed Web of Science ®Google Scholar
• Pfeffer MA, Shah AM, Borlaug BA. Heart failure with preserved ejection fraction in perspective. Circ Res. 2019 May 24; 124(11):1598–1617.
   PubMed Web of Science ®Google Scholar
• Borlaug BA. The pathophysiology of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2014 Sep;11(9):507–515.
   PubMed Web of Science ®Google Scholar
• Abudiab MM, Redfield MM, Melenovsky V, et al. Cardiac output response to exercise in relation to metabolic demand in heart failure with preserved ejection fraction. Eur J Heart Fail. 2013 Jul;15(7):776–785.
   PubMed Web of Science ®Google Scholar
• Del Buono MG, Arena R, Borlaug BA, et al. Exercise intolerance in patients with heart failure: jacc state-of-the-art review. J Am Coll Cardiol. 2019 May 7 73(17):2209–2225.
   PubMed Web of Science ®Google Scholar
• Pacher P, Beckman JS, Liaudet L. Nitric oxide and peroxynitrite in health and disease. Physiol Rev. 2007 Jan;87(1):315–424.
   PubMed Web of Science ®Google Scholar
• Haider N, Boscá L, Zandbergen HR, et al. Transition of macrophages to fibroblast-like cells in healing myocardial infarction. J Am Coll Cardiol. 2019 Dec 24 74(25):3124–3135.
   PubMed Web of Science ®Google Scholar
• Hamdani N, Franssen C, Lourenço A, et al. Myocardial titin hypophosphorylation importantly contributes to heart failure with preserved ejection fraction in a rat metabolic risk model. Circ Heart Fail. 2013 Nov;6(6):1239–1249.
   PubMed Web of Science ®Google Scholar
• Parra V, Eisner V, Chiong M, et al. Changes in mitochondrial dynamics during ceramide-induced cardiomyocyte early apoptosis. Cardiovasc Res. 2008 Jan 15 77(2):387–397.
   PubMed Web of Science ®Google Scholar
• Kuzmicic J, Parra V, Verdejo HE, et al. Trimetazidine prevents palmitate-induced mitochondrial fission and dysfunction in cultured cardiomyocytes. Biochem Pharmacol. 2014 Oct 1 91(3):323–336.
   PubMed Web of Science ®Google Scholar
• Miranda-Silva D, Wüst RCI, Conceição G, et al. Disturbed cardiac mitochondrial and cytosolic calcium handling in a metabolic risk-related rat model of heart failure with preserved ejection fraction. Acta Physiol (Oxf). 2020 Mar;228(3):e13378.
   PubMed Web of Science ®Google Scholar
• Sequeira V, Najafi A, McConnell M, et al. Synergistic role of ADP and Ca(2+) in diastolic myocardial stiffness. J Physiol. 2015 Sep 1 593(17):3899–3916.
   PubMed Web of Science ®Google Scholar
• van Empel V, Brunner-La Rocca HP. Inflammation in HFpEF: key or circumstantial? Int J Cardiol. 2015;189:259–263.
   PubMed Web of Science ®Google Scholar
• Adams V, Linke A, Winzer E. Skeletal muscle alterations in HFrEF vs HFpEF. Current heart failure reports. 2017Dec;14(6):489–497.
   PubMedGoogle Scholar
• Paulus WJ, Tschöpe C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol. 2013 Jul 23; 62(4):263–271.
   PubMed Web of Science ®Google Scholar
• Cohn JN, Archibald DG, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. results of a veterans administration Cooperative Study. N Engl J Med. 1986 Jun 12 314(24):1547–1552.
   PubMed Web of Science ®Google Scholar
• CONSENSUS Trial Study Group, Effects of enalapril on mortality in severe congestive heart failure. results of the cooperative north scandinavian enalapril survival study (CONSENSUS). N Engl J Med. 1987 Jun 4;316(23):1429–1435.
   PubMed Web of Science ®Google Scholar
• Cohn JN, Johnson G. Heart failure with normal ejection fraction. the V-HeFT study. veterans administration cooperative study group. Circulation. 1990 Feb;81(2 Suppl):Iii48–53.
   PubMed Web of Science ®Google Scholar
• Yancy CW, Jessup M, Bozkurt B, et al. ACCF/AHA guideline for the management of heart failure: a report of the american college of cardiology foundation/american heart association task force on practice guidelines. J Am Coll Cardiol. 2013 [2013 Oct 15];62(16):e147–239.
   PubMed Web of Science ®Google Scholar
• Reddy YNV, Carter RE, Obokata M, et al. A simple, evidence-based approach to help guide diagnosis of heart failure with preserved ejection fraction. Circulation. 2018 Aug 28 138(9):861–870.
   PubMed Web of Science ®Google Scholar
• Telles F, Nanayakkara S, Evans S, et al. Impaired left atrial strain predicts abnormal exercise haemodynamics in heart failure with preserved ejection fraction. Eur J Heart Fail. 2019 Apr;21(4):495–505.
   PubMed Web of Science ®Google Scholar
• Bisbal F, Baranchuk A, Braunwald E, et al. Atrial failure as a clinical entity: jacc review topic of the week. J Am Coll Cardiol. 2020Jan 21 75(2):222–232.
   PubMed Web of Science ®Google Scholar
• Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet. 2003 Sep 6 362(9386):777–781.
   PubMed Web of Science ®Google Scholar
• Persson H, Lonn E, Edner M, et al. Diastolic dysfunction in heart failure with preserved systolic function: need for objective evidence:results from the CHARM Echocardiographic Substudy-CHARMES. J Am Coll Cardiol. 2007 Feb 13 49(6):687–694.
   PubMed Web of Science ®Google Scholar
• Cleland JG, Tendera M, Adamus J et al, et al. The perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J. 2006 Oct;27(19):2338–2345.
   PubMed Web of Science ®Google Scholar
• Zile MR, Gottdiener JS, Hetzel SJ, et al. Prevalence and significance of alterations in cardiac structure and function in patients with heart failure and a preserved ejection fraction. Circulation. 2011 Dec 6 124(23):2491–2501.
   PubMed Web of Science ®Google Scholar
• Pitt B, Pfeffer MA, Assmann SF, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014 Apr 10 370(15):1383–1392.
   PubMed Web of Science ®Google Scholar
• Shah AM, Claggett B, Sweitzer NK, et al. Cardiac structure and function and prognosis in heart failure with preserved ejection fraction: findings from the echocardiographic study of the treatment of preserved cardiac function heart failure with an aldosterone antagonist (topcat) trial. Circ Heart Fail. 2014 Sep;7(5):740–751.
   PubMed Web of Science ®Google Scholar
• Solomon SD, Rizkala AR, Lefkowitz MP, et al. Baseline characteristics of patients with heart failure and preserved ejection fraction in the paragon-hf trial. Circ Heart Fail. 2018 Jul;11(7):e004962.
   PubMed Web of Science ®Google Scholar
• Solomon SD, McMurray JJV, Anand IS, et al. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med. 2019 Oct 24 381(17):1609–1620.
   PubMed Web of Science ®Google Scholar
• Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021 Oct 14 385(16):1451–1461.
   PubMed Web of Science ®Google Scholar
• Tanskanen M, Peuralinna T, Polvikoski T, et al., Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: a population-based autopsy study. Ann Med. 40(3): 232–239. 2008.
   PubMed Web of Science ®Google Scholar
• Hahn VS, Yanek LR, Vaishnav J, et al. Endomyocardial biopsy characterization of heart failure with preserved ejection fraction and prevalence of cardiac amyloidosis. JACC Heart Fail. 2020 Sep;8(9):712–724.
   PubMed Web of Science ®Google Scholar
• Ponikowski P, Voors AA, Anker SD, et al. 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. Eur Heart J. 2016 [2016 Jul 14];37(27):2129–2200.
   PubMed Web of Science ®Google Scholar
• Branca L, Sbolli M, Metra M, et al. Heart failure with mid-range ejection fraction: pro and cons of the new classification of heart failure by european society of cardiology guidelines. ESC Heart Fail. 2020 Apr;7(2):381–399.
   PubMed Web of Science ®Google Scholar
• Chioncel O, Lainscak M, Seferovic PM, et al. Epidemiology and one-year outcomes in patients with chronic heart failure and preserved, mid-range and reduced ejection fraction: an analysis of the ESC heart failure long-term registry. Eur J Heart Fail. 2017 Dec;19(12):1574–1585.
   PubMed Web of Science ®Google Scholar
• Tsuji K, Sakata Y, Nochioka K, et al. Characterization of heart failure patients with mid-range left ventricular ejection fraction-a report from the CHART-2 Study. Eur J Heart Fail. 2017 Oct;19(10):1258–1269.
   PubMed Web of Science ®Google Scholar
• Vergaro G, Aimo A, Prontera C, et al. Sympathetic and renin-angiotensin-aldosterone system activation in heart failure with preserved, mid-range and reduced ejection fraction. Int J Cardiol. 2019 Dec 1;296:91–97.
   PubMed Web of Science ®Google Scholar
• Savarese G, Orsini N, Hage C, et al. Associations with and prognostic and discriminatory role of n-terminal pro-b-type natriuretic peptide in heart failure with preserved versus mid-range versus reduced ejection fraction. J Card Fail. 2018 Jun;24(6):365–374.
   PubMed Web of Science ®Google Scholar
• Tromp J, Khan MAF, Mentz RJ, et al. Biomarker profiles of acute heart failure patients with a mid-range ejection fraction. JACC Heart Fail. 2017 Jul;5(7):507–517.
   PubMed Web of Science ®Google Scholar
• Gallo G, Volpe M, Battistoni A, et al. Sacubitril/valsartan as a therapeutic tool across the range of heart failure phenotypes and ejection fraction spectrum. Front Physiol. 2021;12:652163.
   PubMed Web of Science ®Google Scholar
• McDonagh TA, Metra M, Adamo M, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42(36):3599–3726. 2021 Sep 21.
   PubMed Web of Science ®Google Scholar
• Ross J Jr. Mechanisms of cardiac contraction. what roles for preload, afterload and inotropic state in heart failure? Eur Heart J. 1983 Jan;4:19–28. Suppl A.
   PubMed Web of Science ®Google Scholar
• Merillon JP, Fontenier G, Lerallut JF, et al. Aortic input impedance in heart failure: comparison with normal subjects and its changes during vasodilator therapy. Eur Heart J. 1984 Jun;5(6):447–455.
   PubMed Web of Science ®Google Scholar
• Bristow MR, Kao DP, Breathett KK, et al. Structural and functional phenotyping of the failing heart: is the left ventricular ejection fraction obsolete? JACC Heart Fail. 2017 Nov;5(11):772–781.
   PubMed Web of Science ®Google Scholar
• Triposkiadis F, Butler J, Abboud FM, et al. The continuous heart failure spectrum: moving beyond an ejection fraction classification. Eur Heart J. 2019 Jul 1 40(26):2155–2163.
   PubMed Web of Science ®Google Scholar
• Nagueh SF, Abraham TP, Aurigemma GP, et al. Interobserver variability in applying american society of echocardiography/european association of cardiovascular imaging 2016 guidelines for estimation of left ventricular filling pressure. Circ Cardiovasc Imaging. 2019 Dec;12(1):e008122.
   PubMed Web of Science ®Google Scholar
• Gerdes AM, Capasso JM. Structural remodeling and mechanical dysfunction of cardiac myocytes in heart failure. J Mol Cell Cardiol. 1995 Mar;27(3):849–856.
   PubMed Web of Science ®Google Scholar
• Mele D, Andrade A, Bettencourt P, et al. From left ventricular ejection fraction to cardiac hemodynamics: role of echocardiography in evaluating patients with heart failure. Heart Fail Rev. 2020 Mar;25(2):217–230.
   PubMed Web of Science ®Google Scholar
• Potter E, Marwick TH. Assessment of left ventricular function by echocardiography: the case for routinely adding global longitudinal strain to ejection fraction. JACC Cardiovasc Imaging. 2018 Feb;11(2 Pt 1):260–274.
   PubMed Web of Science ®Google Scholar
• Tan YT, Wenzelburger F, Lee E, et al. The pathophysiology of heart failure with normal ejection fraction: exercise echocardiography reveals complex abnormalities of both systolic and diastolic ventricular function involving torsion, untwist, and longitudinal motion. J Am Coll Cardiol. 2009 Jun 30 54(1):36–46.
   PubMed Web of Science ®Google Scholar
• Shah SJ, Katz DH, Deo RC. Phenotypic spectrum of heart failure with preserved ejection fraction. Heart Fail Clin. 2014 Jul;10(3):407–418.
   PubMed Web of Science ®Google Scholar
• Shah SJ, Katz DH, Selvaraj S, et al. Phenomapping for novel classification of heart failure with preserved ejection fraction. Circulation. 2015 Jan 20 131(3):269–279.
   PubMed Web of Science ®Google Scholar
• Woolley RJ, Ceelen D, Ouwerkerk W, et al. Machine learning based on biomarker profiles identifies distinct subgroups of heart failure with preserved ejection fraction. Eur J Heart Fail. 2021 Jun;23(6):983–991.
   PubMed Web of Science ®Google Scholar
• Kao DP, Lewsey JD, Anand IS, et al. Characterization of subgroups of heart failure patients with preserved ejection fraction with possible implications for prognosis and treatment response. Eur J Heart Fail. 2015 Sep;17(9):925–935.
   PubMed Web of Science ®Google Scholar
• Cohen JB, Schrauben SJ, Zhao L, et al. clinical phenogroups in heart failure with preserved ejection fraction: detailed phenotypes, prognosis, and response to spironolactone. JACC Heart Fail. 2020 Mar;8(3):172–184.
   PubMed Web of Science ®Google Scholar
• Shah S, Voors AA, McMurray JJV, et al. Effect of neladenoson bialanate on exercise capacity among patients with heart failure with preserved ejection fraction JAMA . 2019;321(21):1201–2112.
   Web of Science ®Google Scholar
• Å K H, Hage C, Sharma A, et al. Identification of novel pheno-groups in heart failure with preserved ejection fraction using machine learning. Heart. 2020 Mar;106(5):342–349.
   PubMed Web of Science ®Google Scholar
• Ge J. Coding proposal on phenotyping heart failure with preserved ejection fraction: a practical tool for facilitating etiology-oriented therapy. Cardiol J. 2020;27(1):97–98.
   PubMed Web of Science ®Google Scholar
• Valero-Muñoz M, Backman W, Sam F. Murine models of heart failure with preserved ejection fraction: a “fishing expedition.” JACC: Basic to Translational Science. 2017 Dec;2(6): 770–789.
   PubMedGoogle Scholar
• Regan JA, Mauro AG, Carbone S, et al. A mouse model of heart failure with preserved ejection fraction due to chronic infusion of a low subpressor dose of angiotensin II. Am J Physiol Heart Circ Physiol. 2015 Sep;309(5):H771–8.
   PubMed Web of Science ®Google Scholar
• Schiattarella GG, Altamirano F, Tong D, et al. Nitrosative stress drives heart failure with preserved ejection fraction. Nature. 2019;568:351–356.
   PubMed Web of Science ®Google Scholar
• Packer M, Kitzman D. obesity-related heart failure with a preserved ejection fraction: The mechanistic Rationale for Combining Inhibitors of Aldosterone, Neprilysin, and Sodium-Glucose Cotransporter-2.JACC Heart Failure . 6(8 633–639):2018.
   PubMed Web of Science ®Google Scholar
• Porrello ER, Delbridge LMD. HFpEF-time to explore the role of genetic heterogeneity in phenotypic variability: new mechanistic insights offer promise for personalized therapies. Circulation. 2019 Nov 12;140(20):1607–1609.
   PubMed Web of Science ®Google Scholar
• Adamson PB, Abraham WT, Bourge RC, et al. Wireless pulmonary artery pressure monitoring guides management to reduce decompensation in heart failure with preserved ejection fraction. Circ Heart Fail. 2014 Nov;7(6):935–944.
   PubMed Web of Science ®Google Scholar
• Kotecha D, Lam CS, Van Veldhuisen DJ, et al. Heart failure with preserved ejection fraction and atrial fibrillation: vicious twins. J Am Coll Cardiol. 2016 Nov 15 68(20):2217–2228.
   PubMed Web of Science ®Google Scholar
• Wyse DG, Waldo AL, DiMarco JP, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. [2002 Dec 5];347(23):1825–1833.
   PubMed Web of Science ®Google Scholar
• Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008 May 1 358(18):1887–1898.
   PubMed Web of Science ®Google Scholar
• Wright JT Jr., Williamson JD, Whelton PK, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. [2015 Nov 26];373(22):2103–2116.
   PubMed Web of Science ®Google Scholar
• Redfield MM, Anstrom KJ, Levine JA, et al. Isosorbide mononitrate in heart failure with preserved ejection fraction. N Engl J Med. 2015 Dec 10 373(24):2314–2324.
   PubMed Web of Science ®Google Scholar
• Reddy YNV, Lewis GD, Shah SJ, et al. INDIE-HFpEF (inorganic nitrite delivery to improve exercise capacity in heart failure with preserved ejection fraction): rationale and design. Circ Heart Fail. 2017 May;10(5). https://doi.org/10.1161/CIRCHEARTFAILURE.117.003862.
   Google Scholar
• Borlaug BA, Anstrom KJ, Lewis GD, et al. Effect of inorganic nitrite vs placebo on exercise capacity among patients with heart failure with preserved ejection fraction: the indie-hfpef randomized clinical trial. Jama. 2018 Nov 6 320(17):1764–1773.
   PubMed Web of Science ®Google Scholar
• Redfield MM, Chen HH, Borlaug BA, et al. Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial. Jama. 2013 Mar 27 309(12):1268–1277.
   PubMed Web of Science ®Google Scholar
• Guazzi M, Vicenzi M, Arena R, et al. Pulmonary hypertension in heart failure with preserved ejection fraction: a target of phosphodiesterase-5 inhibition in a 1-year study. Circulation. 2011 Jul 12 124(2):164–174.
   PubMed Web of Science ®Google Scholar
• Pieske B, Maggioni AP, Lam CSP, et al. Vericiguat in patients with worsening chronic heart failure and preserved ejection fraction: results of the soluble guanylate cyclase stimulator in heart failure patients with preserved ef (socrates-preserved) study. Eur Heart J. 2017 Apr 14 38(15):1119–1127.
   PubMed Web of Science ®Google Scholar
• López B, González A, Beaumont J, et al. Identification of a potential cardiac antifibrotic mechanism of torasemide in patients with chronic heart failure. J Am Coll Cardiol. 2007 Aug 28 50(9):859–867.
   PubMed Web of Science ®Google Scholar
• Uchida T, Yamanaga K, Nishikawa M, et al. Anti-aldosteronergic effect of torasemide. Eur J Pharmacol. 1991 Nov 26 205(2):145–150.
   PubMed Web of Science ®Google Scholar
• Ellison DH, Felker GM. Diuretic treatment in heart failure. N Engl J Med. 2017 Nov 16; 377(20):1964–1975.
   PubMed Web of Science ®Google Scholar
• Packer M, Zannad F, Anker SD. Heart failure and a preserved ejection fraction: a side-by-side examination of the paragon-hf and emperor-preserved trials. Circulation. 2021;144:1193–1195.
   PubMed Web of Science ®Google Scholar
• Van Tassell BW, Arena R, Biondi-Zoccai G, et al. Effects of interleukin-1 blockade with anakinra on aerobic exercise capacity in patients with heart failure and preserved ejection fraction (from the D-HART pilot study). Am J Cardiol. 2014 Jan 15 113(2):321–327.
   PubMed Web of Science ®Google Scholar
• Van Tassell BW, Buckley LF, Carbone S, et al. Interleukin-1 blockade in heart failure with preserved ejection fraction: rationale and design of the diastolic heart failure anakinra response trial 2 (D-HART2). Clin Cardiol. 2017 Sep;40(9):626–632.
   PubMed Web of Science ®Google Scholar
• Maier LS, Layug B, Karwatowska-Prokopczuk E, et al. RAnoLazIne for the treatment of diastolic heart failure in patients with preserved ejection fraction: the RALI-DHF proof-of-concept study. JACC Heart Fail. 2013 Apr;1(2):115–122.
   PubMed Web of Science ®Google Scholar
• Travers JG, Wennersten SA, Peña B, et al. HDAC inhibition reverses preexisting diastolic dysfunction and blocks covert extracellular matrix remodeling. Circulation. 2021 May 11 143(19):1874–1890.
   PubMed Web of Science ®Google Scholar
• Methawasin M, Strom JG, Slater RE, et al. Experimentally increasing the compliance of titin through rna binding motif-20 (rbm20) inhibition improves diastolic function in a mouse model of heart failure with preserved ejection fraction. Circulation. 2016 Oct 11 134(15):1085–1099.
   PubMed Web of Science ®Google Scholar
• Bayes-Genis A, de Antonio M, Vila J, et al. Head-to-head comparison of 2 myocardial fibrosis biomarkers for long-term heart failure risk stratification: ST2 versus galectin-3. J Am Coll Cardiol. 2014 Jan 21 63(2):158–166.
   PubMed Web of Science ®Google Scholar
• Najjar E, Faxén UL, Hage C, et al. ST2 in heart failure with preserved and reduced ejection fraction. Scand Cardiovasc J. 2019 Feb;53(1):21–27.
   PubMed Web of Science ®Google Scholar
• AbouEzzeddine OF, McKie PM, Dunlay SM, et al. Suppression of tumorigenicity 2 in heart failure with preserved ejection fraction. J Am Heart Assoc. 2017 Feb 18;6(2). https://doi.org/10.1161/JAHA.116.004382.
   Google Scholar
• Duprez DA, Gross MD, Kizer JR, et al. Predictive value of collagen biomarkers for heart failure with and without preserved ejection fraction: mesa (multi-ethnic study of atherosclerosis). J Am Heart Assoc. 2018 Feb 23;7(5). https://doi.org/10.1161/JAHA.117.007885.
   Google Scholar
• Gopal DM, Ayalon N, Wang YC, et al. Galectin-3 is associated with stage b metabolic heart disease and pulmonary hypertension in young obese patients. J Am Heart Assoc. 2019 Apr 2 8(7):e011100.
   PubMed Web of Science ®Google Scholar
• Chamsi-Pasha MA, Zhan Y, Debs D, et al. CMR in the evaluation of diastolic dysfunction and phenotyping of hfpef: current role and future perspectives. JACC Cardiovasc Imaging. 2020 Jan;13(1 Pt 2):283–296.
   PubMed Web of Science ®Google Scholar
• Flachskampf FA, Biering-Sørensen T, Solomon SD, et al. Cardiac imaging to evaluate left ventricular diastolic function. JACC Cardiovasc Imaging. 2015 Sep;8(9):1071–1093.
   PubMed Web of Science ®Google Scholar
• Oghina S, Bougouin W, Bézard M, et al. The impact of patients with cardiac amyloidosis in hfpef trials. JACC Heart Fail. 2021 Mar;9(3):169–178.
   PubMedGoogle Scholar
• Lund LH, Claggett B, Liu J, et al. Heart failure with mid-range ejection fraction in CHARM: characteristics, outcomes and effect of candesartan across the entire ejection fraction spectrum. Eur J Heart Fail. 2018 Aug;20(8):1230–1239.
   PubMed Web of Science ®Google Scholar
• Solomon SD, Claggett B, Lewis EF, et al. Influence of ejection fraction on outcomes and efficacy of spironolactone in patients with heart failure with preserved ejection fraction. Eur Heart J. 2016 Feb 1 37(5):455–462.
   PubMed Web of Science ®Google Scholar
• Volpe M, Bauersachs J, Bayes-Genis A et al. Sacubitril/valsartan for the management of heart failure: a perspective viewpoint on current evidence. Int J Cardiol. 2021;327:138–145.
   PubMed Web of Science ®Google Scholar
• Solomon SD, Vaduganathan M, Claggett BL, et al. Sacubitril/valsartan across the spectrum of ejection fraction in heart failure. Circulation. 2020;141:352–361.
   PubMed Web of Science ®Google Scholar
• Volpe M, Gallo G. Cardiometabolic phenotype of heart failure with preserved ejection fraction as a target of sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide receptor agonists. Cardiovasc Res. 2021 Jul 27; 117(9):1992–1994.
   PubMed Web of Science ®Google Scholar
• Rieger AC, Bagno LL, Salerno A, et al. Growth hormone-releasing hormone agonists ameliorate chronic kidney disease-induced heart failure with preserved ejection fraction. Proc Natl Acad Sci U S A. 2021;118(4):e2019835118.
   PubMed Web of Science ®Google Scholar
• Chiou YA, Hung CL, Lin SF. AI-assisted echocardiographic prescreening of heart failure with preserved ejection fraction on the basis of intrabeat dynamics. JACC Cardiovasc Imaging. 2021 Nov;14(11):2091–2104.
   PubMed Web of Science ®Google Scholar
• Magrì D, Piepoli M, CorrA U, et al. Cardiovascular death risk in recovered mid-range ejection fraction heart failure: insights from cardiopulmonary exercise test. J Card Fail. 2020;26(11):932–943.
   PubMed Web of Science ®Google Scholar