Pharmacologic Therapy for Heart Failure with Preserved Ejection Fraction

Oktay A.A. Rich J.D. Shah S.J.

The emerging epidemic of heart failure with preserved ejection fraction.

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Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes.

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A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation.

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From systemic inflammation to myocardial fibrosis: the heart failure with preserved ejection fraction paradigm Revisited.

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Characterization of health-related quality of life in heart failure patients with preserved versus low ejection fraction in CHARM.

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Heart Failure With Preserved, Borderline, and Reduced Ejection Fraction: 5-Year Outcomes.

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2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure.

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2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of Amer.

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A simple, evidence-based approach to help guide diagnosis of heart failure with preserved ejection fraction.

Circulation. 138: 861-870Pieske B. Tschöpe C. de Boer R.A. et al.

How to diagnose heart failure with preserved ejection fraction: the HFA–PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

Eur J Heart Fail. 22: 391-412Barandiarán Aizpurua A. Sanders-van Wijk S. Brunner-La Rocca H.P. et al.

Validation of the HFA-PEFF score for the diagnosis of heart failure with preserved ejection fraction.

Eur J Heart Fail. 22: 413-421Borlaug B.A. Nishimura R.A. Sorajja P. Lam C.S.P. Redfield M.M.

Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction.

Circ Hear Fail. 3: 588-595Rao V.N. Kelsey M.D. Blazing M.A. Pagidipati N.J. Fortin T. Fudim M.

Unexplained Dyspnea on Exertion: The Difference the Right Test Can Make.

Circ Heart Fail. : 1-4Oghina S. Bougouin W. Bézard M. et al.

The Impact of Patients With Cardiac Amyloidosis in HFpEF Trials.

JACC Hear Fail. 9: 169-178Garcia-Pavia P. Rapezzi C. Adler Y. et al.

Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases.

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Kittleson MM, Maurer MS, Ambardekar A V., et al. Cardiac Amyloidosis: Evolving Diagnosis and Management: A Scientific Statement from the American Heart Association. Circulation. Published online 2020:E7-E22. doi:10.1161/CIR.0000000000000792

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Management of cardiac sarcoidosis in 2020.

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2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy.

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Current evidence supporting the role of diuretics in heart failure: A meta analysis of randomised controlled trials.

Int J Cardiol. 82: 149-158Adamson P.B. Abraham W.T. Bourge R.C. et al.

Wireless pulmonary artery pressure monitoring guides management to reduce decompensation in heart failure with preserved ejection fraction.

Circ Hear Fail. 7: 935-944Sharma K. Vaishnav J. Kalathiya R. et al.

Randomized Evaluation of Heart Failure With Preserved Ejection Fraction Patients With Acute Heart Failure and Dopamine: The ROPA-DOP Trial.

JACC Hear Fail. 6: 859-870

Should torsemide be the loop diuretic of choice in systolic heart failure?.

Future Cardiol. 8: 707-728

Clinical Pharmacokinetics and Pharmacodynamics of Torasemide.

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Torasemide inhibits transcardiac extraction of aldosterone in patients with congestive heart failure [3].

J Am Coll Cardiol. 44: 2252-2253Yamato M. Sasaki T. Honda K. et al.

Effects of torasemide on left ventricular function and neurohumoral factors in patients with chronic heart failure.

Circ J. 67: 384-390Gravez B. Tarjus A. Jimenez-Canino R. et al.

The Diuretic Torasemide Does Not Prevent Aldosterone-Mediated Mineralocorticoid Receptor Activation in Cardiomyocytes.

PLoS One. 8https://doi.org/10.1371/journal.pone.0073737Miles J.A. Hanumanthu B.K. Patel K. Chen M. Siegel R.M. Kokkinidis D.G.

Torsemide versus furosemide and intermediate-term outcomes in patients with heart failure: An updated meta-analysis.

J Cardiovasc Med. 20: 379-388Abraham B. Megaly M. Sous M. et al.

Meta-Analysis Comparing Torsemide Versus Furosemide in Patients With Heart Failure.

Am J Cardiol. 125: 92-99Greene S.J. Velazquez E.J. Anstrom K.J. et al.

Pragmatic Design of Randomized Clinical Trials for Heart Failure: Rationale and Design of the TRANSFORM-HF Trial.

JACC Hear Fail. 9: 325-335Mentz R.J. Kelly J.P. Von Lueder T.G. et al.

Noncardiac comorbidities in heart failure with reduced versus preserved ejection fraction.

J Am Coll Cardiol. 64: 2281-2293Fagard R.H. Celis H. Thijs L. Wouters S.

Regression of left ventricular mass by antihypertensive treatment: A meta-analysis of randomized comparative studies.

Hypertension. 54: 1084-1091Reddy Y.N.V. Obokata M. Verbrugge F.H. Lin G. Borlaug B.A.

Atrial Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction and Atrial Fibrillation.

J Am Coll Cardiol. 76: 1051-1064Kotecha D. Lam C.S.P. Van Veldhuisen D.J. Van Gelder I.C. Voors A.A. Rienstra M.

Heart Failure With Preserved Ejection Fraction and Atrial Fibrillation: Vicious Twins.

J Am Coll Cardiol. 68: 2217-2228Carlisle M.A. Fudim M. DeVore A.D. Piccini J.P.

Heart Failure and Atrial Fibrillation, Like Fire and Fury.

JACC Hear Fail. 7: 447-456Alexandre J. Dolladille C. Douesnel L. et al.

Effects of Mineralocorticoid Receptor Antagonists on Atrial Fibrillation Occurrence: A Systematic Review, Meta-Analysis, and Meta-Regression to Identify Modifying Factors.

J Am Heart Assoc. 8https://doi.org/10.1161/JAHA.119.013267Liu T. Korantzopoulos P. Shao Q. Zhang Z. Letsas K.P. Li G.

Mineralocorticoid receptor antagonists and atrial fibrillation: A meta-analysis.

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Finerenone Reduces New-Onset Atrial Fibrillation in Patients With Chronic Kidney Disease and Type 2 Diabetes.

J Am Coll Cardiol. 78: 142-152Cha Y.M. Wokhlu A. Asirvatham S.J. et al.

Success of ablation for atrial fibrillation in isolated left ventricular diastolic dysfunction: A comparison to systolic dysfunction and normal ventricular function.

Circ Arrhythmia Electrophysiol. 4: 724-732Black-Maier E. Ren X. Steinberg B.A. et al.

Catheter ablation of atrial fibrillation in patients with heart failure and preserved ejection fraction.

Hear Rhythm. 15: 651-657Hwang S.J. Melenovsky V. Borlaug B.A.

Implications of coronary artery disease in heart failure with preserved ejection fraction.

J Am Coll Cardiol. 63: 2817-2827Dunlay S.M. Givertz M.M. Aguilar D. et al.

Type 2 Diabetes Mellitus and Heart Failure a Scientific Statement from the American Heart Association and the Heart Failure Society of America.

Circulation. 140https://doi.org/10.1161/CIR.0000000000000691Yusuf S. Pfeffer M.A. Swedberg K. et al.

Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial.

Lancet. 362: 777-781Lund L.H. 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. 20: 1230-1239Rogers J.K. Pocock S.J. McMurray J.J.V. et al.

Corrigendum to “Analysing recurrent hospitalizations in heart failure: A review of statistical methodology, with application to CHARM-Preserved” [ Eur J Heart Fail 2014;16:33-40].

Eur J Heart Fail. 16: 592Solomon S.D. Janardhanan R. Verma A. et al.

Effect of angiotensin receptor blockade and antihypertensive drugs on diastolic function in patients with hypertension and diastolic dysfunction: a randomised trial.

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The perindopril in elderly people with chronic heart failure (PEP-CHF) study.

Eur Heart J. 27: 2338-2345

Effect of spironolactone on diastolic function in hypertensive left ventricular hypertrophy.

JAMA. Published online. https://doi.org/10.1038/jhh.2014.83

Spironolactone in heart failure with preserved ejection fraction.

N Engl J Med. 258: 10Pfeffer M.A. Claggett B. Assmann S.F. et al.

Regional variation in patients and outcomes in the treatment of preserved cardiac function heart failure with an aldosterone antagonist (TOPCAT) trial.

Circulation. 131: 34-42Pfeffer M.A. Braunwald E.

Treatment of heart failure with preserved ejection fraction: Reflections on its treatment with an aldosterone antagonist.

JAMA Cardiol. 1: 7-8Solomon S.D. Claggett B. Lewis E.F. et al.

Influence of ejection fraction on outcomes and efficacy of spironolactone in patients with heart failure with preserved ejection fraction.

Eur Heart J. 37: 455-462Solomon S.D. McMurray J.J.V. Anand I.S. et al.

Angiotensin–Neprilysin Inhibition in Heart Failure with Preserved Ejection Fraction.

N Engl J Med. 381: 1609-1620Solomon S.D. Vaduganathan M. Claggett B L. et al.

Sacubitril/Valsartan across the Spectrum of Ejection Fraction in Heart Failure.

Circulation. Published online. : 352-361

Effect of Sacubitril/Valsartan vs Standard Medical Therapies on Plasma NT-proBNP Concentration and Submaximal Exercise Capacity in Patients With Heart Failure and Preserved Ejection Fraction The PARALLAX Randomized Clinical Trial.

JAMA. : 1919-1929https://doi.org/10.1001/jama.2021.18463Flather M.D. Shibata M.C. Coats A.J.S. et al.

FASTTRACK Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS).

Eur Heart J. 26: 215-225van Veldhuisen D.J. Cohen-Solal A. Böhm M. et al.

Beta-Blockade With Nebivolol in Elderly Heart Failure Patients With Impaired and Preserved Left Ventricular Ejection Fraction. Data From SENIORS (Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure).

J Am Coll Cardiol. 53: 2150-2158Cleland J.G.F. Bunting K.V. Flather M.D. et al.

Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: An individual patient-level analysis of double-blind randomized trials.

Eur Heart J. 39: 26-35Yamamoto K. Origasa H. Hori M.

Effects of carvedilol on heart failure with preserved ejection fraction: The Japanese Diastolic Heart Failure Study (J-DHF).

Eur J Heart Fail. 15: 110-118Palau P. Seller J. Domínguez E. et al.

Effect of β-Blocker Withdrawal on Functional Capacity in Heart Failure and Preserved Ejection Fraction.

J Am Coll Cardiol. 78: 2042-2056Bhatt D.L. Szarek M. Steg P.G. et al.

Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure.

N Engl J Med. 384: 117-128Anker S.D. Butler J. Filippatos G. et al.

Empagliflozin in Heart Failure with a Preserved Ejection Fraction.

N Engl J Med. 385: 1451-1461Butler J. Packer M. Filippatos G. et al.

Effect of empagliflozin in patients with heart failure across the spectrum of left ventricular ejection fraction.

Eur Heart J. (): 1-11

Butler J, Filippatos G, Siddiqi TJ, et al. Empagliflozin , Health Status , and Quality of Life in Patients with Heart Failure and Preserved Ejection Fraction : The EMPEROR-Preserved Trial.

Nassif M.E. Windsor S.L. Borlaug B.A. et al.

The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial.

Nat Med. 27: 1954-1960Ahmed A. Rich M.W. Fleg J.L. et al.

Effects of digoxin on morbidity and mortality in diastolic heart failure: The ancillary digitalis investigation group trial.

Circulation. 114: 397-403Redfield M.M. Chen H.H. Borlaug B.A. 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. 309: 1268-1277Redfield M.M. Anstrom K.J. Levine J.A. et al.

Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction.

N Engl J Med. 373: 2314-2324Borlaug B.A. Anstrom K.J. Lewis G.D. 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. 320: 1764-1773

Fussing over the middle child.

Circulation. 135: 1279-1280

A Stepwise Guide to the Diagnosis and Treatment of Heart Failure with Preserved Ejection Fraction.

J Card Fail. https://doi.org/10.1016/j.cardfail.2021.12.013Wintrich J. Kindermann I. Ukena C. et al.

Therapeutic approaches in heart failure with preserved ejection fraction: past, present, and future.

Clin Res Cardiol. 109: 1079-1098Kitzman D.W. Brubaker P. Morgan T. et al.

Effect of caloric restriction or aerobic exercise training on peak oxygen consumption and quality of life in obese older patients with heart failure with preserved ejection fraction: A randomized clinical trial.

JAMA - J Am Med Assoc. 315: 36-46Mentz R.J. Whellan D.J. Reeves G.R. et al.

Rehabilitation Intervention in Older Patients With Acute Heart Failure With Preserved Versus Reduced Ejection Fraction.

JACC Hear Fail. 9: 747-757Edelmann F. Gelbrich G. Dngen H.D. et al.

Exercise training improves exercise capacity and diastolic function in patients with heart failure with preserved ejection fraction: Results of the Ex-DHF (exercise training in diastolic heart failure) pilot study.

J Am Coll Cardiol. 58: 1780-1791Feldman T. Mauri L. Kahwash R. et al.

Transcatheter Interatrial Shunt Device for the Treatment of Heart Failure with Preserved Ejection Fraction (REDUCE LAP-HF i [Reduce Elevated Left Atrial Pressure in Patients with Heart Failure]): A Phase 2, Randomized, Sham-Controlled Trial.

Circulation. 137: 364-375Shah S.J. Feldman T. Ricciardi M.J. et al.

One-Year Safety and Clinical Outcomes of a Transcatheter Interatrial Shunt Device for the Treatment of Heart Failure with Preserved Ejection Fraction in the Reduce Elevated Left Atrial Pressure in Patients with Heart Failure (REDUCE LAP-HF I) Trial: A Ran.

JAMA Cardiol. 3: 968-977Berry N. Mauri L. Feldman T. et al.

Transcatheter InterAtrial Shunt Device for the treatment of heart failure: Rationale and design of the pivotal randomized trial to REDUCE Elevated Left Atrial Pressure in Patients with Heart Failure II (REDUCE LAP-HF II): Rationale and design of REDUCE LA.

Am Heart J. 226: 222-231Shah S.J. Borlaug B.A. Chung E.S. et al.

Atrial shunt device for heart failure with preserved and mildly reduced ejection fraction (REDUCE LAP-HF II): a randomised, multicentre, blinded, sham-controlled trial.

Lancet. 6736: 1-11Lindenfeld J.A. Zile M.R. Desai A.S. et al.

Haemodynamic-guided management of heart failure (GUIDE-HF): a randomised controlled trial.

Lancet. 398: 991-1001Greene S.J. DeVore A.D. Sheng S. et al.

Representativeness of a Heart Failure Trial by Race and Sex: Results From ASCEND-HF and GWTG-HF.

JACC Hear Fail. 7: 980-992Greene S.J. Butler J. Albert N.M. et al.

Medical Therapy for Heart Failure With Reduced Ejection Fraction: The CHAMP-HF Registry.

J Am Coll Cardiol. 72: 351-366Greene S.J. Fonarow G.C. DeVore A.D. et al.

Titration of Medical Therapy for Heart Failure With Reduced Ejection Fraction.

J Am Coll Cardiol. 73: 2365-2383Brunner-La Rocca H.P. Linssen G.C. Smeele F.J. et al.

Contemporary Drug Treatment of Chronic Heart Failure With Reduced Ejection Fraction: The CHECK-HF Registry.

JACC Hear Fail. 7: 13-21Solomon S.D. de Boer R.A. DeMets D. et al.

Dapagliflozin in heart failure with preserved and mildly reduced ejection fraction: rationale and design of the DELIVER trial.

Eur J Heart Fail. 23: 1217-1225Zamani P. Rawat D. Shiva-Kumar P. et al.

Effect of inorganic nitrate on exercise capacity in heart failure with preserved ejection fraction.

Circulation. 131: 371-380Borlaug B.A. Koepp K.E. Melenovsky V.

Sodium Nitrite Improves Exercise Hemodynamics and Ventricular Performance in Heart Failure with Preserved Ejection Fraction.

J Am Coll Cardiol. 66: 1672-1682Borlaug B.A. Melenovsky V. Koepp K.E.

Inhaled Sodium Nitrite Improves Rest and Exercise Hemodynamics in Heart Failure with Preserved Ejection Fraction.

Circ Res. 119: 880-886Eggebeen J. Kim-Shapiro D.B. Haykowsky M. et al.

One Week of Daily Dosing With Beetroot Juice Improves Submaximal Endurance and Blood Pressure in Older Patients With Heart Failure and Preserved Ejection Fraction.

JACC Hear Fail. 4: 428-437Fudim M. Abraham W.T. von Bardeleben R.S. et al.

Device Therapy in Chronic Heart Failure: JACC State-of-the-Art Review.

J Am Coll Cardiol. 78: 931-956Rosalia L. Ozturk C. Shoar S. et al.

Device-Based Solutions to Improve Cardiac Physiology and Hemodynamics in Heart Failure With Preserved Ejection Fraction.

JACC Basic to Transl Sci. 6: 772-795DeVore A.D. McNulty S. Alenezi F. et al.

Impaired left ventricular global longitudinal strain in patients with heart failure with preserved ejection fraction: insights from the RELAX trial.

Eur J Heart Fail. 19: 893-900

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